FN Thomson Reuters Web of Science™ VR 1.0 PT J AU VANGELDEREN, P OLSON, A MOONEN, CTW AF VANGELDEREN, P OLSON, A MOONEN, CTW TI A SINGLE-SHOT DIFFUSION EXPERIMENT SO JOURNAL OF MAGNETIC RESONANCE SERIES A LA English DT Note ID GRADIENT C1 NIH,NCRR,BEIP,INVIVO NMR RES CTR,BETHESDA,MD 20892. DELFT UNIV TECHNOL,FAC APPL PHYS,DELFT,NETHERLANDS. RI Moonen, Chrit/K-4434-2016 OI Moonen, Chrit/0000-0001-5593-3121 NR 5 TC 10 Z9 10 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 JUN 1 PY 1993 VL 103 IS 1 BP 105 EP 108 DI 10.1006/jmra.1993.1139 PG 4 WC Physics, Atomic, Molecular & Chemical SC Physics GA LJ625 UT WOS:A1993LJ62500017 ER PT J AU DAVIS, DG AF DAVIS, DG TI SELECTIVE EXCITATION OF PROTONS DIRECTLY BONDED TO C-13 SO JOURNAL OF MAGNETIC RESONANCE SERIES B LA English DT Article ID COUPLING-CONSTANTS; POLARIZATION TRANSFER; SPIN SYSTEMS; SPECTRA; INVERSE; C-13; NMR; OLIGOSACCHARIDES; SIMPLIFICATION; SPECTROSCOPY RP DAVIS, DG (reprint author), NIEHS,MOLEC BIOPHYS LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 25 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 1064-1866 J9 J MAGN RESON SER B JI J. Magn. Reson. Ser. B PD JUN PY 1993 VL 101 IS 3 BP 229 EP 239 DI 10.1006/jmrb.1993.1039 PG 11 WC Physics, Atomic, Molecular & Chemical SC Physics GA LK558 UT WOS:A1993LK55800001 ER PT J AU SPENCER, RGS HORSKA, A FERRETTI, JA WEISS, GH AF SPENCER, RGS HORSKA, A FERRETTI, JA WEISS, GH TI SPILLOVER AND INCOMPLETE SATURATION IN KINETIC MEASUREMENTS SO JOURNAL OF MAGNETIC RESONANCE SERIES B LA English DT Note ID RAT SKELETAL-MUSCLE; CREATINE-KINASE; INVIVO C1 NHLBI,CHEM LAB,BETHESDA,MD 20892. NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. RP SPENCER, RGS (reprint author), NIA,GERONTOL RES CTR,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 13 TC 24 Z9 24 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1064-1866 J9 J MAGN RESON SER B JI J. Magn. Reson. Ser. B PD JUN PY 1993 VL 101 IS 3 BP 294 EP 296 DI 10.1006/jmrb.1993.1045 PG 3 WC Physics, Atomic, Molecular & Chemical SC Physics GA LK558 UT WOS:A1993LK55800007 ER PT J AU POWERS, R CLORE, GM GARRETT, DS GRONENBORN, AM AF POWERS, R CLORE, GM GARRETT, DS GRONENBORN, AM TI RELATIONSHIPS BETWEEN THE PRECISION OF HIGH-RESOLUTION PROTEIN NMR STRUCTURES, SOLUTION-ORDER PARAMETERS, AND CRYSTALLOGRAPHIC B-FACTORS SO JOURNAL OF MAGNETIC RESONANCE SERIES B LA English DT Note ID 3-DIMENSIONAL STRUCTURE; INTERLEUKIN-1-BETA; SPECTROSCOPY; REFINEMENT C1 NIDDKD,CHEM PHYS LAB,BLDG 2,BETHESDA,MD 20892. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 17 TC 26 Z9 27 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1064-1866 J9 J MAGN RESON SER B JI J. Magn. Reson. Ser. B PD JUN PY 1993 VL 101 IS 3 BP 325 EP 327 DI 10.1006/jmrb.1993.1051 PG 3 WC Physics, Atomic, Molecular & Chemical SC Physics GA LK558 UT WOS:A1993LK55800013 ER PT J AU MCNELLIS, D AF MCNELLIS, D TI A VIEW FROM BETHESDA - OB-GYN RESEARCH - IS THERE A PROBLEM SO JOURNAL OF MATERNAL-FETAL INVESTIGATION LA English DT Editorial Material RP MCNELLIS, D (reprint author), NICHHD,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0939-6322 J9 J MATERN-FETAL INVES JI J. Matern.-Fetal Invest. PD SUM PY 1993 VL 3 IS 3 BP 153 EP 154 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA LV661 UT WOS:A1993LV66100003 ER PT J AU RICHARDS, FM MAHER, ER LATIF, F PHIPPS, ME TORY, K LUSH, M CROSSEY, PA OOSTRA, B ENBLAD, P GUSTAVSON, KH GREEN, J TURNER, G YATES, JRW LINEHAN, M AFFARA, NA LERMAN, M ZBAR, B FERGUSONSMITH, MA AF RICHARDS, FM MAHER, ER LATIF, F PHIPPS, ME TORY, K LUSH, M CROSSEY, PA OOSTRA, B ENBLAD, P GUSTAVSON, KH GREEN, J TURNER, G YATES, JRW LINEHAN, M AFFARA, NA LERMAN, M ZBAR, B FERGUSONSMITH, MA TI DETAILED GENETIC-MAPPING OF THE VONHIPPEL-LINDAU DISEASE TUMOR-SUPPRESSOR GENE (VOL 30, PG 104, 1993) SO JOURNAL OF MEDICAL GENETICS LA English DT Correction, Addition C1 NCI,FREDERICK CANC RES FACIL,IMMUNOBIOL LAB,FREDERICK,MD 21701. ERASMUS UNIV ROTTERDAM,3000 DR ROTTERDAM,NETHERLANDS. ICRF,GENET EPIDEMIOL LAB,LEEDS,ENGLAND. UNIV UPPSALA,S-75105 UPPSALA,SWEDEN. MEM UNIV NEWFOUNDLAND,DIV COMMUNITY MED,ST JOHNS A1C 5S7,NEWFOUNDLAND,CANADA. YORKSHIRE REG GENET SERV,LEEDS,ENGLAND. NCI,SURG BRANCH,BETHESDA,MD 20892. RP RICHARDS, FM (reprint author), UNIV CAMBRIDGE,DEPT PATHOL,CAMBRIDGE,ENGLAND. NR 1 TC 1 Z9 1 U1 0 U2 2 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD JUN PY 1993 VL 30 IS 6 BP 528 EP 528 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA LG291 UT WOS:A1993LG29100022 ER PT J AU BIBEN, M AF BIBEN, M TI STILLBIRTH OF TWINS IN A SQUIRREL-MONKEY (SAIMIRI-BOLIVIENSIS-PERUVIENSIS) SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article DE SQUIRREL MONKEY; SAIMIRI; MULTIPLE BIRTHS; STILLBIRTH AB This is the first published report of twinning in a squirrel monkey (genus Saimiri). The mother survived but the twins, both male and close to full term, were stillborn RP BIBEN, M (reprint author), NIH,CTR ANIM,COMPARAT ETHOL LAB,BLDG 112,ROOM 205,POB 529,POOLESVILLE,MD 20837, USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD JUN PY 1993 VL 22 IS 4 BP 276 EP 277 PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA MH768 UT WOS:A1993MH76800009 PM 8230179 ER PT J AU LIANG, CT BARNES, J SACKTOR, B BALAKIR, RA AF LIANG, CT BARNES, J SACKTOR, B BALAKIR, RA TI CHARACTERIZATION OF DIETARY PHOSPHORUS-DEPENDENT DUODENAL CALCIUM-UPTAKE IN VITAMIN-D-DEFICIENT CHICKS SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article DE INTESTINAL CALCIUM UPTAKE; DIETARY PHOSPHORUS AND CALCIUM; INTESTINAL BRUSH-BORDER CALCIUM UPTAKE; VITAMIN-D-DEFICIENT CHICKS ID PHOSPHATE-UPTAKE; RENAL-CELLS; 1,25-DIHYDROXYVITAMIN-D3; METABOLISM; ABSORPTION; INTESTINE; INVITRO; RATS AB The effect of dietary phosphorus on intestinal calcium uptake was examined in duodenal cells isolated from vitamin D-deficient chicks. Cells from chicks on a high phosphorus diet accumulated calcium at a rate 38% higher than cells from animals on a normal phosphorus diet. Diet high in calcium did not affect calcium absorption in duodenal cells. The dietary phosphorus effect on calcium absorption was specific. Uptake of alpha-methyl glucoside was not altered. Increase in calcium absorption by a high phosphorus diet was not due to a change in cellular energy metabolism nor to the content of phosphorus in cells. Kinetically, a high phosphorus diet increased the V(max) of calcium uptake; the affinity for calcium was unaffected. The effectiveness of dietary phosphorus to enhance the intestinal calcium uptake could also be demonstrated in brush border membrane vesicles. The increase in calcium uptake was not due to an alteration in membrane binding capacity nor to calcium efflux from vesicles. To test the hypothesis that a high phosphorus diet may affect membrane transport by altering phospholipid metabolism in duodenal cells, we examined the phospholipid content in isolated brush border membranes. The content of phosphatidylcholine, phosphatidylserine, phosphatidyinositol and phosphatidylethanolamine was not altered by the high phosphorus diet. These findings suggest that the vitamin D-independent and dietary phosphorus-dependent effect on intestinal calcium absorption was primarily due to a change in the calcium flux at the luminal side of the cells. However, the precise mechanism is still not clear. RP LIANG, CT (reprint author), NIA,GERONTOL RES CTR,BALTIMORE,MD 21224, USA. NR 20 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD JUN PY 1993 VL 134 IS 3 BP 189 EP 196 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA LH856 UT WOS:A1993LH85600003 PM 8411122 ER PT J AU MURRAY, PM AF MURRAY, PM TI TREATING HOMELESS PEOPLE WITH ALCOHOL AND OTHER DRUG PROBLEMS - ISSUES FOR PRACTICE AND EVALUATION SO JOURNAL OF MENTAL HEALTH ADMINISTRATION LA English DT Editorial Material RP MURRAY, PM (reprint author), NIAAA,HOMELESS DEMONSTRAT & EVALUAT BRANCH,PARKLAWN BLDG,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 18 TC 3 Z9 3 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 0092-8623 J9 J MENT HEALTH ADMIN JI J. Ment. Health Adm. PD SUM PY 1993 VL 20 IS 2 BP 87 EP 89 DI 10.1007/BF02519233 PG 3 WC Health Policy & Services SC Health Care Sciences & Services GA LU252 UT WOS:A1993LU25200001 ER PT J AU XIAO, RP SPURGEON, HA CAPOGROSSI, MC LAKATTA, EG AF XIAO, RP SPURGEON, HA CAPOGROSSI, MC LAKATTA, EG TI STIMULATION OF OPIOID RECEPTORS ON CARDIAC VENTRICULAR MYOCYTES REDUCES L-TYPE CA2+ CHANNEL CURRENT SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Note DE CARDIAC CELLS; OPIOID RECEPTORS; CALCIUM CURRENT; ACTION POTENTIAL ID CALCIUM CHANNELS; CELLS; RAT; PROTEIN; MECHANISM; PEPTIDES; RELEASE; NEURONS C1 NIA, GERONTOL RES CTR, CARDIOVASC SCI LAB, 4940 EASTERN AVE, BALTIMORE, MD 21224 USA. NR 18 TC 29 Z9 31 U1 1 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD JUN PY 1993 VL 25 IS 6 BP 661 EP 666 DI 10.1006/jmcc.1993.1079 PG 6 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA LP689 UT WOS:A1993LP68900006 PM 8411192 ER PT J AU RIBEIRO, P WANG, YH CITRON, BA KAUFMAN, S AF RIBEIRO, P WANG, YH CITRON, BA KAUFMAN, S TI DELETION MUTAGENESIS OF RAT PC12 TYROSINE-HYDROXYLASE REGULATORY AND CATALYTIC DOMAINS SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE TYROSINE HYDROXYLASE; MUTAGENESIS; DOPAMINE REGULATION ID DEPENDENT PROTEIN-KINASE; BOVINE ADRENAL-MEDULLA; N-TERMINAL REGION; CLONED ENZYME; PHOSPHORYLATION; PURIFICATION; PHENYLALANINE; 3-MONOOXYGENASE; EXPRESSION; ACTIVATION AB The functional organization of rat tyrosine hydroxylase was investigated by deletion mutagenesis of the regulatory and catalytic domains. A series of tyrosine hydroxylase cDNA deletion mutants were amplified by PCR, cloned into the pET3C prokaryotic expression vector, and the mutant proteins were partially purified from E. coli. The results show that the deletion of up to 157 N-terminal amino acids activated the enzyme, but further deletion to position 184 completely destroyed catalytic activity. On the carboxyl end, the removal of 43 amino acids decreased but did not eliminate activity, suggesting that this region may play a different role in the regulation of the enzyme. These findings place the amino end of the catalytic domain between residues 158 and 184 and the carboxyl end at or prior to position 455. Deletions within the first 157 amino acids in the N-terminus caused an increase in hydroxylating activity, a decrease in the apparent K(m) for tyrosine and phenylalanine substrates, and a substantial increase in the K(i) for dopamine inhibition. The results define this region of the N-terminus as the regulatory domain of tyrosine hydroxylase, whose primary functions are to restrict the binding of amino acid substrates and to facilitate catecholamine inhibition. The results also suggest that the well-established role of the regulatory domain in restricting cofactor binding may be secondary to an increase in catecholamine binding, which in tum lowers the affinity for the cofactor. These findings provide new insight into the functional organization and mechanisms of regulation of tyrosine hydroxylase. RP RIBEIRO, P (reprint author), NIMH,NEUROCHEM LAB,BETHESDA,MD 20892, USA. NR 42 TC 29 Z9 29 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD SUM PY 1993 VL 4 IS 2 BP 125 EP 139 DI 10.1007/BF02782125 PG 15 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA LU466 UT WOS:A1993LU46600007 PM 8105857 ER PT J AU HE, XS BROSSI, A AF HE, XS BROSSI, A TI 1,2-DEHYDRORETICULINE - CONVERSION OF IMINIUM SALTS INTO ENAMINES SO JOURNAL OF NATURAL PRODUCTS LA English DT Note AB 1,2-Dehydroreticulinium iodide [3] is converted at pH 8 and above into the enamine 4. It is suggested that the cytosolic NADPH2-dependent enzyme which converts 1,2-dehydroreticulinium salts at alkaline pH 7. may be operating on the enamine rather than a quaternary iminium salt. C1 GEORGETOWN UNIV,DEPT CHEM,WASHINGTON,DC 20057. RP HE, XS (reprint author), NIDDKD,MED CHEM LAB,BETHESDA,MD 20892, USA. NR 12 TC 3 Z9 3 U1 1 U2 7 PU AMER SOC PHARMACOGNOSY PI CINCINNATI PA LLOYD LIBRARY & MUSEUM 917 PLUM ST, CINCINNATI, OH 45202 SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD JUN PY 1993 VL 56 IS 6 BP 973 EP 975 DI 10.1021/np50096a029 PG 3 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA LJ178 UT WOS:A1993LJ17800029 ER PT J AU WIDMER, HR KAPLAN, DR RABIN, SJ BECK, KD HEFTI, F KNUSEL, B AF WIDMER, HR KAPLAN, DR RABIN, SJ BECK, KD HEFTI, F KNUSEL, B TI RAPID PHOSPHORYLATION OF PHOSPHOLIPASE C-GAMMA-1 BY BRAIN-DERIVED NEUROTROPHIC FACTOR AND NEUROTROPHIN-3 IN CULTURES OF EMBRYONIC RAT CORTICAL-NEURONS SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE PHOSPHOLIPASE-C; TYROSINE PHOSPHORYLATION; PHOSPHOINOSITIDE METABOLISM; NEURON CULTURES; NERVE GROWTH FACTOR; BRAIN-DERIVED NEUROTROPHIC FACTOR; NEUROTROPHIN-3; K-252B; TRK ID NERVE GROWTH-FACTOR; TYROSINE PROTEIN-KINASE; SEPTAL CHOLINERGIC NEURONS; TRK PROTOONCOGENE PRODUCT; MOLECULAR-CLONING; PC12 CELLS; FACTOR FAMILY; C-GAMMA; FACTOR RECEPTOR; PHOSPHOINOSITIDE HYDROLYSIS AB Phospholipase C-gamma1 (PLC-gamma1) is involved at an early step in signal transduction of many hormones and growth factors and catalyzes the hydrolysis of phosphatidylinositol (PI) 4,5-bisphosphate to diacylglycerol and inositol trisphosphate, two potent intracellular second messenger molecules. The transformation of PC12 cells into neuron-like cells induced by nerve growth factor is preceded by a rapid stimulation of PLC-gamma1 phosphorylation and PI hydrolysis. The present study analyzed the effects of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) on phosphorylation of PLC-gamma1 in primary cultures of embryonic rat brain cells. BDNF and NT-3 stimulated the phosphorylation of PLC-gamma1, followed by hydrolysis of PI. The stimulation of PLC-gamma1 phosphorylation occurred within 20 s after addition of BDNF or NT-3 and lasted up to 30 min, with a peak after 4 min. ED50 values were similar for BDNF and NT-3, with approximately 25 ng/ml. Phosphorylation of PLC-gamma1 by BDNF and NT-3 was found in cultures from all major brain areas. K-252b, a compound known to inhibit selectively neurotrophin actions by interfering with the phosphorylation of trk-type neurotrophin receptors, prevented the BDNF- and NT-3-stimulated phosphorylation of PLC-gamma1. Receptors of the trk type were coprecipitated with anti-PLC-gamma1 antibodies. The presence of irk-B mRNA in the cultures was substantiated by northern blot analysis. The action of BDNF and NT-3 seems to be neuron specific because no phosphorylation of PLC-gamma1 was observed in cultures of nonneuronal brain cells. The results provide evidence that developing neurons of the cerebral cortex and other brain areas are responsive to BDNF and NT-3, and they indicate that the transduction mechanism of BDNF and NT-3 in the brain involves rapid phosphorylation of PLC-gamma1 followed by PI hydrolysis. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21701. RP WIDMER, HR (reprint author), UNIV SO CALIF,ETHEL PERCY ANDRUS GERONTOL CTR,DIV NEUROGERONTOL,UNIV PK,LOS ANGELES,CA 90089, USA. FU NCI NIH HHS [CO74101]; NIA NIH HHS [AG10480]; NINDS NIH HHS [NS22933] NR 94 TC 72 Z9 73 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUN PY 1993 VL 60 IS 6 BP 2111 EP 2123 DI 10.1111/j.1471-4159.1993.tb03496.x PG 13 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA LC873 UT WOS:A1993LC87300013 PM 8492120 ER PT J AU DIENEL, GA CRUZ, NF AF DIENEL, GA CRUZ, NF TI SYNTHESIS OF DEOXYGLUCOSE-1-PHOSPHATE, DEOXYGLUCOSE-1,6-BISPHOSPHATE, AND OTHER METABOLITES OF 2-DEOXY-D-[C-14]GLUCOSE IN RAT-BRAIN INVIVO - INFLUENCE OF TIME AND TISSUE GLUCOSE LEVEL SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE CEREBRAL GLUCOSE UTILIZATION; HEXOSE DISTRIBUTION SPACES; HYPOGLYCEMIA; HYPERGLYCEMIA ID 2-DEOXYGLUCOSE INCORPORATION; NMR-SPECTROSCOPY; CEREBRAL-CORTEX; LUMPED CONSTANT; 2-DEOXY-D-GLUCOSE; 1,5-ANHYDROGLUCITOL; BISPHOSPHATASE; 6-PHOSPHATE; 2-FLUORO-2-DEOXY-D-GLUCOSE; GLUCOSE-1,6-BISPHOSPHATE AB When the kinetics of interconversion of deoxy[C-14]glucose ([C-14]DG) and [C-14]DG-6-phosphate ([C-14]DG-6-P) in brain in vivo are estimated by direct chemical measurement of precursor and products in acid extracts of brain, the predicted rate of product formation exceeds the experimentally measured rate. This discrepancy is due, in part, to the fact that acid extraction regenerates [C-14]DG from unidentified labeled metabolites in vitro. In the present study, we have attempted to identify the C-14-labeled compounds in ethanol extracts of brains of rats given [C-14]DG. SiX C-14-labeled metabolites. in addition to [C-14]DG-6-P, were detected and separated. The major acid-labile derivatives, DG-1-phosphate (DG-1-P) and DG-1,6-bisphosphate (DG- 1,6-P2), COMPrised approximately 5 and approximately 10-15%, respectively, of the total C-14 in the brain 45 min after a pulse or square-wave infusion of [C-14] DG, and their levels were influenced by tissue glucose concentration. Both of these acid-labile compounds could be synthesized from DG-6-P by phosphoglucomutase in vitro. DG-6-P, DG-1-P, DG-1,6-P2, and ethanol-insoluble compounds were rapidly labeled after a pulse of [C-14]DG, whereas there was a 10-30-min lag before there was significant labeling of minor labeled derivatives. During the time when there was net loss of [C-14]DG-6-P from the brain (i.e., between 60 and 180 min after the pulse), there was also further metabolism of [C-14]DG-6-P into other ethanol-soluble and ethanol-insoluble C-14-labeled compounds. These results demonstrate that DG is more extensively metabolized in rat brain than commonly recognized and that hydrolysis of [C-14] DG-1-P can explain the overestimation of the [C-14]DG content and underestimation of the metabolite pools of acid extracts of brain. Further metabolism of DG does not interfere with the autoradiographic DG method. RP DIENEL, GA (reprint author), NIMH,CEREBRAL METAB LAB,BLDG 36,ROOM 1A-05,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 73 TC 17 Z9 17 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUN PY 1993 VL 60 IS 6 BP 2217 EP 2231 DI 10.1111/j.1471-4159.1993.tb03508.x PG 15 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA LC873 UT WOS:A1993LC87300025 PM 8492127 ER PT J AU LESCH, KP WOLOZIN, BL MURPHY, DL RIEDERER, P AF LESCH, KP WOLOZIN, BL MURPHY, DL RIEDERER, P TI PRIMARY STRUCTURE OF THE HUMAN PLATELET SEROTONIN UPTAKE SITE - IDENTITY WITH THE BRAIN-SEROTONIN TRANSPORTER SO JOURNAL OF NEUROCHEMISTRY LA English DT Note DE HUMAN; SEROTONIN TRANSPORTER; PRIMARY STRUCTURE; PLATELET; BRAIN ID BINDING-SITES; ANTIDEPRESSANTS; EXPRESSION; CLONING AB A cDNA encoding the human platelet serotonin (5-HT) uptake site was isolated and sequenced using the PCR. The cDNA represents a approximately 3. 1-kb mRNA transcript and contains an open reading frame encoding a hydrophobic polypeptide of 630 amino acids with 12 membrane-spanning segments, a calculated molecular mass of 70,320 Da, and an estimated isoelectrical point of 5.84. The human platelet 5-HT uptake site is identical with the human brain 5-HT transporter and approximately 92% homologous to the rat protein. Hydropathicity analysis indicates 12 membrane-spanning segments with two putative glycosylation sites within the second extracellular loop. The human platelet 5-HT uptake site contains two intraplasmatic consensus phosphorylation sites for cyclic AMP-dependent protein kinase recognition located in the cytoplasmatic N-terminal region and three potential protein kinase C phosphorylation sites. The identity of the human platelet 5-HT uptake site and the brain 5-HT transporter indicates that both proteins are encoded by the same single-copy gene, which has been assigned to the human chromosome 17. Our findings are likely to facilitate molecular pharmacologic and genetic investigations of the 5-HT transporter in psychiatric disorders. C1 NIMH,LCS,CTR CLIN,CLIN NEUROPHARMACOL SECT,BETHESDA,MD 20892. RP LESCH, KP (reprint author), UNIV WURZBURG,DEPT PSYCHIAT,FUCHSLEINSTR 15,W-8700 WURZBURG,GERMANY. RI Lesch, Klaus-Peter/J-4906-2013 OI Lesch, Klaus-Peter/0000-0001-8348-153X NR 17 TC 432 Z9 437 U1 3 U2 11 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUN PY 1993 VL 60 IS 6 BP 2319 EP 2322 DI 10.1111/j.1471-4159.1993.tb03522.x PG 4 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA LC873 UT WOS:A1993LC87300039 PM 7684072 ER PT J AU GRAFMAN, J SCHWARTZ, V DALE, JK SCHEFFERS, M HOUSER, C STRAUS, SE AF GRAFMAN, J SCHWARTZ, V DALE, JK SCHEFFERS, M HOUSER, C STRAUS, SE TI ANALYSIS OF NEUROPSYCHOLOGICAL FUNCTIONING IN PATIENTS WITH CHRONIC FATIGUE SYNDROME SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article ID EPSTEIN-BARR VIRUS; COMMON COLD; MONONUCLEOSIS; PERSISTENT; DEPRESSION; ANTIBODIES; INFECTION; SYMPTOMS; DISEASE; STRESS AB Memory impairment dominates the cognitive complaints of patients with chronic fatigue syndrome (CFS). Twenty CFS patients were available for studies with a clinical and experimental battery composed of memory and cognitive tests. The results on objective testing indicated that the CFS patients had some mild memory impairment, but only on tasks requiring conceptually driven encoding and retrieval processes. There were no associations between the nature of the precipitating illness, self ratings of fatigue, physical findings, or laboratory determination and objective memory performance or self report of memory functioning. These generally negative results indicate that memory impairment in CFS patients is typically mild and involves memory processes that participate in conceptualising information. C1 NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. RP GRAFMAN, J (reprint author), NINCDS,MED NEUROL BRANCH,COGNIT NEUROSCI SECT,BLDG 10,ROOM 55209,BETHESDA,MD 20892, USA. OI Grafman, Jordan H./0000-0001-8645-4457 NR 49 TC 78 Z9 80 U1 3 U2 5 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD JUN PY 1993 VL 56 IS 6 BP 684 EP 689 DI 10.1136/jnnp.56.6.684 PG 6 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA LG285 UT WOS:A1993LG28500018 PM 8509784 ER PT J AU SEGRAVES, MA PARK, K AF SEGRAVES, MA PARK, K TI THE RELATIONSHIP OF MONKEY FRONTAL EYE FIELD ACTIVITY TO SACCADE DYNAMICS SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID SUPERIOR COLLICULUS NEURONS; PONTINE RETICULAR-FORMATION; LATERAL INTRAPARIETAL AREA; FUNCTIONAL-PROPERTIES; INTRACORTICAL MICROSTIMULATION; PREFRONTAL CORTEX; LOCAL FEEDBACK; MOVEMENTS; STIMULATION; CONNECTIONS AB 1. In this study, we compared the temporal waveforms of the activity of monkey frontal eye field movement neurons with the dynamics of saccadic eye movements. 2. Movement neurons in the frontal eye field were selected according to previously published criteria. They had little or no response to visual stimuli in a fixation task, and equivalent activity before visually guided and memory-guided saccades. We studied corticotectal neurons and corticopontine neurons identified by antidromic excitation, as well as neurons whose projections were not identified. 3. These neurons had a peak activation at a mean of 13 ms before the saccade began. However, rather than falling off rapidly as the saccade ended, most neurons continued to fire after the saccade, returning to baseline at a mean of 93 ms after the end of the saccade. 4. We measured the decrement in activity for these neurons during the saccade. Although a few neurons showed decrements of >60% of their peak activity level, the average activity dropped only 16.9%, with some neurons actually showing a rise in activity during the saccade. If we ignored the latency between peak in activity and saccade start and measured the fall in activity for a period equal to one saccade duration after the peak, the average drop in activity was still only 34.9%. Thus the activity of these neurons did not appear to be closely related to dynamic motor error, which falls from its maximum value to zero over the time course of a saccade. 5. These results suggest that a focus of movement activity within the topographic map in the frontal eye field specifies the amplitude and direction for an impending saccade, whereas the peak of movement activity signals the time to initiate a saccade. 6. Unlike the superior colliculus, the activity of frontal eye field movement neurons does not appear to be related to dynamic events that occur during the saccade, such as motor error. C1 NEI,SENSORIMOTOR RES LAB,BETHESDA,MD 60892. RP SEGRAVES, MA (reprint author), NORTHWESTERN UNIV,DEPT NEUROBIOL & PHYSIOL,O T HOGAN HALL,EVANSTON,IL 60208, USA. FU NCRR NIH HHS [BRSG RR-07028]; NEI NIH HHS [EY-08212] NR 63 TC 43 Z9 43 U1 1 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JUN PY 1993 VL 69 IS 6 BP 1880 EP 1889 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA LJ310 UT WOS:A1993LJ31000008 PM 8350128 ER PT J AU LI, L MILLER, EK DESIMONE, R AF LI, L MILLER, EK DESIMONE, R TI THE REPRESENTATION OF STIMULUS-FAMILIARITY IN ANTERIOR INFERIOR TEMPORAL CORTEX SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID STATE DEPENDENT ACTIVITY; MONKEY VISUAL-CORTEX; INFEROTEMPORAL CORTEX; ENTORHINAL CORTEX; HIPPOCAMPAL-FORMATION; RECOGNITION MEMORY; MACAQUE MONKEY; RHESUS-MONKEY; NEURONS; RESPONSES AB 1. The inferior temporal (IT) cortex plays an important role in both short- and long-term memory for visual patterns. Most previous studies of IT neurons have tested their responses in recency memory tasks, which require that the memory lasts only the length of a single behavioral trial, which may be < 1 s. To determine the role of IT neurons in longer lasting memories, we measured their responses to initially novel stimuli as the stimuli gradually became familiar to the animal. 2. Two rhesus monkeys were trained on a delayed matching to sample (DMS) task with several intervening stimuli between the sample and the final matching stimulus on each trial. The purpose of the task was to ensure that the animal attended to the stimuli and held them in memory, at least temporarily. Unlike in several previous studies, the focus was not on within-trial effects but rather on the incidental memories that built up across trials as the stimuli became familiar. Each cell was tested with a set of 20 novel stimuli (digitized pictures of objects) that the monkey had not seen before. These stimuli were used in a fixed order over the course of an hour-long recording session, and the number of intervening trials between repetitions of a given sample stimulus was varied. 3. The responses of about one-third of the cells recorded in anterior-ventral IT cortex declined systematically as the novel stimuli became familiar. After six to eight repetitions, responses reached a plateau that was approximately 40% of the peak response. Virtually all of these cells also showed selectivity for particular visual stimuli and thus were not ''novelty detectors'' in the sense of cells that respond to any novel stimulus. Rather, the responses of these cells were a joint function of familiarity and specific object features such as shape and color. A few cells showed increasing responses with repetition over the recording session, but these changes were accompanied by changes in baseline firing rate, suggesting that they were caused by nonspecific effects. 4. The decrement in response with familiarity was stimulus specific and bridged > 150 presentations of other stimuli, the maximum tested. For some cells the maximum decrement in response occurred for those stimuli that initially elicited the largest response. There was no significant change in response to stimuli that were already familiar. 5. The same cells that showed familiarity effects also showed reduced responses to the matching stimuli at the end of each trial, compared with the responses to the samples. The responses to these matching stimuli declined with familiarity in parallel with the decline in responses to the samples over the session. Recency and familiarity effects appear to summate within IT cortex. 6. We examined the time course of responses to novel and familiar stimuli. The population of cells took 100 ms after response onset to distinguish between a novel stimulus and the same stimulus seen once previously, possibly reflecting feedback to IT cortex. However, after a single additional presentation, cells distinguished between novel and familiar stimuli within 10 ms of response onset, that is, by nearly the first action potential. Thus there is virtually no time for the effect of familiarity on the initial phase of the response to be caused either by lengthy temporal processing with IT cortex or by feedback from other structures. 7. The results support the proposal that a subpopulation of IT cells functions as ''adaptive mnemonic filters'' for both short- and long-term memories. A high level of activation in IT cortex may provide a feedback signal to orienting systems that the current stimulus is new and deserving of attention. Because increased contact with a stimulus drives down activity in IT cortex, this feedback between memory and attentional systems may result in an organism driven to seek out contact with new stimuli. C1 NIMH,NEUROPSYCHOL LAB,BLDG 9,RM 1E104,BETHESDA,MD 20892. NR 57 TC 340 Z9 343 U1 0 U2 9 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JUN PY 1993 VL 69 IS 6 BP 1918 EP 1929 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA LJ310 UT WOS:A1993LJ31000011 PM 8350131 ER PT J AU LAIRD, JMA BENNETT, GJ AF LAIRD, JMA BENNETT, GJ TI AN ELECTROPHYSIOLOGICAL STUDY OF DORSAL HORN NEURONS IN THE SPINAL-CORD OF RATS WITH AN EXPERIMENTAL PERIPHERAL NEUROPATHY SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID PAIN-RELATED BEHAVIOR; NERVE INJURY; SOMATOTOPIC ORGANIZATION; SCIATIC-NERVE; CAT; MONONEUROPATHY; CONSTRICTION; HYPERALGESIA; NOCICEPTION; TRANSECTION AB 1. Extracellular single-unit recordings have been made from 295 dorsal horn neurons in the lumbar enlargement of rat spinal cord; 191 neurons in 20 rats with an experimental peripheral neuropathy, and 104 in 1 0 sham-operated rats. Recordings were made 9-11 days after inducing the neuropathy by tying four loose ligatures around the sciatic nerve in the nerve-injured rats or performing a sham procedure in the sham-operated rats. 2. A survey of the general properties of all neurons encountered was made in the 1 0 sham-operated rats ( 104 neurons) and compared with those seen in 17 of the nerve-injured animals ( 1 80 neurons). The vast majority (87%; 156/180) of neurons recorded in the nerve-injured animals showed abnormal characteristics; these included responses to very gentle mechanical stimulation of the nerve-injury site and to manipulations that resulted in movement of this site such as extension of the leg and probing of the skin and muscle of the thigh (53%), absence of detectable peripheral receptive fields (RFs; 56%), and very high spontaneous activity (7%). In the sham-operated rats none of the neurons recorded could be activated by gentle mechanical stimulation of the sciatic nerve, and only 6% had no detectable peripheral RF. 3. In the nerve-injured animals, 31% (55/180) of cells had both a peripheral RF, and a response to gentle mechanical stimulation of the nerve-injury site. All cells of this type tested (n = 5) showed very prolonged responses (up to 10 min long) to 15 s pinch stimuli applied to the RF and to 15 s gentle tapping of the injury site. The majority of cells in this group were excited by noxious stimuli (71%; 39/55) and had C-fiber inputs (60%; 33/55). 4. The mean threshold temperatures for evoking responses to heat stimuli in cells tested in nerve-injured rats and in sham-operated animals were not different. However, there was a group of neurons in the nerve-injured rats that had low thresholds, failed to encode stimulus intensity, and did not have a C-fiber input. 5. There were significantly fewer neurons excited by low-intensity stimulation of the skin in the nerve-injured (24%; 43/180) than in the sham-operated rats (71%; 74/104). Measurements of mechanical threshold with von Frey hairs showed that, although the mean threshold did not change, none of the cells tested in the nerve-injured animals had thresholds < 12 mN, whereas the lowest threshold recorded in the sham-operated animals was 0.2 mN. 6. We conclude that, whereas some of the abnormalities seen in the properties of dorsal horn neurons in the nerve-injured rats are likely to be deficits produced by the substantial damage to the nerve, such as the loss of peripheral RFs and loss of low-threshold inputs, others, such as the response to stimulation of the injury site, abnormally prolonged responses to stimuli applied to RFs, and increased spontaneous activity are likely to be due to central changes and to the presence of a novel source of input at the site of nerve injury. We propose that input from the nerve-injury site accounts for the pain-related guarding behavior seen in the nerve injured rats and may summate with ''normal'' input to produce the lowered thresholds to external stimuli seen in these animals. This input may also serve to maintain a central abnormality. The prominent afterdischarges seen in some cells are likely to contribute to the abnormally prolonged and intense responses of the nerve-injured animals to even mild noxious stimuli. We conclude that dorsal horn mechanisms make a considerable contribution to the abnormal behavior of rats with an experimental peripheral neuropathy and are likely to contribute to abnormal sensations in patients with neuropathic pain. C1 NIDR, NEUROBIOL & ANESTHESIOL BRANCH, BETHESDA, MD 20892 USA. NR 41 TC 199 Z9 202 U1 1 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 EI 1522-1598 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JUN PY 1993 VL 69 IS 6 BP 2072 EP 2085 PG 14 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA LJ310 UT WOS:A1993LJ31000023 PM 8394412 ER PT J AU WEINBERGER, DR AF WEINBERGER, DR TI A CONNECTIONIST APPROACH TO THE PREFRONTAL CORTEX SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; CEREBRAL BLOOD-FLOW; PROGRESSIVE SUPRANUCLEAR PALSY; FRONTAL-LOBE LESIONS; SORTING TEST-PERFORMANCE; HUNTINGTONS-DISEASE; BASAL GANGLIA; PARKINSONS-DISEASE; RHESUS-MONKEY; PHYSIOLOGIC DYSFUNCTION AB Recent data from studies of the prefrontal cortex (PFC) in humans and laboratory animals are reviewed with particular reference to the anatomical substrates of prefrontal neuropsychological function in health and disease. The PFC has been shown to have a unique pattern of supramodal connectivity with intracortical and subcortical circuits that place the PFC in an anatomical position to subserve 'executive' cognitive-functions and modulate limbic information to relate to basal ganglia circuits in a highly specific manner and to uniquely control the neurochemical elements of attention and reward. PFC connectivity is also consistent with current hypotheses about prefrontal neuropsychology, which emphasize conscious, goal-directed behavior guided by past experience. PFC connectivity explains the frequency with which prefrontal dysfunction is seen in disease states, which, on the basis of neuroimaging and neuropathology data, can be categorized as either intrinsic or dysconnection disorders. RP WEINBERGER, DR (reprint author), NIMH, CTR NEUROSCI, CLIN BRAIN DISORDERS BRANCH, INTRAMURAL RES PROGRAM, WASHINGTON, DC 20032 USA. NR 98 TC 167 Z9 169 U1 2 U2 6 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD SUM PY 1993 VL 5 IS 3 BP 241 EP 253 PG 13 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA LU325 UT WOS:A1993LU32500001 PM 8369632 ER PT J AU SCOTT, TF PRICE, TRP GEORGE, MS BRILLMAN, J ROTHFUS, W AF SCOTT, TF PRICE, TRP GEORGE, MS BRILLMAN, J ROTHFUS, W TI MIDLINE CEREBRAL MALFORMATIONS AND SCHIZOPHRENIA SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID SEPTUM-PELLUCIDUM; VENTRICULAR ENLARGEMENT; PARAHIPPOCAMPAL GYRUS; MONOZYGOTIC TWINS; CORPUS-CALLOSUM; TEMPORAL-LOBE; WHITE MATTER; BRAIN RATIO; ABNORMALITIES; CORTEX AB To investigate a possible association of midline cerebral malformations with psychotic disorders, MRI and CT scans were blindly evaluated for 52 patients with schizophrenia, 9 with schizoaffective disease, and 79 consecutive nonpsychotic control subjects. Midline abnormalities were present in 10 of 61 patients (16.4%) versus 4 of 79 control subjects (5.1%; P < 0.05, chi-square). Of 52 schizophrenic patients, 8 had abnormalities of the septum pellucidum (SP): 5 had cavum vergae (CaV), 2 had cavum septum pellucidum (CaSP), and 1 had agenesis of the corpus callosum and SP. Of 9 schizoaffective patients, 2 had SP abnormalities: 1 CaV and 1 CaSP. Abnormalities of the SP, especially CaV, were significantly more frequent in women than in men (P < 0.02, chi-square). C1 MED COLL PENN,DEPT NEUROL,PHILADELPHIA,PA 19129. MED COLL PENN,DEPT PSYCHIAT,PHILADELPHIA,PA 19129. MED COLL PENN,DEPT RADIOL,PHILADELPHIA,PA 19129. ALLEGHENY GEN HOSP,PITTSBURGH,PA 15212. NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. NR 50 TC 45 Z9 45 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD SUM PY 1993 VL 5 IS 3 BP 287 EP 293 PG 7 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA LU325 UT WOS:A1993LU32500007 PM 8369638 ER PT J AU DAWSON, VL DAWSON, TM BARTLEY, DA UHL, GR SNYDER, SH AF DAWSON, VL DAWSON, TM BARTLEY, DA UHL, GR SNYDER, SH TI MECHANISMS OF NITRIC-OXIDE MEDIATED NEUROTOXICITY IN PRIMARY BRAIN CULTURES SO JOURNAL OF NEUROSCIENCE LA English DT Article DE NADPH-DIAPHORASE; GLUTAMATE; NMDA; NITRIC OXIDE SYNTHASE; EXCITOTOXICITY; NEURODEGENERATION ID INTRACELLULAR CALCIUM CONCENTRATIONS; NEURONAL NADPH DIAPHORASE; GLUTAMATE NEUROTOXICITY; SUPEROXIDE-DISMUTASE; STRIATAL NEURONS; SODIUM-NITROPRUSSIDE; HUNTINGTONS-DISEASE; RELAXING FACTOR; NERVOUS-SYSTEM; CELL-DEATH AB In addition to mediating several physiological functions, nitric oxide (NO) has been implicated in the cytotoxicities observed following activation of macrophages or excess stimulation of neurons by glutamate. We extend our previous observations of glutamate-stimulated, NO-mediated neurotoxicity in primary cultures of rat fetal cortical, striatal, and hippocampal neurons. Neurotoxicity elicited by either NMDA or sodium nitroprusside (SNP) exhibits a similar concentration-effect relationship and time course. The concentration-effect curve of NMDA-induced neurotoxicity is shifted to the right in the presence of nitro-L-arginine and farther to the right in arginine-free media. The rank order of potency of several NO synthase (NOS) inhibitors in preventing neurotoxicity is the same as the rank order of these compounds in inhibiting NOS, and this inhibition is stereospecific. NMDA neurotoxicity is also prevented by flavoprotein inhibitors and calmodulin inhibitors, fitting with the roles of flavoproteins and calmodulin as NOS regulators. 8-Bromo-cGMP and guanylyl cyclase inhibitors do not affect neurotoxicity, while superoxide dismutase attenuates neurotoxicity. NOS neurons appear to be the source of neurotoxic NO in culture, as lesions of these neurons with 20 muM quisqualate diminish subsequent NMDA neurotoxicity. Moreover, NMDA neurotoxicity develops over time in culture coincident with the expression of NOS. Immunohistochemical localization of NOS in cultures and intact brain demonstrates widespread distribution of the cell processes suggesting that NOS neurons contact the majority of cortical neurons and so could mediate widespread neurotoxicity. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,725 N WOLFE ST,BALTIMORE,MD 21205. NIDA,ADDICT RES CTR,MOLEC NEUROBIOL LAB,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PHARMACOL & MOLEC SCI,BALTIMORE,MD 21205. OI Dawson, Valina/0000-0002-2915-3970 FU NIDA NIH HHS [DA 271-90-7408, DA-00266]; NIMH NIH HHS [MH-18501] NR 68 TC 916 Z9 944 U1 1 U2 6 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUN PY 1993 VL 13 IS 6 BP 2651 EP 2661 PG 11 WC Neurosciences SC Neurosciences & Neurology GA LE456 UT WOS:A1993LE45600036 PM 7684776 ER PT J AU MORREALE, VM HERMAN, BH DERMINASSIAN, V PALKOVITS, M KLUBES, P PERRY, D CSIFFARY, A LEE, AP AF MORREALE, VM HERMAN, BH DERMINASSIAN, V PALKOVITS, M KLUBES, P PERRY, D CSIFFARY, A LEE, AP TI A BRAIN-TUMOR MODEL UTILIZING STEREOTAXIC IMPLANTATION OF A PERMANENT CANNULA SO JOURNAL OF NEUROSURGERY LA English DT Article DE ASTROCYTOMA; BRAIN NEOPLASM; C6 GLIOMA; TUMOR CELLS; GLIOBLASTOMA MULTIFORME; STEREOTAXIS ID CHEMICAL INDUCTION; BLOOD-FLOW; RAT-BRAIN; GLIOMA; NITROSOUREAS AB A tumor model involving stereotactically implanted culture-reared tumor cells is presented. Stainless steel cannulas were stereotactically and permanently implanted into the caudate nucleus of 30 rats. The animals were separated into two groups. In Group I, 15 animals received a 10-mul injection containing 10(6) C6 glioblastoma cells (five rats), 10(6) Walker 256 breast carcinoma cells (five rats), or cell medium (five rats). The coordinates were A(+1.5), L(+3.0), and DV(-5.0). In Group II, the coordinates were changed to A(+1.0), L(+3.0), and DV(-5.0) and the same number of rats received a 1-mul injection containing 10(5) cells of each tumor in an attempt to produce more focal tumors. Two weeks after implantation, brain sections were stained with cresyl violet and a subset was stained for glial fibrillary acidic protein (GFAP). A computerized morphometric analysis system was used to quantify tumor size. In Group I, the mean C6 tumor areas (+/-standard error of the mean) at specific coordinates were (in sq mm): A(+4.7) 0.4 +/- 0.2; A(+3.7) 3.5 +/- 1.1; A(+2.7) 5.7 +/- 1.7; A(+1.7) 9.5 +/- 2.3; A(+0.7) 7.5 +/- 3.2; A(-0.3) 3.7 +/- 2.9; and A(-1.3) 0.3 +/- 0.3. A nearly identical tumor mass and extension into the brain was produced in rats injected with Walker 256 cells. Similar C6 tumor areas were indicated in adjacent sections stained with cresyl violet and GFAP. Tumor was found in the caudate nucleus in all 10 rats, but not in the nucleus accumbens, fornix, or hippocampus. In Group II animals, tumor magnitude and extension into the brain were greatly reduced. The 10(6) cells in the 10-mul volume was the most reliable tumor load for obtaining uniform tumors in different animals. The similarity of tumor distribution across different animals was indicated by the low variance of tumor area at specific anteroposterior coordinates. Reproducible and well-circumscribed caudate nucleus tumors were produced using this stereotactic procedure. C1 CHILDRENS NATL MED CTR,BRAIN RES CTR,WASHINGTON,DC. GEORGE WASHINGTON UNIV,MED CTR,DEPT PSYCHIAT & BEHAV SCI,WASHINGTON,DC 20037. GEORGE WASHINGTON UNIV,MED CTR,DEPT PEDIAT,WASHINGTON,DC 20037. GEORGE WASHINGTON UNIV,MED CTR,DEPT PHARMACOL,WASHINGTON,DC 20037. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. RI Palkovits, Miklos/F-2707-2013; OI Palkovits, Miklos/0000-0003-0578-0387 NR 32 TC 20 Z9 31 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD JUN PY 1993 VL 78 IS 6 BP 959 EP 965 DI 10.3171/jns.1993.78.6.0959 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA LD500 UT WOS:A1993LD50000015 PM 8487079 ER PT J AU FADEN, AI LABROO, VM COHEN, LA AF FADEN, AI LABROO, VM COHEN, LA TI IMIDAZOLE-SUBSTITUTED ANALOGS OF TRH LIMIT BEHAVIORAL DEFICITS AFTER EXPERIMENTAL BRAIN TRAUMA SO JOURNAL OF NEUROTRAUMA LA English DT Article ID THYROTROPIN-RELEASING-HORMONE; SPINAL-CORD INJURY; INTRACELLULAR FREE MG-2+; CARDIOVASCULAR-SYSTEM; NEUROLOGIC RECOVERY; PROLACTIN-RELEASE; DOSE-RESPONSE; RATS; HYPOTENSION; PEPTIDES AB Treatment with thyrotropin releasing hormone (TRH) or TRH analogues improves outcome after experimental brain or spinal cord trauma. TRH analogues with modifications at the N-terminal position of the tripeptide are effective, whereas analogues with modifications of the C-terminal residue are not. Imidazole-substituted TRH analogues, which modify the middle amino acid (histidine) of the tripeptide, have more recently been developed but have not been evaluated in models of central nervous system (CNS) trauma. In the present studies two imidazole-substituted analogues-4(5)-NO2(Im)TRH and 2,4 diiodo(Im)TRH-are shown to improve behavioral recovery following fluid percussion-induced traumatic brain injury (TBI) in rats. Because 4(5)-NO2(Im)TRH has little endocrine activity and 2,4 diiodo(Im)TRH has minimal cardiovascular effects, these experiments support the hypothesis that the neuroprotective actions of TRH analogues are independent of their endocrine or autonomic actions. C1 NIDDK,BIOORGAN CHEM LAB,BETHESDA,MD. ZYMOGENET INC,SEATTLE,WA. RP FADEN, AI (reprint author), GEORGETOWN UNIV,MED CTR,MED DENT BLDG,NW 101,3900 RESERVOIR RD NW,WASHINGTON,DC 20007, USA. FU PHS HHS [R49/CCR306634-02] NR 36 TC 23 Z9 23 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD SUM PY 1993 VL 10 IS 2 BP 101 EP 108 DI 10.1089/neu.1993.10.101 PG 8 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA LM056 UT WOS:A1993LM05600002 PM 8411214 ER PT J AU MANGELS, AR BLOCK, G FREY, CM PATTERSON, BH TAYLOR, PR NORKUS, EP LEVANDER, OA AF MANGELS, AR BLOCK, G FREY, CM PATTERSON, BH TAYLOR, PR NORKUS, EP LEVANDER, OA TI THE BIOAVAILABILITY TO HUMANS OF ASCORBIC-ACID FROM ORANGES, ORANGE JUICE AND COOKED BROCCOLI IS SIMILAR TO THAT OF SYNTHETIC ASCORBIC-ACID SO JOURNAL OF NUTRITION LA English DT Article DE ASCORBIC ACID; VITAMIN-C; BIOAVAILABILITY; FRUITS; VEGETABLES ID VITAMIN-C; DEHYDROASCORBIC ACID; DEHYDROISOASCORBIC ACID; ISOASCORBIC ACID; PLASMA; ANTIOXIDANT; SEPARATION; FOOD AB The relative bioavailability of ascorbic acid from several sources was compared in 68 male nonsmokers. Subjects underwent two 8-wk ascorbic acid depletion-repletion cycles. In repletion, subjects were randomized to receive 108 mg/d ascorbic acid as tablets with or without iron, as orange segments or juice, or as raw or cooked broccoli with a crossover within each major treatment group (e.g., cooked to raw broccoli) for the second repletion. Relative ascorbic acid bioavailability was estimated based on the slope obtained from linear regression of plasma ascorbic acid on time during each repletion. In the first repletion, slopes for all groups were similar except for the group consuming raw broccoli (20% lower response, P < 0.01). Second repletion responses were attenuated, but were similar to the first repletion. Ascorbic acid ingested as cooked broccoli, orange juice or fruit, or in synthetic form seems to be equally bioavailable. The lower relative bioavailability of ascorbic acid from raw broccoli is unlikely to be of practical importance in mixed diets. C1 USDA ARS, BELTSVILLE AGR RES CTR, BELTSVILLE HUMAN NUTR RES CTR, VITAMIN & MINERAL NUTR LAB, BELTSVILLE, MD 20705 USA. OUR LADY MERCY MED CTR, BIOMED RES DEPT, BRONX, NY 10466 USA. NCI, DIV CANC PREVENT & CONTROL, BETHESDA, MD 20892 USA. RI Block, Gladys/E-3304-2010 FU NCI NIH HHS [Y01-CN-40620] NR 30 TC 49 Z9 51 U1 2 U2 11 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 EI 1541-6100 J9 J NUTR JI J. Nutr. PD JUN PY 1993 VL 123 IS 6 BP 1054 EP 1061 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA LF086 UT WOS:A1993LF08600010 PM 8505665 ER PT J AU OPARA, EC HUBBARD, VS BURCH, WM AKWARI, OE AF OPARA, EC HUBBARD, VS BURCH, WM AKWARI, OE TI ADDITION OF L-GLUTAMINE TO A LINOLEIC-ACID PERIFUSATE PREVENTS THE FATTY ACID-INDUCED DESENSITIZATION OF PANCREATIC-ISLET RESPONSE TO GLUCOSE SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY LA English DT Note DE GLUTAMINE; INSULIN SECRETION; POLYUNSATURATED FATTY ACID; GLUCAGON RELEASE; GLUCOSE REGULATION ID TOTAL PARENTERAL-NUTRITION; INDUCED INSULIN RELEASE; CYSTIC-FIBROSIS; LIPID INFUSION; AMINO-ACIDS; METABOLISM; SECRETION; GLUTATHIONE; ABSORPTION; HUMANS AB Previous studies showed that exposure of pancreatic islets to polyunsaturated fatty acids (PUFA) can render the beta cells unresponsive to glucose, thus suggesting the possibility that prolonged obligatory use of lipid preparations containing high concentrations of essential fatty acids during total parenteral nutrition may adversely affect glucose tolerance. In the present study we examined the effect of pretreatment of isolated murine islets with 10 mmol/L linoleate (18:2, omega6) alone or in the presence of 20 mmol/L-glutamine on the response of both alpha and beta cells to 27.7 mmol/L glucose perifusion at 37-degrees-C. The incremental areas under the curve/20 mins (AUC/20 mins) for insulin output stimulated by 27.7 mmol/L glucose were 1552.8 +/- 276.3 pg and 220.4 +/- 163.9 pg (P < 0.001), (n = 6), respectively, before and after treatment with linoleic acid alone. In experiments in which the islets were treated with linoleate in the presence of L-glutamine there was no difference in the incremental insulin AUC/20 mins, in response to 27.7 mmol/L glucose before and after the fatty acid treatment (2051.8 +/- 420.5 pg versus 2159.2 +/-317.6 pg, respectively, n = 6). Glucose-induced suppression of glucagon secretion, which was lost after perifusion of islets with the fatty acid alone, was observed when glutamine was added to the linoleate perifusate. In conclusion, the addition of L-glutamine to linoleic acid perifusion of isolated islets completely blocked the PUFA-induced desensitization of both pancreatic alpha and beta cells to glucose effect. C1 DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27710. DUKE UNIV,MED CTR,SARA W STEDMAN CTR NUTR STUDIES,DURHAM,NC 27710. NIDDKD,NUTR SCI BRANCH,BETHESDA,MD. RP OPARA, EC (reprint author), DUKE UNIV,MED CTR,DEPT SURG,BOX 3076,DURHAM,NC 27710, USA. NR 41 TC 4 Z9 4 U1 0 U2 0 PU BUTTERWORTH-HEINEMANN PI WOBURN PA 225 WILDWOOD AVE #UNITB PO BOX 4500, WOBURN, MA 01801-2084 SN 0955-2863 J9 J NUTR BIOCHEM JI J. Nutr. Biochem. PD JUN PY 1993 VL 4 IS 6 BP 357 EP 361 DI 10.1016/0955-2863(93)90082-8 PG 5 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA LF596 UT WOS:A1993LF59600007 ER PT J AU NOZAKI, T DVORAK, JA AF NOZAKI, T DVORAK, JA TI INTRASPECIFIC DIVERSITY IN THE RESPONSE OF TRYPANOSOMA-CRUZI TO ENVIRONMENTAL-STRESS SO JOURNAL OF PARASITOLOGY LA English DT Note ID RHODNIUS-PROLIXUS; IDENTIFICATION; PROTEINS AB Epimastigotes of 5 Trypanosoma cruzi stocks were cultivated in liver infusion tryptose (LIT) medium at 23-35 C or cocultivated with vertebrate cells at 35 C. A temperature decrease from 26 to 23 C resulted in a stable 60% increase in population doubling time. In zymodeme I and II stocks, a temperature increase to 35 C resulted in a transient approximately 25% increase in doubling time during the first month followed by a approximately 30% decrease after 2 mo. A zymodeme III stock did not grow at 35 C. Flow cytometric analyses showed that the total DNA/cell, guanine + cytosine (G-C), and adenine + thymidine content of 2 zymodeme II stocks increased by 3-11% when cultivated in LIT at 35 C, whereas the DNA values of 2 zymodeme I stocks did not change. The increased DNA levels, due predominantly to an increased kinetoplast G-C content, returned to normal levels when the culture temperature was reduced to 26 C. The effects of cocultivation with vertebrate cells at 35 C were identical to cultivation in LIT al 35 C except that the DNA increase in a zymodeme II stock was not stable. Total DNA/cell, nuclear, and kinetoplast DNA decreased by 8-13% upon prolonged cocultivation. No change in total protein, antigen profiles, complement sensitivity, or heat shock protein gene expression was observed as a consequence of culturing the parasites above 26 C. RP NOZAKI, T (reprint author), NIAID,PARASIT DIS LAB,BLDG 4,ROOM 138,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 20 TC 9 Z9 9 U1 0 U2 0 PU AMER SOC PARASITOLOGISTS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 SN 0022-3395 J9 J PARASITOL JI J. Parasitol. PD JUN PY 1993 VL 79 IS 3 BP 451 EP 454 DI 10.2307/3283587 PG 4 WC Parasitology SC Parasitology GA LG095 UT WOS:A1993LG09500025 PM 8501607 ER PT J AU BERGEMAN, CS CHIPUER, HM PLOMIN, R PEDERSEN, NL MCCLEARN, GE NESSELROADE, JR COSTA, PT MCCRAE, RR AF BERGEMAN, CS CHIPUER, HM PLOMIN, R PEDERSEN, NL MCCLEARN, GE NESSELROADE, JR COSTA, PT MCCRAE, RR TI GENETIC AND ENVIRONMENTAL-EFFECTS ON OPENNESS TO EXPERIENCE, AGREEABLENESS, AND CONSCIENTIOUSNESS - AN ADOPTION TWIN STUDY SO JOURNAL OF PERSONALITY LA English DT Article ID HUMAN-BEHAVIOR GENETICS; 5-FACTOR MODEL; REARED APART; NATURAL-LANGUAGE; LIFE-SPAN; PERSONALITY; DIMENSIONS; FAMILY; UNIVERSALITY; HERITABILITY AB Previous research has indicated that extraversion and neuroticism are substantially affected both by genotype and environment. This study assesses genetic and environmental influences on the other three components of the five-factor model of personality: Openness to Experience, Agreeableness, and Conscientiousness. An abbreviated version of the NEO Personality Inventory (NEO-PI) was administered to 82 pairs of identical twins and 171 pairs of fraternal twins reared apart and 132 pairs of identical twins and 167 pairs of fraternal twins reared together. Estimates of genetic and environmental effects for Openness and Conscientiousness were similar to those found in other studies of personality: Genetic influence was substantial and there was little evidence of shared rearing environment. Results for Agreeableness were different: Genetic influence accounted for only 12% of the variance and shared rearing environment accounted for 21% of the variance. Few significant gender or age differences for genetic and environmental parameters were found in model-fitting analyses. C1 PENN STATE UNIV,COLL HLTH & HUMAN DEV,UNIV PK,PA 16802. KAROLINSKA INST,DEPT ENVIRONM HYG,S-10401 STOCKHOLM 60,SWEDEN. NIA,GERONTOL RES CTR,BETHESDA,MD 20892. RP BERGEMAN, CS (reprint author), UNIV NOTRE DAME,DEPT PSYCHOL,118 HAGGAR HALL,NOTRE DAME,IN 46556, USA. RI Plomin, Robert/B-8911-2008; Vollrath, Margarete/G-1297-2011; OI Plomin, Robert/0000-0002-0756-3629; Costa, Paul/0000-0003-4375-1712 FU NIA NIH HHS [AG-04563, T32 AG00048-12] NR 73 TC 108 Z9 109 U1 2 U2 12 PU DUKE UNIV PRESS PI DURHAM PA BOX 90660, DURHAM, NC 27708-0660 SN 0022-3506 J9 J PERS JI J. Pers. PD JUN PY 1993 VL 61 IS 2 BP 159 EP 179 DI 10.1111/j.1467-6494.1993.tb01030.x PG 21 WC Psychology, Social SC Psychology GA LL256 UT WOS:A1993LL25600002 PM 8345444 ER PT J AU NOWAK, G TRULLAS, R LAYER, RT SKOLNICK, P PAUL, IA AF NOWAK, G TRULLAS, R LAYER, RT SKOLNICK, P PAUL, IA TI ADAPTIVE-CHANGES IN THE N-METHYL-D-ASPARTATE RECEPTOR COMPLEX AFTER CHRONIC TREATMENT WITH IMIPRAMINE AND 1-AMINOCYCLOPROPANECARBOXYLIC ACID SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID BEHAVIORAL DESPAIR TEST; NMDA RECEPTOR; RAT-BRAIN; EXHIBIT ANTIDEPRESSANT; ANTICONVULSANT MK-801; MK-801 BINDING; GLYCINE; CALCIUM; ANTAGONISTS; SITE AB Chronic (14 daily injections) treatment of mice with the prototypic tricyclic antidepressant imipramine significantly alters ligand binding to the N-methyl-D-aspartate (NMDA) receptor complex. These effects were compared to a chronic regimen of 1-amino-cyclopropanecarboxylic acid, a high-affinity partial agonist at strychnine-insensitive glycine receptors which mimics the effects of imipramine in preclinical models predictive of antidepressant action. Changes in the NMDA receptor complex after chronic, but not acute treatment with imipramine were manifested as: 1) a reduction in the potency of glycine to inhibit [H-3]5,7-dichlorokynurenic acid binding to strychnine-insensitive glycine receptors; 2) a decrease in the proportion of high-affinity glycine sites inhibiting [H-3]CGP 39653 binding to NMDA receptors; and 3) a decrease in basal [H-3]MK-801 binding (under nonequilibrium conditions) to sites within NMDA receptor-coupled cation channels which was reversible by the addition of glutamate. These effects were observed in cerebral cortex, but not in hippocampus, striatum or basal forebrain. Chronic treatment with 1-aminocyclopropanecarboxylic acid resulted in changes which parallelled those of imipramine on ligand binding to the NMDA receptor complex, but the reduction in basal [H-3]MK-801 binding did not achieve statistical significance. These findings indicate that adaptive changes in the NMDA receptor complex could be a feature common to chronic treatment with structurally unrelated antidepressants. C1 NIDDKD,NEUROSCI LAB,BLDG 8,ROOM 111,BETHESDA,MD 20892. RI Trullas, Ramon/D-2197-2016 OI Trullas, Ramon/0000-0001-7951-9881 NR 61 TC 164 Z9 166 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JUN PY 1993 VL 265 IS 3 BP 1380 EP 1386 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LJ015 UT WOS:A1993LJ01500047 PM 8099620 ER PT J AU HARRIS, B WONG, G SKOLNICK, P AF HARRIS, B WONG, G SKOLNICK, P TI NEUROCHEMICAL ACTIONS OF INHALATIONAL ANESTHETICS AT THE GABA-A RECEPTOR COMPLEX SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID CHLORIDE CHANNEL COMPLEX; RAT CEREBRAL-CORTEX; BENZODIAZEPINE RECEPTORS; GENERAL-ANESTHETICS; MOLECULAR-BIOLOGY; BINDING; HALOTHANE; BRAIN; DRUGS; TERT-BUTYLBICYCLOPHOSPHOROTHIONATE AB Pharmacologically relevant concentrations of inhalational anesthetics such as halothane, enflurane and isoflurane enhance [H-3] flunitrazepam (FLU) binding to benzodiazepine receptors prepared from well-washed membranes of murine cerebral cortex and cerebellum. These effects were concentration dependent and markedly enhanced by addition of chloride to the incubation medium. Using halothane as a prototype inhalational agent, it was observed that like barbiturates, increases in [H-3]FLU binding were effected through an increase apparent in the apparent affinity of this radioligand with no accompanying change in the maximum number of binding sites. Although previous reports have demonstrated barbiturates augment gamma-aminobutryic acid-enhanced [H-3]benzodiazepine binding, halothane exerts an additive effect in the nominal absence of chloride. Isoflurane produces a significant reduction in the EC50 of pentobarbital-augmented [H-3]FLU binding. Halothane modestly reduced the binding of a benzodiazepine receptor inverse agonist, [H-3]Ro 15-4513. Significant differences were also observed in the potencies and efficacies of both isoflurane and enflurane to enhance [H-3] FLU binding to benzodiazepine receptors in cerebellar and cortical membranes. These findings provide a possible molecular basis for the clinical observation that benzodiazepines and barbiturates augment the anesthetic properties of inhalational agents. Moreover, the regional differences in anesthetic potency and eff icacy reported here suggest a differential interaction of these inhalational agents among gamma-aminobutryic acid(A) receptor isoforms. RP HARRIS, B (reprint author), NIDDKD,NEUROSCI LAB,BLDG 8,RM 111,BETHESDA,MD 20892, USA. NR 48 TC 23 Z9 24 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JUN PY 1993 VL 265 IS 3 BP 1392 EP 1398 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LJ015 UT WOS:A1993LJ01500049 PM 8389865 ER PT J AU LEWIS, DL DEAIZPURUA, HJ RAUSCH, DM AF LEWIS, DL DEAIZPURUA, HJ RAUSCH, DM TI ENHANCED EXPRESSION OF CA2+ CHANNELS BY NERVE GROWTH-FACTOR AND THE V-SRC ONCOGENE IN RAT PHEOCHROMOCYTOMA CELLS SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID PROTEIN-TYROSINE PHOSPHORYLATION; TRK PROTOONCOGENE PRODUCT; CALCIUM CHANNELS; SYMPATHETIC NEURONS; PC12 CELLS; NEUROTRANSMITTER RELEASE; NEURITE OUTGROWTH; KINASE-ACTIVITY; CA-2+ CHANNELS; C-SRC AB 1. Rat phaeochromocytoma (PC12) cells were used to investigate the expression of Ca2+ channel types during neuronal differentiation. Neuronal differentiation was induced by treatment with nerve growth factor (NGF) or by activation of a temperature-sensitive tyrosine kinase (pp60v-src) in genetically modified PC12 (PC12/v-src) cells. PC12 cells differentiated morphologically in the presence of NGF. When grown at the permissive temperature of 37-degrees-C which activates the kinase activity of pp60v-src, PC12/v-src cells differentiated morphologically with the extension of neurites. In contrast, PC12/v-src cells grown at the non-permissive temperature of 40-degrees-C continued to divide and were morphologically indistinguishable from control PC12 cells. 2. Whole-cell Ca2+ currents were measured in PC12 cells using Ba2+ as the charge carrier. Ba2+ currents measured at the peak of the current-voltage curve from a holding potential of - 80 mV were - 0.28 +/- 0.04 nA (mean +/- s.E.m.) in control PC12 cells compared to - 1.25 +/- 0.16 nA in NGF-differentiated cells. The current density increased from 9-4 +/- 0.7 pA/pF in control PC12 cells to 22-8 +/- 2.4 pA/pF in NGF-differentiated PC12 cells. Ba2+ currents were - 0.24 +/- 0.04 nA in undifferentiated PC12/v-src cells grown at the non-permissive temperature of 40-degrees-C compared to -0.95 +/- 0.16 nA in differentiated PC12/v-src cells grown at the permissive temperature of 37-degrees-C. The current density increased from 4.5 +/- 0.5 pA/pF in PC12/v-src cells grown at the non-permissive temperature of 40-degrees-C to 13.3 +/- 2.4 pA/pF in PC12/V-src cells grown at the permissive temperature of 37-degrees-C. 3. The sensitivity of Ba2+ currents to omega-conotoxin GVIA (omega-CgTX) was determined for currents measured at the peak of the current-voltage curve (0 mV in 10 mm Ba2+) from a holding potential of - 80 mV. In NGF-differentiated PCl 2 cells, 10 mum omega-CgTx inhibited 68.1 +/- 3.2 % of the total Ba2+ current compared to 35.9 +/- 4.1 % in control cells. The density of the omega-CgTX-sensitive current increased from 3.3 +/- 0.4 pA/pF in control cells to 15.7 +/- 2.0 pA/pF in NGF-differentiated cells. In differentiated PC12/v-src cells grown at 37-degrees-C, omega-CgTX inhibited 52.2 +/- 4.2 % of total Ba2+ current compared to 41.1 +/- 3-8% in PC12/v-src cells grown at 40-degrees-C. The density of the omega-CgTX-sensitive current increased from 1.9 +/- 0.3 to 7.4 +/- 2.0 pA/pF with v-src-mediated differentiation. 4. Ba 2+ currents were separated into three components based upon their inhibition by Ca2+ channel antagonists. Ba 2+ currents were measured at the peak of the current-voltage curve from a holding potential of - 60 mV. Sequential additions of omega-CgTX and nifedipine separated the Ba 2+ currents into three components: omega-CgTX sensitive, nifedipine sensitive and omega-CgTX and nifedipine resistant. The Ba 2+ current in control PC12 cells was 27-2 +/- 4.0 % omega-CgTX sensitive, 33.8 +/- 1.1% nifedipine sensitive and 39.0 +/- 2-4 % resistant. In NGF-differentiated PC12 cells, the Ba2+ current was 55.8 +/- 5.3 % omega-CgTX sensitive, 8.4 +/- 2.5% nifedipine sensitive and 35.8 +/- 6.0 % resistant. Similarly, differentiated PC12/v-src cells grown at 37-degrees-C had a Ba2+ current which was 50.3 +/- 4.7 % omega-CgTX sensitive, 8.0 +/- 4.6 % nifedipine sensitive and 41.7 +/- 3.6 % resistant. Control PC12/v-src cells grown at 40-degrees-C had a Ba2+ current which was 30.2 +/- 4.6 % omega-CgTX sensitive, 46.1 +/- 5.8 % nifedipine sensitive and 23.7 +/- 4.8% resistant. 5. Binding of I-125-omega-CgTX increased 6-fold in PC12 cells treated with NGF for 6 days compared to control cells. Differentiated PC12/v-src cells grown at 37-degrees-C showed a 4-fold increase in I-125-omega-CgTX binding compared to control PC12/V-src cells grown at 40-degrees-C. Nifedipine did not displace I-125-omega-CgTX binding indicating independent binding sites. 6. Electrophysiological, pharmacological and radioligand binding studies indicate an enhanced expression of omega-CgTX-sensitive N-type Ca 2+ channels in both NGF-treated and v-src differentiated PC12 cells. Additionally, a current component resistant to block by both omega-CgTX and nifedipine also showed an enhanced density in both NGF-treated and v-src-differentiated PC12 cells. The contribution of the nifedipine-sensitive L-type current to the total whole-cell current decreased in both NGF-treated and V-src-differentiated PC12 cells. C1 ROYAL MELBOURNE HOSP,WALTER & ELIZA HALL INST MED RES,BURNET CLIN RES UNIT,PARKVILLE,VIC 3050,AUSTRALIA. NATL INST MENTAL HLTH,CELL BIOL LAB,MOLEC NEUROSCI SECT,BETHESDA,MD 20892. RP LEWIS, DL (reprint author), MED COLL GEORGIA,DEPT PHARMACOL & TOXICOL,AUGUSTA,GA 30912, USA. FU NINDS NIH HHS [NS28894] NR 48 TC 39 Z9 39 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD JUN PY 1993 VL 465 BP 325 EP 342 PG 18 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA LG002 UT WOS:A1993LG00200018 PM 8229838 ER PT J AU XU, SG BRENNER, B YU, LC AF XU, SG BRENNER, B YU, LC TI STATE-DEPENDENT RADIAL ELASTICITY OF ATTACHED CROSS-BRIDGES IN SINGLE SKINNED FIBERS OF RABBIT PSOAS MUSCLE (VOL 461, PG 283, 1993) SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Correction, Addition ID X-RAY-DIFFRACTION; SKELETAL-MUSCLE; FIBERS; RIGOR; CROSSBRIDGES; STIFFNESS; FORCE; ACTIN; BINDING AB 1. In a single skinned fibre of rabbit psoas muscle, upon attachment of cross-bridges to actin in the presence of ADP or pyrophosphate (PP(i)), the separation between the contractile filaments, as determined by equatorial X-rav diffraction. is found to decrease, suggesting that force is generated in the radial direction. 2. The single muscle fibres were subjected to compression by 0-8% of dextran T500. The changes in lattice spacings by dextran compression were compared with changes induced by cross-bridge attachment to actin. Based on this comparison, the magnitude and the direction of the radial force generated by the attached crossbridges were estimated. The radial cross-bridge force varied with filament separation, and the magnitude of the radial cross-bridge force reached as high as the maximal axial force produced during isometric contraction. 3. One key parameter of the radial elasticity, i.e. the equilibrium spacing where the radial force is zero, was found to depend on the ligand bound to the myosin head. In the presence of ADP, the equilibrium spacing was 36 nm. In the presence of MgPP(i) the equilibrium spacing shifted to 35 nm and Ca2+ had little effect on the equilibrium spacing. 4. The equilibrium spacing was independent of the fraction of cross-bridges attached to actin. The fraction of cross-bridges attached in rigor was modulated from 100% to close to 0% by adding up to 10 mm of ATPgammaS in the rigor solution. The lattice spacing remained at 38 nm, the equilibrium spacing for nucleotide-free cross-bridges at mu = 170 mm. 5. Radial force generated by cross-bridges in rigor at large lattice spacings (38 nm less-than-or-equal-to d10 less-than-or-equal-to 46 nm) appeared to vary linearly with lattice spacing. 6. The titration of ATPgammaS to fibres in rigor provided a correlation between the radial stiffness of the nucleotide-free cross-bridges and the equatorial intensities. The relation between the equatorial intensity ratio I11/I10 and radial stiffness appeared to be approximately linear. 7. The fibres under different conditions showed a wide range of radial stiffness, which was not proportional to the apparent axial stiffness of the fibre. If the apparent axial stiffness is a measure of the fraction of cross-bridges bound to actin, it follows that the radial elastic constant is state dependent; or vice versa. 8. Differences in equilibrium lattice spacing and in radial elastic constant, most probably reflect differences in the molecular structure of the acto-myosin complex and there is more than one single conformation of the various strongly bound cross-bridge states. 9. Determining equilibrium spacings of the radial elasticity appears to be an effective new approach in detecting structural differences among the attached cross-bridges, since this approach is independent of the fraction of cross-bridges attached, a factor that frequently encumbers the interpretation of structural studies of attached cross-bridge states. C1 UNIV ULM,W-7900 ULM,GERMANY. RP XU, SG (reprint author), NIH,BETHESDA,MD 20892, USA. NR 33 TC 14 Z9 14 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD JUN PY 1993 VL 465 BP 749 EP 765 PG 17 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA LG002 UT WOS:A1993LG00200043 PM 7693922 ER PT J AU SHERN, RJ GUCKES, AD LI, SH AF SHERN, RJ GUCKES, AD LI, SH TI A METHOD FOR MEASURING SECRETIONS FROM THE PALATAL MINOR SALIVARY-GLANDS SO JOURNAL OF PROSTHETIC DENTISTRY LA English DT Article ID FLOW AB This study investigated the secretory pattern of unstimulated minor salivary glands in 10 contiguous specified areas of the hard palate in 12 healthy unmedicated adult men and women. Each participant was assessed twice at each of two visits in the same specific palatal areas from the distal portion of the second molar to 30 mm anterior. The 10 areas were isolated, dried, and sampled with a paper strip for 60 seconds. The strips were read with a Periotron device. The rates of flow were significantly influenced by position; higher values were noted posteriorly and medially during testing and retesting at both visits. The rates of flow from the palatal glands were greatest in the area between the maxillary second molars. This method proved to be simple, accurate, and reliable for measuring the secretions of the palatal glands. This method may prove useful for investigating how the relationship between the pattern and the secretory rate of minor salivary glands influences retention of the complete maxillary denture. C1 NIDR,EPIDEMIOL & ORAL DIS PREVENT PROGRAM,BETHESDA,MD 20892. RP SHERN, RJ (reprint author), NIDR,CLIN INVEST & PATIENT CARE BRANCH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 22 TC 9 Z9 9 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-3913 J9 J PROSTHET DENT JI J. Prosthet. Dent. PD JUN PY 1993 VL 69 IS 6 BP 624 EP 629 DI 10.1016/0022-3913(93)90294-X PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA LD847 UT WOS:A1993LD84700016 PM 8320651 ER PT J AU TUGWELL, P CHAMBERS, L TORRANCE, G REYNOLDS, D WOLFSON, M BENNETT, K BADLEY, E JAMIESON, E STOCK, S AF TUGWELL, P CHAMBERS, L TORRANCE, G REYNOLDS, D WOLFSON, M BENNETT, K BADLEY, E JAMIESON, E STOCK, S TI THE POPULATION HEALTH IMPACT OF ARTHRITIS SO JOURNAL OF RHEUMATOLOGY LA English DT Editorial Material DE POPULATION HEALTH IMPACT; MUSCULOSKELETAL DISEASES; QUALITY OF LIFE; PREVALENCE OF ARTHRITIS; TRANSITION PROBABILITIES; RISK MODIFIERS AB The workshop was convened to develop quantitative estimates of the incidence of progressional musculoskeletal diseases in order to estimate the population health impact of arthritis. Estimates were developed for (a) the prevalence of arthritis, (b) a weighting strategy to adjust for the quality of life for the range of health states associated with arthritis, and (c) transition probabilities to represent the likelihood of disease onset and progression through the range of possible health states. A simulation ''game'' was designed to follow the progression of a cohort of 200 healthy persons or persons with arthritis, creating the basis for the estimation of transition probabilities and thus generating simulated longitudinal data that allow calculation of the quantitative estimate of the burden of illness from musculoskeletal diseases within the Canadian population. C1 STAT CANADA,ANALYT STUDIES BRANCH,OTTAWA,ON,CANADA. MANITOBA HLTH UNIT,WINNIPEG,MB,CANADA. MCMASTER UNIV,DEPT CLIN EPIDEMIOL,HAMILTON L8S 4L8,ONTARIO,CANADA. MCMASTER UNIV,DEPT EPIDEMIOL & BIOSTAT,HAMILTON L8S 4L8,ONTARIO,CANADA. MCMASTER UNIV,DEPT FAMILY MED,HAMILTON L8S 4L8,ONTARIO,CANADA. MCMASTER UNIV,DEPT MED,HAMILTON L8S 4L8,ONTARIO,CANADA. UNIV TORONTO,DEPT MED,ARTHRITIS SOC,TORONTO M5S 1A1,ONTARIO,CANADA. UNIV CALGARY,DEPT MED,CALGARY T2N 1N4,ALBERTA,CANADA. UNIV CALIF SAN FRANCISCO,DEPT MED,SAN FRANCISCO,CA 94143. VANDERBILT UNIV,MED CTR,SCH MED,DEPT MED,NASHVILLE,TN 37232. CTR DIS CONTROL,ATLANTA,GA 30333. NIH,BETHESDA,MD 20892. UNIV LIMBURG,ACAD ZIEKENHUIS,DEPT MED,6200 MD MAASTRICHT,NETHERLANDS. UNIV OTTAWA,DEPT EPIDEMIOL,OTTAWA K1H 8L6,ON,CANADA. RP TUGWELL, P (reprint author), UNIV OTTAWA,OTTAWA GEN HOSP,DEPT MED,ROOM LM12,501 SMYTH RD,OTTAWA K1H 8L6,ON,CANADA. OI Tugwell, Peter/0000-0001-5062-0556 NR 5 TC 7 Z9 7 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO ON M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JUN PY 1993 VL 20 IS 6 BP 1048 EP 1051 PG 4 WC Rheumatology SC Rheumatology GA LH112 UT WOS:A1993LH11200025 PM 8102404 ER PT J AU TANGRI, SS LEVITIN, TE AF TANGRI, SS LEVITIN, TE TI AN ENTREE FOR SOCIAL-SCIENTISTS - INTRODUCTION SO JOURNAL OF SOCIAL ISSUES LA English DT Editorial Material ID HEALTH AB This paper presents the reasons for having an issue of JSI on the topic of new medical technologies; the rationale for including perspectives of economists, sociologists, physicians, philosophers, and others; and the organization of the issue. It also presents the framework for the papers that was established by having each author address a common set of questions. Suggestions are made about how psychological theories and methods could be applied to the questions addressed. It is concluded that this is an important area for research, though relatively little work has been done by psychologists. It is hoped that this issue will encourage JSI readers to bring their conceptual and empirical skills to the issues raised in these articles. C1 NIH,BETHESDA,MD 20892. RP TANGRI, SS (reprint author), HOWARD UNIV,DEPT PSYCHOL,525 BRYANT ST NW,WASHINGTON,DC 20059, USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0022-4537 J9 J SOC ISSUES JI J. Soc. Issues PD SUM PY 1993 VL 49 IS 2 BP 1 EP 10 PG 10 WC Social Issues; Psychology, Social SC Social Issues; Psychology GA LK290 UT WOS:A1993LK29000001 ER PT J AU JUENGST, ET AF JUENGST, ET TI DEVELOPING AND DELIVERING NEW MEDICAL TECHNOLOGIES - ISSUES BEYOND ACCESS SO JOURNAL OF SOCIAL ISSUES LA English DT Article AB The articles in this issue illuminate psychosocial issues raised by the development and delivery of new medical technologies. Five kinds of questions surface repeatedly: questions about a technology's purpose(s), the value judgments it presumes, the locus of its control, the external forces that drive it, and its long-term social risks. These questions take the discussion of new technologies beyond the challenge of improving access to their benefits. They also raise issues that will become increasingly important as the capabilities of medical technology expand. For example, they suggest research questions for three other emerging medical technologies: use of biosynthetic growth hormone to treat short stature in hormonally normal children, genetic tests on fetal cells from the circulating maternal blood, and development of clinically reliable biomarkers of the aging process. Part Three of this issue provides a theoretical basis for encouraging psychosocial perspectives in this arena, by illustrating the central role that ''robust,'' multifaceted analysis has come to play within the methods of bioethics. RP JUENGST, ET (reprint author), NIH,BLDG 38A,ROOM 617,BETHESDA,MD 20892, USA. OI Juengst, Eric/0000-0002-8374-5774 NR 17 TC 1 Z9 1 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0022-4537 J9 J SOC ISSUES JI J. Soc. Issues PD SUM PY 1993 VL 49 IS 2 BP 201 EP 210 PG 10 WC Social Issues; Psychology, Social SC Social Issues; Psychology GA LK290 UT WOS:A1993LK29000012 PM 17167923 ER PT J AU GITTERMAN, M WEISS, GH AF GITTERMAN, M WEISS, GH TI THE BEHAVIOR OF A PERIODICALLY-FORCED NONLINEAR-SYSTEM SUBJECT TO ADDITIVE NOISE SO JOURNAL OF STATISTICAL PHYSICS LA English DT Note DE STOCHASTIC RESONANCE; 1ST-PASSAGE TIMES; PERIODIC FORCES AB We continue the study of a nonlinear first-order dynamical system first considered by Chen. This model is characterized by a multiplicative periodic forcing term and additive dichotomous noise in place of the white noise of Chen's analysis. Two parameters are used to characterize the qualitative properties of such a system, the mean first-passage time to the ends of the interval and the Fourier spectrum generated by the solution of the equation. We show that the mean first-passage time is monotonic in the amplitude of the periodic force and exhibits a resonant dependence on its frequency. In addition the substitution of dichotomous for white noise leads to a systematic change in the ability to smooth out the peaks in the Fourier spectrum of the solution. C1 BAR ILAN UNIV,DEPT PHYS,IL-52100 RAMAT GAN,ISRAEL. RP GITTERMAN, M (reprint author), NIH,BETHESDA,MD 20892, USA. NR 4 TC 2 Z9 2 U1 1 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0022-4715 J9 J STAT PHYS JI J. Stat. Phys. PD JUN PY 1993 VL 71 IS 5-6 BP 1213 EP 1220 DI 10.1007/BF01049969 PG 8 WC Physics, Mathematical SC Physics GA LL080 UT WOS:A1993LL08000018 ER PT J AU NORMAN, JE LEVY, D CAMPBELL, G BAILEY, JJ AF NORMAN, JE LEVY, D CAMPBELL, G BAILEY, JJ TI IMPROVED DETECTION OF ECHOCARDIOGRAPHIC LEFT-VENTRICULAR HYPERTROPHY USING A NEW ELECTROCARDIOGRAPHIC ALGORITHM SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID QRS VOLTAGE; CRITERIA; MASS; VALIDATION; DISEASE; DIAGNOSIS; NECROPSY; RISK AB Objectives. The purpose of this study was to use the Framingham data base to devise and test an improvement in an electrocardiographic (ECG) voltage criterion for detecting left ventricular hypertrophy that is gender specific and adjusts for age and obesity. Background. Electrocardiographic detection of left ventricular hypertrophy has been receiving increasing attention. The ''Cornell'' ECG voltage, defined as the sum of voltages for the R wave of lead aVL and the S wave of lead V3, has been shown to correlate strongly with echocardiographically estimated left ventricular mass. Because the magnitude of this voltage varies with both age and obesity, we have proposed a simple formula for its adjustment for these two variables. Methods. Using linear regression, the adjustment formula was estimated from data on 1,468 men and 1,883 women from the Framingham Heart Study cohort who were free of myocardial infarction and who had both an ECG and an echocardiogram recorded during the same clinic examination. A modified receiver operating characteristic curve method was used to compare sensitivities at the same specificity levels. The adjustment formula was estimated from one randomly chosen half of the study cohort and applied to the other half for evaluation. Results. Significant improvement in sensitivity for the detection of left ventricular hypertrophy was realized at all levels of specificity. At a specificity level of 98%, the adjustment increased the sensitivity of the Cornell voltage from 10% to 17% in men and from 12% to 22% in women. For severe hypertrophy, defined as a left ventricular mass >3 SD above the gender-specific mean, the sensitivity increased from 23% to 38% for men and from 22% to 55% for women at a specificity level of 95%. Conclusions. This approach can substantially enhance the utility of the ECG for the detection of left ventricular hypertrophy. If these results are validated in other population groups, this approach may prove valuable in the screening of hypertensive populations and for the monitoring of patients undergoing treatment for hypertension. C1 FRAMINGHAM HEART DIS EPIDEMIOL STUDY,FRAMINGHAM,MA. NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. RP NORMAN, JE (reprint author), NHLBI,ROOM 3A08,FED BLDG,BETHESDA,MD 20892, USA. NR 26 TC 58 Z9 59 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUN PY 1993 VL 21 IS 7 BP 1680 EP 1686 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA LE826 UT WOS:A1993LE82600022 PM 8496537 ER PT J AU GAYNOR, JJ FEUER, EJ TAN, CC WU, DH LITTLE, CR STRAUS, DJ CLARKSON, BD BRENNAN, MF AF GAYNOR, JJ FEUER, EJ TAN, CC WU, DH LITTLE, CR STRAUS, DJ CLARKSON, BD BRENNAN, MF TI ON THE USE OF CAUSE-SPECIFIC FAILURE AND CONDITIONAL FAILURE PROBABILITIES - EXAMPLES FROM CLINICAL ONCOLOGY DATA SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE CAUSE-SPECIFIC FAILURE PROBABILITY; CAUSE-SPECIFIC HAZARD; CONDITIONAL FAILURE PROBABILITY; CUMULATIVE HAZARD; MIXTURE MODEL; NONPARAMETRIC ESTIMATES ID ACUTE LYMPHOBLASTIC-LEUKEMIA; PARTIALLY CENSORED-DATA; SEMI-MARKOV MODELS; MARROW TRANSPLANTATION; COMPETING RISKS; MIXTURE-MODELS; SURVIVAL-DATA; RELAPSE; COHORT AB Nonparametric maximum likelihood estimation of the probability of failing from a particular cause by time t in the presence of other acting causes (i.e., the cause-specific failure probability) is discussed. A commonly used incorrect approach is to take 1 minus the Kaplan-Meier (KM) estimator (1 - KM), whereby patients who fail of extraneous causes are treated as censored observations. Examples showing the extent of bias in using the 1-KM approach are presented using clinical oncology data. This bias can be quite large if the data are uncensored or if a large percentage of patients fail from extraneous causes prior to the occurrence of failures from the cause of interest. Each cause-specific failure probability is mathematically defined as a function of all of the cause-specific hazards. Therefore, nonparametric estimates of the cause-specific failure probabilities may not be able to identify categorized covariate effects on the cause-specific hazards. These effects would be correctly identified by cause-specific cumulative hazard or KM plots in which the extraneous causes of failure are treated as censored observations. Examples are provided. Finally, nonparametric graphical representation of the two distinct cause-specific failure components of the mixture model (i.e., the probability of ever failing from a particular cause and the time-to-failure distribution given that a patient will fail of that cause) are presented. The difficulty in extrapolating the nonparametric estimates beyond the range of observed failure times is highlighted. In addition, the mathematical relationship of a single covariate z and the two cause-specific failure components is shown for the case where z acts multiplicatively on the cause-specific hazards. Examples are considered using the important prognostic factors in adult soft tissue sarcoma (STS) of the extremity and adult acute lymphoblastic leukemia (ALL). In each of the mathematical and actual examples considered, the characteristic that was associated with a higher hazard rate of failure from the disease was also associated with a higher probability of ever failing from the disease as well as a shorter time-to-failure distribution given that failure due to the disease will occur. Thus it may be quite common in chronic disease situations to find prognosticators that are associated with both cause-specific failure components. C1 NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. PURDUE FREDERICK CO,NORWALK,CT 06856. MEM SLOAN KETTERING CANC CTR,HEMATOL LYMPHONA SERV,NEW YORK,NY 10021. MEM SLOAN KETTERING CANC CTR,DEPT MED,NEW YORK,NY 10021. MEM SLOAN KETTERING CANC CTR,DEPT SURG,NEW YORK,NY 10021. RP GAYNOR, JJ (reprint author), MEM SLOAN KETTERING CANC CTR,DEPT EPIDEMIOL & BIOSTAT,NEW YORK,NY 10021, USA. NR 29 TC 346 Z9 346 U1 0 U2 12 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD JUN PY 1993 VL 88 IS 422 BP 400 EP 409 DI 10.2307/2290318 PG 10 WC Statistics & Probability SC Mathematics GA LD680 UT WOS:A1993LD68000002 ER PT J AU GRAUBARD, BI KORN, EL AF GRAUBARD, BI KORN, EL TI HYPOTHESIS-TESTING WITH COMPLEX SURVEY DATA - THE USE OF CLASSICAL QUADRATIC TEST STATISTICS WITH PARTICULAR REFERENCE TO REGRESSION PROBLEMS SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE BALANCED HALF-SAMPLE REPEATED REPLICATION; COMPLEX SURVEY SAMPLE DATA; FAY JACKNIFE CHI-SQUARED TEST; MULTIPLE LINEAR REGRESSION; RAO-SCOTT TESTS; WALD TEST ID CHI-SQUARED TESTS; STRATIFIED SAMPLES; INFERENCE; GOODNESS; TABLES; FIT AB Sample surveys often have complex sample designs with multistage cluster sampling, stratification, and differential selection probabilities. This article is concerned with testing the null hypothesis H-0: theta = 0, where the p-dimensional parameter theta = g(mu) and mu is a q-dimensional vector of means. The asymptotic framework that consists of a sequence of increasing finite populations is used to define mu as the limit of finite population means. As part of the inference, we use replicated estimates of variances that take into account the complex sample design. The Wald statistic can be used to test H-0. But inference for theta based on the Wald statistic can have low power. Thus an alternative to using a Wald test is pursued in this article. First, define a classical quadratic test statistic that would be used if one had a simple random sample of the population. Second, treating this quadratic form as a population parameter, use design-based methods to estimate it from the observed survey data. Last, use a replication method to approximate the distribution of this estimated quadratic form to perform the hypothesis test. Specific applications of this general approach have been used previously in contingency table analysis. For small numbers of sampled first-stage clusters and large p, modified versions of the Fay procedure are proposed. Simulations show that these modified procedures maintain nominal levels better than the original Fay and the Rao-Scott procedures for testing a vector of means and a vector of regression coefficients. An application is given for testing whether design-based regression coefficients differ from ordinary least squares regression coefficients. C1 NCI,BIOMETR RES BRANCH,BETHESDA,MD 20892. RP GRAUBARD, BI (reprint author), NCI,BIOMETRY BRANCH,BETHESDA,MD 20892, USA. NR 23 TC 17 Z9 17 U1 0 U2 1 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD JUN PY 1993 VL 88 IS 422 BP 629 EP 641 DI 10.2307/2290345 PG 13 WC Statistics & Probability SC Mathematics GA LD680 UT WOS:A1993LD68000029 ER PT J AU SAROSY, G REED, E AF SAROSY, G REED, E TI TAXOL DOSE INTENSIFICATION AND ITS CLINICAL IMPLICATIONS SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Article DE TAXOL; OVARIAN CANCER; DOSE INTENSITY AB Taxol is the most exciting new anticancer agent developed in the past two decades. Of great interest is its level of activity in ovarian cancer, as well as substantial activity in breast cancer, nonsmall-cell lung cancer, melanoma, and other malignancies. Recent studies suggest that when taxol is administered in a fashion to increase milligram dosage per unit time (mg/m2/week), the response rate in patients with ovarian cancer is markedly increased. This article reviews studies that suggest taxol dose intensity is important in the treatment of patients with ovarian cancer. RP SAROSY, G (reprint author), NCI,MED BRANCH,MED OVARIAN CANC SECT,BLDG 10,RM 12N226,BETHESDA,MD 20892, USA. NR 0 TC 33 Z9 33 U1 1 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD JUN PY 1993 VL 85 IS 6 BP 427 EP 431 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA LF784 UT WOS:A1993LF78400003 PM 8103561 ER PT J AU PATTERSON, BH ZECH, LA SWANSON, CA LEVANDER, OA AF PATTERSON, BH ZECH, LA SWANSON, CA LEVANDER, OA TI KINETIC MODELING OF SELENIUM IN HUMANS USING STABLE-ISOTOPE TRACERS SO JOURNAL OF TRACE ELEMENTS AND ELECTROLYTES IN HEALTH AND DISEASE LA English DT Article; Proceedings Paper CT 3RD INTERNATIONAL SOC FOR TRACE ELEMENT RESEARCH IN HUMANS / 4TH NORDIC TRACE ELEMENTS SYMP ON TRACE ELEMENTS IN HEALTH AND DISEASE CY MAY 24-29, 1992 CL STOCKHOLM, SWEDEN SP INT SOC TRACE ELEMENT RES HUMANS DE COMPARTMENTAL MODELING; PHARMACOKINETICS; STABLE ISOTOPES; CANCER AB In a study undertaken to investigate the pharmacokinetics of selenium, 3 8 subjects each received a single 200 mug dose of either selenium (Se) as sodium selenite or as L-selenomethionine (SeMet). Plasma, urine and feces were collected for two weeks. Two kinetic models, one for each form, were developed. The Selenite Model includes absorption distributed along the GI tract, transport through 4 plasma components, a subsystem consisting of the liver and pancreas, and a slowly turning-over tissue pool. This model was used as a starting model for SeMet and modified. The amount of label absorbed was increased as was hepato-pancreatic uptake, a pathway from the plasma back to the liver was added that provided for recycling of label, and an additional tissue pool was incorporated into the model. Turnover times were shorter for SeMet than for selenite for the plasma, liver and pancreas, and the tissues, but far longer for the whole body; this reflects the recycling of SeMet, but not of selenite. Such reutilization could be advantageous as it allows the body to redistribute Se. C1 NCI,DCBD,MATH BIOL LAB,BETHESDA,MD 20892. NCI,DCE,BIOSTAT BRANCH,BETHESDA,MD 20892. USDA ARS,BELTSVILLE AGR RES CTR,BELTSVILLE HUMAN NUTR RES CTR,BELTSVILLE,MD 20705. RP PATTERSON, BH (reprint author), NCI,BIOMETRY BRANCH,DCPC,EXECUT PLAZA N,ROOM 344,BETHESDA,MD 20892, USA. NR 5 TC 8 Z9 8 U1 0 U2 1 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 0931-2838 J9 J TRACE ELEM ELECT H PD JUN PY 1993 VL 7 IS 2 BP 117 EP 120 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LX524 UT WOS:A1993LX52400016 ER PT J AU BARTON, EN MORGAN, OS SMIKLE, MF BLATTNER, WA AF BARTON, EN MORGAN, OS SMIKLE, MF BLATTNER, WA TI REACTIVE SEROLOGICAL TESTS FOR SYPHILIS IN TROPICAL SPASTIC PARAPARESIS - A DILEMMA SO JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article DE SYPHILIS; SPASTIC PARAPARESIS; JAMAICA ID ANTIBODIES AB The prevalence of reactive serological tests for syphilis (STS) was investigated in 183 jamaican patients with tropical spastic paraparesis (TSP) and 200 age and sex matched controls. A significantly higher prevalence of reactive STS was found in TSP patients (34.9%) compared with controls (14.0%, P < 0.001). The biological false positive (BFP) rate was also significantly higher in TSP patients (P < 0.01) as well as controls (P < 0.001) over 40 years of age. However, these findings do not imply a pathogenetic role for treponemal disease in TSP. The high prevalence of reactive STS in Jamaican TSP patients may be multifactorial, and include biological false positives (BFP), previous childhood yaws and concurrent syphilis. C1 UNIV W INDIES,DEPT MED,KINGSTON 7,JAMAICA. UNIV W INDIES,DEPT MICROBIOL,KINGSTON 7,JAMAICA. NIH,BETHESDA,MD 20892. NR 15 TC 7 Z9 7 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0022-5304 J9 J TROP MED HYG JI J. Trop. Med. Hyg. PD JUN PY 1993 VL 96 IS 3 BP 172 EP 174 PG 3 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA LG049 UT WOS:A1993LG04900007 PM 8505772 ER PT J AU THEUER, CP FITZGERALD, DJ PASTAN, I AF THEUER, CP FITZGERALD, DJ PASTAN, I TI A RECOMBINANT FORM OF PSEUDOMONAS EXOTOXIN A CONTAINING TRANSFORMING GROWTH FACTOR-ALPHA NEAR ITS CARBOXYL-TERMINUS FOR THE TREATMENT OF BLADDER-CANCER SO JOURNAL OF UROLOGY LA English DT Article DE BLADDER NEOPLASMS; IMMUNOTOXINS; RECEPTORS-EPIDERMAL GROWTH FACTOR-UROGASTRONE ID FUSION PROTEIN; ESCHERICHIA-COLI; FACTOR RECEPTORS; TOXIN; N-BUTYL-N-(4-HYDROXYBUTYL)NITROSAMINE; BINDING; TUMORS; CARCINOGENESIS; QUANTITATION; UROTHELIUM AB The epidermal growth factor receptor (EGFR) is overexpressed on the superficial layers of malignant urothelium and is suspected of playing a role in tumor progression. TP40 is a chimeric protein composed of transforming growth factor-alpha (TGFalpha) fused to a modified form of Pseudomonas exotoxin A (PE) that is selectively cytotoxic to EGFR-bearing cells and is currently undergoing clinical study for the intravesical therapy of bladder cancer. We constructed a recombinant toxin PE35/TGFalpha-KDEL as an improved agent for the local therapy of EGFR-bearing bladder cancer. PE35/TGFalpha-KDEL does not require intracellular proteolysis to generate a carboxyl-terminal fragment capable of reaching the target cell cytosol and contains a modified carboxyl-terminal sequence KDEL, that increases toxin activity. These features make PE35/TGFalpha-KDEL from 10- to 700-fold more potent than TP40 on four human bladder cancer cell lines. PE35/TGFalpha-KDEL may be a useful agent for treatment of EGFR-bearing cancers. C1 NCI,DIV CANC BIOL,MOLEC BIOL LAB,BLDG 37,ROOM 4E16,BETHESDA,MD 20892. NR 39 TC 30 Z9 32 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUN PY 1993 VL 149 IS 6 BP 1626 EP 1632 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA LE819 UT WOS:A1993LE81900074 PM 8501821 ER PT J AU SAIKAWA, T ANDERSON, S MOMOEDA, M KAJIGAYA, S YOUNG, NS AF SAIKAWA, T ANDERSON, S MOMOEDA, M KAJIGAYA, S YOUNG, NS TI NEUTRALIZING LINEAR EPITOPES OF B19 PARVOVIRUS CLUSTER IN THE VP1 UNIQUE AND VP1-VP2 JUNCTION REGIONS SO JOURNAL OF VIROLOGY LA English DT Article ID CANINE PARVOVIRUS; IMMUNE-RESPONSE; CELL EPITOPES; INFECTION; ANTIBODY; HUMANS; SYSTEM AB Presentation of linear epitopes of the B19 parvovirus capsid proteins as peptides might be a useful vaccine strategy. We produced overlapping fusion proteins to span the viral capsid sequence, inoculated rabbits, and determined whether the resulting antisera contained antibodies that neutralized the ability of the virus to infect human erythroid progenitor cells. Antibodies that bound to virus in an enzyme-linked immunosorbent assay were present in antisera raised against 10 of 11 peptides; strongest activity was found for antisera against the carboxyl-terminal half of the major capsid protein. However, strong neutralizing activity was elicited in animals immunized with peptides from the amino-terminal portion of the unique region of the minor capsid protein and peptides containing the sequence of the junction region between the minor and major capsid proteins. The development of neutralizing activity in animals was elicited most rapidly with the fusion peptide from the first quarter of the unique region. A 20-amino-acid region of the unique region of the minor capsid protein was shown to contain a neutralizing epitope. Multiple antigenic peptides, based on the sequence of the unique region and produced by covalent linkage through a polylysine backbone, elicited strong neutralizing antibody responses. Synthetic peptides and fusion proteins containing small regions of the unique portion of the minor capsid protein might be useful as immunogens in a human vaccine against B19 parvovirus. C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 25 TC 99 Z9 108 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 1993 VL 67 IS 6 BP 3004 EP 3009 PG 6 WC Virology SC Virology GA LB794 UT WOS:A1993LB79400005 PM 7684458 ER PT J AU BAGAI, S PURI, A BLUMENTHAL, R SARKAR, DP AF BAGAI, S PURI, A BLUMENTHAL, R SARKAR, DP TI HEMAGGLUTININ-NEURAMINIDASE ENHANCES-F PROTEIN-MEDIATED MEMBRANE-FUSION OF RECONSTITUTED SENDAI VIRUS ENVELOPES WITH CELLS SO JOURNAL OF VIROLOGY LA English DT Article ID ASIALOGLYCOPROTEIN RECEPTOR; HUMAN-ERYTHROCYTES; INSULIN MOLECULES; MEASLES-VIRUS; GLYCOPROTEINS; EXPRESSION; ANTIBODIES; GENE; HVJ; FLUORESCENCE AB Reconstituted Sendai virus envelopes containing both the fusion (F) protein and the hemagglutinin-neuraminidase (HN) (F,HN-virosomes) or only the F protein (F-virosomes) were prepared by solubilization of the intact virus with Triton X-100 followed by its removal by using SM2 Bio-Beads. Viral envelopes containing HN whose disulfide bonds were irreversibly reduced (HN(red)) were also prepared by treating the envelopes with dithiothreitol followed by dialysis (F,HN(red)-virosomes). Both F-virosomes and F,HN(red)-virosomes induced hemolysis of erythrocytes in the presence of wheat germ agglutinin, but the rates and extents were markedly lower than those for hemolysis induced by F,HN-virosomes. Using an assay based on the relief of self-quenching of a lipid probe incorporated in the Sendai virus envelopes, we demonstrate the fusion of both F,HN-virosomes and F-virosomes with cultured HepG2 cells containing the asialoglycoprotein receptor, which binds to a terminal galactose moiety of F. By desialylating the HepG2 cells, the entry mediated by HN-terminal sialic acid receptor interactions was bypassed. We show that both F-virosomes and F,HN-virosomes fuse with desialylated HepG2 cells, although the rate was two- to threefold higher if HN was included in the viral envelope. We also observed enhancement of fusion rates when both F and HN envelope proteins were attached to their specific receptors. C1 NCI,MEMBRANE STRUCT & FUNCT SECT,BLDG 10,ROOM 4A01 LMMB,BETHESDA,MD 20892. UNIV DELHI,DEPT BIOCHEM,NEW DELHI 110021,INDIA. NR 43 TC 51 Z9 52 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 1993 VL 67 IS 6 BP 3312 EP 3318 PG 7 WC Virology SC Virology GA LB794 UT WOS:A1993LB79400042 PM 8388501 ER PT J AU BLASCO, R SISLER, JR MOSS, B AF BLASCO, R SISLER, JR MOSS, B TI DISSOCIATION OF PROGENY VACCINIA VIRUS FROM THE CELL-MEMBRANE IS REGULATED BY A VIRAL ENVELOPE GLYCOPROTEIN - EFFECT OF A POINT MUTATION IN THE LECTIN HOMOLOGY DOMAIN OF THE A34R GENE SO JOURNAL OF VIROLOGY LA English DT Article ID NUCLEOTIDE-SEQUENCE; RELEASE; DISSEMINATION; PROTEIN; DNA; N1-ISONICOTINOYL-N2-3-METHYL-4-CHLOROBENZOYLHYDRAZINE; IDENTIFICATION; POLYPEPTIDE; GENOME; INVIVO AB Vaccinia virus strains vary considerably in the amounts of extracellular enveloped virus (EEV) that they release from infected cells. The IHD-J strain produces up to 40 times more EEV than does the related WR strain and consequently generates elongated comet-shaped virus plaques instead of sharply defined round ones in susceptible monolayer cells under liquid medium. The difference in EEV formation is due to the retention of enveloped WR virions on the cell surface (R. Blasco and B. Moss, J. Virol. 66:4170-4179, 1992). By using WR and IHD-J DNA fragments for marker transfer and analyzing the progeny virus by the comet formation assay, we determined that gene A34R and at least one other gene regulate the release of cell-associated virions. Replacement of the A34R gene of WR with the corresponding gene from IHD-J increased the amount of EEV produced by 10-fold and conferred the ability to form distinctive comet-shaped plaques. Gene A34R encodes an EEV-specific glycoprotein with homology to C-type animal lectins (S. A. Duncan and G. L. Smith, J. Virol. 66:1610-1621, 1992). The nucleotide sequences of the A34R genes of WR and IHD-J strains differed in six positions, of which four were silent. One of the codon mutations (Lys-151-->Glu), which is located in the putative carbohydrate recognition domain, was sufficient to transfer a comet-forming phenotype to WR virus. These data indicate that the A34R-encoded glycoprotein is involved, through its lectin homology domain, in the retention of progeny virus on the surface of parental cells and raise the possibility that the protein also has a role in virus attachment to uninfected cells. C1 NIAID,VIRAL DIS LAB,BLDG 4,ROOM 229,BETHESDA,MD 20892. INST NACL INVEST & TECNOL AGR & ALIMENTARIA,DEPT SANIDAD ANIM,E-28012 MADRID,SPAIN. RI Blasco, Rafael/B-5829-2016 NR 35 TC 108 Z9 109 U1 0 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 1993 VL 67 IS 6 BP 3319 EP 3325 PG 7 WC Virology SC Virology GA LB794 UT WOS:A1993LB79400043 PM 8497053 ER PT J AU BALDICK, CJ MOSS, B AF BALDICK, CJ MOSS, B TI CHARACTERIZATION AND TEMPORAL REGULATION OF MESSENGER-RNAS ENCODED BY VACCINIA VIRUS INTERMEDIATE-STAGE GENES SO JOURNAL OF VIROLOGY LA English DT Article ID TRANSCRIPTION FACTOR; POLY(A) SEQUENCES; PROMOTER REGION; DNA-REPLICATION; 5' ENDS; EXPRESSION; INVITRO; IDENTIFICATION; TERMINATION; POLYMERASE AB The steady-state levels of mRNAs encoded by three intermediate-stage genes of vaccinia virus, AIL, A2L, and G8R, were compared with those encoded by well-characterized early- and late-stage genes. After synchronous infection of HeLa cells, the early mRNA was detected within 20 min and peaked at about 100 min; all three intermediate mRNAs were detected at 100 min and peaked at about 120 min; and the late mRNA was detected at 140 min and increased thereafter. Upon reaching maximum levels, the early and intermediate mRNAs declined at rates consistent with half-lives of about 30 min, providing the basis for rapid changes in gene expression. Intermediate mRNA was not detected when viral DNA synthesis was prevented, whereas its accumulation was enhanced by blocking translation after removal of the replication inhibitor. The 5' ends of the mRNAs initiated within a TAAAT or TAAAAT sequence in the coding DNA strand but contained a poly(A) leader of up to 30 additional bases. Diffuse bands of A1L and G8R RNA, equal to and longer than the coding region, were resolved by agarose gel electrophoresis, suggesting preferred sites of 3'-end formation that did not correlate with early gene termination signals. The cis-regulatory sequences were investigated by constructing recombinant viruses containing mutated intermediate promoters preceding the beta-galactosidase reporter gene. The effects of mutations on expression were similar to those previously obtained by transfection studies (C. J. Baldick, Jr., J. G. Keck, and B. Moss, J. Virol. 66:4710-4719, 1992), providing further evidence for functional core, spacer, and initiator regions. In addition, an up-regulated bifunctional early/intermediate promoter was created by making four single-base substitutions in the G8R promoter. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. NR 54 TC 72 Z9 72 U1 2 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 1993 VL 67 IS 6 BP 3515 EP 3527 PG 13 WC Virology SC Virology GA LB794 UT WOS:A1993LB79400067 PM 8098779 ER PT J AU WILLEY, RL MARTIN, MA AF WILLEY, RL MARTIN, MA TI ASSOCIATION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ENVELOPE GLYCOPROTEIN WITH PARTICLES DEPENDS ON INTERACTIONS BETWEEN THE 3RD VARIABLE AND CONSERVED REGIONS OF GP120 SO JOURNAL OF VIROLOGY LA English DT Note ID SOLUBLE CD4; ENDOPROTEOLYTIC CLEAVAGE; TRANSMEMBRANE PROTEIN; OLIGOMERIC STRUCTURE; FUSION DOMAIN; GP41; BINDING; CELLS; GLYCOSYLATION; BIOSYNTHESIS AB Many regions within the envelope of human immunodeficiency virus type 1 (HIV-1) that affect its structure and function have been identified. We have previously reported that the interaction of the second conserved (C2) and third variable (V3) regions of gp120 influences the ability of HIV-1 to establish a productive infection in susceptible cells. To better understand the basis for this interaction, we have conducted structure-function analyses of envelope expressed from molecular proviral clones of HIV-1 containing defined mutations in C2 and V3 that individually and in combination differentially affect envelope function. The substitution of a glutamine for an asparagine residue (Q-267) at a potential asparagine-linked glycosylation site in C2, which severely impairs virus infectivity, reduces intracellular processing of gp160 into gp120, the association of gp120 with virions, and the ability of gp120 to bind to the HIV-1 cell surface receptor protein, CD4. The change of an arginine to an isoleucine codon in V3 (1-308), in the presence of the Q-267 mutation, restores virus infectivity to near wild-type levels by increasing the amount of gp120 associated with virions as compared with the Q-267 mutant but does not compensate for the Q-267-induced processing defect. The 1-308 change in the context of the wild-type HIV-1 has no affect on processing, association, or CD4 binding. These results indicate that the impaired infectivity of the Q-267 mutant virus is due to a marked reduction in the amount of virion gp120 and suggest that the interaction of C2 and V3 stabilizes the association of gp120 with gp41. RP WILLEY, RL (reprint author), NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892, USA. NR 35 TC 34 Z9 34 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 1993 VL 67 IS 6 BP 3639 EP 3643 PG 5 WC Virology SC Virology GA LB794 UT WOS:A1993LB79400085 PM 8497072 ER PT J AU BRUGGEMAN, LA PELLICORO, JA HORIGAN, EA KLOTMAN, PE AF BRUGGEMAN, LA PELLICORO, JA HORIGAN, EA KLOTMAN, PE TI THROMBOXANE AND PROSTACYCLIN DIFFERENTIALLY REGULATE MURINE EXTRACELLULAR-MATRIX GENE-EXPRESSION SO KIDNEY INTERNATIONAL LA English DT Article ID HEPARAN-SULFATE PROTEOGLYCAN; EXPERIMENTAL DIABETES-MELLITUS; ARACHIDONIC-ACID METABOLISM; BASEMENT-MEMBRANE PROTEINS; HUMAN MESANGIAL CELLS; STEADY-STATE LEVELS; PROSTAGLANDIN SYNTHESIS; MESSENGER-RNA; MULTIDOMAIN PROTEIN; URINARY-EXCRETION AB Alterations in the arachidonic acid metabolites thromboxane and prostacyclin are known to contribute to hemodynamic changes observed in certain models of acute and chronic renal failure. We have previously shown that thromboxane may have an important role in mediating glomerulosclerosis by stimulating the expression of certain extracellular matrix proteins. In the present study, we compared the effects of thromboxane and prostacyclin on the expression of genes encoding basement membrane proteins using a murine teratocarcinoma cell line, that when differentiated to an endodermal phenotype synthesizes abundant extracellular matrix. Incubation of these cells with stable analogs of thromboxane and prostacyclin for four hours resulted in changes in basement membrane gene expression. Thromboxane increased steady-state mRNA levels for all three laminin chains, type IV collagen, and fibronectin, but decreased the level of mRNA for heparan sulfate proteoglycan. In contrast, incubation with carbo-prostacyclin, a stable analog of prostacyclin, decreased the steady-state mRNA level for the laminin A and B1 chains, type IV collagen and fibronectin, and increased the mRNA level for heparan sulfate proteoglycan and laminin B2. Carbo-prostacyclin did not affect cellular proliferation or thymidine incorporation. These results indicate that eicosanoids directly modulate matrix gene expression independently of hemodynamic influence, and independently of effects mediated by platelets, or mitogenesis. Furthermore, these findings suggest that the alterations in renal eicosanoid metabolism may directly participate in the pathogenesis of glomerulosclerosis and thus provide a rationale for therapy directed toward the specific inhibition of thromboxane in the treatment of progressive glomerular sclerosis. RP BRUGGEMAN, LA (reprint author), NIDR,DEV BIOL LAB,MOLEC MED SECT,BETHESDA,MD 20892, USA. NR 55 TC 38 Z9 38 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JUN PY 1993 VL 43 IS 6 BP 1219 EP 1225 DI 10.1038/ki.1993.172 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA LC377 UT WOS:A1993LC37700003 PM 8315934 ER PT J AU DVORAK, AM SEDER, RA PAUL, WE KISSELLRAINVILLE, S PLAUT, M GALLI, SJ AF DVORAK, AM SEDER, RA PAUL, WE KISSELLRAINVILLE, S PLAUT, M GALLI, SJ TI ULTRASTRUCTURAL CHARACTERISTICS OF FC-EPSILON-R-POSITIVE BASOPHILS IN THE SPLEEN AND BONE-MARROW OF MICE IMMUNIZED WITH GOAT ANTI-MOUSE IGD ANTIBODY SO LABORATORY INVESTIGATION LA English DT Article DE MAST CELL; IL-4; NON-B-CELL NON-T-CELL ID SPLENIC NON-B; NON-T CELLS; BLOOD MONONUCLEAR-CELLS; MAST-CELLS; NIPPOSTRONGYLUS-BRASILIENSIS; GROWTH-FACTORS; CROSS-LINKAGE; INTERLEUKIN-4; RECEPTOR; IL-4 AB BACKGROUND: Previous work showed that injection of mice with goat anti-mouse IgD antibodies results in increased numbers of Fc(epsilon)R-positive, non-B, non-T cells in the spleen and Fc(epsilon)R-positive cells in the bone marrow, and that some of these cells had ultrastructural features of basophils. Fc(epsilon)R-positive, non-B, non-T cells express virtually all of the capacity of mouse splenic ''non-B, non-T cells'' to produce interleukin-4 in response to stimulation by cross-linking of Fc(epsilon)R or Fc(gamma)R, or by the calcium ionophore, ionomycin. EXPERIMENTAL DESIGN: The present study is a detailed ultrastructural analysis of Fc(epsilon)R-positive bone marrow cells or Fc(epsilon)R-positive splenic non-B, non-T cells sorted from mice injected with goat anti-mouse IgD antibody and of Fc(epsilon)R-positive bone marrow cells or spleen cells pooled from normal mice not injected with goat anti-IgD. RESULTS: Basophils represented the majority (90%) of the granulated cells present in the Fc(epsilon)R-positive splenic non-B, non-T cells or Fc(epsilon)R-positive bone marrow cells of goat anti-IgD-injected mice. In contrast, the cytoplasmic granule-containing Fc(epsilon)R-negative cells sorted from spleen or bone marrow of goat anti-IgD-injected animals contained predominantly a mixture of neutrophils, eosinophils, monocytes and their precursors. Both the Fc(epsilon)R-positive and -negative preparations contained rare (<5%) cells with ultrastructural features of very immature mast cells. Basophils were also identified in Fc(epsilon)R-positive cells sorted from total bone marrow cells or spleen cells of normal mice not injected with goat anti-IgD. CONCLUSIONS: Taken together with data concerning the numbers of Fc(epsilon)R-positive, non-B, non-T cells in the spleen, and Fc(epsilon)R-positive B220-negative cells in the bone marrow, these ultrastructural findings indicate that injection of mice with goat anti-IgD results in increased numbers of basophils, particularly in the spleen, that exhibit an 8-fold increase in basophils as a result of injection of goat anti-IgD. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. NIAID,IMMUNOL LAB,BETHESDA,MD 20892. BETH ISRAEL HOSP,CHARLES A DANA RES INST,BOSTON,MA 02215. JOHNS HOPKINS UNIV,SCH MED,JOHNS HOPKINS ASTHMA & ALLERGY CTR,DEPT MED,BALTIMORE,MD 21205. RP DVORAK, AM (reprint author), BETH ISRAEL HOSP,DEPT PATHOL,330 BROOKLINE AVE,BOSTON,MA 02215, USA. FU NIAID NIH HHS [AI-23990, AI-22674, AI-33372] NR 34 TC 17 Z9 17 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JUN PY 1993 VL 68 IS 6 BP 708 EP 715 PG 8 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA LJ125 UT WOS:A1993LJ12500011 PM 8515657 ER PT J AU VANDEWOUDE, GF AF VANDEWOUDE, GF TI KIRSTEN,WERNER,H., 1925-1992 SO LEUKEMIA LA English DT Item About an Individual RP VANDEWOUDE, GF (reprint author), FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,POB B,FREDERICK,MD 21702, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0887-6924 J9 LEUKEMIA JI Leukemia PD JUN PY 1993 VL 7 IS 6 BP 781 EP 781 PG 1 WC Oncology; Hematology SC Oncology; Hematology GA LH925 UT WOS:A1993LH92500001 ER PT J AU KEHRL, JH DEGUCHI, Y AF KEHRL, JH DEGUCHI, Y TI POTENTIAL ROLES FOR 2 HUMAN HOMEODOMAIN CONTAINING PROTEINS IN THE PROLIFERATION AND DIFFERENTIATION OF HUMAN HEMATOPOIETIC PROGENITORS SO LEUKEMIA & LYMPHOMA LA English DT Article DE HEMATOPOIESIS; HOMEODOMAIN; TRANSCRIPTION FACTORS; DIFFERENTIATION; LINEAGE DETERMINATION AB Two human homeobox genes, HB9 and HLX, are expressed in hematopoietic progenitors and activated lymphocytes. They are implicated in the proliferation of hematopoietic progenitors in response to growth factors and the differentiation of hematopoietic progenitors to mature cell lineages. RNAs from bone marrow cells of patients with acute myeloid or lymphocytic leukemia have high levels of these two genes while similar RNAs from patients with chronic lymphocytic or myeloid leukemias have nearly normal levels. While the significance of these two genes in leukemogenesis is unknown, they are likely to regulate gene transcription during hematopoiesis and their dysregulation may have dire consequences for hematopoietic cells. RP KEHRL, JH (reprint author), NIAID,IMMUNOREGULAT LAB,BLDG 10,ROOM 11B-13,BETHESDA,MD 20892, USA. OI Kehrl, John/0000-0002-6526-159X NR 0 TC 13 Z9 16 U1 0 U2 0 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD JUN PY 1993 VL 10 IS 3 BP 173 EP 176 DI 10.3109/10428199309145879 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA LT610 UT WOS:A1993LT61000004 PM 8106064 ER PT J AU ROY, MS ROY, A GALLUCCI, WT COLLIER, B YOUNG, K KAMILARIS, TC CHROUSOS, GP AF ROY, MS ROY, A GALLUCCI, WT COLLIER, B YOUNG, K KAMILARIS, TC CHROUSOS, GP TI THE OVINE CORTICOTROPIN-RELEASING HORMONE STIMULATION TEST IN TYPE-I DIABETIC-PATIENTS AND CONTROLS - SUGGESTION OF MILD CHRONIC HYPERCORTISOLISM SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID DEXAMETHASONE SUPPRESSION TEST; CORTISOL SECRETION; PITUITARY; MELLITUS; DEPRESSION; STRESS; STREPTOZOTOCIN; TRANSPORT; STEROIDS; PLASMA C1 NEI,CLIN BRANCH,BETHESDA,MD 20892. NIADA,BETHESDA,MD. NICHHD,DEV ENDOCRINOL BRANCH,BALTIMORE,MD 21224. NR 32 TC 58 Z9 61 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD JUN PY 1993 VL 42 IS 6 BP 696 EP 700 DI 10.1016/0026-0495(93)90235-G PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LG442 UT WOS:A1993LG44200006 PM 8389960 ER PT J AU CHRISTIN, L OCONNELL, M BOGARDUS, C DANFORTH, E RAVUSSIN, E AF CHRISTIN, L OCONNELL, M BOGARDUS, C DANFORTH, E RAVUSSIN, E TI NOREPINEPHRINE TURNOVER AND ENERGY-EXPENDITURE IN PIMA INDIAN AND WHITE MEN SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID SYMPATHETIC NERVOUS-SYSTEM; GLUCOSE-INDUCED THERMOGENESIS; BETA-ADRENERGIC-BLOCKADE; BODY-COMPOSITION; METABOLIC-RATE; RISK; OBESITY; WEIGHT; HUMANS; STIMULATION C1 NIDDKD,CLIN DIABET & NUTR SECT,4212 N 16TH ST,ROOM 541,PHOENIX,AZ 85016. UNIV VERMONT,COLL MED,DIV ENDOCRINOL METAB & NUTR,BURLINGTON,VT 05405. NR 34 TC 52 Z9 52 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD JUN PY 1993 VL 42 IS 6 BP 723 EP 729 DI 10.1016/0026-0495(93)90239-K PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LG442 UT WOS:A1993LG44200010 PM 8510516 ER PT J AU JANE, SM GUMUCIO, DL NEY, PA CUNNINGHAM, JM NIENHUIS, AW AF JANE, SM GUMUCIO, DL NEY, PA CUNNINGHAM, JM NIENHUIS, AW TI METHYLATION-ENHANCED BINDING OF SP1 TO THE STAGE SELECTOR ELEMENT OF THE HUMAN GAMMA-GLOBIN GENE PROMOTER MAY REGULATE DEVELOPMENTAL SPECIFICITY OF EXPRESSION SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID FETAL HEMOGLOBIN PRODUCTION; SICKLE-CELL-ANEMIA; BETA-GLOBIN; TRANSGENIC MICE; DNA METHYLATION; ERYTHROID-CELLS; HEREDITARY PERSISTENCE; CYTOSINE METHYLATION; PROTEIN; SITES AB The human gamma-globin gene promoter contains a stage selector element (SSE) responsible for preferential interaction of the promoter with a powerful erythroid-specific enhancer in the fetal developmental stage (S. M. Jane, P. A. Ney, E. F. Vanin, D. L. Gumucio, and A. W. Nienhuis. EMBO J. 11:2691-2699, 1992). The element binds two proteins, the ubiquitous activator Sp1 and a protein previously known as -50gamma and now named the stage selector protein (SSP). Binding of the second protein correlates with SSE activity in transient-transfection assays. We now report that a de novo binding site for the SSP is created by the -202(C-->G) mutation that causes hereditary persistence of fetal hemoglobin (HPFH). This site functions in an analogous manner to the SSE in hybrid beta-promoter/reporter gene constructs transfected into K562 cells. In contrast, the wild-type -202 sequence, which fails to bind the SSP, is incapable of activating the beta-gene promoter. Both the -50 and -202 HPFH sites for SSP binding overlap a consensus sequence for the transcriptional regulator Spl. In addition, both sites contain CpG dinucleotides that are contact bases for SSP. Since the gamma promoter is known to be hypomethylated in fetal cells but fully methylated at CpG residues in adult erythroid cells, we examined the effects of this DNA modification on protein binding to the two regions. Gel mobility shift assays with nuclear extract from K562 cells (which contain both Sp1 and SSP) demonstrate preferential binding of SSP to the SSE and HPFH sites under conditions in which probe was limiting. Methylation of the CpG residues reverses this preference only in the SSE site, with a marked increase in the binding of Sp1 at the expense of the SSP. Purified Spl binds with 10-fold higher affinity to the methylated than to the nonmethylated -50 probe but with the same affinity to the -202 HPFH probe. The methylation-induced preferential binding of Sp1 to the SSE at the expense of SSP may be part of the mechanism by which the gamma genes are repressed in normal adult erythroid cells. In cells containing the -202 HPFH mutation, the inability of Sp1 to displace SSP in the methylated state may explain the persistence of gamma-promoter activity and gamma-gene expression observed in adults with this mutation. C1 UNIV MICHIGAN,DEPT ANAT & CELL BIOL,ANN ARBOR,MI 48109. RP JANE, SM (reprint author), NHLBI,BETHESDA,MD 20892, USA. RI Jane, Stephen/D-6659-2011 NR 62 TC 84 Z9 84 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUN PY 1993 VL 13 IS 6 BP 3272 EP 3281 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LD733 UT WOS:A1993LD73300015 PM 7684493 ER PT J AU WESTWOOD, JT WU, C AF WESTWOOD, JT WU, C TI ACTIVATION OF DROSOPHILA HEAT-SHOCK FACTOR - CONFORMATIONAL CHANGE ASSOCIATED WITH A MONOMER-TO-TRIMER TRANSITION SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DNA-BINDING; MOLECULAR-CLONING; OLIGOMERIZATION; TRANSCRIPTION; EXPRESSION; PROTEIN AB The induction of heat shock genes in eukaryotic cells is regulated by the transcription factor heat shock factor (HSF). Activation of HSF occurs at two independent levels, DNA binding and the acquisition of transcriptional competence. The binding of HSF to DNA is accomplished by a stress-induced oligomeric switch of HSF protein. We have defined the oligomeric state of the latent and induced forms of HSF by measuring the sedimentation coefficient and the Stokes radius of the protein in Drosophila cell extracts. Calculation of the native molecular mass indicates that the two forms of Drosophila HSF are best described as a monomer and trimer, respectively, of the 77-kDa HSF polypeptide. The monomeric and trimeric states of HSF were verified by chemical cross-linking experiments. The finding of a monomeric composition for the latent form of HSF is incompatible with speculative models which suggest that molecular chaperones such as hsp70 feed back to inhibit trimerization of HSF by forming a stable heteromeric complex. We also found that both HSF monomers and HSF trimers exhibit unusually high frictional ratios, indicating that they have asymmetric shapes. The degree of asymmetry is significantly greater for the HSF trimer, suggesting that the monomer undergoes a conformational change to a more extended structure upon trimerization. These findings are consistent with a model for the inert HSF protein that is based on a monomer constrained by intramolecular coiled-coil interactions between amino- and carboxy-terminal domains. C1 NCI,BIOCHEM LAB,BLDG 37,ROOM 4C-09,BETHESDA,MD 20892. NR 31 TC 174 Z9 178 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUN PY 1993 VL 13 IS 6 BP 3481 EP 3486 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LD733 UT WOS:A1993LD73300035 PM 8497263 ER PT J AU CUDDIHY, AE BRENTS, LA AZIZ, N BENDER, TP KUEHL, WM AF CUDDIHY, AE BRENTS, LA AZIZ, N BENDER, TP KUEHL, WM TI ONLY THE DNA-BINDING AND TRANSACTIVATION DOMAINS OF C-MYB ARE REQUIRED TO BLOCK TERMINAL DIFFERENTIATION OF MURINE ERYTHROLEUKEMIA-CELLS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID V-MYB; GENE-EXPRESSION; TRANSCRIPTIONAL ACTIVATION; ERYTHROID-DIFFERENTIATION; HEMATOPOIETIC-CELLS; CELLULAR PROGENITOR; MYELOID-LEUKEMIA; ONCOGENE PRODUCT; MESSENGER-RNA; PROTEIN AB The c-Myb protein is a transcription factor with an apparent but poorly defined role in hematopoietic cell growth and differentiation. The DNA binding and several transcriptional regulatory domains of the c-Myb protein have been defined by transient transfections into nonhematopoietic cell lines. Although the relationship between these domains and transformation has been studied, little is known about the function of these domains during hematopoietic maturation. Up-regulation of stably transfected c-myb in murine erythroleukemia (MEL) cells blocks terminal differentiation when MEL cells are induced to differentiate with N,N'-hexamethylene bisacetamide. To determine which functional domains of c-Myb are necessary and sufficient to block differentiation, mutated c-myb constructs under the control of a murine metallothionein promoter were transfected into C19 MEL cells, and stable clonal cell lines were established. The ability of Myb mutants to block differentiation paralleled their ability to transactivate transcription of a reporter gene containing Myb-responsive elements, by transient transfection into a lymphoid cell line. The smallest c-Myb mutant able to block differentiation consisted of the DNA binding domain juxtaposed to the transactivation domain. Therefore, the DNA binding domain and the transactivation domain are necessary and sufficient for c-Myb to block differentiation in MEL cells. C1 NCI,NAVY MED ONCOL BRANCH,BETHESDA,MD 20889. UNIV VIRGINIA,HLTH SCI CTR,DEPT MICROBIOL,CHARLOTTESVILLE,VA 22908. FU NCI NIH HHS [CA40042] NR 56 TC 29 Z9 29 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUN PY 1993 VL 13 IS 6 BP 3505 EP 3513 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LD733 UT WOS:A1993LD73300038 PM 8497265 ER PT J AU MARTON, MJ CROUCH, D HINNEBUSCH, AG AF MARTON, MJ CROUCH, D HINNEBUSCH, AG TI GCN1, A TRANSLATIONAL ACTIVATOR OF GCN4 IN SACCHAROMYCES-CEREVISIAE, IS REQUIRED FOR PHOSPHORYLATION OF EUKARYOTIC TRANSLATION INITIATION FACTOR-II BY PROTEIN-KINASE GCN2 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ELONGATION FACTOR-III; AMINO-ACID AVAILABILITY; VIRUS-INFECTED CELLS; TRANSFER-RNA; NUCLEOTIDE-SEQUENCE; GEL-ELECTROPHORESIS; GENERAL CONTROL; MESSENGER-RNA; YEAST; EXPRESSION AB Phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2alpha) by the protein kinase GCN2 mediates increased translation of the transcriptional activator GCN4 in amino acid-starved yeast cells. We show that this key phosphorylation event and the attendant translational induction of GCN4 are dependent on the product of a previously uncharacterized gene, GCN1. Inactivation of GCN1 did not affect the level of eIF-2alpha phosphorylation when mammalian eIF-2alpha kinases were expressed in yeast cells in place of GCN2, arguing against an involvement of GCN1 in dephosphorylation of eIF-2alpha. In addition, while GCN1 is required in vivo for phosphorylation of eIF-2alpha by GCN2, cell extracts from gcn1DELTA strains contained wild-type levels of GCN2 eIF-2alpha-kinase activity. On the basis of these results, we propose that GCN1 is not needed for GCN2 kinase activity per se but is required for in vivo activation of GCN2 in response to the starvation signal, uncharged tRNA. GCN1 encodes a protein of 297 kDa with an 88-kDa region that is highly similar in sequence to translation elongation factor 3 identified in several fungal species. This sequence similarity raises the possibility that GCN1 interacts with ribosomes or tRNA molecules and functions in conjunction with GCN2 in monitoring uncharged tRNA levels during the process of translation elongation. C1 NICHHD,MOLEC GENET LAB,MOLEC GENET LOWER EUKARYOTES SECT,BETHESDA,MD 20892. NR 80 TC 71 Z9 73 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUN PY 1993 VL 13 IS 6 BP 3541 EP 3556 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LD733 UT WOS:A1993LD73300042 PM 8497269 ER PT J AU NOLAN, GP FUJITA, T BHATIA, K HUPPI, C LIOU, HC SCOTT, ML BALTIMORE, D AF NOLAN, GP FUJITA, T BHATIA, K HUPPI, C LIOU, HC SCOTT, ML BALTIMORE, D TI THE BCL-3 PROTOONCOGENE ENCODES A NUCLEAR I-KAPPA-B-LIKE MOLECULE THAT PREFERENTIALLY INTERACTS WITH NF-KAPPA-B P50 AND P52 IN A PHOSPHORYLATION-DEPENDENT MANNER SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DNA-BINDING SUBUNIT; REL-ASSOCIATED PP40; CELL-CYCLE CONTROL; TRANSCRIPTION FACTOR; NUCLEOTIDE-SEQUENCE; DROSOPHILA-NOTCH; GENE-PRODUCT; PROTEINS; INHIBITOR; HOMOLOGY AB The product of the putative proto-oncogene bcl-3 is an IkappaB-like molecule with novel binding properties specific for a subset of the rel family of transcriptional regulators. In vitro, Bcl-3 protein specifically inhibited the DNA binding of both the homodimeric NF-kappaB p50 subunit and a closely related homolog, p52 (previously p49), to immunoglobulin kappa NF-kappaB DNA motifs. Bcl-3 could catalyze the removal of these proteins from DNA. At concentrations that significantly inhibited DNA binding by homodimeric p50, Bcl-3 did not inhibit binding of reconstituted heterodimeric NF-kappaB (p50:p65), a DNA-binding homodimeric form of p65, or homodimers of c-Rel. Phosphatase treatment of Bcl-3 partially inactivated its inhibitory properties, implicating a role for phosphorylation in the regulation of Bcl-3 activity. Bcl-3, like p50, localizes to the cell nucleus. In cells cotransduced with Bcl-3 and p50, both molecules could be found in the nucleus of the same cells. Interestingly, coexpression of Bcl-3 with a p50 mutant deleted for its nuclear-localizing signal resulted in the relocalization of Bcl-3 to the cytoplasm, showing that the proteins interact in the cell. These properties contrast Bcl-3 to classically defined IkappaB, which maintains heterodimeric NF-kappaB p50:p65 in the cytoplasm through specific interactions with the p65 subunit. Bcl-3 appears to be a nuclear, IkappaB-related molecule that regulates the activity of homodimeric nuclear p50 and its homolog p52. C1 NIH,BETHESDA,MD 20892. RP BALTIMORE, D (reprint author), ROCKEFELLER UNIV,1230 YORK AVE,NEW YORK,NY 10021, USA. FU NCI NIH HHS [CA51462]; NIGMS NIH HHS [GM39458] NR 52 TC 188 Z9 189 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUN PY 1993 VL 13 IS 6 BP 3557 EP 3566 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LD733 UT WOS:A1993LD73300043 PM 8497270 ER PT J AU GORSKI, DH LEPAGE, DF PATEL, CV COPELAND, NG JENKINS, NA WALSH, K AF GORSKI, DH LEPAGE, DF PATEL, CV COPELAND, NG JENKINS, NA WALSH, K TI MOLECULAR-CLONING OF A DIVERGED HOMEOBOX GENE THAT IS RAPIDLY DOWN-REGULATED DURING THE G(0)/G(1) TRANSITION IN VASCULAR SMOOTH-MUSCLE CELLS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ACTIN ISOFORM EXPRESSION; ARREST-SPECIFIC GENE; GROWTH ARREST; MOUSE FIBROBLASTS; RETINOIC ACID; PROTEIN; FAMILY; TRANSCRIPTION; HOMEODOMAIN; PURIFICATION AB Adult vascular smooth muscle cells dedifferentiate and reenter the cell cycle in response to growth factor stimulation. Here we describe the molecular cloning from vascular smooth muscle, the structure, and the chromosomal location of a diverged homeobox gene, Gax, whose expression is largely confined to the cardiovascular tissues of the adult. In quiescent adult rat vascular smooth muscle cells, Gax mRNA levels are down-regulated as much as 15-fold within 2 h when these cells are induced to proliferate with platelet-derived growth factor (PDGF) or serum growth factors. This reduction in Gax mRNA is transient, with levels beginning to rise between 8 and 24 h after mitogen stimulation and returning to near normal by 24 to 48 h. The Gax down-regulation is dose dependent and can be correlated with the mitogen's ability to stimulate DNA synthesis. PDGF-AA, a weak mitogen for rat vascular smooth muscle cells, did not affect Gax transcript levels, while PDGF-AB and -BB, potent mitogens for these cells, were nearly as effective as fetal bovine serum. The removal of serum from growing cells induced Gax expression fivefold within 24 h. These data suggest that Gax is likely to have a regulatory function in the G0-to-G1 transition of the cell cycle in vascular smooth muscle cells. C1 CASE WESTERN RESERVE UNIV, SCH MED, DEPT PHYSIOL & BIOPHYS, 10900 EUCLID AVE, CLEVELAND, OH 44106 USA. NCI, FREDERICK CANC RES & DEV CTR, MAMMALIAN GENET LAB, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USA. FU NCI NIH HHS [N01-CO-74101]; NHLBI NIH HHS [HL45345]; NIAMS NIH HHS [AR40197] NR 71 TC 123 Z9 132 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 JUN PY 1993 VL 13 IS 6 BP 3722 EP 3733 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LD733 UT WOS:A1993LD73300059 PM 8098844 ER PT J AU SEGARS, JH MARKS, MS HIRSCHFELD, S DRIGGERS, PH MARTINEZ, E GRIPPO, JF BROWN, M WAHLI, W OZATO, K AF SEGARS, JH MARKS, MS HIRSCHFELD, S DRIGGERS, PH MARTINEZ, E GRIPPO, JF BROWN, M WAHLI, W OZATO, K TI INHIBITION OF ESTROGEN-RESPONSIVE GENE ACTIVATION BY THE RETINOID-X RECEPTOR-BETA - EVIDENCE FOR MULTIPLE INHIBITORY PATHWAYS (VOL 13, PG 2258, 1993) SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Correction, Addition C1 NICHHD,MOLEC GROWTH REGULAT LAB,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DEPT MED,BOSTON,MA 02115. HOFFMANN LA ROCHE INC,DRUG METAB,NUTLEY,NJ 07110. UNIV LAUSANNE,INST BIOL ANIM,CH-1015 LAUSANNE,SWITZERLAND. RI Hirschfeld, Steven/E-2987-2016 OI Hirschfeld, Steven/0000-0003-0627-7249 NR 1 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUN PY 1993 VL 13 IS 6 BP 3840 EP 3840 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LD733 UT WOS:A1993LD73300072 ER PT J AU LEE, WH BONDY, C AF LEE, WH BONDY, C TI INDUCTION OF EGR1/NGFI-A GENE-EXPRESSION BY SPREADING DEPRESSION AND FOCAL CEREBRAL-ISCHEMIA SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article ID C-FOS PROTEIN; GROWTH-FACTORS; BRAIN; DEPOLARIZATION; SEQUENCES; INCREASE; ENCODES; CELLS RP LEE, WH (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892, USA. NR 24 TC 8 Z9 8 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell Neurosci. PD JUN PY 1993 VL 4 IS 3 BP 225 EP 230 DI 10.1006/mcne.1993.1028 PG 6 WC Neurosciences SC Neurosciences & Neurology GA LE606 UT WOS:A1993LE60600001 PM 19912926 ER PT J AU IGARASHI, A OKOCHI, H BRADHAM, DM GROTENDORST, GR AF IGARASHI, A OKOCHI, H BRADHAM, DM GROTENDORST, GR TI REGULATION OF CONNECTIVE-TISSUE GROWTH-FACTOR GENE-EXPRESSION IN HUMAN SKIN FIBROBLASTS AND DURING WOUND REPAIR SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID IMMEDIATE-EARLY GENE; C-FOS GENE; FACTOR-BETA; SIGNAL TRANSDUCTION; ENDOTHELIAL-CELLS; INDUCIBLE GENE; MESSENGER-RNA; 3T3 CELLS; INDUCTION; PROTEIN AB Connective tissue growth factor (CTGF) is a cysteine-rich peptide that exhibits platelet-derived growth factor (PDGF)-like biological and immunological activities. CTGF is a member of a family of peptides that include serum-induced immediate early gene products, a v-src-induced peptide, and a putative avian transforming gene, nov. In the present study, we demonstrate that human foreskin fibroblasts produce high levels of CTGF mRNA and protein after activation with transforming growth factor beta (TGF-beta) but not other growth factors including PDGF, epidermal growth factor, and basic fibroblast growth factor. Because of the high level selective induction of CTGF by TGF-beta, it appears that CTGF is a major autocrine growth factor produced by TGF-beta-treated human skin fibroblasts. Cycloheximide did not block the large TGF-beta stimulation of CTGF gene expression, indicating that it is directly regulated by TGF-beta. Similar regulatory mechanisms appear to function in vivo during wound repair where there is a coordinate expression of TGF-beta1 before CTGF in regenerating tissue, suggesting a cascade process for control of tissue regeneration and repair. C1 NIA,GERONTOL RES CTR,BIOL CHEM LAB,BALTIMORE,MD 21224. RP IGARASHI, A (reprint author), UNIV MIAMI,SCH MED,DEPT CELL BIOL & ANAT,MIAMI,FL 33136, USA. FU NIGMS NIH HHS [GM-37223] NR 49 TC 536 Z9 561 U1 6 U2 20 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD JUN PY 1993 VL 4 IS 6 BP 637 EP 645 PG 9 WC Cell Biology SC Cell Biology GA LH298 UT WOS:A1993LH29800009 PM 8374172 ER PT J AU ROMEO, DS PARK, K ROBERTS, AB SPORN, MB KIM, SJ AF ROMEO, DS PARK, K ROBERTS, AB SPORN, MB KIM, SJ TI AN ELEMENT OF THE TRANSFORMING GROWTH-FACTOR-BETA-1 5'-UNTRANSLATED REGION REPRESSES TRANSLATION AND SPECIFICALLY BINDS A CYTOSOLIC FACTOR SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID MESSENGER-RNA; FACTOR-BETA; CDNA CLONING; EXPRESSION; GENE; PROMOTER; IRON; ACTIVATION; INHIBITION; SEQUENCES AB In many cell types, there is a discrepancy between transforming growth factor-beta1 (TGF-beta1) mRNA and TGF-beta1 protein, suggesting that expression of TGF-beta1 is regulated posttranscriptionally. We have previously shown that a 137-nucleotide (nt) region of the TGF-beta1 5'-untranslated region (UTR) potently inhibits the expression of a heterologous reporter gene, suggesting a role for this region in the posttranscriptional inhibition of TGF-beta1 expression. To study the mechanism of inhibition, a chimeric plasmid containing this region of the TGF-beta1 5'-UTR and the reading frame of the human GH gene was stably transfected into C2Cl2 myoblastic cells. Our results show that the TGF-beta1 5'-UTR inhibits GH expression by inhibiting GH mRNA translation. In vitro gel retardation and cross-linking assays using a radiolabelled RNA probe transcribed from this region of the TGF-beta1 5'-UTR demonstrate the specific binding of a cytosolic factor. Deletion of a potential stem-loop-forming region abolishes binding of this factor and partially restores GH production. These results suggest that posttranscriptional inhibition of TGF-beta1 expression is at the level of mRNA translation and that a cytosolic factor may regulate TGF-beta1 mRNA translation. RP ROMEO, DS (reprint author), NCI, CHEMOPREVENT LAB, BLDG 41, ROOM C629, BETHESDA, MD 20892 USA. NR 37 TC 66 Z9 66 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JUN PY 1993 VL 7 IS 6 BP 759 EP 766 DI 10.1210/me.7.6.759 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LL846 UT WOS:A1993LL84600004 PM 8361501 ER PT J AU DONG, JT LUO, XM AF DONG, JT LUO, XM TI ARSENIC-INDUCED DNA-STRAND BREAKS ASSOCIATED WITH DNA-PROTEIN CROSS-LINKS IN HUMAN FETAL LUNG FIBROBLASTS SO MUTATION RESEARCH LA English DT Article DE SODIUM ARSENITE; DNA-PROTEIN CROSS-LINKS; PROTEIN-ASSOCIATED DNA-STRAND BREAKS ID SISTER CHROMATID EXCHANGES; CHINESE-HAMSTER CELLS; CYTO-TOXICITY; TOPOISOMERASE-II; SODIUM ARSENITE; ESCHERICHIA-COLI; MAMMALIAN-CELLS; HEAVY-METALS; REPAIR; MUTAGENICITY AB Sodium arsenite (As)-induced DNA damage was measured in human fetal lung fibroblasts (2BS cells) by an alkaline elution technique and a fluorometric DNA assay. Sodium arsenite at 1-5 muM produced DNA-protein crosslinks, while at 10 muM this effect was not observed. Deproteinization of DNA-protein complexes revealed protein-associated DNA-strand breaks. Both DNA-protein crosslinks and DNA-strand breaks were concentration-dependent; 3 muM As was the most efficient dose. Arsenic mediated DNA-protein interactions may play a major role in arsenic carcinogenesis, and the induced protein-associated DNA-strand breaks could provide an explanation for chromosome aberrations and sister-chromatid exchanges induced by arsenic in vivo and in vitro. C1 CHINESE ACAD MED SCI,INST CANC,BEIJING 100021,PEOPLES R CHINA. RP DONG, JT (reprint author), NIEHS,MOLEC CARCINOGENESIS LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 38 TC 68 Z9 72 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 JUN PY 1993 VL 302 IS 2 BP 97 EP 102 DI 10.1016/0165-7992(93)90010-S PG 6 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA LD315 UT WOS:A1993LD31500004 PM 7684511 ER PT J AU DILLON, DM COMBES, RD ZEIGER, E AF DILLON, DM COMBES, RD ZEIGER, E TI ACTIVATION OF THE MONOAZO DYE D-AND-C RED NO 9 TO A BACTERIAL MUTAGEN - COMPARISON OF FMN, CECAL REDUCTION AND STANDARD PREINCUBATION PROTOCOLS SO MUTATION RESEARCH LA English DT Meeting Abstract C1 INVERESK RES INT LTD,TRANENT,ENGLAND. NIEHS,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8262 J9 MUTAT RES PD JUN PY 1993 VL 291 IS 3 BP 230 EP 231 PG 2 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA LF118 UT WOS:A1993LF11800025 ER PT J AU RIACH, CG CATTANACH, PJ MITCHELL, A WILLINGTON, SE ZAJAC, WC COMBES, RD CASPARY, WJ AF RIACH, CG CATTANACH, PJ MITCHELL, A WILLINGTON, SE ZAJAC, WC COMBES, RD CASPARY, WJ TI A COMPARISON OF INSITU AND STANDARD SUSPENSION PROTOCOLS FOR THE MOUSE LYMPHOMA TK+/- FORWARD MUTATION ASSAY SO MUTATION RESEARCH LA English DT Meeting Abstract C1 INVERESK RES INT LTD,MUSSELBURGH,SCOTLAND. NIEHS,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8262 J9 MUTAT RES PD JUN PY 1993 VL 291 IS 3 BP 266 EP 266 PG 1 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA LF118 UT WOS:A1993LF11800102 ER PT J AU STOPPER, H KORBER, C SCHIFFMANN, D CASPARY, WJ AF STOPPER, H KORBER, C SCHIFFMANN, D CASPARY, WJ TI INDUCTION OF MICRONUCLEI BY NONGENOTOXIC CARCINOGENS IN L5178Y CELLS SO MUTATION RESEARCH LA English DT Meeting Abstract C1 UNIV WURZBURG,INST TOXICOL,W-8700 WURZBURG,GERMANY. NIEHS,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8262 J9 MUTAT RES PD JUN PY 1993 VL 291 IS 3 BP 276 EP 277 PG 2 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA LF118 UT WOS:A1993LF11800125 ER PT J AU CASPARY, WJ DASTON, DL KELECSENYI, Z WHITAKER, RA HINES, KC TINDALL, KR AF CASPARY, WJ DASTON, DL KELECSENYI, Z WHITAKER, RA HINES, KC TINDALL, KR TI 5-AZACYTIDINE MUTAGENESIS IN AS52 CELLS SO MUTATION RESEARCH LA English DT Meeting Abstract C1 NIEHS,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8262 J9 MUTAT RES PD JUN PY 1993 VL 291 IS 3 BP 295 EP 295 PG 1 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA LF118 UT WOS:A1993LF11800164 ER PT J AU SZALLASI, A CONTE, B GOSO, C BLUMBERG, PM MANZINI, S AF SZALLASI, A CONTE, B GOSO, C BLUMBERG, PM MANZINI, S TI VANILLOID RECEPTORS IN THE URINARY-BLADDER - REGIONAL DISTRIBUTION, LOCALIZATION ON SENSORY NERVES, AND SPECIES-RELATED DIFFERENCES SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Article DE VANILLOID RECEPTOR; [H-3]RESINIFERATOXIN BINDING; CAPSAICIN-SENSITIVE INNERVATION OF THE URINARY BLADDER; SPECIES-RELATED DIFFERENCES ID CAPSAICIN-SENSITIVE INNERVATION; P-LIKE IMMUNOREACTIVITY; GENE-RELATED PEPTIDE; SUBSTANCE-P; MICTURITION REFLEX; EFFERENT FUNCTION; AFFERENT NEURONS; SPINAL-CORD; RAT; RESINIFERATOXIN AB Using selective surgical ablations we have investigated the localization of vanilloid receptors (specific [H-3]resiniferatoxin binding sites) on terminals of the pelvic, hypogastric, and pudendal nerves in the rat urinary bladder. Pelvic and hypogastric nerve resections resulted in 90% and 25% loss of specific [H-3]resiniferatoxin (RTX) binding sites, respectively, whilst pudendic nerve resection had no measurable effect on the binding. In control animals, the density of vanilloid receptors was 1.7-fold higher in the neck than in the dome of the urinary bladder; the B(max) values were 57 +/- 8 and 34 +/- 7 fmol/mg protein, respectively. The binding characteristics of the vanilloid receptor were similar in the urinary bladder of the rat and mouse: K(d) values were 87 +/- 15 and 61 +/- 11 pM, B(max) values were 37 +/- 2 and 60 +/- 10 fmol/mg protein, respectively. In contrast to the findings for the rat and mouse, in the urinary bladder of the guinea pig and the hamster the low level of specific [H-3]RTX binding prevented the detailed characterization of vanilloid receptors. Nonetheless, at a fixed (60 pM) concentration of [H-3]RTX, specific binding both in the guinea pig and hamster urinary bladder was approximately 20% of that in the rat urinary bladder. In the urinary bladder of newborn rats, as in adults, a single class of specific [H-3]RTX binding sites was found which bound RTX with an affinity of 110 +/- 20 pM and with a maximal binding capacity of 30 +/- 5 fmol/mg protein. We conclude that, in accord with the physiological findings, the majority of vanilloid receptors are located on terminals of the pelvic nerve in the rat urinary bladder with higher receptor density in the bladder neck as compared to the bladder dome. Whereas the comparably high density of vanilloid receptors in the rat and mouse urinary bladder and the low receptor density in the hamster are mirrored by the in vivo vanilloid-sensitivity of these species, the low level of vanilloid receptors in the urinary bladder of the guinea pig contrasts to the marked sensitivity of this species to capsaicin. We conclude that the level of vanilloid receptors is an important but not exclusive determinant of vanilloid-sensitivity. C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. RP SZALLASI, A (reprint author), MENARINI SUD,DEPT PHARMACOL,VIA TITO SPERI 10,I-00040 POMEZIA,ITALY. NR 37 TC 26 Z9 28 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD JUN PY 1993 VL 347 IS 6 BP 624 EP 629 DI 10.1007/BF00166945 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LJ886 UT WOS:A1993LJ88600007 PM 7689705 ER PT J AU LIN, WW CHUANG, DM AF LIN, WW CHUANG, DM TI EXTRACELLULAR ATP STIMULATES INOSITOL PHOSPHOLIPID TURNOVER AND CALCIUM INFLUX IN C6 GLIOMA-CELLS SO NEUROCHEMICAL RESEARCH LA English DT Article DE C6 GLIOMA CELLS; PHOSPHOINOSITIDE METABOLISM; CA2+ INFLUX; ATP RECEPTORS; CALCIUM CHANNELS ID SMOOTH-MUSCLE CELLS; RAT VAS-DEFERENS; PHOSPHOINOSITIDE BREAKDOWN; BRAIN SYNAPTONEUROSOMES; SENSORY NEURONS; CORTICAL SLICES; RECEPTOR; HYDROLYSIS; MEMBRANE; MECHANISM AB Extracellular ATP caused a dose-dependent accumulation of inositol phosphates and a rise in cytosolic free Ca2+ ([Ca2+]i) in C6 glioma cells with an EC50 of 60 +/- 4 and 10 +/- 5 muM, respectively. The threshold concentration of ATP (3 muM) for increasing [Ca2+]i was approximately 10-fold less than that for stimulating phosphoinositide (PI) turnover. The PI response showed a preference for ATP; ADP was about 3-fold less potent than ATP but had a comparable maximal stimulation (11-fold of the control). AMP and adenosine were without effect at concentrations up to 1 mM. ATP-stimulated PI metabolism was found to be partially dependent on extracellular Ca2+ and Na+ but was resistant to tetrodotoxin, saxitoxin, amiloride, ouabain, and inorganic blockers of Ca2+ channels (Co2+, Mn2+, La3+, or Cd2+). In Ca2+-free medium, ATP caused only a transient increase in [Ca2+]i as opposed to a sustained [Ca2+]i increase in normal medium. The ATP-induced elevation of [Ca2+]i was resistant to Na+ depletion and treatment with saxitoxin, verapamil and nisoldipine, but was attentuated by La3+. The differences in the characteristics of ATP-caused P1 hydrolysis and [Ca2+]i rise suggest that ATP receptors are independently coupled to phospholipase C and receptor-gated Ca2+ channels. Because of the robust effect of ATP in stimulating PI turnover and the apparent absence of P1-purinergic receptors, the C6 glioma cell line provides a useful model for investigating the transmembrane signalling pathway induced by extracellular ATP. The mechanisms underlying the unexpected finding of [Na+]o dependency for ATP-induced PI turnover require further investigation. C1 NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,ROOM 3N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NATL TAIWAN UNIV,COLL MED,DEPT PHARMACOL,TAIPEI,TAIWAN. OI Lin, Wan Wan/0000-0002-3207-734X NR 37 TC 28 Z9 28 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD JUN PY 1993 VL 18 IS 6 BP 681 EP 687 DI 10.1007/BF00966782 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA KW827 UT WOS:A1993KW82700006 PM 8389991 ER PT J AU STRAUSS, KI JACOBOWITZ, DM AF STRAUSS, KI JACOBOWITZ, DM TI NUCLEOTIDE-SEQUENCE OF RAT CALRETININ CDNA SO NEUROCHEMISTRY INTERNATIONAL LA English DT Article ID CALCIUM-BINDING PROTEIN; IMMUNOHISTOCHEMICAL LOCALIZATION; BRAIN; EXPRESSION; CALBINDIN AB A rat calretinin cDNA clone was selected by antibody screening of a lambdagt11 brain library. The sequence revealed remarkable nucleotide and amino acid homology with human calretinin (91.1% and 98.5%, respectively), with only four amino acid differences. A high degree of homology with chick calretinin was also observed (79.8% and 86.6%, respectively), with 36 amino acid differences. Although the role of this central nervous system protein has not been well characterized, the evolutionarily conserved calcium binding domains and connecting regions, in addition to the limited local changes observed between rat and chick primary structure, lead us to believe that calretinin interacts with other highly conserved constituents of brain cells. This calretinin cDNA clone provides a new probe for the analysis of a specific subset of neurons in the central nervous system. The probe will allow a more detailed analysis of calretinin regulation in the brain and will be useful for screening genomic libraries for the complete chromosomal gene. RP STRAUSS, KI (reprint author), NIMH,CLIN SCI LAB,BLDG 10,ROOM 3D-48,BETHESDA,MD 20892, USA. NR 23 TC 25 Z9 25 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0197-0186 J9 NEUROCHEM INT JI Neurochem. Int. PD JUN PY 1993 VL 22 IS 6 BP 541 EP 546 DI 10.1016/0197-0186(93)90028-4 PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA LC628 UT WOS:A1993LC62800004 PM 8513281 ER PT J AU VAMVAKOPOULOS, NC FUKUHARA, K PATCHEV, V CHROUSOS, GP AF VAMVAKOPOULOS, NC FUKUHARA, K PATCHEV, V CHROUSOS, GP TI EFFECT OF SINGLE AND REPEATED IMMOBILIZATION STRESS ON THE HEAT-SHOCK PROTEIN-70/90 SYSTEM OF THE RAT - GLUCORTICOID-INDEPENDENT, REVERSIBLE REDUCTION OF HSP90 IN THE LIVER AND SPLEEN SO NEUROENDOCRINOLOGY LA English DT Article DE IMMOBILIZATION STRESS; HEAT SHOCK PROTEIN-70/90 SYSTEM; HYPOTHALAMIC-PITUITARY-ADRENAL AXIS; GLUCOCORTICOIDS ID GLUCOCORTICOID RECEPTOR; PROGESTERONE RECEPTORS; DNA-BINDING; CELL; HYPERTHERMIA; INVIVO; PLASMA; BRAIN AB Heat shock proteins (hsps) and glucocorticoids are produced in response to many common stressors. In addition, hsps interact physically with the intracellular glucocorticoid receptor (GR) and facilitate its activation by the hormone. To study the effect of stress on the hsp70/90 system and the potential association of the system with the hypothalamic-pituitary-adrenal (HPA) axis, we subjected 3 month-old male Harlan-Spraque Dawley rats to single or repeated (once daily for 6 consecutive days) immobilizations, and measured hsp70/90 steady-state levels in a panel of tissues, as well as circulating ACTH and corticosterone concentrations before, during and after immobilization. Single or repeated immobilizations had, as expected, a profound stimulatory effect on the HPA axis but did not influence the steady-state levels of hsp70/90 in any of the gross brain regions (pituitary, hypothalamus, hippocampus or brain cortex) or most peripheral tissues (thymus, adrenal glands, testes) examined. The hsp90 levels, however, were markedly and reversibly decreased in the liver and spleen both by single and repeated immobilizations. The potential inhibitory effect of glucocorticoids on liver and spleen hsp90 was investigated in bilaterally adrenalectomized rats treated with placebo or oral pharmacologic doses of corticosterone for 1 week. Neither adrenalectomy nor corticosterone treatment had an effect on the hsp70/90 system, suggesting that factors other than glucocorticoids mediate the effect of stress on hsp90 concentrations in the liver and spleen. We conclude that acute and chronic stress are associated with a reversible reduction of hsp90 in the liver and spleen, and this appears independent of glucocorticoids. Thus, while the hsp system may modulate GR function in vivo, itself does not appear to be modulated by the HPA axis in the paradigm examined. RP VAMVAKOPOULOS, NC (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,BLDG 10,ROOM 10N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 26 TC 28 Z9 28 U1 1 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PD JUN PY 1993 VL 57 IS 6 BP 1057 EP 1065 DI 10.1159/000126471 PG 9 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA LW781 UT WOS:A1993LW78100010 PM 8232764 ER PT J AU KLING, MA DEMITRACK, MA WHITFIELD, HJ KALOGERAS, KT LISTWAK, SJ DEBELLIS, MD CHROUSOS, GP GOLD, PW BRANDT, HA AF KLING, MA DEMITRACK, MA WHITFIELD, HJ KALOGERAS, KT LISTWAK, SJ DEBELLIS, MD CHROUSOS, GP GOLD, PW BRANDT, HA TI EFFECTS OF THE GLUCOCORTICOID ANTAGONIST RU-486 ON PITUITARY-ADRENAL-FUNCTION IN PATIENTS WITH ANOREXIA-NERVOSA AND HEALTHY-VOLUNTEERS - ENHANCEMENT OF PLASMA ACTH AND CORTISOL SECRETION IN UNDERWEIGHT PATIENTS SO NEUROENDOCRINOLOGY LA English DT Article DE ANOREXIA NERVOSA; EATING DISORDERS; HYPERCORTISOLISM; RU-486; ANTIGLUCOCORTICOIDS; PITUITARY-ADRENAL FUNCTION; WEIGHT RESTORATION; ACTH; CORTISOL; SEQUENTIAL BLOOD SAMPLING ID CORTICOTROPIN-RELEASING HORMONE; DEXAMETHASONE SUPPRESSION TEST; ANTIPROGESTIN STEROID RU-486; DEPRESSED-PATIENTS; MAJOR DEPRESSION; STIMULATION TEST; RESPONSES; RECEPTORS; BINDING; ADRENOCORTICOTROPIN AB To further explore whether the hypercortisolism of anorexia nervosa reflects an alteration in the set point for corticotropin-releasing hormone (CRH) secretion or is a manifestation of glucocorticoid resistance, we examined plasma ACTH and cortisol responses to the competitive glucocorticoid antagonist RU 486 (10 mg/kg, p.o. at 8.00 h) versus placebo (PBO) in 7 healthy female volunteers and 8 patients with DSM-III-R anorexia nervosa, all of whom were studied while underweight [64.3 +/- 2.1% average body weight (ABW), mean +/- SE] and 5 of whom were restudied longitudinally following refeeding (greater-than-or-equal-to 85% ABW, mean 87.4 +/- 0.4% ABW). Blood samples were obtained from 16.00 to 16.30 h and from 4.00 to 8.00 h following dosing. Underweight anorexics were significantly hypercortisolemic by 24 h urinary free cortisol excretion compared with controls (239 +/- 37 vs. 119 +/- 12 nmol/day, p < 0.01). Both controls and underweight anorexics had robust early morning (4.00-8.00 h) plasma cortisol responses to RU 486 (465 +/- 61 and 719 +/- 49 nmol/l) compared with PBO (370 +/- 52 and 451 +/- 31 nmol/l; p < 0.02 and p < 0.01, respectively). The under-weight anorexics showed a significant mean early morning plasma ACTH response to RU compared with placebo (3.28 +/- 0.63 vs. 2.01 +/- 0.24 pmol/l, p < 0.05), while the controls showed a trend toward an increase in mean plasma ACTH after RU (3.11 +/- 0.36 pmol/l) compared with PBO (2.31 +/- 0.41 pmol/l, p < 0.13); plasma ACTH means were greater on the RU day than the placebo day at 20 of 25 sampling points (p < 0.001). However, the increment in ACTH on the RU day compared to the placebo day was greater in the underweight anorexics at the first 20 of 25 consecutive time points of the early morning sampling period (p < 0.001). Moreover, underweight anorexics showed a significant plasma ACTH and cortisol response to RU 486 at 16.00-16.30 h (8-8.5 h following administration), while the controls showed no significant response of plasma ACTH or cortisol at this time. When restudied following weight recovery, anorexic patients showed reductions in 24-hour urinary free cortisol excretion (to 191 +/- 40 nmol/day) which were no longer significantly elevated compared with control values. During this phase the anorexic patients did not show a significant plasma ACTH increment following RU 486 administration (2.21 +/- 0.33 vs. 2.19 +/- 0.31 pmol/l), but did show a significant plasma cortisol response to this agent (523 +/- 39 vs. 418 +/- 35 nmol/l, p < 0.01). The plasma cortisol response to RU 486 was relatively greater than the plasma ACTH response in the underweight anorexics compared to controls, and tended towards normal at weight recovery. Plasma RU 486 levels did not differ between groups. These data suggest that hypercortisolism in underweight anorexics reflects hypersecretion of hypothalamic CRH rather than primary glucocorticoid resistance, and are compatible with our previous findings showing adrenal hyperresponsiveness to ACTH in underweight anorexics, with persistent alterations in HPA function following short-term weight restoration. C1 NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. RP KLING, MA (reprint author), NIMH,DIRP NIH CLIN CTR,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892, USA. RI Kling, Mitchel/F-4152-2010; Demitrack, Mark/I-7697-2013 OI Kling, Mitchel/0000-0002-2232-1409; NR 42 TC 33 Z9 34 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PD JUN PY 1993 VL 57 IS 6 BP 1082 EP 1091 DI 10.1159/000126474 PG 10 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA LW781 UT WOS:A1993LW78100013 PM 8232766 ER PT J AU CARLISON, S COLES, W COSTIGAN, D CURTIS, L HEDAYA, E KLEMENTS, D MEREDITH, T STERNBERG, P SWORDS, R BELT, J CORNBLATH, D GEORGOPOULIS, A GRIFFIN, J MURPHY, R RYTEL, D SAUDEK, C CARL, J CIATTO, P DATILES, M KUEHL, E KUPFER, C LEE, J ROY, M AIELLO, L BEASER, R BELL, A CAVICCHI, R COOPAN, R DELFS, J DUNN, F MALOBERTI, M RAND, L SHAH, S TARSY, D VIGNATI, L DOBSON, H GARCIA, C JACKSON, J KEICHIAN, A MATHENY, G ORZECK, E ROONGTA, S RUSSELL, S TULLOCH, B BARR, C BROADSTONE, V BROOKS, S CYRUS, J FUQUA, M HECK, M HEINICKE, H MAHL, L MILLERCRAIN, G PFEIFER, M SAMOLS, E WILLHITE, J DAVIS, M EHRLICH, E EICHMAN, P FLAX, M HARRISON, R KNUTSON, G LEWIS, B LYNGAAS, H MYERS, F NEIDER, M QUACKENBOSS, D SOMERS, G WAGE, M ZACKMAN, S COOMBS, G DOELLE, GC GOTTSCHALK, P HAFERMAN, M KARANJIA, P MCKENZIE, A MASON, CM MATTSON, D MILLER, R NIKOLAI, T WEIR, J BAKER, P FRANKLIN, R FRANKLIN, S GARCIA, C MUELLER, T PARKER, T PENNELL, D ROTHSCHILD, H BIESBROECK, R CHENOWETH, R DIEHL, L DREYER, R GRIMM, R HARE, R LINN, M PAGE, O SMITH, B STEPHENS, J WILSON, R CLARKE, D FORD, K NORD, N TOMKY, D WEINRAUCH, S GODDU, K LESKO, V MEHTA, DJ MUNSTER, E MYERS, R PETERSON, M KUPFER, C SEIGEL, D AF CARLISON, S COLES, W COSTIGAN, D CURTIS, L HEDAYA, E KLEMENTS, D MEREDITH, T STERNBERG, P SWORDS, R BELT, J CORNBLATH, D GEORGOPOULIS, A GRIFFIN, J MURPHY, R RYTEL, D SAUDEK, C CARL, J CIATTO, P DATILES, M KUEHL, E KUPFER, C LEE, J ROY, M AIELLO, L BEASER, R BELL, A CAVICCHI, R COOPAN, R DELFS, J DUNN, F MALOBERTI, M RAND, L SHAH, S TARSY, D VIGNATI, L DOBSON, H GARCIA, C JACKSON, J KEICHIAN, A MATHENY, G ORZECK, E ROONGTA, S RUSSELL, S TULLOCH, B BARR, C BROADSTONE, V BROOKS, S CYRUS, J FUQUA, M HECK, M HEINICKE, H MAHL, L MILLERCRAIN, G PFEIFER, M SAMOLS, E WILLHITE, J DAVIS, M EHRLICH, E EICHMAN, P FLAX, M HARRISON, R KNUTSON, G LEWIS, B LYNGAAS, H MYERS, F NEIDER, M QUACKENBOSS, D SOMERS, G WAGE, M ZACKMAN, S COOMBS, G DOELLE, GC GOTTSCHALK, P HAFERMAN, M KARANJIA, P MCKENZIE, A MASON, CM MATTSON, D MILLER, R NIKOLAI, T WEIR, J BAKER, P FRANKLIN, R FRANKLIN, S GARCIA, C MUELLER, T PARKER, T PENNELL, D ROTHSCHILD, H BIESBROECK, R CHENOWETH, R DIEHL, L DREYER, R GRIMM, R HARE, R LINN, M PAGE, O SMITH, B STEPHENS, J WILSON, R CLARKE, D FORD, K NORD, N TOMKY, D WEINRAUCH, S GODDU, K LESKO, V MEHTA, DJ MUNSTER, E MYERS, R PETERSON, M KUPFER, C SEIGEL, D TI THE SORBINIL RETINOPATHY TRIAL - NEUROPATHY RESULTS SO NEUROLOGY LA English DT Article ID PAINFUL DIABETIC NEUROPATHY; ALDOSE REDUCTASE INHIBITOR; NERVE-CONDUCTION; COMPLICATIONS AB We randomized 497 patients, aged 18 to 56 years with insulin-dependent diabetes mellitus for 1 to 15 years' duration, to treatment with sorbinil, an aldose reductase inhibitor, or to a placebo. Nearly 30% of patients showed worsening of clinical measures of distal symmetric polyneuropathy at maximum follow-up, with very little difference in rates in the two groups. We studied nerve conduction in 192 patients. For the median motor, median sensory, and peroneal nerves, there were no benefits in maximum amplitudes over the follow-up period. For the median motor and median sensory nerves, changes in velocities were not significantly different in the two randomized treatment groups. For the peroneal nerve, at the 30-month and maximum follow-up visits, the distribution of changes in nerve conduction velocity showed an overall improvement in the sorbinil group and a decline in the placebo group. The difference in distributions was statistically significant. Overall, we found no evidence that the early clinical signs and symptoms of diabetic neuropathy were altered by sorbinil. C1 NEI,316A10,BETHESDA,MD 20892. EMORY UNIV CLIN,DEPT OPHTHALMOL,ATLANTA,GA 30322. JOHNS HOPKINS UNIV HOSP,WILMER INST,DEPT OPHTHALMOL,BALTIMORE,MD 21205. JOSLIN DIABET CTR,WILLIE P BEETHAM EYE UNIT,BOSTON,MA. HERMAN EYE CTR,DIABET UNIT,HOUSTON,TX. VET ADM MED CTR,LOUISVILLE,KY 40202. UNIV WISCONSIN,MADISON,WI 53706. MARSHFIELD CLIN FDN MED RES & EDUC,MARSHFIELD,WI. LOUISIANA STATE UNIV,CTR EYE,NEW ORLEANS,LA. GOOD SAMARITAN HOSP,DEPT OPHTHALMOL,PORTLAND,OR 97210. DIABET HLTH CTR,SALT LAKE CITY,UT. PFIZER INC,CENT RES,GROTON,CT 06340. NR 28 TC 19 Z9 19 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 JUN PY 1993 VL 43 IS 6 BP 1141 EP 1149 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA LG421 UT WOS:A1993LG42100019 ER PT J AU JOYCE, JN SHANE, A LEXOW, N WINOKUR, A CASANOVA, MF KLEINMAN, JE AF JOYCE, JN SHANE, A LEXOW, N WINOKUR, A CASANOVA, MF KLEINMAN, JE TI SEROTONIN UPTAKE SITES AND SEROTONIN RECEPTORS ARE ALTERED IN THE LIMBIC SYSTEM OF SCHIZOPHRENICS SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE QUANTITATIVE AUTORADIOGRAPHY; SEROTONIN UPTAKE; SEROTONIN(1A) RECEPTOR; SEROTONIN(2) RECEPTOR; STRIATUM; CORTEX; HIPPOCAMPUS; SCHIZOPHRENIA ID HUMAN-BRAIN POSTMORTEM; KETANSERIN BINDING-SITES; RAT-BRAIN; SUICIDE VICTIMS; FRONTAL-CORTEX; AUTORADIOGRAPHIC ANALYSIS; 5-HT2 RECEPTORS; POST-MORTEM; QUANTITATIVE AUTORADIOGRAPHY; NEUROTRANSMITTER RECEPTORS AB Serotonin (5-HT) uptake sites were mapped by autoradiographic means with [H-3]cyano-imipramine ([H-3]CN-IMI), the 5-HT1A receptor with [H-3]8-hydroxy-2-[di-n-propyl-amino]tetralin ([H-3]8-OH-DPAT), and the 5-HT2 receptor with both [H-3]ketanserin and [I-125]lysergic acid diethylamide ([I-125]LSD) in eight nonneurologic controls and 10 cases with a diagnosis of schizophrenia. In the striatum, there was a marked heterogeneous patterning of 5-HT uptake sites that corresponded to the striosomal/matrix compartmentalization of the striatum. This organization was not matched with an equally heterogeneous pattern of either 5-HT2 or 5-HT1A receptors. For the isocortex, a general organizational scheme was observed with the 5-HT1A receptor expression high in the external laminae and deep laminae, but 5-HT2 receptor expression was higher in the internal laminae. There was a laminar distribution of 5-HT uptake sites that approximated the combined distributions of the 5-HT1A receptor and the 5-HT2 receptor. In the parahippocampal gyrus and hippocampus, the distribution of 5-HT uptake sites was complementary to the distribution of 5-HT1A and 5-HT2 receptors. In schizophrenic cases, there was a large increase in the number and altered striosomal/matrix organization of 5-HT uptake sites in the striatum. There was also an increase in the numbers of 5-HT2 receptors in the nucleus accumbens and ventral putamen of the schizophrenics. The number of 5-HT1A receptors was not modified. There was a marked reduction in 5-HT uptake sites in the external and middle laminae of the anterior cingulate, frontal cortex, and posterior cingulate, and no changes were observed in the motor cortex, temporal cortex, or hippocampus. Increased numbers of 5-HT1A receptors were found in the posterior cingulate, motor cortex, and hippocampus. Serotonin2 receptors were substantially elevated in the posterior cingulate, temporal cortex, and hippocampus, but not in the frontal, anterior cingulate, or motor cortices. Examination of the temporal lobe and hippocampus of a group of nonschizophrenic suicides (n = 8) indicated the alterations in 5-HT system in the limbic regions of the striatum, the limbic cortex, and hippocampus of the schizophrenic cases may be disease specific. C1 ST ELIZABETH HOSP,NATL INST MENTAL HLTH,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. UNIV PENN,SCH MED,DEPT PHARMACOL,PHILADELPHIA,PA 19104. RP JOYCE, JN (reprint author), UNIV PENN,SCH MED,DEPT PSYCHIAT,CHEM NEUROANAT LAB,422 CURRIE BLVD,PHILADELPHIA,PA 19104, USA. FU NIA NIH HHS [AG09215]; NIMH NIH HHS [MH43880, MH43852] NR 77 TC 287 Z9 287 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JUN PY 1993 VL 8 IS 4 BP 315 EP 336 PG 22 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA LD161 UT WOS:A1993LD16100003 PM 8512620 ER PT J AU MCCANN, UD PENETAR, DM SHAHAM, Y THORNE, DR SING, HC THOMAS, ML GILLIN, JC BELENKY, G AF MCCANN, UD PENETAR, DM SHAHAM, Y THORNE, DR SING, HC THOMAS, ML GILLIN, JC BELENKY, G TI EFFECTS OF CATECHOLAMINE DEPLETION ON ALERTNESS AND MOOD IN RESTED AND SLEEP-DEPRIVED NORMAL VOLUNTEERS SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE SLEEP DEPRIVATION; ALERTNESS; MOOD; CATECHOLAMINES; MONOAMINES ID CENTRAL NERVOUS-SYSTEM; REM-SLEEP; DEPRESSED-PATIENTS; RAT-BRAIN; MHPG EXCRETION; DEPRIVATION; DISORDERS; NOREPINEPHRINE; METABOLISM; ILLNESS AB Alpha-methyl-para-tyrosine (AMPT), a tyrosine hydroxylase inhibitor, was used to evaluate the physiologic role of central nervous system catecholamines in modulating alertness and mood. Forty healthy males were randomized to one of four conditions: AMPT in a rested condition; AMPT plus 40.5 hours of total sleep deprivation; placebo plus sleep deprivation; or placebo in a rested condition. Repeated measures of alertness and mood revealed that treatment with AMPT or sleep deprivation increased sleepiness, and combined treatment produced greater sleepiness than either treatment alone. In contrast, although combined treatment with AMPT and sleep deprivation led to large increases in negative mood, neither treatment alone produced consistent mood changes. These findings are consistent with the view that sleep deprivation is associated with decreased functional catecholamine neurotransmission. Furthermore, mood effects following sleep deprivation plus AMPT suggest that catecholamines may be involved in mood changes during sleep deprivation. C1 WALTER REED ARMY INST RES,DEPT BEHAV BIOL,WASHINGTON,DC 20307. VET ADM MED CTR,PSYCHIAT SERV,SAN DIEGO,CA 92161. CONCORDIA UNIV,DEPT PSYCHOL,MONTREAL H3G 1M8,QUEBEC,CANADA. UNIV CALIF SAN DIEGO,DEPT PSYCHIAT,SAN DIEGO,CA 92103. RP MCCANN, UD (reprint author), NIMH,ANXIETY & AFFECT DISORDERS SECT,BLDG 10,ROOM 3S-239,BETHESDA,MD 20892, USA. RI shaham, yavin/G-1306-2014 NR 47 TC 34 Z9 37 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JUN PY 1993 VL 8 IS 4 BP 345 EP 356 PG 12 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA LD161 UT WOS:A1993LD16100005 PM 8099791 ER PT J AU MATOCHIK, JA NORDAHL, TE GROSS, M SEMPLE, WE KING, AC COHEN, RM ZAMETKIN, AJ AF MATOCHIK, JA NORDAHL, TE GROSS, M SEMPLE, WE KING, AC COHEN, RM ZAMETKIN, AJ TI EFFECTS OF ACUTE STIMULANT MEDICATION ON CEREBRAL METABOLISM IN ADULTS WITH HYPERACTIVITY SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE POSITRON EMISSION TOMOGRAPHY; GLUCOSE METABOLISM; HYPERACTIVITY; ATTENTION-DEFICIT DISORDER; DEXTROAMPHETAMINE; METHYLPHENIDATE ID POSITRON EMISSION TOMOGRAPHY; ATTENTION DEFICIT DISORDER; GLUCOSE-UTILIZATION; BLOOD-FLOW; PSYCHIATRIC STATUS; CONSCIOUS RAT; D-AMPHETAMINE; BRAIN; METHYLPHENIDATE; DEXTROAMPHETAMINE AB Recent work in our laboratory has demonstrated both global and regional reductions in cerebral glucose metabolism in adult subjects with attention-deficit hyperactivity disorder (ADHD). The purpose of the present study was to examine the effects of an acute dose of stimulant medication on cerebral metabolism in adults with ADHD using positron emission tomography with fluorodeoxyglucose-18 as the tracer. Each subject underwent scanning twice, once off-drug and again after receiving a single oral dose of either dextroamphetamine (0.25 mg/kg) or methylphenidate (0.35 mglkg). Subjects completed behavioral self-report measures before and after the scan and performed an auditory continuous performance task during the tracer uptake period. Neither drug changed global metabolism. Both drugs increased systolic blood pressure, and dextroamphetamine improved performance on the auditory attention task. Each stimulant produced a differential pattern of increases and decreases in regional metabolism throughout the regions of interest that were sampled. Rather than increasing glucose utilization in specific brain regions with lowered metabolic rates in adults with ADHD, stimulants may act by altering glucose use throughout the brain. RP MATOCHIK, JA (reprint author), NIMH,CEREBRAL METAB LAB,CLIN BRAIN IMAGING SECT,BLDG 10,ROOM 4N317,BETHESDA,MD 20892, USA. RI Nordahl, Thomas/J-7643-2013 OI Nordahl, Thomas/0000-0002-8627-0356 NR 43 TC 86 Z9 87 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JUN PY 1993 VL 8 IS 4 BP 377 EP 386 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA LD161 UT WOS:A1993LD16100009 PM 8512624 ER PT J AU KHACHATURIAN, ZS AF KHACHATURIAN, ZS TI CALCIUM REGULATION - FINAL COMMON PATHWAY FOR AGE-ASSOCIATED NEURODEGENERATIVE PROCESSES SO NEUROSCIENCE RESEARCH COMMUNICATIONS LA English DT Article ID ALZHEIMERS-DISEASE; PATHOGENESIS; RATS RP NIA, NEUROSCI & NEUROPSYCHOL AGING PROGRAM, BETHESDA, MD 20892 USA. NR 14 TC 9 Z9 9 U1 0 U2 0 PU WILEY PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6609 J9 NEUROSCI RES COMMUN JI Neurosci. Res. Commun. PD JUN PY 1993 VL 13 SU 1 BP S3 EP S6 PG 4 WC Neurosciences SC Neurosciences & Neurology GA LQ617 UT WOS:A1993LQ61700002 ER PT J AU PLASCJAK, PS KIM, KK GOOGINS, SW MEYER, WC AF PLASCJAK, PS KIM, KK GOOGINS, SW MEYER, WC TI GASEOUS RADIOACTIVE EFFLUENT RESTRICTIONS, MEASUREMENT, AND MINIMIZATION AT A PET CYCLOTRON FACILITY SO NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION B-BEAM INTERACTIONS WITH MATERIALS AND ATOMS LA English DT Article; Proceedings Paper CT 12TH INTERNATIONAL CONF ON THE APPLICATION OF ACCELERATORS IN RESEARCH AND INDUSTRY CY NOV 02-05, 1992 CL UNIV N TEXAS, DENTON, TX SP US DOE, NATL SCI FDN, OAK RIDGE ASSOC UNIV, UNIV N TEXAS HO UNIV N TEXAS ID F-18 AB In the US, restrictions on the release of radioactive effluents from PET (positron emission tomography)/cyclotron facilities are typically imposed by State regulatory agencies and may be based on various methodologies and limits published by numerous agencies. This work presents suitable effluent concentration limits for various chemical forms of radioisotopes routinely produced in PET/cyclotron facilities. They were determined by application of metabolic models defined by ICRP 53 [International Commission on Radiological Protection, ICRP Publication 53 (1988)] and ICRP 26/30 which will result in compliance with effective dose equivalent limits of 100 mrem per year at the release point. The NIH Cyclotron Facility effluent air monitoring system, environmental dosimetry program, and simple, effective systems for radioactive effluent minimization are also described. RP PLASCJAK, PS (reprint author), NIH,CYCLOTRON FACIL,BETHESDA,MD 20892, USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-583X J9 NUCL INSTRUM METH B JI Nucl. Instrum. Methods Phys. Res. Sect. B-Beam Interact. Mater. Atoms PD JUN PY 1993 VL 79 IS 1-4 BP 942 EP 944 DI 10.1016/0168-583X(93)95505-Y PG 3 WC Instruments & Instrumentation; Nuclear Science & Technology; Physics, Atomic, Molecular & Chemical; Physics, Nuclear SC Instruments & Instrumentation; Nuclear Science & Technology; Physics GA LH984 UT WOS:A1993LH98400239 ER PT J AU HINSHAW, AS AF HINSHAW, AS TI ADVANCES IN CLINICAL NURSING RESEARCH - FOREWORD SO NURSING CLINICS OF NORTH AMERICA LA English DT Editorial Material RP HINSHAW, AS (reprint author), NIH,NATL CTR NURSING RES,ROOM 315B-03,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0029-6465 J9 NURS CLIN N AM JI Nurs. Clin. North Am. PD JUN PY 1993 VL 28 IS 2 BP R13 EP R14 PG 2 WC Nursing SC Nursing GA LK121 UT WOS:A1993LK12100001 ER PT J AU FISCELLA, M ULLRICH, SJ ZAMBRANO, N SHIELDS, MT LIN, D LEESMILLER, SP ANDERSON, CW MERCER, WE APPELLA, E AF FISCELLA, M ULLRICH, SJ ZAMBRANO, N SHIELDS, MT LIN, D LEESMILLER, SP ANDERSON, CW MERCER, WE APPELLA, E TI MUTATION OF THE SERINE 15 PHOSPHORYLATION SITE OF HUMAN P53 REDUCES THE ABILITY OF P53 TO INHIBIT CELL-CYCLE PROGRESSION SO ONCOGENE LA English DT Article ID CASEIN KINASE-II; WILD-TYPE; TRANSCRIPTIONAL ACTIVATION; PROTEIN-KINASE; GROWTH; GENE; SUPPRESSOR; INVITRO; P53-PROTEIN; EXPRESSION AB Overexpression of wild-type p53 prevents cells from entering the S phase of the cell cycle. The amino-terminal transactivation region of p53 is phosphorylated by several protein kinases, including DNA-PK, a nuclear serine/threonine protein kinase that in vitro requires DNA for activity. DNA-PK was recently shown to phosphorylate serines 15 and 37 of human p53 (Lees-Miller et al, 1992. Mol. Cell. Biol., 12, 5041-5049). To prevent phosphorylation at these sites, mutants were constructed that changed the codons for serine 15 or serine 37 to alanine codons. Expression of p53-Ala-37 in stably transformed T98G cells blocked progression of the cells into S phase as well as did the expression of wild-type p53. In contrast, p53-Ala-15 was partially defective in blocking cell cycle progression. Several cell clones transformed with the mutant p53-Ala-15 gene expressed normal levels of p53 mRNA but accumulated little or no detectable p53 protein. However, by using a transient expression system driven by a strong cytomegalovirus promoter, we showed that the inability of p53-Ala-15 to fully block cell cycle progression was not due to inadequate levels of expression or to a failure of the mutant protein to accumulate in the nucleus. These results suggest that phosphorylation of Ser-15 may affect p53 function. C1 NIH,CELL BIOL LAB,BETHESDA,MD 20892. THOMAS JEFFERSON UNIV,JEFFERSON CANC INST,PHILADELPHIA,PA 19107. BROOKHAVEN NATL LAB,DEPT BIOL,UPTON,NY 11973. RI Zambrano, Nicola/B-9352-2014 OI Zambrano, Nicola/0000-0001-9395-3481 FU NCI NIH HHS [CA 42866]; NCRR NIH HHS [BRSG S07 RR05417] NR 59 TC 165 Z9 166 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN PY 1993 VL 8 IS 6 BP 1519 EP 1528 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA LE064 UT WOS:A1993LE06400015 PM 8502477 ER PT J AU MURAKAMI, K MAVROTHALASSITIS, G BHAT, NK FISHER, RJ PAPAS, TS AF MURAKAMI, K MAVROTHALASSITIS, G BHAT, NK FISHER, RJ PAPAS, TS TI HUMAN ERG-2 PROTEIN IS A PHOSPHORYLATED DNA-BINDING PROTEIN - A DISTINCT MEMBER OF THE ETS FAMILY SO ONCOGENE LA English DT Article ID LONG TERMINAL REPEAT; LEUKEMIA-VIRUS; C-FOS; ONCOGENE; GENE; SEQUENCE; ONCOPROTEIN; ACTIVATION; ERYTHROBLASTOSIS; RETROVIRUS-E26 AB We describe the identification of the ERG-2 gene products using an antibody raised against recombinant human ERG-2 protein. ERG-2 is a nuclear phosphoprotein and binds to purine-rich sequences (C/G)(C/a)GG-AA(G/a)T. ERG-2 protein, with a half-life of 21 h, is considerably more stable than the short-lived ETS-1 or ETS-2 proteins. Its phosphorylation is stimulated by phorbal myristate acetate (PMA), but not by Ca2+ ion-phore treatment. ETS-1 protein is phosphorylated by Ca2+-dependent events, whereas ERG-2 protein is phosphorylated by activation of protein kinase C, suggesting their involvement in distinct signal transduction mechanisms. The expression of ERG-2 protein is restricted to few cell types and is high in early myeloid cells, indicating that it may function at an early stage of hematopoietic lineage determination. The DNA-binding sequence for ERG-2 protein is identified by using a random oligonucleotide selection procedure. The selected sequence is very similar to the binding sequence determined for human ETS-1 using the same method. Like other ets proteins, ERG-2 is a sequence-specific DNA-binding protein and is expressed at higher levels in early myeloid cells than in mature lymphoid cells. These results suggest that it may act as a regulator of genes required for maintenance and/or differentiation of early hematopoietic cells. C1 NCI,MOLEC ONCOL LAB,FREDERICK,MD 21702. INC DYNCORP,PROGRAM RESOURCES,FREDERICK,MD 21701. RI Fisher, Robert/B-1431-2009 NR 40 TC 37 Z9 37 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN PY 1993 VL 8 IS 6 BP 1559 EP 1566 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA LE064 UT WOS:A1993LE06400019 PM 8502479 ER PT J AU LI, CCH CHEN, E OCONNELL, CD LONGO, DL AF LI, CCH CHEN, E OCONNELL, CD LONGO, DL TI DETECTION OF C-MOS PROTOONCOGENE EXPRESSION IN HUMAN-CELLS SO ONCOGENE LA English DT Note ID MURINE SARCOMA-VIRUS; MATURATION-PROMOTING FACTOR; KINASE-ACTIVITY; MEIOTIC MATURATION; TRANSFORMING GENE; XENOPUS OOCYTES; CDC2 PROTEIN; DEVELOPMENTAL REGULATION; PROTOONCOGENE PRODUCT; HUMAN NEUROBLASTOMAS AB Although the human c-mos proto-oncogene has been characterized for more than a decade, very little is known about its protein product and its expression in somatic cells. We generated three human c-mos-specific antisera and report here the detection of c-mos protein in a human neuroblastoma cell line, SK-N-BE2 (BE2). Both Western (immuno-) blot and immunoprecipitation analyses detected a p37 as the major form and p40 and p35 as minor forms of the c-mos protein. Using Northern blot analysis, 3.5- and 1.7-kb c-mos messages were detected. Using a highly sensitive method that combines reverse transcription and the polymerase chain reaction (RT-PCR), c-mos RNA was detected in all the human samples examined. With Western blot analysis, we further showed that c-mos proteins are expressed in cervical carcinoma-derived cell lines. This ubiquitous expression of low levels of c-mos suggests a fundamental role for the c-mos proto-oncogene. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. RP LI, CCH (reprint author), INC DYNCORP,PROGRAM RESOURCES,BIOL CARCINOGENESIS & DEV PROGRAM,POB B,BLDG 567,ROOM 202,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102] NR 65 TC 32 Z9 32 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN PY 1993 VL 8 IS 6 BP 1685 EP 1691 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA LE064 UT WOS:A1993LE06400034 PM 8502488 ER PT J AU MUSSER, SM KELLEY, JA AF MUSSER, SM KELLEY, JA TI MECHANISM FOR DEHALOGENATION REACTIONS IN FAST-ATOM-BOMBARDMENT MASS-SPECTROMETRY SO ORGANIC MASS SPECTROMETRY LA English DT Article ID NUCLEOSIDES; OLIGONUCLEOTIDES; DESORPTION; REDUCTION; INVITRO; MATRIX; DRUGS AB The mechanism of a dehalogenation reaction that occurs during fast atom bombardment (FAB) mass spectrometry was examined using halogenated nucleosides as model compounds. For aglycone-halogenated nucleosides, an inverse linear relationship exists between the extent of FAB dehalogenation and the calculated electron affinity of an individual nucleoside. The degree of dehalogenation for a given nucleoside also varies inversely with the calculated electron affinity of most FAB matrices. The observed dehalogenation reaction can be completely inhibited when matrices with positive electron affinities, such as 3-nitrobenzyl alcohol and 2-hydroxyethyl disulfide, are used. High-performance liquid chromatographic analysis of the bulk glycerol matrix following exposure to the FAB beam indicates measurable amounts of dehalogenated product, suggesting that this reaction occurs in the condensed phase prior to gas-phase ion formation. A dehalogenation mechanism involving thermal electron capture and subsequent negative charge stabilization is consistent with these observations. C1 NCI,DIV CANC TREATMENT,MED CHEM LAB,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. NR 28 TC 17 Z9 17 U1 1 U2 3 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0030-493X J9 ORG MASS SPECTROM JI Org. Mass Spectrom. PD JUN PY 1993 VL 28 IS 6 BP 672 EP 678 DI 10.1002/oms.1210280604 PG 7 WC Chemistry, Organic; Spectroscopy SC Chemistry; Spectroscopy GA LH882 UT WOS:A1993LH88200003 ER PT J AU CONNOR, EM PIZZO, PA BALIS, F HUGHES, W KATZ, S MCSHERRY, G OLESKE, J SCOTT, G WARA, D WILFERT, C BURR, C GRUBMAN, S ABRAMS, E AMMANN, AJ BARDEGUEZ, A BALSLEY, JF BROADBENT, PA BROUWERS, P BRYSON, YJ COLLABELLI, N CONNOR, J COOPER, E DIAZ, C DIPAOLO, C FISCHER, GW FOWLER, MG FRENKEL, LM GRANT, R GOLDSMITH, JC GOOSBY, E GORDON, E HALE, AR HERNANDEZ, V HUSSON, R KOVACS, A KRASINSKI, K LUZURIAGA, K MCKINNEY, R MCINTOSH, K MCPHERSON, M MINTZ, M MOFENSON, LM MORETTI, L NYMAN, N OXTOBY, M RICHARTZ, K SANTACROSE, S SPECTOR, SA SPERLING, R TUDORWILLIAMS, G VANDYKE, R VENDRELL, J WINTER, H YOGEV, R BOLAND, M MURPHY, D AF CONNOR, EM PIZZO, PA BALIS, F HUGHES, W KATZ, S MCSHERRY, G OLESKE, J SCOTT, G WARA, D WILFERT, C BURR, C GRUBMAN, S ABRAMS, E AMMANN, AJ BARDEGUEZ, A BALSLEY, JF BROADBENT, PA BROUWERS, P BRYSON, YJ COLLABELLI, N CONNOR, J COOPER, E DIAZ, C DIPAOLO, C FISCHER, GW FOWLER, MG FRENKEL, LM GRANT, R GOLDSMITH, JC GOOSBY, E GORDON, E HALE, AR HERNANDEZ, V HUSSON, R KOVACS, A KRASINSKI, K LUZURIAGA, K MCKINNEY, R MCINTOSH, K MCPHERSON, M MINTZ, M MOFENSON, LM MORETTI, L NYMAN, N OXTOBY, M RICHARTZ, K SANTACROSE, S SPECTOR, SA SPERLING, R TUDORWILLIAMS, G VANDYKE, R VENDRELL, J WINTER, H YOGEV, R BOLAND, M MURPHY, D TI ANTIRETROVIRAL THERAPY AND MEDICAL-MANAGEMENT OF THE HUMAN IMMUNODEFICIENCY VIRUS-INFECTED CHILD SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE HUMAN IMMUNODEFICIENCY VIRUS INFECTION; ANTIRETROVIRAL THERAPY ID PNEUMOCYSTIS-CARINII PNEUMONIA; ZIDOVUDINE THERAPY; ORAL ZIDOVUDINE; HIV-INFECTION; INFUSION C1 NCI, BETHESDA, MD 20892 USA. ST JUDE CHILDRENS RES HOSP, MEMPHIS, TN 38101 USA. DUKE UNIV, MED CTR, DURHAM, NC 27710 USA. CHILDRENS HOSP NEW JERSEY, NEWARK, NJ USA. UNIV MED & DENT NEW JERSEY, NEW JERSEY MED SCH, NEWARK, NJ 07103 USA. UNIV MIAMI, SCH MED, MIAMI, FL 33152 USA. UNIV CALIF SAN FRANCISCO, SAN FRANCISCO, CA 94143 USA. HARLEM HOSP MED CTR, NEW YORK, NY 10037 USA. PEDIAT AIDS FDN, NAVOTA, CA USA. NIAID, BETHESDA, MD 20892 USA. UNIV CALIF LOS ANGELES, SCH MED, LOS ANGELES, CA USA. UNIV CALIF SAN DIEGO, LA JOLLA, CA 92093 USA. BOSTON CITY HOSP, BOSTON, MA 02118 USA. PUERTO RICO MED CTR, SAN JUAN, PR USA. UNIFORMED SERV UNIV HLTH SCI, BETHESDA, MD 20814 USA. UNIV ROCHESTER, ROCHESTER, NY 14627 USA. CHILDRENS HOSP LOS ANGELES, LOS ANGELES, CA USA. BUR HLTH RESOURCES DEV, ROCKVILLE, MD USA. CHILDRENS HOSP MED CTR, BOSTON, MA 02115 USA. ACT UP, NEW YORK, NY USA. UNIV CALIF LOS ANGELES, LOS ANGELES CTY HARBOR MED CTR, TORRANCE, CA 90509 USA. UNIV SO CALIF, LOS ANGELES CTY MED CTR, LOS ANGELES, CA 90033 USA. UNIV MASSACHUSETTS, MED CTR, WORCESTER, MA 01605 USA. HLTH RESOURCES SERV ADM, ROCKVILLE, MD USA. NICHHD, BALTIMORE, MD 21224 USA. CTR DIS CONTROL, ATLANTA, GA 30333 USA. MT SINAI MED CTR, NEW YORK, NY 10029 USA. TULANE UNIV, SCH MED, NEW ORLEANS, LA 70112 USA. CHILDRENS MEM HOSP, CHICAGO, IL 60614 USA. NICHOLSON RES CTR, KENSINGTON, MD USA. RP CONNOR, EM (reprint author), NATL PEDIAT HIV RESOURCE CTR, WORKING GRP ANTIRETROVIRAL THERAPY, 15 S 9TH ST, NEWARK, NJ 07107 USA. NR 38 TC 20 Z9 20 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 EI 1532-0987 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD JUN PY 1993 VL 12 IS 6 BP 513 EP 522 PG 10 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA LG459 UT WOS:A1993LG45900011 ER PT J AU LAFRANCHI, S DUSSAULT, JH FISHER, DA FOLEY, TP MITCHELL, ML SEASHORE, MR CHO, S DESPOSITO, F HALL, JG SHERMAN, J WILSON, MG DELACRUZ, F HANSON, JW LINFU, J MENNUTI, M OAKLEY, G MITCHELL, ML SPENCER, CA RALLISON, ML BECKER, DV GAITAN, E VANMIDDLESWORTH, L AF LAFRANCHI, S DUSSAULT, JH FISHER, DA FOLEY, TP MITCHELL, ML SEASHORE, MR CHO, S DESPOSITO, F HALL, JG SHERMAN, J WILSON, MG DELACRUZ, F HANSON, JW LINFU, J MENNUTI, M OAKLEY, G MITCHELL, ML SPENCER, CA RALLISON, ML BECKER, DV GAITAN, E VANMIDDLESWORTH, L TI NEWBORN SCREENING FOR CONGENITAL HYPOTHYROIDISM - RECOMMENDED GUIDELINES SO PEDIATRICS LA English DT Article ID NEONATAL-HYPOTHYROIDISM; THYROXINE; PROGRAM; THYROTROPIN C1 AMER ACAD PEDIAT,COMM GENET,EVANSTON,IL 60204. NIH,BETHESDA,MD 20892. US DEPT HHS,HLTH RESOURCES & SERV ADM,WASHINGTON,DC 20201. RP LAFRANCHI, S (reprint author), AMER ACAD PEDIAT,ENDOCRINOL SECT,EVANSTON,IL 60204, USA. NR 18 TC 138 Z9 145 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUN PY 1993 VL 91 IS 6 BP 1203 EP 1209 PG 7 WC Pediatrics SC Pediatrics GA LF210 UT WOS:A1993LF21000028 ER PT J AU REIGART, JR ETZEL, RA GOLDMAN, LR HENDRICK, JG MOFENSON, HC SIMON, PR FALK, H MILLER, RW ROGAN, W NEEDLEMAN, HL JACKSON, RJ LANDRIGAN, P LIPSETT, M AF REIGART, JR ETZEL, RA GOLDMAN, LR HENDRICK, JG MOFENSON, HC SIMON, PR FALK, H MILLER, RW ROGAN, W NEEDLEMAN, HL JACKSON, RJ LANDRIGAN, P LIPSETT, M TI AMBIENT AIR-POLLUTION - RESPIRATORY HAZARDS TO CHILDREN SO PEDIATRICS LA English DT Editorial Material ID 0.12 PPM OZONE; INHALED SULFURIC-ACID; PULMONARY-FUNCTION; ASTHMATIC SUBJECTS; EXERCISING CHILDREN; CUMULATIVE EXPOSURE; MODERATE EXERCISE; NITROGEN-DIOXIDE; HEALTH; INHALATION C1 NCI,BETHESDA,MD 20892. NIEHS,RES TRIANGLE PK,NC 27709. RP REIGART, JR (reprint author), CTR DIS CONTROL,ATLANTA,GA 30333, USA. RI Goldman, Lynn/D-5372-2012 NR 47 TC 16 Z9 17 U1 0 U2 2 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUN PY 1993 VL 91 IS 6 BP 1210 EP 1213 PG 4 WC Pediatrics SC Pediatrics GA LF210 UT WOS:A1993LF21000029 ER PT J AU WEISS, SRB POST, RM ANTHONY, P FERRER, J AF WEISS, SRB POST, RM ANTHONY, P FERRER, J TI CONTINGENT TOLERANCE TO CARBAMAZEPINE IS NOT AFFECTED BY CALCIUM-CHANNEL OR NMDA RECEPTOR BLOCKERS SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE CONTINGENT TOLERANCE; NMDA RECEPTORS; CALCIUM CHANNELS; NIMODIPINE; MK-801; CARBAMAZEPINE; KINDLING ID AMYGDALA-KINDLED SEIZURES; LONG-TERM POTENTIATION; SELECTIVE IMPAIRMENT; MORPHINE-TOLERANCE; ANTAGONISTS; NIMODIPINE; ANTICONVULSANT; MEMORY; BLOCKADE; MK-801 AB We previously demonstrated that tolerance to carbamazepine's anticonvulsant effects occurs only with contingent presentation of the drug relative to the seizure (i.e., drug administration before but not after the seizure). Moreover, this tolerance can be reversed by altering the contingencies of drug administration (e.g., giving the drug after the seizure has occurred) without discontinuation of drug treatment. These findings imply an associative component to tolerance development in this model. Thus, we evaluated the effects on contingent tolerance development of two agents that have been shown to affect rate of tolerance development and acquisition or retention in other learning paradigms. Rats were electrically kindled in the amygdala until they reliably experienced seizures with each stimulation. In three separate studies, MK-801 (0.3 and 0.15 mg/kg), an NMDA receptor antagonist, and nimodipine (20 mg/kg), an L-type calcium channel blocker, were coadministered with carbamazepine prior to each kindling stimulation to evaluate the rate of tolerance development compared to controls. No effect of either drug was seen on the rate of contingent tolerance development to carbamazepine, suggesting that neither NMDA receptors nor L-type calcium channels are critically involved in this type of tolerance. The contingent tolerance paradigm may, however, prove useful in elucidating novel biochemical mechanisms of associative learning that might ultimately be explored in clinical situations where tolerance is a problem. RP WEISS, SRB (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,ROOM 3N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 46 TC 3 Z9 3 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD JUN PY 1993 VL 45 IS 2 BP 439 EP 443 DI 10.1016/0091-3057(93)90262-R PG 5 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA LE327 UT WOS:A1993LE32700026 PM 8327549 ER PT J AU POILLON, WN KIM, BC RODGERS, GP NOGUCHI, CT SCHECHTER, AN AF POILLON, WN KIM, BC RODGERS, GP NOGUCHI, CT SCHECHTER, AN TI SPARING EFFECT OF HEMOGLOBIN-F AND HEMOGLOBIN-A2 ON THE POLYMERIZATION OF HEMOGLOBIN-S AT PHYSIOLOGICAL LIGAND SATURATIONS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE SICKLE CELL ANEMIA; POLYMER FRACTION; HYDROXYUREA; FETAL HEMOGLOBIN ID SICKLE-CELL DISEASE; INTRACELLULAR POLYMERIZATION; DEOXYHEMOGLOBIN-S; GELATION; ERYTHROCYTES; HYDROXYUREA; DEPENDENCE; SOLUBILITY; MIXTURES; BINDING AB Recent interest in therapies for sickle cell anemia based on elevating fetal Hb has made accurate estimates of the sparing effect of fetal Hb (Hb F) and other non-sickle Hbs on sickle Hb (Hb S) polymerization essential. We have developed a technique, using HbCO as surrogate for HbO2, that enables us to assess the solubility of Hb S as a function of ligand saturation under conditions that mimic those of the sickling disorders. Equimolar mixtures of unliganded Hb S with Hb F or normal Hb A2 were isosoluble. Solubilities for equimolar mixtures with normal (Hb A) or abnormal (Hb C) Hbs were also identical but were lower than in the prior case. Thus, the sparing effect of both Hb F and Hb A2 should be considered in therapeutic strategies designed to modify Hb S polymerization. Hemolysates, stripped of 2,3-bisphosphoglycerate, from sickle cell disease patients with Hb (F + A2) levels varying from 6 to 25%, as well as from a sickle trait individual, were used to evaluate equilibrium solubility as a function of ligand saturation over the range of pathophysiologic interest (25-70%). Our results show that the sparing effect of Hb (F + A2) increases relative to that of Hb A as ligand saturation increases, and that in the absence of ligand, almost-equal-to 30% Hb (F + A2) is essentially isosoluble with the 60% Hb A of sickle trait. Although detailed knowledge of expected therapeutic benefits is confounded by the heterogeneity of Hb F distribution and other variables, these data should provide a framework for estimating likely clinical benefit from pharmacologic efforts to modulate globin gene expression. C1 HOWARD UNIV,DEPT PEDIAT & CHILD HLTH,WASHINGTON,DC 20059. NIDDKD,CHEM BIOL LAB,BETHESDA,MD 20892. RP POILLON, WN (reprint author), HOWARD UNIV,CTR SICKLE CELL DIS,WASHINGTON,DC 20059, USA. OI Schechter, Alan N/0000-0002-5235-9408 NR 44 TC 60 Z9 61 U1 5 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 JUN 1 PY 1993 VL 90 IS 11 BP 5039 EP 5043 DI 10.1073/pnas.90.11.5039 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LF285 UT WOS:A1993LF28500055 PM 7685112 ER PT J AU PFEIFER, AMA COLE, KE SMOOT, DT WESTON, A GROOPMAN, JD SHIELDS, PG VIGNAUD, JM JUILLERAT, M LIPSKY, MM TRUMP, BF LECHNER, JF HARRIS, CC AF PFEIFER, AMA COLE, KE SMOOT, DT WESTON, A GROOPMAN, JD SHIELDS, PG VIGNAUD, JM JUILLERAT, M LIPSKY, MM TRUMP, BF LECHNER, JF HARRIS, CC TI SIMIAN VIRUS-40 LARGE TUMOR ANTIGEN-IMMORTALIZED NORMAL HUMAN LIVER EPITHELIAL-CELLS EXPRESS HEPATOCYTE CHARACTERISTICS AND METABOLIZE CHEMICAL CARCINOGENS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE SERUM-FREE MEDIUM; AFLATOXIN-B(1); BENZO[A]PYRENE; N-NITROSODIMETHYLAMINE ID ADULT-RAT HEPATOCYTES; LARGE-T-ANTIGEN; NEOPLASTIC TRANSFORMATION; GENE-EXPRESSION; PRIMARY CULTURE; MESSENGER-RNA; OVAL CELLS; P53 GENE; ACTIVATION; MOUSE AB Normal human liver tissue and cultured human hepatocytes are valuable models to study xenobiotic metabolism and toxicity, but they only have a limited in vitro life-span and are not readily available. This report describes the establishment of replicative cultures of human adult liver epithelial cells in serum-free medium. The longevity of three of these cultures, derived from different donors, was extended by introduction of the simian virus 40 large T antigen gene. Two cell lines, THLE-2 and -3, established with a recombinant simian virus 40 large T antigen virus have undergone >100 population doublings, are nontumorigenic when injected into athymic nude mice, have near-diploid karyotypes, and do not express alpha-fetoprotein. The cells express cytokeratin 18 and albumin in early passage, whereas higher-passage cells in logarithmic-phase growth also express cytokeratin 19. THLE-2 and -3 cells metabolize benzo[a]pyrene, N-nitrosodimethyl-amine, and aflatoxin B1 to their ultimate carcinogenic metabolites that adduct DNA, which indicates functional cytochrome P450 pathways. Other enzymes involved in metabolism of chemical carcinogens, such as epoxide hydrolase, NADPH cytochrome P450 reductase, superoxide dismutase, catalase, glutathione S-transferases, and glutathione peroxidase are also retained by THLE cells. Thus, these immortalized human liver cells constitute an in vitro model for pharmacotoxicological studies and for the investigation of etiology and pathogenesis of human hepatocellular carcinoma. C1 NCI,HUMAN CARCINOGENESIS LAB,BLDG 37,ROOM 2C01,BETHESDA,MD 20892. NESTEC LTD,RES CTR,LAUSANNE,SWITZERLAND. LAB ANAT & PATHOL,NANCY,FRANCE. UNIV MARYLAND,DEPT PATHOL,BALTIMORE,MD 21201. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,BALTIMORE,MD 21205. RI Shields, Peter/I-1644-2012 NR 62 TC 162 Z9 164 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 JUN 1 PY 1993 VL 90 IS 11 BP 5123 EP 5127 DI 10.1073/pnas.90.11.5123 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LF285 UT WOS:A1993LF28500073 PM 7685115 ER PT J AU CHEN, YD BRENNER, B AF CHEN, YD BRENNER, B TI ON THE REGENERATION OF THE ACTIN-MYOSIN POWER STROKE IN CONTRACTING MUSCLE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE FORCE TRANSIENTS; CROSS-BRIDGE CYCLE; MUSCLE CONTRACTION; TENSION RECOVERY; STAIRCASE SHORTENING ID CROSS-BRIDGE KINETICS; ACTOMYOSIN-ATPASE; FIBERS AB The transient behavior of muscle in double- or multiple-step length perturbations [Lombardi, V., Piazzesi, G. & Linari, M. (1992) Nature (London) 355, 638-641] is simulated with a ''conventional'' cross-bridge model, which has been reported [Eisenberg, E., Hill, T. L. & Chen, Y. (1980) Biophys. J. 29, 195-227] to account for many mechanical, as well as biochemical, muscle data. The quick recovery of tension after double- or multiple-length perturbations was calculated for the model without any readjustment of its original parameters. The regeneration rate of the quick tension recovery of the model is fast and comparable to that measured experimentally by Lombardi et al. For multiple-step ''stair-case''-type length releases, the tension response reaches a steady-state shape after three or four steps, and the average ATP turnover is much slower than the regeneration of the quick tension recovery. Our simulation shows that the experimental findings of Lombardi et al. can easily be reproduced by this simple conventional cross-bridge model, in which the completion of one work-producing power stroke is coupled to the hydrolysis of one ATP molecule. Thus, to account for the data of Lombardi et al., there is no need to assume that cross-bridges can execute multiple power strokes per ATPase cycle, although cross-bridges may well be able to do so. The mechanism that underlies the fast regeneration of the quick tension recovery in the conventional model used here is discussed. C1 UNIV ULM,DEPT GEN PHYSIOL,W-7900 ULM,GERMANY. RP CHEN, YD (reprint author), NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20891, USA. NR 19 TC 27 Z9 28 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 1 PY 1993 VL 90 IS 11 BP 5148 EP 5152 DI 10.1073/pnas.90.11.5148 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LF285 UT WOS:A1993LF28500078 PM 8506362 ER PT J AU SAKAGUCHI, K ZAMBRANO, N BALDWIN, ET SHAPIRO, BA ERICKSON, JW OMICHINSKI, JG CLORE, GM GRONENBORN, AM APPELLA, E AF SAKAGUCHI, K ZAMBRANO, N BALDWIN, ET SHAPIRO, BA ERICKSON, JW OMICHINSKI, JG CLORE, GM GRONENBORN, AM APPELLA, E TI IDENTIFICATION OF A BINDING-SITE FOR THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 NUCLEOCAPSID PROTEIN SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE RNA BINDING; DIMERIZATION ID MURINE LEUKEMIA-VIRUS; SECONDARY STRUCTURES; CIS ELEMENTS; GENOMIC RNA; DIMERIZATION; SEQUENCE; INVITRO AB The nucleocapsid (NC) protein NCp7 of human immunodeficiency virus type 1 (HIV-1) is important for encapsidation of the virus genome, RNA dimerization, and primer tRNA annealing in vitro. Here we present evidence from gel mobility-shift experiments indicating that NCp7 binds specifically to an RNA sequence. Two complexes were identified in native gels. The more slowly migrating complex contained two RNA molecules and one peptide, while the more rapidly migrating one is composed of one RNA and one peptide. Further, mutational analysis of the RNA shows that the predicted stem and loop structure of stem-loop 1 plays a critical role. Our results show that NCp7 binds to a unique RNA structure within the psi region; in addition, this structure is necessary for RNA dimerization. We propose that NCp7 binds to the RNA via a direct interaction of one zinc-binding motif to stem-loop 1 followed by binding of the other zinc-binding motif to stem-loop 1, stem-loop 2, or the linker region of the second RNA molecule, forming a bridge between the two RNAs. C1 NCI,CELL BIOL LAB,BLDG 37,ROOM 1B04,BETHESDA,MD 20892. NCI,MATH BIOL LAB,BETHESDA,MD 20892. NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,FREDERICK,MD 21702. RI Clore, G. Marius/A-3511-2008; Zambrano, Nicola/B-9352-2014 OI Clore, G. Marius/0000-0003-3809-1027; Zambrano, Nicola/0000-0001-9395-3481 FU NCI NIH HHS [N01-CO-74102] NR 24 TC 128 Z9 129 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 1 PY 1993 VL 90 IS 11 BP 5219 EP 5223 DI 10.1073/pnas.90.11.5219 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LF285 UT WOS:A1993LF28500093 PM 8506369 ER PT J AU GOONEWARDENE, R DAILY, J KASLOW, D SULLIVAN, TJ DUFFY, P CARTER, R MENDIS, K WIRTH, D AF GOONEWARDENE, R DAILY, J KASLOW, D SULLIVAN, TJ DUFFY, P CARTER, R MENDIS, K WIRTH, D TI TRANSFECTION OF THE MALARIA PARASITE AND EXPRESSION OF FIREFLY LUCIFERASE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TRANSMISSION-BLOCKING IMMUNITY; PLASMODIUM-GALLINACEUM; ANTIBODIES; INVITRO; INFECTION; CHICKENS; ZYGOTES AB The goal of this work is to develop a method for the functional analysis of malaria genes using the method of DNA transfection. We have developed a transient transfection vector by constructing a chimeric gene in which the firefly luciferase gene was inserted in frame into the coding region of the pgs28 gene of Plasmodium gallinaceum. This plasmid DNA was introduced into P. gallinaceum gametes and fertilized zygotes by electroporation, and luciferase expression was assayed after 24 hr. This report of successful introduction and expression of a foreign gene in a malaria parasite demonstrates the feasibility of this approach to developing methods for the functional analysis of parasite genes. C1 HARVARD UNIV,SCH PUBL HLTH,DEPT TROP PUBL HLTH,BOSTON,MA 02115. UNIV COLOMBO,DEPT PARASITOL,MALARIA RES UNIT,COLOMBO,SRI LANKA. NIH,MALARIA SECT,BETHESDA,MD 20892. INST ANIM GENET,EDINBURGH EH9 3JN,MIDLOTHIAN,SCOTLAND. FU NIAID NIH HHS [AI27872] NR 11 TC 92 Z9 95 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 1 PY 1993 VL 90 IS 11 BP 5234 EP 5236 DI 10.1073/pnas.90.11.5234 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LF285 UT WOS:A1993LF28500096 PM 8506371 ER PT J AU SELLHEYER, K BICKENBACH, JR ROTHNAGEL, JA BUNDMAN, D LONGLEY, MA KRIEG, T ROCHE, NS ROBERTS, AB ROOP, DR AF SELLHEYER, K BICKENBACH, JR ROTHNAGEL, JA BUNDMAN, D LONGLEY, MA KRIEG, T ROCHE, NS ROBERTS, AB ROOP, DR TI INHIBITION OF SKIN DEVELOPMENT BY OVEREXPRESSION OF TRANSFORMING GROWTH-FACTOR-BETA-1 IN THE EPIDERMIS OF TRANSGENIC MICE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE KERATINOCYTES; GROWTH FACTORS; MITOTIC ARREST; LETHALITY ID DIFFERENTIAL EXPRESSION; TGF BETA-1; KERATINOCYTES; PROLIFERATION; LOCALIZATION; TGF-BETA-3; PATTERNS; MARKERS; INVIVO; GENES AB To assess the effect of transforming growth factor beta1 on the skin in vivo, we have targeted its expression to the epidermis of transgenic mice. To ensure that active TGF-beta1 was expressed, we used a porcine TGF-beta1 cDNA with mutations of Cys-223 --> Ser and Cys-225 --> Ser, which allow constitutive activation. Mice expressing the mutant transforming growth factor beta1 transgene exhibited a marked phenotype at birth. The skin was very shiny and tautly stretched. These animals were rigid and appeared to be restricted in their ability to move and breathe; death occurred within 24 hr. Histologically, the most prominent features of the skin were a compact orthohyperkeratosis and a reduction in the number of hair follicles. Pulse-labeling studies with 5-bromodeoxyuridine demonstrated a marked reduction in the number of replicating cells in the epidermis and hair follicles. Thus, the macro- and microscopic appearance of these mice, as well as their neonatal lethality, most likely result from inhibition of normal skin development and suppression of epithelial cell proliferation by the overexpression of transforming growth factor beta1. C1 BAYLOR COLL MED,DEPT CELL BIOL,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT DERMATOL,HOUSTON,TX 77030. UNIV COLOGNE,DEPT DERMATOL,W-5000 COLOGNE 41,GERMANY. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. RI Rothnagel, Joe/A-4874-2010 OI Rothnagel, Joe/0000-0002-6710-3165 FU NICHD NIH HHS [HD25479] NR 30 TC 198 Z9 203 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 1 PY 1993 VL 90 IS 11 BP 5237 EP 5241 DI 10.1073/pnas.90.11.5237 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LF285 UT WOS:A1993LF28500097 PM 7685120 ER PT J AU BRENNER, B YU, LC AF BRENNER, B YU, LC TI STRUCTURAL-CHANGES IN THE ACTOMYOSIN CROSS-BRIDGES ASSOCIATED WITH FORCE GENERATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE X-RAY DIFFRACTION FROM MUSCLE; PREFORCE-GENERATING STATES IN MUSCLE; WEAK BINDING CROSS-BRIDGE STATES; STRONG BINDING CROSS-BRIDGE STATES ID X-RAY-DIFFRACTION; RABBIT PSOAS FIBERS; FROG SARTORIUS MUSCLE; LOW IONIC-STRENGTH; SKELETAL-MUSCLE; TROPONIN-TROPOMYOSIN; HEAVY-MEROMYOSIN; STRIATED-MUSCLE; ATPASE ACTIVITY; RELAXED MUSCLE AB It is generally thought that to generate active force in muscle, myosin heads (cross-bridges) that are attached to actin undergo large-scale conformational changes. However, evidence for conformational changes of the attached cross-bridges associated with force generation has been ambiguous. In this study, we took advantage of the recent observation that cross-bridges that are weakly attached to actin in a relaxed muscle are apparently in attached preforce-generating states. The experimental conditions were chosen such that there were large fractions of cross-bridges attached under relaxing and activating conditions, and high-resolution equatorial x-ray diffraction patterns obtained under these conditions were compared. Changes brought about by activation in the two innermost intensities, I10 and I11, did not follow the familiar reciprocal changes. Instead, there was almost no change in I11, whereas I10 decreased by 34%. Together with the changes found in the higher-order reflections, the results suggest that the structure of the attached force-generating cross-bridges differs from that of the weakly bound, preforce-generating cross-bridges and possibly also differs from that of the cross-bridges in rigor. These observations support the concept that force generation involves a transition between distinct structural states of the actomyosin cross-bridges. C1 NIH,BETHESDA,MD 20892. UNIV ULM,DEPT GEN PHYSIOL,W-7900 ULM,GERMANY. NR 54 TC 32 Z9 32 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 1 PY 1993 VL 90 IS 11 BP 5252 EP 5256 DI 10.1073/pnas.90.11.5252 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LF285 UT WOS:A1993LF28500100 PM 8506374 ER PT J AU CIGAN, AM BUSHMAN, JL BOAL, TR HINNEBUSCH, AG AF CIGAN, AM BUSHMAN, JL BOAL, TR HINNEBUSCH, AG TI A PROTEIN COMPLEX OF TRANSLATIONAL REGULATORS OF GCN4 MESSENGER-RNA IS THE GUANINE NUCLEOTIDE-EXCHANGE FACTOR FOR TRANSLATION INITIATION FACTOR-II IN YEAST SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE EIF-2; EIF-2B; GCN3; GCD PROTEIN; GENERAL AMINO ACID CONTROL ID POLYPEPTIDE-CHAIN INITIATION; AMINO-ACID BIOSYNTHESIS; SACCHAROMYCES-CEREVISIAE; GENERAL CONTROL; CELLS; PURIFICATION; MUTAGENESIS; MUTATIONS; ACTIVATOR; GCD2 AB In Saccharomyces cerevisiae, phosphorylation of the alpha subunit of translation initiation factor 2 (eIF-2) by protein kinase GCN2 stimulates translation of GCN4 mRNA. In mammalian cells, phosphorylation of eIF-2alpha inhibits the activity of eIF-2B, the GDP-GTP exchange factor for eIF-2. We present biochemical evidence that five translational regulators of GCN4 encoded by GCD1, GCD2, GCD6, GCD7, and GCN3 are components of a protein complex that stably interacts with eIF-2 and represents the yeast equivalent of eIF-2B. In vitro, this complex catalyzes guanine nucleotide exchange on eIF-2 and overcomes the inhibitory effect of GDP on formation of eIEF-2.GTP.Met-initiator tRNA(Met) ternary complexes. This finding suggests that mutations in GCD-encoded subunits of the complex derepress GCN4 translation because they mimic eIF-2alpha phosphorylation in decreasing eIF-2B activity. Our results indicate that translational control of GCN4 involves a reduction in eIF-2B function, a mechanism used in mammalian cells to regulate total protein synthesis in response to stress. C1 NICHHD,MOLEC GENET LOWER EUKARYOTES SECT,MOLEC GENET LAB,BETHESDA,MD 20892. NHLBI,PROT & RNA BIOSYNTH SECT,MOLEC HEMATOL LAB,BETHESDA,MD 20892. NR 29 TC 71 Z9 76 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 1 PY 1993 VL 90 IS 11 BP 5350 EP 5354 DI 10.1073/pnas.90.11.5350 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LF285 UT WOS:A1993LF28500120 PM 8506384 ER PT J AU WOLOSCHAK, M SHENORR, Z LEROITH, D ROBERTS, CT AF WOLOSCHAK, M SHENORR, Z LEROITH, D ROBERTS, CT TI NUTRITIONAL REGULATION OF INSULIN-SENSITIVE GLUCOSE TRANSPORTER GENE-EXPRESSION IN RAT CARDIAC-MUSCLE SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article ID ADIPOSE-CELLS; INVIVO AB The effects of fasting and refeeding on the levels of mRNA encoding the insulin-sensitive glucose transporter (GLUT4) in rat cardiac and skeletal muscle were investigated using solution hybridization/RNase protection assays with a rat GLUT4 antisense RNA probe. In addition, the effects of these nutritional states on GLUT1 mRNA levels in several non-insulin-sensitive tissues were examined using a GLUT1 antisense RNA probe. Fasting for 48 hr significantly decreased GLUT4 mRNA levels in heart, with levels significantly increased over control levels by 24 hr after refeeding. In contrast, GLUT4 mRNA levels in skeletal muscle increased with fasting and returned to control levels with refeeding. No significant changes in GLUT1 mRNA were seen after fasting and refeeding in several non-insulin-sensitive tissues studied. These results suggest that altered GLUT4 gene expression is observed in different nutritional (insulin) states in insulin-sensitive tissues, and suggests a potential role for insulin in mediating these changes in gene expression. C1 NIDDK,MOLEC & CELLULAR PHYSIOL SECT,DIABET BRANCH,BETHESDA,MD 20892. OI Roberts, Charles/0000-0003-1756-5772 NR 7 TC 6 Z9 6 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 JUN PY 1993 VL 203 IS 2 BP 172 EP 174 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LD339 UT WOS:A1993LD33900006 PM 8502658 ER PT J AU MERCHENTHALER, I LOPEZ, FJ NEGROVILAR, A AF MERCHENTHALER, I LOPEZ, FJ NEGROVILAR, A TI ANATOMY AND PHYSIOLOGY OF CENTRAL GALANIN-CONTAINING PATHWAYS SO PROGRESS IN NEUROBIOLOGY LA English DT Review ID GROWTH-HORMONE SECRETION; CENTRAL-NERVOUS-SYSTEM; VASOACTIVE INTESTINAL POLYPEPTIDE; CORTICOTROPIN-RELEASING FACTOR; RAT ANTERIOR-PITUITARY; LOCUS COERULEUS NEURONS; GENE-RELATED PEPTIDE; ROOT GANGLION-CELLS; HYPOTHALAMIC MAGNOCELLULAR NEURONS; NUCLEOTIDE-SEQUENCE ANALYSIS C1 NIEHS, MOLEC & INTEGRAT NEUROSCI LAB, REPROD NEUROENDOCRINOL SECT, RES TRIANGLE PK, NC 27709 USA. RP NIEHS, MOLEC & INTEGRAT NEUROSCI LAB, FUNCT MORPHOL SECT, RES TRIANGLE PK, NC 27709 USA. NR 248 TC 316 Z9 319 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0301-0082 J9 PROG NEUROBIOL JI Prog. Neurobiol. PD JUN PY 1993 VL 40 IS 6 BP 711 EP 769 DI 10.1016/0301-0082(93)90012-H PG 59 WC Neurosciences SC Neurosciences & Neurology GA KX665 UT WOS:A1993KX66500004 PM 7683433 ER PT J AU BECERRA, SP KUMAR, A WILSON, SH AF BECERRA, SP KUMAR, A WILSON, SH TI EXPRESSION OF POLYPEPTIDES OF HUMAN IMMUNODEFICIENCY VIRUS-1 REVERSE-TRANSCRIPTASE IN ESCHERICHIA-COLI SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article ID DNA POLYMERASE-BETA; AIDS VIRUS; HTLV-III; DOMAIN-STRUCTURE; GENE-PRODUCTS; BINDING; PROTEIN; PURIFICATION; MECHANISM C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. NR 36 TC 9 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 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD JUN PY 1993 VL 4 IS 3 BP 187 EP 199 DI 10.1006/prep.1993.1025 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA LC510 UT WOS:A1993LC51000002 PM 7686063 ER PT J AU JUARBEOSORIO, LG GORZIGLIA, M BETENBAUGH, MJ AF JUARBEOSORIO, LG GORZIGLIA, M BETENBAUGH, MJ TI RECOVERY AND CHARACTERIZATION OF A ROTAVIRUS OUTER CAPSID PROTEIN EXPRESSED IN A RECOMBINANT INSECT CELL SYSTEM SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article ID INFLUENZA-VIRUS HEMAGGLUTININ; BACULOVIRUS RECOMBINANT; VECTOR; PURIFICATION; IDENTIFICATION; GLYCOPROTEINS; ATTACHMENT; SECRETION; GENE C1 JOHNS HOPKINS UNIV,DEPT CHEM ENGN,BALTIMORE,MD 21218. NIAID,INFECT DIS LAB,BETHESDA,MD 20892. RI Betenbaugh, Michael J./A-3252-2010 OI Betenbaugh, Michael J./0000-0002-6336-4659 NR 41 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD JUN PY 1993 VL 4 IS 3 BP 232 EP 239 DI 10.1006/prep.1993.1030 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA LC510 UT WOS:A1993LC51000007 PM 8390880 ER PT J AU GOLD, JM HARVEY, PD AF GOLD, JM HARVEY, PD TI COGNITIVE DEFICITS IN SCHIZOPHRENIA SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID CARD SORTING TEST; DORSOLATERAL PREFRONTAL CORTEX; CEREBRAL BLOOD-FLOW; THOUGHT-DISORDER; NEGATIVE SYMPTOMS; PERFORMANCE; MEMORY; DYSFUNCTION; MEDICATION; NEUROPSYCHOLOGY C1 CUNY MT SINAI SCH MED,DEPT PSYCHIAT,NEW YORK,NY 10029. RP GOLD, JM (reprint author), NIMH,NEUROSCI CTR ST ELIZABETHS,2700 MARTIN LUTHER KING JR AVE SE,WASHINGTON,DC 20032, USA. NR 82 TC 193 Z9 202 U1 3 U2 10 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD JUN PY 1993 VL 16 IS 2 BP 295 EP 312 PG 18 WC Psychiatry SC Psychiatry GA LG548 UT WOS:A1993LG54800006 PM 8332566 ER PT J AU RUPP, A KEITH, SJ AF RUPP, A KEITH, SJ TI THE COSTS OF SCHIZOPHRENIA - ASSESSING THE BURDEN SO PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID ECONOMIC COSTS; MENTAL-ILLNESS; CASE MANAGEMENT; CARE RP RUPP, A (reprint author), NIMH,ROOM 10C-06,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 39 TC 146 Z9 149 U1 0 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0193-953X J9 PSYCHIAT CLIN N AM JI Psychiatr. Clin. North Amer. PD JUN PY 1993 VL 16 IS 2 BP 413 EP 423 PG 11 WC Psychiatry SC Psychiatry GA LG548 UT WOS:A1993LG54800013 PM 8332569 ER PT J AU ELMALLAKH, RS CLAUSNITZER, L ZIGUN, JR AF ELMALLAKH, RS CLAUSNITZER, L ZIGUN, JR TI NEGATIVE SYMPTOMS PROBABLY NOT RESPONSIBLE FOR INFECTION ACQUISITION AMONG SCHIZOPHRENIC INPATIENTS SO PSYCHIATRY RESEARCH LA English DT Letter C1 NIMH,HOSP NEUROPSYCHIAT RES,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032. NIMH,HOSP NEUROPSYCHIAT RES,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD JUN PY 1993 VL 47 IS 3 BP 297 EP 298 DI 10.1016/0165-1781(93)90088-X PG 2 WC Psychiatry SC Psychiatry GA LK868 UT WOS:A1993LK86800010 PM 8372167 ER PT J AU RUTTIMANN, UE JOYCE, EM RIO, DE ECKARDT, MJ AF RUTTIMANN, UE JOYCE, EM RIO, DE ECKARDT, MJ TI FULLY AUTOMATED SEGMENTATION OF CEREBROSPINAL-FLUID IN COMPUTED-TOMOGRAPHY SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE ALCOHOL ABUSE; KORSAKOFF SYNDROME; THRESHOLDING TECHNIQUES ID GRAY-MATTER; CT SCANS; IMAGES; SCHIZOPHRENIA; SPACES; WHITE AB A method is presented for automated delineation and measurement of cerebrospinal fluid (CSF) regions in computed tomographic (CT) sections. Regions of skull and scalp are removed by using a linear discriminant analysis approach. Beam-hardening artifact is reduced by subtracting from each section the average radial intensity profile, characterized by a polynomial function. Remaining intensity gradients are suppressed by implementing CSF segmentation with a local thresholding technique based on maximum-entropy principles. CSF fractions from 12 regions of interest (ROIs) were measured in 10 patients with alcoholic Korsakoff syndrome and 9 normal volunteers. The same ROIs were also assessed by an interactive segmentation method, which enabled the operator to compensate for beam-hardening distortions by selecting suitable threshold values for each ROI. Both methods identified the same ROIs as displaying statistically significant differences between the two subject groups. However, interactive segmentation underestimated sulcal CSF by 20-70%, which was confirmed by applying both methods to CT scans of an anthropomorphic phantom. Hence, in contrast to interactive thresholding, unsupervised segmentation relies on firmly fixed criteria that reduce the influence of beam-hardening distortions and provide more objective results. RP RUTTIMANN, UE (reprint author), NIAAA,CLIN STUDIES LAB,9000 ROCKVILLE PIKE,10-3C102,BETHESDA,MD 20892, USA. NR 28 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD JUN PY 1993 VL 50 IS 2 BP 101 EP 119 DI 10.1016/0925-4927(93)90015-A PG 19 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA LK624 UT WOS:A1993LK62400005 PM 8378487 ER PT J AU OSMAN, OT HSIAO, JK POTTER, WZ AF OSMAN, OT HSIAO, JK POTTER, WZ TI DOSE-DEPENDENT EFFECTS OF INTRAVENOUS ALPRAZOLAM ON NEUROENDOCRINE, BIOCHEMICAL, CARDIOVASCULAR, AND BEHAVIORAL PARAMETERS IN HUMANS SO PSYCHOPHARMACOLOGY LA English DT Article DE ALPRAZOLAM; NEUROENDOCRINE PARAMETERS; CARDIOVASCULAR PARAMETERS; BIOCHEMICAL PARAMETERS; BEHAVIORAL PARAMETERS ID GROWTH-HORMONE SECRETION; PROLACTIN SECRETION; CORTISOL SECRETION; DIAZEPAM; BENZODIAZEPINES; NOREPINEPHRINE; DEPRESSION; PLASMA; ACID AB Neuroendocrine, biochemical, cardiovascular, and behavioral parameters were assessed in seven normal volunteers for 2 h after intravenous administration of alprazolam (APZ). Three doses of APZ (0.003, 0.007, and 0.02 mg/kg) were administered to each subject in a random order with at least 4 days between infusions. Plasma growth hormone and sedation increased in a dose dependent manner after APZ, and there was a dose dependent change in the shape of the cortisol response to APZ. No dose-response relationships were evident for plasma ACTH and norepinephrine. These differences in dose-response relationships may reflect the involvement of multiple systems in controlling neuroendocrine, biochemical, and subjective responses to APZ infusion. The optimal dose of APZ needed to produce a neuroendocrine or behavioral change appears to differ depending on the parameter of interest. C1 NIMH,CLIN PHARMACOL SECT,CLIN NEUROSCI BRANCH,BLDG 10,ROOM 2D46,BETHESDA,MD 20892. NR 27 TC 9 Z9 9 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 JUN PY 1993 VL 111 IS 3 BP 295 EP 300 DI 10.1007/BF02244944 PG 6 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA LF209 UT WOS:A1993LF20900005 PM 7870966 ER PT J AU SZALAY, LB CARROLL, JFX TIMS, F AF SZALAY, LB CARROLL, JFX TIMS, F TI REDISCOVERING FREE ASSOCIATIONS FOR USE IN PSYCHOTHERAPY SO PSYCHOTHERAPY LA English DT Article ID DRUG-USE; ABUSE; LOCUS; DELINQUENTS; PERCEPTIONS; DRINKING; BEHAVIOR; PROGRAMS; HEALTH AB Free associations emerge from the present investigations as a rich source of psychological insights useful in therapeutic applications. In light of the early uses of free association by the founding fathers of psychotherapy, Freud and Jung, such application capabilities should come as no surprise. The present approach is enhanced by the progress of empirical semantics and a heavy reliance on computers, yet it relies essentially on realizations similar to those of Freud and Jung in which insights into subjective worlds were revealed in free associations. The present investigations used free associations to reconstruct perceptual and attitudinal dispositions associated with substance abuse to measure changes indicative of the psychological impact of treatment. Associations to words as well as to pictures were used. The results are compared for their information value and relevance to therapeutic applications. C1 NIDA,ROCKVILLE,MD. NR 57 TC 9 Z9 9 U1 0 U2 2 PU AMER PSYCHOLOGICAL ASSOC, DIV PSYCHOTHERAPY PI PHOENIX PA 3900 E CAMELBACK RD #200, PHOENIX, AZ 85018 SN 0033-3204 J9 PSYCHOTHER JI Psychotherapy PD SUM PY 1993 VL 30 IS 2 BP 344 EP 356 DI 10.1037/0033-3204.30.2.344 PG 13 WC Psychology, Clinical SC Psychology GA MT367 UT WOS:A1993MT36700018 ER PT J AU ATWOOD, JR HINSHAW, AS AF ATWOOD, JR HINSHAW, AS TI ASSESSMENT OF CONVERGENT AND DISCRIMINANT VALIDITY SO RESEARCH IN NURSING & HEALTH LA English DT Letter C1 NIH,NATL CTR NURSING,BETHESDA,MD 20892. RP ATWOOD, JR (reprint author), UNC,SCH PUBL HLTH,DEPT EDUC,CHAPEL HILL,NC, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0160-6891 J9 RES NURS HEALTH JI Res. Nurs. Health PD JUN PY 1993 VL 16 IS 3 BP 231 EP 233 DI 10.1002/nur.4770160311 PG 3 WC Nursing SC Nursing GA LD541 UT WOS:A1993LD54100010 PM 8497676 ER PT J AU SMOLEN, P TERMAN, D RINZEL, J AF SMOLEN, P TERMAN, D RINZEL, J TI PROPERTIES OF A BURSTING MODEL WITH 2 SLOW INHIBITORY VARIABLES SO SIAM JOURNAL ON APPLIED MATHEMATICS LA English DT Article DE EXCITABLE MEMBRANES; BURSTING OSCILLATIONS; SINGULAR PERTURBATION ID PANCREATIC BETA-CELLS; CHANNEL; INACTIVATION AB Models for certain excitable cells, such as the pancreatic beta-cell, must reproduce ''bursting'' oscillations of the membrane potential. This has previously been done using one slow variable to drive bursts. The dynamics of such models have been analyzed. However, new models for the beta-cell often include additional slow variables, and therefore the previous analysis is extended to two slow variables, using a simplified version of a beta-cell model. Some unusual time courses of this model motivated a geometric singular perturbation analysis and the application of averaging to reduce the dynamics to the slow-variable phase plane. A geometric understanding of the solution structure and of transitions between various modes of behavior was then developed. A novel use of the bifurcation code AUTO finds nullclines for the slow variables when the fast variables are periodic by averaging over the fast oscillations. In contrast with the ''parabolic'' neuronal burster, this model requires bistability in the fast variables to generate bursting. C1 OHIO STATE UNIV,DEPT MATH,COLUMBUS,OH 43210. RP SMOLEN, P (reprint author), NIDDKD,MATH RES BRANCH,BETHESDA,MD 20892, USA. NR 33 TC 38 Z9 39 U1 0 U2 1 PU SIAM PUBLICATIONS PI PHILADELPHIA PA 3600 UNIV CITY SCIENCE CENTER, PHILADELPHIA, PA 19104-2688 SN 0036-1399 J9 SIAM J APPL MATH JI SIAM J. Appl. Math. PD JUN PY 1993 VL 53 IS 3 BP 861 EP 892 DI 10.1137/0153042 PG 32 WC Mathematics, Applied SC Mathematics GA LE343 UT WOS:A1993LE34300012 ER PT J AU MUNTANER, C OCAMPO, PJ AF MUNTANER, C OCAMPO, PJ TI A CRITICAL-APPRAISAL OF THE DEMAND CONTROL MODEL OF THE PSYCHOSOCIAL WORK-ENVIRONMENT - EPISTEMOLOGICAL, SOCIAL, BEHAVIORAL AND CLASS CONSIDERATIONS SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE WORK STRESS; SOCIAL PSYCHOLOGY; SOCIAL CLASS; CONTROL; DEMANDS ID CORONARY HEART-DISEASE; JOB DECISION LATITUDE; UNITED-STATES; A BEHAVIOR; HEALTH; STRAIN; RISK; INSTRUCTIONS; EPIDEMIOLOGY; PERSONALITY AB During the last decade the demand/control model has emerged as the dominant model to explain the relationship between the psychosocial features of work organization and health. Although originating from the field of occupational social epidemiology, the conceptual and methodological basis of the demand/control model parallel construct based models used in social psychology. Using behavioral and sociological perspectives the current paper discusses the model's limitations. Recommendations regarding incorporation of social levels of analysis, the relationship between self-report and behavior, worker vs expert knowledge, and the generalized effects of stress on mental health are discussed to provide a positive heuristic to the demand/control model. C1 JOHNS HOPKINS SCH HYG & PUBL HLTH,BALTIMORE,MD 21205. RP MUNTANER, C (reprint author), NIMH,SOCIOENVIRONM STUDIES LAB,7550 WISCONSIN AVE,BETHESDA,MD 20892, USA. RI Muntaner, C/A-5043-2010 NR 91 TC 66 Z9 67 U1 1 U2 17 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD JUN PY 1993 VL 36 IS 11 BP 1509 EP 1517 DI 10.1016/0277-9536(93)90393-I PG 9 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA LD204 UT WOS:A1993LD20400014 PM 8511639 ER PT J AU AIN, KB PUCINO, F SHIVER, TM BANKS, SM AF AIN, KB PUCINO, F SHIVER, TM BANKS, SM TI THYROID-HORMONE LEVELS AFFECTED BY TIME OF BLOOD-SAMPLING IN THYROXINE-TREATED PATIENTS SO THYROID LA English DT Article ID SERUM THYROXINE; PRIMARY HYPOTHYROIDISM; REPLACEMENT; THYROTROPIN; TRIIODOTHYRONINE; LEVOTHYROXINE; FEEDBACK; THERAPY; TSH AB Patients receiving exogenous levothyroxine are reported to have higher total and free serum thyroxine levels than euthyroid controls. This may be an artifact of the serum collection time. We explored the effect of collection time on serum levels of thyroid hormones in outpatients receiving levothyroxine for replacement therapy (26 patients) or suppression of thyrotropin (25 patients). Blood samples, obtained during regular clinic visits (random samples) and at more than 22 h from ingestion of levothyroxine (trough samples), were assayed for total and free thyroxine, triiodothyronine, and thyrotropin. Four athyreotic patients on levothyroxine therapy had serial blood sampling over 24 h. Compared to corresponding trough samples, random samples had elevated total thyroxine levels in patients receiving replacement (8.1 +/- 1.2 %, mean +/- SE, p = 0.0001) and in patients undergoing suppression (8.8 +/- 1.6 %, p = 0.0001). Free thyroxine was increased by 12.7 +/- 2.6% (p = 0.0003) and 14.5 +/- 2.3% (p = 0.0001), respectively, compared with trough samples. Thyrotropin levels were 18.9 +/- 6.8% (p = 0.003) lower in patients receiving replacement and triiodothyronine levels showed small or no changes. Time-course analysis showed that free and total thyroxine levels remained significantly elevated above baseline for 9 and 5 h, respectively, after a levothyroxine dose. In conclusion, there is a transient increase in thyroid hormone levels for 9 h after an oral levothyroxine dose. Accurate assessment of thyroid hormone levels in patients receiving levothyroxine therapy should take this into account. This has greatest significance in selecting minimal levothyroxine dosages for suppression of thyrotropin. C1 NEW YORK STATE OFF MENTAL HLTH, MENTAL HLTH INFORMAT UNIT, ALBANY, NY USA. VET ADM MED CTR, LEXINGTON, KY 40511 USA. NIH, WARREN GRANT MAGNUSON CLIN CTR, DEPT PHARM, BETHESDA, MD 20892 USA. BAYLOR COLL MED, METHODIST HOSP, HOUSTON, TX 77030 USA. RP UNIV KENTUCKY, MED CTR, DEPT MED, ROOM MN520, 800 ROSE ST, LEXINGTON, KY 40536 USA. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 22 TC 22 Z9 22 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 EI 1557-9077 J9 THYROID JI Thyroid PD SUM PY 1993 VL 3 IS 2 BP 81 EP 85 DI 10.1089/thy.1993.3.81 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LL927 UT WOS:A1993LL92700002 PM 8369656 ER PT J AU AUST, SD CHIGNELL, CF BRAY, TM KALYANARAMAN, B MASON, RP AF AUST, SD CHIGNELL, CF BRAY, TM KALYANARAMAN, B MASON, RP TI FREE-RADICALS IN TOXICOLOGY SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; CUTANEOUS PHOTOSENSITIZING AGENTS; PROSTAGLANDIN-H SYNTHASE; ELECTRON-SPIN-RESONANCE; SMOOTH-MUSCLE CELLS; IRON OVERLOAD; LIPID-PEROXIDATION; ENDOTHELIAL-CELLS; INDOLIC COMPOUNDS; PULMONARY-EDEMA C1 MED COLL WISCONSIN,BIOPHYS SECT,MILWAUKEE,WI 53226. NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. UNIV GUELPH,DEPT NUTR SCI,GUELPH N1G 2W1,ONTARIO,CANADA. RP AUST, SD (reprint author), UTAH STATE UNIV,CTR BIOTECHNOL,LOGAN,UT 84322, USA. NR 60 TC 141 Z9 144 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 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD JUN PY 1993 VL 120 IS 2 BP 168 EP 178 DI 10.1006/taap.1993.1100 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA LH287 UT WOS:A1993LH28700002 PM 8511786 ER PT J AU JEFFERSON, WN VOELKER, CR NEWBOLD, RR AF JEFFERSON, WN VOELKER, CR NEWBOLD, RR TI INCREASED SENSITIVITY OF WESTERN BLOTS USING VARIOUS SECONDARY ANTIBODY DETECTION METHODS SO TOXICOLOGY METHODS LA English DT Article DE WESTERN BLOT; IMMUNOGOLD; I-125; BIOTINYLATION; ENHANCED CHEMILUMINESCENCE ID MOUSE; LACTOTRANSFERRIN; PROTEINS AB The sensitivity of Western blots using four different secondary antibody detection methods is described and compared. Enhanced chemiluminescence (ECL) and biotinylation are fast and offer many advantages over the other two described methods. Both ECL and biotinylation provide a linear response to increasing known amounts of proteins measured by quantitative analysis. However, ECL was the most sensitive method tested; in addition to an excellent linear response, ECL allowed multiple exposures of the same blot. In summary, ECL is highly sensitive, safe, and fast. This detection method should prove useful for a wide array of applications. C1 NIEHS,DIV INTRAMURAL RES,REPRODUCT & DEV TOXICOL LAB,POB 12233,RES TRIANGLE PK,NC 27709. NR 9 TC 7 Z9 7 U1 0 U2 2 PU TAYLOR & FRANCIS PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 1051-7235 J9 TOXICOL METHOD JI Toxicol. Method. PD JUN PY 1993 VL 3 IS 2 BP 100 EP 108 DI 10.3109/15376519309047234 PG 9 WC Toxicology SC Toxicology GA LJ538 UT WOS:A1993LJ53800003 ER PT J AU LEITMAN, SF AF LEITMAN, SF TI DOSE, DOSIMETRY, AND QUALITY IMPROVEMENT OF IRRADIATED BLOOD COMPONENTS SO TRANSFUSION LA English DT Editorial Material ID VERSUS-HOST DISEASE; GRAFT RP LEITMAN, SF (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BLDG 10,ROOM 1C-711,BETHESDA,MD 20892, USA. NR 19 TC 17 Z9 19 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUN PY 1993 VL 33 IS 6 BP 447 EP 449 DI 10.1046/j.1537-2995.1993.33693296804.x PG 3 WC Hematology SC Hematology GA LH308 UT WOS:A1993LH30800001 PM 8516787 ER PT J AU ADAMS, M LEE, TH BUSCH, MP HEITMAN, J MARSHALL, GJ GJERSET, GF MOSLEY, JW ALEDORT, LM HASSETT, J SACKS, H HILGARTNER, MW STEVENS, CE TAYLOR, PE DONEGAN, E KOERPER, MA PERKINS, HA JOHNSON, RA LEWIS, BH HOLLINGSWORTH, CG NEMO, GJ HOAK, J ALTER, HJ DALLESSIO, DJ GRADY, GJ HOLLAND, PV ROSE, NR SEEFF, LB WITTES, J LEE, IH HEITMAN, J MARSHALL, GJ BREGMAN, DJ BUCKLEY, J GAIENNIE, J JOHNSON, CS KASPER, CK NOWICKI, M OPERSKALSKI, EA PARKER, JW PIKE, MC POWARS, DR SUCCAR, M KLEINMAN, SH HYMAN, C DIETRICH, SL LUSHER, JM SARNAIK, S SCHIFF, ER FLETCHER, MA LIAN, ECY PEGELOW, CH REDDY, KR LENES, BA AF ADAMS, M LEE, TH BUSCH, MP HEITMAN, J MARSHALL, GJ GJERSET, GF MOSLEY, JW ALEDORT, LM HASSETT, J SACKS, H HILGARTNER, MW STEVENS, CE TAYLOR, PE DONEGAN, E KOERPER, MA PERKINS, HA JOHNSON, RA LEWIS, BH HOLLINGSWORTH, CG NEMO, GJ HOAK, J ALTER, HJ DALLESSIO, DJ GRADY, GJ HOLLAND, PV ROSE, NR SEEFF, LB WITTES, J LEE, IH HEITMAN, J MARSHALL, GJ BREGMAN, DJ BUCKLEY, J GAIENNIE, J JOHNSON, CS KASPER, CK NOWICKI, M OPERSKALSKI, EA PARKER, JW PIKE, MC POWARS, DR SUCCAR, M KLEINMAN, SH HYMAN, C DIETRICH, SL LUSHER, JM SARNAIK, S SCHIFF, ER FLETCHER, MA LIAN, ECY PEGELOW, CH REDDY, KR LENES, BA TI RAPID FREEZING OF WHOLE-BLOOD OR BUFFY COAT SAMPLES FOR POLYMERASE CHAIN-REACTION AND CELL-CULTURE ANALYSIS - APPLICATION TO DETECTION OF HUMAN-IMMUNODEFICIENCY-VIRUS IN BLOOD-DONOR AND RECIPIENT REPOSITORIES SO TRANSFUSION LA English DT Article ID INFECTION; TYPE-1 AB Storage of lymphocytes for later use in prospective epidemiologic studies of blood donors and transfusion recipients has been limited by the cost of separating peripheral blood mononuclear cells (PBMCs). When the Transfusion Safety Study began in 1985, it was decided to establish a cell repository of cryopreserved buffy coat (BC) samples, and thus far over 20,000 samples have been accumulated from enrolled subjects. To determine if these specimens could be used for polymerase chain reaction, a simple thawing and pelleting technique for recovering hemoglobin-free total white cells (WBCs) was developed. To validate the technique, parallel analysis was conducted of BCs, whole blood (WB), and PBMC samples from human immunodeficiency virus type 1 (HIV-1)-seropositive subjects. Immediate postthaw cell counts of 29 frozen-thawed (F-T) WB and BC samples averaged 90 percent of the prefreeze (input) values. Representative WBC populations were obtained by immediate pelleting. Amplification of HIV-1 gag sequences from F-T BCs and F-T WB was 94 and 75 percent, respectively, which is as sensitive as that obtained with freshly separated PBMC lysates. Quantitative HIV-1 proviral load analysis by serial dilution of 23 F-T BCs and 8 WB lysates showed results comparable to those obtained with lysates of fresh PBMCs. Values for WBC differential and immunophenotyping could be applied to express viral load relative to total WBCs, PBMCs, or CD4+ cells. These results establish the basis for simplified virologic analysis of cryopreserved BC or WB specimens. C1 IRWIN MEM BLOOD CTR,270 MASONIC AVE,SAN FRANCISCO,CA 94118. UNIV CALIF SAN FRANCISCO,DEPT LAB MED,SAN FRANCISCO,CA 94143. PUGET SOUND BLOOD CTR,SEATTLE,WA 98104. UNIV SO CALIF,SCH MED,LOS ANGELES,CA 90033. MT SINAI MED CTR,NEW YORK,NY 10029. CORNELL UNIV,MED CTR,NEW YORK,NY 10021. UNIV CALIF LOS ANGELES,LOS ANGELES,CA 90024. CEDARS SINAI MED CTR,LOS ANGELES,CA 90048. HUNTINGTON MEM HOSP,PASADENA,CA 91105. WAYNE STATE UNIV,DETROIT,MI 48202. UNIV MIAMI,CORAL GABLES,FL 33124. AMER RED CROSS,BETHESDA,MD 20814. NEW YORK BLOOD CTR,NEW YORK,NY 10021. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94110. ALTA BATES COMMUNITY HOSP,BERKELEY,CA. NHLBI,BETHESDA,MD 20892. UNIV SO CALIF,LOS ANGELES,CA 90089. TRANSFUS SAFETY STUDY,LOS ANGELES,CA. UNIV WASHINGTON,SEATTLE,WA 98195. FU NHLBI NIH HHS [N01-HB-4-7003, N01-HB-9-7074] NR 7 TC 8 Z9 8 U1 1 U2 2 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUN PY 1993 VL 33 IS 6 BP 504 EP 508 DI 10.1046/j.1537-2995.1993.33693296814.x PG 5 WC Hematology SC Hematology GA LH308 UT WOS:A1993LH30800011 PM 8516793 ER PT J AU SHAFFERMAN, A LEWIS, MG MCCUTCHAN, FE BENVENISTE, RE JAHRLING, PB BURKE, DS EDDY, GA AF SHAFFERMAN, A LEWIS, MG MCCUTCHAN, FE BENVENISTE, RE JAHRLING, PB BURKE, DS EDDY, GA TI PREVENTION OF TRANSMISSION OF SIMIAN IMMUNODEFICIENCY VIRUS FROM VACCINATED MACAQUES THAT DEVELOPED TRANSIENT VIRUS-INFECTION FOLLOWING CHALLENGE SO VACCINE LA English DT Article DE SIMIAN IMMUNODEFICIENCY VIRUS; TRANSMISSION; MACAQUES; ENVELOPE PEPTIDE VACCINE ID CYNOMOLGUS MONKEYS; RHESUS MACAQUES; HTLV-III; PROTECTION; RETROVIRUS; AIDS; DISEASE; HIV-2; IMMUNIZATION; LENTIVIRUS AB Macaque immunization with a mixture of four SIV peptides from conserved hydrophilic envelope regions has been shown to prevent virus persistence following challenge with SIV(mne/E11s). Data shown here demonstrate that lymph node cells from all vaccinated monkeys and peripheral blood lymphocytes from one of the vaccinees were positive in a SIV-pol 'nested' polymerase chain reaction (PCR) amplification analysis. However, by 37 months after infection, all immunized monkeys were healthy while two of three controls had died and the remaining animal was virus culture-positive and had declining CD4+ lymphocytes. Viable lymph node cells and peripheral lymphoid cells in blood were transferred from the three immunized macaques to individual susceptible macaques. As a control for the transfer, one of the vaccine experiment controls that was actively producing virus in its peripheral blood was used. None of the recipients of cells from the vaccinated macaques seroconverted and all were virus coculture- and PCR-negative 25 weeks post-transfer (p.t.). The recipient of cells from the control infected macaque became positive in these tests by 2- 3 weeks p. t. These results suggest thal, while peptide-vaccinated macaques permitted some level of SIV replication following challenge, the vaccine prevented disease progression and virus transmission. C1 HENRY M JACKSON FDN,RES LAB,ROCKVILLE,MD 20852. WALTER REED ARMY INST RES,DIV RETROVIROL,ROCKVILLE,MD 20852. NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. USA,MED RES INST INFECT DIS,FREDERICK,MD 21701. RP SHAFFERMAN, A (reprint author), ISRAEL INST BIOL RES,DEPT BIOCHEM,POB 19,IL-70450 NESS ZIONA,ISRAEL. OI /0000-0002-5704-8094 NR 38 TC 9 Z9 9 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 JUN PY 1993 VL 11 IS 8 BP 848 EP 852 DI 10.1016/0264-410X(93)90360-A PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA LH325 UT WOS:A1993LH32500007 PM 8356845 ER PT J AU EMERSON, SU HUANG, YK PURCELL, RH AF EMERSON, SU HUANG, YK PURCELL, RH TI 2B AND 2C MUTATIONS ARE ESSENTIAL BUT MUTATIONS THROUGHOUT THE GENOME OF HAV CONTRIBUTE TO ADAPTATION TO CELL-CULTURE SO VIROLOGY LA English DT Article ID HEPATITIS-A VIRUS; VACCINES; CDNA RP EMERSON, SU (reprint author), NIAID,INFECT DIS LAB,HEPATITIS VIRUSES SECT,BETHESDA,MD 20892, USA. NR 10 TC 50 Z9 53 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 JUN PY 1993 VL 194 IS 2 BP 475 EP 480 DI 10.1006/viro.1993.1286 PG 6 WC Virology SC Virology GA LC575 UT WOS:A1993LC57500005 PM 8389072 ER PT J AU DERSE, D NEWBOLD, SH AF DERSE, D NEWBOLD, SH TI MUTAGENESIS OF EIAV TAT REVEALS STRUCTURAL FEATURES ESSENTIAL FOR TRANSCRIPTIONAL ACTIVATION AND TAR ELEMENT RECOGNITION SO VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; INFECTIOUS-ANEMIA VIRUS; LONG TERMINAL REPEAT; HIV-1 TAT; GENE-EXPRESSION; TRANS-ACTIVATION; RESPONSIVE SEQUENCE; LENTIVIRUS TAT; LOOP SEQUENCE; BASIC DOMAIN RP DERSE, D (reprint author), NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702, USA. NR 40 TC 16 Z9 17 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD JUN PY 1993 VL 194 IS 2 BP 530 EP 536 DI 10.1006/viro.1993.1291 PG 7 WC Virology SC Virology GA LC575 UT WOS:A1993LC57500010 PM 8389074 ER PT J AU GODENY, EK CHEN, L KUMAR, SN METHVEN, SL KOONIN, EV BRINTON, MA AF GODENY, EK CHEN, L KUMAR, SN METHVEN, SL KOONIN, EV BRINTON, MA TI COMPLETE GENOMIC SEQUENCE AND PHYLOGENETIC ANALYSIS OF THE LACTATE DEHYDROGENASE-ELEVATING VIRUS (LDV) SO VIROLOGY LA English DT Article ID STRAND RNA VIRUSES; CYSTEINE PROTEASES; SERINE PROTEASES; CORONAVIRUS-IBV; RECOMBINATION; SUPERFAMILY; POLYMERASE; PROTEIN; IDENTIFICATION; REPLICATION C1 GEORGIA STATE UNIV,DEPT BIOL,POB 4010,ATLANTA,GA 30302. NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. FU NINDS NIH HHS [NS19013] NR 60 TC 125 Z9 135 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 JUN PY 1993 VL 194 IS 2 BP 585 EP 596 DI 10.1006/viro.1993.1298 PG 12 WC Virology SC Virology GA LC575 UT WOS:A1993LC57500017 PM 8389075 ER PT J AU HALABAN, R TYRRELL, L LONGLEY, J YARDEN, Y RUBIN, J AF HALABAN, R TYRRELL, L LONGLEY, J YARDEN, Y RUBIN, J TI PIGMENTATION AND PROLIFERATION OF HUMAN MELANOCYTES AND THE EFFECTS OF MELANOCYTE-STIMULATING HORMONE AND ULTRAVIOLET B-LIGHT SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID FIBROBLAST GROWTH-FACTOR; RECEPTOR TYROSINE KINASE; C-KIT RECEPTOR; W-MUTANT MICE; MURINE MELANOCYTES; PROTO-ONCOGENE; SIGNAL TRANSDUCTION; TRANSGENIC MICE; SI-LOCUS; LIGAND C1 WEIZMANN INST SCI,DEPT CHEM IMMUNOL,IL-76100 REHOVOT,ISRAEL. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. RP HALABAN, R (reprint author), YALE UNIV,SCH MED,DEPT DERMATOL,500 LCI,POB 3333,NEW HAVEN,CT 06510, USA. RI YARDEN, YOSEF/K-1467-2012 FU NCI NIH HHS [1 R29 CA44542, 5 RO1 CA04679] NR 57 TC 48 Z9 51 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD MAY 31 PY 1993 VL 680 BP 290 EP 301 DI 10.1111/j.1749-6632.1993.tb19691.x PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LG191 UT WOS:A1993LG19100022 PM 7685575 ER PT J AU BERGASA, NV VERGALLA, J TURNER, ML LOH, PY JONES, EA AF BERGASA, NV VERGALLA, J TURNER, ML LOH, PY JONES, EA TI ALPHA-MELANOCYTE-STIMULATING HORMONE IN PRIMARY BILIARY-CIRRHOSIS SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article C1 NCI,DIV DERMATOL,BETHESDA,MD 20892. NICHHD,DEV NEUROBIOL LAB,CELLULAR NEUROBIOL SECT,BETHESDA,MD 20892. RP BERGASA, NV (reprint author), NIDDKD,LIVER DIS SECT,BLDG 10,ROOM 4D-52,BETHESDA,MD 20892, USA. NR 4 TC 4 Z9 4 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD MAY 31 PY 1993 VL 680 BP 454 EP 458 DI 10.1111/j.1749-6632.1993.tb19706.x PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LG191 UT WOS:A1993LG19100037 PM 8390167 ER PT J AU CHRONWALL, BM DICKERSON, DS SIBLEY, DR GARY, KA AF CHRONWALL, BM DICKERSON, DS SIBLEY, DR GARY, KA TI PLASTICITY AND ONTOGENY OF MELANOTROPE-D(2A) DOPAMINE-RECEPTOR MESSENGER-RNA AND ISOFORM PROTEIN EXPRESSION SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID RAT PITUITARY; BRAIN C1 NIH,EXPTL THERAPEUT BRANCH,BETHESDA,MD 20892. RP CHRONWALL, BM (reprint author), UNIV MISSOURI,SCH BIOL SCI,KANSAS CITY,MO 64108, USA. NR 8 TC 3 Z9 3 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD MAY 31 PY 1993 VL 680 BP 478 EP 480 DI 10.1111/j.1749-6632.1993.tb19713.x PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LG191 UT WOS:A1993LG19100044 PM 8512223 ER PT J AU HAHN, WC MENZIN, E SAITO, T GERMAIN, RN BIERER, BE AF HAHN, WC MENZIN, E SAITO, T GERMAIN, RN BIERER, BE TI THE COMPLETE SEQUENCES OF PLASMIDS PFNEO AND PMH-NEO - CONVENIENT EXPRESSION VECTORS FOR HIGH-LEVEL EXPRESSION OF EUKARYOTIC GENES IN HEMATOPOIETIC-CELL LINES SO GENE LA English DT Note DE RECOMBINANT DNA; HEMATOPOIETIC EXPRESSION; G418 RESISTANCE; T-CELL HYBRIDOMAS ID RECEPTOR AB The eukaryotic expression vector, pFNeo, confers resistance to the antibiotic G418 and directs hematopoietic-specific expression of proteins under the control of the long terminal repeat from the Friend spleen focus-forming virus. Here, we report the entire nucleotide sequence of pFNeo. We have also constructed and sequenced a pFNeo-based expression vector (pMH-Neo) that carries an improved multiple cloning site region for easier subcloning. The utility of both vectors was demonstrated by transfection of murine T-cell hybridomas by electroporation. Transfection with either pFNeo or pMH-Neo yielded a high frequency (1 in 2 x 10(4)) of G418-resistant cell lines. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,DANA 1610B,44 BINNEY ST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. CHIBA UNIV,SCH MED,CTR NEUROBIOL & MOLEC IMMUNOL,DIV MOLEC GENET,CHIBA,JAPAN. BRIGHAM & WOMENS HOSP,DEPT MED,DIV HEMATOL ONCOL,BOSTON,MA 02115. NIAID,IMMUNOL LAB,BETHESDA,MD 20892. RI Saito, Takashi/C-9684-2009 OI Saito, Takashi/0000-0001-9495-3547 FU NIAID NIH HHS [AI28554, AI34565] NR 6 TC 36 Z9 36 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD MAY 30 PY 1993 VL 127 IS 2 BP 267 EP 268 DI 10.1016/0378-1119(93)90731-H PG 2 WC Genetics & Heredity SC Genetics & Heredity GA LF233 UT WOS:A1993LF23300018 PM 8500769 ER PT J AU BRAUN, MM CAPORASO, N AF BRAUN, MM CAPORASO, N TI TWIN STUDIES IN MEDICAL-RESEARCH SO LANCET LA English DT Letter RP BRAUN, MM (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,6130 EXECUT BLVD,ROCKVILLE,MD 20852, USA. NR 2 TC 2 Z9 2 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD MAY 29 PY 1993 VL 341 IS 8857 BP 1418 EP 1418 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA LE180 UT WOS:A1993LE18000048 PM 8098827 ER PT J AU MASTORAKOS, G WEBSTER, EL CHROUSOS, GP AF MASTORAKOS, G WEBSTER, EL CHROUSOS, GP TI CORTICOTROPIN-RELEASING HORMONE AND ITS RECEPTORS IN THE OVARY - PHYSIOLOGICAL IMPLICATIONS SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID SYMPATHETIC NERVOUS-SYSTEM; RAT SPINAL-CORD; IMMUNOREACTIVE CORTICOTROPIN; BETA-ENDORPHIN; SECRETION; CELLS; LOCALIZATION; MACROPHAGES; STRESS; BRAIN RP NICHHD, DEV ENDOCRINOL BRANCH, BLDG 10, ROOM 10N244, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 43 TC 1 Z9 1 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PD MAY 28 PY 1993 VL 687 BP 20 EP 38 PG 19 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LK217 UT WOS:A1993LK21700005 ER PT J AU BONDY, C ZHOU, JA AF BONDY, C ZHOU, JA TI INSULIN-LIKE GROWTH-FACTOR SYSTEM GENE-EXPRESSION IN THE POSTPUBERTAL HUMAN OVARY SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID FACTOR-BINDING PROTEIN; LOW-MOLECULAR-WEIGHT; I IGF-I; GRANULOSA-CELLS; MESSENGER-RNA; FOLLICULAR-FLUID; RAT OVARY; FOLLICLES RP BONDY, C (reprint author), NICHHD, DEV ENDOCRINOL BRANCH, BLDG 10, ROOM 10N262, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 22 TC 0 Z9 0 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PD MAY 28 PY 1993 VL 687 BP 65 EP 76 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LK217 UT WOS:A1993LK21700011 ER PT J AU MINANNI, SL WAJCHENBERG, BL MARCONDES, JAM CAVALEIROLUNA, AM FORTES, MAHZ REGO, MA MENDONCA, BB VEZOZZO, DP RODBARD, D GIANNELLANETO, D AF MINANNI, SL WAJCHENBERG, BL MARCONDES, JAM CAVALEIROLUNA, AM FORTES, MAHZ REGO, MA MENDONCA, BB VEZOZZO, DP RODBARD, D GIANNELLANETO, D TI PULSATILE SECRETION OF SERUM GONADOTROPINS IN HIRSUTE WOMEN WITH AND WITHOUT POLYCYSTIC OVARIAN SYNDROME SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID LUTEINIZING-HORMONE SECRETION; MENSTRUAL-CYCLE; DISEASE; FREQUENCY; PATTERNS; PEAKS; LH C1 UNIV SAO PAULO, SCH MED, DIV ENDOCRINOL, SAO PAULO, BRAZIL. UNIV SAO PAULO, SCH MED, DEPT RADIOL, SAO PAULO, BRAZIL. UNIV SAO PAULO, SCH MED, HUMAN NUTR & METAB DIS LIM LAB 25, SAO PAULO, BRAZIL. NIH, THEORET & PHYS BIOL LAB, BETHESDA, MD 20892 USA. RI Mendonca, Berenice/C-2827-2012; Fortes, Maria Angela/K-4422-2013 NR 23 TC 0 Z9 0 U1 1 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PD MAY 28 PY 1993 VL 687 BP 136 EP 149 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LK217 UT WOS:A1993LK21700018 ER PT J AU CHROUSOS, GP BRINGER, J TOLIS, G AF CHROUSOS, GP BRINGER, J TOLIS, G TI INTRAOVARIAN REGULATORS AND POLYCYSTIC OVARIAN SYNDROME - RECENT PROGRESS ON CLINICAL AND THERAPEUTIC ASPECTS - INTRODUCTION SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Editorial Material C1 HOP LAPEYRONIE, SERV ENDOCRINOL, F-34059 MONTPELLIER, FRANCE. HIPPOKRATEION HOSP, DEPT ENDOCRINOL, ATHENS, GREECE. RP CHROUSOS, GP (reprint author), NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PD MAY 28 PY 1993 VL 687 BP R13 EP R15 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LK217 UT WOS:A1993LK21700001 ER PT J AU SUBAR, AF HARLAN, LC WYNDER, E RIMM, E HALEY, N BOLTONSMITH, C DIANA, J RENAUD, S HOFFMANN AF SUBAR, AF HARLAN, LC WYNDER, E RIMM, E HALEY, N BOLTONSMITH, C DIANA, J RENAUD, S HOFFMANN TI NUTRIENT AND FOOD GROUP INTAKE BY TOBACCO USE STATUS - THE 1987 NATIONAL-HEALTH INTERVIEW SURVEY SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID NHANES-II SURVEY; UNITED-STATES; CIGARETTE-SMOKING; PHYSICAL-ACTIVITY; QUANTITATIVE DATA; DIETARY HABITS; HEART-DISEASE; AMERICAN DIET; SOCIAL-CLASS; VITAMIN-C C1 AMER HLTH FDN,NEW YORK,NY 10017. HARVARD UNIV,BOSTON,MA 02115. METROPOLITAN LIFE INSURANCE CO,NEW YORK,NY 10021. UNIV DUNDEE,NINEWELLS HOSP & MED SCH,DUNDEE DD1 9SY,SCOTLAND. UNIV KENTUCKY,LEXINGTON,KY 40536. INSERM,U63,F-69500 BRON,FRANCE. AMER HLTH FDN,VALHALLA,NY 10595. RP SUBAR, AF (reprint author), NCI,APPL RES BRANCH,EXECUT PLAZA N,ROOM 313,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 42 TC 38 Z9 39 U1 1 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD MAY 28 PY 1993 VL 686 BP 310 EP 322 DI 10.1111/j.1749-6632.1993.tb39193.x PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LG193 UT WOS:A1993LG19300027 PM 8512257 ER PT J AU JUCKER, M BIALOBOK, P KLEINMAN, HK WALKER, LC HAGG, T INGRAM, DK AF JUCKER, M BIALOBOK, P KLEINMAN, HK WALKER, LC HAGG, T INGRAM, DK TI LAMININ-LIKE AND LAMININ-BINDING PROTEIN-LIKE IMMUNOREACTIVE ASTROCYTES IN RAT HIPPOCAMPUS AFTER TRANSIENT ISCHEMIA - ANTIBODY TO LAMININ-BINDING PROTEIN IS A SENSITIVE MARKER OF NEURAL INJURY AND DEGENERATION SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; BASEMENT-MEMBRANE COMPONENTS; NEUROMUSCULAR-JUNCTION; MAMMALIAN BRAIN; SCHWANN-CELLS; ADULT; CHAIN; CNS; LOCALIZATION; FOREBRAIN C1 FISONS CORP,ROCHESTER,NY 14623. NIDR,DEV BIOL LAB,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,NEUROPATHOL LAB,BALTIMORE,MD 21205. UNIV CALIF SAN DIEGO,DEPT BIOL,LA JOLLA,CA 92093. SWISS FED INST TECHNOL,DEPT NEUROBIOL,CH-8093 ZURICH,SWITZERLAND. RP JUCKER, M (reprint author), NIA,GERONTOL RES CTR,BALTIMORE,MD 21224, USA. OI Walker, Lary/0000-0001-9166-3261 NR 40 TC 13 Z9 13 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD MAY 28 PY 1993 VL 679 BP 245 EP 252 DI 10.1111/j.1749-6632.1993.tb18304.x PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LG188 UT WOS:A1993LG18800021 PM 8512187 ER PT J AU MARINI, AM PAUL, SM AF MARINI, AM PAUL, SM TI INDUCTION OF A NEUROPROTECTIVE STATE IN CEREBELLAR GRANULE CELLS FOLLOWING ACTIVATION OF N-METHYL-D-ASPARTATE RECEPTORS SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID NEUROTOXICITY; ACID; STIMULATION; CULTURE RP MARINI, AM (reprint author), NIMH,CLIN NEUROSCI BRANCH,MOLEC PHARMACOL SECT,BETHESDA,MD 20892, USA. NR 13 TC 14 Z9 14 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD MAY 28 PY 1993 VL 679 BP 253 EP 259 DI 10.1111/j.1749-6632.1993.tb18305.x PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LG188 UT WOS:A1993LG18800022 PM 8099772 ER PT J AU POLLARD, HB ADEYEMO, M DHARIWAL, K LEVINE, M CAOHUY, H MARKEY, S MARKEY, CJ YOUDIM, MBH AF POLLARD, HB ADEYEMO, M DHARIWAL, K LEVINE, M CAOHUY, H MARKEY, S MARKEY, CJ YOUDIM, MBH TI THE GOLDFISH AS A DRUG DISCOVERY VEHICLE FOR PARKINSONS-DISEASE AND OTHER NEURODEGENERATIVE DISORDERS SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID N-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; NEUROTOXICITY; MPTP; DOPAMINE; NEURONS; MODEL C1 NINDCD,CLIN SCI LAB,BETHESDA,MD 20892. TECHNION ISRAEL INST TECHNOL,DEPT PHARMACOL,IL-32000 HAIFA,ISRAEL. TECHNION ISRAEL INST TECHNOL,RAPPAPORT FAMILY CTR,IL-32000 HAIFA,ISRAEL. RP POLLARD, HB (reprint author), NIDDKD,CELL BIOL & GENET,BETHESDA,MD 20892, USA. NR 21 TC 5 Z9 5 U1 1 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD MAY 28 PY 1993 VL 679 BP 317 EP 320 DI 10.1111/j.1749-6632.1993.tb18314.x PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LG188 UT WOS:A1993LG18800031 PM 8512193 ER PT J AU MARKEY, SP MARKEY, CJ WANG, TCL AF MARKEY, SP MARKEY, CJ WANG, TCL TI OXIDATIVE DAMAGE IN DOUBLE-STRANDED GENOMIC DNA AS MEASURED BY GC MS ASSAY OF A THYMINE GLYCOL DERIVATIVE SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID THYMIDINE GLYCOL; CELLS; ESTER RP MARKEY, SP (reprint author), NIMH,CLIN SCI LAB,ANALYT BIOCHEM SECT,BETHESDA,MD 20892, USA. NR 9 TC 0 Z9 0 U1 0 U2 4 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD MAY 28 PY 1993 VL 679 BP 352 EP 357 DI 10.1111/j.1749-6632.1993.tb18321.x PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LG188 UT WOS:A1993LG18800038 PM 8512198 ER PT J AU CHIUEH, CC MURPHY, DL MIYAKE, H LANG, K TULSI, PK HUANG, SJ AF CHIUEH, CC MURPHY, DL MIYAKE, H LANG, K TULSI, PK HUANG, SJ TI HYDROXYL FREE-RADICAL (.OH) FORMATION REFLECTED BY SALICYLATE HYDROXYLATION AND NEUROMELANIN - IN-VIVO MARKERS FOR OXIDANT INJURY OF NIGRAL NEURONS SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID SUBSTANTIA NIGRA; DOPAMINERGIC-NEURONS; PARKINSONS-DISEASE; RAT STRIATUM; MPP+; MPTP; ACID RP CHIUEH, CC (reprint author), NIMH,CLIN SCI LAB,NIH CLIN CTR 10 ROOM 3D-41,BETHESDA,MD 20892, USA. NR 20 TC 41 Z9 41 U1 1 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 SN 0077-8923 J9 ANN NY ACAD SCI JI Ann. N.Y. Acad. Sci. PD MAY 28 PY 1993 VL 679 BP 370 EP 375 DI 10.1111/j.1749-6632.1993.tb18324.x PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LG188 UT WOS:A1993LG18800041 PM 8390147 ER PT J AU GUERRA, FK CIUFFO, GM ELIZALDE, PV CHARREAU, EH SAAVEDRA, JM AF GUERRA, FK CIUFFO, GM ELIZALDE, PV CHARREAU, EH SAAVEDRA, JM TI ENHANCED EXPRESSION OF ANGIOTENSIN-II RECEPTOR SUBTYPES AND ANGIOTENSIN-CONVERTING ENZYME IN MEDROXYPROGESTERONE-INDUCED MOUSE MAMMARY ADENOCARCINOMAS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID CELL-GROWTH; ACETATE; HORMONE; MICE; TUMORS; BRAIN C1 NIMH,CLIN SCI LAB,PHARMACOL SECT,9000 ROCKVILLE PIKE,BLDG 10,ROOM 2D-45,BETHESDA,MD 20892. INST BIOL & EXPTL MED,RA-1428 BUENOS AIRES,ARGENTINA. NR 25 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 MAY 28 PY 1993 VL 193 IS 1 BP 93 EP 99 DI 10.1006/bbrc.1993.1594 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LE381 UT WOS:A1993LE38100014 PM 8389152 ER PT J AU CHEN, LL NARAYANAN, R HIBBS, MS BENN, PA CLAWSON, ML LU, G RHIM, JS GREENBERG, B MENDELSOHN, J AF CHEN, LL NARAYANAN, R HIBBS, MS BENN, PA CLAWSON, ML LU, G RHIM, JS GREENBERG, B MENDELSOHN, J TI ALTERED EPIDERMAL GROWTH-FACTOR SIGNAL-TRANSDUCTION IN ACTIVATED HA-RAS-TRANSFORMED HUMAN KERATINOCYTES SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID FACTOR-ALPHA; CELL-PROLIFERATION; FACTOR-BETA; EXPRESSION; ONCOGENE; RECEPTOR; GENE; DIFFERENTIATION; STIMULATION; INHIBITION C1 UNIV CONNECTICUT, CTR HLTH, DEPT MED, DIV RHEUMATOL, FARMINGTON, CT 06032 USA. UNIV CONNECTICUT, CTR HLTH, DEPT PEDIAT, FARMINGTON, CT 06032 USA. DEPT VET AFFAIRS MED CTR, NEWINGTON, CT 06111 USA. HOFFMANN LA ROCHE INC, DIV ONCOL, NUTLEY, NJ 07110 USA. MEM SLOAN KETTERING CANC CTR, RECEPTOR BIOL LAB, NEW YORK, NY 10021 USA. NCI, BETHESDA, MD 20892 USA. CORNELL UNIV, MED CTR, COLL MED, NEW YORK, NY 10021 USA. RP CHEN, LL (reprint author), UNIV CONNECTICUT, CTR HLTH, DEPT MED, DIV HEMATOL & ONCOL, FARMINGTON, CT 06032 USA. NR 34 TC 21 Z9 21 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 28 PY 1993 VL 193 IS 1 BP 167 EP 174 DI 10.1006/bbrc.1993.1605 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LE381 UT WOS:A1993LE38100025 PM 8503904 ER PT J AU SAKAI, N MILSTIEN, S AF SAKAI, N MILSTIEN, S TI AVAILABILITY OF TETRAHYDROBIOPTERIN IS NOT A FACTOR IN THE INABILITY TO DETECT NITRIC-OXIDE PRODUCTION BY HUMAN MACROPHAGES SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID INTERFERON-GAMMA; BIOSYNTHESIS; SYNTHASE; NITRATE; FIBROBLASTS; ARGININE; CELLS C1 NIMH,NEUROCHEM LAB,BLDG 36,RM 3D-30,BETHESDA,MD 20892. NR 25 TC 38 Z9 38 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 28 PY 1993 VL 193 IS 1 BP 378 EP 383 DI 10.1006/bbrc.1993.1634 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LE381 UT WOS:A1993LE38100054 PM 8503929 ER PT J AU WHEELER, D AF WHEELER, D TI A GEL-CONCENTRATION-INDEPENDENT RETARDATION DETECTED IN 2 FRAGMENTS OF THE RRNB P1 PROMOTER OF ESCHERICHIA-COLI USING TRANSVERSE POLYACRYLAMIDE PORE GRADIENT GEL-ELECTROPHORESIS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID ESCHERICHIA-COLI; KINETOPLAST DNA; CURVED DNA; BENT DNA; REPLICATION ORIGIN; CURVATURE; UPSTREAM; ADENINE; ANGLES RP WHEELER, D (reprint author), NICHHD,THEORET & PHYS BIOL LAB,BETHESDA,MD 20892, USA. NR 27 TC 8 Z9 8 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 28 PY 1993 VL 193 IS 1 BP 413 EP 419 DI 10.1006/bbrc.1993.1639 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LE381 UT WOS:A1993LE38100059 PM 8389150 ER PT J AU URRUTIA, RA JUNG, G HAMMER, JA AF URRUTIA, RA JUNG, G HAMMER, JA TI THE DICTYOSTELIUM MYOSIN-IE HEAVY-CHAIN GENE ENCODES A TRUNCATED ISOFORM THAT LACKS SEQUENCES CORRESPONDING TO THE ACTIN-BINDING SITE IN THE TAIL SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Note DE MYOSIN-I; MEMBRANE BINDING; DEVELOPMENTAL REGULATION; (D-DISCOIDEUM) ID ACANTHAMOEBA-CASTELLANII; DISCOIDEUM; PROTEINS AB We have isolated cDNA and genomic clones which together span the entire coding sequence for the 114.8 kDa heavy chain of Dictyostelium myosin IE (DMIE). The deduced primary sequence reveals a pattern characteristic of all myosins I, i.e., a myosin-like globular head domain fused to a tail domain that shows no similarity to the coiled-coil rod-like tail of type II myosins. The approx. 35 kDa tail domain of DMIE shows some sequence similarity to the membrane interaction region of other myosins I (tail-homology-region 1; TH-1), but lacks completely the sequences that correspond to the second actin binding site (the glycine-, proline- and alanine-rich TH-2 region and the src-like TH-3 region). Therefore, DMIE more closely resembles DMIA (Titus et al. (1989) Cell Regul 1, 55-63), which is also truncated, than DMIB and DMID, both of which possess all three tail homology regions. The similarity between the DMIE and DMIA isoforms extends to their pattern of expression, in which the steady state level of transcript for both genes is highest in vegetative cells and falls gradually after five to ten hours of starvation-induced development. Together, these results have important implications for interpreting and prioritizing gene targeting experiments designed to identify the functions of myosins I in vivo. C1 NHLBI,CELL BIOL LAB,BLDG 3,ROOM B1-22,BETHESDA,MD 20892. NR 23 TC 33 Z9 34 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 MAY 28 PY 1993 VL 1173 IS 2 BP 225 EP 229 DI 10.1016/0167-4781(93)90185-G PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LE830 UT WOS:A1993LE83000014 PM 8504170 ER PT J AU WEAVER, JL SZABO, G PINE, PS GOTTESMAN, MM GOLDENBERG, S ASZALOS, A AF WEAVER, JL SZABO, G PINE, PS GOTTESMAN, MM GOLDENBERG, S ASZALOS, A TI THE EFFECT OF ION-CHANNEL BLOCKERS, IMMUNOSUPPRESSIVE AGENTS, AND OTHER DRUGS ON THE ACTIVITY OF THE MULTIDRUG TRANSPORTER SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID P-GLYCOPROTEIN; MEMBRANE-POTENTIALS; CYCLOSPORIN-A; RESISTANCE; VERAPAMIL; CELLS; REVERSAL; ANALOGS; LYMPHOCYTES; VINCRISTINE AB The MDRI protein is an energy-dependent transport protein responsible for the multi-drug resistance seen in many tumors. A variety of drugs have been shown to inhibit the function of this pump, including compounds known to block various ion channels. The mouse lymphoma cell line L5178Y has been transduced with the human mdrI gene. Using this cell line, we have tested a number of compounds to determine whether there is a correlation between the ability to block a specific type of ion channel, or shift membrane potential, and the ability to act as an MDR-reversing agent using the fluorescent substrates Rhodamine 123 and daunorubicin as test compounds. Our results show no apparent correlation between the ability to block a specific ion channel and reversal of MDR transport ability. We have found active MDR inhibitors in compounds that affect K+, Na+, Ca++, H+, but not Cl- channels. Our data suggest that Cl-channel activity may be distinct from MDR activity. Several immunosuppressive compounds and analogs were also tested and found to be active reversing agents. Measurements suggest a significant difference in resting membrane potential between the L5178YvMDR line and the L5178Y parental cell line used in these experiments. No correlation was found between the ability of drugs to alter membrane potential and to inhibit MDR transport activity. Our results suggest that MDR transport function may be independent of the physiological movement of ions and show that a wide variety of compounds can inhibit MDR transport. C1 US FDA,CDER,DIV RES & TESTING,HFD-471,200 C ST SW,WASHINGTON,DC 20204. DEBRECEN UNIV MED,SCH MED,DEPT BIOPHYS,H-4012 DEBRECEN,HUNGARY. NCI,CELL BIOL LAB,BETHESDA,MD 20892. NR 31 TC 105 Z9 105 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAY 28 PY 1993 VL 54 IS 3 BP 456 EP 461 DI 10.1002/ijc.2910540317 PG 6 WC Oncology SC Oncology GA LE893 UT WOS:A1993LE89300016 PM 7685326 ER PT J AU SALK, J BRETSCHER, PA SALK, PL CLERICI, M SHEARER, GM AF SALK, J BRETSCHER, PA SALK, PL CLERICI, M SHEARER, GM TI A STRATEGY FOR PROPHYLACTIC VACCINATION AGAINST HIV SO SCIENCE LA English DT Editorial Material ID CELL-MEDIATED-IMMUNITY; CYTOTOXIC T-CELLS; SUBSETS; HELPER; LEISHMANIASIS; RESPONSES; INFECTION; IMMUNIZATION; INDUCTION; ENVELOPE C1 UNIV SASKATCHEWAN,DEPT MICROBIOL,SASKATOON S7N 0X0,SK,CANADA. JONAS SALK FDN,LA JOLLA,CA 92037. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. RP SALK, J (reprint author), SALK INST BIOL STUDIES,POB 85800,SAN DIEGO,CA 92138, USA. NR 69 TC 184 Z9 185 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD MAY 28 PY 1993 VL 260 IS 5112 BP 1270 EP 1272 DI 10.1126/science.8098553 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LE025 UT WOS:A1993LE02500032 PM 8098553 ER PT J AU JOHNSTON, MI HOTH, DF AF JOHNSTON, MI HOTH, DF TI PRESENT STATUS AND FUTURE-PROSPECTS FOR HIV THERAPIES SO SCIENCE LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; REVERSE-TRANSCRIPTASE INHIBITORS; AIDS-RELATED COMPLEX; PLACEBO-CONTROLLED TRIAL; RECOMBINANT SOLUBLE CD4; CHRONICALLY INFECTED-CELLS; DEFICIENCY SYNDROME AIDS; BLOOD MONONUCLEAR-CELLS; MURINE LEUKEMIA-VIRUS; REV TRANS-ACTIVATOR AB Since the discovery of human immunodeficiency virus (HIV) in 1983, significant progress has been made toward the discovery, development, and licensing of anti-HIV drugs. In vitro screens against whole virus are now being complemented by screens against specific viral targets, resulting in the development of clinical candidates acting at several critical stages of the viral life cycle. Despite these advances, clinical therapy remains largely palliative. In addition, it has recently been recognized that HIV resistance to most drugs may pose even greater obstacles. Moreover, emerging data on immunopathogenesis raise the possibility that even if virus was eliminated from an infected individual, the patient's immune system might not be capable of restoration to normal function. In the face of such obstacles, deeper insights into the pathogenic mechanisms of disease, aggressive exploitation of those mechanisms for therapeutic gain, and continued commitment of both public and private sectors to support and collaborate in this research are needed. RP JOHNSTON, MI (reprint author), NIAID, DIV AIDS, BASIC RES & DEV PROGRAM, BETHESDA, MD 20892 USA. NR 257 TC 179 Z9 182 U1 1 U2 9 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 MAY 28 PY 1993 VL 260 IS 5112 BP 1286 EP 1293 DI 10.1126/science.7684163 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LE025 UT WOS:A1993LE02500035 PM 7684163 ER PT J AU LATIF, F TORY, K GNARRA, J YAO, M DUH, FM ORCUTT, ML STACKHOUSE, T KUZMIN, I MODI, W GEIL, L SCHMIDT, L ZHOU, FW LI, H WEI, MH CHEN, F GLENN, G CHOYKE, P WALTHER, MM WENG, YK DUAN, DSR DEAN, M GLAVAC, D RICHARDS, FM CROSSEY, PA FERGUSONSMITH, MA LEPASLIER, D CHUMAKOV, I COHEN, D CHINAULT, AC MAHER, ER LINEHAN, WM ZBAR, B LERMAN, MI AF LATIF, F TORY, K GNARRA, J YAO, M DUH, FM ORCUTT, ML STACKHOUSE, T KUZMIN, I MODI, W GEIL, L SCHMIDT, L ZHOU, FW LI, H WEI, MH CHEN, F GLENN, G CHOYKE, P WALTHER, MM WENG, YK DUAN, DSR DEAN, M GLAVAC, D RICHARDS, FM CROSSEY, PA FERGUSONSMITH, MA LEPASLIER, D CHUMAKOV, I COHEN, D CHINAULT, AC MAHER, ER LINEHAN, WM ZBAR, B LERMAN, MI TI IDENTIFICATION OF THE VONHIPPEL-LINDAU DISEASE TUMOR-SUPPRESSOR GENE SO SCIENCE LA English DT Article ID RENAL-CELL CARCINOMA; POINT MUTATIONS; CANCER; CHROMOSOME-5Q21; REGION; FAP AB A gene discovered by positional cloning has been identified as the von Hippel-Lindau (VHL) disease tumor suppressor gene. A restriction fragment encompassing the gene showed rearrangements in 28 of 221 VHL kindreds. Eighteen of these rearrangements were due to deletions in the candidate gene, including three large nonoverlapping deletions. Intragenic mutations were detected in cell lines derived from VHL patients and from sporadic renal cell carcinomas. The VHL gene is evolutionarily conserved and encodes two widely expressed transcripts of approximately 6 and 6.5 kilobases. The partial sequence of the inferred gene product shows no homology to other proteins, except for an acidic repeat domain found in the procyclic surface membrane glycoprotein of Trypanosoma brucei. C1 UNIV CAMBRIDGE,DEPT PATHOL,CAMBRIDGE CB2 1QP,ENGLAND. NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,FREDERICK,MD 21702. NCI,SURG BRANCH,BETHESDA,MD 20892. NCI,CANC DIAG BRANCH,BETHESDA,MD 20892. NCI,DEPT RADIOL,CTR CLIN,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. CTR ETUD POLYMORPHISME HUMAIN,F-75010 PARIS,FRANCE. BAYLOR COLL MED,INST MOLEC GENET,HOUSTON,TX 77030. RI MAHER, EAMONN/A-9507-2008; Dean, Michael/G-8172-2012 OI MAHER, EAMONN/0000-0002-6226-6918; Dean, Michael/0000-0003-2234-0631 NR 37 TC 1886 Z9 1959 U1 8 U2 43 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD MAY 28 PY 1993 VL 260 IS 5112 BP 1317 EP 1320 DI 10.1126/science.8493574 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LE025 UT WOS:A1993LE02500041 PM 8493574 ER PT J AU HOWCROFT, TK STREBEL, K MARTIN, MA SINGER, DS AF HOWCROFT, TK STREBEL, K MARTIN, MA SINGER, DS TI REPRESSION OF MHC CLASS-I GENE PROMOTER ACTIVITY BY 2-EXON TAT OF HIV SO SCIENCE LA English DT Article ID NF-KAPPA-B; EXPRESSION; RECOGNITION; MODULATION; INFECTION; PROTEINS; PRODUCT; DENSITY; H-2KB AB Major histocompatibility complex (MHC) class I molecules are the major receptors for viral peptides and serve as targets for specific cytotoxic T lymphocytes. Human immunodeficiency virus-type 1 (HIV-1) specifically decreased activity of an MHC class I gene promoter up to 12-fold. Repression was effected by the HIV-1 Tat protein derived from a spliced viral transcript (two-exon Tat). These studies define an activity for two-exon Tat distinct from that of one-exon Tat and suggest a mechanism whereby HIV-1-infected cells might be able to avoid immune surveillance, allowing the virus to persist in the infected host. C1 NCI,EXPTL IMMUNOL BRANCH,BLDG 10,ROOM 4B-17,BETHESDA,MD 20892. NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. NR 23 TC 189 Z9 191 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 MAY 28 PY 1993 VL 260 IS 5112 BP 1320 EP 1322 DI 10.1126/science.8493575 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LE025 UT WOS:A1993LE02500042 PM 8493575 ER PT J AU HEINEMANN, JA AF HEINEMANN, JA TI BATESON AND PEACOCKS TAILS SO NATURE LA English DT Letter RP HEINEMANN, JA (reprint author), NIAID,ROCKY MT LABS,HAMILTON,MT 59840, USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD MAY 27 PY 1993 VL 363 IS 6427 BP 308 EP 308 DI 10.1038/363308a0 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LD917 UT WOS:A1993LD91700032 PM 8497313 ER PT J AU CHELAZZI, L MILLER, EK DUNCAN, J DESIMONE, R AF CHELAZZI, L MILLER, EK DUNCAN, J DESIMONE, R TI A NEURAL BASIS FOR VISUAL-SEARCH IN INFERIOR TEMPORAL CORTEX SO NATURE LA English DT Article ID SUPERIOR COLLICULUS; SINGLE UNITS; ATTENTION; FEATURES; NEURONS; MONKEY AB WE often search for a face in a crowd or for a particular object in a cluttered environment. In this type of visual search, memory interacts with attention: the mediating neural mechanisms should include a stored representation of the object and a means for selecting that object from among others in the scene1-4. Here we test whether neurons in inferior temporal cortex, an area known to be important for high-level visual processing, might provide these components. Monkeys were presented with a complex picture (the cue) to hold in memory during a delay period. The cue initiated activity that persisted through the delay among the neurons that were tuned to its features. The monkeys were then given 2-5 choice pictures and were required to make an eye movement to the one (the target) that matched the cue. About 90-120 milliseconds before the onset of the eye movement to the target, responses to non-targets were suppressed and the neuronal response was dominated by the target. The results suggest that inferior temporal cortex is involved in selecting the objects to which we attend and foveate. C1 MRC,APPL PSYCHOL UNIT,CAMBRIDGE CB2 2EF,ENGLAND. RP CHELAZZI, L (reprint author), NIMH,NEUROPSYCHOL LAB,BLDG 9,ROOM 1E104,BETHESDA,MD 20892, USA. RI Chelazzi, Leonardo/B-6084-2011 OI Chelazzi, Leonardo/0000-0001-8566-0611 NR 13 TC 692 Z9 711 U1 6 U2 25 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD MAY 27 PY 1993 VL 363 IS 6427 BP 345 EP 347 DI 10.1038/363345a0 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LD917 UT WOS:A1993LD91700051 PM 8497317 ER PT J AU HUGHES, W LEOUNG, G KRAMER, F BOZZETTE, SA SAFRIN, S FRAME, P CLUMECK, N MASUR, H LANCASTER, D CHAN, C LAVELLE, J ROSENSTOCK, J FALLOON, J FEINBERG, J LAFON, S ROGERS, M SATTLER, F AF HUGHES, W LEOUNG, G KRAMER, F BOZZETTE, SA SAFRIN, S FRAME, P CLUMECK, N MASUR, H LANCASTER, D CHAN, C LAVELLE, J ROSENSTOCK, J FALLOON, J FEINBERG, J LAFON, S ROGERS, M SATTLER, F TI COMPARISON OF ATOVAQUONE (566C80) WITH TRIMETHOPRIM-SULFAMETHOXAZOLE TO TREAT PNEUMOCYSTIS-CARINII PNEUMONIA IN PATIENTS WITH AIDS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; HYDROXYNAPHTHOQUINONE; PENTAMIDINE; POTENT AB Background. Both trimethoprim-sulfamethoxazole and pentamidine are effective as treatments for Pneumocystis carinii pneumonia, but adverse effects frequently limit their use. Atovaquone (566C80) is a new hydroxynaphthoquinone with activity against P. carinii. Methods. We conducted a double-blind, multicenter study in patients with the acquired immunodeficiency syndrome and mild or moderately severe P. carinii pneumonia. They were randomly assigned to 21 days of orally administered treatment three times daily with either atovaquone (750 mg) or trimethoprim (320 mg) plus sulfamethoxazole (1600 mg). Results. Of the 322 patients with histologically confirmed P. carinii pneumonia, 160 received atovaquone and 162 received trimethoprim-sulfamethoxazole. Of those who could be evaluated for therapeutic efficacy, 28 of 138 patients given atovaquone (20 percent) and 10 of 146 patients given trimethoprim-sulfamethoxazole (7 percent) did not respond (P = 0.002). Treatment-limiting adverse effects required a change of therapy in 11 patients in the atovaquone group (7 percent) and 33 patients in the trimethoprim-sulfamethoxazole group (20 percent) (P = 0.001). Therapy involving only the initial drug was successful and free of adverse effects in 62 percent of those assigned to atovaquone and 64 percent of those assigned to trimethoprim-sulfamethoxazole. Within four weeks of the completion of treatment, there were 11 deaths in the atovaquone group (4 due to P. carinii pneumonia) and 1 death in the trimethoprim-sulfamethoxazole group (P = 0.003). Diarrhea at entry was associated with lower plasma drug concentrations (P = 0.009), therapeutic failure (P<0.001), and death (P<0.001) in the atovaquone group but not in the trimethoprim-sulfamethoxazole group. Conclusions. For the treatment of P. carinii pneumonia, atovaquone is less effective than trimethoprim-sulfamethoxazole, but it has fewer treatment-limiting adverse effects. C1 DAVIES MED CTR, DEPT MED, SAN FRANCISCO, CA USA. LOS ANGELES CTY HOSP, LOS ANGELES, CA USA. UNIV SO CALIF, LOS ANGELES, CA 90089 USA. UNIV CALIF SAN DIEGO, LA JOLLA, CA 92093 USA. UNIV CINCINNATI, CINCINNATI, OH 45221 USA. HOP UNIV ST PIERRE, B-1000 BRUSSELS, BELGIUM. NIH, DEPT CRIT CARE MED, BETHESDA, MD 20892 USA. UNIV TENNESSEE CTR HLTH SCI, REG MED CTR, DEPT MED, MEMPHIS, TN 38163 USA. WELLESLEY COLL HOSP, TORONTO M4Y 1J3, ONTARIO, CANADA. GEORGETOWN UNIV, MED CTR, WASHINGTON, DC 20007 USA. SAN FRANCISCO GEN HOSP, SAN FRANCISCO, CA 94110 USA. UNIV CALIF SAN FRANCISCO, SAN FRANCISCO, CA 94143 USA. INFECT DIS RES CONSORTIUM, ATLANTA, GA USA. JOHNS HOPKINS UNIV HOSP, BALTIMORE, MD 21205 USA. BURROUGHS WELLCOME CO, DEPT INFECT DIS & IMMUNOL, RES TRIANGLE PK, NC 27709 USA. NIAID, DIV AIDS, AIDS CLIN TRIALS GRP, BETHESDA, MD 20892 USA. NIAID, CALIF CLIN TRIALS GRP, BETHESDA, MD 20892 USA. RP HUGHES, W (reprint author), ST JUDE CHILDRENS RES HOSP, DEPT INFECT DIS, 332 N LAUDERDALE, MEMPHIS, TN 38105 USA. NR 13 TC 194 Z9 196 U1 1 U2 3 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 27 PY 1993 VL 328 IS 21 BP 1521 EP 1527 DI 10.1056/NEJM199305273282103 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA LC941 UT WOS:A1993LC94100003 PM 8479489 ER PT J AU MERENDINO, JJ SPIEGEL, AM CRAWFORD, JD OCARROLL, AM BROWNSTEIN, MJ LOLAIT, SJ AF MERENDINO, JJ SPIEGEL, AM CRAWFORD, JD OCARROLL, AM BROWNSTEIN, MJ LOLAIT, SJ TI A MUTATION IN THE VASOPRESSIN V2-RECEPTOR GENE IN A KINDRED WITH X-LINKED NEPHROGENIC DIABETES-INSIPIDUS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Note ID RECEPTORS; DNA C1 NIMH,CELL BIOL LAB,BETHESDA,MD 20892. MASSACHUSETTS GEN HOSP,CHILDRENS SERV,BOSTON,MA 02114. RP MERENDINO, JJ (reprint author), NIDDKD,MOLEC PATHOPHYSIOL BRANCH,BLDG 10,RM 8C-101,BETHESDA,MD 20892, USA. RI Brownstein, Michael/B-8609-2009 NR 26 TC 51 Z9 51 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 27 PY 1993 VL 328 IS 21 BP 1538 EP 1541 DI 10.1056/NEJM199305273282106 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA LC941 UT WOS:A1993LC94100006 PM 8479491 ER PT J AU SIDRANSKY, E MARTIN, B GINNS, EI AF SIDRANSKY, E MARTIN, B GINNS, EI TI TREATMENT OF GAUCHERS-DISEASE SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID INHERITED ENZYME DEFICIENCY; REPLACEMENT THERAPY; GLUCOCEREBROSIDASE RP SIDRANSKY, E (reprint author), NIMH,BETHESDA,MD 20892, USA. NR 3 TC 6 Z9 6 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 27 PY 1993 VL 328 IS 21 BP 1566 EP 1566 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA LC941 UT WOS:A1993LC94100016 PM 8479500 ER PT J AU MORRISON, AR AF MORRISON, AR TI EXPERIMENTING ON ANIMALS SO NEW YORK REVIEW OF BOOKS LA English DT Letter RP MORRISON, AR (reprint author), NATL INST MENTAL HEALTH,OFF ANIMAL RES ISS,BETHESDA,MD, USA. NR 5 TC 0 Z9 0 U1 0 U2 1 PU NEW YORK REVIEW PI NEW YORK PA 250 WEST 57TH ST, NEW YORK, NY 10107 SN 0028-7504 J9 NEW YORK REV BOOKS JI N. Y. Rev. Books PD MAY 27 PY 1993 VL 40 IS 10 BP 49 EP 49 PG 1 WC Humanities, Multidisciplinary SC Arts & Humanities - Other Topics GA LA955 UT WOS:A1993LA95500023 ER PT J AU HEALY, B AF HEALY, B TI DOES VASECTOMY CAUSE PROSTATE-CANCER SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP HEALY, B (reprint author), NIH,BLDG 31,ROOM 2B19,BETHESDA,MD 20892, USA. NR 9 TC 18 Z9 18 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 26 PY 1993 VL 269 IS 20 BP 2620 EP 2620 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA LC865 UT WOS:A1993LC86500010 PM 8487436 ER PT J AU WALKER, WG NEATON, JD CUTLER, JA COHEN, JD NEUWIRTH, R AF WALKER, WG NEATON, JD CUTLER, JA COHEN, JD NEUWIRTH, R TI RENAL-DISEASE IN HYPERTENSIVE BLACKS - MRFIT - REPLY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 UNIV MINNESOTA,MINNEAPOLIS,MN 55455. NHLBI,BETHESDA,MD 20892. ST LOUIS UNIV,MED CTR,ST LOUIS,MO 63103. SANDOZ PHARMACEUT CORP,E HANOVER,NJ. RP WALKER, WG (reprint author), JOHNS HOPKINS UNIV,BALTIMORE,MD 21218, USA. NR 4 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 MAY 26 PY 1993 VL 269 IS 20 BP 2630 EP 2630 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA LC865 UT WOS:A1993LC86500025 ER PT J AU MONTI, E MIMNAUGH, EG SINHA, BK AF MONTI, E MIMNAUGH, EG SINHA, BK TI SYNERGISTIC ANTIPROLIFERATIVE EFFECTS OF INTERLEUKIN-1-ALPHA AND DOXORUBICIN AGAINST THE HUMAN OVARIAN-CARCINOMA CELL-LINE (NIH-OVCAR-3) SO BIOCHEMICAL PHARMACOLOGY LA English DT Article ID HUMAN-MELANOMA CELLS; RECEPTORS; EXPRESSION; BINDING; CANCER; IL-1; INTERNALIZATION; FIBROBLASTS; INDUCTION; BIOLOGY AB Interleukin-1alpha (IL-1alpha) exerts antiproliferative effects on a human ovarian carcinoma cell line, NIH:OVCAR-3, which is resistant to clinically relevant concentrations of doxorubicin (DOX) and other chemotherapeutic agents. This action of IL-1alpha depends on the presence of type I (80 kDa) receptors, although no quantitative relationship has been established between receptor occupancy and inhibition of cell growth. When NIH:OVCAR-3 cells were exposed to IL-1alpha and DOX in combination, a mutual potentiation of the antiproliferative effects of the two agents was observed. This synergistic effect was pot due to IL-1 receptor expression up-regulation by DOX, and receptor-dependent internalization of the cytokine was also unaffected. The involvement of IL-1 receptors is supported by the observation that synergism between the two agents was diminished (but not abolished) in the presence of a specific IL-1 receptor antagonist at concentrations blocking more than 75% of IL-1alpha binding. DOX was found to significantly increase IL-1alpha accumulation by NIH: OVCAR-3 cells after long-term (48 hr) exposure to the cytokine at 37-degrees, which might be due to increased nonspecific fluid phase uptake or to interference with cytokine degradation and/or release processes. The potent synergy of IL-1alpha and DOX against ovarian carcinoma cells in vitro suggests that this drug combination may be effective against this disease in the clinic. C1 NCI,CLIN PHARMACOL BRANCH,BIOCHEM & MOLEC PHARMACOL SECT,BLDG 10,ROOM 6N-119,BETHESDA,MD 20892. NR 31 TC 10 Z9 10 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD MAY 25 PY 1993 VL 45 IS 10 BP 2099 EP 2107 DI 10.1016/0006-2952(93)90022-O PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LF228 UT WOS:A1993LF22800022 PM 8512591 ER PT J AU SCHERRER, LC PICARD, D MASSA, E HARMON, JM SIMONS, SS YAMAMOTO, KR PRATT, WB AF SCHERRER, LC PICARD, D MASSA, E HARMON, JM SIMONS, SS YAMAMOTO, KR PRATT, WB TI EVIDENCE THAT THE HORMONE-BINDING DOMAIN OF STEROID-RECEPTORS CONFERS HORMONAL-CONTROL ON CHIMERIC PROTEINS BY DETERMINING THEIR HORMONE-REGULATED BINDING TO HEAT-SHOCK PROTEIN-90 SO BIOCHEMISTRY LA English DT Article ID CELL GLUCOCORTICOID RECEPTOR; HUMAN ESTROGEN-RECEPTOR; DNA-BINDING; PROGESTERONE-RECEPTOR; NUCLEAR-LOCALIZATION; TRANSCRIPTIONAL ENHANCEMENT; DEPENDENT TRANSFORMATION; DEOXYRIBONUCLEIC-ACID; SIGNAL TRANSDUCTION; FUNCTIONAL DOMAINS AB Previously, it has been shown that the hormone binding domain of the glucocorticoid receptor acts as a transferable regulatory cassette that can confer hormonal control onto chimeric proteins [Picard, D., Salser, S. J., & Yamamoto, K. R. (1988) Cell 54,1073-1080]. The hormone binding domain of the glucocorticoid receptor contains its site of interaction with the 90-kDa heat-shock protein, hsp90 [Dalman, F.C., Scherrer, L.C., Taylor, L.P., Akil, H., & Pratt, W. B. (1991) J. Biol. Chem. 266, 3482-3490]. We have now transfected COS cells with cDNAs for fusion proteins containing beta-galactosidase and portions of the glucocorticoid receptor, and we demonstrate a correlation between hormone regulation of fusion protein localization and binding of the fusion proteins to hsp90. The hormone binding domain (residues 540-795) of the rat glucocorticoid receptor is sufficient for conferring hormone regulation onto a fusion protein and for intracellular binding of a fusion protein to hsp90. The hormone binding domain of the rat glucocorticoid or the human estrogen receptor is also sufficient to permit reticulocyte lysate-mediated refolding of a fusion protein into association with hsp90. Consistent with the results of fusion protein localization in intact cells, binding of a fusion protein to hsp90 blocks binding of an antibody directed against the NL1 nuclear localization signal of the glucocorticoid receptor. These observations argue strongly that the hormone binding domain of the glucocorticoid receptor confers hormonal control on fusion proteins by conferring hormone-regulated binding to hsp90. C1 UNIV MICHIGAN,SCH MED,DEPT PHARMACOL,ANN ARBOR,MI 48109. UNIV GENEVA,DEPT BIOL CELLULAIRE,CH-1211 GENEVA 4,SWITZERLAND. UNIFORMED SERV UNIV HLTH SCI,DEPT PHARMACOL,BETHESDA,MD 20814. NIH,MOLEC & CELLULAR BIOL LAB,STEROID HORMONES SECT,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,DEPT BIOCHEM & BIOPHYS,SAN FRANCISCO,CA 94143. FU NCI NIH HHS [CA28010, CA32226] NR 44 TC 98 Z9 99 U1 1 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 MAY 25 PY 1993 VL 32 IS 20 BP 5381 EP 5386 DI 10.1021/bi00071a013 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LD661 UT WOS:A1993LD66100013 PM 8499442 ER PT J AU MUNGER, K PHELPS, WC AF MUNGER, K PHELPS, WC TI THE HUMAN PAPILLOMAVIRUS-E7 PROTEIN AS A TRANSFORMING AND TRANSACTIVATING FACTOR SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Article ID RETINOBLASTOMA GENE-PRODUCT; E2F TRANSCRIPTION FACTOR; ADENOVIRUS E1A PROTEINS; LARGE T-ANTIGEN; PRIMARY HUMAN KERATINOCYTES; CERVICAL-CARCINOMA CELLS; HPV18 REGULATORY REGION; OPEN READING FRAMES; MONKEY COS-1 CELLS; TYPE-16 E7 GENE C1 BURROUGHS WELLCOME CO,DIV VIROL,RES TRIANGLE PK,NC 27709. RP MUNGER, K (reprint author), NCI,TUMOR VIRUS BIOL LAB,BETHESDA,MD 20892, USA. OI Munger, Karl/0000-0003-3288-9935 NR 186 TC 72 Z9 73 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-3002 J9 BIOCHIM BIOPHYS ACTA PD MAY 25 PY 1993 VL 1155 IS 1 BP 111 EP 123 DI 10.1016/0304-419X(93)90025-8 PG 13 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LF800 UT WOS:A1993LF80000007 PM 8389201 ER PT J AU TSAI, SC ADAMIK, R HAUN, RS MOSS, J VAUGHAN, M AF TSAI, SC ADAMIK, R HAUN, RS MOSS, J VAUGHAN, M TI EFFECTS OF BREFELDIN-A AND ACCESSORY PROTEINS ON ASSOCIATION OF ADP-RIBOSYLATION FACTOR-I, FACTOR-III, AND FACTOR-5 WITH GOLGI SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GTP-BINDING PROTEINS; NUCLEOTIDE-BINDING; CHOLERA-TOXIN; BOVINE BRAIN; ACTIVATOR; STIMULATION; EXPRESSION; VESICLES; MEMBRANE; CELLS AB ADP-ribosylation factors (ARFs) are approximately 20-kDa guanine nucleotide-binding proteins initially identified by their ability to enhance in vitro cholera toxin-catalyzed ADP-ribosylation and subsequently shown to participate in vesicular transport in the Golgi and other cellular compartments. By cDNA and genomic cloning, at least six mammalian ARFs were identified. Brefeldin A (BFA) disrupts Golgi membranes and inhibits binding of soluble high molecular weight proteins to Golgi fractions. We examined the effects of BFA on binding of ARF1, -3, and -5 to a Golgi fraction in the presence of an ATP-regenerating system and a fraction of soluble, high molecular weight, accessory proteins (SAP), presumably containing complexes identified by others as coatomers that are involved in vesicular transport. ARF binding in all instances was dependent on guanosine 5'-O-(3-thiotriphosphate) and increased by the ATP-regenerating system. Binding of ARF1 and -3, but not ARF5, was enhanced by SAP. BFA inhibited the SAP-dependent, but not the SAP-independent, binding of ARF1 and -3. It had no effect on the increment in binding produced by an ATP-regenerating system. B36, an inactive derivative of BFA, did not inhibit SAP-dependent binding of ARF1 and -3. Binding of ARF5, which was SAP-independent, was not affected by BFA. These observations are consistent with the conclusion that mammalian ARFs differ in their dependence on accessory proteins for interaction with Golgi and, perhaps, other cellular membranes and that BFA specifically inhibits SAP-dependent ARF binding. RP TSAI, SC (reprint author), NHLBI,CELLULAR METAB LAB,RM 5N-307,BLDG 10,BETHESDA,MD 20892, USA. NR 38 TC 55 Z9 55 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 25 PY 1993 VL 268 IS 15 BP 10820 EP 10825 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LD466 UT WOS:A1993LD46600020 PM 8496147 ER PT J AU YANG, YS RAMASWAMY, S JAKOBY, WB AF YANG, YS RAMASWAMY, S JAKOBY, WB TI RAT-LIVER IMIDASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DIHYDROPYRIMIDINE AMIDOHYDROLASE; PURIFICATION; ACID AB Imidase, an enzyme variously identified as dihydropyrimidinase (EC 3.5.2.2), hydantoinase, dihydropyrimidine hydrase, and dihydropyrimidine amidohydrolase, has been purified to electrophoretic homogeneity from rat liver. Although a component in the chain of pyrimidine catabolism, imidase is capable of serving in a broader role that includes detoxication of xenobiotics. The enzyme catalyzes the hydrolytic cleavage of imides that range from the linear to the heterocyclic and that include hydantoins, dihydropyrimidines, and phthalimide. For some substrates, the reaction is experimentally reversible. The pH activity curves are a function of the pK(a) of the individual substrate's imino group, with cleavage favored at a pH near the respective pK(a) value. There is evidence for stereoselectivity and for stereospecificity. A mechanism is proposed for the enzyme-catalyzed reaction. C1 NIDDKD,BIOCHEM & METAB LAB,BLDG 10,ROOM 9N119,BETHESDA,MD 20892. NR 20 TC 34 Z9 38 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 25 PY 1993 VL 268 IS 15 BP 10870 EP 10875 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LD466 UT WOS:A1993LD46600026 PM 8388376 ER PT J AU LEBRUN, C BARON, V KALIMAN, P GAUTIER, N DOLAISKITABGI, J TAYLOR, S ACCILI, D VANOBBERGHEN, E AF LEBRUN, C BARON, V KALIMAN, P GAUTIER, N DOLAISKITABGI, J TAYLOR, S ACCILI, D VANOBBERGHEN, E TI ANTIBODIES TO THE EXTRACELLULAR RECEPTOR DOMAIN RESTORE THE HORMONE-INSENSITIVE KINASE AND CONFORMATION OF THE MUTANT INSULIN-RECEPTOR VALINE-382 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-FREE SYSTEM; TYROSINE KINASE; PHOSPHORYLATION; BINDING; MUTATION; IMPAIRS; DEFECT AB A mutation substituting a valine for phenylalanine at residue 382 in the insulin receptor alpha-subunit has been found in two sisters with a genetic form of extreme insulin resistance. This receptor mutation impairs the ability of the hormone to activate autophosphorylation of solubilized receptors and phosphorylation of substrates (Accili, D., Mosthaf, L., Ullrich, A., and Taylor, S. I. (1991) J. Biol. Chem. 266, 434-439). We have previously demonstrated that in native receptors insulin induces a conformational change in the receptor beta-subunit, which is thought to be necessary for receptor activation (Baron, V., Gautier, N., Komoriya, A., Hainaut, P., Scimeca, J. C., Mervic, M., Lavielle, S., Dolais-Kitabgi, J., and Van Obberghen, E. (1990) Biochemistry 29, 4634-4641). Hence, it was thought that a defect in this conformational change might explain the functional defect of the mutant receptor. This appears to be the case, as we demonstrate here that the mutant receptor is locked in its inactive configuration. However, we found two monoclonal antibodies, directed to the extracellular domain, which are capable of restoring the mutant receptor kinase activity. The activation of the mutant receptor was accompanied by restoration of conformational changes in the beta-subunit C terminus. From these data, we draw the two following conclusions. (i) A causal link exists between receptor kinase activation and the occurrence of conformational changes. (ii) Ligands other than insulin, such as antibodies, which perturb the extracellular domain, can function as alternative ways to restore the mutant receptor kinase. C1 FAC MED NICE,INSERM,U145,AVE VALOMBROSE,F-06107 NICE 2,FRANCE. NIDDKD,DIABET BRANCH,BETHESDA,MD 20892. NR 22 TC 20 Z9 21 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 25 PY 1993 VL 268 IS 15 BP 11272 EP 11277 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LD466 UT WOS:A1993LD46600081 PM 8388389 ER PT J AU ZINOVIEVA, RD TOMAREV, SI PIATIGORSKY, J AF ZINOVIEVA, RD TOMAREV, SI PIATIGORSKY, J TI ALDEHYDE DEHYDROGENASE-DERIVED OMEGA-CRYSTALLINS OF SQUID AND OCTOPUS - SPECIALIZATION FOR LENS EXPRESSION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MOLECULAR-CLONING; CORNEAL PROTEIN; RAT; RECRUITMENT; CDNA; SEQUENCE; SITE; EVOLUTION; ENZYMES; EYE AB OMEGA-crystallin of the octopus lens is related to aldehyde dehydrogenases (ALDH) of vertebrates (Tomarev, S. I., Zinovieva, R. D., and Piatigorsky, J. (1991) J. Biol. Chem. 266, 24226-24231) and ALDH1/eta-crystallin of elephant shrews (Wistow, G., and Kim, H. (1991) J. Mol. Evol. 32, 262-269). Only very low amounts of OMEGA-crystallin are present in the squid lens. Here, we have cloned OMEGA-crystallin cDNAs of the octopus (Octopus dofleini) and squid (Ommastrephes sloani pacificus) lenses. The deduced amino acid sequences of OMEGA-crystallin from these species are 78% identical to each other, 56-58% identical to cytoplasmic ALDH1 and mitochondrial ALDH2 of vertebrates (which are 66-68% identical to each other), and 40% identical to Escherichia coli and spinach ALDHs. These data are consistent with the idea that the ALDH1/ALDH2 gene duplication in vertebrates occurred after divergence of cephalopods from the line giving rise to vertebrates, but before the separation of squid and octopus. Southern blot hybridization indicated that OMEGA-crystallin is encoded by few genes (possibly just one) in octopus and squid. Northern blot hybridization revealed two bands (2.7 and 9.0 kilobases) of OMEGA-crystallin RNA in the octopus lens and one band (4.2 kilobases) in the squid lens; OMEGA-crystallin RNAs were undetectable in numerous non-lens tissues of octopus and squid, suggesting lens-specific expression of this gene(s). Finally, extracts of the octopus lens had no detectable ALDH activity using different substrates, consistent with OMEGA-crystallin having no enzymatic activity. Taken together, our results suggest that OMEGA-crystallin evolved by duplication of an ancestral gene encoding ALDH and subsequently specialized for refraction in the transparent lens while losing ALDH activity and expression in other tissues. C1 NEI,MOLEC & DEV BIOL LAB,BETHESDA,MD 20892. NR 46 TC 46 Z9 48 U1 2 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 25 PY 1993 VL 268 IS 15 BP 11449 EP 11455 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LD466 UT WOS:A1993LD46600105 PM 7684383 ER PT J AU GREENE, JM OTANI, H GOOD, PJ DAWID, IB AF GREENE, JM OTANI, H GOOD, PJ DAWID, IB TI A NOVEL FAMILY OF RETROTRANSPOSON-LIKE ELEMENTS IN XENOPUS-LAEVIS WITH A TRANSCRIPT INDUCIBLE BY 2 GROWTH-FACTORS SO NUCLEIC ACIDS RESEARCH LA English DT Article ID TRANSPOSABLE ELEMENT; NUCLEOTIDE-SEQUENCE; RETROVIRAL PROTEINS; GENE; DNA; HOMOLOGY; EMBRYOS; EXPRESSION; GENOME; YEAST AB A cDNA clone named 1A11 was isolated in a screen for genes that are activated by both mesoderm inducing factors FGF and activin in animal explants of Xenopus laevis embryos. In undisturbed embryos, 1A11 is expressed during the gastrula stage in the entire marginal zone where mesoderm originates, and later in the somites, the tailbud, and at much lower levels in lateral mesoderm. The 1A11 sequence of 4.5 Kb has a 220 bp repeat at its ends, indicative of a retrotransposon-like structure. A long open reading frame encodes a predicted protein with only short homologies to the gag and protease regions of retroviruses and retrotransposons. Multiple copies of 1A11-related sequences were found in the Xenopus genome, constituting solo LTRs (long terminal repeats) of 1267 bp, and unique region copies (i.e., sequences internal to the repeats in the cDNA). Inverted repeats of 5 bp and apparent target site duplications of 5 bp surround the sequenced solo LTR. Thus, 1A11 is a new retrotransposon-like element in Xenopus laevis. C1 NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892. SHIMANE MED UNIV,DEPT ANAT,IZUMO,SHIMANE 693,JAPAN. NR 53 TC 21 Z9 21 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 MAY 25 PY 1993 VL 21 IS 10 BP 2375 EP 2381 DI 10.1093/nar/21.10.2375 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LF503 UT WOS:A1993LF50300014 PM 8389440 ER PT J AU LE, SY CHEN, JH SONENBERG, N MAIZEL, JV AF LE, SY CHEN, JH SONENBERG, N MAIZEL, JV TI CONSERVED TERTIARY STRUCTURAL ELEMENTS IN THE 5' NONTRANSLATED REGION OF CARDIOVIRUS, APHTHOVIRUS AND HEPATITIS-A VIRUS RNAS SO NUCLEIC ACIDS RESEARCH LA English DT Article ID MOUTH-DISEASE VIRUS; INTERNAL TRANSLATION INITIATION; MESSENGER-RNA; ENCEPHALOMYOCARDITIS VIRUS; POLIOVIRUS RNA; PROTEIN-SYNTHESIS; SECONDARY STRUCTURE; FUNCTIONAL-ANALYSIS; STATISTICAL SIGNIFICANCE; 5'-NONCODING REGION AB Statistical analyses of RNA folding in 5' nontranslated regions (5'NTR) of encephalomyocarditis virus, Theiler's murine encephalomyelitis virus, foot-and-mouth disease virus, and hepatitis A virus indicate that two highly significant folding regions occur in the 5' and 3' portions of the 5'NTR. The conserved tertiary structural elements are predicted in the unusual folding regions (UFR) for these viral RNAs. The theoretical, common structural elements predicted in the 3' parts of the 5'NTR occur in a cis-acting element that is critical for internal ribosome binding. These structural motifs are expected to be highly significant from extensive Monte Carlo simulations. Nucleotides (nt) in the conserved single-stranded polypyrimidine tract for these RNAs are involved in a distinctively tertiary interaction that is located at about 15 nt prior to the initiator AUG. Intriguingly, the proposed common tertiary structure in this study shares a similar structural feature to that proposed in human enteroviruses and rhinoviruses. Based on these common structural features, plausible base pairing models between these viral RNAs and 18 S rRNA are suggested, which are consistent with a general mechanism for regulation of internal initiation of cap-independent translation. C1 NCI FCRDC DYNCORP,PROGRAM RESOURCES INC,FREDERICK BIOMED SUPERCOMP CTR,FREDERICK,MD 21702. MCGILL UNIV,DEPT BIOCHEM,MONTREAL H3G 1Y6,QUEBEC,CANADA. MCGILL UNIV,MCGILL CANC CTR,MONTREAL H3G 1Y6,QUEBEC,CANADA. RP LE, SY (reprint author), NCI,DIV CANC BIOL DIAGN & CTR,MATH BIOL LAB,BLDG 469,ROOM 151,FREDERICK,MD 21702, USA. NR 50 TC 55 Z9 57 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 MAY 25 PY 1993 VL 21 IS 10 BP 2445 EP 2451 DI 10.1093/nar/21.10.2445 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LF503 UT WOS:A1993LF50300024 PM 8389442 ER PT J AU KOONIN, EV DEUTSCHER, MP AF KOONIN, EV DEUTSCHER, MP TI RNASE T-SHARES CONSERVED SEQUENCE MOTIFS WITH DNA PROOFREADING EXONUCLEASES SO NUCLEIC ACIDS RESEARCH LA English DT Note ID ESCHERICHIA-COLI; MUTATOR; GENE C1 UNIV CONNECTICUT,CTR HLTH,DEPT BIOCHEM,FARMINGTON,CT 06030. RP KOONIN, EV (reprint author), NIH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BLDG 38A,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. NR 11 TC 28 Z9 28 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 MAY 25 PY 1993 VL 21 IS 10 BP 2521 EP 2522 DI 10.1093/nar/21.10.2521 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LF503 UT WOS:A1993LF50300043 PM 8506149 ER PT J AU KLASSE, PJ PIPKORN, R BLOMBERG, J HAN, KH HILTON, B FERRETTI, JA AF KLASSE, PJ PIPKORN, R BLOMBERG, J HAN, KH HILTON, B FERRETTI, JA TI 3-DIMENSIONAL STRUCTURE AND ANTIGENICITY OF TRANSMEMBRANE-PROTEIN PEPTIDES OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 - EFFECTS OF A NEUTRALIZATION-ESCAPE SUBSTITUTION SO FEBS LETTERS LA English DT Article DE ANTIGENIC PEPTIDE; 3D STRUCTURE; ESCAPE MUTANT; HUMAN IMMUNODEFICIENCY VIRUS TYPE-1 ID NUCLEAR-MAGNETIC-RESONANCE; GROWTH FACTOR-ALPHA; ENVELOPE GLYCOPROTEIN; SECONDARY STRUCTURE; SYNTHETIC PEPTIDES; POINT MUTATION; SPECTROSCOPY; HIV-1; GP41; CONFORMATIONS AB A point mutation (Ala-589 to Thr) in the transmembrane protein of the human immunodeficiency virus type 1 (HIV-1) has been shown to decrease the sensitivity of the virus to the neutralizing effect of human HIV-1 specific antibodies [(1990) J. Virol. 64, 3240-3248]. Here 17-residue peptides with the parental and mutant sequences were compared: the parental peptide bound antibodies of sera from HIV-1 infected persons more frequently and with higher affinity than the mutant peptide. However, according to circular dichroism (CD), NMR spectroscopy and molecular modelling the peptides have indistinguishable backbone conformations under a variety of experimental conditions. These techniques showed for both peptides that no ordered helix was present in water solution. However, for both peptides in alcohol-water solutions approximately 60% alpha-helix could be induced. The three-dimensional structures of these peptides provide a basis for understanding how this mutation in the transmembrane protein may affect the interaction with both the outer envelope glycoprotein and with antibodies. C1 NHLBI,BIOPHYS CHEM LAB,BLDG 3,ROOM 418,BETHESDA,MD 20892. LUND UNIV,DEPT MED MICROBIOL,VIROL SECT,S-22101 LUND,SWEDEN. REPLICO AB,LOMMA,SWEDEN. PROGRAM RESOURCES INC DYNCORP,NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NR 23 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD MAY 24 PY 1993 VL 323 IS 1-2 BP 68 EP 72 DI 10.1016/0014-5793(93)81450-E PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA LC956 UT WOS:A1993LC95600016 ER PT J AU BAGDY, G KALOGERAS, KT AF BAGDY, G KALOGERAS, KT TI STIMULATION OF 5-HT(1A) AND 5-HT(2)/5-HT(1C) RECEPTORS INDUCE OXYTOCIN RELEASE IN THE MALE-RAT SO BRAIN RESEARCH LA English DT Article DE SEROTONIN 5-HT(1A) RECEPTOR; SEROTONIN 5-HT(1C) RECEPTOR; SEROTONIN 5-HT(2) RECEPTOR; OXYTOCIN; VASOPRESSIN; MALE RAT; BUSPIRONE; DOI (1-(2,5-DIMETHOXY-4-IODOPHENYL)2-AMINOPROPANE); IPSAPIRONE; 8-OH-DPAT (8-HYDROXY-2-(DI-N-PROPYLAMINO)TETRALIN); RITANSERIN; NAN-190 ID ENHANCED SEROTONERGIC TRANSMISSION; ACTIVATION; VASOPRESSIN; SECRETION; PITUITARY; NUCLEUS; SYSTEM; AGONISTS; FIBERS AB Plasma oxytocin responses to the 5-HT1A receptor agonists 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), buspirone and ipsapirone, and the 5-HT2/5-HT1C receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)2-aminopropane (DOI) have been studied in conscious, freely moving male rats. All four compounds caused dose-related increases in plasma oxytocin concentrations after intravenous administration. Oxytocin responses to 8-OH-DPAT were significantly attenuated by pretreatment with the 5-HT1A receptor antagonist NAN-190 while responses to DOI were blocked by pretreatment with the 5-HT2/5-HT1C receptor antagonist ritanserin. Since vasopressin concentration did not change despite the marked elevation in plasma oxytocin, these results suggest that 5-HT1A and 5-HT2/5-HT1C receptors all stimulate oxytocin secretion, and this effect does not reflect a general neurohypophyseal hormone release. C1 NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. RP BAGDY, G (reprint author), NATL INST PSYCHIAT & NEUROL,EXPTL MED LAB,HUVOSVOLGYI UT 116,POB 1,H-1281 BUDAPEST 27,HUNGARY. OI Bagdy, Gyorgy/0000-0001-8141-3410 NR 20 TC 53 Z9 53 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAY 21 PY 1993 VL 611 IS 2 BP 330 EP 332 DI 10.1016/0006-8993(93)90521-N PG 3 WC Neurosciences SC Neurosciences & Neurology GA LD968 UT WOS:A1993LD96800021 PM 8334526 ER PT J AU NJAR, VCO SAFI, E SILVERTON, JV ROBINSON, CH AF NJAR, VCO SAFI, E SILVERTON, JV ROBINSON, CH TI NOVEL 10-BETA-AZIRIDINYL STEROIDS - INHIBITORS OF AROMATASE SO JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1 LA English DT Article ID HUMAN PLACENTAL AROMATASE; CYTOCHROME-P-450 AROMATASE; 10-BETA-THIIRANYL STEROIDS; AROMATIZATION; ENZYME; C-19 AB The novel 10beta-aziridinylestr-4-ene-3,17-diones 17 and 18 and the corresponding 10beta-aziridinyl-17beta-hydroxyestr-4-en-3-ones 19 and 20 have been synthesized from the 19-oximino-19-methyl intermediate 12b. The key reaction was the conversion of the 19-oxime 12b into the diastereoisomeric 10beta-aziridines 13 and 14 by lithium aluminium hydride (LAH). Compounds 17-20 are powerful and stereoselective inhibitors of human placental microsomal aromatase. The most potent compound was 17(Ki = 3.4 nmol dm-3). The 19R-isomers 17 and 19 are more effective than the corresponding 19S-isomers 18 and 20, respectively. Unlike the corresponding 10beta-oxiranes and -thiiranes which are classical competitive inhibitors, the (19R)-aziridines 17 and 19 appear to be slow-binding inhibitors. Spectroscopic studies with microsomal aromatase preparations indicate that the inhibition process involves binding of aziridine nitrogen to the heme-iron of the enzyme. C1 NHLBI,CHEM LAB,BETHESDA,MD 20892. NR 33 TC 19 Z9 20 U1 0 U2 3 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK MILTON ROAD, CAMBRIDGE, CAMBS, ENGLAND CB4 4WF SN 0300-922X J9 J CHEM SOC PERK T 1 JI J. Chem. Soc.-Perkin Trans. 1 PD MAY 21 PY 1993 IS 10 BP 1161 EP 1168 DI 10.1039/p19930001161 PG 8 WC Chemistry, Organic SC Chemistry GA LE179 UT WOS:A1993LE17900014 ER PT J AU VARLEY, P GRONENBORN, AM CHRISTENSEN, H WINGFIELD, PT PAIN, RH CLORE, GM AF VARLEY, P GRONENBORN, AM CHRISTENSEN, H WINGFIELD, PT PAIN, RH CLORE, GM TI KINETICS OF FOLDING OF THE ALL BETA-SHEET PROTEIN INTERLEUKIN-1-BETA SO SCIENCE LA English DT Article ID NMR-SPECTROSCOPY; SECONDARY STRUCTURE; INTERMEDIATE; RESOLUTION; RESONANCE; ASSIGNMENT; FRAMEWORK; STABILITY; H-1 AB The folding of the all-beta sheet protein, interleukin-1beta, was studied with nuclear magnetic resonance (NMR) spectroscopy, circular dichroism, and fluorescence. Ninety percent of the beta structure present in the native protein, as monitored by far-ultraviolet circular dichroism, was attained within 25 milliseconds, correlating with the first kinetic phase determined by tryptophan and 1-anilinonaphthalene-8-sulfonate fluorescence. In contrast, formation of stable native secondary structure, as measured by quenched-flow deuterium-hydrogen exchange experiments, began after only 1 second. Results from the NMR experiments indicated the formation of at least two intermediates with half-lives of 0.7 to 1.5 and 15 to 25 seconds. The final stabilization of the secondary structure, however, occurs on a time scale much greater than 25 seconds. These results differ from previous results on mixed alpha helix-beta sheet proteins in which both the alpha helices and beta sheets were stabilized very rapidly (less than 10 to 20 milliseconds). C1 NIDDKD,CHEM PHYS LAB,BLDG 5,ROOM 132,BETHESDA,MD 20892. UNIV NEWCASTLE UPON TYNE,DEPT BIOCHEM & GENET,NEWCASTLE TYNE NE2 4HH,ENGLAND. NIH,PROT EXPRESS LAB,BETHESDA,MD 20892. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 24 TC 160 Z9 161 U1 1 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 MAY 21 PY 1993 VL 260 IS 5111 BP 1110 EP 1113 DI 10.1126/science.8493553 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LC942 UT WOS:A1993LC94200025 PM 8493553 ER PT J AU ALEXANDROV, IA MASHKOVA, TD ROMANOVA, LY YUROV, YB KISSELEV, LL AF ALEXANDROV, IA MASHKOVA, TD ROMANOVA, LY YUROV, YB KISSELEV, LL TI SEGMENT SUBSTITUTIONS IN ALPHA-SATELLITE DNA - UNUSUAL STRUCTURE OF HUMAN CHROMOSOME-3-SPECIFIC ALPHA-SATELLITE REPEAT UNIT SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Note DE ALPHA-SATELLITE; EVOLUTION; RECOMBINATION; GENE CONVERSION; DNA REPEATS ID REPETITIVE DNA; CHROMOSOME; ORGANIZATION; SEQUENCES; FAMILY C1 NATL RES CTR MENTAL HLTH,CYTOGENET LAB,MOSCOW,RUSSIA. ENGELHARDT INST MOLEC BIOL,MOLEC BASIS ONCOGENESIS LAB,MOSCOW,RUSSIA. NCI,CLIN PHARMACOL BRANCH,BLDG 10,ROOM 12C103,BETHESDA,MD 20892. RI Yurov, Yuri/D-9051-2016 OI Yurov, Yuri/0000-0002-9251-2286 NR 22 TC 6 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD MAY 20 PY 1993 VL 231 IS 2 BP 516 EP 520 DI 10.1006/jmbi.1993.1302 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LF055 UT WOS:A1993LF05500034 PM 8510162 ER PT J AU HEINEMANN, JA AF HEINEMANN, JA TI DIFFERENTIAL SALARY SCALES SO NATURE LA English DT Letter RP HEINEMANN, JA (reprint author), NIAID,LMSF,ROCKY MT LABS,HAMILTON,MT 59840, USA. NR 2 TC 1 Z9 1 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD MAY 20 PY 1993 VL 363 IS 6426 BP 202 EP 202 DI 10.1038/363202b0 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LC866 UT WOS:A1993LC86600016 PM 8487856 ER PT J AU DASILVA, AMT KAULBACH, HC CHUIDIAN, FS LAMBERT, DR SUFFREDINI, AF DANNER, RL AF DASILVA, AMT KAULBACH, HC CHUIDIAN, FS LAMBERT, DR SUFFREDINI, AF DANNER, RL TI SHOCK AND MULTIPLE-ORGAN DYSFUNCTION AFTER SELF-ADMINISTRATION OF SALMONELLA ENDOTOXIN SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Note ID TUMOR-NECROSIS-FACTOR; HUMAN SEPTIC SHOCK; CARDIOVASCULAR DYSFUNCTION; INTRAVENOUS ENDOTOXIN; ESCHERICHIA-COLI; CANINE MODEL; MORTALITY; INTERLEUKIN-1; SERUM C1 GEORGETOWN UNIV,DIV PULM & CRIT CARE MED,WASHINGTON,DC 20057. GEORGETOWN UNIV,DEPT MED,WASHINGTON,DC 20057. NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT CRIT CARE MED,BETHESDA,MD 20892. NR 26 TC 144 Z9 146 U1 0 U2 2 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 20 PY 1993 VL 328 IS 20 BP 1457 EP 1460 DI 10.1056/NEJM199305203282005 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA LB783 UT WOS:A1993LB78300005 ER PT J AU RODGERS, GP AF RODGERS, GP TI HIGH-DOSE ERYTHROPOIETIN FOR UNSTABLE HEMOGLOBIN BURKE IN A PATIENT RECEIVING HEMODIALYSIS - REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP RODGERS, GP (reprint author), NIH,BETHESDA,MD 20892, USA. NR 5 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 MAY 20 PY 1993 VL 328 IS 20 BP 1498 EP 1499 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA LB783 UT WOS:A1993LB78300028 ER PT J AU HUDZIK, TJ DECOSTA, BR MCMILLAN, DE AF HUDZIK, TJ DECOSTA, BR MCMILLAN, DE TI SIGMA-RECEPTOR-MEDIATED EMETIC RESPONSE IN PIGEONS - AGONISTS, ANTAGONISTS AND MODIFIERS SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE SIGMA RECEPTORS; EMESIS; DTG (1,3-DI-(2-TOLYL)GUANIDINE); (AGONISTS); (ANTAGONISTS); (MODIFIERS); (PIGEON) ID GUINEA-PIG BRAIN; CENTRAL NERVOUS-SYSTEM; BINDING-SITES; PHENCYCLIDINE; DRUGS; PCP; AFFINITY; LIGANDS; HALOPERIDOL AB In order to more fully characterize sigma ligand-induced emesis in the pigeon, the effects of a number of compounds were tested alone or in combination with ditolylguanidine (DTG). The drugs tested could be categorized into three types: agonists, which produced the emetic response (DTG > amitriptyline > BD 737 > thioridazine), antagonists, which effectively antagonized the effects of DTG (haloperidol > BMY 14802 > BD 1139 > chlorpromazine), and agents which did not produce the emetic response on their own, but potently enhanced the emetic effect of DTG (BD-1008 greater-than-or-equal-to phencyclidine > (+)-n-allylnormetazocine greater-than-or-equal-to propranolol). Chronic haloperidol resulted in a markedly diminished emetic response to DTG, which returned to control levels by 24.5 days. Haloperidol, but not BMY 14802, was effective in antagonizing the lethal effects of DTG. These data suggest further in vivo evidence for a functional mediation by sigma sites of the emetic response to DTG in the pigeon, and may provide in vivo evidence for potential allosteric modification of sigma ligands. C1 NIDDKD,MED CHEM LAB,BETHESDA,MD. UNIV ARKANSAS MED SCI HOSP,DEPT PHARMACOL & TOXICOL,LITTLE ROCK,AR 72205. NR 35 TC 7 Z9 7 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 MAY 19 PY 1993 VL 236 IS 2 BP 279 EP 287 DI 10.1016/0014-2999(93)90599-D PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LE019 UT WOS:A1993LE01900014 PM 8100532 ER PT J AU GRZESIEK, S ANGLISTER, J REN, H BAX, A AF GRZESIEK, S ANGLISTER, J REN, H BAX, A TI C-13 LINE NARROWING BY H-2 DECOUPLING IN H-2/C-13/N-15-ENRICHED PROTEINS - APPLICATION TO TRIPLE-RESONANCE 4D J-CONNECTIVITY OF SEQUENTIAL AMIDES SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Note ID NUCLEAR MAGNETIC-RESONANCE; NMR; ASSIGNMENT; SYSTEMS; SPECTRA; PHASE C1 NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. NCI,BIOCHEM LAB,BETHESDA,MD 20892. NR 23 TC 202 Z9 206 U1 1 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD MAY 19 PY 1993 VL 115 IS 10 BP 4369 EP 4370 DI 10.1021/ja00063a068 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA LC953 UT WOS:A1993LC95300068 ER PT J AU FREEDMAN, LS PRENTICE, RL CLIFFORD, C HARLAN, W HENDERSON, M ROSSOUW, J AF FREEDMAN, LS PRENTICE, RL CLIFFORD, C HARLAN, W HENDERSON, M ROSSOUW, J TI DIETARY-FAT AND BREAST-CANCER - WHERE WE ARE SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID RISK; FEASIBILITY; PREVENTION; REDUCTION C1 FRED HUTCHINSON CANC RES CTR,DIV PUBL HLTH SCI,CANC PREVENT RES PROGRAM,SEATTLE,WA 98104. NIH,OFF DIS PREVENT,BETHESDA,MD 20892. RP FREEDMAN, LS (reprint author), NCI,DIV CANC PREVENT & CONTROL,BIOMETRY BRANCH,EXECUT PLAZA N,BETHESDA,MD 20892, USA. NR 18 TC 35 Z9 35 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY 19 PY 1993 VL 85 IS 10 BP 764 EP 765 DI 10.1093/jnci/85.10.764 PG 2 WC Oncology SC Oncology GA LE267 UT WOS:A1993LE26700002 ER PT J AU DUNNICK, JK MELNICK, RL AF DUNNICK, JK MELNICK, RL TI ASSESSMENT OF THE CARCINOGENIC POTENTIAL OF CHLORINATED WATER - EXPERIMENTAL STUDIES OF CHLORINE, CHLORAMINE, AND TRIHALOMETHANES SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID DRINKING-WATER; SODIUM-HYPOCHLORITE; STATISTICAL ISSUES; B6C3F1 MICE; TOXICITY; RATS; BROMODICHLOROMETHANE; CHLOROFORM; TESTS AB Background: Water chlorination has been one of the major disease prevention treatments of this century. While epidemiologic studies suggest an association between cancer in humans and consumption of chlorination byproducts in drinking water, these studies have not been adequate to draw definite conclusions about the carcinogenic potential of the individual byproducts. Purpose: The purpose of this study was to investigate the carcinogenic potential of chlorinated or chloraminated drinking water and of four organic trihalomethane byproducts of chlorination (chloroform, bromodichloromethane, chlorodibromomethane, and bromoform) in rats and mice. Methods: Bromodichloromethane, chlorodibromomethane, bromoform, chlorine, or chloramine was administered to both sexes of F344/N rats and (C57BL/6 X C3H)F1 mice (hereafter called B6C3F1 mice). Chloroform was given to both sexes of Osborne-Mendel rats and B6C3F1 mice. Chlorine or chloramine was administered daily in the drinking water for 2 years at doses ranging from 0.05 to 0.3 mmol/kg per day. The trihalomethanes were administered by gavage in corn oil at doses ranging from 0.15 to 4.0 mmol/kg per day for 2 years, with the exception of chloroform, which was given for 78 weeks. Results: The trihalomethanes were carcinogenic in the liver, kidney, and/or intestine of rodents. There was equivocal evidence for carcinogenicity in female rats that received chlorinated or chloraminated drinking water; this evidence was based on a marginal increase in the incidence of mononuclear cell leukemia. Rodents were generally exposed to lower doses of chlorine and chloramine than to the trihalomethanes, but the doses in these studies were the maximum that the animals would consume in the drinking water. The highest doses used in the chlorine and chloramine studies were equivalent to a daily gavage dose of bromodichloromethane that induced neoplasms of the large intestine in rats. In contrast to the results with the trihalomethanes, administration of chlorine or chloramine did not cause a clear carcinogenic response in rats or mice after long-term exposure. Conclusion: These results suggest that organic byproducts of chlorination are the chemicals of greatest concern in assessment of the carcinogenic potential of chlorinated drinking water. RP DUNNICK, JK (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 31 TC 65 Z9 67 U1 3 U2 14 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY 19 PY 1993 VL 85 IS 10 BP 817 EP 822 DI 10.1093/jnci/85.10.817 PG 6 WC Oncology SC Oncology GA LE267 UT WOS:A1993LE26700016 PM 8487327 ER PT J AU JOHNSON, KA BRAWLEY, OW PERLMAN, JA FORD, LG AF JOHNSON, KA BRAWLEY, OW PERLMAN, JA FORD, LG TI CHEMOPREVENTION STUDIES IN THE COMMUNITY CLINICAL ONCOLOGY PROGRAM SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 NCI,DIV CANC PREVENT & CONTROL,COMMUNITY ONCOL & REHABIL BRANCH,BETHESDA,MD 20892. NR 8 TC 0 Z9 0 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY 19 PY 1993 VL 85 IS 10 BP 832 EP 832 DI 10.1093/jnci/85.10.832 PG 1 WC Oncology SC Oncology GA LE267 UT WOS:A1993LE26700019 PM 8487329 ER PT J AU REMETA, DP MUDD, CP BERGER, RL BRESLAUER, KJ AF REMETA, DP MUDD, CP BERGER, RL BRESLAUER, KJ TI THERMODYNAMIC CHARACTERIZATION OF DAUNOMYCIN DNA INTERACTIONS - COMPARISON OF COMPLETE BINDING PROFILES FOR A SERIES OF DNA HOST DUPLEXES SO BIOCHEMISTRY LA English DT Article ID SEQUENCE SPECIFICITY; DEOXYRIBONUCLEIC-ACID; ANTITUMOR ANTHRACYCLINES; MOLECULAR-STRUCTURE; TOPOISOMERASE-II; COIL TRANSITION; STRAND SCISSION; DAUNORUBICIN; EQUILIBRIUM; ADRIAMYCIN AB Using a combination of spectroscopic and calorimetric techniques, we have determined complete thermodynamic binding profiles (DELTAG-degrees, DELTAH-degrees, and DELTAS-degrees) for the complexation of daunomycin to a series of 10 polymeric DNA duplexes. We find the resulting drug binding data to be sensitive to the base composition and sequence of the host duplex, with the binding free energies ranging from -7.5 to -10.8 kcal/mol of bound drug and the binding enthalpies ranging from +4.11 to -10.76 kcal/mol of bound drug at 25-degrees-C. The smaller range in the free energy term reflects the impact of large enthalpy-entropy compensations. We observe that the three synthetic duplexes which exhibit the highest daunomycin binding affinities all contain GC (or IC) base pairs as part of alternating purine/pyrimidine sequence motifs, with these high binding affinities being strongly enthalpy driven at 25-degrees-C. Specific comparisons between the binding profiles for daunomycin complexation with select pairs of host duplexes lead to the following observations: (1) The presence or absence of a major-groove methyl group does not alter daunomycin binding thermodynamics. (2) The presence or absence of a minor-groove amino group does alter daunomycin binding thermodynamics. (3) Duplexes with different base compositions but identical minor-groove functionality exhibit similar daunomycin binding thermodynamics. (4) Homopolymeric duplexes composed of either AT or AU base pairs, but not GC base pairs, exhibit large enthalpy-entropy compensations in their daunomycin binding profiles. We propose interpretations of these and other features of our thermodynamic data in terms of specific daunomycin-DNA interactions deduced from available structural data. C1 RUTGERS UNIV,DEPT CHEM,NEW BRUNSWICK,NJ 08903. NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. NHLBI,DIV RES SERV,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. FU NIGMS NIH HHS [GM23509, GM34469] NR 68 TC 55 Z9 55 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 18 PY 1993 VL 32 IS 19 BP 5064 EP 5073 DI 10.1021/bi00070a014 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LC721 UT WOS:A1993LC72100014 PM 8494883 ER PT J AU PERRELLA, M SHRAGER, RI RIPAMONTI, M MANFREDI, G BERGER, RL ROSSIBERNARDI, L AF PERRELLA, M SHRAGER, RI RIPAMONTI, M MANFREDI, G BERGER, RL ROSSIBERNARDI, L TI MECHANISM OF THE OXIDATION REACTION OF DEOXYHEMOGLOBIN AS STUDIED BY ISOLATION OF THE INTERMEDIATES SUGGESTS TERTIARY STRUCTURE DEPENDENT COOPERATIVITY SO BIOCHEMISTRY LA English DT Article ID HEME-HEME INTERACTION; HYDROGEN-EXCHANGE; HEMOGLOBIN; METHEMOGLOBIN AB The intermediates in the oxidation of deoxyhemoglobin by ferricyanide in 0.1 M KCl, at 20-degrees-C and three pH values, were studied by cryogenic techniques. Data analysis was carried out according to a simple four rate constant model, ignoring the functional heterogeneity of the subunits, to simulate the time courses of the oxidation reaction, as studied by the stopped-flow technique [Antonini et al., (1965) Biochemistry 4, 345], which show anticooperativity at neutral pH and cooperativity at alkaline pH. Data analysis according to a 12 rate constant model indicated that the rate of oxidation of the beta subunit in the first oxidation reaction was 4 times faster than the rate of oxidation of the alpha subunit at pH 6.2 and 12 times faster at pH 8.5. The reactions involving the alpha subunit were noncooperative except for the last oxidation step at acid and neutral pH, but were cooperative at alkaline pH. The reactions involving the beta subunit were partly noncooperative and partly anticooperative. These complex mechanistic patterns suggest that a simple two-state model requiring the concerted transition of the tertiary structures of the subunits from the T to the R conformation is not adequate to interpret the oxidation reaction and that tertiary structures contribute, positively and negatively, to cooperativity. A structural hypothesis is suggested to explain the difference in the reactivities of the alpha and beta subunits. C1 CNR,IST TECNOL BIOMED AVANZATE,I-20133 MILAN,ITALY. NIH,BETHESDA,MD 20892. RP PERRELLA, M (reprint author), UNIV MILAN,DIPARTIMENTO SCI & TECNOL BIOMED,VIA CELORIA 2,I-20133 MILAN,ITALY. OI RIPAMONTI, MARILENA/0000-0001-9403-9915 NR 26 TC 13 Z9 13 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 18 PY 1993 VL 32 IS 19 BP 5233 EP 5238 DI 10.1021/bi00070a035 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LC721 UT WOS:A1993LC72100035 PM 8494900 ER PT J AU JORNVALL, H PERSSON, B DUBOIS, GC LAVERS, GC CHEN, JH GONZALEZ, P RAO, PV ZIGLER, JS AF JORNVALL, H PERSSON, B DUBOIS, GC LAVERS, GC CHEN, JH GONZALEZ, P RAO, PV ZIGLER, JS TI ZETA-CRYSTALLIN VERSUS OTHER MEMBERS OF THE ALCOHOL-DEHYDROGENASE SUPER-FAMILY - VARIABILITY AS A FUNCTIONAL CHARACTERISTIC SO FEBS LETTERS LA English DT Article DE CRYSTALLIN; ALCOHOL DEHYDROGENASE; STRUCTURE FUNCTION RELATIONSHIP; SEGMENT VARIABILITY; GLYCINE CONSERVATION ID GUINEA-PIG LENS; BINDING-PROTEIN; ENZYME; GENE AB Species variability of the lens protein zeta-crystallin was correlated with those of alcohol dehydrogenases of classes I and III and sorbitol dehydrogenase in the same protein family. The extent of overall variability, nature of residues conserved, and patterns of segment variability, all fall within the limits typical of the 'variable' group of medium-chain alcohol dehydrogenases. This shows that zeta-crystallin is subject to restrictions similar to those of classical liver alcohol dehydrogenase and therefore derived from a metabolically active enzyme like other enzyme crystallins. Special residues at the active site, however, differ substantially, including an apparent lack of a zinc-binding site. This is compatible with altered functional properties and makes the spread within this medium-chain dehydrogenase family resemble the wide spread within the short-chain dehydrogenases. Schematic plotting is useful for illustrating the differences between 'variable' and 'constant' enzymes. C1 JEFFERSON CANC INST,DEPT PHARMACOL,PHILADELPHIA,PA 19107. NEI,MECHANISMS OCULAR DIS LAB,BETHESDA,MD 20892. NYU,CTR DENT,DIV BASIC SCI BIOCHEM,NEW YORK,NY 10010. RP JORNVALL, H (reprint author), KAROLINSKA INST,DEPT CHEM 1,S-10401 STOCKHOLM 60,SWEDEN. FU NEI NIH HHS [EY03173, EY02352] NR 32 TC 20 Z9 20 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD MAY 17 PY 1993 VL 322 IS 3 BP 240 EP 244 DI 10.1016/0014-5793(93)81578-N PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA LB597 UT WOS:A1993LB59700009 PM 8486156 ER PT J AU BENCHEKROUN, MN SINHA, BK ROBERT, J AF BENCHEKROUN, MN SINHA, BK ROBERT, J TI DOXORUBICIN-INDUCED OXYGEN-FREE RADICAL FORMATION IN SENSITIVE AND DOXORUBICIN-RESISTANT VARIANTS OF RAT GLIOBLASTOMA CELL-LINES SO FEBS LETTERS LA English DT Article DE ANTHRACYCLINE; ELECTRON SPIN RESONANCE SPECTROSCOPY; FREE RADICAL; ANTICANCER DRUG; REDOX ACTIVATION; LIPID PEROXIDATION ID GLUTATHIONE; ADRIAMYCIN; ASSAY AB We have studied the formation of hydroxyl radical (OH') induced by doxorubicin in a series of doxorubicin- or vincristine-selected variants of C6 rat glioblastoma cells in culture by electron-spin resonance spectroscopy using 5,5'-dimethyl-1-pyrroline-1-oxide as a spin trap. Wild-type cells, sensitive to doxorubicin, exhibited in the presence of this drug a concentration-dependent OH.formation which could be inhibited by preincubation with superoxide dismutase, catalase or an antibody against cytochrome P450-reductase. In highly doxorubicin-resistant cells, OH' formation was reduced to about 20% of the level obtained in sensitive cells. In cells presenting a very low level of resistance to doxorubicin or in cells selected with vincristine, both presenting a pure multidrug-resistant phenotype, OH' formation was identical to that obtained in sensitive cells. In cells of intermediate resistance or in revertant cells, intermediate levels of OH' formation were obtained. Protection against OH' formation and action can be identified at the levels of superoxide dismutase and glutathione peroxidase activities, which are both enhanced in the resistant cells. C1 UNIV BORDEAUX 2,DEPT BIOCHIM MED & BIOL MOLEC,146 RUE LEO SAIGNAT,F-33076 BORDEAUX,FRANCE. FDN BERGONIE,BIOCHIM & PHARMACOL LAB,F-33076 BORDEAUX,FRANCE. NCI,CLIN PHARMACOL BRANCH,BIOCHEM & MOLEC PHARMACOL SECT,BETHESDA,MD 20892. NR 15 TC 12 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD MAY 17 PY 1993 VL 322 IS 3 BP 295 EP 298 DI 10.1016/0014-5793(93)81589-R PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA LB597 UT WOS:A1993LB59700020 ER PT J AU STEWART, W FEDER, N AF STEWART, W FEDER, N TI STEWART-FEDER - REASSIGNMENT IS A MORAL NOT AN ADMINISTRATIVE MATTER SO SCIENTIST LA English DT Editorial Material AB STATING THEIR CASE: Recently deposed NIH investigators Walter Stewart and Ned Feder contend that their controversial reassignment caps a decade in which their employer sent them mixed messages about what was expected of them, and frequently repressed their findings for no clear and consistent reason. RP STEWART, W (reprint author), NIDDKD,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SCIENTIST INC PI PHILADELPHIA PA 3600 MARKET ST SUITE 450, PHILADELPHIA, PA 19104 SN 0890-3670 J9 SCIENTIST JI Scientist PD MAY 17 PY 1993 VL 7 IS 10 BP 11 EP & PG 0 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA LB508 UT WOS:A1993LB50800009 ER PT J AU STRUDLER, P AF STRUDLER, P TI E-MAIL EFFICIENCY SO SCIENTIST LA English DT Letter RP STRUDLER, P (reprint author), NIH,RADIAT STUDY SECT,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SCIENTIST INC PI PHILADELPHIA PA 3600 MARKET ST SUITE 450, PHILADELPHIA, PA 19104 SN 0890-3670 J9 SCIENTIST JI Scientist PD MAY 17 PY 1993 VL 7 IS 10 BP 14 EP 14 PG 1 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA LB508 UT WOS:A1993LB50800013 ER PT J AU FERNICOLA, DJ ROBERTS, WC AF FERNICOLA, DJ ROBERTS, WC TI CLINICOPATHOLOGICAL FEATURES OF ACTIVE INFECTIVE ENDOCARDITIS ISOLATED TO THE NATIVE MITRAL-VALVE SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID NECROPSY PATIENTS; OPIATE ADDICTS; FREQUENCY AB Although a number of clinicopathologic studies in patients with active infective endocarditis (IE) have been reported, none have focused on patients studied at necropsy with active IE isolated to the mitral valve. We studied at necropsy 63 patients (aged 12 to 88 years [mean 50], 44 males [70%]) with active IE limited to the native mitral valve: 21 (33%) had preexisting mitral valve disease (rheumatic in 8, prolapse in 3, hypertrophic cardiomyopathy in 1, and mitral annular calcium in 9), and the other 42 patients (67%) had previously normal mitral valves. Of the latter 42 patients, 22 (52%) had recognized predisposing factors to IE: opiate addition in 14, habitual alcoholism in 6 and/or chronic hemodialysis in 4. Staphylococcus aureus or epidermidis was the responsible organism in 32 patients (51%), and the active IE was associated with an infection elsewhere in the body in 31 patients (50%). The active IE caused rupture of mitral chordae tendineae in 11 patients (18%), perforation of the anterior mitral leaflet in 7 patients (16%). Grossly visible systemic emboli were found in 44 patients (70%) and 33 (52%) had infarcts in 1 or more body organs. Thus, active IE isolated to the mitral valve in necropsied patients appears to be more common in males than females (2 to 1); the infection more commonly than not involves a preexisting anatomically normal valve rather than a preexisting abnormal one (2 to 1); the vegetations often do not cause or worsen valvular dysfunction; a predisposing factor is commonly present (2 of 3 patients), and the IE commonly is part of a generalized or systemic infection (1 of 2 patients). RP FERNICOLA, DJ (reprint author), NHLBI,PATHOL BRANCH,BLDG 10,ROOM 2N258,BETHESDA,MD 20892, USA. NR 17 TC 17 Z9 17 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAY 15 PY 1993 VL 71 IS 13 BP 1186 EP 1197 DI 10.1016/0002-9149(93)90644-R PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA LA713 UT WOS:A1993LA71300010 PM 8480645 ER PT J AU WILCOX, AJ AF WILCOX, AJ TI BIRTH-WEIGHT AND PERINATAL-MORTALITY - THE EFFECT OF MATERNAL SMOKING SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE BIRTH WEIGHT; INFANT, PREMATURE; MORTALITY; SMOKING ID CIGARETTE-SMOKING; INFANT-MORTALITY; PREGNANCY; ALTITUDE AB Infants born to mothers who smoke are a few hundred grams smaller, on average, than the infants of nonsmokers. This effect on fetal growth is regarded as evidence of the reproductive toxicity of cigarette smoking. In this paper, data from nearly 260,000 births in the state of Missouri (1980-1984) were analyzed using a method based on adjustment to relative birth weight. Two additional effects of smoking are demonstrated with this analysis; i.e., smokers are at higher risk of delivering very small preterm infants, and their infants have higher perinatal mortality at every relative birth weight. The latter is not apparent on an absolute birth weight scale and thus is not generally recognized. A supplementary analysis of births at high altitude is carried out to suggest that effects on fetal growth (whether from smoking or other factors) can occur independently of effects on mortality. RP WILCOX, AJ (reprint author), NIEHS,EPIDEMIOL BRANCH,POB 12233,RES TRIANGLE PK,NC 27709, USA. OI Wilcox, Allen/0000-0002-3376-1311 NR 27 TC 104 Z9 105 U1 0 U2 3 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAY 15 PY 1993 VL 137 IS 10 BP 1098 EP 1104 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA LK525 UT WOS:A1993LK52500006 PM 8317439 ER PT J AU KENWORTHY, L PARK, T CHARNAS, LR AF KENWORTHY, L PARK, T CHARNAS, LR TI COGNITIVE AND BEHAVIORAL PROFILE OF THE OCULOCEREBRORENAL SYNDROME OF LOWE SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE AGGRESSION; TANTRUMS; INTELLIGENCE; PHENOTYPE; STEREOTYPY ID PARENTING STRESS; MENTAL HANDICAP; RATING-SCALE; CHECKLIST; DISORDERS; CHILDREN; XQ24-Q26 AB Background: The oculocerebrorenal syndrome of Lowe (OCRL) is an X-linked disorder characterized by congenital cataracts, cognitive impairment, and renal tubular dysfunction. Significant behavioral difficulties have been reported, but no formal study of intelligence or behavior has been described. Methods: We surveyed IQ and behavior using archival data and standardized instruments in 47 affected males. Results: Mean IQ was in the moderate mental retardation range (40 less-than-or-equal-to IQ less-than-or-equal-to 54), with 25% of tested individuals in the normal range (IQ greater-than-or-equal-to 70). The OCRL population was comparable to a normative population with mental retardation in language, communication, and socialization skills, but lower in independent living skills than means of either populations of individuals with mental retardation or visual impairment. Maladaptive behaviors, particularly stubbornness, temper tantrums, and stereotypic behaviors, were very frequent (>80%). Conclusions: The diagnosis of OCRL is compatible with normal intelligence. Maladaptive behaviors significantly interfere with adaptive functions. These behaviors appear to define a characteristic behavioral phenotype in OCRL. C1 NICHHD,HUMAN GENET BRANCH,9000 ROCKVILLE PIKE,BLDG 10,ROOM 9S242,BETHESDA,MD 20892. NICHHD,BIOMETRY & MATH STAT BRANCH,BETHESDA,MD 20892. NR 54 TC 26 Z9 26 U1 1 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD MAY 15 PY 1993 VL 46 IS 3 BP 297 EP 303 DI 10.1002/ajmg.1320460312 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA KZ610 UT WOS:A1993KZ61000011 PM 8488875 ER PT J AU NUSSENBLATT, RB DESMET, MD RUBIN, B FREIDLIN, V WHITCUP, SM DAVIS, J HERMAN, D BLOOM, JN SRAN, PK WHITCHER, S PALESTINE, A AUSTIN, H AF NUSSENBLATT, RB DESMET, MD RUBIN, B FREIDLIN, V WHITCUP, SM DAVIS, J HERMAN, D BLOOM, JN SRAN, PK WHITCHER, S PALESTINE, A AUSTIN, H TI A MASKED, RANDOMIZED, DOSE-RESPONSE STUDY BETWEEN CYCLOSPORINE-A AND CYCLOSPORINE-G IN THE TREATMENT OF SIGHT-THREATENING UVEITIS OF NONINFECTIOUS ORIGIN SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID EXPERIMENTAL AUTOIMMUNE UVEITIS; BEHCETS-DISEASE; VISUAL-ACUITY; RATS AB Thirty-two patients with sight-threatening uveitis and a decrease in visual acuity requiring systemic therapy were randomly assigned to either cyclosporine A or G in a dose-escalation study. Groups received from 2.5 mg/kg of body weight/day to 10 mg/kg of body weight/day of either drug along with low-dose prednisone. More patients taking cyclosporine G had improved visual acuity and a decrease in macular edema, which occurred more rapidly than in the other group, even at the lower doses tested. No difference in renal function was noted between groups at any doses tested. Four patients receiving cyclosporine G had hepatic alterations, but only one required cessation of the drug. The study indicates the potential usefulness of cyclosporine G, particularly at lower doses (4 mg/kg of body weight/day), which could lower the potential for serious renal complications. C1 NIDDKD,KIDNEY SECT,BETHESDA,MD. NEI,CLIN RES BRANCH,BETHESDA,MD 20892. RP NUSSENBLATT, RB (reprint author), NEI,IMMUNOL LAB,BLDG 10,ROOM 10N202,BETHESDA,MD 20892, USA. NR 24 TC 25 Z9 28 U1 0 U2 0 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD MAY 15 PY 1993 VL 115 IS 5 BP 583 EP 591 PG 9 WC Ophthalmology SC Ophthalmology GA LA791 UT WOS:A1993LA79100004 PM 8488909 ER PT J AU PHILLIPS, LR SUPKO, JG MALSPEIS, L AF PHILLIPS, LR SUPKO, JG MALSPEIS, L TI ANALYSIS OF BREFELDIN-A IN PLASMA BY GAS-CHROMATOGRAPHY WITH ELECTRON-CAPTURE DETECTION SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID SECRETORY PROTEINS; INTRACELLULAR-TRANSPORT; (+)-BREFELDIN-A; ACCUMULATION; BLOCKADE; CELLS; GOLGI RP PHILLIPS, LR (reprint author), NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,PHARMACEUT CHEM LAB,FREDERICK,MD 21702, USA. NR 26 TC 16 Z9 16 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD MAY 15 PY 1993 VL 211 IS 1 BP 16 EP 22 DI 10.1006/abio.1993.1225 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA LC622 UT WOS:A1993LC62200003 PM 8323029 ER PT J AU WOLKOWITZ, OM WEINGARTNER, H RUBINOW, DR JIMERSON, D KLING, M BERRETINI, W THOMPSON, K BREIER, A DORAN, A REUS, VI PICKAR, D AF WOLKOWITZ, OM WEINGARTNER, H RUBINOW, DR JIMERSON, D KLING, M BERRETINI, W THOMPSON, K BREIER, A DORAN, A REUS, VI PICKAR, D TI STEROID MODULATION OF HUMAN-MEMORY - BIOCHEMICAL CORRELATES SO BIOLOGICAL PSYCHIATRY LA English DT Note ID DEMENTIA C1 UNIV CALIF SAN FRANCISCO,SCH MED,DEPT PSYCHIAT,SAN FRANCISCO,CA 94143. NIAAA,BETHESDA,MD. NIMH,BETHESDA,MD 20892. HARVARD UNIV,BETH ISRAEL HOSP,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT PSYCHIAT,BOSTON,MA 02115. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT PSYCHIAT,PHILADELPHIA,PA 19107. UNIV MARYLAND,SCH MED,MARYLAND PSYCHIAT RES CTR,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,DEPT PSYCHIAT,BALTIMORE,MD 21201. CANYON SPRINGS HOSP,CATHEDRAL CITY,CA. RI reus, victor/I-7923-2015 OI reus, victor/0000-0002-8193-5697 NR 17 TC 25 Z9 27 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 MAY 15 PY 1993 VL 33 IS 10 BP 744 EP 746 DI 10.1016/0006-3223(93)90125-W PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA LJ396 UT WOS:A1993LJ39600009 PM 8102553 ER PT J AU THORGEIRSSON, SS AF THORGEIRSSON, SS TI ENDOGENOUS DNA DAMAGE AND BREAST-CANCER SO CANCER LA English DT Editorial Material ID OXYGEN RADICALS; LIVER; FISH; 8-HYDROXYDEOXYGUANOSINE; 8-HYDROXYGUANINE; CARCINOGENESIS; ETIOLOGY RP THORGEIRSSON, SS (reprint author), NCI,DIV CANC ETIOL,EXPTL CARCINOGENESIS LAB,BLDG 37,ROOM 3C28,BETHESDA,MD 20892, USA. NR 26 TC 10 Z9 10 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD MAY 15 PY 1993 VL 71 IS 10 BP 2897 EP 2899 DI 10.1002/1097-0142(19930515)71:10<2897::AID-CNCR2820711002>3.0.CO;2-4 PG 3 WC Oncology SC Oncology GA LD041 UT WOS:A1993LD04100001 PM 8490816 ER PT J AU HERRINTON, LJ SAFTLAS, AF STANFORD, JL BRINTON, LA WOLFE, JN AF HERRINTON, LJ SAFTLAS, AF STANFORD, JL BRINTON, LA WOLFE, JN TI DO ALCOHOL INTAKE AND MAMMOGRAPHIC DENSITIES INTERACT IN REGARD TO THE RISK OF BREAST-CANCER SO CANCER LA English DT Article DE ALCOHOL; BREAST NEOPLASMS; CASE-CONTROL STUDIES; MAMMOGRAPHY; RISK FACTORS ID PARENCHYMAL PATTERNS; BEVERAGE CONSUMPTION; FEATURES; HEALTH AB Background. The effect of alcohol intake on mammographic densities and the possible interaction between these two factors in regard to the risk of breast cancer were assessed using information from the Breast Cancer Detection and Demonstration Project. Methods. Mammograms taken during the first year of screening for patients whose breast cancer was detected in the 5th year of follow-up (n = 266) and their matched controls (n = 301) were blindly assessed for the percent of mammographic densities, which were measured by planimetry. Results. Among controls, alcohol intake was weakly, positively associated with the percent of mammographic densities (Spearman rank correlation coefficient, 0.09), although the association may have been the result of chance (P = 0.12). After adjustment for confounding factors, the lifetime alcohol intake did not appear to modify the effect of the percent mammographic densities on the risk of breast cancer (P for the interaction, 0.09). Conclusions. Longitudinal studies and larger case-control studies should be conducted to assess the relationship between diet and changes in mammographic densities further. C1 UNIV WASHINGTON,DEPT EPIDEMIOL,SEATTLE,WA 98195. CTR DIS CONTROL,NATL CTR CHRON DIS PREVENT & HLTH PROMOT,DIV REPROD HLTH,ATLANTA,GA 30333. NCI,DIV CANC ETIOL,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892. HUTZEL HOSP,DEPT RADIOL,DETROIT,MI 48201. RP HERRINTON, LJ (reprint author), FRED HUTCHINSON CANC RES CTR,DIV PUBL HLTH SCI,MP-381,SEATTLE,WA 98104, USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 FU NCI NIH HHS [T32 CA09168-17, T32 CA09314-07] NR 25 TC 18 Z9 19 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD MAY 15 PY 1993 VL 71 IS 10 BP 3029 EP 3035 DI 10.1002/1097-0142(19930515)71:10<3029::AID-CNCR2820711024>3.0.CO;2-K PG 7 WC Oncology SC Oncology GA LD041 UT WOS:A1993LD04100023 PM 8490831 ER PT J AU ISRAEL, MA AF ISRAEL, MA TI DISORDERED DIFFERENTIATION AS A TARGET FOR NOVEL APPROACHES TO THE TREATMENT OF NEUROBLASTOMA SO CANCER LA English DT Article; Proceedings Paper CT WORKSHOP ON CHILDREN WITH CANCER CY SEP 05-06, 1991 CL NAPLES, FL SP AMER CANC SOC DE NEUROBLASTOMA; DIFFERENTIATION; NEURAL CREST; ADRENAL MEDULLA; INSULIN-LIKE GROWTH FACTOR-II; CHROMAFFIN CELLS ID GROWTH FACTOR-II; NEURO-BLASTOMA; ADRENAL-GLAND; CELLS; CHROMAFFIN; EXPRESSION; GANGLION; MEDULLA; RAT AB Some childhood malignant neoplasms are thought to arise in embryonic tissues. These tumors present unique opportunities for studying the maturation of specific cellular lineages and examining the possible role of alterations in the regulation of differentiation in tumor development. Several features of neuroblastoma, a tumor thought to arise in cells originating in the embryonic neural crest, suggest that it may be particularly useful in this regard. The identification of a series of markers that characterize the various cell types of the peripheral nervous system that are detectable in neuroblastoma tumor tissues has made it possible to recognize that the cells of neuroblastoma tumor cell lines and tissues correspond to specific stages of adrenal gland development. Experiments directed at understanding the cellular signals by which neural crest cell maturation is mediated may provide insights of therapeutic import because neuroblastoma tumors corresponding to some stages of differentiation respond very differently to nonspecific cytotoxic therapies than tumors corresponding to other stages. C1 NCI,PEDIAT BRANCH,BETHESDA,MD 20892. NR 23 TC 11 Z9 11 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD MAY 15 PY 1993 VL 71 IS 10 SU S BP 3310 EP 3313 DI 10.1002/1097-0142(19930515)71:10+<3310::AID-CNCR2820711728>3.0.CO;2-G PG 4 WC Oncology SC Oncology GA LD570 UT WOS:A1993LD57000025 PM 8490873 ER PT J AU ABOULAFIA, AJ MALAWER, MM AF ABOULAFIA, AJ MALAWER, MM TI SURGICAL-MANAGEMENT OF PELVIC AND EXTREMITY OSTEOSARCOMA SO CANCER LA English DT Article; Proceedings Paper CT WORKSHOP ON CHILDREN WITH CANCER CY SEP 05-06, 1991 CL NAPLES, FL SP AMER CANC SOC DE OSTEOSARCOMA; LIMB-SPARING SURGERY; NEOADJUVANT CHEMOTHERAPY; ENDOPROSTHESIS; ALLOGRAFT ID OSTEO-SARCOMA; MAGNETIC-RESONANCE; COMPUTED-TOMOGRAPHY; INTRAARTERIAL CISPLATIN; BONE-SCINTIGRAPHY; CHEMOTHERAPY; TUMORS; EXPERIENCE; RESECTION; LESIONS AB Between 60-80% of all patients with osteosarcomas of the pelvis and the extremities can now he safely treated with limb-sparing surgery. Results (as defined by rates of local recurrence, overall survival, and function) are equal to or better than those associated with amputation. Successful use of limb-sparing procedures, however, depends on a well-developed surgical plan. An understanding of the biologic behavior and growth patterns of these lesions is fundamental. Staging of the primary tumor must involve a full complement of imaging modalities, including plain radiography, bone scintigraphy, computerized axial tomography (CAT), magnetic resonance imaging (MRI), and angiography. The biopsy must be well placed to reduce the possibility of tissue contamination, which is a common reason for amputation. Restaging is necessary before surgery for patients who have undergone neoadjuvant therapy; there is recent evidence that preoperative therapy may make limb-sparing surgery possible in more than 50% of patients who otherwise would have required amputation. Relative contraindications to limb-sparing surgery include major involvement of the neurovascular bundle, pathologic fracture, inappropriate biopsy site, infection, immature skeletal age, and extensive muscle involvement. Each of these factors is relative, and patient selection decisions must be made on an individual basis. Limb-sparing surgery consists of the following three phases: tumor resection, skeletal reconstruction, and soft tissue and muscle transfers. The range of reconstruction techniques has been broadened by developments in bioengineering. Among the more commonly used techniques are custom endoprostheses and allograft replacements. Future progress in induction regimens and reconstructive techniques will undoubtedly enable limb-sparing surgery to be a satisfactory alternative to amputation in even more patients. C1 CHILDRENS NATL MED CTR,WASHINGTON,DC. NIH,SURG BRANCH,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,SCH MED,WASHINGTON,DC 20052. RP ABOULAFIA, AJ (reprint author), WASHINGTON HOSP CTR,INST CANC,DEPT ORTHOPED,110 IRVING ST NW,WASHINGTON,DC 20010, USA. NR 78 TC 46 Z9 49 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD MAY 15 PY 1993 VL 71 IS 10 SU S BP 3358 EP 3366 DI 10.1002/1097-0142(19930515)71:10+<3358::AID-CNCR2820711738>3.0.CO;2-O PG 9 WC Oncology SC Oncology GA LD570 UT WOS:A1993LD57000035 PM 8490883 ER PT J AU NICHOLSON, HS BYRNE, J AF NICHOLSON, HS BYRNE, J TI FERTILITY AND PREGNANCY AFTER TREATMENT FOR CANCER DURING CHILDHOOD OR ADOLESCENCE SO CANCER LA English DT Article DE SURVIVORS OF CHILDHOOD CANCER; FERTILITY; STERILITY; GONADS; BIRTH DEFECTS; CHEMOTHERAPY; ALKYLATING AGENTS; RADIATION ID LONG-TERM SURVIVORS; ACUTE LYMPHOBLASTIC-LEUKEMIA; INDUCED OVARIAN FAILURE; HODGKINS-DISEASE; COMBINATION CHEMOTHERAPY; TESTICULAR IRRADIATION; REPRODUCTIVE FUNCTION; GONADAL DAMAGE; WILMS TUMOR; CHILDREN AB Because most children and adolescents with cancer now survive, issues regarding the late effects of therapy, including fertility and the health of offspring, are increasingly important. This article summarizes the literature regarding issues related to fertility in survivors of cancer, including actual fertility, gonadal function, menarche, menopause, and birth defects and cancer in the offspring. Radiation therapy to the gonads and alkylating agent chemotherapy, either alone or in combination, impair actual fertility in survivors of childhood and adolescent cancer. Males are particularly affected by alkylating agents, and females who have had radiation therapy to the abdomen have decreased fertility and an increased risk of adverse pregnancy outcomes. Consequently, these women should be followed up as high-risk obstetrical patients. Offspring of survivors of cancer appear to have little risk of childhood cancer or birth defects. Thus, in most instances, survivors of cancer should not be discouraged from having children and can expect a good outcome of pregnancy. This article concludes with advice to survivors and clinicians who counsel survivors. C1 CHILDRENS NATL MED CTR, WASHINGTON, DC USA. RP NICHOLSON, HS (reprint author), NCI, CLIN EPIDEMIOL BRANCH, EPN 400, BETHESDA, MD 20892 USA. NR 47 TC 103 Z9 103 U1 2 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD MAY 15 PY 1993 VL 71 IS 10 SU S BP 3392 EP 3399 DI 10.1002/1097-0142(19930515)71:10+<3392::AID-CNCR2820711743>3.0.CO;2-F PG 8 WC Oncology SC Oncology GA LD570 UT WOS:A1993LD57000040 PM 8490888 ER PT J AU SMITH, M SIMON, R CAIN, D UNGERLEIDER, RS AF SMITH, M SIMON, R CAIN, D UNGERLEIDER, RS TI CHILDREN AND CANCER - A PERSPECTIVE FROM THE CANCER-THERAPY EVALUATION PROGRAM, NATIONAL-CANCER-INSTITUTE SO CANCER LA English DT Article; Proceedings Paper CT WORKSHOP ON CHILDREN WITH CANCER CY SEP 05-06, 1991 CL NAPLES, FL SP AMER CANC SOC DE RANDOMIZED CLINICAL TRIALS; PEDIATRIC ONCOLOGY; DOSE INTENSITY; OSTEOSARCOMA; EWING SARCOMA; DOXORUBICIN ID DOXORUBICIN DOSE INTENSITY; NON-HODGKINS-LYMPHOMA; EWINGS-SARCOMA; ADJUVANT CHEMOTHERAPY; MULTIMODAL THERAPY; CLINICAL-TRIALS; FREE SURVIVAL; WILMS TUMOR; CHILDHOOD; MANAGEMENT AB The Cancer Therapy Evaluation Program, National Cancer Institute (CTEP, NCI) strongly supports the role of controlled clinical trials in improving the care of children with cancer, and particularly the central role that the pediatric Cooperative Groups play in this process. Trends that threaten the ability to perform these trials include the increasingly limited financial resources available for clinical investigations and the sentiment within some circles that controlled clinical trials may be inappropriate for ethical reasons. The inherent risks of accepting a new therapy without rigorous comparison to existing therapy strongly support the need for randomized trials with adequate accrual to answer important therapeutic questions in a timely and reliable fashion. Retrospective analysis of multiple clinical trials is one method for identifying compelling hypotheses to be tested prospectively. Using this method, we have demonstrated the association between doxorubicin dose intensity and positive response and outcome for patients with Ewing sarcoma and osteosarcoma, thereby providing direction for the selection of important therapeutic questions to be addressed in future clinical trials for these malignancies. RP SMITH, M (reprint author), NCI,EPN,CANC THERAPY EVALUAT PROGRAM,ROOM 741,BETHESDA,MD 20892, USA. NR 29 TC 8 Z9 8 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 0008-543X J9 CANCER JI Cancer PD MAY 15 PY 1993 VL 71 IS 10 SU S BP 3422 EP 3428 DI 10.1002/1097-0142(19930515)71:10+<3422::AID-CNCR2820711748>3.0.CO;2-4 PG 7 WC Oncology SC Oncology GA LD570 UT WOS:A1993LD57000045 PM 8490893 ER PT J AU CURTI, BD URBA, WJ ALVORD, WG JANIK, JE SMITH, JW MADARA, K LONGO, DL AF CURTI, BD URBA, WJ ALVORD, WG JANIK, JE SMITH, JW MADARA, K LONGO, DL TI INTERSTITIAL PRESSURE OF SUBCUTANEOUS NODULES IN MELANOMA AND LYMPHOMA PATIENTS - CHANGES DURING TREATMENT SO CANCER RESEARCH LA English DT Note ID INTERLEUKIN-1; HYPERTENSION AB Interstitial pressure (IP) is a physiological variable that may have its greatest influence on the transport of high-molecular-weight therapeutic agents. IP in tumor nodules was measured in patients with metastatic melanoma or non-Hodgkin's lymphoma to determine the influence of this physiological variable on treatment outcome. The wick-in-needle technique was used to measure IP at time points before and after treatment with a variety of immunotherapy and chemotherapy regimens. Selected patients had IP measurements during chemotherapy or immunotherapy infusions. Ultrasound or computed tomography was used to evaluate the size of the studied lesions and their relationship to normal structures. The mean baseline IP in melanoma nodules (n = 22) and lymphoma nodules (n = 7) was 29.8 and 4.7 mm Hg, respectively (P = 0.013 for the difference between tumor types). tn a subset of melanoma nodules for which IP had been measured before and after treatment, the IP increased significantly over time for nonresponding melanoma lesions from a baseline of 24.4 to 53.9 mm Hg after treatment (P = 0.005) and decreased in melanoma lesions that responded to treatment where the mean baseline and post-treatment IPs were 12.2 and 0 mm Hg, respectively (P = 0.001 for the difference in IP profiles between responding and nonresponding lesions). Six of seven lymphoma nodules responded completely to chemotherapy or radiation. The single nodule that did not respond had a baseline IP of 1 mm Hg that increased to 30 mm Hg after treatment. Tumor IP differs significantly between melanoma and non-Hodgkin's lymphoma. The changes in IP over time differ significantly between responding and nonresponding melanoma lesions. IP that increases during treatment appears to be associated with tumor progression in these tumor types. C1 FREDERICK MEM HOSP,FREDERICK,MD 21701. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYN CORP,CLIN SERV PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,DATA MANAGEMENT SERV INC,FREDERICK,MD 21702. RP CURTI, BD (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,FREDERICK,MD 21701, USA. NR 20 TC 109 Z9 109 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 15 PY 1993 VL 53 IS 10 BP 2204 EP 2207 PG 4 WC Oncology SC Oncology GA LB957 UT WOS:A1993LB95700002 PM 8485703 ER PT J AU RAO, JS STECK, PA MOHANAM, S STETLERSTEVENSON, WG LIOTTA, LA SAWAYA, R AF RAO, JS STECK, PA MOHANAM, S STETLERSTEVENSON, WG LIOTTA, LA SAWAYA, R TI ELEVATED LEVELS OF M(R) 92,000 TYPE-IV COLLAGENASE IN HUMAN BRAIN-TUMORS SO CANCER RESEARCH LA English DT Note ID EXTRACELLULAR-MATRIX PROTEINS; BRONCHIAL EPITHELIAL-CELLS; RAT GLIOMA-CELLS; TISSUE INVITRO; BASEMENT-MEMBRANE; INVASION; METALLOPROTEINASES; INHIBITORS; EXPRESSION; PROTEASE AB Local invasive growth is one of the key features of primary malignant brain tumors accompanied by remodeling of the vasculature and destruction of normal brain tissue. Tissue invasiveness is an essential biological function used by a tumor to overcome the various barriers to its progression. The expression of metalloproteases has been shown to play a critical role in the invasive process in a number of tumors; however, their expression in human brain tumors has not been previously reported. In this study we showed metalloprotease activities at M(r) 240,000, 123,000, 92,000, 72,000, and 67,000 in brain tumor extracts. These enzyme activities were inhibited by EDTA, an inhibitor of metalloproteases. Significant increases in levels of protease bands at M(r) 92,000, 123,000, and 240,000 were observed in glioblastoma and metastatic lung tumors. Enzymatic inhibition and Western blotting with M(r) 92,000 type IV collagenase antibody confirmed the presence of M(r) 92,000 type IV collagenase in all samples. Quantitative analysis by densitometry showed 8-10-fold and 6-8-fold increases in M(r) 92,000 type IV collagenase activity in glioblastoma and metastatic lung carcinoma samples, respectively when compared with normal brain, meningioma, astrocytoma, metastatic colon, and breast carcinoma samples. These findings provide evidence for elevated levels of metalloproteases in glioblastomas and suggest a therapeutic target for minimizing the invasive propensity of gliomas using protease inhibitors. C1 UNIV TEXAS,MD ANDERSON CANC CTR,DEPT NEUROONCOL,HOUSTON,TX 77030. NCI,PATHOL LAB,BETHESDA,MD 20892. RP RAO, JS (reprint author), UNIV TEXAS,MD ANDERSON CANC CTR,DEPT NEUROSURG,1515 HOLCOMBE BLVD,HOUSTON,TX 77030, USA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 35 TC 236 Z9 239 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 15 PY 1993 VL 53 IS 10 BP 2208 EP 2211 PG 4 WC Oncology SC Oncology GA LB957 UT WOS:A1993LB95700003 PM 8485704 ER PT J AU DARWICHE, N CELLI, G SLY, L LANCILLOTTI, F DE LUCA, LM AF DARWICHE, N CELLI, G SLY, L LANCILLOTTI, F DE LUCA, LM TI RETINOID STATUS CONTROLS THE APPEARANCE OF RESERVE CELLS AND KERATIN EXPRESSION IN MOUSE CERVICAL EPITHELIUM SO CANCER RESEARCH LA English DT Article ID SERUM VITAMIN-A; PHASE-I TRIAL; COLLAGEN SPONGE; INTRAEPITHELIAL NEOPLASIA; TERMINAL DIFFERENTIATION; RNA-POLYMERASE; SEX STEROIDS; ACID; METAPLASIA; DYSPLASIA AB We describe an animal model to induce the histogenesis of squamous metaplasia of the cervical columnar epithelium, a condition usually preceding cervical neoplasia. This model is based on dietary retinoid depletion in female mice. Control sibling mice fed the same diet but with all-trans-retinoic acid (at 3 mug/g diet) showed the normal endocervical epithelial and glandular columnar morphology, typical of a simple epithelium without subcolumnar reserve cells. The stratified squamous ectocervical epithelium of these mice fed all-trans retinoic acid showed intense immunohistochemical staining in basal and suprabasal cells with monospecific antibodies against keratins K5, K14, K6, K13, and, suprabasally, with antibodies specific for Kl and K10. At the squamocolumnar junction, the adjacent columnar epithelium (termed ''suprajunctional'') did not show staining for K5, K14, K6, K13, K1, and K10 but specifically stained for keratin K8, typical of simple epithelia and absent from the adjacent ectocervical squamous stratified lining (termed ''subjunctional''), in striking contrast. Sections of the squamocolumnar junction from mice kept on the vitamin A-deficient diet for 10 weeks showed suprajunctional isolated patches of reserve cells, proximal and distal to the junction. These cells were detected prior to any symptoms of vitamin A deficiency, such as loss of body weight or respiratory discomfort. The subcolumnar reserve cells induced by vitamin A deficiency displayed positive staining for K5 and K14. As deficiency became severe, the reserve cells occupied the entirety of the suprajunctional basement membrane. This epithelium eventually became stratified and squamous metaplastic, the squamocolumnar junction was no longer discernible, and the entire endocervical epithelium and the endometrial glands lost K8 positivity, while acquiring K5, K14, K6. K13, K1. and K10 keratins typical of the ectocervix under normal conditions of vitamin A nutriture. Vitamin A deficiency also altered keratin expression and localization in squamous subjunctional epithelium. In situ hybridization studies for K1 and K5 mRNA showed their major site of expression at the basal (K5) and immediately suprabasal (K1) cell layers. The localization of both K5 and KI proteins in these same cell layers, and above, is consistent with transcriptional regulation of these keratins. Early vitamin A deficiency caused the appearance of single subcolumnar reserve cells expressing K5 mRNA. After these cells grew into a squamous focus. K1 mRNA became expressed suprabasally. We conclude that retinoid status plays a key role in maintaining differentiative characteristics of the cervical and glandular epithelia and, as such, may be a modulating factor in the development of cervical cancer. C1 NCI, CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB, BLDG 37, ROOM 3A-17, BETHESDA, MD 20892 USA. OI Darwiche, Nadine/0000-0002-1862-5426 NR 71 TC 53 Z9 54 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 15 PY 1993 VL 53 IS 10 BP 2287 EP 2299 PG 13 WC Oncology SC Oncology GA LB957 UT WOS:A1993LB95700017 PM 7683571 ER PT J AU WALLACE, PK PALMER, LD PERRYLALLEY, D BOLTON, ES ALEXANDER, RB HORAN, PK YANG, JC MUIRHEAD, KA AF WALLACE, PK PALMER, LD PERRYLALLEY, D BOLTON, ES ALEXANDER, RB HORAN, PK YANG, JC MUIRHEAD, KA TI MECHANISMS OF ADOPTIVE IMMUNOTHERAPY - IMPROVED METHODS FOR INVIVO TRACKING OF TUMOR-INFILTRATING LYMPHOCYTES AND LYMPHOKINE-ACTIVATED KILLER-CELLS SO CANCER RESEARCH LA English DT Article ID PERIPHERAL-BLOOD LYMPHOCYTES; METASTATIC MELANOMA; ANTITUMOR-ACTIVITY; RECOMBINANT INTERLEUKIN-2; AUTOLOGOUS HUMAN; ADHERENT; MICE; REGRESSION; CANCER AB Adoptive immunotherapy with tumor-infiltrating lymphocytes and lymphokine-activated killer cells has been demonstrated to mediate regression of tumors in murine models and in selected patients with advanced cancer. Improved methods for monitoring immune cell traffic, particularly to sites of tumor, are needed to elucidate mechanisms of antitumor activity and optimize treatment protocols. Traditional cell tracking methods such as fluorescent protein labeling and radiolabeling using In-111, I-125, or Cr-51 are limited by isotope half-life, leakage or transfer of label from immune cells, and toxicity or altered cell function caused by the labeling process. Labeling with genetic markers allows long-term cell tracking but is laborious to perform and difficult to quantitate. We have used two recently described lipophilic cell tracking compounds (PKH26 and I-125-PKH95) which stably partition into lipid regions of the cell membrane to track immune cells in vivo. Concentrations of each tracking compound which had no adverse effects were determined for a variety of murine TIL and lymphokine-activated killer cell functions. Viability was unimpaired at labeling concentrations of up to 5 muM for PKH95 and 20 muM for PKH26. TIL proliferation was unaltered by labeling with up to 5 muM PKH95, 20 muM PKH26, or a combination of 15 muM PKH26 and 5 muM PKH95. In vitro cytotoxic effector function and in vivo therapeutic efficacy of lymphokine-activated killer cells and TIL were also unimpaired by labeling with 20 muM PKH26 or 1 muM I-125-PKH95. Subsequent studies in an adoptive transfer immunotherapy model used I-125-PKH95 to track the biodistribution of TIL in tumor and in non-tumor-bearing animals and PKH26 fluorescence to monitor microdistribution within tissues and distinguish TIL from host T-cells. The results suggest that differential accumulation. selective retention, or proliferation at the tumor site cannot account for the observed pattern of therapeutic efficacy. We hypothesize that a minimum number of TIL must reach the tumor site in order to achieve a demonstrable therapeutic effect. C1 ZYNAXIS CELL SCI INC,371 PHOENIXVILLE PIKE,MALVERN,PA 19355. NCI,SURG BRANCH,BETHESDA,MD 20892. FU NIAID NIH HHS [AI28600] NR 38 TC 69 Z9 70 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 15 PY 1993 VL 53 IS 10 BP 2358 EP 2367 PG 10 WC Oncology SC Oncology GA LB957 UT WOS:A1993LB95700028 PM 8485722 ER PT J AU OLOPADE, OI BUCHHAGEN, DL MALIK, K SHERMAN, J NOBORI, T BADER, S NAU, MM GAZDAR, AF MINNA, JD DIAZ, MO AF OLOPADE, OI BUCHHAGEN, DL MALIK, K SHERMAN, J NOBORI, T BADER, S NAU, MM GAZDAR, AF MINNA, JD DIAZ, MO TI HOMOZYGOUS LOSS OF THE INTERFERON GENES DEFINES THE CRITICAL REGION ON 9P THAT IS DELETED IN LUNG CANCERS SO CANCER RESEARCH LA English DT Article ID TUMOR SUPPRESSOR GENES; ALPHA-INTERFERON; CELL CARCINOMA; ABNORMALITIES; CHROMOSOME-3; ADENOCARCINOMA; DELETIONS; FRAGMENTS; LEUKEMIA; LINKAGE AB Cytogenetic analyses of non-small cell lung cancer have revealed deletions of the short arm of chromosome 9 with breakpoints at 9p11-pter in a significant proportion of tumors. Recent evidence suggests that homozygous loss of the interferon (IFN) and methylthioadenosine phosphorylase (MTAP) genes located on 9p and a tumor suppressor gene closely linked to them is associated with acute lymphoblastic leukemia and with gliomas. We have observed alterations of DNA sequences on 9p which include the IFN genes at a significant frequency in all types of human lung cancers (20 of 56 or 36%). The genetic alterations observed include homozygous or hemizygous deletions of the IFN genes as well as rearrangement of contiguous DNA sequences. In addition to these genomic alterations. 10 of 22 (45%) cell lines examined lacked MTAP enzyme activity. Overall, 24 of 56 (43%) lung cancer cell lines examined had hemizygous or homozygous loss of DNA sequences which include the IFN or MTAP genes. These findings suggest that the putative tumor suppressor gene at this locus contributes to the malignant process in lung cancers, as well as other types of human cancer. C1 NCI,NAVY MED ONCOL BRANCH,BETHESDA,MD 20814. SW MED CTR,HAROLD C SIMMONS COMPREHENS CANC CTR,DALLAS,TX 75235. UNIV CALIF SAN DIEGO,DEPT MED,LA JOLLA,CA 92093. RP OLOPADE, OI (reprint author), UNIV CHICAGO,DEPT MED,HEMATOL ONCOL SECT,CHICAGO,IL 60637, USA. FU NCI NIH HHS [CA-14599-19, CA-49133] NR 35 TC 167 Z9 169 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 15 PY 1993 VL 53 IS 10 BP 2410 EP 2415 PG 6 WC Oncology SC Oncology GA LB957 UT WOS:A1993LB95700035 PM 7683574 ER PT J AU CANTOR, KP BLAIR, A BROWN, LM BURMEISTER, LF EVERETT, G AF CANTOR, KP BLAIR, A BROWN, LM BURMEISTER, LF EVERETT, G TI PESTICIDES AND OTHER AGRICULTURAL RISK-FACTORS FOR NON-HODGKINS-LYMPHOMA AMONG MEN IN IOWA AND MINNESOTA SO CANCER RESEARCH LA English DT Letter C1 UNIV IOWA,DEPT PREVENT MED,IOWA CITY,IA. ORLANDO REG MED CTR INC,DEPT INTERNAL MED,ORLANDO,FL. RP CANTOR, KP (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892, USA. NR 3 TC 11 Z9 11 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 15 PY 1993 VL 53 IS 10 BP 2421 EP 2421 PG 1 WC Oncology SC Oncology GA LB957 UT WOS:A1993LB95700037 PM 8329071 ER PT J AU CLIFFORD, CK AF CLIFFORD, CK TI FUNDING MECHANISMS FOR RESEARCH THROUGH THE NATIONAL-CANCER-INSTITUTE SO CANCER RESEARCH LA English DT Editorial Material RP CLIFFORD, CK (reprint author), NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 15 PY 1993 VL 53 IS 10 BP S2434 EP S2435 PG 2 WC Oncology SC Oncology GA LB957 UT WOS:A1993LB95700042 ER PT J AU YANAGISHITA, M AF YANAGISHITA, M TI A BRIEF-HISTORY OF PROTEOGLYCANS SO EXPERIENTIA LA English DT Article RP YANAGISHITA, M (reprint author), NIDR,BONE RES BRANCH,BETHESDA,MD 20892, USA. NR 34 TC 5 Z9 5 U1 0 U2 3 PU BIRKHAUSER VERLAG AG PI BASEL PA PO BOX 133 KLOSTERBERG 23, CH-4010 BASEL, SWITZERLAND SN 0014-4754 J9 EXPERIENTIA JI Experientia PD MAY 15 PY 1993 VL 49 IS 5 BP 366 EP 368 DI 10.1007/BF01923581 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LD651 UT WOS:A1993LD65100002 PM 8500592 ER PT J AU FEDARKO, NS AF FEDARKO, NS TI ISOLATION AND PURIFICATION OF PROTEOGLYCANS SO EXPERIENTIA LA English DT Review DE PROTEOGLYCANS; ASSAYS; PURIFICATION; EXTRACTION; ULTRACENTRIFUGATION; CHROMATOGRAPHY ID HEPARAN-SULFATE PROTEOGLYCAN; HUMAN-LUNG FIBROBLASTS; NEWLY SYNTHESIZED PROTEOGLYCANS; HYALURONATE-BINDING-PROPERTIES; GLOMERULAR EPITHELIAL-CELLS; BOVINE ARTICULAR-CARTILAGE; FIELD FLOW FRACTIONATION; CHONDROITIN SULFATE; GROWTH-FACTOR; BASEMENT-MEMBRANE AB Purification of a protein typically involves development of a quantitative assay to track protein integrity (e.g. enzyme activity) during subsequent isolation steps. The generalized procedure involves choosing the source of the protein, defining extraction conditions, developing bulk purification methods followed by refined, more selective methods. The purification of proteoglycans is often complicated by a) limited source quantities, b) necessity of chaotropic solvents for efficient extraction, c) their large molecular size and d) lack of defined functions to enable purity (i.e. activity, conformation) to be assessed. Because the usual goal of proteoglycan purification is physical characterization (intact molecular weight, core protein and glycosaminoglycan class and size), the problems of a suitable assay and/or native conformation are avoided. The 'assay' for tracking proteoglycan isolation typically utilizes uronic acid content or radiolabel incorporation as a marker. Once extracted from their cellular/extracellular environment, proteoglycans can be isolated by density gradient centrifugation and/or column chromatography techniques. Recent advances in the composition of chromatographic supports have enabled the application of ion-exchange. gel permeation, hydrophobic interaction and affinity chromatography resins using efficient high-pressure liquid chromatography to proteoglycan purification. RP NIDR, BONE RES BRANCH, BETHESDA, MD 20892 USA. OI Fedarko, Neal/0000-0001-6055-6279 NR 162 TC 17 Z9 19 U1 0 U2 4 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 0014-4754 J9 EXPERIENTIA JI Experientia PD MAY 15 PY 1993 VL 49 IS 5 BP 369 EP 383 DI 10.1007/BF01923582 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LD651 UT WOS:A1993LD65100003 PM 8500593 ER PT J AU HU, WS WANG, RYH SHIH, JWK LO, SC AF HU, WS WANG, RYH SHIH, JWK LO, SC TI IDENTIFICATION OF A PUTATIVE INFC-RPMI-RPLT OPERON FLANKED BY LONG INVERTED REPEATS IN MYCOPLASMA-FERMENTANS (INCOGNITUS STRAIN) SO GENE LA English DT Article ID ESCHERICHIA-COLI; INFECTIOUS AGENT; AIDS; INITIATION; SEQUENCE; GENE; TRANSCRIPTION; TRYPTOPHAN; MECHANISM; CLONING AB A specific 1542-bp DNA fragment was amplified from Mycoplasma fermentans (incognitus strain) using a unique 23-nucleotide (nt) synthetic deoxyribonucleotide (oligo) (5'-TCCAAAAAGTCCGGAATTTGGGG) as the primer pair in the polymerase chain reaction (PCR). The 23-nt sequence is part of the 29-bp terminal inverted repeat (IR) which forms the left potential stem-and-loop (s&1) structure of the previously identified M. fermentans insertion-sequence(IS)-like genetic element [Hu et al., Gene 93 (1990) 67-72]. The amplified DNA was cloned and sequenced. A pair of 27-bp IR containing the 23-nt synthetic oligo was identified at both termini. Between the IR, there are four potential open reading frames (ORFs) which are arranged adjacent to each other in the order, ORF-1, ORF-2, ORF-3 and ORF-4, with parts of ORF-1 and ORF-2 overlapping. The deduced amino acid (aa) sequences of ORF-2, ORF-3 and ORF-4 are 34 to 60% identical to the translation initiation factor IF3 (encoded by the infC gene), ribosomal proteins L35 (rpmI gene) and L20 (rplT gene) of Escherichia coli and Bacillus stearothermophilus, respectively. In bacteria, the infC-rpmI-rplT genes are organized to function as an operon. There are multiple sites with promoter-like sequences identified upstream from the putative infC gene in the mycoplasma closely resembling the gene arrangement in the bacterial operon. All three genes of ORF-2, ORF-3 and ORF-4 are preceded individually by a strong appropriately spaced (7 and 10 bp) putative Shine-Dalgamo sequence (5'-AAGGA). In addition, ORF-2 uses the unusual triplet, ATT, as the start codon, the same as that for infC in the bacterial operon. Thus, the cluster of genes (ORF-2, ORF-3 and ORF-4) is identified as a putative mycoplasma infC-rpmI-rplT operon. Most interestingly, our study reveals that this operon potentially constitutes a part of a mobile genetic element in the incognitus strain of M. fermentans. C1 ARMED FORCES INST PATHOL,DEPT INFECT & PARASIT DIS PATHOL,AMER REGISTRY PATHOL,WASHINGTON,DC 20306. NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BETHESDA,MD 20892. FU NIAID NIH HHS [AI-31830] NR 23 TC 11 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD MAY 15 PY 1993 VL 127 IS 1 BP 79 EP 85 DI 10.1016/0378-1119(93)90619-E PG 7 WC Genetics & Heredity SC Genetics & Heredity GA LB881 UT WOS:A1993LB88100010 PM 8486291 ER PT J AU FERRIS, FL AF FERRIS, FL TI ISSUES IN MANAGEMENT OF DIABETIC-RETINOPATHY SO HOSPITAL PRACTICE LA English DT Article AB Panretinal photocoagulation could prevent most blindness from proliferative disease-if risk is identified early. This makes it essential that primary physicians include annual ophthalmologic evaluation in the management of patients at risk. Meanwhile, studies are under way on promising medical approaches, including intensive insulin regimens, aldose reductase blockers, and angiogenesis inhibitors. RP FERRIS, FL (reprint author), NEI,CLIN TRIALS BRANCH,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MCGRAW HILL HEALTHCARE PUBLICATIONS PI MINNEAPOLIS PA 4530 WEST 77TH ST, MINNEAPOLIS, MN 55435-5000 SN 8750-2836 J9 HOSP PRACT JI Hosp. Pract. PD MAY 15 PY 1993 VL 28 IS 5 BP 79 EP & PG 0 WC Medicine, General & Internal SC General & Internal Medicine GA LC352 UT WOS:A1993LC35200009 PM 8491803 ER PT J AU KIM, YS LIOTTA, LA KOHN, EC AF KIM, YS LIOTTA, LA KOHN, EC TI CANCER INVASION AND METASTASIS .4. SO HOSPITAL PRACTICE LA English DT Article AB Mechanisms by which primary tumors invade local tissues and spread to distant sites are beginning to be understood. Included are factors involved in cell-to-cell and cell-to-extracellular matrix interactions, motility factors, and genetic controls. Knowledge of such mechanisms is spurring development of novel therapeutic agents for clinical study. RP KIM, YS (reprint author), NCI,PATHOL LAB,BETHESDA,MD 20892, USA. NR 0 TC 7 Z9 7 U1 0 U2 1 PU MCGRAW HILL HEALTHCARE PUBLICATIONS PI MINNEAPOLIS PA 4530 WEST 77TH ST, MINNEAPOLIS, MN 55435-5000 SN 8750-2836 J9 HOSP PRACT JI Hosp. Pract. PD MAY 15 PY 1993 VL 28 IS 5 BP 92 EP 96 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA LC352 UT WOS:A1993LC35200010 PM 8491804 ER PT J AU IKEDA, M OGATA, F CURTIS, SW LUBAHN, DB FRENCH, FS WILSON, EM KORACH, KS AF IKEDA, M OGATA, F CURTIS, SW LUBAHN, DB FRENCH, FS WILSON, EM KORACH, KS TI CHARACTERIZATION OF THE DNA-BINDING DOMAIN OF THE MOUSE UTERINE ESTROGEN-RECEPTOR USING SITE-SPECIFIC POLYCLONAL ANTIBODIES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEAT-SHOCK PROTEIN; GLUCOCORTICOID RECEPTOR; DEOXYRIBONUCLEIC-ACID; RESPONSIVE ELEMENT; NUCLEAR RECEPTORS; STEROID-RECEPTORS; COMPLEXES; FORM; SUPERFAMILY; ESTRADIOL AB The DNA-binding domain of the mouse uterine estrogen receptor (ER) was characterized using site-specific polyclonal antibodies. The peptides used as antigens have sequences corresponding to amino acids 185-199 and 227-245, the two zinc finger regions of the DNA-binding domain of the human ER, and produced antisera designated A-1542 and A-1554, respectively. Mouse uterine nuclear ER and salt-activated 4 S cytosol receptor, as well as 8 S untransformed cytosol receptor, were observed to react with the antisera by Western blot and sucrose density gradient centrifugation analyses indicating that the DNA-binding domain of the 8 S cytosol receptor is not completely masked by heat shock protein 90 or other proteins. Only A-1554 detected a nuclear-specific doublet form of the ER on Western blot analysis. In a gel shift assay, neither antisera altered the pattern of the nuclear ER interaction with the vitellogenin A2 estrogen response element (VRE). In contrast, antiserum A-1554 partially shifted the 8 S cytosol receptor-VRE complex. This concurs with mutational analysis and x-ray crystallography studies with the human ER that have shown that the second finger is not in contact with the DNA. The results of the gel shift assay were confirmed by sucrose density gradient analysis using the same buffer conditions. The nuclear receptor-VRE complex did not react with either antisera, suggesting that when the dimeric nuclear receptor form binds the VRE, the specific receptor epitopes involved with the DNA binding may be blocked and unable to bind the antisera. The cytosol receptor-VRE complex reacted only partially with the second finger antisera A-1554, suggesting that on receptor monomers the second finger epitope is not completely blocked by DNA binding or dimer formation. C1 NIEHS,REPROD & DEV TOXICOL LAB,RECEPTOR BIOL SECT,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,SCH MED,REPROD BIOL LAB,CHAPEL HILL,NC 27514. OI Korach, Kenneth/0000-0002-7765-418X FU NICHD NIH HHS [HD16910, P30-HD18968, HD04466] NR 34 TC 12 Z9 12 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 15 PY 1993 VL 268 IS 14 BP 10296 EP 10302 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LB800 UT WOS:A1993LB80000051 PM 8486692 ER PT J AU ABBOTTS, J BEBENEK, K KUNKEL, TA WILSON, SH AF ABBOTTS, J BEBENEK, K KUNKEL, TA WILSON, SH TI MECHANISM OF HIV-1 REVERSE-TRANSCRIPTASE - TERMINATION OF PROCESSIVE SYNTHESIS ON A NATURAL DNA-TEMPLATE IS INFLUENCED BY THE SEQUENCE OF THE TEMPLATE-PRIMER STEM SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID I LARGE FRAGMENT; POLYMERASE-I; OLIGONUCLEOTIDES; ALPHA; IDENTIFICATION; SPECIFICITY; REPLICATION; BINDING; SITE AB During processive DNA synthesis in vitro, the human immunoefficiency virus, type 1 (HIV-1) reverse transcriptase encounters template nucleotide positions at which continued synthesis is difficult. At these positions, the enzyme has a relatively high probability of dissociating from the template, and product molecules of corresponding length accumulate as the incubation proceeds. These positions, which are known as termination sites, could be associated with template secondary structures in some cases, but many termination sites appear to be template sequence-related rather than secondary structure-related. Mechanisms producing these blocks in processive DNA synthesis are not well understood. In this study, to examine further the effects of template sequence on termination, we engineered selected single-base changes in the M13mp2 template, and we found that such changes can influence termination. Several general trends emerged from the study. First, strong termination sites rarely correspond to dATP as the ''incoming'' substrate opposite template T. Second, the sequence of the template-primer stem is more important for termination than the sequence of the single-stranded template ahead of the primer. Thus, we note the phenomenon of action at a distance: changing sequence at one nucleotide position in the template-primer stem alters termination at other positions, a few nucleotides distant at the primer 3' end. A and C as template bases in the template-primer stem have opposite effects. A is the strongest terminator residue, and C is the weakest terminator residue, followed by G. Since termination sites are produced by reverse transcriptase dissociation from the template-primer, the results suggest that the HIV-1 reverse transcriptase has properties reminiscent of a sequence-specific double-stranded DNA-binding protein in that its binding mechanism can distinguish both base residues and positions in the double-stranded DNA template-primer stem. C1 NIEHS, MOLEC GENET LAB E3-01, POB 12233, RES TRIANGLE PK, NC 27709 USA. NIH, BIOCHEM LAB, BETHESDA, MD 20892 USA. NR 25 TC 77 Z9 76 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 15 PY 1993 VL 268 IS 14 BP 10312 EP 10323 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LB800 UT WOS:A1993LB80000053 PM 7683674 ER PT J AU BEBENEK, K ABBOTTS, J WILSON, SH KUNKEL, TA AF BEBENEK, K ABBOTTS, J WILSON, SH KUNKEL, TA TI ERROR-PRONE POLYMERIZATION BY HIV-1 REVERSE-TRANSCRIPTASE - CONTRIBUTION OF TEMPLATE-PRIMER MISALIGNMENT, MISCODING, AND TERMINATION PROBABILITY TO MUTATIONAL HOT-SPOTS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN IMMUNODEFICIENCY VIRUS; EUKARYOTIC DNA-POLYMERASES; BASE SUBSTITUTION; TRANSIENT MISALIGNMENT; FIDELITY; MUTAGENESIS; SPECIFICITY; REPLICATION; FRAMESHIFT; MECHANISM AB We have observed previously that DNA template-directed polymerization by the type 1 human immunodeficiency virus reverse transcriptase is error-prone for single-nucleotide substitution, addition and deletion errors at homopolymeric sequences. We have also noted strong termination of processive synthesis at these positions (Bebenek, K., Abbotts, J., Roberts, J. D., Wilson, S. H., and Kunkel, T. A. (1989) J. Biol. Chem. 264, 16948-16956). Here we have tested three models to explain errors at these hot spots: template-primer misalignment for deletion errors, and dislocation and direct miscoding for substitution errors. The approach involves introducing single-nucleotide changes within or flanking the homopolymeric hot spots and examining the effects that these changes have on human immunodeficiency virus type 1 (HIV-1) reverse transcriptase error rate, error specificity, and termination probability. The results obtained suggest that single-nucleotide deletion errors in homopolymeric runs result from template-primer misalignment and that both direct miscoding and template-primer dislocation contribute to the base substitution hot spots. The data also suggest that base substitution errors at one position can be templated by the preceding nucleotide or either of the next two nucleotides. Frameshift error rates at homopolymeric sites were affected by changes in the sequences flanking the runs, including single-nucleotide differences in the single-stranded template strand and in the double-stranded primer region as many as six nucleotides distant from the hot spot. Both increases and decreases in frameshift fidelity were observed, and most of these correlated with concomitant increases or decreases in the probability that HIV-1 reverse transcriptase terminated processive synthesis within the run. These data provide further support for a relationship between the frameshift fidelity and the processivity of DNA-dependent DNA synthesis by HIV-1 reverse transcriptase. C1 NIEHS, MOLEC GENET LAB E3-01, POB 12233, RES TRIANGLE PK, NC 27709 USA. NIH, BIOCHEM LAB, BETHESDA, MD 20892 USA. NR 21 TC 142 Z9 144 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 15 PY 1993 VL 268 IS 14 BP 10324 EP 10334 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LB800 UT WOS:A1993LB80000054 PM 7683675 ER PT J AU JIANG, WP SADLER, PM JENKINS, NA GILBERT, DJ COPELAND, NG BOND, JS AF JIANG, WP SADLER, PM JENKINS, NA GILBERT, DJ COPELAND, NG BOND, JS TI TISSUE-SPECIFIC EXPRESSION AND CHROMOSOMAL LOCALIZATION OF THE ALPHA-SUBUNIT OF MOUSE MEPRIN-A SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IMMUNOHISTOCHEMICAL LOCALIZATION; KIDNEY; GENE; METALLOENDOPEPTIDASES; EXTRACTION; MEMBRANE; MEP-1; MICE; RAT; DNA AB Meprins, membrane-bound oligomeric metalloendopeptidases, contain alpha and/or beta subunits. Their activities have been found in the mouse and rat kidney. The cloned cDNA for the mouse alpha subunit of meprin A (EC 3.4.24.18) was used here to survey mRNA expression in kidney of different mouse strains and in various tissues of mice and rats. A single message of 3.6 kilobases was found in kidney of random bred (ICR) and inbred mice (C57BL/6, DBA/2) that contain high meprin A activity and in Sprague-Dawley rat kidney. The alpha subunit message was undetectable in the kidney of C3H/He and CBA mice, inbred strains that do not express meprin A activity. Therefore, meprin A activity in the kidney of mouse strains correlates with the amount of alpha subunit mRNA present. The 3.6-kilobase mRNA meprin alpha subunit message was also detected in the small intestine of the rat but not in mice. No message was detected in brain, heart, skeletal muscle, liver, lung, or spleen of mice or rats. Polymerase chain reaction amplification or Southern blot analysis of genomic DNA revealed that the gene for the alpha subunit is present in all mouse strains as well as in human, monkey, rat, mouse, dog, cow, rabbit, and chicken, but it was not detected in yeast. There is one gene copy present in the mouse genome. The gene was localized to mouse chromosome 17 centromeric to the major histocompatibility complex (H-2) by the interspecific backcrossing method. The localization of this allele to Mep-1, the gene previously found to regulate the expression of meprin A activity in mice, supports the proposal that Mep-1 is the structural gene for the alpha subunit. C1 VIRGINIA POLYTECH INST & STATE UNIV,DEPT BIOCHEM,BLACKSBURG,VA 24061. NCI,FREDERICK CANC RES & DEV CTR,BASIC RES PROGRAM,ADV BIOSCI LABS INC,MAMALIAN GENET LAB,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101]; NIDDK NIH HHS [DK 19691] NR 32 TC 29 Z9 29 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 15 PY 1993 VL 268 IS 14 BP 10380 EP 10385 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LB800 UT WOS:A1993LB80000061 PM 7683677 ER PT J AU FALZON, M FEWELL, JW KUFF, EL AF FALZON, M FEWELL, JW KUFF, EL TI EBP-80, A TRANSCRIPTION FACTOR CLOSELY RESEMBLING THE HUMAN AUTOANTIGEN KU, RECOGNIZES SINGLE-STRAND TO DOUBLE-STRAND TRANSITIONS IN DNA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LONG TERMINAL REPEAT; AUTO-ANTIGEN; PROTEIN; BINDING; CDNA; SEQUENCE; PROMOTER; AUTOANTIBODIES; PURIFICATION; MECHANISM AB We have previously reported the purification and characterization of the transcription factor EBP-80 (Falzon, M., and Kuff, E. L. (1989) J. Biol. Chem. 264, 21915-21922). EBP-80 mediates the DNA methylation effect on transcription from an endogenous proviral long terminal repeat. Here we show that EBP-80 is very similar if not identical to the Ku autoantigen, a heterodimeric nuclear protein first detected by antibodies from autoimmune patients (Mimori, T., Akizuki, M., Yamagata, H., Inada, S., Yoshida, S., and Homma, M. (1981) J. Clin. Invest. 68, 611-620). A number of laboratories have shown that the Ku protein complex binds to free double-stranded DNA ends. In this study, we have examined the binding properties of EBP-80. EBP-80 binds single-stranded DNA with low affinity. Binding to random sequence double-stranded DNA depends on the length of the duplex and is optimal with oligomers of 30 and 32 base pairs; the protein complexes formed with these oligomers have K(d) values of 15-20 pM. It binds with comparable high affinities to blunt-ended duplex DNA, to duplex DNA ending in hairpin loops, and to constructs in which an internal segment of duplex DNA is flanked by single-strand extensions. EBP-80 also interacts effectively with circular duplex molecules containing a 30-nucleotide single-stranded region (gap) or a double-stranded segment of nonhomology (bubble), but only weakly with the corresponding closed circular construct made up entirely of duplex DNA. EBP-80 prefers A/T to G/C ends. The binding properties of EBP-80 are consistent with the hypothesis that it recognizes single- to double-strand transitions in DNA. A model is presented for the interaction of EBP-80 with its target sequence in the proviral long terminal repeat. RP FALZON, M (reprint author), NCI,BIOCHEM LAB,BLDG 37,RM 4C03,BETHESDA,MD 20892, USA. NR 30 TC 205 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 MAY 15 PY 1993 VL 268 IS 14 BP 10546 EP 10552 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LB800 UT WOS:A1993LB80000082 PM 8486707 ER PT J AU EHRENREICH, H RIECKMANN, P SINOWATZ, F WEIH, KA ARTHUR, LO GOEBEL, FD BURD, PR COLIGAN, JE CLOUSE, KA AF EHRENREICH, H RIECKMANN, P SINOWATZ, F WEIH, KA ARTHUR, LO GOEBEL, FD BURD, PR COLIGAN, JE CLOUSE, KA TI POTENT STIMULATION OF MONOCYTIC ENDOTHELIN-1 PRODUCTION BY HIV-1 GLYCOPROTEIN-120 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CENTRAL-NERVOUS-SYSTEM; AIDS DEMENTIA COMPLEX; IMMUNE-DEFICIENCY-SYNDROME; CEREBRAL-ARTERIES; ENVELOPE PROTEIN; GLIAL-CELLS; SOLUBLE CD4; MACROPHAGES; INFECTION AB Monocytes/macrophages play a critical role in the pathogenesis of HIV infection, both as targets for virus replication and as sources of production of multifunctional cytokines. Endothelins, peptides with potent vasoconstricting activities originally isolated from endothelial cells, are also produced and secreted by macrophages in a manner similar to that of other cytokines. In an attempt to explore the potential role of endothelins in HIV-infection, we investigated the effect of the HIV-1 envelope glycoprotein, glycoprotein 120, on monocytic endothelin-1 production. This glycoprotein has been identified as a potent stimulator of monokines such as TNF-alpha and IL-6, which have been implicated as potential mediators of HIV-encephalopathy. We found that glycoprotein 120, similar to LPS, stimulates the secretion of endothelin-1, as well as TNF-alpha, from macrophages in a concentration-dependent manner. Using reverse transcriptase polymerase chain reaction, we found that circulating monocytes in HIV-infected individuals show a distinct expression of the endothelin-1 gene that is not detectable in healthy controls, indicating chronic activation of this gene in HIV-infection. In addition, cerebral macrophages in patients with HIV-encephalopathy were strongly positive for endothelin. Thus, monocytic endothelins appear to be stimulated during HIV infection. Their potent vasoactive properties render them potential candidates for mediating alterations in the cerebral perfusion pattern associated with the AIDS dementia complex. C1 NIAID, IMMUNOREGULAT LAB, BETHESDA, MD 20892 USA. NIAID, CLIN INVEST LAB, BETHESDA, MD 20892 USA. NIAID, BIOL RESOURCES BRANCH, BETHESDA, MD 20892 USA. UNIV GOTTINGEN, DEPT NEUROL, W-3400 GOTTINGEN, GERMANY. UNIV GOTTINGEN, DEPT PSYCHIAT, W-3400 GOTTINGEN, GERMANY. UNIV MUNICH, MED POLIKLIN, W-8000 MUNICH 2, GERMANY. US FDA, CTR BIOLOG EVALUAT & RES, BETHESDA, MD 20014 USA. NCI, PROGRAM RESOURCES INC DYN CORP, FREDERICK, MD 21701 USA. FU NCI NIH HHS [N01-CO-74102] NR 51 TC 109 Z9 112 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 1993 VL 150 IS 10 BP 4601 EP 4609 PG 9 WC Immunology SC Immunology GA LB650 UT WOS:A1993LB65000044 PM 8482849 ER PT J AU SHI, X DALAL, NS KASPRZAK, KS AF SHI, X DALAL, NS KASPRZAK, KS TI GENERATION OF FREE-RADICALS IN REACTIONS OF NI(II)-THIOL COMPLEXES WITH MOLECULAR-OXYGEN AND MODEL LIPID HYDROPEROXIDES SO JOURNAL OF INORGANIC BIOCHEMISTRY LA English DT Article ID ANTIOXIDANT DEFENSE SYSTEMS; HYDROGEN-PEROXIDE; NICKEL CARCINOGENESIS; DIFFERENT STRAINS; DNA DAMAGE; TOXICITY; METAL; REDUCTION; RATS; AUTOXIDATION AB The generation of free radicals from reactions of nickel(II)-thiol complexes with molecular oxygen and model lipid hydroperoxides was investigated by electron spin resonance (ESR) utilizing 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) as a spin trap. Incubation of nickel(II) [Ni(II)] with cysteine in an aerobic environment generated hydroxyl (.OH) radical, which then reacted with cysteine to generate a carbon-centered alkyl (.R) radical. Radical generation was inhibited under a nitrogen atmosphere. Model lipid hydroperoxides, cumene hydroperoxide, and t-butyl hydroperoxide enhanced the yield of these radicals and also generated an alkoxyl (.OR) radical. Radical yield decreased by approximately half under a nitrogen atmosphere. Although histidine did not cause radical formation in the reaction between Ni(II) and cumene hydroperoxide under aerobic conditions, the addition of histidine to a mixture containing Ni(II), cysteine, and cumene hydroperoxide under the same experimental conditions increased the yield of .R radical but lowered the yield of .OR and .OH radical adducts. It thus appears that histidine caused the .OH attack to be more site-specific. Similar results were obtained utilizing t-butyl hydroperoxide. Penicillamine or N-acetylcysteine yielded similar results except that under aerobic conditions, reaction between Ni(II) and N-acetylcysteine without hydroperoxide did not generate a significant concentration of free radicals. Under the same experimental conditions, cystine did not generate any detectable free radicals, suggesting an important role of the -SH group in Ni(II)-mediated free radical generation. The results indicate that free radical generation from the reaction of Ni(II)-thiol complexes and molecular oxygen, and/or lipid hydroperoxides, may play an important role in the mechanism(s) of Ni(II) toxicity and carcinogenesis. C1 W VIRGINIA UNIV,DEPT CHEM,MORGANTOWN,WV 26506. RP SHI, X (reprint author), FCRDC,NCI,COMPARAT CARCINOGENESIS LAB,BLDG 538,ROOM 205,FREDERICK,MD 21702, USA. RI Shi, Xianglin/B-8588-2012 NR 47 TC 37 Z9 40 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0162-0134 J9 J INORG BIOCHEM JI J. Inorg. Biochem. PD MAY 15 PY 1993 VL 50 IS 3 BP 211 EP 225 DI 10.1016/0162-0134(93)80026-6 PG 15 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA LA477 UT WOS:A1993LA47700005 PM 8388916 ER PT J AU LAGAKOS, S PETTINELLI, C STEIN, D AF LAGAKOS, S PETTINELLI, C STEIN, D TI THE CONCORDE TRIAL SO LANCET LA English DT Letter C1 UNIV CALIF SAN FRANCISCO,SAN FRANCISCO GEN HOSP,AIDS PROGRAM,SAN FRANCISCO,CA 94110. NIH,DIV AIDS,BETHESDA,MD 20892. RP LAGAKOS, S (reprint author), HARVARD UNIV,SCH PUBL HLTH,SDAC,DEPT BIOSTAT,BOSTON,MA 02115, USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD MAY 15 PY 1993 VL 341 IS 8855 BP 1276 EP 1276 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA LC497 UT WOS:A1993LC49700025 PM 8098408 ER PT J AU WONG, FL MELLEMGAARD, A BOICE, JD GOLDMAN, MB FRAUMENI, JF AF WONG, FL MELLEMGAARD, A BOICE, JD GOLDMAN, MB FRAUMENI, JF TI HUSBANDS AND WIVES WITH HYPERTHYROIDISM SO LANCET LA English DT Letter C1 HORSHOLM HOSP,HORSHOLM,DENMARK. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. RP WONG, FL (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,ROCKVILLE,MD 20852, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD MAY 15 PY 1993 VL 341 IS 8855 BP 1278 EP 1279 DI 10.1016/0140-6736(93)91180-T PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA LC497 UT WOS:A1993LC49700032 PM 8098415 ER PT J AU MOODY, TW ZIA, F DRAOUI, M BRENNEMAN, DE FRIDKIN, M DAVIDSON, A GOZES, I AF MOODY, TW ZIA, F DRAOUI, M BRENNEMAN, DE FRIDKIN, M DAVIDSON, A GOZES, I TI A VASOACTIVE-INTESTINAL-PEPTIDE ANTAGONIST INHIBITS NONSMALL CELL LUNG-CANCER GROWTH SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE VASOACTIVE INTESTINAL PEPTIDE RECEPTORS; CAMP ID GASTRIN-RELEASING PEPTIDE; ADENYLATE-CYCLASE ACTIVITY; VIP RECEPTORS; HIGH-AFFINITY; CYCLIC-AMP; LINES; EXPRESSION; RAT; GENE; TUMOR AB The most prevalent lung cancer, non-small cell lung cancer (NSCLC) has receptors for vasoactive intestinal peptide (VIP). Here the effects of a VIP antagonist (VIPhyb) on NSCLC growth were investigated. In vivo, when VIPhyb (10 mug, s.c.) was daily injected into nude mice, xenograft formation was significantly inhibited by almost-equal-to 80%. In vitro, VIP (100 nM) stimulated colony formation almost-equal-to 2-fold, whereas 1 muM VIPhyb inhibited colony formation by almost-equal-to 50% when adenocarcinoma cell line NCI-H838 was used. The attenuation of tumor proliferation is receptor mediated, as VIPhyb inhibited specific I-125-labeled VIP binding to cell lines NCI-H157 and NCI-H838 with an IC50 of 0.7 muM. VIP (10 nM) increased the cAMP levels 5-fold when cell line NCI-H838 was used, and 10 muM VIPhyb inhibited the increase in cAMP caused by VIP. Northern blot analysis and radioimmunoassays have shown VIP mRNA and VIP-like immunoreactivity in NSCLC cells. These data suggest that VIP may be a regulatory peptide in NSCLC and that VIPhyb is a VIP receptor antagonist that inhibits proliferation. C1 NICHHD,DEV NEUROBIOL LAB,NEUROCHEM UNIT,BETHESDA,MD 20892. WEIZMANN INST SCI,DEPT ORGAN CHEM,IL-78100 REHOVOT,ISRAEL. TEL AVIV UNIV,SACKLER SCH MED,DEPT CHEM PATHOL,IL-69978 TEL AVIV,ISRAEL. RP MOODY, TW (reprint author), GEORGE WASHINGTON UNIV,SCH MED & HLTH SCI,DEPT BIOCHEM & MOLEC BIOL,2300 EYE ST NW,WASHINGTON,DC 20037, USA. FU NCI NIH HHS [CA-48071, CA-53477] NR 47 TC 127 Z9 127 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 MAY 15 PY 1993 VL 90 IS 10 BP 4345 EP 4349 DI 10.1073/pnas.90.10.4345 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LC720 UT WOS:A1993LC72000006 PM 8389448 ER PT J AU KOZMA, L BALTENSPERGER, K KLARLUND, J PORRAS, A SANTOS, E CZECH, MP AF KOZMA, L BALTENSPERGER, K KLARLUND, J PORRAS, A SANTOS, E CZECH, MP TI THE RAS SIGNALING PATHWAY MIMICS INSULIN ACTION ON GLUCOSE TRANSPORTER TRANSLOCATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MOUSE 3T3-L1 CELLS; HEXOSE-TRANSPORT; GROWTH-FACTOR; TYROSINE KINASE; GENE-EXPRESSION; PLASMA-MEMBRANE; PROTEIN; ADIPOCYTES; STIMULATION; ACTIVATION AB Recent observations suggest that insulin increases cellular levels of activated, GTP-bound Ras protein. We tested whether the acute actions of insulin on hexose uptake and glucose-transporter redistribution to the cell surface are mimicked by activated Ras. 3T3-L1 flbroblasts expressing an activated mutant (Lys-61) N-Ras protein exhibited a 3-fold increase in 2-deoxyglucose uptake rates compared with non-transfected cells. Insulin stimulated hexose uptake by almost-equal-to 2-fold in parental flbroblasts but did not stimulate hexose uptake in the N-Ras61K-expressing fibroblasts. Overexpression of N-Ras61K also mimicked the large effect of insulin on 2-deoxyglucose transport in 3T3-L1 adipocytes, and again the effects of the two agents were not additive. Total glucose transporter protein (GLUT) 1 was similar between parental and N-Ras61K-expressing 3T3-L1 fibroblasts or adipocytes, whereas total GLUT-4 protein was actually lower in the N-Ras61K-expressing compared with parental adipocytes. However, expression of N-RaS61K in 3T3-L1 adipocytes markedly elevated both GLUT-1 and GLUT-4 in plasma membranes relative to intracellular membranes, and insulin had no further effect. These modulations of glucose transporters by N-Ras61K expression are not due to upstream regulation of insulin receptors because receptor tyrosine phosphorylation and association of phosphatidylinositol 3-kinase with tyrosine-phosphorylated proteins were unaffected. These results show that activated Ras mimics the actions of insulin on membrane trafficking of glucose transporters, consistent with the concept that Ras proteins function as intermediates in this insulin signaling pathway. C1 UNIV MASSACHUSETTS,DEPT BIOCHEM & MOLEC BIOL,WORCESTER,MA 01605. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. RP KOZMA, L (reprint author), UNIV MASSACHUSETTS,PROGRAM MOLEC MED,373 PLANTAT ST,WORCESTER,MA 01605, USA. RI Porras, Almudena/N-2121-2015 OI Porras, Almudena/0000-0002-6495-3308 FU NIDDK NIH HHS [DK30648] NR 50 TC 97 Z9 97 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 MAY 15 PY 1993 VL 90 IS 10 BP 4460 EP 4464 DI 10.1073/pnas.90.10.4460 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LC720 UT WOS:A1993LC72000030 PM 8389451 ER PT J AU BONDY, C CHIN, E SMITH, BL PRESTON, GM AGRE, P AF BONDY, C CHIN, E SMITH, BL PRESTON, GM AGRE, P TI DEVELOPMENTAL GENE-EXPRESSION AND TISSUE DISTRIBUTION OF THE CHIP28 WATER-CHANNEL PROTEIN SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE INSITU HYBRIDIZATION; FETAL DEVELOPMENT; RED CELL; KIDNEY; CHOROID PLEXUS ID INTEGRAL MEMBRANE-PROTEIN; FAMILY AB The CHIP28 water channel is a major component of red cell and renal tubule membranes; however, its ontogeny and tissue distribution remain undefined. Three patterns of expression were identified when CHIP28 mRNA was surveyed by in situ hybridization histochemistry in rats between embryonic day 14 and maturity. (i) CHIP28 mRNA and protein were very abundant in hematopoietic tissue and kidneys of mature rats, but strong expression did not occur until after birth, when it appeared in renal proximal tubules and descending thin limbs, red pulp of the spleen, and membranes of circulating red cells. (ii) CHIP28 mRNA was abundant in choroid plexus epithelium throughout fetal development and maturity. (iii) CHIP28 mRNA was transiently observed in periosteum, heart, vascular endothelium, and cornea during fetal development. The ontogeny of kidney and red cell CHIP28 expression coincides with the ability of kidneys to concentrate urine, suggesting that CHIP28 promotes water reabsorption in the proximal nephron and provides red cell osmoregulation needed for passage through the hypertonic medulla. Its presence in the choroid plexus suggests that CHIP28-mediated water transport contributes to secretion of cerebrospinal fluid. The functional role of CHIP28 in developing bone, heart, and eye is unclear. These findings further establish the general physiologic role of CHIP28 as a water channel involved in reabsorption, osmoregulation, and secretion. The studies also suggest other possible functions during fetal development and predict that complex mechanisms will be needed for regulation of CHIP28 gene expression in diverse tissues at distinct points in development. C1 NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT CELL BIOL & ANAT,BALTIMORE,MD 21205. NR 16 TC 150 Z9 154 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 15 PY 1993 VL 90 IS 10 BP 4500 EP 4504 DI 10.1073/pnas.90.10.4500 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LC720 UT WOS:A1993LC72000038 PM 8506291 ER PT J AU WAHL, SM ALLEN, JB WEEKS, BS WONG, HL KLOTMAN, PE AF WAHL, SM ALLEN, JB WEEKS, BS WONG, HL KLOTMAN, PE TI TRANSFORMING GROWTH-FACTOR-BETA ENHANCES INTEGRIN EXPRESSION AND TYPE-IV COLLAGENASE SECRETION IN HUMAN MONOCYTES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE RECRUITMENT; INFLAMMATION; METALLOPROTEINASES; GROWTH FACTORS; ADHESION ID HUMAN MONONUCLEAR PHAGOCYTES; HUMAN FIBRONECTIN RECEPTOR; HUMAN-PLASMA FIBRONECTIN; CELL-ADHESION RECEPTORS; HUMAN-LUNG FIBROBLASTS; SYNOVIAL INFLAMMATION; EXTRACELLULAR-MATRIX; SURFACE RECEPTORS; HUMAN MACROPHAGES; IDENTIFICATION AB Transforming growth factor beta (TGF-beta), secreted within an inflammatory site or injected locally, induces leukocyte margination, chemotaxis, and accumulation. In addition to its potent direct chemotactic activity, TGF-beta may promote this leukocyte response by influencing cell surface integrin expression. At picomolar concentrations, TGF-beta increases steady-state mRNA levels for both the alpha5 and the beta1 chain of the fibronectin receptor in human blood monocytes. This increase in gene expression is reflected by selectively enhanced expression of alpha5 (CDw49e), beta1 (CDw29), and also alpha3 (CDw49c) adhesion molecules on the cell surface. Functionally, TGF-beta promotes, in a dose- and time-dependent fashion, monocyte adhesion to type IV collagen, laminin, and fibronectin. Potentially facilitating the movement of monocytes through the extracellular matrix, TGF-beta triggers transcriptional and posttranscriptional regulation of both the 92-kDa and the 72-kDa gelatinase/type IV collagenase. Thus, TGF-beta may play a pivotal role in the early phases of inflammation and repair through its ability to mediate monocyte adhesion, chemotaxis, and enzymatic digestion of extracellular matrix, whereas in chronic lesions, excess TGF-beta may contribute to persistent leukocyte accumulation. C1 NIDR, DEV BIOL LAB, BETHESDA, MD 20892 USA. RP WAHL, SM (reprint author), NIDR, IMMUNOL LAB, BETHESDA, MD 20892 USA. NR 46 TC 182 Z9 187 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 15 PY 1993 VL 90 IS 10 BP 4577 EP 4581 DI 10.1073/pnas.90.10.4577 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LC720 UT WOS:A1993LC72000054 PM 8506302 ER PT J AU DEVER, TE CHEN, JJ BARBER, GN CIGAN, AM FENG, L DONAHUE, TF LONDON, IM KATZE, MG HINNEBUSCH, AG AF DEVER, TE CHEN, JJ BARBER, GN CIGAN, AM FENG, L DONAHUE, TF LONDON, IM KATZE, MG HINNEBUSCH, AG TI MAMMALIAN EUKARYOTIC INITIATION FACTOR-2-ALPHA KINASES FUNCTIONALLY SUBSTITUTE FOR GCN2 PROTEIN-KINASE IN THE GCN4 TRANSLATIONAL CONTROL MECHANISM OF YEAST SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE PHOSPHORYLATION; INITIATION FACTORS; DOUBLE-STRANDED RNA-DEPENDENT EIF-2-ALPHA KINASE; P68 KINASE; HEME-REGULATED EUKARYOTIC INITIATION FACTOR-2-ALPHA KINASE ID SACCHAROMYCES-CEREVISIAE; EIF-2-ALPHA KINASE; EXPRESSION; INTERFERON; HOMOLOGY; CLONING AB Phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (eIF-2alpha) in Saccharomyces cerevisiae by the GCN2 protein kinase stimulates the translation of GCN4 mRNA. The protein kinases heme-regulated inhibitor of translation (HRI) and double-stranded RNA-dependent eIF-2alpha protein kinase (dsRNA-PK) inhibit initiation of translation in mammalian cells by phosphorylating Ser-51 of eIF-2alpha. We show that HRI and dsRNA-PK phosphorylate yeast eIF-2alpha in vitro and in vivo and functionally substitute for GCN2 protein to stimulate GCN4 translation in yeast. In addition, high-level expression of either mammalian kinase in yeast decreases the growth rate, a finding analogous to the inhibition of total protein synthesis by these kinases in mammalian cells. Phosphorylation of eIF-2alpha inhibits initiation in mammalian cells by sequestering eIF-2B, the factor required for exchange of GTP for GDP on eIF-2. Mutations in the GCN3 gene, encoding a subunit of the yeast eIF-2B complex, eliminate the effects of HRI and dsRNA-PK on global and GCN4-specific translation in yeast. These results provide further in vivo evidence that phosphorylation of eIF-2alpha inhibits translation by impairing eIF-2B function and identify GCN3 as a regulatory subunit of eIF-2B. These results also suggest that GCN4 translational control will be a good model system to study how mammalian eIF-2alpha kinases are modulated by environmental signals and viral regulatory factors. C1 HARVARD UNIV MIT,DIV HLTH SCI & TECHNOL,CAMBRIDGE,MA 02139. MIT,DEPT BIOL,CAMBRIDGE,MA 02139. UNIV WASHINGTON,SCH MED,SCH MED,DEPT OCCUPAT MED,SEATTLE,WA 98195. INDIANA UNIV,DEPT BIOL,BLOOMINGTON,IN 47405. RP DEVER, TE (reprint author), NICHHD,MOLEC GENET LOWER EUKARYOTES,BETHESDA,MD 20892, USA. FU NCRR NIH HHS [RR00166]; NIAID NIH HHS [AI22646]; NIDDK NIH HHS [DK16272, R01 DK016272] NR 20 TC 177 Z9 181 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 15 PY 1993 VL 90 IS 10 BP 4616 EP 4620 DI 10.1073/pnas.90.10.4616 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LC720 UT WOS:A1993LC72000062 PM 8099443 ER PT J AU BARBER, GN WAMBACH, M WONG, ML DEVER, TE HINNEBUSCH, AG KATZE, MG AF BARBER, GN WAMBACH, M WONG, ML DEVER, TE HINNEBUSCH, AG KATZE, MG TI TRANSLATIONAL REGULATION BY THE INTERFERON-INDUCED DOUBLE-STRANDED-RNA-ACTIVATED 68-KDA PROTEIN-KINASE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID VIRUS-INFECTED CELLS; MESSENGER-RNAS; FUNCTIONAL EXPRESSION; GENE-EXPRESSION; MR 68,000; AUTOPHOSPHORYLATION; 2-AMINOPURINE; INHIBITION; MECHANISM; INDUCTION AB Activation of the interferon-inducible 68-kDa protein kinase (referred to as P68) by double-stranded RNA catalyzes phosphorylation of the alpha subunit of eukaryotic protein synthesis initiation factor 2. We have analyzed the transient expression of mutant and wild-type kinase molecules in transfected COS cells to examine the effects of the kinase on gene expression in the absence of other interferon-induced gene products. The wild-type P68 kinase was expressed inefficiently whereas a catalytically inactive P68 was expressed at 30- to 40 -fold higher levels. Protein stability measurements and primer-extension analysis of human kinase-specific mRNA levels provided evidence that kinase expression was regulated at the level of mRNA translation. Further, cotransfection experiments revealed that the domain II catalytically inactive mutant could stimulate reporter gene protein synthesis in a transdominant manner. We also examined the expression of mutants with deletions in the N-terminal double-stranded RNA binding domains and found that a kinase construct lacking aa 156-243 was expressed at levels comparable to the wild type whereas a P68 construct lacking aa 91-243 was expressed at levels 70-fold higher. Both the inactive domain II P68 mutant and the deletion mutant lacking aa 91-243 were less inhibitory to growth in yeast due to the reduced ability to phosphorylate initiation factor 2alpha in vivo. In conclusion we have demonstrated that the P68 kinase can regulate mRNA translation primarily of its own mRNA and to a lesser extent of a heterologous mRNA and that this regulation is notably affected by mutations in either the catalytic or N-terminal regulatory domains. C1 UNIV WASHINGTON,SCH MED,DEPT MICROBIOL,SC-42,SEATTLE,WA 98195. NICHHD,MOLEC GENET LOWER EUKARYOTES SECT,BETHESDA,MD 20892. FU NCRR NIH HHS [RR 00166]; NIAID NIH HHS [AI 22646] NR 52 TC 91 Z9 91 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 15 PY 1993 VL 90 IS 10 BP 4621 EP 4625 DI 10.1073/pnas.90.10.4621 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LC720 UT WOS:A1993LC72000063 PM 8099444 ER PT J AU WHITESELL, L GESELOWITZ, D CHAVANY, C FAHMY, B WALBRIDGE, S ALGER, JR NECKERS, LM AF WHITESELL, L GESELOWITZ, D CHAVANY, C FAHMY, B WALBRIDGE, S ALGER, JR NECKERS, LM TI STABILITY, CLEARANCE, AND DISPOSITION OF INTRAVENTRICULARLY ADMINISTERED OLIGODEOXYNUCLEOTIDES - IMPLICATIONS FOR THERAPEUTIC APPLICATION WITHIN THE CENTRAL-NERVOUS-SYSTEM SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ANTISENSE; PHOSPHOROTHIOATE OLIGONUCLEOTIDE; BRAIN TUMOR; CHEMOTHERAPEUTIC ID CEREBROSPINAL-FLUID; RAT AB We report experiments in the rat demonstrating the feasibility of intraventricular administration of oligodeoxynucleotides (ODNs) as a regional treatment approach to disorders within the central nervous system (CNS). Although we find little intrinsic nuclease activity in cerebrospinal fluid (CSF), phosphodiester ODNs are rapidly degraded by brain-associated alpha-exonuclease activity. Phosphorothioate ODNs, however, appear resistant to degradation in the CNS and, after intraventricular administration, we find they are cleared in a manner consistent with CSF bulk flow. Continuous infusion of ODN at 1.5 nmol/hr by miniosmotic pump can maintain micromolar concentrations of intact phosphorothioate ODN in CSF for at least 1 week without obvious neurologic or systemic toxicity. After infusion, extensive brain penetration and marked cellular uptake, especially by astrocytic cells, is demonstrated. C1 NINCDS,SURG NEUROL BRANCH,BETHESDA,MD 20892. NINCDS,NEUROIMAGING BRANCH,BETHESDA,MD 20892. RP WHITESELL, L (reprint author), NCI,CLIN PHARMACOL BRANCH,TUMOR CELL BIOL SECT,BLDG 10,ROOM 13N262,BETHESDA,MD 20892, USA. NR 12 TC 177 Z9 177 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 15 PY 1993 VL 90 IS 10 BP 4665 EP 4669 DI 10.1073/pnas.90.10.4665 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LC720 UT WOS:A1993LC72000072 PM 8506315 ER PT J AU BALASUNDARAM, D TABOR, CW TABOR, H AF BALASUNDARAM, D TABOR, CW TABOR, H TI OXYGEN-TOXICITY IN A POLYAMINE-DEPLETED SPE2-DELTA MUTANT OF SACCHAROMYCES-CEREVISIAE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID S-ADENOSYLMETHIONINE DECARBOXYLASE; SUPEROXIDE-DISMUTASE; YEAST; SPERMIDINE; MEMBRANE; LIPOPEROXIDATION; INHIBITION; INDUCTION; MUTATION AB When a mutant of Saccharomyces cerevisiae (spe2DELTA) that cannot make spermidine or spermine was incubated in a polyamine-deficient medium in oxygen, there was a rapid cessation of cell growth and associated cell death. In contrast, when the mutant cells were incubated in the polyamine-deficient medium in air or anaerobically, the culture stopped growing more gradually, and there was no significant loss of cell viability. We also found that the polyamine-deficient cells grown in air, but not those grown anaerobically, showed a permanent loss of functional mitochondria (''respiratory competency''), as evidenced by their inability to grow on glycerol as the sole carbon source. These data support the postulation that polyamines act, in part, by protecting cell components from damage resulting from oxidation. However, since the mutant cells still required spermidine or spermine for growth when incubated under strictly anaerobic conditions, polyamines must also have other essential functions. RP BALASUNDARAM, D (reprint author), NIDDKD,BIOCHEM PHARMACOL LAB,PHARMACOL SECT,BLDG 8,ROOM 223,BETHESDA,MD 20892, USA. NR 33 TC 37 Z9 37 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 15 PY 1993 VL 90 IS 10 BP 4693 EP 4697 DI 10.1073/pnas.90.10.4693 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LC720 UT WOS:A1993LC72000078 PM 8506320 ER PT J AU WEINBERG, CR BAIRD, DD ROWLAND, AS AF WEINBERG, CR BAIRD, DD ROWLAND, AS TI PITFALLS INHERENT IN RETROSPECTIVE TIME-TO-EVENT STUDIES - THE EXAMPLE OF TIME TO PREGNANCY SO STATISTICS IN MEDICINE LA English DT Article ID FECUNDABILITY; AIDS AB Retrospective studies of time from initiation of risk (for example, transfusion of HIV-infected blood) to the occurrence of an endpoint of interest are useful in epidemiology. One example is studies of time to pregnancy, which have evaluated exposures that may affect human fertility. One can reconstruct the non-contracepting interval required for each woman's most recent pregnancy and then treat the data as if the couples had been studied prospectively. As we illustrate, however, failure-time models can be dangerously misleading when there have been trends over calendar time in exposures under study. We propose an ad hoc method for evaluating possible effects on fertility despite this bias, by making use of external data on trends in the exposure over time. This approach applies a prospective model and generates an empirical p-value, based on comparing the data-based estimated exposure coefficient with its null distribution estimated by simulation. A second method maximizes a conditional likelihood, and we show that this is equivalent to logistically modelling the relative odds for the subject's exposure as related to the reported time she required to achieve pregnancy. C1 NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC 27709. RP WEINBERG, CR (reprint author), NIEHS,STAT & BIOMATH BRANCH,MD B3-02,PO 12233,RES TRIANGLE PK,NC 27709, USA. OI Baird, Donna/0000-0002-5544-2653 NR 14 TC 39 Z9 40 U1 1 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD MAY 15 PY 1993 VL 12 IS 9 BP 867 EP 879 DI 10.1002/sim.4780120906 PG 13 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA LD776 UT WOS:A1993LD77600005 PM 8327803 ER PT J AU ROE, DJ KORN, EL AF ROE, DJ KORN, EL TI TIME-PERIOD EFFECTS IN LONGITUDINAL-STUDIES MEASURING AVERAGE RATES OF CHANGE SO STATISTICS IN MEDICINE LA English DT Article ID MODELS; DIISOCYANATE; DISEASE AB Random time-period effects are unexplained increases or decreases in the observed value for all individuals measured at a particular time point in a longitudinal study. They can be caused by learning effects, changes in equipment, personnel and overall subject co-operation. We investigate the consequences of time-period effects in random coefficient regression models, where interest is in the average rate of change (slope) of a continuous outcome. In a study with a single group of subjects, they can lead to conditionally biased estimates of the mean slope and its variance (conditional on the time-period effects). Calculations suggest that the increase in sample size required to maintain a specified precision of the mean slope estimate over repeated studies may be substantial. In a study with a concurrent control group, however, time-period effects do not distort the expectation, estimated variance or the distribution of the difference between the mean slopes. With missing data, in addition to time-period effects, an unbiased estimate of a single mean slope remains problematic, but one can use standard maximum likelihood techniques to obtain consistent estimators of the difference in mean slopes and its variance. This suggests the importance of a concurrent control group when potential time-period effects are of concern. C1 NCI,BIOMETR RES BRANCH,BETHESDA,MD 20892. RP ROE, DJ (reprint author), UNIV ARIZONA,COLL MED,DEPT FAMILY & COMMUNITY MED,TUCSON,AZ 85724, USA. NR 24 TC 2 Z9 2 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD MAY 15 PY 1993 VL 12 IS 9 BP 893 EP 900 DI 10.1002/sim.4780120908 PG 8 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA LD776 UT WOS:A1993LD77600007 PM 8392217 ER PT J AU ROBERTSTHOMSON, SJ MCMANUS, ME TUKEY, RH GONZALEZ, FF HOLDER, GM AF ROBERTSTHOMSON, SJ MCMANUS, ME TUKEY, RH GONZALEZ, FF HOLDER, GM TI THE CATALYTIC ACTIVITY OF 4 EXPRESSED HUMAN CYTOCHROME-P450S TOWARDS BENZO[A]PYRENE AND THE ISOMERS OF ITS PROXIMATE CARCINOGEN SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID HUMAN-LIVER; MESSENGER-RNA; METABOLISM; GENE; BENZO(A)PYRENE; IDENTIFICATION; FAMILY; FORMS; CDNA; CYTOCHROMES-P-450 C1 UNIV SYDNEY,DEPT PHARM,SYDNEY,NSW 2006,AUSTRALIA. UNIV QUEENSLAND,DEPT PHYSIOL & PHARMACOL,ST LUCIA,QLD 4072,AUSTRALIA. UNIV CALIF SAN DIEGO,DEPT PHARMACOL & MED,LA JOLLA,CA 92093. NIH,NACHRICHTENTECH LAB,BETHESDA,MD 20892. RI Roberts-Thomson, Sarah/B-4282-2011 OI Roberts-Thomson, Sarah/0000-0001-8202-5786 FU NIGMS NIH HHS [GM36590] NR 33 TC 60 Z9 61 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 14 PY 1993 VL 192 IS 3 BP 1373 EP 1379 DI 10.1006/bbrc.1993.1568 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LC531 UT WOS:A1993LC53100056 PM 8507205 ER PT J AU JACOBSON, KA GALLORODRIGUEZ, C MELMAN, N FISCHER, B MAILLARD, M VANBERGEN, A VANGALEN, PJM KARTON, Y AF JACOBSON, KA GALLORODRIGUEZ, C MELMAN, N FISCHER, B MAILLARD, M VANBERGEN, A VANGALEN, PJM KARTON, Y TI STRUCTURE-ACTIVITY-RELATIONSHIPS OF 8-STYRYLXANTHINES AS A(2)-SELECTIVE ADENOSINE ANTAGONISTS SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID A1-ADENOSINE RECEPTORS; SPECIES-DIFFERENCES; BINDING-SITES; RAT-BRAIN; AGONISTS; POTENT; SUBSTITUTION; INHIBITORS; AFFINITY; ANALOGS AB A series of substituted 8-styryl derivatives of 1,3,7-alkylxanthines was synthesized as potential A2-selective adenosine receptor antagonists, and the potency at rat brain A1- and A2-receptors was studied in radioligand binding experiments. At the xanthine 7-position, only small hydrophobic substituents were tolerated in receptor binding. 7-Methyl analogues were roughly 1 order of magnitude more selective for A2 versus A1 receptors than the corresponding 7-H analogues. 1,3-Dimethylxanthine derivatives tended to be more selective for A2-receptors than the corresponding 1,3-diallyl, diethyl, or dipropyl derivatives. Substitutions of the phenyl ring at the 3-(monosubstituted) and 3,5-(disubstituted) positions were favored. 1,3,7-Trimethyl-8-(3-chlorostyryl)xanthine was a moderately potent (K(i) vs [H-3]CGS 21680 was 54 nM) and highly A2-selective (520-fold) adenosine antagonist. 1,3,7-Trimethyl-8-[3-[(3-carboxy-1-oxopropyl)amino]styryl]xanthine was highly A2-selective (250-fold) and of enhanced water solubility (max 19 mM). 1,3-Dipropyl-7-methyl-8-(3,5-dimethoxystyryl)xanthine was a potent (K(i) = 24 nM) and very A2-selective (110-fold) adenosine antagonist. C1 ISRAEL INST BIOL RES,DEPT ORGAN CHEM,IL-70450 NESS ZIONA,ISRAEL. RP JACOBSON, KA (reprint author), NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892, USA. RI Gallo-Rodriguez, Carola/E-1732-2012; Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999] NR 25 TC 134 Z9 135 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD MAY 14 PY 1993 VL 36 IS 10 BP 1333 EP 1342 DI 10.1021/jm00062a005 PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA LC996 UT WOS:A1993LC99600005 PM 8496902 ER PT J AU SUN, L HAMEL, E LIN, CM HASTIE, SB PYLUCK, A LEE, KH AF SUN, L HAMEL, E LIN, CM HASTIE, SB PYLUCK, A LEE, KH TI ANTITUMOR AGENTS .141. SYNTHESIS AND BIOLOGICAL EVALUATION OF NOVEL THIOCOLCHICINE ANALOGS - N-ACYL-(SUBSTITUTED BENZYL)DEACETYLTHIOCOLCHICINES, AND N-AROYL-(SUBSTITUTED BENZYL)DEACETYLTHIOCOLCHICINES, AND (SUBSTITUTED BENZYL)DEACETYLTHIOCOLCHICINES AS POTENT CYTOTOXIC AND ANTIMITOTIC COMPOUNDS SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID TUBULIN; COLCHICINES; BINDING AB Three series of novel thiocolchicine analogs, N-acyl-, N-aroyl-, and N-(substituted benzyl)-deacetylthiocolchicinoids, have been synthesized and evaluated for their cytotoxicity against various tumor cell lines, especially solid tumor cell lines, and for their inhibitory effects on tubulin polymerization in vitro. Most of these compounds showed strong inhibitory effects on tubulin polymerization comparable to that obtained with thiocolchicine and greater than that obtained with colchicine. Only compounds with a long side chain at the C(7) position, such as 22-24, did not inhibit tubulin polymerization. Several of the active N-aroyldeacetylthiocolchicine analogs had positive optical rotations, in contrast to the negative optical rotation observed with most colchicinoids. This property might be attributed to a reversal of biaryl configuration from the normal aS to aR. Therefore, the N-aroyl analogs were further evaluated by circular dichroism, which readily distinguishes between the aS and aR biaryl configurations. This latter technique demonstrated that the active N-aroyl analogs do have an aS configuration despite their positive optical rotations. However, comparison of H-1 NMR and UV spectral data of N-(substituted benzyl)-deacetylthiocolchicines with those of corresponding N-aroyldeacetylthiocolchicines suggested a different biaryl dihedral angle [even though these compounds have the same aS biaryl configuration]. The similar tubulin binding properties of these compounds suggest that a biaryl dihedral angle of 53-degrees is not essential for colchicinoid-tubulin interaction. The increased cytotoxicity of N-(substituted benzyl)deacetylthiocolchicines compared to the N-aroyldeacetylthiocolchicines may be attributed to different lipophilicity, drug uptake, or drug metabolism in the tumor cells. The side chain at the C(7) position affects inhibition of tubulin polymerization and the cytotoxic activity of colchicinoids as a function of its size and its contribution to lipophilicity. C1 UNIV N CAROLINA,SCH PHARM,DIV MED CHEM & NAT PROD,NAT PROD LAB,CHAPEL HILL,NC 27599. SUNY,DEPT CHEM,BINGHAMTON,NY 13902. NCI,DIV CANC TREATMENT,MOLEC PHARMACOL DEV THERAPEUT PROGRAM LAB,BETHESDA,MD 20892. RI Bane, Susan/C-1414-2013 OI Bane, Susan/0000-0002-4270-6314 FU NCI NIH HHS [CA 17625] NR 21 TC 23 Z9 25 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD MAY 14 PY 1993 VL 36 IS 10 BP 1474 EP 1479 DI 10.1021/jm00062a021 PG 6 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA LC996 UT WOS:A1993LC99600021 PM 8496915 ER PT J AU CHABNER, BA LEVY, R AF CHABNER, BA LEVY, R TI FUNDING FOR GENE-THERAPY SO SCIENCE LA English DT Letter C1 STANFORD UNIV,MED CTR,SCH MED,STANFORD,CA 94305. RP CHABNER, BA (reprint author), NCI,FAC CANC TREATMENT,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 MAY 14 PY 1993 VL 260 IS 5110 BP 877 EP 878 DI 10.1126/science.8338577 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LB791 UT WOS:A1993LB79100004 PM 8338577 ER PT J AU BOMMERT, K CHARLTON, MP DEBELLO, WM CHIN, GJ BETZ, H AUGUSTINE, GJ AF BOMMERT, K CHARLTON, MP DEBELLO, WM CHIN, GJ BETZ, H AUGUSTINE, GJ TI INHIBITION OF NEUROTRANSMITTER RELEASE BY C2-DOMAIN PEPTIDES IMPLICATES SYNAPTOTAGMIN IN EXOCYTOSIS SO NATURE LA English DT Article ID SQUID GIANT SYNAPSE; PROTEIN KINASE-C; TRANSMITTER RELEASE; BINDING; FAMILY; P65; DNA AB NEUROTRANSMITTER release is triggered by Ca2+ ions binding to an unknown Ca2+ receptor within presynaptic terminals1,2. Synaptotagmin, a Ca2+-binding protein of synaptic and other secretory vesicles3, has been proposed to mediate vesicle-plasma membrane interactions during neurotransmitter release4-9. Here we test this hypothesis using the giant synapse of the squid Loligo pealei, which because of its unusually large size and well established physiology is uniquely suited for dissecting presynaptic events10. We find that injection of peptides from the C2 domains of synaptotagmin into squid giant presynaptic terminals rapidly and reversibly inhibits neurotransmitter release. Our data are consistent with these peptides competitively blocking release after synaptic vesicle docking and indicate that Ca2+ probably initiates neurotransmitter release by regulating the interaction of synaptotagmin with an acceptor protein. C1 MAX PLANCK INST BRAIN RES,DEPT NEUROCHEM,W-6000 FRANKFURT 71,GERMANY. UNIV TORONTO,DEPT PHYSIOL,TORONTO M5S 1A8,ONTARIO,CANADA. DUKE UNIV,MED CTR,DEPT NEUROBIOL,DURHAM,NC 27710. NIH,DEV NEUROBIOL LAB,BETHESDA,MD 20892. RP BOMMERT, K (reprint author), MARINE BIOL LAB,WOODS HOLE,MA 02543, USA. RI Augustine, George/J-9228-2013 NR 31 TC 274 Z9 274 U1 1 U2 3 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD MAY 13 PY 1993 VL 363 IS 6425 BP 163 EP 165 DI 10.1038/363163a0 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA LB801 UT WOS:A1993LB80100048 PM 8097867 ER PT J AU BAPTISTA, T WEISS, SRB POST, RM AF BAPTISTA, T WEISS, SRB POST, RM TI CARBAMAZEPINE ATTENUATES COCAINE-INDUCED INCREASES IN DOPAMINE IN THE NUCLEUS-ACCUMBENS - AN INVIVO DIALYSIS STUDY SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE CARBAMAZEPINE; COCAINE; DOPAMINE; NUCLEUS ACCUMBENS; MICRODIALYSIS; (RAT) ID 6-HYDROXYDOPAMINE LESIONS; SEIZURES; RATS AB Carbamazepine's effects on cocaine-induced increases in dopamine overflow in the nucleus accumbens were studied using in vivo microdialysis in anesthetized rats. Rats were chronically treated with a diet containing carbamazepine or no drug for one week prior to microdialysis procedures. The basal levels of dopamine in the nucleus accumbens did not differ between groups; however, the increases in dopamine following cocaine administration (4 mg/kg i.v.) were significantly reduced by carbamazepine. In addition, basal levels of dihydroxyphenyl acetic acid (DOPAC) were significantly diminished in the carbamazepine group and a trend in the same direction was observed for homovanilic acid (HVA). These results are consistent with reports that carbamazepine might decrease dopamine synthesis. Further studies are required to determine the mechanism of carbamazepine's inhibition of cocaine-induced dopamine overflow and its potential clinical implications. C1 NIMH,BIOL PSYCHIAT BRANCH,BEHAV BIOL UNIT,BLDG 10,ROOM 3N12,BETHESDA,MD 20892. NR 33 TC 6 Z9 6 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD MAY 12 PY 1993 VL 236 IS 1 BP 39 EP 42 DI 10.1016/0014-2999(93)90224-6 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LC380 UT WOS:A1993LC38000006 PM 8319744 ER PT J AU DUNBAR, CE NIENHUIS, AW AF DUNBAR, CE NIENHUIS, AW TI MULTIPLE-MYELOMA - NEW APPROACHES TO THERAPY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID BONE-MARROW TRANSPLANTATION; CASTLEMANS DISEASE; GENE-TRANSFER; CELL-GROWTH; INTERLEUKIN-6; CHEMOTHERAPY; EXPRESSION; LEUKEMIA RP DUNBAR, CE (reprint author), NHLBI,HEMATOL BRANCH,BLDG 10,ROOM 7C-103,BETHESDA,MD 20892, USA. NR 32 TC 17 Z9 17 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 12 PY 1993 VL 269 IS 18 BP 2412 EP 2416 DI 10.1001/jama.269.18.2412 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA LA675 UT WOS:A1993LA67500037 PM 7683062 ER PT J AU CHU, E TAKIMOTO, CH VOELLER, D GREM, JL ALLEGRA, CJ AF CHU, E TAKIMOTO, CH VOELLER, D GREM, JL ALLEGRA, CJ TI SPECIFIC BINDING OF HUMAN DIHYDROFOLATE-REDUCTASE PROTEIN TO DIHYDROFOLATE-REDUCTASE MESSENGER-RNA INVITRO SO BIOCHEMISTRY LA English DT Article ID R17 COAT PROTEIN; THYMIDYLATE SYNTHASE; UNTRANSLATED REGION; NUCLEOTIDE-SEQUENCE; MOUSE FIBROBLASTS; CRYSTAL-STRUCTURE; HUMAN-BREAST; CELLS; METHOTREXATE; TRANSLATION AB Dihydrofolate reductase (DHFR) is a critical enzyme in de novo purine and thymidylate biosynthesis. An RNA gel mobility shift assay was used to demonstrate a specific interaction between human recombinant DHFR protein and its corresponding DHFR mRNA. Incubation of DHFR protein with either its substrates, dihydrofolate or NADPH, or with an inhibitor, methotrexate, repressed its ability to interact with DHFR mRNA. An in vitro rabbit reticulocyte lysate translation system was used to show that the addition of exogenous human recombinant DH FR protein to in vitro translation reactions specifically inhibited DHFR mRNA translation. These studies suggest that the direct interaction between DHFR protein and its mRNA may be a mechanism for regulation of DHFR synthesis. RP CHU, E (reprint author), NCI,NAVY MED ONCOL BRANCH,DIV CANC TREATMENT,BETHESDA,MD 20892, USA. NR 44 TC 107 Z9 107 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 11 PY 1993 VL 32 IS 18 BP 4756 EP 4760 DI 10.1021/bi00069a009 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LB647 UT WOS:A1993LB64700009 PM 8490020 ER PT J AU LE, SY CHEN, JH MAIZEL, JV AF LE, SY CHEN, JH MAIZEL, JV TI PREDICTION OF ALTERNATIVE RNA SECONDARY STRUCTURES BASED ON FLUCTUATING THERMODYNAMIC PARAMETERS SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SINGLE-STRANDED RNA; RIBOSOMAL-RNA; FREE-ENERGY; SEQUENCES; ALGORITHM; STABILITY; HELICES; MODEL AB In this paper we present a new method for predicting a set of RNA secondary structures that are thermodynamically favored in RNA folding simulations. This method uses a large number of 'simulated energy rules' (SER) generated by perturbing the free energy parameters derived experimentally within the range of the experimental errors. The structure with the lowest free energy is computed for each SER. Structural comparisons are used to avoid multiple generation of similar structures. Computed structures are evaluated using the energy distribution of the lowest free energy structures derived in the simulation. Predicted structures and all possible occurring helical stems can be graphically displayed with their occurring frequencies in the simulation by dot-plot representations. On average, about 90% of phylogenetic helixes in the known models of tRNA, Group I self-splicing intron, and Escherichia coli 16 S rRNA, were predicted using the method. C1 NCI,FCRDC,DYNCORP,PROGRAM RESOURCES INC,FREDERICK BIOMED SUPERCOMP CTR,FREDERICK,MD 21702. RP LE, SY (reprint author), NATL CANC INST,DIV CANC BIOL & DIAGNOSIS CTR,MATH BIOL LAB,BLDG 469,RM 151,FREDERICK,MD 21702, USA. NR 37 TC 21 Z9 22 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 MAY 11 PY 1993 VL 21 IS 9 BP 2173 EP 2178 DI 10.1093/nar/21.9.2173 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LD430 UT WOS:A1993LD43000022 PM 7684834 ER PT J AU ALEXANDROV, IA MEDVEDEV, LI MASHKOVA, TD KISSELEV, LL ROMANOVA, LY YUROV, YB AF ALEXANDROV, IA MEDVEDEV, LI MASHKOVA, TD KISSELEV, LL ROMANOVA, LY YUROV, YB TI DEFINITION OF A NEW ALPHA-SATELLITE SUPRACHROMOSOMAL FAMILY CHARACTERIZED BY MONOMERIC ORGANIZATION SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HUMAN X-CHROMOSOME; SEQUENCE-ANALYSIS; DNA-SEQUENCES; EVOLUTION; DOMAINS; GORILLA AB We have analyzed more than 500 alphoid monomers either sequenced in our laboratory or available in the literature. Most of them belonged to the well studied suprachromosomal families 1, 2 and 3 characterized by dimeric (1 and 2) and pentameric (3) ancestral periodicities. The sequences that did not belong to the previously known families were subjected to further analysis. About a half of them formed a relatively homogenous family. Its members were on average 80.5% identical and 89.5% homologous to the Ml consensus sequence derived from this group (39 monomers). In the genome they do not form any ancestral periodicities other than a monomeric one, and are found at least in chromosomes 13, 14, 15, 21, 22 and Y. The newly defined family was termed suprachromosomal family 4. Comparison of all 10 alphoid monomeric groups identified so far showed that the Ml sequence is closely related to the J1-D2-W4-W5 homology grouping. Notably the African Green Monkey alpha satellite, also characterized by monomeric construction, appears to be a member of the same group. C1 NATL RES CTR MENT HLTH,MOSCOW,RUSSIA. ENGELHARDT INST MOLEC BIOL,MOSCOW,RUSSIA. RP ALEXANDROV, IA (reprint author), NCI,CLIN PHARMACOL BRANCH,BLDG 10,ROOM 12C103,BETHESDA,MD 20892, USA. RI Yurov, Yuri/D-9051-2016 OI Yurov, Yuri/0000-0002-9251-2286 NR 29 TC 51 Z9 52 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 MAY 11 PY 1993 VL 21 IS 9 BP 2209 EP 2215 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LD430 UT WOS:A1993LD43000027 PM 8502563 ER PT J AU KARSCHMIZRACHI, I HAYNES, SR AF KARSCHMIZRACHI, I HAYNES, SR TI THE RB97D GENE ENCODES A POTENTIAL RNA-BINDING PROTEIN REQUIRED FOR SPERMATOGENESIS IN DROSOPHILA SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SMALL NUCLEAR RIBONUCLEOPROTEIN; MELANOGASTER-VERMILION GENE; A-PROTEIN; U1 RNA; POLY(A)-BINDING PROTEIN; XENOPUS-LAEVIS; HNRNP PROTEIN; DOMAIN; EXPRESSION; IDENTIFICATION AB Many proteins that bind RNA contain a common RNA-binding domain, the RNP motif. We have been studying two Drosophila RNP motif proteins, Hrb98DE and Hrb87F, which are hnRNA-binding proteins. We report here the characterization of the Rb97D gene, which encodes a protein that is closely related to the Hrb proteins in the RNP motif domain, but has a distinctive proline-rich C-terminal domain. The gene is located at 97D on the right arm of the third chromosome, near the rough gene. Multiple transcripts from the Rb97D gene are present at varying levels throughout development. The transcripts are generated by alternative processing in the coding and 3' untranslated regions, and can encode two protein isoforms. Analysis of a mutant containing a P element inserted into the 5' untranslated region of the gene demonstrates that Rb97D is required for male fertility. Possible models for the function of Rb97D in testes are discussed. C1 NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892. NR 50 TC 45 Z9 46 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD MAY 11 PY 1993 VL 21 IS 9 BP 2229 EP 2235 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LD430 UT WOS:A1993LD43000030 PM 8502565 ER PT J AU DROPULIC, B LIN, NH JEANG, KT AF DROPULIC, B LIN, NH JEANG, KT TI A METHOD TO INCREASE THE CUMULATIVE CLEAVAGE EFFICIENCY OF RIBOZYMES - THERMAL CYCLING SO NUCLEIC ACIDS RESEARCH LA English DT Note ID RNA C1 NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. RI Jeang, Kuan-Teh/A-2424-2008 FU NIAID NIH HHS [K08 AI081545] NR 9 TC 9 Z9 9 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 MAY 11 PY 1993 VL 21 IS 9 BP 2273 EP 2274 DI 10.1093/nar/21.9.2273 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LD430 UT WOS:A1993LD43000051 PM 8502581 ER PT J AU NAKATA, H AF NAKATA, H TI DEVELOPMENT OF AN ANTISERUM TO RAT-BRAIN A1 ADENOSINE RECEPTOR - APPLICATION FOR IMMUNOLOGICAL AND STRUCTURAL COMPARISON OF A1 ADENOSINE RECEPTORS FROM VARIOUS TISSUES AND SPECIES SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Article DE ANTIBODY; A1 ADENOSINE RECEPTOR; GLYCOSYLATION; IMMUNOPRECIPITATION; (RAT BRAIN) ID POLYACRYLAMIDE GELS; MEMBRANES; PURIFICATION; BINDING; EXPRESSION; CLONING AB An antiserum was developed in a rabbit against rat-brain A1 adenosine receptor. This antiserum recognized the denatured form of the purified rat-brain A1 adenosine receptor in immunoblot analysis and the native form of the receptor in the immunoprecipitation analysis. Immunoblot analysis of unpurified or purified adenosine receptor preparations from rat-brain membranes revealed a major immunoreactive band at a position of molecular mass of approx. 35 kDa, which corresponds to the position of purified rat-brain A1 adenosine receptor. Although A1 adenosine receptors from other rat tissues such as testis and adipocyte were also found to be immunoreactive with this antiserum by immunoblot analysis, purified human-brain A1 adenosine receptors showed a poor reactivity with this antibody. The order of the relative immunoreactivity of these A1 adenosine receptors, with the antiserum was found to be brain > adipocyte greater-than-or-equal-to testis. Moreover, the immunoreactivity of these receptors significantly increased after these receptor preparations were deglycosylated by endoglycosidase F. After the deglycosylation, no significant differences in both the immunoreactivity and molecular mass among these receptor preparations were found on the immunoblot. These results suggest that the differences in the molecular mass or immunoreactivity among the A1 adenosine receptor preparations from three rat tissues were mainly due to the difference of sugar moiety present in each receptor molecule. These data are the first to provide analyses of immunological characteristics of A1 adenosine receptors from different tissues and species. C1 NIMH,CLIN SCI LAB,BETHESDA,MD 20892. RP NAKATA, H (reprint author), TOKYO METROPOLITAN INST NEUROSCI,DEPT MOLEC & CELLULAR NEUROBIOL,2-6 MUSASHIDAI,FUCHU,TOKYO 183,JAPAN. NR 21 TC 13 Z9 13 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 MAY 8 PY 1993 VL 1177 IS 1 BP 93 EP 98 DI 10.1016/0167-4889(93)90163-J PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LB956 UT WOS:A1993LB95600015 PM 8485173 ER PT J AU GONZALEZGARCIA, C CENA, V KEISER, HR ROJAS, E AF GONZALEZGARCIA, C CENA, V KEISER, HR ROJAS, E TI CATECHOLAMINE SECRETION INDUCED BY TETRAETHYLAMMONIUM FROM CULTURED BOVINE ADRENAL CHROMAFFIN CELLS SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Article DE ADRENAL MEDULLA; CATECHOLAMINE SECRETION; INTRACELLULAR CALCIUM ION; CALCIUM ION, INTRACELLULAR; POTASSIUM ION CHANNEL ID CA-2+-ACTIVATED K+ CHANNELS; POTASSIUM CHANNELS; CALCIUM CHANNELS; MEDULLARY CELLS; RELEASE; NORADRENALINE; CURRENTS; 4-AMINOPYRIDINE; EXOCYTOSIS; ACTIVATION AB The resting potential in adrenal medullary chromaffin cells is maintained by the activity of different K+-channels. Blockade of K+-channels should, at least in principle, lead to membrane depolarization, and the ensuing activation of voltage-gated Ca2+-channels should promote Ca2+ entry and catecholamine (CA) secretion. In support of this mechanism we found and report here that the K+-channel blocker tetraethylammonium (TEA) depolarized the chromaffin cell membrane, induced a substantial elevation in Cytosolic [Ca2+], and a dose-dependent CA secretion reaching a maximum at 50 mM of approx. 10% of the total CA in the cells. In addition, TEA-induced CA secretion was found to be absolutely dependent on [Ca2+]o. In the presence of [Ca2+]o, TEA-stimulated CA release was blocked completely by elevated [MgCl2]o (12 mM), and inhibited in part by the Ca2+-channel antagonist nifedipine. The Ca2+-channel agonist Bay K-8644 markedly enhanced TEA-evoked CA release suggesting the involvement of L-type Ca2+-channels. Since, external application of TEA (30-50 mM) markedly blocked outward K+ currents but not inward currents carried by Na+ and Ca2+, we concluded that TEA stimulates CA secretion by blocking those K+-channels involved in the maintenance of the resting membrane potential. C1 NIDDK,CELL BIOL & GENET LAB,BETHESDA,MD 20892. FAC MED ALICANTE,DEPT NEUROQUIM,DIV FARMACOL,ALICANTE,SPAIN. NHLBI,HYPERTENS ENDOCRINE BRANCH,BETHESDA,MD 20892. NR 27 TC 19 Z9 19 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-3002 J9 BIOCHIM BIOPHYS ACTA PD MAY 8 PY 1993 VL 1177 IS 1 BP 99 EP 105 DI 10.1016/0167-4889(93)90164-K PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA LB956 UT WOS:A1993LB95600016 PM 8387344 ER PT J AU SHEN, Q LIU, SF DAWSEY, SM CAO, J ZHOU, B WANG, DY CAO, SG ZHAO, HZ LI, GY TAYLOR, PR GUO, WD LIU, FS BLOT, WJ LI, JY LI, B AF SHEN, Q LIU, SF DAWSEY, SM CAO, J ZHOU, B WANG, DY CAO, SG ZHAO, HZ LI, GY TAYLOR, PR GUO, WD LIU, FS BLOT, WJ LI, JY LI, B TI CYTOLOGIC SCREENING FOR ESOPHAGEAL CANCER - RESULTS FROM 12,877 SUBJECTS FROM A HIGH-RISK POPULATION IN CHINA SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article AB Linxian, China, has one of the highest esophageal-cancer mortality rates in the world. In 1983, esophageal balloon-cytology screening was performed to identify subjects eligible for 2 nutrition-intervention trials in Linxian; 12,877 subjects had cytology slides which were satisfactory for diagnosis. Of the 12,649 subjects with squamous-cell diagnoses, 31% were normal by Chinese cytologic criteria; 38% showed hyperplasia; 21% showed dysplasia 1; 6% showed dysplasia 2; 2% showed near-cancer; and 2% showed cancer. Of the 1,471 subjects with columnar-cell diagnoses, 31% were normal; 44% showed hyperplasia; 16% showed dysplasia 1; 4% showed dysplasia 2; 2% showed near-cancer; and 3% showed cancer. Squamous dysplasia and cancer were more common among females than males, while columnar dysplasia and cancer showed male predominance. The prevalence of dysplasia and cancer of both cell types increased with age. The prevalence of squamous dysplasia was significantly higher than in earlier balloon-cytology screenings in Linxian, probably reflecting changes in cytologic classification. C1 NCI,DIV CANC PREVENT & CONTROL,CANC PREVENT STUDIES BRANCH,BETHESDA,MD 20892. NCI,DIV CANC PREVENT & CONTROL,BIOSTAT BRANCH,BETHESDA,MD 20892. HENAN MED UNIV,DEPT PRECANC STUDIES,HENAN,PEOPLES R CHINA. CHINESE ACAD SCI,INST CANC,BEIJING,PEOPLES R CHINA. NR 17 TC 38 Z9 38 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAY 8 PY 1993 VL 54 IS 2 BP 185 EP 188 DI 10.1002/ijc.2910540204 PG 4 WC Oncology SC Oncology GA LB688 UT WOS:A1993LB68800003 ER PT J AU STANFORD, JL BRINTON, LA BERMAN, ML MORTEL, R TWIGGS, LB BARRETT, RJ WILBANKS, GD HOOVER, RN AF STANFORD, JL BRINTON, LA BERMAN, ML MORTEL, R TWIGGS, LB BARRETT, RJ WILBANKS, GD HOOVER, RN TI ORAL-CONTRACEPTIVES AND ENDOMETRIAL CANCER - DO OTHER RISK-FACTORS MODIFY THE ASSOCIATION SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID GENITAL-TRACT; ESTROGENS; CARCINOMA; PROGESTOGENS; BREAST AB The joint effect of use of combination-type oral contraceptives and other exposure factors on risk of endometrial cancer was examined in data from a multicenter case-control study conducted in 5 areas of the United States. Cases were 405 women with histologically confirmed invasive epithelial endometrial cancer first treated at one of 7 participating hospitals. A total of 297 population-based controls of similar age, race, and geographic area were selected as a comparison group. Information on exposure factors was derived from in-person interviews. Combination-type oral contraceptive (COC) use was associated with a significant reduction in risk of endometrial cancer, with an adjusted odds ratio (OR) of 0.4 (95% confidence interval 0.3 to 0.7) for ever compared to never use. Long-term (greater-than-or-equal-to 10 years) users experienced a markedly lower risk (OR = 0.2). Women who discontinued COC use greater-than-or-equal-to 20 years earlier remained at reduced risk (OR = 0.7) compared with non-users. The negative association with COC use was apparent regardless of the presence or level of several other risk factors for endometrial cancer, including age, menopausal status, parity, obesity, ever-use of menopausal estrogens, smoking history, or history of infertility. The magnitude of the negative association observed in COC users, however, was considerably diminished in women with no full-term births and in women who subsequently used replacement estrogens for 3 or more years. These results provide new evidence that the protective effect of COC use lasts for 20 or more years after use is discontinued, and highlight several sub-groups of users in whom the level of protection is attenuated by the presence of other risk factors for this disease. C1 UNIV WASHINGTON,DEPT EPIDEMIOL,SEATTLE,WA 98104. NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892. UNIV CALIF IRVINE,MED CTR,DEPT OBSTET & GYNECOL,IRVINE,CA 92717. PENN STATE UNIV,MILTON S HERSHEY MED CTR,DEPT OBSTET & GYNECOL,HERSHEY,PA 17033. UNIV MINNESOTA,SCH MED,DEPT OBSTET & GYNECOL,MINNEAPOLIS,MN 55455. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT OBSTET & GYNECOL,WINSTON SALEM,NC 27103. RUSH MED COLL,DEPT OBSTET & GYNECOL,CHICAGO,IL 60612. RP STANFORD, JL (reprint author), UNIV WASHINGTON,FRED HUTCHINSON CANC RES CTR,DIV PUBL HLTH SCI,1124 COLUMBIA ST,SEATTLE,WA 98104, USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 FU NCI NIH HHS [CA01364] NR 31 TC 21 Z9 22 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAY 8 PY 1993 VL 54 IS 2 BP 243 EP 248 DI 10.1002/ijc.2910540214 PG 6 WC Oncology SC Oncology GA LB688 UT WOS:A1993LB68800013 PM 8486426 ER PT J AU MADELEINE, MM WIKTOR, SZ GOEDERT, JJ MANNS, A LEVINE, PH BIGGAR, RJ BLATTNER, WA AF MADELEINE, MM WIKTOR, SZ GOEDERT, JJ MANNS, A LEVINE, PH BIGGAR, RJ BLATTNER, WA TI HTLV-I AND HTLV-II WORLDWIDE DISTRIBUTION - REANALYSIS OF 4,832 IMMUNOBLOT RESULTS SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID VIRUS TYPE-I; CELL LEUKEMIA-VIRUS; PAPUA-NEW-GUINEA; SOLOMON-ISLANDS; LYMPHOMA VIRUS; GUAYMI INDIANS; VIRAL LATENCY; DRUG-ABUSERS; ANTIBODIES; INFECTION AB Mapping the geographic distribution of human T-lymphotrophic virus types I and 2 (HTLV-I and -II) has been complicated because conventional serologic approaches cannot distinguish between these 2 viruses. To more precisely define the epidemiology of HTLV-I and HTLV-II, we evaluated a convenience sample of 4,832 HTLV-I immunoblot results from over 140,000 samples screened for HTLV-I, collected in 16 countries for 35 separate studies. An algorithm that compares reactivity against p19 and p24, 2 gag (HTLV-I core) proteins, was employed to characterize the immunoblots: type I, p19 stronger than p24 (presumptive HTLV-I), type 2, p24 stronger than p19 (presumptive HTLV-II), or indeterminate (p19 and p24 weakly positive or p19 weakly positive in the presence of p21 e). Geographic areas could be grouped into 4 patterns. Patterns A (> 75% type 1) and B (> 75% type 2) were usually observed where the specific type of HTLV or its characteristic diseases had been found. Pattern C (mixed type 1 and 2 pattern) was observed predominantly in intravenous-drug-using and other populations in which both virus types have been reported. Pattern D (> 10% indeterminate), suggests the presence of non-specific reactivity, perhaps resulting from exposure to non-virus-related antigens or an HTLV-related virus. HTLV-I predominates in southern Japan, the South Pacific, parts of West Africa, and in Afro-populations of the Western hemisphere. HTLV-II clusters in Native American populations and among intravenous drug users. Pattern-D areas in Africa and Venezuela might prove to be fertile in the search for new and variant HTLV virus types. RP MADELEINE, MM (reprint author), NCI,VIRAL EPIDEMIOL SECT,EPN 434,6130 EXECUT BLVD,ROCKVILLE,MD 20852, USA. NR 27 TC 26 Z9 27 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAY 8 PY 1993 VL 54 IS 2 BP 255 EP 260 DI 10.1002/ijc.2910540216 PG 6 WC Oncology SC Oncology GA LB688 UT WOS:A1993LB68800015 PM 8486428 ER PT J AU STOLL, J BALBO, A AULT, B RAPOPORT, SI FINE, A AF STOLL, J BALBO, A AULT, B RAPOPORT, SI FINE, A TI LONG-TERM TRANSPLANTS OF MOUSE TRISOMY 16 HIPPOCAMPAL-NEURONS, A MODEL FOR DOWNS-SYNDROME, DO NOT DEVELOP ALZHEIMERS-DISEASE NEUROPATHOLOGY SO BRAIN RESEARCH LA English DT Article DE NEURAL GRAFT; ALZ-50; BETA-AMYLOID; NEURODEGENERATION; NEUROFIBRILLARY TANGLE; PLAQUE; IMMUNOCYTOCHEMISTRY; HIPPOCAMPUS; ANIMAL MODEL ID AMYLOID PROTEIN DEPOSITION; NEUROFIBRILLARY TANGLES; BRAIN; DEMENTIA; IDENTIFICATION; ANTIBODIES; RECOGNIZES; PRECURSOR; PATHOLOGY; PLAQUES AB Hippocampal tissue from embryonic day 15-17 fetal mice, euploid or trisomic for chromosome 16, was transplanted into the striatum or the lateral ventricle of 6-8 week old female C57B1/6 mice. After 6-14 months of survival, host brains were sectioned and the grafts were examined by histochemical techniques and by immunocytochemistry for antigens present in pathological brain structures of Alzheimer's disease (AD) patients. Nissl-stained grafts contained aggregations of neurons similar to the pyramidal or the granule cell layers of the normal adult mouse hippocampus. No obvious morphological difference was detected between trisomic and control transplants. The monoclonal antibody Alz-50, which recognizes the paired helical filaments characteristic of AD, or an antibody raised to beta-amyloid peptide, did not reveal neurodegeneration in these grafts. Antibodies against ubiquitin, 200 kDa subunit of neurofilament, alpha1-antichymotrypsin and tau also did not demonstrate AD-type immunoreactivity in the trisomic or control grafts. Thioflavin S- or silver stained-sections were also negative. We conclude that transplanted hippocampal tissue from the trisomy 16 mouse does not represent an animal model for AD-type neurodegeneration. These results differ from those of Richards et al., EMBO J. (10) (1991) 297-303, who reported AD-type degeneration in trisomy 16 hippocampal transplants. C1 DALHOUSIE UNIV, FAC MED, INST NEUROSCI, HALIFAX B3H 4H2, NS, CANADA. DALHOUSIE UNIV, FAC MED, DEPT PHYSIOL & BIOPHYS, HALIFAX B3H 4H2, NS, CANADA. RP NIA, NEUROSCI LAB, BLDG 10, RM 6C103, BETHESDA, MD 20892 USA. NR 43 TC 16 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD MAY 7 PY 1993 VL 610 IS 2 BP 295 EP 304 DI 10.1016/0006-8993(93)91413-M PG 10 WC Neurosciences SC Neurosciences & Neurology GA LB530 UT WOS:A1993LB53000015 PM 8319091 ER PT J AU BLOUGH, BE MASCARELLA, SW ROTHMAN, RB CARROLL, FI AF BLOUGH, BE MASCARELLA, SW ROTHMAN, RB CARROLL, FI TI SYNTHESIS OF 3-HALOMETHYL-2,3,4,5-TETRAHYDRO-2,5-METHANO-1H-2-BENZAZEPINES AND THEIR REARRANGEMENT TO 4-HALO-1,2,3,4,5,6-HEXAHYDRO-2,6-METHANO-2-BENZAZOCINES SO JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS LA English DT Article AB This study reports a three-step synthesis of 3-halomethyl-2,3,4,5-tetrahydro-2,5-methano-1 H-2-benzazepines 2a-c and the rearrangement of 2a-b to 4-iodo- and 4-bromo-1,2,3,4,5,6-hexahydro-2,6-methano-2-methano-2-benzazocines 1a-b. C1 RES TRIANGLE INST,POB 12194,RES TRIANGLE PK,NC 27709. NIDA,ADDICT RES CTR,CLIN PSYCHOPHARMACOL SECT,BALTIMORE,MD 21224. OI Mascarella, Wayne/0000-0003-0092-8178 NR 6 TC 14 Z9 14 U1 0 U2 0 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK MILTON ROAD, CAMBRIDGE, CAMBS, ENGLAND CB4 4WF SN 0022-4936 J9 J CHEM SOC CHEM COMM JI J. Chem. Soc.-Chem. Commun. PD MAY 7 PY 1993 IS 9 BP 758 EP 760 DI 10.1039/c39930000758 PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA LC022 UT WOS:A1993LC02200022 ER PT J AU PIZZO, PA AF PIZZO, PA TI MANAGEMENT OF FEVER IN PATIENTS WITH CANCER AND TREATMENT-INDUCED NEUTROPENIA SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID COLONY-STIMULATING FACTOR; BONE-MARROW TRANSPLANTATION; FEBRILE GRANULOCYTOPENIC PATIENTS; GRAM-NEGATIVE BACTEREMIA; INTRAVENOUS IMMUNE GLOBULIN; PEDIATRIC ONCOLOGY PATIENTS; CYTOMEGALO-VIRUS PNEUMONIA; PLACEBO-CONTROLLED TRIAL; ACUTE-LEUKEMIA; DOUBLE-BLIND RP PIZZO, PA (reprint author), NCI,PEDIAT BRANCH,BLDG 10,RM 13N240,BETHESDA,MD 20892, USA. NR 120 TC 616 Z9 627 U1 3 U2 8 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 6 PY 1993 VL 328 IS 18 BP 1323 EP 1332 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA KZ640 UT WOS:A1993KZ64000008 PM 8469254 ER PT J AU SOLTOFF, SP MCMILLIAN, MK TALAMO, BR CANTLEY, LC AF SOLTOFF, SP MCMILLIAN, MK TALAMO, BR CANTLEY, LC TI BLOCKADE OF ATP BINDING-SITE OF P(2) PURINOCEPTORS IN RAT PAROTID ACINAR-CELLS BY ISOTHIOCYANATE COMPOUNDS SO BIOCHEMICAL PHARMACOLOGY LA English DT Note ID EXTRACELLULAR ATP; RECEPTOR; P2-PURINOCEPTOR; ACTIVATION; RESPONSES; AGONISTS; I; CHANNELS; CALCIUM; FLUXES AB Extracellular ATP activates a P2Z-type purinergic receptor (purinoceptor) in rat parotid acinar cells that increases the intracellular free Ca2+ concentration via the entry of extracellular Ca2+ through an ATP-sensitive cation channel (Soltoff et al., Am J Physiol 262: C934-C940, 1992). To learn more about the ATP binding site of the purinoceptor, we examined the effects of several stilbene isothiocyanate analogs of DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid), which block the binding of [P-32]ATP to intact parotid cells (McMillian et al., Biochem J 255: 291-300, 1988) and blocked the activation of the P2Z purinoceptor. The ATP-stimulated Ca-45(2+) uptake was blocked by DIDS, H2DIDS (dihydro-DIDS; 4,4'-diisothiocyanatodihydrostilbene-2,2'-disulfonic acid), and SIT'S (4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid), but not by DNDS (4,4'-dinitrostilbene-2,2'-disulfonic acid), a stilbene disulfonate compound lacking isothiocyanate (SCN-) groups, or by KSCN. The potency of the stilbene disulfonates was related to the number of isothiocyanate groups on each compound. Under the experimental conditions, the IC50 value of DIDS (approximately 35 muM), which has two SCN-groups, was much lower than that of SITS (approximately 125 muM), which has only one SCN- group. The inhibitory effects of DIDS appeared to be much more potent than those of SITS due to the kinetics of their binding to the purinoceptors. Eosin-5-isothiocyanate (EITC) and fluoroscein-5-isothiocyanate (FITC), non-stilbene isothiocyanate compounds with single SCN- groups, also blocked the response to ATP and were less potent than DIDS. Trinitrophenyl-ATP (TNP-ATP), an ATP derivative that is not an effective agonist of the parotid P2Z receptor, blocked the covalent binding of DIDS to the plasma membrane, suggesting that ATP and DIDS bind to the same site. Reactive Blue 2 (Cibacron Blue 3GA), an anthraquinone-sulfonic acid derivative that is a noncovalent purinergic antagonist, also blocked the covalent binding of DIDS to the plasma membrane. These results suggest that isothiocyanate compounds interact with the ATP binding site of this P2 purinoceptor, and that isothiocyanate groups make an important contribution in determining the effectiveness of the stilbene disulfonate compounds in blocking the binding of nucleotide agonists to this purinoceptor. C1 TUFTS UNIV,DEPT PHYSIOL,BOSTON,MA 02111. TUFTS UNIV,DIV NEUROSCI,BOSTON,MA 02111. NIEHS,RES TRIANGLE PK,NC 27709. RP SOLTOFF, SP (reprint author), BETH ISRAEL HOSP,DEPT MED,DIV SIGNAL TRANSDUCT,EQRF ROOM 148,200 LONGWOOD AVE,BOSTON,MA 02215, USA. RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NIDCR NIH HHS [R55DE09596]; NIGMS NIH HHS [GM36133]; NINDS NIH HHS [NS28556] NR 20 TC 43 Z9 44 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 MAY 5 PY 1993 VL 45 IS 9 BP 1936 EP 1940 DI 10.1016/0006-2952(93)90455-6 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LC526 UT WOS:A1993LC52600029 PM 7684222 ER PT J AU QUEZADO, ZMN NATANSON, C ALLING, DW BANKS, SM KOEV, CA ELIN, RJ HOSSEINI, JM BACHER, JD DANNER, RL HOFFMAN, WD AF QUEZADO, ZMN NATANSON, C ALLING, DW BANKS, SM KOEV, CA ELIN, RJ HOSSEINI, JM BACHER, JD DANNER, RL HOFFMAN, WD TI A CONTROLLED TRIAL OF HA-1A IN A CANINE MODEL OF GRAM-NEGATIVE SEPTIC SHOCK SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID MONOCLONAL ANTIENDOTOXIN ANTIBODIES; CARDIOVASCULAR DYSFUNCTION; ESCHERICHIA-COLI; INITIAL EVALUATION; IGM ANTIBODY; LIPID-A; BACTEREMIA; ENDOTOXEMIA; MORTALITY; THERAPY AB Objective.-To investigate the therapeutic efficacy and microbiological and physiological effects of a human IgM monoclonal antibody (HA-1A) directed against the lipid A component of endotoxin in a canine model of sepsis that simulates the cardiovascular abnormalities of human septic shock. Design.-Blinded, placebo-controlled 28-day trial. Interventions.-Purpose-bred beagles were implanted with an intraperitoneal clot infected with Escherichia coli O111:B4. At clot placement, animals received HA-1A (10 mg.kg-1), control human IgM antibody (10 mg.kg-1), or control human serum albumin intravenously. All animals were given antibiotic and fluid therapy. Measures.-Survival and microbiological and physiological events. Results.-Only two (15%) of 13 animals in the HA-1A group, compared with eight (57%) of 14 control animals (combined control human IgM antibody and control human serum albumin groups) (P=.05), survived 28 days. At 24 hours, the HA-1A group had lower mean arterial pressure (P=.04) and cardiac index (P=.004) and higher lactate levels (P=.05) compared with the combined-controls group. In addition, these parameters in the HA-1A group were significantly more predictive of death. The HA-1A and combined-controls groups had similar significant increases in the level of endotoxemia and bacteremia. Studies of toxic effects showed no harmful effects of control human IgM antibody in infected animals or HA-1A in non-infected animals. Conclusion.-In a canine model of E coli sepsis, HA-1 A did not alter levels of bacteremia or endotoxemia and actually decreased survival. If these data are relevant to human septic shock, HA-1A therapy should be limited until the conditions under which this monoclonal antibody has beneficial or deleterious effects are more completely defined. C1 NIH,DEPT CLIN PATHOL,BETHESDA,MD 20892. NIH,NATL CTR RES RESOURCES,VET RESOURCES PROGRAM,BETHESDA,MD 20892. RP QUEZADO, ZMN (reprint author), NIH,DEPT CRIT CARE MED,BLDG 10,ROOM 7D43,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Quezado, Zenaide/O-4860-2016 OI Quezado, Zenaide/0000-0001-9793-4368 NR 33 TC 95 Z9 96 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 5 PY 1993 VL 269 IS 17 BP 2221 EP 2227 DI 10.1001/jama.269.17.2221 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA KZ406 UT WOS:A1993KZ40600029 PM 8474201 ER PT J AU YANOVSKI, JA CUTLER, GB CHROUSOS, GP NIEMAN, LK AF YANOVSKI, JA CUTLER, GB CHROUSOS, GP NIEMAN, LK TI CORTICOTROPIN-RELEASING HORMONE STIMULATION FOLLOWING LOW-DOSE DEXAMETHASONE ADMINISTRATION - A NEW TEST TO DISTINGUISH CUSHINGS-SYNDROME FROM PSEUDO-CUSHINGS STATES SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID PITUITARY-ADRENAL AXIS; DIFFERENTIAL-DIAGNOSIS; SUPPRESSION TEST; CORTISOL; DISEASE; DEPRESSION; RESPONSES; CLEARANCE; ACTH; CRF AB Objective.-The biochemical and phenotypic presentation of mild hypercortisolism in Cushing's syndrome is often indistinguishable from that seen in pseudo-Cushing's states such as depression. Both dexamethasone suppression and corticotropin-releasing hormone (CRH) stimulation tests have been used individually to distinguish these conditions, but neither approach has achieved a diagnostic accuracy greater than 85%. Therefore, we sought to develop a combined dexamethasone-CRH test that would take advantage of the altered sensitivity of patients with Cushing's syndrome to both dexamethasone and CRH and would achieve greater accuracy in the diagnosis of Cushing's syndrome. Design.-Prospective cohort study. Setting.-Tertiary care research hospital. Patients.-A total of 58 adults referred for evaluation of mild hypercortisolism (urine free cortisol level < 1000 nmol/d). The diagnosis of Cushing's syndrome was confirmed at surgery in 39 patients. The diagnosis of a pseudo-Cushing's state was made in 19 patients on the basis of extended follow-up (mean, 28 months) without progression of cushingoid features. Intervention.-The low-dose dexamethasone suppression test, the CRH stimulation test, and the CRH stimulation test started 2 hours after completion of low-dose dexamethasone suppression (the dexamethasone-CRH test) were performed in all patients. Main Outcome Measures.-Sensitivity, specificity, and accuracy of the three procedures for diagnosis of Cushing's syndrome were calculated from plasma corticotropin, plasma cortisol, urine free cortisol, and urine 17-hydroxycorticosteroid values. Results.-The low-dose dexamethasone suppression test had 74% specificity, 69% sensitivity, and 71% diagnostic accuracy, using the standard criterion (1 7-hydroxycorticosteroid excretion level > 11.0 mumol/d on the second day of dexamethasone administration). With a urine free cortisol criterion for Cushing's syndrome of greater than 100 nmol/d, the low-dose dexamethasone suppression test had 100% specificity, 56% sensitivity, and 71% diagnostic accuracy. The CRH stimulation test without dexamethasone pretreatment had 1 00% specificity, 640/. sensitivity, and 76% diagnostic accuracy. The diagnostic accuracy of the dexamethasone-CRH test for Cushing's syndrome was significantly greater than the accuracy of either the low-dose dexamethasone test or the CRH test alone (P<.01). A plasma cortisol concentration greater than 38 nmol/L measured 15 minutes after the administration of CRH correctly identified all cases of Cushing's syndrome and all cases of pseudo-Cushing's states (100% specificity sensitivity, and diagnostic accuracy). Conclusion.-The dexamethasone-CRH test is a more accurate test to distinguish Cushing's syndrome from pseudo-Cushing's states in patients with mild hypercortisolism. RP YANOVSKI, JA (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,BLDG 10,ROOM 10N262,BETHESDA,MD 20892, USA. OI Yanovski, Jack/0000-0001-8542-1637 NR 41 TC 183 Z9 187 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 MAY 5 PY 1993 VL 269 IS 17 BP 2232 EP 2238 DI 10.1001/jama.269.17.2232 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA KZ406 UT WOS:A1993KZ40600031 PM 8386285 ER PT J AU BOTTARO, DP FORTNEY, E RUBIN, JS AARONSON, SA AF BOTTARO, DP FORTNEY, E RUBIN, JS AARONSON, SA TI A KERATINOCYTE GROWTH-FACTOR RECEPTOR-DERIVED PEPTIDE ANTAGONIST IDENTIFIES PART OF THE LIGAND-BINDING SITE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID EXPRESSION; CLONING AB Keratinocyte growth factor (KGF) is a fibroblast growth factor (FGF) family member that acts specifically on cells of epithelial origin. Its receptor (KGFR) is a membrane-spanning tyrosine kinase, which also binds acidic FGF (aFGF) with equally high affinity, and basic FGF (bFGF) with much lower affinity. The KGFR is encoded by the bek/FGFR-2 gene, whose alternative transcript specifies a receptor with high affinity for aFGF and bFGF, but no detectable binding of KGF. The only structural difference between these two receptors is a 49-amino acid segment in the extracellular domain that is determined by single alternative exons. We report that a synthetic peptide (NH2-His199...Tyr223-COOH) corresponding to part of the predicted sequence of the KGFR alternative exon blocks KGF mitogenic activity and the interaction between KGF and its receptor. The peptide also blocks the interaction between KGF and a neutralizing monoclonal antibody raised against this growth factor. These results demonstrate that the peptide binds directly and specifically to KGF and argue that this region of the receptor constitutes part or all of the KGF binding site. RP BOTTARO, DP (reprint author), NCI,CELLULAR & MOLEC BIOL LAB,BLDG 37,RM 1E24,BETHESDA,MD 20892, USA. RI Bottaro, Donald/F-8550-2010 OI Bottaro, Donald/0000-0002-5057-5334 NR 10 TC 55 Z9 56 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 5 PY 1993 VL 268 IS 13 BP 9180 EP 9183 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LA689 UT WOS:A1993LA68900007 PM 8387485 ER PT J AU MARTINYBARON, G KAZANIETZ, MG MISCHAK, H BLUMBERG, PM KOCHS, G HUG, H MARME, D SCHACHTELE, C AF MARTINYBARON, G KAZANIETZ, MG MISCHAK, H BLUMBERG, PM KOCHS, G HUG, H MARME, D SCHACHTELE, C TI SELECTIVE-INHIBITION OF PROTEIN-KINASE-C ISOZYMES BY THE INDOLOCARBAZOLE GO 6976 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID PHORBOL ESTER RECEPTOR; HEMATOPOIETIC-CELLS; ISOTYPE-ALPHA; EXPRESSION; FAMILY; POTENT; STAUROSPORINE; HETEROGENEITY; PURIFICATION; ACTIVATION AB Indolocarbazoles have been identified as novel inhibitors of protein kinase C (PKC), with Go 6976 as one of its most potent and selective representatives. Recombinant PKC isozymes alpha, beta1, delta, epsilon, and zeta were used in in vitro kinase assays to investigate Go 6976 with respect to isozyme-specific PKC inhibition. Go 6850, identical with GF 109203X, another PKC-specific kinase inhibitor, was included in this study as a reference compound. Nanomolar concentrations of the indolocarbazole Go 6976 inhibited the Ca2+-dependent isozymes alpha and beta1, whereas even micromolar concentration of Go 6976 had no effect on the kinase activity of the Ca2+-independent PKC subtypes delta, epsilon, and zeta. In contrast, the bisindolymaleimide Go 6850 inhibited all PKC isozymes, however, with a ranked order of potency (alpha > beta1 > epsilon > delta > zeta). Kinetic analysis revealed that PKC inhibition by Go 6976 was competitive with respect to ATP, non-competitive with respect to the protein substrate, and mixed type with respect to phosphatidylserine. Further experiments in the presence of different amounts of free Ca2+ indicated that interference with Ca2+ or its binding site is not responsible for the differential inhibition of PKC isozymes by Go 6976. C1 GODECKE AG, DEPT BIOCHEM PHARMACOL, MOOSWALDALLEE 1-9, W-7800 FREIBURG, GERMANY. UNIV FREIBURG, INST MOLEC CELL BIOL, W-7800 FREIBURG, GERMANY. NCI, MOLEC MECHANISMS TUMOR PROMOT SECT, BETHESDA, MD 20892 USA. NCI, MOLEC GENET SECT, GENET LAB, BETHESDA, MD 20892 USA. RI Mischak, Harald/E-8685-2011 NR 45 TC 1411 Z9 1420 U1 1 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 5 PY 1993 VL 268 IS 13 BP 9194 EP 9197 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LA689 UT WOS:A1993LA68900011 PM 8486620 ER PT J AU BACH, LA HSIEH, S SAKANO, K FUJIWARA, H PERDUE, JF RECHLER, MM AF BACH, LA HSIEH, S SAKANO, K FUJIWARA, H PERDUE, JF RECHLER, MM TI BINDING OF MUTANTS OF HUMAN INSULIN-LIKE GROWTH FACTOR-II TO INSULIN-LIKE GROWTH-FACTOR BINDING PROTEINS-1-6 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HIGH-AFFINITY BINDING; IGF-II; FACTOR (IGF)-I; CELL-LINE; RECEPTOR; FIBROBLASTS; EXPRESSION; SECRETION; RESIDUES AB A family of six specific insulin-like growth factor binding proteins (IGFBPs) modulates the biological actions of the insulin-like growth factors, IGF-I and IGF-II. In the present study, we determined the binding affinity of purified human IGFBPs 1-6 for recombinant human IGF-II mutants whose binding to IGF-I, IGF-II/mannose 6-phosphate, and insulin receptors was previously reported (Sakano, K., Enjoh, T., Numata, F., Fujiwara, H., Marumoto, Y., Higashihashi, N., Sato, Y., Perdue, J. F., and Fujita-Yamaguchi, Y. (1991) J. Biol. Chem. 266, 20626-20635). Of the regions studied, the most important determinants of IGF-II binding to the IGFBPs were A-domain residues 4850 and B-domain residue 26. Substitution of residues 48-50 with the analogous residues from human insulin (Thr-Ser-Ile) reduced binding to IGFBP-1, -5, and -6 more than 50-fold and to IGFBP-4 by 15-50-fold; binding to IGFBP-2 and -3 was reduced 6-12-fold. The same substitution markedly reduced binding to the IGF-II/mannose 6-phosphate receptor but not to IGF-I or insulin receptors. Although substitution of residues 54 and 55 with the analogous residues from IGF-I (Arg-Arg) abolished binding to the IGF-II/mannose 6-phosphate receptor, binding to IGFBPs was not substantially affected. Substitution of Phe26 with Ser or Leu, which decreased binding to the IGF-I and insulin receptors, reduced binding to IGFBP-1 and -6 up to 80-fold, but had lesser effects on the other IGFBPs. [Leu27]IGF-II and [Leu43]IGF-II, which had a more markedly reduced affinity for the IGF-I and insulin receptors than did [Ser26]IGF-II, were bound by the IGFBPs with relatively unchanged affinity compared with IGF-II. Thus, the determinants of IGF-II binding to IGFBPs partially overlap those for the IGF-II/mannose 6-phosphate receptor and overlap those for the IGF-I receptor to a lesser extent. IGFBP-I and IGFBP-6 are most sensitive to changes in IGF-II structure, although IGFBP-I binds IGF-I and IGF-II with equal affinity, whereas IGFBP-6 has a marked preferential binding affinity for IGF-II. IGF-II mutants with selective impairment in recognition by specific IGFBPs or receptors will provide a useful tool for dissecting the role of the different IGF binding macromolecules in the mediation of IGF-II actions. C1 DAIICHI PHARMACEUT CO LTD,MOLEC BIOL RES LAB,EDOGAWA KU,TOKYO 134,JAPAN. AMER RED CROSS,JEROME H HOLLAND LAB,MOLEC BIOL LAB,ROCKVILLE,MD 20855. RP BACH, LA (reprint author), NIDDKD,MOLEC & CELLULAR ENDOCRINOL BRANCH,GROWTH & DEV SECT,BLDG 10,RM 8D14,BETHESDA,MD 20892, USA. OI Bach, Leon/0000-0002-9062-1518 FU NCI NIH HHS [CA 47150] NR 38 TC 118 Z9 118 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 5 PY 1993 VL 268 IS 13 BP 9246 EP 9254 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LA689 UT WOS:A1993LA68900018 PM 7683646 ER PT J AU SCHOCH, C BLUMENTHAL, R AF SCHOCH, C BLUMENTHAL, R TI ROLE OF THE FUSION PEPTIDE SEQUENCE IN INITIAL-STAGES OF INFLUENZA HEMAGGLUTININ-INDUCED CELL-FUSION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INDUCED MEMBRANE-FUSION; VIRUS HEMAGGLUTININ; SURFACE-DENSITY; FLUORESCENCE; GLYCOPROTEIN; EVENTS; FIBROBLASTS; MICROSCOPY; KINETICS; BILAYERS AB The fusion activity of influenza hemagglutinin (HA) and of HA proteins altered in the amino terminus of HA2 (fusion peptide) by site-directed mutagenesis (Gething, M.