FN Thomson Reuters Web of Science™ VR 1.0 PT J AU AMBURGEY, JC SHUEY, SW PEDERSEN, LG HISKEY, RG AF AMBURGEY, JC SHUEY, SW PEDERSEN, LG HISKEY, RG TI SMALL-MOLECULE ANALOGS OF PHOSPHOLIPID METAL-ION BINDING-SITES - SYNTHESIS AND MOLECULAR MODELING OF CYCLOHEXANE-1,2,4-TRIOL TRISPHOSPHATES SO BIOORGANIC CHEMISTRY LA English DT Article ID INOSITOL TRISPHOSPHATE; NUCLEIC-ACIDS; FORCE-FIELD; PROTEINS; CALCIUM; 1,4,5-TRISPHOSPHATE; COMPLEXES; MEMBRANES; HYDRATION; SYSTEMS AB Four diastereomeric cyclohexane-1,2,4-triol trisphosphates were synthesized to serve as small molecule analogs of putative phospholipid-metal ion binding sites. The parent cyclehexane-1,2,4-triols were prepared and phosphorylated. Deprotection of the tris(diphenylphosphates) provided four regiochemical isomers: two with the trans-1,2-phosphate moiety, (+/-)-(1R,2R,4S)- and (+/-)-(1R,2R,4R)-cyclohexane-1,2,4-triol tris(ammonium hydrogen phosphate), and two with the cis-1,2-phosphate moiety, (+/-)-(1R,2S,4R)- and (+/-)-(1R,2S, 4S)-cyclohexane-1,2,4-triol tris(ammonium hydrogen phosphate). Molecular mechanics calculations for each trisphosphate and the Ca(II) and Mg(II) complex were performed using MacroModel. Results from the molecular modeling studies indicate that two of the criteria for the suitability of the trisphosphates as analogs of phospholipid-metal ion binding sites are satisfied: (1) anionic groups which can interactively bind a metal ion and (2) interphosphate distances comparable to the phosphate-phosphate distances of a computational phospholipid surface. (C) 1994 Academic Press, Inc. C1 UNIV N CAROLINA,DEPT CHEM,CHAPEL HILL,NC 27599. NIEHS,RES TRIANGLE PK,NC 27709. RI Pedersen, Lee/E-3405-2013 OI Pedersen, Lee/0000-0003-1262-9861 NR 41 TC 3 Z9 3 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0045-2068 J9 BIOORG CHEM JI Bioorganic Chem. PD JUN PY 1994 VL 22 IS 2 BP 172 EP 197 DI 10.1006/bioo.1994.1014 PG 26 WC Biochemistry & Molecular Biology; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA NT480 UT WOS:A1994NT48000005 ER PT J AU AMBURGEY, JC HUH, NW PEDERSEN, LG HISKEY, RG AF AMBURGEY, JC HUH, NW PEDERSEN, LG HISKEY, RG TI SMALL-MOLECULE ANALOGS OF PHOSPHOLIPID METAL-ION BINDING-SITES - POTENTIOMETRIC AND SPECTROSCOPIC STUDIES OF MG(II) AND CA(II) COMPLEXES OF CYCLOHEXANE-1,2,4-TRIOL TRISPHOSPHATES SO BIOORGANIC CHEMISTRY LA English DT Article ID MEMBRANE-BINDING; CALCIUM; PHOSPHATIDYLSERINE; PROTHROMBIN; ADSORPTION; SYSTEMS; CATIONS; ACID AB Studies on the Mg(II) and Ca(II) complexes of four diastereomeric cyclohexane-1,2,4-triol trisphosphates were conducted using H-1 NMR, P-31 NMR, and calcium ion selective electrode (ISE) titrations. Based on the trends in Mg(II) and Ca(II) ion affinity, the 2,4-phosphate groups were concluded to be the primary determinants of the metal ion binding behavior of the 1,2,4-trisphosphates. Results from the proton and metal ion binding studies of the 1,2,4-trisphosphates indicate that the 1,2,4-trisphosphates satisfy two of the criteria as analogs of phospholipid-metal ion binding sites: (1) anionic groups which interact in metal ion binding, and (2) metal ion affinity constants determined by both ISE and P-31 NMR titrations are comparable to the metal ion affinity observed for phosphatidylserine vesicles. In particular, the all-cis trisphosphate diastereomer, (+/-)-(1R, 2S, 4S)-cyclohexane-1,2,4-triol trisphosphate, is the only 1,2,4-trisphosphate to exhibit a higher affinity for Ca(II) ion than Mg(II) ion. A higher Ca(II) ion affinity than Mg(II) ion affinity is characteristic of the behavior observed for phosphatidylserine vesicles or monolayers. (C) 1994 Academic Press, Inc. C1 UNIV N CAROLINA,DEPT CHEM,CHAPEL HILL,NC 27599. NIEHS,RES TRIANGLE PK,NC 27709. RI Pedersen, Lee/E-3405-2013 OI Pedersen, Lee/0000-0003-1262-9861 NR 25 TC 3 Z9 3 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0045-2068 J9 BIOORG CHEM JI Bioorganic Chem. PD JUN PY 1994 VL 22 IS 2 BP 198 EP 215 DI 10.1006/bioo.1994.1015 PG 18 WC Biochemistry & Molecular Biology; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA NT480 UT WOS:A1994NT48000006 ER PT J AU SIMON, SA DISALVO, EA GAWRISCH, K BOROVYAGIN, V TOONE, E SCHIFFMAN, SS NEEDHAM, D MCINTOSH, TJ AF SIMON, SA DISALVO, EA GAWRISCH, K BOROVYAGIN, V TOONE, E SCHIFFMAN, SS NEEDHAM, D MCINTOSH, TJ TI INCREASED ADHESION BETWEEN NEUTRAL LIPID BILAYERS - INTERBILAYER BRIDGES FORMED BY TANNIC-ACID SO BIOPHYSICAL JOURNAL LA English DT Article ID X-RAY-DIFFRACTION; PHOSPHATIDYLCHOLINE BILAYERS; PHOSPHOLIPID-BILAYERS; MAGNETIC-RESONANCE; SOLVATION PRESSURE; HYDROCARBON CHAINS; HYDRATION PRESSURE; DIPOLE POTENTIALS; LECITHIN BILAYERS; HYDROPHOBIC IONS AB Tannic acid (TA) is a naturally occurring polyphenolic compound that aggregates membranes and neutral phospholipid vesicles and precipitates many proteins. This study analyzes TA binding to lipid membranes and the ensuing aggregation. The optical density of dispersions of phosphatidylcholine (PC) vesicles increased upon the addition of TA and electron micrographs showed that TA caused the vesicles to aggregate and form stacks of tightly packed disks. Solution calorimetry showed that TA bound to PC bilayers with a molar binding enthalpy of -8.3 kcal/mol and zeta potential measurements revealed that TA imparted a small negative charge to PC vesicles. Monolayer studies showed that TA bound to PC with a dissociation constant of 1.5 mu M and reduced the dipole potential by up to 250 mV. Both the increase in optical density and decrease in dipole potential produced by TA could be reversed by the addition of polyvinylpyrrolidone, a compound that chelates TA by providing H-bond acceptor groups. NMR, micropipette aspiration, and x-ray diffraction experiments showed that TA incorporated into liquid crystalline PC membranes, increasing the area per lipid molecule and decreasing the bilayer thickness by 2 to 4%. H-2-NMR quadrupole splitting measurements also showed that TA associated with a PC molecule for times much less than 10(-4) s. In gel phase bilayers, TA caused the hydrocarbon chains from apposing monolayers to fully interdigitate. X-ray diffraction measurements of both gel and liquid crystalline dispersions showed that TA, at a critical concentration of about 1 mM, reduced the fluid spacing between adjacent bilayers by 8-10 Angstrom. These data place severe constraints on how TA can pack between adjacent bilayers and cause vesicles to adhere. We conclude that TA promotes vesicle aggregation by reducing the fluid spacing between bilayers by the formation of transient interbilayer bridges by inserting its digallic acid residues into the interfacial regions of adjacent bilayers and spanning the interbilayer space. C1 DUKE UNIV,MED CTR,DEPT PSYCHIAT,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT CELL BIOL,DURHAM,NC 27710. DUKE UNIV,DEPT CHEM,DURHAM,NC 27706. DUKE UNIV,DEPT MECH ENGN & MAT SCI,DURHAM,NC 27706. NIAAA,MEMBRANE BIOCHEM & BIOPHYS LAB,BETHESDA,MD 20852. RP SIMON, SA (reprint author), DUKE UNIV,MED CTR,DEPT NEUROBIOL,DURHAM,NC 27710, USA. FU NIDCD NIH HHS [DC-01065]; NIGMS NIH HHS [GM-27278, GM-40162] NR 98 TC 37 Z9 37 U1 1 U2 8 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUN PY 1994 VL 66 IS 6 BP 1943 EP 1958 PG 16 WC Biophysics SC Biophysics GA NN129 UT WOS:A1994NN12900023 PM 8075329 ER PT J AU CHEN, YD TSONG, TY AF CHEN, YD TSONG, TY TI ON THE EFFICIENCY AND REVERSIBILITY OF ACTIVE LIGAND TRANSPORT INDUCED BY ALTERNATING RECTANGULAR ELECTRIC PULSES SO BIOPHYSICAL JOURNAL LA English DT Article ID FREE-ENERGY; FIELD; ACTIVATION; (NA,K)-ATPASE; TRANSDUCTION; ATPASES; ENZYME; NOISE AB The stationary-state kinetic properties of a simplified two-state electro-conformational coupling model (ECC) in the presence of alternating rectangular electric potential pulses are derived analytically. Analytic expressions for the transport flux, the rate of electric energy dissipation, and the efficiency of the transducing system are obtained as a function of the amplitude and frequency of the oscillation. These formulas clarify some fundamental concept of the ECC model and are directly applicable to the interpretation and design of experiments. Based on these formulas, the reversibility and the degree of coupling of the system can be studied quantitatively. It is found that the oscillation-induced free energy transduction is reversible and tight-coupled only when the amplitude of the oscillating electric field is infinitely large. In general, the coupling is not tight when the amplitude of the electric field is finite. Furthermore, depending on the kinetic parameters of the model, there may exist a ''critical'' electric field amplitude, below which free energy transduction is not reversible. That is, energy may be transduced from the electric to the chemical, but not from the chemical to the electric. C1 HONG KONG UNIV SCI & TECHNOL,DEPT BIOCHEM,KOWLOON,HONG KONG. RP CHEN, YD (reprint author), NIDDK,CHEM PHYS LAB,BLDG 5,ROOM 134,BETHESDA,MD 20892, USA. NR 24 TC 14 Z9 14 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUN PY 1994 VL 66 IS 6 BP 2151 EP 2158 PG 8 WC Biophysics SC Biophysics GA NN129 UT WOS:A1994NN12900043 PM 8075348 ER PT J AU DUBOIS, CM RUSCETTI, FW STANKOVA, J KELLER, JR AF DUBOIS, CM RUSCETTI, FW STANKOVA, J KELLER, JR TI TRANSFORMING GROWTH-FACTOR-BETA REGULATES C-KIT MESSAGE STABILITY AND CELL-SURFACE PROTEIN EXPRESSION IN HEMATOPOIETIC PROGENITORS SO BLOOD LA English DT Article ID BONE-MARROW CELLS; MESSENGER-RNA; STEM-CELLS; MAST-CELLS; W-LOCUS; GM-CSF; RECEPTOR; LIGAND; PROLIFERATION; FACTOR-BETA-1 C1 PRI DYNCORP,BIOL RESPONSE MODIFIERS PROGRAM,LEUKOCYTE BIOL LAB,FREDERICK,MD 21701. PRI DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21701. NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD. RP DUBOIS, CM (reprint author), UNIV SHERBROOKE,FAC MED,DEPT PEDIAT,DIV IMMUNOL,3001 N 12TH AVE,SHERBROOKE J1H 5N4,PQ,CANADA. FU NCI NIH HHS [N01-CO-74102] NR 45 TC 92 Z9 93 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 JUN 1 PY 1994 VL 83 IS 11 BP 3138 EP 3145 PG 8 WC Hematology SC Hematology GA NN988 UT WOS:A1994NN98800006 PM 7514900 ER PT J AU ESPINOZADELGADO, I BOSCO, MC MUSSO, T MOOD, K RUSCETTI, FW LONGO, DL VARESIO, L AF ESPINOZADELGADO, I BOSCO, MC MUSSO, T MOOD, K RUSCETTI, FW LONGO, DL VARESIO, L TI INHIBITORY CYTOKINE CIRCUITS INVOLVING TRANSFORMING GROWTH-FACTOR-BETA, INTERFERON-GAMMA, AND INTERLEUKIN-2 IN HUMAN MONOCYTE ACTIVATION SO BLOOD LA English DT Article ID TUMOR-NECROSIS-FACTOR; RECEPTOR EXPRESSION; GENE-EXPRESSION; IL-2 RECEPTOR; IFN-GAMMA; KILLER CELLS; TOXICITY; MACROPHAGE; INDUCTION; IDENTIFICATION C1 NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,MED BRANCH,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,EXPTL IMMUNOL LAB,MACROPHAGE CELL BIOL SECT,FREDERICK,MD. NCI,FREDERICK CANC RES & DEV CTR,LEUKOCYTE BIOL LAB,FREDERICK,MD. RP ESPINOZADELGADO, I (reprint author), NCI,FREDERICK CANC RES & DEV CTR,EXPTL IMMUNOL LAB,BIOL RESPONSE MODIFIERS PROGRAM,BLDG 560,FREDERICK,MD 21702, USA. RI Bosco, Maria Carla/J-7928-2016; varesio, luigi/J-8261-2016 OI Bosco, Maria Carla/0000-0003-1857-7193; varesio, luigi/0000-0001-5659-2218 NR 41 TC 22 Z9 23 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 JUN 1 PY 1994 VL 83 IS 11 BP 3332 EP 3338 PG 7 WC Hematology SC Hematology GA NN988 UT WOS:A1994NN98800030 PM 8193369 ER PT J AU KASAI, R BIANCO, P ROBEY, PG KAHN, AJ AF KASAI, R BIANCO, P ROBEY, PG KAHN, AJ TI PRODUCTION AND CHARACTERIZATION OF AN ANTIBODY AGAINST THE HUMAN BONE GLA PROTEIN (BGP/OSTEOCALCIN) PROPEPTIDE AND ITS USE IN IMMUNOCYTOCHEMISTRY OF BONE-CELLS SO BONE AND MINERAL LA English DT Article DE OSTEOCALCIN; OSTEOBLAST; OSTEOCYTE; NONCOLLAGENOUS PROTEINS; BONE ID GAMMA-CARBOXYGLUTAMIC ACID; MONOCLONAL-ANTIBODIES; POLYACRYLAMIDE GELS; OSTEOCALCIN; RAT; IMMUNOGLOBULIN; INACTIVATION; EXPRESSION; INVITRO; INVIVO AB We have generated and characterized an antibody that recognizes the C-terminal sequence of the propeptide of human bone GLA protein (BGP/osteocalcin) (amino acid -26 to -1, with +1 being the amino terminus of the mature protein). The range of sensitivity of the antibody, as determined by enzyme-linked immunosorbent assay (ELISA), was 0.5-250 ng/ml. The antibody effectively recognized pro-BGP in cell layer extracts of transformed cells (KT-005), but did not recognize mature, propetide-less BGP in the medium from the same cultures. Strong labelling was obtained using this antibody in immunoperoxidase staining or immunofluorescence of both transformed and normal human bone cells in vitro. Monensin significantly altered the intracellular pattern of labelling in immunofluorescence studies, indicating that the recognized antigen was associated with the cellular secretory pathway. We also obtained a specific and strong staining of cells in tissue sections of human fetal bone. Antibodies against the mature protein strongly stained the mineralization front, but did not stain cells to any appreciable level. Newly embedded osteocytes were the predominant cell type stained in such material, suggesting that they may represent the major sourer of BGP in the intact tissue. These observations indicate that BGP synthesis is a late event in osteoblastic development and that antibodies generated against the propeptide sequence are a potentially powerful tool in the analysis of bone tumors and evaluation of osteoblastic differentiation. C1 NIDR,BONE RES BRANCH,BETHESDA,MD 20892. KYOTO UNIV,FAC MED,DEPT ORTHOPAED SURG,KYOTO 606,JAPAN. UNIV ROMA LA SAPIENZA,DIP BIOPATOL UMANA,ROME,ITALY. UNIV CALIF SAN FRANCISCO,SCH DENT,DEPT GROWTH & DEV,SAN FRANCISCO,CA 94143. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 28 TC 17 Z9 17 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-6009 J9 BONE MINER JI Bone Miner. PD JUN PY 1994 VL 25 IS 3 BP 167 EP 182 DI 10.1016/S0169-6009(08)80237-1 PG 16 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NQ339 UT WOS:A1994NQ33900001 PM 8086856 ER PT J AU SIMON, R ALTMAN, DG AF SIMON, R ALTMAN, DG TI STATISTICAL ASPECTS OF PROGNOSTIC FACTOR STUDIES IN ONCOLOGY SO BRITISH JOURNAL OF CANCER LA English DT Editorial Material ID BREAST-CANCER; REGRESSION-MODELS; MULTIVARIATE-ANALYSIS; PATIENT SUBSETS; CLINICAL-TRIALS; WORKING PARTY; CHEMOTHERAPY; PROPOSAL; LEUKEMIA; HEAD C1 IMPERIAL CANC RES FUND,MED STAT LAB,LONDON WC2A 3PX,ENGLAND. RP SIMON, R (reprint author), NCI,BIOMETR RES BRANCH,6130 EXECUT BLVD,ROOM 739,ROCKVILLE,MD 20852, USA. NR 46 TC 436 Z9 442 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JUN PY 1994 VL 69 IS 6 BP 979 EP 985 DI 10.1038/bjc.1994.192 PG 7 WC Oncology SC Oncology GA NN557 UT WOS:A1994NN55700001 PM 8198989 ER PT J AU MACIEJEWSKI, JP ANDERSON, S KATEVAS, P YOUNG, NS AF MACIEJEWSKI, JP ANDERSON, S KATEVAS, P YOUNG, NS TI PHENOTYPIC AND FUNCTIONAL-ANALYSIS OF BONE-MARROW PROGENITOR-CELL COMPARTMENT IN BONE-MARROW FAILURE SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE CD34+ CELLS; APLASTIC ANEMIA; PROGENITORS; HEMATOPOIESIS; BONE MARROW FAILURE ID APLASTIC-ANEMIA; MYELODYSPLASTIC SYNDROMES; STROMAL CELLS; CULTURE AB Many laboratory findings have demonstrated that the haemopoietic stem cell compartment is defective in aplastic anaemia (AA). AA bone marrow (BM) and peripheral blood (PB) are profoundly deficient in colony-forming cells, and AA progenitors fail to proliferate in longterm assays even in the presence of an intact stroma. Our study was designed to characterize some quantitative and qualitative aspects of the progenitor cell defect in AA. Using now cytometric analysis of BM from new AA patients and from those recovering after immunosuppressive therapy, we determined that the numbers of CD34(+) and CD33(+) cells were markedly decreased in AA. Although PB neutrophil counts did not correlate with BM CD34(+) cell numbers in acute disease, there was an association between the overall severity of the disease and the degree of CD34(+) cell reduction. A decrease in BM CD33(+) cells was a common finding in MDS patients, but reduction in CD34(+) cells was found only in some hypoplastic MDS cases. Sorting experiments demonstrated lower plating efficiency for purified CD34(+) cells from AA BM in comparison to controls. Thus, diminished colony formation of total BM appeared to result from both quantitative and qualitative defects. Based on the association between increased cycling and c-kit receptor expression on CD34(+) cells, we found that the mitotically active CD34(+) cells bearing the c-kit antigen were reduced in AA. With clinical improvement, CD34(+) and CD33(+) cells increased in correlation with PB parameters, but they did not return to normal values. Sorted CD34(+) cells from recovered patents showed improved plating efficiency. In patients with aplastic anaemia, use of CD34 antigen as a phenotypic marker of progenitor cells may be helpful for the analysis of the early haemopoietic cell compartment and BM recovery. RP MACIEJEWSKI, JP (reprint author), NHLBI,HEMATOL BRANCH,BLDG 10,ROOM 7C103,BETHESDA,MD 20892, USA. NR 23 TC 77 Z9 84 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUN PY 1994 VL 87 IS 2 BP 227 EP 234 DI 10.1111/j.1365-2141.1994.tb04903.x PG 8 WC Hematology SC Hematology GA NR794 UT WOS:A1994NR79400002 PM 7524621 ER PT J AU HYDE, TM EMSELLEM, HA RANDOLPH, C RICKLER, KC WEINBERGER, DR AF HYDE, TM EMSELLEM, HA RANDOLPH, C RICKLER, KC WEINBERGER, DR TI ELECTROENCEPHALOGRAPHIC ABNORMALITIES IN MONOZYGOTIC TWINS WITH TOURETTES-SYNDROME SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID EEG SLEEP; GILLES; FEATURES AB The association of attentional, neuropsychological, and behavioural abnormalities with Tourette's syndrome (TS) suggests that the abnormal function of the disorder extends beyond the motor circuits of the basal ganglia. To explore this possibility we studied, with conventional 18-channel electroencephalography, monozygotic twins ranging from 8 to 26 years of age, where at least one member of the twin pair suffered from TS. In nine out of the 1 1 twin pairs that differed in clinical severity of the tic disorder, the twin with the more severe course of illness had a significantly more abnormal electroencephalogram (EEG) by qualitative visual analysis. Most of the differences were due to excessive frontocentral theta activity, suggesting dysfunction outside the basal ganglia. There was also a significant relationship between a lower global neuropsychological testing score and a worse overall EEG. In eight of nine twin sets with different global neuropsychological testing scores, the twin with the lower score had a worse EEG. A similar relationship was found between birth weight and overall EEG quality. In the nine sets that differed in birth weight, the twin with a lower birth weight had a worse EEG in seven of the sets. The EEG findings are unlikely to be a medication effect because the same result was seen in the six twin pairs who had been medication-free for at least six months before entry into the study. The origin of this slowing may relate to the interaction between environmental insults to the central nervous system and the genetic component of TS, an interaction producing damage to the cortex, thalamus, or both. C1 GEORGE WASHINGTON UNIV,MED CTR,WASHINGTON,DC 20037. NIMH,ST ELIZABETHS HOSP,INTRAMURAL RES PROGRAM,BRAIN DISORDERS BRANCH,NEUROPSYCHOL SECT,WASHINGTON,DC 20032. RP HYDE, TM (reprint author), NIMH,ST ELIZABETHS HOSP,INTRAMURAL RES PROGRAM,CLIN BRAIN DISORDERS BRANCH,NEUROLOGY CONSULTANT,WASHINGTON,DC 20032, USA. NR 40 TC 15 Z9 17 U1 1 U2 1 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON, ENGLAND SW1X 8PG SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD JUN PY 1994 VL 164 BP 811 EP 817 DI 10.1192/bjp.164.6.811 PG 7 WC Psychiatry SC Psychiatry GA NR864 UT WOS:A1994NR86400014 PM 7952989 ER PT J AU SAKAGUCHI, K KODAMA, H OGINO, Y COSTA, T NOSE, T SHIMOHIGASHI, Y AF SAKAGUCHI, K KODAMA, H OGINO, Y COSTA, T NOSE, T SHIMOHIGASHI, Y TI STRUCTURAL ESSENTIALS OF SER-1 IN TETHERED PEPTIDE LIGAND OF HUMAN THROMBIN RECEPTOR FOR PHOSPHOINOSITIDE HYDROLYSIS SO BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN LA English DT Article ID MOLECULAR-CLONING; AGONIST PEPTIDES; SMOOTH-MUSCLE; ACTIVATION; MECHANISM AB In order to inspect the structural elements of Ser-1 in receptor activation by SFLLRNP (one-letter amino acid code), a ligand peptide tethered to the thrombin receptor, a series of analogs with such replacements as D-Ser, Ala, Thr, and Ac-Ser have been synthesized. These analogs were evaluated for their ability to hydrolyze the phosphoinositide in human neuroblastoma SH-EP cells. It was found that the alpha-amino group and L-configuration of Ser-1 are very important in the activation of receptors. N-Acetylation or deletion of Ser1 completely eliminated the activity of SFLLRNP (a half-maximal effective concentration, EC50 = 0.89 muM (1 M = 1 mol dm-3)), and these modifications induced no antagonist activity. Incorporation of D-Ser also drastically diminished the activity, but retained about 50% activity of the maximal response by 100 muM SFLLRNP. The Ser/Ala substitution sustained 30% of the activity of SFLLRNP to elicit a full stimulation. The Ser/Thr substitution, however, enhanced the activity (20%) in spite of its decreased activity (60%) reported for platelet aggregation. These results indicated that the beta-hydroxyl group of Ser-1 is important to receptor activation, but not essential. The effect of chemical modifications on the receptor activities of the tethered ligand is discussed with regard to the efficacy between phosphoinositide hydrolysis and biological activities. C1 SAGA UNIV, FAC SCI & ENGN, DEPT CHEM, SAGA 840, JAPAN. TEIKYO UNIV, SCH MED, DEPT INTERNAL MED 3, ICHIHARA 29901, JAPAN. IST SUPER SANITA, FARMACOL LAB, ROME, ITALY. KYUSHU UNIV, FAC SCI, DEPT CHEM, BIOCHEM LAB, FUKUOKA 812, JAPAN. RP SAKAGUCHI, K (reprint author), NCI, CELL BIOL LAB, BETHESDA, MD 20892 USA. NR 21 TC 10 Z9 10 U1 0 U2 0 PU CHEMICAL SOC JAPAN PI TOKYO PA 1-5 KANDA-SURUGADAI CHIYODA-KU, TOKYO, 101-8307, JAPAN SN 0009-2673 EI 1348-0634 J9 B CHEM SOC JPN JI Bull. Chem. Soc. Jpn. PD JUN PY 1994 VL 67 IS 6 BP 1659 EP 1663 DI 10.1246/bcsj.67.1659 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA NY043 UT WOS:A1994NY04300023 ER PT J AU WU, ZH AF WU, ZH TI CONFLICTS BETWEEN CHINESE TRADITIONAL ETHICS AND BIOETHICS SO CAMBRIDGE QUARTERLY OF HEALTHCARE ETHICS LA English DT Article AB China's National People's Congress is considering eugenics and health protection legislation, including state-ordered sterilizations and abortions to avoid births of inferior quality (Preventing ''inferior'' people in China [editorial]. New York Times 1993 Dec. 27:A16). Aggressive government-sponsored eugenics programs are not compatible with traditional Chinese medical ethics. Contemporary Chinese philosophers, however, recognize the tensions generated from a modern medical technology that offers the opportunity for individuals to avoid the birth of seriously compromised children coupled with the strains of an enlarged population and very limited material means to sustain that population. C1 NIH,WASHINGTON,DC. RP WU, ZH (reprint author), HUBEI COLL TRADIT CHINESE MED,HUBEI,PEOPLES R CHINA. NR 0 TC 4 Z9 4 U1 0 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0963-1801 J9 CAMB Q HEALTHC ETHIC JI Camb. Q. Healthc. Ethics PD SUM PY 1994 VL 3 IS 3 BP 367 EP 371 PG 5 WC Health Care Sciences & Services; Health Policy & Services; Social Sciences, Biomedical SC Health Care Sciences & Services; Biomedical Social Sciences GA PW636 UT WOS:A1994PW63600007 PM 7994460 ER PT J AU KURTTI, TJ MUNDERLOH, UG HAYES, SF KRUEGER, DE AHLSTRAND, CG AF KURTTI, TJ MUNDERLOH, UG HAYES, SF KRUEGER, DE AHLSTRAND, CG TI ULTRASTRUCTURAL ANALYSIS OF THE INVASION OF TICK CELLS BY LYME-DISEASE SPIROCHETES (BORRELIA-BURGDORFERI) IN-VITRO SO CANADIAN JOURNAL OF ZOOLOGY-REVUE CANADIENNE DE ZOOLOGIE LA English DT Article ID HUMAN ENDOTHELIAL-CELLS; IXODES-DAMMINI ACARI; VERO CELLS; IXODIDAE; CULTURE; ADHERENCE; TISSUES; PENETRATION; ANTIBODIES; VECTORS AB The association of Lyme disease spirochetes, Borrelia burgdorferi, with tick cell cultures was characterized by electron microscopy. These cells were active in endocytosis and intracellular digestion, containing coated vesicles, pits, and phagosomes. Borrelia burgdorferi in tick cell cultures resembled those described in tick tissues. In RAE25 cultures, isolated from Rhipicephalus appendiculatus embryos, invasion of cells was mediated by coated pits, indicating active host cell participation. The invading, tapered end of B. burgdorferi contained an electron-dense body that persisted throughout invasion. A host-derived membrane surrounded invading and intracellular borreliae as observed by transmission electron microscopy of cross and longitudinal sections, whereas degenerating ones lay inside secondary lysosomes. Borrelia burgdorferi cocultivated with cell lines from bodes scapularis were mainly found at the cell surface or within lysosomes. The differences seen in invasion of these cell lines are interpreted to reflect differences in cell types rather than species. Gemmae, indicative of degenerative changes in the spirochetes, were observed extra- and intra-cellularly. Membrane blebs were liberated by the spirochetes into the medium and onto the cells, and were avidly endocytosed. Tick cell cultures are a useful tool to elucidate spirochete - vector cell interactions that may be obscured in vivo. C1 NATL INST HLTH,ROCKY MT LABS,HAMILTON,MT 59840. UNIV MINNESOTA,DEPT ENTOMOL,ST PAUL,MN 55108. UNIV MINNESOTA,DEPT PLANT PATHOL,ST PAUL,MN 55108. RP KURTTI, TJ (reprint author), UNIV MINNESOTA,DEPT ENTOMOL,ST PAUL,MN 55108, USA. NR 59 TC 16 Z9 16 U1 0 U2 0 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA ON K1A 0R6, CANADA SN 0008-4301 J9 CAN J ZOOL JI Can. J. Zool.-Rev. Can. Zool. PD JUN PY 1994 VL 72 IS 6 BP 977 EP 994 DI 10.1139/z94-134 PG 18 WC Zoology SC Zoology GA PP591 UT WOS:A1994PP59100003 ER PT J AU MOTZER, RJ REED, E PERERA, F TANG, DL SHAMKHANI, H POIRIER, MC TSAI, WY PARKER, RJ BOSL, GJ AF MOTZER, RJ REED, E PERERA, F TANG, DL SHAMKHANI, H POIRIER, MC TSAI, WY PARKER, RJ BOSL, GJ TI PLATINUM-DNA ADDUCTS ASSAYED IN LEUKOCYTES OF PATIENTS WITH GERM-CELL TUMORS MEASURED BY ATOMIC ABSORBENCY SPECTROMETRY AND ENZYME-LINKED-IMMUNOSORBENT-ASSAY SO CANCER LA English DT Article DE GERM CELL TUMOR; PLATINUM-DNA ADDUCTS; CLINICAL RESPONSE ID OVARIAN-CANCER PATIENTS; CISPLATIN CHEMOTHERAPY; PROGNOSTIC VARIABLES; TESTICULAR CANCER; QUANTITATION; INDUCTION; REGIMEN; BINDING; REMOVAL; DAMAGE AB Background. Platinum-DNA adducts can be measured in peripheral blood cells, and high adduct levels have previously been correlated with favorable clinical response to platinum-based therapy in patients with germ cell tumors and ovarian cancer. Methods. To evaluate the relationship between platinum-DNA adducts and clinical response to chemotherapy, 36 patients with germ cell tumors treated with cisplatin-based chemotherapy had platinum-DNA adducts assayed in leukocytes by atomic absorption spectrometry (AAS) and cisplatin-DNA enzyme-linked immunosorbent assay (ELISA). Three chemotherapy regimens were involved: cisplatin and etoposide (Regimen A); carboplatin and etoposide (Regimen B); and cyclophosphamide, vinblastine, dactinomycin, bleomycin, and cisplatin [VAB-6] with or without high dose carboplatin plus etoposide plus autologous bone marrow rescue (Regimen C). Blood samples were drawn before and after each cycle of chemotherapy. C1 NCI,MED BRANCH,BETHESDA,MD 20892. COLUMBIA UNIV,SCH PUBL HLTH,DIV ENVIRONM SCI,NEW YORK,NY 10032. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. MEM SLOAN KETTERING CANC CTR,DEPT MED,DIV SOLID TUMOR ONCOL,GENITOURINARY ONCOL SERV,NEW YORK,NY 10021. FU NCI NIH HHS [CA 47351, CA 13696] NR 26 TC 29 Z9 29 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 JUN 1 PY 1994 VL 73 IS 11 BP 2843 EP 2852 DI 10.1002/1097-0142(19940601)73:11<2843::AID-CNCR2820731130>3.0.CO;2-D PG 10 WC Oncology SC Oncology GA NP079 UT WOS:A1994NP07900029 PM 7514956 ER PT J AU WADLER, S TENTEROMANO, L CAZENAVE, L SPARANO, JA GREENWALD, ES ROZENBLIT, A KALEYA, R WIERNIK, PH AF WADLER, S TENTEROMANO, L CAZENAVE, L SPARANO, JA GREENWALD, ES ROZENBLIT, A KALEYA, R WIERNIK, PH TI PHASE-II TRIAL OF ECHINOMYCIN IN PATIENTS WITH ADVANCED OR RECURRENT COLORECTAL-CANCER SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE ECHINOMYCIN; COLORECTAL CANCER; PHASE II ID ONCOLOGY-GROUP AB Echinomycin is a novel bifunctional intercalating agent derived from Streptomyces echinatus. A phase II clinical trial of echinomycin in patients with advanced, measurable colorectal cancer was initiated to determine the efficacy and toxicities of this agent. Echinomycin, 1.5 mg/ m(2), was given initially as a 30- to 60-min infusion every 4 weeks. After 4 episodes of anaphylaxis had occurred among the first 14 patients, the schedule was changed to a 24-h infusion, and an additional 16 patients were treated on this schedule. Treatment was given every 3 weeks. A total of 30 patients were eligible and evaluable; there were 3 (10%; 90% confidence interval, 3%-23%) clinical responses lasting 3, 3+, and 12 months, respectively. The most serious toxicity encountered was anaphylaxis, which occurred in 5 patients, although with no serious sequelae. A premedication regimen with dexamethasone, diphenhydramine, and cimetidine and a change in the duration of the infusion to 24 h reduced the incidence of this complication. Grade 2-3 vomiting occurred among earlier patients treated; however, with the 24-h schedule this toxicity was substantially reduced. The sole important case of hematologic toxicity was a single patient with grade 3 thrombocytopenia. Echinomycin employed in this dose and schedule had modest activity against colorectal cancer, comparable with that observed with 5-fluorouracil. Further studies in patients with gastrointestinal malignancies using a 24-h infusion with a dexamethasone premedication regimen similar to that employed prior to administration of taxol may be warranted. C1 NCI,INVEST DRUG BRANCH,CANC THERAPY & EVALUAT PROGRAM,BETHESDA,MD 20892. MONTEFIORE MED CTR,ALBERT EINSTEIN CANC CTR,DEPT RADIOL,BRONX,NY 10467. MONTEFIORE MED CTR,ALBERT EINSTEIN CANC CTR,DEPT SURG,BRONX,NY 10467. RP WADLER, S (reprint author), MONTEFIORE MED CTR,ALBERT EINSTEIN CANC CTR,DEPT ONCOL,HOFHEIMER 1,111 E 210TH ST,BRONX,NY 10467, USA. NR 16 TC 23 Z9 23 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD JUN PY 1994 VL 34 IS 3 BP 266 EP 269 PG 4 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA NR195 UT WOS:A1994NR19500014 PM 8004762 ER PT J AU HSING, AW WANG, RT GU, FL LEE, M WANG, T LENG, TJ SPITZ, M BLOT, WJ AF HSING, AW WANG, RT GU, FL LEE, M WANG, T LENG, TJ SPITZ, M BLOT, WJ TI VASECTOMY AND PROSTATE-CANCER RISK IN CHINA SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID TRENDS; COHORT; MEN AB Vasectomy has been reported to be associated with an increased risk of prostate cancer in western countries. A hospital-based case-control study was conducted in 12 cities in China to evaluate the relationship between vasectomy and prostate cancer risk in China, a low-risk country with rising incidence and increasing use of vasectomy. Interviews were conducted with 138 histologically confirmed prostate cancer cases diagnosed during 1989-1992 and 638 controls (158 hospital cancer, 158 hospital noncancer, and 322 neighborhood controls) of similar ages. Vasectomy at least 10 years prior to interview was reported by 10% of the cases versus 3% of the controls. Odds ratios for prostate cancer associated with vasectomy were 2.0 (95% confidence interval, 0.7-6.1), 3.3 (95% confidence interval, 1.0-11.3), and 6.7 (95% confidence interval, 2.1-21.6), respectively, when hospital cancer, hospital noncancer, and neighborhood controls were used for comparison. Although detection bias is of concern, the data suggest that in China, men with a history of vasectomy may experience an increased risk of prostate cancer. C1 UNIV CALIF SAN FRANCISCO,DEPT EPIDEMIOL & BIOSTAT,SAN FRANCISCO,CA 94143. BEIJING MED UNIV,DEPT EPIDEMIOL,BEIJING 10083,PEOPLES R CHINA. BEIJING MED UNIV,DEPT UROL,BEIJING 10083,PEOPLES R CHINA. ARMY MED UNIV 3,BEIJING,PEOPLES R CHINA. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT EPIDEMIOL,HOUSTON,TX 77030. RP HSING, AW (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,EPN 415,6130 EXECUTIVE BLVD,BETHESDA,MD 20892, USA. NR 20 TC 35 Z9 38 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 JUN PY 1994 VL 3 IS 4 BP 285 EP 288 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA NR189 UT WOS:A1994NR18900001 PM 8061575 ER PT J AU ENDO, S KODAMA, S NEWBOLD, R MCLACHLAN, J BARRETT, JC AF ENDO, S KODAMA, S NEWBOLD, R MCLACHLAN, J BARRETT, JC TI CYTOGENETIC ANALYSIS OF MURINE CELL-LINES FROM DIETHYLSTILBESTROL-INDUCED UTERINE ENDOMETRIAL ADENOCARCINOMAS SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID TRANSFORMATION; CARCINOGENESIS; CHROMOSOMES; ANEUPLOIDY; PATTERNS AB Treatment of female CD-1 mice with the synthetic estrogen diethylstilbestrol (DES) on days 1 through 5 after birth results in a 90% incidence of endometrial adenocarcinomas by 18 months of age. Three cell lines were established from DES-induced uterine carcinomas and studied for specific chromosomal changes. Each cell line exhibited numerical decreases in chromosomes 9, 11, 13, and X as common abnormalities. Structural alterations involving chromosomes 3, 6, 11, and 19 occurred nonrandomly among the three cell lines. Every cell line showed a rearrangement in the long arm of chromosome 3 (3q+), a translocation between chromosomes 3 and 19 [t(3;19)], isochromosome of chromosome 11 [i(11)], and a marker chromosome (M2) either as common abnormalities or recurrent abnormalities. t(3;19), i(11), and M2 were observed also in the primary colonies from which the cell lines arose. The changes were not observed in a cell line derived from the uterus of one untreated control mouse, suggesting that these chromosomal alterations may have occurred during DES-induced neoplastic transformation. The chromosomal alterations found in the present study may prove useful in investigating the genetic changes involved in DES carcinogenesis. C1 NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. NIEHS,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC 27709. NR 19 TC 12 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD JUN PY 1994 VL 74 IS 2 BP 99 EP 103 DI 10.1016/0165-4608(94)90005-1 PG 5 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA NU724 UT WOS:A1994NU72400005 PM 8019968 ER PT J AU SHUIN, T KONDO, K TORIGOE, S KISHIDA, T KUBOTA, Y HOSAKA, M NAGASHIMA, Y KITAMURA, H LATIF, F ZBAR, B LERMAN, MI YAO, M AF SHUIN, T KONDO, K TORIGOE, S KISHIDA, T KUBOTA, Y HOSAKA, M NAGASHIMA, Y KITAMURA, H LATIF, F ZBAR, B LERMAN, MI YAO, M TI FREQUENT SOMATIC MUTATIONS AND LOSS OF HETEROZYGOSITY OF THE VON HIPPEL-LINDAU TUMOR-SUPPRESSOR GENE IN PRIMARY HUMAN RENAL-CELL CARCINOMAS SO CANCER RESEARCH LA English DT Note ID SHORT ARM; CHROMOSOME-3; CANCER AB We analyzed 47 primary sporadic human renal cell carcinomas (39 clear cell and 8 non-clear cell) for mutations of the von Hippel-Lindau (VHL) tumor suppressor gene using the polymerase chain reaction and single strand conformational polymorphism analysis of DNA. All of the positive cases in single strand conformational polymorphism analyses were further characterized by direct sequencing. Somatic mutations were detected in 22 (56%) of 39 clear cell renal carcinomas including 15 deletions, 3 insertions, 3 missense mutations, and 1 nonsense mutation. Nineteen of these mutations predicted to produce truncation of the VHL protein. These mutations mainly occurred in the last one-third region of exons 1, 2, and 3. In addition, loss of heterozygosity of the VHL gene was observed in 16 (84%) of 19 informative clear cell renal carcinomas. No somatic mutations were detected in 8 non-clear cell carcinomas. These results show that the VHL tumor suppressor gene is one of the major tumor suppressor genes in human renal cell carcinomas, especially in the clear cell subtype renal cell carcinoma. Clear cell carcinoma might be distinguished from other pathological types of renal cell carcinomas by molecular genetic techniques. C1 YOKOHAMA CITY UNIV,SCH MED,DEPT RADIOL,YOKOHAMA 236,JAPAN. YOKOHAMA CITY UNIV,SCH MED,DEPT PATHOL 2,YOKOHAMA 236,JAPAN. YOKOHAMA CITY UNIV MED,DEPT CLIN PATHOL,YOKOHAMA 236,JAPAN. NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,FREDERICK,MD 21702. RP SHUIN, T (reprint author), YOKOHAMA CITY UNIV,SCH MED,DEPT UROL,KANAZAWA KU,3-9 FUKUURA,YOKOHAMA 236,JAPAN. NR 15 TC 388 Z9 394 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 JUN 1 PY 1994 VL 54 IS 11 BP 2852 EP 2855 PG 4 WC Oncology SC Oncology GA NN724 UT WOS:A1994NN72400010 PM 8187067 ER PT J AU RAM, Z SAMID, D WALBRIDGE, S OSHIRO, EM VIOLA, JJ TAOCHENG, JH SHACK, S THIBAULT, A MYERS, CE OLDFIELD, EH AF RAM, Z SAMID, D WALBRIDGE, S OSHIRO, EM VIOLA, JJ TAOCHENG, JH SHACK, S THIBAULT, A MYERS, CE OLDFIELD, EH TI GROWTH-INHIBITION, TUMOR MATURATION, AND EXTENDED SURVIVAL IN EXPERIMENTAL BRAIN-TUMORS IN RATS TREATED WITH PHENYLACETATE SO CANCER RESEARCH LA English DT Article ID CANCER; PROSTATE; ACID AB Phenylacetate is a naturally occurring plasma component that suppresses the growth of tumor cells and induces differentiation in vitro. To evaluate the in vivo potential and preventive and therapeutic antitumor efficacy of sodium phenylacetate against malignant brain tumors, Fischer 344 rats (n = 50) bearing cerebral 9L gliosarcomas received phenylacetate by continuous s.c. release starting on the day of tumor inoculation (n = 10) using s.c. osmotic minipumps (550 mg/kg/day for 28 days). Rats with established brain tumors (n = 12) received continuous s.c. phenylacetate supplemented with additional daily i.p. dose (300 mg/kg). Control rats (n = 25) were treated in a similar way with saline. Rats were sacrificed during treatment for electron microscopic studies of their tumors, in vivo proliferation assays, and measurement of phenylacetate levels in the serum and cerebrospinal fluid. Treatment with phenylacetate extended survival when started on the day of tumor inoculation (P < 0.01) or 7 days after inoculation (P < 0.03) without any associated adverse effects. In the latter group, phenylacetate levels in pooled serum and cerebrospinal fluid samples after 7 days of treatment were in the therapeutic range as determined in vitro (2.45 mM in serum and 3.1 mM in cerebrospinal fluid). Electron microscopy of treated tumors demonstrated marked hypertrophy and organization of the rough endoplasmic reticulum, indicating cell differentiation, in contrast to the scant and randomly distributed endoplasmic reticulum in tumors from untreated animals. In addition, in vitro studies demonstrated dose-dependent inhibition of the rate of tumor proliferation and restoration of anchorage dependency, a marker of phenotypic reversion. Phenylacetate, used at clinically achievable concentrations, prolongs survival of rats with malignant brain tumors through induction of tumor differentiation. Its role in the treatment of brain tumors and other cancers should be explored further. C1 NINCDS,ELECTRON MICROSCOPY UNIT,BETHESDA,MD 20892. NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. RP RAM, Z (reprint author), NINCDS,SURG NEUROL BRANCH,BLDG 10,ROOM 5D-37,9000 ROCKVILLE PK,BETHESDA,MD 20892, USA. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 18 TC 40 Z9 45 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 1994 VL 54 IS 11 BP 2923 EP 2927 PG 5 WC Oncology SC Oncology GA NN724 UT WOS:A1994NN72400023 PM 8187079 ER PT J AU GHOSH, P SICA, A YOUNG, HA YE, JP FRANCE, JL WILTROUT, RH LONGO, DL RICE, NR KOMSCHLIES, KL AF GHOSH, P SICA, A YOUNG, HA YE, JP FRANCE, JL WILTROUT, RH LONGO, DL RICE, NR KOMSCHLIES, KL TI ALTERATIONS IN NF-KAPPA-B/REL FAMILY PROTEINS IN SPLENIC T-CELLS FROM TUMOR-BEARING MICE AND REVERSAL FOLLOWING THERAPY SO CANCER RESEARCH LA English DT Article ID MURINE RENAL-CANCER; ACID; IL-2; EXPRESSION; CARCINOMA; GENE AB It has recently been shown that T-cell signal transduction molecules are altered in tumor-bearing mice. We have examined the expression of NF kappa B/Rel family proteins in T-cells from mice bearing Renca, a murine renal carcinoma. T-cells from Renca-bearing mice expressed undetectable levels of nuclear c-Rel, NF kappa B p65, and p50; however two shorter forms of p50 (p48 and p46), truncated at the NH2-terminus, were present exclusively in the nucleus and were able to bind DNA. These T-cells have reduced expression of gamma-interferon mRNA. In mice successfully treated with flavone 8-acetic acid and recombinant human interleukin 2, the T-cells expressed normal levels of all three nuclear NF kappa B/Rel proteins. These results suggest that alterations in transcription factors may accompany changes in signal transduction molecules in T-cells from tumor-bearing animals; however, the changes are reversed with successful biological therapy. C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,MOLEC VIROL & CARCINOGENESIS LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. RP GHOSH, P (reprint author), NCI,FREDERICK CANC RES & DEV CTR,EXPTL IMMUNOL LAB,BLDG 560,RM 31-16B,FREDERICK,MD 21702, USA. NR 23 TC 78 Z9 79 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 1994 VL 54 IS 11 BP 2969 EP 2972 PG 4 WC Oncology SC Oncology GA NN724 UT WOS:A1994NN72400030 PM 8187083 ER PT J AU CHEN, LC MATSUMURA, K DENG, G KURISU, W LJUNG, BM LERMAN, MI WALDMAN, FM SMITH, HS AF CHEN, LC MATSUMURA, K DENG, G KURISU, W LJUNG, BM LERMAN, MI WALDMAN, FM SMITH, HS TI DELETION OF 2 SEPARATE REGIONS ON CHROMOSOME 3P IN BREAST CANCERS SO CANCER RESEARCH LA English DT Article ID FLUORESCENCE INSITU HYBRIDIZATION; COPY NUMBER; HETEROZYGOSITY; LOSSES; CELLS; GRADE AB We have characterized the copy number of various loci on chromosome 3p in a series of breast cancers. To determine the precise region(s) involved, restriction fragment length polymorphism (RFLP) analysis for loss of heterozygosity (LOH) was performed using a panel of RFLP probes at 3p13-14, 3p21-22, and 3p24-26. The incidence of LOH at the three loci was 41, 32, and 45%, respectively. To validate the LOH data and to gain insights into the mechanisms resulting in LOH, chromosome 3 pericentromeric and 3p region-specific DNA probes were used to determine the DNA copy number by fluorescence in situ hybridization (FISH). Among 22 cases examined, 15 showed loss by both LOH and FISH, indicating that the dominant mechanism of LOH at 3p in breast cancer is a physical deletion. Two of the 22 cases showed loss by RPLP analysis but not by FISH, suggesting either mitotic recombination or loss and endoreduplication. In three cases, RFLP analysis indicated allelic imbalance, which was incorrectly interpreted as LOH, since a gain of one allele was suggested by FISH. By constructing a deletion map, we found that 2 separate regions, 3p13-14 and 3p24-26, were independently deleted in some breast cancers. Additionally, four cases had break points within the 3p24-26 region and one case had a homozygous deletion at 3p13, further supporting the hypothesis that there are tumor suppressor genes at both 3p13-14 and 3p24-26. Although high frequency of LOH was observed at the 3p21-22 region, there was no direct evidence supporting the existence of a breast cancer tumor suppressor gene there as opposed to codeletion with either the proximal or distal region. C1 CALIF PACIFIC MED CTR,GERALDINE BRUSH CANC RES INST,SAN FRANCISCO,CA 94115. UNIV CALIF SAN FRANCISCO,DEPT LAB MED,DIV MOLEC CYTOMETRY,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,SCH MED,SAN FRANCISCO,CA 94143. NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,FREDERICK,MD 20892. FU NCI NIH HHS [P01 CA44768] NR 19 TC 112 Z9 113 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 1994 VL 54 IS 11 BP 3021 EP 3024 PG 4 WC Oncology SC Oncology GA NN724 UT WOS:A1994NN72400039 PM 7910519 ER PT J AU STANLEY, LA BLACKBURN, DR DEVEREAUX, S FOLEY, J LORD, PG MARONPOT, RR ORTON, TC ANDERSON, MW AF STANLEY, LA BLACKBURN, DR DEVEREAUX, S FOLEY, J LORD, PG MARONPOT, RR ORTON, TC ANDERSON, MW TI RAS MUTATIONS IN METHYLCLOFENAPATE-INDUCED B6C3F1 AND C57BL/10J MOUSE-LIVER TUMORS SO CARCINOGENESIS LA English DT Article ID PEROXISOME PROLIFERATOR NAFENOPIN; HEPATOCYTE GROWTH-FACTOR; DNA-SYNTHESIS; ACTIVATED ONCOGENES; MET PROTOONCOGENE; FISCHER-344 RATS; CLOFIBRIC ACID; TUMORS; HEPATOCARCINOGENESIS; INDUCTION AB The majority of genotoxic carcinogen-induced liver tumours of the sensitive B6C3F1 mouse contain activated H-ras oncogenes. Such mutations also occur in hepatocarcinogenesis-resistant strains. In order to determine whether this is true of non-genotoxic carcinogen-induced tumours, liver tumours induced in B6C3F1 and C57BL/10J mice by methylclofenapate (MCP) were compared. Polymerase chain reaction (PCR) analysis revealed H-ras codon 61 mutations in 11/46 B6C3F1 and 4/31 C57BL/10J liver tumours. The nude mouse tumorigenicity (NMT) assay was used to analyse tumours without codon 61 mutations. Of the 12 B6C3F1 liver tumour DNAs subjected to this assay, one contained a H-ras codon 117 mutation. Further PCR analysis on frozen tumour samples (46 B6C3F1 and 15 C57BL/10J) revealed no codon 12 mutations; one additional codon 117 mutation was identified in a B6C3F1 tumour. Overall, then, H-ras codon 61 mutations were detected in MCP-induced B6C3F1 tumours less frequently than in genotoxin-induced tumours. Two B6C3F1 tumours contained codon 117 mutations similar to those previously found in tumours induced by ciprofibrate, furan and furfural, and in at least one spontaneous tumour. Ras mutations were also detected in some C57BL/10J tumours, providing further evidence that ras oncogenes can participate in hepatocarcinogenesis in resistant mice. C1 NIEHS,RES TRIANGLE PK,NC 27709. ZENECA PHARMACEUT,MACCLESFIELD SK10 4TG,CHESHIRE,ENGLAND. ZENECA CENT TOXICOL LAB,MACCLESFIELD SK10 4TG,CHESHIRE,ENGLAND. NR 55 TC 20 Z9 20 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 1994 VL 15 IS 6 BP 1125 EP 1131 DI 10.1093/carcin/15.6.1125 PG 7 WC Oncology SC Oncology GA NV157 UT WOS:A1994NV15700008 PM 8020144 ER PT J AU NELSON, KG SAKAI, Y EITZMAN, B STEED, T MCLACHLAN, J AF NELSON, KG SAKAI, Y EITZMAN, B STEED, T MCLACHLAN, J TI EXPOSURE TO DIETHYLSTILBESTROL DURING A CRITICAL DEVELOPMENTAL PERIOD OF THE MOUSE REPRODUCTIVE-TRACT LEADS TO PERSISTENT INDUCTION OF 2 ESTROGEN-REGULATED GENES SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID GROWTH-FACTOR-ALPHA; NEONATAL EXPOSURE; TRANSGENIC MICE; GENITAL-TRACT; MAMMARY-GLAND; TGF-ALPHA; PERIIMPLANTATION PERIOD; FACTOR-I; RECEPTOR; EXPRESSION AB Exposure to estrogens during critical periods of development induces teratogenic and carcinogenic lesions in the reproductive tracts of humans and experimental animals. It is important to determine the molecular and cellular targets of estrogenic chemicals and to establish the mechanisms by which interactions of estrogens with the developing genital tract results in permanent lesions of growth and differentiation. The experiments presented here were designed to examined the effects of neonatal estrogen exposure on the expression of two genes, lactoferrin and epidermal growth factor, that are subject to steroid hormone regulation. Using in situ and Northern RNA hybridization, immunoblotting, and immunohistochemistry, our data demonstrate that exposure to the synthetic estrogen, diethylstilbestrol, during a critical neonatal period results in the persistent ovary-independent induction of mRNA and protein encoded by these two genes in the mouse uterus and vagina. The constitutive expression of lactoferrin and EGF, and probably other estrogen-regulated genes, may contribute to the establishment of a permanently ''estrogenized'' phenotype which is then instrumental in the development of abnormal tissue morphogenesis, function, and neoplasia in the rodent reproductive tract. C1 NIEHS,DEV & REPROD TOXICOL LAB,POB 12233,RES TRIANGLE PK,NC 27709. NR 60 TC 115 Z9 116 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD JUN PY 1994 VL 5 IS 6 BP 595 EP 606 PG 12 WC Cell Biology SC Cell Biology GA NP799 UT WOS:A1994NP79900005 PM 8086337 ER PT J AU HENNIGHAUSEN, L MCKNIGHT, R BURDON, T BAIK, M WALL, RJ SMITH, GH AF HENNIGHAUSEN, L MCKNIGHT, R BURDON, T BAIK, M WALL, RJ SMITH, GH TI WHEY ACIDIC PROTEIN EXTRINSICALLY EXPRESSED FROM THE MOUSE MAMMARY-TUMOR VIRUS LONG TERMINAL REPEAT RESULTS IN HYPERPLASIA OF THE COAGULATION GLAND EPITHELIUM AND IMPAIRED MAMMARY DEVELOPMENT SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID TRANSGENIC MICE; ALVEOLAR DEVELOPMENT; GROWTH-FACTOR; GENE-PRODUCT; TGF-ALPHA; INDUCTION; MOLECULES; ADHESION; BREAST; INT-2 AB The whey acidic protein (WAP) is a milk protein that contains a cysteine-rich motif. This characteristic WAP signature has also been found in some protease inhibitors and certain proteins involved in tissue modeling. WAP is specifically synthesized in mammary tissue from late pregnant and lactating animals, and precocious synthesis results in impaired lobuloalveolar development of the gland in some transgenic lines. To determine whether growth modulatory effects of WAP are confined to mammary tissue, we expressed the WAP gene under the control of the mouse mammary tumor virus long terminal repeat in transgenic mice. The transgene was expressed at high levels in organs with exocrine function, such as mammary and salivary glands, prostate, seminal vesicle, and the coagulation gland. In addition to impaired mammary development, we observed hyperplasia and dysplasia of the coagulation gland epithelium. These findings suggest that WAP or a member of the WAP signature family can, in certain tissue contexts, function as an epithelial growth regulator. It appears from the present study that growth regulatory effects of WAP are restricted in the mouse to the mammary and coagulation gland epithelium. C1 NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20982. USDA ARS,BELTSVILLE,MD 20725. RP HENNIGHAUSEN, L (reprint author), NIDDKD,BIOCHEM & METAB LAB,BLDG 10,RM 9N113,BETHESDA,MD 20982, USA. NR 30 TC 34 Z9 34 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD JUN PY 1994 VL 5 IS 6 BP 607 EP 613 PG 7 WC Cell Biology SC Cell Biology GA NP799 UT WOS:A1994NP79900006 PM 7522033 ER PT J AU VICENZI, E POLI, G AF VICENZI, E POLI, G TI ULTRAVIOLET-IRRADIATION AND CYTOKINES AS REGULATORS OF HIV LATENCY AND EXPRESSION SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Article; Proceedings Paper CT Conference on the Place of Oxygen Free Radicals in HIV Infections CY JAN, 1993 CL LES DEUX ALPES, FRANCE SP FREE RAD CLUB GRENOBLE DE ULTRAVIOLET LIGHT; CYTOKINES; HIV; LATENCY; LTR; NF-KAPPA-B ID HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR-NECROSIS-FACTOR; LONG TERMINAL REPEAT; PRIMARY MONONUCLEAR PHAGOCYTES; DEFICIENCY SYNDROME AIDS; GROWTH-FACTOR-BETA; KAPPA-B-SITES; TRANSGENIC MICE; FACTOR-ALPHA; TYPE-1 HIV-1 AB The ability of the human immunodeficiency virus (HIV) to persist and replicate in human CD4+ T lymphocytes and mononuclear phagocytes is under the control of both virally encoded proteins and a variety of host-related factors. Ultraviolet (UV) light has been shown to induce transcription and expression of HIV. Both DNA damage and repair and DNA damage/repair-independent pathways caused by UV irradiation lead to expression of proviral HIV genomes via activation of the cellular transcription factor NF-kappaB. Transgenic mice that contain either long terminal repeat (LTR)-reporter genes or HIV genomes, either full length or deleted in the gag-pol region, express RNA and proteins at the epidermal level, particularly after UV irradiation. Furthermore, UV-triggered release of soluble factors capable of inducing expression of HIV in non-irradiated cells has been observed. Among other host factors, the functional network of pro-inflammatory and immunoregulatory cytokines has been demonstrated to act as a potent regulator of HIV replication, at least in different in vitro systems of infection. C1 UNIV MILAN,OSPED SAN RAFFAELE,CTR SAN LUIGI,AIDS IMMUNOPATHOGENESIS UNIT,I-20127 MILAN,ITALY. NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD. OI Vicenzi, Elisa/0000-0003-0051-3968 NR 66 TC 17 Z9 17 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0009-2797 J9 CHEM-BIOL INTERACT JI Chem.-Biol. Interact. PD JUN PY 1994 VL 91 IS 2-3 BP 101 EP 109 DI 10.1016/0009-2797(94)90030-2 PG 9 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA NP605 UT WOS:A1994NP60500004 PM 8194127 ER PT J AU BIESSMANN, H MASON, JM AF BIESSMANN, H MASON, JM TI TELOMERIC REPEAT SEQUENCES SO CHROMOSOMA LA English DT Article ID G-QUARTET FORMATION; DNA-SEQUENCES; SACCHAROMYCES-CEREVISIAE; DROSOPHILA-MELANOGASTER; CHROMOSOME ENDS; REPETITIVE DNA; PARAMECIUM-PRIMAURELIA; PLASMODIUM-FALCIPARUM; KARYOTYPIC EVOLUTION; ASCARIS-LUMBRICOIDES AB Chromosomes not only carry transcribed genes and their regulatory DNA sequences, but also contain regions that are required for the stability and maintenace of the chromosome as a unit. These include centromeres, telomeres and origins of replication. It is clear for replication origins and centromeres that the positions of these chromosomal organelles are determined by sites of the appropriate DNA sequences, but also that functional performance requires one or more contributing proteins. Telomeres are also structurally complex, with one or more DNA components, including simple telomeric repeats and more complex telomere-associated sequences, as well as one or more specific proteins that recognize these sequences. Accumulating evidence suggests that the simple telomeric repeats are required in most, but not all species, although they are not sufficient to determine the chromosomal position of a telomere. C1 NIEHS,MOLEC GENET LAB,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 92 TC 61 Z9 62 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0009-5915 J9 CHROMOSOMA JI Chromosoma PD JUN PY 1994 VL 103 IS 3 BP 154 EP 161 DI 10.1007/BF00368007 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA NU295 UT WOS:A1994NU29500001 PM 7924617 ER PT J AU LENFANT, C AF LENFANT, C TI NHLBI REVIEW PROCEDURES - REVERSING THE REVERSE SITE VISIT SO CIRCULATION LA English DT Editorial Material RP LENFANT, C (reprint author), NHLBI,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN PY 1994 VL 89 IS 6 BP 2487 EP 2487 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA NQ830 UT WOS:A1994NQ83000002 ER PT J AU SHAH, AM MEBAZAA, A WETZEL, RC LAKATTA, EG AF SHAH, AM MEBAZAA, A WETZEL, RC LAKATTA, EG TI NOVEL CARDIAC MYOFILAMENT DESENSITIZING FACTOR RELEASED BY ENDOCARDIAL AND VASCULAR ENDOTHELIAL-CELLS SO CIRCULATION LA English DT Note DE MYOCARDIAL CONTRACTION; INOTROPIC AGENTS; DIASTOLE ID PROTEIN KINASE-C; MYOCARDIAL-CONTRACTION; NITRIC-OXIDE; MYOCYTES; MUSCLE; RELAXATION; CALCIUM AB Background Recent studies suggest that both endocardial endothelium and coronary vascular endothelium influence myocardial contraction, but the mediators responsible and their mechanisms of action are not well defined. Methods and Results We investigated the effects of cultured endocardial endothelial and vascular endothelial cell superfusate on contraction and intracellular calcium transients of isolated rat cardiac myocytes. Endothelial cell superfusate induced a potent negative inotropic effect, with a rapid reversible decrease in myocyte twitch amplitude, earlier twitch relaxation, and a significant increase in diastolic length. This effect was not associated with significant changes in intracellular calcium or pH; was not attributable to nitric oxide, prostanoids, cGMP, or protein kinase C activation; and did not pertussis toxin-sensitive G proteins. The activity was stable at 37 degrees C for several hours, was not destroyed by protease treatment, and was found in low-molecular-weight (<<1 kD) superfusate fractions. Conclusions These data suggest the tonic release by endothelial cells of a novel, stable factor that acts predominantly by reducing the response of cardiac myofilaments to calcium (ie, ''desensitizes'' them). This ''desensitizing factor'' could rapidly modulate cardiac contraction-relaxation coupling and diastolic tonus and exert distant effects because of its stability. C1 NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. JOHNS HOPKINS MED INST,DEPT ANESTHESIOL & CRIT CARE MED,PULM ANESTHESIOL LAB,BALTIMORE,MD 21205. RP SHAH, AM (reprint author), UNIV WALES COLL MED,DEPT CARDIOL,HEATH PK,CARDIFF CF4 4XN,S GLAM,WALES. OI Shah, Ajay/0000-0002-6547-0631 NR 26 TC 36 Z9 36 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN PY 1994 VL 89 IS 6 BP 2492 EP 2497 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA NQ830 UT WOS:A1994NQ83000005 PM 8205654 ER PT J AU RODRIGUEZ, BL CURB, JD BURCHFIEL, CM ABBOTT, RD PETROVITCH, H MASAKI, K CHIU, D AF RODRIGUEZ, BL CURB, JD BURCHFIEL, CM ABBOTT, RD PETROVITCH, H MASAKI, K CHIU, D TI PHYSICAL-ACTIVITY AND 23-YEAR INCIDENCE OF CORONARY HEART-DISEASE MORBIDITY AND MORTALITY AMONG MIDDLE-AGED MEN - THE HONOLULU HEART PROGRAM SO CIRCULATION LA English DT Article DE EXERCISE; CORONARY HEART DISEASE; JAPANESE-AMERICANS; MIDDLE AGE ID FACTOR INTERVENTION TRIAL; CARDIOVASCULAR-DISEASE; LEISURE-TIME; MYOCARDIAL-INFARCTION; HEALTH BENEFITS; COLLEGE ALUMNI; RISK; EXERCISE; DEATH; PREVENTION AB Background The purpose of the study was to examine the association between physical activity and 23-year incidence of coronary heart disease morbidity and mortality. This cohort study continues to follow 8006 Japanese-American men who were 45 to 68 years of age and living on Oahu, Hawaii, in 1965, for the development of coronary heart disease morbidity and mortality. Methods and Results The Framingham physical activity index was calculated by summing the product of average hours spent at each activity level and a weighting factor based on oxygen consumption. Study subjects were divided into tertiles of physical activity index at baseline. Relative risks and 95% confidence intervals (CI) for incidence of coronary heart disease morbidity and mortality were obtained using the Cox model. After age adjustment and using the lowest physical activity index tertile as a reference group, the relative risk for coronary heart disease incidence for the highest tertile of physical activity was 0.83 (CI, 0.70 to 0.99). After adjusting for age, hypertension, smoking, alcohol intake, diabetes, cholesterol, and body mass index, the relative risk was 0.95 and CI included 1 (CI, 0.80 to 1.14). For coronary heart disease mortality, the age-adjusted relative risk was 0.74 (CI, 0.56 to 0.97) and 0.85 (CI, 0.65 to 1.13) after risk factor adjustment. Conclusions The results suggest that the impact of physical activity index on coronary heart disease is mediated through its effects on hypertension, diabetes, cholesterol, and body mass index. These findings support the hypothesis that physical activity is inversely associated with coronary heart disease morbidity and mortality and suggest that physical activity interventions in middle-aged men, by improving cardiovascular risk factor levels, may have significant public health implications in the prevention of coronary heart disease. C1 UNIV HAWAII MANOA,JOHN A BURNS SCH MED,HONOLULU,HI 96822. NHLBI,HONOLULU HEART PROGRAM,HONOLULU,HI. UNIV VIRGINIA,SCH MED,DEPT MED,DIV BIOSTAT,CHARLOTTESVILLE,VA 22908. RP RODRIGUEZ, BL (reprint author), KUAKINI MED CTR,HONOLULU HEART PROGRAM,347 N KUAKINI ST,HONOLULU,HI 96817, USA. FU NHLBI NIH HHS [N01-HC-05102] NR 33 TC 101 Z9 101 U1 1 U2 4 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN PY 1994 VL 89 IS 6 BP 2540 EP 2544 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA NQ830 UT WOS:A1994NQ83000013 PM 8205662 ER PT J AU GILLIGAN, DM QUYYUMI, AA CANNON, RO JOHNSON, GB SCHENKE, WH AF GILLIGAN, DM QUYYUMI, AA CANNON, RO JOHNSON, GB SCHENKE, WH TI EFFECTS OF PHYSIOLOGICAL LEVELS OF ESTROGEN ON CORONARY VASOMOTOR FUNCTION IN POSTMENOPAUSAL WOMEN SO CIRCULATION LA English DT Article DE ESTROGEN; MENOPAUSE; CORONARY ARTERY DISEASE; ENDOTHELIUM; NITRIC OXIDE ID DEPENDENT VASCULAR RELAXATION; ENDOTHELIAL DYSFUNCTION; ESSENTIAL-HYPERTENSION; INDUCED SENSITIZATION; UTERINE ARTERY; HEART-DISEASE; NITRIC-OXIDE; GUINEA-PIG; 17-BETA-ESTRADIOL; ACETYLCHOLINE AB Background Estrogen replacement therapy has been associated with a reduction in cardiovascular events in postmenopausal women. One of the mechanisms responsible may be a beneficial effect of estrogen on coronary vascular function. We therefore studied the short-term effects of estrogen on coronary artery dimensions and microvascular resistance in postmenopausal women. Methods and Results Twenty postmenopausal women 61+/-7 years old participated in this study. Seven had angiographic evidence of atherosclerosis of the left coronary artery. Coronary artery diameters were measured by quantitative coronary angiography. Blood flow velocity was measured with a Doppler wire placed in a proximal left coronary artery segment. Left coronary artery infusions of acetylcholine (range, 10(-8) to 10(-5) mol/L estimated delivered concentrations) and of adenosine (n=18) and sodium nitroprusside (n=10) were performed before and during concomitant continuous intracoronary infusion of 17 beta estradiol to test endothelium-dependent and independent vasodilation, respectively. Intracoronary infusion of estradiol increased coronary sinus estradiol levels from postmenopausal (16+/-11 pg/mL) to premenopausal (282+/-121 pg/mL) levels. Estradiol did not affect basal coronary artery diameter, blood flow, or resistance. Epicardial coronary artery constriction induced by acetylcholine infusion in the control study (maximum, 10+/-15% from baseline) was prevented during repeat acetylcholine infusion with concomitant estradiol administration (P<.001). Estradiol potentiated the vasodilator coronary microvascular response to acetylcholine as manifest by significantly greater coronary flow (P<.001) and lower coronary resistance (P<.02). The reduction in coronary resistance from baseline in response to acetylcholine was significantly potentiated by estradiol (P=.01), with a mean decrease in coronary vascular resistance during acetylcholine infusion of 20+/-38% before and 35+/-33% during concomitant estradiol administration. The effect of estradiol on coronary dynamics was similar in women with and women without angiographically apparent left coronary artery atherosclerosis and was most prominent in women with the most impaired responses to acetylcholine at both the epicardial (r=-.72, P<.001) and microvascular (r=-.59, P=.006) coronary artery levels. In contrast, estradiol did not affect the coronary epicardial or microvascular vasodilator responses to adenosine or sodium nitroprusside. Conclusions Physiological levels of 17 beta-estradiol acutely and selectively potentiate endothelium-dependent vasodilation in both large coronary conductance arteries and coronary microvascular resistance arteries of postmenopausal women. This effect may contribute to the reduction in cardiovascular events observed with estrogen replacement therapy. C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. NR 34 TC 455 Z9 463 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN PY 1994 VL 89 IS 6 BP 2545 EP 2551 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA NQ830 UT WOS:A1994NQ83000014 PM 8205663 ER PT J AU SHIOTA, T JONES, M TEIEN, DE YAMADA, I PASSAFINI, A GE, SP SHANDAS, R VALDESCRUZ, LM SAHN, DJ AF SHIOTA, T JONES, M TEIEN, DE YAMADA, I PASSAFINI, A GE, SP SHANDAS, R VALDESCRUZ, LM SAHN, DJ TI EVALUATION OF MITRAL REGURGITATION USING A DIGITALLY DETERMINED COLOR DOPPLER FLOW CONVERGENCE CENTERLINE ACCELERATION METHOD - STUDIES IN AN ANIMAL-MODEL WITH QUANTIFIED MITRAL REGURGITATION SO CIRCULATION LA English DT Article DE REGURGITATION; VALVES; ECHOCARDIOGRAPHY; FLOW ID VALVULAR REGURGITATION; ORIFICE; REGION; INVITRO; JET; ECHOCARDIOGRAPHY; LIMITATIONS; VALIDATION; MOMENTUM; GEOMETRY AB Background The imaging and measurement of the proximal flow convergence region in the left ventricle have been reported to be useful for identifying the site of mitral regurgitation (MR) and for evaluating its severity. However, the application of this method has not gained general acceptance. There have been few in vivo studies with quantified reference standards for determining regurgitant volume, and those that have been reported used spectral Doppler standards and/or nonsimultaneously performed contrast ventriculography. The purpose of the present study was to evaluate the proximal flow convergence centerline velocity-distance profile method applied to chronic MR resulting from flail mitral leaflets in an animal model in which regurgitant flow rates and regurgitant volumes were determined simultaneously with electromagnetic flow probes and flowmeters. Methods and Results In six sheep, a total of 18 hemodynamically different states were obtained when the animals were restudied 6 months after surgical induction of MR produced by severing chordae tendineae to the anterior (three sheep) or posterior (three sheep) mitral leaflet. Echocardiographic studies with a Vingmed 750 were performed to obtain complete proximal axial flow acceleration velocity-distance profiles for each hemodynamic state. The color Doppler velocity data were directly transferred in digital format from the ultrasound instrumentation to a microcomputer. The severity of MR was assessed by the magnitude of the mitral regurgitant fraction determined using both mitral and aortic electromagnetic flow probes balanced against each other to yield regurgitant volume. MR was classified as grade I when the regurgitant fraction was <20%, as grade II when it was 20% to 35%, and as grade III to IV when it was >35%. Thus, of the 18 hemodynamic states, 4 (from two sheep) were grade I, 7 (from five sheep) were grade II, and 7 (from three sheep) were grade III to IV. All of the velocity-distance acceleration curves showed organized acceleration fields with highly significant correlations using multiplicative regression fits (y=a . x(-b) r=.90 to .99, all P<.01). Grade III to IV MR resulted in rightward and upward shifts of the velocity-distance profile curves compared with those produced by grade II and grade I MR. All of the centerline velocity-distance profiles for grade III or IV regurgitation resided in a domain encompassed by velocities >0.5 m/s at distances from the orifice >0.6 cm; the profiles for grade I regurgitation resided in a domain encompassed by velocities <0.3 mis at distances from the orifice of <0.45 cm. The profiles for grade II regurgitations resided in a domain between them. Regression analysis for the distance at which a velocity of 0.5 mis was first reached bore a close relation to regurgitant fraction (r=.92, P<.0001) and peak regurgitant flow rate (r=.89, P<.0001). In addition, an equation for quantitatively correlating both a and b (coefficients from the multiplicative regression fits) with the peak regurgitant flow rate (Q(peak) in L/min) was derived from stepwise regression analysis: Q(peak)=12a+2.7b-2.4 (r=.96, P<.0001, SEE=.45 L/min). Conclusions In this study, using quantified MR volume, we demonstrate that the proximal flow convergence axial centerline velocity-distance profile method can be used for evaluating the severity of MR without any assumption about isovelocity surface shape geometry. C1 OREGON HLTH SCI UNIV,CLIN CARE CTR CONGENITAL HEART DIS,PORTLAND,OR 97201. NHLBI,ANIM MED & SURG LAB,BETHESDA,MD 20892. MAIMONIDES HOSP,NEW YORK,NY. OI Shandas, Robin/0000-0002-9473-7542 FU NHLBI NIH HHS [R01-HL-43287] NR 39 TC 57 Z9 57 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN PY 1994 VL 89 IS 6 BP 2879 EP 2887 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA NQ830 UT WOS:A1994NQ83000056 PM 8205704 ER PT J AU ZHENG, JS BOLUYT, MO ONEILL, L CROW, MT LAKATTA, EG AF ZHENG, JS BOLUYT, MO ONEILL, L CROW, MT LAKATTA, EG TI EXTRACELLULAR ATP INDUCES IMMEDIATE-EARLY GENE-EXPRESSION BUT NOT CELLULAR HYPERTROPHY IN NEONATAL CARDIAC MYOCYTES SO CIRCULATION RESEARCH LA English DT Article DE PURINERGIC RECEPTORS; C-FOS; JUN-B; CARDIAC MYOCYTES ID RAT MYOCARDIAL-CELLS; C-FOS; PROTOONCOGENE INDUCTION; VENTRICULAR MYOCYTES; SIGNAL TRANSDUCTION; CA-2+ TRANSIENTS; HEART-CELLS; GROWTH; JUN; NOREPINEPHRINE AB It is well-documented that norepinephrine (NE) induces the expression of immediate-early genes (IEGs), such as c-fos, c-jun, and jun-B, in cultured neonatal heart cells and leads to cell growth without cell division (ie, hypertrophy). Although purinergic receptors activated by ATP are present on cardiac myocytes and ATP is coreleased with NE from sympathetic nerve endings within the heart, the potential role of the purinergic system in the cascade of events that leads to cardiac hypertrophy is unknown. We report in the present study that stimulation of purinergic receptors by micromolar concentrations of extracellular ATP increased the levels of c-fos and jun-B mRNA as well as FOS and JUN-B proteins in neonatal cardiac myocytes. The magnitude of response to micromolar ATP was comparable to that elicited by NE. The increase in IEG expression induced by ATP was preceded by a rapid transient increase in cytosolic Ca2+. Pretreatment of myocytes with the intracellular Ca2+ chelator BAPTA-AM prevented the ATP-stimulated increase in cytosolic Ca2+ and attenuated the ATP-stimulated increase in c-fos expression. In contrast, NE did not increase cytosolic Ca2+ in quiescent myocytes, and pretreatment with BAPTA-AM did not inhibit the NE-stimulated increase in c-fos gene expression. Furthermore, although NE markedly increased [C-14]phenylalanine incorporation into protein and myocyte hypertrophy measured by cell size, ATP did not. These results demonstrate that stimulation of purinergic receptors by ATP activates IEGs via a Ca2+-dependent pathway in cardiac myocytes that differs from the NE-stimulated activation of these genes. Since ATP activated IEG expression but did not increase the rate of protein synthesis nor augment cell size, we conclude that the activation of c-fos and jun-B expression is not sufficient to induce cellular hypertrophy in neonatal cardiac myocytes. C1 NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. NR 47 TC 48 Z9 48 U1 1 U2 3 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD JUN PY 1994 VL 74 IS 6 BP 1034 EP 1041 PG 8 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA NN386 UT WOS:A1994NN38600003 PM 8187273 ER PT J AU SAMPSON, M RUDDEL, M ELIN, RJ AF SAMPSON, M RUDDEL, M ELIN, RJ TI LITHIUM DETERMINATIONS EVALUATED IN 8 ANALYZERS SO CLINICAL CHEMISTRY LA English DT Article DE ION-SELECTIVE ELECTRODES; ATOMIC ABSORPTION SPECTROSCOPY; ATOMIC EMISSION SPECTROSCOPY; INTERMETHOD COMPARISON; VARIATION, SOURCE OF AB We compared five ion-selective electrodes (ISEs; AVL 985S, Baxter Lytening 2Z, Beekman EL-ISE, Ciba-Corning 654 Na/K/Li, and Nova CRT II) and a colorimetric method (Ektachem) for determination of lithium with flame atomic absorption and atomic emission spectroscopy. We evaluated precision, recovery, interference by drugs (procainamide, N-acetylprocainamide, quinidine, lidocaine, carbamazepine, and valproic acid) and inorganic analytes (Na, K, Ca, Mg, and Br), and performance with sera from patients receiving lithium. Imprecision was <5% (CV) for all analyzers except Ektachem and Beckman. Analytical recovery was 100%+/-5% for all analyzers except Ektachem and Baxter. Some drug interference was seen with all analyzers except AVL and Coming. Calcium caused interference with AVL, Coming, and Ektachem analyzers, and sodium and potassium interfered with the Ektachem analyzer. The results with the Baxter, Beekman, and Coming analyzers were closest to those by flame atomic emission (mean differences, 0.01 to 0.02 mmol/L); the AVL and Nova analyzers gave lower results (mean differences, -0.11 to -0.13 mmol/L) and the Ektachem gave higher results (mean difference, 0.08 mmol/l). RP SAMPSON, M (reprint author), NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT CLIN PATHOL,CLIN CHEM SERV,BLDG 10,ROOM 2C-407,BETHESDA,MD 20892, USA. NR 5 TC 26 Z9 27 U1 0 U2 3 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 JUN PY 1994 VL 40 IS 6 BP 869 EP 872 PG 4 WC Medical Laboratory Technology SC Medical Laboratory Technology GA NR366 UT WOS:A1994NR36600005 PM 8087980 ER PT J AU BLACK, JR FEINBERG, J MURPHY, RL FASS, RJ FINKELSTEIN, D AKIL, B SAFRIN, S CAREY, JT STANSELL, J PLOUFFE, JF HE, WL SHELTON, B SATTLER, FR AF BLACK, JR FEINBERG, J MURPHY, RL FASS, RJ FINKELSTEIN, D AKIL, B SAFRIN, S CAREY, JT STANSELL, J PLOUFFE, JF HE, WL SHELTON, B SATTLER, FR TI CLINDAMYCIN AND PRIMAQUINE THERAPY FOR MILD-TO-MODERATE EPISODES OF PNEUMOCYSTIS-CARINII PNEUMONIA IN PATIENTS WITH AIDS - AIDS CLINICAL-TRIALS GROUP-044 SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; TRIMETHOPRIM-SULFAMETHOXAZOLE; TOXOPLASMIC ENCEPHALITIS; PLASMODIUM-FALCIPARUM; RANDOMIZED TRIAL; PENTAMIDINE; PROPHYLAXIS; EFFICACY; 8-AMINOQUINOLINES; INSTITUTE AB The objective of this prospective, noncomparative study was to assess the safety and efficacy of clindamycin and primaquine therapy for mild-to-moderate pneumocystis pneumonia (defined as a difference of < 40 mm Hg between the alveolar and the arterial oxygen determinations) in patients with AIDS. In the first part of the study, 22 patients were treated with iv clindamycin (900 mg every 8 hours) for the first 10 days, and then their therapy was switched to oral clindamycin (450 mg every 6 hours) for an additional 11 days. In the second part of the study, 38 patients were treated entirely with oral clindamycin (600 mg every 8 hours). All patients were treated with oral primaquine base (30 mg once daily). Fifty-five (92%) of 60 patients responded to the study treatment. Forty-six (77%) of 60 patients completed a full course of therapy. Of the nine patients with treatment-limiting toxic effects, four had only a mild rash. This study indicates that the combination of clindamycin and primaquine is an effective and well-tolerated therapy for mild-to-moderate pneumocystis pneumonia in patients with AIDS. Entirely oral therapy appears to be as effective as initial therapy with iv clindamycin. C1 NIAID,DIV AIDS,BETHESDA,MD 20892. INDIANA UNIV,INDIANAPOLIS,IN 46204. NORTHWESTERN UNIV,SCH MED,CTR COMPREHENS AIDS,CHICAGO,IL 60611. OHIO STATE UNIV,COLL MED,DIV INFECT DIS,COLUMBUS,OH 43210. CASE WESTERN RESERVE UNIV,CLEVELAND,OH 44106. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,CTR STAT & DATA ANAL,AIDS CLIN TRIALS GRP,BOSTON,MA 02115. UNIV SO CALIF,LOS ANGELES,CA. SAN FRANCISCO GEN HOSP,SAN FRANCISCO,CA 94110. RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. OI Murphy, Robert/0000-0003-3936-2052 NR 37 TC 27 Z9 28 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUN PY 1994 VL 18 IS 6 BP 905 EP 913 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA NQ826 UT WOS:A1994NQ82600010 PM 8086551 ER PT J AU ADLERSBERG, S TOREN, P MESTER, R REHAVI, M SKOLNICK, P WEIZMAN, A AF ADLERSBERG, S TOREN, P MESTER, R REHAVI, M SKOLNICK, P WEIZMAN, A TI VERAPAMIL IS NOT AN ANTIDEPRESSANT IN PATIENTS RESISTANT TO TRICYCLIC ANTIDEPRESSANTS SO CLINICAL NEUROPHARMACOLOGY LA English DT Review DE VERAPAMIL; CALCIUM CHANNEL BLOCKERS; DEPRESSION; ANXIETY; TRICYCLIC ANTIDEPRESSANTS ID NMDA RECEPTOR COMPLEX; CALCIUM-ANTAGONISTS; DOUBLE-BLIND; SCHIZOPHRENIC-PATIENTS; AFFECTIVE-DISORDERS; ADAPTATION; DEPRESSION; IMIPRAMINE; THERAPY; SHOCK AB The effects of a calcium channel blocker (verapamil, 160-320 mg/day for 4 weeks) were studied in seven unipolar major-depressed patients resistant to treatment with tricyclic antidepressants. This regimen of verapamil did not alter either the Hamilton rating scales for depression and anxiety or the Beck depression inventory score in these patients. Thus, verapamil appears devoid of antidepressant properties in patients resistant to tricyclic antidepressants. C1 BEILINSON MED CTR,GEHA PSYCHIAT HOSP,IL-49100 PETAH TIQWA,ISRAEL. NESS ZIONA MENT HLTH CTR,TEL AVIV,ISRAEL. TEL AVIV UNIV,SACKLER FAC MED,DEPT PHYSIOL & PHARMACOL,IL-69978 TEL AVIV,ISRAEL. NIDDKD,NEUROSCI LAB,BETHESDA,MD 20892. TEL AVIV UNIV,SACKLER FAC MED,FELSENSTEIN MED RES CTR,IL-69978 TEL AVIV,ISRAEL. NR 28 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0362-5664 J9 CLIN NEUROPHARMACOL JI Clin. Neuropharmacol. PD JUN PY 1994 VL 17 IS 3 BP 294 EP 297 PG 4 WC Clinical Neurology; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA NM870 UT WOS:A1994NM87000009 PM 9316675 ER PT J AU WERNER, MH CLORE, GM GRONENBORN, AM NASH, HA AF WERNER, MH CLORE, GM GRONENBORN, AM NASH, HA TI SYMMETRY AND ASYMMETRY IN THE FUNCTION OF ESCHERICHIA-COLI INTEGRATION HOST FACTOR - IMPLICATIONS FOR TARGET IDENTIFICATION BY DNA-BINDING PROTEINS SO CURRENT BIOLOGY LA English DT Article ID SITE-SPECIFIC RECOMBINATION; POLYACRYLAMIDE-GEL ELECTROPHORESIS; BACTERIOPHAGE-LAMBDA; GLUCOCORTICOID RECEPTOR; REGULATORY PROTEINS; IHF PROTEIN; RECOGNITION; SELECTION; ELEMENTS; PROMOTER AB Background: Escherichia coli integration host factor (IHF) is a DNA-binding protein that participates in a wide variety of biochemical functions. In many of its activities, IHF appears to act as an architectural element, dramatically distorting the conformation of bound DNA. IHF is a dimer of non-identical subunits, each about 30 amino acids long. One dimer interacts specifically with a 30 base pair (bp) target, but well-conserved sequences are found in only half of this binding site. Thus, the IHF-DNA system has long been viewed as a paradigm of asymmetry in a protein-DNA interaction. Results: We have isolated the subunits of IHF and show that either subunit is capable of specifically recognizing natural IHF-binding sites and supporting lambda site-specific recombination in vitro. Mobility shift and footprinting data indicate that the isolated subunits interact with DNA as homodimers. We also describe the design of symmetric duplexes to which heterodimeric and homodimeric IHFs can bind by recognizing specific sequences. Conclusions: Our in vitro manipulation of the IHF system demonstrates that binding and bending of target DNA can be accomplished symmetrically. The prevalence of asymmetry found for this system in nature suggests that additional selective forces may operate. We suggest that these follow from the disparity between the size of the DNA that IHF protects (30 bp) and the length of DNA that the protein can initially contact (10 bp). This disparity implies that an IHF target is recognized in stages and may dispose the part of the protein-DNA system used for initial recognition to evolve distinctly from the remainder of the interaction surface. We suggest that a limitation in the length of DNA that can be initially contacted is a general property of DNA-binding proteins. In that case, many proteins can be expected to identify complex targets by step-wise, rather than simultaneous, contact between sequence elements and DNA-binding domains. C1 NIMH,MOLEC BIOL LAB,BETHESDA,MD 20892. RP WERNER, MH (reprint author), NIDDKD,PHYS CHEM LAB,BETHESDA,MD 20892, USA. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 38 TC 25 Z9 25 U1 1 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD JUN 1 PY 1994 VL 4 IS 6 BP 477 EP 487 DI 10.1016/S0960-9822(00)00108-1 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NU410 UT WOS:A1994NU41000001 PM 7922368 ER PT J AU WOLFFE, AP AF WOLFFE, AP TI TRANSCRIPTIONAL ACTIVATION - SWITCHED-ON CHROMATIN SO CURRENT BIOLOGY LA English DT Note ID HISTONE OCTAMER; DNA; SNF2/SWI2 RP WOLFFE, AP (reprint author), NICHHD,MOLEC EMBRYOL LAB,BLDG 6,ROOM B1A-13,BETHESDA,MD 20892, USA. NR 17 TC 44 Z9 45 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD JUN 1 PY 1994 VL 4 IS 6 BP 525 EP 528 DI 10.1016/S0960-9822(00)00114-7 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NU410 UT WOS:A1994NU41000007 PM 7922373 ER PT J AU RENGARAJAN, K DESMET, MD CHADER, GJ WIGGERT, B AF RENGARAJAN, K DESMET, MD CHADER, GJ WIGGERT, B TI IDENTIFICATION OF HEAT-SHOCK PROTEINS BINDING TO AN IMMUNODOMINANT UVEITOPATHOGENIC PEPTIDE OF IRBP (VOL 13, PG 289, 1994) SO CURRENT EYE RESEARCH LA English DT Correction, Addition C1 NEI,IMMUNOL LAB,BETHESDA,MD 20892. RP RENGARAJAN, K (reprint author), NEI,RETINAL CELL & MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 1 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 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD JUN PY 1994 VL 13 IS 6 BP 469 EP 469 DI 10.3109/02713689408999877 PG 1 WC Ophthalmology SC Ophthalmology GA NT807 UT WOS:A1994NT80700012 ER PT J AU WOOTTON, JC AF WOOTTON, JC TI SEQUENCES WITH UNUSUAL AMINO-ACID COMPOSITIONS SO CURRENT OPINION IN STRUCTURAL BIOLOGY LA English DT Article ID CRYSTAL-STRUCTURE; NUCLEOTIDE-SEQUENCES; LOCAL COMPLEXITY; HELICAL PEPTIDES; ALPHA-HELICES; DATA-BANK; PROTEIN; DOMAIN; RNA; EVOLUTION AB Amino acid sequences of very non-random composition ('low-complexity' segments) are abundant in natural proteins. From recent statistical analyses of protein sequence databases, approximately 15% of the residues occur in segments of extreme compositional bias, and approximately 34% of proteins have at least one such interspersed segment. Sequences of many elongated non-globular domains also have non-random compositional bias, and these regions increase the proportion of residues in statistically deviant segments to approximately 25% of the database. In contrast, less than 1% of residues in known ordered crystal structures are in segments of reduced complexity. Increasingly, low-complexity segments have been implicated in crucial biological functions, shown by genetic engineering and mutagenesis experiments, variations in human disease and locations of autoimmune epitopes, but relatively little is known about their range of possible molecular structures, dynamics and interactions. RP WOOTTON, JC (reprint author), NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,8TH FLOOR,BLDG 38A,BETHESDA,MD 20894, USA. NR 56 TC 99 Z9 100 U1 0 U2 5 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0959-440X J9 CURR OPIN STRUC BIOL JI Curr. Opin. Struct. Biol. PD JUN PY 1994 VL 4 IS 3 BP 413 EP 421 DI 10.1016/S0959-440X(94)90111-2 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NW296 UT WOS:A1994NW29600014 ER PT J AU LUNDGREN, B AF LUNDGREN, B TI PNEUMOCYSTIS-CARINII - ANTIGENIC, IMMUNOLOGICAL, AND MOLECULAR CHARACTERIZATION SO DANISH MEDICAL BULLETIN LA English DT Review ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; IMMUNE-DEFICIENCY SYNDROME; POLYMERASE CHAIN-REACTION; HIV-INFECTED PATIENTS; THYMIDYLATE SYNTHASE GENE; LARGE DNA-MOLECULES; MONOCLONAL-ANTIBODIES; SURFACE-ANTIGEN; GEL-ELECTROPHORESIS; DIHYDROFOLATE-REDUCTASE C1 NIH,CTR CLIN,DEPT CRIT CARE MED,BETHESDA,MD 20892. HVIDOVRE UNIV HOSP,DEPT CLIN MICROBIOL,COPENHAGEN,DENMARK. HVIDOVRE UNIV HOSP,DEPT INFECT DIS,COPENHAGEN,DENMARK. NR 175 TC 5 Z9 5 U1 0 U2 0 PU DANISH MEDICAL ASSN PI COPENHAGEN PA TRONDHJEMSGADE 9, DK-2100 COPENHAGEN, DENMARK SN 0011-6092 J9 DAN MED BULL JI Dan. Med. Bull. PD JUN PY 1994 VL 41 IS 3 BP 306 EP 318 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA NR885 UT WOS:A1994NR88500005 PM 7523034 ER PT J AU TAIRA, M OTANI, H JAMRICH, M DAWID, IB AF TAIRA, M OTANI, H JAMRICH, M DAWID, IB TI EXPRESSION OF THE LIM CLASS HOMEOBOX GENE XLIM-1 IN PRONEPHROS AND CNS CELL LINEAGES OF XENOPUS-EMBRYOS IS AFFECTED BY RETINOIC ACID AND EXOGASTRULATION SO DEVELOPMENT LA English DT Article DE XENOPUS LAEVIS; NOTOCHORD; PRONEPHROS; CENTRAL NERVOUS SYSTEM; RETINOIC ACID; EXOGASTRULATION; HOMEOBOX GENE; LIM DOMAIN; XLIM-1 ID CENTRAL-NERVOUS-SYSTEM; TOUCH RECEPTOR NEURONS; CAENORHABDITIS-ELEGANS; LAEVIS EMBRYOS; PROTEIN ISL-1; DEVELOPING FOREBRAIN; SPEMANN ORGANIZER; NEURAL INDUCTION; EARLY RESPONSE; INSULIN GENE AB The LIM class homeobox gene Xlim-1 is expressed in Xenopus embryos in the lineages leading to (i) the notochord, (ii) the pronephros, and (iii) certain cells of the central nervous system (CNS). In its first expression phase, Xlim-1 mRNA arises in the Spemann organizer region, accumulates in prechordal mesoderm and notochord during gastrulation, and decays in these tissues during neurula stages except that it persists in the posterior tip of the notochord. In the second phase, expression in lateral mesoderm begins at late gastrula, and converges to the pronephros at tailbud stages. Expression in a central location of the neural plate also initiates at late gastrula, expands anteriorly and posteriorly, and becomes established in the lateral regions of the spinal cord and hindbrain at tailbud stages. Thus Xlim-1 expression precedes morphogenesis, suggesting that it may be involved in cell specification in these lineages. Enhancement of Xlim-1 expression by retinoic acid (RA) was first detectable in the dorsal mesoderm at initial gastrula. During gastrulation and early neurulation, RA strongly enhanced Xlim-1 expression in all three lineages and also expanded its expressing domains; this overexpression correlated well with RA phenotypes such as enlarged pronephros and hindbrain-like structure. Exogastrulation reduced Xlim-1 expression in the lateral mesoderm and ectoderm but not in the notochord, suggesting that the second phase of Xlim-1 expression requires mesoderm/ectoderm interactions. RA treatment of exogastrulae did not revert this reduction. C1 US FDA,CTR BIOL EVALUAT & RES,DEV BIOL LAB,BETHESDA,MD 20892. RP TAIRA, M (reprint author), NICHHD,GENET MOLEC LAB,BETHESDA,MD 20892, USA. FU NICHD NIH HHS [NICHD N01-HD-2-3144] NR 69 TC 116 Z9 117 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD JUN PY 1994 VL 120 IS 6 BP 1525 EP 1536 PG 12 WC Developmental Biology SC Developmental Biology GA NT555 UT WOS:A1994NT55500015 PM 7914163 ER PT J AU BUCHMAN, VL SPORN, M DAVIES, AM AF BUCHMAN, VL SPORN, M DAVIES, AM TI ROLE OF TRANSFORMING GROWTH-FACTOR-BETA ISOFORMS IN REGULATING THE EXPRESSION OF NERVE GROWTH-FACTOR AND NEUROTROPHIN-3 MESSENGER-RNA LEVELS IN EMBRYONIC CUTANEOUS CELLS AT DIFFERENT STAGES OF DEVELOPMENT SO DEVELOPMENT LA English DT Article DE TRANSFORMING GROWTH FACTOR-BETA; NERVE GROWTH FACTOR; NEUROTROPHIN-3; MOUSE ID MESSENGER-RNA EXPRESSION; NEGATIVE AUTOCRINE REGULATION; FACTOR NGF SYNTHESIS; RAT SCIATIC-NERVE; FACTOR FAMILY; SYMPATHETIC-GANGLIA; MOLECULAR-CLONING; LIMBIC SEIZURES; NONNEURONAL CELLS; DEVELOPING SKIN AB We have investigated if transforming growth factor-beta (TGF-beta) isoforms influence the level of expression of nerve growth factor (NGF) mRNA and neurotrophin-3 (NT-3) mRNA in embryonic tissues innervated by neurons that depend on NGF and NT-3 for survival. Presumptive dermal and epidermal cells from the maxillary territory of the embryonic mouse trigeminal ganglion were cultured in defined medium during the early stages of innervation when trigeminal neurons switch their survival dependence from NT-3 to NGF. In E11 and E12 cultures, when the in vivo levels of NGF mRNA and NT-3 mRNA are increasing, TGF-beta 1, TGF-beta 2 and TGF-beta 3 each increased the level of NGF mRNA but had no effect on NT-3 mRNA. In E13 cultures, when the in vivo levels of NGF mRNA and NT-3 mRNA reach a peak (relative to actin mRNA) prior to a marked fall in the level of NT-3 mRNA and a gradual decrease in the level of NGF mRNA, TGF-beta s promoted further increases in the level of NGF mRNA but caused a decrease in the level of NT-3 mRNA. All three TGF-beta mRNAs were detected in the maxillary territory in vivo before the arrival of the earliest axons and their levels rose throughout the period in which sensory axons reach this territory. Our findings demonstrate age-related changes in the influence of TGF-beta s on the expression of neurotrophins in developing cutaneous cells and raise the possibility that TGF-beta s play a role in regulating the changing patterns of neurotrophin gene expression in sensory neuron target fields. C1 NCI, CHEMOPREVENT LAB, BETHESDA, MD 20892 USA. RP UNIV ST ANDREWS, SCH BIOL & MED SCI, BUTE MED BLDGS, ST ANDREWS KY16 9TS, FIFE, SCOTLAND. RI Davies, Alun/A-4334-2010; Buchman, Vladimir/A-4814-2010 OI Davies, Alun/0000-0001-5841-8176; Buchman, Vladimir/0000-0002-7631-8352 FU Wellcome Trust NR 71 TC 49 Z9 49 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 EI 1477-9129 J9 DEVELOPMENT JI Development PD JUN PY 1994 VL 120 IS 6 BP 1621 EP 1629 PG 9 WC Developmental Biology SC Developmental Biology GA NT555 UT WOS:A1994NT55500024 PM 8050368 ER PT J AU CHEN, LS KRAUSE, M SEPANSKI, M FIRE, A AF CHEN, LS KRAUSE, M SEPANSKI, M FIRE, A TI THE CAENORHABDITIS-ELEGANS MYOD HOMOLOG HLH-1 IS ESSENTIAL FOR PROPER MUSCLE FUNCTION AND COMPLETE MORPHOGENESIS SO DEVELOPMENT LA English DT Article DE HLH-1; MYOD; MYOGENIN; C-ELEGANS; MYOGENESIS ID MYOGENIC-DETERMINATION GENES; MYOSIN HEAVY-CHAIN; C-ELEGANS; PHENOTYPIC CHARACTERIZATION; REGULATORY GENE; EXPRESSION; CELLS; IDENTIFICATION; MUTATIONS; EMBRYOS AB A family of muscle-specific helix-loop-helix transcription factors (myoD, myogenin, myf-5 and MRF4) has been implicated in the control of vertebrate skeletal myogenesis. Searches for homologues of this family in Caenorhabditis elegans identified a single family member, hlh-1, which is expressed in striated muscles and their clonal precursors. We have isolated a null allele of hlh-1 following chemical mutagenesis. Animals homozygous for the null mutation produce contractile body-wall muscles, although muscle contractions are weak and coordination is defective. In addition to the evident muscle defects, mutant animals fail to complete embryonic elongation and die as larvae or young adults. Ultrastructural analysis of the mutant muscle reveals an apparently normal local lattice of thick and thin filaments, with more global defects in sarcomere organization and muscle cell placement. Mosaic studies using the point mutation and an extrachromosomal transgene indicate that the requirement for hlh-1 is fully zygotic, with no maternal hlh-1 requirement for either muscle development or viability. C1 NIDDK,MOLEC BIOL LAB,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,GRAD PROGRAM BIOL,BALTIMORE,MD. RP CHEN, LS (reprint author), CARNEGIE INST WASHINGTON,DEPT EMBRYOL,115 W UNIV PKWY,BALTIMORE,MD 21210, USA. OI Krause, Michael/0000-0001-6127-3940 FU NIGMS NIH HHS [GM37706, R01 GM037706] NR 54 TC 79 Z9 84 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD JUN PY 1994 VL 120 IS 6 BP 1631 EP 1641 PG 11 WC Developmental Biology SC Developmental Biology GA NT555 UT WOS:A1994NT55500025 PM 8050369 ER PT J AU TOYAMA, R OCONNELL, ML WRIGHT, CVE KUEHN, MR DAWID, IB AF TOYAMA, R OCONNELL, ML WRIGHT, CVE KUEHN, MR DAWID, IB TI AXIS DUPLICATION IN ZEBRAFISH EMBRYOS INDUCED BY NODAL SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892. VANDERBILT UNIV,DEPT CELL BIOL,NASHVILLE,TN 37252. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 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 JUN PY 1994 VL 163 IS 2 BP 535 EP 535 PG 1 WC Developmental Biology SC Developmental Biology GA NP335 UT WOS:A1994NP33500045 ER PT J AU BOUVET, P WOLFFE, A AF BOUVET, P WOLFFE, A TI ROLE OF THE Y-BOX PROTEIN FRGY2 IN THE CONTROL OF TRANSLATION IN XENOPUS-LAEVIS OOCYTES SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract C1 NIH,MOLEC EMBRYOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 JUN PY 1994 VL 163 IS 2 BP 537 EP 537 PG 1 WC Developmental Biology SC Developmental Biology GA NP335 UT WOS:A1994NP33500054 ER PT J AU TAYLOR, SI ACCILI, D IMAI, Y AF TAYLOR, SI ACCILI, D IMAI, Y TI INSULIN-RESISTANCE OR INSULIN DEFICIENCY - WHICH IS THE PRIMARY CAUSE OF NIDDM SO DIABETES LA English DT Article ID DEPENDENT DIABETES-MELLITUS; BETA-CELL DYSFUNCTION; PIMA-INDIANS; ISLET CELL; RECEPTOR GENE; SECRETION; MUTATIONS; GLUCOSE; GLUCOKINASE; PARENTS RP TAYLOR, SI (reprint author), NIDDK,DIABET BRANCH,BLDG 10,ROOM 8S-239,BETHESDA,MD 20892, USA. NR 38 TC 253 Z9 260 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD JUN PY 1994 VL 43 IS 6 BP 735 EP 740 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NM883 UT WOS:A1994NM88300001 PM 8194657 ER PT J AU HARRIS, MI COWIE, CC EASTMAN, R AF HARRIS, MI COWIE, CC EASTMAN, R TI HEALTH-INSURANCE COVERAGE FOR ADULTS WITH DIABETES IN THE US POPULATION SO DIABETES CARE LA English DT Article DE NHIS, NATIONAL HEALTH INTERVIEW SURVEY; IDDM, INSULIN-DEPENDENT DIABETES MELLITUS; NIDDM, NON-INSULIN-DEPENDENT DIABETES MELLITUS AB OBJECTIVE - To compare the extent and types of health insurance coverage for adults with diabetes to coverage for those without diabetes in the U.S. population. RESEARCH DESIGN AND METHODS - Nationally representative samples of 2,405 adults with diabetes and 20,131 adults who were not known to have diabetes in the U.S. completed a questionnaire on current health insurance, including coverage through Medicare, private insurance, the military, and Medicaid and other public programs. RESULTS - Among all adults with diabetes, 92.0% have some form of health insurance, including 86.5% of those 18-64 years of age and 98.8% of those greater than or equal to 65 years of age. Approximately 41% are covered by more than one health insurance mechanism, but almost 600,000 people with diabetes do not have any form of health-care coverage. Little difference was found by type of diabetes in the proportion who have health insurance. Only small differences exist between people with diabetes and those without diabetes in the percentages covered and the types of health-care coverage. Government-funded programs are responsible for health-care coverage of 57.4% of adults with diabetes, including 26.4% of those 18-64 years of age and 96.0% of those greater than or equal to 65 years of age. Private health insurance is held by 69.3% of diabetic people. Lack of private insurance appears to be attributable primarily to lower income. CONCLUSIONS - Almost all patients with diabetes who are greater than or equal to 65 years of age have health-care coverage, but 13.5% of those 18-64 years of age have no health insurance. Few differences exist in coverage between individuals with and without diabetes. However, the absence of insurance should have a substantially greater impact on the ability of patients with diabetes to obtain services necessary for care of their disease, compared with those without diabetes. Government-funded insurance mechanisms cover a large proportion of diabetic patients, which indicates a significant societal burden associated with diabetes. Any changes in government reimbursement and coverage policies could have a major impact on health care for patients with diabetes. C1 SOCIAL & SCI SYST INC,BETHESDA,MD. RP HARRIS, MI (reprint author), NIDDKD,WESTWOOD BLDG,ROOM 620,BETHESDA,MD 20892, USA. NR 13 TC 31 Z9 31 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 JUN PY 1994 VL 17 IS 6 BP 585 EP 591 DI 10.2337/diacare.17.6.585 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NN154 UT WOS:A1994NN15400010 PM 8082529 ER PT J AU MCCANCE, DR PETTITT, DJ HANSON, RL JACOBSSON, LTH BENNETT, PH KNOWLER, WC AF MCCANCE, DR PETTITT, DJ HANSON, RL JACOBSSON, LTH BENNETT, PH KNOWLER, WC TI GLUCOSE, INSULIN CONCENTRATIONS AND OBESITY IN CHILDHOOD AND ADOLESCENCE AS PREDICTORS OF NIDDM SO DIABETOLOGIA LA English DT Article DE DIABETES MELLITUS; RISK FACTORS; GLUCOSE; INSULIN; CHILDHOOD ID DEPENDENT DIABETES-MELLITUS; PIMA-INDIANS; RISK-FACTORS; FOLLOW-UP; TOLERANCE; RESISTANCE; HYPERINSULINEMIA; PARENTS; PREVALENCE; MUSCLE AB Metabolic abnormalities antedate the development of non-insulin-dependent diabetes mellitus (NIDDM) by some years. How these metabolic abnormalities relate to the genetic component of the disease and to the subsequent prediction of diabetes is unknown. The present study was designed to examine the association of parental diabetes with relative weight, fasting and 2-h plasma glucose and fasting and 2-h serum insulin in childhood, and to identify which of these variables were most predictive of subsequent NIDDM. Subjects comprised 1258 Pima Indians aged 5-19 years with normal glucose tolerance participating in a longitudinal population-based study. Age-sex-adjusted values of relative weight, fasting and 2-h glucose and fasting and 2-h insulin were positively associated with parental diabetes. Only one of 138 subjects with two non-diabetic parents developed diabetes. Among 1120 subjects with at least one diabetic parent, 101 (9.0%) developed diabetes during a mean follow up of 8.4 years. Fasting insulin was a significant predictor of diabetes, but did not add to the predictive value of relative weight. Relative weight and 2-h and fasting plasma glucose were the variables most predictive of NIDDM in childhood and adolescence. Against a background of parental diabetes, high fasting insulin concentrations predict diabetes, compatible with the hypothesis that insulin resistance is an early metabolic abnormality leading to NIDDM. In this study, however, its predictive power did not add significantly to that of relative weight, with which it was correlated. Both relative weight and 2-h plasma glucose in youth in those with diabetic parents are highly predictive of subsequent diabetes, and these may be the best measures currently available for identifying high-risk subjects in whom preventive measures might be targeted. C1 NIDDKD,PHOENIX EPIDEMIOL & CLIN RES BRANCH,DIABET & ARTHRITI EPIDEMIOL SECT,PHOENIX,AZ. MALMO GEN HOSP,DEPT RHEUMATOL,MALMO,SWEDEN. RP MCCANCE, DR (reprint author), ROYAL VICTORIA HOSP,SIR GEORGE E CLARK METAB UNIT,GROSVENOR RD,BELFAST BT12 6BA,ANTRIM,NORTH IRELAND. RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 NR 39 TC 84 Z9 89 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 JUN PY 1994 VL 37 IS 6 BP 617 EP 623 DI 10.1007/BF00403382 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NN779 UT WOS:A1994NN77900012 PM 7926348 ER PT J AU MORENOOTERO, R MURAKAWA, Y KANOF, ME CIVEIRA, MP JONES, EA JAMES, SP AF MORENOOTERO, R MURAKAWA, Y KANOF, ME CIVEIRA, MP JONES, EA JAMES, SP TI DEFECTIVE PROLIFERATION AND REGULATORY FUNCTION OF CD4+ T-CELLS BEARING LEU-8 HOMING RECEPTOR IN PRIMARY BILIARY-CIRRHOSIS SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE LEU-8; MEL-14; PRIMARY BILIARY CIRRHOSIS; PHORBOL MYRISTATE ACETATE; PROTEIN KINASE C ID PROTEIN KINASE-C; ADHESION MOLECULES; ANTIGEN RECEPTOR; IGG CHIMERA; ACTIVATION; ANTIBODY; DISEASE; INVITRO; NEUTROPHILS; ANTI-LEU-8 AB The majority of circulating CD4(+) T cells express the Leu-peripheral lymph node homing receptor, and these cells have previously been shown to have suppressor-inducer and suppressor function. In the present study, it was found that CD4(+) Leu-8(+) T cells from patients with primary biliary cirrhosis (PBC) have a significantly (P < 0.01) lower proliferative response when stimulated with phytohemagglutinin (PHA), concanavalin A (Con A), or pokeweed mitogen (PWM) compared to normal controls. The proliferative response of CD4(+), Leu-8(-) T cells was similar in patients and controls. However; the proliferative responses of CD4(+) Leu-8(+) from patients with PBC was normal when cells were stimulated with PHA, Con A, anti-CD3 monoclonal antibody, or ionomycin in combination with phorbol myristate acetate (PMA). CD4(+) T cells from patients with PBC mediated normal helper function for PWM-stimulated immunoglobulin synthesis at high T/B ratios and their regulatory function was similar to that of normal CD4(+) T cells that had been irradiated to inactivate their suppressor activity. When CD4(+) T cells from patients with PBC were precultured with the combination of Con A and PMA, they mediated potent inhibitory activity similar to that of normal CD4(+) T cells. Thus; CD4(+), Leu-8(+) T cells from patients with PBC have a defect of proliferation and suppressor function that is reversed by coculture with PMA. This finding suggests that impairment of a PMA-inducible lymphocyte activation pathway contributes to abnormal lymphocyte function in PBC. C1 NIAID,CLIN INVEST LAB,MUCOSAL IMMUN SECT,BETHESDA,MD 20892. NIDDKD,DIGEST DIS BRANCH,LIVER DIS SECT,BETHESDA,MD 20892. FU NIAID NIH HHS [AI-07439] NR 46 TC 4 Z9 4 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD JUN PY 1994 VL 39 IS 6 BP 1329 EP 1336 DI 10.1007/BF02093801 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA NR922 UT WOS:A1994NR92200025 PM 7515343 ER PT J AU ROSEBOOM, PH WELLER, JL BABILA, T AITKEN, A SELLERS, LA MOFFETT, JR NAMBOODIRI, MAA KLEIN, DC AF ROSEBOOM, PH WELLER, JL BABILA, T AITKEN, A SELLERS, LA MOFFETT, JR NAMBOODIRI, MAA KLEIN, DC TI CLONING AND CHARACTERIZATION OF THE EPSILON-ISOFORM AND ZETA-ISOFORM OF THE 14-3-3-PROTEINS SO DNA AND CELL BIOLOGY LA English DT Article ID KINASE-C INHIBITOR; AMINO-ACID-SEQUENCE; CALCIUM-DEPENDENT EXOCYTOSIS; N-ACETYLTRANSFERASE ACTIVITY; ADRENAL CHROMAFFIN CELLS; MOLECULAR-CLONING; RAT PINEAL; DEVELOPMENTAL REGULATION; TRYPTOPHAN HYDROXYLASES; NEURONAL EXPRESSION AB Two prominent proteins (30 and 33 kD) in a purified preparation of the sheep pineal gland were studied. Amino acid analysis of tryptic peptides indicated that the 33-kD protein was the epsilon isoform of the 14-3-3 family of proteins, and that the 30-kD protein was the zeta- isoform. The sheep pineal gland was found to have six other 14-3-3 isoforms in addition to the epsilon and zeta, suggesting that copurification of the epsilon and zeta forms may reflect the existence of home- or heterodimers comprised of these isoforms. To characterize 14-3-3 proteins further in the pineal gland, the full sequence of the epsilon isoform and a partial sequence of the zeta isoform were cloned from a rat pineal cDNA library and are reported here. Tissue distribution studies using Western blot analysis revealed that rat pineal and retina have levels of 14-3-3 protein similar to those found in brain, and that relatively low levels occur in other tissues. This investigation also revealed the E isoform was present at high levels in the rat pineal gland early in development and decreased steadily thereafter and that 30-kD isoforms exhibited the inverse developmental pattern. C1 NICHHD,DEV NEUROBIOL LAB,NEUROENDOCRINOL SECT,BETHESDA,MD 20892. NATL INST MED RES,PROTEIN STRUCT LAB,LONDON NW7 1AA,ENGLAND. GEORGETOWN UNIV,DEPT BIOL,WASHINGTON,DC 20057. FU NIDDK NIH HHS [DK37024] NR 49 TC 53 Z9 56 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD JUN PY 1994 VL 13 IS 6 BP 629 EP 640 DI 10.1089/dna.1994.13.629 PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA NV988 UT WOS:A1994NV98800007 PM 8024705 ER PT J AU PASCUALLEONE, A COHEN, LG BRASILNETO, JP VALLSSOLE, J HALLETT, M AF PASCUALLEONE, A COHEN, LG BRASILNETO, JP VALLSSOLE, J HALLETT, M TI DIFFERENTIATION OF SENSORIMOTOR NEURONAL STRUCTURES RESPONSIBLE FOR INDUCTION OF MOTOR EVOKED-POTENTIALS, ATTENUATION IN DETECTION OF SOMATOSENSORY STIMULI, AND INDUCTION OF SENSATION OF MOVEMENT BY MAPPING OF OPTIMAL CURRENT DIRECTIONS SO ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY LA English DT Article DE MOTOR CORTEX; SENSORY CORTEX; TRANSCRANIAL MAGNETIC STIMULATION; CURRENT DIRECTION, VECTOR; PHYSIOLOGY; ELECTROMYOGRAPHY (EMG); (HUMAN) ID FOCAL MAGNETIC STIMULATION; CORTEX; COIL; REORGANIZATION; PULSE; BRAIN AB Transcranial magnetic stimulation (TMS) of the sensorimotor cortex can evoke motor evoked potentials (MEPs), attenuation in detection of somatosensory stimuli (ADSS), and sensation of movement (SOM) referred to the same body part. In this study we tried to differentiate the substrates responsible for these effects. In 6 normal volunteers; TMS was applied with a nearly monopolar Dantec stimulator and a butterfly coil. Optimal scalp location and current direction were determined for induction of MEPs in abductor pollicis brevis (APB), first dorsal interosseous (FDI), and adductor digiti minimi (ADM); SOM in digits 2 and 5 in an ischemically paralyzed hand; and ADSS applied to digits 2 and 5. All 3 muscles' MEPs and SOM and ADSS in both digits were optimally activated from a single scalp position. In all subjects, optimal current directions for MEPs pointed anteriorly; those for ADSS and SOM pointed posteriorly. Optimal current directions showed the same progression in all subjects for MEPs (ADM, FDI, and APB from antero-lateral to antero-medial), ADSS (digit 5 postero-medial, 2 postero-lateral), and SOM (digit 1 through 5 postero-lateral to postero-medial). We conclude that neuronal networks targeting corticospinal neurons responsible for MEPs are different from those leading to SOM and ADSS (which could not be differentiated). C1 NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,HUMAN CORT PHYSIOL UNIT,BETHESDA,MD 20892. RI Brasil-Neto, Joaquim/A-1171-2009 NR 14 TC 27 Z9 28 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0013-4694 J9 ELECTROEN CLIN NEURO JI Electroencephalogr. Clin. Neurophysiol. PD JUN PY 1994 VL 93 IS 3 BP 230 EP 236 DI 10.1016/0168-5597(94)90045-0 PG 7 WC Engineering, Biomedical; Clinical Neurology SC Engineering; Neurosciences & Neurology GA NT244 UT WOS:A1994NT24400010 PM 7515800 ER PT J AU RASMUSSEN, C GAREN, C BRINING, S KINCAID, RL MEANS, RL MEANS, AR AF RASMUSSEN, C GAREN, C BRINING, S KINCAID, RL MEANS, RL MEANS, AR TI THE CALMODULIN-DEPENDENT PROTEIN PHOSPHATASE CATALYTIC SUBUNIT (CALCINEURIN-A) IS AN ESSENTIAL GENE IN ASPERGILLUS-NIDULANS SO EMBO JOURNAL LA English DT Article DE ASPERGILLUS NIDULANS; CALCINEURIN A; CALMODULIN; CELL CYCLE PROGRESSION; CNAA+ GENE ID CELL-CYCLE; SACCHAROMYCES-CEREVISIAE; KINASE; EXPRESSION; CLONING; CALCIUM; YEAST; ACTIVATION; MITOSIS; NIMA AB The gene encoding the homologue of the catalytic subunit of the Ca2+/calmodulin-regulated protein phosphatase 2B (calcineurin A) has been isolated from Aspergillus nidulans. This gene, cnaA(+), is essential in this fungal system. Analysis of growth-arrested cells following gene disruption by homologous recombination reveals that they are blocked early in the cell cycle. The cnaA(+) gene encodes a 2.5 kb mRNA and the deduced protein sequence is highly homologous to the calcineurin A subunit of other species. The mRNA varies in a cell cycle-dependent manner with maximal levels found early in G(1) and considerably before the G(1)/S boundary. As calmodulin is also essential for A.nidulans cell cycle progression and levels rise before the G(1)/S boundary, our data suggest that calcineurin may represent a primary target for calmodulin at this cell cycle transition point. C1 DUKE UNIV,MED CTR,DEPT PHARMACOL,DURHAM,NC 27710. UNIV ALBERTA,DEPT BIOCHEM,EDMONTON,AB,CANADA. UNIV ALBERTA,DEPT ANAT & CELL BIOL,EDMONTON,AB,CANADA. UNIV ALBERTA,NCI,MOLEC MECHANISMS GROWTH CONTROL GRP,EDMONTON,AB,CANADA. NIAAA,IMMUNOL SECT,ROCKVILLE,MD. NR 37 TC 57 Z9 59 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD JUN 1 PY 1994 VL 13 IS 11 BP 2545 EP 2552 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NU205 UT WOS:A1994NU20500008 PM 8013455 ER PT J AU CARACI, P NALDONI, C COSTANTINI, M ANGELI, A AF CARACI, P NALDONI, C COSTANTINI, M ANGELI, A TI CATIONIC CATEGORIZATION OF BREAST CYST FLUID AND BREAST-CANCER RISK SO ENDOCRINE-RELATED CANCER LA English DT Article; Proceedings Paper CT Workshop on Gross Cystic Breast Disease CY MAR 05, 1994 CL WROCLAW, POLAND ID ACTIVE ANDROGENS; NATURAL-HISTORY; DISEASE; SUBSEQUENT; PROTEINS; SULFATE; DEHYDROEPIANDROSTERONE; CLASSIFICATION; BIOCHEMISTRY; ASSOCIATION C1 CANC PREVENT CTR,RAVENNA,ITALY. NATL CANC INST,CLIN EPIDEMIOL UNIT,GENOA,ITALY. RP CARACI, P (reprint author), UNIV TURIN,DEPT CLIN & BIOL SCI,TURIN,ITALY. RI costantini, massimo/G-1443-2012; OI costantini, massimo/0000-0002-5293-7079 NR 56 TC 1 Z9 1 U1 1 U2 1 PU J ENDOCRINOLOGY LTD PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, ALMONDSBURY, BRISTOL, ENGLAND BS12 4NQ SN 1351-0088 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD SUM PY 1994 VL 1 IS 2 BP 15 EP 26 PG 12 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA QA945 UT WOS:A1994QA94500003 ER PT J AU CHIN, E ZHOU, J DAI, J BAXTER, RC BONDY, CA AF CHIN, E ZHOU, J DAI, J BAXTER, RC BONDY, CA TI CELLULAR-LOCALIZATION AND REGULATION OF GENE-EXPRESSION FOR COMPONENTS OF THE INSULIN-LIKE GROWTH-FACTOR TERNARY BINDING-PROTEIN COMPLEX SO ENDOCRINOLOGY LA English DT Article ID ACID-LABILE SUBUNIT; FACTOR SYSTEM; ANATOMY AB Insulin-like growth factors (IGFs) are present in the circulation, largely as part of a high mol wt complex including IGF-binding protein-3 (IGFBP-3) and an acid-labile subunit (ALS). This study used in situ hybridization to investigate the cellular sites of synthesis of these factors in the rat and to evaluate changes in transcript levels during development and after hypophysectomy and GH treatment. IGFBP-3 transcripts are considerably more abundant and widely expressed than ALS at birth, but both are present in liver and kidney. Hepatic IGFBP-3 gene expression increases slightly, whereas ALS increases dramatically in the first few weeks after birth. IGFBP-3 mRNA is concentrated in portal venous and sinusoidal endothelium, but is not detected in hepatocytes, whereas ALS mRNA is diffusely expressed by hepatocytes, but is not detected in nonparenchymal cells. Both transcripts are localized in the renal cortex; however, IGFBP-3 mRNA is concentrated in interstitial cells, whereas ALS is expressed in proximal tubule epithelium. Hypophysectomy results in a 90% reduction in hepatic ALS and an approximately 50%, decrease in IGFBP-3 mRNA level. ALS, but not IGFBP-3, transcripts were also reduced in the kidney. GPI receptor mRNA is coexpressed with ALS in liver and kidney, suggesting that the effects of GH on ALS gene expression may be direct. In summary, the fact that IGFBP-3 gene expression is far more widespread than that of ALS in both spatial and temporal parameters suggests that IGFBP-3 has a role apart from contribution to the ternary complex. We have also shown that IGFBP-3 and ALS are synthesized by distinct hepatic cell types in an anatomical organization that may serve to ensure efficient formation of the ternary complex in the blood passing through the sinusoids. Finally, the present data suggest that regulation of ALS synthesis may be the primary site of GH regulation of ternary complex formation. C1 UNIV SYDNEY,DEPT MED,SYDNEY,NSW 2006,AUSTRALIA. RP CHIN, E (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,BLDG 10-10N262,BETHESDA,MD 20892, USA. RI Baxter, Robert/F-3927-2012 OI Baxter, Robert/0000-0001-5061-2142 NR 15 TC 156 Z9 157 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 1994 VL 134 IS 6 BP 2498 EP 2504 DI 10.1210/en.134.6.2498 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NP581 UT WOS:A1994NP58100027 PM 7515002 ER PT J AU JACOBSON, JD NISULA, BC STEINBERG, AD AF JACOBSON, JD NISULA, BC STEINBERG, AD TI MODULATION OF THE EXPRESSION OF MURINE LUPUS BY GONADOTROPIN-RELEASING-HORMONE ANALOGS SO ENDOCRINOLOGY LA English DT Article ID LUTEINIZING-HORMONE; IMMUNE-RESPONSES; LHRH RECEPTORS; MESSENGER-RNA; ESTRADIOL; CELLS; RAT; ESTROGEN; MICE; TESTOSTERONE AB Recent studies have suggested that hypothalamic and pituitary hormones may directly influence the immune system. One such hormone with immunomodulatory properties is GnRH. We hypothesized that GnRH and/or the gonadotropins might alter the severity of autoimmune disease through mechanisms distinct from their effects on gonadal hormones. This possibility was tested in a murine model of lupus. We assessed disease severity over time in intact and castrated, male and female, lupus-prone (SWR x NZB) F1 hybrid mice during treatment with GnRH agonist, GnRH antagonist, or vehicle. Compared to vehicle administration, GnRH antagonist administration significantly decreased total serum immunoglobulin G and anti-DNA antibodies in castrated male and female mice and significantly improved survival. In contrast, GnRH agonist administration exerted reciprocal effects in castrated mice, leading to early increases in serum anti-DNA and total immunoglobulin G levels. We conclude that GnRH and/or the gonadotropins can modify the expression of murine lupus independently of their regulation of gonadal steroid secretion. C1 NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NIAMS,ARTHRITIS & RHEUMATISM BRANCH,BETHESDA,MD 20892. MITRE CORP,MCLEAN,VA 22102. NR 40 TC 58 Z9 58 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUN PY 1994 VL 134 IS 6 BP 2516 EP 2523 DI 10.1210/en.134.6.2516 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NP581 UT WOS:A1994NP58100029 PM 8194477 ER PT J AU MORGAN, DL DUNNICK, JK GOEHL, T JOKINEN, MP MATTHEWS, HB ZEIGER, E MENNEAR, JH AF MORGAN, DL DUNNICK, JK GOEHL, T JOKINEN, MP MATTHEWS, HB ZEIGER, E MENNEAR, JH TI SUMMARY OF THE NATIONAL TOXICOLOGY PROGRAM BENZIDINE DYE INITIATIVE SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Review DE BENZIDINE; 3,3'-DIMETHOXYBENZIDINE; CI DIRECT BLUE 15; CI ACID RED 114; CHEMISTRY; METABOLISM; CARCINOGENESIS; MUTAGENICITY; 3,3'DIMETHYLBENZIDINE; CI DIRECT BLUE 218 ID SALMONELLA MUTAGENICITY TESTS; CARCINOGENIC AROMATIC-AMINES; DIRECT BLACK 38; AZO DYES; 3,3'-DIMETHOXYBENZIDINE DIHYDROCHLORIDE; BILIARY METABOLITES; N-ACETYLBENZIDINE; TISSUE MICROSOMES; BALB/C MICE; RAT-LIVER AB The benzidine dye initiative is a research program established by the National Toxicology Program to generate an integrated body of scientific information regarding the potential health risks associated with exposure to beozidine- and benzidine-congener-derived dyes. Because an in-depth evaluation of each of the hundreds of benzidine-congener-derived dyes was considered impractical, the research program was designed to study the metabolism and disposition, genetic toxicity, and in vivo toxicity and carcinogenicity of two primary benzidine congeners, 3,3'-dimethylbenzidine and 3,3'-dimethoxybenzidine, and a select group of prototypical dyes derived from those amines. It was anticipated that by applying the basic information generated in these extensive studies, it would be possible to make regulatory decisions about other dyes after conducting only a minimal number of experiments such as studies of disposition and metabolism, and in vitro mutagenicity. This paper summarizes the results of studies conducted to evaluate the metabolism, disposition, mutagenicity, toxicity, and carcinogenicity oi representative benzidine congeners and derived dyes. C1 CAMPBELL UNIV,BUIES CREEK,NC. RP MORGAN, DL (reprint author), NIEHS,MDIF-00,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 58 TC 23 Z9 24 U1 1 U2 9 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUN PY 1994 VL 102 SU 2 BP 63 EP 78 DI 10.2307/3431822 PG 16 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA NW701 UT WOS:A1994NW70100003 PM 7925189 ER PT J AU MAKELA, S DAVIS, VL TALLY, WC KORKMAN, J SALO, L VIHKO, R SANTTI, R KORACH, KS AF MAKELA, S DAVIS, VL TALLY, WC KORKMAN, J SALO, L VIHKO, R SANTTI, R KORACH, KS TI DIETARY ESTROGENS ACT THROUGH ESTROGEN RECEPTOR-MEDIATED PROCESSES AND SHOW NO ANTIESTROGENICITY IN CULTURED BREAST-CANCER CELLS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE ANTIESTROGENS; BREAST CANCER; ESTROGEN METABOLISM; ESTROGEN RECEPTOR; GENE EXPRESSION; PHYTOESTROGENS ID KINASE INHIBITOR GENISTEIN; TYROSINE-KINASE; PHYTOESTROGENS; EXPRESSION; WOMEN; GENE AB Dietary estrogens are believed to exert their estrogenic or antiestrogenic (chemopreventive) action in estrogen responsive cells by interacting with the estrogen receptor (ER). The present study was undertaken to evaluate a direct role of ER in estrogenic or antiestrogenic activities of three dietary estrogens (coumestrol, genistein and zearalenone). HeLa cells were transiently co-transfected with an expression vector for ER and an estrogen-responsive reporter gene construct. Coumestrol, genistein, and zearalenone all increased the activity of the reporter gene, only in the presence of the ER, and the activation was blocked with the ER antagonist ICI 164,384, demonstrating an ER-specific, agonist response. In addition, in MCF-7 cells, coumestrol and zearalenone increased the expression of the estrogen-responsive pS2 gene. Coumestrol and genistein inhibited the purified estrogen-specific 17 beta-hydroxysteroid oxidoreductase enzyme and the conversion of estrone to 17 beta-estradiol in T-47D cells, which contain this enzyme. However, they did not inhibit the estrone-induced proliferation of T-47D cells. In conclusion, coumestrol, genistein, and zearalenone are all potent estrogens in vitro, and they act through ER mediated mechanism. Our findings give no evidence to support the idea that these compounds act as antiestrogens through competition for the binding sites of ER or by inhibition of the conversion of estrone to 17 beta-estradiol in breast cancer cells, since this effect was nullified by their agonist action on cell proliferation. Therefore, their suggested chemopreventive action in estrogen-related cancers must be mediated through other mechanisms. C1 NIEHS,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC 27709. UNIV TURKU,INST BIOMED,SF-20520 TURKU,FINLAND. UNIV OULU,BIOCTR,SF-90220 OULU,FINLAND. UNIV OULU,DEPT CLIN CHEM,SF-90220 OULU,FINLAND. OI Korach, Kenneth/0000-0002-7765-418X NR 24 TC 153 Z9 155 U1 0 U2 5 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUN-JUL PY 1994 VL 102 IS 6-7 BP 572 EP 578 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA PA773 UT WOS:A1994PA77300014 ER PT J AU MELNICK, RL DUNNICK, JK SANDLER, DP ELWELL, MR BARRETT, JC AF MELNICK, RL DUNNICK, JK SANDLER, DP ELWELL, MR BARRETT, JC TI TRIHALOMETHANES AND OTHER ENVIRONMENTAL-FACTORS THAT CONTRIBUTE TO COLORECTAL-CANCER SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material RP MELNICK, RL (reprint author), NIEHS,POB 12233,B3-05,RES TRIANGLE PK,NC 27709, USA. OI Sandler, Dale/0000-0002-6776-0018 NR 4 TC 12 Z9 13 U1 1 U2 3 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUN-JUL PY 1994 VL 102 IS 6-7 BP 586 EP 588 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA PA773 UT WOS:A1994PA77300016 ER PT J AU KOCHHAR, KS LINNEKIN, D IYER, AP AF KOCHHAR, KS LINNEKIN, D IYER, AP TI PDGF-INDEPENDENT ACTIVATION OF PDGF-BETA RECEPTORS IN NIH-3T3 CELLS TRANSFORMED BY C-MET PROTOONCOGENE SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; TYROSINE KINASE-ACTIVITY; SIMIAN SARCOMA-VIRUS; SCATTER FACTOR; SIGNAL TRANSDUCTION; MOLECULAR-CLONING; AUTOCRINE STIMULATION; EPITHELIAL-CELLS; B-CHAIN; PROTEIN AB We have previously reported that c-met protooncogene, a member of a new class of receptor tyrosine-kinase gene family, is transforming when overexpressed in NIH-3T3 cells. In this paper, we report that the c-met protooncogene-transformed cells proliferate in a serum- and growth factor-free medium and exhibit constitutive tyrosine phosphorylation of several cellular proteins including the met protooncogene-encoded p145 and p185. Further investigations revealed platelet-derived growth factor (PDGF)-independent phosphorylation of PDGF-beta receptors in the transformed cells. Phosphoamino acid analysis revealed phosphorylation of PDGF receptors at tyrosine and serine residues. The PDGF receptor phosphorylation is unlikely to occur via autocrine production of PDGF since we could not detect PDGF activity both at the RNA level and at a functional protein level. Additionally, phospholipase C-gamma (PLC-gamma) a substrate of activated PDGF receptors, was found to be physically associated with PDGF receptors in the absence of PDGF stimulation in transformed cells. Furthermore, PDGF receptors coimmunoprecipitated along with PLC-gamma. Taken together, our results demonstrate a PDGF-independent phosphorylation and activation of PDGF-beta receptor in NIH-3T3 cells transformed by c-met protooncogene. (C) 1994 Academic Press, Inc. C1 NCI,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,MOLEC IMMUNOREGULAT LAB,FREDERICK,MD 21701. RP KOCHHAR, KS (reprint author), NORTHWESTERN UNIV,DEPT PATHOL,DIV ORAL PATHOL,303 E CHICAGO AVE,CHICAGO,IL 60611, USA. NR 58 TC 6 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD JUN PY 1994 VL 212 IS 2 BP 414 EP 421 DI 10.1006/excr.1994.1162 PG 8 WC Oncology; Cell Biology SC Oncology; Cell Biology GA NN501 UT WOS:A1994NN50100031 PM 7514539 ER PT J AU LI, J MCCONKEY, GA ROGERS, MJ WATERS, AP MCCUTCHAN, TR AF LI, J MCCONKEY, GA ROGERS, MJ WATERS, AP MCCUTCHAN, TR TI PLASMODIUM - THE DEVELOPMENTALLY-REGULATED RIBOSOME SO EXPERIMENTAL PARASITOLOGY LA English DT Review ID RNA GENES; FALCIPARUM; IDENTIFICATION; BERGHEI C1 NIAID,MALARIA RES LAB,BETHESDA,MD 20892. LEIDEN UNIV,PARASITOL LAB,LEIDEN,NETHERLANDS. RP LI, J (reprint author), UNIFORMED SERV UNIV HLTH SCI,DEPT PREVENT MED & BIOMETR,4801 JONES BRIDGE RD,BETHESDA,MD 20814, USA. RI Waters, Andy/C-9377-2009 OI Waters, Andy/0000-0001-8900-2982 NR 15 TC 31 Z9 37 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 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD JUN PY 1994 VL 78 IS 4 BP 437 EP 441 DI 10.1006/expr.1994.1051 PG 5 WC Parasitology SC Parasitology GA NT239 UT WOS:A1994NT23900015 PM 8206146 ER PT J AU CONNOR, HD GAO, WS MASON, RP THURMAN, RG AF CONNOR, HD GAO, WS MASON, RP THURMAN, RG TI NEW REACTIVE OXIDIZING SPECIES CAUSES FORMATION OF CARBON-CENTERED RADICAL ADDUCTS IN ORGANIC EXTRACTS OF BLOOD FOLLOWING LIVER-TRANSPLANTATION SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Note DE CARBON-CENTERED RADICAL ADDUCTS; LIVER TRANSPLANTATION; ELECTRON PARAMAGNETIC RESONANCE SPECTROSCOPY; FOLCH METHOD; FREE RADICALS ID CAROLINA RINSE SOLUTION; CORONARY SINUS; SURVIVAL-TIME; RAT-LIVER; INVIVO; TETRACHLORIDE; METABOLISM; INVITRO AB alpha-(4-pyridyl-1-oxide)-N-t-butylnitrone (4-POBN) radical adducts from Folch (chloroform:methanol) extraction of blood of transplanted Livers exhibited a large 6-line electron paramagnetic resonance (EPR) spectrum. Slow EPR sample preparation involving freezing and thawing prior to extraction over 15 min yielded a spectrum assigned as a lipid-derived free radical species, whereas rapid (< 1 min) extraction without a freeze-thaw cycle yielded a mixture of radicals, one with coupling constants similar to the alpha-hydroxymethyl-4-POBN adduct (4-POBN/(CH2OH)-C-.). Extraction with purified chloroform, however, yielded a much weaker, probably lipid-derived signal. Use of C-13-methanol in the Folch extracting solution yielded a 12-line EPR spectrum, indicating that a new, highly reactive oxidant species from blood following liver transplantation can convert organic solvents used in tissue extractions to free radicals. This hypothesis was supported by simulation of EPR spectra of free radicals extracted rapidly with Folch, which indicated that the spectrum contained two carbon-centered species, one with hyperfine coupling constants similar to the alpha-methylhydroxyl-4-POBN adduct, the other probably lipid-derived. Because the former originates from methanol in the Folch, extraction of samples with alcohol free organic solvent is most likely superior when the potential for formation of stable oxidant species exists, such as after liver transplantation. C1 UNIV N CAROLINA,DEPT PHARMACOL,HEPATOBIOL & TOXICOL LAB,CHAPEL HILL,NC 27599. KENTUCKY WESLEYAN COLL,DEPT CHEM,OWENSBORO,KY 42301. NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. FU NCEH CDC HHS [NIEHS 5T32ESO7126]; NIAAA NIH HHS [AA-09156] NR 14 TC 11 Z9 11 U1 0 U2 1 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 JUN PY 1994 VL 16 IS 6 BP 871 EP 875 DI 10.1016/0891-5849(94)90207-0 PG 5 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA NL951 UT WOS:A1994NL95100026 PM 8070695 ER PT J AU LEVY, AD BAUMANN, MH VANDEKAR, LD AF LEVY, AD BAUMANN, MH VANDEKAR, LD TI MONOAMINERGIC REGULATION OF NEUROENDOCRINE FUNCTION AND ITS MODIFICATION BY COCAINE SO FRONTIERS IN NEUROENDOCRINOLOGY LA English DT Review DE COCAINE; ACTH; CORTICOSTERONE; PROLACTIN; RENIN; SEROTONIN ID HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; CORTICOTROPIN-RELEASING-FACTOR; DORSAL RAPHE NUCLEUS; ANTERIOR-PITUITARY HORMONES; VENTRAL TEGMENTAL AREA; PLASMA-RENIN ACTIVITY; ALPHA-2-ADRENERGIC RECEPTOR AGONISTS; ENHANCED SEROTONERGIC TRANSMISSION; INHIBITORY DOPAMINERGIC REGULATION; POSTSYNAPTIC 5-HT(1A) RECEPTORS AB Neuroendocrine pharmacology represents a potentially valuable approach to the assessment of alterations in neuronal function in the brain of human cocaine abusers. Neuroendocrine effects of the monoamine uptake inhibitor cocaine have predominantly been examined in laboratory animals. These preclinical studies may help to identify the optimal challenge tests to be performed in clinical studies. In laboratory animals, acute administration of cocaine activates the hypothalamic-pituitary-adrenal axis, via actions on serotonergic and dopaminergic neurons in the brain. Cocaine also reduces prolactin secretion, probably by dopaminergic mechanisms, although the necessary studies to confirm this hypothesis have not been performed. Cocaine also reduces renin secretion, and increases vasopressin and luteinizing hormone secretion, by mechanisms which have not been clearly established. The adrenocorticotropin, corticosterone, prolactin, and renin responses to cocaine are generally unaltered by prior cocaine exposure, suggesting that tolerance or sensitization to the endocrine effects of cocaine does not occur. However, several studies have determined that prior cocaine exposure alters the serotonergic regulation of hormone secretion. Chronic cocaine exposure reduces some of the hormone responses to the serotonin (5-HT) releasers p-chloroamphetamine and d-fenfluramine, suggesting deficits in the functional status of serotonergic nerve terminals. Additionally, repeated cocaine exposure produces subsensitive 5-HT1A-mediated hormone responses, and supersensitive 5-HT2-mediated responses. Alterations in dopaminergic- or noradrenergic-mediated hormone responses have not been examined in animals chronically exposed to cocaine. Endocrine studies in human cocaine abusers have largely examined basal hormone levels or the hormone responses to cocaine. Strong conclusions from these studies are limited because (1) many neuronal and nonneuronal systems regulate secretion of each hormone, so that alterations in basal hormone levels cannot be attributed to only one neurotransmitter; and (2) hormone responses to cocaine cannot he examined in cocaine-naive subjects due to ethical considerations, making it impossible to determine whether the response in cocaine abusers is abnormal. It may be more beneficial for studies in cocaine abusers to examine the hormone responses to drugs that specifically affect monoaminergic neurons and compare the data with cocaine-naive individuals. (C) 1994 Academic Press, Inc. C1 NIDA,ADDICT RES CTR,CLIN PSYCHOPHARMACOL SECT,BALTIMORE,MD 21224. LOYOLA UNIV,STRITCH SCH MED,DEPT PHARMACOL,MAYWOOD,IL 60153. RP LEVY, AD (reprint author), CHILDRENS NATL MED CTR,BRAIN RES CTR,111 MICHIGAN AVE NW,WASHINGTON,DC 20010, USA. NR 359 TC 56 Z9 57 U1 2 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0091-3022 J9 FRONT NEUROENDOCRIN JI Front. Neuroendocrinol. PD JUN PY 1994 VL 15 IS 2 BP 85 EP 156 DI 10.1006/frne.1994.1006 PG 72 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA PE342 UT WOS:A1994PE34200001 PM 7813744 ER PT J AU MAEDA, H DANEL, C CRYSTAL, RG AF MAEDA, H DANEL, C CRYSTAL, RG TI ADENOVIRUS-MEDIATED TRANSFER OF HUMAN LIPASE COMPLEMENTARY-DNA TO THE GALLBLADDER SO GASTROENTEROLOGY LA English DT Article ID CYSTIC-FIBROSIS GENE; HUMAN PANCREATIC LIPASE; IDENTIFICATION; INSUFFICIENCY; CLONING; INVIVO; INFECTIVITY; EPITHELIUM; NUTRITION; TYPE-5 C1 CORNELL UNIV,MED CTR,NEW YORK HOSP,DIV PULM & CRIT CARE MED,NEW YORK,NY 10021. RP MAEDA, H (reprint author), NHLBI,PULM BRANCH,ROOM 6D03,BLDG 10,BETHESDA,MD 20892, USA. NR 44 TC 36 Z9 36 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUN PY 1994 VL 106 IS 6 BP 1638 EP 1644 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA NP350 UT WOS:A1994NP35000030 PM 8194711 ER PT J AU MCDONALD, JP ROTHSTEIN, R AF MCDONALD, JP ROTHSTEIN, R TI UNREPAIRED HETERODUPLEX DNA IN SACCHAROMYCES-CEREVISIAE IS DECREASED IN RAD1 RAD52-INDEPENDENT RECOMBINATION SO GENETICS LA English DT Article ID SPONTANEOUS MITOTIC RECOMBINATION; DIRECT-REPEAT RECOMBINATION; MISMATCH REPAIR GENE; STRAND-BREAK REPAIR; NUCLEOTIDE-SEQUENCE; INTRACHROMOSOMAL RECOMBINATION; STREPTOCOCCUS-PNEUMONIAE; SALMONELLA-TYPHIMURIUM; ESCHERICHIA-COLI; YEAST SUGGESTS AB A direct repeat recombination assay between SUP4 heteroalleles detects unrepaired heteroduplex DNA (hDNA) as sectored colonies. The frequency of unrepaired heteroduplex is dependent on the mismatch and is highest in a construct that generates C:C or G:G mispairs and lowest in one that generates T:G or C:A mispairs. In addition, unrepaired hDNA increases for all mismatches tested in pms1 mismatch repair-deficient strains. These results support the notion that hDNA is formed across the SUP4 repeats during the recombination event and is then subject to mismatch repair. The effects of various repair and recombination defective mutations on this assay were examined. Unrepaired heteroduplex increases significantly only in rad52 mutant strains. In addition, direct repeat recombination is reduced 2-fold in rad52 mutant strains, while in rad51, rad54, rad55 and rad57 mutants direct repeat recombination is increased 3-4-fold. Mutations in the excision repair gene, RAD1, do not affect the frequency of direct repeat recombination. However, the level of unrepaired heteroduplex is slightly decreased in rad1 mutant strains. Similar to previous studies, rad1 rad52 double mutants show a synergistic reduction in direct repeat recombination (35-fold). Interestingly, unrepaired heteroduplex is reduced 4-fold in the double mutants. Experiments with shortened repeats suggest that the reduction in unrepaired heteroduplex is due to decreased hDNA tract length in the double mutant strain. RP MCDONALD, JP (reprint author), NICHHD,SDRRM,BETHESDA,MD 20892, USA. FU NCI NIH HHS [CA21111]; NHGRI NIH HHS [HG00452]; NIGMS NIH HHS [GM34587] NR 90 TC 71 Z9 71 U1 0 U2 0 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD JUN PY 1994 VL 137 IS 2 BP 393 EP 405 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA NM107 UT WOS:A1994NM10700007 PM 8070653 ER PT J AU ZABAROVSKY, ER KASHUBA, VI PETTERSSON, B PETROV, N ZAKHARYEV, V GIZATULLIN, R LEBEDEVA, T BANNIKOV, V POKROVSKAYA, ES ZABAROVSKA, VI ALLIKMETS, R ERLANDSSON, R DOMNINSKY, D SUMEGI, J STANBRIDGE, EJ WINBERG, G UHLEN, M KISSELEV, LL KLEIN, G AF ZABAROVSKY, ER KASHUBA, VI PETTERSSON, B PETROV, N ZAKHARYEV, V GIZATULLIN, R LEBEDEVA, T BANNIKOV, V POKROVSKAYA, ES ZABAROVSKA, VI ALLIKMETS, R ERLANDSSON, R DOMNINSKY, D SUMEGI, J STANBRIDGE, EJ WINBERG, G UHLEN, M KISSELEV, LL KLEIN, G TI SHOT-GUN SEQUENCING STRATEGY FOR LONG-RANGE GENOME MAPPING - A PILOT-STUDY SO GENOMICS LA English DT Article ID RENAL-CELL CARCINOMA; HUMAN CHROMOSOME-3; GENE MARKERS; CPG ISLANDS; SHORT ARM; CONSTRUCTION; REGION AB We have recently proposed a strategy for construction of long-range physical maps based on random sequencing of NotI linking and jumping clones. Here, we present results of sequence comparison between 168 NotI linking (100 of them were sequenced from both sides) and 81 chromosome 3-specific jumping clones. We were able to identify 14 NotI jumping clones (17%), each joined with two NotI linking clones. The average size of chromosomal jumps was about 650 kb. The assembled 42 NotI genomic fragments correspond to 12-15% of chromosome 3. These results demonstrate the value of random sequencing of NotI linking and jumping clones for genome mapping. This mapping proposal can be used for connecting physical and genetic maps of the human genome and will be a valuable supplement to YAC and cosmid library based mapping projects. (C) 1994 Academic Press, Inc. C1 VA ENGELHARDT MOLEC BIOL INST,MOSCOW 117984,RUSSIA. UKRAINIAN ACAD SCI,INST MOLEC BIOL & GENET,KIEV 252627,UKRAINE. ROYAL INST TECHNOL,DEPT BIOCHEM & BIOTECHNOL,S-10044 STOCKHOLM,SWEDEN. VECTOR INC,NOVOSIBIRSK,RUSSIA. NCI,FREDERICK,MD 21702. NAT RES CTR HEMATOL,MOSCOW,RUSSIA. UNIV NEBRASKA,MED CTR,DEPT PATHOL & MICROBIOL,OMAHA,NE 68198. UNIV CALIF IRVINE,COLL MED,DEPT MICROBIOL & MOLEC GENET,IRVINE,CA 92717. RP ZABAROVSKY, ER (reprint author), KAROLINSKA INST,CTR MICROBIOL & TUMOR BIOL,S-17177 STOCKHOLM,SWEDEN. RI Zabarovsky, Eugene/A-6645-2010; Winberg, Gosta/I-5686-2013; OI Winberg, Gosta/0000-0002-3371-4056 FU NCI NIH HHS [5 RO1 CA14054-15]; NIDCD NIH HHS [P01DC01813-01] NR 22 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 0888-7543 J9 GENOMICS JI Genomics PD JUN PY 1994 VL 21 IS 3 BP 495 EP 500 DI 10.1006/geno.1994.1307 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA NT135 UT WOS:A1994NT13500005 PM 7959725 ER PT J AU BUXTON, RS WHEELER, GN PIDSLEY, SC MARSDEN, MD ADAMS, MJ JENKINS, NA GILBERT, DJ COPELAND, NG AF BUXTON, RS WHEELER, GN PIDSLEY, SC MARSDEN, MD ADAMS, MJ JENKINS, NA GILBERT, DJ COPELAND, NG TI MOUSE DESMOCOLLIN (DSC3) AND DESMOGLEIN (DSG1) GENES ARE CLOSELY LINKED IN THE PROXIMAL REGION OF CHROMOSOME-18 SO GENOMICS LA English DT Article ID CELL-ADHESION MOLECULES; AMINO-ACID-SEQUENCE; N-CADHERIN GENE; DESMOSOMAL CADHERINS; PEMPHIGUS-VULGARIS; LINKAGE MAP; HYBRIDS; GLYCOPROTEIN; ASSIGNMENT; EXPRESSION AB Mouse cDNA clones coding for a desmocollin and a desmoglein, desmosomal cadherins that are putative adhesion molecules of the desmosome type of cell-cell junction characteristically found in epithelial tissues, have been isolated and sequenced. From sequence comparisons with the known human and bovine desmosomal cadherins, these clones represent a mouse Dsc3 and Dsg1. By interspecific backcross analysis, these genes were found to be closely linked in the proximal region of mouse chromosome 18, a region having conserved synteny with human chromosome 18. From these results, and recently reported linkage of DSG1 and DSG2 on human chromosome 18 at 18q12.1 in a deletion panel of somatic cell hybrids, all the desmosomal cadherins genes so far examined are clustered on chromosome 18 in human and mouse, which may have implications for gene expression. We further show that the human DSC3 gene, previously reported to be located on chromosome 9, also maps to human chromosome 18. (C) 1994 Academic Press, Inc. C1 MIT,CTR CANC RES,DEPT BIOL,CAMBRIDGE,MA 02139. NCI,FREDERICK CANC RES & DEV CTR,ABL,MAMMALIAN GENET LAB,BASIC RES PROGRAM,FREDERICK,MD 21702. RP BUXTON, RS (reprint author), NATL INST MED RES,EUKARYOT MOLEC GENET LAB,MILL HILL,LONDON NW7 1AA,ENGLAND. RI Wheeler, Grant/D-3023-2009 FU NCI NIH HHS [N01-CO-74101, R01 CA17007] NR 41 TC 32 Z9 34 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JUN PY 1994 VL 21 IS 3 BP 510 EP 516 DI 10.1006/geno.1994.1309 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA NT135 UT WOS:A1994NT13500007 PM 7959727 ER PT J AU YAMANAKA, S JOHNSON, ON NORFLUS, F BOLES, DJ PROIA, RL AF YAMANAKA, S JOHNSON, ON NORFLUS, F BOLES, DJ PROIA, RL TI STRUCTURE AND EXPRESSION OF THE MOUSE BETA-HEXOSAMINIDASE GENES, HEXA AND HEXB SO GENOMICS LA English DT Article ID N-ACETYLHEXOSAMINIDASE-A; SEQUENCE-ANALYSIS; ALPHA-SUBUNIT; EXTENSIVE HOMOLOGY; ACTIVATOR PROTEIN; HUMAN ENZYME; CDNA; CLONING; ORGANIZATION; CHAIN AB Two genes, HEXA and HEXB, encode the alpha- and beta-subunits, respectively, of human beta-hexosaminidase. In the mouse, the corresponding genes are termed Hexa and Hexb. The subunits dimerize to yield three isozymes, beta-hexosaminidase A (alpha beta), B (beta beta), and S (alpha alpha), that have the capacity to degrade a variety of substrates containing beta-linked N-acetylglucosamine and N-acetylgalactosamine residues. Mutations in the HEXA or HEXB gene resulting in a beta-hexosaminidase deficiency cause Tay-Sachs or Sandhoff disease, respectively. As a prelude to the creation of mouse models of these lysosomal storage diseases, we have characterized the molecular biology of the mouse beta-hexosaminidase system. Protein sequences derived from the cloned Hexa and Hexb cDNAs were 55% identical to each other and were also very similar to the cognate human sequences: 84% sequence identity with human HEXA and 75% with HEXB. The mouse hexosaminidase subunits, when expressed in HeLa cells from the cDNAs, displayed specificity toward synthetic substrates similar to the human subunits. The Hexa and Hexb genes were 25 and 22 kb in length, respectively. Each gene was divided into 14 exons, with the positions of introns precisely matching those of the corresponding human genes. The 5' flanking regions of the mouse genes demonstrated promoter activity as ascertained by their ability to drive chloramphenicol acetyltransferase gene expression in transfected NIH 3T3 cells. The sequences of these regulatory regions were G + C-rich in the 200 bp upstream of the respective initiator ATGs. Several putative promoter elements were present, including Sp1, AP2, CAAT, and TATA motifs. The widespread tissue distribution of the Hexa and Hexb transcripts conformed to the housekeeping role of the enzyme. However, the expression pattern of the genes was not coincident, implying tissue-specific differences in promoter function. (C) 1994 Academic Press, Inc. C1 NIDDKD,GENET & BIOCHEM BRANCH,BIOCHEM GENET SECT,BETHESDA,MD 20892. RI Proia, Richard/A-7908-2012 NR 43 TC 43 Z9 46 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JUN PY 1994 VL 21 IS 3 BP 588 EP 596 DI 10.1006/geno.1994.1318 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA NT135 UT WOS:A1994NT13500016 PM 7959736 ER PT J AU SPRING, J GOLDBERGER, OA JENKINS, NA GILBERT, DJ COPELAND, NG BERNFIELD, M AF SPRING, J GOLDBERGER, OA JENKINS, NA GILBERT, DJ COPELAND, NG BERNFIELD, M TI MAPPING OF THE SYNDECAN GENES IN THE MOUSE - LINKAGE WITH MEMBERS OF THE MYC GENE FAMILY SO GENOMICS LA English DT Article ID HEPARAN-SULFATE PROTEOGLYCAN; MOLECULAR-CLONING; CORE PROTEINS; EXPRESSION; LOCALIZATION; EVOLUTION; MAP; ORGANIZATION; SEQUENCE; GENOME AB The syndecans are a family of four cell surface heparan sulfate proteoglycans in vertebrates that mediate a variety of cell behaviors, including cell adhesion and the action of growth factors. Their core proteins contain conserved transmembrane and cytoplasmic domains but divergent extracellular regions in which only the glycosaminoglycan attachment sites are conserved. By extensive PCR analyses based on the conserved sequences, we find only four syndecan-related sequences in the mouse. These correspond to the previously described core proteins of syndecan proteoglycans from other vertebrates. We have mapped the genes for syndecan-2 to chromosome 15, syndecan-3 to chromosome 4, and syndecan-4 to chromosome 2 in the mouse. Together with the previous localization of the gene for syndecan-1 to chromosome 12, these data establish that the four syndecan genes are dispersed on different chromosomes and that each syndecan gene is located near a member of the nye gene family. Synd1 is next to Nmyc, Synd2 close to myc, Synd3 near Lmyc, and Synd4 on the same chromosome as Bmyc. The physical relationship between the members of these two gene families appears to be ancient and conserved after the two genome duplications thought to have occurred during vertebrate evolution. (C) 1994 Academic Press, Inc. C1 HARVARD UNIV,SCH MED,JOINT PROGRAM NEONATOL,BOSTON,MA 02115. NCI,FREDERICK CANC RES & DEV CTR,ABL,MAMMALIAN GENET LAB,BASIC RES PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N0I-CO-74101, CA28735]; NICHD NIH HHS [HDO6763] NR 35 TC 21 Z9 21 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JUN PY 1994 VL 21 IS 3 BP 597 EP 601 DI 10.1006/geno.1994.1319 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA NT135 UT WOS:A1994NT13500017 PM 7959737 ER PT J AU KOU, K JAMES, PL CLEMMONS, DR COPELAND, NG GILBERT, DJ JENKINS, NA ROTWEIN, P AF KOU, K JAMES, PL CLEMMONS, DR COPELAND, NG GILBERT, DJ JENKINS, NA ROTWEIN, P TI IDENTIFICATION OF 2 CLUSTERS OF MOUSE INSULIN-LIKE GROWTH-FACTOR BINDING-PROTEIN GENES ON CHROMOSOME-1 AND CHROMOSOME-11 SO GENOMICS LA English DT Note ID LINKAGE MAP; LOCALIZATION; ORGANIZATION; GENOME AB The genes for insulin-like growth factor binding proteins (IGFBPs) encode secreted proteins that bind insulin-like growth factors I and II with high affinity and modulate their biological activities. In this report we have used interspecific backcross mapping and gene cloning to define the chromosomal locations of 4 mouse Igfbp genes. Igfbp1 and 3 are found in the proximal part of chromosome 1. In the human genome these two loci map within 20 kb of one another on chromosome 7p14-p12, and the genes are organized in a tail-to-tail configuration. Mouse Igfbp2 and 5 colocalize to a proximal region of chromosome 1 that is syntenic with human chromosome 2q33-q36, and the two genes are 5 kb apart in a tail-to-tail orientation. These results suggest an evolutionary scheme in which a primordial IGFBP gene duplicated to form a cluster that was later replicated to create second linkage group. (C) 1994 Academic Press, Inc. C1 WASHINGTON UNIV,SCH MED,DEPT BIOCHEM & MOLEC BIOPHYS,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DEPT MED,ST LOUIS,MO 63110. UNIV N CAROLINA,SCH MED,DEPT MED,CHAPEL HILL,NC 27599. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101]; NHLBI NIH HHS [HL26309]; NIDDK NIH HHS [DK42748, R01 DK042748] NR 21 TC 14 Z9 15 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JUN PY 1994 VL 21 IS 3 BP 653 EP 655 DI 10.1006/geno.1994.1329 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA NT135 UT WOS:A1994NT13500027 PM 7525452 ER PT J AU AVRAHAM, KB GIVOL, D AVIVI, A YAYON, A COPELAND, NG JENKINS, NA AF AVRAHAM, KB GIVOL, D AVIVI, A YAYON, A COPELAND, NG JENKINS, NA TI MAPPING OF MURINE FIBROBLAST GROWTH-FACTOR RECEPTORS REFINES REGIONS OF HOMOLOGY BETWEEN MOUSE AND HUMAN-CHROMOSOMES SO GENOMICS LA English DT Note ID EXPRESSION; PROTEIN AB The genes for the fibroblast growth factor receptors Fgfr2, Fgfr3, and Fgfr4 have been mapped in the mouse using an interspecific backcross mapping panel. The Fgfr loci map to previously defined regions of homology between human and mouse chromosomes and provide additional information regarding human/mouse comparative mapping. (C) 1994 Academic Press, Inc. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. WEIZMANN INST SCI,DEPT CHEM IMMUNOL,IL-76100 REHOVOT,ISRAEL. FU NCI NIH HHS [N01-CO-74101]; NIGMS NIH HHS [1F32GM15909-01] NR 16 TC 24 Z9 24 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JUN PY 1994 VL 21 IS 3 BP 656 EP 658 DI 10.1006/geno.1994.1330 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA NT135 UT WOS:A1994NT13500028 PM 7959747 ER PT J AU KOZAK, CA FILIE, J ADAMSON, MC CHEN, Y YU, L AF KOZAK, CA FILIE, J ADAMSON, MC CHEN, Y YU, L TI MURINE CHROMOSOMAL LOCATION OF THE MU-OPIOID AND KAPPA-OPIOID RECEPTOR GENES SO GENOMICS LA English DT Note ID MOLECULAR-CLONING; EXPRESSION AB Opioid receptors are the membrane proteins that mediate the pain-relieving effect of opioid drugs, such as morphine and fentanyl as well as endogenous opioid peptides enkephalins and endorphins. Using cDNAs for the mu and the kappa opioid receptors, we mapped the chromosomal locations of their genes in mouse. Multilocus cross analysis located the mu receptor gene Oprm on Chr 10 and the kappa receptor gene Oprk1 on Chr 1. Both genes are near centromere, with no markers more centromeric. These data indicate that the two opioid receptors are different gene products, ruling out the possibility that they may be differential splicing products from the same gene. (C) 1994 Academic Press, Inc. C1 INDIANA UNIV,SCH MED,DEPT MED & MOLEC GENET,INDIANAPOLIS,IN 46202. NIAID,DEPT MED & MOLEC GENET,BETHESDA,MD 20892. FU NINDS NIH HHS [NS01557, NS28190] NR 19 TC 49 Z9 49 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JUN PY 1994 VL 21 IS 3 BP 659 EP 661 DI 10.1006/geno.1994.1331 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA NT135 UT WOS:A1994NT13500029 PM 7959748 ER PT J AU MCBRIDE, OW YI, HF SRIVASTAVA, M AF MCBRIDE, OW YI, HF SRIVASTAVA, M TI THE HUMAN CYTOCHROME B561 GENE (CYB561) IS LOCATED AT 17Q11-QTER SO GENOMICS LA English DT Note ID ADRENAL CHROMAFFIN GRANULES; ELECTRON-TRANSPORT; MEMBRANES; PROTEIN C1 NIDDKD,CELL BIOL & GENET LAB,BETHESDA,MD 20892. NCI,BIOCHEM LAB,BETHESDA,MD 20892. NR 12 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 0888-7543 J9 GENOMICS JI Genomics PD JUN PY 1994 VL 21 IS 3 BP 662 EP 663 DI 10.1006/geno.1994.1332 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA NT135 UT WOS:A1994NT13500030 PM 7959749 ER PT J AU GALLO, V PATNEAU, DK MAYER, ML VACCARINO, FM AF GALLO, V PATNEAU, DK MAYER, ML VACCARINO, FM TI EXCITATORY AMINO-ACID RECEPTORS IN GLIAL PROGENITOR CELLS - MOLECULAR AND FUNCTIONAL-PROPERTIES SO GLIA LA English DT Article DE O-2A PROGENITORS; CG-4 CELLS; KAINATE RECEPTORS; GLUTAMATE CHANNELS; NGFI-A ID IMMEDIATE EARLY GENES; RAT CEREBELLAR CULTURES; GLUTAMATE RECEPTOR; NERVOUS-SYSTEM; C-FOS; OLIGODENDROCYTE DEVELOPMENT; KAINATE RECEPTORS; TYPE-2 ASTROCYTES; MACROGLIAL CELLS; CORPUS-CALLOSUM AB We have analyzed the molecular and biophysical properties of glutamate-gated channels in cells of the oligodendrocyte lineage, using both the CG-4 primary cell line (Louis et al: J. Neurosci. Res. 31:193-204, 1992a) and oligodendrocyte progenitors purified from the rat cerebral cortex. CG-4 progenitor cells, as well as primary progenitors, were stained with a specific anti-GABA antibody. In whole-cell patch-clamp recordings, rapid perfusion of the agonists L-glutamate, kainate, and AMPA produced rapidly desensitizing currents in CG-4 cells. NMDA was ineffective. Both rapidly desensitizing and steady-state components of responses to kainate were inhibited by the kainate/AMPA receptor antagonist CNQX. Northern blot analysis of total mRNA isolated from CG-4 cells revealed co-expression of both AMPA- and kainate-preferring glutamate receptor subunits. The activation of glutamate receptors in CG-4 cells caused a rapid and transient elevation of mRNAs for the immediate early gene NGFI-A. (C) 1994 Wiley-Liss, Inc. C1 YALE UNIV,CTR CHILD STUDY,NEW HAVEN,CT 06510. RP GALLO, V (reprint author), NICHHD,CELLULAR & MOLEC NEUROPHYSIOL LAB,BLDG 49,ROOM 5A-78,BETHESDA,MD 20892, USA. RI Mayer, Mark/H-5500-2013; OI Vaccarino, Flora/0000-0003-2167-981X NR 54 TC 77 Z9 77 U1 1 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0894-1491 J9 GLIA JI Glia PD JUN PY 1994 VL 11 IS 2 BP 94 EP 101 DI 10.1002/glia.440110204 PG 8 WC Neurosciences SC Neurosciences & Neurology GA NP160 UT WOS:A1994NP16000003 PM 7927651 ER PT J AU MIDURA, RJ SALUSTRI, A CALABRO, A YANAGISHITA, M HASCALL, VC AF MIDURA, RJ SALUSTRI, A CALABRO, A YANAGISHITA, M HASCALL, VC TI HIGH-RESOLUTION SEPARATION OF DISACCHARIDE AND OLIGOSACCHARIDE-ALDITOLS FROM CHONDROITIN SULFATE, DERMATAN SULFATE AND HYALURONAN USING CARBOPAC PA1 CHROMATOGRAPHY SO GLYCOBIOLOGY LA English DT Article DE BOROHYDRIDE REDUCTION; GLYCOSAMINOGLYCANS; INTEGRATED PULSED AMPEROMETRY ID HEPARAN-SULFATE PROTEOGLYCANS; ANION-EXCHANGE CHROMATOGRAPHY; PULSED AMPEROMETRIC DETECTION; FIBROBLAST GROWTH-FACTOR; PERFORMANCE LIQUID-CHROMATOGRAPHY; CAPILLARY ZONE ELECTROPHORESIS; SWARM RAT CHONDROSARCOMA; PROTEIN-LINKAGE REGION; HIGH-AFFINITY RECEPTOR; CELL-OOCYTE COMPLEX AB Recent literature indicates that specific glycosaminoglycan structures are involved in various biological processes, such as anticoagulation, growth factor activation and viral infection. The initial step in the structural analysis of glycosaminoglycans is a definitive compositional analysis of its characteristic disaccharide repeat structures. Current chromatographic or electrophoretic procedures may have limitations in analysing glycosaminoglycan samples that are in low abundance, contain novel structures that need to be further characterized, or are metabolically labelled from radioactive precursors as a result of biosynthetic experiments. This study presents a new methodology for analysing disaccharides and oligosaccharides derived from chondroitin sulphate, dermatan sulphate and hyaluronan that fulfils the above criteria. The procedure involves the separation of reduced forms of these glycoconjugates on a CarboPac PA1 column using alkaline eluants. This study adopted a strategy which uses specific enzymes to release these disaccharides from their glycosaminoglycan forms. A borohydride reduction reaction was modified to be compatible with the buffer conditions commonly used with these enzymes in order to quantitatively reduce the disaccharides to their alditol forms (thereby stabilizing them to alkaline pH). Chromatography conditions were established which separated all known disaccharide alditol structures from chondroitin sulphate, dermatan sulphate and hyaluronan with extremely high resolution in a single run. Integrated pulsed amperometry was compared to UV absorbance measurement at 232 nm as two sensitive methods for detecting these reduced disaccharides; most of them could be routinely detected in the range of 50-500 ng. Data are presented applying this method to quantify hyaluronan in a biological sample which contains similar to 5000 cells and only similar to 10 ng of hyaluronan. Additional data are presented to demonstrate that this procedure will also separate oligosaccharide alditols derived from hyaluronan. C1 UNIV ROMA TOR VERGATA, FAC MED, DEPT SANITA PUBBL & BIOL CELLULARE, I-00173 ROME, ITALY. NIDR, BONE RES BRANCH, BETHESDA, MD 20892 USA. RP MIDURA, RJ (reprint author), UNIV IOWA, DEPT ORTHOPAED SURG, 180 MED LABS, IOWA CITY, IA 52242 USA. NR 48 TC 35 Z9 36 U1 0 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 EI 1460-2423 J9 GLYCOBIOLOGY JI Glycobiology PD JUN PY 1994 VL 4 IS 3 BP 333 EP 342 DI 10.1093/glycob/4.3.333 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NV781 UT WOS:A1994NV78100012 PM 7949659 ER PT J AU MORENOOTERO, R CIVEIRA, MP SUOU, T KANOF, ME JAMES, SP JONES, EA AF MORENOOTERO, R CIVEIRA, MP SUOU, T KANOF, ME JAMES, SP JONES, EA TI REDUCED NUMBERS OF CD8+ T-CELLS AND B-CELL EXPRESSION OF LEU-8 ANTIGEN IN PERIPHERAL-BLOOD OF PATIENTS WITH PRIMARY BILIARY-CIRRHOSIS SO HEPATO-GASTROENTEROLOGY LA English DT Article DE PRIMARY BILIARY CIRRHOSIS; LEU-8 ANTIGEN; PERIPHERAL BLOOD LYMPHOCYTES; T-CELLS; B-CELLS ID MONOCLONAL-ANTIBODY; HUMAN-LYMPHOCYTES; RHEUMATOID-FACTOR; LIVER-DISEASE; SUBSETS; ANTI-LEU-8; INVITRO; DEFICIENCY; ACTIVATION; SECRETION AB The presence of Leu-8 antigen, the human homologue of the murine MEL-14 peripheral lymph node homing receptor, defines subsets of peripheral blood mononuclear cells (PBMC) with different functions. Since it has been suggested that abnormal function of Leu-8 subsets may contribute to the immunopathogenesis of primary biliaryx cirrhosis (PBC), this study was undertaken to define whether abnormal expression of the Leu-8 antigen occurs in this disease. We studied 25 PBC patients, 12 with other chronic liver diseases, and 21 normal controls. PBMC were tested by direct immunofluorescence using monoclonal antibodies and flow cytometry. In PBC the proportion of PBMC that were CD4+ was normal; in contrast, the proportion that were CD8+ was decreased (p < 0.01). A negative correlation was found between absolute numbers of CD8+ T cells and total serum bilirubin levels (r=-0.50, p<0.05). The distribution of Leu-8 antigen on T cells was normal; however, the proportion of PBMC that were B cells was increased (p < 0.01) and the fraction of these that were Leu-8 negative was also increased (p < 0.01). The expression of antigens of activation on B cells was similar to that for normal controls. These findings suggest that in peripheral blood of PBC patients reduced numbers of T cells may occur due to a selective intrahepatic sequestration of CD8+ T cells, and that the decreased expression of Leu-8 antigen by B cells may be associated with their participation in autoimmune processes. C1 NIDDKD,DIGEST DIS BRANCH,LIVER DIS SECT,BETHESDA,MD. NIAID,CLIN INVEST LAB,MUCOSAL IMMUN SECT,BETHESDA,MD 20892. FU NIAID NIH HHS [AI-07 439] NR 32 TC 10 Z9 10 U1 0 U2 0 PU H G E UPDATE MEDICAL PUBL LTD. PI ATHENS PA PO BOX 17160, ATHENS GR-10024, GREECE SN 0172-6390 J9 HEPATO-GASTROENTEROL JI Hepato-Gastroenterol. PD JUN PY 1994 VL 41 IS 3 BP 239 EP 243 PG 5 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA NW901 UT WOS:A1994NW90100008 PM 7525431 ER PT J AU DESMET, VJ GERBER, M HOOFNAGLE, JH MANNS, M SCHEUER, PJ AF DESMET, VJ GERBER, M HOOFNAGLE, JH MANNS, M SCHEUER, PJ TI CLASSIFICATION OF CHRONIC HEPATITIS - DIAGNOSIS, GRADING AND STAGING SO HEPATOLOGY LA English DT Article ID CHRONIC ACTIVE HEPATITIS; PRIMARY BILIARY-CIRRHOSIS; ENDOPLASMIC-RETICULUM AUTOANTIBODIES; MICROSOME ANTIBODY TYPE-1; C VIRUS-INFECTION; AUTOIMMUNE-HEPATITIS; CONTROLLED TRIAL; VIRAL-HEPATITIS; INTERFERON-ALFA; LIVER C1 CATHOLIC UNIV LEUVEN,DEPT PATHOL,B-3000 LOUVAIN,BELGIUM. TULANE UNIV,DEPT PATHOL,NEW ORLEANS,LA 70118. NIDDKD,DIV DIGEST DIS & NUTR,BETHESDA,MD 20892. HANNOVER MED SCH,ZENTRUM INNERE MED,DEPT GASTROENTEROL & HEPATOL,W-3000 HANNOVER,GERMANY. ROYAL FREE HOSP,DEPT HISTOPATHOL,LONDON NW3 2QG,ENGLAND. UNIV LONDON SCH MED,LONDON,ENGLAND. NR 43 TC 2080 Z9 2142 U1 14 U2 49 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JUN PY 1994 VL 19 IS 6 BP 1513 EP 1520 DI 10.1016/0270-9139(94)90250-X PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA NP547 UT WOS:A1994NP54700028 PM 8188183 ER PT J AU CARDON, LR CARMELLI, D FABSITZ, RR REED, T AF CARDON, LR CARMELLI, D FABSITZ, RR REED, T TI GENETIC AND ENVIRONMENTAL CORRELATIONS BETWEEN OBESITY AND BODY-FAT DISTRIBUTION IN ADULT MALE TWINS SO HUMAN BIOLOGY LA English DT Article ID CARDIOVASCULAR-DISEASE; MASS INDEX; ADOPTION; FOLLOW; RISK; MEN AB Genetic and environmental correlations between measures of obesity [body mass index (BMI)] and body fat distribution [waist/hip ratio (WHR) and subscapular/triceps ratio (SSTR)] were examined in 133 monozygotic and 129 dizygotic pairs of elderly white male twins, age 59 to 70 years, participating in the third cardiovascular examination of the National Heart, Lung, and Blood Institute Twin Study, The BMI, WHR, and SSTR fat measures were significantly correlated in these twins, with BMI more closely related to WHR (r = 0.52) than to SSTR (r = 0.18), and the WHR-SSTR association intermediate (r = 0.27). Multivariate genetic analyses of the three indexes using the LISREL modeling approach indicated a significant heritable component for each fatness variable, h(2) = 0.66, 0.46, and 0.25 for BMI, WHR, and SSTR, respectively, and a significant correlation between genetic influences on BMI and WHR (genetic r = 0.51). The common genetic component accounted for 54% of the observed BMI-WHR correlation, suggesting that overall obesity and abdominal adiposity distribution are mediated to some extent by similar genetic influences. The genetic correlations between SSTR and BMI and between SSTR and WHR were not significantly different from zero, suggesting that genetic influences on skinfold distribution are independent of those on abdominal body fat and overall obesity. The genetic findings support the hypothesis that the WHR and SSTR indexes do not assess the same dimensions of fat patterning. C1 NHLBI,BETHESDA,MD 20892. INDIANA UNIV,DEPT MED GENET,INDIANAPOLIS,IN 46204. RP CARDON, LR (reprint author), SRI INT,HLTH SCI PROGRAM,MENLO PK,CA 94025, USA. FU NIAAA NIH HHS [ADAMHA AA08925] NR 28 TC 32 Z9 32 U1 0 U2 0 PU WAYNE STATE UNIV PRESS PI DETROIT PA 4809 WOODWARD AVE, DETROIT, MI 48201-1309 SN 0018-7143 J9 HUM BIOL JI Hum. Biol. PD JUN PY 1994 VL 66 IS 3 BP 465 EP 479 PG 15 WC Biology; Genetics & Heredity SC Life Sciences & Biomedicine - Other Topics; Genetics & Heredity GA NF063 UT WOS:A1994NF06300008 PM 8026816 ER PT J AU COUTURE, LA MULLEN, CA MORGAN, RA AF COUTURE, LA MULLEN, CA MORGAN, RA TI RETROVIRAL VECTORS CONTAINING CHIMERIC PROMOTER/ENHANCER ELEMENTS EXHIBIT CELL-TYPE-SPECIFIC GENE-EXPRESSION SO HUMAN GENE THERAPY LA English DT Article ID MURINE LEUKEMIA-VIRUS; LONG TERMINAL REPEAT; HEMATOPOIETIC STEM-CELLS; THYMIDINE KINASE GENE; EMBRYONAL CARCINOMA; PACKAGING CELLS; ENHANCER; SEQUENCES; LINE; CONSTRUCTION AB Retroviral vectors were constructed in which the U3 promoter/enhancer of Moloney murine leukemia (MoMLV) was replaced by the corresponding region from five related murine retroviruses-AKR murine leukemia virus (AKV), Harvey murine sarcoma virus (HaMSV), myeloproliferative sarcoma virus (MPSV), SL3-3, and the NZB-xenotropic virus (Xeno). In these vectors the chimeric long terminal repeat (chLTR) drives the expression of the chloramphenicol acetyl transferase (CAT) reporter gene that is followed by an internal SV40 virus early region promoter linked to the neomycin phosphotransferase II (NEO) gene. As an initial measure of the relative promoter/enhancer strength of the chLTR vectors, the murine NIH-3T3 cell line and the human JURKAT cell lines were transfected and assayed for CAT reporter activity. Relative to the MoMLV vector, the HaMSV construct was the most active in NIH-3T3 cells whereas the SL3-3 vector displayed the greatest activity in JURKAT cells. Retroviral vector producer cell populations and cell clones were established for each chLTR vector, and all were capable of yielding high vector titers (>10(5) G418(R) cfu/ml on NIH-3T3). Supernatant from these cells was used to transduce both mouse and human cell lines and primary cells. In NIH-3T3 cells and two murine fibrobrosarcoma cell lines, the HaMSV chLTR vector was slightly more active than the MoMLV chLTR vector. In the human HepG2 and HeLa cell lines, the MPSV chLTR vector was the most active. Data from the human JURKAT T-cell line and a T cell line derived from an ADA-deficient severe combined immunodeficiency (SCID) patient demonstrate that the SL3-3 chLTR is the most active in these lymphoid cell lines. The greatest difference in the comparison of the different chLTR vectors was observed in primary human umbilical vein endothelial cells, where the MoMLV vector produced up to 100 times more CAT activity than the SL3-3 vector. These data suggest that the use of specific promoter/enhancer elements may lead to higher levels of gene expression following retroviral-mediated gene transfer into specific cell types and these observations may be useful in the design of human gene therapy experiments. C1 NHLBI,BETHESDA,MD 20892. NCI,BETHESDA,MD 20892. NR 55 TC 33 Z9 33 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JUN PY 1994 VL 5 IS 6 BP 667 EP 677 DI 10.1089/hum.1994.5.6-667 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA NU779 UT WOS:A1994NU77900002 PM 7948129 ER PT J AU RIVERO, JL LACORAZZA, HD KOZHICH, A NUSSENBLATT, RB JENDOUBI, M AF RIVERO, JL LACORAZZA, HD KOZHICH, A NUSSENBLATT, RB JENDOUBI, M TI RETROVIRUS-MEDIATED GENE-TRANSFER AND EXPRESSION OF HUMAN ORNITHINE DELTA-AMINOTRANSFERASE INTO EMBRYONIC FIBROBLASTS SO HUMAN GENE THERAPY LA English DT Article ID BETA-GLOBIN GENE; GYRATE ATROPHY; FACTOR-IX; LYMPHOCYTES; THERAPY; CELLS; HEPATOCYTES; DEFICIENCY; MOUSE; SAFE AB Ornithine delta aminotransferase (OAT) is a nuclear-encoded mitochondrial matrix enzyme that catalyzes the reversible transamination of ornithine to glutamate semialdehyde. In humans, genetic deficiency of OAT results in gyrate atrophy of the choroid and retina, a blinding chorioretinal degeneration usually beginning in late childhood. This disorder has been shown to be autosomal recessive, and is often caused by missense, nonsense, and/or frameshift mutations in the OAT gene. With the view of applying gene therapy, a Moloney murine leukemia virus (MoMLV)-based recombinant retrovirus vector has been constructed. The human OAT cDNA was placed under the control of the enhancer-promoter regulatory elements derived from the MoMLV long terminal repeat (LTR). The construct was transfected into the retroviral packaging cell lines GP + E - 86 and psi CRIP to produce virus particles. Supernatant from these OAT retrovirus producer cell lines were used to transduce mouse C57Bl/6 embryonal fibroblasts. We showed that the recombinant retrovirus transfers the OAT gene to the recipient cells, which produce an OAT RNA transcript when analyzed by Northern blot. Western blot analysis and enzymatic assays confirmed the presence of an OAT polypeptide that has a high enzymatic activity in the transduced cell lines, even after a long period of time in vitro. C1 NEI,IMMUNOL LAB,BETHESDA,MD 20892. NR 24 TC 8 Z9 8 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JUN PY 1994 VL 5 IS 6 BP 701 EP 707 DI 10.1089/hum.1994.5.6-701 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA NU779 UT WOS:A1994NU77900005 PM 7948132 ER PT J AU ROOTWELT, H CHOU, J GHAL, WA BERGER, R COSKUN, T BRODTKORB, E KVITTINGEN, EA AF ROOTWELT, H CHOU, J GHAL, WA BERGER, R COSKUN, T BRODTKORB, E KVITTINGEN, EA TI 2 MISSENSE MUTATIONS CAUSING TYROSINEMIA TYPE-1 WITH PRESENCE AND ABSENCE OF IMMUNOREACTIVE FUMARYLACETOACETASE SO HUMAN GENETICS LA English DT Article ID HEREDITARY TYROSINEMIA; NUCLEOTIDE-SEQUENCE; DNA-POLYMERASE; PLASMID DNA; HYDROLASE; IDENTIFICATION; EXPRESSION; PROTEIN; PATIENT; CLONING AB Hereditary tyrosinemia type 1, due to a deficiency of fumarylacetoacetase (FAH), is characterized by progressive liver damage and renal tubular dysfunction and may occur in an acute or a chronic form. An Ala 134 to Asp (GCT to GAT) transition was found in one Turkish and two Norwegian patients with chronic tyrosinemia. SphI digestion of polymerase chain reaction (PCR) amplified genomic DNA identified the mutation and showed that the patients were heterozygous. All these patients had immunoreactive FAH protein in fibroblasts. Another Norwegian patient with chronic disease, without FAH immunoreactive material in fibroblasts, had a Pro 342 to Leu mutation (CCG to CTG). This mutation was identified by MspI digestion of PCR amplified genomic DNA, and the patient was heterozygous. Northern blotting showed FAH mRNA of normal size and amounts in all patients. Site directed mutagenesis and translation in a rabbit reticulocyte lysate demonstrated that both mutations abolished FAH activity. C1 NICHHD,BETHESDA,MD 20892. WILHILMINA KINDERZIEKENHUIS,UTRECHT,NETHERLANDS. HACETTEPE UNIV,INST CHILD HLTH,ANKARA,TURKEY. RP ROOTWELT, H (reprint author), UNIV OSLO,RIKSHOSP,INST CLIN BIOCHEM,N-0027 OSLO,NORWAY. NR 28 TC 20 Z9 21 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD JUN PY 1994 VL 93 IS 6 BP 615 EP 619 DI 10.1007/BF00201558 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA NP565 UT WOS:A1994NP56500001 PM 8005583 ER PT J AU GLAVAC, D RAVNIKGLAVAC, M OBRIEN, SJ DEAN, M AF GLAVAC, D RAVNIKGLAVAC, M OBRIEN, SJ DEAN, M TI POLYMORPHISMS IN THE 3' UNTRANSLATED REGION OF THE I-KAPPA-B/MAD-3 (NFKBI)GENE LOCATED ON CHROMOSOME-14 SO HUMAN GENETICS LA English DT Note ID NF-KAPPA-B; DNA-BINDING SUBUNIT; POINT MUTATIONS; REL; GENES; NFKB2; LOCI; P50 AB The NF-kappa B transcription factor regulates the expression of a number of genes, including immune function and growth control loci, and several viruses. For example, the long terminal repeat of the human immunodeficiency virus contains NF-kappa B binding sites. NF-kappa B activity in the nucleus is regulated by a cellular inhibitory protein I kappa B. To analyze the potential role of these genes in genetic disease we have mapped the NF-kappa B (NFKB2) and I kappa B/MAD-3 (NFKBI) loci in a panel of somatic cell hybrids to chromosomes 4 and 14, respectively. Amplification of the 3' untranslated region of NFKBI allows the detection of three independent polymorphisms within 410 bp. In combination these polymorphisms were informative in 27 of 36 CEPH families and allowed the gene to be placed onto the linkage map of chromosome 14, between the D14S32 and D14S42 markers. C1 NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. PROGRAM RESOURCES INC,GEN DYNAM CORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 NR 22 TC 14 Z9 14 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD JUN PY 1994 VL 93 IS 6 BP 694 EP 696 DI 10.1007/BF00201573 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA NP565 UT WOS:A1994NP56500016 PM 8005595 ER PT J AU PHIPPS, ME LATIF, F PROWSE, A PAYNE, SJ DIETZBAND, J LEVERSHA, M AFFARA, NA MOORE, AT TOLMIE, J SCHINZEL, A LERMAN, MI FERGUSONSMITH, MA MAHER, ER AF PHIPPS, ME LATIF, F PROWSE, A PAYNE, SJ DIETZBAND, J LEVERSHA, M AFFARA, NA MOORE, AT TOLMIE, J SCHINZEL, A LERMAN, MI FERGUSONSMITH, MA MAHER, ER TI MOLECULAR-GENETIC ANALYSIS OF THE 3P--SYNDROME SO HUMAN MOLECULAR GENETICS LA English DT Article ID VONHIPPEL-LINDAU DISEASE; DINUCLEOTIDE REPEAT POLYMORPHISMS; TUMOR-SUPPRESSOR GENE; HUMAN CHROMOSOME-3; LINKAGE MAP; SHORT ARM; DELETION; IDENTIFICATION; HYBRIDIZATION; 3P25-PTER AB Molecular genetic analysis of five cases of 3p - syndrome (del(3)(qter-->p25:)) was performed to investigate the relationship between the molecular pathology and clinical phenotype. Fluorescence in situ hybridization studies and analysis of polymorphic DNA markers from chromosome 3p25 - p26 demonstrated that all four informative cases had distal deletions. However, the extent of the deletion was variable: in two patients with the most extensive deletions the deletion breakpoint mapped between RAF1 and D3S1250, in one patient the deletion breakpoint was between D3S1250 and D3S601, and in two patients the deletion commenced telomeric to D3S601 (and telomeric to D3S1317 in one of these). All five patients displayed the classical features of 3p - syndrome (mental retardation, growth retardation, microcephaly, ptosis and micrognathia) demonstrating that loss of sequences centromeric to D3S1317 is not required for expression of the characteristic 3p - syndrome phenotype. The three patients with the most extensive deletions had cardiac septal defects suggesting that a gene involved in normal cardiac development is contained in the interval D3S1250 and D3S18. The PMCA2 gene is contained within this region and deletion of this gene may cause congenital heart defects. At least three patients were deleted for the von Hippel - Lindau (VHL) disease gene although none had yet developed evidence of VHL disease. We conclude that molecular analysis of 3p - syndrome patients enhances the management of affected patients by identifying those at risk for VHL disease, and can be used to elucidate the critical regions for the 3p - syndrome phenotype. C1 UNIV CAMBRIDGE,ADDENBROOKES HOSP,DEPT PATHOL,CAMBRIDGE CB2 2QQ,ENGLAND. NCI,FREDERICK CANC RES FACIL,IMMUNOBIOL LAB,FREDERICK,MD. ADDENBROOKES HOSP,GENET MOLEC LAB,CAMBRIDGE,ENGLAND. MOLEC ONCOL INC,GAITHERSBURG,MD 20877. ADDENBROOKES HOSP,DEPT OPHTHALMOL,CAMBRIDGE,ENGLAND. DUNCAN GUTHRIE INST MED GENET,GLASGOW G3 8SJ,SCOTLAND. UNIV ZURICH,INST MED GENET,ZURICH,SWITZERLAND. RI MAHER, EAMONN/A-9507-2008 OI MAHER, EAMONN/0000-0002-6226-6918 NR 22 TC 37 Z9 39 U1 0 U2 5 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 JUN PY 1994 VL 3 IS 6 BP 903 EP 908 DI 10.1093/hmg/3.6.903 PG 6 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA NU390 UT WOS:A1994NU39000009 PM 7951234 ER PT J AU SAXENA, R SHAW, GL RELLING, MV FRAME, JN MOIR, DT EVANS, WE CAPORASO, N WEIFFENBACH, B AF SAXENA, R SHAW, GL RELLING, MV FRAME, JN MOIR, DT EVANS, WE CAPORASO, N WEIFFENBACH, B TI IDENTIFICATION OF A NEW VARIANT CYP2D6 ALLELE WITH A SINGLE-BASE DELETION IN EXON-3 AND ITS ASSOCIATION WITH THE POOR METABOLIZER PHENOTYPE SO HUMAN MOLECULAR GENETICS LA English DT Article ID LUNG-CANCER; SPARTEINE POLYMORPHISM; DEBRISOQUINE; GENE; MUTATIONS; SUSCEPTIBILITY; POPULATION; OXIDATION; GENOTYPE; DEFECT AB The human CYP2D6 gene codes for the enzyme, debrisoquine 4-hydroxylase, which metabolizes over 25 therapeutically important drugs. The inability to metabolize these drugs, which results in a 'poor metabolizer' (PM) phenotype, can be attributed, in some cases, to the presence of any of three previously described mutations in the CYP2D6 gene. To identify new alleles responsible for the PM phenotype, we have examined the CYP2D6 gene from individuals whose phenotypes were not consistent with their apparent genotypes. DNA sequencing revealed a single base deletion in exon 3, T1795, resulting in a frame shift and generating a stop codon one codon after the deletion. A PCR-based test was designed for this new allele (designated CYP2DG(T)) and 236 unrelated individuals from a lung cancer case control study were tested for the presence of the CYP2DG(T) mutation. Eight unrelated individuals were found to carry the D6(T) allele. Four subjects also carry the non-functional D6(B) allele and the drug metabolism phenotypes of these four D6(B)/D6(T) individuals are consistent with the D6m allele being responsible for reduced debrisoquine 4-hydroxylase activity. The frequency of the D6(T) allele among Caucasian controls of the case-control study was 1.8% (4/220 chromosomes). C1 COLLABORAT RES INC, DEPT HUMAN GENET & MOLEC BIOL, WALTHAM, MA 02154 USA. NCI, BIOMARKERS & PREVENT RES BRANCH, ROCKVILLE, MD 20850 USA. ST JUDE CHILDRENS RES HOSP, DEPT PHARMACEUT, MEMPHIS, TN 38101 USA. UNIV TENNESSEE, COLL PHARM, MEMPHIS, TN 38101 USA. UNIV TENNESSEE, COLL MED, MEMPHIS, TN 38101 USA. NATL NAVAL MED CTR, DEPT INTERNAL MED, DIV MED ONCOL, BETHESDA, MD 20889 USA. NCI, GENET EPIDEMIOL BRANCH, FAMILY STUDIES SECT, BETHESDA, MD 20892 USA. FU NCI NIH HHS [CA21765, NCI N43-CP-05694, R37 CA36401] NR 24 TC 93 Z9 98 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUN PY 1994 VL 3 IS 6 BP 923 EP 926 DI 10.1093/hmg/3.6.923 PG 4 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA NU390 UT WOS:A1994NU39000013 PM 7951238 ER PT J AU ROSEN, DR BOWLING, AC PATTERSON, D USDIN, TB SAPP, P MEZEY, E MCKENNAYASEK, D OREGAN, J RAHMANI, Z FERRANTE, RJ BROWNSTEIN, MJ KOWALL, NW BEAL, MF HORVITZ, HR BROWN, RH AF ROSEN, DR BOWLING, AC PATTERSON, D USDIN, TB SAPP, P MEZEY, E MCKENNAYASEK, D OREGAN, J RAHMANI, Z FERRANTE, RJ BROWNSTEIN, MJ KOWALL, NW BEAL, MF HORVITZ, HR BROWN, RH TI A FREQUENT ALA-4 TO VAL SUPEROXIDE DISMUTASE-1 MUTATION IS ASSOCIATED WITH A RAPIDLY PROGRESSIVE FAMILIAL AMYOTROPHIC-LATERAL-SCLEROSIS SO HUMAN MOLECULAR GENETICS LA English DT Article ID RECOMBINANT HUMAN; SPINAL-CORD; GENE; SEQUENCE; BRAIN; DNA; CHROMOSOME-21; POLYMORPHISMS; NEUROTOXICITY; PROTEINS AB Familial amyotrophic lateral sclerosis (FALS), a degenerative disorder of motor neurons, is associated with mutations in the Cu/Zn superoxide dismutase gene SOD1 in some affected families. We confirm a recently reported ala4-->val mutation in exon 1 of the SOD1 gene and report that this mutation is both the most commonly detected of all SOD1 mutations and among the most clinically severe. By comparision with our other FALS families, the exon 1 mutation is associated with reduced survival time after onset: 1.2 years, as compared to 2.5 years for all other FALS patients. We also demonstrate that SOD1 is prominently expressed in normal motor neurons and that neural expression of SOD1 is not prevented by this exon 1 mutation. Assays of SOD1 enzymatic activity in extracts from red blood cells, lymphoblastoid cells, and brain tissues revealed an approximately 50% reduction in activity of cytosolic SOD1 in patients with this mutation compared to normal individuals. By contrast, patients with sporadic ALS had normal levels of SOD1 enzymatic activity. Why this SOD1 mutation causes motor neuron death in FALS remains to be established. While it may be that FALS is a consequence of loss of SOD1 function, it is also possible that motor neuron death in this dominantly inherited disease occurs because the mutations confer an additional, cytotoxic function on the SOD1 protein. C1 MASSACHUSETTS GEN HOSP E,DAY NEUROMUSCULAR RES LAB,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP E,NEUROCHEM LAB,BOSTON,MA 02129. MASSACHUSETTS GEN HOSP E,NEUROL SERV,BOSTON,MA 02129. ELANOR ROOSEVELT INST CANC RES,DENVER,CO. UNIV COLORADO,HLTH SCI CTR,DENVER,CO. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. MIT,HOWARD HUGHES MED INST,DEPT BIOL,CAMBRIDGE,MA 02139. BEDFORD VA MED CTR,CTR GERIATR RES EDUC & CLIN,BEDFORD,MA. BOSTON UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02118. BOSTON UNIV,SCH MED,DEPT PATHOL,BOSTON,MA 02118. RI Kowall, Neil/G-6364-2012 OI Kowall, Neil/0000-0002-6624-0213 FU DS NIH HHS [NINDS16367]; NIAAA NIH HHS [NIAA-G05134]; NINDS NIH HHS [1PO1NS31248-01] NR 42 TC 119 Z9 119 U1 1 U2 4 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 JUN PY 1994 VL 3 IS 6 BP 981 EP 987 DI 10.1093/hmg/3.6.981 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA NU390 UT WOS:A1994NU39000024 PM 7951249 ER PT J AU ORTMANN, O CATT, KJ SCHULZ, KD EMONS, G AF ORTMANN, O CATT, KJ SCHULZ, KD EMONS, G TI MODULATORY ACTION OF PROGESTERONE AND PROGESTERONE ANTAGONISTS ON HYPOTHALAMIC-PITUITARY FUNCTION SO HUMAN REPRODUCTION LA English DT Article; Proceedings Paper CT Symposium on Progesterone Antagonists in Reproductive Medicine and Oncology CY 1992 CL NEW YORK, NY DE ANTIPROGESTINS; HYPOTHALAMUS; LH SECRETION; PITUITARY; PROGESTERONE ID GONADOTROPIN-RELEASING-HORMONE; LUTEINIZING-HORMONE; MENSTRUAL-CYCLE; PROTEIN-KINASE; PHORBOL ESTER; LH-SECRETION; ADULT-RAT; CELLS; ESTRADIOL; RU-486 AB The ability of ovarian steroids to sensitize and desensitize the pituitary gonadotroph to hypothalamic gonadotrophin-releasing hormone (GnRH) is essential for their modulatory actions on gonadotrophin secretion. The time-dependent actions of progesterone on GnRH-stimulated gonadotrophin secretion from cultured pituitary cells obtained from female rats were examined. Progesterone induced an acute stimulatory effect on luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion in cell perifusion studies, from as early as 50 min after the onset of progesterone treatment. Long-term incubation (52 h) of pituitary cells in static culture reduced the responsiveness of the gonadotroph to GnRH. The antiprogestins RU486, ZK 98.299, and ZK 98.734 blocked both the acute facilitatory and the long-term inhibitory action of progesterone. In the absence of progesterone, the antiprogestins per se induced marked inhibitory and stimulatory effects on GnRH-stimulated LH secretion. In brief, short-term treatment of non-oestrogen-primed cells with antiprogestins was ineffective (ZK compounds) or reduced LH secretion (RU486), while long-term treatment was stimulatory. Oestrogen-primed cells exerted exclusively inhibitory effects on GnRH-induced LH secretion. In conclusion, antiprogestins are effective antagonists of progesterone actions in the gonadotroph. However, they exert diverse actions on gonadotrophin secretion in the absence of progesterone, which might interfere with their antagonistic properties. C1 UNIV MARBURG,DEPT GYNECOL,D-35033 MARBURG,GERMANY. UNIV LUBECK,D-23538 LUBECK,GERMANY. NICHHD,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892. RP ORTMANN, O (reprint author), UNIV MARBURG,DEPT OBSTET,D-35033 MARBURG,GERMANY. NR 37 TC 4 Z9 7 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD JUN PY 1994 VL 9 SU 1 BP 53 EP 62 PG 10 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA NX798 UT WOS:A1994NX79800008 PM 7962470 ER PT J AU COUTO, JR PADLAN, EA BLANK, EW PETERSON, JA CERIANI, RL AF COUTO, JR PADLAN, EA BLANK, EW PETERSON, JA CERIANI, RL TI HUMANIZATION OF KC4G3, AN ANTI-HUMAN CARCINOMA ANTIBODY SO HYBRIDOMA LA English DT Article ID MONOCLONAL-ANTIBODY; CHIMERIC ANTIBODY; VARIABLE DOMAINS; EXPRESSION; CONSTRUCTION; REGIONS; CLONING AB We have previously constructed a chimeric version of KC4G3, a murine antibody that reacts with several human epithelial cancers and binds to the human breast epithelial mucin. We have now successfully humanized KC4G3 using positional consensus data, previously compiled after examining several other antibody structures, listing residues in the V-H and V-kappa, frameworks that could influence antigen binding. We have previously showed that a fraction of the kappa chains of murine and chimeric KC4G3 migrates abnormally on SDS-PAGE most likely due to N-linked glycosylation in V-kappa. The glycosylation signal has now been removed from V-kappa, as a consequence of humanization. As expected, the humanized kappa chain migrates normally on SDS-PAGE. We detected no significant differences either in the affinities (1.6 x 10(9) M(-1) vs. 1.4 x 10(9) M(-1), respectively) or in the ability to compete for antigen binding, between the murine and the humanized antibodies. The humanized version is an IgG(1), kappa immunoglobulin produced by mouse myeloma SP2/0-Ag14 cells and is designated HuKC4v2. The HuKC4v2 frameworks conform to the VkappaII and VHIII human consensus in all but six positions in V-kappa and three positions in V-H. C1 NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892. RP COUTO, JR (reprint author), CANC RES FUND CONTRA COSTA,WALNUT CREEK,CA 94596, USA. NR 14 TC 8 Z9 8 U1 1 U2 3 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0272-457X J9 HYBRIDOMA JI Hybridoma PD JUN PY 1994 VL 13 IS 3 BP 215 EP 219 DI 10.1089/hyb.1994.13.215 PG 5 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA NW525 UT WOS:A1994NW52500006 PM 7927365 ER PT J AU BASSER, PJ AF BASSER, PJ TI FOCAL MAGNETIC STIMULATION OF AN AXON SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article ID PERIPHERAL-NERVE; ELECTROMAGNETIC INDUCTION; MODEL AB The induced electric field produced by a circular coil during magnetic stimulation of an axon is derived from Maxwell's equations. The foci and virtual cathodal and anodal regions are predicted as a function of coil radius and orientation. Two virtual anode and cathode pairs are predicted, one lying outside the coil's perimeter and predominant in the far field? and one lying within the perimeter of the coil which may stimulate the axon when the coil and nerve are in close proximity. When the coil is positioned tangent to the nerve, an orientation commonly used in clinical magnetic stimulation, the foci of the predominant cathode acid anode pair are extremely sensitive to changes tn coil placement. In addition, the radius of curvature of the activating function, a measure of the size of the virtual cathode at threshold, is predicted to decrease with decreasing coil diameter and distance to the nerve. These predictions may help explain observed variability in measurements of conduction velocity and latency during magnetic stimulation of peripheral axons. RP BASSER, PJ (reprint author), NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892, USA. RI Basser, Peter/H-5477-2011 NR 24 TC 37 Z9 37 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD JUN PY 1994 VL 41 IS 6 BP 601 EP 606 DI 10.1109/10.293248 PG 6 WC Engineering, Biomedical SC Engineering GA NX628 UT WOS:A1994NX62800011 PM 7927380 ER PT J AU CARRINGTON, M HARDING, A AF CARRINGTON, M HARDING, A TI SEQUENCE-ANALYSIS OF 2 NOVEL HLA-DMA ALLELES SO IMMUNOGENETICS LA English DT Note RP CARRINGTON, M (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702, USA. NR 4 TC 33 Z9 35 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD JUN PY 1994 VL 40 IS 2 BP 165 EP 165 PG 1 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA NR669 UT WOS:A1994NR66900015 PM 8026867 ER PT J AU AHUJA, SK GAO, JL MURPHY, PM AF AHUJA, SK GAO, JL MURPHY, PM TI CHEMOKINE RECEPTORS AND MOLECULAR MIMICRY SO IMMUNOLOGY TODAY LA English DT Review ID MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA; HUMAN INTERLEUKIN-8 RECEPTOR; FUNCTIONAL EXPRESSION; HERPESVIRUS SAIMIRI; HUMAN CYTOMEGALOVIRUS; VACCINIA VIRUS; MYXOMA VIRUS; PROTEIN; IDENTIFICATION; CELLS AB Chemokines are small pro-inflammatory peptides that are best known for their leukocyte-chemoattractant activity. The cloned leukocyte chemokine receptors, interleukin 8 receptor (IL-8R) types A and B and the macrophage inflammatory protein 1 alpha (MIP-1 alpha)/RANTES receptor, are related by sequence and chemokine binding to two herpesvirus products, and to the Duffy antigen that mediates erythrocyte invasion by the malaria-causing parasite Plasmodium vivax. Here, Sunil Ahuja, Ji-Liang Gao and Philip Murphy suggest that, in addition to the activation of leukocytes, chemokines may be important in the function of erythrocytes and, through molecular mimicry, in microbial pathogenesis. RP AHUJA, SK (reprint author), NIAID,HOST DEF LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 42 TC 102 Z9 103 U1 1 U2 3 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 JUN PY 1994 VL 15 IS 6 BP 281 EP 287 DI 10.1016/0167-5699(94)90008-6 PG 7 WC Immunology SC Immunology GA NQ722 UT WOS:A1994NQ72200008 PM 8068175 ER PT J AU BAKER, PJ HRABA, T TAYLOR, CE STASHAK, PW FAUNTLEROY, MB ZAHRINGER, U TAKAYAMA, K SIEVERT, TR HRONOWSKI, XP COTTER, RJ PEREZPEREZ, G AF BAKER, PJ HRABA, T TAYLOR, CE STASHAK, PW FAUNTLEROY, MB ZAHRINGER, U TAKAYAMA, K SIEVERT, TR HRONOWSKI, XP COTTER, RJ PEREZPEREZ, G TI MOLECULAR-STRUCTURES THAT INFLUENCE THE IMMUNOMODULATORY PROPERTIES OF THE LIPID-A AND INNER-CORE REGION OLIGOSACCHARIDES OF BACTERIAL LIPOPOLYSACCHARIDES SO INFECTION AND IMMUNITY LA English DT Article ID III PNEUMOCOCCAL POLYSACCHARIDE; SUPPRESSOR T-CELLS; ANTIBODY-PRODUCING CELLS; GRAM-NEGATIVE BACTERIA; A-SUBUNIT ANALOGS; PSEUDOMONAS-AERUGINOSA; ESCHERICHIA-COLI; HELICOBACTER-PYLORI; CELLULAR LEVEL; MICE AB The relationship between chain length as well as the position of fatty acyl groups to the ability of lipid A to abolish the expression of suppressor T-cell (Ts) activity was examined. Fatty acyl chain lengths of C-12 to C-14, as in the lipid A of Escherichia coli and Salmonella minnesota, appear to be optimal for this bioactivity, since lipid A preparations with fatty acyl groups of relatively short chain length (C-10 to C-12 for Pseudomonas aeruginosa and Chromobacterium violaceum) or predominantly long chain length (C-18 for Helicobacter pylori) are without effect. The presence of an acyloxyacyl group of appropriate chain length at the 3' position of the glucosamine disaccharide backbone of lipid A also plays a decisive role. By contrast, the lipid A proximal inner core region oligosaccharides of some bacterial lipopolysaccharides increase the expression of Ts activity; this is due mainly to the capacity of such oligosaccharides, which are relatively conserved in structure among gram-negative bacteria, to enlarge or expand upon the population of CD8(+) Ts generated during the course of a normal antibody response to unrelated microbial antigens. The minimal structure required for the expression of the added immunosuppression observed appears to be a hexasaccharide containing one 2-keto-3-deoxyoctonate residue, two glucose residues, and three heptose residues to which are attached two pyrophosphorylethanolamine groups. The relevance of these findings to virulence and to the pathogenesis of gram-negative infections is discussed. C1 NIAID, TWINBROOK RES FACIL 2, IMMUNOGENET LAB, ROCKVILLE, MD USA. FORSCHUNGSINST BORSTEL, INST EXPTL BIOL & MED, W-2061 BORSTEL, GERMANY. WILLIAM S MIDDLETON MEM VET ADM MED CTR, MYCOBACTERIOL RES LAB, MADISON, WI 53705 USA. UNIV WISCONSIN, COLL AGR & LIFE SCI, DEPT BACTERIOL, MADISON, WI 53706 USA. JOHNS HOPKINS SCH MED, DEPT PHARMACOL & MOLEC SCI, BALTIMORE, MD 21205 USA. VANDERBILT UNIV, SCH MED, DEPT MED, DIV INFECT DIS, NASHVILLE, TN 37232 USA. FU NIGMS NIH HHS [GM-36054] NR 60 TC 31 Z9 32 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUN PY 1994 VL 62 IS 6 BP 2257 EP 2269 PG 13 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA NM782 UT WOS:A1994NM78200017 PM 8188347 ER PT J AU DELACRUZ, F AF DELACRUZ, F TI SPECIAL ISSUE DEDICATED TO MENTAL-RETARDATION RESEARCH CENTERS SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Editorial Material RP DELACRUZ, F (reprint author), NICHHD,MENTAL RETARDAT & DEV DISABIL BRANCH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0736-5748 J9 INT J DEV NEUROSCI JI Int. J. Dev. Neurosci. PD JUN PY 1994 VL 12 IS 4 BP R5 EP R5 PG 1 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA PC300 UT WOS:A1994PC30000001 ER PT J AU GUO, WD BLOT, WJ LI, JY TAYLOR, PR LIU, BQ WANG, W WU, YP ZHENG, W DAWSEY, SM LI, B FRAUMENI, JF AF GUO, WD BLOT, WJ LI, JY TAYLOR, PR LIU, BQ WANG, W WU, YP ZHENG, W DAWSEY, SM LI, B FRAUMENI, JF TI A NESTED CASE-CONTROL STUDY OF ESOPHAGEAL AND STOMACH CANCERS IN THE LINXIAN NUTRITION INTERVENTION TRIAL SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article ID ESOPHAGEAL CANCER; RISK-FACTORS; CHINA; MORTALITY; DIET; POPULATION; VEGETABLES; SHANXI AB Background. Rates of oesophageal/gastric cardia cancer in Linxian, a rural county in north central China, are among the world's highest, but the risk factors are not well understood. Methods. A nested case-control study of oesophageal and stomach cancers was conducted within a cohort of 29 584 adults who participated in a randomized nutrition intervention trial. Information on participant characteristics collected during interviews before the trial began was compared between individuals who subsequently developed cancers of the oesophagus (N = 640) or stomach (N = 539), mainly cardia, and individually matched controls (control/case ratio = 5). Analyses were performed separately for oesophageal and stomach cancers using conditional logistic regression. Results. For oesophageal cancer, tobacco smoking was associated with a significantly elevated risk, with a twofold increase among long-term smokers. Alcohol consumption was uncommon and not related to risk. High consumption of eggs or fresh vegetables was associated with 20% reductions in risk, and risk significantly declined as pre-trial body mass index (BMI), an indicator of long-term nutritional status, increased. No increases in risk were associated with intake of pickled vegetables or mouldy foods, although consumption levels at the start of the trial were low. Excess risks of 40-80% were found among individuals who had reported a history of cancer, notably of the oesophagus and stomach, in parents or sibs. For stomach cancer, only low BMI was significantly associated with elevated risk. Conclusions. This study indicates that several risk factors for oesophageal and stomach cancers in Linxian, including smoking, nutritional deficiency, and familial cancer occurrence, resemble those in other areas of the world and contribute partly to the remarkably elevated rates in this area of China. C1 NCI,BETHESDA,MD. RP GUO, WD (reprint author), CHINESE ACAD MED SCI,INST CANC,BEIJING,PEOPLES R CHINA. NR 26 TC 99 Z9 103 U1 0 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD JUN PY 1994 VL 23 IS 3 BP 444 EP 450 DI 10.1093/ije/23.3.444 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PD338 UT WOS:A1994PD33800002 PM 7960367 ER PT J AU HAYASHI, T NOTKINS, AL AF HAYASHI, T NOTKINS, AL TI CLEARANCE OF LDH-5 FROM THE CIRCULATION OF INBRED MICE CORRELATES WITH BINDING TO MACROPHAGES SO INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY LA English DT Article DE ENZYME CLEARANCE; LDH-5; LACTIC DEHYDROGENASE VIRUS (LDV); MACROPHAGES ID LACTIC-DEHYDROGENASE VIRUS; ENZYME CLEARANCE AB Flow cytometry showed that the enzyme lactate dehydrogenase (LDH-5) binds to peritoneal macrophages. The degree of binding appears to be genetically controlled and varies depending on the inbred strain of mouse. The rate at which LDH-5 is cleared from the circulation correlates with the degree of binding to macrophages. These findings suggest that the binding of LDH-5 to macrophages may serve as an in-vitro index of enzyme clearance. C1 NIDR,ORAL MED LAB,BETHESDA,MD 20892. RP HAYASHI, T (reprint author), YAMAGUCHI UNIV,VET PATHOL LAB,YAMAGUCHI 753,JAPAN. NR 10 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0959-9673 J9 INT J EXP PATHOL JI Int. J. Exp. Pathol. PD JUN PY 1994 VL 75 IS 3 BP 165 EP 168 PG 4 WC Pathology SC Pathology GA NR355 UT WOS:A1994NR35500003 PM 8086313 ER PT J AU BERRY, KK SIEGAL, GP BOYD, JA SINGH, RK FIDLER, IJ AF BERRY, KK SIEGAL, GP BOYD, JA SINGH, RK FIDLER, IJ TI DEVELOPMENT OF A METASTATIC MODEL FOR HUMAN ENDOMETRIAL CARCINOMA USING ORTHOTOPIC IMPLANTATION IN NUDE-MICE SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE ENDOMETRIUM; ADENOCARCINOMA; METASTASIS; ORTHOTOPIC TRANSPLANTATION; NUDE MICE ID GROWTH-FACTOR RECEPTOR; HUMAN CANCER METASTASIS; SEROUS PAPILLARY CARCINOMA; HUMAN-COLON CARCINOMAS; CELL-LINES; EXTRACELLULAR-MATRIX; TUMOR ANGIOGENESIS; BREAST-CARCINOMA; ORGAN ENVIRONMENT; DIFFERENT SITES AB We have developed an orthotopic model for human endometrial carcinoma in nude mice. The human serous papillary endometrial carcinoma cell line SPEC-2 was injected into the subcutis (ectopic site) or uterine wall (orthotopic site) of athymic mice. Tumors grew in both locations locally. However, only uterine wall tumors produced metastases in regional and distant lymph nodes and to the lungs and liver. Cell lines were established in culture from these uterine tumors and from lung and liver metastases, and then these cells were injected into the uteri of additional mice. The metastatic potential of the lines subsequently established from tumors growing in vivo was not significantly higher than the already highly metastatic parental culture cells. All SPEC-2 cell lines expressed high levels of both 72-kDa and 92-kDa collagenase type IV activity. mRNA for transforming growth factor-alpha, basic fibroblast growth factor, and epidermal growth factor-receptor was constant among the cell lines. These data support the concept that the orthotopic implantation of human endometrial carcinoma cells into the uteri of nude mice provides a valuable model for studying the biology of human endometrial adenocarcinoma. C1 UNIV TEXAS,MD ANDERSON CANC CTR,DEPT CELL BIOL,BOX 173,1515 HOLCOMBE BLVD,HOUSTON,TX 77030. NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. UNIV ALABAMA,SCH MED,DEPT PATHOL,BIRMINGHAM,AL 35294. UNIV ALABAMA,SCH MED,DEPT CELL BIOL,BIRMINGHAM,AL 35294. UNIV ALABAMA,SCH MED,DEPT SURG,BIRMINGHAM,AL 35294. RI Siegal, Gene/A-8653-2009 NR 75 TC 6 Z9 6 U1 0 U2 1 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 JUN PY 1994 VL 4 IS 6 BP 1163 EP 1171 PG 9 WC Oncology SC Oncology GA NN515 UT WOS:A1994NN51500003 PM 21567033 ER PT J AU FONG, DS SEDDON, JM AF FONG, DS SEDDON, JM TI DIAGNOSTIC-TESTS - AN OVERVIEW SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article RP FONG, DS (reprint author), NEI,BLDG 31,ROOM 6A52,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD SUM PY 1994 VL 34 IS 3 BP 187 EP 195 DI 10.1097/00004397-199403430-00017 PG 9 WC Ophthalmology SC Ophthalmology GA PE202 UT WOS:A1994PE20200016 PM 7960513 ER PT J AU MAGNO, BV FREIDLIN, V DATILES, MB AF MAGNO, BV FREIDLIN, V DATILES, MB TI REPRODUCIBILITY OF THE NEI SCHEIMPFLUG CATARACT IMAGING-SYSTEM SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE NEI SCHEIMPFLUG CATARACT IMAGING SYSTEM; NUCLEAR CATARACTS; 99-PERCENT RANGE; DENSITOMETRY; LOCS II ID LENS OPACITIES; CLASSIFICATION; CAMERA AB Purpose. The NEI Scheimpflug Cataract Imaging System was developed to allow for easy, accurate and reproducible image analysis of nuclear cataracts. This study was undertaken to determine the reproducibility of densitometric measurements of the lens nucleus using this modified system. Methods. Replicate Zeiss Scheimpflug images of the lenses in 143 eyes were obtained by one photographer. Normal and cataractous lenses (without central cortical or anterior subcapsular opacities) were sampled. Images were stored after testing for adequacy using immediate exposure checking. Densitometry of the nuclear region was then performed for each image. The interval within which 99% of the differences between repeat measurements may be expected to lie was used as a measure of reproducibility (99% range). Results. A 99% range of +/-0.023 optical density units (odu) was obtained for nuclear densities < 0.30 odu (125 eyes). For lenses with nuclear densities greater than or equal to 0.30 odu (18 eyes), the 99% range was +/-0.14 times the first measurement. Conclusion. This study shows the excellent reproducibility of this Scheimpflug imaging system in the nuclear region and demonstrates its usefulness in studies on nuclear cataracts, particularly for natural history studies and clinical trials of anti-cataract drugs. C1 NEI,BIOMETRY & EPIDEMIOL PROGRAM,BETHESDA,MD. RP MAGNO, BV (reprint author), NEI,OPHTHALM GENET & CLIN SERV BRANCH,BLDG 10,ROOM 10N226,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. OI Datiles, Manuel III B./0000-0003-4660-1664 NR 20 TC 32 Z9 32 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 JUN PY 1994 VL 35 IS 7 BP 3078 EP 3084 PG 7 WC Ophthalmology SC Ophthalmology GA NR053 UT WOS:A1994NR05300022 PM 8206726 ER PT J AU ANDLEY, UP RHIM, JS CHYLACK, LT FLEMING, TP AF ANDLEY, UP RHIM, JS CHYLACK, LT FLEMING, TP TI PROPAGATION AND IMMORTALIZATION OF HUMAN LENS EPITHELIAL-CELLS IN CULTURE SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE LENS EPITHELIUM; HUMAN; TISSUE CULTURE; IMMORTALIZED CELLS; VIRUS; CRYSTALLINS ID TISSUE-CULTURE; NEOPLASTIC TRANSFORMATION; PROLIFERATIVE CAPACITY; CRYSTALLIN EXPRESSION; ALPHA-CRYSTALLIN; GENE-EXPRESSION; DIFFERENTIATION; INVITRO; LINE; MODEL AB Purpose. To establish primary and immortalized cell cultures of human lens epithelial cells for a model system investigating human lens epithelial physiology and cataract. Methods. Human lens epithelial cells in culture were grown by isolating epithelium fragments from infant human lenses from patients who underwent treatment for retinopathy of prematurity and by allowing epithelial cells to grow from explants. To immortalize cells, the cultures were infected with an adenovirus 12-SV40 virus (Ad12-SV40). Results. The primary cells from infant eyes proliferated for three passages before senescence was observed. However, the immortalized Cells remained proliferative and retained the morphology of the primary cells. Immunohistochemical analysis demonstrated that these immortalized cells were SV40 large T antigen-positive and ceased to produce infectious virus after a few passages. Immortalized cells passaged to population doubling levels of 76 continued to form confluent cultures within 7 days of subculture. Analysis of proteins by SDS-PAGE and immunoblotting showed that immortalized cells produce a protein with molecular weight of about 25 kD, which reacted with an antibody to beta H-crystallin. Conclusions. This report constitutes the first successful immortalization of human lens epithelial cells. Currently, two cell lines have been created (B-3 and B-4) and passaged to population doubling levels of 76 and 52, respectively. These cells may provide an important human cell line specific to in vivo human lens epithelial cell physiology and would be of interest in establishing a human model to study lens cell differentiation and the etiology of cataract. These cells may also provide a constant and reproducible source of lens epithelial cells for eye-related toxicology studies and to assay inhibitory drugs for the prevention of cataracts and posterior capsular opacification observed after cataract extraction. C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD. HARVARD UNIV,SCH MED,DEPT OPHTHALMOL,BOSTON,MA. RP ANDLEY, UP (reprint author), WASHINGTON UNIV,SCH MED,DEPT OPHTHALMOL & VISUAL SCI,CAMPUS BOX 8096,660 S EUCLID AVE,ST LOUIS,MO 63110, USA. FU NEI NIH HHS [EY02687, EY05681] NR 40 TC 160 Z9 166 U1 0 U2 4 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUN PY 1994 VL 35 IS 7 BP 3094 EP 