-J., Doms, R. W., York, D., and White, J. (1986) J. Cell Biol. 102, 11-23) was analyzed following expression in CV-1 cells using SV40-HA recombinant virus vectors. Fusion was monitored by the redistribution of lipid and cytoplasmic dyes between fluorescently labeled erythrocytes and HA-expressing CV-1 cells using spectrofluorometry and fluorescence microscopy. The kinetics of lipid redistribution after lowering the pH showed the same pattern for wild type HA and nonlethal mutants, although there were shifts in the pH threshold. The time for commitment to the fusogenic state and the temperature dependence of the processes leading to HA-mediated fusion were also the same for wild type and nonlethal mutants. However, striking differences were observed between wild type HA and the nonlethal mutants in their ability to induce pH-dependent redistribution from erythrocytes to HA-expressing cells of large molecular weight (M(r) > 10,000) fluorescently labeled dextran molecules. The data indicate that the kinetic processes which are measurable in the time range of seconds are insensitive to the structure of the fusion peptide. Surprisingly, however, the fusion peptide plays an important role in later processes related to pore widening which eventually results in delivery of the nucleocapsid into the cell. C1 NCI,MEMBRANE STRUCT & FUNCT SECT,BETHESDA,MD 20892. NR 41 TC 60 Z9 62 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 5 PY 1993 VL 268 IS 13 BP 9267 EP 9274 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LA689 UT WOS:A1993LA68900021 PM 8387488 ER PT J AU HEIDARAN, MA BEELER, JF YU, JC ISHIBASHI, T LAROCHELLE, WJ PIERCE, JH AARONSON, SA AF HEIDARAN, MA BEELER, JF YU, JC ISHIBASHI, T LAROCHELLE, WJ PIERCE, JH AARONSON, SA TI DIFFERENCES IN SUBSTRATE SPECIFICITIES OF ALPHA-PLATELET-DERIVED AND BETA-PLATELET-DERIVED GROWTH-FACTOR (PDGF) RECEPTORS - CORRELATION WITH THEIR ABILITY TO MEDIATE PDGF TRANSFORMING FUNCTIONS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GTPASE-ACTIVATING PROTEIN; CYTOPLASMIC SIGNALING PROTEINS; PHOSPHOLIPASE-C-GAMMA; KINASE INSERT DOMAIN; PHOSPHATIDYLINOSITOL KINASE; TYROSINE PHOSPHORYLATION; CELL LINES; A-CHAIN; TRANSDUCTION; ASSOCIATION AB Recombinant expression of either the alpha or beta platelet-derived growth factor (PDGF) receptors in 32D hematopoietic cells allows efficient coupling of PDGF with mitogenic and chemotactic signaling pathways inherently expressed by those cells. PDGF-BB stimulation of 32D-alphaR or betaR cells results in anti-P-Tyr recovery of cellular proteins possessing similar as well as distinct phosphotyrosine signals. Comparison of the ability of each receptor to couple with known second messengers revealed that both receptors associated with and/or tyrosine phosphorylated phospholipase C-gamma (PLC-gamma) and phosphatidylinositol 3-kinase (p85) with similar stoichiometry. However, the beta platelet-derived growth factor receptor (PDGFR) was significantly more efficient at in vivo tyrosine phosphorylation of GTPase-activating protein (GAP). Similar differences in binding affinity for GAP were observed in NIH/3T3 cells which express both receptors. To quantitate the affinities of each receptor for GAP or PLCgamma, we utilized baculovirus-expressed alpha and beta PDGFRs purified by anti-P-Tyr affinity chromatography. Exposure of immunoblots containing bacterially expressed GAP or PLCgamma to activated alpha or beta PDGF receptors led to a comparable high affinity binding of each receptor to PLCgamma, while the beta PDGFR showed a 5-fold higher binding affinity for GAP. In an effort to correlate differences in their substrate specificities with biological properties of the receptors, we compare their abilities to enhance PDGF-A transforming function in NIH/3T3 cells. Cotransfection of PDGF-A with the alpha PDGFR increased PDGF-A transforming activity by approximately 2-fold. However, cotransfection with a chimeric receptor with the catalytic domain of the beta PDGFR but possessing a PDGFR ligand binding properties resulted in 17-fold enhancement of PDGF-A transformation. These findings argue that differences in alpha and beta PDGF receptor substrate specificity in NIH/3T3 fibroblasts correlate with greater transforming activity mediated by the beta PDGFR. C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. NR 54 TC 79 Z9 80 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 5 PY 1993 VL 268 IS 13 BP 9287 EP 9295 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LA689 UT WOS:A1993LA68900024 PM 8387491 ER PT J AU GIBSON, KR VANEK, PG KALOSS, WD COLLIER, GB CONNAUGHTON, JF ANGELICHIO, M LIVI, GP FLEMING, PJ AF GIBSON, KR VANEK, PG KALOSS, WD COLLIER, GB CONNAUGHTON, JF ANGELICHIO, M LIVI, GP FLEMING, PJ TI EXPRESSION OF DOPAMINE-BETA-HYDROXYLASE IN DROSOPHILA SCHNEIDER 2 CELLS - EVIDENCE FOR A MECHANISM OF MEMBRANE-BINDING OTHER THAN UNCLEAVED SIGNAL PEPTIDE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BOVINE ADRENAL-MEDULLA; CHROMAFFIN GRANULES; INSECT CELLS; MAMMALIAN-CELLS; MESSENGER-RNA; BOUND FORMS; SEQUENCE; VECTOR; CDNA; IMMUNOFLUORESCENCE AB To characterize the mechanism of membrane attachment of dopamine beta-hydroxylase, an expression system producing the processed form of this enzyme has been developed. We have replaced the endogenous signal peptide of bovine dopamine beta-hydroxylase with a heterologous signal peptide which is efficiently recognized and cleaved in Drosophila Schneider 2 cells. A cDNA encoding this chimeric recombinant bovine enzyme has been stably transfected into Schneider 2 cells. The inducible expression of active dopamine beta-hydroxylase in these cells has been verified by Western blotting and enzyme activity assays. N-terminal sequence analysis of purified recombinant enzyme demonstrates complete removal of the signal peptide. Subcellular analysis shows that the recombinant enzyme exists as both a soluble and a membrane-bound form in these cells. These data demonstrate that the endogenous signal peptide is not required for the formation of the membranous dopamine beta-hydroxylase and further that the enzyme can be bound to membranes via a mechanism other than uncleaved signal sequence. C1 GEORGETOWN UNIV,MED CTR,DEPT BIOCHEM & MOLEC BIOL,WASHINGTON,DC 20007. NCI,MOLEC ONCOL LAB,FREDERICK,MD 21701. ONCOR INC,GAITHERSBURG,MD 20877. SMITHKLINE BEECHAM,KING OF PRUSSIA,PA 19406. RI Fleming, Karen/E-7892-2011 FU NIGMS NIH HHS [GM27695]; NIMH NIH HHS [MH10223] NR 61 TC 21 Z9 22 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 5 PY 1993 VL 268 IS 13 BP 9490 EP 9495 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LA689 UT WOS:A1993LA68900053 PM 8486639 ER PT J AU RANDAZZO, PA YANG, YC RULKA, C KAHN, RA AF RANDAZZO, PA YANG, YC RULKA, C KAHN, RA TI ACTIVATION OF ADP-RIBOSYLATION FACTOR BY GOLGI MEMBRANES - EVIDENCE FOR A BREFELDIN A-SENSITIVE AND PROTEASE-SENSITIVE ACTIVATING FACTOR ON GOLGI MEMBRANES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GTP-BINDING-PROTEIN; BOVINE BRAIN; ADENYLATE-CYCLASE; SUCCESSIVE COMPARTMENTS; REGULATORY COMPONENT; GUANINE-NUCLEOTIDES; CHOLERA-TOXIN; PURIFICATION; COFACTOR; ALPHA AB Recent evidence has implicated ADP-ribosylation factor (ARF) proteins as critical regulators of the protein secretory pathway, particularly in the endoplasmic reticulum-Golgi pathway. We have examined whether Golgi membranes contain activators of ARF and the consequences of ARF activation and acylation on its membrane association. Two means were used to assess ARF activation. First, guanosine 5'-3-O-(thio)triphosphate (GTPgammaS) binding to protein was found to be greater when ARF and Golgi were incubated together than when either was incubated alone. These data suggested that ARF . GTPgammaS was formed. This was confirmed by showing that the GTPgammaS-bound protein functioned as a cofactor for cholera toxin-stimulated ADP-ribosylation of G(salpha), a reaction for which activated ARF is a necessary cofactor. Trypsin treatment of Golgi, an inhibitory ARF peptide, and brefeldin A each inhibited Golgi-mediated activation by approximately 70%, demonstrating that a specific protein interaction is required for the majority of the ARF activation. This ARF-activating protein is a strong candidate for the molecular target for brefeldin A. The ubiquitous nature of ARF proteins and their importance in both the exocytic and endocytic pathways may explain the effects of brefeldin A on both exocytic and endocytic membrane traffic in animal cells. A protease-insensitive activation of ARF by Golgi could also be demonstrated and was the dominant activity observed in submicromolar concentrations of magnesium. We believe this to be the lipid-mediated process described previously for purified ARF proteins. ARF activation resulted in tight association of ARF with phospholipid vesicles. Vesicle association required amino-terminal myristoylation of ARF whereas activation did not. These studies indicate that the brefeldin A-sensitive ARF-activating protein and other factors that determine the level of activation of ARF in animal cells are fundamental regulators of membrane traffic in animal cells. C1 NCI, DIV CANC TREATMENT,DEV THERAPEUT PROGRAM, BIOL CHEM LAB,REGULATORY MECHANISMS SECT, BLDG 37, FREDERICK, MD 21701 USA. NR 35 TC 123 Z9 123 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 5 PY 1993 VL 268 IS 13 BP 9555 EP 9563 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LA689 UT WOS:A1993LA68900063 PM 8486645 ER PT J AU SHIMIZU, K SUGINO, A AF SHIMIZU, K SUGINO, A TI PURIFICATION AND CHARACTERIZATION OF DNA HELICASE-III FROM THE YEAST SACCHAROMYCES-CEREVISIAE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LARGE TUMOR-ANTIGEN; ESCHERICHIA-COLI; DEPENDENT ATPASE; GENE-PRODUCT; PROTEIN COMPLEX; POLYMERASE-I; CALF THYMUS; REPLICATION; ENZYME; SEQUENCE AB Two forms of DNA helicase activity, Rad3 and ATPase III, were previously purified from the yeast Saccharomyces cerevisiae and characterized. Here, we have identified and purified an additional DNA helicase activity from S. cerevisiae to near homogeneity. This helicase differs from those described previously in its chromatographic behavior, molecular weight, enzymatic properties, and genetic properties. Thus, we named it DNA helicase III. Its apparent molecular mass is about 120 kDa as determined by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. DNA helicase III requires a divalent cation Mg2+ or Mn2+, either ATP or dATP, and a single-stranded portion on the duplex substrate. Helicase III moves in the 5' --> 3' direction on single-stranded portions of the substrate and unwinds the strand of DNA in the 3' --> 5' direction. It also has an intrinsic DNA-dependent ATPase (dATPase) activity that hydrolyzes either ATP or dATP to ADP or dADP and orthophosphate in the presence of DNA. DNA helicase III activity was not affected by either rad3 or radH mutations, suggesting that it is encoded by a gene different from RAD3 and RADH. C1 NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709. OSAKA UNIV,MICROBIAL DIS RES INST,DEPT MOLEC IMMUNOL,SUITA,OSAKA 565,JAPAN. NR 50 TC 15 Z9 15 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 5 PY 1993 VL 268 IS 13 BP 9578 EP 9584 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LA689 UT WOS:A1993LA68900066 PM 8387501 ER PT J AU IWAMOTO, M YAGAMI, K VALLE, PL OLSEN, BR PETROPOULOS, CJ EWERT, DL PACIFICI, M AF IWAMOTO, M YAGAMI, K VALLE, PL OLSEN, BR PETROPOULOS, CJ EWERT, DL PACIFICI, M TI EXPRESSION AND ROLE OF C-MYC IN CHONDROCYTES UNDERGOING ENDOCHONDRAL OSSIFICATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CULTURED CHICK CHONDROCYTES; COLLAGEN GENE-EXPRESSION; FIBROBLAST GROWTH-FACTOR; X COLLAGEN; EMBRYONIC CHICK; MESSENGER-RNA; TERMINAL DIFFERENTIATION; EPIPHYSEAL CARTILAGE; MAMMALIAN-CELLS; DNA AB To analyze the relationship between c-myc gene expression and chondrocyte proliferation and maturation during endochondral ossification, Day 18-19 chick embryo sterna were pulse-labeled with [H-3]thymidine, and serial sections were processed for autoradiography and in situ hybridization. Proliferating chondrocytes, located in four distinct areas of the developing sternum, all contained high levels of c-myc transcripts, whereas postmitotic chondrocytes (such as hypertrophic chondrocytes) contained undetectable amounts. These findings were confirmed by Northern blot analysis and by the observation that antisense c-myc oligomer treatment inhibited proliferation in cultured chondrocytes. Constitutive overexpression of c-myc by retroviral vectors in immature chondrocyte cultures (c-myc cultures) maintained the cells in a proliferative state and blocked their maturation into hypertrophic chondrocytes. The lack of maturation in the c-myc cultures was corroborated by analysis of type X collagen gene regulation. Control immature cultures contained strong repressor activity for the type X collagen gene promoter, as revealed by transfection assays; repressor activity was lost upon maturation and activation of type X collagen synthesis. In the c-myc cultures, however, repressor activity persisted. Thus, c-myc participates in the normal changes in proliferation accompanying chondrocyte maturation in vivo and in culture. The decreases in c-myc expression and cell proliferation appear to be required for completion of maturation. C1 HARVARD UNIV,SCH MED,DEPT ANAT & CELL BIOL,BOSTON,MA 02115. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. WISTAR INST ANAT & BIOL,PHILADELPHIA,PA 19104. RP IWAMOTO, M (reprint author), UNIV PENN,SCH DENT,DEPT ANAT HISTOL,PHILADELPHIA,PA 19104, USA. FU NIAMS NIH HHS [AR 39705, AR 36820, AR 36819] NR 55 TC 35 Z9 35 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 5 PY 1993 VL 268 IS 13 BP 9645 EP 9652 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LA689 UT WOS:A1993LA68900074 PM 8486652 ER PT J AU ATTAASAFOADJEI, E LAWTON, MP PHILPOT, RM AF ATTAASAFOADJEI, E LAWTON, MP PHILPOT, RM TI CLONING, SEQUENCING, DISTRIBUTION, AND EXPRESSION IN ESCHERICHIA-COLI OF FLAVIN-CONTAINING MONOOXYGENASE 1C1 - EVIDENCE FOR A 3RD GENE SUBFAMILY IN RABBITS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FUNCTION AMINE OXIDASE; PIG-LIVER-MICROSOMES; MULTIPLE FORMS; GEL-ELECTROPHORESIS; PRIMARY ALKYLAMINES; COVALENT STRUCTURE; RIBONUCLEIC-ACID; DNA; PURIFICATION; MOUSE AB Two full-length cDNA clones (2.2 kilobases) encoding a newly recognized form of mammalian flavin-containing monooxygenase (FMO) have been isolated from independent libraries constructed with mRNA from different rabbits. The cDNAs encode a polypeptide of 533 amino acids which contains two putative pyrophosphate binding domains and a hydrophobic carboxyl terminus characteristic of FMOs. This sequence is 52 and 57% identical to sequences of the rabbit ''hepatic'' and ''pulmonary'' FMOs, respectively, and 55% identical to the sequence of ''liver form 2'' published recently by Ozols (Ozols, J. (1991) Arch. Biochem. Biophys. 290, 103-115). cDNA for the new FMO (FMO 1C1) hybridizes with two species of mRNA, one of 2.6 kilobases and one of about 5.4 kilobases, from liver or kidney, but not lung. Guinea pig, hamster, rat, and mouse all express this form of FMO in liver, kidney, and lung. FMO 1C1 has been tentatively characterized following expression in Escherichia coli. It is inactive with methimazole as substrate but highly active with n-octylamine. The temperature lability, responses to ions and detergent, and pH optimum of FMO 1C1 are similar to values reported for hepatic FMO. Sequence comparisons and analysis of rabbit and human genomic DNA indicate that FMO 1C1, as well as the pulmonary and hepatic FMOs, comprise a single gene family made up of distinct gene subfamilies (A, B,C, D,...N), each appearing to contain a single gene. A nomenclature, based on these interrelationships and following the same designations used for classifying cytochromes P-450, is proposed. C1 NIEHS,CELLULAR & MOLEC PHARMACOL LAB,POB 12233,RES TRIANGLE PK,NC 27709. NR 50 TC 65 Z9 67 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 5 PY 1993 VL 268 IS 13 BP 9681 EP 9689 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LA689 UT WOS:A1993LA68900079 PM 8486656 ER PT J AU ROSS, FP CHAPPEL, J ALVAREZ, JI SANDER, D BUTLER, WT FARACHCARSON, MC MINTZ, KA ROBEY, PG TEITELBAUM, SL CHERESH, DA AF ROSS, FP CHAPPEL, J ALVAREZ, JI SANDER, D BUTLER, WT FARACHCARSON, MC MINTZ, KA ROBEY, PG TEITELBAUM, SL CHERESH, DA TI INTERACTIONS BETWEEN THE BONE-MATRIX PROTEINS OSTEOPONTIN AND BONE SIALOPROTEIN AND THE OSTEOCLAST INTEGRIN ALPHA-V-BETA-3 POTENTIATE BONE-RESORPTION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ARG-GLY-ASP; AMINO-ACID-SEQUENCE; CELL-ADHESION; VITRONECTIN RECEPTOR; RAT BONE; ALPHA-V; PHOSPHORYLATED GLYCOPROTEIN; MONONUCLEAR PHAGOCYTES; EXTRACELLULAR-MATRIX; VONWILLEBRAND-FACTOR AB We have investigated the mechanism by which osteoclasts adhere to and resorb bone. We show that these cells express beta1 and beta3 integrins which are involved in attachment to purified bone matrix proteins. Binding to osteopontin and bone sialoprotein is mediated by alpha(v)beta3, while a beta1 integrin is responsible for attachment to fibronectin. Both the rapid attachment by osteoclasts to intact bone particles and their subsequent resorption are blocked by a monoclonal antibody directed to the alpha(v)beta3 complex but not by an antibody against beta1 integrins. Attachment of osteoclasts to bone is also inhibited with soluble osteopontin, Arg-Gly-Asp-containing peptides derived from both osteopontin and bone sialoprotein, or a monospecific polyclonal antibody against osteopontin. We conclude that both osteoclast adherence to bone and subsequent resorption of its matrix are dependent on interactions between the bone matrix proteins osteopontin and/or bone sialoprotein and the integrin alpha(v)beta3. Moreover, collagen, which constitutes 90% of its organic matrix, is minimally involved in binding of chicken osteoclasts to bone. C1 Scripps Res Inst, DEPT IMMUNOL, LA JOLLA, CA 92037 USA. UNIV TEXAS, HLTH SCI CTR, DENT BRANCH, DEPT BIOL CHEM, HOUSTON, TX 77225 USA. NIDR, BONE RES BRANCH, BETHESDA, MD 20892 USA. RP ROSS, FP (reprint author), WASHINGTON UNIV, JEWISH HOSP ST LOUIS, MED CTR, DEPT PATHOL & LAB MED, 216 S KINGSHIGHWAY, ST LOUIS, MO 63110 USA. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 FU NCI NIH HHS [CA50286, CA47526]; NIAMS NIH HHS [AR39273] NR 57 TC 442 Z9 459 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 5 PY 1993 VL 268 IS 13 BP 9901 EP 9907 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LA689 UT WOS:A1993LA68900106 PM 8486670 ER PT J AU MASIBAY, AS BALAJI, PV BOEGGEMAN, EE QASBA, PK AF MASIBAY, AS BALAJI, PV BOEGGEMAN, EE QASBA, PK TI MUTATIONAL ANALYSIS OF THE GOLGI RETENTION SIGNAL OF BOVINE BETA-1,4-GALACTOSYLTRANSFERASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHOSPHATIDYLCHOLINE MODEL MEMBRANES; ENDOPLASMIC-RETICULUM; CELL-SURFACE; TRANSMEMBRANE PROTEINS; NEUTRON-DIFFRACTION; MESSENGER-RNA; ALPHA-SUBUNIT; GALACTOSYLTRANSFERASE; EXPRESSION; LOCALIZATION AB To examine the role of the NH2-terminal region of the 402-residue-long beta-1,4-galactosyltransferase (beta-1,4-GT), a series of mutants and chimeric cDNA were constructed by polymerase chain reaction and transiently expressed in COS-7 cells, the enzyme activities were measured, and the protein was localized in the cells by subcellular fractionation or indirect immunofluorescence microscopy. We showed earlier that the deletion of the amino-terminal cytoplasmic tail and transmembrane domain from GT abolishes the stable expression of this protein in mammalian cells (Masibay, A. S., Boeggeman, E., and Qasba, P. K. (1992) Mol. Biol. Rep. 16, 99-104). Further deletion analyses of the amino-terminal region show that the first 21 amino acids of beta-1,4-GT are not essential for the stable production of the protein and are consistently localized in the Golgi apparatus. In addition, analysis of hybrid constructs showed that residues 1-25 of alpha-1,3-galactosyltransferase can functionally replace the beta-1,4-GT amino-terminal domain (residues 1-43). This fusion protein also showed Golgi localization. On the other hand, the alpha-2,6-sialyltransferase/beta-1,4-GT fusion protein (alpha-2,6-ST/beta-1,4-GT) needed additional COOH-terminal sequences flanking the transmembrane domain of the alpha-2,6-ST for stability and Golgi localization. Substitution of Arg-24, Leu-25, Leu-26, and His-33 of the beta-1,4-GT transmembrane by Ile (pLFM) or substitution of Tyr by Ile at positions 40 and 41 coupled with the insertion of 4 Ile residues at position 43 (pLB) released the mutant proteins from the Golgi and was detected on the cell surface. Our results show that (a) the transmembrane domains of beta-1,4-GT, alpha-1,3-galactosyltransferase, and alpha-2,6-ST, along with its stem region, all play a role in Golgi targeting and participate in a common mechanism that allows the protein to be processed properly and not be degraded in vivo; (b) increasing the length of the transmembrane domain overrides the Golgi retention signal and directs the enzyme to the plasma membrane; and (c) the length of the hydrophobic region of the transmembrane domain of beta-1,4-GT is an important parameter but is not sufficient by itself for Golgi retention. C1 NCI,DIV CANC BIOL DIAGNOSIS & CTR,MATH BIOL LAB,PK 5,ROOM 410,BETHESDA,MD 20892. NR 62 TC 117 Z9 117 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 5 PY 1993 VL 268 IS 13 BP 9908 EP 9916 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LA689 UT WOS:A1993LA68900107 PM 8387508 ER PT J AU TRENN, G SYKORA, J TESCHENDORF, C TAFFS, R BRITTINGER, G SITKOVSKY, MV AF TRENN, G SYKORA, J TESCHENDORF, C TAFFS, R BRITTINGER, G SITKOVSKY, MV TI DETECTION OF DISTINCT SETS OF NEWLY SYNTHESIZED POLYPEPTIDES IN SUPERNATANTS OF TCR-TRIGGERED T-CELL CLONES - IMPLICATION FOR THE SEARCH FOR NEW LYMPHOKINES SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE LYMPHOKINE; T-LYMPHOKINE; SECRETION; CYCLOSPORINE-A ID TOXIC LYMPHOCYTES-T; MONOCLONAL-ANTIBODY; ANTIGEN RECEPTOR; MITOGENIC ACTIVATION; CYTOKINE; TARGET; LYSIS; IDENTIFICATION; CYCLOPHILIN; SECRETION AB Using metabolic radiolabelling of proteins, which are newly synthesized during TCR-triggered T cell activation we were able to visualize distinct patterns of secreted polypeptides (with molecular weights ranging from 6 to 44 kDa) in supernatants of different T helper-1, T helper-2 and cytotoxic T cell clones. Most of these detected proteins are secreted in -response to TCR-crosslinking (or to combined action of PMA and A231287), in an extracellular Ca2+-dependent manner and their appearance in supernatants was completely blocked by the addition of RNA synthesis or protein synthesis inhibitors or EGTA. Cyclosporin A (CsA) blocks secretion of several detected polypeptides, but does not affect TCR-triggered synthesis and secretion of others reflecting the existence of TCR-triggered, CsA-insensitive protein synthesis and secretion pathway. The insensitivity of secretion of several easily detectable polypeptides to inhibition by CsA offers a promising approach to further define the CsA-resistant and calcineurin-independent molecular pathways of TCR-triggered T cell activation. Several lymphokines (e.g., interferon-gamma, tumor necrosis factor, interleukin-4 and interleukin-10) are identified among the visualized set of secreted polypeptides. Since other, yet unidentified, secreted polypeptides in the same set of secreted proteins share important properties with known lymphokines it seems promising to use described approach in search for new lymphokines. C1 NIAID,IMMUNOL LAB,BLDG 10,RM 11N311,BETHESDA,MD 20892. UNIV ESSEN GESAMTHSCH,DEPT INTERNAL MED,DIV HEMATOL,W-4300 ESSEN 1,GERMANY. NR 30 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD MAY 5 PY 1993 VL 161 IS 1 BP 41 EP 57 DI 10.1016/0022-1759(93)90196-E PG 17 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA LB376 UT WOS:A1993LB37600005 PM 8486928 ER PT J AU YANNELLI, JR HYATT, C JOHNSON, S HWU, P ROSENBERG, SA AF YANNELLI, JR HYATT, C JOHNSON, S HWU, P ROSENBERG, SA TI CHARACTERIZATION OF HUMAN TUMOR-CELL LINES TRANSDUCED WITH THE CDNA-ENCODING EITHER TUMOR-NECROSIS-FACTOR-ALPHA (TNF-A) OR INTERLEUKIN-2 (IL-2) SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE MELANOMA; TUMOR NECROSIS FACTOR-ALPHA; INTERLEUKIN-2; IMMUNOTHERAPY; GENE THERAPY ID COLONY-STIMULATING FACTOR; INFILTRATING LYMPHOCYTES; GENE-TRANSFER; REDUCED TUMORIGENICITY; AUTOLOGOUS TUMOR; EXPRESSION; IMMUNITY; INVIVO; IMMUNOTHERAPY; MELANOMA AB Tumor cell lines were generated from cancer patients, 17 with metastatic melanoma and one with colon adenocarcinoma. The lines were characterized as tumor cells by the presence of tumor associated antigens demonstrated by indirect immunofluorescence and analysed using a fluorescence activated cell sorter (FACS). The tumor cell lines were transduced using retroviruses encoding neomycin phosphotransferase and either human tumor necrosis factor alpha (TNF-alpha) or interleukin-2 (IL-2). Following transduction, cells were selected and grown in the neomycin analogue G418. Fibroblasts overgrew tumor cells in 6/18 cases following selection in G418 and 1/18 lines did not grow at all after selection. In the remaining 11 lines the expression of tumor associated antigens, growth, and susceptibility to lysis by LAK cells was similar between the selected transduced tumor cell lines and the nontransduced controls. Of the lines tested, all were positive for the presence of the cytokine gene by Southern blot or PCR analysis. In addition, no replication competent retrovirus was detected in the cell lines following transduction using an extended mink S+L- focus assay. The amount of specific cytokine produced per 10(5) transduced tumor cells in 24 h ranged from 0.2 ng to 5.8 ng of TNF-alpha for the TNF transduced lines and from 0.1 ng to 3.6 ng of IL-2 for the IL-2 transduced tumor cell lines. One transduced tumor cell line examined maintained consistent levels of cytokine production when studied at 15 different time intervals over a period of 198 days. Additionally, 40,000 rads of gamma irradiation did not stop cytokine production from two transduced tumor cell lines when studied over 6 days. This study demonstrates the feasibility of growing human tumor cell lines from surgical biopsies and genetically modifying those lines to produce a cytokine of choice for possible use as a tumor cell vaccine. RP YANNELLI, JR (reprint author), NCI,SURG BRANCH,BLDG 10,ROOM 2B12,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 28 TC 41 Z9 41 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD MAY 5 PY 1993 VL 161 IS 1 BP 77 EP 90 DI 10.1016/0022-1759(93)90199-H PG 14 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA LB376 UT WOS:A1993LB37600008 PM 8486931 ER PT J AU MUKHOPADHYAY, G CHATTORAJ, DK AF MUKHOPADHYAY, G CHATTORAJ, DK TI CONFORMATION OF THE ORIGIN OF P1-PLASMID REPLICATION - INITIATOR PROTEIN-INDUCED WRAPPING AND INTRINSIC UNSTACKING SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE PLASMID; DNA REPLICATION; DNA BENDING; DNA WRAPPING; KMNO4 FOOTPRINTING ID P1 PLASMID REPLICATION; COMPLETE NUCLEOTIDE-SEQUENCE; SITE-SPECIFIC RECOMBINATION; DOUBLE HELICAL DNA; ESCHERICHIA-COLI; BEND DNA; BINDING; REPA; TRANSCRIPTION; PURIFICATION RP MUKHOPADHYAY, G (reprint author), NCI,BIOCHEM LAB,BETHESDA,MD 20892, USA. NR 55 TC 26 Z9 26 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD MAY 5 PY 1993 VL 231 IS 1 BP 19 EP 28 DI 10.1006/jmbi.1993.1253 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LD434 UT WOS:A1993LD43400003 PM 8496963 ER PT J AU KAPLAN, RS AF KAPLAN, RS TI SUPRATENTORIAL MALIGNANT GLIOMAS - RISK PATTERNS AND THERAPY SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID ANAPLASTIC GLIOMAS; PROGNOSTIC IMPORTANCE; RADIOTHERAPY; BCNU RP KAPLAN, RS (reprint author), NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,CLIN INVEST BRANCH,EPN 741,BETHESDA,MD 20892, USA. NR 10 TC 14 Z9 14 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY 5 PY 1993 VL 85 IS 9 BP 690 EP 691 DI 10.1093/jnci/85.9.690 PG 2 WC Oncology SC Oncology GA LA672 UT WOS:A1993LA67200001 PM 8478948 ER PT J AU REICHMAN, ME JUDD, JT LONGCOPE, C SCHATZKIN, A CLEVIDENCE, BA NAIR, PP CAMPBELL, WS TAYLOR, PR AF REICHMAN, ME JUDD, JT LONGCOPE, C SCHATZKIN, A CLEVIDENCE, BA NAIR, PP CAMPBELL, WS TAYLOR, PR TI EFFECTS OF ALCOHOL-CONSUMPTION ON PLASMA AND URINARY HORMONE CONCENTRATIONS IN PREMENOPAUSAL WOMEN SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID BREAST-CANCER RISK; BEVERAGE CONSUMPTION; SEX-HORMONES; CIGARETTE-SMOKING; BINDING GLOBULIN; GONADAL-HORMONES; DEHYDROEPIANDROSTERONE SULFATE; POSTMENOPAUSAL WOMEN; NULLIPAROUS WOMEN; NORMAL FEMALES AB Background: Most epidemiologic studies of the relationship between alcohol consumption and breast cancer risk over the past decade have shown that persons who consume a moderate amount of alcohol are at 40%-100% greater risk of breast cancer than those who do not consume alcohol. Dose-response effects have been observed, but no causal relationship has been established. Purpose: This study examines the hypothesis that alcohol consumption affects levels of reproductive hormones. Methods: A controlled-diet study lasting for six consecutive menstrual cycles was conducted. Participants were randomly assigned to two groups, and a crossover design was used. During the last three menstrual cycles, alcohol consumption of the two groups was reversed. Thirty-four premenopausal women, aged 21-40 years, with a history of regular menstrual cycles, consumed 30 g of ethanol (equivalent to approximately two average drinks) per day for three menstrual cycles and no alcohol for the other three. All food and alcohol consumed were provided by the study. Caloric intake was monitored to ensure that each woman would maintain body weight at approximately the baseline level. Hormone assays were performed on pooled plasma or 24-hour urine specimens collected during the follicular (days 5-7), peri-ovulatory (days 12-15), and mid-luteal (days 21-23) phases of the third menstrual cycle for subjects on each diet. Results: Alcohol consumption was associated with statistically significant increases in levels of several hormones. Plasma dehydroepiandrosterone sulfate levels were 7.0% higher in the follicular phase (P = .05). In the peri-ovulatory phase, there were increases of 21.2% (P = .01) in plasma estrone levels, 27.5% (P = .01) in plasma estradiol levels, and 31.9% (P = .009) in urinary estradiol levels. In the luteal phase, urinary estrone levels rose 15.2% (P = .05), estradiol levels increased 21.6% (P = .02), and estriol levels rose 29.1 % (P = .03). No changes were found in the percent of bioavailable estradiol, defined by the sum of percent free estradiol and percent albumin-bound estradiol. However, increased total estradiol levels in the peri-ovulatory phase suggest elevated absolute amounts of bioavailable estradiol. Conclusion: This study has shown increases in total estrogen levels and amount of bioavailable estrogens in association with alcohol consumption in premenopausal women. Implication: This possible explanatory mechanism for a positive association between alcohol consumption and breast cancer risk merits further investigation. C1 NCI,DIV CANC PREVENT & CONTROL,CANC PREVENT STUDIES BRANCH,BETHESDA,MD 20892. USDA,BELTSVILLE HUMAN NUTR RES CTR,LIPID NUTR LAB,BELTSVILLE,MD 20705. UNIV MASSACHUSETTS,SCH MED,DEPT MED,WORCESTER,MA 01605. UNIV MASSACHUSETTS,SCH MED,DEPT OBSTET & GYNECOL,WORCESTER,MA 01605. NR 67 TC 256 Z9 259 U1 2 U2 8 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY 5 PY 1993 VL 85 IS 9 BP 722 EP 727 DI 10.1093/jnci/85.9.722 PG 6 WC Oncology SC Oncology GA LA672 UT WOS:A1993LA67200012 PM 8478958 ER PT J AU SBURLATI, AR DELAROSA, A BATEY, DW KURYS, GL MANROW, RE PANNELL, LK MARTIN, BM SHEELEY, DM BERGER, SL AF SBURLATI, AR DELAROSA, A BATEY, DW KURYS, GL MANROW, RE PANNELL, LK MARTIN, BM SHEELEY, DM BERGER, SL TI PHOSPHORYLATION OF HUMAN AND BOVINE PROTHYMOSIN-ALPHA INVIVO SO BIOCHEMISTRY LA English DT Article ID NUCLEOSOME ASSEMBLY INVITRO; XENOPUS-LAEVIS OOCYTES; AMINO-ACID SEQUENCE; MASS-SPECTROMETRY; NUCLEAR-PROTEIN; AMPHIBIAN OOCYTE; RAT THYMUS; NUCLEOPLASMIN; GENE; CDNA AB Prothymosin alpha is post-translationally modified. When human myeloma cells were metabolically labeled with [P-32] orthophosphoric acid, they synthesized [P-32] prothymosin alpha. The incorporated radioactivity was resistant to DNase and RNases A, T1, and T2, but could be completely removed by alkaline phosphatase. No evidence was found for an RNA adduct as postulated by Vartapetian et al. [Vartapetian, A., Makarova, T., Koonin, E.V., Agol, V.I., & Bogdanov, A. (1988) FEBS Lett. 232, 35-38]. Thin-layer electrophoresis of partially hydrolyzed [P-32]prothymosin alpha indicated that serine residues were phosphorylated. Analysis of peptides derived from bovine prothymosin alpha and human [P-32]prothymosin alpha by treatment with endoproteinase Lys-C revealed that the amino-terminal 14-mer, with serine residues at positions 1, 8, and 9, was phosphorylated at a single position. Approximately 2% of the peptide in each case contained phosphate. Further digestion of the phosphopeptide with Asp-N followed by C 1 8 reversed-phase column chromatography produced two peptides: a phosphate-free 9-mer containing amino acids 6-14 and a labeled peptide migrating slightly faster than the N-terminal 5-mer derived from the unmodified 14-mer. Positive identification of the phosphorylated amino acid was obtained by colliding the 14-residue phosphopeptide with helium in the mass spectrometer and finding phosphate only in a nested set of phosphorylated fragments composed of the first three, four, and five amino acids. The results prove that prothymosin alpha contains N-terminal acetylserine phosphate. In a synchronized population of human myeloma cells, phosphorylation occurred throughout the cell cycle. Furthermore, prothymosin alpha appeared to be stable, with a half-life slightly shorter than the generation time. Although prothymosin alpha is known to be essential for cell division, the constancy of both the amount of the protein and the degree of its phosphorylation suggests that prothymosin alpha does not directly govern mitosis. C1 NCI,BIOCHEM LAB,GENES & GENE PROD SECT,BETHESDA,MD 20892. NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD. NIMH,CLIN SCI BRANCH,MOLEC NEUROGENET,BETHESDA,MD 20892. NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. NR 57 TC 35 Z9 37 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 4 PY 1993 VL 32 IS 17 BP 4587 EP 4596 DI 10.1021/bi00068a015 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LA560 UT WOS:A1993LA56000015 PM 8485135 ER PT J AU ROSENBERG, SA AF ROSENBERG, SA TI THE END OF THE BEGINNING - A CITATION-CLASSIC COMMENTARY ON A PROGRESS REPORT ON THE TREATMENT OF 157 PATIENTS WITH ADVANCED CANCER USING LYMPHOKINE-ACTIVATED KILLER-CELLS AND INTERLEUKIN-2 OR HIGH-DOSE INTERLEUKIN-2 ALONE BY ROSENBERG,S.A., LOTZE,M.T., MUUL,L.M., CHANG,A.E., AVIS,F.P., LEITMAN,S., LINEHAN,W.M., ROBERTSON,C.N., LEE,R.E., RUBIN,J.T., SEIPP,C.A., SIMPSON,C.G., AND WHITE,D.E. SO CURRENT CONTENTS/CLINICAL MEDICINE LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; RECOMBINANT INTERLEUKIN-2; IMMUNOTHERAPY; MELANOMA RP ROSENBERG, SA (reprint author), NCI,SURG BRANCH,BETHESDA,MD 20892, USA. NR 7 TC 0 Z9 0 U1 0 U2 3 PU INST SCI INFORM INC PI PHILADELPHIA PA 3501 MARKET ST, PHILADELPHIA, PA 19104 SN 0891-3358 J9 CC/CLIN MED PD MAY 3 PY 1993 IS 18 BP 8 EP 8 PG 1 WC Multidisciplinary Sciences; Social Sciences, Interdisciplinary SC Science & Technology - Other Topics; Social Sciences - Other Topics GA KX311 UT WOS:A1993KX31100001 ER PT J AU MIHALY, A RAPP, UR AF MIHALY, A RAPP, UR TI NEURONAL EXPRESSION OF THE RAF PROTOONCOGENE IN THE SPINAL-CORD OF ADULT GUINEA-PIGS SO ACTA HISTOCHEMICA LA English DT Article DE GUINEA PIG; NEURONS; SPINAL CORD; RAF PROTOONCOGENE ID PROTEIN-KINASE; SIGNAL TRANSDUCTION; IMMUNOREACTIVITY; STIMULATION; INDUCTION; INCREASE; FAMILY AB The cellular raf oncogenes encode cytoplasmic serine/threonine specific protein kinases. Since there are some indications that they are involved in neuronal plasticity, we investigated the localization of raf protein kinases immunohistochemically. The spinal cord of adult guinea pigs was fixed by means of transcardial perfusion, transverse sections were cut from each segment and stained with monoclonal and polyclonal antibodies, raised against synthetic raf peptide and recombinant raf protein, respectively. The motor neurons of the ventral horn and the large- and medium sized neurons of laminae I, IV, V, VI, VII and VII were stained in every segment of the spinal cord. The widespread occurrence of raf kinases in the spinal cord and the literature data indicating their participation in growth factor mediated processes, raise the possibility that the raf protooncogenes play a fundamental role in the regulation of transmembrane signalling of these neurons. C1 NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. RP MIHALY, A (reprint author), ALBERT SZENT GYORGYI MED UNIV,DEPT ANAT,POB 512,H-6701 SZEGED,HUNGARY. RI Mihaly, Andras/K-5096-2012 NR 25 TC 3 Z9 4 U1 0 U2 0 PU GUSTAV FISCHER VERLAG PI JENA PA VILLENGANG 2, D-07745 JENA, GERMANY SN 0065-1281 J9 ACTA HISTOCHEM JI Acta Histochem. PD MAY PY 1993 VL 94 IS 2 BP 189 EP 196 PG 8 WC Cell Biology SC Cell Biology GA LG834 UT WOS:A1993LG83400010 PM 8351980 ER PT J AU BAKKETEIG, LS JACOBSEN, G HOFFMAN, HJ LINDMARK, G BERGSJO, P MOLNE, K RODSTEN, J AF BAKKETEIG, LS JACOBSEN, G HOFFMAN, HJ LINDMARK, G BERGSJO, P MOLNE, K RODSTEN, J TI PREPREGNANCY RISK-FACTORS OF SMALL-FOR-GESTATIONAL-AGE BIRTHS AMONG PAROUS WOMEN IN SCANDINAVIA SO ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA LA English DT Article DE INTRAUTERINE GROWTH RETARDATION (IUGR); SMALL-FOR-GESTATIONAL-AGE (SGA); RISK FACTORS; PREGNANCY; SCANDINAVIA ID GROWTH-RETARDATION; MATERNAL SMOKING; WEIGHT; DELIVERY; POPULATION; INFANT; FETAL AB To study the etiology and consequences of intrauterine growth retardation (IUGR), a prospective study was organized by the National Institute of Child Health and Human Development, NIH, with the Universities of Trondheim and Bergen in Norway, Uppsala in Sweden, and Alabama in the United States. This paper reports on the Scandinavian portion of the study. 6,354 women were referred to the study and 5,722 women, who were expecting their second or third child between January 1986 and March 1988, were eligible and made their first appointment for the study. Of these, 1,945 women and their births were selected for follow-up at four prenatal visits, delivery, and during the first year of life. This report analyzes the relative impact of various maternal pre-pregnancy risk factors associated with SGA birth. For example, mothers who smoked cigarettes around the time of conception, but who had none of the other major risk factors, nearly doubled their risk of SGA birth. A previous low birth weight (LBW) delivery increased the risk nearly two and a half times among non-smokers. If a mother both smoked and had a previous LBW, the relative risk rose to nearly five and a half. Low maternal pre-pregnancy weight (<50 kg) increased the risk of SGA birth almost twofold among non-smokers, while low pre-pregnancy weight and smoking together increased the risk of SGA birth fourfold. A low weight mother who smoked and also had a previous LBW delivery, had a risk of SGA birth that was nearly six times that of a mother without those characteristics. C1 NATL INST PUBL HLTH,DEPT COMMUNITY HLTH,OSLO 1,NORWAY. NIH,DIV EPIDEMIOL STAT & PREVENT RES,BETHESDA,MD 20892. UNIV UPPSALA,DEPT OBSTET & GYNECOL,S-75105 UPPSALA,SWEDEN. UNIV BERGEN,DEPT OBSTET & GYNECOL,N-5014 BERGEN,NORWAY. UNIV TRONDHEIM,DEPT OBSTET & GYNECOL,TRONDHEIM,NORWAY. RP BAKKETEIG, LS (reprint author), UNIV TRONDHEIM,DEPT COMMUNITY MED & GEN PRACTICE,N-7005 TRONDHEIM,NORWAY. FU NICHD NIH HHS [NICHD 1-HD-4-2803] NR 23 TC 119 Z9 120 U1 0 U2 7 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-6349 J9 ACTA OBSTET GYN SCAN JI Acta Obstet. Gynecol. Scand. PD MAY PY 1993 VL 72 IS 4 BP 273 EP 279 DI 10.3109/00016349309068037 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA LD775 UT WOS:A1993LD77500010 PM 8389514 ER PT J AU DEJONG, JA ROY, A AF DEJONG, JA ROY, A TI PATERNAL LINEAGE OF ALCOHOLISM, COHORT EFFECTS, AND ALCOHOLISM CRITERIA SO ADDICTION LA English DT Article AB Adoption studies have led to the suggestion that there may be two distinct subgroups of alcoholics with differing genetic contributions. Among 249 male alcoholics we used discriminant analysis to relate the features of type 1 and type 2 alcoholism to the presence or absence of a family history of alcoholism in male paternal relatives. We found that guilt and binging, features usually attributed to type 1 (milieu-limited) alcoholism, were in fact more prevalent in the family history positive group. An additional cohort analysis found cohort-related variations in type 1/type 2 characteristics. The possible implications of these findings are discussed. C1 NIAAA,DICBR,CLIN STUDIES LAB,BETHESDA,MD 20892. NR 11 TC 3 Z9 3 U1 2 U2 2 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0965-2140 J9 ADDICTION JI Addiction PD MAY PY 1993 VL 88 IS 5 BP 623 EP 629 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA LC845 UT WOS:A1993LC84500008 PM 8518712 ER PT J AU WINDLE, C AF WINDLE, C TI NIMH-SUPPORTED STUDIES OF THE MENTAL-HEALTH-SERVICE SYSTEM SO ADMINISTRATION AND POLICY IN MENTAL HEALTH LA English DT Article RP WINDLE, C (reprint author), NIMH,DIV EPIDEMIOL & SERV RES,5600 FISHERS LANE,ROOM 10C06,ROCKVILLE,MD 20857, USA. NR 33 TC 2 Z9 2 U1 0 U2 0 PU HUMAN SCI PRESS INC PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 SN 0894-587X J9 ADM POLICY MENT HLTH JI Adm. Policy. Ment. Health PD MAY PY 1993 VL 20 IS 5 BP 393 EP 397 DI 10.1007/BF00706394 PG 5 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA LH448 UT WOS:A1993LH44800008 ER PT J AU DSOUZA, MP KENT, KA THIRIART, C COLLIGNON, C MILMAN, G AF DSOUZA, MP KENT, KA THIRIART, C COLLIGNON, C MILMAN, G TI INTERNATIONAL COLLABORATION COMPARING NEUTRALIZATION AND BINDING ASSAYS FOR MONOCLONAL-ANTIBODIES TO SIMIAN IMMUNODEFICIENCY VIRUS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID SEROEPIDEMIOLOGIC SURVEY; TRANSMEMBRANE PROTEIN; ENVELOPE GLYCOPROTEIN; CERCOCEBUS-ATYS; SOOTY MANGABEY; RHESUS-MONKEYS; INFECTION; MACAQUES; CELLS; GP120 AB Thirteen laboratories characterized a coded panel of 10 MAbs to SIV(mac)251 envelope protein in a collaboration organized by the National Institute of Allergy and Infectious Diseases (NIAID). The MAbs were examined against SIV isolates in neutralization and radioimmune precipitation, immunoblot, enzyme-linked immunosorbent, and radioimmune assays. Although laboratories employed diverse neutralization assays that varied in sensitivity there was agreement on the relative ability of the MAbs to neutralize SIV(mac)251. Additionally, even though the quantity of any single MAb required to neutralize SIV(mac)7251 varied between laboratories, there was agreement on the rank-order strength for the rive neutralizing MAbs. Based on the data from this study, the MAbs were classified according to their neutralization potential as high efficiency (MAb concentration, <5 mug/ml), low efficiency (MAb concentration, 5-100 mug/ml), or nonneutralizing (MAb concentration, >100 mug/ml). The MAbs could be assigned to four serological groups based on ability to cross-neutralize and bind different SIV isolates. The distinction between groups I, II, and III were based on the limited neutralization data obtained with the sooty mangabey isolate. C1 NATL INST BIOL STAND & CONTROLS,POTTERS BAR EN6 3QG,HERTS,ENGLAND. SMITHKLINE BEECHAM BIOL SA,B-1330 RIXENSART,BELGIUM. RP DSOUZA, MP (reprint author), NIAID,DIV AIDS,PATHOGENESIS BRANCH,6003 EXECUT BLVD,SOLAR BLDG,ROOM 2B35,BETHESDA,MD 20892, USA. NR 49 TC 12 Z9 12 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 1993 VL 9 IS 5 BP 415 EP 422 DI 10.1089/aid.1993.9.415 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA LD673 UT WOS:A1993LD67300006 PM 7686385 ER PT J AU TRUCKENMILLER, ME KULAGA, H COGGIANO, M WYATT, R SNYDER, SH SWEETNAM, PM AF TRUCKENMILLER, ME KULAGA, H COGGIANO, M WYATT, R SNYDER, SH SWEETNAM, PM TI HUMAN CORTICAL NEURONAL CELL-LINE - A MODEL FOR HIV-1 INFECTION IN AN IMMATURE NEURONAL SYSTEM SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; IMMUNE-DEFICIENCY SYNDROME; HUMAN GLIAL-CELLS; REVERSE-TRANSCRIPTASE; PRODUCTIVE INFECTION; BRAIN-TISSUE; AIDS; CHILDREN; TYPE-1; ENCEPHALOPATHY AB HCN-1A is a human cerebral cortical neuronal cell line having properties consistent with cells of immature neuronal origin. This article details evidence for productive low-level infection of HCN-1A cells with human immunodeficiency virus type 1 (HIV-1). In vitro exposure to HCN-1A monolayers to a high titer of either LAV/HTLV-III(B) or HTLV-III(MN) resulted in HIV-1 p24 antigen production and a moderate increase in reverse transcriptase activity in cell-free supernatants. The cells in both LAV/HTLV-III(B)- and HTLV-III(MN)-infected cultures were passaged and proliferated as long as 5 weeks while continuing to express low levels of viral antigen. Virus-positive cells were detected by indirect immunofluorescence, using serum from an individual with acquired immune deficiency syndrome (AIDS) as well as with a gp120 monoclonal antibody. Confirmation of HCN-1A infection was provided by polymerase chain reaction analyses of both nuclear and cytoplasmic DNA and by de novo synthesis of viral proteins as shown by metabolic labeling and immunoprecipitation. Virus in cell-free supernatants from infected HCN-1A cultures was passaged to a permissive human T cell line (A3.01). HCN-1A cells had no detectable surface CD4 protein or CD4 message. However, the cells expressed the membrane glycolipids, galactocerebroside and sulfatide, possible receptors for gp120 on cells of neuronal origin. Undifferentiated HCN-1A cells provide an in vitro model for investigating potential interactions of HIV-1 with a homogeneous population of immature cortical neurons. C1 NOVASCREEN,BALTIMORE,MD 21224. NIMH,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. FU NIDA NIH HHS [DA-00266]; NIMH NIH HHS [MH-185A]; PHS HHS [U01A127221-02] NR 51 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 MAY PY 1993 VL 9 IS 5 BP 445 EP 453 DI 10.1089/aid.1993.9.445 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA LD673 UT WOS:A1993LD67300010 PM 8318271 ER PT J AU SARVER, N ROSSI, J AF SARVER, N ROSSI, J TI GENE-THERAPY - A BOLD DIRECTION FOR HIV-1 TREATMENT SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Editorial Material C1 CITY HOPE NATL MED CTR,BECKMAN RES INT,DEPT MOLEC GENET,DUARTE,CA 91010. RP SARVER, N (reprint author), NIAID,DIV AIDS,BASIC RES & DEV PROGRAM,DEV THERAPEUT BRANCH,BETHESDA,MD 20892, USA. NR 2 TC 26 Z9 26 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 1993 VL 9 IS 5 BP 483 EP 487 DI 10.1089/aid.1993.9.483 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA LD673 UT WOS:A1993LD67300014 PM 8391287 ER PT J AU COHEN, SG AF COHEN, SG TI SPAIN, PORTUGAL, COLUMBUS,CHRISTOPHER, AND THE JEWISH PHYSICIAN .3. SO ALLERGY PROCEEDINGS LA English DT Article RP COHEN, SG (reprint author), NIAID,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 SN 1046-9354 J9 ALLERGY PROC JI Allergy Proc. PD MAY-JUN PY 1993 VL 14 IS 3 BP 209 EP 221 DI 10.2500/108854193778878646 PG 13 WC Allergy SC Allergy GA LK286 UT WOS:A1993LK28600007 PM 7689069 ER PT J AU METCALFE, DD AF METCALFE, DD TI MAY,CHARLES,D. - A TRIBUTE SO ALLERGY PROCEEDINGS LA English DT Item About an Individual RP METCALFE, DD (reprint author), NIAID,CLIN INVEST LAB,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 SN 1046-9354 J9 ALLERGY PROC JI Allergy Proc. PD MAY-JUN PY 1993 VL 14 IS 3 BP 234 EP 234 DI 10.2500/108854193778878619 PG 1 WC Allergy SC Allergy GA LK286 UT WOS:A1993LK28600011 ER PT J AU SHIRANI, J ROBERTS, WC AF SHIRANI, J ROBERTS, WC TI SUBEPICARDIAL MYOCARDIAL LESIONS SO AMERICAN HEART JOURNAL LA English DT Article ID NECROPSY PATIENTS AB Subepicardial myocardial lesions are rarely seen at necropsy, and a description of them and their causes has not been reported. Over the last 13 years we have studied 22 patients with subepicardial myocardial lesions. They ranged in age from 14 to 73 years (mean 47), and 20 were men. The lesions were associated with atherosclerotic coronary artery disease in six patients, sarcoidosis in five, idiopathic dilated cardiomyopathy in four, lymphocytic myocarditis in two, and hypoplastic right and left circumflex coronary arteries in one. In four patients the cause was unclear. In the patients with atherosclerotic coronary artery disease, the subepicardial myocardial lesions were small, few in number, and located in the left ventricular posterior wall. In patients with sarcoidosis or myocarditis, the subepicardial lesions were extensive and commonly associated with transmural left and right ventricular lesions. The right ventricular half of the ventricular septum also was frequently affected. In the remaining nine patients, the subepicardial lesions were small and unassociated with transmural left ventricular lesions. Thus subepicardial myocardial lesions occur in a variety of cardiac diseases. RP SHIRANI, J (reprint author), NHLBI,PATHOL BRANCH,BLDG 10,ROOM 2N258,BETHESDA,MD 20892, USA. NR 3 TC 9 Z9 9 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 MAY PY 1993 VL 125 IS 5 BP 1346 EP 1352 DI 10.1016/0002-8703(93)91005-Y PN 1 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA LA596 UT WOS:A1993LA59600020 PM 8480587 ER PT J AU VASLEF, SN ROBERTS, WC AF VASLEF, SN ROBERTS, WC TI EARLY DESCRIPTIONS OF AORTIC-VALVE STENOSIS SO AMERICAN HEART JOURNAL LA English DT Editorial Material C1 NHLBI,PATHOL BRANCH,BETHESDA,MD 20892. NR 120 TC 5 Z9 5 U1 1 U2 2 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 MAY PY 1993 VL 125 IS 5 BP 1465 EP 1474 DI 10.1016/0002-8703(93)91036-E PN 1 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA LA596 UT WOS:A1993LA59600051 PM 8480616 ER PT J AU VASLEF, SN ROBERTS, WC AF VASLEF, SN ROBERTS, WC TI EARLY DESCRIPTIONS OF AORTIC REGURGITATION SO AMERICAN HEART JOURNAL LA English DT Editorial Material ID VALVE REPLACEMENT; MITRAL VALVE; ECHOCARDIOGRAPHY; ENDOCARDITIS; DISSECTION C1 NHLBI,CTR PATHOL,BETHESDA,MD 20892. NR 116 TC 2 Z9 2 U1 1 U2 2 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 MAY PY 1993 VL 125 IS 5 BP 1475 EP 1483 DI 10.1016/0002-8703(93)91037-F PN 1 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA LA596 UT WOS:A1993LA59600052 PM 8480617 ER PT J AU ROBERTS, WC OLUWOLE, BO FERNICOLA, DJ AF ROBERTS, WC OLUWOLE, BO FERNICOLA, DJ TI COMPARISON OF ACTIVE INFECTIVE ENDOCARDITIS INVOLVING A PREVIOUSLY STENOTIC VERSUS A PREVIOUSLY NONSTENOTIC AORTIC-VALVE SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID NECROPSY PATIENTS; ECHOCARDIOGRAPHIC OBSERVATIONS; OPIATE ADDICTS; RING ABSCESS; REPLACEMENT; FREQUENCY AB No previous studies, either clinical or morphologic, have compared findings in patients with active infective endocarditis (IE) involving a previously stenotic versus a previously nonstenotic aortic valve. Clinical and cardiac necropsy findings were analyzed in 96 patients with active IE involving the aortic valve. Of the 96 patients, 25 (26%) had active IE superimposed on a previously stenotic aortic valve and 71 (74%) on a previously nonstenotic aortic valve. The patients with stenotic aortic valves compared with those with nonstenotic aortic valves had significantly higher mean ages (61 vs 47 years), a higher percentage >60 years of age (52 vs 24%), a higher percentage of men (92 vs 73%), a higher frequency of an absent or unknown predisposing factor to infection (68 vs 38%), a lower frequency of a precordial murmur of aortic regurgitation (44 vs 79%), a lower percent with a long duration (>60 days) of signs and symptoms of active IE (4 vs 23%), a larger mean heart weight (594 vs 514 g), a higher percentage with aortic valve calcific deposits (100 vs 24%), and a higher frequency of associated ring abscess (84 vs 52%). Thus, active IE superimposed on a stenotic aortic valve differs in some features compared with active IE on a nonstenotic aortic valve. Because ring abscess is so common when active IE involves a stenotic aortic valve in adults, operative intervention at an early stage may be warranted. C1 NHLBI,PATHOL BRANCH,BETHESDA,MD 20892. NR 43 TC 7 Z9 7 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAY 1 PY 1993 VL 71 IS 12 BP 1082 EP 1088 DI 10.1016/0002-9149(93)90577-Y PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA KY438 UT WOS:A1993KY43800014 PM 8475873 ER PT J AU MARON, BJ MCINTOSH, CL KLUES, HG CANNON, RO ROBERTS, WC AF MARON, BJ MCINTOSH, CL KLUES, HG CANNON, RO ROBERTS, WC TI MORPHOLOGIC BASIS FOR OBSTRUCTION TO RIGHT VENTRICULAR OUTFLOW IN HYPERTROPHIC CARDIOMYOPATHY SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID TWO-DIMENSIONAL ECHOCARDIOGRAPHY; SYSTOLIC ANTERIOR MOTION; CLINICAL MANIFESTATIONS; SUBAORTIC STENOSIS; PATHO-PHYSIOLOGY; WALL THICKNESS; FEATURES; INTERRELATIONS; PATTERNS; THERAPY AB The mechanism by which obstruction to right ventricular (RV) outflow occurs in patients with hypertrophic cardiomyopathy (HC) is not well understood. To clarify this issue, 5 severely symptomatic patients (aged 18 to 55 years, mean 30) with HC and marked subpulmonic obstruction (basal peak systolic pressure gradients 60 to 118 mm Hg) were studied. Four patients also had obstruction to left ventricular outflow (maximal basal or provocable pressure gradient 12 to 110 mm Hg). The RV outflow obstruction in each patient resulted from greatly hypertrophied musculature comprised of crista supraventricularis, moderator band or trabeculae. Operative resection of portions of this muscle resulted in abolition or substantial reduction of the RV outflow gradient (to 0 to 11 mm Hg) in the 3 patients with both pre- and postoperative hemodynamic studies. The left ventricular wall and ventricular septum also were massively thickened (32 to 40 mm) in each patient. These findings support the view that marked RV outflow tract obstruction in patients with HC is due to greatly hypertrophied RV muscle, and that operative resection will relieve the outflow gradients and normalize RV systolic pressure. The muscular RV hypertrophy causing obstruction appeared to constitute a primary and excessive hypertrophic process involving both ventricles. C1 NHLBI,SURG BRANCH,BETHESDA,MD 20892. NHLBI,PATHOL BRANCH,BETHESDA,MD 20892. RP MARON, BJ (reprint author), NHLBI,CARDIOL BRANCH,BLDG 10,ROOM 7B-15,BETHESDA,MD 20892, USA. NR 31 TC 24 Z9 27 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAY 1 PY 1993 VL 71 IS 12 BP 1089 EP 1094 DI 10.1016/0002-9149(93)90578-Z PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA KY438 UT WOS:A1993KY43800015 PM 8475874 ER PT J AU LEVIN, EY BIER, DM AF LEVIN, EY BIER, DM TI RESEARCH DIRECTIONS IN NUTRITION - VIEW FROM THE NICHD SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Note C1 WASHINGTON UNIV,SCH MED,DIV METAB,ST LOUIS,MO 63110. RP LEVIN, EY (reprint author), NICHHD,CTR RES MOTHERS & CHILDREN,ENDOCRINOL NUTR & GROWTH BRANCH,BETHESDA,MD 20892, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998 SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD MAY PY 1993 VL 57 IS 5 BP 603 EP 604 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA LA004 UT WOS:A1993LA00400001 PM 8480672 ER PT J AU OVASKAINEN, ML VIRTAMO, J ALFTHAN, G HAUKKA, J PIETINEN, P TAYLOR, PR HUTTUNEN, JK AF OVASKAINEN, ML VIRTAMO, J ALFTHAN, G HAUKKA, J PIETINEN, P TAYLOR, PR HUTTUNEN, JK TI TOENAIL SELENIUM AS AN INDICATOR OF SELENIUM INTAKE AMONG MIDDLE-AGED MEN IN AN AREA WITH LOW SOIL SELENIUM SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE SELENIUM INTAKE; DIET; TOENAIL SELENIUM; MIDDLE-AGED MEN; SELENIUM SUPPLEMENTS ID GLUTATHIONE-PEROXIDASE ACTIVITY; SELENIFEROUS AREA; SERUM SELENIUM; HUMAN HEALTH; FINNISH MEN; CANCER; NAILS; BLOOD; DIET AB Toenail selenium concentration has been proposed as a long-term (6-12 mo) indicator of human selenium status. This study investigated the association between toenail selenium concentration and selenium intake and other dietary factors among 166 urban men aged 55-69 y. The dietary information was collected by food records covering a 6-mo period. Toenail clippings were collected by mail 9-10 mo after food recording. The mean selenium intake from food was 42.5 mug/d and the dietary intake was equal to that of users and nonusers of selenium supplements. The mean toenail selenium concentration was 0.47 mg/kg. The mean selenium intake from supplements was 29.7 mug/d among supplement users. In the analysis of covariance the best predictors of toenail selenium concentration were selenium intake from supplements and food, and among supplement users dietary beta-carotene also. C1 NCI,BETHESDA,MD 20892. RP OVASKAINEN, ML (reprint author), NATL PUBL HLTH INST,KALLIOLINNANTIE 4,SF-00140 HELSINKI,FINLAND. RI Haukka, Jari/G-1484-2014 OI Haukka, Jari/0000-0003-1450-6208 FU NCI NIH HHS [N01-CN-45165] NR 25 TC 44 Z9 45 U1 0 U2 1 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998 SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD MAY PY 1993 VL 57 IS 5 BP 662 EP 665 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA LA004 UT WOS:A1993LA00400012 PM 8480683 ER PT J AU SWINBURN, B RAVUSSIN, E AF SWINBURN, B RAVUSSIN, E TI ENERGY-BALANCE OR FAT BALANCE SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE OBESITY; WEIGHT LOSS; DIETARY FAT; INDIRECT CALORIMETRY ID DIETARY-FAT; DENOVO LIPOGENESIS; INSULIN RESISTANCE; HIGH-CARBOHYDRATE; ALCOHOL INTAKE; SHORT-TERM; OBESITY; OXIDATION; WEIGHT; EXPENDITURE AB Under normal conditions, carbohydrate, protein, and alcohol are not converted to fat. Glycogen and protein stores are closely controlled, and increasing the intake of nonfat nutrients stimulates their oxidation rates proportionally. Thus, chronic imbalance between intake and oxidation of nonfat nutrients cannot lead to obesity. On the other hand, fat stores are not controlled and their capacity for expansion is enormous. Because an increase in fat intake does not stimulate fat oxidation, a positive fat balance results, which has the potential to become chronic. Obesity is therefore due to a long-standing positive fat balance, which may simply be due to a high-fat diet. The use of the fat-balance equation instead of the energy-balance equation adds another option for the treatment of obesity-that of changing the quality of the diet, ie, lowering the fat content. C1 NIDDKD, PHOENIX, AZ USA. RP UNIV AUCKLAND, SCH MED, DEPT COMMUNITY HLTH, AUCKLAND, NEW ZEALAND. NR 42 TC 19 Z9 20 U1 1 U2 3 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD MAY PY 1993 VL 57 IS 5 SU S BP 766 EP 771 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA LB148 UT WOS:A1993LB14800010 ER PT J AU BHAGAT, SKM MEDEIROS, LJ WEISS, LM WANG, J RAFFELD, M STETLERSTEVENSON, M AF BHAGAT, SKM MEDEIROS, LJ WEISS, LM WANG, J RAFFELD, M STETLERSTEVENSON, M TI BCL-2 EXPRESSION IN HODGKINS-DISEASE - CORRELATION WITH THE T(14,18) TRANSLOCATION AND EPSTEIN-BARR-VIRUS SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE HODGKINS DISEASE; T(14,18)(Q32,Q21); BCL-2 ONCOGENE; EPSTEIN-BARR VIRUS; IMMUNOHISTOCHEMISTRY; INSITU HYBRIDIZATION ID POLYMERASE CHAIN-REACTION; REED-STERNBERG CELLS; NEOPLASTIC-CELLS; GENE; LYMPHOMA; HYBRIDIZATION; INVOLVEMENT; TISSUES AB In a prior study from our laboratory using the polymerase chain reaction (PCR) technique, the t(14;18)(q32;q21) translocation was detected in low copy number in 32% of Hodgkin's disease cases. The cell of origin of the t(14;18), however, was not determined. To further investigate the role of bcl-2 in Hodgkin's disease and the possibility that the translocation resides in Reed-Sternberg and Hodgkin's (RS-H) cells, we analyzed selected cases of Hodgkin's disease immunohistologically using a monoclonal antibody reactive with bcl-2. Because Epstein-Barr virus (EBV) has been reported to upregulate bcl-2 expression, we also used an in situ method for detecting EBV in these tissues. Thirteen cases of Hodgkin's disease were studied, including seven cases with the t(14;18) translocation and six cases without it, as determined by PCR in a prior study. bcl-2 protein was detected immunohistologically in the RS-H cells in eight cases: three with the t(14; 18) translocation and five in which the translocation was not detected. EBV RNA was detected in the RS-H cells of four patients, including two in which the RS-H cells also were bcl-2 positive. The presence of bcl-2 staining of the RS-H cells in this series of cases did not correlate with clinical features, histologic subtype, the presence of the t(14;18) translocation, or EBV-positivity. The lack of consistent bcl-2 protein expression in RS-H cells, including EBV-positive RS-H cells, may suggest that the t(14;18) translocation does not reside in RS-H cells in at least a subset of cases of Hodgkin's disease. If this is true, the t(14;18) translocation may not play an important role in the pathogenesis of Hodgkin's disease. C1 NCI,PATHOL LAB,BLDG 10,ROOM 2A33,BETHESDA,MD 20892. CITY HOPE NATL MED CTR,DUARTE,CA 91010. NR 22 TC 32 Z9 33 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD MAY PY 1993 VL 99 IS 5 BP 604 EP 608 PG 5 WC Pathology SC Pathology GA LC624 UT WOS:A1993LC62400016 PM 8388163 ER PT J AU SHIONO, PH KLEBANOFF, MA AF SHIONO, PH KLEBANOFF, MA TI CAFFEINE AND BIRTH OUTCOMES SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Editorial Material ID GESTATIONAL-AGE; FETAL GROWTH; WEIGHT; PREGNANCY; CONSUMPTION; SMOKING; ALCOHOL; ASSOCIATION; COFFEE C1 NICHHD,DIV EPIDEMIOL STAT & PREVENT RES,BETHESDA,MD 20892. RP SHIONO, PH (reprint author), DAVID & LUCILE PACKARD FDN,CTR FUTURE,RES & GRANTS EPIDEMIOL,300 2ND ST,SUITE 102,LOS ALTOS,CA 94022, USA. NR 22 TC 10 Z9 11 U1 0 U2 1 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAY 1 PY 1993 VL 137 IS 9 BP 951 EP 954 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA LJ317 UT WOS:A1993LJ31700003 PM 8317452 ER PT J AU RICHARD, CW BOEHNKE, M BERG, DJ LICHY, JH MEEKER, TC HAUSER, E MYERS, RM COX, DR AF RICHARD, CW BOEHNKE, M BERG, DJ LICHY, JH MEEKER, TC HAUSER, E MYERS, RM COX, DR TI A RADIATION HYBRID MAP OF THE DISTAL SHORT ARM OF HUMAN CHROMOSOME-11, CONTAINING THE BECKWITH-WEIDEMANN AND ASSOCIATED EMBRYONAL TUMOR DISEASE LOCI SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID SOMATIC-CELL HYBRIDS; WIEDEMANN SYNDROME; WILMS TUMOR; ADRENOCORTICAL CARCINOMA; INSITU HYBRIDIZATION; TRISOMY 11P15; REGION; GENE; PCR; HETEROZYGOSITY AB We describe a high-resolution radiation hybrid (RH) map of the distal short arm of human chromosome 11 containing the Beckwith-Weidemann gene and the associated embryonal tumor disease loci. Thirteen human 11p15 genes and 17 new anonymous probes were mapped by a statistical analysis of the cosegregation of markers in 102 rodent-human radiation hybrids retaining fragments of human chromosome 11. The 17 anonymous probes were generated from lambda phage containing human 11p15.5 inserts, by using ALU-PCR. A comprehensive map of all 30 loci and a framework map of nine clusters of loci ordered at odds of 1,000:1 were constructed by a multipoint maximum-likelihood approach by using the computer program RHMAP. This RH map localizes one new gene to chromosome 11p15 (WEE1), provides more precise order information for several 11p15 genes (CTSD, H19, HPX, ST5, RNH, and SMPD1), confirms previous map orders for other 11p15 genes (CALCA, PTH, HBBC, TH, HRAS, and DRD4), and maps 17 new anonymous probes within the 11p15.5 region. This RH map should prove useful in better defining the positions of the Beckwith-Weidemann and associated embryonal tumor disease-gene loci. C1 UNIV MICHIGAN,SCH PUBL HLTH,DEPT BIOSTAT,ANN ARBOR,MI 48109. NCI,TUMOR VIRUS BIOL LAB,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,DEPT PSYCHIAT,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT PHYSIOL,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT MED,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT BIOCHEM & BIOPHYS,SAN FRANCISCO,CA 94143. FU NHGRI NIH HHS [HG00206]; NICHD NIH HHS [HD24610]; NIMH NIH HHS [MH00802] NR 41 TC 32 Z9 32 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 MAY PY 1993 VL 52 IS 5 BP 915 EP 921 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA LB889 UT WOS:A1993LB88900008 PM 8387721 ER PT J AU MCDOWELL, GA BLITZER, MG AF MCDOWELL, GA BLITZER, MG TI IS THE PRESENCE OF 2 DIFFERENT TAY-SACHS DISEASE MUTATIONS IN A CAJUN POPULATION AN UNEXPECTED OBSERVATION - REPLY SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Letter ID ASHKENAZI JEWS; CARRIERS C1 UNIV MARYLAND,SCH MED,DEPT PEDIAT,DIV HUMAN GENET,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,DEPT OBSTET & GYNECOL,BALTIMORE,MD 21201. RP MCDOWELL, GA (reprint author), NICHHD,HUMAN GENET BRANCH,HUMAN BIOCHEM GENET SECT,BETHESDA,MD 20892, USA. NR 6 TC 0 Z9 0 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 MAY PY 1993 VL 52 IS 5 BP 1015 EP 1016 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA LB889 UT WOS:A1993LB88900023 ER PT J AU BLAIR, A DOSEMECI, M HEINEMAN, EF AF BLAIR, A DOSEMECI, M HEINEMAN, EF TI CANCER AND OTHER CAUSES OF DEATH AMONG MALE AND FEMALE FARMERS FROM 23 STATES SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE LEUKEMIA; LYMPHOMA; BRAIN CANCER; PROSTATE CANCER; AGRICULTURE; ACCIDENTS; NONWHITE MORTALITY; FEMALE MORTALITY ID PROPORTIONATE MORTALITY RATIO; TESTICULAR CANCER; AGRICULTURE; RISK; OCCUPATION; EMPLOYMENT; CAROLINA; ACCURACY AB Occupation and industry codes on death certificates from 23 states for 1984-1988 were used to evaluate mortality risks among white and nonwhite, male and female farmers. Proportionate mortality and proportionate cancer mortality ratios were calculated using deaths among nonfarmers from the same states to generate expected numbers. Among farmers there were 119,648 deaths among white men, 2,400 among white women, 11,446 among nonwhite men, and 2,066 among nonwhite women. Deficits occurred in all race-sex groups for infective and parasitic diseases, all cancer combined, lung cancer, liver cancer, diseases of the nervous system, multiple sclerosis, hypertension, and emphysema. As reported in other studies, white male farmers had excesses of cancer of the lymphatic and hematopoietic system, lip, eye, brain, and prostate. Excesses of cancers of the pancreas, kidney, bone, and thyroid were new findings. Regional patterns were evident, particularly among white men. Significant excesses for accidents, vascular lesions of the central nervous system (CNS), and cancers of the prostate tended to occur in most geographic regions, while excesses for mechanical suffocation, non-Hodgkin's lymphoma, and cancers of the lip, brain, and the lymphatic and hematopoietic system were limited to the Central states. Increases among nonwhite men were similar to those in white men for some causes of death (vascular lesions of the CNS and cancers of the pancreas and prostate), but were absent for others (lymphatic and hematopoietic system, lip, eye, kidney, and brain). Women (white and nonwhite) had excesses for vascular lesions of the CNS, disease of the genitourinary system (white women only), and cancers of the stomach and cervix (nonwhite women only). Cancer of the buccal cavity and pharynx was slightly elevated among women, and white women had nonsignificant excesses of multiple myeloma and leukemia. Excesses for leukemia and non-Hodgkin's lymphoma occurred among white men and women, but not among nonwhites. Excesses for several types of accidental deaths were seen among all race-sex groUpS. RP BLAIR, A (reprint author), NCI,OCCUPAT STUDIES SECT,EXECUT PLAZA N,ROOM 418,BETHESDA,MD 20892, USA. NR 39 TC 130 Z9 131 U1 0 U2 9 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD MAY PY 1993 VL 23 IS 5 BP 729 EP 742 DI 10.1002/ajim.4700230507 PG 14 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA KZ254 UT WOS:A1993KZ25400006 PM 8506851 ER PT J AU SHORE, D BERG, K WYNNE, D FOLSTEIN, MF AF SHORE, D BERG, K WYNNE, D FOLSTEIN, MF TI LEGAL AND ETHICAL ISSUES IN PSYCHIATRIC GENETIC RESEARCH SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE CONFIDENTIALITY; RESEARCH RISKS; INFORMED CONSENT; PSYCHIATRIC GENETICS ID CONSENT AB Genetic research may uncover the causes of severe mental disorders, and many projects have been undertaken to locate the genes responsible for schizophrenia, bipolar disorder, and Alzheimer disease. A number of sensitive legal and ethical issues have been raised, including 1) protection of confidential data concerning research subjects; 2) the assessment of types and degree of risk to subjects who participate in such studies; 3) the legal and ethical acceptability of substituted judgment on behalf of patients who may not be competent to provide informed consent; and 4) the separation of research and clinical roles in areas such as genetic counseling. Federal regulations and other guidelines are of limited value in dealing with such concerns, and many important human subjects issues will need to be dealt with by the investigator, subject to approval by a local Institutional Review Board. There does seem to be general agreement that informed consent must be obtained, potential risks of research need to be minimized, and confidentiality of sensitive data must be protected. C1 NIMH,GENET RES PROGRAM,ROCKVILLE,MD 20857. NIMH,DIAGNOST CTR PSYCHIAT LINKAGE COOPERAT AGREEMENT,ROCKVILLE,MD 20857. JOHNS HOPKINS UNIV,BALTIMORE,MD 21218. NIMH,DIAGNOST CTR PSYCHIAT LINKAGE LEGAL,ETH ISSUES COMM,BETHESDA,MD 20892. RP SHORE, D (reprint author), NIMH,DIV CLIN & TREATMENT RES,SCHIZOPHRENIA RES BRANCH,ROOM 18C-14,ROCKVILLE,MD 20857, USA. NR 9 TC 15 Z9 15 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD MAY 1 PY 1993 VL 48 IS 1 BP 17 EP 21 DI 10.1002/ajmg.1320480106 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA KY349 UT WOS:A1993KY34900005 PM 8357032 ER PT J AU COON, H HOFF, M HOLIK, J DELISI, LE CROWE, T FREEDMAN, R SHIELDS, G BOCCIO, AM LERMAN, M GERSHON, ES GEJMAN, PV LEPPERT, M BYERLEY, W AF COON, H HOFF, M HOLIK, J DELISI, LE CROWE, T FREEDMAN, R SHIELDS, G BOCCIO, AM LERMAN, M GERSHON, ES GEJMAN, PV LEPPERT, M BYERLEY, W TI C-NUCLEOTIDE TO T-NUCLEOTIDE SUBSTITUTION IN CODON 713 OF AMYLOID PRECURSOR PROTEIN GENE NOT FOUND IN 86 UNRELATED SCHIZOPHRENICS FROM MULTIPLEX FAMILIES SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE SCHIZOPHRENIA; AMYLOID PRECURSOR PROTEIN GENE; MUTATION ANALYSIS ID LINKAGE; POLYMORPHISMS; DISORDERS AB Jones et al. Nature Genet 1:306-309, [1992] recently detected a C to T nucleotide transition (codon 713) in a highly conserved region of the beta-amyloid precursor gene in a single case of schizophrenia. Although the sequence variant may be a natural polymorphism, it is crucial to determine whether the mutation might be present in a small subset of schizophrenics. We isolated DNA from 86 unrelated chronic schizophrenics who had a first degree relative with chronic schizophrenia or chronic schizoaffective disorder. After PCR amplification of exon 17, we were unable to detect the presence of the codon 713 variant in these schizophrenic cases, as well as in 156 controls. Unless additional cases are found with the codon 713 mutation, it is unlikely that the sequence variant is pathogenic for schizophrenia. C1 UNIV UTAH,MED CTR,DEPT PSYCHIAT,SALT LAKE CITY,UT 84132. UNIV UTAH,HOWARD HUGHES MED INST,SALT LAKE CITY,UT 84132. SUNY STONY BROOK,DEPT PSYCHIAT,STONY BROOK,NY 11794. CLIN RES CTR,DIV PSYCHIAT,HARROW,MIDDX,ENGLAND. UNIV COLORADO,HLTH SCI CTR,DEPT PSYCHIAT,DENVER,CO 80262. NIMH,CLIN NEUROGENET BRANCH,BETHESDA,MD 20892. OI Coon, Hilary/0000-0002-8877-5446 FU NCRR NIH HHS [MO1-RR0064]; NIMH NIH HHS [MH-44212, MH-44245] NR 27 TC 11 Z9 11 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD MAY 1 PY 1993 VL 48 IS 1 BP 36 EP 39 DI 10.1002/ajmg.1320480109 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA KY349 UT WOS:A1993KY34900008 PM 8102836 ER PT J AU LABUDA, MC GOTTESMAN, II PAULS, DL AF LABUDA, MC GOTTESMAN, II PAULS, DL TI USEFULNESS OF TWIN STUDIES FOR EXPLORING THE ETIOLOGY OF CHILDHOOD AND ADOLESCENT PSYCHIATRIC-DISORDERS SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Review DE TWINS; CHILDHOOD PSYCHOPATHOLOGY; GENETICS ID OBSESSIVE-COMPULSIVE DISORDER; MULTIPLE-REGRESSION ANALYSIS; LA-TOURETTES SYNDROME; ANOREXIA-NERVOSA; BEHAVIORAL-GENETICS; RESEARCH STRATEGIES; READING-DISABILITY; MATERNAL AGE; SCHIZOPHRENIA; PAIRS AB It is estimated that approximately 12% of the individuals under the age of 18 in the United States have a diagnosable mental illness [Institute of Medicine, 1989]; however, only a minority of the etiological research in psychopathology focuses on disorders with childhood onset. The present report demonstrates the usefulness of twin studies in exploring the etiology of childhood and adolescent psychiatric psychopathology and reviews the design, methodology, and results from traditional twin studies of various behavioral disorders. Alternative twin designs are also reviewed in an effort to address the future direction of twin studies in the area of childhood and adolescent psychopathology and to illustrate that twin data have much more to offer the field of psychopathology than merely an initial test to rule in or to rule out a significant genetic contribution to the development of such behaviors. C1 UNIV VIRGINIA,DEPT PSYCHOL,CHARLOTTESVILLE,VA 22903. YALE UNIV,CTR CHILD STUDY,NEW HAVEN,CT 06520. YALE UNIV,DEPT GENET,NEW HAVEN,CT 06520. RP LABUDA, MC (reprint author), NIDA,ADDICT RES CTR,POB 5180,BALTIMORE,MD 21224, USA. RI G, I/D-8042-2011 FU NIMH NIH HHS [MH-18268] NR 104 TC 30 Z9 30 U1 1 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD MAY 1 PY 1993 VL 48 IS 1 BP 47 EP 59 DI 10.1002/ajmg.1320480111 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA KY349 UT WOS:A1993KY34900010 PM 8357036 ER PT J AU NAUMAN, J WOLFF, J AF NAUMAN, J WOLFF, J TI IODIDE PROPHYLAXIS IN POLAND AFTER THE CHERNOBYL REACTOR ACCIDENT - BENEFITS AND RISKS SO AMERICAN JOURNAL OF MEDICINE LA English DT Review ID CHILDHOOD C1 NIDDKD,BLDG 8,ROOM 2A-25,BETHESDA,MD 20892. UNIV WARSAW,SCH MED,DEPT ENDOCRINOL,PL-00325 WARSAW,POLAND. NR 31 TC 82 Z9 91 U1 0 U2 8 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9343 J9 AM J MED JI Am. J. Med. PD MAY PY 1993 VL 94 IS 5 BP 524 EP 532 DI 10.1016/0002-9343(93)90089-8 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA LC874 UT WOS:A1993LC87400013 PM 8498398 ER PT J AU GHIDINI, A SEPULVEDA, W LOCKWOOD, CJ ROMERO, R AF GHIDINI, A SEPULVEDA, W LOCKWOOD, CJ ROMERO, R TI COMPLICATIONS OF FETAL BLOOD-SAMPLING SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE FETAL BLOOD SAMPLING; PRENATAL DIAGNOSIS ID UMBILICAL-CORD; INTRAVASCULAR TRANSFUSION; CORDOCENTESIS; FUNIPUNCTURE; EXPERIENCE; ULTRASOUND; PREGNANCY; DISTRESS AB To examine the incidence and significance of complications related to percutaneous fetal blood sampling, we reviewed all the articles published in the English literature on this procedure. Risks of complications and adverse outcomes depend mainly on the gestational age at the time of the procedure, the operator's experience, and the indication for the procedure. To determine the incidence of fetal losses, we pooled the data from series with > 100 cases. After exclusion of cases where some fetal pathologic condition was present, we determined the incidence of adverse outcomes in a low-risk population. In this population fetal blood sampling performed by an experienced operator carries about a 1.4% risk of fetal loss before 28 weeks' gestation and a 1.4% risk of perinatal death (after 28 weeks). C1 WASHINGTON STATE UNIV,HUTZEL HOSP,DEPT OBSTET & GYNECOL,PULLMAN,WA 99164. NICHHD,PERINATOL BRANCH,BETHESDA,MD 20892. RP GHIDINI, A (reprint author), CUNY MT SINAI SCH MED,DEPT OBSTET GYNECOL & REPROD SCI,NEW YORK,NY 10029, USA. NR 25 TC 143 Z9 147 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 MAY PY 1993 VL 168 IS 5 BP 1339 EP 1344 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA LD672 UT WOS:A1993LD67200001 PM 8498409 ER PT J AU BATISTA, MC BRAVO, N CARTLEDGE, TP ZELLMER, AW MERRIAM, GR LORIAUX, DL NIEMAN, LK AF BATISTA, MC BRAVO, N CARTLEDGE, TP ZELLMER, AW MERRIAM, GR LORIAUX, DL NIEMAN, LK TI COMPARATIVE-ANALYSIS OF PROGESTERONE AND PLACENTAL PROTEIN 14 MEASUREMENTS IN THE EVALUATION OF LUTEAL FUNCTION SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE PROGESTERONE; PLACENTAL PROTEIN 14; ENDOMETRIAL PROTEIN; LUTEAL PHASE; LUTEAL INSUFFICIENCY ID CORPUS-LUTEUM; PHASE DEFECTS; ENDOMETRIAL ALPHA-2-GLOBULIN; SECRETORY ENDOMETRIAL; PLASMA PROGESTERONE; MENSTRUAL-CYCLE; SERUM; OVULATION; RADIOIMMUNOASSAY; FERTILITY AB OBJECTIVE: Our purpose was to investigate the diagnostic accuracy of single or summed measurements of progesterone and placental protein 14, a progestin-dependent endometrial glycoprotein, in the evaluation of luteal function. STUDY DESIGN: Forty-five healthy women had daily blood measurements of luteinizing hormone, progesterone, and placental protein 14 during one menstrual cycle. RESULTS: Thirty-nine women had normal and six had deficient luteal function on the basis of serial progesterone determinations. Luteal insufficiency was not accurately diagnosed by single progesterone or placental protein 14 values or by integrated placental protein 14 measurements. In contrast, the condition was correctly identified in all but one cycle when the sum of progesterone on days 4 and 7 was < 49 nmol/L (1 5.4 ng/ml). A poor correlation was found between peak or integrated measurements of progesterone and placental protein 14. CONCLUSION: Measurement of serum progesterone, but not placental protein 14, on 2 days of the midluteal phase provides a convenient and reliable test of luteal function. C1 NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NR 25 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAY PY 1993 VL 168 IS 5 BP 1522 EP 1527 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA LD672 UT WOS:A1993LD67200033 PM 8498438 ER PT J AU THORGEIRSSON, SS AF THORGEIRSSON, SS TI HEPATIC STEM-CELLS SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Note ID LIVER EPITHELIAL-CELLS; ADULT-RAT LIVER; OVAL CELLS; HEPATOCYTES; EXPRESSION; DIFFERENTIATION; CARCINOGENESIS; TRANSFORMATION; CYTOKERATIN; CULTURE RP THORGEIRSSON, SS (reprint author), NCI,EXPTL CARCINOGENESIS LAB,BLDG 37,ROOM 3C28,BETHESDA,MD 20892, USA. NR 26 TC 95 Z9 102 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD MAY PY 1993 VL 142 IS 5 BP 1331 EP 1333 PG 3 WC Pathology SC Pathology GA LC123 UT WOS:A1993LC12300001 PM 8494039 ER PT J AU CICALA, C POMPETTI, F CARBONE, M AF CICALA, C POMPETTI, F CARBONE, M TI SV40 INDUCES MESOTHELIOMAS IN HAMSTERS SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID SMALL-T-ANTIGEN; VIABLE DELETION MUTANTS; SIMIAN VIRUS-40; MALIGNANT MESOTHELIOMA; PROTEIN PHOSPHATASE-2A; ASBESTOS; CELLS; ESTABLISHMENT AB In the course of studies to elucidate the relative contribution of simian virus 40 (SV40) large T and small t proteins during oncogenesis, we observed the appearance of pericardial and pleural tumors in 100% of Syrian hamsters injected in the pleural space with wild type SV40. When SV40 was injected via the intracardiac or intraperitoneal routes, more than 50% of hamsters developed mesothelial tumors. Macroscopic, microscopic, ultramicroscopic, and bistochemical characteristics identify these neoplasms and derived cell lines as mesotheliomas and mesothelioma-derived cell lines. The SV40 genome was integrated and expressed in the mesotheliomas and derived cell lines. The absence of mesotheliomas in hamsters injected with SV40 small t deletion mutants indicates that the small t protein plays an important role in the development of SV40-induced mesotheliomas. To the best of our knowledge, this is the first definitive report of virus-induced mesotheliomas in mammals. C1 NICHHD,VIRUES & CELLULAR BIOL SECT,BLDG 6,ROOM 1A1,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 39 TC 175 Z9 182 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD MAY PY 1993 VL 142 IS 5 BP 1524 EP 1533 PG 10 WC Pathology SC Pathology GA LC123 UT WOS:A1993LC12300022 PM 8388174 ER PT J AU WOODWORTH, CD SIMPSON, S AF WOODWORTH, CD SIMPSON, S TI COMPARATIVE LYMPHOKINE SECRETION BY CULTURED NORMAL HUMAN CERVICAL KERATINOCYTES, PAPILLOMAVIRUS-IMMORTALIZED, AND CARCINOMA CELL-LINES SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID WART VIRUS-INFECTION; EPITHELIAL-CELLS; INTRAEPITHELIAL NEOPLASIA; LANGERHANS CELLS; MOLECULAR-CLONING; UTERINE CERVIX; EXPRESSION; TYPE-16; INVITRO; DNA AB The pathogenesis of cervical human papillomavirus (HPV) infection is influenced by the host's immune response. This response depends upon secretion of specific lymphokines to recruit and activate immune cells at the site of infection. To examine whether cervical cells enhance immune-responsiveness, secretion of lymphokines by cultures of normal cervical cells, HPV-immortalized cervical lines, and carcinoma lines was compared Normal cervical cells constitutively secreted interleukin-I alpha (IL-1 alpha), IL-1 beta IL-1 receptor antagonist, IL-6, IL-8, tumor necrosis factor-alpha, and granulocyte macrophage colony stimulating factor. Lymphokines were also produced by exo- and endocervical epithelia in vivo. In contrast, four cervical cell lines immortalized by HPV DNAs and three carcinoma lines secreted selected lymphokines at significantly reduced levels. Interferon-gamma induced major histocompatibility class I and II proteins and intercellular adhesion molecule-I in normal cells, but results in immortal or carcinoma lines were variable. These results suggest that cervical epithelial cells have the potential to influence inflammation and immunity in the cervical mucosa. Furthermore, decreased expression of lymphokines and histocompatibility molecules by HPV-immortalized cervical cells suggests that similar alterations might ''company persistent HPV infections in vivo. RP WOODWORTH, CD (reprint author), NCI,BIOL LAB,BLDG 37,ROOM 2A23,BETHESDA,MD 20892, USA. NR 54 TC 104 Z9 107 U1 1 U2 2 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD MAY PY 1993 VL 142 IS 5 BP 1544 EP 1555 PG 12 WC Pathology SC Pathology GA LC123 UT WOS:A1993LC12300024 PM 8098584 ER PT J AU HILGARTNER, MW DONFIELD, SM WILLOUGHBY, A CONTANT, CF EVATT, BL GOMPERTS, ED HOOTS, WK JASON, J LOVELAND, KA MCKINLAY, SM STEHBENS, JA AF HILGARTNER, MW DONFIELD, SM WILLOUGHBY, A CONTANT, CF EVATT, BL GOMPERTS, ED HOOTS, WK JASON, J LOVELAND, KA MCKINLAY, SM STEHBENS, JA TI HEMOPHILIA GROWTH AND DEVELOPMENT STUDY - DESIGN, METHODS, AND ENTRY DATA SO AMERICAN JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE HEMOPHILIA; HUMAN IMMUNODEFICIENCY VIRUS; PHYSICAL GROWTH; SEXUAL MATURATION; IMMUNE FUNCTION; NEUROLOGIC FUNCTIONING; NEUROPSYCHOLOGICAL FUNCTIONING ID ACQUIRED IMMUNODEFICIENCY SYNDROME; IMMUNE-DEFICIENCY SYNDROME; VIRUS-INFECTION; CHILDREN; AIDS AB Purpose: The study design, research questions, and baseline data are presented from a multicenter longitudinal epidemiologic investigation of the impact of human immunodeficiency virus (HIV) infection on three areas of functioning in children and adolescents with hemophilia: physical growth and sexual maturation, immune function, and neurological and neuropsychological functioning. Patients and Methods: Sixty-nine percent (n = 333) of a population of males between the ages of 6 and 19 years with moderate to severe hemophilia participated in a comprehensive baseline examination. Approximately 62% of the study group was HIV seropositive and 38% HIV seronegative. Results: Adjusted for age, HIV-positive participants were three times as likely as HIV-negative participants to exhibit declines in height-for-age attainment (p = 0.05), twice as likely to have delays in sexual maturation (p = 0.414), and more than three times as likely to exhibit antibody levels that were not indicative of prior exposure or vaccination (p < 0.001). In addition, analysis of a comprehensive battery of neuropsychological tests showed that HIV-positive participants were 50% more likely to show scores approximately 1 SD below expected levels in three of nine functional areas (p = NS) compared with HIV-negative participants. Conclusions: Entry data for this study reveal a greater likelihood for HIV-positive children and adolescents with moderate to severe hemophilia to have abnormal growth, and to exhibit antibody levels not indicative of prior exposure to disease or vaccination, which could be attributed to HIV infection. Lowered neuropsychological test performance in both groups may be attributable to the deleterious effects of chronic illness. Data are being collected from a group of non-HIV infected non-hemophiliac siblings for comparison. C1 NEW ENGLAND RES INST,WATERTOWN,MA. NICHHD,PEDIAT ADOLESCENT & MATERNAL AIDS BRANCH,BETHESDA,MD 20892. BAYLOR COLL MED,DEPT ARCTIC BIOL,HOUSTON,TX 77030. CTR DIS CONTROL,DIV HIV AIDS,NATL AIDS INFORMAT & EDUC PROGRAM,ATLANTA,GA 30333. CHILDRENS HOSP LOS ANGELES,LOS ANGELES,CA. UNIV TEXAS,SCH MED,DEPT PEDIAT,HOUSTON,TX 77025. UNIV TEXAS,SCH MED,DEPT INTERNAL MED,HOUSTON,TX 77025. UNIV TEXAS,SCH MED,DEPT PSYCHIAT & BEHAV SCI,HOUSTON,TX 77025. UNIV IOWA,DEPT PSYCHIAT & BEHAV SCI,IOWA CITY,IA 52242. RP HILGARTNER, MW (reprint author), CORNELL UNIV,MED CTR,NEW YORK HOSP,DIV PEDIAT HEMATOL & ONCOL,525 E 68TH ST,ROOM N-740,NEW YORK,NY 10021, USA. FU NCRR NIH HHS [M01-RR06020]; NICHD NIH HHS [N01-HD-8-2908]; PHS HHS [MCJ-060570] NR 15 TC 104 Z9 104 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0192-8562 J9 AM J PEDIAT HEMATOL PD MAY PY 1993 VL 15 IS 2 BP 208 EP 218 PG 11 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA KX827 UT WOS:A1993KX82700009 PM 8498644 ER PT J AU FLESSNER, MF KNEPPER, MA AF FLESSNER, MF KNEPPER, MA TI AMMONIUM AND BICARBONATE TRANSPORT IN ISOLATED-PERFUSED RODENT ASCENDING LIMBS OF THE LOOP OF HENLE SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE AMMONIA; ACID-BASE; UREA; CARBONIC ANHYDRASE; PERMEABILITY; RENAL EPITHELIUM ID DISEQUILIBRIUM PH; COLLECTING DUCT; RAT; KIDNEY; SEGMENTS; TUBULES; NH4+; NH3; GRADIENTS; NEPHRONS AB Ammonoium accumulates in the renal medullas of antidiuretic animals, presumably due to countercurrent multiplication, driven by NH4+ absorption from ascending loops of Henle in the outer and inner medulla. Active absorption of NH4+ occurs in the thick ascending limb (TAL). But the passive transport properties of NH3 in the TAL and the transport of ammonium or HCO3- in the ascending thin limb (ATL) have not been studied in rodents. To investigate the potential role of the ascending limb segments in medullary accumulation of ammonium, we perfused isolated subsegments of the chinchilla ATL and of the rat ATL and TAL. After imposing concentration gradients of total ammonia or total CO2 across ATL subsegments, we found very high rates of transfer of both substances, implying that at physiological flow rates the tubule luminal fluid quickly equilibrates with the interstitium. In the medullary TAL, we found a passive NH4+ permeability of 17 x 10(-5) cm/s but a relatively low NH3 permeability of <0.003 cm/s. The low NH3 permeability prevents backleak of NH3 when NH4+ is actively transported from the lumen. We conclude that the ATL acts as an equilibrating segment and the TAL has special permeability properties that enhance net ammonium absorption and therefore enhance medullary ammonium accumulation. C1 NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BLDG 10,RM 6N-307,BETHESDA,MD 20892. NR 34 TC 6 Z9 6 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 MAY PY 1993 VL 264 IS 5 BP F837 EP F844 PN 2 PG 8 WC Physiology SC Physiology GA LD347 UT WOS:A1993LD34700096 PM 8498537 ER PT J AU LIANG, CT BARNES, J HANAI, H LEVINE, MA AF LIANG, CT BARNES, J HANAI, H LEVINE, MA TI DECREASE IN G(S) PROTEIN EXPRESSION MAY IMPAIR ADENYLATE-CYCLASE ACTIVATION IN OLD KIDNEYS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE PARATHYROID HORMONE; FORSKOLIN; G-PROTEINS; MESSENGER RIBONUCLEIC ACID ID GTP-BINDING PROTEIN; PARATHYROID-HORMONE; AGED RATS; RENAL-CELLS AB The possibility that alteration in stimulatory guanine nucleotide-binding protein (G(s)) expression may contribute to the blunting of renal parathyroid hormone (PTH)-stimulated adenylate cyclase in aged rats was examined. Using rat cDNA probe, we identified a G(s) alpha-subunit (G(s)alpha) of 1.9 kb. Age did not alter the size of G(s)alpha mRNA. The level of G(s)alpha mRNA [normalized to poly(A)+ RNA] was decreased 23%, which was consistent with our previous report that G(s)alpha protein decreased in senescence. In contrast, mRNA level of G(i)alpha2 increased with age. Level of beta-actin mRNA did not change with age. Nuclear runoff assay was performed to determine the transcription rate of G(s) mRNA. Synthesis of poly(A)+ RNA and total RNA was reduced 39% and 37%, respectively, in nuclei prepared from old kidney, which suggested a general decline in RNA synthesis capacity in old rats. Our results also showed the transcription rate of G(s)alpha mRNA in aged rats was reduced 89%, a decrease far exceeding that observed for total RNA or poly(A)+ RNA. We concluded that the decrease in steady-state level of G(s)alpha MRNA was specific and probably was due to a reduction in the transcription activity. Thus alteration in G(s) transcription may contribute, at least in part, to the impaired renal adenylate cyclase activation in aged rats. C1 JOHNS HOPKINS UNIV,DEPT MED,DIV ENDOCRINOL & METAB,BALTIMORE,MD 21205. RP LIANG, CT (reprint author), NIA,GERONTOL RES CTR,BIOL CHEM LAB,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 19 TC 9 Z9 9 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 MAY PY 1993 VL 264 IS 5 BP F770 EP F773 PN 2 PG 4 WC Physiology SC Physiology GA LD347 UT WOS:A1993LD34700086 PM 8498529 ER PT J AU XIA, YY FENG, LL YOSHIMURA, T WILSON, CB AF XIA, YY FENG, LL YOSHIMURA, T WILSON, CB TI LPS-INDUCED MCP-1, IL-1-BETA, AND TNF-ALPHA MESSENGER-RNA EXPRESSION IN ISOLATED ERYTHROCYTE-PERFUSED RAT-KIDNEY SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE CYTOKINES; RIBONUCLEASE PROTECTION ASSAY; RENAL VASCULAR RESISTANCE; ENDOTOXIN ID TUMOR-NECROSIS-FACTOR; MONOCYTE CHEMOATTRACTANT PROTEIN-1; GLOMERULAR MESANGIAL CELLS; COMPETENCE GENE-JE; MONONUCLEAR LEUKOCYTES; INTERLEUKIN-1 GENE; ENDOTHELIAL-CELLS; ENDOTOXIN; CLONING; GLOMERULONEPHRITIS AB The capacity of the lipopolysaccharide (LPS)-stimulated isolated erythrocyte-perfused rat kidney (IEPK) to produce monocyte chemoattractant protein-1 (MCP-1), interleukin-1beta (IL-1beta), and tumor necrosis factor-alpha (TNF-alpha) mRNA was investigated. The IEPK was chosen to exclude the influence of circulating neutrophils and monocytes that can produce both these mediators when exposed to LPS. The control minimal LPS group (LPS < 10 pg/ml) showed a small increase in mRNA expression for MCP-1, IL-1beta, and TNF-alpha in the cortex and medulla after 80 min of perfusion when compared with the unperfused left kidney in which no IL-1beta or TNF-alpha mRNA and only minimal amounts of MCP-1 mRNA were detected. LPS stimulation (1 mug/ml for 40 or 80 min) increased MCP-1, IL-1beta, and TNF-alpha mRNA expression, which was found predominately in peritubular capillary endothelial cells by in situ hybridization. The changes were not due to a marked perturbation of LPS on renal hemodynamics. The renal vascular resistance (RVR) remained constant (40 min LPS exposure) or increased only slightly during the last 5-10 min (80 min LPS exposure) compared with a progressive increase in RVR of the minimal LPS group. The hemodynamic effects of LPS on the IEPK appear to counteract the gradual increase in RVR seen in the minimal LPS group. C1 Scripps Res Inst, DEPT IMMUNOL IMM5, 10666 N TORREY PINES RD, LA JOLLA, CA 92037 USA. NCI, CTR CANC RES & DEV, IMMUNOPATHOL SECT, FREDERICK, MD 21702 USA. FU NIDDK NIH HHS [DK-40251] NR 28 TC 61 Z9 62 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 MAY PY 1993 VL 264 IS 5 BP F774 EP F780 PN 2 PG 7 WC Physiology SC Physiology GA LD347 UT WOS:A1993LD34700087 PM 8498530 ER PT J AU HILDEBRAND, P MROZINSKI, JE MANTEY, SA PATTO, RJ JENSEN, RT AF HILDEBRAND, P MROZINSKI, JE MANTEY, SA PATTO, RJ JENSEN, RT TI PANCREATIC ACINI POSSESS ENDOTHELIN RECEPTORS WHOSE INTERNALIZATION IS REGULATED BY PLC-ACTIVATING AGENTS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE RAT PANCREAS; CHOLECYSTOKININ; RECEPTOR REGULATION ID EPIDERMAL GROWTH-FACTOR; VASCULAR SMOOTH-MUSCLE; GUINEA-PIG PANCREAS; PHORBOL-ESTERS; INTRACELLULAR CA-2+; DISPERSED ACINI; LIGAND-BINDING; MESSENGER-RNA; RAT PANCREAS; CELLS AB Endothelin-1 (ET-1) and ET-3 mRNA have been found in the pancreas. We investigated the ability of ET-1, ET-2, and ET-3 to interact with and alter dispersed rat pancreatic acinar cell function. Radiolabeled ETs bound in a time- and temperature-dependent fashion, which was specific and saturable. Analysis demonstrated two classes of receptors, one class (ET(A) receptor) had a high affinity for ET-1 but a low affinity for ET-3, and the other class (ET(B) receptor) had equally high affinities for ET-1 and ET-3. No specific receptor for ET-2 was identified. Pancreatic secretagogues that activate phospholipase C (PLC) inhibited binding of I-125-labeled ET-1 (I-125-ET-1) or I-125-ET-3, whereas agents that act through adenosine 3',5'-cyclic monophosphate (cAMP) did not. A23187 had no effect on I-125-ET-1 or I-125-ET-3 binding, whereas the phorbol ester 12-O-tetradecanoylphorbol 13-acetate reduced binding. The effect of cholecystokinin octapeptide (CCK-8) was mediated through its own receptor. Stripping of surface bound ligand studies demonstrated that both I-125-labeled ET-1 and I-125-labeled ET-3 were rapidly internalized. CCK-8 decreased the internalization but did not change the amount of surface bound ligand. Endothelins neither stimulate nor alter changes in enzyme secretion, intracellular calcium, cAMP, or [H-3]inositol trisphosphate (IP3). This study demonstrates the presence of ET(A) and ET(B) receptors on rat pancreatic acini; occupation of both receptors resulted in rapid internalization, which is regulated by PLC-activating secretagogues. Occupation of either ET receptor did not alter intracellular calcium, cAMP, IP3, or stimulate amylase release. C1 NIDDKD,DIGEST DIS BRANCH,BLDG 10,RM 9C-103,BETHESDA,MD 20892. UNIV HOSP BASEL,DEPT GASTROENTEROL,CH-4031 BASEL,SWITZERLAND. NR 39 TC 30 Z9 30 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 MAY PY 1993 VL 264 IS 5 BP G984 EP G993 PN 1 PG 10 WC Physiology SC Physiology GA LD346 UT WOS:A1993LD34600083 PM 7684569 ER PT J AU RAMIREZVICK, J VARGAS, FF AF RAMIREZVICK, J VARGAS, FF TI ALBUMIN MODULATION OF PARACELLULAR PERMEABILITY OF PIG VENA-CAVAL ENDOTHELIUM SHOWS SPECIFICITY FOR PIG ALBUMIN SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE ALBUMIN SPECIFICITY; ENDOTHELIAL PERMEABILITY; PIG VENA CAVA ID FROG MESENTERIC CAPILLARIES; HYDRAULIC CONDUCTIVITY; ELECTRICAL-RESISTANCE; DOG ALBUMIN; BINDING; MUSCLE; CELLS; ABSENCE; SULFATE; SITES AB We measured endothelial hydraulic conductivity (L(p,e)) and endothelial electrical resistance (R(e)) of pig vena cava in pig serum albumin (PSA) and bovine serum albumin (BSA) to determine whether specificity for the autologous albumin found in dog vena cava is a general property of mammalian endothelium. Pigs were anesthetized with pentobarbital sodium for surgical removal of the thoracic inferior vena cava. A vessel segment was placed as a membrane separating two compartments in a chamber. Vessels kept in 30 mg/ml BSA had L(p,e) values of 1.30 +/- 0.81 x 10(-7), cm . s-1 . cmH2O-1 (n = 9) and R(e) values of 13.8 +/- 2.6 OMEGA . cm2 (n = 3). Vessels kept in PSA had L(p,e) values of 0.257 +/- 0.125 X 10(-7) cm . s-1 . cmH2O-1 (n = 5) and R(e) values of 21 +/- 6.3 OMEGA . cm2 (n = 4). The differences between L(p,e) and R(e) in BSA and PSA were statistically significant (P < 0.05). In vessels kept in PSA, switching to BSA caused a doubling of L(p,e). Lower L(p,e) and higher R(e) in PSA as compared with those in BSA suggest that specificity for the autologous albumin is a general phenomenon in mammalian endothelium and that albumin binding to specific sites is associated with its permeability effect. C1 NIDDKD,CELL BIOL & GENET LAB,BLDG 8,RM 403,BETHESDA,MD 20892. UNIV PUERTO RICO,DEPT CHEM ENGN,MAYAGUEZ,PR 00709. UNIV PUERTO RICO,DEPT PHYSIOL,SAN JUAN,PR 00936. US FDA,DIV CARDIORENAL DRUG PROD,BETHESDA,MD 20892. NR 35 TC 13 Z9 13 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 MAY PY 1993 VL 264 IS 5 BP H1382 EP H1387 PN 2 PG 6 WC Physiology SC Physiology GA LD347 UT WOS:A1993LD34700007 ER PT J AU UNGER, EF SHOU, M SHEFFIELD, CD HODGE, E JAYE, M EPSTEIN, SE AF UNGER, EF SHOU, M SHEFFIELD, CD HODGE, E JAYE, M EPSTEIN, SE TI EXTRACARDIAC TO CORONARY ANASTOMOSES SUPPORT REGIONAL LEFT-VENTRICULAR FUNCTION IN DOGS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE NEOVASCULARIZATION; ACIDIC FIBROBLAST GROWTH FACTOR; CARDIOVASCULAR MODELS; MAMMARY ARTERIES; CORONARY CIRCULATION ID FIBROBLAST GROWTH-FACTOR; MYOCARDIAL BLOOD-FLOW; HUMAN-ENDOTHELIAL CELLS; CONSCIOUS DOGS; HEPARIN; LOCALIZATION; INFARCTION; RAT; MICROSPHERES; ARTERY AB Intramyocardial implantation of a systemic artery the internal mammary artery (IMA)] causes angiogenesis, with formation of systemic to coronary anastomoses. In dogs, we assessed the magnitude of IMA-derived nutritive flow and determined its influence on regional contraction. We also sought to determine whether acidic fibroblast growth factor (FGF), an angiogenic peptide, could enhance myocardial neovascularization. Ameroid constrictors and hydraulic balloon occluders were placed on the left anterior descending coronary artery (LAD) of 23 dogs, and the left IMA was implanted in the LAD territory. Dogs were randomized to receive continuous infusions of acidic FGF with heparin, heparin alone, or placebo directly into the IMA for 8 wk. Regional myocardial blood flow was assessed in the conscious state 3 days and 8 wk after operation. Left ventricular function was determined in the anesthetized state at the 8-wk conclusion of treatment. In all dogs, IMA occlusion reduced mean maximal LAD zone perfusion by 28% (P < 0.001), without influencing regional contraction. When IMA occlusion was superimposed on left circumflex coronary artery (LCX) occlusion, LAD zone perfusion declined by 34% (relative to LCX occlusion alone), significantly impairing regional contraction. Treatment with either acidic FGF plus heparin or heparin alone improved IMA-derived collateral flow; however, addition of acidic FGF to heparin afforded no additional advantage over heparin by itself. We conclude that acidic FGF did not enhance myocardial angiogenesis in this model. IMA-derived collateral flow has significant functional importance; however, it is evident in the dog only when other sources of collateral flow are compromised. C1 RHONE POULENC RORER CENT RES,HORSHAM,PA 19044. RP UNGER, EF (reprint author), NHLBI,CARDIOL BRANCH,EXPTL PHYSIOL & PHARMACOL LAB,9000 ROCKVILLE PIKE,BLDG 10,RM 7B15,BETHESDA,MD 20892, USA. NR 39 TC 20 Z9 20 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 MAY PY 1993 VL 264 IS 5 BP H1567 EP H1574 PN 2 PG 8 WC Physiology SC Physiology GA LD347 UT WOS:A1993LD34700032 ER PT J AU MILLER, DS STEWART, DE PRITCHARD, JB AF MILLER, DS STEWART, DE PRITCHARD, JB TI INTRACELLULAR COMPARTMENTATION OF ORGANIC-ANIONS WITHIN RENAL-CELLS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE FLUORESCEIN; KIDNEY; GLUTARATE; P-AMINOHIPPURATE; CRAB URINARY BLADDER; OPOSSUM KIDNEY CELLS; TELEOST PROXIMAL TUBULES; RENAL PROXIMAL TUBULES ID URINARY-BLADDER; TRANSPORT; TOXICITY; LINE; OK AB Epifluorescence microscopy and video-image analysis were used to measure the distribution of the monovalent organic anion fluorescein (FL) within the cells of three organic anion-secreting renal epithelia: crab urinary bladder (a proximal tubule analogue), opossum kidney (OK) cells in culture, and intact, teleost proximal tubules. In all three preparations the intracellular FL distribution was nonuniform. Two distinct intracellular compartments were detected, one being diffuse and cytoplasmic and the other punctate. With low FL concentrations in the medium (1 muM and below) dye accumulation in the punctate compartment exceeded that of the cytoplasm. In crab bladder epithelium FL uptake into both compartments was inhibited by external probenecid, p-aminohippurate (PAH), and LiCl and stimulated by 10-50 muM external glutarate, suggesting that the punctate compartment loaded by a two-step mechanism: transport into the cytoplasm at the basolateral membrane, followed by accumulation at specific intracellular sites. Experiments in which FL was microinjected into OK cells directly demonstrated movement of FL from the cytoplasmic to the punctate compartment. Accumulation in the latter was specific, i.e., inhibitable by coinjected PAH and probenecid, and energy dependent. Together, these findings indicate that during secretion organic anions are sequestered within renal cells. The role of sequestration in overall transport remains to be determined. C1 NIEHS,CELLULAR & MOLEC PHARMACOL LAB,COMPARAT MEMBRANE PHARMACOL SECT,RES TRIANGLE PK,NC 27709. MT DESERT ISL BIOL LAB,SALSBURY COVE,ME 04672. RP MILLER, DS (reprint author), NIEHS,CELLULAR & MOLEC PHARMACOL LAB,INTRACELLULAR REGULAT SECT,RES TRIANGLE PK,NC 27709, USA. NR 21 TC 56 Z9 56 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 MAY PY 1993 VL 264 IS 5 BP R882 EP R890 PN 2 PG 9 WC Physiology SC Physiology GA LD347 UT WOS:A1993LD34700063 PM 8498598 ER PT J AU WOLKOWITZ, OM REUS, VI MANFREDI, F INGBAR, J BRIZENDINE, L WEINGARTNER, H AF WOLKOWITZ, OM REUS, VI MANFREDI, F INGBAR, J BRIZENDINE, L WEINGARTNER, H TI KETOCONAZOLE ADMINISTRATION IN HYPERCORTISOLEMIC DEPRESSION SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Note ID CUSHINGS-SYNDROME; THERAPY AB Ketoconazole, an antiglucocorticoid drug, was administered to 10 hypercortisolemic depressed patients for up to 6 weeks. Three patients dropped out because of side effects or intercurrent illness. The remaining seven had significant ketoconazole-associated decreases in serum cortisol levels and in depression ratings. Antiglucocorticoid agents may be useful probes for investigating the sequelae of hypercortisolemia in patients with major depression. C1 NIAAA,BETHESDA,MD. UNIV CALIF SAN FRANCISCO,DEPT PSYCHIAT,SAN FRANCISCO,CA 94143. UNIV KANSAS,MED CTR,DEPT INTERNAL MED,KANSAS CITY,KS 66103. RI reus, victor/I-7923-2015 OI reus, victor/0000-0002-8193-5697 FU NCRR NIH HHS [RR-05755] NR 16 TC 101 Z9 104 U1 1 U2 1 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAY PY 1993 VL 150 IS 5 BP 810 EP 812 PG 3 WC Psychiatry SC Psychiatry GA LA323 UT WOS:A1993LA32300022 PM 8480829 ER PT J AU GRADY, TA PIGOTT, TA LHEUREUX, F HILL, JL BERNSTEIN, SE MURPHY, DL AF GRADY, TA PIGOTT, TA LHEUREUX, F HILL, JL BERNSTEIN, SE MURPHY, DL TI DOUBLE-BLIND-STUDY OF ADJUVANT BUSPIRONE FOR FLUOXETINE-TREATED PATIENTS WITH OBSESSIVE-COMPULSIVE DISORDER SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Note ID CONTROLLED TRIAL; AUGMENTATION; CLOMIPRAMINE; FLUVOXAMINE; LITHIUM; EFFICACY; PLACEBO AB In a double-blind, crossover study, 13 fluoxetine-treated patients with obsessive-compulsive disorder were given adjuvant buspirone and placebo for 4 weeks each. There were no significant differences between buspirone and placebo in obsessive-compulsive, depressive, or anxiety symptoms. C1 GEORGETOWN UNIV,MED CTR,DEPT PSYCHIAT,WASHINGTON,DC 20007. UNIV MONTREAL,SCH MED,DEPT PSYCHIAT,MONTREAL H3C 3J7,QUEBEC,CANADA. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. RP GRADY, TA (reprint author), DUKE UNIV,MED CTR,DEPT PSYCHIAT,BOX 3837,DURHAM,NC 27710, USA. NR 25 TC 81 Z9 82 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 MAY PY 1993 VL 150 IS 5 BP 819 EP 821 PG 3 WC Psychiatry SC Psychiatry GA LA323 UT WOS:A1993LA32300025 PM 8480832 ER PT J AU HO, SC BACON, WE HARRIS, T LOOKER, A MAGGI, S AF HO, SC BACON, WE HARRIS, T LOOKER, A MAGGI, S TI HIP FRACTURE RATES IN HONG-KONG AND THE UNITED-STATES, 1988 THROUGH 1989 SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID PROXIMAL FEMUR; JAPANESE; OSTEOPOROSIS; HAWAII AB Objectives. Prior studies have suggested that hip fracture rates are substantially lower in Asian countries than in the United States. However, comparisons have been limited by unavailability of recent data, differences in case definition, lack of data from similar time periods, and small sample sizes. This study sought to examine trends by age and sex, with separate statistics for those aged 85 or older. Methods. Hospital discharge data were used to obtain hip fracture incidence in Hong Kong and the United States from 1988 through 1989. Results. Within each population, women had higher hip fracture rates than men. Fracture rates in the United States were significantly higher for both sexes than rates in Hong Kong. For persons over the age of 80, rates of hip fracture among White US males exceeded those for Hong Kong women. Inclusion of transferred cases in hip fracture rates minimized differences between the countries. Conclusions. Despite increasing hip fracture rates in Hong Kong, those rates are still substantially lower than the rates in the United States. Identifying factors responsible for this variation may prove useful in the search for preventive strategies. C1 CTR DIS CONTROL,DIV HLTH CARE STAT,ROOM 952,6525 BELCREST RD,HYATTSVILLE,MD 20782. CHINESE UNIV HONG KONG,DEPT COMMUNITY & FAMILY MED,SHA TIN,HONG KONG. NIH,WHO,RES PROGRAM AGING,BETHESDA,MD 20892. NR 27 TC 62 Z9 66 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD MAY PY 1993 VL 83 IS 5 BP 694 EP 697 DI 10.2105/AJPH.83.5.694 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA LB825 UT WOS:A1993LB82500016 PM 8484451 ER PT J AU OSORNIOVARGAS, AR KALTER, VG BADGETT, A HERNANDEZRODRIGUEZ, N AGUILARDELFIN, I BRODY, AR AF OSORNIOVARGAS, AR KALTER, VG BADGETT, A HERNANDEZRODRIGUEZ, N AGUILARDELFIN, I BRODY, AR TI EARLY-PASSAGE RAT LUNG FIBROBLASTS DO NOT MIGRATE IN-VITRO TO TRANSFORMING GROWTH-FACTOR-BETA SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Note ID TGF-BETA; CHEMOTACTIC MIGRATION; ALVEOLAR MACROPHAGES; PROLIFERATION; STIMULATION; MONOCYTES; HOMOLOG; CELLS AB Lung fibrosis has been postulated to be mediated by the production of macrophage-derived growth factors that are both mitogenic and chemotactic for fibroblasts. In vitro studies from our laboratory demonstrated that alveolar and interstitial macrophages treated with iron and asbestos release platelet-derived growth factor (PDGF) and transforming growth factor-beta (TGF-beta) into the media. This conditioned media was capable of inducing proliferation and chemotaxis of primary rat lung fibroblasts (RLF). TGF-beta is known to be present in the media, and RLF have high-affinity receptors for TGF-beta. However, we found that > 95% of the chemotaxis was blocked by a polyclonal anti-PDGF antibody, whereas anti-TGF-beta did not change cell migration. TGF-beta has been described previously as a potent chemoattractant for fibroblasts. Thus, we tested the potential of purified TGF-beta to induce RLF chemotaxis in an attempt to address this apparent contradiction in results. Four separate preparations of RLFs from four different rats, Swiss 3T3 cells, human and rat fetal skin fibroblasts, and human foreskin fibroblasts were tested for chemotaxis using purified porcine TGF-beta1 as well as human TGF-beta. None of these cells responded chemotactically to TGF-beta over a broad range of concentrations used (0.004 pg/ml to 50 ng/ml). RLF plated at different densities also did not respond to TGF-beta. On the other hand, all the fibroblast types migrated vigorously to PDGF (4 ng/ml). In addition, all of the TGF-beta samples induced rat mononuclear leukocyte chemotaxis (0.5 pg/ml optimal) and clearly inhibited H-3-thymidine incorporation by the RLF as expected (0.005 ng/ml caused 50% inhibition and 0.1 ng/ml maximal inhibition). Although no clear explanation can be offered for the apparent contradiction with current dogma, variables such as cell type, source of TGF-beta, and specific experimental conditions could be contributors to the TGF-beta-induced chemotaxis observed by others. Thus, RLF have high-affinity TGF-beta receptors, yet they lack a chemotactic response to this factor, suggesting that specific intracellular signaling mechanisms regulating biologic activities must be understood before the role of growth factors as chemotactic agents can be clarified. C1 NIEHS,PULM PATHOBIOL LAB,RES TRIANGLE PK,NC 27709. INST NACL CANCEROL,DIV INVEST BAS,MEXICO CITY,MEXICO. RI Osornio Vargas, Alvaro/D-4012-2009; Osornio Vargas, Alvaro/B-4645-2010 OI Osornio Vargas, Alvaro/0000-0001-8287-7102 NR 24 TC 11 Z9 11 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 MAY PY 1993 VL 8 IS 5 BP 468 EP 471 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA LJ669 UT WOS:A1993LJ66900002 PM 8481230 ER PT J AU KUNZELMANN, K SCHWIEBERT, EM ZEITLIN, PL KUO, WL STANTON, BA GRUENERT, DC AF KUNZELMANN, K SCHWIEBERT, EM ZEITLIN, PL KUO, WL STANTON, BA GRUENERT, DC TI AN IMMORTALIZED CYSTIC-FIBROSIS TRACHEAL EPITHELIAL-CELL LINE HOMOZYGOUS FOR THE DELTA-F508 CFTR MUTATION SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID CHLORIDE CONDUCTANCE; MESSENGER-RNA; EXPRESSION; TRANSPORT; GENE; CURRENTS AB The development of transformed human airway epithelial cell lines has been important in advancing the understanding of the biochemical and genetic mechanisms underlying the cystic fibrosis (CF) defect. Since the most common mutation associated with CF is a phenylalanine deletion at position 508 (DELTAF508) in the CF transmembrane conductance regulator (CFTR) gene, a transformed airway epithelial cell line homozygous for this mutation will be important for determining the biologic significance of this mutation in the airways. We report the genotypic and phenotypic characterization of a DELTAF508 homozygote cell line derived from luminal epithelium in the trachea. The cells were transformed with a plasmid containing an origin of replication defective SV40 genome and have progressed through crisis. Immunocytochemical characterization of the cells shows that they express keratin, indicating epithelial cell origin, and that a calcium-dependent cell adhesion molecule, cellCAM 120/80, is present at plasma membrane junctions between cells. Electrophysiologically, the cells show no cAMP-dependent Cl transport. However, after treatment with the calcium ionophore, ionomycin, cells secrete Cl, albeit at a lower level than that observed in normal cells. Genetically, the cells express CFTR mRNA as determined by polymerase chain reaction amplification and CFTR protein as determined by Western hybridization analysis. Karyotypic analysis shows that 70% of the cells contain two copies of chromosome 7. C1 UNIV CALIF SAN FRANCISCO,CARDIOVASC RES INST,DEPT LAB MED,SU203,BOX 0911,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,NIH,CYST FIBROSIS RES CTR,SAN FRANCISCO,CA 94143. DARTMOUTH COLL,DEPT PHYSIOL,NEW LONDON,NH. JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PHYSIOL,BALTIMORE,MD 21205. OI Kunzelmann, Karl/0000-0002-4583-7037 FU NHLBI NIH HHS [HL42368]; NIDDK NIH HHS [DK39619, DK30713] NR 35 TC 84 Z9 85 U1 0 U2 2 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD MAY PY 1993 VL 8 IS 5 BP 522 EP 529 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA LJ669 UT WOS:A1993LJ66900010 PM 7683197 ER PT J AU RANDELL, SH SHIMIZU, T BAKEWELL, W RAMAEKERS, FCS NETTESHEIM, P AF RANDELL, SH SHIMIZU, T BAKEWELL, W RAMAEKERS, FCS NETTESHEIM, P TI PHENOTYPIC MARKER EXPRESSION DURING FETAL AND NEONATAL DIFFERENTIATION OF RAT TRACHEAL EPITHELIAL-CELLS SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID INTERMEDIATE FILAMENT PROTEINS; LUNG; ANTIBODIES; ADULT; PANEL AB The expression of phenotypic markers was examined during fetal and neonatal differentiation of rat tracheal epithelial (RTE) cells. The rat counterpart of human keratin 18 was predominantly found in columnar cells in the adult trachea. It was detected in the primordial tracheal epithelium first seen on gestational day (GD) 12 (term = 21.5 days). Staining intensity gradually increased, and by GD 17 it was principally localized to the apical portion of the epithelium. The rat counterpart of human keratin 19 was barely detectable in the trachea on GD 13 but became abundant in almost all RTE cells on and after GD 19. Morphologically and immunocytochemically identifiable secretory and ciliated cells appeared on GD 18. Ciliated cell number slowly rose while secretory cells increased dramatically on GD 19 through postnatal day 1. The secretory granule antigens detected by monoclonal antibodies RTE 9 and 11 were rare in the adult trachea but were highly expressed in virtually all of the perinatal secretory cells. In contrast, the epitope detected by monoclonal antibody RTE 12, which was present in all adult tracheal surface secretory cells, did not appear until postnatal day 1 and slowly increased. These results demonstrate marked shifts in the biochemical composition of secretory cells during development and postnatal maturation. For the above-mentioned molecules, a similar expression pattern was observed during epithelial regeneration in tracheal grafts (Am. J. Respir. Cell Mol. Biol. 1992; 7:30-41). Pseudostratification of the epithelium and basal cells was first observed on GD 20. Keratin 14, which is confined to basal cells in the normal adult trachea, was not present in the nascent basal cells but appeared after postnatal day 1. In contrast to the present results, during epithelial regeneration in tracheal grafts keratin 14 appeared before markers of highly differentiated secretory or ciliated cells. Thus, the biochemical sequence of cellular differentiation during regeneration did not precisely recapitulate development. C1 MIE UNIV,SCH MED,DEPT OTORHINOLARYNGOL,MIE,JAPAN. UNIV LIMBURG,DEPT MOLEC CELL BIOL & GENET,6200 MD MAASTRICHT,NETHERLANDS. RP RANDELL, SH (reprint author), NIEHS,PULM PATHOBIOL LAB,POB 12233,MD D2-01,RES TRIANGLE PK,NC 27709, USA. NR 18 TC 18 Z9 18 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 MAY PY 1993 VL 8 IS 5 BP 546 EP 555 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA LJ669 UT WOS:A1993LJ66900013 PM 7683198 ER PT J AU CENTER, SA THOMPSON, M GUIDA, L AF CENTER, SA THOMPSON, M GUIDA, L TI 3-ALPHA-HYDROXYLATED BILE-ACID PROFILES IN CLINICALLY NORMAL CATS, CATS WITH SEVERE HEPATIC LIPIDOSIS, AND CATS WITH COMPLETE EXTRAHEPATIC BILE-DUCT OCCLUSION SO AMERICAN JOURNAL OF VETERINARY RESEARCH LA English DT Article ID RAT-LIVER PEROXISOMES; HEPATOBILIARY DISEASES; CHOLIC-ACID; METABOLISM; CIRRHOSIS; SERUM; CONJUGATION; URINE; OBSTRUCTION; TAURINE AB Concentrations of 3alpha-hydroxylated bile acids were measured in serum and urine of clinically normal (healthy) cats (n = 6), cats with severe hepatic lipidosis (n = 9), and cats with complete bile duct occlusion (n = 4). Bile acid concentrations were measured by use of a gradient flow high-performance liquid chromatography procedure with an acetonitrile and ammonium phosphate mobile phase and an in-line postanalytic column containing 3alpha-hydroxysteroid dehydrogenase and a fluorescence detector. Specific identification of all bile acid peaks was not completed; unidentified moieties were represented in terms of their elution time (in minutes). Significant differences in serum and urine bile acid concentrations, quantitative and proportional, were determined among groups of cats. Cats with hepatic lipidosis and bile duct occlusion had significantly (p greater-than-or-equal-to 0.05) greater total serum and urine bile acids concentrations than did healthy cats. The proportion of hydrophobic bile acids in serum, those eluting at greater-than-or-equal-to 400 minutes, was 1.9% for healthy cats, 3.3% for cats with lipidosis, and 5.4% for bile duct-obstructed cats. Both groups of ill cats had a broader spectrum of unidentified late-eluting serum bile acids than did healthy cats; the largest spectrum developed in bile duct-occluded cats. The trihydroxy-to-dihydroxy serum bile acids ratio was 8.8:1 for healthy cats; 24.1:1 for cats with lipidosis; and 20:1 for cats with bile duct obstruction. There was a paucity of glycine-conjugated bile acids in all cats and small quantities of secondary bile acids in ill cats. A significantly (p < 0.05) smaller proportion of unconjugated primary bile acids was detected in sera from ill cats. Serum taurolithocholic acid was detected only in small quantities in cats of each group. There was significantly increased quantity, but lower proportion, of trihydroxy-cholestanoic acid in serum from ill cats, compared with healthy cats. A significantly (p < 0.05) greater proportional amount of unidentified moieties eluting at 130 and 277 minutes was detected in urine of cats with hepatic lipidosis; we believe that the unidentified moiety eluting at 277 minutes is taurocholic acid. Large proportional amounts of taurocholic and cholic acids were detected in urine of all cats, but ill cats had significantly (P < 0.05) greater quantities (quantitatively and proportional). Ill cats had significantly (P < 0.05) more taurocholic than cholic acid in urine. Because taurine is an essential amino acid for cats and is a necessary daily dietary constituent, large urinary losses of taurine in conjugated bile acids may further compromise the health of anorectic cats with severe hepatic lipidosis. C1 NIEHS,RES TRIANGLE PK,NC 27709. S BAY VET GRP,BOSTON,MA 02118. RP CENTER, SA (reprint author), CORNELL UNIV,NEW YORK STATE COLL VET MED,DEPT CLIN SCI,ITHACA,NY 14853, USA. NR 40 TC 13 Z9 13 U1 0 U2 0 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 SN 0002-9645 J9 AM J VET RES JI Am. J. Vet. Res. PD MAY PY 1993 VL 54 IS 5 BP 681 EP 688 PG 8 WC Veterinary Sciences SC Veterinary Sciences GA LA712 UT WOS:A1993LA71200005 PM 8317759 ER PT J AU GAIL, DB AF GAIL, DB TI NATIONAL-INSTITUTES-OF-HEALTH - NATIONAL-HEART-LUNG-AND-BLOOD-INSTITUTE - WORKSHOP ON PULMONARY NEUROENDOCRINE CELLS IN HEALTH AND DISEASE - SEPTEMBER 5-6, 1991 - PREFACE SO ANATOMICAL RECORD LA English DT Editorial Material RP GAIL, DB (reprint author), NHLBI,DIV LUNG DIS,CELL & DEV BIOL BRANCH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0003-276X J9 ANAT REC JI Anat. Rec. PD MAY PY 1993 VL 236 IS 1 BP 4 EP 4 DI 10.1002/ar.1092360103 PG 1 WC Anatomy & Morphology SC Anatomy & Morphology GA KZ646 UT WOS:A1993KZ64600002 ER PT J AU POLAK, JM SPIERS, V CUTZ, E SCHEUERMANN, DW SUNDAY, ME LINNOILA, I GAIL, DB AGUAYO, SM STEPHENS, NL BECKER, KL SOROKIN, SP MILLER, YE CUTTITTA, F JOHNSON, DE HOYT, RF MCDOWELL, EM GOSNEY, JR HUNG, KS SPRINGALL, D AF POLAK, JM SPIERS, V CUTZ, E SCHEUERMANN, DW SUNDAY, ME LINNOILA, I GAIL, DB AGUAYO, SM STEPHENS, NL BECKER, KL SOROKIN, SP MILLER, YE CUTTITTA, F JOHNSON, DE HOYT, RF MCDOWELL, EM GOSNEY, JR HUNG, KS SPRINGALL, D TI SESSION-1 THE ROLE OF PULMONARY NEUROENDOCRINE CELLS DURING DEVELOPMENT INVIVO AND INVITRO SO ANATOMICAL RECORD LA English DT Discussion CT WORKSHOP ON PULMONARY NEUROENDOCRINE CELLS IN HEALTH AND DISEASE CY SEP 05-06, 1991 CL BETHESDA, MD SP NHLBI C1 HAMMERSMITH HOSP,ROYAL POSTGRAD MED SCH,DEPT HISTOPATHOL,LONDON W12 0HS,ENGLAND. HOSP SICK CHILDREN,DEPT PATHOL,TORONTO M5G 1X8,ONTARIO,CANADA. UNIV INSTELLING ANTWERP,DEPT MORPHOL,HISTOL & MICROSCOP ANAT LAB,B-2610 WILRIJK,BELGIUM. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115. NCI,BIOMARKERS & PREVENT RES BRANCH,EXPTL PATHOL SECT,KENSINGTON,MD. NHLBI,DIV LUNG DIS,CELL & DEV BIOL BRANCH,BETHESDA,MD 20892. ATLANTA DEPT VET AFFAIRS MED CTR,PULM DIS SECT,DECATUR,GA. UNIV MANITOBA,WINNIPEG R3T 2N2,MANITOBA,CANADA. GEORGE WASHINGTON UNIV,SCH MED,WASHINGTON,DC 20052. BOSTON UNIV,SCH MED,BOSTON,MA 02118. DEPT VET AFFAIRS MED CTR,DENVER,CO. NIH,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. UNIV MINNESOTA HOSP & CLIN,MINNEAPOLIS,MN 55455. UNIV MARYLAND,SCH MED,DEPT PATHOL,BALTIMORE,MD 21201. UNIV KANSAS,MED CTR,KANSAS CITY,KS 66103. UNIV TORONTO,TORONTO M5S 1A1,ONTARIO,CANADA. RP POLAK, JM (reprint author), HAMMERSMITH HOSP,ROYAL POSTGRAD MED SCH,HISTOCHEM UNIT,LONDON W12 0HS,ENGLAND. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0003-276X J9 ANAT REC JI Anat. Rec. PD MAY PY 1993 VL 236 IS 1 BP 62 EP 67 PG 6 WC Anatomy & Morphology SC Anatomy & Morphology GA KZ646 UT WOS:A1993KZ64600011 ER PT J AU POLAK, JM MILLER, Y SUNDAY, ME CUTTITTA, F SPRINGALL, D STEPHENS, NL SCHEUERMANN, DW AF POLAK, JM MILLER, Y SUNDAY, ME CUTTITTA, F SPRINGALL, D STEPHENS, NL SCHEUERMANN, DW TI SESSION-2 - NEUROENDOCRINE CELLS IN ADULT LUNG SO ANATOMICAL RECORD LA English DT Article; Proceedings Paper CT WORKSHOP ON PULMONARY NEUROENDOCRINE CELLS IN HEALTH AND DISEASE CY SEP 05-06, 1991 CL BETHESDA, MD SP NHLBI C1 HAMMERSMITH HOSP,ROYAL POSTGRAD MED SCH,DEPT HISTOPATHOL,LONDON W12 0HS,ENGLAND. DEPT VET AFFAIRS MED CTR,DENVER,CO. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115. NIH,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. UNIV MANITOBA,WINNIPEG R3T 2N2,MANITOBA,CANADA. UNIV INSTELLING ANTWERP,DEPT MORPHOL,HISTOL & MICROSCOP ANAT LAB,B-2610 WILRIJK,BELGIUM. RP POLAK, JM (reprint author), HAMMERSMITH HOSP,ROYAL POSTGRAD MED SCH,NEONATAL UNIT,LONDON W12 0HS,ENGLAND. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0003-276X J9 ANAT REC JI Anat. Rec. PD MAY PY 1993 VL 236 IS 1 BP 68 EP 69 PG 2 WC Anatomy & Morphology SC Anatomy & Morphology GA KZ646 UT WOS:A1993KZ64600012 ER PT J AU CUTTITTA, F AF CUTTITTA, F TI PEPTIDE AMIDATION - SIGNATURE OF BIOACTIVITY SO ANATOMICAL RECORD LA English DT Article; Proceedings Paper CT WORKSHOP ON PULMONARY NEUROENDOCRINE CELLS IN HEALTH AND DISEASE CY SEP 05-06, 1991 CL BETHESDA, MD SP NHLBI DE PEPTIDE GROWTH FACTORS; GASTRIN-RELEASING PEPTIDE; CRYPTIC PEPTIDE GROWTH FACTORS; PEPTIDYL-GLYCINE; ALPHA-AMIDATING MONOOXYGENASE; POSTTRANSLATIONAL MODIFICATION; PULMONARY NEUROENDOCRINE CELLS; SMALL-CELL CARCINOMA RP CUTTITTA, F (reprint author), NCI,DIV CANC PREVENT & CONTROL,BIOMARKERS & PREVENT RES BRANCH,9610 MED CTR DR,BLDG C,SUITE 300,ROCKVILLE,MD 20850, USA. NR 0 TC 40 Z9 41 U1 1 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0003-276X J9 ANAT REC JI Anat. Rec. PD MAY PY 1993 VL 236 IS 1 BP 87 EP 95 DI 10.1002/ar.1092360112 PG 9 WC Anatomy & Morphology SC Anatomy & Morphology GA KZ646 UT WOS:A1993KZ64600014 PM 8389534 ER PT J AU MILLER, YE SOROKIN, SP SUNDAY, ME BATTEY, JF KEITH, IM BECKER, KC JOHNSON, DE AF MILLER, YE SOROKIN, SP SUNDAY, ME BATTEY, JF KEITH, IM BECKER, KC JOHNSON, DE TI SESSION-3 - CLINICAL ASPECTS OF NEUROENDOCRINE CELL-FUNCTION SO ANATOMICAL RECORD LA English DT Article; Proceedings Paper CT WORKSHOP ON PULMONARY NEUROENDOCRINE CELLS IN HEALTH AND DISEASE CY SEP 05-06, 1991 CL BETHESDA, MD SP NHLBI C1 BOSTON UNIV,SCH MED,BOSTON,MA 02118. HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,BOSTON,MA 02115. NCI,DEV THERAPEUT PROGRAM,MOLEC STRUCT SECT LBC,BETHESDA,MD 20892. UNIV WISCONSIN,SCH VET MED,DEPT COMPARAT BIOSCI,MADISON,WI 53706. GEORGE WASHINGTON UNIV,SCH MED,WASHINGTON,DC 20052. UNIV MINNESOTA HOSP & CLIN,MINNEAPOLIS,MN 55455. RP MILLER, YE (reprint author), DEPT VET AFFAIRS MED CTR,DENVER,CO 80220, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0003-276X J9 ANAT REC JI Anat. Rec. PD MAY PY 1993 VL 236 IS 1 BP 113 EP 114 PG 2 WC Anatomy & Morphology SC Anatomy & Morphology GA KZ646 UT WOS:A1993KZ64600017 ER PT J AU NYLEN, ES BECKER, KL SNIDER, RH TABASSIAN, AR CASSIDY, MM LINNOILA, RI AF NYLEN, ES BECKER, KL SNIDER, RH TABASSIAN, AR CASSIDY, MM LINNOILA, RI TI CHOLINERGIC-NICOTINIC CONTROL OF GROWTH AND SECRETION OF CULTURED PULMONARY NEUROENDOCRINE CELLS SO ANATOMICAL RECORD LA English DT Article; Proceedings Paper CT WORKSHOP ON PULMONARY NEUROENDOCRINE CELLS IN HEALTH AND DISEASE CY SEP 05-06, 1991 CL BETHESDA, MD SP NHLBI DE PNE CELL CULTURE; NICOTINE; CALCITONIN ID INTRAPULMONARY NEUROEPITHELIAL BODIES; BABY MOUSE LUNGS; ENDOCRINE-CELLS; CIGARETTE-SMOKE; CALCITONIN SECRETION; CAROTID-BODY; L-DOPA; RECEPTORS; CANCER; BOMBESIN AB Dispersed newborn hamster lung cells were established in vitro in a defined, low-serum growth medium. Neuroendocrine markers (immunohistochemistry for bombesin/gastrin-releasing peptide and calcitonin) revealed a cellular predominance of pulmonary neuroendocrine (PNE) cells. While the supernatant concentration remained stable, the concentration of PNE cell immunoreactive calcitonin (iCT) gradually declined over 4 weeks. Supplementation of the medium with nicotine for 3 weeks prevented this decline in cellular iCT. Concurrently, the number of cells and [H-3]thymidine incorporation were significantly increased. The stimulatory effect of chronic nicotine was reversed by the coadministration of the nicotinic antagonist hexamethonium. In another set of experiments, prior multiple transplacental nicotine pretreatments resulted in a significant increase in iCT in the lungs of newborns; when these lungs were subsequently placed in cell culture without nicotine, despite the higher concentration of iCT, there was a drop in iCT similar to that observed in the control culture. In contrast, in vivo, the lung iCT remained significantly elevated at 1 week postparturition. Cell culture supernatants were analyzed at week 4 for the evoked release of iCT; cholinergic-nicotinic agonists promptly increased the supernatant iCT, which was blocked by nicotinic but not by muscarinic antagonists. We suggest that this in vitro system provides a useful tool to study directly the PNE cell. The acute and chronic effects of nicotine are most likely related to stimulation of cholinergic-nicotinic receptors on iCT-containing PNE cells. C1 GEORGE WASHINGTON UNIV,SCH MED,VET AFFAIRS MED CTR,DEPT ENDOCRINOL,WASHINGTON,DC 20422. NCI,USN,ONCOL BRANCH,BETHESDA,MD 20892. RP NYLEN, ES (reprint author), GEORGE WASHINGTON UNIV,SCH MED,VET AFFAIRS MED CTR,DEPT PHYSIOL,50 IRVING ST NW,WASHINGTON,DC 20422, USA. NR 48 TC 22 Z9 22 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 0003-276X J9 ANAT REC JI Anat. Rec. PD MAY PY 1993 VL 236 IS 1 BP 129 EP 135 DI 10.1002/ar.1092360117 PG 7 WC Anatomy & Morphology SC Anatomy & Morphology GA KZ646 UT WOS:A1993KZ64600020 PM 8506998 ER PT J AU BATTEY, JF SOROKIN, SP POLAK, JM HOYT, RF CUTZ, E MONTAG, A CUTTITTA, F LINNOILA, I MILLER, YE STEPHENS, NL AF BATTEY, JF SOROKIN, SP POLAK, JM HOYT, RF CUTZ, E MONTAG, A CUTTITTA, F LINNOILA, I MILLER, YE STEPHENS, NL TI SESSION-4 - NEW APPROACHES AND FUTURE-DIRECTIONS SO ANATOMICAL RECORD LA English DT Article; Proceedings Paper CT WORKSHOP ON PULMONARY NEUROENDOCRINE CELLS IN HEALTH AND DISEASE CY SEP 05-06, 1991 CL BETHESDA, MD SP NHLBI C1 BOSTON UNIV,SCH MED,DEPT ANAT & NEUROBIOL,PULM CELL BIOL LAB,BOSTON,MA 02118. HAMMERSMITH HOSP,ROYAL POSTGRAD MED SCH,HISTOCHEM UNIT,LONDON W12 0HS,ENGLAND. HAMMERSMITH HOSP,ROYAL POSTGRAD MED SCH,DEPT HISTOPATHOL,LONDON W12 0HS,ENGLAND. UNIV TORONTO,TORONTO M5S 1A1,ONTARIO,CANADA. HOSP SICK CHILDREN,TORONTO M5G 1X8,ONTARIO,CANADA. UNIV CHICAGO,CHICAGO,IL 60637. NIH,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. NCI,BIOMARKERS & PREVENT RES BRANCH,EXPTL PATHOL SECT,KENSINGTON,MD. DEPT VET AFFAIRS MED CTR,DENVER,CO. UNIV MANITOBA,WINNIPEG R3T 2N2,MANITOBA,CANADA. RP BATTEY, JF (reprint author), NCI,DEV THERAPEUT PROGRAM,MOLEC STRUCT SECT LBC,BETHESDA,MD 20892, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0003-276X J9 ANAT REC JI Anat. Rec. PD MAY PY 1993 VL 236 IS 1 BP 144 EP 151 PG 8 WC Anatomy & Morphology SC Anatomy & Morphology GA KZ646 UT WOS:A1993KZ64600022 PM 8389530 ER PT J AU LINNOILA, RI GAZDAR, AF FUNA, K BECKER, KL AF LINNOILA, RI GAZDAR, AF FUNA, K BECKER, KL TI LONG-TERM SELECTIVE CULTURE OF HAMSTER PULMONARY ENDOCRINE-CELLS SO ANATOMICAL RECORD LA English DT Article; Proceedings Paper CT WORKSHOP ON PULMONARY NEUROENDOCRINE CELLS IN HEALTH AND DISEASE CY SEP 05-06, 1991 CL BETHESDA, MD SP NHLBI DE DIFFUSE NEUROENDOCRINE SYSTEM; IMMUNOREACTIVE CALCITONIN; SMALL CELL LUNG CANCER; SPECIFIC PRODUCTS; GENERAL NE MARKERS ID L-DOPA DECARBOXYLASE; LUNG-CANCER; SUPPLEMENTED MEDIUM; GROWTH-FACTOR; CALCITONIN; INVITRO; LINES; DIETHYLNITROSAMINE; DIFFERENTIATION; EXPRESSION AB We describe, for the first time, the development of a technique for a long-term selective culture of endocrine (PE) cells from the lungs of normal animals. Epithelial cells were isolated from 1-day-old hamster lungs through mechanical and enzymatic dissociation with collagenase type II. Cells were then cultured in HITES medium which contained RPMI 1640, hydrocortisone, insulin, transferrin, estradiol, sodium selenite, and supplemented with 5% fetal bovine serum (FBS), or medium which contained HITES medium supplemented with bovine serum albumin, phosphoethanolamine, arginine vasopressin, bombesin, and 2% FBS (9N). HITES medium, originally developed for establishment and long-term culture of human small cell lung cancer (SCLC) cell lines, allowed propagation of normal hamster PE cells up to 12 months as a mixed floating-attached cell culture. No difference was noted in the results using HITES or 9N. By 3 months, 80% of the cultured cells contained characteristic dense-core (endocrine type) granules. The cultured PE cells also expressed creatine kinase brain isoenzyme, and general NE markers including neuron specific enolase, and amine handling enzyme activity within the range of SCLC cell lines. Moreover, cultured PE cells contained and secreted immunoreactive calcitonin (iCT) which had a molecular profile similar to that of intact hamster lung. This long-term culture technique should markedly assist in elucidating the role of PE cells in health and disease. C1 NCI,USN,MED ONCOL BRANCH,BETHESDA,MD 20892. UNIV TEXAS,SW MED CTR,SIMMONS MED CTR,DALLAS,TX 75230. UNIV TEXAS,SW MED CTR,DEPT PATHOL,DALLAS,TX 75230. GEORGE WASHINGTON UNIV,WASHINGTON,DC 20052. VET AFFAIRS MED CTR,WASHINGTON,DC. NR 31 TC 10 Z9 10 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 0003-276X J9 ANAT REC JI Anat. Rec. PD MAY PY 1993 VL 236 IS 1 BP 231 EP 240 DI 10.1002/ar.1092360128 PG 10 WC Anatomy & Morphology SC Anatomy & Morphology GA KZ646 UT WOS:A1993KZ64600033 PM 8389531 ER PT J AU SNELLER, MC STROBER, W EISENSTEIN, E JAFFE, JS CUNNINGHAMRUNDLES, C AF SNELLER, MC STROBER, W EISENSTEIN, E JAFFE, JS CUNNINGHAMRUNDLES, C TI NEW INSIGHTS INTO COMMON VARIABLE IMMUNODEFICIENCY SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE COMMON VARIABLE IMMUNODEFICIENCY; AGAMMAGLOBULINEMIA; AUTOIMMUNE DISEASES; BACTERIAL INFECTIONS; LYMPHOPROLIFERATIVE DISORDERS ID EPSTEIN-BARR VIRUS; LINKED LYMPHOPROLIFERATIVE SYNDROME; PERIPHERAL-BLOOD LYMPHOCYTES; INTRAVENOUS GAMMA-GLOBULIN; T-CELL; VARIED IMMUNODEFICIENCY; HYPOGAMMAGLOBULINEMIA; DEFICIENCY; INFECTION; IMMUNOGLOBULIN AB Common variable immunodeficiency (CVI) is a heterogenous immunodeficiency syndrome characterized by hypogammaglobulinemia, recurrent bacterial infections, and various immunologic abnormalities. In addition to recurrent infections, patients with this syndrome also have an increased incidence of autoimmune disease and malignancy. Because the spectrum of associated diseases is broad, patients with CVI are seen by various medical specialists. This review discusses the pathogenesis, clinical manifestations, diagnosis, and treatment of CVI. C1 NIAID,IMMUNOREGULAT LAB,BLDG 10,ROOM 11N250,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. HAHNEMANN UNIV,PHILADELPHIA,PA 19102. MT SINAI MED CTR,DEPT MED,NEW YORK,NY 10029. MT SINAI MED CTR,DEPT PEDIAT,NEW YORK,NY 10029. NR 60 TC 188 Z9 190 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAY 1 PY 1993 VL 118 IS 9 BP 720 EP 730 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA KY502 UT WOS:A1993KY50200011 PM 8460860 ER PT J AU SMITH, ME STONE, LA ALBERT, PS FRANK, JA MARTIN, R ARMSTRONG, M MALONI, H MCFARLIN, DE MCFARLAND, HF AF SMITH, ME STONE, LA ALBERT, PS FRANK, JA MARTIN, R ARMSTRONG, M MALONI, H MCFARLIN, DE MCFARLAND, HF TI CLINICAL WORSENING IN MULTIPLE-SCLEROSIS IS ASSOCIATED WITH INCREASED FREQUENCY AND AREA OF GADOPENTETATE DIMEGLUMINE ENHANCING MAGNETIC-RESONANCE-IMAGING LESIONS SO ANNALS OF NEUROLOGY LA English DT Article ID GADOLINIUM-DTPA ENHANCEMENT; RELAPSING PATIENTS; MRI; SERIAL AB It is now well established that clinically stable patients with relapsing-remitting multiple sclerosi have ongoing disease activity when evaluated by serial gadolinium-enhanced (Gd-DTPA) magnetic resonance imaging (MRI) scans. Despite this, the relationship between clinical disease and MRI lesions, though suspected, has not been extensively documented. The relationship between Gd-DTPA MRI lesions and clinical disease was examined in this study of 9 patients with mild relapsing-remitting multiple sclerosis (Expanded Disability Status Scale [EDSS] <3.5) who had 24 to 37 monthly Gd-DTPA MRI scans, neurological examinations, and EDSS score assignments. The area and frequency of Gd-DTPA lesions were examined during months with and without clinical worsening as measured by EDSS. Forty-one episodes of clinical worsening were noted during the study. A significant association was observed between these periods of clinical worsening and MRI parameters, including increases in total number, number of new lesions, and the total area of enhancement. Logistic regression analysis showed a significant effect of the number and area of Gd-DTPA MRI lesions on both the onset and continuation of clinical worsening, confirming an important relationship between clinical disease and an increase in cerebral Gd-DTPA MRI activity. A relationship with long-term disability was suggested, but cannot be confirmed without longer follow-up of these patients. C1 NINCDS,BIOMETRY & FIELD STUDIES BRANCH,BETHESDA,MD. NIH,DIAGNOST RADIOL RES PROGRAM,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. UNIV TUBINGEN,DEPT NEUROL,W-7400 TUBINGEN 1,GERMANY. RP SMITH, ME (reprint author), NINCDS,NEUROIMMUNOL BRANCH,BLDG 10,ROOM 5B16,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 32 TC 224 Z9 225 U1 1 U2 3 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD MAY PY 1993 VL 33 IS 5 BP 480 EP 489 DI 10.1002/ana.410330511 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA LB681 UT WOS:A1993LB68100010 PM 8498825 ER PT J AU SMITH, ME KATZ, DA HARRIS, JO FRANK, JA KUFTA, CV MCFARLIN, DE AF SMITH, ME KATZ, DA HARRIS, JO FRANK, JA KUFTA, CV MCFARLIN, DE TI SYSTEMIC HISTIOCYTOSIS PRESENTING AS MULTIPLE-SCLEROSIS SO ANNALS OF NEUROLOGY LA English DT Note ID ERDHEIM-CHESTER DISEASE AB A patient resembling one with Progressive multiple sclerosis in clinical presentation and by magnetic resonance imaging was studied in detail. Some features atypical for multiple sclerosis prompted a persistent search for an alternative cause. The diagnosis of a non-Langerhans systemic histiocytosis involving brain and bone was established and showed a partial response to radiation therapy. This patient illustrates the continued importance of a broad approach to the evaluation of possible multiple sclerosis, with particular attention to atypical features. C1 NINCDS,SURG NEUROL BRANCH,BETHESDA,MD 20892. NINCDS,OFF CLID DIRECTOR,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. NIH,DIAGNOST REDIOL RES PROGRAM,BETHESDA,MD 20892. RP SMITH, ME (reprint author), NINCDS,NEUROIMMUNOL BRANCH,BLDG 10,ROOM 5B-16,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 17 TC 24 Z9 24 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD MAY PY 1993 VL 33 IS 5 BP 549 EP 554 DI 10.1002/ana.410330521 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA LB681 UT WOS:A1993LB68100020 PM 8498832 ER PT J AU DEBENEDETTI, L VARESCO, L PELLEGATA, NS LOSI, L GISMONDI, V CASARINO, L SCIALLERO, S BONELLI, L BITICCHI, R BAFICO, A MASETTI, E JAMES, R HEOUAINE, A RANZANI, GN ASTE, H FERRARA, G AF DEBENEDETTI, L VARESCO, L PELLEGATA, NS LOSI, L GISMONDI, V CASARINO, L SCIALLERO, S BONELLI, L BITICCHI, R BAFICO, A MASETTI, E JAMES, R HEOUAINE, A RANZANI, GN ASTE, H FERRARA, G TI GENETIC EVENTS IN SPORADIC COLORECTAL ADENOMAS - K-RAS AND P53 HETEROZYGOUS MUTATIONS ARE NOT SUFFICIENT FOR MALIGNANT PROGRESSION SO ANTICANCER RESEARCH LA English DT Article DE K-RAS; P53; COLORECTAL CANCER ID TUMORIGENESIS; DNA; IDENTIFICATION; ONCOGENES; CANCER; COLON; OCCUR AB Twenty-four sporadic colorectal adenomas were analysed for the presence of allelic loss on the short arm of chromosome 17 as well as mutations in the K-ras and p53 genes. Chromosome 17p13 allelic loss was not present in 14 out of 14 informative cases. K-ras mutations were observed in 15 out of 24 cases. A p53 gene mutation (GGC --> GAC at codon 245) was detected in two biopsies taken at a four year interval from a recurrent rectal villous adenoma. Both biopsies also contained the same K-ras gene mutation (GGT --> GTT at codon 12). The data from the recurrent rectal adenoma provide in vivo evidence that K-ras and p53 heterozygous mutations confer a proliferative advantage but together are not sufficient for malignant transformation. C1 NATL CANC INST,IST,VIALE BENEDETTO XV10,I-16132 GENOA,ITALY. UNIV MODENA,INST PATHOL,I-41100 MODENA,ITALY. UNIV PAVIA,DEPT GENET & MICROBIOL,I-27100 PAVIA,ITALY. UNIV PAVIA,IMMUNOGENET LAB,I-27100 PAVIA,ITALY. UNIV PAVIA,EPIDEMIOL & TRIALS UNIT,I-27100 PAVIA,ITALY. RI Losi, Lorena/B-2583-2012; Pellegata, Natalia/I-1256-2012; OI Losi, Lorena/0000-0002-8483-3936; Pellegata, Natalia S./0000-0002-8000-7784 NR 23 TC 13 Z9 13 U1 0 U2 1 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD MAY-JUN PY 1993 VL 13 IS 3 BP 667 EP 670 PG 4 WC Oncology SC Oncology GA LK374 UT WOS:A1993LK37400019 PM 8317895 ER PT J AU CHEN, JM ZHANG, YP SUI, JL MOSCHEL, RC IKENAGA, M AF CHEN, JM ZHANG, YP SUI, JL MOSCHEL, RC IKENAGA, M TI MODULATION OF O-6-METHYLGUANINE-DNA METHYLTRANSFERASE-MEDIATED 1-(4-AMINO-2-METHYL-5-PYRIMIDINYL) METHYL-3-(2-CHLOROETHYL)-3-NITROSOUREA RESISTANCE BY O-6-BENZYLGUANINE IN-VITRO AND IN-VIVO SO ANTICANCER RESEARCH LA English DT Article DE O-6-METHYLGUANINE-DNA METHYLTRANSFERASE; ACNU RESISTANCE; CANCER CHEMOTHERAPY; O-6-BENZYLGUANINE ID HUMAN-TUMOR-CELLS; MAMMALIAN O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; ALKYLATING-AGENTS; CROSS-LINKING; DNA; REPAIR; SENSITIVITY; STRAINS; CHLOROETHYLNITROSOUREA; O6-METHYLGUANINE AB Our previous studies have indicated that O6-methylguanine-DNA methyltransferase (MGMT) is a key factor determining tumor cellular resistance to 1- (4-amino-2-methyl- 5- pyrimidinyl) methyl-3-(2-chloroethyl)-3- nitrosourea (ACNU). This study describes the modulation of MGMT-mediated ACNU resistance by O6-benzylguanine pretreatment. The ACNU sensitivity of MGMT proficient human tumor HeLa S3, SMMC-7721, anti Cc801 cells in tissue culture was markly enhanced by 10 mm O6 -benzylguanine, and a correlation between the extent of enhancement and the level of MGMT acitivities was observed. A single i.p. injection of 100 mg/kg of O6-benzylguanine caused a complete inhibition of MGMT acitivities in HeLa S3 tumor xenografts and combination of O6-benzylguanine with ACNU (7.5 mg/kg) significantly inhibited HeLa S3 tumor growth. The results demonstrated that O6-benzylguanine could be used as a potential adjuvant in combination chemotherapy with ACNU to treat MGMT proficient tumors. C1 INST RADIAT MED,DEPT BIOCHEM,27 TAI PING RD,BEIJING 100850,PEOPLES R CHINA. KYOTO UNIV,CTR RADIAT BIOL,SAKYO KU,KYOTO 606,JAPAN. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,CHEM CARCINOGENESIS LAB,FREDERICK,MD 21702. NR 24 TC 12 Z9 14 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD MAY-JUN PY 1993 VL 13 IS 3 BP 801 EP 806 PG 6 WC Oncology SC Oncology GA LK374 UT WOS:A1993LK37400042 PM 8317915 ER PT J AU HIZI, A TAL, R SHAHARABANY, M CURRENS, MJ BOYD, MR HUGHES, SH MCMAHON, JB AF HIZI, A TAL, R SHAHARABANY, M CURRENS, MJ BOYD, MR HUGHES, SH MCMAHON, JB TI SPECIFIC-INHIBITION OF THE REVERSE-TRANSCRIPTASE OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 AND THE CHIMERIC ENZYMES OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 AND TYPE-2 BY NONNUCLEOSIDE INHIBITORS SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ESCHERICHIA-COLI; ANTIVIRAL ACTIVITY; HIV-1 REPLICATION; DERIVATIVES; RESISTANCE; AIDS; SENSITIVITY; MUTANTS; AZT AB We have studied the effects of four nonnucleoside inhibitors, including the novel natural product inhibitor calanolide A, on molecular chimeras containing complementary segments of human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) reverse transcriptases (RTs). All four compounds specifically inhibited the DNA polymerase activity of HIV-1 RT but had no apparent effect on the RNase H activity of this enzyme or on the DNA polymerase or RNase H activity of HIV-2 RT. Three of these compounds showed the generally expected patterns of resistance and susceptibility with the various chimeric RTs. However, the inhibition patterns of the chimeric RTs by calanolide A provided evidence that there is a segment between residues 94 and 157 in HIV-1 RT that is critical for inhibition. However, the data also suggest that there may be a second segment located between amino acids 225 and 427 in HIV-1 RT that is also important for specifying susceptibility to the drug. C1 NCI,FREDERICK CANC RES & DEV CTR,ADV BIOSCI LABS,BASIC RES PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,DRUG DISCOVERY RES & DEV LAB,FREDERICK,MD 21702. RP HIZI, A (reprint author), TEL AVIV UNIV,SACKLER SCH MED,DEPT CELL BIOL & HISTOL,IL-69978 TEL AVIV,ISRAEL. FU NCI NIH HHS [N01-CO-74101]; NIAID NIH HHS [R01-AI27035] NR 44 TC 80 Z9 82 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAY PY 1993 VL 37 IS 5 BP 1037 EP 1042 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA LA017 UT WOS:A1993LA01700019 PM 7685994 ER PT J AU JAPOUR, AJ MAYERS, DL JOHNSON, VA KURITZKES, DR BECKETT, LA ARDUINO, JM LANE, J BLACK, RJ REICHELDERFER, PS DAQUILA, RT CRUMPACKER, CS BALFOUR, H ERICE, A COOMBS, R KATZENSTEIN, D LATHEY, J RICHMAN, D MCINTOSH, K RANGAN, S REICHMAN, R SCOTT, W USSERY, M ABRAMS, L MCCUTCHAN, F BURKE, D GARDNER, L ROBERTS, C CHUNG, R HICKS, C SHELLIE, E FOWLER, A MERRITT, L FUJIMURAJUSTICE, M RUIZ, N WAGNER, K GAIL, M AF JAPOUR, AJ MAYERS, DL JOHNSON, VA KURITZKES, DR BECKETT, LA ARDUINO, JM LANE, J BLACK, RJ REICHELDERFER, PS DAQUILA, RT CRUMPACKER, CS BALFOUR, H ERICE, A COOMBS, R KATZENSTEIN, D LATHEY, J RICHMAN, D MCINTOSH, K RANGAN, S REICHMAN, R SCOTT, W USSERY, M ABRAMS, L MCCUTCHAN, F BURKE, D GARDNER, L ROBERTS, C CHUNG, R HICKS, C SHELLIE, E FOWLER, A MERRITT, L FUJIMURAJUSTICE, M RUIZ, N WAGNER, K GAIL, M TI STANDARDIZED PERIPHERAL-BLOOD MONONUCLEAR CELL-CULTURE ASSAY FOR DETERMINATION OF DRUG SUSCEPTIBILITIES OF CLINICAL HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ISOLATES SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID HIV-1 REVERSE-TRANSCRIPTASE; ZIDOVUDINE AZT; REDUCED SENSITIVITY; RESISTANT; INHIBITORS; THERAPY; INVITRO AB A standardized antiviral drug susceptibility assay for clinical human immunodeficiency virus type 1 (HIV-1) isolates has been developed for use in clinical trials. The protocol is a two-step procedure that first involves cocultivation of patient infected peripheral blood mononuclear cells (PBMC) with seronegative phytohemag-glutinin-stimulated donor PBMC to obtain an HIV-1 stock. The virus stock is titrated for viral infectivity (50% tissue culture infective dose) by use of serial fourfold virus dilutions in donor PBMC. A standardized inoculum of 1,000 50% tissue culture infective doses per 10(6) cells is used in the second step of the procedure to acutely infect seronegative donor PBMC in a 7-day microtiter plate assay with triplicate wells containing zidovudine (ZDV) concentrations ranging from 0 to 5.0 muM. The ZDV 50% inhibitory concentrations (IC50) for reference ZDV-susceptible and ZDV-resistant HIV-1 isolates ranged from 0.002 to 0.113 muM and from 0.15 to >5.0 muM, respectively. Use of this consensus protocol reduced interlaboratory variability for ZDV IC50 determinations with reference HIV-1 isolates. Among eight laboratories, the coefficient of variation ranged from 0.85 to 1.25 with different PBMC protocols and was reduced to 0.39 to 0.98 with the standardized assay. Among the clinical HIV-1 isolates assayed by the standardized drug susceptibility assay, the median ZDV IC50 increased gradually with more ZDV therapy. This protocol provides an efficient and reproducible means to assess the in vitro susceptibility to antiretroviral agents of virtually all clinical HIV-1 isolates. C1 WALTER REED ARMY INST RES, DEPT DIAGNOST RETROVIROL, ROCKVILLE, MD 20850 USA. USN, MED RES INST, ROCKVILLE, MD 20850 USA. SRA TECHNOL, ROCKVILLE, MD 20850 USA. UNIV ALABAMA, SCH MED, DIV INFECT DIS, BIRMINGHAM, AL 35294 USA. UNIV COLORADO, HLTH SCI CTR, DIV INFECT DIS, DENVER, CO 80262 USA. HARVARD UNIV, SCH PUBL HLTH, CTR STAT DATA ANAL, BOSTON, MA 02115 USA. NIAID, DIV AIDS, BETHESDA, MD 20892 USA. NATL NAVAL MED CTR, BETHESDA, MD 20814 USA. HARVARD UNIV, MASSACHUSETTS GEN HOSP E, SCH MED, INFECT DIS UNIT, BOSTON, MA 02129 USA. UNIV MINNESOTA, MINNEAPOLIS, MN 55455 USA. STANFORD UNIV, MED CTR, SCH MED, STANFORD, CA 94305 USA. UNIV WASHINGTON, SEATTLE, WA 98195 USA. UNIV CALIF SAN DIEGO, LA JOLLA, CA 92093 USA. HARVARD UNIV, CHILDRENS HOSP, SCH MED, BOSTON, MA 02115 USA. TULANE UNIV, MED CTR, NEW ORLEANS, LA 70118 USA. UNIV ROCHESTER, ROCHESTER, NY 14627 USA. UNIV MIAMI, SCH MED, MIAMI, FL 33152 USA. HENRY M JACKSON FDN, BETHESDA, MD USA. WALTER REED ARMY INST RES, WASHINGTON, DC 20307 USA. WALTER REED ARMY MED CTR, WASHINGTON, DC 20307 USA. RP JAPOUR, AJ (reprint author), HARVARD UNIV, BETH ISRAEL HOSP, SCH MED, DIV INFECT DIS, BOSTON, MA 02215 USA. OI /0000-0002-5704-8094 FU NIAID NIH HHS [AI 62534, AI 27659, AI 29173] NR 31 TC 250 Z9 260 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAY PY 1993 VL 37 IS 5 BP 1095 EP 1101 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA LA017 UT WOS:A1993LA01700028 PM 8517697 ER PT J AU LEWIS, EN TREADO, PJ LEVIN, IW AF LEWIS, EN TREADO, PJ LEVIN, IW TI A MINIATURIZED, NO-MOVING-PARTS RAMAN SPECTROMETER SO APPLIED SPECTROSCOPY LA English DT Article DE RAMAN SPECTROSCOPY; INSTRUMENTATION; SPECTROMETRY; ACOUSTOOPTICS; ACOUSTOOPTIC TUNABLE FILTER (AOTF); SILICON AVALANCHE PHOTODIODE; PHOTON-COUNTING; KRYPTON LASER; HOLOGRAPHIC FILTER; REMOTE SENSING; ENVIRONMENTAL MONITORING; PROCESS MONITORING ID SPECTROSCOPY; FILTER AB A solid-state acousto-optic tunable filter (AOTF) is combined with krypton laser excitation (647 nm), holographic Raman filters, and photon-counting silicon avalanche photodiode (APD) detection to construct a miniaturized Raman spectrometer with no moving parts. The physically compact AOTF and the highly integrated APD provide a rugged, digitally controlled spectrometer of moderate spectral resolution and with a footprint comparable in size to a laboratory notebook. Instrument design details are considered and representative spectra are reported. Potential areas of application for this prototype Raman spectrometer are also discussed. C1 UNIV PITTSBURGH,DEPT CHEM,PITTSBURGH,PA 15260. RP LEWIS, EN (reprint author), NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892, USA. NR 31 TC 49 Z9 49 U1 0 U2 5 PU SOC APPLIED SPECTROSCOPY PI FREDERICK PA PO BOX 1438, FREDERICK, MD 21701 SN 0003-7028 J9 APPL SPECTROSC JI Appl. Spectrosc. PD MAY PY 1993 VL 47 IS 5 BP 539 EP 543 DI 10.1366/0003702934067144 PG 5 WC Instruments & Instrumentation; Spectroscopy SC Instruments & Instrumentation; Spectroscopy GA LE575 UT WOS:A1993LE57500004 ER PT J AU SCHAFER, SJ LUYTEN, FP YANAGISHITA, M REDDI, AH AF SCHAFER, SJ LUYTEN, FP YANAGISHITA, M REDDI, AH TI PROTEOGLYCAN METABOLISM IS AGE-RELATED AND MODULATED BY ISOFORMS OF PLATELET-DERIVED GROWTH-FACTOR IN BOVINE ARTICULAR-CARTILAGE EXPLANT CULTURES SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID MONOLAYER-CULTURE; CHONDROCYTES; BIOSYNTHESIS; SERUM C1 JOHNS HOPKINS UNIV,SCH MED,DEPT ORTHOPAED SURG,MUSCULOSKELETAL CELL BIOL LAB,720 RUTLAND AVE,BALTIMORE,MD 21205. NIDR,BONE RES BRANCH,BETHESDA,MD 20892. NIH,HOWARD HUGHES MED INST,RES SCHOLARS PROGRAM,BETHESDA,MD 20892. NR 28 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 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD MAY 1 PY 1993 VL 302 IS 2 BP 431 EP 438 DI 10.1006/abbi.1993.1236 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA KZ267 UT WOS:A1993KZ26700021 PM 8489248 ER PT J AU CALVO, JC GANDJBAKHCHE, AH NOSSAL, R HASCALL, VC YANAGISHITA, M AF CALVO, JC GANDJBAKHCHE, AH NOSSAL, R HASCALL, VC YANAGISHITA, M TI RHEOLOGICAL EFFECTS OF THE PRESENCE OF HYALURONIC-ACID IN THE EXTRACELLULAR MEDIA OF DIFFERENTIATED 3T3-L1 PREADIPOCYTE CULTURES SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID LIPOPROTEIN-LIPASE ACTIVITY; CARTILAGE PROTEOGLYCANS; AGGREGATION; ADIPOCYTES; CELLS; PROTEIN C1 NIH,DIV COMP RES & TECHNOL,PHYS SCI LAB,BETHESDA,MD 20892. RP CALVO, JC (reprint author), NIDR,BONE RES BRANCH,PROTEOGLYCAN CHEM SECT,BETHESDA,MD 20892, USA. NR 27 TC 10 Z9 10 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD MAY 1 PY 1993 VL 302 IS 2 BP 468 EP 475 DI 10.1006/abbi.1993.1241 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA KZ267 UT WOS:A1993KZ26700026 PM 7683859 ER PT J AU PRUSSICK, R THIBAULT, A TURNER, ML AF PRUSSICK, R THIBAULT, A TURNER, ML TI RECALL OF CUTANEOUS TOXICITY FROM FLUOROURACIL SO ARCHIVES OF DERMATOLOGY LA English DT Letter ID COLONY-STIMULATING FACTOR; GRANULOCYTE C1 NCI,ONCOL BRANCH,BETHESDA,MD 20892. RP PRUSSICK, R (reprint author), NCI,DERMATOL BRANCH,BETHESDA,MD 20892, USA. NR 10 TC 5 Z9 5 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD MAY PY 1993 VL 129 IS 5 BP 644 EP 645 PG 2 WC Dermatology SC Dermatology GA LB403 UT WOS:A1993LB40300019 PM 8481029 ER PT J AU MILSTONE, LM BALE, SJ INSOGNA, KL AF MILSTONE, LM BALE, SJ INSOGNA, KL TI SECONDARY HYPERPARATHYROIDISM IN PATIENTS WITH ICHTHYOSIS IS NOT CAUSED BY VITAMIN-D DEFICIENCY OR INGESTION OF RETINOIDS SO ARCHIVES OF DERMATOLOGY LA English DT Letter C1 NIAID,SKIN BIOL BRANCH,BETHESDA,MD 20892. YALE UNIV,SCH MED,DEPT MED,NEW HAVEN,CT 06510. RP MILSTONE, LM (reprint author), YALE UNIV,SCH MED,DEPT DERMATOL,NEW HAVEN,CT 06510, USA. NR 1 TC 9 Z9 9 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD MAY PY 1993 VL 129 IS 5 BP 648 EP 648 PG 1 WC Dermatology SC Dermatology GA LB403 UT WOS:A1993LB40300022 PM 8481031 ER PT J AU ZAMETKIN, AJ LIEBENAUER, LL FITZGERALD, GA KING, AC MINKUNAS, DV HERSCOVITCH, P YAMADA, EM COHEN, RM AF ZAMETKIN, AJ LIEBENAUER, LL FITZGERALD, GA KING, AC MINKUNAS, DV HERSCOVITCH, P YAMADA, EM COHEN, RM TI BRAIN METABOLISM IN TEENAGERS WITH ATTENTION-DEFICIT HYPERACTIVITY DISORDER SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; GLUCOSE-METABOLISM; CHILDREN; METHYLPHENIDATE; DYSFUNCTION; ADOLESCENTS; SYMPTOMS; PARENT AB Objectives: We sought to obtain and compare values of cerebral glucose metabolism in normal minors and minors with Attention Deficit Hyperactivity Disorder (ADHD). We also sought to confirm our earlier findings of reduced brain metabolism in adults with ADHD, and to examine whether these results might be diagnostically useful. Design: Case-control study. Setting: Adolescents were recruited to National Institutes of Health Clinical Center/Research Facility through advertisement at local high schools and ADHD organizations. Patients: Subjects were 10 normal adolescents and 10 adolescents with ADHD diagnosed with structured interviews using DSM-III-R criteria. Main Outcome Measures: Positron emission tomography and fludeoxyglucose F18 were used to study cerebral glucose metabolism in minors while they performed an auditory-attention task. Results: Global or absolute measures of metabolism did not statistically differ between groups, although hyperactive girls had a 17.6% lower absolute brain metabolism than normal girls. As compared with the values for the controls, normalized glucose metabolism was significantly reduced in six of 60 specific regions of the brain, including an area of the left anterior frontal lobe (P<.05). Lower metabolism in that specific region of the left anterior frontal lobe was significantly inversely correlated with measures of symptom severity (P<.001-.009, r=-.56 to -.67). Conclusions: Global or absolute measures of metabolism using positron emission tomography and fludeoxyglucose F18 did not statistically differentiate between normal adolescents with ADHD. Positron emission tomography scans can be performed and are well tolerated by normal teenagers and teenagers with ADHD. The feasibility of normal minors participating in research involving radiation was established. C1 NIH,PET IMAGING SYST,BETHESDA,MD 20892. RP ZAMETKIN, AJ (reprint author), NIMH,CLIN BRAIN IMAGING SECT,BLDG 10,ROOM 4N317,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 30 TC 237 Z9 239 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD MAY PY 1993 VL 50 IS 5 BP 333 EP 340 PG 8 WC Psychiatry SC Psychiatry GA LB877 UT WOS:A1993LB87700001 PM 8489322 ER PT J AU MURPHY, DGM BOTTOMLEY, PA SALERNO, JA DECARLI, C MENTIS, MJ GRADY, CL TEICHBERG, D GIACOMETTI, KR ROSENBERG, JM HARDY, CJ SCHAPIRO, MB RAPOPORT, SI ALGER, JR HORWITZ, B AF MURPHY, DGM BOTTOMLEY, PA SALERNO, JA DECARLI, C MENTIS, MJ GRADY, CL TEICHBERG, D GIACOMETTI, KR ROSENBERG, JM HARDY, CJ SCHAPIRO, MB RAPOPORT, SI ALGER, JR HORWITZ, B TI AN INVIVO STUDY OF PHOSPHORUS AND GLUCOSE-METABOLISM IN ALZHEIMERS-DISEASE USING MAGNETIC-RESONANCE SPECTROSCOPY AND PET SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; P-31 NMR; BRAIN; DEMENTIA; INVITRO AB Objectives: To study phosphorus and glucose metabolism in whole-brain slices of otherwise healthy patients with dementia of the Alzheimer type (DAT) and healthy controls. Design: We used proton nuclear magnetic resonance imaging phosphorus spectroscopy and positron emission tomography to study in vivo brain phosphorus and glucose metabolism. Patients: Whole-brain slice phosphorus metabolism was studied in nine drug free patients with mild to moderately severe dementia of the Alzheimer type (DAT) and in eight age- and sex-matched healthy controls. Mean ages (+/-SD) of the patients and controls were 60+/-10 years and 64+/-16 years, respectively. Positron emission tomography was used to study cerebral glucose metabolism in seven of the patients with DAT and seven of the healthy controls. Results: Patients with DAT had significant brain glucose hypometabolism compared with controls, but there was no significant group difference in any phosphorus metabolite concentration or ratio in the same volume of brain tissue. Also, within patients with DAT there was no correlation between any phosphorus metabolite concentration or ratio and either severity of dementia or glucose metabolism. Conclusions: We suggest glucose metabolism is reduced early in DAT (reflecting decreased basal synaptic functioning) and is unrelated to a rate limitation in glucose delivery, abnormal glucose metabolism, or abnormal coupling between oxidation and phosphorylation. Normal or near-normal levels of phosphorus metabolites are maintained in mild, moderate, and severe DAT. Therefore, altered high-energy phosphate levels are not a consequence of reduced glucose metabolism in DAT, and do not play a major role in the pathophysiology of the disorder, at least in whole-brain sections. C1 NINCDS,NEUROIMAGING BRANCH,BETHESDA,MD 20892. GE CO,CTR RES & DEV,SCHENECTADY,NY 12345. RP MURPHY, DGM (reprint author), NIA,NEUROSCI LAB,BLDG 10,ROOM 6C 414,BETHESDA,MD 20892, USA. RI DeCarli, Charles/B-5541-2009 NR 44 TC 46 Z9 46 U1 1 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD MAY PY 1993 VL 50 IS 5 BP 341 EP 349 PG 9 WC Psychiatry SC Psychiatry GA LB877 UT WOS:A1993LB87700002 PM 8489323 ER PT J AU ENGEL, LW AF ENGEL, LW TI THE HUMAN GENOME PROJECT - HISTORY, GOALS, AND PROGRESS TO DATE SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID ENZYMATIC AMPLIFICATION; GEL-ELECTROPHORESIS; DNA; YEAST; HYBRIDIZATION; SEQUENCES AB This article presents an overview of the Human Genome Project. The goals of the program are outlined; the genetic, physical, and DNA sequence maps that will be its products are defined; the brief origins of the project are traced; the management structure of the US Human Genome Project, in which the Department of Energy and the National Institutes of Health participate as partners, is outlined; international dimensions are discussed; the excellent progress to date with respect to each of the eight scientific goals is reported; and the projected impact of the project on biology and medicine is discussed. RP ENGEL, LW (reprint author), NATL CTR HUMAN GENOME RES, OFF SCI REVIEW, BETHESDA, MD 20892 USA. NR 50 TC 13 Z9 14 U1 0 U2 3 PU COLL AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD MAY PY 1993 VL 117 IS 5 BP 459 EP 465 PG 7 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA LA787 UT WOS:A1993LA78700002 PM 8489331 ER PT J AU YIN, SY MING, HA JAHAN, N MANAK, M JAFFE, ES LEVINE, PH AF YIN, SY MING, HA JAHAN, N MANAK, M JAFFE, ES LEVINE, PH TI INSITU HYBRIDIZATION DETECTION OF HUMAN HERPESVIRUS-6 IN BIOPSY SPECIMENS FROM CHINESE PATIENTS WITH NON-HODGKINS-LYMPHOMA SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID VIRUS HUMAN HERPESVIRUS-6; EPSTEIN-BARR-VIRUS; LYMPHOPROLIFERATIVE DISORDERS; EXANTHEM SUBITUM; EMBEDDED TISSUES; CELL LYMPHOMAS; HHV-6; IDENTIFICATION; INFECTION; SEQUENCES AB An in situ hybridization assay was developed for the detection of human herpesvirus 6 in formaldehyde-fixed, paraffin-embedded tissue. This test was applied to specimens obtained from 45 patients with non-Hodgkin's lymphoma seen in Fujian, People's Republic of China, who had been classified by the working formulation and immunohistologically characterized. Human herpesvirus 6 sequences were detected in eight of 45 (mean incidence +/- SD, 18% +/- 6%) non-Hodgkin's lymphoma tumor samples tested. The significance of human herpesvirus 6-infected cells in lymphoma tissue remains to be determined. C1 CAMBRIDGE BIOTECH CORP,ROCKVILLE,MD. NCI,BETHESDA,MD 20892. OI Manak, Mark /0000-0002-9217-9129 FU NIAID NIH HHS [N44-AI-82502] NR 30 TC 13 Z9 14 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD MAY PY 1993 VL 117 IS 5 BP 502 EP 506 PG 5 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA LA787 UT WOS:A1993LA78700012 PM 8387767 ER PT J AU ALEXANDER, EL PLITT, JR ANSARI, A EHRLICH, H BUGAWAN, D FRONEK, Z AF ALEXANDER, EL PLITT, JR ANSARI, A EHRLICH, H BUGAWAN, D FRONEK, Z TI GENE DOSAGE EFFECT IN PRIMARY SJOGRENS-SYNDROME (PSS) AND PRESUMED LUPUS VARIANTS (PLVS) - MULTIPLE DQA1/DQB1 ALLELES LINKED TO HLA-DRE1 GENES ENCODING-9 EYSTS-13 CONTAINING HLA-DR3, DR5, OR DRW6 (DQA1/DQB1 EYSTS) SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21205. NIH,BETHESDA,MD 20892. CETUS CORP,EMERYVILLE,CA 94608. UNIV CALIF SAN DIEGO,LA JOLLA,CA 92093. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD MAY PY 1993 VL 36 IS 5 SU S BP R24 EP R24 PG 1 WC Rheumatology SC Rheumatology GA LD569 UT WOS:A1993LD56900107 ER PT J AU BOLSTER, MB ALLEN, NB HEYES, MP SILVER, RM AF BOLSTER, MB ALLEN, NB HEYES, MP SILVER, RM TI KYNURENINE PATHWAY OF L-TRYPTOPHAN METABOLISM IN EOSINOPHILIC FASCIITIS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 MED UNIV S CAROLINA,CHARLESTON,SC 29425. NIMH,BETHESDA,MD 20892. DUKE UNIV,DURHAM,NC 27706. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD MAY PY 1993 VL 36 IS 5 SU S BP R17 EP R17 PG 1 WC Rheumatology SC Rheumatology GA LD569 UT WOS:A1993LD56900064 ER PT J AU GHARAVI, AE SAMMARITANO, LR MORSE, JH ZARRABI, MH LOCKSHIN, MD AF GHARAVI, AE SAMMARITANO, LR MORSE, JH ZARRABI, MH LOCKSHIN, MD TI BINDING CHARACTERISTICS OF HIV AND CHLORPROMAZINE-INDUCED ANTIPHOSPHOLIPID ANTIBODIES SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 HOSP SPECIAL SURG,NEW YORK,NY 10021. COLUMBIA UNIV COLL PHYS & SURG,NEW YORK,NY 10032. VET ADM MED CTR,NORTHPORT,NY 11768. NIH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD MAY PY 1993 VL 36 IS 5 SU S BP R34 EP R34 PG 1 WC Rheumatology SC Rheumatology GA LD569 UT WOS:A1993LD56900150 ER PT J AU HOCHBERG, MC LETHBRIDGECEJKU, M SCOTT, WW PLATO, CC TOBIN, JD AF HOCHBERG, MC LETHBRIDGECEJKU, M SCOTT, WW PLATO, CC TOBIN, JD TI BIOCHEMICAL MARKERS OF BONE AND CARTILAGE METABOLISM IN SUBJECTS WITH HAND OSTEOARTHRITIS (OA) - DATA FROM THE BALTIMORE LONGITUDINAL-STUDY OF AGING (BLSA) SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV MARYLAND,SCH MED,BALTIMORE,MD 21201. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21205. NIA,GERONTOL RES CTR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD MAY PY 1993 VL 36 IS 5 SU S BP R23 EP R23 PG 1 WC Rheumatology SC Rheumatology GA LD569 UT WOS:A1993LD56900100 ER PT J AU HOCHBERG, MC LETHBRIDGECEJKU, M SCOTT, WW PLATO, CC TOBIN, JD AF HOCHBERG, MC LETHBRIDGECEJKU, M SCOTT, WW PLATO, CC TOBIN, JD TI AGE PREDICTS PROGRESSION OF HAND OSTEOARTHRITIS IN WOMEN - DATA FROM THE BALTIMORE LONGITUDINAL-STUDY OF AGING SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 UNIV MARYLAND,SCH MED,BALTIMORE,MD 21201. JOHNS HOPKINS MED INST,BALTIMORE,MD 21205. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. NR 0 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD MAY PY 1993 VL 36 IS 5 SU S BP R15 EP R15 PG 1 WC Rheumatology SC Rheumatology GA LD569 UT WOS:A1993LD56900056 ER PT J AU HOFFMAN, GS LEAVITT, RY KERR, GS ROTTEM, M SNELLER, MC FAUCI, AS AF HOFFMAN, GS LEAVITT, RY KERR, GS ROTTEM, M SNELLER, MC FAUCI, AS TI TREATMENT OF TAKAYASU ARTERITIS WITH METHOTREXATE SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD MAY PY 1993 VL 36 IS 5 SU S BP R9 EP R9 PG 1 WC Rheumatology SC Rheumatology GA LD569 UT WOS:A1993LD56900025 ER PT J AU KATZ, P WHALEN, G KEHRL, JH AF KATZ, P WHALEN, G KEHRL, JH TI CHARACTERIZATION OF A NEW-PROTEIN KINASE PREFERENTIALLY EXPRESSED IN GERMINAL CENTER VERSUS MANTLE ZONE B-LYMPHOCYTES SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 GEORGETOWN UNIV,WASHINGTON,DC. NIAID,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD MAY PY 1993 VL 36 IS 5 SU S BP R16 EP R16 PG 1 WC Rheumatology SC Rheumatology GA LD569 UT WOS:A1993LD56900057 ER PT J AU KERR, GS HALLAHAN, C LEAVITT, RY FAUCI, AS HOFFMAN, GS AF KERR, GS HALLAHAN, C LEAVITT, RY FAUCI, AS HOFFMAN, GS TI A STUDY OF 60 PATIENTS WITH TAKAYASU ARTERITIS - PRESENTATION, TREATMENT AND LONG-TERM OUTCOME SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD MAY PY 1993 VL 36 IS 5 SU S BP R5 EP R5 PG 1 WC Rheumatology SC Rheumatology GA LD569 UT WOS:A1993LD56900001 ER PT J AU OHANLON, TP DALAKAS, MC PLOTZ, PH MILLER, FW AF OHANLON, TP DALAKAS, MC PLOTZ, PH MILLER, FW TI PREDOMINANT T-CELL RECEPTOR (TCR) V-ALPHA, V-BETA, AND J-BETA GENE USAGE IN MUSCLE OF PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOPATHIES (IIM) SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. US FDA,BETHESDA,MD 20014. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD MAY PY 1993 VL 36 IS 5 SU S BP R18 EP R18 PG 1 WC Rheumatology SC Rheumatology GA LD569 UT WOS:A1993LD56900072 ER PT J AU SILVER, R LUDWICKA, A OHBA, T HAMPTON, M MAIZE, J HEYES, M AF SILVER, R LUDWICKA, A OHBA, T HAMPTON, M MAIZE, J HEYES, M TI EOSINOPHILIA-MYALGIA-SYNDROME (EMS) - ADDITIONAL STUDIES OF A MURINE MODEL SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 MED UNIV S CAROLINA,CHARLESTON,SC 29425. NIMH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD MAY PY 1993 VL 36 IS 5 SU S BP R17 EP R17 PG 1 WC Rheumatology SC Rheumatology GA LD569 UT WOS:A1993LD56900063 ER PT J AU STAFFORD, FJ FLEISHER, TA LEE, G AUSTIN, H BALOW, JE KLIPPEL, JH AF STAFFORD, FJ FLEISHER, TA LEE, G AUSTIN, H BALOW, JE KLIPPEL, JH TI A PILOT-STUDY USING ANTI-CD5 RICIN A CHAIN IMMUNOCONJUGATE IN SYSTEMIC LUPUS-ERYTHEMATOSUS SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD MAY PY 1993 VL 36 IS 5 SU S BP R24 EP R24 PG 1 WC Rheumatology SC Rheumatology GA LD569 UT WOS:A1993LD56900105 ER PT J AU KUSCHINSKY, W BUNGER, R SCHROCK, H MALLET, RT SOKOLOFF, L AF KUSCHINSKY, W BUNGER, R SCHROCK, H MALLET, RT SOKOLOFF, L TI LOCAL GLUCOSE-UTILIZATION AND LOCAL BLOOD-FLOW IN HEARTS OF AWAKE RATS SO BASIC RESEARCH IN CARDIOLOGY LA English DT Article DE DEOXYGLUCOSE; IODOANTIPYRINE; HEART METABOLISM; RAT HEART; TRANSMURAL GRADIENTS; CORONARY BLOOD FLOW; SPATIAL HETEROGENEITY ID MYOCARDIAL METABOLIC-RATE; TRANSMURAL DISTRIBUTION; DEOXYGLUCOSE; INSULIN; FLUORODEOXYGLUCOSE; TOMOGRAPHY; PRESSURE; EXERCISE; BRAIN; WORK AB Local cardiac glucose utilization and local cardiac blood flow in rat heart were measured in vivo by quantitative autoradiographic techniques with 2-[C-14] deoxyglucose and [C-14] iodoantipyrine, respectively. [C-14]methylmethacrylate standards were calibrated for quantitative autoradiography of dried sections of heart tissue, the calibration values for heart tissue differed from those for brain by 8 %, probably because of differences in self-absorption within the tissues. The lumped constant required by the deoxyglucose method was determined in isolated, perfused, working rat hearts and found to be 1.11 +/- 0.36 (mean +/- SD, n = 21). The heart: blood partition coefficient for iodoantipyrine required by the [C-14]iodoantipyrine method was measured and found to be 1.25. The results obtained in awake rats showed: 1) overall cardiac glucose utilization varied considerably among animals with a mean of 53 (left ventricle) and 30 (right ventricle) mumol/100 g/min; 2) cardiac blood flow was less variable among animals with a mean of 592 (left ventricle) and 420 (right ventricle) ml/100 g/min; 3) glucose utilization was found to be particularly high in the papillary muscle; 4) systematic gradients of glucose utilization or blood flow in the ventricular wall were not observed; 5) glucose utilization and blood flow were not closely correlated on a local level. It is concluded that autoradiographic methods are suitable for the quantification of local glucose utilization and local blood flow in the rat heart in vivo. These methods could not demonstrate transmural gradients for glucose utilization and blood flow between epi- and endocardium in awake rats. C1 NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,DEPT PHYSIOL,BETHESDA,MD 20814. RP KUSCHINSKY, W (reprint author), UNIV HEIDELBURG,INST PHYSIOL,DEPT PHYSIOL,IM NEUENHEIMER FELD 326,D-69120 HEIDELBERG,GERMANY. FU NHLBI NIH HHS [R01 HL-37067] NR 36 TC 18 Z9 18 U1 2 U2 2 PU DR DIETRICH STEINKOPFF VERLAG PI BERLIN 33 PA C/O SPRINGER-VERLAG, HEIDELBERGER PLATZ 3, 1000 BERLIN 33, GERMANY SN 0300-8428 J9 BASIC RES CARDIOL JI Basic Res. Cardiol. PD MAY-JUN PY 1993 VL 88 IS 3 BP 233 EP 249 PG 17 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA LM602 UT WOS:A1993LM60200005 PM 8216175 ER PT J AU WILLIAMSON, PR HUBER, MA BENNETT, JE AF WILLIAMSON, PR HUBER, MA BENNETT, JE TI ROLE OF MALTASE IN THE UTILIZATION OF SUCROSE BY CANDIDA-ALBICANS SO BIOCHEMICAL JOURNAL LA English DT Article ID SACCHAROMYCES-CEREVISIAE; ALPHA-GLUCOSIDASE; EXTRACELLULAR GLUCOAMYLASE; ESCHERICHIA-COLI; PURIFICATION; TRANSPORT; YEAST; CARLSBERGENSIS; STELLATOIDEA; PERMEASE AB Two isoenzymes of maltase (EC 3.2.1.20) were purified to homogeneity from Candida albicans. Isoenzymes I and II were found to have apparent molecular masses of 63 and 66 kDa on SDS/PAGE with isoelectric points of 5.0 and 4.6 respectively. Both isoenzymes resembled each other in similar N-terminal sequence, specificity for the alpha(1 --> 4) glycosidic linkage and immune cross-reactivity on Western blots using a maltase II antigen-purified rabbit antibody. Maltase was induced by growth on sucrose whereas beta-fructofuranosidase activity could not be detected under similar conditions. Maltase I and II were shown to be unglycosylated enzymes by neutral sugar assay, and more than 90% of alpha-glucosidase activity was recoverable from spheroplasts. These data, in combination with other results from this laboratory [Geber, Williamson, Rex, Sweeney and Bennett (1992) J. Bacteriol. 174, 6992-6996] showing lack of a plausible leader sequence in genomic or mRNA transcripts, suggest an intracellular localization of the enzyme. To establish further the mechanism of sucrose assimilation by maltase, the existence of a sucrose-inducible H+/sucrose syn-transporter was demonstrated by (1) the kinetics of sucrose-induced [C-14]sucrose uptake, (2) recovery of intact [C-14]sucrose from ground cells by t.l.c. and (3) transport of 0.83 mol of H+/mol of [C-14]sucrose. In total, the above is consistent with a mechanism whereby sucrose is transported into C. albicans to be hydrolysed by an intracellular maltase. RP WILLIAMSON, PR (reprint author), NIAID,CLIN INVEST LAB,CLIN MYCOL SECT,BETHESDA,MD 20892, USA. NR 42 TC 24 Z9 25 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD MAY 1 PY 1993 VL 291 BP 765 EP 771 PN 3 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LA824 UT WOS:A1993LA82400017 PM 8489504 ER PT J AU MCMURRY, TJ BRECHBIEL, M WU, CC GANSOW, OA AF MCMURRY, TJ BRECHBIEL, M WU, CC GANSOW, OA TI SYNTHESIS OF 2-(P-THIOCYANATOBENZYL)-1,4,7-TRIAZACYCLONONANE-1,4,7-TRIACETIC ACID - APPLICATION OF THE 4-METHOXY-2,3,6-TRIMETHYLBENZENESULFONAMIDE PROTECTING GROUP IN THE SYNTHESIS OF MACROCYCLIC POLYAMINES SO BIOCONJUGATE CHEMISTRY LA English DT Article ID CRYSTAL-STRUCTURES; METAL-IONS; LIGANDS; COMPLEX; STABILITY; 1,4,7-TRIAZACYCLONONANE-N,N',N''-TRIACETATE; GALLIUM(III); DERIVATIVES; CHEMISTRY; SYSTEMS AB A synthesis of the bifunctional chelator 2-(p-thiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid [2-(p-NCS-Bz)-NOTA] is described which illustrates the especial utility of the (4-methoxy-2,3,6-trimethylphenyl)sulfonyl (Mtr) protecting group as an alternative to the p-tolylsulfonyl (Ts) moiety commonly used for Richman-Atkins type cyclizations. Reaction of N,N'- bis(p-tolylsulfonyl)-1-(p-benzamidobenzyl)ethylenediamine with NN-bis[2-[(p-tolylsulfonyl)oxy]ethyl]-p-toluenesulfonamide gave 2-(p-benzamidobenzyl)-1,4,7-tris(p-tolylsulfonyl)-1,4,7-triazacyclononane in 55% yield, whereas the analogous reaction using the Mtr-protected starting materials gave the corresponding Mtr-protected macrocycle in 34% yield. However, deprotection of the Ts- and Mtr-protected macrocycles (H2SO4, 90-degrees-C) afforded 2-(p-benzamidobenzyl)-1,4,7-triazacyclononane in 23% and 60% yield, respectively, illustrating the relatively facile cleavage of the Mtr moiety. A modest improvement in overall percent conversion of (p-nitrobenzyl)ethylenediamine into substituted macrocyclic polyamine was observed when comparing the Mtr vs Ts protection (12.6 vs 10.6%). The macrocyclic triamine was converted to 2-(p-NCS-Bz)-NOTA by alkylation with bromoacetic acid (pH 9,73 %) followed by hydrolysis of the benzamide protecting group (6 M HCl, 70-degrees-C, 87%) and reaction with thiophosgene (90%). The serum stability of the 67CU Complexes of 1,4,7-triazacyclononane (I), 2-(p-nitrobenzyl)-1,4,7,10-tetraazacyclododecane (11), 2-(p-nitrobenzyl)-1,4,8,11-tetraazacyclotetradecane (III), 2-(p-PhCONH-Bz)-NOTA (IV), 2-(p-nitrobenzyl)-1,4,7,10-tetraazadodecane-1,4,7,10-tetraaceticacid (V), 2-(p-nitrobenzyl)-1,4,8,11-tetraazatetradecane-1,4,8,11-tetraacetic acid (VI), and the acyclic ligand 1-(p-nitrobenzyl)-4-meth-yldiethylenetriamine-N,N,N',N'',N''-pentaacetic acid (VII) was measured at 37-degrees-C (5% CO2) and showed the following order of relative stability: I < VII much less than VI much less than IV < V approximately II C1 NCI, RADIAT ONCOL BRANCH, BETHESDA, MD 20892 USA. NR 41 TC 40 Z9 40 U1 0 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD MAY-JUN PY 1993 VL 4 IS 3 BP 236 EP 245 DI 10.1021/bc00021a009 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA LF195 UT WOS:A1993LF19500009 PM 8324015 ER PT J AU PARK, MH WOLFF, EC FOLK, JE AF PARK, MH WOLFF, EC FOLK, JE TI HYPUSINE - ITS POSTTRANSLATIONAL FORMATION IN EUKARYOTIC INITIATION FACTOR-5A AND ITS POTENTIAL ROLE IN CELLULAR-REGULATION SO BIOFACTORS LA English DT Review DE DEOXYHYPUSINE; EUKARYOTIC TRANSLATION INITIATION FACTOR; HYPUSINE; POLYAMINES; POSTTRANSLATIONAL MODIFICATION ID HAMSTER OVARY CELLS; NATURALLY-OCCURRING POLYAMINES; PROTEIN-SYNTHESIS; AMINO-ACID; FACTOR EIF-4D; SACCHAROMYCES-CEREVISIAE; DEOXYHYPUSINE HYDROXYLASE; BOVINE BRAIN; FACTOR 4D; ORNITHINE DECARBOXYLASE AB The amino acid, hypusine [N(epsilon)-(4-amino-2-hydroxybutyl) lysine], a unique component of one cellular protein, eukaryotic translation initiation factor 5A (eIF-5A, old terminology eIF-4D), is formed post-translationally in two enzymatic steps: (i) transfer of the 4-aminobutyl moiety of the polyamine spermidine to the epsilon-amino group of a single specific lysine residue in the eIF-5A precursor protein to form an intermediate, deoxyhypusine, and (ii) subsequent hydroxylation in this 4-aminobutyl portion. Hypusine is produced soon after the translation of eIF-5A mRNA; the modification is essentially irreversible. Hypusine is found in all eukaryotes examined as well as in archaebacteria; it does not occur in eubacteria. The protein containing hypusine from each species displays a high degree of amino acid identity; the sequence of amino acids surrounding the hypusine residue is strictly conserved, suggesting the importance of the hypusine modification throughout evolution. Expression of one of the two yeast eIF-5A genes is required for survival and the lysine codon at the site of hypusine synthesis is vital for yeast growth. The precise cellular function of eIF-5A remains to be elucidated; however, eIF-5A stimulates methionyl-puromycin synthesis in a model assay for translation initiation and eIF-5A precursors containing lysine in place of hypusine are inactive in this assay. This provides evidence that the hypusine modification is needed for eIF-5A activity. In view of the important role of hypusine in eIF-5A and because of the narrow specificities of the enzymes involved in formation of this unusual amino acid, the hypusine biosynthetic steps offer promising targets for intervention in cellular proliferation. Spermidine analogs that are inhibitors of deoxyhypusine synthase in vitro also cause inhibition of hypusine formation in cells, together with a reduction in protein synthesis and in cell growth. In addition, certain metal chelating inhibitors of deoxyhypusine hydroxylase exhibit anti-proliferative effects by arresting mammalian cells at the G1/S boundary of the cell cycle. These results lay the foundation for the potential regulation of cellular events through the application of specific and potent inhibitors of hypusine biosynthesis. RP PARK, MH (reprint author), NIDR,CELLULAR DEV & ONCOL LAB,ENZYME CHEM SECT,BETHESDA,MD 20892, USA. NR 88 TC 197 Z9 208 U1 0 U2 9 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0951-6433 J9 BIOFACTORS JI Biofactors PD MAY PY 1993 VL 4 IS 2 BP 95 EP 104 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA LG273 UT WOS:A1993LG27300004 PM 8347280 ER PT J AU CHEEORTS, MN OPTICAN, LM AF CHEEORTS, MN OPTICAN, LM TI CLUSTER METHOD FOR ANALYSIS OF TRANSMITTED INFORMATION IN MULTIVARIATE NEURONAL DATA SO BIOLOGICAL CYBERNETICS LA English DT Article AB A new method for quantifying the transmitted information and channel capacity of high-dimensional data, based on cluster formation, is described. The method's ability to handle high-dimensional data allows for a complete measurement of information transmitted by neuronal data. It is computationally efficient in terms of both processing time and memory storage. Application of the method to the responses of a V1 neuron shows that more information was transmitted about the pattern of stimuli than about their color. RP CHEEORTS, MN (reprint author), NEI,SENSORIMOTOR RES LAB,BLDG 10,ROOM 10C101,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 15 TC 14 Z9 14 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-1200 J9 BIOL CYBERN JI Biol. Cybern. PD MAY PY 1993 VL 69 IS 1 BP 29 EP 35 DI 10.1007/BF00201406 PG 7 WC Computer Science, Cybernetics; Neurosciences SC Computer Science; Neurosciences & Neurology GA LG598 UT WOS:A1993LG59800004 PM 8334188 ER PT J AU KIM, HY SAWAZAKI, S AF KIM, HY SAWAZAKI, S TI STRUCTURAL-ANALYSIS OF HYDROXY FATTY-ACIDS BY THERMOSPRAY LIQUID-CHROMATOGRAPHY TANDEM MASS-SPECTROMETRY SO BIOLOGICAL MASS SPECTROMETRY LA English DT Article ID ARACHIDONIC-ACID; PLATELETS; LIPOXYGENASE; METABOLISM; SYSTEM AB Thermospray liquid chromatography/tandem mass spectrometry provides a sensitive and convenient technique for the structural analysis of oxygenated polyunsaturates. Analysis of pentafluorobenzyl derivatives in the negative ion mode under the filament- or discharge-on condition generated abundant [M-PFB]- ions. These ions were further fragmented by collision with argon and detected in the negative ion mode. The negative ion fragmentation pattern was examined for various oxygenated polyunsaturated fatty acid standards as well as their deuterated and/or hydrogenated forms. Characteristic fragmentation occurs at the oxygenated C-C bonds, allowing unambiguous determination of the sites of oxygenation. The sample amount required is typically in the low tens of nanogram range. Using this method the structures of epoxy, hydroxy derivatives of 4,7,10,13,16,19-docosahexaenoic acid (22.6w3) formed by soybean lipoxygenase were determined. They were 13-hydroxy-16,17-epoxy-22:5w3 and 15-hydroxy-16,17-epoxy-22:5w3. RP KIM, HY (reprint author), NIAAA,DICBR,LMBB,MASS SPECTROMETRY SECT,BLDG 10,ROOM 3C-102,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 16 TC 13 Z9 13 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 1052-9306 J9 BIOL MASS SPECTROM JI Biol. Mass Spectrom. PD MAY PY 1993 VL 22 IS 5 BP 302 EP 310 DI 10.1002/bms.1200220506 PG 9 WC Biophysics; Spectroscopy SC Biophysics; Spectroscopy GA KZ279 UT WOS:A1993KZ27900005 PM 8507674 ER PT J AU OKABE, M KISHI, Y YING, X KOHAMA, Y MIMURA, T LI, SSL AF OKABE, M KISHI, Y YING, X KOHAMA, Y MIMURA, T LI, SSL TI CHARACTERIZATION OF CAPACITATION INHIBITORY PROTEIN FROM RABBIT SEMINAL PLASMA - HOMOLOGY WITH HUMAN ANNEXINS SO BIOLOGICAL & PHARMACEUTICAL BULLETIN LA English DT Article DE CAPACITATION; SPERM; ANNEXIN; DECAPACITATION FACTOR ID PLACENTAL ANTICOAGULANT PROTEIN; ACROSOME STABILIZING FACTOR; AMINO-ACID-SEQUENCE; BINDING-PROTEIN; HUMAN PROSTATE; INVITRO; SURFACE; MOUSE; FERTILIZATION; SPERMATOZOA AB A protein was purified from rabbit seminal plasma using preparative acrylamide disc electrophoresis, ammonium sulfate precipitation and gel filtration. The protein inhibited the in vitro fertilization of mouse ova inseminated with epididymal sperm and with capacitated sperm. The inhibition was not observed, however, when only ova were exposed to the protein prior to mixing with sperm. The partial protein sequence analysis revealed the strong homology of the rabbit fertilization inhibitory protein to human annexin V. C1 OSAKA UNIV, FAC PHARMACEUT SCI, SUITA, OSAKA 565, JAPAN. NIEHS, GENET LAB, RES TRIANGLE PK, NC 27709 USA. RI Okabe, Masaru/B-6917-2015 OI Okabe, Masaru/0000-0002-0803-9044 NR 31 TC 6 Z9 6 U1 0 U2 3 PU PHARMACEUTICAL SOC JAPAN PI TOKYO PA 2-12-15 SHIBUYA, SHIBUYA-KU, TOKYO, 150-0002, JAPAN SN 0918-6158 J9 BIOL PHARM BULL JI Biol. Pharm. Bull. PD MAY PY 1993 VL 16 IS 5 BP 453 EP 456 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LC932 UT WOS:A1993LC93200004 PM 8364490 ER PT J AU KURTZ, A BRISTOL, LA TOTH, BE LAZARWESLEY, E TAKACS, L KACSOH, B AF KURTZ, A BRISTOL, LA TOTH, BE LAZARWESLEY, E TAKACS, L KACSOH, B TI MAMMARY EPITHELIAL-CELLS OF LACTATING RATS EXPRESS PROLACTIN MESSENGER-RIBONUCLEIC-ACID SO BIOLOGY OF REPRODUCTION LA English DT Article ID COMPLEMENTARY DEOXYRIBONUCLEIC-ACID; HUMAN DECIDUA; CDNA CLONE; GENE; MILK; IDENTIFICATION; PLACENTA; INVITRO; GROWTH; HORMONE AB The presence of prolactin (PRL) mRNA in the mammary gland, placenta, and pituitary gland of lactating and pregnant rats was investigated by polymerase chain reaction (PCR). Polyadenylated RNA was prepared from total RNA samples by Oligo(dT)-cellulose chromatography, and complementary cDNAs were synthesized. A standardized amount of cDNA from each sample was used as the template in a Taq PCR under high-stringency conditions. PCR amplified a signal with the predicted size of approximately 375 bp in mammary and pituitary glands of lactating and pregnant rats, and in placentae of pregnant rats. This band specifically hybridized with a probe overlapping the entire sequence of the mature rat (r) PRL mRNA in Southern blot analysis. When the rPRL-specific primers were used, PCR revealed no signal in the liver or in lactating mammary gland explants cultured in vitro for 48 h, while the same cDNA preparations gave strong signals for beta-actin. The viability of the mammary gland explants was also suggested by their ability to secrete immunoreactive casein in vitro. PRL mRNA was localized in the epithelium of alveoli and ducts of the lactating mammary gland by in situ hybridization. These data provide evidence that the PRL gene is expressed in the mammary gland of pregnant and lactating rats, and suggest that the mammary gland might contribute to PRL in milk by de novo synthesis. Thus, while the placenta is an exogenous source of PRL-like activities for the fetus in utero, the mammary gland might take over this function after birth. C1 NIAAA,ADAMHA,LPPS,ROCKVILLE,MD 20852. SEMMELWEIS UNIV MED,DEPT ANAT HISTOL & EMBRYOL 2,H-1450 BUDAPEST,HUNGARY. NIMH,LCB,DEV BIOL UNIT,BETHESDA,MD 20892. RP KURTZ, A (reprint author), NIAAA,ADAMHA,SPECIAL PROJECTS UNIT,ROCKVILLE,MD 20852, USA. FU NICHD NIH HHS [HD-04358] NR 36 TC 59 Z9 59 U1 0 U2 4 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD MAY PY 1993 VL 48 IS 5 BP 1095 EP 1103 DI 10.1095/biolreprod48.5.1095 PG 9 WC Reproductive Biology SC Reproductive Biology GA LE636 UT WOS:A1993LE63600020 PM 7683213 ER PT J AU DURAND, D FIELD, MJ QUILICHINI, M SMITH, JC AF DURAND, D FIELD, MJ QUILICHINI, M SMITH, JC TI LATTICE-VIBRATIONS IN CRYSTALLINE L-ALANINE SO BIOPOLYMERS LA English DT Article ID PROTEIN DYNAMICS; TEMPERATURE-DEPENDENCE; SCATTERING; SPECTRA AB Zwitterionic L-alanine forms crystals containing strong hydrogen-bonding and methyl-methyl interactions. Well-defined low-frequency lattice vibrations exist in the crystals involving correlated intermolecular motions on the picosecond timescale. A characterization of these vibrations is expected to provide useful information on the nature of nonbonded interactions in peptides and proteins. We examine some of the vibrations using coherent inelastic neutron scattering and computer simulation techniques. The neutron scattering measurements are used to determine phonon dispersion relations for the acoustic and some low-frequency optic modes in the crystal. There is evidence for interaction between the two lowest frequency optical phonons and the longitudinal acoustic mode. The velocity of sound is anisotropic and can be correlated with the hydrogen-bonding arrangement in the crystal. Corresponding phonon dispersion relations are derived from normal mode analyses of the crystal using the program CHARMM. Although some calculated vibrational frequencies are somewhat too high, the form of the calculated dispersion relations are in good agreement with experiment. C1 CTR ETUD SACLAY,DEPT BIOL CELLULAIRE & MOLEC,BIOPHYS PROT & MEMBRANES SECT,F-91191 GIF SUR YVETTE,FRANCE. NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. RP DURAND, D (reprint author), CTR ETUD SACLAY,LAB LEON BRILLOUIN,F-91191 GIF SUR YVETTE,FRANCE. RI smith, jeremy/B-7287-2012 OI smith, jeremy/0000-0002-2978-3227 NR 28 TC 9 Z9 9 U1 0 U2 3 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PD MAY PY 1993 VL 33 IS 5 BP 725 EP 733 DI 10.1002/bip.360330502 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA KZ440 UT WOS:A1993KZ44000001 PM 8343574 ER PT J AU HASEGAWA, S RODGERS, GP SHIO, H SCHECHTER, AN UYESAKA, N AF HASEGAWA, S RODGERS, GP SHIO, H SCHECHTER, AN UYESAKA, N TI IMPAIRED DEFORMABILITY OF HEINZ BODY-FORMING RED-CELLS SO BIORHEOLOGY LA English DT Article DE RED BLOOD CELL (RBC); DEFORMABILITY; HEINZ BODIES; UNSTABLE HEMOGLOBIN; SPECTRIN; OXIDATIVE DAMAGE ID HEMOGLOBIN DENATURATION; NICKEL MESH; MEMBRANE; PROTEINS; FILTERABILITY; DISEASE; BAND-3; HEME AB Although a decrease in the deformability of red blood cells (RBCs) has been suspected in Heinz body-forming hemolytic anemia, it remains uncertain whether the formation of Heinz bodies themselves impairs RBC deformability or not. To elucidate this question, we used RBCs treated with phenylhydrazine and RBCs from patients with unstable hemoglobin (Hb) disease (Hb Yokohama) to investigate the effect of Heinz body formation on deformability in terms of RBC filterability through nickel mesh and viscosity of the RBC suspension. The phenylhydrazine-treated RBCs exhibited a marked decrease in deformability in a dose-dependent manner. The Heinz body-forming RBCs from the patients also showed a marked decrease in deformability. Thus we confirmed that Heinz body formation impairs RBC deformability. Further, both phenylhydrazine-treated RBCs and RBCs from the patient showed a degradation of spectrin without any cross-linking of membrane proteins, thereby suggesting that the im aired deformability is associated with the oxidative degradation of the cytoskeletal framework. In summary, this study supports the conclusion that RBC deformability is impaired by the presence of Heinz bodies as well as the related oxidative damage involved in their formation. C1 NIPPON MED COLL,DEPT PHYSIOL,1-1-5 SENDAGI,BUNKYO KU,TOKYO 113,JAPAN. NIDDKD,CHEM BIOL LAB,BETHESDA,MD 20892. OI Schechter, Alan N/0000-0002-5235-9408 NR 35 TC 10 Z9 11 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-355X J9 BIORHEOLOGY JI Biorheology PD MAY-AUG PY 1993 VL 30 IS 3-4 BP 275 EP 286 PG 12 WC Biophysics; Engineering, Biomedical; Hematology SC Biophysics; Engineering; Hematology GA MD242 UT WOS:A1993MD24200009 PM 8286728 ER PT J AU BECKWITH, J AF BECKWITH, J TI A HISTORICAL VIEW OF SOCIAL-RESPONSIBILITY IN GENETICS SO BIOSCIENCE LA English DT Article ID HUMAN GENOME; LINKAGE; PROJECT; BIOLOGY C1 NIH,HUMAN GENOME PROJECT,WORKING GRP ETH LEGAL & SOCIAL IMPLICAT,BETHESDA,MD 20892. NATL ACAD SCI,WASHINGTON,DC 20418. RP BECKWITH, J (reprint author), HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115, USA. NR 63 TC 10 Z9 11 U1 1 U2 2 PU AMER INST BIOLOGICAL SCI PI WASHINGTON PA 1444 EYE ST, NW, STE 200, WASHINGTON, DC 20005 SN 0006-3568 J9 BIOSCIENCE JI Bioscience PD MAY PY 1993 VL 43 IS 5 BP 327 EP 333 DI 10.2307/1312065 PG 7 WC Biology SC Life Sciences & Biomedicine - Other Topics GA KX575 UT WOS:A1993KX57500006 ER PT J AU YOUNG, HA AF YOUNG, HA TI RESCUE OF PLASMID DNA FROM NONVIABLE BACTERIAL GLYCEROL STOCKS SO BIOTECHNIQUES LA English DT Note RP YOUNG, HA (reprint author), NCI,FCRDC,EXPTL IMMUNOL LAB,BLDG 560-31-23,FREDERICK,MD 21702, USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD MAY PY 1993 VL 14 IS 5 BP 745 EP 745 PG 1 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LA812 UT WOS:A1993LA81200014 PM 8512692 ER PT J AU PATTERSON, RM WITCHER, LL HE, C SELKIRK, JK MERRICK, BA AF PATTERSON, RM WITCHER, LL HE, C SELKIRK, JK MERRICK, BA TI IMPROVED PROTEIN-DETECTION WITH A POLYVINYLIDENE FLUORIDE TRANSFER MEMBRANE FOR 2-DIMENSIONAL GEL-ELECTROPHORESIS SO BIOTECHNIQUES LA English DT Note C1 NIEHS,MOLEC CARCINOGENESIS LAB,MD D4-03,POB 12233,RES TRIANGLE PK,NC 27709. NR 4 TC 4 Z9 4 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 MAY PY 1993 VL 14 IS 5 BP 752 EP 753 PG 2 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LA812 UT WOS:A1993LA81200017 PM 7685610 ER PT J AU MILLAR, DB AF MILLAR, DB TI FLUORSTAMP SO BIOTECHNIQUES LA English DT Note RP MILLAR, DB (reprint author), NIMH,CTR NEUROSCI,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032, USA. NR 1 TC 0 Z9 0 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 MAY PY 1993 VL 14 IS 5 BP 764 EP 764 PG 1 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA LA812 UT WOS:A1993LA81200022 PM 8512698 ER PT J AU EMERY, DW SHAFER, GE KARSON, EM SACHS, DH LEGUERN, C AF EMERY, DW SHAFER, GE KARSON, EM SACHS, DH LEGUERN, C TI RETROVIRUS-MEDIATED TRANSFER AND EXPRESSION OF AN ALLOGENEIC MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II DRB CDNA IN SWINE BONE-MARROW CULTURES SO BLOOD LA English DT Article ID HEMATOPOIETIC PROGENITOR CELLS; LONG-TERM CULTURES; MINIATURE SWINE; GENE-TRANSFER; TRANSPLANTATION TOLERANCE; STEM-CELLS; HLA-DR; VECTOR; IDENTIFICATION; RECOMBINATION C1 MASSACHUSETTS GEN HOSP,TRANSPLANTAT BIOL RES CTR,MGH E,BLDG 149,13TH ST,BOSTON,MA 02129. NCI,IMMUNOL BRANCH,BETHESDA,MD 20892. NHLBI,MOLEC HEMATOL BRANCH,BETHESDA,MD 20892. FU NHLBI NIH HHS [HL46532]; NIAID NIH HHS [AI33053] NR 35 TC 24 Z9 26 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD MAY 1 PY 1993 VL 81 IS 9 BP 2460 EP 2465 PG 6 WC Hematology SC Hematology GA KZ991 UT WOS:A1993KZ99100031 PM 8386951 ER PT J AU HILAKIVICLARKE, LA ARORA, PK CLARKE, R WRIGHT, A LIPPMAN, ME DICKSON, RB AF HILAKIVICLARKE, LA ARORA, PK CLARKE, R WRIGHT, A LIPPMAN, ME DICKSON, RB TI OPPOSING BEHAVIORAL ALTERATIONS IN MALE AND FEMALE TRANSGENIC TGF-ALPHA MICE - ASSOCIATION WITH TUMOR SUSCEPTIBILITY SO BRITISH JOURNAL OF CANCER LA English DT Article ID GROWTH FACTOR-ALPHA; BREAST-CANCER; HEPATOCELLULAR-CARCINOMA; CELLS; OVEREXPRESSION; TRANSFORMATION; HYPERPLASIA; EXPRESSION; DEPRESSION; NEOPLASIA AB Psychosocial factors are thought to influence risk and survival from cancer. We have previously studied specific behaviours in transgenic male CD-1 MT42 mice, which overexpress the gene encoding human transforming growth factor alpha (TGFalpha) in multiple tissues, and which develop a high incidence of spontaneous hepatocellular carcinoma. The male TGFalpha mice spent a lengthened time immobile in the swim test, were highly aggressive, had increased plasma levels of 17beta-estradiol (E2), and reduced natural killer (NK) cell activity. The female transgenic MT42 TGFalpha mice do not develop an increased rate of tumours at any site. We hypothesised that if the alterations in male TGFalpha mice are associated with their development of hepatocellular carcinomas, female TGFalpha should not show these alterations. The data in the present study indicate that female TGFalpha mice display shortened immobility in the swim test, suggesting an improved ability to cope with stress, and appear less aggressive in the resident-intruder test than non-transgenic female CD-1 mice. The female TGFalpha mice also exhibit a 3-fold increase in the plasma levels of E2, and a 3-fold increase in NK cell activity. These findings suggest that the elevated expression of TGFalpha in the transgenic mice is associated with gender-specific behavioural alterations, and the development of spontaneous hepatocellular tumours in the males. Furthermore, TGFalpha alters hormonal and immune parameters similarly in both sexes. It remains to be determined whether the development of hepatocarcinoma in the male TGFalpha animals is associated with an impaired ability to cope with stress and elevated aggressive tendencies and/or whether manipulations leading to an impaired ability to cope with stress will promote tumourigenesis in female TGFalpha mice. C1 GEORGETOWN UNIV,SCH MED,DEPT PSYCHIAT,WASHINGTON,DC 20007. NIDDK,NEUROSCI LAB,BETHESDA,MD 20892. RP HILAKIVICLARKE, LA (reprint author), GEORGETOWN UNIV,SCH MED,VINCENT T LOMBARDI CANC RES CTR,ROOM S128,3800 RESERVOIR RD NW,WASHINGTON,DC 20007, USA. RI Clarke, Robert/A-6485-2008 OI Clarke, Robert/0000-0002-9278-0854 NR 36 TC 16 Z9 17 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD MAY PY 1993 VL 67 IS 5 BP 1026 EP 1030 DI 10.1038/bjc.1993.188 PG 5 WC Oncology SC Oncology GA LA813 UT WOS:A1993LA81300025 PM 8494695 ER PT J AU KUSAMA, T SPIVAK, CE WHITING, P DAWSON, VL SCHAEFFER, JC UHL, GR AF KUSAMA, T SPIVAK, CE WHITING, P DAWSON, VL SCHAEFFER, JC UHL, GR TI PHARMACOLOGY OF GABA RHO-1 AND GABA ALPHA/BETA RECEPTORS EXPRESSED IN XENOPUS OOCYTES AND COS CELLS SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE GABA RHO-1 RECEPTOR; GABA-A RECEPTOR; OOCYTE; COS CELLS; GABA AGONIST; PARTIAL AGONIST ID MOLECULAR-BIOLOGY; A RECEPTORS; ACID; AGONISTS; CDNA AB 1 The rho1 protein, which we previously cloned from retina, assembles as a homooligomer that transduces the binding of gamma-aminobutyric acid (GABA) into robust chloride currents. However, its insensitivity to bicuculline, pentobarbitone and benzodiazepines, all potent agents at typical GABA(A) receptors, suggested that it may react atypically to other GABA agonists and antagonists. 2 cDNAs for the rho1 and the alpha,beta1 receptors for GABA were expressed as homo- and heterooligomers, respectively, in Xenopus oocytes. The selectivities of the respective receptors for various agonists were investigated using concentration-response experiments in voltage clamped cells. 3 The most potent agonists at the rho1 receptor were trans-4-aminocrotonic acid (TACA) > GABA > muscimol; at the alpha5beta1 receptor the rank order was muscimol > GABA > 4,5,6,7-tetrahydro-isoxazole[4,5-c]pyridine-3-ol (THIP). The most specific agonists were cis-(2-(aminomethyl)-cyclopropyl-carboxylic acid (CAMP) and THIP for the rho1 and the alpha5beta1 receptors, respectively. 4 Comparing GABA, TACA and cis-aminocrotonic acid (CACA) at rho1 receptors expressed in COS cells gave results almost indistinguishable from those found at oocytes; the pharmacology of rho1 seems independent of the expression system. 5 Agonists THIP, piperidine-4-sulphonic acid (P4S), and isoguvacine, whose C-C-C-N chains are constrained by rings into a folded conformation and were potent at the alpha5beta1 receptor, were among the weakest at the rho1 receptor. However CACA and CAMP, which align better with the extended than the folded conformation, were weakest at the alpha5beta1 receptor but moderately potent at the rho1 receptor. These findings suggest that the rho1 receptor recognizes agonists in the extended conformation, in contrast to GABA(A) receptors, which are believed to recognize agonists in the partially folded conformation. 6 In contrast to the alpha5beta1 receptor, gradations in maximum responses were apparent in the rho1 receptor, suggesting various degrees of partial agonism. In particular, imidazole-4-acetic acid (14AA), whose maximum response was only 3% of GABA's maximum, had an apparent K(d) for activating the rho1 receptor of 16 mum; but it had an apparent K(d) for competitively blocking the receptor of 0.64 mum. This difference suggests that steric constraints in the activated (open channel) receptor are tighter than in the resting receptor. 7 Hill coefficients approached 2 at the rho1 receptor, but were closer to unity at the alpha5beta1 receptor. Thus, the rho1 receptor displayed higher cooperativity. 8 Unlike typical GABA(A) receptors, the rho1 receptor was insensitive to the competitive antagonists bicuculline, SR95531, securinine, and (+)-tubocurarine. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21224. NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. MERCK SHARP & DOHME LTD,NEUROSCI RES CTR,HARLOW,ESSEX,ENGLAND. CALIF STATE UNIV NORTHRIDGE,DEPT CHEM,NORTHRIDGE,CA 91330. NR 24 TC 148 Z9 148 U1 0 U2 5 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD MAY PY 1993 VL 109 IS 1 BP 200 EP 206 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA KY993 UT WOS:A1993KY99300033 PM 8388298 ER PT J AU STAFFORD, FJ KLIPPEL, JH AF STAFFORD, FJ KLIPPEL, JH TI APHERESIS AND THE RHEUMATIC DISEASES SO BULLETIN ON THE RHEUMATIC DISEASES LA English DT Article ID SYSTEMIC LUPUS-ERYTHEMATOSUS; RANDOMIZED TRIAL; PLASMAPHERESIS; ARTHRITIS; THERAPY RP STAFFORD, FJ (reprint author), NIH,BETHESDA,MD 20892, USA. NR 22 TC 1 Z9 1 U1 0 U2 0 PU ARTHRITIS FOUNDATION PI ATLANTA PA 1314 SPRING STREET NW, ATLANTA, GA 30309 SN 0007-5248 J9 B RHEUM DIS JI Bull. Rheum. Dis. PD MAY PY 1993 VL 42 IS 3 BP 6 EP 8 PG 3 WC Rheumatology SC Rheumatology GA LF608 UT WOS:A1993LF60800002 PM 8334479 ER PT J AU POTISCHMAN, N SWANSON, CA BRINTON, LA MCADAMS, M BARRETT, RJ BERMAN, ML MORTEL, R TWIGGS, LB WILBANKS, GD HOOVER, RN AF POTISCHMAN, N SWANSON, CA BRINTON, LA MCADAMS, M BARRETT, RJ BERMAN, ML MORTEL, R TWIGGS, LB WILBANKS, GD HOOVER, RN TI DIETARY ASSOCIATIONS IN A CASE-CONTROL STUDY OF ENDOMETRIAL CANCER SO CANCER CAUSES & CONTROL LA English DT Article DE CARBOHYDRATE; CASE-CONTROL STUDY; DIET; ENDOMETRIAL CANCER; FAT; PROTEIN; UNITED STATES AB Despite the established role of obesity in the etiology of endometrial cancer, limited data are available from analytical epidemiologic studies on the association of risk with dietary factors. A case-control study of 399 cases and 296 controls conducted in five areas of the United States from 1 June 1987 to 15 May 1990, enabled evaluation of risk related to dietary intakes adjusted for potential confounders. Caloric intake was associated modestly with increased risk (odds ratio [OR] = 1.5, 95 percent confidence interval [CI] = 0.9-2.5 for highest cf lowest quartiles of intake), with the principal contributors being fat and protein calories. After adjustment for other risk factors, including body mass, increased risk was associated with higher intakes of fat. Several components of fat investigated were associated with increased risk, although associations were slightly stronger for saturated fat (OR = 2.1, CI = 1.2-3.7) and oleic acid (OR = 2.2, CI = 1.2-4.0) than for linoleic acid (OR = 1.6, CI = 0.9-2.8). Food-group analyses showed intake of complex carbohydrates-and specifically of breads and cereals-associated with reduced risks (OR = 0.6, CI = 0.4-1.1), whereas animal fat and fried foods were associated with elevated risks (OR = 1.5 and 1.7, respectively). The relations of endometrial cancer with animal fat and complex carbohydrates were independent. No consistent associations were noted for intakes of cholesterol, fiber, vitamins A and C, individual carotenoids, or folate-rich foods. These data imply an etiologic role for a diet rich in total fat and/or animal fat and low in complex carbohydrates with endometrial cancer. These associations are consistent with a hormonal mechanism and were independent of the associations of obesity and other risk factors. RP POTISCHMAN, N (reprint author), NCI,DIV CANC ETIOL,ENVIRONM EPIDEMIOL BRANCH,NUTR EPIDEMIOL SECT,BETHESDA,MD 20892, USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 0 TC 83 Z9 84 U1 0 U2 4 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAY PY 1993 VL 4 IS 3 BP 239 EP 250 PG 12 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA LC885 UT WOS:A1993LC88500009 PM 8318640 ER PT J AU DORGAN, JF ZIEGLER, RG SCHOENBERG, JB HARTGE, P MCADAMS, MJ FALK, RT WILCOX, HB SHAW, GL AF DORGAN, JF ZIEGLER, RG SCHOENBERG, JB HARTGE, P MCADAMS, MJ FALK, RT WILCOX, HB SHAW, GL TI RACE AND SEX-DIFFERENCES IN ASSOCIATIONS OF VEGETABLES, FRUITS, AND CAROTENOIDS WITH LUNG-CANCER RISK IN NEW-JERSEY (UNITED-STATES) SO CANCER CAUSES & CONTROL LA English DT Article DE BLACKS; CAROTENOIDS; DIET; FRUIT; LUNG NEOPLASMS; SEX; UNITED-STATES; VEGETABLES; WHITES AB We used data from a case-control study conducted in New Jersey between 1980 and 1983 to evaluate race and sex differences in associations of vegetable, fruit, and carotenoid consumption with lung cancer. Cases included 736 White males, 860 White females, 269 Black males, and 86 Black females with incident, histologically confirmed, primary cancer of the trachea, bronchus, or lung. Controls were identified through drivers' license and Health Care Financing Administration files and included 548 White males, 473 White females, 170 Black males, and 47 Black females. Usual intakes of vegetables (predominantly yellow/green) and fruit (predominantly yellow/orange) as well as other food sources of carotenoids were ascertained by a food frequency questionnaire. White females showed significant inverse associations of lung cancer with vegetables, fruit, and carotenoids. White males showed nonsignificant inverse associations with vegetables and carotenoids, and Black females just with vegetables. No inverse associations were found for Black males. Vegetable consumption was associated with risk of all histologic types of lung cancer, but the pattern of increasing risk with decreasing intake was limited to smokers. We infer that consumption of yellow/green vegetables and carotenoids confer protection from lung cancer to White male and White female smokers. Further studies are needed to clarify the effect in Blacks. RP DORGAN, JF (reprint author), NCI,DIV CANC PREVENT & CONTROL,EXECUT PLAZA N,ROOM 211,BETHESDA,MD 20892, USA. NR 0 TC 36 Z9 36 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAY PY 1993 VL 4 IS 3 BP 273 EP 281 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA LC885 UT WOS:A1993LC88500012 PM 8318643 ER PT J AU POMMIER, Y AF POMMIER, Y TI DNA TOPOISOMERASE-I AND TOPOISOMERASE-II IN CANCER-CHEMOTHERAPY - UPDATE AND PERSPECTIVES SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article; Proceedings Paper CT 4TH ARTAC INTERNATIONAL WORKSHOP ON THERAPEUTIC TRIALS IN CANCER AND AIDS CY SEP, 1991 CL PARIS, FRANCE SP ASSOC RECH THERAPEUT ANTICANC DE DNA TOPOISOMERASE; CHEMOTHERAPY ID CHINESE-HAMSTER CELLS; SISTER CHROMATID EXCHANGES; CYTO-TOXICITY; DROSOPHILA-MELANOGASTER; CHROMOSOME CONDENSATION; MAMMALIAN-CELLS; GENE-EXPRESSION; LEUKEMIA-CELLS; STRAND BREAKS; SACCHAROMYCES-CEREVISIAE RP POMMIER, Y (reprint author), NCI,DIV CANC TREATMENT,MOLEC PHARMACOL LAB,BLDG 37,RM 5C27,BETHESDA,MD 20892, USA. NR 100 TC 184 Z9 188 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD MAY PY 1993 VL 32 IS 2 BP 103 EP 108 DI 10.1007/BF00685611 PG 6 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA KY106 UT WOS:A1993KY10600006 PM 8387398 ER PT J AU COMSTOCK, GW GORDON, GB HSING, AW AF COMSTOCK, GW GORDON, GB HSING, AW TI THE RELATIONSHIP OF SERUM DEHYDROEPIANDROSTERONE AND ITS SULFATE TO SUBSEQUENT CANCER OF THE PROSTATE SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CAROTENOIDS; CARCINOMA AB Levels of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) in sera collected and frozen in 1974 were studied among 81 prostate cancer cases diagnosed in the following 12 years and 81 age- and race-matched controls. Although mean levels of DHEA were 11% lower among cases than controls and DHEA-S levels were 12% lower than among controls, no dose-response association was noted for either DHEA or DHEA-S. It seems unlikely that serum levels of DHEA or DHEA-S are important risk factors for prostate cancer. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD 21218. JOHNS HOPKINS UNIV,SCH MED,CTR ONCOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PHARMACOL & MOLEC SCI,BALTIMORE,MD 21205. NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. FU NCI NIH HHS [CA44530, CA36390, CA09314] NR 18 TC 35 Z9 35 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY-JUN PY 1993 VL 2 IS 3 BP 219 EP 221 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA LB421 UT WOS:A1993LB42100007 PM 8318873 ER PT J AU GUPTABURT, S SHAMKHANI, H REED, E TARONE, RE ALLEGRA, CJ PAI, LH POIRIER, MC AF GUPTABURT, S SHAMKHANI, H REED, E TARONE, RE ALLEGRA, CJ PAI, LH POIRIER, MC TI RELATIONSHIP BETWEEN PATIENT RESPONSE IN OVARIAN AND BREAST-CANCER AND PLATINUM DRUG-DNA ADDUCT FORMATION SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CISPLATIN CHEMOTHERAPY; LEUKOCYTE DNA; BLOOD-CELLS; CARBOPLATIN; INVITRO; QUANTITATION; SPECTROMETRY; REMOVAL; DAMAGE AB Nucleated blood cell DNA samples from ovarian (n = 27) and breast (n = 25) cancer patients receiving either cis-diamminedichloroplatinum 11 (cisplatin) and/or diamminecyclobutanecarboxylatoplatinum 11 were examined for the presence of platinum drug bound to DNA during several cycles of therapy. Platinum-DNA adducts were quantitated by cisplatin-DNA enzyme-linked immunosorbent assay (ELISA) and atomic absorbance spectroscopy, techniques that measure either a fraction of the intrastrand cis-diammineplatinum-d(ApG) and -d(GpG) adducts (ELISA) or the total platinum bound to DNA (atomic absorbance spectroscopy), respectively. For either the complete study, or for samples obtained during the early cycles, individuals with progressive disease had severalfold lower overall cisplatin-DNA ELISA-measurable adduct levels than the individuals with more favorable clinical responses (complete response, partial response, or stable disease), who were grouped together and termed nonprogressive disease. In the case of the ovarian cancer patients, who experienced a 59% rate of complete and partial response, the correlation of high adduct values with disease response was statistically significant by the Wilcoxon rank-sum test (P = 0.028). In contrast, the breast cancer patients achieved only an 11.5% rate of complete and partial response, and the correlation of high adduct formation with disease response was not statistically significant. Levels of total DNA-bound platinum, measured by atomic absorbance spectroscopy, showed no correlation with disease response for either cancer by any analysis. The study supports previous observations demonstrating a consistent correlation between high cisplatin-DNA ELISA measurements and positive clinical outcome in ovarian cancer patients. In addition, the study provides insights into human interindivudal variability in the formation of DNA adducts under controlled administration that may eventually contribute to the validation of DNA adduct-based human risk assessment. C1 NCI,DIV CANC ETIOL,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BLDG 37,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,MED BRANCH,BETHESDA,MD 20892. NCI,DIV CANC ETIOL,BIOSTAT BRANCH,BETHESDA,MD 20892. NR 25 TC 32 Z9 32 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY-JUN PY 1993 VL 2 IS 3 BP 229 EP 234 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA LB421 UT WOS:A1993LB42100009 PM 8318875 ER PT J AU JONES, IM MOORE, DH THOMAS, CB THOMPSON, CL STROUT, CL BURKHARTSCHULTZ, K AF JONES, IM MOORE, DH THOMAS, CB THOMPSON, CL STROUT, CL BURKHARTSCHULTZ, K TI FACTORS AFFECTING HPRT MUTANT FREQUENCY IN T-LYMPHOCYTES OF SMOKERS AND NONSMOKERS SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HUMAN PERIPHERAL-BLOOD; POLYMERASE CHAIN-REACTION; BREAST-CANCER PATIENTS; MUTATION ASSAY; CLONING ASSAY; LUNG-CANCER; CIRCULATING LYMPHOCYTES; XERODERMA-PIGMENTOSUM; MOLECULAR ANALYSES; SOMATIC MUTATIONS AB The frequency of thioguanine-resistant, hypoxanthine phosphoribosyltransferase-deficient lymphocytes in the peripheral blood of human subjects was used to study the genotoxic effects of smoking. Sixty-two nonsmokers and 58 smokers, aged 19 to 45 years with average ages of 30 and 32 years, respectively, and with no other known exposures, were studied using an in vitro assay of the frequency of mutant lymphocyte clones. Analysis of variance explained 68% of the variation in the mutant frequencies. Mutant frequency was dependent upon lymphocyte cloning efficiency, length of smoking history, age, and interactions between these variables. Four nonsmokers and three smokers had high mutant frequencies that were not explained by these variables. Mutant frequencies were inversely related to lymphocyte cloning efficiencies; the effect was twice as great for smokers as for nonsmokers. The time-dependent effect of smoking dominated, with mutant frequency increasing 10%/year of smoking as compared with an independent 1%/year of age. Smoking had a greater effect on young smokers' lymphocytes. Heterogeneity of mutant frequency among both smokers and nonsmokers and its implications for use of lymphocyte mutation assays as biomarkers are discussed. C1 NIEHS,DIV BIOMETRY & RISK ASSESSMENT,RES TRIANGLE PK,NC 27709. RP JONES, IM (reprint author), LAWRENCE LIVERMORE NATL LAB,DIV BIOMED SCI,L-452,POB 808,LIVERMORE,CA 94551, USA. FU NIEHS NIH HHS [Y01-ES-80171] NR 67 TC 43 Z9 43 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY-JUN PY 1993 VL 2 IS 3 BP 249 EP 260 PG 12 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA LB421 UT WOS:A1993LB42100012 PM 8318878 ER PT J AU DEVESA, SS JIN, F ZHENG, W BLOT, WJ FRAUMENI, JF GAO, YT AF DEVESA, SS JIN, F ZHENG, W BLOT, WJ FRAUMENI, JF GAO, YT TI RISING INCIDENCE OF COLON CANCER IN SHANGHAI SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Letter ID COLORECTAL-CANCER; REPRODUCTIVE FACTORS; CHINESE C1 SHANGHAI CANC INST,DEPT EPIDEMIOL,SHANGHAI,PEOPLES R CHINA. RP DEVESA, SS (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892, USA. NR 7 TC 7 Z9 8 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY-JUN PY 1993 VL 2 IS 3 BP 293 EP 294 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA LB421 UT WOS:A1993LB42100017 PM 8318883 ER PT J AU IRVINE, K SCHLOM, J AF IRVINE, K SCHLOM, J TI INDUCTION OF DELAYED-TYPE HYPERSENSITIVITY RESPONSES BY MONOCLONAL ANTIIDIOTYPIC ANTIBODIES TO TUMOR-CELLS EXPRESSING CARCINOEMBRYONIC ANTIGEN AND TUMOR-ASSOCIATED GLYCOPROTEIN-72 SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE CARCINOEMBRYONIC ANTIGEN; ANTIIDIOTYPE ANTIBODY; DELAYED-TYPE HYPERSENSITIVITY ID CANCER-PATIENTS; IMMUNE-RESPONSE; INTERNAL IMAGE; B72.3; CARCINOMA; MELANOMA; REACTIVITY; INVITRO; INVIVO; LINES AB The use of anti-idiotypic antibodies as immunogens represents one potential approach to active specific immunotherapy of cancer. Two panels of syngeneic monoclonal anti-idiotypic antibodies were generated. One panel was directed against mAb CC49 and the other to mAb COL-1. mAb CC49 recognizes the pancarcinoma antigen (Ag), tumor-associated glycoprotein-72 (TAG-72), and mAb COL-1 recognizes carcinoembryonic antigen CEA). Seven anti-idiotypic (AI) antibodies (Ab2) designated AI49-1-7 were generated that recognize the variable region of mAb CC49. These mAb were shown to inhibit the interaction of mAb CC49 (Ab1) with TAG-72 (Ag). Five anti-idiotypic antibodies designated CAI-1-5 were also generated to the anti-CEA mAb, COL-1 (Ab1). These Ab2 were shown to inhibit the interaction between COL-1 (Ab1) and CEA (Ag). Immunization of mice, rats, and rabbits with Ab2 directed against CC49 or COL-1 could not elicit specific Ab3 humoral immune responses, i.e., antibody selectively reactive with their respective target antigens. However, immunization of mice with the CC49 anti-idiotypic antibody (Ab2), designated AI49-3, could induce a delayed-type hypersensitivity response (DTH) specific for tumor cells that express TAG-72. Similarly, immunization of mice with an anti-idiotypic antibody directed against COL-1, designated CAI-1, could induce specific DTH cell-mediated immune responses to murine tumor cells that express human CEA on their surface. These results thus demonstrate that while some anti-idiotype mAb may not be potent immunogens in eliciting Ab3 humoral responses, they are capable of eliciting specific cellular immune responses against human carcinoma-associated antigens. This type of mAb may ultimately be useful in active immunotherapy protocols for human carcinoma. C1 NCI,TUMOR IMMUNOL & BIOL LAB,9000 ROCKVILLE PIKE,BLDG 10,ROOM 8B07,BETHESDA,MD 20892. NR 55 TC 12 Z9 12 U1 1 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD MAY PY 1993 VL 36 IS 5 BP 281 EP 292 DI 10.1007/BF01741166 PG 12 WC Oncology; Immunology SC Oncology; Immunology GA KV814 UT WOS:A1993KV81400001 PM 7682893 ER PT J AU KANTOR, JD MCCORMICK, B STEEG, PS ZETTER, BR AF KANTOR, JD MCCORMICK, B STEEG, PS ZETTER, BR TI INHIBITION OF CELL MOTILITY AFTER NM23 TRANSFECTION OF HUMAN AND MURINE TUMOR-CELLS SO CANCER RESEARCH LA English DT Note ID NUCLEOSIDE DIPHOSPHATE KINASE; DUCTAL BREAST CARCINOMAS; MELANOMA-CELLS; GOOD PROGNOSIS; GROWTH-FACTOR; EXPRESSION; GENE; RESPONSIVENESS; ASSOCIATION; METASTASIS AB Abstractnm23 gene expression has been inversely correlated with tumor metastatic potential in certain tumors including melanomas, breast carcinomas, and hepatocellular carcinomas. The cellular mechanisms by which the nm23 protein may directly or indirectly modulate the metastatic phenotype is not yet known. Because cell motility plays an essential role in metastatic dissemination, we have studied whether tumor cells transfected with nm23 complementary DNA have any alterations in their ability to migrate. Our results demonstrate that nm23 transfection inhibits the ability of murine melanoma and human breast carcinoma cells to migrate in response to serum or to defined factors such as platelet derived growth factor or insulin-like growth factor 1. Random, unstimulated cell motility was not depressed in the nm23 transfectants. The results suggest that the nm23 gene product may interact with intracellular molecules that are essential for stimulated cell motility in two different tumor cell systems. C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT PHYSIOL,300 LONGWOOD AVE,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT SURG,BOSTON,MA 02115. NCI,PATHOL LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA37393] NR 23 TC 187 Z9 200 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 MAY 1 PY 1993 VL 53 IS 9 BP 1971 EP 1973 PG 3 WC Oncology SC Oncology GA LA561 UT WOS:A1993LA56100002 PM 8481897 ER PT J AU BIECHE, I CHAMPEME, MH MATIFAS, F CROPP, CS CALLAHAN, R LIDEREAU, R AF BIECHE, I CHAMPEME, MH MATIFAS, F CROPP, CS CALLAHAN, R LIDEREAU, R TI 2 DISTINCT REGIONS INVOLVED IN 1P DELETION IN HUMAN PRIMARY BREAST-CANCER SO CANCER RESEARCH LA English DT Note ID HUMAN CHROMOSOME-1; TUMOR PROGRESSION; CELL-LINE; CARCINOMA AB Alteration of chromosome 1 is the most consistent cytogenetic abnormality found in human breast carcinoma. Cytogenetic studies have shown independent alterations on the two arms of chromosome 1, increased copy number of the long arm and loss of the short arm of chromosome 1. These deletions are thought to coincide with the location of tumor suppressor gene(s). We carried out deletion analysis of the lp region by using restriction fragment length polymorphism markers mapping to the long (six markers) and short arm (22 markers). Thirty-five of the 74 (47.3%) human breast tumors tested showed somatic loss of heterozygosity at one or more loci on the short arm. Two commonly deleted regions, 1p13-p21 and 1p32-pter, were identified. The latter region is frequently involved in other types of tumors, suggesting that it harbors a common tumor suppressor gene. Our findings suggest that two tumor suppressor genes involved in the development of human breast carcinoma may occur on the short arm of the chromosome 1. C1 CTR RENE HUGUENIN,ONCOVIROL LAB,5 RUE GASTON LATOUCHE,F-92211 ST CLOUD,FRANCE. NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. NR 22 TC 117 Z9 117 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 MAY 1 PY 1993 VL 53 IS 9 BP 1990 EP 1994 PG 5 WC Oncology SC Oncology GA LA561 UT WOS:A1993LA56100007 PM 8097672 ER PT J AU NOGUCHI, M MURAKAMI, M BENNETT, W LUPU, R HUI, F HARRIS, CC GERWIN, BI AF NOGUCHI, M MURAKAMI, M BENNETT, W LUPU, R HUI, F HARRIS, CC GERWIN, BI TI BIOLOGICAL CONSEQUENCES OF OVEREXPRESSION OF A TRANSFECTED C-ERBB-2 GENE IN IMMORTALIZED HUMAN BRONCHIAL EPITHELIAL-CELLS SO CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR-RECEPTOR; HUMAN-BREAST-CANCER; C-MYC PROTOONCOGENES; NEU ONCOGENE; EGF RECEPTOR; NEOPLASTIC TRANSFORMATION; TYROSINE PHOSPHORYLATION; PROTO-ONCOGENE; OVARIAN-CANCER; POOR SURVIVAL AB In order to examine the effects of the overexpression of c-erbB-2 (HER-2, neu) on human bronchial epithelial cells. a human c-erbB-2 expression vector was introduced into the simian virus 40 large T-antigen-immortalized human bronchial epithelial cell line BEAS-2B. Isolation of multiple clonal cell lines after selection revealed a wide range of expression of the gene product gp185erbB-2. While three of six clones tested expressed gp185erbB-2 at levels detectable by immunocytochemistry, only one, B2BE6, induced adenocarcinoma-like tumors in athymic nude mice. Both a nontumorigenic clone, B2BE2, and a tumorigenic clone, B2BE6, expressed comparable amounts of gp185erbB-2, which became phosphorylated on tyrosine in response to treatment with the c-erbB-2 ligands gp30 and p75. These data suggest that overexpression of c-erhB-2 in human bronchial epithelial cells can contribute to, but is not sufficient for, induction of tumorigenicity in this human model system. C1 NCI,DIV CANC ETIOL,HUMAN CARCINOGENESIS LAB,BLDG 37,ROOM 2C08,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,SCH MED,LOMBARDI CANC CTR,WASHINGTON,DC 20007. NR 64 TC 47 Z9 47 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 1993 VL 53 IS 9 BP 2035 EP 2043 PG 9 WC Oncology SC Oncology GA LA561 UT WOS:A1993LA56100014 PM 7683250 ER PT J AU LIEBMANN, JE HAHN, SM COOK, JA LIPSCHULTZ, C MITCHELL, JB KAUFMAN, DC AF LIEBMANN, JE HAHN, SM COOK, JA LIPSCHULTZ, C MITCHELL, JB KAUFMAN, DC TI GLUTATHIONE DEPLETION BY L-BUTHIONINE SULFOXIMINE ANTAGONIZES TAXOL CYTOTOXICITY SO CANCER RESEARCH LA English DT Article ID CYTO-TOXICITY; CELLS; CHEMOTHERAPY; TUBULIN; MICROTUBULES; CANCER AB Taxol is a naturally occurring chemotherapeutic agent that is active against a variety of tumors. Taxol is believed to act by binding tightly to microtubules and preventing their disaggregation. Others have shown that depletion of cellular glutathione results in the disaggregation of microtubules, presumably by allowing the oxidation of some or all of the cysteine residues in tubulins. We studied the effect of glutathione (GSH) depletion by L-buthionine sulfoximine (L-BSO) on taxol cytotoxicity in two human tumor lines. After a 24-h incubation in 5 mM L-BSO, the breast adenocarcinoma line MCF-7 and the lung adenocarcinoma line A549 were exposed to varying concentrations of taxol for 24 h. GSH levels were undetectable in cells treated with L-BSO. At the highest concentrations of taxol (50 nM), control MCF-7 cells had 10% cell survival and control A549 cells had only 1% cell survival as assessed by clonogenic assay. Pretreatment with 5 mM L-BSO resulted in a 3-fold increase in survival of MCF-7 cells and a 10-fold increase in survival of A549 cells. Pretreatment with L-BSO had no effect on taxol uptake into A549 or MCF-7 cells, as assessed by measurement of binding of [H-3]taxol to cells. Following exposure to 37 nM taxol for 24 h, both cell lines had over 80% of their population in G2/M and bromodoxyuridine labeling showed that taxol markedly reduced the percentage of cells in S phase. L-BSO pretreatment had no effect on the cell cycle in either cell line in the absence of taxol. However, in cells treated with taxol, L-BSO increased the percentage of cells in S phase by 3-fold in both cell lines. We conclude that depletion of cellular GSH by L-BSO results in resistance to taxol in MCF-7 and A549 cells. Resistance to taxol mediated by GSH depletion is not due to alterations in cellular uptake of taxol by L-BSO. L-BSO increased the S-phase fraction of taxol-treated cells in both cell lines. These data suggest that GSH depletion interferes with cell cycle changes induced by taxol. The alteration in taxol-induced cell cycle effects may account for the resistance to taxol produced by L-BSO. C1 NCI,DIV CANC TREATMENT,BETHESDA,MD 20892. RP LIEBMANN, JE (reprint author), NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892, USA. NR 22 TC 77 Z9 77 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 1993 VL 53 IS 9 BP 2066 EP 2070 PG 5 WC Oncology SC Oncology GA LA561 UT WOS:A1993LA56100019 PM 8097674 ER PT J AU SEYNAEVE, CM STETLERSTEVENSON, M SEBERS, S KAUR, G SAUSVILLE, EA WORLAND, PJ AF SEYNAEVE, CM STETLERSTEVENSON, M SEBERS, S KAUR, G SAUSVILLE, EA WORLAND, PJ TI CELL-CYCLE ARREST AND GROWTH-INHIBITION BY THE PROTEIN-KINASE ANTAGONIST UCN-01 IN HUMAN BREAST-CARCINOMA CELLS SO CANCER RESEARCH LA English DT Article ID LIGHT CHAIN KINASE; SELECTIVE INHIBITOR; MAMMALIAN-CELLS; CANCER; POTENT; FIBROBLASTS; EXPRESSION; TISSUE; K-252A; KT5926 AB UCN-01 is a derivative of staurosporine, initially developed as a potentially selective inhibitor of the Ca2+- and phospholipid-dependent protein kinase C, but with the capacity to inhibit a number of tyrosine and serine/threonine kinases. UCN-01 inhibits the growth of 5 breast carcinoma cell lines with a 50% inhibitory concentration range of 30-100 nM during 6 days of continuous exposure. In MCF-7, MDA-MB453, and SK-BR-3 cells, UCN-01 is 5-fold more potent in growth inhibition than its diastereomer UCN-02, but the 2 compounds are equipotent in the inhibition of MDA-MB468 and H85787 cell growth. A differential sensitivity to a 24-h period of exposure to UCN-01 followed by drug removal and growth for 5 subsequent days was observed. The rank order for persistent inhibition of cells by UCN-01 was MCF-7, MDA-MB453 >> SK-BR-3 > H85787 > MDA-MB468. MCF-7 and MDA-MB453 cells did not resume proliferation within the 5 days after brief exposure to UCN-01. In contrast, MDA-MB468 and H85787 cells showed no net growth inhibition after a 24-h pulse of UCN-01, followed by 5 more days of growth in drug-free medium. In MDA-MB468 cells, 150 nm UCN-01 retards but does not prevent cell cycle progression through S phase, but the cells are clearly blocked from exit of G1 and entry into S. Progression through S phase is completely inhibited by 600 nm UCN-01. The development of a G1 to S block by UCN-01 in MDA-MB468 cells occurs in conjunction with inhibition of [P-32]orthophosphate labeling and decreased phosphotyrosine mass of discrete cellular phosphoproteins. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. RP SEYNAEVE, CM (reprint author), NCI,BIOL CHEM LAB,BLDG 37,ROOM 5D02,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 31 TC 141 Z9 141 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 1993 VL 53 IS 9 BP 2081 EP 2086 PG 6 WC Oncology SC Oncology GA LA561 UT WOS:A1993LA56100022 PM 7683251 ER PT J AU SUNG, C DEDRICK, RL HALL, WA JOHNSON, PA YOULE, RJ AF SUNG, C DEDRICK, RL HALL, WA JOHNSON, PA YOULE, RJ TI THE SPATIAL-DISTRIBUTION OF IMMUNOTOXINS IN SOLID TUMORS - ASSESSMENT BY QUANTITATIVE AUTORADIOGRAPHY SO CANCER RESEARCH LA English DT Article ID HUMAN-LUNG CANCER; MONOCLONAL-ANTIBODIES; DIPHTHERIA-TOXIN; ATHYMIC MICE; HUMAN-COLON; NUDE-MICE; CELLS; XENOGRAFTS; LOCALIZATION; MELANOMA AB The spatial distribution of i.v. administered immunotoxins in s.c. human rhabdomyosarcoma RD2 xenografts was studied. The toxin and immunotoxins were: (a) diphtheria toxin (DT); (b) a binding-deficient form of DT (CRM107) linked to a monoclonal IgG1 antibody (454A12) directed against the human transferrin receptor (454A12-107); (c) the binding-deficient form of DT linked to the Fab' fragment of 454A12 (Fab'-107); and (d) the binding-deficient form of DT coupled to MOPC21, a monoclonal IgG1 with no significant binding to RD2 cells. DT and the immunotoxins were radiolabeled with I-125 and injected via the tail vein into tumor-bearing athymic mice (median tumor weight, 0.25 g). Tumors were removed 2, 6, and 24 h after injection of DT or immunotoxin. Film images of 20-mum frozen sections were digitized by video microscopy, and gray levels were converted to tissue concentrations based upon the film response to radioactivity standards and the specific activity of the radiolabeled toxins. Images of the tumors were characterized quantitatively by the kurtosis and the area above threshold; the kurtosis is a measure of the spatial heterogeneity of the radiolabeled immunotoxins, and the area above threshold is defined here as the fractional tumor area that reaches or exceeds 1.5% of the initial plasma concentration. The spatial distribution of DT in the tumors was extremely uniform, characterized by low kurtosis values. In contrast, the autoradiograms of 454A12-107 were punctate in appearance and were characterized by very high kurtosis values. Fab'-107, which has approximately one-half the molecular weight of the intact immunotoxin and binds only monovalently, also produced punctate images with kurtosis values similar to those for 454A12-107. The nonbinding immunotoxin distributed somewhat less uniformly than DT but much more homogeneously than either of the binding immunotoxins. DT, 454A12-107, and Fab'-107 have similar affinities for their respective receptors, but the concentration of binding sites for DT on RD2 cells (<3,000 receptors/cell) is much lower than the concentration of transferrin receptor (60,000 receptors/cell). Thus, the heterogeneous distribution of 454A12-107 and Fab'-107 probably reflects retarded penetration due tp binding to the tumor cells. The area above threshold was greatest for DT and lowest for 454A12-107; the fragment and nonbinding immunotoxins had intermediate values. The lower area above threshold for the nonbinding immunotoxin as compared with DT may be due to the considerably larger molecular weight and hence the lower capillary permeability and diffusion coefficient of the immunotoxin. DT and 454A12-107 show comparable potency to RD2 cells in culture, but in preliminary in vivo experiments growth of s.C. RD2 tumors in athymic mice was inhibited by DT but not by 454A12-107. These results suggest a possible correlation between the pattern of the spatial distribution of an immunotoxin and the therapeutic response. C1 NINCDS,SURG NEUROL BRANCH,BETHESDA,MD 20892. RP SUNG, C (reprint author), NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BLDG 13,BETHESDA,MD 20892, USA. NR 46 TC 36 Z9 37 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 MAY 1 PY 1993 VL 53 IS 9 BP 2092 EP 2099 PG 8 WC Oncology SC Oncology GA LA561 UT WOS:A1993LA56100024 PM 8481911 ER PT J AU SALGALLER, ML BEI, R SCHLOM, J POOLE, DJ ROBBINS, PF AF SALGALLER, ML BEI, R SCHLOM, J POOLE, DJ ROBBINS, PF TI BACULOVIRUS RECOMBINANTS EXPRESSING THE HUMAN CARCINOEMBRYONIC ANTIGEN GENE SO CANCER RESEARCH LA English DT Article ID MONOCLONAL-ANTIBODIES; INSECT CELLS; CDNA CLONE; FAMILY; GLYCOPROTEIN; EPITOPES; VACCINE; TUMORS; NCA AB Carcinoembryonic antigen (CEA), one of the most extensively studied human tumor-associated antigens, represents a potential target for passive as well as active immunotherapy. We describe here the first baculovirus recombinants expressing the human CEA gene. Eight baculovirus clones were isolated which expressed products of varying molecular weights; one clone, termed BVCEA-140, was shown to contain multiple CEA epitopes by reactivity to a panel of anti-CEA monoclonal antibodies. When purified protein isolated from this clone was deglycosylated, immunoreactive species ranging from M(r) 50,000 to M(r) 110,000 were found. Results of Southern blot analysis carried out on BVCEA-140 DNA were consistent with the hypothesis that these products result from the stable expression of variants which have recombined within the repeated domains of CEA. Other baculovirus recombinants expressing products comprising different portions of the CEA gene were also derived. One, termed BVCEA-35, was shown to be a recombination between the first 87 bases of domains I and III of the CEA gene. A variant, termed BVCEA-16, contained only the NH2-terminal domain of the CEA gene. Moreover, a recombinant expressing the closely related molecule nonspecific cross-reactive antigen was also derived. As shown here, commercially available preparations of CEA, which are derived from tumor biopsies or cell line supernatants, may contain non-specific cross-reacting antigens and other contaminants. Thus, the recombinant CEA molecules described should have numerous uses including validation of the use of monoclonal antibodies as standards in CEA serum assays, the characterization of immune responses to CEA, the use as immunogen, and the study of structure function relationships. C1 NCI,TUMOR IMMUNOL & BIOL LAB,BLDG 10,ROOM 8B07,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 26 TC 16 Z9 16 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 1993 VL 53 IS 9 BP 2154 EP 2161 PG 8 WC Oncology SC Oncology GA LA561 UT WOS:A1993LA56100034 PM 8481918 ER PT J AU ANDERSON, MW MARONPOT, RR AF ANDERSON, MW MARONPOT, RR TI METHYLENE CHLORIDE-INDUCED TUMORIGENESIS SO CARCINOGENESIS LA English DT Editorial Material RP ANDERSON, MW (reprint author), NIEHS,MOLEC TOXICOL LAB,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 13 Z9 13 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 MAY PY 1993 VL 14 IS 5 BP 787 EP 788 DI 10.1093/carcin/14.5.787 PG 2 WC Oncology SC Oncology GA LD408 UT WOS:A1993LD40800001 PM 8504469 ER PT J AU ZIELENSKA, M AHMED, A PIENKOWSKA, M ANDERSON, M GLICKMAN, BW AF ZIELENSKA, M AHMED, A PIENKOWSKA, M ANDERSON, M GLICKMAN, BW TI MUTATIONAL SPECIFICITIES OF ENVIRONMENTAL CARCINOGENS IN THE LACI GENE OF ESCHERICHIA-COLI .6. ANALYSIS OF METHYLENE CHLORIDE-INDUCED MUTATIONAL DISTRIBUTION IN UVR+ AND UVRB- STRAINS SO CARCINOGENESIS LA English DT Article ID AMINO-ACID REPLACEMENTS; SALMONELLA-TYPHIMURIUM; DNA-REPAIR; FORMALDEHYDE MUTAGENESIS; MOLECULAR ANALYSIS; GLUTATHIONE; DICHLOROMETHANE; REPRESSOR; MUTAGENICITY; METABOLISM AB To better understand the mechanisms of mutagenesis by the carcinogen, methylene chloride (DCM), we have determined the nature and distribution of forward mutations induced by DCM in the N-terminal region of the lacI gene of Escherichia coli. A total of 116 lacI(-d) mutations (50 from Uvr+, 66 from UvrB- strain) were characterized by DNA sequencing. Both similarities and differences were observed. Although in both strains base substitutions predominated (74-88%) the distribution among the classes differed. In the case of the Uvr+ strain, DCM substantially increased the frequency of G:C --> C:G transversion and duplication events. Direct repeats were not observed at the endpoints of the duplications, however, all endpoints were in an A:T-rich region. In contrast, in the UvrB- strain, DCM induced A:T --> G:C, A:T --> C:G, G:C --> C:G events as well as deletions. The mutational spectra presented here represent a first step in the elucidation of the mechanism(s) of DCM-induced mutation. C1 UNIV VICTORIA,CTR ENVIRONM HLTH,DEPT BIOL,VICTORIA V8W 2Y2,BC,CANADA. NIEHS,MOLEC TOXICOL LAB,RES TRIANGLE PK,NC 27709. NR 59 TC 7 Z9 7 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 1993 VL 14 IS 5 BP 789 EP 794 DI 10.1093/carcin/14.5.789 PG 6 WC Oncology SC Oncology GA LD408 UT WOS:A1993LD40800002 PM 8504470 ER PT J AU DEVEREUX, TR FOLEY, JF MARONPOT, RR KARI, F ANDERSON, MW AF DEVEREUX, TR FOLEY, JF MARONPOT, RR KARI, F ANDERSON, MW TI RAS PROTOONCOGENE ACTIVATION IN LIVER AND LUNG-TUMORS FROM B6C3F1 MICE EXPOSED CHRONICALLY TO METHYLENE-CHLORIDE SO CARCINOGENESIS LA English DT Article ID POLYMERASE CHAIN-REACTION; K-RAS; MOUSE-LIVER; CARBON-MONOXIDE; PROTOONCOGENE; DICHLOROMETHANE; DNA; MUTATIONS; DIHALOMETHANES; METABOLISM AB Methylene chloride has been the subject of recent toxicological and carcinogenesis studies because of significant human exposure and widespread use in industrial processing, food preparation and agriculture. In this study, liver and lung tumors, induced in female B6C3F1 mice by inhalation of 2000 p.p.m. methylene chloride (6 h/day, 5 days/week continuous exposure), were examined for the presence of activated ras proto-oncogenes. DNA was isolated from 49 spontaneous and 50 methylene chloride-induced liver tumors and screened by oligonucleotide hybridization of PCR amplified H-ras gene fragments for codon 61 mutations. In the chemically induced tumors, 38 mutations were detected, 16 C to A transversions in base 1, 16 A to G transitions in base 2 and 6 A to T transversions in base 2. This mutation profile was similar to that identified for the H-ras gene in the spontaneous liver tumors and suggests that methylene chloride acts in liver by promoting cells with spontaneous lesions. Tumors in which H-ras codon 61 mutations were not detected were examined for the presence of transforming genes by the nude mouse tumorigenicity assay. Except for activated K-ras genes detected in DNA from two methylene chloride induced tumors and one spontaneous tumor, no other transforming genes were identified. DNA from 54 lung tumors was screened by direct sequencing of PCR amplified DNA fragments of the K-ras gene for first and second exon mutations, and 12 mutations were identified, 5 in exon one and 7 in exon 2. The low number of spontaneous tumors available in this study limits the interpretation of the data, and thus the frequency and spectrum of K-ras activation in the methylene chloride induced tumors was not significantly different from that in the seven spontaneous tumors analyzed. Since K-ras activation was not detected in 80% of the tumors, the nude mouse tumorigenicity assay was used to examine the lung tumors for the presence of other transforming genes. At present no transforming genes other than ras genes were identified in either liver or lung tumors. C1 NIEHS,CHEM PATHOL BRANCH,RES TRIANGLE PK,NC 27709. NIEHS,SYST TOXIC BRANCH,RES TRIANGLE PK,NC 27709. RP DEVEREUX, TR (reprint author), NIEHS,MOLEC TOXICOL LAB,RES TRIANGLE PK,NC 27709, USA. NR 39 TC 60 Z9 60 U1 0 U2 2 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 MAY PY 1993 VL 14 IS 5 BP 795 EP 801 DI 10.1093/carcin/14.5.795 PG 7 WC Oncology SC Oncology GA LD408 UT WOS:A1993LD40800003 PM 8504471 ER PT J AU HEGI, ME SODERKVIST, P FOLEY, JF SCHOONHOVEN, R SWENBERG, JA KARI, F MARONPOT, R ANDERSON, MW WISEMAN, RW AF HEGI, ME SODERKVIST, P FOLEY, JF SCHOONHOVEN, R SWENBERG, JA KARI, F MARONPOT, R ANDERSON, MW WISEMAN, RW TI CHARACTERIZATION OF P53 MUTATIONS IN METHYLENE CHLORIDE-INDUCED LUNG-TUMORS FROM B6C3F1 MICE SO CARCINOGENESIS LA English DT Article ID COLORECTAL TUMORIGENESIS; SUPPRESSOR GENE; ANTIGEN P53; PROTEIN; DNA; DICHLOROMETHANE; CARCINOMAS; CANCER; POLYMERASE; COMPLEX AB Mutations of the p53 tumor suppressor gene are the most common defined genetic alterations seen in a wide variety of human cancers. In contrast, little is known about the importance of the p53 gene in chemically induced tumors of rodents, which are widely used as models for the evaluation of human health risks. In this study we examined 54 methylene chloride-induced and seven spontaneously arising lung tumors from female B6C3F1 mice for losses of heterozygosity (LOH) at markers near the p53 gene on chromosome 11. LOH was detected in seven methylene chloride-induced lung carcinomas by Southern analysis of a restriction fragment length polymorphism and PCR analysis of five simple sequence length polymorphisms. In each case allele loss was observed at all six markers; thus, these chromosomal alterations were likely to have resulted from mitotic nondisjunction. In contrast, LOH was not detected in 20 liver tumors from methylene chloride-treated mice at the Acrb locus, which is tightly linked to the p53 gene on chromosome 11. In addition single strand conformation polymorphism analysis was performed to screen for mutations in the most conserved regions of the p53 gene (exons 5 to 8). Consequently, potential mutations identified by direct sequencing, were only detected in four of the seven tumor samples with LOH, but not in any of the remaining lung tumors. Overexpression of the p53 protein by immunohistochemical staining was detected only in the four tumors that contained p53 point mutations and in a focal area of another tumor. Finally, using a simple sequence length polymorphism within the retinoblastoma tumor suppressor gene, LOH on mouse chromosome 14 was also detected in three lung carcinomas and one liver tumor. Inactivation of p53 and possibly the retinoblastoma tumor suppressor gene appear to be infrequent events in lung and liver tumors from methylene chloride treated mice. C1 NIEHS,SYST TOXIC LAB,RES TRIANGLE PK,NC 27709. NIEHS,CHEM PATHOL LAB,RES TRIANGLE PK,NC 27709. NIEHS,MOLEC TOXICOL LAB,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,SCH PUBL HLTH,DEPT ENVIRONM SCI & ENGN,CHAPEL HILL,NC 27599. RP HEGI, ME (reprint author), NIEHS,MOLEC CARCINOGENESIS LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. RI Hegi, Monika/O-4796-2015 OI Hegi, Monika/0000-0003-0855-6495 NR 62 TC 87 Z9 87 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 MAY PY 1993 VL 14 IS 5 BP 803 EP 810 DI 10.1093/carcin/14.5.803 PG 8 WC Oncology SC Oncology GA LD408 UT WOS:A1993LD40800004 PM 8504472 ER PT J AU FOLEY, JF TUCK, PD TON, TVT FROST, M KARI, F ANDERSON, MW MARONPOT, RR AF FOLEY, JF TUCK, PD TON, TVT FROST, M KARI, F ANDERSON, MW MARONPOT, RR TI INHALATION EXPOSURE TO A HEPATOCARCINOGENIC CONCENTRATION OF METHYLENE-CHLORIDE DOES NOT INDUCE SUSTAINED REPLICATIVE DNA-SYNTHESIS IN HEPATOCYTES OF FEMALE B6C3F1 MICE SO CARCINOGENESIS LA English DT Article ID CELL NUCLEAR ANTIGEN; LIVER; DICHLOROMETHANE; CARCINOGENESIS; MORTALITY; MOUSE AB We have used methlyene chloride as a model to study cellular and molecular processes responsible for liver tumor induction by chlorinated hydrocarbons. Because of current interest in the role of enhanced cell proliferation in tumor induction, measurement of S-phase hepatocytes was incorporated into recently conducted toxicity and carcinogenicity studies. In prechronic studies, female B6C3F1 mice were exposed to 0, 1000, 2000 or 8000 p.p.m. methylene chloride by inhalation, 5 days per week, for up to 4 weeks followed by a 1 and 2 week recovery period. Mice exposed to concentrations of 2000, 4000 or 8000 p.p.m. methylene chloride had sustained increased liver weight commencing after 1 week of exposure and returning to normal after the 1 or 2 week recovery period. The increased liver weight was attributed to hepatocellular hypertrophy secondary to intracellular glycogen accumulation. Tritiated thymidine was administered by osmotic minipumps to label S-phase hepatocytes over a 6 day period. At most intervals examined there was decreased hepatocyte labeling in mice exposed to methylene chloride. However, there was a transitory increased number of S-phase heptocytes observed at the 2 week interval in the 1000, 4000 and 8000 p.p.m. methylene chloride groups. In a chronic study, female mice were exposed to 2000 p.p.m. methylene chloride for up to two years. Following labeling with BRDU using 6 day minipumps, a statistically significant decrease in S-phase hepatocytes was observed after 13 weeks of methylene chloride exposure. A minor increased labeling index (LI) observed at 52 weeks was not considered to be a methylene chloride treatment-related effect. Retrospective immunohistochemical staining for proliferating cell nuclear antigen (PCNA) in liver sections containing foci of cellular alteration allowed demonstration of S-phase hepatocytes in these clonally expanded preneoplasic lesions. While foci frequently had higher LI's than surrounding normal hepatocytes, there was no difference in the mean LI of foci from methylene chloride-treated mice versus foci occurring spontaneously in control mice. The absence of a sustained increase in S-phase hepatocytes in female B6C3F1 mice suggests that enhanced cell proliferation is not a major mechanistic factor associated with the observed hepatocarcinogenicity of methylene chloride. RP FOLEY, JF (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 25 TC 18 Z9 18 U1 0 U2 2 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 MAY PY 1993 VL 14 IS 5 BP 811 EP 817 DI 10.1093/carcin/14.5.811 PG 7 WC Oncology SC Oncology GA LD408 UT WOS:A1993LD40800005 PM 8099314 ER PT J AU KARI, FW FOLEY, JF SEILKOP, SK MARONPOT, RR ANDERSON, MW AF KARI, FW FOLEY, JF SEILKOP, SK MARONPOT, RR ANDERSON, MW TI EFFECT OF VARYING EXPOSURE REGIMENS ON METHYLENE CHLORIDE-INDUCED LUNG AND LIVER-TUMORS IN FEMALE B6C3F1 MICE SO CARCINOGENESIS LA English DT Article ID STRAIN-A MICE; SALMONELLA-TYPHIMURIUM; DICHLOROMETHANE AB Methylene chloride is a high production chemical used in a variety of applications resulting in estimated occupational and consumer exposures of at least one million people per day. Results of previously reported chronic evaluations of inhaled methylene chloride indicated that it caused mammary tumors in Fischer 344 rats and neoplasia in the lungs and liver of B6C3F1 mice. Mechanism(s) for methylene chloride-induced carcinogenesis have not been adequately elucidated. In this paper we describe the histologic evaluation of animals at a number of intermittent times for the purposes of assessing the progressive development of liver and lung neoplasia. Additionally, a series of stop-exposure treatments was conducted to evaluate the role of different methylene chloride exposure durations on the induction of hepatic and pulmonary neoplasia in female mice. Inhalation exposure to 2000 p.p.m. methylene chloride for 6 h per day, 5 days per week, for 104 weeks resulted in an 8-fold increase in the incidence of exposed animals having a lung adenoma or carcinoma (63 versus 7.5%; P < 0.01) and a 13-fold increase in the total number of pulmonary adenomas and carcinomas per animal at risk (0.97 versus 0.075; P < 0.01). This exposure also caused a 2.5-fold increase in the incidence of mice having liver tumors (69 versus 27%; P < 0.01) and a 3-fold increase in the total number of hepatic adenomas and carcinomas per animal at risk (1.34 versus 0.46; P < 0.01). Methylene chloride exposure hastened the first appearance of lung tumors (by 1 year) compared to that observed in control animals; chemical-induced and spontaneous liver tumors first occurred simultaneously. A shorter exposure duration was sufficient to attain maximal numbers of lung tumors than that needed for a maximal liver tumor burden. Lung tumor multiplicity was substantially increased by having additional time after cessation of the chemical treatment. This contrasts with the findings in liver, where additional post-exposure latency time did not effect tumor multiplicity compared to that of mice evaluated immediately after cessation of exposure. The incidence of lung alveolar hyperplasia in methylene chloride exposed animals was very low, even in tumor-bearing animals and the hyperplasias were not seen until at least 13 weeks after appearance of adenomas and carcinomas. Thus, the genesis of methylene chloride induced lung tumors in B6C3F1 mice is not preceeded by overt cytotoxicity, enhanced cell proliferation nor observed hyperplasia. The differential behavior of the target organs to varying exposure regimens, suggests to us that the mechanisms responsible for its tumorigenicity are different in the lung and the liver. C1 ANALYT SCI INC,DURHAM,NC 27713. RP KARI, FW (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 23 TC 40 Z9 40 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 MAY PY 1993 VL 14 IS 5 BP 819 EP 826 DI 10.1093/carcin/14.5.819 PG 8 WC Oncology SC Oncology GA LD408 UT WOS:A1993LD40800006 PM 8504473 ER PT J AU LEHMAN, TA MODALI, R BOUKAMP, P STANEK, J BENNETT, WP WELSH, JA METCALF, RA STAMPFER, MR FUSENIG, N ROGAN, EM HARRIS, CC AF LEHMAN, TA MODALI, R BOUKAMP, P STANEK, J BENNETT, WP WELSH, JA METCALF, RA STAMPFER, MR FUSENIG, N ROGAN, EM HARRIS, CC TI P53 MUTATIONS IN HUMAN IMMORTALIZED EPITHELIAL-CELL LINES SO CARCINOGENESIS LA English DT Article ID HUMAN PAPILLOMAVIRUS TYPE-16; TUMOR SUPPRESSOR GENE; WILD-TYPE P53; T-ANTIGEN; TRANSFORMED-CELLS; SV40-TRANSFORMED CELLS; RAS ONCOGENE; SV40; CARCINOMA; DNA AB Although rodent celts have been immortalized following transfection with a mutant p53 gene, the role of p53 in the immortalization of human cells is unknown. Therefore, human epithelial cell tines were examined for p53 mutations in exons 4-9 which include the evolutionarily conserved regions. A spontaneously immortalized skin keratinocyte cell line, HaCat, and three ras-transfected clones, have a p53 mutational spectrum that is typical of ultraviolet light induced mutations. A normal finite lifespan cell strain (184) and two benzo[a]pyrene immortalized mammary epithelial cell lines derived from 184 (184A1 and 184B5) contain wild type p53 sequences in exons 4-9, although elevated levels of nuclear p53 indicate an alteration in the stability of the normally transient protein. Wild type p53 was found in human bronchial, esophageal and hepatic epithelial cells immortalized by SV40 T antigen gene and human renal epithelial cells immortalized by adenovirus 5. BEAS-2B, an SV40 T antigen immortalized bronchial epithelial cell line and two subclones, have a germline polymorphism at codon 47. Inactivation of p53 by mechanisms such as mutation or complexing with proteins of DNA tumor viruses appears to be important in the immortalization of human epithelial celts. C1 LAWRENCE BERKELEY LAB, BERKELEY, CA 94720 USA. GERMAN CANC RES CTR, W-6900 HEIDELBERG 1, GERMANY. NCI, HUMAN CARCINOGENESIS LAB, BETHESDA, MD 20892 USA. CHILDRENS MED RES INST, WESTMEAD, NSW, AUSTRALIA. RP LEHMAN, TA (reprint author), BIOSERVE BIOTECHNOL LTD, LAUREL, MD 20707 USA. FU NCI NIH HHS [CA24844] NR 79 TC 318 Z9 320 U1 2 U2 14 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 1993 VL 14 IS 5 BP 833 EP 839 DI 10.1093/carcin/14.5.833 PG 7 WC Oncology SC Oncology GA LD408 UT WOS:A1993LD40800008 PM 8504475 ER PT J AU ZHEN, WP EVANS, MK HAGGERTY, CM BOHR, VA AF ZHEN, WP EVANS, MK HAGGERTY, CM BOHR, VA TI DEFICIENT GENE-SPECIFIC REPAIR OF CISPLATIN-INDUCED LESIONS IN XERODERMA-PIGMENTOSUM AND FANCONI-ANEMIA CELL-LINES SO CARCINOGENESIS LA English DT Article ID INTERSTRAND CROSS-LINKS; CHINESE-HAMSTER CELLS; RIBOSOMAL-RNA GENES; INDUCED DNA DAMAGE; EXCISION REPAIR; MAMMALIAN GENES; TRANSCRIBED STRAND; PYRIMIDINE DIMERS; DHFR GENE; ADDUCTS AB Cisplatin is a chemotherapeutic agent known to cause DNA damage. The cytotoxicity of this drug is believed to result from the formation of DNA intrastrand adducts (IA) and DNA interstrand crosslinks (ICL). While there are many studies on DNA repair of cisplatin damage at the overall level of the genome in various human cell lines, there is little information on the gene-specific repair. In this report, we have measured the formation and repair of cisplatin induced DNA adducts in the dihydrofolate reductase (DHFR) and ribosomal RNA (rRNA) genes in three cell tines: normal human fibroblasts, Fanconi's anemia complementation group A (FAA) and Xeroderma pigmentosum complementation group A (XPA). It is generally thought that XPA cells lack nucleotide excision repair and that FAA cells are deficient in the repair of DNA ICL. We find that normal human fibroblast cells repair 84% of the ICL in the DHFR gene after 24 h, whereas XPA and FAA cell lines only repaired 32 and 50% of the ICL respectively. Furthermore, 69% of the cisplatin IA in the DHFR gene were repaired in 24 h in normal human fibroblasts compared to 22% for XPA and 24% for FAA cells. The repair of the rRNA gene was less efficient than in the DHFR gene, but the relative pattern between the different cell tines was similar to that of the DHFR gene. We thus find that FAA cells are deficient not only in the gene specific repair of cisplatin ICL, but also in the gene specific repair of the more common cisplatin IA. XPA cells are normally thought to be without any nucleotide excision repair capacity, but our data could support a slight ICL unhooking activity. RP ZHEN, WP (reprint author), NCI,MOLEC PHARMACOL LAB,BLDG 37,ROOM 5C-25,BETHESDA,MD 20892, USA. NR 42 TC 45 Z9 45 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 MAY PY 1993 VL 14 IS 5 BP 919 EP 924 DI 10.1093/carcin/14.5.919 PG 6 WC Oncology SC Oncology GA LD408 UT WOS:A1993LD40800022 PM 8504485 ER PT J AU HSU, IC TOKIWA, T BENNETT, W METCALF, RA WELSH, JA SUN, T HARRIS, CC AF HSU, IC TOKIWA, T BENNETT, W METCALF, RA WELSH, JA SUN, T HARRIS, CC TI P53 GENE MUTATION AND INTEGRATED HEPATITIS-B VIRAL-DNA SEQUENCES IN HUMAN LIVER-CANCER CELL-LINES SO CARCINOGENESIS LA English DT Article ID HEPATOCELLULAR-CARCINOMA; TUMORS; CARCINOGENESIS; ESTABLISHMENT; MUTAGENESIS; EXPRESSION; ONCOGENES; GENOME; STATE; RAS AB A G:C --> T:A mutational hotspot at codon 249 of the p53 tumor suppressor gene has previously been identified in hepatocellular carcinoma (HCC) of patients from Qidong, China and southern Africa in which aflatoxin B1 (AFB1) and hepatitis B virus (HBV) are known synergistic risk factors. We have examined p53 mutation patterns of HCC from geographic areas in which the risk factors vary. Nine HCC lines and four hepatoblastoma lines (HB) were examined for p53 gene mutations and the relationship with HBV infection. Five of the nine HCC lines had homozygous mutation or deletion randomly distributed in exons 6-8, whereas none of the four HB cell lines had p53 mutations. One of the four HB lines (HepG2) had an N-ras mutation at codon 61 position 2. The p53 point mutations in the three HCC cell lines from Japan resulted in the amino acid changes of cysteine for tyrosine in cell line HuH 7 at codon 220 (A:T --> G:C), alanine for glycine in cell line HLF at codon 244 (G:C --> C:G), and serine for arginine in cell line HLE at codon 249 (G:C --> C:G). In addition, the deletion of 18 base pairs from codon 264 position 3 to codon 270 position 1 has resulted in the deletion of Leu-Gly-Arg-Asn-Ser-Phe from the amino acids sequences 256 - 270 in the Japanese cell line HuH 4. The cell line PLC/ PRF/5 that showed p53 mutation at codon 249 (G:C --> T:A) with substitution of serine for arginine was derived from a South African patient. Our results indicate that whereas the p53 gene is not mutated in the HB cell lines, the HCC cell lines frequently contain an abnormal p53 gene. In addition, p53 point mutations were not detected in the four Japanese HCC cell lines that were positive for genomic integration of HBV X-gene and surface antigen gene. The three Japanese HCC cell lines with p53 mutations did not contain HBV sequences, indicating that hepatocarcinogenesis associated with p53 mutation does not require the genomic integration of HBV sequences. C1 NCI,DIV CANC ETIOL,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. CAMS,INST CANC,BEIJING,PEOPLES R CHINA. RP HSU, IC (reprint author), UNIV MARYLAND,SCH MED,DEPT PATHOL,BALTIMORE,MD 21201, USA. NR 55 TC 187 Z9 189 U1 0 U2 5 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 MAY PY 1993 VL 14 IS 5 BP 987 EP 992 DI 10.1093/carcin/14.5.987 PG 6 WC Oncology SC Oncology GA LD408 UT WOS:A1993LD40800033 PM 8389256 ER PT J AU WESTON, A BOWMAN, ED CARR, P ROTHMAN, N STRICKLAND, PT AF WESTON, A BOWMAN, ED CARR, P ROTHMAN, N STRICKLAND, PT TI DETECTION OF METABOLITES OF POLYCYCLIC AROMATIC-HYDROCARBONS IN HUMAN URINE SO CARCINOGENESIS LA English DT Note ID DNA ADDUCTS; DIOL EPOXIDE; BENZOPYRENE; ANTIBODIES AB A non-invasive assay has been developed for the recovery of r-7,t-8,t-9,c-10-tetrahydroxy-7,8,9,10-tetrahydrobenzo[alpha]pyrene (BP-7,1018,9-tetrol) from human urine. This tetrol is excreted as a metabolite of benzo[alpha]pyrene (BP) in a process catalyzed by cytochrome P450 enzymes and epoxide hydrolases. Urine was hydrolysed to release activated benzo[alpha]-pyrene-diol-epoxides covalently bound to macromolecular species or conjugated tetrols. The relatively non-polar organic molecules from urine hydrolysates were collected on octadecasilane chromatography columns (Sep-Paks). Materials eluted in solvent (80% CH3OH), were further purified on immunoaffinity columns with antibodies raised against anti-N2-[10(7,8,9-trihydroxy-7,8,9,10-tetra-hydrobenzo[alpha]pyrenyl)]-guanosine. HPLC was then used to isolate BP-7,10/8,9-tetrol, which was quantitated by synchronous fluorescence spectroscopy (SFS). This assay detected 0.24-3.12 pmol BP-7,10/8,9-tetrol per ml urine (limit of detection 0.01 pmol/ml, given 10 ml urine), in four study subjects. Reproducibility was assessed by adding tritium labeled BP-7,10/8,9-tetrol (1500 fmol) to a urine sample previously identified to contain the tetrol at levels below the limit of detection of the fluorescence assay; a recovery of > 30% of the added radioactivity was achieved (510 +/- 64 fmol, mean +/- SD, n = 3). Because HPLC alone was not sufficient to isolate materials for quantitation by SFS directly from human urine, immunoaffinity chromatography was found to be a necessary preparatory step in BP-7,10/8,9-tetrol isolation. These data demonstrate the presence of tetrahydrotetrol metabolites of BP in human urine and suggest that measurement of BP-7,10/8,9-tetrol and other polycyclic aromatic hydrocarbon-tetrols may prove to be valuable dosimeters of human internal exposure to polycyclic aromatic hydrocarbons. C1 NCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV HOSP,SCH HYG & PUBL HLTH,BALTIMORE,MD 21205. NR 17 TC 45 Z9 45 U1 2 U2 7 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 MAY PY 1993 VL 14 IS 5 BP 1053 EP 1055 DI 10.1093/carcin/14.5.1053 PG 3 WC Oncology SC Oncology GA LD408 UT WOS:A1993LD40800043 PM 8504465 ER PT J AU CHEN, JM ZHANG, YP MOSCHEL, RC IKENAGA, M AF CHEN, JM ZHANG, YP MOSCHEL, RC IKENAGA, M TI DEPLETION OF O-6-METHYLGUANINE DNA METHYLTRANSFERASE AND POTENTIATION OF 1,3-BIS(2-CHLOROETHYL)-1-NITROSOUREA ANTITUMOR-ACTIVITY BY O-6-BENZYLGUANINE INVITRO SO CARCINOGENESIS LA English DT Note ID HUMAN-TUMOR-CELLS; MAMMALIAN O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; ALKYLATING-AGENTS; O6-METHYLGUANINE-DNA METHYLTRANSFERASE; O6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; CANCER-CHEMOTHERAPY; CROSS-LINKING; SENSITIVITY; REPAIR; STRAINS AB The overcoming effect of O6-benzylguanine on O6-methylguanine-DNA methyltransferase (MGMT)-mediated 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) resistance in vitro was evaluated. Depletion of MGMT activity in Mer+ HeLa S3 cells by O6-benzylguanine was dose-dependent and a complete loss of MGMT activity was achieved at a concentration of 0.5 muM. The cytotoxic potential of BCNU on MGMT proficient HeLa S3 (1.10 pmol/mg of protein), SMMC-7721 (0.72 pmol/mg of protein) and Cc801 (0.39 pmol/mg of protein) was greatly enhanced when cells were exposed to 10 muM O6-benzylguanine for 1 h, but there was a lack of potentiation of BCNU sensitivity in Mer- HeLa MR cells due to its nearly undetectable level of MGMT. There existed a correlation between the extent of enhancement and the amount of MGMT activity. The intensity of enhancement expressed as dose modifying factor = IC50 (BCNU alone)/IC50 (10 muM O6-benzylguanine + BCNU) was 4.56, 3.89, 3.67 and 0.97 in HeLa S3, SMMC-7721, Cc801 and HeLa MR cells respectively. The results further demonstrated that O6-benzylguanine may have potential utility as an adjuvant in combination chemotherapy with chloroethylnitrosourea agents. C1 INST RADIAT MED,DEPT BIOCHEM,27 TAI-PING RD,BEIJING 100850,PEOPLES R CHINA. NCI,FREDERICK CANC RES & DEV CTR,CHEM CARCINOGENESIS LAB,ABL,BASIC RES PROGRAM,FREDERICK,MD 21702. KYOTO UNIV,CTR RADIAT BIOL,KYOTO 606,JAPAN. NR 31 TC 30 Z9 31 U1 1 U2 3 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 MAY PY 1993 VL 14 IS 5 BP 1057 EP 1060 DI 10.1093/carcin/14.5.1057 PG 4 WC Oncology SC Oncology GA LD408 UT WOS:A1993LD40800044 PM 8504466 ER PT J AU UNGER, EF BANAI, S SHOU, M JAKLITSCH, M HODGE, E CORREA, R JAYE, M EPSTEIN, SE AF UNGER, EF BANAI, S SHOU, M JAKLITSCH, M HODGE, E CORREA, R JAYE, M EPSTEIN, SE TI A MODEL TO ASSESS INTERVENTIONS TO IMPROVE COLLATERAL BLOOD-FLOW - CONTINUOUS ADMINISTRATION OF AGENTS INTO THE LEFT CORONARY-ARTERY IN DOGS SO CARDIOVASCULAR RESEARCH LA English DT Article DE CARDIOVASCULAR MODELS; NEOVASCULARIZATION; ACIDIC FIBROBLAST GROWTH FACTOR; CORONARY CIRCULATION; COLLATERAL BLOOD FLOW ID FIBROBLAST GROWTH-FACTOR; EXTRACELLULAR-MATRIX; HEPARIN; ANASTOMOSES; ANGIOGENESIS; MYOCARDIUM; RAT AB Objective: The aim was to develop an experimental model in which angiogenic growth factor(s) could be targeted locally to enhance myocardial collateral formation. A preparation was developed in which agents could be infused selectively into the left main coronary artery on a chronic basis to assess the potential of acidic fibroblast growth factor (FGF) to improve collateral blood flow. Methods: Ameroid constrictors were placed on the left circumflex coronary artery of mixed hounds. Five weeks after ameroid placement, the artery was ligated and transected at the point of ameroid occlusion; a catheter was inserted and passed retrogradely into the left main coronary artery. The catheter was connected to an implantable infusion pump that provided continuous intracoronary drug infusion for 4 weeks. Dogs were randomised to receive acidic FGF with heparin (30 mug-h-1 and 30 IU.h-1, respectively, n=16) or heparin alone (30 IU.h-1, n=14). Regional myocardial blood flow was determined in the conscious state at the beginning and end of treatment. Results: There were no deaths or important surgical complications related to the establishment of the coronary artery infusions. During the treatment interval (5-9 weeks after ameroid placement) the ratio of maximum ischaemic zone/normal zone blood flow increased from 0.39(SD 0.10) to 0.50(0.11) (p<0.01) in dogs treated with acidic FGF plus heparin; however, similar improvement was noted in dogs treated with heparin alone. Ischaemic zone and normal zone vascular density was also equivalent in the two groups. Conclusions: This preparation makes possible the chronic intracoronary administration of agents which may promote myocardial angiogenesis, and allows assessment of collateral blood flow before and after treatment. As given in this investigation, acidic FGF had no demonstrable effect on collateral blood flow; however, this model may facilitate the identification of agents that do enhance myocardial collateral formation. C1 RHONE POULENC RORER CENT RES,HORSHAM,PA. RP UNGER, EF (reprint author), NHLBI,EXPTL PHYSIOL & PHARMACOL LAB,CARDIOL BRANCH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 26 TC 37 Z9 37 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD MAY PY 1993 VL 27 IS 5 BP 785 EP 791 DI 10.1093/cvr/27.5.785 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA LD417 UT WOS:A1993LD41700015 PM 7688663 ER PT J AU TORTORA, G PEPE, S CIRAFICI, AM CIARDIELLO, F PORCELLINI, A CLAIR, T COLLETTA, G YOON, SCC BIANCO, AR AF TORTORA, G PEPE, S CIRAFICI, AM CIARDIELLO, F PORCELLINI, A CLAIR, T COLLETTA, G YOON, SCC BIANCO, AR TI THYROID-STIMULATING HORMONE-REGULATED GROWTH AND CELL-CYCLE DISTRIBUTION OF THYROID-CELLS INVOLVE TYPE-I ISOZYME OF CYCLIC AMP-DEPENDENT PROTEIN-KINASE SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID SELECTIVE CAMP ANALOGS; MOLECULAR-CLONING; MESSENGER-RNA; ANTISENSE OLIGODEOXYNUCLEOTIDE; CATALYTIC SUBUNIT; RECEPTOR PROTEINS; EPITHELIAL-CELLS; FOLLICULAR CELLS; GENE-EXPRESSION; LEUKEMIA-CELLS AB Optimal growth and differentiation of normal rat thyroid FRTL5 cells depend strictly on the presence of thyroid-stimulating hormone (TSH). FRTL5 cells deprived of TSH cease dividing and become quiescent. Addition of TSH to quiescent cells, which activates the cyclic AMP-mediated pathway, is sufficient to stimulate cell entry into S phase of the cell cycle. We have previously shown that the differential expression of the two isozymes, type I and type II, of the cyclic AMP-dependent protein kinase (PKA) correlates with cell growth and differentiation of several rodent and human cell lines. We have studied the role of PKA in the TSH-regulated growth and cell cycle distribution of FRTL5 cells. Upon addition of TSH to FRTL5 cells deprived of hormone, a rapid induction of RIalpha mRNA species occurred within 30 min after treatment, reaching the levels of proliferating FRTL5 cells at 12 h. RIIalpha mRNA levels slightly increased after TSH addition, whereas Calpha mRNA levels did not show major changes. Photoaffinity labeling of PKA receptor proteins showed that addition of TSH to quiescent FRTL5 cells induced a progressive increase in RIalpha levels starting at 6 h after stimulation, whereas RIIalpha receptor levels increased only slightly. When FRTL5 cells were treated with an antisense oligodeoxynucleotide targeted against the RIalpha regulatory subunit, their growth was arrested, whereas an antisense against the RIIalpha regulatory subunit produced only a mild growth inhibition. Moreover, exposure to the antisense RIalpha oligomer resulted in accumulation of cells in the G0-G1 compartment, as during TSH deprivation. Unlike FRTL5 cells deprived of TSH, cells arrested by the specific RIalpha antisense oligomer failed to enter S phase upon stimulation with TSH. These results demonstrate that type I isozyme of PKA is directly involved in TSH-regulated cell proliferation and may be involved in cell cycle distribution of thyroid FRTL5 cells. C1 UNIV NAPLES,FAC MED & CHIRURG 2,CNR,CTR ENDOCRINOL & ONCOL SPERIMENTALE,I-80131 NAPLES,ITALY. UNIV CHIETI,FAC MED & CHIRURG,IST PATOL UMANA & MED SOCIALE,I-66100 CHIETI,ITALY. UNIV REGGIO CALABRIA,FAC MED & CHIRURG CATANZARO,DIPARTIMENTO MED SPERIMENTALE & CLIN,I-88100 CATANZARO,ITALY. NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. RP TORTORA, G (reprint author), UNIV NAPLES,FAC MED & CHIRURG 2,CATTEDRA ONCOL MED,VIA S PANSINI 5,I-80131 NAPLES,ITALY. RI Porcellini, Antonio/E-1900-2011; OI Porcellini, Antonio/0000-0001-6882-9518; Ciardiello, Fortunato/0000-0002-3369-4841 NR 39 TC 30 Z9 30 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 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD MAY PY 1993 VL 4 IS 5 BP 359 EP 365 PG 7 WC Cell Biology SC Cell Biology GA LA841 UT WOS:A1993LA84100002 PM 8518230 ER PT J AU WOODWORTH, CD WANG, H SIMPSON, S ALVAREZSALAS, LM NOTARIO, V AF WOODWORTH, CD WANG, H SIMPSON, S ALVAREZSALAS, LM NOTARIO, V TI OVEREXPRESSION OF WILD-TYPE P53 ALTERS GROWTH AND DIFFERENTIATION OF NORMAL HUMAN KERATINOCYTES BUT NOT HUMAN PAPILLOMAVIRUS-EXPRESSING CELL-LINES SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID EPIDERMAL DIFFERENTIATION; TUMOR-ANTIGEN; PROTEIN; INVITRO; DNA; ONCOGENE; SEQUENCE; GENE; TRANSFORMATION; TRANSCRIPTION AB To examine whether the tumor suppressor gene p53 influences epidermal differentiation, primary cultures of human foreskin keratinocytes and six human papillomavirus (HPV)-positive cell lines were infected with recombinant retroviruses encoding wild-type p53. Overexpression of p53 in organotypic cultures of normal keratinocytes decreased their growth rate and induced premature cell flattening and involucrin expression, a marker of squamous differentiation. However, overexpression of p53 inhibited or delayed production of other epidermal proteins, keratin 10, profilaggrin, and keratinocyte transglutaminase. Furthermore, levels of endogenous cellular p53 dramatically decreased during epidermal differentiation, suggesting that down-regulation of p53 permits complete expression of specific epidermal proteins. Three HPV-immortalized keratinocyte cell lines and three HPV-positive cervical carcinoma-derived cell lines expressed significantly less (<3-fold) p53 protein than normal keratinocytes. Up-regulation of wild-type p53 (>5-fold) by retrovirus infection did not significantly inhibit growth or restore normal epithelial differentiation in any line. Thus, overexpression of wild-type p53 can either induce or inhibit expression of specific epidermal proteins in normal keratinocytes but does not reverse immortality or aberrant differentiation of HPV-immortalized or carcinoma-derived cell lines. C1 GEORGETOWN UNIV,DEPT RADIAT MED,WASHINGTON,DC 20007. RP WOODWORTH, CD (reprint author), NCI,BIOL LAB,BLDG 37,ROOM 2A23,BETHESDA,MD 20892, USA. NR 51 TC 52 Z9 53 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 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD MAY PY 1993 VL 4 IS 5 BP 367 EP 376 PG 10 WC Cell Biology SC Cell Biology GA LA841 UT WOS:A1993LA84100003 PM 7686043 ER PT J AU BATTEY, JF FATHI, Z WADA, E HELLMICH, MR WAY, JM AF BATTEY, JF FATHI, Z WADA, E HELLMICH, MR WAY, JM TI MOLECULAR-GENETIC APPROACHES TO THE ANALYSIS OF NEUROPEPTIDE RECEPTORS SO CELLULAR PHYSIOLOGY AND BIOCHEMISTRY LA English DT Article; Proceedings Paper CT SYMP ON STRATEGIES FOR ANALYZING NEUROPEPTIDE SYSTEMS, AT THE 1991 ANNUAL MEETING OF THE AMERICAN SOC OF ZOOLOGISTS CY DEC 28, 1991 CL ATLANTA, GA SP AMER SOC ZOOLOGISTS DE CDNA CLONING; NEUROPEPTIDES; RECEPTORS ID SWISS 3T3 CELLS; BOMBESIN-LIKE PEPTIDES; OLIGONUCLEOTIDE PROBES; FUNCTIONAL EXPRESSION; MESSENGER-RNAS; CDNA CLONING; HYBRIDIZATION; DIVERSITY; SUBTYPES; PROTEINS AB Within the last few years, an increasing number of neuropeptide receptors have been structurally and functionally characterized. The analysis of these receptors, along with a precise understanding of their pharmacology and signal transduction pathways, has been facilitated by the use of molecular genetic techniques. This review will highlight some of the techniques currently being used to study neuropeptide receptors. Methods for isolation of complementary DNA clones for receptors, analysis of receptor messenger RNA expression and characterization of cloned receptors expressed in cultured cells are reviewed. In addition, a genetic approach for the analysis of neuropeptide receptor function in the context of a whole mammalian organism is discussed. RP BATTEY, JF (reprint author), NCI,BIOL CHEM LAB,DTP,DCT,NIH,BLDG 35,RM 5002,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 35 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-8987 J9 CELL PHYSIOL BIOCHEM JI Cell. Physiol. Biochem. PD MAY-AUG PY 1993 VL 3 IS 3-4 BP 213 EP 230 DI 10.1159/000154685 PG 18 WC Cell Biology; Physiology SC Cell Biology; Physiology GA LL360 UT WOS:A1993LL36000006 ER PT J AU SHI, XL DALAL, NS KASPRZAK, KS AF SHI, XL DALAL, NS KASPRZAK, KS TI GENERATION OF FREE-RADICALS FROM MODEL LIPID HYDROPEROXIDES AND H2O2 BY CO(II) IN THE PRESENCE OF CYSTEINYL AND HISTIDYL CHELATORS SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID METAL-COMPOUNDS; DNA DAMAGE; PEROXIDATION; HYDROXYL; HOMOCARNOSINE; COBALT(II); OXIDATION; CARNOSINE; ANSERINE; INVIVO AB Electron spin resonance spin trapping was utilized to investigate the generation of free radicals from cumene hydroperoxide (cumene-OOH), tert-butyl hydroperoxide (tert-butyl-OOH), and H2O2 at pH 7.2 by Co(II) in the presence of cysteinyl and histidyl chelating agents. The spin trap used was 5,5-dimethyl-1-pyrroline N-oxide. Incubation of Co(II) with cumene-OOH or tert-butyl-OOH did not generate any detectable amounts of free radicals. However, in the presence of glutathione, cysteine, penicillamine, or N-acetylcysteine, Co(II) generated cumene-OOH-derived carbon-centered radicals, cumene alkoxyl radicals, and hydroxyl (.OH) radicals. Oxidized glutathione and cystine used instead of reduced glutathione or cysteine did not generate any free radical, indicating an important role of the -SH group in radical generation. While the addition of diethylenetriaminepentaacetic acid (DTPA) prevented radical generation, deferoxamine had only a slightly inhibitory effect. Similar results to those obtained using cumene-OOH were obtained utilizing tert-butyl-OOH in place of cumene-OOH. The yields of free radicals were in the order of glutathione > cysteine > penicillamine > N-acetylcysteine. Incubation of Co(II) with cumene-OOH or t-butyl-OOH in the presence of the histidyl oligopeptide Gly-Gly-His also generated lipid hydroperoxide-derived free radicals, with the yield being comparable to that obtained using thiols. In contrast, histidine, anserine, bomocarnosine, or carnosine did not cause any free radical generation from Co(II) and lipid hydroperoxides. Incubation of Co(II) with H2O2 produced only a small amount of 'OH radicals. Addition of glutathione to the mixture of Co(II) and H2O2 resulted in generation of both glutathionyl (GS.) and .OH radicals, which could be inhibited by DTPA and deferoxamine. Deferoxamine nitroxide radical was produced from deferoxamine incubated with Co(II) and H2O2. Under the same experimental conditions, cysteine, penicillamine, and N-acetylcysteine inhibited free radical generation from the reaction of Co(II) with H2O2. Histidine and histidyl oligopeptides, homocarnosine, and carnosine did not have a significant effect. However, anserine enhanced the .OH radical generation from this reaction. The results indicate that Co(II) is capable of generating free radicals from lipid hydroperoxides and H2O2 in the presence of proper chelating agents, which may be relevant to the mechanism(s) of Co(II)-related toxicity and carcinogenicity. C1 W VIRGINIA UNIV,DEPT CHEM,MORGANTOWN,WV 26506. RP SHI, XL (reprint author), NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702, USA. RI Shi, Xianglin/B-8588-2012 NR 35 TC 33 Z9 33 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD MAY-JUN PY 1993 VL 6 IS 3 BP 277 EP 283 DI 10.1021/tx00033a005 PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA LD004 UT WOS:A1993LD00400005 PM 8318649 ER PT J AU JANINI, GM CHAN, KC BARNES, JA MUSCHIK, GM ISSAQ, HJ AF JANINI, GM CHAN, KC BARNES, JA MUSCHIK, GM ISSAQ, HJ TI EFFECT OF ORGANIC-SOLVENTS ON SOLUTE MIGRATION AND SEPARATION IN CAPILLARY ZONE ELECTROPHORESIS SO CHROMATOGRAPHIA LA English DT Article DE CAPILLARY ZONE ELECTROPHORESIS; ORGANIC BUFFER ADDITIVES; ELECTROOSMOTIC MOBILITY; ELECTROPHORETIC MOBILITY; BUFFER VISCOSITY ID OPEN-TUBULAR CAPILLARY; INFLUENCE MOBILITY; SILICA CAPILLARIES; MICELLAR SOLUTIONS; FUSED-SILICA; BUFFER TYPE; RESOLUTION; PROTEINS; CHROMATOGRAPHY; SELECTIVITY AB The effect of organic modifiers on mobility and selectivity in capillary zone electrophoresis was investigated. Test solutes having different functionalities were electropherographed at acidic and neutral pH with aqueousorganic buffers. The results show that the electroosmotic mobility is mainly influenced by buffer viscosity. The role of the dielectric constant, zeta-potential and modifier-capillary wall interactions, which may be significant at trace levels of organic modifier, is very much diminished as the organic content is increased. Buffers having equivalent viscosities generate similar electroosmotic mobilities irrespective of the type and percentage of the organic modifier. Solute electrophoretic mobility is affected similarly because of the identical nature of the forces responsible for the electroosmotic and electrophoretic flow phenomena. However, solute electrophoretic mobility is also influenced by the degree to which the organic modifier affects the equilibrium that generates the electrophoretically-active solute ions. As a consequence, the order of elution of some solutes may change with increasing buffer organic content. The separation of weakly-hydrophilic solutes is improved with increasing organic proportions. The separation of dipeptides first improved with the addition of up to 15 % ACN, then deteriorated with further increase of ACN proportion. An example showing change in migration order and peak cross-over is presented and discussed. C1 NCI,FREDERICK CANC RES & DEV CTR,DYNCORP,PROGRAM RESOURCES INC,POB B,FREDERICK,MD 21702. NR 52 TC 67 Z9 68 U1 0 U2 6 PU FRIEDR VIEWEG SOHN VERLAG GMBH PI WIESBADEN 1 PA PO BOX 5829, W-6200 WIESBADEN 1, GERMANY SN 0009-5893 J9 CHROMATOGRAPHIA JI Chromatographia PD MAY-JUN PY 1993 VL 35 IS 9-12 BP 497 EP 502 DI 10.1007/BF02267906 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA LF563 UT WOS:A1993LF56300004 ER PT J AU BIESSMANN, H KASRAVI, B JAKES, K BUI, T IKENAGA, K MASON, JM AF BIESSMANN, H KASRAVI, B JAKES, K BUI, T IKENAGA, K MASON, JM TI THE GENOMIC ORGANIZATION OF HET-A RETROPOSONS IN DROSOPHILA-MELANOGASTER SO CHROMOSOMA LA English DT Article ID T DNA-SEQUENCES; CHIRONOMUS TELOMERES; ARABIDOPSIS-THALIANA; CHROMOSOME ENDS; MAMMALIAN LINES; FAMILY; ELEMENTS; HETEROCHROMATIN; CLONING; REGIONS AB Members of the Drosophila HeT-A family of transposable elements are LINE-like retroposons that are found at telomeres and in centric heterochromatin. We recently characterized an active HeT-A element that had transposed to a broken chromosome end fewer than nine generations before it was isolated. The sequence arrangement of this element, called 9D4, most likely represents the organization of an actively transposing member of the HeT-A family. Here we assess the degree of divergence among members of the HeT-A family and test a model of telomere length maintenance based on HeT-A transposition. The region containing the single open reading frame of this element appears to be more highly conserved than the non-coding regions. The HeT-A element has been implicated in the Drosophila telomere elongation process, because frequent transpositions to chromosome ends are sufficient to counter-balance nucleotide loss due to incomplete DNA replication. The proposed elongation model and the hypothetical mechanism of HeT-A transposition predict a predominant orientation of HeT-A elements with their oligo (A) tails facing proximally at chromosome ends, as well as the existence of irregular tandem arrays of HeT-A elements at chromosome ends resulting from transposition of new HeT-A elements onto chromosome ends with existing elements. Twenty-nine different HeT-A fragments were isolated from directional libraries that were enriched in terminal DNA fragments. Sequence analyses of these fragments and comparisons with the organization of the HeT-A element, 9D4, fit these two predictions and support the model of Drosophila telomere elongation by transposition of HeT-A elements. C1 NIEHS,EXPTL CARCINOGENESIS & MUTAGENESIS BRANCH,RES TRIANGLE PK,NC 27709. RP BIESSMANN, H (reprint author), UNIV CALIF IRVINE,CTR DEV BIOL,IRVINE,CA 92717, USA. FU NIGMS NIH HHS [GM46211] NR 37 TC 26 Z9 26 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0009-5915 J9 CHROMOSOMA JI Chromosoma PD MAY PY 1993 VL 102 IS 5 BP 297 EP 305 DI 10.1007/BF00661272 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA LB423 UT WOS:A1993LB42300001 PM 8391971 ER PT J AU POULEUR, H ROUSSEAU, MF VANEYLL, C MELIN, J YOUNGBLOOD, M YUSUF, S AF POULEUR, H ROUSSEAU, MF VANEYLL, C MELIN, J YOUNGBLOOD, M YUSUF, S TI CARDIAC MECHANICS DURING DEVELOPMENT OF HEART-FAILURE SO CIRCULATION LA English DT Article DE LEFT VENTRICULAR VOLUME; MYOCARDIAL CONTRACTILITY ID MYOCARDIAL-CONTRACTILITY; DYSFUNCTION; DISEASE; PRELOAD; RAT AB The changes in myocardial performance responsible for the progression from a stage of asymptomatic left ventricular dysfunction toward overt congestive heart failure are still poorly understood. Accordingly, using invasive methods, we examined the differences in baseline left ventricular function between a subgroup of patients enrolled in the treatment arm (presence of congestive heart failure) and in the prevention arm (asymptomatic patients) of the Studies of Left Ventricular Dysfunction. Methods and Results. High-fidelity left ventricular pressures and frame-by-frame angiographic volumes were simultaneously obtained under baseline conditions in 65 patients with left ventricular ejection fraction less-than-or-equal-to 35%. Sixteen patients had New York Heart Association congestive heart failure (class II or III), whereas the remaining 49 patients had no clinical signs of heart failure and did not receive therapy for this syndrome. A second set of data was obtained an average of 12.4 months later in 42 patients. The group with heart failure had significantly greater end-diastolic and end-systolic volumes than the asymptomatic group (both p <0.001), but the stroke index at rest was similar in both groups. Accordingly, ejection fraction was significantly lower in the heart failure group (19.6+/-7.0% versus 26.3+/-7.2%; p<0.02). Left ventricular end-diastolic pressure was greater and peak +dP/dt was lower in heart failure patients, but the difference did not reach statistical significance after Bonferroni correction for multiple comparisons. Moreover, the individual end-systolic stress/end-systolic volume data of the heart failure patients fell within the 95% confidence interval of the relation observed in the patients without heart failure both at baseline and after 1 year of follow-up irrespective of their changes in functional status. It was also noted that during follow-up, the changes in end-diastolic and end-systolic volumes correlated linearly, as if both dimensions always shifted in parallel, whereas alterations in contractility primarily influence end-systolic volume. Conclusions. These observations are compatible with the hypothesis that a depression in the mechanical performance of the viable myocardial areas is not the major determinant for the progression from asymptomatic to symptomatic left ventricular dysfunction. Abnormalities in left ventricular diastolic distensibility, on the other hand, might underlie the progressive ventricular dilation and create a vicious cycle through the afterload mismatch. C1 UNIV N CAROLINA,DEPT PULM,CHAPEL HILL,NC 27514. NHLBI,BETHESDA,MD 20892. RP POULEUR, H (reprint author), UNIV CATHOLIQUE LOUVAIN,DIV CARDIOL,AVE HIPPOCRATE 55-5560,B-1200 BRUSSELS,BELGIUM. NR 20 TC 29 Z9 30 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 MAY PY 1993 VL 87 IS 5 SU 4 BP 14 EP 20 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA LB362 UT WOS:A1993LB36200004 ER PT J AU PANZA, JA CASINO, PR KILCOYNE, CM QUYYUMI, AA AF PANZA, JA CASINO, PR KILCOYNE, CM QUYYUMI, AA TI ROLE OF ENDOTHELIUM-DERIVED NITRIC-OXIDE IN THE ABNORMAL ENDOTHELIUM-DEPENDENT VASCULAR RELAXATION OF PATIENTS WITH ESSENTIAL-HYPERTENSION SO CIRCULATION LA English DT Article DE HYPERTENSION; ENDOTHELIUM; ENDOTHELIUM-DERIVED RELAXING FACTOR; NITRIC OXIDE; ACETYLCHOLINE; NITROPRUSSIDE ID CORONARY SMOOTH-MUSCLE; RELAXING FACTOR; L-ARGININE; TONE; RELEASE; CELLS AB Background. Patients with essential hypertension have abnormal endothelium-dependent vasodilation. Because the endothelium exerts its action on the vascular smooth muscle through the release of several substances, it is important to identify which of these factors is involved in the abnormal response of hypertensive arteries. Methods and Results. To investigate the role of endothelium-derived nitric oxide in this abnormality, we studied the vascular effect of the arginine analogue N(G)-monomethyl-L-arginine, an inhibitor of the endothelial synthesis of nitric oxide, under baseline conditions and during infusion of acetylcholine, an endothelium-dependent vasodilator, and sodium nitroprusside, a direct smooth muscle dilator. The study included 11 hypertensive patients (seven men; age, 46.5+/-9 years) and 10 normal control subjects (seven men; age, 45.7+/-7 years). Drugs were infused into the brachial artery, and the response of the forearm vasculature was measured by strain-gauge plethysmography. Basal blood How was similar in normal control subjects and hypertensive patients (2.97+/-0.7 versus 2.86+/-1.1 mL . min-1 . 100 mL-1, respectively). N(G)-monomethyl-L-arginine produced a significantly greater decrease in blood flow in control subjects than in patients (1.08+/-0.6 versus 0.32+/-0.4 mL . min-1 . 100 mL-1; p < 0.004). The vasodilator response to acetylcholine was reduced in patients compared with control subjects (maximum flow, 8.2+/-4 versus 16.4+/-8 mL . min-1 . 100 mL-1; p<0.001). N(G)-monomethyl-L-arginine blunted the vasodilator response to acetylcholine in control subjects (maximum flow decreased from 16.4+/-8 to 7.01+/-3 mL . min-1 . 100 mL-1; p<0.004); however, the arginine analogue did not significantly alter the response to acetylcholine in hypertensive patients (maximum flow, 8.2+/-4 versus 8.01+/-5 mL . min-1 . 100 mL-1). N(G)-monomethyl-L-arginine did not modify the vasodilator response to sodium nitroprusside in either control subjects or patients. Conclusions. These findings indicate that patients with essential hypertension have a defect in the endothelium-derived nitric oxide system that may at least partly account for both the increased vascular resistance under basal conditions and the impaired response to endothelium-dependent vasodilators. RP PANZA, JA (reprint author), NHLBI,CARDIOL BRANCH,BLDG 10,ROOM 7B-15,BETHESDA,MD 20892, USA. NR 25 TC 576 Z9 601 U1 0 U2 9 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY PY 1993 VL 87 IS 5 BP 1468 EP 1474 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA LB084 UT WOS:A1993LB08400005 PM 8491001 ER PT J AU PANZA, JA CASINO, PR BADAR, DM QUYYUMI, AA AF PANZA, JA CASINO, PR BADAR, DM QUYYUMI, AA TI EFFECT OF INCREASED AVAILABILITY OF ENDOTHELIUM-DERIVED NITRIC-OXIDE PRECURSOR ON ENDOTHELIUM-DEPENDENT VASCULAR RELAXATION IN NORMAL SUBJECTS AND IN PATIENTS WITH ESSENTIAL-HYPERTENSION SO CIRCULATION LA English DT Article DE ENDOTHELIUM-DERIVED RELAXING FACTOR; NITRIC OXIDE; ARGININE; HYPERTENSION ID CORONARY SMOOTH-MUSCLE; L-ARGININE; RELAXING FACTOR; ARTERIES; TONE; ACETYLCHOLINE; VASODILATION; RELEASE; CELLS AB Background. Patients with essential hypertension have a deficit in the endothelium-derived nitric oxide system that results in impaired endothelium-dependent vascular relaxation. The objective of this study was to determine whether this abnormality is caused by a deficiency of substrate for nitric oxide synthesis. Methods and Results. The vascular responses to acetylcholine (an endothelium-dependent vasodilator infused at 7.5, 15, and 30 mug/min) and sodium nitroprusside (a direct smooth muscle dilator infused at 0.8, 1.6, and 3.2 mug/min) were studied during combined administration of dextrose 5% or L-arginine (substrate for nitric oxide synthesis infused at 40 mumol/min) in 12 normal control subjects (seven men and five women; age, 49.3+/-7 years) and 14 hypertensive patients (nine men and five women; age, 48.4+/-7 years). In addition, the effect Of D-arginine (stereoisomer of arginine that is not a precursor of nitric oxide) on the vascular responses to acetylcholine was studied in eight normal control subjects and seven hypertensive patients. Drugs were infused into the brachial artery, and the response of the forearm vasculature was measured by strain gauge plethysmography. The vasodilator response to acetylcholine was significantly blunted in hypertensive patients compared with normal control subjects (maximum flow, 8.9+/-5 versus 15.7+/-6 mL . min-1 . 100 mL-1, respectively; p < 0.007); however, no difference was observed in the response to sodium nitroprusside (11.4+/-6 and 11.7+/-mL . min-1 . 100 mL-1, respectively). L-Arginine did not significantly change basal blood flow or vascular resistance in either group. In normal control subjects, the infusion Of L-arginine significantly augmented the vasodilator response to acetylcholine (maximum How, 15.7+/-6 versus 21.4+/-8 mL . min-1 . 100 ml-1 before and after L-arginine, respectively p < 0.001). In contrast, in hypertensive patients, the infusion of L-arginine did not alter the response to acetylcholine (maximum flow, 8.9+/-5 and 8.4+/-4 mL . min-1 . 100 mL-1 before and after L-arginine, respectively). The administration of L-arginine did not modify the response to sodium nitroprusside in either group. Similarly, the infusion of D-arginine did not alter the response to acetylcholine in either group. Conclusions. In normal humans, availability of substrate for production of nitric oxide is a rate-limiting step for endothelium-dependent vascular relaxation. In contrast, increased availability of nitric oxide precursor does not modify endothelium-mediated vasodilation in hypertensive patients. These findings provide further evidence of a defect in the endothelium-derived nitric oxide system in hypertension and indicate that this abnormality is not related to decreased availability of substrate for nitric oxide production. RP PANZA, JA (reprint author), NHLBI,CARDIOL BRANCH,BLDG 10,ROOM 7B-15,BETHESDA,MD 20892, USA. NR 30 TC 251 Z9 260 U1 0 U2 3 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY PY 1993 VL 87 IS 5 BP 1475 EP 1481 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA LB084 UT WOS:A1993LB08400006 PM 8491002 ER PT J AU KLUES, HG ROBERTS, WC MARON, BJ AF KLUES, HG ROBERTS, WC MARON, BJ TI MORPHOLOGICAL DETERMINANTS OF ECHOCARDIOGRAPHIC PATTERNS OF MITRAL-VALVE SYSTOLIC ANTERIOR MOTION IN OBSTRUCTIVE HYPERTROPHIC CARDIOMYOPATHY SO CIRCULATION LA English DT Article DE HYPERTROPHIC CARDIOMYOPATHY; MITRAL VALVE; SYSTOLIC ANTERIOR MOTION; SUBAORTIC OBSTRUCTION ID VENTRICULAR OUTFLOW OBSTRUCTION; DYNAMIC SUBAORTIC OBSTRUCTION; PRESSURE-GRADIENT; CLINICAL MANIFESTATIONS; PATHO-PHYSIOLOGY; STENOSIS; MECHANISM; INTERRELATIONS; REPLACEMENT; THERAPY AB Background. The morphological determinants of mitral valve systolic anterior motion (SAM) and obstruction to left ventricular outflow in patients within the broad clinical spectrum of hypertrophic cardiomyopathy (HCM) are not completely understood, particularly the contribution of mitral leaflet length and size. Methods and Results. To clarify this issue, mitral valve specimens from 43 patients with HCM and basal outflow obstruction were used to relate morphometric measurements of leaflet area to certain morphological and functional assessments of left ventricular outflow tract geometry and valvular motion obtained from echocardiograms in the same patients. Twenty-four patients (56%) had mitral valves of normal size (leaflet area <12.0 cm2) and 19 patients (44%) had enlarged and elongated valves (area greater-than-or-equal-to 12.0 cm2). Compared with normal-sized mitral valves, the enlarged valves were situated more posteriorly in a larger left ventricular outflow tract (cross-sectional area, 3.3+/-1.0 versus 1.9+/-0.7 cm2 for normal-sized valves; p<0.001) and also had greater systolic excursion of the anterior leaflet (16.2+/-4.5 versus 13.3+/-3.3 mm, p<0.02), usually with a distinctive sharp-angled bend and localized contact of the leaflet tip with ventricular septum (''typical'' SAM); this pattern of SAM was possible because the central and distal portions of the leaflet were relatively free of fibrous thickening. In contrast, normal-sized mitral valves were situated more anteriorally in a smaller left ventricular outflow tract and frequently showed a different mechanism of SAM and subaortic obstruction with relatively limited leaflet motion, absence of a sharp bend, and septal contact involving more substantial portions of the anterior leaflet and contiguous chordae (''atypical'' SAM); mitral-septal apposition was effected in large measure by posterior ventricular septal motion. This pattern of SAM was invariably associated with a more diffuse pattern of fibrous thickening. Conclusions. Patients with obstructive HCM show patterns of mitral valve SAM that are diverse and determined largely by the interrelation of left ventricular outflow tract geometry, the size and mobility of the mitral leaflets, and the presence and distribution of fibrous thickening. C1 NHLBI,CARDIOL BRANCH,BLDG 10,ROOM 7B-15,BETHESDA,MD 20892. NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. NR 52 TC 80 Z9 83 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 MAY PY 1993 VL 87 IS 5 BP 1570 EP 1579 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA LB084 UT WOS:A1993LB08400018 PM 8491013 ER PT J AU LEMARCHAND, P JONES, M YAMADA, I CRYSTAL, RG AF LEMARCHAND, P JONES, M YAMADA, I CRYSTAL, RG TI INVIVO GENE-TRANSFER AND EXPRESSION IN NORMAL UNINJURED BLOOD-VESSELS USING REPLICATION-DEFICIENT RECOMBINANT ADENOVIRUS VECTORS SO CIRCULATION RESEARCH LA English DT Note DE ADENOVIRUS; GENE EXPRESSION; GENE TRANSFER; ENDOTHELIUM ID ENDOTHELIAL-CELLS; RETROVIRAL VECTORS; SKIN FIBROBLASTS; ARTERIAL-WALL; FACTOR-IX AB Replication-deficient recombinant adenovirus vectors do not require target cell replication for transfer and expression of exogenous genes and thus may be useful for in vivo gene therapy in the endothelium. To evaluate the feasibility of adenovirus-mediated gene transfer in vivo in normal intact blood vessels, adenovirus vectors containing the Escherichia coli lacZ gene or a human alpha1-antitrypsin (alpha1AT) cDNA were injected in vivo into the lumen of an occluded vessel segment of sheep jugular vein and/or carotid artery. After 15 minutes of incubation, circulation was restored; the vessels were harvested 1-28 days later and evaluated for gene transfer and expression. Three days after in vivo exposure to the lacZ adenovirus vector, the endothelium of jugular veins and carotid arteries expressed beta-galactosidase. Exposure of jugular veins and carotid arteries in vivo to the alpha1AT adenovirus vector resulted in the expression of alpha1AT mRNA transcripts detected by Northern analysis and in the synthesis and secretion of alpha1AT detected by ex vivo [S-35]methionine labeling. Expression with the adenovirus vectors was efficient and easily detectable 1-14 days after injection, with maximum expression at 7 days. Expression was no longer evident at 28 days. Thus, adenovirus vectors are capable of transferring exogenous genes to the endothelium of normal arteries and veins with expression for at least 2 weeks, suggesting that these vectors have the potential for a variety of cardiovascular experimental and clinical applications. C1 NHLBI,PULM BRANCH,BETHESDA,MD 20892. NHLBI,LAB ANIM MED & SURG SECT,BETHESDA,MD 20892. RI lemarchand, patricia/C-3247-2011 NR 33 TC 259 Z9 260 U1 0 U2 4 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD MAY PY 1993 VL 72 IS 5 BP 1132 EP 1138 PG 7 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA KY091 UT WOS:A1993KY09100022 PM 8477524 ER PT J AU SIEGEL, KL STANHOPE, SJ CALDWELL, GE AF SIEGEL, KL STANHOPE, SJ CALDWELL, GE TI KINEMATIC AND KINETIC ADAPTATIONS IN THE LOWER-LIMB DURING STANCE IN GAIT OF UNILATERAL FEMORAL NEUROPATHY PATIENTS SO CLINICAL BIOMECHANICS LA English DT Article DE QUADRICEPS FEMORIS; FEMORAL NERVE; GAIT; BIOMECHANICS ID NORMAL WALKING AB This study aimed to quantify the impact of a unilateral femoral neuropathy on joint kinematic and kinetic strategies employed in the lower limbs during gait. The stance phase of gait of four subjects with proximal femoral nerve injury occurring 5-15 months previously was investigated with a video-based data collection system. Kinematic and kinetic data of the pelvis and lower limb segments were sampled unilaterally from both the involved and uninvolved lower extremities. Results revealed that the uninvolved limb demonstrated no clear compensatory strategies except for prolonged stance phase in three of the four subjects. In the involved limb the knee was maintained near full extension throughout much of the stance phase. This was accomplished by minimizing the posterior ground reaction force in early stance, increasing eccentric plantarflexor control of the tibia, and increasing concentric hip extensor control of the femur. These adaptations appeared to be more successful in the subject who was stronger in the uninvolved musculature. The strategies in the other three subjects appeared to be less effective, based on the subjects' slow velocity of gait, knee hyperextension, and use of assistive devices. C1 UNIV MARYLAND,DEPT KINESIOL,COLL PK,MD 20742. RP SIEGEL, KL (reprint author), NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT REHABIL MED,BIOMECH LAB,BETHESDA,MD 20892, USA. NR 22 TC 6 Z9 6 U1 0 U2 1 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0268-0033 J9 CLIN BIOMECH JI Clin. Biomech. PD MAY PY 1993 VL 8 IS 3 BP 147 EP 155 PG 9 WC Engineering, Biomedical; Orthopedics; Sport Sciences SC Engineering; Orthopedics; Sport Sciences GA LC057 UT WOS:A1993LC05700006 ER PT J AU YUSUF, S AF YUSUF, S TI CLINICAL-EXPERIENCE IN PROTECTING THE FAILING HEART SO CLINICAL CARDIOLOGY LA English DT Article; Proceedings Paper CT SYMP ON PROTECTING THE OVERLOADED HEART, AT THE 41ST ANNUAL SCIENTIFIC SESSION OF THE AMERICAN COLLEGE OF CARDIOLOGY CY APR 11, 1992 CL DALLAS, TX SP AMER COLL CARDIOL, UNIV CONNECTICUT SCH MED FARMINGTON DE CONGESTIVE HEART FAILURE; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; VASODILATORS; INOTROPIC AGENTS; MILRINONE; DIGITALIS; ANTIARRHYTHMIC AGENTS; AMIODARONE; BETA-BLOCKERS; CALCIUM CHANNEL BLOCKERS ID ACUTE MYOCARDIAL-INFARCTION; SMOOTH-MUSCLE CELLS; ANGIOTENSIN-II; MORTALITY; HYPERTROPHY; FAILURE; PLACEBO; TRIAL; RAT AB Several large, carefully randomized studies of pharmaceutical agents in the treatment of patients with congestive heart failure (CHF) and left ventricular dysfunction have demonstrated conclusively that angiotensin-converting enzyme (ACE) inhibitors reduce mortality among patients with CHF, as well as the number of hospitalizations for heart failure, myocardial infarction (MI), and angina. ACE inhibitors also have been shown to prevent the development of heart failure in patients with asymptomatic left ventricular dysfunction. Phosphodiesterase inhibitors and the beta agonists have been shown to increase mortality with no beneficial effect on morbidity. The role of digitalis remains controversial. On the one hand, the limited data available suggest that digoxin prevents clinical deterioration in patients with heart failure, even in the presence of sinus rhythm. On the other hand, when administered after MI, digoxin has been associated with increased mortality. Such conclusions are unreliable, however, since it is impossible to adjust statistically for the fact that digoxin is used in sicker patients. This question will be addressed in a large randomized study currently being conducted by the Digitalis Investigation Group. Pharmacologic approaches to the reduction of sudden death currently being explored include amiodarone, oral magnesium supplements, and beta blockers. According to the Cardiac Arrhythmia Suppression Trial and other studies, the class I antiarrhythmic agents appear unpromising or even harmful. The calcium channel blockers also appear to be contraindicated as routine therapy for CHF. C1 NHLBI,CLIN TRIALS BRANCH,BETHESDA,MD 20892. NR 18 TC 2 Z9 2 U1 0 U2 0 PU CLINICAL CARDIOLOGY PUBL CO PI MAHWAH PA PO BOX 832, MAHWAH, NJ 07430-0832 SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD MAY PY 1993 VL 16 IS 5 SU 2 BP 25 EP 29 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA LA961 UT WOS:A1993LA96100006 ER PT J AU KATZ, AM DZAU WEBER COHN MESSERLI YUSUF AF KATZ, AM DZAU WEBER COHN MESSERLI YUSUF TI PROTECTING THE OVERLOADED HEART - PANEL DISCUSSION - QUESTION AND ANSWER SESSION SO CLINICAL CARDIOLOGY LA English DT Discussion CT SYMP ON PROTECTING THE OVERLOADED HEART, AT THE 41ST ANNUAL SCIENTIFIC SESSION OF THE AMERICAN COLLEGE OF CARDIOLOGY CY APR 11, 1992 CL DALLAS, TX SP AMER COLL CARDIOL, UNIV CONNECTICUT SCH MED FARMINGTON ID HYPERTROPHY C1 STANFORD UNIV,MED CTR,SCH MED,FALK CARDIOVASC RES CTR,DIV CARDIOVASC MED,STANFORD,CA 94305. UNIV MISSOURI,HLTH SCI CTR,DEPT INTERNAL MED,COLUMBIA,MO 65212. ALTON OCHSNER MED FDN & OCHSNER CLIN,DEPT INTERNAL MED,NEW ORLEANS,LA 70121. UNIV MINNESOTA,SCH MED,DEPT MED,DIV CARDIOVASC,MINNEAPOLIS,MN 55455. NHLBI,CLIN TRIALS BRANCH,BETHESDA,MD 20892. RP KATZ, AM (reprint author), UNIV CONNECTICUT,SCH MED,DIV CARDIOL,263 FARMINGTON AVE,FARMINGTON,CT 06032, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU CLINICAL CARDIOLOGY PUBL CO PI MAHWAH PA PO BOX 832, MAHWAH, NJ 07430-0832 SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD MAY PY 1993 VL 16 IS 5 SU 2 BP 30 EP 31 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA LA961 UT WOS:A1993LA96100007 ER PT J AU EMANCIPATOR, K KROLL, MH AF EMANCIPATOR, K KROLL, MH TI A QUANTITATIVE MEASURE OF NONLINEARITY SO CLINICAL CHEMISTRY LA English DT Article DE QUALITY CONTROL; STATISTICS AB Quantitative measures of the nonlinearity of an analytical method are defined as follows: the ''(dimensional) nonlinearity'' of a method is the square root of the mean of the square of the deviation of the response curve from a straight line, where the straight line is chosen to minimize the nonlinearity. The ''relative nonlinearity'' is defined as the dimensional nonlinearity divided by the difference between the maximum and minimum assayed values. These definitions may be used to develop practical criteria for linearity that are still objective. Calculation of the nonlinearity requires a method of curve-fitting. In this article, we use polynomial regression to demonstrate calculations, but the definition of nonlinearity also accommodates alternative nonlinear regression procedures. C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT CLIN PATHOL,BETHESDA,MD 20892. RP EMANCIPATOR, K (reprint author), CORNELL UNIV,MED CTR,NEW YORK HOSP,DEPT PATHOL,525 E 68TH ST,NEW YORK,NY 10021, USA. NR 11 TC 37 Z9 41 U1 0 U2 2 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD MAY PY 1993 VL 39 IS 5 BP 766 EP 772 PG 7 WC Medical Laboratory Technology SC Medical Laboratory Technology GA LB546 UT WOS:A1993LB54600004 PM 8485866 ER PT J AU CSAKO, G BENSON, CC ELIN, RJ AF CSAKO, G BENSON, CC ELIN, RJ TI FALSE-POSITIVE KETONE REACTIONS IN CAP SURVEYS SO CLINICAL CHEMISTRY LA English DT Letter ID URINARY KETONES; MESNA; THERAPY RP CSAKO, G (reprint author), NIH,WG MAGNUSON CLIN CTR,CLIN CHEM SERV,BLDG 10,RM 2C-407,BETHESDA,MD 20892, USA. NR 9 TC 4 Z9 4 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD MAY PY 1993 VL 39 IS 5 BP 915 EP 917 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA LB546 UT WOS:A1993LB54600046 PM 8485898 ER PT J AU SHI, YE TORRI, J YIEH, L SOBEL, ME YAMADA, Y LIPPMAN, ME DICKSON, RB THOMPSON, EW AF SHI, YE TORRI, J YIEH, L SOBEL, ME YAMADA, Y LIPPMAN, ME DICKSON, RB THOMPSON, EW TI EXPRESSION OF 67 KDA LAMININ RECEPTOR IN HUMAN BREAST-CANCER CELLS - REGULATION BY PROGESTINS SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE ADHESION; ANTIPROGESTINS; HUMAN BREAST CANCER; LAMININ RECEPTOR; PROGESTINS ID GROWTH-FACTOR RECEPTOR; AMINO-ACID-SEQUENCE; BINDING-PROTEIN; PROGESTERONE ANTAGONISTS; EXTRACELLULAR-MATRIX; CARCINOMA-CELLS; MESSENGER-RNA; TUMOR-CELLS; METASTASIS; RAT AB The level of 67 kDa laminin receptor (67LR) expression on breast and colon tumor cell surfaces was previously shown to be correlated with the capacity of tumor cells to metastasize. In the present work we investigate the effects of progestins and estrogen on the expression of 67LR in two sublines of the T47D human breast cancer cells: weakly tumorigenic, poorly invasive parental T47D cells and a highly tumorigenic, more invasive T47Dco subclone. Immunoblotting with an affinity purified antibody directed against a synthetic peptide recognizes the 67LR in these cells. 67LR expression in the T47Dco subclone is 5.5-fold higher than in their parental T47D cells. Treatment of T47D cells with 1 nM of the synthetic progestin R5020 results' in a 4-fold increase in 67LR protein expression. Estrogen also induced 67LR expression, but only by 1.5-fold. The progestin-stimulated expression of the 67LR correlates with a 4.3-fold increase in attachment of T47D cells to laminin. A monoclonal antibody, mAb 13, directed against beta1 integrin, completely blocks the attachment of T47D cells to fibronectin, only partially inhibits the attachment of T47D cells to laminin, and appears not to affect the progestin-stimulated laminin attachment of T47D cells. A new antiprogestin, ZK 112.993, significantly inhibits both progestin-stimulated 67LR expression and the increased attachment to laminin. These results suggest a possible role for progestin in mediating one of the multiple events thought to be important in metastasis of steroid receptor positive human breast cancer cells. C1 NIDR,DEV BIOL LAB,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. RP SHI, YE (reprint author), GEORGETOWN UNIV,MED CTR,VINCENT T LOMBARDI CANC RES CTR,3800 RESERVOIR RD NW,WASHINGTON,DC 20007, USA. RI Thompson, Erik/A-1425-2009 OI Thompson, Erik/0000-0002-9723-4924 NR 55 TC 24 Z9 24 U1 0 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD MAY PY 1993 VL 11 IS 3 BP 251 EP 261 DI 10.1007/BF00121168 PG 11 WC Oncology SC Oncology GA LA388 UT WOS:A1993LA38800003 PM 8472397 ER PT J AU MOJCIK, CF GOURLEY, MF KLINMAN, DM KRIEG, AM GMELIGMEYLING, F STEINBERG, AD AF MOJCIK, CF GOURLEY, MF KLINMAN, DM KRIEG, AM GMELIGMEYLING, F STEINBERG, AD TI ADMINISTRATION OF A PHOSPHOROTHIOATE OLIGONUCLEOTIDE ANTISENSE TO MURINE ENDOGENOUS RETROVIRAL MCF ENV CAUSES IMMUNE EFFECTS INVIVO IN A SEQUENCE-SPECIFIC MANNER SO CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article ID HUMAN IMMUNODEFICIENCY VIRUS; FELINE LEUKEMIA-VIRUS; GENE-EXPRESSION; T-CELLS; OLIGODEOXYNUCLEOTIDES; ANALOGS; OLIGODEOXYRIBONUCLEOTIDES; REPLICATION; INHIBITION; PROTEIN C1 US FDA,CBER,DIV VIROL,BETHESDA,MD 20892. MITRE CORP,MCLEAN,VA 22102. RP MOJCIK, CF (reprint author), NIAMSD,ARTHRIT & RHEUMATISM BRANCH,CELLULAR IMMUNOL SECT,BETHESDA,MD 20892, USA. NR 37 TC 29 Z9 30 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 0090-1229 J9 CLIN IMMUNOL IMMUNOP JI Clin. Immunol. Immunopathol. PD MAY PY 1993 VL 67 IS 2 BP 130 EP 136 DI 10.1006/clin.1993.1055 PG 7 WC Immunology; Pathology SC Immunology; Pathology GA KY917 UT WOS:A1993KY91700006 PM 7686091 ER PT J AU WHITCUP, SM DEBARGE, LR CASPI, RR HARNING, R NUSSENBLATT, RB CHAN, CC AF WHITCUP, SM DEBARGE, LR CASPI, RR HARNING, R NUSSENBLATT, RB CHAN, CC TI MONOCLONAL-ANTIBODIES AGAINST ICAM-1 (CD54) AND LFA-1 (CD11A/CD18) INHIBIT EXPERIMENTAL AUTOIMMUNE UVEITIS SO CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article ID INTERCELLULAR-ADHESION MOLECULE-1; RETINOID-BINDING PROTEIN; INTERFERON-GAMMA; ANTIGEN; INDUCTION; PRIMATES; DISEASE; MICE; UVEORETINITIS; MODULATION C1 ROBERTS PHARMACEUT CORP,EATONTOWN,NJ 07724. RP WHITCUP, SM (reprint author), NEI,IMMUNOL LAB,BETHESDA,MD 20892, USA. NR 33 TC 85 Z9 85 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 MAY PY 1993 VL 67 IS 2 BP 143 EP 150 DI 10.1006/clin.1993.1057 PG 8 WC Immunology; Pathology SC Immunology; Pathology GA KY917 UT WOS:A1993KY91700008 PM 8100190 ER PT J AU PICKWORTH, WB JOHNSON, RE HOLICKY, BA CONE, EJ AF PICKWORTH, WB JOHNSON, RE HOLICKY, BA CONE, EJ TI SUBJECTIVE AND PHYSIOLOGICAL-EFFECTS OF INTRAVENOUS BUPRENORPHINE IN HUMANS SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID HEROIN-ADDICTS; DEPENDENCE; AGONIST; AGENT; ABUSE; DRUG; PHARMACOLOGY; METHADONE AB The pharmacologic profile of sublingual and subcutaneous buprenorphine, a partial opioid agonist, indicates it may be useful as a maintenance drug in the treatment of opioid dependence. However, illicit intravenous self-administration suggests that it may have a greater abuse potential by this route of administration. Physiologic and subjective effects of intravenous buprenorphine (0.0, 0.3, 0.6, and 1.2 mg) were determined in a dose-escalation study in six nondependent volunteers with histories of opioid use. Buprenorphine caused miosis and decreased respiratory rate, increased diastolic blood pressure, and transiently increased heart rate. Buprenorphine increase d positive responses on a ''feel drug'' question and scores on scales of ''liking,'' ''good effects,'' euphoria, and apathetic sedation. Physiologic and subjective responses were not consistently dose related, a finding compatable with the pharmacologic profile of a partial agonist. The findings indicate that buprenorphine has substantial potential for abuse when administered intravenously. C1 NIDA,ADDICT RES CTR,CLIN PHARMACOL BRANCH,POB 5180,BALTIMORE,MD 21224. NR 37 TC 60 Z9 62 U1 1 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAY PY 1993 VL 53 IS 5 BP 570 EP 576 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA LE147 UT WOS:A1993LE14700010 PM 8491067 ER PT J AU WOLFOVITZ, E GROSSMAN, E FOLIO, CJ KEISER, HR KOPIN, IJ GOLDSTEIN, DS AF WOLFOVITZ, E GROSSMAN, E FOLIO, CJ KEISER, HR KOPIN, IJ GOLDSTEIN, DS TI DERIVATION OF URINARY DOPAMINE FROM PLASMA DIHYDROXYPHENYLALANINE IN HUMANS SO CLINICAL SCIENCE LA English DT Article DE CATECHOLAMINES; DIHYDROXYPHENYLALANINE; DOPAMINE; NATRIURESIS; SYMPATHETIC NERVOUS SYSTEM ID PERFUSED RAT-KIDNEY; VOLUME EXPANSION; TUBULE CELLS; RENAL TUBULE; EXCRETION; CATECHOLAMINES; SODIUM; NOREPINEPHRINE; HYPERTENSION; 3,4-DIHYDROXYPHENYLALANINE AB 1. Dihydroxyphenylalanine is the precursor of all endogenous catecholamines. In laboratory animals, renal uptake and decarboxylation of circulating dihydroxyphenylalanine accounts for most of dopamine in urine. Dopamine is natriuretic, and in rats, dietary salt loading increases renal dihydroxyphenylalanine uptake by increasing the rate of entry (spillover) of dihydroxyphenylalanine into arterial plasma. In experimental animals and in humans, dietary salt loading increases urinary excretion of dihydroxyphenylalanine and dopamine. The present study examined in humans the extent to which circulating dihydroxyphenylalanine is the source of urinary dopamine and of the dopamine metabolite dihydroxyphenylacetic acid, and whether, as in animals, dietary salt loading affects dihydroxyphenylalanine spillover. 2. L-Dihydroxyphenylalanine (0.33 mug min-1 kg-1) was infused intravenously for 300 min after 7 days of a low-salt (mean 41 mmol/day) or a high-salt (mean 341 mmol/day) diet in 12 healthy subjects. Concentrations of dihydroxyphenylalanine, dopamine and dihydroxyphenylacetic acid were measured in urine and in antecubital venous plasma. Infusion of L-dihydroxyphenylalanine produced a steady-state mean dihydroxyphenylalanine level about 10 times the endogenous level. About 30% of infused dihydroxyphenylalanine estimated to be delivered to the kidneys via the arterial plasma was excreted as dopamine, and about 30% was excreted as dihydroxyphenylacetic acid. 3. Dietary salt loading increased urinary excretion rates of dihydroxyphenylalanine [from 0.08+/-(SEM) 0.01 to 0.14+/-0.03 nmol/min, t=2.80, P<0.02] and dopamine (from 1.03+/-0.19 to 1.30+/-0.28 nmol/min, t=2.35, P<0.05), whereas dihydroxyphenylalanine spillover appeared to be unchanged. 4. Renal uptake and decarboxylation of circulating dihydroxyphenylalanine accounted for virtually all the urinary excretion of endogenous dopamine, but for only a minor portion of the excreted endogenous dihydroxyphenylacetic acid. 5. We conclude that in humans: (1) circulating dihydroxyphenylalanine is the main source of urinary dopamine but only a minor source of urinary dihydroxyphenylacetic acid; and (2) increased spillover of endogenous dihydroxyphenylalanine does not account for the increased excretion of these compounds during salt loading. C1 NINCDS,CLIN NEUROSCI BRANCH,BLDG 10,ROOM 5N262,BETHESDA,MD 20892. CHAIM SHEBA MED CTR,HYPERTENS UNIT,IL-52621 TEL HASHOMER,ISRAEL. NHLBI,HYPERTENS ENDOCRINE BRANCH,BETHESDA,MD 20892. NR 42 TC 64 Z9 64 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0143-5221 J9 CLIN SCI JI Clin. Sci. PD MAY PY 1993 VL 84 IS 5 BP 549 EP 557 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LB085 UT WOS:A1993LB08500009 PM 8504632 ER PT J AU COLE, PM AF COLE, PM TI EMOTION AND ITS REGULATION IN EARLY DEVELOPMENT - EISENBERG,N, FABES,RA SO CONTEMPORARY PSYCHOLOGY LA English DT Book Review RP COLE, PM (reprint author), NIMH,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 1 U2 7 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0010-7549 J9 CONTEMP PSYCHOL JI Comtemp. Psychol. PD MAY PY 1993 VL 38 IS 5 BP 481 EP 482 PG 2 WC Psychology, Multidisciplinary SC Psychology GA LB424 UT WOS:A1993LB42400015 ER PT J AU TANDON, P POPE, C PADILLA, S TILSON, HA HARRY, GJ AF TANDON, P POPE, C PADILLA, S TILSON, HA HARRY, GJ TI DEVELOPMENTAL-CHANGES IN CARBACHOL-STIMULATED INOSITOLPHOSPHATE RELEASE IN PIGMENTED RAT RETINA SO CURRENT EYE RESEARCH LA English DT Article ID INOSITOL PHOSPHATE FORMATION; CENTRAL NERVOUS-SYSTEM; RABBIT RETINA; PHOSPHOINOSITIDE METABOLISM; CHOLINE-ACETYLTRANSFERASE; MUSCARINIC RECEPTORS; OUTER SEGMENTS; BRAIN; ACETYLCHOLINE; HYDROLYSIS AB Carbachol-stimulated release of inositolphosphates (IP) was studied in the whole retina from Long-Evans rats of different ages (day 5, 10, 15, 20, adult) following in vitro incorporation of [H-3]myo-inositol. Unlike the albino rat retina, the pigmented retina was highly light-sensitive, making it necessary to dark adapt the animals and perform retinal dissections under low illumination to prevent light-induced IP release. Retinae from postnatal day 10 rats showed the highest amount of carbachol-stimulated IP released. This response to carbachol decreased with age until postnatal day 20 when it reached adult levels. The pigmented rat retina showed a sharp fall in the degree of carbachol (1 mM)-stimulated IP released at the time of eye-opening (450% above basal in retinae from 10 day old animals, as compared to 230% above basal in 15 day old retinae). Basal release of IP was not altered in the retina during development. Muscarinic cholinergic receptor density was, however, found to increase 5 fold with age, reaching adult levels by PND 20. Retinal weight and protein per retina also increased (four fold) from day 5 to adult; however, the in vitro incorporation of [H-3]myoinositol into phosphoinositides (calculated as per mg protein) did not change during development. Thus, in animals prior to eye opening, a much higher proportion of phosphoinositides appears to be hydrolyzed upon muscarinic receptor stimulation. During retinal development a change in sensitivity to the agonist-sensitive pool(s) of phosphoinositides may occur and/or there may be alterations in the efficacy of receptor coupling to the second messenger system resulting in the disassociation observed between the drastic increase in receptor number and the apparent decrease in receptor-stimulated release of IP. C1 NE LOUISIANA UNIV, SCH PHARM, TOXICOL PROGRAM, MONROE, LA 71209 USA. UNIV N CAROLINA, CTR ENVIRONM MED & LUNG BIOL, CHAPEL HILL, NC 27514 USA. NIEHS, RES TRIANGLE PK, NC 27709 USA. RP US EPA, DIV NEUROTOXICOL, MD-74B, RES TRIANGLE PK, NC 27711 USA. NR 47 TC 3 Z9 3 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0271-3683 EI 1460-2202 J9 CURR EYE RES JI Curr. Eye Res. PD MAY PY 1993 VL 12 IS 5 BP 439 EP 449 DI 10.3109/02713689309024626 PG 11 WC Ophthalmology SC Ophthalmology GA LH747 UT WOS:A1993LH74700007 PM 8344068 ER PT J AU TAUB, DD OPPENHEIM, JJ AF TAUB, DD OPPENHEIM, JJ TI REVIEW OF THE CHEMOKINE MEETING THE 3RD INTERNATIONAL-SYMPOSIUM OF CHEMOTACTIC CYTOKINES SO CYTOKINE LA English DT Editorial Material ID FAMILY; RECEPTOR RP TAUB, DD (reprint author), NCI,FCRDC,BIOL RESPONSE MODIFIER PROGRAM,MOLEC IMMUNOREGULAT LAB,FREDERICK,MD 21702, USA. NR 13 TC 78 Z9 88 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1043-4666 J9 CYTOKINE JI Cytokine PD MAY PY 1993 VL 5 IS 3 BP 175 EP 179 DI 10.1016/1043-4666(93)90001-L PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA LX573 UT WOS:A1993LX57300001 PM 8218927 ER PT J AU WANG, JM HISHINUMA, A OPPENHEIM, JJ MATSUSHIMA, K AF WANG, JM HISHINUMA, A OPPENHEIM, JJ MATSUSHIMA, K TI STUDIES OF BINDING AND INTERNALIZATION OF HUMAN RECOMBINANT MONOCYTE CHEMOTACTIC AND ACTIVATING FACTOR (MCAF) BY MONOCYTIC CELLS SO CYTOKINE LA English DT Article DE DOWN-REGULATION; INTERNALIZATION; MONOCYTES; RECEPTORS; RHMCAF ID RECEPTOR-MEDIATED ENDOCYTOSIS; HUMAN INTERLEUKIN-8 RECEPTOR; EPIDERMAL GROWTH-FACTOR; TUMOR-NECROSIS-FACTOR; SMOOTH-MUSCLE CELLS; AMINO-ACID ANALYSIS; ENDOTHELIAL-CELLS; HUMAN-NEUTROPHILS; EXPRESSION; PURIFICATION C1 KANAZAWA UNIV,CANC RES INST,DEPT PHARMACOL,KANAZAWA,ISHIKAWA 920,JAPAN. RP WANG, JM (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702, USA. NR 40 TC 33 Z9 33 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1043-4666 J9 CYTOKINE JI Cytokine PD MAY PY 1993 VL 5 IS 3 BP 264 EP 275 DI 10.1016/1043-4666(93)90014-V PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA LX573 UT WOS:A1993LX57300014 PM 8218939 ER PT J AU WOLFFE, AP AF WOLFFE, AP TI REPLICATION TIMING AND XENOPUS 5S RNA GENE-TRANSCRIPTION INVITRO SO DEVELOPMENTAL BIOLOGY LA English DT Article ID CELL-FREE SYSTEM; DNA-REPLICATION; DEVELOPMENTAL REGULATION; 5S-RNA GENE; CHROMATIN; COMPLEX; LAEVIS; INITIATION; NUCLEI; EGGS RP WOLFFE, AP (reprint author), NICHHD,MOLEC EMBRYOL LAB,BLDG 6,ROOM B1A-13,BETHESDA,MD 20892, USA. NR 37 TC 17 Z9 17 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD MAY PY 1993 VL 157 IS 1 BP 224 EP 231 DI 10.1006/dbio.1993.1126 PG 8 WC Developmental Biology SC Developmental Biology GA LA370 UT WOS:A1993LA37000021 PM 8482412 ER PT J AU PHELPS, DE DRESSLER, GR AF PHELPS, DE DRESSLER, GR TI ABERRANT EXPRESSION OF PAX-2 IN DANFORTH SHORT TAIL (SD) MICE SO DEVELOPMENTAL BIOLOGY LA English DT Article ID DEVELOPING EXCRETORY SYSTEM; FLOOR PLATE; NERVOUS-SYSTEM; SPINAL-CORD; NEUROGENESIS; GUIDANCE; MOUSE; AXONS; GENE C1 NICHHD,MAMMALIAN GENES & DEV LAB,BETHESDA,MD 20892. NR 29 TC 33 Z9 33 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD MAY PY 1993 VL 157 IS 1 BP 251 EP 258 DI 10.1006/dbio.1993.1129 PG 8 WC Developmental Biology SC Developmental Biology GA LA370 UT WOS:A1993LA37000024 PM 8482415 ER PT J AU SOKOLOFF, L AF SOKOLOFF, L TI SITES AND MECHANISMS OF FUNCTION-RELATED CHANGES IN ENERGY-METABOLISM IN THE NERVOUS-SYSTEM SO DEVELOPMENTAL NEUROSCIENCE LA English DT Article; Proceedings Paper CT Satellite Meeting on Functional Aspects of Energy Metabolism in Neural Tissue CY AUG 28-SEP 01, 1993 CL CARCASSONNE, FRANCE SP INT SOC NEUROCHEM DE ATPASE; BRAIN; DEOXYGLUCOSE; ELECTRICAL ACTIVITY; GLUCOSE ID CEREBRAL GLUCOSE-UTILIZATION; ELECTRICAL-STIMULATION; RAT; GANGLION; MONKEY AB Traditional neuroanatomical and electrophysiological methods to localize functional activities in the nervous system focus on perikarya as the sites of activity. Metabolic mapping of local functional activity in the nervous system with the deoxyglucose method has directed interest toward the activity in neuropil. Studies of local glucose utilization (lCMR(glc)) indicate that energy metabolism is increased by functional activation mainly in terminal projection zones of activated pathways. Electrical stimulation of a pathway raises lCMR(glc) in the projection zones of the pathway in almost direct proportion to the spike frequency. For example, stimulation of the sciatic nerve produces frequency-dependent metabolic activation in the dorsal horn of the lumbar cord, where the axonal terminals of the afferent pathway reside, with no apparent metabolic effects in the cell bodies of the pathway in the dorsal root ganglia. Functional activation of the hypothalamo-hypophysial pathway by salt-loading increases lCMR(glc) in the neurohypophysis, the site of the terminal axons of the pathway, but not in the paraventricular and supraoptic nuclei, where the cell bodies of origin of the pathway reside. Activation by hypotension of pathways to these nuclei from brain stem structures involved in baroceptor reflexes does, however, increase lCMR(glc) in these nuclei. Depolarization induced by electrical stimulation, increased extracellular K+, or opening of Na+ channels with veratridine stimulate lCMR(glc) in neural tissues, and this increase is blocked by ouabain, a specific inhibitor of Na+, K+-ATPase. Activation of this enzyme to restore ionic gradients across cellular membranes appears to trigger the function-related increase in energy metabolism. The metabolic activation is the consequence not of the functional activity itself but of processes operating to recover from that activity. RP SOKOLOFF, L (reprint author), NIMH,CEREBRAL METAB LAB,BLDG 36,ROOM 1A-05,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 25 TC 67 Z9 68 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-5866 J9 DEV NEUROSCI-BASEL JI Dev. Neurosci. PD MAY-OCT PY 1993 VL 15 IS 3-5 BP 194 EP 206 DI 10.1159/000111335 PG 13 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA PD865 UT WOS:A1993PD86500007 PM 7805571 ER PT J AU LEO, GC DRISCOLL, BF SHANK, RP KAUFMAN, E AF LEO, GC DRISCOLL, BF SHANK, RP KAUFMAN, E TI ANALYSIS OF [1-C-13]D-GLUCOSE METABOLISM IN CULTURED ASTROCYTES AND NEURONS USING NUCLEAR-MAGNETIC-RESONANCE SPECTROSCOPY SO DEVELOPMENTAL NEUROSCIENCE LA English DT Article; Proceedings Paper CT Satellite Meeting on Functional Aspects of Energy Metabolism in Neural Tissue CY AUG 28-SEP 01, 1993 CL CARCASSONNE, FRANCE SP INT SOC NEUROCHEM DE ASTROCYTES; CITRATE; C-13-NMR; GLUTAMINE; LACTATE ID INVIVO; SYNAPTOSOMES; RELEASE; INVITRO; CELLS; NMR AB The metabolism of [1-C-13]D-glucose by astrocytes, neurons and mixed astroglial/neuronal cultures derived from the striatum of fetal rats was studied using NMR. Metabolic activity was studied in resting and depolarized cells (55 mM K+), with dibutyryl cyclic-AMP added to the medium to promote cell differentiation, and with glutamate (0.1 mM) included in the medium. Due to sample limitations the accumulation of C-13 label in metabolites within the cells was not sufficient to quantitate. Of the metabolites released into the medium by the astrocyte cultures and the mixed astroglial/neuronal cultures, measurable amounts of label were present in lactate C-3 and C-2, glutamine C-2, C-3 and C-4, acetate C-2, citrate C-2 or C-4 and C-3, glycerol C-1 or C-3, succinate C-2 or C-3 and several unidentified metabolites. Of the labeled metabolites released into the medium, only succinate was markedly affected by K+-induced depolarization, dBcAMP, or glutamate. The label in succinate was increased, especially in the K+-depolarized astrocyte cultures (3- to 6-fold). The neuronal cultures consumed [1-C-13]D-glucose much more slowly than the astrocyte cultures or the mixed cultures. Except for lactate C-3, there was no measurable C-13 in metabolites in the medium of the neuronal cultures. C1 NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20892. RP LEO, GC (reprint author), RW JOHNSON PHARMACEUT RES INST,SPRING HOUSE,PA 19477, USA. NR 25 TC 31 Z9 33 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-5866 J9 DEV NEUROSCI-BASEL JI Dev. Neurosci. PD MAY-OCT PY 1993 VL 15 IS 3-5 BP 282 EP 288 DI 10.1159/000111346 PG 7 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA PD865 UT WOS:A1993PD86500018 PM 7805580 ER PT J AU KAUFMAN, EE DRISCOLL, BF AF KAUFMAN, EE DRISCOLL, BF TI EVIDENCE FOR COOPERATIVITY BETWEEN NEURONS AND ASTROGLIA IN THE REGULATION OF CO2 FIXATION IN-VITRO SO DEVELOPMENTAL NEUROSCIENCE LA English DT Article; Proceedings Paper CT Satellite Meeting on Functional Aspects of Energy Metabolism in Neural Tissue CY AUG 28-SEP 01, 1993 CL CARCASSONNE, FRANCE SP INT SOC NEUROCHEM DE ASTROGLIA; CO2 FIXATION; NEURONS; POTASSIUM ID PYRUVATE-CARBOXYLASE; METABOLISM; CELLS AB Increases in the extracellular potassium concentration which correspond to the increased potassium concentration seen with both normal and abnormal neuronal stimulation produce marked increases in the rate of CO2 fixation in astroglial cells in primary culture. This increase in CO2 fixation is seen only in astroglial cells; the low rate of CO2 fixation seen in the neurons did not respond to the increased potassium concentration. Cultures of astroglia and mixed astroglia-neurons were labeled with NaH[C-14]O-3 for 20 h to obtain material for preliminary identification of the labeled products of CO2 fixation in the extracellular and intracellular compartments. While both cultures had similar intracellular levels of labeled products (mainly amino acids), astroglial cultures released 4-fold more labeled products into the extracellular fluid. While labeled glutamine is a prominent product of astroglia, the bulk of the released labeled products are nonamino acids. These are presumably the products available to be recycled back to surrounding neurons (which cannot fix CO2) to replenish intermediates of the TCA cycle lost due to release of the neurotransmitters glutamate, aspartate and GABA. RP KAUFMAN, EE (reprint author), NIMH,CEREBRAL METAB LAB,BLDG 36,ROOM 1A-05,BETHESDA,MD 20892, USA. NR 10 TC 15 Z9 15 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-5866 J9 DEV NEUROSCI-BASEL JI Dev. Neurosci. PD MAY-OCT PY 1993 VL 15 IS 3-5 BP 299 EP 305 DI 10.1159/000111348 PG 7 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA PD865 UT WOS:A1993PD86500020 PM 7805582 ER PT J AU SIEBERT, C LIPSETT, LF GREENBLATT, J SILVERMAN, RE AF SIEBERT, C LIPSETT, LF GREENBLATT, J SILVERMAN, RE TI SURVEY OF PHYSICIAN PRACTICE BEHAVIORS RELATED TO DIABETES-MELLITUS IN THE UNITED-STATES 1. DESIGN AND METHODS SO DIABETES CARE LA English DT Article ID PRIMARY-CARE; CHILDREN; RATES AB OBJECTIVE - To conduct a survey among a representative sample of primary care physicians in the U.S. to assess practice behaviors, treatment goals, and beliefs related to management of diabetes mellitus and prevention of its complications. RESEARCH DESIGN AND METHODS - A mail survey with telephone follow-up was conducted among 3481 primary care physicians in active practice in the continental U.S. A stratified probability sample was selected using the files of the American Medical Association and American Osteopathic Association. Four specialties were selected to be included in the study: family physician, general practitioner, internist, and pediatrician. Two versions of a questionnaire were constructed: one for pediatricians containing questions about IDDM only and one for the other three specialties containing questions about both IDDM and NIDDM. Physicians who were not actively engaged in practice or did not see patients with diabetes were excluded. RESULTS - Completed questionnaires were received from 1502 of 3481 sampled physicians. Based on various assumptions of eligibility among nonresponders, an overall response rate to the survey was estimated to be between 65.7 and 86.5%. Discrepancies between specialty identifications as noted on the American Medical Association/American Osteopathic Association files and as self-designated were noted. CONCLUSIONS - This report describes the methodology used in the design and conduct of the survey, and data are provided to document the technical success of survey execution. This report provides the methodological basis for a series of separate reports on demographic characteristics of the physicians, their practices and their patients, and on specific attitudes, beliefs, and practice behaviors of primary care physicians in the U.S. with regard to diabetes mellitus. C1 PROSPECT ASSOCIATES,ROCKVILLE,MD. RP SIEBERT, C (reprint author), NIDDK,DDEM,WESTWOOD BLDG,ROOM 628,BETHESDA,MD 20892, USA. FU NIDDK NIH HHS [N01-DK-8-2233] NR 18 TC 10 Z9 10 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 MAY PY 1993 VL 16 IS 5 BP 759 EP 764 DI 10.2337/diacare.16.5.759 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KZ456 UT WOS:A1993KZ45600014 PM 8495617 ER PT J AU TUTTLEMAN, M LIPSETT, L HARRIS, MI AF TUTTLEMAN, M LIPSETT, L HARRIS, MI TI ATTITUDES AND BEHAVIORS OF PRIMARY CARE PHYSICIANS REGARDING TIGHT CONTROL OF BLOOD-GLUCOSE IN IDDM PATIENTS SO DIABETES CARE LA English DT Article ID DEPENDENT DIABETES-MELLITUS; INTENSIVE INSULIN THERAPY; RENAL-DISEASE; UNITED-STATES; RISK-FACTORS; RETINOPATHY; NEPHROPATHY; SUSCEPTIBILITY; PREDISPOSITION; HYPOGLYCEMIA AB OBJECTIVE - To evaluate attitudes and practices of primary-care physicians toward tight blood glucose control in IDDM. RESEARCH DESIGN AND METHODS - A mail and telephone questionnaire survey was conducted on a systematic, stratified sample of 1429 family-practice physicians, general practitioners, internists, and pediatricians in active practice in the United States who treated patients with IDDM. Physicians were asked about methods they used for clinical and laboratory assessment of blood glucose control and about their attitudes and beliefs in treating IDDM. They were asked also what they consider to be acceptable ranges for blood glucose and HbA1 in IDDM patients. A score was developed reflecting three criteria for tight blood glucose control: fasting glucose 70-120 mg/dl (3.9-6.7 mM), 2-h postprandial glucose < 180 mg/dl (< 10 mM), and HbA1 less-than-or-equal-to 8% the nondiabetic value was specified as 5-7%). Physicians were accorded one point when their acceptable range agreed with an intensive treatment criterion (range for score 0-3). RESULTS - Only 3 1% of physicians agreed with all three criteria for tight control of blood glucose; 37% agreed with none or only one of the standards. Pediatricians were particularly low in their agreement with the HbA, standard. Physicians who agreed with one of the three criteria often did not agree with the other two. With increasing value for the score, there was a greater proportion of physicians whose management practices (e.g., frequent measurement of HbA1, multiple insulin injections, patient SMBG, use of dietitian/educator in care of patients) are conducive toward tight control of blood glucose. However, even among physicians with a score of 3, HbA, was ordered infrequently, three or more insulin injections/day was prescribed rarely, patient SMBG was less than fully endorsed, and both a dietitian and diabetes educator were used by a minority of physicians. CONCLUSIONS - it appears that primary-care physicians are not fully aware of recommended criteria for intensive treatment of blood glucose in IDDM patients or of the importance of multiple insulin injections, use of HbA1, and patient SMBG. Physician practice behaviors are less than optimal for intensive management of IDDM patients, even among physicians who agree with all three standards for intensive treatment of blood glucose in IDDM. C1 NIAMSK, BETHESDA, MD USA. RP TUTTLEMAN, M (reprint author), NIDDK, NATL DIABETES DATA GRP, WESTWOOD BLDG, ROOM 620, BETHESDA, MD 20892 USA. NR 37 TC 62 Z9 63 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD MAY PY 1993 VL 16 IS 5 BP 765 EP 772 DI 10.2337/diacare.16.5.765 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KZ456 UT WOS:A1993KZ45600015 PM 8495618 ER PT J AU LIU, QZ PETTITT, DJ HANSON, RL CHARLES, MA KLEIN, R BENNETT, PH KNOWLER, WC AF LIU, QZ PETTITT, DJ HANSON, RL CHARLES, MA KLEIN, R BENNETT, PH KNOWLER, WC TI GLYCATED HEMOGLOBIN, PLASMA-GLUCOSE AND DIABETIC-RETINOPATHY - CROSS-SECTIONAL AND PROSPECTIVE ANALYSES SO DIABETOLOGIA LA English DT Article DE GLYCATED HEMOGLOBIN-A1; PLASMA GLUCOSE; DIABETIC RETINOPATHY; RISK FACTOR; RECEIVER OPERATING CHARACTERISTIC (ROC) ANALYSIS; PIMA INDIANS ID AGAR-GEL ELECTROPHORESIS; RISK-FACTORS; GLYCOSYLATED HEMOGLOBIN; PIMA-INDIANS; BLOOD-PRESSURE; PROGRESSION; NEPHROPATHY; IDDM AB Among Pima Indians with Type 2 (non-insulin-dependent) diabetes mellitus the relationships between glycated haemoglobin (HbA1), fasting or 2-h post-load plasma glucose and diabetic retinopathy were examined by cross-sectional and prospective analyses, and the strengths of the associations were directly compared by receiver operating characteristic analysis. In the cross-sectional analysis, HbA1, fasting and 2-h plasma glucose were each significantly related to retinopathy among 789 diabetic subjects by separate logistic models. In a stepwise multiple logistic model in which HbA1, fasting and 2-h plasma glucose were included, HbA, was selected as having the strongest association with retinopathy and neither fasting nor 2-h plasma glucose contributed significantly to the model once HbA1 was entered. Similarly, in the prospective analysis, HbA1, fasting and 2-h plasma glucose all predicted retinopathy in 227 diabetic subjects by separate proportional-hazards models. In a stepwise proportional-hazards model with HbA1, fasting and 2-h plasma glucose available to the model, HbA, was again selected as having the strongest association with the incidence of retinopathy, and neither fasting nor 2-h plasma glucose significantly added to the prediction of retinopathy. A receiver operating characteristic analysis was used to determine if HbA, was statistically significantly better than fasting or 2-h plasma glucose in assessing the risk for retinopathy. In neither the cross-sectional nor the prospective data did the area under the receiver operating characteristic curve for HbA, differ significantly from that for fasting or 2-h plasma glucose (p > 0.05 for each). In conclusion, HbA1, an integrated measure of blood glucose concentration over a period of 2-3 months, is slightly more closely associated with the prevalence and incidence of diabetic retinopathy than a single blood glucose determination. However, the differences between HbA1 and fasting or 2-h plasma glucose in assessing the association with or the risk for retinopathy are not significant. C1 NIDDK,PHOENIX EPIDEMIOL & CLIN RES BRANCH,DIABET & ARTHRIT EPIDEMIOL SECT,1550 E INDIAN SCH RD,PHOENIX,AZ 85014. UNIV WISCONSIN,SCH MED,DEPT OPHTHALMOL,MADISON,WI 53706. RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 NR 23 TC 52 Z9 52 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD MAY PY 1993 VL 36 IS 5 BP 428 EP 432 DI 10.1007/BF00402279 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA KY736 UT WOS:A1993KY73600010 PM 8314447 ER PT J AU PERKINS, JR PARKER, CE TOMER, KB AF PERKINS, JR PARKER, CE TOMER, KB TI THE CHARACTERIZATION OF SNAKE-VENOMS USING CAPILLARY ELECTROPHORESIS IN CONJUNCTION WITH ELECTROSPRAY MASS-SPECTROMETRY - BLACK-MAMBAS SO ELECTROPHORESIS LA English DT Article; Proceedings Paper CT 5TH INTERNATIONAL SYMP ON HIGH PERFORMANCE CAPILLARY ELECTROPHORESIS CY JAN, 1993 CL ORLANDO, FL ID NAJA-MOSSAMBICA-MOSSAMBICA; FAST ATOM BOMBARDMENT; AMINO-ACID-SEQUENCE; ZONE ELECTROPHORESIS; LIQUID-CHROMATOGRAPHY; IONIZATION INTERFACE; SECONDARY STRUCTURE; CARDIOTOXIN-CTXIIB; AQUEOUS-SOLUTION; PROTEINS AB Capillary electrophoresis has been used in conjunction with electrospray mass spectrometry using both full-scan and selected ion monitoring modes to supply as much information as possible about the venom of Dendroaspis polylepis polylepis (Black Mamba). As an example of the application of capillary electrophoresis/electrospray mass spectrometry (CE/ESI/MS) to the analysis of a complex mixture of small proteins, we have analyzed the venom of Dendroaspis polylepis polylepis using the combined techniques. Both full-scan and selected ion monitoring modes were employed. CE/ESI/MS provides a rapid and extremely sensitive method for molecular weight determination, particularly when selected ion monitoring is employed. It has been utilized to provide sequence confirmation for those toxins which have already been described in the literature. Our methodology indicates the presence of at least 70 peptides in the molecular weight range 6000-9000. C1 NIEHS,MOLEC BIOPHYS LAB,POB 12233,RES TRIANGLE PK,NC 27709. RI Tomer, Kenneth/E-8018-2013 NR 65 TC 20 Z9 20 U1 0 U2 4 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD MAY-JUN PY 1993 VL 14 IS 5-6 BP 458 EP 468 DI 10.1002/elps.1150140171 PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA LJ421 UT WOS:A1993LJ42100010 PM 8354229 ER PT J AU GUSZCZYNSKI, T PULYAEVA, H TIETZ, D GARNER, MM CHRAMBACH, A AF GUSZCZYNSKI, T PULYAEVA, H TIETZ, D GARNER, MM CHRAMBACH, A TI CAPILLARY ZONE ELECTROPHORESIS OF LARGE DNA SO ELECTROPHORESIS LA English DT Article; Proceedings Paper CT 5TH INTERNATIONAL SYMP ON HIGH PERFORMANCE CAPILLARY ELECTROPHORESIS CY JAN, 1993 CL ORLANDO, FL ID PULSED ELECTRIC-FIELDS; GEL-ELECTROPHORESIS; AGAROSE GELS; SEPARATION; POLYACRYLAMIDE; FRAGMENTS AB Capillary zone electrophoresis (CZE) of DNA 23.1 to 48.5 kb in length in polyacrylamide solutions of several concentrations provides evidence for polymer concentration and DNA length-dependent stretching and orientation of these species and suggests an effective separation at a polymer concentration of about 0.6%. Applying a 0.1% polyacrylamide concentration to the lambda-phage DNA ladder, at least 5 components are separated; separation improves with lowering of the field strength to 2 V/cm and, correspondingly, extended duration of CZE. Saccharomyces pombe chromosomal DNA separates into 3 major components on CZE at high field strength (270 V/cm) in 0.9% polyacrylamide solution, confirming a previous finding made on electrophoresis in a 1.1 mm ID tube at low field strength. However, the finding is limited to one source of the DNA plug, and the chromosomal identity of the components remains unknown. Methodological problems in the CZE of large DNA relate to the need for extended duration of pressure injection if absorbance detection is applied, the need to define the starting zone after extended pressure injection, the need to melt and digest agarose plugs prior to loading, and related needs for thermostating of the sample chamber and for soft-ware compatible with low voltage operation. C1 NICHHD,THEORET & PHYS BIOL LAB,MACROMOLEC ANAL SECT,BLDG 10,RM 6C101,BETHESDA,MD 20892. FU NHGRI NIH HHS [NCHGR IM0008-M] NR 24 TC 33 Z9 33 U1 0 U2 1 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD MAY-JUN PY 1993 VL 14 IS 5-6 BP 523 EP 530 DI 10.1002/elps.1150140180 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA LJ421 UT WOS:A1993LJ42100019 PM 8354238 ER PT J AU JHAPPAN, C GEISER, AG KORDON, EC BAGHERI, D HENNIGHAUSEN, L ROBERTS, AB SMITH, GH MERLINO, G AF JHAPPAN, C GEISER, AG KORDON, EC BAGHERI, D HENNIGHAUSEN, L ROBERTS, AB SMITH, GH MERLINO, G TI TARGETING EXPRESSION OF A TRANSFORMING GROWTH-FACTOR-BETA-1 TRANSGENE TO THE PREGNANT MAMMARY-GLAND INHIBITS ALVEOLAR DEVELOPMENT AND LACTATION SO EMBO JOURNAL LA English DT Article DE BREAST; LACTATION DEFICIENCY; TGF-BETA-1; TRANSGENIC MICE; WAP ID FACTOR-BETA; CELLS; FIBROBLASTS; PRECURSOR; RELEASE; EMBRYO; MICE; GENE AB Transforming growth factor-beta1 (TGF-beta1) possesses highly potent, diverse and often opposing cell-specific activities, and has been implicated in the regulation of a variety of physiologic and developmental processes. To determine the effects of in vivo overexpression of TGF-beta1 on mammary gland function, transgenic mice were generated harboring a fusion gene consisting of the porcine TGF-beta1 cDNA placed under the control of regulatory elements of the pregnancy-responsive mouse whey-acidic protein (WAP) gene. Females from two of four transgenic lines were unable to lactate due to inhibition of the formation of lobuloalveolar structures and suppression of production of endogenous milk protein. In contrast, ductal development of the mammary glands was not overtly impaired. There was a complete concordance in transgenic mice between manifestation of the lactation-deficient phenotype and expression of RNA from the WAP/TGF-beta1 transgene, which was present at low levels in the virgin gland, but was greatly induced at mid-pregnancy. TGF-beta1 was localized to numerous alveoli and to the periductal extracellular matrix in the mammary gland of transgenic females late in pregnancy by immunohistochemical analysis. Glands reconstituted from cultured transgenic mammary epithelial cells duplicated the inhibition of lobuloalveolar development observed in situ in the mammary glands of pregnant transgenic mice. Results from this transgenic model strongly support the hypothesis that TGF-beta1 plays an important in vivo role in regulating the development and function of the mammary gland. C1 NCI,MOLEC BIOL LAB,9000 ROCKVILLE PIKE,36-1D28,BETHESDA,MD 20892. NCI,DIV CANC BIOL DIAG & CTR,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. NCI,DIV CANC ETIOL,CHEMOPREVENT LAB,BETHESDA,MD 20892. NIDDKD,BIOCHEM & METAB LAB,BETHESDA,MD 20892. NR 49 TC 189 Z9 195 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 MAY PY 1993 VL 12 IS 5 BP 1835 EP 1845 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LC948 UT WOS:A1993LC94800012 PM 8491177 ER PT J AU MAYER, U NISCHT, R POSCHL, E MANN, K FUKUDA, K GERL, M YAMADA, Y TIMPL, R AF MAYER, U NISCHT, R POSCHL, E MANN, K FUKUDA, K GERL, M YAMADA, Y TIMPL, R TI A SINGLE EGF-LIKE MOTIF OF LAMININ IS RESPONSIBLE FOR HIGH-AFFINITY NIDOGEN BINDING SO EMBO JOURNAL LA English DT Article DE ANTIBODY INHIBITION; BASEMENT MEMBRANES; PROTEIN INTERACTION; RECOMBINANT EXPRESSION ID BASEMENT-MEMBRANE PROTEIN; COLLAGEN TYPE-IV; HEPARAN-SULFATE PROTEOGLYCAN; AMINO-ACID SEQUENCE; A-CHAIN; DROSOPHILA LAMININ; DOMAINS; LOCALIZATION; COMPLEX; BM-40 AB A major nidogen binding site of mouse laminin was previously localized to about three EGF-like repeats (Nos 3-5) of its B2 chain domain III [M.Gerl et al. (1991) Eur. J. Biochem., 202, 167]. The corresponding cDNA was amplified by polymerase chain reaction and inserted into a eukaryotic expression vector tagged with a signal peptide. Stably transfected human kidney cell clones were shown to process and secrete the resulting fragment B2III3-5 in substantial quantities. It possessed high binding activity for recombinant nidogen in ligand assays, with an affinity comparable with that of authentic laminin fragments. In addition, complexes of B2III3-5 and nidogen could be efficiently converted into a covalent complex by cross-linking reagents. Proteolytic degradation of the covalent complex demonstrated the association of B2III3-5 with a approximately 80 residue segment of nidogen domain G3 to which laminin binding has previously been attributed. The correct formation of most of the 12 disulfide bridges in B2III3-5 was indicated from its protease resistance and the complete loss of cross-reacting epitopes as well as of nidogen-binding activity after reduction and alkylation. Smaller fragments were prepared by the same recombinant procedure and showed that combinations of EGF-like repeats 3-4 and 4-5 and the single repeat 4 but not repeats 3 or 5 possess full nidogen-binding activity. This identifies repeat 4 as the only binding structure. The sequence of repeat 4 is well conserved in the human and in part in the Drosophila laminin B2 chain. It was further shown that antibodies against B2III3-5 inhibit laminin binding to nidogen, indicating that repeat 4 represents the only high affinity binding site of laminin. C1 MAX PLANCK INST BIOCHEM,W-8033 MARTINSRIED,GERMANY. UNIV COLOGNE,DEPT DERMATOL,W-5000 COLOGNE,GERMANY. NIDR,BETHESDA,MD 20892. HOECHST AG,W-6230 FRANKFURT,GERMANY. RI Mann, Karlheinz/C-4254-2008; Poschl, Ernst /E-2103-2011 NR 38 TC 222 Z9 224 U1 0 U2 4 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 MAY PY 1993 VL 12 IS 5 BP 1879 EP 1885 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA LC948 UT WOS:A1993LC94800016 PM 8491180 ER PT J AU HAASCH, ML PRINCE, R WEJKSNORA, PJ COOPER, KR LECH, JJ AF HAASCH, ML PRINCE, R WEJKSNORA, PJ COOPER, KR LECH, JJ TI CAGED AND WILD FISH - INDUCTION OF HEPATIC CYTOCHROME-P-450 (CYP1A1) AS AN ENVIRONMENTAL BIOMONITOR SO ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY LA English DT Article DE ENVIRONMENTAL BIOMONITOR; CYTOCHROME P-450; KILLIFISH; CATFISH; LARGEMOUTH BASS ID MESSENGER-RNA LEVELS; RAINBOW-TROUT; MONOOXYGENASE ACTIVITY; BETA-NAPHTHOFLAVONE; O-DEALKYLATION; POLLUTION; LIVER; XENOBIOTICS; ENZYMES; RIVER AB Hepatic monooxygenase activity can be induced by many different environmental chemical contaminants, and measurement of this activity has been proposed as an environmental biomonitor. Using in situ caged catfish and largemouth bass, and collected wild killifish, environmental induction of hepatic CYP1A1 was investigated using catalytic enzyme assays, regiospecific metabolism, immunodetection, and nucleic acid hybridization. The purpose of these studies was to evaluate these techniques for detection of CYP1A1 induction as a potential environmental biomonitor of environmental chemical contamination. Exposure of catfish in cages to polyaromatic hydrocarbon-(PAH-) and polychlorinated biphenyl- (PCB-) contaminated river water for two, four, or six weeks resulted in fourfold increases in ethoxyresorufin-0-deethylase (EROD) activity and three- and fivefold increases in immunoreactive CYP1A1 protein and hybridizable CYP1A1 mRNA, respectively, when compared to laboratory water control values. Hybridizable CYP1A1 mRNA in caged largemouth bass increased 5. 