3102 PG 9 WC Ophthalmology SC Ophthalmology GA NR053 UT WOS:A1994NR05300024 PM 8206728 ER PT J AU BULTE, JWM DOUGLAS, T MANN, S FRANKEL, RB MOSKOWITZ, BM BROOKS, RA BAUMGARNER, CD VYMAZAL, J FRANK, JA AF BULTE, JWM DOUGLAS, T MANN, S FRANKEL, RB MOSKOWITZ, BM BROOKS, RA BAUMGARNER, CD VYMAZAL, J FRANK, JA TI MAGNETOFERRITIN - BIOMINERALIZATION AS A NOVEL MOLECULAR APPROACH IN THE DESIGN OF IRON-OXIDE-BASED MAGNETIC-RESONANCE CONTRAST AGENTS SO INVESTIGATIVE RADIOLOGY LA English DT Article; Proceedings Paper CT 1993 Meeting of Contrast Media Research (CMR 93) CY OCT 03-08, 1993 CL SAN ANTONIO, TX SP BRACCO IND CHIM, MILAN, BRISTOL MYERS SQUIBB, PRINCETON, LAB GUERBET, PARIS, MALLINCKRODT MED, ST LOUIS, NYCOMED, OSLO, SCHERING, BERLIN, STERLING WINTHROP, COLLEGEVILLE, ADV MAGNET, CAMBRIDGE, ALLIANCE, SAN DIEGO, BERLEX, WAYNE, BRACCO RES, GENEVA, BYK GULDEN, KONSTANZ, COOK IMAGING, BLOOMINGTON, DAIICHI PHARM, TOKYO, IMARX, TUCSON, JUSTESA IMAGEN, MADRID, METASYN, CAMBRIDGE, MOLEC BIOSYST, SAN DIEGO, NIHON SCHERING, OSAKA, SALUTAR, SUNNYVALE DE SUPERPARAMAGNETIC IRON OXIDE; FERRITIN; MAGNETIC RESONANCE CONTRAST AGENT; RELAXOMETRY ID ESCHERICHIA-COLI; PROTEIN; CHAIN C1 NINCDS,NEUROIMAGING BRANCH,BETHESDA,MD 20892. NIH,BEIP,BETHESDA,MD. UNIV BATH,SCH CHEM,BATH BA2 7AY,AVON,ENGLAND. CALIF POLYTECH STATE UNIV SAN LUIS OBISPO,DEPT PHYS,SAN LUIS OBISPO,CA 93407. UNIV MINNESOTA,DEPT GEOL & GEOPHYS,MINNEAPOLIS,MN 55455. RP BULTE, JWM (reprint author), NIH,OID,OD,DIAGNOST RADIOL RES LAB,BLDG 10,ROOM BIN256,BETHESDA,MD 20892, USA. RI Bulte, Jeff/A-3240-2008; Mann, Stephen/D-1332-2012; Douglas, Trevor/F-2748-2011 OI Bulte, Jeff/0000-0003-1202-1610; Mann, Stephen/0000-0003-3012-8964; NR 9 TC 32 Z9 34 U1 1 U2 8 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD JUN PY 1994 VL 29 SU 2 BP S214 EP S216 DI 10.1097/00004424-199406001-00071 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NX795 UT WOS:A1994NX79500071 PM 7928235 ER PT J AU FRANK, JA MATTAY, VS DUYN, J SOBERING, G BARRIOS, FA ZIGUN, J SEXTON, R KWOK, P WOO, J MOONEN, C WEINBERGER, DR AF FRANK, JA MATTAY, VS DUYN, J SOBERING, G BARRIOS, FA ZIGUN, J SEXTON, R KWOK, P WOO, J MOONEN, C WEINBERGER, DR TI MEASUREMENT OF RELATIVE CEREBRAL BLOOD-VOLUME CHANGES WITH VISUAL-STIMULATION BY DOUBLE-DOSE GADOPENTETATE-DIMEGLUMINE-ENHANCED DYNAMIC MAGNETIC-RESONANCE-IMAGING SO INVESTIGATIVE RADIOLOGY LA English DT Article; Proceedings Paper CT 1993 Meeting of Contrast Media Research (CMR 93) CY OCT 03-08, 1993 CL SAN ANTONIO, TX SP BRACCO IND CHIM, MILAN, BRISTOL MYERS SQUIBB, PRINCETON, LAB GUERBET, PARIS, MALLINCKRODT MED, ST LOUIS, NYCOMED, OSLO, SCHERING, BERLIN, STERLING WINTHROP, COLLEGEVILLE, ADV MAGNET, CAMBRIDGE, ALLIANCE, SAN DIEGO, BERLEX, WAYNE, BRACCO RES, GENEVA, BYK GULDEN, KONSTANZ, COOK IMAGING, BLOOMINGTON, DAIICHI PHARM, TOKYO, IMARX, TUCSON, JUSTESA IMAGEN, MADRID, METASYN, CAMBRIDGE, MOLEC BIOSYST, SAN DIEGO, NIHON SCHERING, OSAKA, SALUTAR, SUNNYVALE DE MAGNETIC RESONANCE IMAGING; DYNAMIC; CONTRAST AGENT; GADOPENTETATE DIMEGLUMINE; CEREBRAL BLOOD VOLUME; FUNCTIONAL IMAGING; PHOTIC STIMULATION; CALCARINE CORTEX; LATERAL GENICULUS ID HUMAN BRAIN-FUNCTION; SENSORY STIMULATION; CORTEX; TIME; MRI; PHYSIOLOGY; PERFUSION; IMAGES; FLOW; EPI C1 NIMH,NATL CTR RES RESOURCES,IN VIVO NMR RES CTR BIOMED ENGN,BETHESDA,MD 20892. NIMH,NATL CTR RES RESOURCES,INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. NIMH,CLIN BRAIN DISORDERS BRANCH,BETHESDA,MD 20892. COMPUTAT PHYS INC,FAIRFAX,VA. RP FRANK, JA (reprint author), NIMH,OFF DIRECTOR,DIAGNOST RADIOL RES LAB,9000 ROCKVILLE PIKE,BLDG 10,ROOM B1N256,BETHESDA,MD 20892, USA. RI Duyn, Jozef/F-2483-2010; Barrios, Fernando/B-4295-2012; Barrios, Fernando/D-1591-2016; Moonen, Chrit/K-4434-2016 OI Barrios, Fernando/0000-0002-5699-4222; Moonen, Chrit/0000-0001-5593-3121 NR 28 TC 10 Z9 10 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD JUN PY 1994 VL 29 SU 2 BP S157 EP S160 DI 10.1097/00004424-199406001-00052 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NX795 UT WOS:A1994NX79500052 PM 7928216 ER PT J AU HAMM, B CLEMENT, O CAVAGNA, FM BULTE, JWM KOENIG, SH MULLER DEHAEN, C AF HAMM, B CLEMENT, O CAVAGNA, FM BULTE, JWM KOENIG, SH MULLER DEHAEN, C TI PROCEEDINGS OF THE CONTRAST-MEDIA RESEARCH SYMPOSIUM - SAN-ANTONIO, TEXAS - OCTOBER 3-8, 1993 - DISCUSSION 12 SO INVESTIGATIVE RADIOLOGY LA English DT Discussion C1 FAC MED NECKER ENFANTS MALAD,RECH IMAGERIE LAB,PARIS,FRANCE. BRACCO IND CHIM SPA,DIV RES & DEV,MILAN,ITALY. STANFORD UNIV,SCH MED,DEPT RADIOL,CONTRAST MEDIA LAB,STANFORD,CA 94305. DARTMOUTH COLL SCH MED,DEPT RADIOL,LEBANON,NH. NIH,OIR,OD,DIAGNOST RADIOL RES,BETHESDA,MD. RP HAMM, B (reprint author), HUMBOLDT UNIV BERLIN,KLINIKUM CHARITE,DEPT RADIOL,D-10117 BERLIN,GERMANY. RI Bulte, Jeff/A-3240-2008; CLEMENT, Olivier/D-5221-2014 OI Bulte, Jeff/0000-0003-1202-1610; 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 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD JUN PY 1994 VL 29 SU 2 BP S229 EP S229 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NX795 UT WOS:A1994NX79500076 ER PT J AU NUNNALLY VEXLER, VS TWEEDLE, M KOENIG, SH LANGE DUNCAN, JR WATSON, AD FRANK, JA BRASCH, RC SPECK DEHAEN, C DESSER, TS UNGER, E DEAN DAVIS, MA MATSUNAGA, T WOLF, GL CAVAGNA, FM LIPTON, MJ NUNN ADAMS AF NUNNALLY VEXLER, VS TWEEDLE, M KOENIG, SH LANGE DUNCAN, JR WATSON, AD FRANK, JA BRASCH, RC SPECK DEHAEN, C DESSER, TS UNGER, E DEAN DAVIS, MA MATSUNAGA, T WOLF, GL CAVAGNA, FM LIPTON, MJ NUNN ADAMS TI PROCEEDINGS OF THE CONTRAST-MEDIA RESEARCH SYMPOSIUM - SAN-ANTONIO, TEXAS - OCTOBER 3-8, 1993 - DISCUSSION-4 SO INVESTIGATIVE RADIOLOGY LA English DT Discussion C1 UNIV CALIF SAN FRANCISCO, DEPT RADIOL, CONTRAST MEDIA LAB, SAN FRANCISCO, CA 94143 USA. BRISTOL MYERS SQUIBB CO, PHARMACEUT RES INST, PRINCETON, NJ 08543 USA. RELAXOMETRY INC, MAHOPAC, NY 10541 USA. WASHINGTON UNIV, SCH MED, EDWARD MALLINCKRODT INST RADIOL, ST LOUIS, MO 63110 USA. NYCOMED SALUTAR INC, SUNNYVALE, CA 94086 USA. NIH, DIAGNOST RADIOL RES LAB, BETHESDA, MD 20892 USA. UNIV CALIF SAN FRANCISCO, DEPT RADIOL, CONTRAST MEDIA LAB, SAN FRANCISCO, CA 94143 USA. BRACCO IND CHIM SPA, DIV RES & DEV, I-20134 MILAN, ITALY. STANFORD UNIV, SCH MED, DEPT RADIOL, CONTRAST MEDIA LAB, STANFORD, CA 94305 USA. UNIV ARIZONA, ARIZONA HLTH SCI CTR, DEPT RADIOL, TUCSON, AZ 85724 USA. UNIV MASSACHUSETTS, MED CTR, DEPT RADIOL, DIV RADIOL RES, WORCESTER, MA 01655 USA. MASSACHUSETTS GEN HOSP E, CTR IMAGING & PHARMACEUT RES, BOSTON, MA USA. UNIV CHICAGO, DEPT RADIOL, CHICAGO, IL 60637 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD JUN PY 1994 VL 29 SU 2 BP S71 EP S74 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NX795 UT WOS:A1994NX79500024 ER PT J AU KARP, JE BRODER, S AF KARP, JE BRODER, S TI ONCOLOGY AND HEMATOLOGY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID GUANINE-NUCLEOTIDE EXCHANGE; CHRONIC MYELOGENOUS LEUKEMIA; ADAPTER PROTEIN; TYROSINE KINASE; EGF RECEPTOR; RAS; GRB2; CELLS; SOS; TRANSFORMATION RP KARP, JE (reprint author), NCI,BETHESDA,MD 20892, USA. NR 25 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 1 PY 1994 VL 271 IS 21 BP 1693 EP 1695 DI 10.1001/jama.271.21.1693 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA NN117 UT WOS:A1994NN11700035 PM 8182856 ER PT J AU GOODWIN, FK AF GOODWIN, FK TI PSYCHIATRY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID DEPRESSION; DISORDER; STRESS RP GOODWIN, FK (reprint author), NIMH,BETHESDA,MD 20892, USA. NR 18 TC 7 Z9 7 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 1 PY 1994 VL 271 IS 21 BP 1707 EP 1708 DI 10.1001/jama.271.21.1707 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA NN117 UT WOS:A1994NN11700043 PM 8182864 ER PT J AU GUO, WD CHOW, WH ZHENG, W LI, JY BLOT, WJ AF GUO, WD CHOW, WH ZHENG, W LI, JY BLOT, WJ TI DIET, SERUM MARKERS AND BREAST-CANCER MORTALITY IN CHINA SO JAPANESE JOURNAL OF CANCER RESEARCH LA English DT Article DE BREAST CANCER MORTALITY; DIET; SERUM MARKER; CHINA ID BODY IRON STORES; EPIDEMIOLOGIC EVIDENCE; ASCORBIC-ACID; RISK-FACTORS; DISEASE; FAT; SHANGHAI; WOMEN AB This county-based correlation study examined associations of breast cancer mortality with dietary habits and certain serum biochemical markers, utilizing data collected from an ecological survey in 65 Chinese rural counties. Univariate correlation and multivariate regression analysis showed that consumption of animal foods, including eggs, fish and meat, was positively linked to county-wide mortality rates of breast cancer in Chinese women. No clear associations between breast cancer mortality rates and consumption of green vegetables, carrots and fruits were observed in this study. A modest inverse correlation between serum vitamin C levels and breast cancer mortality was observed, while selenium levels were positively related to the mortality rates. Positive correlations for serum ferritin and hemoglobin were found, in agreement with recent reports of an elevated cancer risk with increased body iron stores. Limitations of these ecological data preclude causal inferences, but the findings provide clues to breast cancer risk and protective factors in a low incidence area of the world. C1 NCI,BETHESDA,MD 20892. RP GUO, WD (reprint author), CHINESE ACAD MED SCI,INST CANC,BEIJING 100021,PEOPLES R CHINA. NR 32 TC 29 Z9 29 U1 4 U2 5 PU JAPANESE CANCER ASSOCIATION PI TOKYO PA EDITORIAL OFFICE 7TH FLOOR, JOHKOH BLDG 2-23-11, KOISHIKAWA, TOKYO 112, JAPAN SN 0910-5050 J9 JPN J CANCER RES JI Jpn. J. Cancer Res. PD JUN PY 1994 VL 85 IS 6 BP 572 EP 577 PG 6 WC Oncology SC Oncology GA NT936 UT WOS:A1994NT93600003 PM 8063609 ER PT J AU OHTA, T HAYAKAWA, T ITO, A ANDO, K OZAKI, N KOGAWA, S IMAI, M YAMAGUCHI, N KOYAMA, E YAMAMOTO, S ABIRU, T IWATA, T KAYUKAWA, Y OKADA, T AF OHTA, T HAYAKAWA, T ITO, A ANDO, K OZAKI, N KOGAWA, S IMAI, M YAMAGUCHI, N KOYAMA, E YAMAMOTO, S ABIRU, T IWATA, T KAYUKAWA, Y OKADA, T TI LONG-TERM FOLLOW-UP-STUDY ON SLEEP-WAKE RHYTHM DISORDERS - COMPREHENSIVE SURVEY OF PATIENTS IN ADOLESCENT AND ADULT SO JAPANESE JOURNAL OF PSYCHIATRY AND NEUROLOGY LA English DT Article; Proceedings Paper CT 8th Workshop for the Clinical Research on Chronobiology CY SEP 30-OCT 01, 1993 CL KYOTO, JAPAN C1 FUJITA HLTH UNIV,SCH MED,DEPT PSYCHIAT,TOYOAKE,JAPAN. UCSD,DEPT PSYCHIAT,SAN DIEGO,CA. NIMH,CLIN PSYCHOBIOL BRANCH,BETHESDA,MD 20892. AKITA UNIV,SCH MED,DEPT PSYCHIAT,AKITA 010,JAPAN. KASADERA SEICHIRYO HOSP,NAGOYA,JAPAN. NAGOYA UNIV,COLL MED TECHNOL,NAGOYA,AICHI 464,JAPAN. RP OHTA, T (reprint author), NAGOYA UNIV,SCH MED,DEPT PSYCHIAT,NAGOYA,AICHI 466,JAPAN. RI Ozaki, Norio/M-8908-2014 OI Ozaki, Norio/0000-0002-7360-4898 NR 1 TC 0 Z9 0 U1 0 U2 0 PU FOLIA PUBL SOC PI TOKYO PA ACADEMIC SOCIETIES BLDG 2-4-16 YAYOI, BUNKYO-KU, TOKYO 113, JAPAN SN 0912-2036 J9 JPN J PSYCHIAT NEUR PD JUN PY 1994 VL 48 IS 2 BP 455 EP 457 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA PG185 UT WOS:A1994PG18500085 ER PT J AU ZUCCONI, SL JACOBSON, LP SCHRAGER, LK KASS, NE LAVE, JR CARSON, CA MORGENSTERN, H ARNO, PS GRAHAM, NMH SAAH, AJ PALENICEK, J ARMENIAN, H FARZADEGAN, H MARGOLICK, J MACARTHUR, J PHAIR, JP CHMIEL, J COHEN, B OGORMAN, M VARIAKOJIS, D WESCH, J WOLINSKY, S DETELS, R VISSCHER, B CHEN, I DUDLEY, J FAHEY, J GIORGI, J LEE, M MARTINEZMAZA, O MILLER, E NISHANIAN, P TAYLOR, J ZACK, J RINALDO, C KINGSLEY, L BECKER, J GUPTA, P HO, M MUNOZ, A BEATY, T EPSTEIN, L GALAI, N HOOVER, D MEINERT, C NELSON, K PIANTADOSI, S SU, S SCHRAGER, L VERMUND, S KASLOW, R VANRADEN, M SEMINARA, D AF ZUCCONI, SL JACOBSON, LP SCHRAGER, LK KASS, NE LAVE, JR CARSON, CA MORGENSTERN, H ARNO, PS GRAHAM, NMH SAAH, AJ PALENICEK, J ARMENIAN, H FARZADEGAN, H MARGOLICK, J MACARTHUR, J PHAIR, JP CHMIEL, J COHEN, B OGORMAN, M VARIAKOJIS, D WESCH, J WOLINSKY, S DETELS, R VISSCHER, B CHEN, I DUDLEY, J FAHEY, J GIORGI, J LEE, M MARTINEZMAZA, O MILLER, E NISHANIAN, P TAYLOR, J ZACK, J RINALDO, C KINGSLEY, L BECKER, J GUPTA, P HO, M MUNOZ, A BEATY, T EPSTEIN, L GALAI, N HOOVER, D MEINERT, C NELSON, K PIANTADOSI, S SU, S SCHRAGER, L VERMUND, S KASLOW, R VANRADEN, M SEMINARA, D TI IMPACT OF IMMUNOSUPPRESSION ON HEALTH-CARE USE BY MEN IN THE MULTICENTER AIDS COHORT STUDY (MACS) SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE IMMUNOSUPPRESSION; HIV; HEALTH CARE USE; COST ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; UNITED-STATES; MEDICAL-CARE; HOMOSEXUAL MEN; SERVICE USE; HIV; COSTS; EXPERIENCE AB The effects of human immunodeficiency virus type 1 (HIV-1) serostatus, AIDS, and level of immunosuppression on health service use were examined in the Multicenter AIDS Cohort Study. Data on self-reported hospitalizations, outpatient medical services (non-emergency room) and emergency room care during the preceding 6 months were collected for 3,447 homosexual/bisexual men returning for their 14th and/or 15th semiannual visits in Chicago, Baltimore, Los Angeles, and Pittsburgh. AIDS-free seropositive men with CD4(+) cells <200/mu l were more likely to be hospitalized [odds ratio (OR) = 2.3, 95% confidence limits (CL) = 1.4, 3.8] and use outpatient medical care (OR = 7.9, 95% CL = 4.9, 12.6), compared with seronegative men. Increased outpatient care was initiated at the earliest stages of HIV-1 infection, even when CD4(+) cells were >500/mu l. Dramatic increases in outpatient care for each level of immunosuppression were observed. HIV-1-related symptoms were associated with increased hospitalizations (OR = 4.8, 95% CL = 3.2, 7.3), use of outpatient medical services (OR = 3.3, 95% CL = 1.9, 5.6), and emergency room care (OR = 3.1, 95% CL = 2.1, 4.6). Persons with AIDS and less than or equal to 50 CD4(+) cells/mu l were most likely to be hospitalized (OR = 8.1; 95% CL = 4.4, 14.9). No significant difference (p > 0.05) in emergency room use was observed according to HIV-1 serostatus, AIDS, or immunosuppression, after adjusting for insurance and clinical symptoms. To the extent that CD4(+) cell counts are used as one of the criteria for an AIDS diagnosis and such a diagnosis broadens available benefits to persons with HIV disease, the pattern of health care services described here will be important for health care providers and planners. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT HLTH POLICY & MANAGEMENT,BALTIMORE,MD. NIAID,DIV AIDS,VACCINE TRIALS & EPIDEMIOL BRANCH,ROCKVILLE,MD. UNIV MELBOURNE,DEPT OPHTHALMOL,MELBOURNE,VIC,AUSTRALIA. UNIV CALIF LOS ANGELES,SCH PUBL HLTH,DEPT EPIDEMIOL,LOS ANGELES,CA 90024. MONTEFIORE MED CTR,ALBERT EINSTEIN COLL MED,DEPT EPIDEMIOL & SOCIAL MED,BRONX,NY 10467. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. HOWARD BROWN HLTH CTR,CHICAGO,IL. NORTHWESTERN UNIV,SCH MED,CHICAGO,IL. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA. JOHNS HOPKINS UNIV,CTR DATA COORDINATING,SCH HYG & PUBL HLTH,BALTIMORE,MD 21218. NCI,BETHESDA,MD. RP ZUCCONI, SL (reprint author), UNIV PITTSBURGH,GRAD SCH PUBL HLTH,INST HLTH POLICY,PITTSBURGH,PA 15261, USA. RI Wolinsky, Steven/B-2893-2012 FU NIAID NIH HHS [UO1-AI-35039, UO1-AI-35040, UO1-AI-35041] NR 29 TC 18 Z9 18 U1 2 U2 3 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 JUN PY 1994 VL 7 IS 6 BP 607 EP 616 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA NL968 UT WOS:A1994NL96800010 PM 7909846 ER PT J AU MANN, DL HAMLINGREEN, G WILLOUGHBY, A LANDESMAN, SH GOEDERT, JJ AF MANN, DL HAMLINGREEN, G WILLOUGHBY, A LANDESMAN, SH GOEDERT, JJ TI IMMUNOGLOBULIN CLASS AND SUBCLASS ANTIBODIES TO HIV PROTEINS IN MATERNAL SERUM - ASSOCIATION WITH PERINATAL TRANSMISSION SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE IMMUNOGLOBULIN CLASS/SUBCLASS ANTIBODIES; HIV-1; MATERNAL-INFANT TRANSMISSION ID HUMAN-IMMUNODEFICIENCY-VIRUS; B-CELL ACTIVATION; IGG SUBCLASS; CHILDREN BORN; INFECTION; PEPTIDES; GP120; ENHANCEMENT; ELEVATION; EPITOPES AB A flow cytometry-based assay for detection of immunoglobulin (Ig) class and subclass antibodies in human serum or plasma was developed. With use of this procedure, the presence and relative frequency of antibody activity in the Ig classes and subclasses (IgA1, IgA2, IgD, IgE, IgG1, IgG2, IgG3, IgG4, and IgM) to human immunodeficiency virus type 1 (HIV-1) proteins (gp160, gp120, p66, and p24) was determined in serum or plasma from a cohort of 47 HIV-1-infected, pregnant women. Antibody activity in each of the classes and subclasses was found with differences in frequency depending on the Ig class/ subclass and the HIV-1 protein. IgG1 antibodies were the most frequently reactive Ig class/subclass to each protein. Intermediate frequencies of reactivity were found in IgA1, IgG2, IgG3, and IgM class and subclasses and antibodies of the IgA2, IgE, and IgG4 class/subclass the least frequently detected. An unexpected finding was the presence of IgD antibodies to HIV-1 proteins in similar to 50% of the individuals. The distributions of Ig class/subclass antibodies to the different HIV-1 proteins were compared in sera from 14 mothers giving birth to infants who were determined to be HIV-1 infected with sera from 25 individuals whose infants were not infected. Sera from transmitting mothers contained a broader distribution of class and subclass antibodies compared to sera from nontransmitting women. The single most frequent antibody-antigen combination that was found in the transmitting mother was IgG2-gp160. Combinations of IgG1-IgG2, IgD-IgG2 antibodies to gp160 and IgA1-IgE antibodies to p66 were present more frequently in transmitters compared with the same combinations in nontransmitting mothers' sera. Whereas the significance of these findings are not apparent, increased activity of class and subclass antibodies in transmitting mothers suggest the possibility that previously described antibody-mediated enhancement may be operative in HIV-1 mother-infant transmission. C1 NCI,VIRAL EPIDEMIOL BRANCH,FREDERICK,MD 21701. NICHHD,FREDERICK,MD. NICHHD,ROCKVILLE,MD. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. SUNY HLTH SCI CTR,BROOKLYN,NY 11203. RP MANN, DL (reprint author), NCI,FREDERICK CANC RES & DEV CTR,IMMUNOGENET SECT,VIRAL CARCINOGENESIS LAB,BLDG 560,ROOM 21-78,FREDERICK,MD 21702, USA. NR 24 TC 14 Z9 14 U1 0 U2 1 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 JUN PY 1994 VL 7 IS 6 BP 617 EP 622 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA NL968 UT WOS:A1994NL96800011 PM 7513762 ER PT J AU KLINE, RL DADA, A BLATTNER, W QUINN, TC AF KLINE, RL DADA, A BLATTNER, W QUINN, TC TI DIAGNOSIS AND DIFFERENTIATION OF HIV-1 AND HIV-2 INFECTION BY 2 RAPID ASSAYS IN NIGERIA SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE HIV-1; HIV-2; NIGERIA; RAPID ASSAYS; TESTING STRATEGY ID HUMAN IMMUNODEFICIENCY VIRUS; ENZYME IMMUNOASSAYS; TYPE-2; ANTIBODY; AIDS AB We evaluated the reliability, sensitivity, and specificity of two rapid assays, TestPack HIV-1/HIV-2 and Genie HIV-1/HIV-2, in Lagos, Nigeria. An alternative algorithm to EIA and Western blot was then examined with the TestPack HIV-1/HIV-2 used as the screening test and the Genie HIV-1/HIV-2 used as the supplemental test to differentiate HIV-1 and HIV-2 infection. In all, 845 prostitutes were evaluated for HIV-1 and HIV-2 infection using one of the two rapid tests and compared to EIA and Western blot results. Of these 845 cases, 437 samples were analyzed by both assays. Overall, 109 (12.7%) prostitutes were antibody positive for HIV-1, 13 (1.5%) for HIV-2, and six (0.7%) were dually reactive for both HIV-1 and HIV-2. Compared to Western blot, the Genie HIV-1/HIV-2 had a slightly higher sensitivity and specificity (98.4% and 99.7%) than the TestPack HIV-1/HIV-2 (97.6% and 99.3%). The alternative algorithm using both rapid assays had a sensitivity of 96.9% and a specificity of 99.9%. The Genie HIV-1/HIV-2 correctly identified 104 of 108 HIV-1 positive sera, 12 of 13 HIV-2 positive sera, and all six dually positive sera. Both assays performed well in the field. They required <10 min to complete, no equipment, and little training. An algorithm incorporating two rapid assays can be used as a less expensive alternative to traditional testing strategies comparable in reliability to ELISA and Western blot; it provides the additional advantage of differentiating between HIV-1 and HIV-2. C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NCI,BETHESDA,MD 20892. MINIST HLTH,LAGOS,NIGERIA. NR 20 TC 13 Z9 13 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 JUN PY 1994 VL 7 IS 6 BP 623 EP 626 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA NL968 UT WOS:A1994NL96800012 PM 8176645 ER PT J AU GALLO, RC AF GALLO, RC TI TEMIN,HOWARD,M - A TRIBUTE - IN-MEMORIAM SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Item About an Individual RP GALLO, RC (reprint author), NCI,BETHESDA,MD 20892, USA. NR 2 TC 0 Z9 0 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 JUN PY 1994 VL 7 IS 6 BP 633 EP 634 PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA NL968 UT WOS:A1994NL96800020 ER PT J AU LEMARCHAND, P JONES, M DANEL, C YAMADA, I MASTRANGELI, A CRYSTAL, RG AF LEMARCHAND, P JONES, M DANEL, C YAMADA, I MASTRANGELI, A CRYSTAL, RG TI IN-VIVO ADENOVIRUS-MEDIATED GENE-TRANSFER TO LUNGS VIA PULMONARY-ARTERY SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Note DE CYSTIC FIBROSIS; ENDOTHELIUM; EPITHELIUM; PULMONARY CIRCULATION ID TRANSMEMBRANE CONDUCTANCE REGULATOR; HUMAN ENDOTHELIAL-CELLS; SYSTEMIC BLOOD-FLOW; AIRWAY EPITHELIUM; INVIVO; EXPRESSION; SHEEP; MICE; VECTORS; THERAPY AB On the basis of the knowledge that the pulmonary and bronchial circulations have extensive anastomoses, we hypothesized that gene transfer to the endothelium of both pulmonary and bronchial circulations might be achieved with replication-deficient recombinant adenovirus (Ad) vectors administered to the pulmonary circulation. To evaluate this concept, the right upper lobe branches of the sheep pulmonary artery and vein were temporarily occluded and a replication-deficient recombinant Ad vector containing the Escherichia coli lacZ reporter gene coding for beta-galactosidase (beta-Gal) was infused into the lumen of the occluded pulmonary artery. After 15 min, the pulmonary circulation was restored, and 1 or 4 days later the lungs were evaluated by histochemical analysis for beta-Gal activity. Gene transfer and expression were positive in 13 of 17 evaluated sheep. No beta-Gal activity was detected in any category of cells of uninfected lobes. As hypothesized, beta-Gal activity was detected in endothelial cells of the right upper lobe pulmonary and bronchial circulations. Unexpectedly, gene transfer was also observed in epithelial cells of the alveoli and the airways (bronchi and bronchioles) as well as in the epithelium of submucosal glands. These studies demonstrate that it is possible to use Ad vectors for transfer and expression of genes to lung parenchymal cells served by both the pulmonary and bronchial circulations. Furthermore, whereas administration of such vectors via the airways results in gene transfer only to the epithelium, pulmonary artery administration permits gene transfer to both endothelium and epithelium, thus expanding the target range of Ad gene transfer to the lungs. C1 NHLBI,PULM BRANCH,BETHESDA,MD 20892. NHLBI,ANIM MED & SURG LAB,BETHESDA,MD 20892. CORNELL UNIV,COLL MED,DIV PULM & CRIT CARE MED,NEW YORK,NY 10021. RI lemarchand, patricia/C-3247-2011 NR 36 TC 45 Z9 45 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD JUN PY 1994 VL 76 IS 6 BP 2840 EP 2845 PG 6 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA NR916 UT WOS:A1994NR91600079 PM 7928919 ER PT J AU OHANLON, TP DALAKAS, MC PLOTZ, PH MILLER, FW AF OHANLON, TP DALAKAS, MC PLOTZ, PH MILLER, FW TI THE ALPHA-BETA-T-CELL RECEPTOR REPERTOIRE IN INCLUSION-BODY MYOSITIS - DIVERSE PATTERNS OF GENE-EXPRESSION BY MUSCLE-INFILTRATING LYMPHOCYTES SO JOURNAL OF AUTOIMMUNITY LA English DT Article ID IDIOPATHIC INFLAMMATORY MYOPATHIES; MULTIPLE-SCLEROSIS; RHEUMATOID-ARTHRITIS; POLYMYOSITIS; DISEASE; PROTEIN; RECOGNITION; USAGE; DERMATOMYOSITIS; AUTOANTIBODIES C1 NINCDS,BETHESDA,MD 20892. NIAMSD,BETHESDA,MD 20892. RP OHANLON, TP (reprint author), US FDA,CTR BIOL EVALUAT & RES,MOLEC IMMUNOL LAB,BLDG 29,ROOM 507,HFM-521,BETHESDA,MD 20205, USA. NR 51 TC 33 Z9 34 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD JUN PY 1994 VL 7 IS 3 BP 321 EP 333 DI 10.1006/jaut.1994.1023 PG 13 WC Immunology SC Immunology GA NP269 UT WOS:A1994NP26900003 PM 7916906 ER PT J AU ROBRISH, SA FALES, HM GENTRYWEEKS, C THOMPSON, J AF ROBRISH, SA FALES, HM GENTRYWEEKS, C THOMPSON, J TI PHOSPHOENOLPYRUVATE-DEPENDENT MALTOSE-PHOSPHOTRANSFERASE ACTIVITY IN FUSOBACTERIUM-MORTIFERUM ATCC-25557 - SPECIFICITY, INDUCIBILITY, AND PRODUCT ANALYSIS SO JOURNAL OF BACTERIOLOGY LA English DT Article ID GRAM-POSITIVE BACTERIA; STREPTOCOCCUS-MUTANS; SUCROSE-6-PHOSPHATE HYDROLASE; NUCLEATUM ATCC-10953; ESCHERICHIA-COLI; SUGAR-TRANSPORT; METABOLISM; SYSTEM; PHOSPHORYLATION; PURIFICATION AB Phosphoenolpyruvate-dependent maltose:phosphotransferase activity was induced in cells of Fusobacterium mortiferum ATCC 25557 during growth on maltose. The disaccharide was rapidly metabolized by washed cells maintained under anaerobic conditions, but fermentation ceased immediately upon exposure of the cell suspension to air. Coincidentally, high levels of a phosphorylated derivative accumulated within the cells. Chemical and enzymatic analyses, in conjunction with data from H-1, C-13, and P-31 nuclear magnetic resonance spectroscopy, established the structure of the purified compound as 6-O-phosphoryl-alpha-D-glucopyranosyl-(1-4)-D-glucose (maltose 6-phosphate). A method for the preparation of substrate amounts of this commercially unavailable disaccharide phosphate is described. Permeabilized cells of F. mortiferum catalyzed the phosphoenolpyruvate-dependent phosphorylation of maltose under aerobic conditions. However, the hydrolysis of maltose 6-phosphate (to glucose 6-phosphate and glucose) by permeabilized cells or cell-free preparations required either an anaerobic environment or addition of dithiothreitol to aerobic reaction mixtures. The first step in dissimilation of the phosphorylated disaccharide appears to be catalyzed by an oxygen-sensitive maltose 6-phosphate hydrolase. Cells of F. mortiferum, grown previously on maltose, fermented a variety of alpha-linked glucosides, including maltose, turanose, palatinose, maltitol, alpha-methylglucoside, trehalose, and isomaltose. Conversely, cells grown on the separate alpha-glucosides also metabolized maltose. For this anaerobic pathogen, we suggest that the maltose:phosphotransferase and maltose 6-phosphate hydrolase catalyze the phosphorylative translocation and cleavage not only of maltose but also of structurally analogous alpha-linked glucosides. C1 NIDR, MICROBIAL ECOL LAB, BETHESDA, MD 20892 USA. NHLBI, BIOPHYS CHEM LAB, BETHESDA, MD 20892 USA. NR 38 TC 14 Z9 16 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JUN PY 1994 VL 176 IS 11 BP 3250 EP 3256 PG 7 WC Microbiology SC Microbiology GA NN851 UT WOS:A1994NN85100020 PM 8195080 ER PT J AU DITTO, MD ROBERTS, D WEISBERG, RA AF DITTO, MD ROBERTS, D WEISBERG, RA TI GROWTH-PHASE VARIATION OF INTEGRATION HOST FACTOR LEVEL IN ESCHERICHIA-COLI SO JOURNAL OF BACTERIOLOGY LA English DT Article ID SITE-SPECIFIC RECOMBINATION; HISTONE-LIKE PROTEINS; BINDING-SITES; DNA-BINDING; BACTERIOPHAGE-LAMBDA; HIMA GENE; H-NS; MUTATIONAL ANALYSIS; SALMONELLA-TYPHIMURIUM; ATTACHMENT SITE AB We have measured the intracellular abundance of integration host factor (IHF), a site-specific, heterodimeric DNA-binding protein, in exponential- and stationary-phase cultures of Escherichia coli K-12. Western immunoblot analysis showed that cultures that had been growing exponentially for several generations contained 0.5 to 1.0 ng of IHF subunits per mu g of total protein and that this increased to 5 to 6 ng/mu g in late-stationary-phase cultures. IHF is about one-third to one-half as abundant in exponentially growing cells as MU, a structurally related protein that binds DNA with little or no site specificity. Wild-type IHF is metabolically stable, but deletion mutations that eliminated one subunit reduced the abundance of the other when cells enter stationary phase. We attribute this reduction to the loss of stabilizing interactions between subunits. A mutation that inactivates IHF function but not subunit interaction increased IHF abundance, consistent with results of previous work showing that IHF synthesis is negatively autoregulated. We estimate that steady-state exponential-phase cultures contain about 8,500 to 17,000 IHF dimers per cell, a surprisingly large number for a site-specific DNA-binding protein with a limited number of specific sites. Nevertheless, small reductions in IHF abundance had significant effects on several IHF-dependent functions, suggesting that the wild-type exponential phase level is not in large excess of the minimum required for occupancy of physiologically important IHF-binding sites. C1 NICHHD,MICROBIOL GENET SECT,MOLEC GENET LAB,BETHESDA,MD 20892. COLD SPRING HARBOR LAB,COLD SPRING HARBOR,NY 11724. NR 92 TC 110 Z9 112 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 JUN PY 1994 VL 176 IS 12 BP 3738 EP 3748 PG 11 WC Microbiology SC Microbiology GA NQ764 UT WOS:A1994NQ76400034 PM 8206852 ER PT J AU SHLYAKHTENKO, LS REKESH, D LINDSAY, SM KUTYAVIN, I APPELLA, E HARRINGTON, RE LYUBCHENKO, YL AF SHLYAKHTENKO, LS REKESH, D LINDSAY, SM KUTYAVIN, I APPELLA, E HARRINGTON, RE LYUBCHENKO, YL TI STRUCTURE OF 3-WAY DNA JUNCTIONS .1. NONPLANAR DNA GEOMETRY SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Article ID SUPERCOILED DNA; CRO PROTEIN; CURVED DNA; COMPLEX; CONFORMATION; ENERGETICS; RESOLUTION; SITE AB Three-way junctions were obtained by annealing two synthetic DNA-oligomers. One of the strands contains a short palindrome sequence,leading to the formation of a hairpin with four base pairs in the stem and four bases in the loop. Another strand is complementary to the linear arms of the first hairpin-containing strand. Both strands were annealed to form a three-way branched structure with sticky ends on the linear arms. The branched molecules were ligated, and the ligation mixture was analysed on a two-dimensional gel in conditions which separated linear and circular molecules. Analysis of 2D-electrophoresis data shows that circular molecules with high mobility are formed. Formation of circular molecules is indicative of bends between linear arms. We estimate the magnitude of the angle between linear arms from the predominant size of the circular molecules formed. When the junction-to-junction distance is 20-21 bp, trimers and tetramers are formed predominately, giving an angle between linear arms as small as 60-90 degrees. Rotation of the hairpin position in the three-way junction allowed us to measure angles between other arms, yielding similar values. C1 ARIZONA STATE UNIV,DEPT MICROBIOL,TEMPE,AZ 85287. ARIZONA STATE UNIV,DEPT PHYS,TEMPE,AZ 85287. UNIV NEVADA,DEPT BIOCHEM,RENO,NV 89557. MICROPROBE CORP,BOTHELL,WA 98021. NCI,CELL BIOL LAB,BETHESDA,MD 20892. FU NHGRI NIH HHS [1R21HG0081801A1] NR 30 TC 19 Z9 19 U1 0 U2 7 PU ADENINE PRESS INC PI GUILDERLAND PA PO BOX 355/340, GUILDERLAND, NY 12084 SN 0739-1102 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PD JUN PY 1994 VL 11 IS 6 BP 1175 EP 1189 PG 15 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PC517 UT WOS:A1994PC51700002 PM 7946068 ER PT J AU DIEUDONNE, SC SEMEINS, CM GOEI, SW VUKICEVIC, S NULEND, JK SAMPATH, TK HELDER, M BURGER, EH AF DIEUDONNE, SC SEMEINS, CM GOEI, SW VUKICEVIC, S NULEND, JK SAMPATH, TK HELDER, M BURGER, EH TI OPPOSITE EFFECTS OF OSTEOGENIC PROTEIN AND TRANSFORMING GROWTH-FACTOR-BETA ON CHONDROGENESIS IN CULTURED LONG-BONE RUDIMENTS SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID OSTEOBLASTIC MC3T3-E1 CELLS; EMBRYONIC-DEVELOPMENT; DIFFERENTIATION INVITRO; ARTICULAR CHONDROCYTES; ALKALINE-PHOSPHATASE; EXPRESSION PATTERNS; RABBIT CHONDROCYTES; PHENOTYPES INVITRO; FORMATION INVIVO; SARCOMA CELLS AB Osteogenic protein-1 (OF-1, also called BMF-7) is a bone morphogenetic member of the TGF-beta superfamily. In the present study, we examined the effect of recombinant human OP-1 on cartilage and bone formation in organ cultures of metatarsal long bones of mouse embryos and compared the OP-1 effects with those of human TGF-beta(1) and porcine TGF-beta(1) and beta(1). Cartilage formation was determined by measurement of longitudinal growth of whole bone rudiments during culture and by the incorporation of (SO4)-S-35 into glycosaminoglycans. Mineralization was monitored by Ca-45 incorporation in the acid-soluble fraction and by measuring the length of the calcifying center of the rudiment. Toluidine blue-stained histologic sections were used for quantitative histomorphometric analysis. We found that OP-1 stimulated cartilage growth as determined by sulfate incorporation and that it increased remarkably the width of the long bones ends compared with controls. This effect was partly caused by differentiation of perichondrial cells into chondrocytes, resulting in increased appositional growth. In contrast to OP-1, TGF-beta(1) and beta(2) inhibited cartilage growth and reduced the length of whole bone rudiments compared with controls. In the ossifying center of the bone rudiments, both OP-1 and TGF-beta inhibited cartilage hypertrophy, growth of the bone collar, and matrix mineralization. These data demonstrate that OP-1 and TGF-beta exhibit opposite effects on cartilage growth but similar effects on osteogenesis in embryonic mouse long bone cultures. Since both OP-1 and TGF-beta have been demonstrated in embryonic cartilage and bone, these results suggest that they act as autocrine or paracrine regulators of embryonic bone development. C1 VRIJE UNIV AMSTERDAM,ACAD CTR DENT AMSTERDAM,DEPT ORAL CELL BIOL,AMSTERDAM,NETHERLANDS. NIDR,BONE RES BRANCH,BETHESDA,MD 20892. CREAT BIOMOLEC,HOPKINTON,MA. NR 45 TC 64 Z9 67 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JUN PY 1994 VL 9 IS 6 BP 771 EP 780 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NN314 UT WOS:A1994NN31400002 PM 8079653 ER PT J AU BISGAARD, HC NAGY, P TON, PT HU, ZY THORGEIRSSON, SS AF BISGAARD, HC NAGY, P TON, PT HU, ZY THORGEIRSSON, SS TI MODULATION OF KERATIN-14 AND ALPHA-FETOPROTEIN EXPRESSION DURING HEPATIC OVAL CELL-PROLIFERATION AND LIVER-REGENERATION SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID ADULT-RAT LIVER; EPITHELIAL-CELLS; POLYCHLORINATED-BIPHENYLS; INTERMEDIATE FILAMENTS; CULTURED-CELLS; STEM-CELL; DIFFERENTIATION; TRANSFORMATION; HEPATOCYTES; LINEAGES AB Keratin 14 (K14) expression has recently been demonstrated in cell lines of nonparenchymal hepatic origin (Bisgaard et al., 1993, Mel. Carcinog., 7:60-66; Bisgaard et al., 1991, J. Cell. Physiol., 747:333-343). These cell lines are thought to represent a progeny of a dormant stem cell compartment present in the adult rat liver, which may participate in the restoration of the liver mass after experimental liver injury. Utilizing a combination of 2-acetylaminofluorene (2-AAF) administration and partial hepatectomy to activate liver regeneration by proliferation of oval cells, we examined the modulation of K14 as well as alpha-fetoprotein (AFP) expression in proliferating oval cells and lineages hypothesized to be derived here from. We showed by Northern blot and in situ hybridization analyses that K14 and AFP transcripts were initially accumulating in epithelial cells located in subsets of ductal structures in the portal areas. As oval cells infiltrated the liver parenchyma, K14 transcripts were detected in oval cells, in foci of small basophilic hepatocytes, and in structures resembling glandular intestinal-type epithelium. AFP was expressed in oval cells, and at low but detectable levels in foci of basophilic hepatocytes, but not in glandular intestinal-type epithelium. Neither K14 nor AFP transcripts were detected in bile ducts or mature hepatocytes at any time during oval cell proliferation and reconstitution of the liver mass. To further study the modulation of K14 and AFP expression we utilized an in vitro model in which spontaneous transformation of rat liver epithelial (RLE) cells appeared to mimic the process of early differentiation along the hepatic lineage in vivo. We demonstrated that undifferentiated RLE cells at a late passage expressed K14 and vimentin, whereas transformation and differentiation to hepatoblast-like progeny resulted in an abrogation of K14 and vimentin expression and an induction of K18 and AFP. We propose that K14 and AFP are sequentially modulated in subpopulations of oval cells involved in the ongoing reconstitution of the liver mass. (C) 1994 Wiley-Liss, Inc. RP BISGAARD, HC (reprint author), NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892, USA. NR 41 TC 66 Z9 67 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD JUN PY 1994 VL 159 IS 3 BP 475 EP 484 DI 10.1002/jcp.1041590312 PG 10 WC Cell Biology; Physiology SC Cell Biology; Physiology GA NM399 UT WOS:A1994NM39900011 PM 7514611 ER PT J AU BISGAARD, HC TON, PT NAGY, P THORGEIRSSON, SS AF BISGAARD, HC TON, PT NAGY, P THORGEIRSSON, SS TI PHENOTYPIC MODULATION OF KERATINS, VIMENTIN, AND ALPHA-FETOPROTEIN IN CULTURED RAT-LIVER EPITHELIAL-CELLS AFTER CHEMICAL, ONCOGENE, AND SPONTANEOUS TRANSFORMATION SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID OVAL CELLS; INTERMEDIATE FILAMENTS; RAF-1 PHOSPHORYLATION; SIGNAL-TRANSDUCTION; EXPRESSION; DIFFERENTIATION; MOUSE; LINEAGES; PROTEIN; TISSUES AB Several lines of evidence have indicated that rat liver epithelial (RLE) cell lines may be related to a dormant stem cell compartment in the liver in vivo. We have demonstrated that keratin 14 (K14) is expressed together with vimentin in undifferentiated RLE cells. However, upon spontaneous transformation and differentiation to hepatoblast-like progeny the expression of these intermediate filaments (IF) is abrogated, while expression of another set of genes, among others keratin 18 (K18) and alpha-fetoprotein (AFP), is induced (Bisgaard et al., 1994, J. Cell. Physiol., in press). To better understand the mechanisms underlying IF expression during transformation and differentiation of RLE cells we examined the expression and regulation of IFs in clonal cell lines of chemically, oncogene, and spontaneously transformed RLE cells and their resulting tumors. These clonal lines provided a wide variety of tumor phenotypes including trabecular, solid and tubular adenocarcinomas, undifferentiated carcinomas, and spindle cell carcinomas. Northern blot analysis of the cell lines confirmed the differential expression of IF mRNAs. While keratin 8 (K8) was expressed at similar steady-state levels in all cell lines, K14 and vimentin but not K18 were expressed in the majority of cell lines chemically transformed with aflatoxin B-1 or by transduction of oncogenes. In contrast, cell lines transformed spontaneously by prolonged passage in vitro expressed K18, while K14 and vimentin were absent. The keratin expression pattern in vitro was retained in the majority of the resulting tumors. However, the keratins expressed in vitro did not accurately predict the tumor phenotype in vivo. In particular, in tumors typed morphologically as adenocarcinomas, the keratin pair typically expressed in chemically transformed tumor cells was K8/K14, whereas K8/K18 was expressed in the tumors derived from spontaneously transformed cell lines. Finally we showed by nuclear run-on and in vitro translation analyses that the expression of K14, K18, and vimentin in transformed RLE cell lines was regulated at the transcriptional level, whereas that of K8 appeared to be posttranslational. These findings suggest that events controlling the differential expression of IF genes are involved in the processes leading to transformation and differentiation of the RLE cell lines. We conclude that the transformed RLE cell lines provide a valuable model to further examine the regulatory mechanisms involved in hepatic differentiation of undifferentiated ''progenitor-like'' RLE cells. (C) 1994 Wiley-Liss, Inc. RP BISGAARD, HC (reprint author), NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892, USA. NR 45 TC 29 Z9 30 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD JUN PY 1994 VL 159 IS 3 BP 485 EP 494 DI 10.1002/jcp.1041590313 PG 10 WC Cell Biology; Physiology SC Cell Biology; Physiology GA NM399 UT WOS:A1994NM39900012 PM 7514612 ER PT J AU HOAGWOOD, K AF HOAGWOOD, K TI INTRODUCTION TO THE SPECIAL SECTION - ISSUES IN DESIGNING AND IMPLEMENTING STUDIES IN NON MENTAL-HEALTH-CARE SECTORS SO JOURNAL OF CLINICAL CHILD PSYCHOLOGY LA English DT Article ID OUTCOME RESEARCH; META-ANALYSIS; THERAPY AB Describes research issues related to design, methodology, and implementation of studies on service use and effectiveness of services for children and adolescents with mental disorders. This article provides an overview for methodological issues common across multiple service systems (i.e., schools, primary health care settings, the juvenile justice system) and issues that are affected differentially by the unique service sector in which the research is embedded. This article also serves as an introduction to a special section of articles related to research challenges for researchers of child mental health services in non-mental health settings. RP HOAGWOOD, K (reprint author), NIMH,SERV RES BRANCH,DIV EPIDEMIOL & SERV RES,ROOM 10C-06,ROCKVILLE,MD 20857, USA. NR 23 TC 9 Z9 9 U1 0 U2 0 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 SN 0047-228X J9 J CLIN CHILD PSYCHOL JI J. Clin. Child Psychol. PD JUN PY 1994 VL 23 IS 2 BP 114 EP 120 DI 10.1207/s15374424jccp2302_1 PG 7 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA NT465 UT WOS:A1994NT46500001 ER PT J AU ELROEIY, A CHEN, XH ROBERTS, VJ SHIMASAKI, S LING, N LEROITH, D ROBERTS, CT YEN, SSC AF ELROEIY, A CHEN, XH ROBERTS, VJ SHIMASAKI, S LING, N LEROITH, D ROBERTS, CT YEN, SSC TI EXPRESSION OF THE GENES ENCODING THE INSULIN-LIKE GROWTH-FACTORS (IGF-I AND IGF-II), THE IGF AND INSULIN-RECEPTORS, AND IGF-BINDING PROTEINS-1-6 AND THE LOCALIZATION OF THEIR GENE-PRODUCTS IN NORMAL AND POLYCYSTIC-OVARY-SYNDROME OVARIES SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MESSENGER-RIBONUCLEIC-ACID; HUMAN GRANULOSA-CELLS; FOLLICULAR-FLUID; MULTICYSTIC OVARIES; AROMATASE-ACTIVITY; MOLECULAR-CLONING; COHORT FOLLICLES; NORMAL DOMINANT; HORMONE; HYPERANDROGENISM AB To discern the potential role of the insulin-like growth factors (IGFs) in polycystic ovary syndrome (PCOS), we examined the expression of the genes encoding the IGFs, IGF receptors (IGFr), insulin receptor (Ir), and IGF-binding proteins (IGFBPs-1-6) as well as the localization of the gene products in specific cellular compartments of normal and PCOS human ovaries. Messenger ribonucleic acid (mRNA) was localized by in situ hybridization with specific S-35-labeled human antisense RNA probes, and protein was detected by immunohistochemistry using specific antisera. Thecal cells, but not granulosa cells (GC), of small antral follicles (3-6 mm) from PCOS ovaries expressed both IGF-I and IGF-II transcripts. Abundant IGF-Ir mRNA was found only in GC, IGF-IIr mRNA was found in both granulosa and thecal cells, and Ir mRNA was detected in all cell types, including granulosa, thecal, and stromal cells. Localization of the gene products revealed no IGF-I immunoreactivity; however, immunostaining for each of the other gene products was colocalized with its corresponding mRNA. The cellular distribution of mRNA and protein in PCOS follicles was indistinguishable from that observed in small antral follicles from normal ovaries. In dominant follicles, however, IGF-I mRNA was no longer detectable, but abundant IGF-II mRNA was expressed exclusively in GC. Although IGF-Ir mRNA was expressed in CC, IGF-IIr mRNA was found in both granulosa and thecal cells. In follicles taken from PCOS ovaries, no IGFBP-1 mRNA was detected, IGFBP-2 mRNA was abundant in both granulosa and thecal cells, moderate IGFBP-3 mRNA was found only in thecal cells, IGFBP-4 and -5 mRNAs were present in all cellular compartments, and IGFBP-6 mRNA was not detected. Localization of the gene products by immunostaining revealed that each protein colocalized with its corresponding mRNA. The cellular distribution of IGFBP mRNA and protein in PCOS follicles was also indistinguishable from that in small antral follicles of normal ovaries, but remarkable differences were found in dominant follicles, where abundant IGFBP-1 mRNA was seen exclusively in GC, IGFBP-2 mRNA in thecal cells, and IGFBP-3 mRNA in both granulosa and thecal cells. Moderate expression of the IGFBP-4 and IGFBP-5 genes was seen in all cell types, including stromal cells, but no IGFBP-6 mRNA was detected. Again, each of the gene products colocalized with its corresponding mRNA. We conclude the following. 1) Although remarkable difference exist between PCOS follicles and dominant follicles, the expression of mRNAs encoding the IGFs, IGFrs, Ir, and IGFBPs and localization of the proteins are similar to those seen in small antral follicles of normal ovaries, suggesting that common mechanisms may be involved in follicular maturational arrest in both situations. 2) In GC of both PCOS follicles and small antral follicles of normal ovaries, no IGFBP-1 and IGFBP-3 mRNA were seen, whereas abundant IGFBP-2 mRNA was expressed. Thus, secreted IGFBP-2 may function as an inhibitor of FSH action in the GC. 3) The presence of Ir mRNA and protein in all cellular compartments of the PCOS ovary lends support to an endocrine role of hyperinsulinemia in ovarian hyperandrogenism in PCOS. C1 UNIV CALIF SAN DIEGO, SCH MED, DEPT REPROD MED, LA JOLLA, CA 92093 USA. WHITTIER INST DIABET & ENDOCRINOL, LA JOLLA, CA 92093 USA. NIDDK, DIABET BRANCH, BETHESDA, MD 20892 USA. OI Roberts, Charles/0000-0003-1756-5772 FU NICHD NIH HHS [HD-07203-10, HD-07203-11, HD-12303-16] NR 53 TC 162 Z9 166 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 1994 VL 78 IS 6 BP 1488 EP 1496 DI 10.1210/jc.78.6.1488 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NQ265 UT WOS:A1994NQ26500036 PM 7515389 ER PT J AU BONKOVSKY, FO AF BONKOVSKY, FO TI HELPING PINES,KEN AND PINES,MARIE SO JOURNAL OF CLINICAL ETHICS LA English DT Article RP BONKOVSKY, FO (reprint author), NIH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV PUBL GROUP, INC PI FREDERICK PA 12 SOUTH MARKET ST, STE 301, FREDERICK, MD 21701 SN 1046-7890 J9 J CLIN ETHIC JI J. Clin. Ethics PD SUM PY 1994 VL 5 IS 2 BP 126 EP 126 PG 1 WC Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Biomedical Social Sciences GA NV225 UT WOS:A1994NV22500008 PM 7919481 ER PT J AU PINCUS, SH MESSER, KG NARA, PL BLATTNER, WA COLCLOUGH, G REITZ, M AF PINCUS, SH MESSER, KG NARA, PL BLATTNER, WA COLCLOUGH, G REITZ, M TI TEMPORAL ANALYSIS OF THE ANTIBODY-RESPONSE TO HIV ENVELOPE PROTEIN IN HIV-INFECTED LABORATORY WORKERS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE HIV; AIDS; ANTIBODY ID HUMAN-IMMUNODEFICIENCY-VIRUS; NEUTRALIZING ANTIBODIES; TYPE-1 GP120; CELLS; INFECTIVITY; GENERATION; EPITOPE; DOMAIN; GP160; ASSAY AB Three laboratory workers have been infected with the IIIB strain of HIV; their antibody response to HIV has been studied in serial serum specimens. Because the infecting virus is known, the fine specificity of the antibody response was studied on the homologous strain of HIV. Anti-p17, anti-p24, anti-gp160, CD4/gp120 blocking and neutralizing antibodies developed in parallel. Epitope mapping of the anti-gp160 response indicated several regions that consistently induced an antibody response. Serum contained antibody which reacted with V3-specific peptides corresponding to the very tip of the loop and crossreactivity was seen with V3 loop peptides from other sequence divergent strains of HIV. Antibody to the V1 loop was produced at levels comparable with that seen for the V3-loop. Anti-V1 neutralized HIV with a titration curve equivalent to an anti-V3 monoclonal antibody. Because the infecting virus is known and serial reisolates have been obtained, we explored the relationship between production of antibody to a given epitope and mutation in the virus. The data suggest that an association exists, but do not clearly indicate that antibody drives the selection for mutant viruses. The findings presented here provide a fine specificity analysis of the evolution of the antibody response to HIV in greater detail than has previously been performed. C1 NCI,BETHESDA,MD 20892. FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. RES TRIANGLE INST,ROCKVILLE,MD 20852. RP PINCUS, SH (reprint author), NIAID,ROCKY MT LABS,MICROBIAL STRUCT & FUNCT LAB,HAMILTON,MT 59840, USA. NR 30 TC 49 Z9 49 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 JUN PY 1994 VL 93 IS 6 BP 2505 EP 2513 DI 10.1172/JCI117260 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NP577 UT WOS:A1994NP57700030 PM 7515393 ER PT J AU RADER, DJ CAIN, W IKEWAKI, K TALLEY, G ZECH, LA USHER, D BREWER, HB AF RADER, DJ CAIN, W IKEWAKI, K TALLEY, G ZECH, LA USHER, D BREWER, HB TI THE INVERSE ASSOCIATION OF PLASMA LIPOPROTEIN(A) CONCENTRATIONS WITH APOLIPOPROTEIN(A) ISOFORM SIZE IS NOT DUE TO DIFFERENCES IN LP(A) CATABOLISM BUT TO DIFFERENCES IN PRODUCTION-RATE SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE LIPOPROTEIN(A); APOLIPOPROTEIN(A); ATHEROSCLEROSIS; LIPOPROTEINS; KINETICS ID CORONARY-ARTERY DISEASE; HEART-DISEASE; RISK FACTOR; MYOCARDIAL-INFARCTION; MESSENGER-RNA; GENE; MEN; HETEROGENEITY; POPULATION; PHENOTYPES AB Lipoprotein(a) (Lp[a]) is an atherogenic lipoprotein which is similar in structure to low density lipoproteins (LDL) but contains an additional protein called apolipoprotein(a) (apo[a]). Apo(a) is highly polymorphic in size, and there is a strong inverse association between the size of the apo(a) isoform and the plasma concentration of Lp(a). We directly compared the in vivo catabolism of Lp(a) particles containing different size apo(a) isoforms to establish whether there is an effect of apo(a) isoform size on the catabolic rate of Lp(a). In the first series of studies, four normal subjects were injected with radiolabeled S1-Lp(a) and S2-Lp(a) and another four subjects were injected with radiolabeled S2-Lp(a) and S4-Lp(a). No significant differences in fractional catabolic rate were found between Lp(a) particles containing different apo(a) isoforms. To confirm that apo(a) isoform size does not influence the rate of Lp(a) catabolism, three subjects heterozygous for apo(a) were selected for preparative isolation of both Lp(a) particles. The first was a B/S3-apo(a) subject, the second a S4/S6-apo(a) subject, and the third an F/S3-apo(a) subject. From each subject, both Lp(a) particles were preparatively isolated, radiolabeled, and injected into donor subjects and normal volunteers. In all cases, the catabolic rates of the two forms of Lp(a) were not significantly different. In contrast, the allele-specific apo(a) production rates were more than twice as great for the smaller apo(a) isoforms than for the larger apo(a) isoforms. In a total of 17 studies directly comparing Lp(a) particles of different apo(a) isoform size, the mean fractional catabolic rate of the Lp(a) with smaller size apo(a) was 0.329+/-0.090 day(-1) and of the Lp(a) with the larger size apo(a) 0.306+/-0.079 day(-1) not significantly different. In summary, the inverse association of plasma Lp(a) concentrations with apo(a) isoform size is not due to differences in the catabolic rates of Lp(a) but rather to differences in Lp(a) production rates. C1 NHLBI,MOLEC DIS BRANCH,BETHESDA,MD 20892. NR 34 TC 153 Z9 156 U1 0 U2 5 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 JUN PY 1994 VL 93 IS 6 BP 2758 EP 2763 DI 10.1172/JCI117292 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA NP577 UT WOS:A1994NP57700062 PM 8201014 ER PT J AU CONVILLE, PS WITEBSKY, FG MACLOWRY, JD AF CONVILLE, PS WITEBSKY, FG MACLOWRY, JD TI ANTIMICROBIAL SUSCEPTIBILITIES OF MYCOBACTERIA AS DETERMINED BY DIFFERENTIAL LIGHT-SCATTERING AND CORRELATION WITH RESULTS FROM MULTIPLE REFERENCE LABORATORIES SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID TUBERCULOSIS AB The DAWN Model B laser light scattering instrument (Wyatt Technology Corporation, Santa Barbara, Calif.) was evaluated to assess its potential to provide rapid mycobacterial antimicrobial susceptibility test results. For Mycobacterium tuberculosis there was a clear separation between susceptible and resistant results with the isolates tested, and there was excellent correlation with reference laboratory results. For Mycobacterium avium there was no obvious breakpoint between susceptible and resistant results with the isolates tested, and correlation with reference laboratory results was less good than for M. tuberculosis. However, for M. avium there was also less agreement among reference laboratory results than for M. tuberculosis. Significant instrument design and software program changes would be required for the instrument to become a useful tool for mycobacterial susceptibility testing in the diagnostic laboratory. RP CONVILLE, PS (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT CLIN PATHOL,MICROBIOL SERV,BLDG 10,ROOM 2C-385,BETHESDA,MD 20892, USA. NR 8 TC 4 Z9 4 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUN PY 1994 VL 32 IS 6 BP 1554 EP 1559 PG 6 WC Microbiology SC Microbiology GA NL918 UT WOS:A1994NL91800026 PM 8077403 ER PT J AU ENGLER, HD SELEPAK, ST AF ENGLER, HD SELEPAK, ST TI EFFECT OF CENTRIFUGING SHELL VIALS AT 3,500XG ON DETECTION OF VIRUSES IN CLINICAL SPECIMENS SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Note ID HERPES-SIMPLEX VIRUS; RAPID DETECTION; MONOCLONAL-ANTIBODIES; CYTOMEGALO-VIRUS; URINE SPECIMENS; INFECTIONS; CULTURES; ASSAY; CELLS AB An increase in shell vial centrifugation force to 3,500 x g and a concomitant reduction in spin time to 15 min did not decrease the sensitivity of detecting viruses in clinical specimens compared with the accepted practice of using 700 x g for 40 min. No damage to the cell monolayer (ML) at the higher g force was observed. Toxicity to the ML is decreased with the shorter spin, probably because of reduced time of contact between the specimen and the ML. RP ENGLER, HD (reprint author), NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT CLIN PATHOL,MICROBIOL SERV,BLDG 10,ROOM 2C-385,BETHESDA,MD 20892, USA. NR 13 TC 22 Z9 23 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUN PY 1994 VL 32 IS 6 BP 1580 EP 1582 PG 3 WC Microbiology SC Microbiology GA NL918 UT WOS:A1994NL91800031 PM 8077407 ER PT J AU OREN, DA MOUL, DE SCHWARTZ, PJ WEHR, TA ROSENTHAL, NE AF OREN, DA MOUL, DE SCHWARTZ, PJ WEHR, TA ROSENTHAL, NE TI A CONTROLLED TRIAL OF LEVODOPA PLUS CARBIDOPA IN THE TREATMENT OF WINTER SEASONAL AFFECTIVE-DISORDER - A TEST OF THE DOPAMINE HYPOTHESIS SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID LIGHT THERAPY; DEPRESSION; MELATONIN AB The objectives of this study were to test the hypothesis that a dopaminergic deficiency plays a role in the pathogenesis of winter seasonal affective disorder (SAD) and to test the efficacy of levodopa plus carbidopa as a treatment for SAD. Two weeks of double-blind placebo washout were followed by random assignment to parallel treatments for 2 weeks with levodopa and carbidopa versus placebo. Observations were made during weekly outpatient visits. All subjects met criteria for SAD. Fifty patients entered the study. Twenty-four were significantly depressed after the washout period and were randomly assigned to medication or placebo. Twenty-three completed the study. Twelve patients received placebo capsules four times a day during the 2-week drug comparison period. On an identical schedule, 11 patients received capsules containing levodopa (up to 7 mg/kg per day by the end of the second week) and carbidopa (100 mg/day). Twenty-one item Hamilton Rating Scale for Depression scores were used to determine antidepressant efficacy. No differences were found in the rates of response. There is no evidence to support the use of levodopa for the treatment of SAD patients in general. A model of systemic dopaminergic deficiency does not readily explain the pathology of SAD. C1 NIMH,EPIDEMIOL & PATHOL RES BRANCH,BETHESDA,MD. RP OREN, DA (reprint author), NIMH,CLIN PSYCHOBIOL BRANCH,ENVIRONM PSYCHIAT SECT,BLDG 10,ROOM 45-239,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 29 TC 25 Z9 26 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD JUN PY 1994 VL 14 IS 3 BP 196 EP 200 PG 5 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA NL869 UT WOS:A1994NL86900006 PM 8027416 ER PT J AU AVILA, NA SHAWKER, TH FRAKER, D AF AVILA, NA SHAWKER, TH FRAKER, D TI COLOR-FLOW DOPPLER ULTRASONOGRAPHY IN METASTATIC MELANOMA OF THE GALLBLADDER SO JOURNAL OF CLINICAL ULTRASOUND LA English DT Note ID PRIMARY-CARCINOMA; SONOGRAPHY C1 NCI,SURG BRANCH,BETHESDA,MD 20892. HENRY M JACKSON FDN,ROCKVILLE,MD. RP AVILA, NA (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BLDG 10,ROOM 1C660,BETHESDA,MD 20892, USA. NR 23 TC 15 Z9 15 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0091-2751 J9 J CLIN ULTRASOUND JI J. Clin. Ultrasound PD JUN PY 1994 VL 22 IS 5 BP 342 EP 347 DI 10.1002/jcu.1870220510 PG 6 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA NL785 UT WOS:A1994NL78500009 PM 8046045 ER PT J AU BAUMAN, LJ WIENER, L AF BAUMAN, LJ WIENER, L TI PRIORITIES IN PSYCHOSOCIAL RESEARCH IN PEDIATRIC HIV-INFECTION - INTRODUCTION SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Editorial Material C1 NCI,PEDIAT HIV PSYCHOSOCIAL SUPPORT PROGRAM,BETHESDA,MD 20892. RP BAUMAN, LJ (reprint author), YESHIVA UNIV ALBERT EINSTEIN COLL MED,PREVENT INTERVENT RES CTR,BRONX,NY 10461, USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD JUN PY 1994 VL 15 IS 3 SU S BP S1 EP S2 PG 2 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA NR094 UT WOS:A1994NR09400001 ER PT J AU BOSE, S MOSS, HA BROUWERS, P PIZZO, P LORION, R AF BOSE, S MOSS, HA BROUWERS, P PIZZO, P LORION, R TI PSYCHOLOGIC ADJUSTMENT OF HUMAN IMMUNODEFICIENCY VIRUS-INFECTED SCHOOL-AGE-CHILDREN SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article DE CHILDREN; PEDIATRIC HUMAN IMMUNODEFICIENCY VIRUS; COPING; RISK FACTORS ID CHRONIC-ILLNESS; SELF-ESTEEM; RESISTANCE FACTORS; STRESS; PSYCHOPATHOLOGY; ADOLESCENTS; ANXIETY; RISK; ILL AB We investigated the psychosocial adjustment of school-aged, human immunodeficiency virus-positive children and factors associated with level of adjustment. Participants were primarily transfusion-infected children living in middle-class families. We administered measures of depression, anxiety, and self-concept to children, and measures of behavior problems, social functioning, personality characteristics, and life events to parents. An index of disease stage was also collected. Children reported experiencing low levels of depressive and anxious affect and generally felt positively about themselves. By contrast, parents saw their children as more anxious and less socially active than respective standardization samples. A greater than expected proportion of these children, as reported by their parents, scored in the maladaptive range on measures of social functioning, anxiety, and conduct problems. Experience of adversive life events and progression of the disease were associated with more behavioral and social problems. Findings are discussed in terms of their generalizability and implications for future research. C1 NCI,PEDIAT BRANCH,BLDG 10,ROOM 13N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. MED ILLNESS COUNSELING CTR,CHEVY CHASE,MD. UNIV MARYLAND,DEPT PSYCHOL,COLL PK,MD 20742. FU NCI NIH HHS [CM-17529] NR 33 TC 25 Z9 25 U1 1 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD JUN PY 1994 VL 15 IS 3 SU S BP S26 EP S33 PG 8 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA NR094 UT WOS:A1994NR09400006 PM 8063915 ER PT J AU FANOS, JH WIENER, L AF FANOS, JH WIENER, L TI TOMORROWS SURVIVORS - SIBLINGS OF HUMAN IMMUNODEFICIENCY VIRUS-INFECTED CHILDREN SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article DE SIBLINGS; HUMAN IMMUNODEFICIENCY VIRUS; MOURNING ID DEATH AB There has been no empirical research on the psychologic effects on siblings of children afflicted with human immunodeficiency virus (HIV). This article therefore draws from existing sources: the literature of siblings of children with other chronic illnesses and the clinical experiences of those working with HIV-infected children and their siblings. Topics covered include secrecy and communication within the family, the parent-child relationship, the sibling relationship, school issues, the impact of parental mourning on siblings, the sibling's mourning, and recommendations for future research. The goals of this review are to alert researchers to issues that need to be addressed, and to inform the development of interventions for siblings. C1 CALIF PACIFIC MED CTR,DEPT MED,SAN FRANCISCO,CA. CALIF PACIFIC MED CTR,DEPT PSYCHIAT,SAN FRANCISCO,CA. NCI,PEDIAT HIV PSYCHOSOCIAL PROGRAM,BETHESDA,MD 20892. RP FANOS, JH (reprint author), CALIF PACIFIC MED CTR,RES INST,DEPT PEDIAT,2330 CLAY ST,STERN BLDG,SAN FRANCISCO,CA 94115, USA. FU NHGRI NIH HHS [1R01HG 00639] NR 38 TC 15 Z9 15 U1 0 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD JUN PY 1994 VL 15 IS 3 SU S BP S43 EP S48 PG 6 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA NR094 UT WOS:A1994NR09400008 PM 8063918 ER PT J AU AUCHUS, RJ MASTORAKOS, G FRIEDMAN, TC CHROUSOS, GP AF AUCHUS, RJ MASTORAKOS, G FRIEDMAN, TC CHROUSOS, GP TI CORTICOTROPIN-RELEASING HORMONE PRODUCTION BY A SMALL-CELL CARCINOMA IN A PATIENT WITH ACM-DEPENDENT CUSHINGS-SYNDROME SO JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION LA English DT Note DE CORTICOTROPIN-RELEASING HORMONE; ECTOPIC HORMONES; CUSHINGS SYNDROME; SMALL-CELL LUNG CANCER; HYPERCORTISOLEMIA; IMMUNOCYTOCHEMISTRY; ADRENOCORTICOTROPIC HORMONE ID DOSE DEXAMETHASONE SUPPRESSION; DIFFERENTIAL-DIAGNOSIS; ECTOPIC PRODUCTION; ADRENOCORTICOTROPIN; SECRETION; CORTISOL; DISEASE; ACTH; PLASMA; TUMOR AB We describe a patient with Cushing's syndrome and metastatic small cell lung cancer. The plasma ACTH concentrations were markedly elevated (91.6 pmol/L), and the AM cortisol did not suppress by >50% overnight after administration of 8 mg dexamethasone, both consistent with the ectopic ACTH syndrome. Immunohistochemical studies of a single metastatic tumor specimen, however, demonstrated an absence of ACTH and yet an abundance of corticotropin-releasing hormone (CRH). In addition, radioimmunoassay of the patient's plasma demonstrated persistently elevated CRH concentrations. The majority of the plasma CRH immunoreactivity exhibited the same chromatographic mobility as synthetic r/h CRH (1-41) on HPLC. Failure to evaluate the tumor tissue for the presence of ACTH and/or CRH would have led to the erroneous conclusion that this patient's Cushing's syndrome resulted from paraneoplastic ACTH production. We conclude that immunoassay of plasma for both ACTH and CRH and, perhaps, immunostaining of tumor samples are required to distinguish between the ectopic ACTH and CRH syndromes. C1 UNIV TEXAS,HLTH SCI CTR,DIV ENDOCRINOL,SAN ANTONIO,TX. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD. NICHHD,DEV NEUROBIOL LAB,BETHESDA,MD. RP AUCHUS, RJ (reprint author), WILFORD HALL USAF MED CTR,PSME,DEPT ENDOCRINOL & METAB,2200 BERGQUIST DR STE 1,LACKLAND AFB,TX 78236, USA. NR 28 TC 12 Z9 12 U1 0 U2 0 PU EDITRICE KURTIS S R L PI MILANO PA VIA LUIGI ZOJA, 30-20153 MILANO, ITALY SN 0391-4097 J9 J ENDOCRINOL INVEST JI J. Endocrinol. Invest. PD JUN PY 1994 VL 17 IS 6 BP 447 EP 452 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NU988 UT WOS:A1994NU98800010 PM 7930390 ER PT J AU VACCHIO, MS PAPADOPOULOS, V ASHWELL, JD AF VACCHIO, MS PAPADOPOULOS, V ASHWELL, JD TI STEROID-PRODUCTION IN THE THYMUS - IMPLICATIONS FOR THYMOCYTE SELECTION SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID SIDE-CHAIN CLEAVAGE; T-CELL REPERTOIRE; MONOCLONAL-ANTIBODY; ADRENAL-CORTEX; FREE CORTICOSTERONE; CD4+8+ THYMOCYTES; ANTAGONIST RU-486; TRANSGENIC MICE; SELF-TOLERANCE; ACTIVATION AB The mouse thymus was assessed for its ability to produce steroids. Cultured thymic non-T cells produced soluble pregnenolone and deoxycorticosterone, and immunohistochemistry demonstrated steroidogenic enzymes in radioresistant thymic epithelial cells but not in thymocytes. Inhibition of thymic corticosterone production or blockade of the glucocorticoid receptor with RU-486 resulted in enhanced TCR-mediated, antigen-specific deletion of immature thymocytes. These data indicate that locally produced glucocorticoids, because of their antagonism of TCR-mediated signaling for death, may be a key element of antigen-specific thymocyte selection. C1 NCI,IMMUNE CELL BIOL LAB,BIOL RESPONSE MODIFIERS PROGRAM,BETHESDA,MD 20892. GEORGETOWN UNIV,SCH MED,DEPT ANAT & CELL BIOL,WASHINGTON,DC 20007. OI Papadopoulos, Vassilios/0000-0002-1183-8568 FU NIDDK NIH HHS [DK-43358] NR 49 TC 294 Z9 295 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUN 1 PY 1994 VL 179 IS 6 BP 1835 EP 1846 DI 10.1084/jem.179.6.1835 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA NN510 UT WOS:A1994NN51000009 PM 8195711 ER PT J AU ROCKEN, M URBAN, J SHEVACH, EM AF ROCKEN, M URBAN, J SHEVACH, EM TI ANTIGEN-SPECIFIC ACTIVATION, TOLERIZATION, AND REACTIVATION OF THE INTERLEUKIN-4 PATHWAY IN-VIVO SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CD4+ T-CELLS; STIMULATORY FACTOR-I; MONOCLONAL-ANTIBODY; IL-4 PRODUCTION; CLONAL ANERGY; MURINE LEISHMANIASIS; AUTOIMMUNE-DISEASE; INTERFERON-GAMMA; TRANSGENIC MICE; TOLERANCE AB The outcome of immune responses critically depends on the pattern of lymphokines secreted by CD4(+) T cells. CD4(+) T cells may differentiate into interleukin 2 (IL-2) and interferon gamma secreting T helper 1 (Th1)-like cells or IL-4/IL-5/IL-10 secreting Th2-like cells. However, the mechanisms that regulate production of IL-4 or other T cell lymphokines in vivo remain unknown. We use the superantigen, Staphylococcus enterotoxin A (SEA), as a model antigen to characterize the signals that regulate the production of IL-4 in vivo. Induction of IL-4 in normal CD4(+) T cells required stimulation with both antigen and IL-4. SEA-specific CD4(+) T cells produced large amounts of IL-4 when restimulated within 10 d after in vivo priming. Repetitive application of both signals was required to prevent downregulation of IL-4 production. Although controversy exists regarding the susceptibility of Th2-like cells to tolerogenic signals, high doses of superantigen readily abolished the capacity to produce IL-4 in both naive T cells and in T cells already primed for IL-4 production. Infection with the nematode, Nippostrongylus brasiliensis, reversed the established T cell tolerance, whereas the signals which induced IL-4 production in normal T cells, antigen and IL-4, were not capable of reversing superantigen-specific tolerance in vivo. The major parameter that correlated with the capacity of parasitic infection to break tolerance was the magnitude of the lymphoproliferation seen during the course of the infection. The capacity to activate or tolerize the IL-4 pathway in an antigen-specific fashion should prove useful in the design of antigen-specific therapies for autoimmune and allergic diseases. C1 NIAID,IMMUNOL LAB,BETHESDA,MD 20892. USDA ARS,BELTSVILLE AGR RES CTR,INST LIVESTOCK & POULTRY SCI,HELMINTH DIS LAB,BELTSVILLE,MD 20705. OI Urban, Joseph/0000-0002-1590-8869 NR 43 TC 67 Z9 67 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 JUN 1 PY 1994 VL 179 IS 6 BP 1885 EP 1893 DI 10.1084/jem.179.6.1885 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA NN510 UT WOS:A1994NN51000014 PM 7910842 ER PT J AU ROBEY, E ITANO, A FANSLOW, WC FOWLKES, BJ AF ROBEY, E ITANO, A FANSLOW, WC FOWLKES, BJ TI CONSTITUTIVE CD8 EXPRESSION ALLOWS INEFFICIENT MATURATION OF CD4+ HELPER T-CELLS IN CLASS-II MAJOR HISTOCOMPATIBILITY COMPLEX MUTANT MICE SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID DEFICIENT MICE; CD40 LIGAND; SELECTION; RECEPTOR; LINEAGE; DIFFERENTIATION; INSTRUCTION; LYMPHOCYTES; THYMOCYTES; COMMITMENT AB Although mature CD4(+) T cells bear T cell receptors (TCRs) that recognize class II major histocompatibility complex (MHC) and mature CD8(+) T cells bear TCRs that recognize class I MHC, it is possible that the initial commitment of an immature thymocyte to a CD4 or CD8 lineage is made without regard to the specificity of the TCR. According to this model, CD4(+) cells with class I TCR do not mature because the CD8 coreceptor is required for class I MHC recognition and positive selection. If this model is correct, constitutive expression of CD8 should allow CD4(+) T cells with class I-specific TCRs to develop. In this report, we show that mature peripheral CD4(+) cells are present in class II MHC-deficient mice that express a constitutive CD8.1 transgene. These cells share a number of properties with the major class II MHC-selected CD4 population, including the ability to express CD40 ligand upon activation. Although mature CD4 cells are also detectable in the thymus of class II MHC mutant/CD8.1 transgenic mice, they represent a small fraction of the mature CD4 cells found in mice that express class II MHC. These results indicate that some T cells choose the CD4 helper lineage independent of their antigen receptor specificity; however, the inefficiency of generating class I-specific CD4 cells leaves open the possibility that an instructive signal generated upon MHC recognition may bias lineage commitment. C1 NIAID,CELLULAR & MOLEC IMMUNOL LAB,BETHESDA,MD 20892. UNIV CALIF BERKELEY,DEPT MOLEC & CELL BIOL,BERKELEY,CA 94720. IMMUNEX RES & DEV CORP,SEATTLE,WA 98101. FU NIAID NIH HHS [AI-32985-01] NR 27 TC 62 Z9 62 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 JUN 1 PY 1994 VL 179 IS 6 BP 1997 EP 2004 DI 10.1084/jem.179.6.1997 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA NN510 UT WOS:A1994NN51000024 PM 7515104 ER PT J AU KARASEV, AV NIKOLAEVA, OV KOONIN, EV GUMPF, DJ GARNSEY, SM AF KARASEV, AV NIKOLAEVA, OV KOONIN, EV GUMPF, DJ GARNSEY, SM TI SCREENING OF THE CLOSTEROVIRUS GENOME BY DEGENERATE PRIMER-MEDIATED POLYMERASE CHAIN-REACTION SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID BEET YELLOWS CLOSTEROVIRUS; CITRUS TRISTEZA VIRUS; DOUBLE-STRANDED-RNA; NUCLEIC-ACID; KDA PROTEIN; PURIFICATION; SEQUENCES; GENES; HYBRIDIZATION; TRANSLATION AB The genome of beet yellows virus (BYV), the type representative of the closterovirus group, encodes a homologue of the cellular heat-shock protein (HSP) 70 family. A pair of degenerate primers targeted to motifs A and E, which are highly conserved in HSP70s, was synthesized. Genomes of several definite and possible members of the closterovirus group were screened for the presence of the HSP70 gene with PCR using these degenerate primers. BYV, citrus tristeza virus (CTV), beet yellow stunt virus (BYSV) and carnation necrotic fleck virus templates produced 1 kb amplification products, which were shown by sequencing to represent fragments of the respective HSP70 genes. Further screening was performed with an additional degenerate primer targeted to the motif IV of the putative viral polymerase. This degenerate primer and specific primers complementary to the 5' region of the HSP70 genes of the respective viruses were used to estimate the distance between polymerase motif IV and the start point of the HSP70 gene for BYV (approximately 1.1 kb), CTV and BYSV (around 2.0 kb) by PCR. The amplified genome regions of CTV (3026 nucleotides) and BYSV (2837 nucleotides) were cloned and sequenced. CTV and BYSV were found to encode the gene for an additional 30K (BYSV) or 33K (CTV) protein between the polymerase and the small hydrophobic protein genes, which was absent in BYV. These two 30K proteins displayed very weak similarity to each other, unlike the highly conserved polymerases, hydrophobic proteins and HSP70s of BYV, CTV and BYSV. Degenerate primer-mediated PCR proved to be an efficient tool for rapid screening and subsequent cloning of the viral genomes. C1 UNIV CALIF RIVERSIDE,DEPT PLANT PATHOL,RIVERSIDE,CA 92521. NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. USDA ARS,HORT RES LAB,ORLANDO,FL 32803. NR 34 TC 45 Z9 46 U1 0 U2 2 PU SOC GENERAL MICROBIOLOGY PI READING PA HARVEST HOUSE 62 LONDON ROAD, READING, BERKS, ENGLAND RG1 5AS SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD JUN PY 1994 VL 75 BP 1415 EP 1422 DI 10.1099/0022-1317-75-6-1415 PN 6 PG 8 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA NQ490 UT WOS:A1994NQ49000023 PM 8207405 ER PT J AU BLOOM, JR KESSLER, L AF BLOOM, JR KESSLER, L TI EMOTIONAL SUPPORT FOLLOWING CANCER - A TEST OF THE STIGMA AND SOCIAL ACTIVITY HYPOTHESES SO JOURNAL OF HEALTH AND SOCIAL BEHAVIOR LA English DT Article; Proceedings Paper CT 1991 Annual Meeting of the American-Sociological-Association CY AUG 23-27, 1991 CL CINCINNATI, OH SP Amer Sociol Assoc ID NETWORKS; IMPACT AB Reports of changes in emotional support following surgery for breast cancer can be attributed to one of two factors: (1) the stigma associated with cancer, or (2) illness-imposed restrictions in one's activities. These explanations were assessed using data from a longitudinal study of women, following their surgical treatment for early breast cancer (N = 145), gallbladder disease (N = 90), benign breast disease (N = 87), or no surgery (N = 90). Multiple regression analysis was used to test the two models. Contrary to the cancer stigma hypothesis, women with breast cancer initially perceived themselves to have more emotional support, rather than less. Type of surgery did not explain the level of emotional support as post-surgery time increased. Instead, support for the social activity hypothesis was found. The results are interpreted as indicating that breast cancer no longer carries with it a stigma, at least not to the extent of reducing the level of women's emotional support. C1 NCI,BETHESDA,MD 20892. RP BLOOM, JR (reprint author), UNIV CALIF BERKELEY,SCH PUBL HLTH,409 WARREN HALL,BERKELEY,CA 94720, USA. FU NCI NIH HHS [N01-CN-55313, N01-CN-55312, N01-CN-55311] NR 47 TC 66 Z9 70 U1 1 U2 3 PU AMER SOCIOLOGICAL ASSOC PI WASHINGTON PA 1722 N ST NW, WASHINGTON, DC 20036-2981 SN 0022-1465 J9 J HEALTH SOC BEHAV JI J. Health Soc. Behav. PD JUN PY 1994 VL 35 IS 2 BP 118 EP 133 DI 10.2307/2137360 PG 16 WC Public, Environmental & Occupational Health; Psychology, Social SC Public, Environmental & Occupational Health; Psychology GA PQ260 UT WOS:A1994PQ26000002 PM 8064120 ER PT J AU LARSEN, CP RITCHIE, SC HENDRIX, R LINSLEY, PS HATHCOCK, KS HODES, RJ LOWRY, RP PEARSON, TC AF LARSEN, CP RITCHIE, SC HENDRIX, R LINSLEY, PS HATHCOCK, KS HODES, RJ LOWRY, RP PEARSON, TC TI REGULATION OF IMMUNOSTIMULATORY FUNCTION AND COSTIMULATORY MOLECULE (B7-1 AND B7-2) EXPRESSION ON MURINE DENDRITIC CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EPIDERMAL LANGERHANS CELLS; COLONY-STIMULATING FACTOR; HEAT-STABLE ANTIGEN; MIGRATION PATTERNS; LYMPHOCYTES-T; MOUSE; BLOOD; ACTIVATION; COOPERATION; POPULATIONS AB Dendritic cells (DC) play a critical role in the initiation of T cell-mediated immune responses, and express costimulatory molecules that are required for optimal activation of unprimed T cells. Studies on the regulation of the costimulatory molecules on DC have produced evidence from several systems that GM-CSF can up-regulate expression of CTLA4 counter receptor (CTLA4-CR) (but not intercellular adhesion molecule 1 (ICAM-1) and heat stable Ag (HsAg)) on DC. This is demonstrated on splenic DC, Langerhans cells, kidney DC in culture, and in a skin-explant culture system, in which the increased expression of CTLA4-CR on Langerhans cells (LC) occurs concomitantly with their migration out of skin. Interestingly, despite the ability of both CM-CSF and IFN-gamma increase CTLA4-CR and maintain similar levels of ICAM-1, HsAg, and MHC molecule expression, the functional consequences of these cytokines on splenic DC are distinctly different. GM-CSF enhances the ability of DC to stimulate both T cell proliferation and cytokine release, whereas IFN-gamma causes no increase in immunostimulatory function. Further analysis of the CTLA4-CR on these cell populations by using the GL-1 and IG10 mAbs has shown that GM-CSF-cultured DC express high levels of both B7-1 and B7-2, whereas IFN-gamma-cultured DC express increased levels of only B7-2. These results suggest that optimal stimulation of unprimed T cells to proliferate and release cytokines may require participation of both of these CTLA4 counter receptors, and confirm the importance of CM-CSF for the maturation of DC into potent stimulators of T cell activation. C1 EMORY UNIV,SCH MED,DEPT SURG,ATLANTA,GA 30322. EMORY UNIV,SCH MED,DEPT SURG,ATLANTA,GA 30322. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. NIA,BETHESDA,MD 20892. RI Larsen, Christian/B-6906-2012 OI Larsen, Christian/0000-0001-6573-2649 FU NIAID NIH HHS [R01-AI30322, 1R29-AI33588-01A1] NR 41 TC 352 Z9 358 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 1 PY 1994 VL 152 IS 11 BP 5208 EP 5219 PG 12 WC Immunology SC Immunology GA NM615 UT WOS:A1994NM61500006 PM 7514631 ER PT J AU SNIDER, DE LAMONTAGNE, JR AF SNIDER, DE LAMONTAGNE, JR TI THE NEGLECTED GLOBAL TUBERCULOSIS PROBLEM - A REPORT OF THE 1992 WORLD CONGRESS ON TUBERCULOSIS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MYCOBACTERIUM-TUBERCULOSIS; EPIDEMIOLOGY; COUNTRIES AB Tuberculosis is the single leading cause of death from any single infectious agent. A world congress on tuberculosis was held to highlight the problem and to discuss recent scientific advances and global strategies for prevention and control. About one-third of the world population is latently infected with Mycobacterium tuberculosis. Over 8 million new cases and nearly 3 million deaths occur each year. The situation is deteriorating due, in part, to the human immunodeficiency virus pandemic and shifts in the age distribution of the population. Resistance to antituberculosis drugs has also emerged as an important obstacle to control. Tuberculosis control programs in many developing and some industrialized countries have inadequate resources to combat the problem. Despite these trends, successful strategies and programs have been developed that, if implemented, would likely significantly reduce morbidity and mortality. Furthermore, recent research findings suggest that technologic advances will soon lead to improved methods for prevention and control. C1 NIH,DIV MICROBIOL & INFECT DIS,BETHESDA,MD. RP SNIDER, DE (reprint author), CTR DIS CONTROL & PREVENT,NATL CTR PREVENT SERV,MS E-07,1600 CLIFTON RD NE,ATLANTA,GA 30333, USA. NR 25 TC 74 Z9 78 U1 0 U2 6 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN PY 1994 VL 169 IS 6 BP 1189 EP 1196 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA NX991 UT WOS:A1994NX99100001 PM 7910834 ER PT J AU KASLOW, RA MANN, DL AF KASLOW, RA MANN, DL TI THE ROLE OF THE MAJOR HISTOCOMPATIBILITY COMPLEX IN HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION - EVER MORE COMPLEX SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material ID TRANSPORTER C1 NCI,IMMUNOGENET SECT,VIRAL CARCINOGENESIS LAB,BETHESDA,MD. RP KASLOW, RA (reprint author), NIAID,DMID,EPIDEMIOL & BIOMETRY BRANCH,SOLAR BLDG 3A24,BETHESDA,MD 20892, USA. NR 11 TC 22 Z9 22 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN PY 1994 VL 169 IS 6 BP 1332 EP 1333 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA NX991 UT WOS:A1994NX99100021 PM 8195612 ER PT J AU LEW, JF VALDESUSO, J VESIKARI, T KAPIKIAN, AZ JIANG, X ESTES, MK GREEN, KY AF LEW, JF VALDESUSO, J VESIKARI, T KAPIKIAN, AZ JIANG, X ESTES, MK GREEN, KY TI DETECTION OF NORWALK VIRUS OR NORWALK-LIKE VIRUS-INFECTIONS IN FINNISH INFANTS AND YOUNG-CHILDREN SO JOURNAL OF INFECTIOUS DISEASES LA English DT Note ID SERUM ANTIBODY; CAPSID ANTIGEN; ROTAVIRUS; GASTROENTERITIS; RESPONSES; ACQUISITION; PREVALENCE; CHALLENGE; DIARRHEA; ADULTS AB Norwalk virus (NV) and Norwalk-like viruses are important causes of epidemic nonbacterial gastroenteritis in older children and adults. Serologic responses to NV of 154 Finnish infants and young children participating in a rotavirus vaccine study were examined by ELISA with a recently available baculovirus-expressed recombinant NV capsid protein. In 4 serially collected sera (at the median ages of 3, 4, 14, and 23 months), 49% of children had at least one NV infection over the similar to 2-year study period. Children with low NV-specific IgG titers (<1:50) at the median age of 4 or 14 months were significantly more likely to acquire an NV infection by the median age of 14 or 23 months, respectively, than children who had higher NV IgG titers (>1:50) (P < .05). Thus, NV or Norwalk-like virus infections are more common in infants and young children than previously believed, and antibody to NV may be protective against such infections. C1 BAYLOR COLL MED,DEPT MOLEC VIROL,HOUSTON,TX. TAMPERE UNIV HOSP,DEPT BIOMED SCI,TAMPERE,FINLAND. RP LEW, JF (reprint author), NIAID,INFECT DIS LAB,RM 129,BLDG 7,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. FU NIAID NIH HHS [AI-30448] NR 15 TC 53 Z9 55 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN PY 1994 VL 169 IS 6 BP 1364 EP 1367 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA NX991 UT WOS:A1994NX99100029 PM 8195618 ER PT J AU VOELLER, DM ALLEGRA, CJ AF VOELLER, DM ALLEGRA, CJ TI DIHYDROPTEROATE SYNTHETASE ANTIBODIES SO JOURNAL OF INFECTIOUS DISEASES LA English DT Letter ID SYNTHASE C1 USN HOSP,NCI,MED ONCOL BRANCH,BETHESDA,MD 20889. NR 9 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN PY 1994 VL 169 IS 6 BP 1414 EP 1415 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA NX991 UT WOS:A1994NX99100048 PM 8195633 ER PT J AU WILMER, JL BURLESON, FG KAYAMA, F KANNO, J LUSTER, MI AF WILMER, JL BURLESON, FG KAYAMA, F KANNO, J LUSTER, MI TI CYTOKINE INDUCTION IN HUMAN EPIDERMAL-KERATINOCYTES EXPOSED TO CONTACT IRRITANTS AND ITS RELATION TO CHEMICAL-INDUCED INFLAMMATION IN MOUSE SKIN SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; CULTURED HUMAN KERATINOCYTES; ULTRAVIOLET-RADIATION; FACTOR-ALPHA; INTERLEUKIN-1; EXPRESSION; IRRADIATION; ENDOTHELIUM; MODULATION; ACTIVATION AB In response to exogenous stimuli such as phorbol-12-myristate 13-acetate, ultraviolet B radiation, and lipopolysaccharide, human keratinocytes produce soluble mediators that are important in primary contact irritancy including cytokines that are associated with proinflammatory properties (interleukin-1 alpha [IL-1 alpha], tumor necrosis factor alpha), chemotaxis (IL-8), and growth activation (granulocyte/macrophage colony stimulating factor, IL-6, transforming growth factor alpha). We examined qualitative and quantitative changes in selected intracellular and secreted cytokines in human keratinocyte cultures in response to non-sensitizing contact irritants (croton oil, sodium lauryl sulfate, methyl salicylate, ethyl phenylpropiolate), sensitizing irritants (oxazolone, dinitrofluorobenzene), and ulcerative agents (phenol, benzalkonium chloride, chromium trioxide). The chemicals were also applied to mouse skin to assess whether the chemical-specific pattern of inflammation correlated with the in vitro production of keratinocyte-derived cytokines. Although all agents elicited neutrophils to the site of chemical application, time dependent and chemical-specific patterns of inflammation could be detected. Sodium lauryl sulfate, phenol, and croton oil induced increases in IL-8 production at noncytotoxic concentrations in semi-confluent human keratinocyte cultures. Phenol and croton oil stimulated tumor necrosis factor a production, whereas croton oil was the only agent found to induce granulocyte/macrophage colony-stimulating factor production. Croton oil, phenol, benzalkonium chloride, and dinitrofluorobenzene induced the intracellular production of IL-1 alpha without a concomitant release into the medium. The release of cytokines occurred in parallel with a relative increase in cytokine-specific mRNA transcripts. Studies using neutralizing antibodies to tumor necrosis factor alpha and IL-1 alpha demonstrated that IL-8 induction by croton oil and phenol occurred directly rather than through autocrine circuits. These data suggest that a given pattern of cytokine production is chemical-specific and may predict the contribution of keratinocytes to skin inflammation. C1 UNIV OCCUPAT & ENVIRONM HLTH MED,DEPT ENVIRONM HLTH,KITAKYUSHU,FUKUOKA,JAPAN. TOKYO MED & DENT UNIV,DEPT PATHOL,TOKYO 113,JAPAN. RP WILMER, JL (reprint author), NIEHS,ENVIRONM IMMUNOL & NEUROBIOL SECT,MD C1-04,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 39 TC 159 Z9 162 U1 1 U2 5 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUN PY 1994 VL 102 IS 6 BP 915 EP 922 DI 10.1111/1523-1747.ep12383512 PG 8 WC Dermatology SC Dermatology GA NT864 UT WOS:A1994NT86400017 PM 8006454 ER PT J AU AMOS, CI BALE, SJ AF AMOS, CI BALE, SJ TI GENETIC EPIDEMIOLOGIC STUDIES IN THE ETIOLOGY OF SKIN DISEASES SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article; Proceedings Paper CT Workshop on the Epidemiology of Skin Diseases CY MAR 25-26, 1993 CL BETHESDA, MD SP NIAMSD ID EPIDERMOLYSIS-BULLOSA SIMPLEX; REGRESSIVE MODELS; GORLIN SYNDROME; MAJOR LOCUS; HYPERKERATOSIS; LINKAGE; MUTATION; DISEQUILIBRIUM; CHROMOSOME-12; INFORMATION AB Genetic epidemiologic studies have provided critical insights into the etiology of both rare and common skin diseases. Designs for these studies are distinct from those generally employed in epidemiologic studies. Here, we review the types of data collected for various genetic epidemiologic designs, inherent strengths and weaknesses. and their similarities to more classic epidemiologic methods. Examples from the study of skin diseases are provided to highlight the successful application of these methods. C1 NIAMS,SKIN BIOL LAB,GENET STUDIES SECT,BETHESDA,MD 20892. MD ANDERSON CANC CTR,DEPT EPIDEMIOL,HOUSTON,TX. NR 41 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUN PY 1994 VL 102 IS 6 BP S46 EP S48 DI 10.1111/1523-1747.ep12388573 PG 3 WC Dermatology SC Dermatology GA NT864 UT WOS:A1994NT86400045 PM 8006436 ER PT J AU BALE, SJ DOYLE, SZ AF BALE, SJ DOYLE, SZ TI THE GENETICS OF ICHTHYOSIS - A PRIMER FOR EPIDEMIOLOGISTS SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article; Proceedings Paper CT Workshop on the Epidemiology of Skin Diseases CY MAR 25-26, 1993 CL BETHESDA, MD SP NIAMSD ID STEROID SULFATASE DEFICIENCY; X-LINKED ICHTHYOSIS; EPIDERMOLYTIC HYPERKERATOSIS; PRENATAL-DIAGNOSIS; MUTATIONS; KERATIN-1; LINKAGE; CLUSTER RP BALE, SJ (reprint author), NIAMS,SKIN BIOL LAB,GENET STUDIES SECT,BLDG 6,ROOM 429,BETHESDA,MD 20892, USA. NR 26 TC 18 Z9 19 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUN PY 1994 VL 102 IS 6 BP S49 EP S50 DI 10.1111/1523-1747.ep12388591 PG 2 WC Dermatology SC Dermatology GA NT864 UT WOS:A1994NT86400046 PM 8006437 ER PT J AU MATTIELLO, J BASSER, PJ LEBIHAN, D AF MATTIELLO, J BASSER, PJ LEBIHAN, D TI ANALYTICAL EXPRESSIONS FOR THE B-MATRIX IN NMR DIFFUSION IMAGING AND SPECTROSCOPY SO JOURNAL OF MAGNETIC RESONANCE SERIES A LA English DT Article ID COEFFICIENTS; MUSCLE; WATER AB General analytical expressions are presented for the b matrix used in diffusion NMR imaging and spectroscopy. These expressions are evaluated in the case of a two-dimensional Fourier-transform spin-echo imaging sequence and show the effect of "cross terms" between gradient pulses. The diagonal and off-diagonal components of the b matrix are calculated for the anisotropic diffusion tensor. The proposed analysis allows diffusion coefficients and tensors to be determined accurately and with greater efficiency. (C) 1994 Academic Press, Inc. C1 NIH, WARREN G MAGNUSON CLIN CTR, DEPT DIAGNOST RADIOL, BETHESDA, MD 20892 USA. RP MATTIELLO, J (reprint author), NIH, NATL CTR RES RESOURCES, BIOMED ENGN & INSTRUMENTAT PROGRAM, BETHESDA, MD 20892 USA. RI Basser, Peter/H-5477-2011 NR 23 TC 120 Z9 122 U1 0 U2 11 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 PY 1994 VL 108 IS 2 BP 131 EP 141 DI 10.1006/jmra.1994.1103 PG 11 WC Physics, Atomic, Molecular & Chemical SC Physics GA NT496 UT WOS:A1994NT49600001 ER PT J AU DULING, DR AF DULING, DR TI SIMULATION OF MULTIPLE ISOTROPIC SPIN-TRAP EPR-SPECTRA SO JOURNAL OF MAGNETIC RESONANCE SERIES B LA English DT Article ID RESONANCE AB A computer program has been developed for fitting EPR data with multiple free radicals as formed in biochemical and chemical spin-trapping systems. Simulation of these spectra requires as many as 40 independent parameters, creating a chaotic analysis environment. Accurate simulation of these systems is essential for correct identification of the free radicals, which often show only slight differences in spin-Hamiltonian parameters. This method consists of rule-based perturbations with trial and error calculations and has proven successful in several applications. Details of the algorithm, example data, and a discussion of the difficulties of this analysis are presented in this report. (C) 1994 Academic Press, Inc. RP DULING, DR (reprint author), NIEHS,MOLEC BIOPHYS LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 7 TC 741 Z9 744 U1 3 U2 20 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 1994 VL 104 IS 2 BP 105 EP 110 DI 10.1006/jmrb.1994.1062 PG 6 WC Physics, Atomic, Molecular & Chemical SC Physics GA NR302 UT WOS:A1994NR30200001 PM 8049862 ER PT J AU MCNELLIS, D AF MCNELLIS, D TI A VIEW FROM THE BETHESDA - THE MATERNAL-FETAL MEDICINE UNITS (MFMU) NETWORK 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 1994 VL 4 IS 3 BP 127 EP 128 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA PF807 UT WOS:A1994PF80700001 ER PT J AU MANGIA, A VALLARI, DS DIBISCEGLIE, AM AF MANGIA, A VALLARI, DS DIBISCEGLIE, AM TI USE OF CONFIRMATORY ASSAYS FOR DIAGNOSIS OF HEPATITIS-C VIRAL-INFECTION IN PATIENTS WITH HEPATOCELLULAR-CARCINOMA SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE IMMUNOBLOT ASSAY; VIRAL HEPATITIS; LIVER CANCER ID NON-B HEPATITIS; VIRUS-ANTIBODIES; UNITED-STATES; NON-A; PREVALENCE AB Serum samples from 87 patients with hepatocellular carcinoma (HCC) in the United States were tested for evidence of hepatitis C viral (HCV) infection using an immunoblot assay for antibodies to the hepatitis C virus and the polymerase chain reaction to detect HCV RNA. The findings with these assays were compared to those with a first generation enzyme-linked immunoassay (EIA). Antibody to HCV (anti-HCV) was detected in 14 patients (16%) by EIA; only eight of these were also positive by immunoblot and four had HCV RNA by reverse transcription polymerase chain reaction (RT-PCR). An additional four cases, negative by EIA, were found to be positive by immunoblot; two of these had HCV RNA in serum. Evidence of previous hepatitis B viral infection was noted in 15 patients (17%). Only two patients with antibody to hepatitis B core antigen also had anti-HCV by the immunoblot assay, suggesting that concomitant infection with the hepatitis B and C viruses was not common. Th us, HCV infection appears to play a less important role in the pathogenesis of HCC in the United States than in southern Europe and Japan and other etiologic factors should be sought in this population. (C) 1994 Wiley-Liss, Inc.* C1 NIDDKD,LIVER DIS SECT,BETHESDA,MD 20892. ABBOTT LABS,ABBOTT DIAGNOST DIV,ABBOTT PK,IL. NR 27 TC 21 Z9 21 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD JUN PY 1994 VL 43 IS 2 BP 125 EP 128 DI 10.1002/jmv.1890430205 PG 4 WC Virology SC Virology GA NM387 UT WOS:A1994NM38700004 PM 7521900 ER PT J AU TSAREV, SA TSAREVA, TS EMERSON, SU YARBOUGH, PO LEGTERS, LJ MOSKAL, T PURCELL, RH AF TSAREV, SA TSAREVA, TS EMERSON, SU YARBOUGH, PO LEGTERS, LJ MOSKAL, T PURCELL, RH TI INFECTIVITY TITRATION OF A PROTOTYPE STRAIN OF HEPATITIS-E VIRUS IN CYNOMOLGUS MONKEYS SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE HEV GENOME; PCR; BACULOVIRUS EXPRESSED ANTIGEN; BACTERIA EXPRESSED ANTIGEN; ANTI-HEV ID NON-B HEPATITIS; TRANSMITTED NON-A; LINKED-IMMUNOSORBENT-ASSAY; MACACA-FASCICULARIS; MOLECULAR-CLONING; IDENTIFICATION; HEV; TRANSMISSION; OUTBREAK; PAKISTAN AB The infectivity titer of a standard stock of the SAR-55 strain of hepatitis E virus (HEV) was determined in cynomolgus macaques (Macaca fascicularis) and the effect of dose on the course of the infection was examined by weekly monitoring of alanine aminotransferase (ALT) and anti-HEV levels. Antibody to HEV (anti-HEV) was measured with ELISAs based on ORF-2 recombinant antigens consisting of either a 55 kDa region expressed in insect cells or shorter regions expressed as fusion proteins in bacteria. The ELISA based on the 55 kDa antigen was generally more sensitive. The infectivity titer of SAR-55 was 10(6) cynomolgus 50% infectious doses per gram of feces. The infectivity titer corresponded to the HEV genome titer of the inoculum as determined by reverse transcriptase-polymerase chain reaction (RT-PCR). Anti-HEV IgM was detected in only a portion of the anima Is that had an anti-HEV IgG response. Biochemical evidence of hepatitis was most prominent in animals that were inoculated with the higher concentrations of virus and the incubation period to seroconversion was prolonged in animals that received the lower doses. (C) 1994 Wiley-Liss, Inc.* C1 GENELABS INC,REDWOOD CITY,CA 94063. UNIFORMED SERV UNIV HLTH SCI,DEPT PREVENT MED & BIOMETR,BETHESDA,MD 20814. BIOQUAL INC,ROCKVILLE,MD. RP TSAREV, SA (reprint author), NIAID,INFECT DIS LAB,HEPATITIS VIRUSES SECT,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 30 TC 87 Z9 88 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD JUN PY 1994 VL 43 IS 2 BP 135 EP 142 DI 10.1002/jmv.1890430207 PG 8 WC Virology SC Virology GA NM387 UT WOS:A1994NM38700006 PM 8083660 ER PT J AU FONG, TL DIBISCEGLIE, AM BISWAS, R WAGGONER, JG WILSON, L CLAGGETT, J HOOFNAGLE, JH AF FONG, TL DIBISCEGLIE, AM BISWAS, R WAGGONER, JG WILSON, L CLAGGETT, J HOOFNAGLE, JH TI HIGH-LEVELS OF VIRAL REPLICATION DURING ACUTE HEPATITIS-B INFECTION PREDICT PROGRESSION TO CHRONICITY SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE HEPATITIS B VIRUS; CHRONIC HEPATITIS B; HEPATITIS B VIRUS DNA; SEROLOGY OF HEPATITIS B ID ANTIGEN-POSITIVE HEPATITIS; VIRUS-INFECTION; SERUM; DNA AB To assess the pattern of development of sero9logic markers during acute hepatitis B, levels of HBsAg, HBeAg, and hepatitis B virus (HBV) DNA were assayed in stored serum samples obtained sequentially from 12 subjects infected with HBV during experimental studies conducted in the 1950s. Six patients developed acute self-limited hepatitis, three developed chronic hepatitis, and three had an asymptomatic infection with out HBsAg. HBsAg was the first serologic marker detected (mean = 52 days after exposure), followed by HBeAg (62 days) and HBV DNA (72 days). Peak HBsAg levels occurred before onset of symptoms and correlated with peak titers of HBeAg and HBV DNA. Patients who developed chronic hepatitis had higher peak levels of viral markers than those with self-limited disease: HBsAg (30 versus 5.4 mu g/ml), HBeAg (1:2,000 versus 1:60 titer) and HBV DNA (3,192 versus 444 pg/ml). Thus, chronic HBV infection is characterized by high levels of viral replication appearing early during the acute phase of infection. (C) 1994 Wiley-Liss, Inc.