1-fold at 1 d of exposure. Caged largemouth bass had 5-, 1.4-, and 0.8-fold increases at 3 d and 6-, 2.4-, 0.4-fold increases at 7 d of river water exposure in EROD, immunoreactive CYP1A1 protein, and CYP1A1 mRNA, respectively, when compared to laboratory water control values. Livers of killifish from a 2,3,7,8-tetrachlorodibenzo-p-dioxin-contaminated area had threefold higher EROD activity and similarly elevated immunoreactive CYP1A1 protein, a two- to fourfold increase in CYP1A1 mRNA, and a four- to eightfold increase in 6beta-hydroxyprogesterone activity, when compared to killifish livers sampled from a ''clean'' site. These results indicate that catalytic activity measurements, immunodetection, and nucleic acid hybridization may be used to detect environmental hepatic CYP1A1 induction in fish, and may be useful for the biomonitoring or screening of selected environments for chemical contamination. C1 UNIV WISCONSIN,NIEHS MARINE FRESHWATER BIOMED RES CORE CTR,MILWAUKEE,WI 53204. RUTGERS STATE UNIV,JOINT GRAD PROGRAM TOXICOL,PISCATAWAY,NJ 08854. UNIV WISCONSIN,DEPT BIOL,MILWAUKEE,WI 53211. RP HAASCH, ML (reprint author), MED COLL WISCONSIN,DEPT PHARMACOL & TOXICOL,MILWAUKEE,WI 53226, USA. NR 46 TC 73 Z9 80 U1 2 U2 9 PU SETAC PRESS PI PENSACOLA PA 1010 NORTH 12TH AVE, PENSACOLA, FL 32501-3370 SN 0730-7268 J9 ENVIRON TOXICOL CHEM JI Environ. Toxicol. Chem. PD MAY PY 1993 VL 12 IS 5 BP 885 EP 895 DI 10.1897/1552-8618(1993)12[885:CAWFIO]2.0.CO;2 PG 11 WC Environmental Sciences; Toxicology SC Environmental Sciences & Ecology; Toxicology GA KX607 UT WOS:A1993KX60700013 ER PT J AU CARL, GF BLACKWELL, LK BARNETT, FC THOMPSON, LA RISSINGER, CJ OLIN, KL CRITCHFIELD, JW KEEN, CL GALLAGHER, BB AF CARL, GF BLACKWELL, LK BARNETT, FC THOMPSON, LA RISSINGER, CJ OLIN, KL CRITCHFIELD, JW KEEN, CL GALLAGHER, BB TI MANGANESE AND EPILEPSY - BRAIN GLUTAMINE-SYNTHETASE AND LIVER ARGINASE ACTIVITIES IN GENETICALLY EPILEPSY-PRONE AND CHRONICALLY SEIZURED RATS SO EPILEPSIA LA English DT Article DE MANGANESE; EPILEPSY; GLUTAMINE SYNTHETASE; ARGINASE; GENETICALLY EPILEPSY-PRONE RAT; CONVULSIONS ID TRACE-ELEMENT CONCENTRATIONS; BLOOD MANGANESE; TISSUE; METALS AB Low blood manganese (Mn2+) concentration is associated with epilepsy in humans and rats. The low Mn2+ concentration is attributed by some investigators to the seizure activity associated with the epilepsy, whereas others propose that the low Mn2+ concentration may be secondary to genetic mechanisms underlying the epilepsy. To begin to differentiate between these possibilities, Mn2+-binding enzymes of liver and brain (i.e., arginase and glutamine synthetase, respectively) were assayed in rats exposed to chronically induced seizures and in genetically epilepsy-prone rats (GEPRs). Chronic seizures caused a decrease in whole blood Mn2+ levels but did not affect brain Mn2+ concentrations. Arginase activity was increased in livers of rats with chronic seizure as compared with controls, but this difference was eliminated when Mn2+ was added to the assay. Brain glutamine synthetase activity was unaffected by chronic seizures, but the activity of this enzyme was significantly lower in GEPR brain than in control brain. Liver arginase activity tended to be lower in GEPRs, although the difference was not statistically significant. These data indicate that seizures affect liver arginase activity through changes in liver Mn2+ concentration, but GEPRs show abnormalities in Mn2+-dependent enzymes apparently independent of seizure activity. C1 MED COLL GEORGIA,DEPT NEUROL,AUGUSTA,GA 30912. UNIV CALIF DAVIS,DEPT NUTR,DAVIS,CA 95616. UNIV CALIF DAVIS,DEPT INTERNAL MED,DAVIS,CA 95616. NCI,FCRDC,NUTR & MOLEC REGULAT LAB,FREDERICK,MD 21701. RP CARL, GF (reprint author), VET ADM MED CTR,MED RES 151,AUGUSTA,GA 30904, USA. NR 20 TC 34 Z9 34 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD MAY-JUN PY 1993 VL 34 IS 3 BP 441 EP 446 DI 10.1111/j.1528-1157.1993.tb02584.x PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA LJ962 UT WOS:A1993LJ96200006 PM 8099325 ER PT J AU ROBBINS, JH BRUMBACK, RA MOSHELL, AN AF ROBBINS, JH BRUMBACK, RA MOSHELL, AN TI CLINICALLY ASYMPTOMATIC XERODERMA-PIGMENTOSUM NEUROLOGICAL DISEASE IN AN ADULT - EVIDENCE FOR A NEURODEGENERATION IN LATER LIFE CAUSED BY DEFECTIVE-DNA REPAIR SO EUROPEAN NEUROLOGY LA English DT Article DE XERODERMA-PIGMENTOSUM; NEURODEGENERATION; DNA REPAIR; PERIPHERAL NEUROPATHY; SENSORINEURAL DEAFNESS ID MANIFESTATIONS AB Xeroderma pigmentosum is a genetically heterogeneous disease caused by DNA repair defects resulting in skin cancer and, in some patients, a primary neuronal degeneration which has in all previous reports become symptomatic prior to age 21 years. A 47-year-old xeroderma pigmentosum patient is described who, although neurologically asymptomatic, has sensorineural hearing loss together with clinical signs and electrophysiologic evidence of a developing peripheral neuropathy. This case suggests that defective DNA repair may cause neurodegeneration in adults as well as in children. C1 UNIV OKLAHOMA,COLL MED,DEPT PATHOL NEUROPATHOL,OKLAHOMA CITY,OK. VET AFFAIRS MED CTR,OKLAHOMA CITY,OK. RP ROBBINS, JH (reprint author), NCI,DERMATOL BRANCH,BLDG 10,ROOM 12N238,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Brumback, Roger/A-2404-2008 NR 15 TC 25 Z9 25 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0014-3022 J9 EUR NEUROL JI Eur. Neurol. PD MAY-JUN PY 1993 VL 33 IS 3 BP 188 EP 190 DI 10.1159/000116932 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA KW774 UT WOS:A1993KW77400002 PM 8467834 ER PT J AU CHEN, P YU, YM REDDI, AH AF CHEN, P YU, YM REDDI, AH TI CHONDROGENESIS IN CHICK LIMB BUD MESODERMAL CELLS - RECIPROCAL MODULATION BY ACTIVIN AND INHIBIN SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID GROWTH-FACTOR-BETA; EMBRYONAL CARCINOMA-CELLS; TGF-BETA; EXPRESSION; RNA; DIFFERENTIATION; EMBRYOGENESIS; RAT; IDENTIFICATION; STIMULATION C1 JOHNS HOPKINS UNIV,SCH MED,DEPT ORTHOPAED SURG,MUSCULOSKELETAL CELL BIOL LAB,ROOM 225,BALTIMORE,MD 21205. NIDR,BONE CELL BIOL SECT,BETHESDA,MD 20892. NR 37 TC 33 Z9 34 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD MAY PY 1993 VL 206 IS 1 BP 119 EP 127 DI 10.1006/excr.1993.1127 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA LA655 UT WOS:A1993LA65500015 PM 8482353 ER PT J AU ARNOLD, DR MOSHAYEDI, P SCHOEN, TJ JONES, BE CHADER, GJ WALDBILLIG, RJ AF ARNOLD, DR MOSHAYEDI, P SCHOEN, TJ JONES, BE CHADER, GJ WALDBILLIG, RJ TI DISTRIBUTION OF IGF-I AND IGF-II, IGF BINDING-PROTEINS (IGFBPS) AND IGFBP MESSENGER-RNA IN OCULAR FLUIDS AND TISSUES - POTENTIAL SITES OF SYNTHESIS OF IGFBPS IN AQUEOUS AND VITREOUS SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE INSULIN-LIKE GROWTH FACTOR; IGF-BINDING PROTEINS; CORNEA; CILIARY BODY; EYE; VITREOUS; AQUEOUS ID BOVINE NEURAL RETINA; GROWTH FACTOR-II; INSULIN-RECEPTORS; EXPRESSION; GENE; RADIOIMMUNOASSAY; BARRIERS; RABBIT; SYSTEM; LENS C1 NEI,RETINAL CELL & MOLEC BIOL LAB,BLDG 6,ROOM 304,BETHESDA,MD 20892. NR 36 TC 65 Z9 68 U1 0 U2 2 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 MAY PY 1993 VL 56 IS 5 BP 555 EP 565 DI 10.1006/exer.1993.1069 PG 11 WC Ophthalmology SC Ophthalmology GA LC928 UT WOS:A1993LC92800005 PM 7684697 ER PT J AU RAO, CM ZIGLER, JS AF RAO, CM ZIGLER, JS TI ARE CRYSTALLINS DESIGNED FOR HIGH INTRACELLULAR STABILITY SO EXPERIMENTAL EYE RESEARCH LA English DT Letter ID HEAT-SHOCK PROTEINS; ALPHA-CRYSTALLIN; SEQUENCES; TISSUES C1 CTR CELLULAR & MOLEC BIOL,HYDERABAD 500007,INDIA. RP RAO, CM (reprint author), NEI,MECHANISMS OCULAR DIS LAB,BETHESDA,MD 20892, USA. NR 15 TC 4 Z9 4 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD MAY PY 1993 VL 56 IS 5 BP 615 EP 619 DI 10.1006/exer.1993.1077 PG 5 WC Ophthalmology SC Ophthalmology GA LC928 UT WOS:A1993LC92800013 PM 8500572 ER PT J AU LEVINE, AS AF LEVINE, AS TI WORKSHOP ON MOLECULAR, CELLULAR, AND CLINICAL ASPECTS OF FANCONI-ANEMIA SO EXPERIMENTAL HEMATOLOGY LA English DT Editorial Material C1 NHLBI,CELLULAR HEMATOL BRANCH,BETHESDA,MD. NR 0 TC 3 Z9 4 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD MAY PY 1993 VL 21 IS 5 BP 703 EP 706 PG 4 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA MW610 UT WOS:A1993MW61000018 ER PT J AU YOUNG, NS LIU, J AF YOUNG, NS LIU, J TI BONE-MARROW FAILURE SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 NHLBI,CELL BIOL SECT,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD MAY PY 1993 VL 21 IS 5 BP 711 EP 712 PG 2 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA MW610 UT WOS:A1993MW61000030 ER PT J AU LIU, JM YOUNG, NS AF LIU, JM YOUNG, NS TI NOVEL APPROACHES TO THE TREATMENT OF FANCONI-ANEMIA SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 NHLBI,CELL BIOL SECT,CLIN HEMATOL BRANCH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD MAY PY 1993 VL 21 IS 5 BP 715 EP 715 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA MW610 UT WOS:A1993MW61000039 ER PT J AU NIENHUIS, AW DONAHUE, RE KESSLER, SW BODINE, D MCDONAGH, K DUNBAR, C WALSH, C GOODMAN, S LIU, J YOUNG, NS AF NIENHUIS, AW DONAHUE, RE KESSLER, SW BODINE, D MCDONAGH, K DUNBAR, C WALSH, C GOODMAN, S LIU, J YOUNG, NS TI GENE-THERAPY APPROACHES FOR ENZYME DEFICIENCIES SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 NHLBI,CLIN HEMATOL BRANCH,BETHESDA,MD 20892. USN,RES INST,IMMUNE CELL BIOL PROGRAM,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD MAY PY 1993 VL 21 IS 5 BP 716 EP 716 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA MW610 UT WOS:A1993MW61000041 ER PT J AU FREED, WJ DILLONCARTER, O KLEINMAN, JE AF FREED, WJ DILLONCARTER, O KLEINMAN, JE TI PROPERTIES OF [H-3] AMPA BINDING IN POSTMORTEM HUMAN BRAIN FROM PSYCHOTIC SUBJECTS AND CONTROLS - INCREASES IN CAUDATE-NUCLEUS ASSOCIATED WITH SUICIDE SO EXPERIMENTAL NEUROLOGY LA English DT Article ID AMINO-ACID RECEPTORS; TRITIATED IMIPRAMINE BINDING; FRONTAL-CORTEX; AUTORADIOGRAPHIC ANALYSIS; GLUTAMIC-ACID; RAT CORTEX; SITES; QUISQUALATE; SCHIZOPHRENIA; MEMBRANES C1 ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. RP FREED, WJ (reprint author), ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,NEUROPSYCHIAT BRANCH,PRECLIN NEUROSCI SECT,WASHINGTON,DC 20032, USA. NR 39 TC 42 Z9 44 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 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD MAY PY 1993 VL 121 IS 1 BP 48 EP 56 DI 10.1006/exnr.1993.1070 PG 9 WC Neurosciences SC Neurosciences & Neurology GA LF220 UT WOS:A1993LF22000005 PM 7684336 ER PT J AU SCHMIDT, PJ RUBINOW, DR AF SCHMIDT, PJ RUBINOW, DR TI PLACEBO-EFFECT - HOW POWERFUL SO FERTILITY AND STERILITY LA English DT Letter RP SCHMIDT, PJ (reprint author), NIMH,BEHAV ENDOCRINOL SECT,REPROD ENDOCRINE STUDIES UNIT,BETHESDA,MD 20892, USA. NR 2 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC REPRODUCTIVE MEDICINE PI BIRMINGHAM PA 1209 MONTGOMERY HIGHWAY, BIRMINGHAM, AL 35216-2809 SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD MAY PY 1993 VL 59 IS 5 BP 1144 EP 1144 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA LB269 UT WOS:A1993LB26900045 PM 8486192 ER PT J AU DANIEL, LN MAO, Y SAFFIOTTI, U AF DANIEL, LN MAO, Y SAFFIOTTI, U TI OXIDATIVE DNA DAMAGE BY CRYSTALLINE SILICA SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE SILICA; SILICOSIS; FREE RADICAL; HYDROXYL RADICAL; HYDROGEN PEROXIDE; SUPEROXIDE; SUPEROXIDE DISMUTASE; DEFEROXAMINE ID DOUBLE-STRAND BREAKS; SUPEROXIDE-DISMUTASE; GEL-ELECTROPHORESIS; MAMMALIAN-CELLS; RADICALS; ASSAY; DUST; GENERATION; ASBESTOS; SURFACES AB Using a simple DNA strand breakage assay, we detected the production of oxidant species, probably hydroxyl free radicals, in buffered suspensions of crystalline silica at pH 7.4. DNA damage was affected by the presence of oxygen and was accelerated by superoxide dismutase and by hydrogen peroxide. Deferoxamine blocked damage by hydrogen peroxide and silica but accelerated DNA damage by silica alone and by superoxide dismutase and silica. DNA damage was blocked by catalase and by the scavenging agents dimethyl sulfoxide and sodium benzoate. Chemical etching of crystalline silica to remove impurities by treatment of the surface with hydrofluoric acid resulted in markedly diminished DNA damaging ability. Even preparations of crystalline silica previously characterized as highly pure contained trace iron impurities in amounts significant enough to produce oxygen free radicals in aqueous suspension. Both superoxide and Fenton reaction oxidants were produced. We conclude that silica is able to mediate DNA strand breakage in vitro and that this DNA damage may be an important factor in silica toxicity. C1 NANJING UNIV,DEPT CHEM,NANJING,PEOPLES R CHINA. RP DANIEL, LN (reprint author), NCI,EXPTL PATHOL LAB,BLDG 41,ROOM C-105,BETHESDA,MD 20892, USA. NR 43 TC 71 Z9 73 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD MAY PY 1993 VL 14 IS 5 BP 463 EP 472 DI 10.1016/0891-5849(93)90103-2 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA KY414 UT WOS:A1993KY41400002 PM 8394268 ER PT J AU TYL, RW PRICE, CJ MARR, MC MYERS, CB SEELY, JC HEINDEL, JJ SCHWETZ, BA AF TYL, RW PRICE, CJ MARR, MC MYERS, CB SEELY, JC HEINDEL, JJ SCHWETZ, BA TI DEVELOPMENTAL TOXICITY EVALUATION OF ETHYLENE-GLYCOL BY GAVAGE IN NEW-ZEALAND WHITE-RABBITS SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID ZERO DOSE CONTROL; RATS; TERATOGENICITY C1 PATHCO INC,RES TRIANGLE PK,NC 27709. NIEHS,NATL TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709. RP TYL, RW (reprint author), RES TRIANGLE INST,CTR LIFE SCI & TOXICOL,POB 12194,RES TRIANGLE PK,NC 27709, USA. FU NIEHS NIH HHS [N01-ES-95255] NR 32 TC 24 Z9 24 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD MAY PY 1993 VL 20 IS 4 BP 402 EP 412 DI 10.1006/faat.1993.1052 PG 11 WC Toxicology SC Toxicology GA LB925 UT WOS:A1993LB92500002 PM 8314457 ER PT J AU FUNG, VA HUFF, J WEISBURGER, EK HOEL, DG AF FUNG, VA HUFF, J WEISBURGER, EK HOEL, DG TI PREDICTIVE STRATEGIES FOR SELECTING 379 NCI NTP CHEMICALS EVALUATED FOR CARCINOGENIC POTENTIAL - SCIENTIFIC AND PUBLIC-HEALTH IMPACT SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID NATIONAL-CANCER-INSTITUTE; PROGRAM C1 NIEHS,RES TRIANGLE PK,NC 27709. RP FUNG, VA (reprint author), NIH,NATL TOXICOL PROGRAM,BLDG 31,ROOM B1C02,BETHESDA,MD 20892, USA. NR 20 TC 36 Z9 36 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD MAY PY 1993 VL 20 IS 4 BP 413 EP 436 DI 10.1006/faat.1993.1053 PG 24 WC Toxicology SC Toxicology GA LB925 UT WOS:A1993LB92500003 PM 8314458 ER PT J AU MATTHEWS, HB EUSTIS, SL HASEMAN, J AF MATTHEWS, HB EUSTIS, SL HASEMAN, J TI TOXICITY AND CARCINOGENICITY OF CHRONIC EXPOSURE TO TRIS(2-CHLOROETHYL)PHOSPHATE SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID FLAME RETARDANTS; PHOSPHATE; RATS; METABOLISM RP MATTHEWS, HB (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 30 TC 42 Z9 43 U1 8 U2 29 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD MAY PY 1993 VL 20 IS 4 BP 477 EP 485 DI 10.1006/faat.1993.1058 PG 9 WC Toxicology SC Toxicology GA LB925 UT WOS:A1993LB92500008 PM 8314462 ER PT J AU DRWINGA, HL TOJI, LH KIM, CH GREENE, AE MULIVOR, RA AF DRWINGA, HL TOJI, LH KIM, CH GREENE, AE MULIVOR, RA TI NIGMS HUMAN RODENT SOMATIC-CELL HYBRID MAPPING PANEL-1 AND PANEL-2 SO GENOMICS LA English DT Article ID HUMAN-CHROMOSOMES; GENES; DNA; EXPRESSION; ASSIGNMENT; LEUKEMIA; CLONING; LINKAGE; PROTEIN; REGION C1 CORIEL INST MED RES,NIGMS,HUMAN GENET MUTANT CELL REPOSITORY,401 HADDON AVE,CAMDEN,NJ 08103. FU NIGMS NIH HHS [N01-GM-9-2102] NR 30 TC 171 Z9 171 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD MAY PY 1993 VL 16 IS 2 BP 311 EP 314 DI 10.1006/geno.1993.1190 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA LB928 UT WOS:A1993LB92800002 PM 8314568 ER PT J AU DANCIGER, M FARBER, DB KOZAK, CA AF DANCIGER, M FARBER, DB KOZAK, CA TI GENETIC-MAPPING OF 3 GABA(A) RECEPTOR-SUBUNIT GENES IN THE MOUSE SO GENOMICS LA English DT Article ID MESSENGER-RNAS; ALPHA-SUBUNIT; DIFFERENTIAL DISTRIBUTION; BOVINE CEREBELLUM; A RECEPTORS; LOCALIZATION; BRAIN; CHROMOSOME-7; EXPRESSION; SEQUENCE C1 UNIV CALIF LOS ANGELES, SCH MED, JULES STEIN EYE INST, 100 STEIN PLAZA, LOS ANGELES, CA 90024 USA. LOYOLA MARYMOUNT UNIV, LOS ANGELES, CA 90045 USA. NIAID, BETHESDA, MD 20892 USA. FU NEI NIH HHS [EY 00331, EY 08285] NR 39 TC 25 Z9 25 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD MAY PY 1993 VL 16 IS 2 BP 361 EP 365 DI 10.1006/geno.1993.1198 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA LB928 UT WOS:A1993LB92800010 PM 8390964 ER PT J AU YOUNG, HA JENKINS, NA COPELAND, NG SIMEK, S LERMAN, MI ZBAR, B GLENN, G ORTALDO, JR ANDERSON, SK AF YOUNG, HA JENKINS, NA COPELAND, NG SIMEK, S LERMAN, MI ZBAR, B GLENN, G ORTALDO, JR ANDERSON, SK TI LOCALIZATION OF A NOVEL NATURAL-KILLER TRIGGERING RECEPTOR LOCUS TO HUMAN CHROMOSOME-3P23-P21 AND MOUSE CHROMOSOME-9 SO GENOMICS LA English DT Note ID GENETIC-LINKAGE MAP; A-BINDING-PROTEIN; CYCLOPHILIN; MECHANISM; ENCODES; CELLS C1 PROGRAM RESOURCES INC,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. PROGRAM RESOURCES INC,DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. PROGRAM RESOURCES INC,DYNCORP,BIOL RESPONSE MODIFIERS PROGRAM,EXPT IMMUNOL LAB,FREDERICK,MD 21702. RP YOUNG, HA (reprint author), NCI,FCRDC,BLDG 560,RM 31-93,FREDERICK,MD 21702, USA. RI Anderson, Stephen/B-1727-2012 OI Anderson, Stephen/0000-0002-7856-4266 FU NCI NIH HHS [N01-CO-74101, N01-CO-74102] NR 11 TC 10 Z9 10 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 0888-7543 J9 GENOMICS JI Genomics PD MAY PY 1993 VL 16 IS 2 BP 548 EP 549 DI 10.1006/geno.1993.1229 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA LB928 UT WOS:A1993LB92800041 PM 8314596 ER PT J AU SCHRENK, D GANT, TW PREISEGGER, KH SILVERMAN, JA MARINO, PA THORGEIRSSON, SS AF SCHRENK, D GANT, TW PREISEGGER, KH SILVERMAN, JA MARINO, PA THORGEIRSSON, SS TI INDUCTION OF MULTIDRUG-RESISTANCE GENE-EXPRESSION DURING CHOLESTASIS IN RATS AND NONHUMAN-PRIMATES SO HEPATOLOGY LA English DT Article ID KB CARCINOMA-CELLS; P-GLYCOPROTEIN; MALLORY BODY; FAMILY; VINBLASTINE; MOUSE; OVEREXPRESSION; AMPLIFICATION; PHARMACOKINETICS; VINCRISTINE AB P-glycoprotein, an energy-dependent plasma membrane drug-efflux pump capable of reducing the intracellular concentration of a variety of hydrophobic xenobiotics, is encoded by mdr1, a member of the multidrug-resistant (mdr) gene family. The physiological function of this protein is unknown. Because of its location on the bile canalicular domain of the hepatocyte, we and others have hypothesized that P-glycoprotein may have a physiological role as a biliary transporter of xenobiotics and endobiotics and that its expression may therefore be altered in cholestasis. Both obstructive and alpha-naphthylisothiocyanate-induced cholestasis increased mdr1a and 1b gene expression in rat liver. Hepatic P-glycoprotein levels were also increased, and the protein remained localized at the biliary hepatocyte domain. Induction of mdr1a and mdr1b gene expression in rat liver was accomplished by means of increased transcription. Alpha-naphthylisothiocyanate-induced cholestasis in cynomolgus monkeys increased hepatic expression of both the mdr1 and 2 genes. To investigate the possible role of P-glycoprotein as a biliary efflux transporter, biliary excretion of vinblastine, a representative substrate of P-glycoprotein, was studied in rats. Increased hepatic mdr messenger RNA and P-glycoprotein levels, mediated by the xenobiotic inducer 2-acetylaminofluorene, resulted in a significant increase in biliary excretion of vinblastine, which was antagonized by the P-glycoprotein inhibitor verapamil. These findings suggest that P-glycoprotein functions as a biliary efflux pump for xenobiotics and, possibly, for unidentified physiological inducers that may mediate increased transcription of the mdr gene observed during cholestasis. C1 NCI,EXPTL CARCINOGENESIS LAB,BLDG 37,ROOM 3C28,BETHESDA,MD 20892. NR 36 TC 106 Z9 108 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAY PY 1993 VL 17 IS 5 BP 854 EP 860 DI 10.1016/0270-9139(93)90162-G PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA LC825 UT WOS:A1993LC82500015 PM 8098315 ER PT J AU BRINI, AT SCHMIDT, L ZBAR, B KINET, JP AF BRINI, AT SCHMIDT, L ZBAR, B KINET, JP TI A DINUCLEOTIDE REPEAT POLYMORPHISM IN THE GENE FOR THE GAMMA-SUBUNIT OF THE HUMAN FC-EPSILON RECEPTORS (FLER16) SO HUMAN MOLECULAR GENETICS LA English DT Note C1 PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NCI,IMMUNBIOL LAB,FREDERICK,MD 21702. RP BRINI, AT (reprint author), NIAID,MOLEC ALLERGY & IMMUNOL SECT,ROCKVILLE,MD 20852, USA. OI Brini, Anna Teresa/0000-0002-7848-8099 NR 2 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAY PY 1993 VL 2 IS 5 BP 619 EP 619 DI 10.1093/hmg/2.5.619 PG 1 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA LA746 UT WOS:A1993LA74600041 PM 8518818 ER PT J AU TAKEYA, M YOSHIMURA, T LEONARD, EJ TAKAHASHI, K AF TAKEYA, M YOSHIMURA, T LEONARD, EJ TAKAHASHI, K TI DETECTION OF MONOCYTE CHEMOATTRACTANT PROTEIN-1 IN HUMAN ATHEROSCLEROTIC LESIONS BY AN ANTI-MONOCYTE CHEMOATTRACTANT PROTEIN-1 MONOCLONAL-ANTIBODY SO HUMAN PATHOLOGY LA English DT Article DE MONOCYTE CHEMOATTRACTANT PROTEIN-1; ATHEROSCLEROSIS; ANTI-MONOCYTE CHEMOATTRACTANT PROTEIN-1; MONOCLONAL ANTIBODY; DOUBLE IMMUNOHISTOCHEMICAL STAINING ID LOW-DENSITY-LIPOPROTEIN; SMOOTH-MUSCLE CELLS; INTERLEUKIN-1 GENE-EXPRESSION; BLOOD MONONUCLEAR LEUKOCYTES; FATTY STREAK CONVERSION; HUMAN ENDOTHELIAL-CELLS; TUMOR NECROSIS FACTOR; AMINO-ACID ANALYSIS; NONHUMAN PRIMATE; FIBROUS PLAQUE C1 NCI,FCRDC,IMMUNOBIOL LAB,IMMUNOPATHOL SECT,FREDERICK,MD 21701. RP TAKEYA, M (reprint author), KUMAMOTO UNIV,SCH MED,DEPT PATHOL 2,2-2-1 HONJO,KUMAMOTO 860,JAPAN. NR 40 TC 232 Z9 242 U1 1 U2 7 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD MAY PY 1993 VL 24 IS 5 BP 534 EP 539 DI 10.1016/0046-8177(93)90166-E PG 6 WC Pathology SC Pathology GA LB934 UT WOS:A1993LB93400012 PM 7684023 ER PT J AU TSANG, KY KASHMIRI, SVS QI, CF NIERODA, C CALVO, B DEFILIPPI, R GREINER, JW PRIMUS, FJ SCHLOM, J AF TSANG, KY KASHMIRI, SVS QI, CF NIERODA, C CALVO, B DEFILIPPI, R GREINER, JW PRIMUS, FJ SCHLOM, J TI TRANSFER OF THE IL-6 GENE INTO A HUMAN COLORECTAL-CARCINOMA CELL-LINE AND CONSEQUENT ENHANCEMENT OF TUMOR-ANTIGEN EXPRESSION SO IMMUNOLOGY LETTERS LA English DT Article DE IL-6 GENE; RETROVIRAL VECTOR; TRANSFECTION; COLORECTAL CARCINOMA CELLS ID ACTIVATED KILLER-CELLS; RECOMBINANT INTERLEUKIN-6; RETROVIRAL VECTORS; IFN-BETA-2 IL-6; GROWTH-FACTOR; INDUCTION; LYMPHOCYTES; INVIVO; ICAM-1; BSF-2 AB cDNA encoding the human IL gene (580 bp), inserted into a retroviral expression vector carrying neomycin resistance selective marker, was introduced into HT-29 human colon carcinoma cells by lipofection. Interleukin-6 activity was measured by ELISA and bioassay using B9 cells. Interleukin-6 secreted by transfected HT-29 cells was shown to be biologically active. The expression of the human tumor associated antigen CEA (carcinoembryonic antigen), HLA classes I and II, and ICAM-1 antigens in the transfected HT-29 cells were also analyzed by flow cytometry. Significant enhancement in the expression of CEA but not in the expression of HLA class I, HLA class II and ICAM-1 antigens, was observed in the transfected HT-29 cells as compared to the parental HT-29 cells. These results provide experimental evidence that enhancement of tumor antigen expression on tumor cells can be induced by IL-6 gene transfection, and suggest another potential role for the use of IL-6 gene transfer in the immunotherapy of human cancers. C1 NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. NR 47 TC 9 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 J9 IMMUNOL LETT JI Immunol. Lett. PD MAY PY 1993 VL 36 IS 2 BP 179 EP 186 DI 10.1016/0165-2478(93)90050-C PG 8 WC Immunology SC Immunology GA LH408 UT WOS:A1993LH40800010 PM 8102353 ER PT J AU BEAVEN, MA METZGER, H AF BEAVEN, MA METZGER, H TI SIGNAL-TRANSDUCTION BY FC-RECEPTORS - THE FC-EPSILON-RI CASE SO IMMUNOLOGY TODAY LA English DT Review ID PROTEIN-KINASE-C; BASOPHILIC LEUKEMIA-CELLS; HIGH-AFFINITY RECEPTOR; NATURAL-KILLER-CELLS; MAST-CELLS; IMMUNOGLOBULIN-E; PHOSPHOLIPASE-C; GAMMA RECEPTOR; TYROSINE PHOSPHORYLATION; SYNERGISTIC SIGNALS AB The family of proteins collectively known as Fc receptors (FcR) plays a variety of roles both in the initiation of the immune response and in its consequences. During the past five years the structure of these proteins and the genes that code for them have been largely elucidated. The most unexpected finding has been their extensive diversity Considerable efforts are now being expended to define the molecular events initiated by these various FcR and these events are the focus of our review. C1 NIAMSD,ARTHRITIS & RHEUMATISM BRANCH,BETHESDA,MD 20892. RP BEAVEN, MA (reprint author), NHLBI,CHEM PHARMACOL LAB,BETHESDA,MD 20892, USA. NR 78 TC 351 Z9 352 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD MAY PY 1993 VL 14 IS 5 BP 222 EP 226 DI 10.1016/0167-5699(93)90167-J PG 5 WC Immunology SC Immunology GA LC724 UT WOS:A1993LC72400009 PM 8517921 ER PT J AU OPPENHEIM, JJ GERY, I AF OPPENHEIM, JJ GERY, I TI FROM LYMPHODREK TO INTERLEUKIN-1 (IL-1) SO IMMUNOLOGY TODAY LA English DT Article ID LYMPHOCYTE-ACTIVATING FACTOR; FACTOR ETAF; CELL; POTENTIATION; MACROPHAGES; STIMULATION; ENDOTOXIN; MITOGENS; PYROGEN; MICE C1 NEI,IMMUNOL LAB,BETHESDA,MD 20892. RP OPPENHEIM, JJ (reprint author), NCI,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702, USA. NR 37 TC 11 Z9 11 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD MAY PY 1993 VL 14 IS 5 BP 232 EP 234 DI 10.1016/0167-5699(93)90169-L PG 3 WC Immunology SC Immunology GA LC724 UT WOS:A1993LC72400011 PM 8147958 ER PT J AU BETTS, M BEINING, P BRUNSWICK, M INMAN, J ANGUS, RD HOFFMAN, T GOLDING, B AF BETTS, M BEINING, P BRUNSWICK, M INMAN, J ANGUS, RD HOFFMAN, T GOLDING, B TI LIPOPOLYSACCHARIDE FROM BRUCELLA-ABORTUS BEHAVES AS A T-CELL-INDEPENDENT TYPE-1 CARRIER IN MURINE ANTIGEN-SPECIFIC ANTIBODY-RESPONSES SO INFECTION AND IMMUNITY LA English DT Article ID GAMMA-INTERFERON; NORMAL MICE; COVALENT; PROTEINS; INVITRO; IMMUNODEFICIENCY; LYMPHOCYTES; EXPRESSION; INDUCTION; SURFACES AB In order to determine the carrier nature of lipopolysaccharide from Brucella abortus (LPS-BA) in evoking humoral responses, normal and immunodeficient mice were immunized with trinitrophenyl (TNP)-conjugated LPS-BA (TNP-LPS-BA) and the responses were compared with those to known T-dependent and T-independent antigens. TNP-LPS-BA, like T-independent type 1 (TI-1) antigens such as TNP-BA and TNP-LPS from Escherichia coli (TNP-LPS-EC), generated anti-TNP responses in BALB/c, athymic BALB/c nu/nu, and CBA/N mice. In contrast, N-2,4-dinitrophenyl-beta-alanylglycylglycyl-substituted keyhole limpet hemocyanin, a typical T-dependent antigen, was not immunogenic in athymic mice, and TNP-Ficoll (T-independent type 2) was ineffective in eliciting humoral responses in CBA/N mice. These results indicate that LPS from B. abortus acts as a TI-1 carrier in generating antibody responses. In C3H/HeJ mice, TNP-LPS-BA generated higher-titer immunoglobulin G1 (IgG1), IgG2a, and IgG2b anti-TNP antibodies than TNP-LPS-EC. Compared with those from BALB/c mice, pure resting B cells isolated from C3H/Hej mice exhibited a 30-fold lower proliferative response to LPS-EC, whereas the LPS-BA response was reduced to a lesser extent (5-fold). This suggests that the disparity observed in antibody titers was due to different abilities of LPS from B. abortus and E. coli to stimulate C3H/HeJ B cells. The ability of LPS from B. abortus to act as a carrier in generating humoral immune responses indicates that LPS-BA can be substituted for whole B. abortus organisms in vaccine development. C1 US FDA,CTR BIOL EVALUAT & RES,DIV HEMATOL,CELL BIOL LAB,BETHESDA,MD 20892. NIAID,IMMUNOL LAB,BETHESDA,MD 20892. USDA,NATL VET SERV LABS,SCI & TECHNOL ANIM & PLANT HLTH INSPECT SERV,AMES,IA 50010. NR 33 TC 22 Z9 22 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 1993 VL 61 IS 5 BP 1722 EP 1729 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA KZ177 UT WOS:A1993KZ17700017 PM 8478060 ER PT J AU GRANT, CCR KONKEL, ME CIEPLAK, W TOMPKINS, LS AF GRANT, CCR KONKEL, ME CIEPLAK, W TOMPKINS, LS TI ROLE OF FLAGELLA IN ADHERENCE, INTERNALIZATION, AND TRANSLOCATION OF CAMPYLOBACTER-JEJUNI IN NONPOLARIZED AND POLARIZED EPITHELIAL-CELL CULTURES SO INFECTION AND IMMUNITY LA English DT Article ID ESCHERICHIA-COLI; SALMONELLA-TYPHIMURIUM; SURFACE-PROTEINS; HEP-2 CELLS; HELA-CELLS; INVASION; INFECTION; GENES; IDENTIFICATION; COLONIZATION AB Previous studies of Campylobacter jejuni have suggested that flagellin is an adhesin for epithelial cells and that motility is a virulence factor of this bacterium. The role of flagella in the interactions of C jejuni with nonpolarized and polarized epithelial cells was examined with flagellar mutants. Flagellated, nonmotile (flaA flaB+ Mot-) and nonflagellated, nonmotile (flaA flaB Mot-) mutants of C jejuni were constructed by in vivo homologous recombination and gene replacement techniques. Both classes of mutants were found to adhere to cells of human epithelial origin (INT 407) equally well; however, on the basis of the percentage of the inoculum internalized, internalization of the flaA flaB Mot- mutants was decreased by factors ranging from approximately 30 to 40 compared with the parent. The flaA flaB+ Mot- mutant was internalized by the INT 407 cells at levels six- to sevenfold higher than the flaA flaB Mot- mutants. Both classes of mutants, unlike the parent, were unable to translocate across polarized Caco-2 monolayers. These results indicate that flagella are not involved in C. jejuni adherence to epithelial cells but that they do play a role in internalization. Furthermore, the results suggest that either the motility of C. jejuni or the product of flaA is essential for the bacterium to cross polarized epithelial cell monolayers. C1 STANFORD UNIV,MED CTR,DEPT MICROBIOL & IMMUNOL,STANFORD,CA 94305. STANFORD UNIV,MED CTR,DEPT MED,DIV INFECT DIS,STANFORD,CA 94305. RP GRANT, CCR (reprint author), NIAID,ROCKY MT LABS,VECTORS & PATHOGENS LAB,HAMILTON,MT 59840, USA. FU NIAID NIH HHS [AI23796-07] NR 45 TC 169 Z9 172 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 1993 VL 61 IS 5 BP 1764 EP 1771 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA KZ177 UT WOS:A1993KZ17700023 PM 8478066 ER PT J AU HEINZEN, RA HAYES, SF PEACOCK, MG HACKSTADT, T AF HEINZEN, RA HAYES, SF PEACOCK, MG HACKSTADT, T TI DIRECTIONAL ACTIN POLYMERIZATION ASSOCIATED WITH SPOTTED-FEVER GROUP RICKETTSIA INFECTION OF VERO CELLS SO INFECTION AND IMMUNITY LA English DT Article ID CHICKEN-EMBRYO FIBROBLASTS; LISTERIA-MONOCYTOGENES; SHIGELLA-FLEXNERI; F-ACTIN; INVITRO; SPREAD; IDENTIFICATION; PENETRATION; PROWAZEKII; VIRULENCE AB Members of the spotted fever group (SFG) of rickettsiae spread rapidly from cell to cell by an unknown mechanism(s). Staining of Rickettsia rickettsii-infected Vero cells with rhodamine phalloidin demonstrated unique actin filaments associated with one pole of intracellular rickettsiae. F-actin tails greater than 70 mum in length were seen extending from rickettsiae. Treatment of infected cells with chloramphenicol eliminated rickettsia-associated F-actin tails, suggesting that de novo protein synthesis of one or more rickettsial proteins is required for tail formation. Rickettsiae were coated with F-actin as early as 15 min postinfection, and tail formation was detected by 30 min. A survey of virulent and avirulent species within the SFG rickettsiae demonstrated that all formed actin tails. Typhus group rickettsiae, which do not spread directly from cell to cell, lacked F-actin tails entirely or exhibited only very short tails. Transmission electron microscopy demonstrated fibrillar material in close association with R. rickettsii but not Rickettsia prowazekii. Biochemical evidence that actin polymerization plays a role in movement was provided by showing that transit of R. rickettsii from infected cells into the cell culture medium was inhibited by treatment of host cells with cytochalasin D. These data suggest that the cell-to-cell transmission of SFG rickettsiae may be aided by induction of actin polymerization in a fashion similar to that described for Shigella flexneri and Listeria monocytogenes. C1 NIAID,ROCKY MT LAB,INTRACELLULAR PARASITES LAB,HAMILTON,MT 59840. NR 51 TC 151 Z9 154 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 1993 VL 61 IS 5 BP 1926 EP 1935 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA KZ177 UT WOS:A1993KZ17700045 PM 8478082 ER PT J AU WASSERMAN, GM KUMAR, S AHLERS, J RAMSDELL, F BERZOFSKY, JA MILLER, LH AF WASSERMAN, GM KUMAR, S AHLERS, J RAMSDELL, F BERZOFSKY, JA MILLER, LH TI AN APPROACH TO DEVELOPMENT OF SPECIFIC T-LYMPHOCYTE LINES BY USE OF PREPROCESSED ANTIGENS IN PLASMODIUM-VINCKEI-VINCKEI MURINE MALARIA SO INFECTION AND IMMUNITY LA English DT Article ID STIMULATORY FACTOR-I; VACCINE DEVELOPMENT; CELL LINE; MONOCLONAL-ANTIBODY; IMMUNE-RESPONSE; CLONES; IMMUNOSUPPRESSION; PROTECTION; DEFINITION; CHABAUDI AB The development of parasite-specific T-cell lines represents one approach to the potential identification of relevant immunogens in erythrocytic malarial infection. However, the use of parasitized-erythrocyte lysates as antigens inhibits the proliferation of T cells. To circumvent this problem, we preincubated antigen-presenting cells (APCs) from spleens of malaria-naive, BALB/c mice with a Plasmodium vinckei vinckei (hereafter referred to as P. vinckei)-parasitized erythrocyte lysate. APCs were subsequently irradiated and washed prior to being incubated with T lymphocytes from P. vinckei-immune, histocompatible mice. After 8 to 10 cycles of antigenic stimulation and rest, two T-cell lines were analyzed. Both lines were predominantly CD4+. Proliferation assays demonstrated marked lymphocyte blastogenesis to syngeneic but not allogeneic APCs that had preprocessed malarial antigen. Antigen incubated directly with T cells and nonpulsed APCs in vitro did not result in T-cell proliferation. Assays of interleukin-2 (IL-2), IL-4, IL-5, and gamma interferon were compatible with one cell line being predominantly T(H)1 and the other being T(H)2. Thus, APCs that have preprocessed malarial antigen and are free of extraneous parasite material induce highly reactive, antigen-specific, major histocompatibility complex-restricted T-cell lines that functionally appear capable of inducing humoral and/or cell-mediated immunity. C1 NIAID,MALARIA RES LAB,BETHESDA,MD 20892. NIAID,CELLULAR & MOLEC IMMUNOL LAB,BETHESDA,MD 20892. NCI,IMMUNOGENET & VACCINE RES SECT,BETHESDA,MD 20892. WALTER REED ARMY INST RES,WASHINGTON,DC 20307. NR 41 TC 2 Z9 3 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 1993 VL 61 IS 5 BP 1958 EP 1963 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA KZ177 UT WOS:A1993KZ17700049 PM 8478085 ER PT J AU MARGOLIS, N ROSA, PA AF MARGOLIS, N ROSA, PA TI REGULATION OF EXPRESSION OF MAJOR OUTER SURFACE-PROTEINS IN BORRELIA-BURGDORFERI SO INFECTION AND IMMUNITY LA English DT Article ID LYME-DISEASE SPIROCHETE; POLYMERASE CHAIN-REACTION; MONOCLONAL-ANTIBODY; MOLECULAR ANALYSIS; POLYMORPHISMS; STRAINS; AGENT; OSPA AB We have characterized a Borrelia burgdorferi clone (CA-11 2A) that does not synthesize the major outer surface proteins, OspA and OspB. While the osp operon is intact and capable of expression, no mRNA transcript is detectable in this clone. These results suggest that osp operon expression in the B. burgdorferi clone can be regulated at the level of transcription. RP MARGOLIS, N (reprint author), NIAID,ROCKY MT LABS,MICROBIAL STRUCT & FUNCT LAB,HAMILTON,MT 59840, USA. NR 35 TC 50 Z9 50 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 1993 VL 61 IS 5 BP 2207 EP 2210 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA KZ177 UT WOS:A1993KZ17700084 PM 8478112 ER PT J AU MURPHY, BR AF MURPHY, BR TI USE OF LIVE ATTENUATED COLD-ADAPTED INFLUENZA A REASSORTANT VIRUS-VACCINES IN INFANTS, CHILDREN, YOUNG-ADULTS, AND ELDERLY ADULTS SO INFECTIOUS DISEASES IN CLINICAL PRACTICE LA English DT Review ID WILD-TYPE VIRUS; A-VIRUS; DOSE-RESPONSE; INACTIVATED VACCINE; H1N1 VIRUSES; H3N2; VOLUNTEERS; RESISTANCE; INFECTION; CHALLENGE C1 NIAID,INFECT DIS LAB,BETHESDA,MD 20892. NR 35 TC 41 Z9 41 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1056-9103 J9 INFECT DIS CLIN PRAC JI Infect. Dis. Clin. Pract. PD MAY-JUN PY 1993 VL 2 IS 3 BP 174 EP 181 DI 10.1097/00019048-199305000-00003 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA MF195 UT WOS:A1993MF19500003 ER PT J AU KILLEN, JD TAYLOR, CB HAMMER, LD LITT, I WILSON, DM RICH, T HAYWARD, C SIMMONDS, B KRAEMER, H VARADY, A AF KILLEN, JD TAYLOR, CB HAMMER, LD LITT, I WILSON, DM RICH, T HAYWARD, C SIMMONDS, B KRAEMER, H VARADY, A TI AN ATTEMPT TO MODIFY UNHEALTHFUL EATING ATTITUDES AND WEIGHT REGULATION PRACTICES OF YOUNG ADOLESCENT GIRLS SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article ID ANOREXIA-NERVOSA; BULIMIA; OBESITY; PREVENTION; DISORDERS; INDEXES; FEAR AB This is the first long-term, controlled study evaluating the effectiveness of a prevention curriculum designed to modify the eating attitudes and unhealthful weight regulation practices of young adolescent girls. Nine hundred sixty-seven sixth and seventh-grade girls were randomized to experimental healthy weight regulation curriculum or no-treatment control classes. A prevention intervention was developed around three principal components: (1) Instruction on the harmful effects of unhealthful weight regulation; (2) promotion of healthful weight regulation through the practice of sound nutrition and dietary principles and regular aerobic physical activity; (3) development of coping skills for resisting the diverse sociocultural influences that appear linked to the current popular obsessions with thinness and dieting. The intervention failed to achieve the hoped-for impact. We did observe a significant increase in knowledge among girls receiving the intervention and among high-risk students only, there was a small albeit statistically significant effect on body mass index. These findings question the wisdom of providing a curriculum directed at all young adolescents, most of whom are not at risk to develop an eating disorder. Rather than targeting the entire population, a healthy weight curriculum designed to modify the eating attitudes and unhealthful weight regulation practices of young adolescent girls might better focus on ''at risk'' students. C1 STANFORD UNIV, MED CTR, SCH MED, STANFORD, CA 94305 USA. RP KILLEN, JD (reprint author), NICHHD, DIV EPIDEMIOL STAT & PREVENT RES, 6100 EXECUT BLVD, BETHESDA, MD 20852 USA. FU NICHD NIH HHS [R01 HD24240-01] NR 33 TC 120 Z9 121 U1 5 U2 7 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD MAY PY 1993 VL 13 IS 4 BP 369 EP 384 DI 10.1002/1098-108X(199305)13:4<369::AID-EAT2260130405>3.0.CO;2-0 PG 16 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA KZ503 UT WOS:A1993KZ50300004 PM 8490639 ER PT J AU WONG, ML LICINIO, J GOLD, PW GLOWA, J AF WONG, ML LICINIO, J GOLD, PW GLOWA, J TI ACTIVITY-INDUCED ANOREXIA IN RATS DOES NOT AFFECT HYPOTHALAMIC NEUROPEPTIDE GENE-EXPRESSION CHRONICALLY SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article ID CORTICOTROPIN-RELEASING FACTOR; SEQUENCE-ANALYSIS; BULIMIA-NERVOSA; MESSENGER-RNAS; CHOLECYSTOKININ; IMMUNOREACTIVITY; CLONING; WEIGHT; CDNA AB Hypothalamic neuropeptides are thought to contribute to the pathophysiology of eating disorders. In an animal model with chronic abnormalities of energy expenditure, appetitive behavior, and body weight, without acute food restriction, we found alterations in peripheral levels of adrenocorticotropic hormone and corticosterone, but no alterations in the expression of neuropeptides genes that are known to regulate ingestive behavior and food intake acutely. Our data suggest that activation of hypothalamic-pituitary-adrenal function in activity anorexia may not be due to increased transcription of corticotropin-releasing hormone gene, but might be related to posttranscriptional events or to other neuropeptides, such as arginine vasopressin. Furthermore, we suggest that abnormalities in neuropeptides observed in eating disorders may be caused by acute food restriction, rather than by chronic hyper-activity, anorexia, and low weight. C1 YALE UNIV, SCH MED, VAMC, 116A, 950 CAMPBELL AVE, NEW HAVEN, CT 06510 USA. NIMH, CLIN NEUROENDOCRINOL BRANCH, W HAVEN, CT USA. NIDDKD, W HAVEN, CT USA. YALE UNIV, SCH MED, AFFECT DISORDERS UNIT, NEW HAVEN, CT 06510 USA. W HAVEN VET AFFAIRS MED CTR, MOLEC NEUROENDOCRINOL LAB, W HAVEN, CT USA. RI Wong, Ma-Li/D-7903-2011; Licinio, Julio/L-4244-2013 OI Licinio, Julio/0000-0001-6905-5884 NR 25 TC 13 Z9 13 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0276-3478 EI 1098-108X J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD MAY PY 1993 VL 13 IS 4 BP 399 EP 405 DI 10.1002/1098-108X(199305)13:4<399::AID-EAT2260130408>3.0.CO;2-J PG 7 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA KZ503 UT WOS:A1993KZ50300007 PM 8387855 ER PT J AU BHATIA, K SPANGLER, G ADVANI, S KAMEL, A HAMDY, N IYER, RS APLAN, P MAGRATH, IT AF BHATIA, K SPANGLER, G ADVANI, S KAMEL, A HAMDY, N IYER, RS APLAN, P MAGRATH, IT TI MOLECULAR CHARACTERIZATION OF SCL REARRANGEMENTS IN T-CELL ALL FROM INDIA AND EGYPT SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE MOLECULAR EPIDEMIOLOGY; SCL; T-CELL ALL VARIANT BREAKPOINTS ID ACUTE LYMPHOBLASTIC-LEUKEMIA; FRAGMENTS; PATTERN; GENE AB SCL gene rearrangement is the most common molecular lesion (25%) identified so far in T-cell acute lymphoblastic leukemia (T-ALL). Since the frequency of T-ALL appears to be relatively higher in developing countries, we wished to determine as to what fraction of T-ALL from this population harbor SCL rearrangements. We show in this study that although the overall frequency of SCL/SIL rearrangements in T-ALL is similar to the Western countries this is at the expense of increased type A rearrangements. Whether the paucity of type B rearrangements reflects a difference in disease etiology in this part of the world is to be determined. C1 TATA MEM HOSP,BOMBAY,INDIA. NATL CANC INST,CAIRO,EGYPT. RP BHATIA, K (reprint author), NCI,PEDIAT BRANCH,LYMPHOMA BIOL SECT,BLDG 10,ROOM 13N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Aplan, Peter/K-9064-2016; OI Kamel, Azza/0000-0002-9744-1851 NR 16 TC 8 Z9 8 U1 0 U2 0 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD MAY PY 1993 VL 2 IS 5 BP 725 EP 730 PG 6 WC Oncology SC Oncology GA KY165 UT WOS:A1993KY16500002 PM 21573616 ER PT J AU SETH, A MARIANO, J METCALF, R LI, H PANAYIOTAKIS, A PANOTOPOULOU, E PAPAEVANGELOU, ME KOTTARIDIS, SD PAPAS, TS AF SETH, A MARIANO, J METCALF, R LI, H PANAYIOTAKIS, A PANOTOPOULOU, E PAPAEVANGELOU, ME KOTTARIDIS, SD PAPAS, TS TI RELATIVE PAUCITY OF P53 GENE-MUTATIONS IN MALE BREAST CARCINOMAS SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE P53 GENE MUTATIONS; PCR AMPLIFICATION; SSCP ANALYSIS ID TUMOR SUPPRESSOR; CANCER; NEOPLASMS AB Mutations of the p53 suppressor -ene are the most common genetic lesion noted in human cancers and appear to be relatively common (30%) as somatic cell mutations in female breast cancer. p53 mutations have also been frequently reported in familial breast cancers as in Li-Fraumeni syndrome (LFS). Males with breast cancer are far rarer than females. We investigated the mutational spectra of the p53 gene in male breast cancers. Of 10 samples analyzed for p53 mutations in exons 5, 6. 7 and 8, only two showed point mutations corresponding to amino acid residues 248 and 290. One of the point mutations turned out to be a silent change, thus representing only DNA polymorphism. Although the number of male breast cancer samples thus far examined is small, the p53 mutations in male breast cancer (10%), unlike females (30%), does not appear to be as frequent. C1 US FDA,CBER,MOLEC MED GENET LAB,BETHESDA,MD 20892. DYN CORP,PROGRAM RESOURCES INC,FREDERICK,MD 21702. PAPANIKOLAOU RES CTR ONCOL & EXPTL SURG,HELLEN ANTICANC INST,ATHENS,GREECE. RP SETH, A (reprint author), NCI,MOLEC ONCOL LAB,POB B,FREDERICK,MD 21702, USA. NR 25 TC 5 Z9 5 U1 0 U2 2 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD MAY PY 1993 VL 2 IS 5 BP 739 EP 744 PG 6 WC Oncology SC Oncology GA KY165 UT WOS:A1993KY16500004 PM 21573618 ER PT J AU FASSINA, G PAGLIALUNGA, G NOONAN, DM CHADER, GJ ALBINI, A AF FASSINA, G PAGLIALUNGA, G NOONAN, DM CHADER, GJ ALBINI, A TI MODULATION OF Y-79 RETINOBLASTOMA CELL-DIFFERENTIATION AND IRBP EXPRESSION BY DIBUTYRYL-CYCLIC-AMP AND LAMININ SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE RETINOBLASTOMA; DIFFERENTIATION; CYCLIC AMP; LAMININ ID RETINOID-BINDING PROTEIN; ATTACHMENT CULTURE; MESSENGER-RNA; GENE; BUTYRATE; ACID AB Y-79 retinoblastoma cells grown on a poly-D-lysine-coated substratum can assume a photoreceptor-like morphology and they express the retina-specific interphotoreceptor-retinoid-binding protein (IRBP) mRNA in abundance. In contrast, cells in suspension culture remain morphologically undifferentiated and exhibit a much lower IRBP message level. After treatment with the differentiating agent dibutyryl cyclic AMP (dbcAMP), monolayer cultures of Y-79 cells grown in serum-containing medium show a partial morphological and biochemical differentiation towards a Muller-glial-like phenotype. This is accompanied by a decrease in IRBP mRNA level with respect to that in Y-79 cells grown on poly-D-lysine. Attached cells which had been pretreated with laminin for three days do not demonstrate an altered IRBP mRNA level in response to dbcAMP as compared to cells not pretreated. Surprisingly, however, cells in suspension culture that were exposed to laminin and then to dbcAMP showed a 3-fold increase in IRBP mRNA level. Thus, expression of an important photoreceptor-specific marker is clearly modulated by both dbcAMP and laminin. Moreover, attachment itself may be a significant factor in determination of a neural or neuro-retinal cell phenotype. C1 CNR,CTR NEUROFISIOL CEREBRALE,I-16132 GENOA,ITALY. NEI,BETHESDA,MD 20892. RP FASSINA, G (reprint author), IST NAZL RIC CANC,DEPT CHEM CARCINOGENESIS,VIALE BENEDETTO XV 10,I-16132 GENOA,ITALY. RI Noonan, Douglas/A-8620-2010 OI Noonan, Douglas/0000-0001-8058-0719 NR 33 TC 6 Z9 6 U1 0 U2 2 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD MAY PY 1993 VL 2 IS 5 BP 745 EP 751 PG 7 WC Oncology SC Oncology GA KY165 UT WOS:A1993KY16500005 PM 21573619 ER PT J AU LAVER, NM ROBISON, WG PFEFFER, BA AF LAVER, NM ROBISON, WG PFEFFER, BA TI NOVEL PROCEDURES FOR ISOLATING INTACT RETINAL VASCULAR BEDS FROM DIABETIC HUMANS AND ANIMAL-MODELS SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE RETINA; CAPILLARIES; DIABETES; ELASTASE; TRYPSIN DIGESTION ID CELLS; RAT AB Purpose. To improve the 30-year-old ''trypsin digestion'' procedure for isolation of the complete retinal vasculature, which, in its time, was a revolutionary advance that allowed important discoveries about diabetic retinopathy; to provide a method that will yield more consistent results when applied to retinas representing a wide range of ages, species, and severity of vascular disease, such as that occurring in diabetes. Methods. Because the Difco trypsin preparation (Difco Laboratories, Detroit, MI) is a crude pancreatic extract, containing variable amounts of chymotrypsin, elastase, amylase, lipase, ribonuclease, collagenase, and other contaminants, an attempt was made to determine which of the major enzymes alone (using purified preparations), or what combination of enzymes, might be most effective in providing consistently clean yet intact retinal vasculatures from eyes of different origins. Results. Purified elastase alone (40 U/ml) in 100 mmol/l sodium phosphate buffer with 150 mmol/l sodium chloride and 5 mmol/l EDTA at pH 6.5 and 37-degrees-C gave better results than various concentrations of purified trypsin or chymotrypsin alone, or mixtures of trypsin/chymotrypsin, trypsin/elastase, chymotrypsin/elastase, or the crude trypsin preparation. Conclusions. Elastase, which exhibits broad protease activity, and not trypsin, is the most important enzyme of the standard, crude trypsin digestion procedure for removal of the nonvascular tissues of the retina. C1 NEI,BLDG 6,RM 316,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 30 TC 27 Z9 27 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 1993 VL 34 IS 6 BP 2097 EP 2104 PG 8 WC Ophthalmology SC Ophthalmology GA LB755 UT WOS:A1993LB75500027 PM 8491560 ER PT J AU MAGNO, BV DATILES, MB LASA, SM AF MAGNO, BV DATILES, MB LASA, SM TI SENILE CATARACT PROGRESSION STUDIES USING THE LENS OPACITIES CLASSIFICATION SYSTEM-II SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Note DE SENILE CATARACT; CATARACT CLASSIFICATION; CATARACT PROGRESSION; CATARACT REGRESSION; PERSON DATA ID RETROILLUMINATION PHOTOGRAPHS; LOCS-II AB Purpose. To determine cataract progression rates at 6-mo intervals as evaluated using the Lens Opacities Classification System II (LOCS II). Methods. Idiopathic age-related cataracts in both eyes of 50 cataract patients and 17 normal control subjects were graded. The lenses were reexamined at 6 and 12 mo (+/-2 mo) from baseline to determine rates of change. Progression or regression in patients or control subjects was considered to have occurred at the 6-mo examination if a one or more step change in the LOCS II grading was noted in at least one eye at 6 mo and maintained at the 12-mo visit. Results. Six months from baseline, 38% of patients' conditions worsened in the nuclear area, 34% of patients' conditions worsened in the cortical region, and 8% of patients' conditions worsened in the posterior subcapsular region. Regression rates were 4% in each region. The percentages of patients progressing in the nuclear and cortical regions were significantly greater than the corresponding regression rates (P < .001). Greater progression was noted in the nuclear (P = .06) and posterior subcapsular (P < . 0 1) regions in patients with early opacities (LOCS + 1/+2) as compared to patients with no opacities initially in the same lenticular areas. Conclusion. This study suggests that the LOCS II is capable of detecting changes in lens opacities in a relatively short period of time among persons with early to moderate opacities. C1 NEI,OPHTHALM GENET & CLIN SERV BRANCH,BLDG 10,RM 10N226,BETHESDA,MD 20892. OI Datiles, Manuel III B./0000-0003-4660-1664 NR 11 TC 22 Z9 22 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 1993 VL 34 IS 6 BP 2138 EP 2141 PG 4 WC Ophthalmology SC Ophthalmology GA LB755 UT WOS:A1993LB75500032 PM 8491564 ER PT J AU DIXON, DO RIDA, WN FAST, PE HOTH, DF AF DIXON, DO RIDA, WN FAST, PE HOTH, DF TI HIV VACCINE TRIALS - SOME DESIGN ISSUES INCLUDING SAMPLE-SIZE CALCULATION SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Review DE CLINICAL TRIALS; PREVENTION; HIV VACCINES ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEPATITIS-B VACCINE; ENVELOPE GLYCOPROTEIN; CONFERS PROTECTION; CLINICAL-TRIAL; GP160 VACCINE; FOLLOW-UP; INFECTION; ANTIBODY; CHIMPANZEES AB Anticipating the availability of one or more candidate HIV vaccines for efficacy testing in the next few years, public health agencies are now planning for the conduct of large-scale efficacy trials. We expect these trials to be randomized, double-blind, placebo-controlled studies with prevention of infection as the primary goal. We discuss in detail factors that influence sample size. Factors most influential are the incidence rate of HIV infection in the study population and the minimum efficacy at which a vaccine is still considered acceptable. The smaller either of these factors is, the larger the sample size will be. The desire to complete trials quickly, the gradual accrual of benefit from vaccination, the inaccuracies of assays to detect infection, the need to counsel participants to avoid exposure to HIV, and loss to follow-up all tend to drive up sample size. To illustrate, 83 subjects per study arm suffice to detect 90% efficacy in a population with a 7% annual risk of infection. This assumes a 3-year study with accrual completed in 1 year, no loss to follow-up, and Types I and II error rates of 5 and 10%, respectively. In contrast, 4,254 subjects per arm are required to identify a 60% effective vaccine in a population with a 1% annual risk. The study is also shortened to 2 years, assumes a 5% annual loss to follow-up, and supposes that the full benefit of vaccination is achieved in 6 months. The most realistic assumptions indicate that trials are very likely to require several thousand participants. Limitations of the proposed designs are also discussed. C1 NIAID,BIOSTAT RES BRANCH,BETHESDA,MD 20892. RP DIXON, DO (reprint author), NIAID,DIV AIDS,VACCINE RES & DEV BRANCH,SOLAR BLDG,2B21,BETHESDA,MD 20892, USA. NR 58 TC 36 Z9 36 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD MAY PY 1993 VL 6 IS 5 BP 485 EP 496 PG 12 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA KY565 UT WOS:A1993KY56500009 PM 8483112 ER PT J AU IGARASHI, Y KALINER, MA HAUSFELD, JN IRANI, AMA SCHWARTZ, LB WHITE, MV AF IGARASHI, Y KALINER, MA HAUSFELD, JN IRANI, AMA SCHWARTZ, LB WHITE, MV TI QUANTIFICATION OF RESIDENT INFLAMMATORY CELLS IN THE HUMAN NASAL-MUCOSA SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE INFLAMMATORY CELLS; NASAL MUCOSA; IMMUNOHISTOCHEMISTRY ID HUMAN MAST-CELLS; INTERLEUKIN-2 RECEPTOR; MONOCLONAL-ANTIBODIES; INTERFERON-GAMMA; PATHO-PHYSIOLOGY; LYMPHOCYTES-T; HUMAN NOSE; IDENTIFICATION; HETEROGENEITY; SUBSETS AB Background: To define the normal resident inflammatory cell population in the nasal mucosa, surgical specimens of human nasal turbinates were immunohistologically stained for various cell markers. Methods: Freeze-dried paraffin-embedded sections were stained for lymphocyte cell-surface markers, and Carnoy's fixed sections were stained for mast cells and immunoglobulins. The numbers of stained cells were microscopically counted. Results: T cells (CD3+ cells) were abundant in the lamina propria, and the number of CD4+ cells and CD8+ cells accounted for two thirds and one third of CD3+ cell number, respectively. Cells that stained for the alpha-chain of the interleukin-2 receptor (activated cells, CD25+) were limited and accounted for only 0.6% of CD3+ cell number. B cells (CD22+ cells) and monocytes and macrophages (CD14+ cells) were observed less frequently than T cells. Many immunoglobulin-producing cells were found in close proximity to the submucosal glands, and those cells were predominantly IgA+. Mast cells were widely distributed in the nasal mucosa, and about one third of these cells were stained for IgE molecules. Nonmast cells bearing IgE were rarely observed Conclusion: Thus the dominant cell in the nasal mucosa is a CD3+, CD4+, CD25-lymphocyte. C1 NIAID,CLIN INVEST LAB,ALLERG DIS SECT,BLDG 10,ROOM 11C207,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. WASHINGTON HOSP CTR,DEPT FACIAL PLAST & RECONSTRUCT SURG,WASHINGTON,DC 20010. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT MED,RICHMOND,VA 23298. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT PEDIAT,RICHMOND,VA 23298. NR 38 TC 38 Z9 38 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD MAY PY 1993 VL 91 IS 5 BP 1082 EP 1093 DI 10.1016/0091-6749(93)90223-3 PG 12 WC Allergy; Immunology SC Allergy; Immunology GA LC978 UT WOS:A1993LC97800017 PM 8491941 ER PT J AU CONE, EJ DICKERSON, S PAUL, BD MITCHELL, JM AF CONE, EJ DICKERSON, S PAUL, BD MITCHELL, JM TI FORENSIC DRUG-TESTING FOR OPIATES .5. URINE TESTING FOR HEROIN, MORPHINE, AND CODEINE WITH COMMERCIAL OPIATE IMMUNOASSAYS SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID GAS-CHROMATOGRAPHY; 6-ACETYLMORPHINE; METABOLITE; ASSAY C1 USN,DRUG SCREENING LAB,NORFOLK,VA 23511. USN,DRUG SCREENING LAB,JACKSONVILLE,FL 32212. RP CONE, EJ (reprint author), NIDA,POB 5180,ADDICT RES CTR,BALTIMORE,MD 21224, USA. NR 12 TC 23 Z9 23 U1 1 U2 3 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD MAY-JUN PY 1993 VL 17 IS 3 BP 156 EP 164 PG 9 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA LD480 UT WOS:A1993LD48000007 PM 8336489 ER PT J AU CONE, EJ HUESTIS, MA MITCHELL, JM AF CONE, EJ HUESTIS, MA MITCHELL, JM TI DO CONSECUTIVE URINE CATCHES DIFFER IN MARIJUANA METABOLITE CONCENTRATION SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Letter C1 USN,DRUG SCREENING LAB,JACKSONVILLE,FL 32212. RP CONE, EJ (reprint author), NIDA,ADDICT RES CTR,POB 5180,BALTIMORE,MD 21224, USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD MAY-JUN PY 1993 VL 17 IS 3 BP 186 EP 187 PG 2 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA LD480 UT WOS:A1993LD48000012 PM 8336494 ER PT J AU CHEN, L COLEMAN, WG AF CHEN, L COLEMAN, WG TI CLONING AND CHARACTERIZATION OF THE ESCHERICHIA-COLI K-12 RFA-2 (RFAC) GENE, A GENE REQUIRED FOR LIPOPOLYSACCHARIDE INNER CORE SYNTHESIS SO JOURNAL OF BACTERIOLOGY LA English DT Article ID SALMONELLA-TYPHIMURIUM; SEQUENCE-ANALYSIS; BIOSYNTHESIS; EXPRESSION; POLYMERASE; MUTANTS AB A genetically defined mutation, designated rfa-2, results in altered lipopolysaccharide (LPS) biosynthesis. rfa-2 mutants produce a core-defective LPS that contains lipid A and a single sugar moiety, 2-keto-3-deoxyoctulosonic acid, in the LPS core region. Such LPS core-defective or deep-rough (R) mutant structures were previously designated chemotype Re. Phenotypically, rfa-2 mutants exhibit increased permeability to a number of hydrophilic and hydrophobic agents. By restriction analyses and complementation studies, we clearly defined the rfa-2 gene on a 1,056-bp AluI-DraI fragment. The rfa-2 gene and the flanking rfa locus regions were completely sequenced. Additionally, the location of the rfa-2 gene on the physical map of the Escherichia coli chromosome was determined. The rfa-2 gene encodes a 36,000-dalton polypeptide in an in vivo expression system. N-terminal analysis of the purified rfa-2 gene product confirmed the first 24 amino acid residues as deduced from the nucleotide sequence of the rfa-2 gene coding region. By interspecies complementation, a Salmonella typhimurium rfaC mutant (LPS chemotype Re) is transformed with the E. coli rfa-2 + gene, and the transformant is characterized by wild-type sensitivity to novobiocin (i.e., uninhibited growth at 600 mug of novobiocin per ml) and restoration of the ability to synthesize wild-type LPS structures. On the basis of the identity and significant similarity of the rfa-2 gene sequence and its product to the recently defined (D. M. Sirisena, K. A. Brozek, P. R. MacLachlan, K. E. Sanderson, and C. R. H. Raetz, J. Biol. Chem. 267:18874-18884, 1992), the S. typhimurium rfaC gene sequence and its product (heptosyltransferase 1), the E. coli K-12 rfa-2 locus will be designated rfaC. RP COLEMAN, WG (reprint author), NIDDK,BIOCHEM PHARMACOL LAB,PHARMACOL SECT,BLDG 8,ROOM 2A-03,BETHESDA,MD 20892, USA. NR 31 TC 43 Z9 45 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAY PY 1993 VL 175 IS 9 BP 2534 EP 2540 PG 7 WC Microbiology SC Microbiology GA KZ483 UT WOS:A1993KZ48300007 PM 8478319 ER PT J AU TERCERO, JC DINMAN, JD WICKNER, RB AF TERCERO, JC DINMAN, JD WICKNER, RB TI YEAST MAK3 N-ACETYLTRANSFERASE RECOGNIZES THE N-TERMINAL 4 AMINO-ACIDS OF THE MAJOR COAT PROTEIN (GAG) OF THE L-A DOUBLE-STRANDED-RNA VIRUS SO JOURNAL OF BACTERIOLOGY LA English DT Note ID SACCHAROMYCES-CEREVISIAE; ALPHA-ACETYLTRANSFERASE; METHIONINE AMINOPEPTIDASE; MITOCHONDRIAL; GENE; IDENTIFICATION; SPECIFICITIES; ACETYLATION; FORMS AB The MAK3 gene of Saccharomyces cerevisiae encodes an N-acetyltransferase whose acetylation of the N terminus of the L-A double-stranded RNA virus major coat protein (gag) is necessary for viral assembly. We show that the first 4 amino acids of the L-A gag protein sequence, MLRF, are a portable signal for N-terminal acetylation by MAK3. Amino acids 2, 3, and 4 are each important for acetylation by the MAK3 enzyme. In yeast cells, only three mitochondrial proteins are known to have the MAK3 acetylation signal, suggesting an explanation for the slow growth of mak3 mutants on nonfermentable carbon sources. C1 NIDDKD, GENET SIMPLE EUKARYOTES SECT, BIOCHEM PHARMACOL LAB, BETHESDA, MD 20892 USA. NR 25 TC 40 Z9 40 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 EI 1098-5530 J9 J BACTERIOL JI J. Bacteriol. PD MAY PY 1993 VL 175 IS 10 BP 3192 EP 3194 PG 3 WC Microbiology SC Microbiology GA LB792 UT WOS:A1993LB79200051 PM 8491733 ER PT J AU URRUTIA, R MCNIVEN, MA KACHAR, B AF URRUTIA, R MCNIVEN, MA KACHAR, B TI SYNTHESIS OF RNA PROBES BY THE DIRECT INVITRO TRANSCRIPTION OF PCR-GENERATED DNA TEMPLATES SO JOURNAL OF BIOCHEMICAL AND BIOPHYSICAL METHODS LA English DT Article DE POLYMERASE CHAIN REACTION; INVITRO TRANSCRIPTION; RNA PROBE; HYBRIDIZATION; KINESIN ID PROMOTER; ACID AB We describe a novel method for the generation of RNA probes based on the direct in vitro transcription of DNA templates amplified by polymerase chain reaction (PCR) using primers with sequence hybrids between the target gene and those of the T7 and T3 RNA polymerases promoters. This method circumvents the need for cloning and allows rapid generation of strand-specific RNA molecules that can be used for the identification of genes in hybridization experiments. We have successfully applied this method to the identification of DNA sequences by Southern blot analysis and library screening. C1 MAYO CLIN & MAYO FDN,CTR BASIC RES DIGEST DIS,ROCHESTER,MN 55905. RP URRUTIA, R (reprint author), NIDCD,CELLULAR BIOL LAB,BLDG 10,ROOM 5 D50,BETHESDA,MD 20892, USA. FU PHS HHS [EK44650] NR 11 TC 13 Z9 13 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-022X J9 J BIOCHEM BIOPH METH JI J. Biochem. Biophys. Methods PD MAY PY 1993 VL 26 IS 2-3 BP 113 EP 120 DI 10.1016/0165-022X(93)90041-L PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA KY854 UT WOS:A1993KY85400003 PM 8509599 ER PT J AU MUDD, CP GERSHFELD, NL BERGER, RL TAJIMA, K AF MUDD, CP GERSHFELD, NL BERGER, RL TAJIMA, K TI A DIFFERENTIAL HEAT-CONDUCTION MICROCALORIMETER FOR HEAT-CAPACITY MEASUREMENTS OF FLUIDS SO JOURNAL OF BIOCHEMICAL AND BIOPHYSICAL METHODS LA English DT Article DE HEAT-CAPACITY TEMPERATURE DEPENDENCE; HEAT-CONDUCTION CALORIMETER; PHOSPHOLIPID; MULTILAMELLAR-UNILAMELLAR TRANSFORMATION; THERMAL MODELING ID PHOSPHOLIPID SURFACE BILAYERS; AIR-WATER-INTERFACE; STATE AB A heat-conduction calorimeter has been developed for measuring small changes in heat capacity of milligram samples of membrane lipid dispersed in water as a function of temperature. The operation of the instrument is based on the principle that the thermal response of the sample to a short (10 s), electrically generated heat burst is a function of the diffusivity of the sample. Modeling studies of the instrument's performance have revealed that the output response after the heat burst is a function of only the heat capacity, rhoC(p). Calibration of the instrument experimentally confirmed this behavior. This feature obviated the need to measure the thermal conductivity in order to determine rhoC(p) from the diffusivity equation, eta = lambda/rhoC(p). The calorimeter has the following characteristics: reproducibility of loading: +/-400 muJ/C-degrees.cm3; baseline stability: +/-10 muJ/C-degrees.cm3 per 36 h; resolution (+/- 1 S.D.): +/-50 muJ/C-degrees.cm3; sample size 600 mul. C1 NIAMSD,PHYS BIOL LAB,BETHESDA,MD. NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. RP MUDD, CP (reprint author), NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BLDG 10,ROOM B2S245,BETHESDA,MD 20892, USA. NR 19 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-022X J9 J BIOCHEM BIOPH METH JI J. Biochem. Biophys. Methods PD MAY PY 1993 VL 26 IS 2-3 BP 149 EP 171 DI 10.1016/0165-022X(93)90045-P PG 23 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA KY854 UT WOS:A1993KY85400007 PM 8509603 ER PT J AU VUISTER, GW YAMAZAKI, T TORCHIA, DA BAX, A AF VUISTER, GW YAMAZAKI, T TORCHIA, DA BAX, A TI MEASUREMENT OF 2-BOND AND 3-BOND C-13-H-1 J-COUPLINGS TO THE C-DELTA CARBONS OF LEUCINE RESIDUES IN STAPHYLOCOCCAL NUCLEASE SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE 3D NMR; LONG-RANGE J-COUPLING; CARBON CARBON J-COUPLING; CHI-2 TORSION ANGLE; STEREOSPECIFIC ASSIGNMENT; PROTEIN DYNAMICS ID 2D NMR-SPECTRA; 3-DIMENSIONAL NMR; CRYSTAL-STRUCTURE; PROTEINS; CONSTANTS; MACROMOLECULES; RELAXATION; SPECTROSCOPY; RESOLUTION; SYSTEMS AB A new H-1-detected 3D NMR experiment is described that permits quantitative measurement of two- and three-bond C-13-H-1 couplings in proteins with selectively C-enriched methyl sites. The method is demonstrated for staphylococcal nuclease selectively [5,5 C-13]-labeled in all 11 leucine positions and ligated with thymidine 3',5'-biphosphate and Ca2+. Two- and three-bond C-13 methyl-proton couplings are reported and, together with the measured three-bond J(CalphaCdelta) in uniformly C-13-enriched staphylococcal nuclease, the chi2-angles and the stereospecific assignments of the C(delta) methyl group with respect to the prochiral beta-protons were determined. The same residues that were previously found to have high degrees of internal mobility on the basis of C-13 relaxation times have measured coupling constants that are indicative of motional averaging. C1 NIDR,BONE RES BRANCH,BETHESDA,MD 20892. RP VUISTER, GW (reprint author), NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892, USA. NR 34 TC 43 Z9 43 U1 0 U2 2 PU ESCOM SCI PUBL BV PI LEIDEN PA PO BOX 214, 2300 AE LEIDEN, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD MAY PY 1993 VL 3 IS 3 BP 297 EP 306 DI 10.1007/BF00212516 PG 10 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA LE201 UT WOS:A1993LE20100005 PM 8358233 ER PT J AU BUXTON, RS COWIN, P FRANKE, WW GARROD, DR GREEN, KJ KING, IA KOCH, PJ MAGEE, AI REES, DA STANLEY, JR STEINBERG, MS AF BUXTON, RS COWIN, P FRANKE, WW GARROD, DR GREEN, KJ KING, IA KOCH, PJ MAGEE, AI REES, DA STANLEY, JR STEINBERG, MS TI NOMENCLATURE OF THE DESMOSOMAL CADHERINS SO JOURNAL OF CELL BIOLOGY LA English DT Review ID CELL-ADHESION MOLECULES; AMINO-ACID-SEQUENCE; GLYCOPROTEIN-3 DESMOCOLLINS; PEMPHIGUS AUTOANTIBODIES; DESMOGLEIN; COMPONENTS; IDENTIFICATION; HETEROGENEITY; EXPRESSION; EPIDERMIS C1 NYU MED CTR,SCH MED,NEW YORK,NY 10016. GERMAN CANC RES CTR,INST ZELL & TUMORBIOL,W-6900 HEIDELBERG 1,GERMANY. UNIV MANCHESTER,DEPT BIOL SCI,MANCHESTER M13 9PT,LANCS,ENGLAND. NORTHWESTERN UNIV,SCH MED,DEPT PATHOL,CHICAGO,IL 60611. NCI,DERMATOL BRANCH,BETHESDA,MD 20892. PRINCETON UNIV,DEPT MOLEC BIOL,PRINCETON,NJ 08544. RP BUXTON, RS (reprint author), NATL INST MED RES,EUKARYOT MOLEC GENET LAB,MILL HILL,LONDON NW7 1AA,ENGLAND. NR 38 TC 260 Z9 263 U1 2 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD MAY PY 1993 VL 121 IS 3 BP 481 EP 483 DI 10.1083/jcb.121.3.481 PG 3 WC Cell Biology SC Cell Biology GA KZ423 UT WOS:A1993KZ42300001 PM 8486729 ER PT J AU SODEIK, B DOMS, RW ERICSSON, M HILLER, G MACHAMER, CE VANT HOF, W VAN MEER, G MOSS, B GRIFFITHS, G AF SODEIK, B DOMS, RW ERICSSON, M HILLER, G MACHAMER, CE VANT HOF, W VAN MEER, G MOSS, B GRIFFITHS, G TI ASSEMBLY OF VACCINIA VIRUS - ROLE OF THE INTERMEDIATE COMPARTMENT BETWEEN THE ENDOPLASMIC-RETICULUM AND THE GOLGI STACKS SO JOURNAL OF CELL BIOLOGY LA English DT Article ID NEURONAL ENDOMEMBRANE SYSTEM; MONOCLONAL-ANTIBODY; CIS-GOLGI; INTRACELLULAR TRANSLOCATION; POLYPEPTIDE COMPOSITION; CULTURED FIBROBLASTS; CELLULAR MEMBRANES; FROZEN-SECTIONS; PLASMA-MEMBRANE; E1 GLYCOPROTEIN AB Vaccinia virus, the prototype of the Poxviridae, is a large DNA virus which replicates in the cytoplasm of the host cell. The assembly pathway of vaccinia virus displays several unique features, such as the production of two structurally distinct, infectious forms. One of these, termed intracellular naked virus (INV), remains cell associated while the other, termed extracellular enveloped virus (EEV), is released from the cell. In addition, it has long been believed that INVs acquire their lipid envelopes by a unique example of de novo membrane biogenesis. To examine the structure and assembly of vaccinia virus we have used immunoelectron microscopy using antibodies to proteins of different subcellular compartments as well as a phospholipid analysis of purified INV and EEV. Our data are not consistent with the de novo model of viral membrane synthesis but rather argue that the vaccinia virus DNA becomes enwrapped by a membrane cisterna derived from the intermediate compartment between the ER and the Golgi stacks, thus acquiring two membranes in one step. Phospholipid analysis of purified INV supports its derivation from an early biosynthetic compartment. This unique assembly process is repeated once more when the INV becomes enwrapped by an additional membrane cisterna, in agreement with earlier reports. The available data suggest that after fusion between the outer envelope and the plasma membrane, mature EEV is released from the cell. C1 UNIV PENN, SCH MED, DEPT PATHOL & LAB MED, PHILADELPHIA, PA 19104 USA. BOEHRINGER MANNHEIM GMBH, W-6800 MANNHEIM, GERMANY. JOHNS HOPKINS UNIV, SCH MED, DEPT CELL BIOL & ANAT, BALTIMORE, MD 21205 USA. UNIV UTRECHT, SCH MED, DEPT CELL BIOL, 3584 CH UTRECHT, NETHERLANDS. NIAID, VIRAL DIS LAB, BETHESDA, MD 20892 USA. RP SODEIK, B (reprint author), EUROPEAN MOLEC BIOL LAB, CELL BIOL PROGRAM, W-6900 HEIDELBERG, GERMANY. RI Sodeik, Beate/C-9732-2010 NR 73 TC 259 Z9 260 U1 1 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 EI 1540-8140 J9 J CELL BIOL JI J. Cell Biol. PD MAY PY 1993 VL 121 IS 3 BP 521 EP 541 DI 10.1083/jcb.121.3.521 PG 21 WC Cell Biology SC Cell Biology GA KZ423 UT WOS:A1993KZ42300006 PM 8486734 ER PT J AU JAFFE, LA GALLO, CJ LEE, RH HO, YK JONES, TLZ AF JAFFE, LA GALLO, CJ LEE, RH HO, YK JONES, TLZ TI OOCYTE MATURATION IN STARFISH IS MEDIATED BY THE BETA-GAMMA-SUBUNIT COMPLEX OF A G-PROTEIN SO JOURNAL OF CELL BIOLOGY LA English DT Article ID GTP-BINDING PROTEINS; ROD OUTER SEGMENTS; HORMONE-DEPENDENT PERIOD; MUSCARINIC K+-CHANNEL; ADENYLATE-CYCLASE; MEIOSIS REINITIATION; MEIOTIC MATURATION; ESCHERICHIA-COLI; ALPHA-SUBUNITS; M-PHASE AB The stimulation of meiotic maturation of starfish oocytes by the hormone 1-methyladenine is mimicked by injection of betagamma subunits of G-proteins from either retina or brain. Conversely, the hormone response is inhibited by injection of the GDP-bound forms of alpha(i1) or alpha(t) subunits, or by injection of phosducin; all of these proteins should bind free betagamma. alpha-subunit forms with reduced affinity for betagamma (alpha(i1) or alpha(t) bound to hydrolysis-resistant GTP analogs, or alpha(i1)-GMPPCP treated with trypsin to remove the amino terminus of the protein) are less effective inhibitors of 1-methyladenine action. These results indicate that the betagamma subunit of a G-protein mediates 1-methyladenine stimulation of oocyte maturation. C1 NIDDKD,MOLEC PATHOPHYSIOL BRANCH,BETHESDA,MD 20892. UNIV CALIF LOS ANGELES,SCH MED,DEPT ANAT & CELL BIOL,SEPULVEDA,CA 91343. VET ADM MED CTR,DEPT DEV NEUROBIOL,SEPULVEDA,CA 91343. UNIV ILLINOIS,DEPT BIOCHEM & OPHTHALMOL,CHICAGO,IL 60612. RP JAFFE, LA (reprint author), UNIV CONNECTICUT,CTR HLTH,DEPT PHYSIOL,FARMINGTON,CT 06032, USA. FU NEI NIH HHS [EY-05788]; NICHD NIH HHS [HD-14939] NR 96 TC 66 Z9 66 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD MAY PY 1993 VL 121 IS 4 BP 775 EP 783 DI 10.1083/jcb.121.4.775 PG 9 WC Cell Biology SC Cell Biology GA LB638 UT WOS:A1993LB63800006 PM 8491771 ER PT J AU CAMPAIN, JA PADMANABHAN, R HWANG, J GOTTESMAN, MM PASTAN, I AF CAMPAIN, JA PADMANABHAN, R HWANG, J GOTTESMAN, MM PASTAN, I TI CHARACTERIZATION OF AN UNUSUAL MUTANT OF HUMAN-MELANOMA CELLS RESISTANT TO ANTICANCER DRUGS THAT INHIBIT TOPOISOMERASE-II SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID P-GLYCOPROTEIN EXPRESSION; BREAST-CANCER-CELLS; MULTIDRUG RESISTANCE; LEUKEMIA-CELLS; DNA CLEAVAGE; MITOXANTRONE RESISTANCE; CATALYTIC ACTIVITY; MEMBRANE-PROTEIN; CDNA CLONES; TUMOR-CELLS AB The topoisomerase II inhibitor, VP-1 6 (etoposide), is an important component in many chemotherapeutic regimens. To characterize resistance to this drug, the human melanoma cell line, FEM-X, was selected in multiple steps with VP-16. To prevent the development of typical multidrug resistance, an inhibitor of P-glycoprotein, the tiapamil analog, RO-11-2933, was added to the selections. The resultant clone FVP3 is 56-fold resistant to VP-16 and cross-resistant to doxorubicin (Adriamycin) (9-fold) and VM-26 (27-fold). These cells are also two- to four-fold resistant to m-AMSA, daunorubicin, and mitoxantrone. FVP3 is not resistant to the P-glycoprotein substrate vinblastine, does not express the MDRI gene at detectable levels, and does not show reduced H-3-VP-16 accumulation. Unlike other cell lines that exhibit resistance to inhibitors of topoisomerase II, FVP3 has the same level of topoisomerase II expression and activity as FEM-X. Using live cells treated with VP-16, band depletion assays and KCl/SDS precipitation assays show that topoisomerase II from FVP3 is much less susceptible to drug-induced cleavable complex formation than is that from FEM-X. This difference in sensitivity to VP-16 is also detected using lysates from disrupted cells, but not with isolated nuclei devoid of cytoplasmic and membrane components. In addition, the topoisomerase II present in nuclear extracts from FVP3 is not resistant to the effects of VP-16 as measured by: (1) inhibition of strand passing activity during decatenation of kinetoplast DNA, (2) drug-induced linearization of plasmid DNA, and (3) immunodepletion by VP-16. These results suggest that some component of the cytoplasm or cellular membranes, or a factor depleted from nuclei during their isolation, is responsible for the resistance to VP-16 in FVP3. C1 NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. NCI,CELL BIOL LAB,BETHESDA,MD 20892. NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. ACAD SINICA,INST MOLEC BIOL,TAIPEI 115,TAIWAN. NR 42 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 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD MAY PY 1993 VL 155 IS 2 BP 414 EP 425 DI 10.1002/jcp.1041550224 PG 12 WC Cell Biology; Physiology SC Cell Biology; Physiology GA KZ501 UT WOS:A1993KZ50100023 PM 8097746 ER PT J AU AZARI, NP PETTIGREW, KD SCHAPIRO, MB HAXBY, JV GRADY, CL PIETRINI, P SALERNO, JA HESTON, LL RAPOPORT, SI HORWITZ, B AF AZARI, NP PETTIGREW, KD SCHAPIRO, MB HAXBY, JV GRADY, CL PIETRINI, P SALERNO, JA HESTON, LL RAPOPORT, SI HORWITZ, B TI EARLY DETECTION OF ALZHEIMERS-DISEASE - A STATISTICAL APPROACH USING POSITRON EMISSION TOMOGRAPHIC DATA SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE ALZHEIMERS DISEASE; POSITRON EMISSION TOMOGRAPHY; DISCRIMINANT ANALYSIS; 18FDG; BRAIN; METABOLISM ID CEREBRAL GLUCOSE-METABOLISM; ADRDA WORK GROUP; BRAIN-REGIONS; PSYCHOMETRIC DIFFERENTIATION; CLINICAL-DIAGNOSIS; SENILE DEMENTIA; RATES; INTERCORRELATIONS; HUNTINGTONS; ADULTS AB Correlational analysis of regional cerebral glucose metabolism (rCMR(glc)) obtained by high-resolution positron emission tomography (PET) has demonstrated reduced neocortical rCMR(glc) interactions in mildly/moderately demented patients with probable Alzheimer's disease (AD). Thus, identification of individual differences in patterns of rCMR(glc) interactions may be important for the early detection of AD, particularly among individuals at greater risk for developing AD (e.g., those with a family history of AD). Recently, a statistical procedure, using multiple regression and discriminant analysis, was developed to assess individual differences in patterns of rCMR(glc) interdependencies. We applied this new statistical procedure to resting rCMR(glc) PET data from mildly/moderately demented patients with probable AD and age/sex-matched controls. The aims of the study were to identify a discriminant function that would (a) distinguish patients from controls and (b) identify an AD pattern in an individual at risk for AD with isolated memory impairment whose initial PET scan showed minor abnormalities, but whose second scan showed parietal hypometabolism, coincident with further cognitive decline. Two discriminant functions, reflecting interactions involving regions most involved in reduced correlations in probable AD, correctly classified 87% of the patients and controls, and successfully identified the first scan of the at-risk individual as AD (probability >0.70). The results suggest that this statistical approach may be useful for the early detection of AD. C1 NIMH,DIV EPIDEMIOL APPL & SERV RES,BETHESDA,MD 20892. WASHINGTON STATE MENTAL ILLNESS RES & TRAINING INST,FT STEILACOON,WA. RP AZARI, NP (reprint author), NIA,NEUROSCI LAB,BLDG 10,ROOM 6C414,BETHESDA,MD 20892, USA. NR 54 TC 77 Z9 81 U1 1 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD MAY PY 1993 VL 13 IS 3 BP 438 EP 447 PG 10 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA KY458 UT WOS:A1993KY45800011 PM 8478402 ER PT J AU BERECZKI, D WEI, L OTSUKA, T ACUFF, V PETTIGREW, K PATLAK, C FENSTERMACHER, J AF BERECZKI, D WEI, L OTSUKA, T ACUFF, V PETTIGREW, K PATLAK, C FENSTERMACHER, J TI HYPOXIA INCREASES VELOCITY OF BLOOD-FLOW THROUGH PARENCHYMAL MICROVASCULAR SYSTEMS IN RAT-BRAIN SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE CAPILLARIES; ARTERIOLES; VENULES; CAPILLARY RECRUITMENT; BLOOD VOLUME; MICROVESSEL DIAMETER ID INTRACEREBRAL ARTERIOLES; CAPILLARY ENDOTHELIUM; CEREBRAL-CORTEX; CARBON-DIOXIDE; VASODILATION; HYPERCAPNIA; METABOLISM AB The postulation that hypoxia increases local cerebral blood flow (ICBF) mainly by perfusing more capillaries (the capillary recruitment hypothesis) was tested in awake adult male Sprague-Dawley rats exposed to 10% O2 and control rats. The [C-14]iodoantipyrine technique was used to measure ICBF. Local cerebral blood volume was determined by measuring plasma and red cell distribution spaces within the brain parenchyma with I-125-labeled serum albumin (RISA) and Fe-55-labeled red cells (RBC), respectively. Tissue radioactivity in 44 brain areas was estimated by quantitative autoradiography. Hypoxia raised ICBF by 25-90% in all brain areas. In about one-quarter of the brain areas, the rise in blood flow was associated with a small increase in microvascular plasma and blood volumes. This change in blood volume, which could be the result of perfusing more parenchymal microvessels and/or increasing parenchymal microvessel diameter, is not sufficient to account for the observed rise in ICBF. In the remaining areas the RISA, RBC, and blood spaces were either unchanged or only marginally increased by hypoxia. For this hypoxic perturbation, the major mechanism of raising blood flow appears to be increased velocity of microvessel perfusion and not perfusion of more capillaries. These findings provide only limited support for the capillary recruitment hypothesis. C1 SUNY STONY BROOK,DEPT NEUROL SURG,HSC,T12-080,STONY BROOK,NY 11794. NIMH,DIV EPIDEMIOL & SERV RES,BETHESDA,MD 20892. FU NINDS NIH HHS [NS-26004, NS-21157] NR 39 TC 84 Z9 84 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD MAY PY 1993 VL 13 IS 3 BP 475 EP 486 PG 12 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA KY458 UT WOS:A1993KY45800015 PM 8478406 ER PT J AU WEI, L OTSUKA, T ACUFF, V BERECZKI, D PETTIGREW, K PATLAK, C FENSTERMACHER, J AF WEI, L OTSUKA, T ACUFF, V BERECZKI, D PETTIGREW, K PATLAK, C FENSTERMACHER, J TI THE VELOCITIES OF RED-CELL AND PLASMA FLOWS THROUGH PARENCHYMAL MICROVESSELS OF RAT-BRAIN ARE DECREASED BY PENTOBARBITAL SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article ID PERFUSED CAPILLARY NETWORK; HUMAN CEREBRAL-ARTERIES; BLOOD-FLOW; HYPERCAPNIA; RESPONSES; HYPOXIA; CATS AB Local cerebral blood flow is lowered in many brain areas of the rat by high-dose pentobarbital (50 mg/kg). In the present study, the mechanism of this flow change was examined by measuring the distribution of radiolabeled red blood cells (RBCs) and albumin (RISA) in small parenchymal microvessels and calculating the microvascular distribution spaces and mean transit times of RBCs, RISA, and blood. In most brain areas, pentobarbital slightly decreased the RISA space, modestly increased the RBC space, and did not alter the blood space. The mean transit times of RBCs, RISA. and blood through the perfused microvessels were considerably greater in treated rats than in controls. These findings indicate that the mechanism by which high-dose pentobarbital diminishes local cerebral blood flow in rat brain is, in the main, a lowered linear velocity of plasma and RBC flow through small parenchymal microvessels and not decreased percentage of perfused capillaries (capillary retirement). This response is probably driven mainly by lowered local metabolism and may well entail a slight increase in the number of small microvessels that are perfused by RBCs. C1 SUNY STONY BROOK,HLTH SCI CTR,DEPT NEUROL SURG,T12-080,STONY BROOK,NY 11794. NIMH,DIV EPIDEMIOL & SERV RES,BETHESDA,MD 20892. FU NINDS NIH HHS [NS-26004] NR 28 TC 41 Z9 41 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD MAY PY 1993 VL 13 IS 3 BP 487 EP 497 PG 11 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA KY458 UT WOS:A1993KY45800016 PM 8478407 ER PT J AU LUZAR, MA DEVLEESCHOUWER, M DONY, J AF LUZAR, MA DEVLEESCHOUWER, M DONY, J TI AN EPIDEMIOLOGIC INVESTIGATION OF STAPHYLOCOCCUS-AUREUS NASAL CARRIAGE IN PATIENTS UNDERGOING CONTINUAL AMBULATORY PERITONEAL-DIALYSIS SO JOURNAL OF CHEMOTHERAPY LA English DT Article; Proceedings Paper CT 8th Mediterranean Congress of Chemotherapy CY MAY 24-29, 1992 CL ATHENS, GREECE RP LUZAR, MA (reprint author), NIAID,PHARMACEUT & REGULATORY AFFAIRS DIV AIDS,SOLAR BLDG 2A02,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU E I F T SRL PI FLORENCE PA VIA XX SETTEMBRE 102, 50129 FLORENCE, ITALY SN 1120-009X J9 J CHEMOTHERAPY JI J. Chemother. PD MAY PY 1993 VL 5 SU 1 BP 585 EP 586 PG 2 WC Oncology; Infectious Diseases; Pathology; Pharmacology & Pharmacy SC Oncology; Infectious Diseases; Pathology; Pharmacology & Pharmacy GA MN665 UT WOS:A1993MN66500337 ER PT J AU ZIMERING, MB KATSUMATA, N SATO, Y BRANDI, ML AURBACH, GD MARX, SJ FRIESEN, HG AF ZIMERING, MB KATSUMATA, N SATO, Y BRANDI, ML AURBACH, GD MARX, SJ FRIESEN, HG TI INCREASED BASIC FIBROBLAST GROWTH-FACTOR IN PLASMA FROM MULTIPLE ENDOCRINE NEOPLASIA TYPE-1 - RELATION TO PITUITARY-TUMOR SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HEPARIN; BFGF AB Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by tumors of the parathyroids, pancreatic islets, and anterior pituitary. We previously reported a basic fibroblast growth factor (bFGF)-like substance in the plasma of subjects with MEN1. In the present study we used a novel sensitive specific 2-site immunoradiometric assay to test for bFGF in plasma. The assay employs immobilized affinity-purified N-terminal-specific anti-bFGF antibodies (antigen capture) and high affinity binding to radioiodinated heparin. bFGF-like immunoreactivity was undetectable (<0.2 ng/mL) in normal subjects and in most unaffected relatives of MEN1 subjects. We found detectable bFGF ranging from 0.24-1.28 ng/mL in 21 of 50 subjects with MEN1. Seven of 8 MEN1 subjects with untreated pituitary tumors had detectable plasma bFGF-like immunoreactivity. Plasma bFGF-like immunoreactivity decreased after surgery for pituitary tumor in 4 patients and after initiation of bromocryptine therapy in 4 patients. bFGF was increased in the plasma of several subjects with sporadic endocrine disorders, including 3 with untreated or persistent acromegaly. We conclude that pituitary tumor is a possible source of high circulating bFGF immunoreactivity in MEN1 plasma. C1 UNIV MANITOBA, FAC MED, DEPT PHYSIOL, WINNIPEG R3E 0W3, MANITOBA, CANADA. UNIV FLORENCE, SCH MED, DEPT PHYSIOPATHOL, I-60139 FLORENCE, ITALY. NIDDKD, METAB DIS BRANCH, BETHESDA, MD 20992 USA. NR 20 TC 77 Z9 78 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 1993 VL 76 IS 5 BP 1182 EP 1187 DI 10.1210/jc.76.5.1182 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LD045 UT WOS:A1993LD04500017 PM 8098714 ER PT J AU GIUSTINA, A LICINI, M BUSSI, AR GIRELLI, A PIZZOCOLO, G SCHETTINO, M NEGROVILAR, A AF GIUSTINA, A LICINI, M BUSSI, AR GIRELLI, A PIZZOCOLO, G SCHETTINO, M NEGROVILAR, A TI EFFECTS OF SEX AND AGE ON THE GROWTH-HORMONE RESPONSE TO GALANIN IN HEALTHY-HUMAN SUBJECTS SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Note ID GH-RELEASING HORMONE; SECRETION; RAT; PEPTIDE AB The aim of our study was to analyze the effects of sex an age on the GH response to galanin infusion in healthy subjects. We have studied 12 young (age, <40 yr) nonobese healthy volunteers [6 females: age, 31.0 +/- 2.5 yr; body mass index (BMI), 21.6 +/- 0.9 kg/m2; 6 males: age, 29.2 +/- 1.4 yr; BMI, 23.3 +/- 0.4 kg/m2] and 11 old (age, >65 yr) healthy subjects (5 females: age, 83.8 +/- 3.8 yr; BMI, 23.4 +/- 1.4 k g/M2; 6 males: age, 79.7 +/- 4.6 yr; BMI, 23.3 +/- 0.2 kg/m2). All subjects received an infusion of synthetic porcine galanin (500 mug, iv) in 100 mL saline from 0-45 min. Blood samples for GH measurement were drawn at -15, 0, 15, 30, 45, 60, 90, and 120 min. The GH peaks after galanin treatment in young females (11.9 +/- 2.9 mug/L) were significantly (P < 0.05) higher than those in the young males (5.1 +/- 1.8 mug/L). Old males showed significantly higher peak GH levels after galanin treatment (8.6 +/- 3.1 mug/L) than old females (2.4 +/- 0.6 mug/L). The GH peaks and areas under the curve after galanin treatment were significantly (P < 0.05) higher in young than in old females. On the contrary, no significant differences were observed after galanin treatment in young and old males. The magnitude of galanin-induced GH secretion significantly correlated with estradiol levels in young women. Our data seem to suggest that circulating estrogen levels play a crucial permissive role in galanin-induced GH secretion in humans. C1 UNIV BRASILIA, CATTEDRA CLIN MED & CHIM, BR-70910 BRASILIA, DF, BRAZIL. NIEHS, MOLEC & INTEGRAT NEUROSCI LAB, RES TRIANGLE PK, NC 27709 USA. NR 20 TC 49 Z9 49 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 1993 VL 76 IS 5 BP 1369 EP 1372 DI 10.1210/jc.76.5.1369 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA LD045 UT WOS:A1993LD04500050 PM 7684394 ER PT J AU MAGRUDERHABIB, K STEVENS, HA ALLING, WC AF MAGRUDERHABIB, K STEVENS, HA ALLING, WC TI RELATIVE PERFORMANCE OF THE MAST, VAST, AND CAGE VERSUS DSM-III-R CRITERIA FOR ALCOHOL DEPENDENCE SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE ALCOHOLISM; ALCOHOL DEPENDENCE; SCREENING MAST; VAST; CAGE ID OPERATING CHARACTERISTIC ANALYSIS; SCREENING-TEST MAST; MICHIGAN; QUESTIONNAIRE; VALIDATION; INSTRUMENT; SELF AB A number of instruments have been developed to screen for alcoholism. With the advent of DSM-III and lay administered psychiatric diagnostic instruments, a test of the performance of these screens relative to diagnostic instruments is critical. In this paper, we document the relative effectiveness in a general medical clinic of the Michigan Alcoholism Screening Test (MAST), the Veterans Alcoholism Screening Test (VAST), and the CAGE questions in comparison to the DSM-III-R criteria for alcohol dependence as measured in the Composite International Diagnostic Interview (CIDI). All of the screens performed at acceptable levels, but the MAST and VAST tended to have higher performance characteristics. At the recommended cut points, they had higher sensitivity for lifetime alcohol dependence (VAST 95.1%, MAST 90.2%, CAGE 78.0%) as well as higher specificity (VAST 80.3%, MAST 81.7%, CAGE 76.1%). For present alcohol dependence only, at the recommended cut points the MAST and CAGE had sensitivity of 100% but specificity of 62.0 and 61.0% respectively. The VAST had sensitivity of 83.3% and specificity of 89.0%. We conclude that all three perform well relative to DSM-III-R criteria. C1 DUKE UNIV,MED CTR,DURHAM,NC 27710. UNIV N CAROLINA,SCH MED,CHAPEL HILL,NC 27514. UNIV N CAROLINA,SCH SOCIAL WORK,CHAPEL HILL,NC 27599. RP MAGRUDERHABIB, K (reprint author), NIMH,DIV EPIDEMIOL & SERV RES,SERV RES BRANCH,PARKLAWN BLDG,ROOM 10C-04,ROCKVILLE,MD 20857, USA. FU NIAAA NIH HHS [R01-AA-07138] NR 28 TC 67 Z9 67 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD MAY PY 1993 VL 46 IS 5 BP 435 EP 441 DI 10.1016/0895-4356(93)90020-2 PG 7 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA LG763 UT WOS:A1993LG76300004 PM 8501469 ER PT J AU VASUDEVACHARI, MB SALZMAN, NP WOLL, DR MAST, C UFFELMAN, KW TOEDTER, G HOEFHEINZ, D METCALF, JA LANE, HC AF VASUDEVACHARI, MB SALZMAN, NP WOLL, DR MAST, C UFFELMAN, KW TOEDTER, G HOEFHEINZ, D METCALF, JA LANE, HC TI CLINICAL UTILITY OF AN ENHANCED HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 P24 ANTIGEN CAPTURE ASSAY SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE HUMAN IMMUNODEFICIENCY VIRUS TYPE-1; ACQUIRED IMMUNODEFICIENCY SYNDROME; P24; CLINICAL TRIALS ID SEROPOSITIVE HOMOSEXUAL MEN; PRIMARY HIV INFECTION; AIDS-RELATED COMPLEX; IMMUNE-COMPLEXES; PROGRESSION; ANTIBODY; CELL; LYMPHADENOPATHY; IMMUNOASSAY; EXPRESSION AB The presence of p24 core antigen in the serum of individuals with human acquired immunodeficiency syndrome has been used as one of the important prognostic markers of HIV-1 infection and also as an end point in evaluating antiviral drugs and vaccines. Unfortunately the majority of p24 antigen present in serum exists as an antigen-antibody complex and is not detected with the commercial kits currently available to measure p24 antigen. In this study, we report a simple procedure utilizing treatment of serum samples with glycine buffer (pH 1.85) to dissociate antigen-antibody complexes prior to assaying for p24 antigen. A 300% increase in the number of p24-reactive samples and a 3- to 12-fold increase in the quantity of antigen detected were observed when samples were pretreated with 1.5 M glycine buffer (pH 1.85) for 1 hr. Glycine treatment of samples did not result in nonspecific positive tests and samples previously shown to be reactive remained positive. In reconstruction experiments the release of antigen was found to be inversely proportional to the amount of p24 antibody present in the serum. The percentage of HIV-1-infected patients positive for p24 antigen was clearly a function of CD4 count. Forty-nine percent of patients with more than 500 CD4 cells and 100% of patients with less than 200 CD4 were p24 positive. The improved sensitivity for detection of p24 provided by this procedure enhances our understanding of the pathogenesis of AIDS by showing that the majority of patients with HIV-1 infection is p24 positive and facilitates the analysis of data obtained in clinical trials involving anti-HIV compounds. C1 NIAID,BLDG 10,ROOM 11B-13,BETHESDA,MD 20892. COULTER IMMUNOL,HIALEAH,FL 33010. GEORGETOWN UNIV,SCH MED,DEPT MICROBIOL,MOLEC RETROVIROL LAB,WASHINGTON,DC 20057. FU NIAID NIH HHS [N01-AI-05058] NR 23 TC 11 Z9 11 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD MAY PY 1993 VL 13 IS 3 BP 185 EP 192 DI 10.1007/BF00919971 PG 8 WC Immunology SC Immunology GA LD276 UT WOS:A1993LD27600003 PM 8100572 ER PT J AU SWAIN, MG PATCHEV, V VERGALLA, J CHROUSOS, G JONES, EA AF SWAIN, MG PATCHEV, V VERGALLA, J CHROUSOS, G JONES, EA TI SUPPRESSION OF HYPOTHALAMIC-PITUITARY-ADRENAL AXIS RESPONSIVENESS TO STRESS IN A RAT MODEL OF ACUTE CHOLESTASIS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE CORTICOTROPIN RELEASING FACTOR; CORTICOSTERONE; CHOLESTASIS; ACTH ID CORTICOTROPIN-RELEASING HORMONE; TUMOR NECROSIS FACTOR; ADRENOCORTICAL ACTIVITY; SECRETION; VASOPRESSIN; COLD; CDNA AB Cholestatic patients undergoing surgery have increased mortality and demonstrate clinical features suggestive of adrenal insufficiency. To examine whether cholestasis influences the status of the hypothalamic-pituitary-adrenal axis, we evaluated rats with acute cholestasis caused by bile duct resection (BDR) and sham-operated and unoperated controls. Basal unstressed plasma concentrations of ACTH and corticosterone were similar in BDR and sham-operated and unoperated control rats. However, exposure of BDR rats to saturated ether vapor resulted in significantly less ACTH and corticosterone release in plasma than in the control animals. To understand the mechanism(s) of decreased HPA axis responsiveness to ether stress in cholestasis, we administered corticotropin-releasing factor (CRF) and measured hypothalamic content, mRNA levels and in vitro secretion of CRF and arginine vasopressin (AVP), the two principal secretagogues of ACTH. In BDR animals, ACTH responses to CRF were decreased and hypothalamic content of CRF and CRF mRNA expression in the paraventricular nucleus were decreased by 25 and 37%, respectively. Furthermore, CRF release from hypothalamic explants of BDR rats was 23% less than that of controls. In contrast to CRF, hypothalamic content of AVP was 35% higher, AVP mRNA in the paraventricular nucleus was increased by 6.6-fold, and hypothalamic explant release of AVP was 24% higher in BDR rats than in control animals. Pituitary ACTH contents were similar in BDR and sham resected rats, but higher than unoperated controls. These findings demonstrate that acute cholestasis in the rat is associated with suppression of hypothalamic-pituitary-adrenal axis responsiveness to stress and demonstrate a dissociation between mechanisms of ACTH regulation mediated by CRF and AVP. C1 NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. RP SWAIN, MG (reprint author), NIDDKD,LIVER DIS SECT,BLDG 10,ROOM 4D-52,BETHESDA,MD 20892, USA. NR 37 TC 64 Z9 65 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 1993 VL 91 IS 5 BP 1903 EP 1908 DI 10.1172/JCI116408 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LA726 UT WOS:A1993LA72600010 PM 8387536 ER PT J AU PINCUS, SH MESSER, KG SCHWARTZ, DH LEWIS, GK GRAHAM, BS BLATTNER, WA FISHER, G AF PINCUS, SH MESSER, KG SCHWARTZ, DH LEWIS, GK GRAHAM, BS BLATTNER, WA FISHER, G TI DIFFERENCES IN THE ANTIBODY-RESPONSE TO HUMAN IMMUNODEFICIENCY VIRUS-1 ENVELOPE GLYCOPROTEIN (GP160) IN INFECTED LABORATORY WORKERS AND VACCINEES SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE HIV; AIDS; IMMUNOGLOBULIN; VACCINE ID NEUTRALIZING ANTIBODIES; MONOCLONAL-ANTIBODIES; SYNTHETIC PEPTIDES; RECOMBINANT GP160; TYPE-1 GP120; HIV; CELLS; CHIMPANZEES; INFECTIVITY; CHALLENGE AB Studies of the immune response to the human immunodeficiency virus (HIV) have been hampered by the antigenic diversity of the HIV envelope protein. In an effort to predict the efficacy of vaccination we have compared the systemic anti-envelope antibody response in seronegative volunteers immunized with recombinant gp160 (either in vaccinia or as soluble protein produced in baculovirus) derived from the HTLV-IIIB strain of HIV-1 and in two laboratory workers accidentally infected with the same strain. 11 of 14 vaccinees responded to immunization by producing anti-gp160 of similar titer and the same isotype as that seen in the laboratory workers. Four vaccinees also had antibody to the principal neutralizing domain (V3 loop) that was comparable in titer with that seen in the laboratory workers, but the fine specificity of anti-V3 antibody was qualitatively different in the two groups. Antibody that can block the interaction between CD4 and gp120 was present at comparable levels in three vaccinees and the lab workers. Neutralizing antibody titers were markedly lower in the vaccinees than in the laboratory workers. In seven of the vaccinees, an immunodominant epitope was at amino acid 720-740. Analyses of monoclonal antibodies to this region indicate that they do not neutralize, bind to infected cells, nor function as immunotoxins. Although the anti-gp160 antibody response was of similar magnitude in both infected and vaccinated individuals, there were important qualitative differences. C1 JOHNS HOPKINS SCH PUBL HLTH,BALTIMORE,MD 21205. UNIV MARYLAND,SCH MED,BALTIMORE,MD 21201. NCI,BETHESDA,MD 20892. VANDERBILT UNIV,MED CTR,SCH MED,NASHVILLE,TN 37232. RP PINCUS, SH (reprint author), NIAID,ROCKY MT LABS,MICROBIAL STRUCT LAB,HAMILTON,MT 59840, USA. FU NIAID NIH HHS [AI-25862, N01-AI-05061, N01-AI 05062] NR 44 TC 57 Z9 57 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 1993 VL 91 IS 5 BP 1987 EP 1996 DI 10.1172/JCI116420 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LA726 UT WOS:A1993LA72600022 PM 7683694 ER PT J AU SAMID, D SHACK, S MYERS, CE AF SAMID, D SHACK, S MYERS, CE TI SELECTIVE GROWTH ARREST AND PHENOTYPIC REVERSION OF PROSTATE-CANCER CELLS-INVITRO BY NONTOXIC PHARMACOLOGICAL CONCENTRATIONS OF PHENYLACETATE SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Note DE ATHYMIC MICE; HUMAN HISTOCOMPATIBILITY LEUKOCYTE ANTIGENS; SURAMIN; TUMOR GROW FACTOR-BETA; TUMOR INVASION; UROKINASE ID PLASMINOGEN-ACTIVATOR; TUMOR-CELLS; CARCINOMA; UROKINASE; ACID; LINES; DIFFERENTIATION; METASTASES; GLUTAMINE; RESECTION AB Differentiation therapy may provide an alternative for treatment of cancers that do not respond to cytotoxic chemotherapy or hormonal manipulations. This hypothesis led us to evaluate the effect of a nontoxic differentiation inducer, sodium phenylacetate (NaPA), on hormone-refractory prostate cancer, the second most common cause of cancer deaths in men. NaPA treatment of androgen-independent PC3 and DU145 prostate cell lines, like that of hormone-responsive LNCaP cultures, resulted in dose-dependent inhibition of cell proliferation. Similar treatments were not significantly inhibitory to replicating normal endothelial cells and skin fibroblasts. In addition to the selective cytostatic effect, NaPA induced reversion of the prostatic cells to a nonmalignant phenotype, evidenced by their reduced invasiveness and loss of tumorigenicity in athymic mice. Phenotypic reversion was accompanied by alterations in gene expression, including selective reduction in tumor growth factor-beta2 mRNA levels and increased amounts of class I major histocompatibility complex HLA transcripts. Furthermore, there was a decrease in tumor-associated proteolysis mediated by urokinase plasminogen activator, a molecular marker of disease progression in humans. When tumor cells were treated with NaPA together with suramin, a drug with demonstrable activity in patients, there was complete abrogation of cell growth under conditions in which each treatment alone produced only a partial effect. The in vitro antineoplastic activity was observed with drug concentrations that have been achieved in humans with no significant toxicities, suggesting that PA, used alone or in combination with other antitumor agents, warrants evaluation in the treatment of advanced prostatic cancer. RP SAMID, D (reprint author), NCI,DIV CANC TREATMENT,CLIN PHARMACOL BRANCH,BLDG 10,ROOM 12C103,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 59 TC 137 Z9 140 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 1993 VL 91 IS 5 BP 2288 EP 2295 DI 10.1172/JCI116457 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LA726 UT WOS:A1993LA72600059 PM 8486788 ER PT J AU MIXSON, AJ HAUSER, P TENNYSON, G RENAULT, JC BODENNER, DL WEINTRAUB, BD AF MIXSON, AJ HAUSER, P TENNYSON, G RENAULT, JC BODENNER, DL WEINTRAUB, BD TI DIFFERENTIAL EXPRESSION OF MUTANT AND NORMAL BETA-T3 RECEPTOR ALLELES IN KINDREDS WITH GENERALIZED RESISTANCE TO THYROID-HORMONE SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Note DE MESSENGER RNA; THYROID HORMONE RECEPTOR; PHENOTYPE; GENE EXPRESSION; THYROID HORMONE RESISTANCE ID MESSENGER-RNA; BINDING; MUTATION; LOCALIZATION; ONCOGENE AB Thyroid hormone resistance (THR) is primarily an autosomal dominant inherited disease characterized by resistance of pituitary and peripheral tissues to the action of thyroid hormone. We investigated whether the heterogeneous phenotypic features that occur not only among kindreds hut also within the same kindred might be due to the expression of differing ratios of mutant and normal receptors in tissues. Using an allele-specific primer extension method, we determined the relative expression of normal and mutant mRNAs from the fibroblasts of affected and unaffected members of two kindreds with TRH: A-H and N-N. While two affected members of A-H, as expected, had nearly equal amounts of normal and mutant hTRbeta mRNA, two other members had mutant mRNA levels that accounted for at least 70% of the hTRbeta mRNA. Phenotypic variability within and between kindreds with generalized resistance to thyroid hormone GRTH may be due to this differential expression of the mutant and wild type mRNA. Furthermore, when several clinical parameters of THR were compared in several affected members from two kindreds with GRTH, we found that two cases in one kindred exhibited a high mutant-to-normal hTRbeta ratio and had considerably more bone resistance during their development. In certain kindreds with THR, differing ratios of normal and mutant hTR receptors may be age and growth related and may account for the reported attenuation of phenotypic symptoms with age. C1 NIDDKD,MOLEC & CELLULAR ENDOCRINOL BRANCH,BETHESDA,MD 20892. VET ADM MED CTR,DEPT MED,IOWA CITY,IA 52246. NR 26 TC 49 Z9 51 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 1993 VL 91 IS 5 BP 2296 EP 2300 DI 10.1172/JCI116458 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LA726 UT WOS:A1993LA72600060 PM 8486789 ER PT J AU GAO, WY SHIRASAKA, T JOHNS, DG BRODER, S MITSUYA, H AF GAO, WY SHIRASAKA, T JOHNS, DG BRODER, S MITSUYA, H TI DIFFERENTIAL PHOSPHORYLATION OF AZIDOTHYMIDINE, DIDEOXYCYTIDINE, AND DIDEOXYINOSINE IN RESTING AND ACTIVATED PERIPHERAL-BLOOD MONONUCLEAR-CELLS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Note DE AZIDOTHYMIDINE; DIDEOXYCYTIDINE; DIDEOXYINOSINE; ANTIVIRAL DRUGS; PHOSPHORYLATION ID HUMAN-IMMUNODEFICIENCY-VIRUS; AIDS-RELATED COMPLEX; PHASE-I TRIAL; 2',3'-DIDEOXYINOSINE DDI; CELLULAR PHARMACOLOGY; DEOXYCYTIDINE KINASE; PRIMARY LYMPHOCYTES; T-CELLS; DNA; 3'-AZIDO-3'-DEOXYTHYMIDINE AB The antiviral activity of azidothymidine (AZT), dideoxycytidine (ddC), and dideoxyinosine (ddl) against HIV-1 was comparatively evaluated in PHA-stimulated PBM. The mean drug concentrations which yielded 50% p24 Gag negative cultures were substantially different: 0.06, 0.2, and 6 muM for AZT, ddC, and ddl, respectively. We found that AZT was preferentially phosphorylated to its triphosphate (TP) form in PHA-PBM rather than unstimulated, resting PBM (R-PBM), producing 10- to 17-fold higher ratios of AZTTP/dTTP in PHA-PBM than in R-PBM. The phosphorylation of ddC and ddl to their TP forms was, however, much less efficient in PHA-PBM, resulting in approximately 5-fold and approximately 15-fold lower ratios of ddCTP/dCTP and ddATP/dATP, respectively, in PHA-PBM than in R-PBM. The comparative order of PHA-induced increase in cellular enzyme activities examined was: thymidine kinase > uridine kinase > deoxycytidine kinase > adenosine kinase > 5'-nucleotidase. We conclude that AZT, ddC, and ddl exert disproportionate antiviral effects depending on the activation state of the target cells, i.e., ddI and ddC exert antiviral activity more favorably in resting cells than in activated cells, while AZT preferentially protects activated cells against HIV infection. Considering that HIV-1 proviral DNA synthesis in resting lymphocytes is reportedly initiated at levels comparable with those of activated lymphocytes, the current data should have practical relevance in the design of anti-HIV chemotherapy, particularly combination chemotherapy. C1 NCI,MED BRANCH,EXPTL RETROVIROL SECT,BETHESDA,MD 20892. NCI,MED CHEM LAB,BETHESDA,MD 20892. NR 41 TC 236 Z9 238 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 1993 VL 91 IS 5 BP 2326 EP 2333 DI 10.1172/JCI116463 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA LA726 UT WOS:A1993LA72600065 PM 8387546 ER PT J AU JASCHEK, G GAYDOS, CA WELSH, LE QUINN, TC AF JASCHEK, G GAYDOS, CA WELSH, LE QUINN, TC TI DIRECT DETECTION OF CHLAMYDIA-TRACHOMATIS IN URINE SPECIMENS FROM SYMPTOMATIC AND ASYMPTOMATIC MEN BY USING A RAPID POLYMERASE CHAIN-REACTION ASSAY SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID ENZYME-IMMUNOASSAY; URETHRITIS; DIAGNOSIS; INFECTIONS; ANTIGENS; SWABS AB Screening for Chlamydia trachomatis infection in men has traditionally been limited to men who present with urethral symptoms, thereby limiting the detection of asymptomatic chlamydia infection in men. In order to effectively screen both symptomatic and asymptomatic men, we evaluated a newly developed polymerase chain reaction (PCR) assay, Amplicor C. trachomatis, from Roche Molecular Systems for the detection of C. trachomatis in urine specimens in comparison with urethral culture. A total of 530 male urine specimens were collected from 322 symptomatic and 208 asymptomatic men attending two sexually transmitted disease clinics in Baltimore, Md. The prevalence of C. trachomatis by culture was 9.8% (10.6% in symptomatic men and 8.2% in asymptomatic men). Compared with culture, the sensitivity of the PCR was 92.8%, the specificity was 94.7%, the positive predictive value was 68.4%, and the negative predictive value was 99.1%. Discrepant results between culture and PCR were further analyzed by direct fluorescent-antibody staining of elementary bodies in urine sediment and in culture transport vials and by major outer membrane protein PCR of transport media for specimens with negative culture. The revised sensitivity and specificity of PCR for urine were 95.0 and 99.8%, respectively, and the positive and negative predictive values were 98.7 and 99.1%, respectively. The sensitivity of culture compared with PCR and/or direct fluorescent-antibody staining was 68.4%. These results indicate that the PCR assay is a highly sensitive and specific assay for the detection of C. trachomatis in male urine specimens and provides a noninvasive technique for routine screening of chlamydia infection in both symptomatic and asymptomatic men. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV INFECT DIS,BALTIMORE,MD 21205. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. RI Gaydos, Charlotte/E-9937-2010; Quinn, Thomas/A-2494-2010 NR 18 TC 169 Z9 173 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAY PY 1993 VL 31 IS 5 BP 1209 EP 1212 PG 4 WC Microbiology SC Microbiology GA KY463 UT WOS:A1993KY46300032 PM 8501220 ER PT J AU ALKORTA, I VILLAR, HO CACHAU, RE AF ALKORTA, I VILLAR, HO CACHAU, RE TI CONFORMATIONAL-ANALYSIS OF 2,3,6,7-TETRAHYDROAZEPINES WITH IMPLICATIONS FOR D1-SELECTIVE BENZAZEPINES SO JOURNAL OF COMPUTATIONAL CHEMISTRY LA English DT Article ID MOLECULAR-ORBITAL METHODS; BASIS-SETS; MECHANICS; AGONISTS AB A conformational study of the 2,3,6,7-tetrahydroazepine (THA) and closely related systems has been carried out using MM3 and CHARMm molecular mechanics, AMI semiempirical, as well as Hartree-Fock and local density functional (LDF) ab initio methods. For THA, all methods give similar optimal geometries; however, only MM3 agrees with the Hartree-Fock calculations using a 6-31G* basis set and LDF in the rank order of energies and nature of the stationary points characterized. AM1 shows serious disagreements with those results. Tetrahydrobenzazepines and a D1 receptor agonist containing the THA nucleus were studied using CHARMm, MM3, and AM1 calculations. All methods provide similar descriptions of the geometries of the conformations accessible to these compounds. However, the same disparities in the rank order of energies are observed. C1 NCI,FREDERICK CANC RES & DEV CTR,DYNCORP,PRI,CTR BIOMED SUPERCOMP,STRUCT BIOCHEM LAB,FREDERICK,MD 21702. RP ALKORTA, I (reprint author), MOLEC RES INST,PALO ALTO,CA 94304, USA. RI alkorta, ibon/I-7828-2014 OI alkorta, ibon/0000-0001-6876-6211 NR 19 TC 6 Z9 6 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0192-8651 J9 J COMPUT CHEM JI J. Comput. Chem. PD MAY PY 1993 VL 14 IS 5 BP 571 EP 578 DI 10.1002/jcc.540140510 PG 8 WC Chemistry, Multidisciplinary SC Chemistry GA KX328 UT WOS:A1993KX32800009 ER PT J AU NEVILLE, DM SCHARFF, J SRINIVASACHAR, K AF NEVILLE, DM SCHARFF, J SRINIVASACHAR, K TI ANTI-T CELL IMMUNOTOXINS - A LOOK AT POST-ENDOCYTOTIC RECEPTOR-MEDIATED ROUTING SO JOURNAL OF CONTROLLED RELEASE LA English DT Article; Proceedings Paper CT 2ND EUROPEAN SYMP ON CONTROLLED DRUG DELIVERY CY APR 01-03, 1992 CL NOORDWIJK AAN ZEE, NETHERLANDS SP DUTCH EXECUT AGCY TECHNOL POLICY, ORGANON INT, SANDOZ PHARMA, DUPHAR, SCHWARZ PHARMA, THERATECH, HOFFMANN LA ROCHE, MEDISOB TECHNOL, THREE M MEDICA DE ROUTING; IMMUNOTOXIN; ANTI-T CELL; RECEPTOR-MEDIATED ENDOCYTOSIS; RECEPTOR-LIGAND COMPLEX ID DIPHTHERIA-TOXIN RECEPTOR; RICIN-A-CHAIN; PROTEIN-SYNTHESIS INACTIVATION; HODGKINS-DISEASE; CULTURED-CELLS; BINDING; TRANSLOCATION; FRAGMENT; ENTRY; PURIFICATION AB Many types of targeted drug delivery systems utilize cell surface receptor binding to achieve targeting specificity. Receptor-mediated endocytosis also provides internalization of the targeted drug. What has not been previously appreciated is the fact that cell surface receptors play an important post-endocytotic role. After endocytosis the receptor ligand interaction determines how the ligand-drug complex will be routed. In many cases this routing uniquely determines the overall efficacy of the drug delivery system. In this paper we will show that a unique anti-T cell immunotoxin, anti-CD3+-CRM9, constructed with a diphtheria toxin binding site mutant, CRM9, is a highly effective reagent for inducing in vivo T cell ablation. The high degree of efficacy and the wide therapeutic margin of this reagent is a consequence of the obligatory intracellular routing pathway required for diphtheria toxin (DT) intoxication. The DT receptor (DTR) typically fulfills this function in diphtheria toxin intoxication. In the case of the anti-CD3+ toxin conjugate the routing function is performed by CD3. This epitope routes parallel with DTR. This fact accounts for the high toxicity of anti-CD3 conjugates made with diphtheria toxin binding site mutants such as CRM9. CRM9 a one is incapable of entering the optimal routing pathway and hence has very low systemic toxicity. The anti-CD3 antibody doubly complements the CRM9 defect: It facilitates ( 1 ) the entrance of CRM9 into the targeted cell endosomes and (2 directs the entrance of CRM9 into the DT intoxication pathway. It is likely that these concepts will have relevance to other cell type-specific immunotoxins and other cell type-specific targeted delivery systems which depend on the membrane translocation of bio-active macromolecules into the cytosol or nuclear compartments. RP NEVILLE, DM (reprint author), NIMH,BIOPHYS CHEM SECT,MOLEC BIOL LAB,9000 ROCKVILLE PIKE 36-1BO8,BETHESDA,MD 20892, USA. NR 41 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-3659 J9 J CONTROL RELEASE JI J. Control. Release PD MAY 1 PY 1993 VL 24 IS 1-3 BP 133 EP 144 DI 10.1016/0168-3659(93)90173-3 PG 12 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA LF865 UT WOS:A1993LF86500011 ER PT J AU TANZER, JM GRANT, LP MCMAHON, T CLINTON, D EANES, ED AF TANZER, JM GRANT, LP MCMAHON, T CLINTON, D EANES, ED TI SIMULTANEOUS CARIES INDUCTION AND CALCULUS FORMATION IN RATS SO JOURNAL OF DENTAL RESEARCH LA English DT Article ID SALIVARIUS TOVE-R; STREPTOCOCCUS-SOBRINUS; MUTANS STREPTOCOCCI; DENTAL PLAQUE; INHIBITION AB Weanling specific pathogen-free Osborne-Mendel rats were fed a high-calcium, high-phosphorus diet with various levels of sucrose and inoculated with Streptococcus sobrinus strain 6715-13WT and Actinomyces viscosus strain OMZ-105 in order to determine whether calculus and caries could develop simultaneously. Rats consumed diets designated RC-16-5, RC-16-25, or RC-16-50 which partially replaced the corn starch component with progressively higher levels of sucrose, thus, to 5, 25, or 50% sucrose. In general, bacterial recoveries of A. viscosus declined with higher sucrose content of the diet, but a pattern of recovery for S. sobrinus was less clear with respect to dietary sucrose. S. sobrinus, however, was recovered at higher percentages from the tooth surface flora at the later two of three sampling dates. Most calculus-identified by the brittle quality, staining characteristics, and apatitic x-ray diffraction patterns of tooth surface deposits-was formed on the maxillary molars, and most carious lesions occurred on mandibular molars. While there was minimal association of the calculus score with the amount of sucrose in the diet, calculus scores increased greatly from 23 to 43 days after infectious challenge. Caries scores, of both fissure and smooth surfaces, by contrast, increased in a dose-response fashion with increasing dietary sucrose and with time. It is thus possible to induce calculus formation and caries simultaneously in specific pathogen-free Osborne-Mendel rats consuming a high-calcium and -phosphorus diet conducive to calculus formation and containing sucrose. This model appears to be well-suited for simultaneous evaluation of the putative calculus-inhibitory and caries-inhibitory effects of oral therapeutic agents. C1 UNIV CONNECTICUT,SCH MED,FARMINGTON,CT 06030. NIDR,BETHESDA,MD 20892. RP TANZER, JM (reprint author), UNIV CONNECTICUT,SCH DENT MED,FARMINGTON,CT 06030, USA. NR 46 TC 5 Z9 6 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD MAY PY 1993 VL 72 IS 5 BP 858 EP 864 DI 10.1177/00220345930720050501 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA LC418 UT WOS:A1993LC41800004 PM 8501282 ER PT J AU DIAMOND, LS CLARK, CG AF DIAMOND, LS CLARK, CG TI A REDESCRIPTION OF ENTAMOEBA-HISTOLYTICA SCHAUDINN, 1903 (EMENDED WALKER, 1911) SEPARATING IT FROM ENTAMOEBA-DISPAR BRUMPT, 1925 SO JOURNAL OF EUKARYOTIC MICROBIOLOGY LA English DT Article DE AMEBIASIS; ANTIBODIES; DIAGNOSIS; GENES; ISOENZYME ANALYSIS; SPECIATION ID POLYMERASE CHAIN-REACTION; SURFACE-ANTIGEN; ISOENZYME PATTERNS; MONOCLONAL-ANTIBODIES; PATHOGENIC ZYMODEMES; DNA PROBES; DIFFERENTIATION; STRAINS; VIRULENCE; IDENTIFICATION AB Explaining the low incidence of invasive disease (10%) in humans infected with Entamoeba histolytica has occupied the attention of generations of both clinical and nonclinical investigators. One possible explanation would be the existence of two morphologically identical species-one an invasive pathogen, the other noninvasive. This was first proposed by Brumpt in 1925, but his explanation was virtually ignored until 1978 when the first of several publications appeared suggesting that E. histolytica did indeed consist of two species. We have reexamined Brumpt's claim in light of recent biochemical, immunological and genetic studies and conclude that the data derived from these investigations provide unequivocal evidence supporting his hypothesis. With this in mind, we redescribe the invasive parasite retaining the name Entamoeba histolytica Schaudinn, 1903 (Emended Walker, 1911), and set it apart from the noninvasive parasite described by Brumpt, Entamoeba dispar Brumpt, 1925. RP DIAMOND, LS (reprint author), NIAID,PARASIT DIS LAB,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. RI Clark, C Graham/H-3683-2011 OI Clark, C Graham/0000-0002-0521-0977 NR 57 TC 363 Z9 383 U1 1 U2 12 PU SOC PROTOZOOLOGISTS PI LAWRENCE PA 810 E 10TH ST, LAWRENCE, KS 66044 SN 1066-5234 J9 J EUKARYOT MICROBIOL JI J. Eukaryot. Microbiol. PD MAY-JUN PY 1993 VL 40 IS 3 BP 340 EP 344 DI 10.1111/j.1550-7408.1993.tb04926.x PG 5 WC Microbiology SC Microbiology GA LE432 UT WOS:A1993LE43200019 PM 8508172 ER PT J AU GAO, JL KUHNS, DB TIFFANY, HL MCDERMOTT, D LI, X FRANCKE, U MURPHY, PM AF GAO, JL KUHNS, DB TIFFANY, HL MCDERMOTT, D LI, X FRANCKE, U MURPHY, PM TI STRUCTURE AND FUNCTIONAL EXPRESSION OF THE HUMAN MACROPHAGE INFLAMMATORY PROTEIN 1-ALPHA RANTES RECEPTOR SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID HUMAN INTERLEUKIN-8 RECEPTOR; CYTOKINE FAMILY; LYMPHOCYTES; CLONING AB The chemokine beta family is comprised of at least six distinct cytokines that regulate trafficking of phagocytes and lymphocytes in mammalian species; at least one of these, macrophage inflammatory protein 1alpha (MIP-1alpha), also regulates the growth of hematopoietic stem cells. We now show that MIP-1alpha and the related beta chemokine, R-ANTES, induce transient alterations in intracellular Ca2+ Concentration in polymorphonuclear leukocytes that can be reciprocally and specifically desensitized, suggesting a common receptor. Moreover, we have now cloned both the cDNA and the gene for this receptor, functionally expressed the receptor in Xenopus oocytes, and mapped the gene to human chromosome 3p21. Transcripts for the receptor were found in mature and immature myeloid cells as well as B cells. The receptor is a member of the G protein-coupled receptor superfamily. It has approximately 33% amino acid identity with receptors for the alpha chemokine, interleukin 8, and may be the human homologue of the product of US28, an open reading frame of human cytomegalovirus. C1 NIAID,HOST DEF LAB,BLDG 10,ROOM 11N113,BETHESDA,MD 20892. NCI,FREDERICK RES & DEV CTR,INC DYNCORP,PROGRAM RESOURCES INC,CLIN IMMUNOL SERV,FREDERICK,MD 21072. STANFORD UNIV,MED CTR,DEPT GENET,STANFORD,CA 94305. STANFORD UNIV,MED CTR,HOWARD HUGHES MED INST,STANFORD,CA 94305. OI McDermott, David/0000-0001-6978-0867 FU NHGRI NIH HHS [R01 HG-00298] NR 28 TC 349 Z9 356 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAY 1 PY 1993 VL 177 IS 5 BP 1421 EP 1427 DI 10.1084/jem.177.5.1421 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA KY849 UT WOS:A1993KY84900019 PM 7683036 ER EF