* C1 NIDDKD,DIGEST DIS BRANCH,LIVER DIS SECT,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV TRANSFUS SCI,HEPATATIS LAB,BETHESDA,MD. NR 19 TC 45 Z9 47 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 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD JUN PY 1994 VL 43 IS 2 BP 155 EP 158 DI 10.1002/jmv.1890430210 PG 4 WC Virology SC Virology GA NM387 UT WOS:A1994NM38700009 PM 8083663 ER PT J AU CHATTON, JY SPRING, KR AF CHATTON, JY SPRING, KR TI ACIDIC PH OF THE LATERAL INTERCELLULAR SPACES OF MDCK CELLS CULTURED ON PERMEABLE SUPPORTS SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Article DE EPITHELIA; FLUID TRANSPORT; FLUORESCENCE MICROSCOPY; TISSUE CULTURE ID MICROCLIMATE; TRANSPORT; INTESTINE; EXCHANGE; NA+/H+; ATPASE AB The pH of the lateral intercellular space (LIS) of Madin-Darby canine kidney (MDCK) cell monolayers grown on permeable supports was investigated by microspectrofluorimetry using BCECF (2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein). The permeability of the support was selectively reduced by growing ZnAl-silicate crystals inside its pores. The diffusion of BCECF across the filter was sufficiently retarded to allow measurements of fluorescence in the LIS. The LIS pH and intracellular pH of the cells surrounding them were determined in HEPES-buffered solutions. When the perfusate pH was 7.4, the LIS pH was more acidic (7.06 +/- 0.02) and equaled the cytoplasmic pH (7.08 +/- 0.05). When perfusate was changed to pH 7.0 or 7.8, the LIS changed linearly by about half the magnitude of the perfusate pH. Intracellular pH followed LIS pH variations between perfusate pH 7.0 and 7.4 but was significantly higher when perfusate pH was 7.8. Tight junctional H+ permeability was undetectably low. The low steady-state pH in the LIS was not altered by inhibitors of acid transport or low temperature. Rapid perturbations of pH in the LIS showed that protons were not immobilized in the LIS, The acidic microenvironment within the LIS may be the result of buffering by the cell surface proteins. C1 NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BETHESDA,MD 20892. NR 25 TC 26 Z9 26 U1 0 U2 1 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 1994 VL 140 IS 2 BP 89 EP 99 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA NN757 UT WOS:A1994NN75700001 PM 7932651 ER PT J AU KIMURA, S SCHAUMANN, BA PLATO, CC AF KIMURA, S SCHAUMANN, BA PLATO, CC TI PALMAR AND PLANTAR PADS AND FLEXION CREASES OF THE RAT (RATTUS-NORVEGICUS) SO JOURNAL OF MORPHOLOGY LA English DT Article ID VOLAR PADS AB The recent detection of dermal ridge configurations on the volar pads of the rat (Rattus norvegicus) has created opportunities for experimental studies of dermatoglyphics. In the present work, the palmar and plantar surfaces of the rat were studied to establish the feasibility of comparative rat and human dermatoglyphic investigations. The studied features included the volar pads and flexion creases. The number and location of the palmar and plantar pads in the rat were found to be similar to those of humans. The exception was a previously unrecognized small pad on the palms and soles of the rat, located on the radial and tibial side, respectively, of the proximal component of the first interdigital pad. This pad has no parallel in human embryos. Rats were found to have flexion creases in the non-pad areas between the neighboring pads, similar in location and appearance to those of humans. Unlike humans, however, rats also have boundary creases, separating the pad and non-pad areas. The marked similarities in the morphology of the volar areas between rats and humans make the rat ideally suitable for experimental studies of dermatoglyphics and flexion creases. Results of such studies should be applicable to human developmental dermatoglyphics, including those pertaining to medical disorders. (C) 1994 Wiley-Liss, Inc. C1 NIHON UNIV,SCH DENT,DEPT ANAT 1,TOKYO 101,JAPAN. VET AFFAIRS MED CTR,PORTLAND,OR 97207. OREGON HLTH SCI UNIV,PORTLAND,OR 97207. NIA,BALTIMORE,MD 21224. NR 10 TC 11 Z9 12 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 0362-2525 J9 J MORPHOL JI J. Morphol. PD JUN PY 1994 VL 220 IS 3 BP 237 EP 242 DI 10.1002/jmor.1052200303 PG 6 WC Anatomy & Morphology SC Anatomy & Morphology GA NR271 UT WOS:A1994NR27100002 PM 8035464 ER PT J AU SAWAZAKI, S SALEM, N KIM, HY AF SAWAZAKI, S SALEM, N KIM, HY TI LIPOXYGENATION OF DOCOSAHEXAENOIC ACID BY THE RAT PINEAL-BODY SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE LIPOXYGENATION; DOCOSAHEXAENOIC ACID (22/6N3); PINEAL; RAT BRAIN HYDROXYDOCOSAHEXAENOIC ACID; HEPOXILIN-LIKE COMPOUND ID CENTRAL NERVOUS-SYSTEM; HYDROXY FATTY-ACIDS; ARACHIDONIC-ACID; MASS-SPECTROMETRY; HUMAN-PLATELETS; HYDROXYEICOSATETRAENOIC ACIDS; BRAIN; METABOLITES; PRODUCTS; 12-LIPOXYGENASE AB Based on the inhibitor profile, production rate, and stereochemical purity of the hydroxylated products, it was demonstrated that lipoxygenation in rat brain occurs only in the pineal. Both positional and stereochemical specificities of the hydroxylation were observed only in pineal, clearly indicating that only the pineal is capable of lipoxygenating polyunsaturated fatty acids among the rat brain regions examined. Cerebral cortex also produced hydroxy products; however, they were racemic mixtures, indicating that peroxidation was responsible for their production. Rat pineal homogenate, obtained after the brain was perfused, metabolized [C-14]docosahexaenoic acid ([1-C-14]22:6n3) to monohydroxy derivatives, primarily by the 12- and, to a lesser extent, by the 15-lipoxygenase (LO) reaction. The resulting metabolites were 14(S)- and 17(S)-hydroxydocosahexaenoic acid (HDoHE), as determined by reversed-phase HPLC, chiral-phase HPLC, thermospray liquid chromatography-mass spectrometry, and gas chromatography-mass spectrometry. Because blood was removed by perfusion of the brain before incubation, it was clear that the observed LO activity was not due to contamination with blood cell components. The production rate of 17-HDoHE from 22:6n3 was higher than that of 15-hydroxyperoxy-5,8,11,13-eicosatetraenoic acid from 20:4n6, whereas 12-LO activity toward these two substrates was comparable. These monohydroxy metabolites were also detected in the pineal body lipid extract using negative ion chemical ionization mass spectrometry. This is the first observation of endogenous production of hydroxylated compounds in pineal. The ratio of endogenous 15-LO to 12-LO products was considerably higher than that of the in vitro production from exogenous substrate. In some cases, 15-LO products were the major LO metabelites present in the lipid extract of pineal body for both 20:4n6 and 22:6n3. Both 12- and 15-LO activities were recovered mainly in the microsomal plus cytosolic fraction. In addition to monohydroxy products, epoxy, hydroxy derivatives were formed from 22:6n3 by the pineal. The major isomer was identified as 12-hydroxy-13,14-epoxy-22:5n3. C1 NIAAA, DIV INTRAMURAL CLIN & BIOL RES, MASS SPECTROMETRY SECT, MEMBRANE BIOCHEM & BIOPHYS LAB, BETHESDA, MD 20892 USA. NR 41 TC 40 Z9 41 U1 0 U2 3 PU WILEY PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD JUN PY 1994 VL 62 IS 6 BP 2437 EP 2447 PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA NN316 UT WOS:A1994NN31600046 PM 8189247 ER PT J AU LASLOP, A MAHATA, SK WOLKERSDORFER, M MAHATA, M SRIVASTAVA, M SEIDAH, NG FISCHERCOLBRIE, R WINKLER, H AF LASLOP, A MAHATA, SK WOLKERSDORFER, M MAHATA, M SRIVASTAVA, M SEIDAH, NG FISCHERCOLBRIE, R WINKLER, H TI LARGE DENSE-CORE VESICLES IN RAT ADRENAL AFTER RESERPINE - LEVELS OF MESSENGER-RNAS OF SOLUBLE AND MEMBRANE-BOUND CONSTITUENTS IN CHROMAFFIN AND GANGLION-CELLS INDICATE A BIOSYNTHESIS OF VESICLES WITH HIGHER SECRETORY QUANTA SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE CHROMOGRANIN; SECRETOGRANIN II; MONOAMINE TRANSPORTER; PROHORMONE CONVERTASE 2; CARBOXYPEPTIDASE H; CYTOCHROME B(561); CLUSTERIN ID MESSENGER-RNA LEVELS; ALPHA-AMIDATING MONOOXYGENASE; DOPAMINE BETA-HYDROXYLASE; VESICULAR AMINE TRANSPORTER; NERVE GROWTH-FACTOR; SECRETOGRANIN-II; CHROMOGRANIN-B; CARBOXYPEPTIDASE-H; NEUROPEPTIDE-Y; INSITU HYBRIDIZATION AB Rats were injected with a large dose of reserpine known to stimulate the adrenal medulla. Various times after drug treatment the mRNA levels of several constituents of large dense-core vesicles were determined by northern blot analysis and in situ hybridization. The latter method allowed detection of changes in mRNA levels not only in chromaffin cells, but also in the ganglion cells found in adrenal medulla. Levels of the mRNAs of secretory components of large dense-core vesicles (chromogranins A and B, secretogranin II, VGF, and neuropeptide Y) increased in chromaffin cells by 215-857% after 1-3 days of drug treatment. For partly membrane-bound components (dopamine beta-hydroxylase, prohormone convertase 2, carboxypeptidase H, and peptidylglycine alpha-amidating monooxygenase) the changes ranged from 182 to 315%, whereas for glycoprotein III and for intrinsic membrane proteins (cytochrome b(561) and vesicle monoamine transporter 2) no change occurred. In ganglion cells the mRNAs that could be detected for VGF, neuropeptide Y, secretogranin II, carboxypeptidase H, and vesicle monoamine transporter 1 showed an analogous pattern of change, with significant increases for the secretory proteins and no change for the membrane components. From these and previous results we suggest the following concept: Long-lasting stimulation of chromaffin cells or neurons does not induce the biosynthesis of a larger number of vesicles but rather leads to the formation of vesicles containing higher secretory quanta of chromogranins and neuropeptides. C1 NIDDKD, CELL BIOL & GENET LAB, BETHESDA, MD 20892 USA. CLIN RES INST MONTREAL, JA DE SEVE LABS BIOCHEM NEUROENDOCRINOL, MONTREAL H2W 1R7, PQ, CANADA. RP UNIV INNSBRUCK, DEPT PHARMACOL, PETER MAYR STR 1A, A-6020 INNSBRUCK, AUSTRIA. RI Seidah, Nabil/I-3596-2013 OI Seidah, Nabil/0000-0001-6503-9342 NR 68 TC 32 Z9 32 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD JUN PY 1994 VL 62 IS 6 BP 2448 EP 2456 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA NN316 UT WOS:A1994NN31600047 PM 8189248 ER PT J AU WILLIAMS, JR INSEL, TR HARBAUGH, CR CARTER, CS AF WILLIAMS, JR INSEL, TR HARBAUGH, CR CARTER, CS TI OXYTOCIN ADMINISTERED CENTRALLY FACILITATES FORMATION OF A PARTNER PREFERENCE IN FEMALE PRAIRIE VOTES (MICROTUS-OCHROGASTER) SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE OXYTOCIN; PAIR BONDING; FEMALE VOLES; SEXUAL BEHAVIOR; MONOGAMY ID SOCIAL-ORGANIZATION; MATERNAL-BEHAVIOR; VOLES; VASOPRESSIN; SHEEP; RATS AB Prairie voles (Microtus ochrogaster) are monogamous mammals that form male-female pair bonds. Partner preference formation, one component of the pair bond in prairie voles, occurs following male-female cohabitation and is facilitated by mating. The peptide hormone oxytocin is released during physical contact and particularly following vaginal stimulation. Oxytocin has been implicated in mother-infant bond formation. The present study tested the hypothesis that oxytocin participates in the partner preference component of pair bond formation in adult prairie voles. Ovariectomized female prairie voles were implanted with osmotic mini-pumps releasing oxytocin (1-100 ng/h) or artificial cerebrospinal fluid (CSF). Pumps were implanted intracerebroventricularly or subcutaneously and females then were housed for 6h with a male partner, followed by a preference test in which females could elect to spend time with either the partner or an unfamiliar male. Females in groups that received centrally-administered oxytocin (10 or 100 ng/h), but not CSF, exhibited a significant preference for the partner present during infusion. The induction of a partner preference after oxytocin administration appeared specific for central oxytocin pathways as peripheral oxytocin administration was ineffective. Moreover, central administration of a selective oxytocin receptor antagonist inhibited the behavioral effect of exogenous oxytocin. These results suggest that oxytocin may be one factor contributing to the development of partner preferences in this monogamous rodent. C1 UNIV MARYLAND,DEPT ZOOL,COLL PK,MD 20742. NIMH,NEUROPHYSIOL LAB,POOLESVILLE,MD 20837. FU NIMH NIH HHS [NIMH MH45836] NR 27 TC 281 Z9 286 U1 5 U2 49 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD JUN PY 1994 VL 6 IS 3 BP 247 EP 250 DI 10.1111/j.1365-2826.1994.tb00579.x PG 4 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA NR811 UT WOS:A1994NR81100002 PM 7920590 ER PT J AU AGUILERA, G PHAM, QC RABADANDIEHL, C AF AGUILERA, G PHAM, QC RABADANDIEHL, C TI REGULATION OF PITUITARY VASOPRESSIN RECEPTORS DURING CHRONIC STRESS - RELATIONSHIP TO CORTICOTROPH RESPONSIVENESS SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE HPA AXIS; STRESS; VASOPRESSIN; V1 RECEPTORS; ACTH ID ADRENAL AXIS; ADRENOCORTICOTROPIN SECRETION; STIMULATED ADRENOCORTICOTROPIN; PARAVENTRICULAR NUCLEUS; HYPOTHALAMIC NUCLEI; DOWN-REGULATION; MESSENGER-RNA; RESPONSES; RAT; RELEASE AB The relationship between vasopressin (VP) receptor levels in the anterior pituitary and VP-stimulated ACTH release in vitro was studied in rats subjected to Various chronic stress paradigms. The stress models used were water deprivation for 60 h and administration of 2% NaCl in the drinking water (both of which are associated with decreased pituitary ACTH responsiveness), and repeated i.p. hypertonic saline injections or repeated daily immobilization for 14 days (associated with increased ACTH responsiveness to novel stimuli). VP receptors were measured by binding of [H-3]arginine-VP to anterior pituitary membrane-rich fractions, and ACTH responses to VP in collagenase dispersed anterior pituitary cells. In control rats, binding of [H-3]AVP was saturable and high affinity, with a Kd of 0.45 +/- 0.05 nM and a B-max of 138.8 +/- 8.1 fmol/mg. In pituitary membranes from stressed rats, binding affinity was unchanged, but B-max changed according to the type of stress. While VP binding was markedly reduced after water deprivation and 2% saline (25% and 49%, respectively), it was significantly increased after repeated i.p. hypertonic saline injections and repeated immobilization (126% and 154% of controls, respectively). The changes in VP binding were associated to parallel changes in maximum VP-stimulated ACTH production in vitro, with a 34% decrease in water deprived rats and a 25% increase in hypertonic saline injected rats. The potentiating effect of VP on corticotropin releasing hormone-stimulated ACTH was also reduced in cells from water-restricted rats, and increased in cells from rats given repeated injections of hypertonic saline. The data show a direct relationship between changes in corticotroph responsiveness and changes in pituitary VP receptors during chronic stress, suggesting that pituitary VP receptor regulation is involved in the adaptation of the HPA axis during chronic stress. RP AGUILERA, G (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,ENDOCRINE PHYSIOL SECT,BLDG 10,RM 10N 262,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 43 TC 75 Z9 75 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD JUN PY 1994 VL 6 IS 3 BP 299 EP 304 DI 10.1111/j.1365-2826.1994.tb00586.x PG 6 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA NR811 UT WOS:A1994NR81100009 PM 7612075 ER PT J AU WONG, LA MAYER, ML JANE, DE WATKINS, JC AF WONG, LA MAYER, ML JANE, DE WATKINS, JC TI WILLARDIINES DIFFERENTIATE AGONIST BINDING-SITES FOR KAINATE-PREFERRING VERSUS AMPA-PREFERRING GLUTAMATE RECEPTORS IN DRG-NEURONS AND HIPPOCAMPAL-NEURONS SO JOURNAL OF NEUROSCIENCE LA English DT Article DE GLUTAMATE; KAINATE; AMPA; WILLARDIINE; DESENSITIZATION; DOSE-RESPONSE; DORSAL ROOT GANGLION; HIPPOCAMPUS ID AMINO-ACID RECEPTORS; METHYL-D-ASPARTATE; SYNAPTIC CURRENTS; QUISQUALATE RECEPTORS; MOLECULAR-CLONING; CONCANAVALIN-A; CHANNEL; DESENSITIZATION; ACTIVATION; RAT AB Concentration jump responses to ti-substituted (S)-willardiines were recorded from dorsal root ganglion (DRG) and hippocampal neurons under voltage clamp. After block of desensitization by concanavalin-A, dose-response analysis for activation of kainate-preferring receptors in DRG neurons gave the potency sequence trifluoromethyl > iodo > bromo approximate to chloro > nitro approximate to cyano > kainate > methyl > fluoro > (R,S)-AMPA >> willardiine; EC(50) values for the most and least potent willardiine derivatives, 5-trifluoromethyl (70 nM) and 5-fluoro (69 mu M), differed 1000-fold. The potency sequence for equilibrium responses at AMPA-preferring receptors in hippocampal neurons was strikingly different from that obtained in DRG neurons: fluoro > cyano approximate to trifluoromethyl approximate to nitro > chloro approximate to bromo > (R,S)-AMPA > iodo > willardiine > kainate > methyl. In hippocampal neurons EC(50) values for the most and least potent willardiine derivatives, 5-fluoro (1.5 mu M) and 5-methyl (251 mu M), differed only 170-fold. Consistent with equilibrium potency measurements, in DRG neurons the kinetics of deactivation for willardiines, recorded following a return to agonist-free solution, were rapid for 5-fluoro (tau(off) = 43 msec) but slow for 5-iodo (tau(off) = 4.2 sec), while the opposite sequence was observed for hippocampal neurons, slow for 5-fluoro (tau(off) = 2.1 sec) and rapid for 5-iodo (tau(off) = 188 msec). The kinetics of recovery from desensitization showed comparable agonist- and cell-dependent differences. Structure-activity analysis for agonist responses recorded from DRG and hippocampal neurons suggests that for both kainate-preferring and AMPA-preferring receptors the binding of willardiines involves interactions with polar groups such that potency is related to ionization of the uracil ring, and hence the electron-withdrawing ability of the 5-position substituent. However, kainate-preferring receptors differ from AMPA-preferring receptors in possessing a lipophilic pocket that further enhances agonist potency by hydrophobic bonding of the 5-substituent. In contrast, AMPA-preferring receptors lack such a lipophilic site, and for 5-position substituents of the same electron-withdrawing ability, potency decreases with increase in size. C1 NICHHD, CELLULAR & MOLEC NEUROPHYSIOL LAB, BETHESDA, MD 20892 USA. UNIV BRISTOL, SCH MED SCI, DEPT PHARMACOL, BRISTOL BS8 1TD, ENGLAND. RI Mayer, Mark/H-5500-2013 NR 36 TC 100 Z9 102 U1 0 U2 1 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 1994 VL 14 IS 6 BP 3881 EP 3897 PG 17 WC Neurosciences SC Neurosciences & Neurology GA NR138 UT WOS:A1994NR13800039 PM 7515954 ER PT J AU DELEON, M NAHIN, RL MENDOZA, ME RUDA, MA AF DELEON, M NAHIN, RL MENDOZA, ME RUDA, MA TI SR13/PMP-22 EXPRESSION IN RAT NERVOUS-SYSTEM, IN PC12 CELLS, AND C6 GLIAL-CELL LINES SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE GAS3; MYELIN PROTEINS; SATELLITE CELLS; NERVE GROWTH FACTOR ID TOOTH DISEASE TYPE-1A; PERIPHERAL MYELIN PROTEIN; GROWTH-FACTOR-RECEPTOR; ARREST-SPECIFIC GENE; TREMBLER-J MOUSE; SCIATIC-NERVE; SCHWANN-CELLS; MESSENGER-RNA; INSITU HYBRIDIZATION; DIFFERENTIAL REGULATION AB SR13/PMP-22 is a protein that was identified after screening a sciatic nerve cDNA library. Our study focused on comparing the level and pattern of expression of SR13/PMP-22 protein and RNA. Northern blot analysis revealed that although SR13/PMP-22 mRNA was present in all nervous tissues and cells studied, levels were at least seven fold higher in the sciatic nerve and the spinal cord. During sciatic nerve postnatal development and maturation, the SR13/PMP-22 mRNA was detected at 2 days after birth, reached a maximal level at day 24, and decreased to 1/3 of the maximum in adult animals. Nerve transection reduced the level of SR13/PMP-22 mRNA to less than 5% in the segment distal to the nerve injury. Experiments using in situ hybridization localized the SR13/PMP-22 mRNA in Schwann cells. Schwann cells present in the vicinity or distal to the nerve cut repressed the signal for the message. In situ hybridization experiments also demonstrated that dorsal root ganglia satellite cells contained the message for SR13/PMP-22. The SR13/PMP-22 antisera used in our study showed a complex pattern of staining. As expected, the SR13/PMP-22 antibody peptide 1 immunoreacted with the sciatic nerve sheath. However, immunocytochemistry of the dorsal root ganglia revealed that the staining was contained in the neuron's cell body and processes and also in satellite cells. We also identified immunoreactive cell bodies and fibers in the spinal cord dorsal horn. Tissue culture studies demonstrated that SR13/PMP-22 mRNA is induced in NGF treated PC12 but not in C6 glioma cell lines grown under experimental conditions that stimulated cell growth arrest. Our experiments suggest that SR13/PMP-22 may have some other function(s) in addition to its hypothesized role in peripheral myelination. (C) 1994 Wiley-Liss, Inc.* C1 NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD 20892. RI De Leon, Marino/A-6922-2009 OI De Leon, Marino/0000-0001-6576-785X NR 60 TC 16 Z9 16 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD JUN 1 PY 1994 VL 38 IS 2 BP 167 EP 181 DI 10.1002/jnr.490380207 PG 15 WC Neurosciences SC Neurosciences & Neurology GA NM078 UT WOS:A1994NM07800006 PM 8078102 ER PT J AU JOHNSON, DL MCCABE, MA NICHOLSON, HS JOSEPH, AL GETSON, PR BYRNE, J BRASSEUX, C PACKER, RJ REAMAN, G AF JOHNSON, DL MCCABE, MA NICHOLSON, HS JOSEPH, AL GETSON, PR BYRNE, J BRASSEUX, C PACKER, RJ REAMAN, G TI QUALITY OF LONG-TERM SURVIVAL IN YOUNG-CHILDREN WITH MEDULLOBLASTOMA SO JOURNAL OF NEUROSURGERY LA English DT Article DE MEDULLOBLASTOMA; BRAIN NEOPLASM; LONG-TERM SURVIVAL; RADIATION THERAPY; OUTCOME; CHILDREN ID BRAIN-TUMORS; CHILDHOOD; AGE; IRRADIATION; LIFE; CNS AB The reported success of treatment for children with medulloblastoma must be balanced against the effect that treatment has on the quality of life of long-term survivors. The outcome of long-term survivors reported in previous studies has been conflicting. The authors evaluate the mental and behavioral skills of a group of medulloblastoma survivors from their institution, all of whom had survived for more than 5 years postdiagnosis. A review of the institutional records yielded 32 patients. Twenty-three families were interviewed by telephone and, of these, 13 subjects came to the hospital for detailed neuropsychological and neurological evaluations. Intelligence quotient (IQ) was less than 90 for all participants tested, and patients diagnosed before the age of 3 years had lower IQ scores on average than those diagnosed later. Mean IQ and achievement test scores in reading, spelling, and mathematics were all higher in survivors who had undergone shunting. Achievement test results were often not in accord with intellectual potential, and individual intellectual skills varied widely. Perceptual-motor task performance was below average in more than 50% of the participants, but motor dexterity was more severely affected than perception. Problems in learning and a delay in both physical growth and development were seen in a majority of participants. This study directs attention to the serious difficulties faced by long-term survivors of medulloblastoma and their families, and underscores the importance of routine neuropsychological testing. Moreover, the study provides further impetus to seek alternatives to irradiation in the treatment of malignant brain tumors. C1 CHILDRENS NATL MED CTR,DEPT NEUROSURG,WASHINGTON,DC 20010. CHILDRENS NATL MED CTR,DEPT HEMATOL ONCOL,WASHINGTON,DC 20010. CHILDRENS NATL MED CTR,DEPT PSYCHOL,WASHINGTON,DC 20010. CHILDRENS NATL MED CTR,DEPT NEUROL,WASHINGTON,DC 20010. GEORGE WASHINGTON UNIV,SCH MED & HLTH SCI,DEPT NEUROSURG,WASHINGTON,DC 20052. GEORGE WASHINGTON UNIV,SCH MED & HLTH SCI,DEPT PEDIAT,WASHINGTON,DC 20052. GEORGE WASHINGTON UNIV,SCH MED & HLTH SCI,DEPT NEUROL,WASHINGTON,DC 20052. NCI,CLIN EPIDEMIOL BRANCH,BETHESDA,MD 20892. NR 33 TC 84 Z9 84 U1 0 U2 6 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 1994 VL 80 IS 6 BP 1004 EP 1010 DI 10.3171/jns.1994.80.6.1004 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA NN146 UT WOS:A1994NN14600007 PM 8189255 ER PT J AU TAKESHIMA, H KURATSU, JI TAKEYA, M YOSHIMURA, T USHIO, Y AF TAKESHIMA, H KURATSU, JI TAKEYA, M YOSHIMURA, T USHIO, Y TI EXPRESSION AND LOCALIZATION OF MESSENGER-RNA AND PROTEIN FOR MONOCYTE CHEMOATTRACTANT PROTEIN-1 IN HUMAN-MALIGNANT GLIOMA SO JOURNAL OF NEUROSURGERY LA English DT Article DE MONOCYTE CHEMOATTRACTANT PROTEIN-1; CYTOKINE; GLIOMA GENE EXPRESSION; MACROPHAGE INFILTRATION ID MONOCLONAL-ANTIBODIES; CLONING; TUMORS; JE; PURIFICATION; MACROPHAGES; GROWTH; MCP-1; ACID AB Expression of monocyte chemoattractant protein-1 (MCP-1) in human glioma cell lines and surgical specimens was studied by Northern blot analysis, reverse-transcription polymerase chain reaction, in situ hybridization, and immunohistochemistry. The samples tested consisted of 11 human glioma cell lines and eight specimens of human malignant glioma (seven from glioblastomas and one from a malignant ependymoma). Messenger ribonucleic acid (mRNA) of MCP-1 was detected by either Northern blot or reverse-transcription polymerase chain reaction analysis in all cell lines and tumor specimens examined. In vivo expression of MCP-1 mRNA and protein was found predominantly in glioma cells with large and pleomorphic nuclei rather than in areas of small nucleated glioma cells. Adjacent brain tissue did not produce a significant level of MCP-1 mRNA or protein. Tumor vessels with endothelial proliferation expressed a moderate level of MCP-1 protein. Macrophages were found among the glioma cells, and the degree of macrophage infiltration was grossly correlated with the level of MCP-1 expression. The study results suggest that MCP-1 produced by the glioma cells may mediate macrophage infiltration into the glioma tissue. C1 KUMAMOTO UNIV,SCH MED,DEPT NEUROSURG,KUMAMOTO 860,JAPAN. KUMAMOTO UNIV,SCH MED,DEPT PATHOL,KUMAMOTO 860,JAPAN. NCI,IMMUNOBIOL LAB,IMMUNOPATHOL SECT,FREDERICK,MD 21701. NR 27 TC 75 Z9 78 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 1994 VL 80 IS 6 BP 1056 EP 1062 DI 10.3171/jns.1994.80.6.1056 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA NN146 UT WOS:A1994NN14600013 PM 8189261 ER PT J AU PLUTA, RM RAM, Z PATRONAS, NJ KEISER, H AF PLUTA, RM RAM, Z PATRONAS, NJ KEISER, H TI LONG-TERM EFFECTS OF RADIATION-THERAPY FOR A CATECHOLAMINE-PRODUCING GLOMUS-JUGULARE TUMOR - CASE-REPORT SO JOURNAL OF NEUROSURGERY LA English DT Article DE GLOMUS JUGULARE TUMOR; NOREPINEPHRINE; BONE NECROSIS; RADIATION THERAPY; OTORRHEA; EMPTY SELLA ID TEMPORAL BONE; BRAIN-TUMORS; SKULL BASE; CHEMODECTOMA; PARAGANGLIOMAS; MANAGEMENT; SURGERY AB A 42-year-old woman presented with otorrhea 22 years after extracranial resection of a norepinephrine-secreting glomus jugulare tumor with intravascular embolization and radiation therapy to the intracranial portion of the tumor. Tumor growth was arrested and was associated with a decrease in blood and urine norepinephrine levels. Extensive evaluation of the otorrhea, including computerized tomography-cisternography, gadolinium-enhanced magnetic resonance imaging, and arteriography showed marked diffuse necrosis of the temporal bone and skull base with limited tumor vascularity. Cerebrospinal fluid (CSF) collected from the right ear showed norepinephrine levels of 2975 pg/ml; plasma norepinephrine levels were normal. The precise site of CSF leakage could not be delineated. Exploration of the posterior fossa revealed a large dural defect at the anteromedial aspect of the petrous bone through which CSF flowed over the surface of the residual extradural glomus tumor. The defect was successfully sealed with a fascial patch. Postoperatively, CSF norepinephrine levels were normal and no further leakage was observed. C1 NIH,CTR CLIN,DEPT RADIOL,BETHESDA,MD 20892. NHLBI,HYPERTENS ENDOCRINE BRANCH,BETHESDA,MD 20892. RP PLUTA, RM (reprint author), NINCDS,SURG NEUROL BRANCH,BLDG 10,ROOM 5D37,BETHESDA,MD 20892, USA. NR 36 TC 18 Z9 19 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD JUN PY 1994 VL 80 IS 6 BP 1091 EP 1094 DI 10.3171/jns.1994.80.6.1091 PG 4 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA NN146 UT WOS:A1994NN14600018 PM 8189265 ER PT J AU GOLDSTEIN, DS CORONADO, L KOPIN, IJ AF GOLDSTEIN, DS CORONADO, L KOPIN, IJ TI 6-[FLUORINE-18]FLUORODOPAMINE PHARMACOKINETICS AND DOSIMETRY IN HUMANS SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE 6-[FLUORINE-18]FLUORODOPAMINE; SYMPATHETIC INNERVATION; DOSIMETRY; NOREPINEPHRINE ID CARDIAC SYMPATHETIC INNERVATION; F-18 6-FLUORODOPAMINE; NOREPINEPHRINE; 6-FLUORODOPAMINE; DIHYDROXYPHENYLGLYCOL; NEUROTRANSMITTERS; 2-FLUORODOPAMINE; METABOLISM; REMOVAL; PLASMA AB PET scanning after injection of 6-[F-18]fluorodopamine visualizes tissue sympathetic innervation. Organ dosimetric estimates for 6-[F-18]fluorodopamine have relied on studies of rats and dogs and on literature about the fate of other radiolabeled catecholamines. This report uses empirical clinical findings in healthy volunteers to refine and extend these estimates. Methods: Thoracic PET scanning was conducted and arterial blood and urine samples were obtained after intravenous injection of 6-[F-18]fluorodopamine into 10 normal volunteers. Results: The main target organs for 6-[F-18]fluorodopamine-derived radioactivity were the walt of the urinary bladder (3.3 rem for a 4-mCi dose and 3.31-hr voiding interval) and the kidneys (2.9 rem for a 4-mCi dose) due to urinary excretion of radioactive metabolites of [F-18]-6F-DA. The estimates were about one-fourth those predicted from studies of laboratory animals. Conclusions: At administered doses required to visualize the left ventricular myocardium in humans, a 6-[F-18]fluorodopamine injection produces acceptable absorbed radiation doses, with the highest doses to the urinary collecting system. C1 NIH,DIV SAFETY,RADIAT SAFETY BRANCH,BETHESDA,MD 20892. RP GOLDSTEIN, DS (reprint author), NINCDS,CLIN NEUROSCI BRANCH,BLDG 10 ROOM 5N262,BETHESDA,MD 20892, USA. NR 22 TC 13 Z9 13 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD JUN PY 1994 VL 35 IS 6 BP 964 EP 973 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NP288 UT WOS:A1994NP28800010 PM 8195883 ER PT J AU MEREDITH, RF BUESCHEN, AJ KHAZAELI, MB PLOTT, WE GRIZZLE, WE WHEELER, RH SCHLOM, J RUSSELL, CD LIU, TP LOBUGLIO, AF AF MEREDITH, RF BUESCHEN, AJ KHAZAELI, MB PLOTT, WE GRIZZLE, WE WHEELER, RH SCHLOM, J RUSSELL, CD LIU, TP LOBUGLIO, AF TI TREATMENT OF METASTATIC PROSTATE CARCINOMA WITH RADIOLABELED ANTIBODY CC49 SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE PROSTATE CARCINOMA; RADIOLABELED ANTIBODY ID 2ND-GENERATION MONOCLONAL-ANTIBODIES; COLORECTAL-CANCER; IMMUNE-RESPONSE; CARCINOEMBRYONIC ANTIGEN; PHASE-I; B72.3; BIODISTRIBUTION; THERAPY; PHARMACOKINETICS; XENOGRAFTS AB A Phase II trial of 75 mCi/m(2) I-131-anti-TAG-72 high-affinity antibody CC49 was studied in 15 patients with hormone-resistant metastatic prostate cancer. Methods: Patients had adequate renal, liver and hematopoietic function. No previous cytotoxic chemotherapy was allowed and previous radiation was limited to 20% of the active bone marrow. Results: No acute adverse reactions occurred, but all patients had evidence of an immune response to CC49 by 4 wk. Six of 10 symptomatic patients had bone pain relief, but no patients met the radiographic or PSA criteria for objective response. Positive imaging of bone and/or soft-tissue lesions was noted for 13 of the 15 patients. Conclusions: CC49 had a high frequency of tumor localization with evidence of anti-tumor effects (pain relief). C1 UNIV ALABAMA,DEPT UROL,BIRMINGHAM,AL. UNIV ALABAMA,DEPT MED,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT PATHOL,DIV RADIOL & NUCL MED,BIRMINGHAM,AL 35294. NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. RP MEREDITH, RF (reprint author), UNIV ALABAMA,CTR COMPREHENS CANC,LB WALLACE TUMOR INST 117,DEPT RADIAT ONCOL,BIRMINGHAM,AL 35294, USA. FU NCI NIH HHS [NCI CM87215]; NCRR NIH HHS [M01-RR-00032] NR 40 TC 104 Z9 108 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD JUN PY 1994 VL 35 IS 6 BP 1017 EP 1022 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NP288 UT WOS:A1994NP28800018 PM 8195861 ER PT J AU CHOW, WH MALKER, HSR HSING, AW MCLAUGHLIN, JK WEINER, JA STONE, BJ ERICSSON, JLE BLOT, WJ AF CHOW, WH MALKER, HSR HSING, AW MCLAUGHLIN, JK WEINER, JA STONE, BJ ERICSSON, JLE BLOT, WJ TI OCCUPATIONAL RISKS FOR COLON-CANCER IN SWEDEN SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID COLORECTAL-CANCER; PHYSICAL-ACTIVITY; ASBESTOS; SUBSITE; RECTUM; MALES AB Using the Cancer-Environment Registry of Sweden, which links census information (1960) with cancer incidence data (1961 to 1979), we conducted a systematic, population-based assessment of colon cancer incidence among cohorts defined by industry and occupation for all employed persons in Sweden. Small but statistically significant excesses of colon cancer were observed among white-collar occupations, including administrators, professionals, and clerical and sales workers, whereas a reduction in incidence was found among workers in agricultural and related jobs, such as farmers, fishermen, and hunters. Analysis by subsite within the colon revealed little difference in results. The observed risk patterns are consistent with previous reports on colon cancer risk and occupational physical activity levels, ie, elevated risk among sedentary white-collar workers and reduced risk among agricultural workers. Few craftsman and production processing jobs were linked to colon cancer, although statistically significant excesses were observed among shoe and leather workers, metal smiths, and foundry workers in the metal manufacturing industry. The findings indicate that occupation in general is likely to play a relatively small role in colon cancer etiology, with perhaps its major contribution an indirect one via physical activity. C1 NATL BOARD OCCUPAT SAFETY & HLTH,SOLNA,SWEDEN. NATL BOARD HLTH & WELF,STOCKHOLM,SWEDEN. RP CHOW, WH (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,6130 EXECUT BLVD,BETHESDA,MD 20892, USA. NR 27 TC 20 Z9 21 U1 1 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD JUN PY 1994 VL 36 IS 6 BP 647 EP 651 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PK090 UT WOS:A1994PK09000013 PM 8071728 ER PT J AU MORRISON, JA BARTON, B BIRO, FM SPRECHER, DL FALKNER, F OBARZANEK, E AF MORRISON, JA BARTON, B BIRO, FM SPRECHER, DL FALKNER, F OBARZANEK, E TI SEXUAL-MATURATION AND OBESITY IN 9-YEAR-OLD AND 10-YEAR-OLD BLACK-AND-WHITE GIRLS - THE NATIONAL-HEART-LUNG-AND-BLOOD-INSTITUTE GROWTH AND HEALTH STUDY SO JOURNAL OF PEDIATRICS LA English DT Article ID UNITED-STATES; YOUNG-ADULTS; WEIGHT; MENARCHE; OVERWEIGHT; FATNESS; RACE; AGE AB Objective: To assess the relationship between pubertal maturation and obesity in 9- and 10-year-old black and white girls. Method: Cross-sectional analysis of cohort baseline data. Subjects: A cohort of 2379 girls recruited from selected schools in Richmond, Calif., and greater Cincinnati, Ohio, and from the membership rolls of a prepaid group practice in greater Washington, D.C. C1 MARYLAND MED RES INST, BALTIMORE, MD 21010 USA. CHILDRENS HOSP, CTR MED, DIV CARDIOL, CINCINNATI, OH USA. CHILDRENS HOSP, MED CTR, DIV ADOLESCENT MED, CINCINNATI, OH USA. UNIV CINCINNATI, COLL MED, DEPT INTERNAL MED, CINCINNATI, OH USA. UNIV CALIF BERKELEY, DEPT PUBL HLTH, BERKELEY, CA USA. NHLBI, BETHESDA, MD 20892 USA. FU NHLBI NIH HHS [HC 55023-25] NR 21 TC 108 Z9 109 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD JUN PY 1994 VL 124 IS 6 BP 889 EP 895 DI 10.1016/S0022-3476(05)83176-2 PG 7 WC Pediatrics SC Pediatrics GA NQ521 UT WOS:A1994NQ52100009 PM 8201472 ER PT J AU PITHA, J GERLOCZY, A OLIVI, A AF PITHA, J GERLOCZY, A OLIVI, A TI PARENTERAL HYDROXYPROPYL CYCLODEXTRINS - INTRAVENOUS AND INTRACEREBRAL ADMINISTRATION OF LIPOPHILES SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article ID BETA-CYCLODEXTRINS; DRUGS; RAT; 2-HYDROXYPROPYL-BETA-CYCLODEXTRIN; DERIVATIVES; DISPOSITION; DISSOLUTION; CHOLESTEROL; VEHICLE; BRAIN AB Hydroxypropyl cyclodextrins are nontoxic carbohydrate derivatives of moderate molecular weight(1030-1750 Dal which form water-soluble complexes with many lipophiles. The fate of hydroxypropyl beta-cyclodextrin alone and in complex with testosterone or cholesterol injected intravenously or intracerebrally into rats was followed. More than 90% of intravenously administered hydroxypropyl beta-cyclodextrin was cleared into urine in 4 h, as previously described (Monbaliu, J.; Van Beijsterveld, L.; Meuldermans, W.; Szathmary, S.; Haykants, J. Abstracts, 5th International Symposium on Cyclodextrins, Paris, 1990; Abstract 65). After the injection of steroids in complex with hydroxypropyl beta-cyclodextrin into the tail vein of rats, the steroid component was released from the complex, before it reached the kidneys; the release occurred mainly into the proteins and lipoproteins of serum. Hydroxypropyl beta-cyclodextrins injected alone into the brain were cleared within less than 24 h, presumably via the flow of interstitial and cerebrospinal fluids, and eventually were excreted in urine. Testosterone, incorporated in a hydroxypropyl beta-cyclodextrin complex, after intracerebral injection was cleared from the brain even more rapidly than hydroxypropyl beta-cyclodextrin, presumably by crossing the blood-brain barrier and later removal to the liver by the specific carrier proteins in serum. Complexed cholesterol, in a similar experiment, was largely retained in the brain and its distribution there was uneven and remained that way for at least 3 days. It is clear that lipophilic agents, after their incorporation into hydroxypropyl beta-cyclodextrin complexes and subsequent in vivo administration, are rapidly released and exchanged into the plasma. In absence of plasma they enter tissues surrounding the injection site and thus are also promptly transferred into the organism's lipid systems. The manner in which different lipophilic agents are transported in vivo appears not to be greatly affected by their previous complexation; rather hydroxypropyl cyclodextrins just enable their entry in a larger amount and in an exchangeable, nonaggregated form. C1 CYCOLAB INC,H-1525 BUDAPEST,HUNGARY. JOHNS HOPKINS UNIV HOSP,DEPT NEUROSURG,BALTIMORE,MD 21205. RP PITHA, J (reprint author), NIA,GERONTOL RES CTR,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. RI Olivi, Alessandro/K-6531-2016 OI Olivi, Alessandro/0000-0002-4489-7564 NR 32 TC 31 Z9 32 U1 1 U2 5 PU AMER PHARMACEUTICAL ASSN PI WASHINGTON PA 2215 CONSTITUTION AVE NW, WASHINGTON, DC 20037 SN 0022-3549 J9 J PHARM SCI JI J. Pharm. Sci. PD JUN PY 1994 VL 83 IS 6 BP 833 EP 837 DI 10.1002/jps.2600830615 PG 5 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA NP296 UT WOS:A1994NP29600014 PM 9120816 ER PT J AU LIN, WW CHUANG, DM AF LIN, WW CHUANG, DM TI DIFFERENT SIGNAL-TRANSDUCTION PATHWAYS ARE COUPLED TO THE NUCLEOTIDE RECEPTOR AND THE P-2Y RECEPTOR IN C-6 GLIOMA-CELLS SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID PROTEIN KINASE-C; FRTL-5 THYROID-CELLS; EXTRACELLULAR ATP; PHOSPHOLIPASE-C; P2Y-PURINERGIC RECEPTOR; ADENYLATE-CYCLASE; RAT HEPATOCYTES; HUMAN-PLATELETS; INHIBITION; STIMULATION AB In C-6 glioma cells, extracellular ATP and other nucleotide analogs stimulated phosphoinositide (Pl) breakdown and inhibited isoproterenol-induced cyclic AMP (cAMP) accumulation. The rank orders of potencies of 15 nucleotide analogs for both responses were clearly different. ATP and adenosine 5'-O-(3-thiotriphosphate) are the most potent agonists for stimulating Pl hydrolysis; 2-methylthio-ATP (2-MeSATP) is the most potent agonist for inhibiting cAMP accumulation. P-1-mediated responses of Pl turnover and cAMP formation are not present in C-6 glioma cells. Pertussis toxin (PTX) blocked the nucleotide-induced inhibition of cAMP accumulation but exerted no effect on inositol phosphate formation. Short-term treatment with phorbol 12-myristate 13-acetate inhibited both signal transduction pathways. The effects of three P-2 purinergic antagonists, suramin, reactive blue and 4,4'-diisothiocyanatostilbene sulfonic acid (DIDS), on ATP-and 2-MeSATP-induced stimulation of Pl turnover and inhibition of cAMP formation, respectively, were compared. For stimulating Pl turnover, suramin is a competitive antagonist (pA(2), 4.4); reactive blue and DIDS are noncompetitive antagonists at 30 mu M and 100 mu M, respectively. For the inhibition of cAMP formation, reactive blue and DIDS competitively antagonized the response of 2-MeSATP (pA(2) values, 6.3 for reactive blue and 5.7 for DIDS); suramin was only slightly effective at 100 mu M. If was concluded that the nucleotide receptor is linked to phospholipase C by a PTX-insensitive Gp protein and the P-2Y receptor is linked to adenylyl cyclase by a PTX-sensitive Gi protein. Suramin is a competitive antagonist for the nucleotide receptor; reactive blue and DIDS are more selective antagonists for the P-2Y receptor. C1 NIMH,BIOL PSYCHIAT BRANCH,MOLEC NEUROBIOL SECT,BETHESDA,MD 20892. RP LIN, WW (reprint author), NATL TAIWAN UNIV,COLL MED,DEPT PHARMACOL,TAIPEI 10764,TAIWAN. OI Lin, Wan Wan/0000-0002-3207-734X NR 39 TC 37 Z9 37 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 1994 VL 269 IS 3 BP 926 EP 931 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PB548 UT WOS:A1994PB54800006 PM 8014879 ER PT J AU PILOTTE, NS SHARPE, LG KUHAR, MJ AF PILOTTE, NS SHARPE, LG KUHAR, MJ TI WITHDRAWAL OF REPEATED INTRAVENOUS INFUSIONS OF COCAINE PERSISTENTLY REDUCES BINDING TO DOPAMINE TRANSPORTERS IN THE NUCLEUS-ACCUMBENS OF LEWIS RATS SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID BASAL EXTRACELLULAR DOPAMINE; INVIVO MICRODIALYSIS; MOLECULAR MECHANISMS; CEREBRAL METABOLISM; CHRONIC MORPHINE; REWARD REGIONS; H-3 GBR-12935; ADDICTION; BRAIN; SYSTEM AB Mate, Lewis rats were administered cocaine or saline i.v. in an intermittent fashion for 5, 10 or 20 days and killed at various times afterwards. Dopamine transporter binding was then measured in dorsal striatum and nucleus accumbens. Transporter binding was not changed in dorsal striatum under any conditions tested. In the nucleus accumbens, however, binding was decreased in animals given cocaine (10 mg/kg total) far 10 days and withdrawn for 10, 30 or 60 days, but not in animals withdrawn for 0, 1, 3 and 6 days. There were no changes in animals given cocaine for 5 days and withdrawn for 10, or in animals given drug for 20 days and withdrawn for 1 day. Animals given only 1/10 of the cocaine dose had no changes in nucleus accumbens after 10 days of administration and 10 days of withdrawal. Scatchard analysis in control animals indicated that there were significant differences in both K-d and B-max when comparing nucleus accumbens with dorsal striatum. Within the nucleus accumbens, decreases in binding after a cessation of cocaine administration were associated with a change in B-max and not in K-d. These data indicate that long-lasting changes in the mesolimbic dopaminergic system can occur during the withdrawal period, and may contribute to behavioral effects during this period. C1 NIDA,ADDICT RES CTR,NEUROSCI BRANCH,BALTIMORE,MD 21224. NATL INST DRUG ABUSE,ADDICT RES CTR,PRECLIN PHARMACOL BRANCH,BALTIMORE,MD 21224. NR 54 TC 79 Z9 79 U1 3 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JUN PY 1994 VL 269 IS 3 BP 963 EP 969 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PB548 UT WOS:A1994PB54800011 PM 7912283 ER PT J AU HIRAMATSU, Y KAWAI, R REBA, RC BLASBERG, RG BAUM, BJ AF HIRAMATSU, Y KAWAI, R REBA, RC BLASBERG, RG BAUM, BJ TI KINETIC-ANALYSIS OF RAT EXOCRINE GLAND MUSCARINIC RECEPTORS IN-VIVO SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; ACETYLCHOLINE-RECEPTORS; BINDING-SITES; BLOOD-FLOW; INVIVO; BRAIN; ANTAGONISTS; TRANSPORT; MEMBRANES; AFFINITY AB Recently we employed two enantiomers of the muscarinic antagonist quinuclidinyl iodobenzilate (IQNB), and pharmacokinetic analyses, to define and quantitate nonspecific and specific binding to rat parotid gland muscarinic acetylcholine receptors (mAChRs) in vivo (Hiramatsu et al., 1993). The present studies were designed to utilize this same approach for evaluating mAChRs in three other morphologically different rat exocrine glands: the submandibular, sublingual and lacrimal glands. The metabolism and tissue distribution of the intravenously injected IQNB enantiomers were determined, and the resulting data were assessed in terms of their goodness of fit to several multicompartmental models. All three exocrine glands showed substantial nonspecific ligand distribution as measured with the receptor-inert enantiomer (SS)-IQNB. Nonspecific distribution represented 45, 21 and 36% of total ligand distribution in submandibular, sublingual and lacrimal glands, respectively, as measured with the receptor-active enantiomer (RR)-IQNB. The rank order of the binding potential, kinetically equivalent to B-max/K-d, for(RR)-IQNB and these mAChRs was lacrimal > sublingual > submandibular glands (674 +/- 235 > 575 +/- 109 > 345 +/- 29). These results demonstrate that specific mAChRs in the exocrine glands can be measured in vivo with the (RR)-IQNB enantiomer and that despite some small quantitative differences, the distribution of (RR)- and (SS)-IQNB is similar in the three exocrine glands but is substantially different from that in brain and heart. C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT NUCL MED,BETHESDA,MD 20892. UNIV CHICAGO,DEPT RADIOL,CHICAGO,IL 60637. MEM SLOAN KETTERING CANC CTR,DEPT NEUROONCOL,NEW YORK,NY 10021. FU NINDS NIH HHS [NS-22215] NR 31 TC 3 Z9 3 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 1994 VL 269 IS 3 BP 1205 EP 1212 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PB548 UT WOS:A1994PB54800042 PM 8014864 ER PT J AU WOLFE, BE AF WOLFE, BE TI ADAPTING PSYCHOTHERAPY OUTCOME RESEARCH TO CLINICAL REALITY - COMMENT SO JOURNAL OF PSYCHOTHERAPY INTEGRATION LA English DT Note RP WOLFE, BE (reprint author), NIMH,BETHESDA,MD 20892, USA. NR 0 TC 11 Z9 11 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 1053-0479 J9 J PSYCHOTHER INTEGR JI J. Psychother. Integr. PD JUN PY 1994 VL 4 IS 2 BP 160 EP 166 PG 7 WC Psychology, Clinical SC Psychology GA PH952 UT WOS:A1994PH95200005 ER PT J AU MCKENNA, K GORDON, CT LENANE, M KAYSEN, D FAHEY, K RAPOPORT, JL AF MCKENNA, K GORDON, CT LENANE, M KAYSEN, D FAHEY, K RAPOPORT, JL TI LOOKING FOR CHILDHOOD-ONSET SCHIZOPHRENIA - THE 1ST 71 CASES SCREENED SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE CHILDHOOD; SCHIZOPHRENIA; PSYCHOSIS ID PSYCHIATRICALLY DISTURBED-CHILDREN; BORDERLINE CHILDREN; PSYCHOSES; DISORDERS; HALLUCINATIONS; CLASSIFICATION; PHENOMENOLOGY AB Objective: To review psychiatric referrals to a study of childhood-onset schizophrenia. Method: Children and adolescents (N = 71) and their parents selected from a total of 260 patients referred to the National Institute of Mental Health between 1990 and 1993, with onset of psychosis at or before age 12 years, were screened in person, using the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Epidemiologic Version, portions of the Diagnostic Interview for Children and Adolescents-Parent Version, and clinical interview. Best-estimate diagnoses using all sources of information were determined. Thought disorder was rated on a subset of subjects using standardized videotaped speech samples. Results: Interrater reliability (kappa) between two child psychiatrists for best-estimate primary diagnoses ranged from .65 to .81. Schizophrenia was diagnosed for 19 children who by history had had onset at or before age 12, but all were in puberty when interviewed. Affective disorders (N = 14) and Asperger's syndrome and pervasive developmental disorder not otherwise specified (N = 6) were also diagnosed. A large group of reliably identifiable children not completely described by any DSM-III-R category and provisionally called ''multidimensionally impaired'' (N = 21) with multiple language or learning disorders, mood lability, and transient psychotic symptoms was seen. Conclusions: Childhood-onset schizophrenia is often misdiagnosed, perhaps because of the rarity of the disorder and the ambiguity in applying primary criteria. An array of developmental disturbances are seen with less pervasive childhood-onset psychotic symptoms. RP MCKENNA, K (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,ROOM 6N240,BETHESDA,MD 20892, USA. NR 40 TC 141 Z9 142 U1 4 U2 6 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUN PY 1994 VL 33 IS 5 BP 636 EP 644 DI 10.1097/00004583-199406000-00003 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA NN869 UT WOS:A1994NN86900003 PM 8056726 ER PT J AU FRAZIER, JA GORDON, CT MCKENNA, K LENANE, MC JIH, D RAPOPORT, JL AF FRAZIER, JA GORDON, CT MCKENNA, K LENANE, MC JIH, D RAPOPORT, JL TI AN OPEN TRIAL OF CLOZAPINE IN 11 ADOLESCENTS WITH CHILDHOOD-ONSET SCHIZOPHRENIA SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE CLOZAPINE; ADOLESCENTS; SCHIZOPHRENIA; HALOPERIDOL ID CHILDREN AB To review the response of 11 adolescents with childhood-onset schizophrenia to a 6-week open clozapine trial. Method: Eleven children meeting DSM-III-R criteria for schizophrenia had a 6-week open trial of clozapine (mean sixth week daily dose 370 mg). Behavioral ratings included the Brief Psychiatric Rating Scale and Children's Global Assessment Scale. Results: More than half showed marked improvement in Brief Psychiatric Rating Scale ratings by 6 weeks of clozapine therapy compared to admission drug rating and compared to a systematic 6-week trial of haloperidol. Conclusions: This open trial indicates that clozapine may be a promising treatment for children and adolescents with schizophrenia who do not respond well to typical neuroleptics. A double-blind placebo-controlled study is ongoing. RP FRAZIER, JA (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,ROOM 6N240,BETHESDA,MD 20892, USA. RI Louza, Mario/H-8540-2013 OI Louza, Mario/0000-0003-1359-4111 NR 32 TC 100 Z9 100 U1 2 U2 5 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUN PY 1994 VL 33 IS 5 BP 658 EP 663 DI 10.1097/00004583-199406000-00006 PG 6 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA NN869 UT WOS:A1994NN86900006 PM 8056728 ER PT J AU CHATOOR, I HERMAN, BH HARTZLER, J AF CHATOOR, I HERMAN, BH HARTZLER, J TI EFFECTS OF THE OPIATE ANTAGONIST, NALTREXONE, ON BINGING ANTECEDENTS AND PLASMA BETA-ENDORPHIN CONCENTRATIONS SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE NALTREXONE; BINGING ANTECEDENTS; BULIMIA NERVOSA; BETA-ENDORPHIN ID SELF-INJURIOUS-BEHAVIOR; AUTISTIC-CHILDREN; BULIMIA; PEPTIDES; WEIGHT AB The effects of the opiate receptor antagonist, naltrexone, were examined on antecedent thoughts of binging and plasma beta-endorphin concentrations in an adolescent girl who was hospitalized with bulimia nervosa. Significant decreases in urge to binge were obtained during naltrexone administration compared with control sessions. Baseline plasma beta-endorphin concentrations for the bulimic adolescent were not different from those of nonbulimic controls, but plasma beta-endorphins increased significantly during naltrexone administration. After discharge from the hospital, the adolescent refused to take naltrexone because she felt she could not deal with her life without the ''pleasure of binging.'' The case points to the interplay of biological and psychological factors in bulimia nervosa. C1 GEORGE WASHINGTON UNIV,SCH MED,WASHINGTON,DC 20052. NIDA,DIV MED DEV,CLIN TRIALS BRANCH,CLIN OPIOID PROGRAMS,LEXINGTON,KY 40583. RP CHATOOR, I (reprint author), CHILDRENS NATL MED CTR,DEPT PSYCHIAT,111 MICHIGAN AVE NW,EATING DISORDERS & INFANT PSYCHIAT,WASHINGTON,DC 20010, USA. NR 21 TC 9 Z9 9 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUN PY 1994 VL 33 IS 5 BP 748 EP 752 DI 10.1097/00004583-199406000-00016 PG 5 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA NN869 UT WOS:A1994NN86900016 PM 8056738 ER PT J AU HAUSER, P ZAMETKIN, AJ MARTINEZ, P VITIELLO, B MATOCHIK, JA MIXSON, AJ WEINTRAUB, BD AF HAUSER, P ZAMETKIN, AJ MARTINEZ, P VITIELLO, B MATOCHIK, JA MIXSON, AJ WEINTRAUB, BD TI ADHD AND THE THYROID CONTROVERSY SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Letter ID DEFICIT HYPERACTIVITY DISORDER; GENERALIZED RESISTANCE; HORMONE RP HAUSER, P (reprint author), NIH,BETHESDA,MD 20892, USA. NR 6 TC 0 Z9 0 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUN PY 1994 VL 33 IS 5 BP 756 EP 757 DI 10.1097/00004583-199406000-00018 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA NN869 UT WOS:A1994NN86900018 PM 8056740 ER PT J AU PANZA, JA CASINO, PR KILCOYNE, CM QUYYUMI, AA AF PANZA, JA CASINO, PR KILCOYNE, CM QUYYUMI, AA TI IMPAIRED ENDOTHELIUM-DEPENDENT VASODILATION IN PATIENTS WITH ESSENTIAL-HYPERTENSION - EVIDENCE THAT THE ABNORMALITY IS NOT AT THE MUSCARINIC RECEPTOR LEVEL SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CORONARY SMOOTH-MUSCLE; NITRIC-OXIDE; VASCULAR RELAXATION; SUBSTANCE-P; L-ARGININE; ACETYLCHOLINE; CONTRACTIONS; CIRCULATION; ARTERIES; AORTA AB Objectives. The purpose of this study was to determine whether the impaired endothelium dependent vasodilation of hypertensive patients is related to a specific defect of the muscarinic receptor or to a broader abnormality of the vascular endothelium. Background. Patients with essential hypertension have abnormal endothelium dependent vasodilator response to acetylcholine. However, whether this results from an isolated dysfunction of the endothelial cell muscarinic receptor is unknown. Methods. The responses of the forearm vasculature to acetyl choline and substance P (endothelium dependent agents acting on different receptors) and to sodium nitroprusside (a direct dilator of vascular smooth muscle) were studied in eight hypertensive patients (six men, two women; mean age [+/-SD] 50 +/- 12 years) and eight normal control subjects (four men, four women; mean age 49 +/- 9 years). To determine the nitric oxide contribution to substance P-induced vasodilation, the vascular responses to substance P were also measured after inhibition of nitric oxide synthesis with N-G-monomethyl-L-arginine. Drugs were infused into the brachial artery, and forearm blood flow was measured by strain gauge plethysmography. Results. The response to acetylcholine was significantly blunted in hypertensive patients (highest blood now [mean +/- SD] 8.4 +/- 4 vs. 13.8 +/- 4 ml/min per 100 mi in control subjects, p < 0.03). Similarly, the vasodilator effect of substance P was significantly reduced in hypertensive patients (highest blood flow [mean +/- SD] 8.8 +/- 4 vs. 13.9 +/- 4 ml/min per 100 mi in control subjects, p < 0.03). A significant correlation was found between the maximal blood Bow with acetylcholine and that with substance P (r = 0.68, p < 0.004). The vasodilator response to sodium nitroprusside was similar in patients and control subjects, The nitric oxide contribution to substance P-induced vasodilation was reduced in hypertensive patients, such that the responses to substance P measured during infusion of N-G-monomethyl L arginine were not significantly different between the two groups. Conclusions. These findings indicate that the endothelial abnormality of patients with essential hypertension is not restricted to the muscarinic cell receptor. RP PANZA, JA (reprint author), NHLBI,CARDIOL BRANCH,BLDG 10,ROOM 7B-15,BETHESDA,MD 20892, USA. NR 27 TC 113 Z9 116 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUN PY 1994 VL 23 IS 7 BP 1610 EP 1616 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PH374 UT WOS:A1994PH37400015 PM 7515084 ER PT J AU KANT, AK SCHATZKIN, A AF KANT, AK SCHATZKIN, A TI CONSUMPTION OF ENERGY-DENSE, NUTRIENT-POOR FOODS BY THE US POPULATION - EFFECT ON NUTRIENT PROFILES SO JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION LA English DT Article DE DIET QUALITY; EMPTY CALORIES; FOOD GROUPS; NHANES II; NUTRIENT ADEQUACY; NUTRIENT DENSITY; OTHER FOODS ID UNITED-STATES POPULATION; NHANES-II; PATTERNS; ALCOHOL; DIET AB Objective: To examine the association of consumption of foods from the fats, sweets, and the alcohol group (''other'' group) with nutrient profiles. Methods: Using data from the NHANES II survey of 1976-80, we categorized the foods reported to be consumed by adults (n = 11,528) into six groups: meat, dairy, grain, fruit, vegetable, and ''other.'' Results: Nearly one-third of total daily energy intake was contributed by foods from the ''other'' category. As the proportion of daily energy intake from ''other'' foods increased, total daily energy intake also increased, as did the percent energy from carbohydrate and alcohol. However, percent energy from fat and protein, intake of all examined micronutrients (except vitamin E), nutrient density, and the proportion of the population meeting the RDA of various nutrients declined with increasing intake of ''other'' foods. Respondents were more likely to report no servings as well as less than the recommended servings of foods from the major food groups with increasing intake of ''other'' foods. Conclusion: The data suggest that consumption of foods from the ''other'' group displaced nutrient-dense foods from the diets of NHANES II respondents. C1 NCI,BETHESDA,MD 20892. RP KANT, AK (reprint author), CUNY QUEENS COLL,REMSEN HALL,ROOM 306E,65-30 KISSENA BLVD,FLUSHING,NY 11367, USA. NR 33 TC 33 Z9 33 U1 1 U2 4 PU AMER COLL NUTRITION PI NEW YORK PA C/O HOSP. JOINT DIS. 301 E. 17TH ST., NEW YORK, NY 10003 SN 0731-5724 J9 J AM COLL NUTR JI J. Am. Coll. Nutr. PD JUN PY 1994 VL 13 IS 3 BP 285 EP 291 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA NP531 UT WOS:A1994NP53100013 PM 8077578 ER PT J AU CRAWFORD, PB OBARZANEK, E MORRISON, J SABRY, ZI AF CRAWFORD, PB OBARZANEK, E MORRISON, J SABRY, ZI TI COMPARATIVE ADVANTAGE OF 3-DAY FOOD RECORDS OVER 24-HOUR RECALL AND 5-DAY FOOD FREQUENCY VALIDATED BY OBSERVATION OF 9-YEAR-OLD AND 10-YEAR-OLD GIRLS SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID DIETARY ASSESSMENT; ENERGY-INTAKE; SELF-REPORTS; CHILDREN; ACCURACY; QUESTIONNAIRE; METHODOLOGY; VALIDITY; OBESE AB Objective The validity of the 24-hour recall, 3-day food record, and 5-day food frequency was assessed to decide on a dietary assessment method for the National Heart, Lung, and Blood Institute (NHLBI) Growth and Health Study. Design All subjects were assigned to one of three dietary assessment methods. Unobtrusive observers recorded types and amounts of foods eaten during lunch, and these were compared with the foods reported by the girls in the study. Setting School lunchrooms in California and Ohio. Subjects 58 girls, aged 9 and 10 years. Main outcome measures Reporting errors for dietary assessment methods. Statistical analyses performed Descriptive statistics, matched Pair t tests, and Spearman correlation coefficients. Results Comparison of the intakes of energy and selected macronutrients showed different ranges of, and median Percentage absolute errors for, each dietary assessment method. Percentage absolute errors ranged between 20 and 33 for the 5-day food frequency method; 19 and 39 for the 24-hour recall; and 12 and 22 for the 3-day food record. The proportion of missing foods (ie, observed food items not reported) and phantom foods (ie, reported food items not observed) by each method were 46% and 40%, respectively, for the 5-day food frequency; 30% and 33%, respectively, for the 24-hour recall; and 25% and 10%, respectively, for the 3-day food record. Applications/conclusions Errors in food reporting and quantification can vary with the type of dietary methodology. Agreement between observed and reported intakes from 3-day food records made it the best overall choice. On this basis, it was selected as the method of assessment for the NBLBI Growth and Health Study. C1 NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. RP CRAWFORD, PB (reprint author), UNIV CALIF BERKELEY,SCH PUBL HLTH,140 WARREN HALL,BERKELEY,CA 94720, USA. FU NHLBI NIH HHS [N01-HC-55023-26] NR 21 TC 197 Z9 198 U1 2 U2 20 PU AMER DIETETIC ASSN PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD JUN PY 1994 VL 94 IS 6 BP 626 EP 630 DI 10.1016/0002-8223(94)90158-9 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA NQ249 UT WOS:A1994NQ24900009 PM 8195550 ER PT J AU HODES, RJ AF HODES, RJ TI ALZHEIMERS-DISEASE - TREATMENT RESEARCH FINDS NEW TARGETS SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article RP HODES, RJ (reprint author), NIA,OFF DIRECTOR,BLDG 31,ROOM 5C35,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 10 TC 5 Z9 5 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JUN PY 1994 VL 42 IS 6 BP 679 EP 681 PG 3 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA NQ251 UT WOS:A1994NQ25100019 PM 8201156 ER PT J AU TANIZAWA, A FUJIMORI, A FUJIMORI, Y POMMIER, Y AF TANIZAWA, A FUJIMORI, A FUJIMORI, Y POMMIER, Y TI COMPARISON OF TOPOISOMERASE-I INHIBITION, DNA-DAMAGE, AND CYTOTOXICITY OF CAMPTOTHECIN DERIVATIVES PRESENTLY IN CLINICAL-TRIALS SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CARCINOMA HT-29 CELLS; HAMSTER DC3F CELLS; ANTITUMOR-ACTIVITY; CYTO-TOXICITY; ANALOGS; CPT-11; 10,11-METHYLENEDIOXYCAMPTOTHECIN; REPLICATION; XENOGRAFTS; CANCER AB Background: Camptothecins belong to a group of anticancer agents with a unique mechanism of action: poisoning of eukaryotic DNA topoisomerase I. Two camptothecin derivatives, topotecan (TPT) and CPT-11, are in clinical trials and their chemotherapeutic efficacy appears promising. Purpose: Our aim was to compare simultaneously the molecular and cellular pharmacology of the various camptothecin derivatives that are presently in clinical trials. Methods: Cytotoxicity of drugs toward human colon carcinoma HT-29 cells was determined by colony-forming assays. DNA single-strand breaks (SSB) were measured by alkaline elution. Drug potency to induce topoisomerase I-mediated DNA cleavage and the sequence selectivity of the breaks were determined by sequencing gel autoradiography. Results: SN-38 and CPT were more cytotoxic than 9-AC and TPT, and CPT-11 was almost inactive toward HT-29 cells. IC50 values were 8.8 nM for SN-38, 10 nM for CPT, 19 nM for 9-AC, 33 nM for TPT, and greater than 100 nM for CPT-11. In drug-induced DNA damage measured by alkaline elution drug concentrations producing 1000-rad-equivalents (C-1000), values were 0.037 mu M for SN-38, 0.051 mu M for CPT, 0.085 mu M for 9-AC, 0.28 mu M for TPT, and greater than 1 mu M for CPT-11. SN-38 remained the most potent compound in isolated nuclei, and CPT-11 was still inactive. The potency ranking was the same as in whole cells, and the C-1000 values were 0.0025 mu M for SN-38, 0.012 mu M for CPT, 0.021 mu M for 9-AC, 0.44 mu M for TPT, and greater than 0.1 mu M for CPT-11. Potency difference between SN-38 and the other compounds was greater in isolated nuclei than in whole cells. Conclusions: Kinetics of the reversal of drug-induced SSB in isolated nuclei suggest that dissociation of SN-38 from cleavable complexes is much slower than that of CPT. Cleavage patterns of CPT and 9-AC were similar but differed from those of TPT and SN-38. Although in vitro analyses do not necessarily reflect chemotherapeutic efficacy, this study found that SN-38 is the most potent compound and that 9-AC and TPT are less active than CPT in this system. The effect of CPT-11 is minimal. Therefore, the clinical activity of CPT-11 may strongly depend on its hydrolysis to SN-38. Differences in DNA sequence selectivity and the stability of cleavable complexes induced by the drugs may also contribute to differences among CPT derivatives.- C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. NR 28 TC 265 Z9 266 U1 0 U2 11 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 1 PY 1994 VL 86 IS 11 BP 836 EP 842 DI 10.1093/jnci/86.11.836 PG 7 WC Oncology SC Oncology GA NN212 UT WOS:A1994NN21200008 PM 8182764 ER PT J AU GRIEM, ML KLEINERMAN, RA BOICE, JD STOVALL, M SHEFNER, D LUBIN, JH AF GRIEM, ML KLEINERMAN, RA BOICE, JD STOVALL, M SHEFNER, D LUBIN, JH TI CANCER FOLLOWING RADIOTHERAPY FOR PEPTIC-ULCER SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID GASTRIC-CANCER; PARTIAL GASTRECTOMY; AMSTERDAM COHORT; BENIGN DISEASE; STOMACH-CANCER; LATE MORTALITY; RISK; SURGERY; CERVIX; SITES AB Background: Radiotherapy for peptic ulcer was used between 1937 and 1965 to control excessive gastric acid secretions (mean dose, 14.8 Gy). Patients with this benign condition live many years after treatment and are at risk for late effects. Purpose: Our purpose was to investigate the risk of death from cancer following radiotherapy for peptic ulcer. Methods: A mortality study was conducted of 3609 patients with peptic ulcer; 1831 were treated with radiation and 1778 were treated by other means. Extensive methods were used to trace patients. Radiation doses to specific organs were reconstructed from the original radiotherapy records. Results: Nearly 70% of patients were found to have died. The average period of observation was 21.5 years (maximum 51 years). Compared with the general population, patients treated with or without radiation were at significantly increased risk of dying of cancer and nonmalignant diseases of the digestive system. Risk of death due to heart disease was slightly higher following radiotherapy. Cancers of the stomach, pancreas, lung, and prostate mere increased in both irradiated and nonirradiated patients. Radiotherapy was linked to significantly high relative risks (RRs) for all cancers combined (RR = 1.53; 95% confidence interval [CI] = 1.3-1.8), for cancers of the stomach (RR = 2.77; 95% CI = 1.6-4.8), pancreas (RR = 1.87; 95% CI = 1.0-3.4), and lung (RR = 1.70; 95% CI = 1.2-2.4), and for leukemia (RR = 3.28; 95% CI = 1.0-10.6). Radiation combined with surgery, or given to treat gastric ulcer, appeared to increase the risk of stomach cancer 10-fold, which was greater than the sum of individual effects. Patients with gastric ulcers were at higher risk for stomach cancer than patients with duodenal ulcers. Conclusions: Patients with peptic ulcer are at increased risk of dying of cancer, related in part to lifestyle factors and treatment. Radiotherapy and surgery together appear to induce carcinogenic processes that greatly enhance the development of stomach cancer. The risk of radiation-induced stomach cancer was 0.25 extra deaths per 10 000 persons per year per Gy, somewhat lower than reported in other studies. High-dose radiation may have increased the risk of pancreatic cancer, a condition rarely found elevated in irradiated populations, but misclassified death notices may have contributed to the excess. Cancer mortality remained high for up to 50 years, indicating that radiation damage may persist to the end of life. C1 NCI,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. UNIV TEXAS,CTR CANC,DEPT RADIAT PHYS,HOUSTON,TX. RP GRIEM, ML (reprint author), UNIV CHICAGO,DEPT RADIAT ONCOL,5841 S MARYLAND AVE,CHICAGO,IL 60637, USA. OI Kleinerman, Ruth/0000-0001-7415-2478 FU NCI NIH HHS [N01CP95614, N01CP41011, N01CP85604] NR 31 TC 68 Z9 70 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 1 PY 1994 VL 86 IS 11 BP 842 EP 849 DI 10.1093/jnci/86.11.842 PG 8 WC Oncology SC Oncology GA NN212 UT WOS:A1994NN21200009 PM 8182765 ER PT J AU GAO, YT MCLAUGHLIN, JK BLOT, WJ JI, BT DAI, Q FRAUMENI, JF AF GAO, YT MCLAUGHLIN, JK BLOT, WJ JI, BT DAI, Q FRAUMENI, JF TI REDUCED RISK OF ESOPHAGEAL CANCER-ASSOCIATED WITH GREEN TEA CONSUMPTION SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID POPULATION; LINXIAN; DIET AB Background: Studies in laboratory animals have suggested inhibitory effects of green tea on the induction of some cancers, notably, esophageal cancer. However, only a few epidemiologic studies have evaluated green tea as a potential inhibitor of human esophageal cancer. Purpose: Our purpose was to evaluate the relationship between green tea consumption and the risk of esophageal cancer. Methods: This esophageal cancer study was part of a larger multicenter, case-control study that included three other gastrointestinal sites (pancreas, colon, and rectum). Medical records of patients aged 30-74 years old who were diagnosed with esophageal cancer from October 1, 1990, through January 31, 1993, were identified from the Shanghai Cancer Registry, which covers 6.8 million people in the urban area of Shanghai, People's Republic of China. During the ascertainment period, records of 1016 eligible cases of esophageal cancer were identified. Control subject records were selected by frequency matching in accordance with the age-sex distribution of the four gastrointestinal cancers ascertained by the cancer registry during 1986-1987. Patient interviews were then conducted using a structured, standardized questionnaire to obtain information on demographic characteristics, residential history, height and weight, diet, smoking, alcohol and tea drinking, medical history, family history of cancer, occupation, physical activity, and reproductive history. Results: Of the 902 patients interviewed, 734 (81.4%) had their disease pathologically confirmed. There were 1552 control subjects interviewed, including 240 alternates. All analyses of tea effects were conducted separately among men and women and all were adjusted for age. After further adjustment for other known confounders, a protective effect of green tea drinking on esophageal cancer was observed among women (odds ratio [OR] = 0.50; 95% confidence interval [CI] = 0.30-0.83), and this risk decreased (P for trend less than or equal to .01) as tea consumption increased. Among men, the ORs were also below 1.00, although not statistically significant. ORs for green tea intake were estimated among those persons who neither smoked nor drank alcohol. In this subset, statistically significant decreases in risk among tea drinkers were observed for both men (OR = 0.43; 95% CI 0.22-0.86; P for trend = .05) and women (OR = 0.40; 95% CI = 0.20-0.77; P for trend < .001). Conclusions: This population-based, case-control study of esophageal cancer in urban Shanghai suggests a protective effect of green tea consumption. Although these findings are consistent with studies in laboratory animals, indicating that green tea can inhibit esophageal carcinogenesis, further investigations are definitely needed. C1 NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. SHANGHAI CANC INST,SHANGHAI,PEOPLES R CHINA. NR 27 TC 239 Z9 248 U1 3 U2 18 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 1 PY 1994 VL 86 IS 11 BP 855 EP 858 DI 10.1093/jnci/86.11.855 PG 4 WC Oncology SC Oncology GA NN212 UT WOS:A1994NN21200011 PM 8182766 ER PT J AU BERG, SL BALIS, FM MCCULLY, CL POPLACK, DG AF BERG, SL BALIS, FM MCCULLY, CL POPLACK, DG TI TOXICITY OF INTRATHECAL MELPHALAN - REPLY SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 TEXAS CHILDRENS HOSP,BAYLOR COLL MED,HOUSTON,TX 77030. RP BERG, SL (reprint author), NCI,DIV CANC TREATMENT,PEDIAT BRANCH,BLDG 10,RM 13N240,BETHESDA,MD 20892, USA. NR 1 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 JUN 1 PY 1994 VL 86 IS 11 BP 871 EP 871 DI 10.1093/jnci/86.11.871 PG 1 WC Oncology SC Oncology GA NN212 UT WOS:A1994NN21200018 ER PT J AU ZIEGLER, RG BYERS, T AF ZIEGLER, RG BYERS, T TI HEALTH CLAIMS ABOUT VITAMIN-C AND CANCER SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID RANDOMIZED TRIAL; PREVENTION; RECURRENCE; POLYPOSIS C1 NCI,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. CTR DIS CONTROL & PREVENT,CHRON DIS PREVENT BRANCH,ATLANTA,GA 30341. NR 16 TC 2 Z9 2 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 1 PY 1994 VL 86 IS 11 BP 871 EP 872 DI 10.1093/jnci/86.11.871-a PG 2 WC Oncology SC Oncology GA NN212 UT WOS:A1994NN21200019 PM 8182771 ER PT J AU REED, E AF REED, E TI THE USE OF COLONY-STIMULATING FACTORS AS BONE-MARROW SUPPORT FOR SYSTEMIC ANTICANCER CHEMOTHERAPY SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Article DE GRANULOCYTE COLONY-STIMULATING FACTOR (G-CSF); GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR (GM-CS); INTERLEUKIN; ERYTHROPOIETIN (EPO) AB Colony-stimulating factors (CSFs) are proteins that play normal roles in human hematopoietic physiology. Many of these factors have been cloned and sequenced. This has led to recombinant DNA technology that now allows for production of large quantities of pharmacologically pure compounds. Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are two such compounds that have been approved by the US Food and Drug Administration for human use in specific medical circumstances. This article summarizes the experience of one institution in using these two CSFs and adds brief commentary on four other CSFs that are expected to come to general use in the near future-interleukin-1, interleukin-3, interleukin-6, and erythropoietin. Both G-CSF and GM-CSF are effective in protecting patients from the leukotoxic effects of cancer chemotherapy, but GM-CSF appears to have a comparatively narrow ''dosing window,'' wherein the agent is effective and tolerable. Future studies should address combining these agents with platelet protective compounds to improve patient safety. RP REED, E (reprint author), NCI,MED BRANCH,GYNECOL ONCOL SECT,BLDG 10,RM 12N226,BETHESDA,MD 20892, USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD JUN PY 1994 VL 86 IS 6 BP 459 EP 464 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA NQ185 UT WOS:A1994NQ18500011 PM 7521398 ER PT J AU SHIRAISHI, N REHM, S WAALKES, MP AF SHIRAISHI, N REHM, S WAALKES, MP TI EFFECT OF CHLORPROMAZINE PRETREATMENT ON CADMIUM TOXICITY IN THE MALE WISTAR (WF/NCR) RAT SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH LA English DT Article ID BINDING PROTEINS; TESTICULAR CADMIUM; METAL TOXICITY; INBRED MICE; CD-113 NMR; CALMODULIN; METALLOTHIONEIN; TESTES; ZINC; RESISTANCE AB A recent report has indicated that cadmium-induced testicular damage in CF-1 mice can be prevented by pretreatment with calmodulin inhibitors such as chlorpromazine (CPZ), trifluoperazine, or N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W-7). However, the basis of this tolerance to cadmium is unclear and has not been demonstrated in any species other than mice. Thus, we examined the effects of the calmodulin inhibitor CPZ on cadmium toxicity in male Wistar (WF/NCr) rats. A single sc injection of 25 mu mol CdCl2/kg proved nonlethal over 24 h but caused the typical spectrum of testicular lesions and increases in hemoglobin content (as assessed by hemoglobin absorbance in testicular supernatant). Pretreatment with 40 mu mol CPZ/kg had no effect on cadmium-induced testicular lesions but did reduce testicular hemoglobin content, while 120 mu mol CPZ/kg moderately reduced the severity of testicular lesions and hemoglobin contents. CPZ pretreatment in some cases increased cadmium content in liver and reduced testicular content but had no effect on renal levels. Cadmium treatment markedly increased hepatic and renal metallothionein (MT), a metal-binding protein often associated with tolerance to cadmium. CPZ alone likewise increased hepatic MT and MT mRNA, but did not modify renal MT, renal MT mRNA, or testicular MT mRNA. In contrast to liver and kidney, testicular cadmium-binding protein (TCBP) decreased in rats exposed only to cadmium or to CPZ, while CPZ pretreatment had no further effect on cadmium-induced reductions in TCBP levels. These results indicate that, like mice, CPZ in rats can reduce the testicular toxicity oi cadmium as indicated by CPZ-induced reductions in testicular vascular lesions and hemoglobin contents. However, in rats CPZ has a less dramatic effect on such cadmium-induced lesions than in mice. The CPZ-induced stimulation of hepatic MT gene expression or modification of toxicokinetics may both play roles in this acquired tolerance to cadmium. C1 NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,INORGAN CARCINOGENESIS SECT,FREDERICK,MD 21702. NR 41 TC 12 Z9 12 U1 0 U2 1 PU TAYLOR & FRANCIS PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0098-4108 J9 J TOXICOL ENV HEALTH JI J. Toxicol. Environ. Health PD JUN PY 1994 VL 42 IS 2 BP 193 EP 208 PG 16 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA NT046 UT WOS:A1994NT04600006 PM 8207755 ER PT J AU SHINDO, M DIBISCEGLIE, AM SILVER, J LIMJOCO, T HOOFNAGLE, JH FEINSTONE, SM AF SHINDO, M DIBISCEGLIE, AM SILVER, J LIMJOCO, T HOOFNAGLE, JH FEINSTONE, SM TI DETECTION AND QUANTITATION OF HEPATITIS-C VIRUS-RNA IN SERUM USING THE POLYMERASE CHAIN-REACTION AND A COLORIMETRIC ENZYMATIC DETECTION SYSTEM SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE HCV RNA; QUANTITATION; PCR; COLORIMETRIC ASSAY ID NON-B HEPATITIS; NON-A; VIRAL-RNA; GENOME; ORGANIZATION; HEMOPHILIACS; SEQUENCES; REGION AB A sensitive, non-isotopic method for detecting and quantifying hepatitis C virus (HCV) RNA in serum using the reverse transcriptase-polymerase chain reaction (RT-PCR) and a hybridization specific, colorimetric biotin-avidin peroxidase detection system has been developed. The sensitivity of the PCR-colorimetric system was determined using RNA synthesized from cloned HCV cDNA. The assay could detect as few as 10 molecules of HCV RNA, comparable to the sensitivity achieved with double PCR using nested primers. Thus, this colorimetric assay can detect low levels of HCV RNA in serum and appears to be quantitative, suggesting that this technique may be applied to rapid screening of large numbers of samples and to monitor the effect of antiviral therapy. C1 NIDDK,HEPATITIS STUDIES SECT,BETHESDA,MD. NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. NR 22 TC 12 Z9 12 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD JUN PY 1994 VL 48 IS 1 BP 65 EP 72 DI 10.1016/0166-0934(94)90089-2 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA NX562 UT WOS:A1994NX56200007 PM 7962261 ER PT J AU WILSON, CA EIDEN, MV MARSH, JW AF WILSON, CA EIDEN, MV MARSH, JW TI QUANTITATIVE MICRO P-30 AND REVERSE-TRANSCRIPTASE ASSAYS FOR MOLONEY MURINE LEUKEMIA-VIRUS SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE REVERSE TRANSCRIPTASE; RETROVIRUS; MOMLV; MOLONEY MURINE LEUKEMIA VIRUS; P-30 ID PLAQUE ASSAY AB An anti-P30 immunohistochemical and a reverse transcriptase assay for Moloney murine leukemia virus (MoMLV) are adapted to 96-well plates. The assay results are shown to be directly proportional to the number of infectious particles, and can therefore be used to estimate the infective titers of a virus preparation. The micro P30 assay yields a direct estimate of infectious centers; and the reverse transcriptase assay quantitates progeny from a single cycle of replication. The semi-automated nature of these assays is well suited to the analysis of a large number of samples and therefore permits the examination of the efficiency of the process of retroviral/MoMLV infection under varied times or conditions. C1 NIMH,MOLEC BIOL LAB,BETHESDA,MD 20892. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. NR 6 TC 10 Z9 10 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD JUN PY 1994 VL 48 IS 1 BP 109 EP 117 DI 10.1016/0166-0934(94)90093-0 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA NX562 UT WOS:A1994NX56200011 PM 7525623 ER PT J AU ROBERTGUROFF, M LOUIE, A MYAGKIKH, M MICHAELS, F KIENY, MP WHITESCHARF, ME POTTS, B GROGG, D REITZ, MS AF ROBERTGUROFF, M LOUIE, A MYAGKIKH, M MICHAELS, F KIENY, MP WHITESCHARF, ME POTTS, B GROGG, D REITZ, MS TI ALTERATION OF V3 LOOP CONTEXT WITHIN THE ENVELOPE OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ENHANCES NEUTRALIZATION SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODY; SYNTHETIC PEPTIDES; MACROPHAGE TROPISM; CD4 BINDING; HTLV-III; GP120; HIV-1; GLYCOPROTEIN; EPITOPES; CELLS AB Neutralization of a chimeric human immunodeficiency virus (HIV) type 1, containing the V3 loop of the MN isolate substituted within the HXB2 envelope, was enhanced up to 20-fold compared with the HXB2 or MN parental isolates by human HIV-positive sera. MN V3 loop-specific monoclonal antibodies were better able to recognize the chimeric virus compared with MN, staining a greater percentage of infected cells and exhibiting slight increases in relative affinity with a concomitant increase in neutralization titer. Competition analysis revealed that enhanced neutralization by human HIV-positive sera of the chimera was attributable in some cases to better reactivity with the linear V3 loop epitope but in others to conformational loop epitopes or previously cryptic or poorly recognized epitopes outside the loop region. Mice primed with a vaccinia virus-chimeric envelope recombinant and boosted with gp160 developed a spectrum of antibodies different from that of mice similarly immunized with HXB2 or MN recombinants or that of naturally infected humans. The chimeric envelope elicited antibodies with enhanced binding to the native MN V3 loop; however, the sites seen by the BALB/c mice were not neutralizing epitopes. Nevertheless, similar to the observations made with use of human sera, the chimeric virus was more readily neutralized by all of the immune mouse sera, an effect apparently mediated by non-V3 loop epitopes. These studies illustrate that not only the V3 loop sequence and conformation but also its context within the viral envelope influence neutralization. C1 TRANSGENE SA,STRASBOURG,FRANCE. REPLIGEN CORP,CAMBRIDGE,MA 02139. RP ROBERTGUROFF, M (reprint author), NCI,TUMOR CELL BIOL LAB,BLDG 37,ROOM 6A09,BETHESDA,MD 20892, USA. NR 48 TC 12 Z9 12 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 1994 VL 68 IS 6 BP 3459 EP 3466 PG 8 WC Virology SC Virology GA NL349 UT WOS:A1994NL34900002 PM 7514675 ER PT J AU LAWSON, CM BENNINK, JR RESTIFO, NP YEWDELL, JW MURPHY, BR AF LAWSON, CM BENNINK, JR RESTIFO, NP YEWDELL, JW MURPHY, BR TI PRIMARY PULMONARY CYTOTOXIC T-LYMPHOCYTES INDUCED BY IMMUNIZATION WITH A VACCINIA VIRUS RECOMBINANT EXPRESSING INFLUENZA-A VIRUS NUCLEOPROTEIN PEPTIDE DO NOT PROTECT MICE AGAINST CHALLENGE SO JOURNAL OF VIROLOGY LA English DT Article ID ENDOGENOUSLY SYNTHESIZED PEPTIDE; A VIRUS; ANTIGEN; INFECTION; CELLS; HEMAGGLUTININ; INVIVO; SEQUENCE; SPECIFICITY; VACCINATION AB The nucleoprotein (NP) of influenza A virus is the dominant antigen recognized by influenza virus-specific cytotoxic T lymphocytes (CTLs), and adoptive transfer of NP-specific CTLs protects mice from influenza A virus infection. BALB/c mouse cells (H-2(d)) recognize a single K-d-restricted CTL epitope of NP consisting of amino acids 147 to 155. In the present study, mice were immunized with various vaccinia virus recombinant viruses to examine the effect of the induction of primary pulmonary CTLs on resistance to challenge with influenza A/Puerto Rico/8/34 virus. The minigene ESNP(147-155)-VAC construct, composed of a signal sequence from the adenovirus E3/19K glycoprotein (designated ES) and expressing the 9-amino-acid NP natural determinant (amino acids 147 to 155) preceded by an alanine residue, a similar minigene NP(Met 147-155)-VAC lacking ES, and a full-length NP-VAC recombinant of influenza virus were analyzed. The two minigene NP-VAC recombinants induced a greater primary pulmonary CTL response than the full-length NP-VAC recombinant. However, NP-specific CTLs induced by immunization with ESNP(147-155)-VAC did not decrease peak virus titer or accelerate clearance of virus in the lungs of mice challenged intranasally with A/PR/8/34. Furthermore, NP-specific CTLs induced by immunization did not protect mice challenged intranasally with a lethal dose of A/PR/8/34. Sequence analysis of the NP CTL epitope of A/PR/8/34 challenge virus obtained from lungs after 8 days of replication in ESNP(147-155)-VAC-immunized mice showed identity with that of the input virus, demonstrating that an escape mutant had not emerged during replication in vivo. Thus, in contrast to adoptively transferred CTLs, pulmonary NP-specific CTLs induced by recombinant vaccinia virus immunization do not have protective in vivo antiviral activity against influenza virus infection. C1 NIAID,INFECT DIS LAB,BETHESDA,MD 20892. NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. NCI,SURG BRANCH,BETHESDA,MD 20892. RI Restifo, Nicholas/A-5713-2008; yewdell, jyewdell@nih.gov/A-1702-2012; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999] NR 43 TC 75 Z9 77 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 1994 VL 68 IS 6 BP 3505 EP 3511 PG 7 WC Virology SC Virology GA NL349 UT WOS:A1994NL34900008 PM 7514677 ER PT J AU KLINEDINST, DK CHALLBERG, MD AF KLINEDINST, DK CHALLBERG, MD TI HELICASE-PRIMASE COMPLEX OF HERPES-SIMPLEX VIRUS TYPE .1. A MUTATION IN THE UL52 SUBUNIT ABOLISHES PRIMASE ACTIVITY SO JOURNAL OF VIROLOGY LA English DT Article ID DNA-BINDING PROTEIN; TEMPERATURE-SENSITIVE MUTANTS; AMINO-ACID MOTIF; GENE-4 PROTEIN; POLYMERASE LOCUS; GENETIC-ANALYSIS; SEQUENCE MOTIF; INSECT CELLS; REPLICATION; ORIGIN AB The UL52 gene product of herpes simplex virus type 1 (HSV-1) comprises one subunit of a 3-protein helicase-primase complex that is essential for replication of viral DNA. The functions of the individual subunits of the complex are not known with certainty, although it is clear that the UL8 subunit is not required for either helicase or primase activity. Examination of the predicted amino acid sequence of the UL5 gene reveals the existence of conserved helicase motifs; it seems likely, therefore, that UL5 is responsible for the helicase activity of the complex. We have undertaken mutational analysis of UL52 in an attempt to understand the functional contribution of this protein to the helicase-primase complex. Amino acid substitution mutations were introduced into five regions of the UL52 gene that are highly conserved among HSV-1 and the related herpesviruses equine herpesvirus 1, human cytomegalovirus, Epstein-Barr virus, and varicella-zoster virus. Of seven mutants analyzed by an in,ice replication assay, three mutants, in three different conserved regions of the protein, failed to support DNA replication. Within one of the conserved regions is a 6-amino-acid motif (IL)(VIM)(LF)DhD (where h is a hydrophobic residue), which is also conserved in mouse, yeast, and T7 primases. Mutagenesis of the first aspartate residue of the motif, located at position 628 of the UL52 protein, abolished the ability of the complex to support replication of an origin-containing plasmid in vivo and to synthesize oligoribonucleotide primers in vitro. The ATPase and helicase activities were unaffected, as was the ability of the mutant enzyme to support displacement synthesis on a preformed fork substrate. These results provide experimental support for the idea that UL52 is responsible for the primase activity of the HSV helicase-primase complex. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. NR 58 TC 67 Z9 68 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 1994 VL 68 IS 6 BP 3693 EP 3701 PG 9 WC Virology SC Virology GA NL349 UT WOS:A1994NL34900028 PM 8189507 ER PT J AU OGRYZKO, VV HIRAI, TH SHIH, CE HOWARD, BH AF OGRYZKO, VV HIRAI, TH SHIH, CE HOWARD, BH TI DISSOCIATION OF RETINOBLASTOMA GENE PROTEIN HYPERPHOSPHORYLATION AND COMMITMENT TO ENTER S-PHASE SO JOURNAL OF VIROLOGY LA English DT Article ID LARGE-T-ANTIGEN; SV40 LARGE-T; SIMIAN-VIRUS 40; SUSCEPTIBILITY GENE; CELL-CYCLE; TRANSCRIPTION FACTOR; CARCINOMA-CELLS; TUMOR-SUPPRESSOR; SODIUM-BUTYRATE; RB PROTEIN AB Mitogenic activities of simian virus 40 large T and small t antigens were studied in serum-deprived human diploid fibroblasts. Wild-type large T and small t cooperated in stimulating DNA synthesis and in inducing hyperphosphorylation of the Rb gene product (pRb). In contrast. a T antigen mutant defective for pRb binding (Rb-T) possessed no detectable mitogenic activity alone and failed to complement small t in stimulating DNA synthesis. Surprisingly, Rb-T and small t cooperated as strongly as wild-type T and small t with respect to pRb hyperphosphorylation. As a consequence, in two closely related conditions (i.e., stimulation by small t plus wild-type T versus small t plus Rb-T), the fraction of pRb in hyperphosphorylated forms dissociated from the fraction of cells in the S phase. These results indicate that pRb hyperphosphorylation is not always tightly coupled with a commitment to initiate DNA replication. C1 NICHHD,MOLEC GROWTH REGULAT LAB,BETHESDA,MD 20892. RI Ogryzko, Vasily/M-6665-2015 OI Ogryzko, Vasily/0000-0002-8548-1389 NR 71 TC 13 Z9 13 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 1994 VL 68 IS 6 BP 3724 EP 3732 PG 9 WC Virology SC Virology GA NL349 UT WOS:A1994NL34900031 PM 8189510 ER PT J AU PORTIS, JL SPANGRUDE, GJ MCATEE, FJ AF PORTIS, JL SPANGRUDE, GJ MCATEE, FJ TI IDENTIFICATION OF A SEQUENCE IN THE UNIQUE 5' OPEN READING FRAME OF THE GENE ENCODING GLYCOSYLATED GAG WHICH INFLUENCES THE INCUBATION PERIOD OF NEURODEGENERATIVE DISEASE INDUCED BY A MURINE RETROVIRUS SO JOURNAL OF VIROLOGY LA English DT Article ID COMPLETE NUCLEOTIDE-SEQUENCE; WILD MOUSE RETROVIRUS; MOTOR NEURON DISEASE; LONG TERMINAL REPEAT; C RNA VIRUS; CAS-BR-E; LEUKEMIA-VIRUS; NEUROTROPIC RETROVIRUS; ENVELOPE GENE; MICE AB Neonatal inoculation of the wild-mouse ecotropic retrovirus CasBrE (clone 15-1) causes a noninflammatory spongiform neurodegenerative disease with an incubation period of greater than or equal to 6 months. Introduction of sequences from Friend murine leukemia virus (clone FB29) into the genome of CasBrE results in a marked shortening of the incubation period. The FB29 sequences which influence the incubation period were previously localized to the 5' leader sequence of the viral genome (M. Czub, F. J. McAtee, and J. L. Portis, J. Virol. 66:3298-3305, 1992). In the current study, we constructed a series of chimeric viruses consisting of the genome of CasBrE containing various segments of the leader sequence from FB29. A 41-nucleotide element (positions 481 through 521) near the 3' end of the leader was found to have e a strong influence on the incubation period. This element influenced the kinetics of virus replication and/or spread in nonneuronal tissues, a property which was shown previously to determine the extent of central nervous system infection (M. Czub, F. J. McAtee, and J. L. Portis, J Virol. 66:3298-3305, 1992). Curiously, this sequence had no demonstrable effect on virus replication in vitro in a fibroblastic cell line from Mus dunni. This segment encodes 14 of the unique 88-amino-acid N terminus of pr75(gag), the precursor of a glycosylated form of the gag polyprotein which is expressed at the cell surface. Previous in vitro studies of mutants of Moloney murine leukemia virus lacking expression of glycosylated Gag failed to reveal a function for this protein in virus replication. We mutated the Kozak consensus sequence around the initiation codon for this protein in the chimeric virus CasFr(KP), a virus which induces neurologic disease with a short (18- to 23-day) incubation period. M. dunni cells infected with the mutants lacked detectable cell surface Gag, but, compared with CasFr(KP), no effect on replication kinetics in vitro was observed. In contrast, there was a marked slowing of the replication kinetics in vivo and a dramatic attenuation of neurovirulence. These studies indicate that glycosylated Gag has an important function in virus replication and/or spread in the mouse and further suggest that the sequence of its N terminus is a critical, though likely indirect, determinant of neurovirulence. RP PORTIS, JL (reprint author), NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,903 S 4TH ST,HAMILTON,MT 59840, USA. NR 43 TC 42 Z9 42 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 1994 VL 68 IS 6 BP 3879 EP 3887 PG 9 WC Virology SC Virology GA NL349 UT WOS:A1994NL34900047 PM 8189525 ER PT J AU TAYLOR, JP POMERANTZ, RJ RAJ, GV KASHANCHI, F BRADY, JN AMINI, S KHALILI, K AF TAYLOR, JP POMERANTZ, RJ RAJ, GV KASHANCHI, F BRADY, JN AMINI, S KHALILI, K TI CENTRAL NERVOUS SYSTEM-DERIVED CELLS EXPRESS A KAPPA-B-BINDING ACTIVITY THAT ENHANCES HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 TRANSCRIPTION IN-VITRO AND FACILITATES TAR-INDEPENDENT TRANSACTIVATION BY TAT SO JOURNAL OF VIROLOGY LA English DT Article ID LONG TERMINAL REPEAT; TRANS-ACTIVATOR GENE; NECROSIS-FACTOR-ALPHA; HUMAN GLIAL-CELLS; HIV-1 TAT; KAPOSIS-SARCOMA; NASCENT RNA; HTLV-III; T-CELLS; PROTEIN AB The Tat protein of human immunodeficiency virus type 1 (HIV-1) is a potent activator of long terminal repeat-directed transcription. while in most cell types, activation requires interaction of Tat with the unusual transcription element TAR, astrocytic glial cells support TAR-independent transactivation of HIV-1 transcription by Tat. This alternative pathway of Tat activation is mediated by the viral enhancer, a kappa B domain capable of binding the prototypical form of the transcription factor nuclear factor kappa B (NF-kappa B) present in many cell types, including T lymphocytes. Tat transactivation mediated by the kappa B domain is sufficient to allow replication of TAR-deleted mutant HIV-1 in astrocytes. The present study demonstrates the existence of kappa B-specific binding factors present in human glial astrocytes that differ from prototypical NF-kappa B. The novel astrocyte-derived kappa B-binding activity is retained on an HIV-1 Tat affinity, column, while prototypical NF-kappa B from Jurkat T cells is not. In vitro transcription studies demonstrate that astrocyte-derived kappa B-binding factors activate transcription of the HIV-1 long terminal repeat and that this activation is dependent on the kappa B domain. Moreover, TAR-independent transactivation of HIV-1 transcription is reproduced in vitro in an astrocyte factor-dependent manner which correlates with kappa B-binding activity. The importance of the central nervous system-enriched kappa B transcription factor in the regulation of HIV-1 expression is discussed. C1 THOMAS JEFFERSON UNIV,JEFFERSON INST MOLEC MED,DEPT BIOCHEM & MOLEC BIOL,MOLEC NEUROVIROL SECT,PHILADELPHIA,PA 19107. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT MED,DIV INFECT DIS,PHILADELPHIA,PA 19107. NCI,MOLEC VIROL LAB,BETHESDA,MD 20892. NR 64 TC 42 Z9 42 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 1994 VL 68 IS 6 BP 3971 EP 3981 PG 11 WC Virology SC Virology GA NL349 UT WOS:A1994NL34900057 PM 8189531 ER PT J AU CAUGHEY, B BROWN, K RAYMOND, GJ KATZENSTEIN, GE THRESHER, W AF CAUGHEY, B BROWN, K RAYMOND, GJ KATZENSTEIN, GE THRESHER, W TI BINDING OF THE PROTEASE-SENSITIVE FORM OF PRP (PRION PROTEIN) TO SULFATED GLYCOSAMINOGLYCAN AND CONGO RED (VOL 68, PG 2135, 1994) SO JOURNAL OF VIROLOGY LA English DT Correction, Addition C1 OREGON STATE UNIV,DEPT BIOCHEM & BIOPHYS,CORVALLIS,OR 97331. RP CAUGHEY, B (reprint author), NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840, USA. NR 1 TC 6 Z9 6 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 1994 VL 68 IS 6 BP 4107 EP 4107 PG 1 WC Virology SC Virology GA NL349 UT WOS:A1994NL34900081 ER PT J AU MACKAY, AR GOMEZ, DE NASON, AM THORGEIRSSON, UP AF MACKAY, AR GOMEZ, DE NASON, AM THORGEIRSSON, UP TI STUDIES ON THE EFFECTS OF LAMININ, E-8 FRAGMENT OF LAMININ AND SYNTHETIC LAMININ PEPTIDES PA22-2 AND YIGSR ON MATRIX METALLOPROTEINASES AND TISSUE INHIBITOR OF METALLOPROTEINASE EXPRESSION SO LABORATORY INVESTIGATION LA English DT Article DE TIMP; IKVAV; YIGSR ID HUMAN FIBROBLAST COLLAGENASE; AMINO-ACID-SEQUENCE; BASEMENT-MEMBRANE; A-CHAIN; IV COLLAGENASE; EXTRACELLULAR-MATRIX; PLASMINOGEN-ACTIVATOR; ENDOTHELIAL-CELLS; EPITHELIAL-CELLS; TUMOR-CELLS AB BACKGROUND: Based on a previous observation of laminin-mediated increase in type IV collagenolytic activity of human melanoma (A-2058) and fibrosarcoma (HT-1080) cell lines (Turpeenniemi-Hujanen T, ct al. Laminin increases the release of type IV collagenase from malignant cells. J Biol Chem 1986;261:1883-1889), the goal of this study was to identify the proteinases involved. EXPERIMENTAL DESIGN: A soluble type IV collagenase assay and substrate gel electrophoresis were used to assess the effect of laminin and laminin peptides on type IV collagenolytic activity. RESULTS: The laminin-mediated increase in type IV collagenolytic activity was not due to augmented expression or induction of three known type IV collagenolytic matrix metalloproteinases (MMP), i.e., 72-kilodalton gelatinase/type IV collagenase (MMP-2), stromelysin (MMP-3), and 92 kilodalton gelatinase/type IV collagenase (MMP-9). Furthermore, laminin did not modulate the expression of the tissue inhibitors of metalloproteinases (TIMP), TIMP-1 and TIMP-2. The E-8 fragment of laminin and the YIGSR laminin peptide had no effect on type IV collagenolytic or MMP/TIMP activities. However, the IKVAV containing PA22-2 laminin peptide selectively stimulated type IV collagenolytic activity of the A-2058 melanoma cell line, although it did not modulate MMP/TIMP activity. Laminin from three different sources of the Engelbreth-Holm-Swarm tumor was found to contain type IV collagenolytic activity. When laminin was added to harvested culture supernatants of the A-2058 and HT-1080 cell lines, the increase in type IV collagenolytic activity was comparable with that observed in supernatants from cells incubated with laminin for 48 hours. Analysis of the laminin preparations revealed five MMP forms ranging in molecular weight from approximately 58 to 105 kilodalton, which may represent latent and active forms of MMP-2 and MMP-9. CONCLUSIONS: These findings suggest that proteinases present in the Engelbreth-Holm-Swarm laminin may account for most, if not all, of the observed laminin-mediated increase in type IV collagenolytic activity. However, the PA22-2-mediated increase in type IV collagenolytic activity of the A-2058 melanoma line remains to be elucidated. C1 NCI,DIV CANC ETIOL,OFF DIRECTOR,BETHESDA,MD 20892. OI Mackay, Andrew Reay/0000-0001-7096-3759; Gomez, Daniel E/0000-0002-8629-0787 NR 47 TC 17 Z9 17 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JUN PY 1994 VL 70 IS 6 BP 800 EP 806 PG 7 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA NU620 UT WOS:A1994NU62000003 PM 8015284 ER PT J AU FELIX, CA WASSERMAN, R LANGE, BJ BROWN, DL NAU, MM COLE, DE MINNA, JD POPLACK, DG AF FELIX, CA WASSERMAN, R LANGE, BJ BROWN, DL NAU, MM COLE, DE MINNA, JD POPLACK, DG TI DIFFERENTIATION STAGES OF CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIAS WITH P53 MUTATIONS SO LEUKEMIA LA English DT Article ID RECEPTOR GENE PATTERNS; TUMOR SUPPRESSOR GENE; WILD-TYPE P53; T-CELL; LYMPHOID LEUKEMIA; MYELOID-LEUKEMIA; MULTIPLE-MYELOMA; IMMUNOGLOBULIN; DISEASE; REARRANGEMENT AB Based upon in vitro evidence of p53 involvement in lymphoid differentiation, we assessed immunoglobulin (Ig) and T-cell receptor (TCR) genes in five acute lymphoblastic leukemias (ALLs) with, and 24 ALLs without p53 mutations to compare their genotypic stages. Using Southern blot analysis and complementarity determining region III polymerase chain reaction (CDRIII PCR), 18 cases of B-lineage ALL and 11 cases of T-ALL were studied. Of 20 specimens from 18 B-lineage ALLs, two of four with p53 mutation and two of 16 without mutation had an unrearranged Ig and TCR genotype (p=0.16; Fisher's exact test). Of 11 cases of T-ALL, the one case with p53 mutation had a rearranged TCR and Ig genotype and a case without mutation was unrearranged. The study indicates that p53 mutation is an infrequent feature of ALL found, nonetheless, in every genotypic subset. The p53 mutations in cases that do not further rearrange may support p53 involvement in lymphoid differentiation, but the heterogeneity in differentiation stages in cases both with and without p53 mutations suggests that regulation of early lymphoid maturation is multifactorial. C1 NCI,NAVY MED ONCOL BRANCH,BETHESDA,MD 20892. NCI,PEDIAT BRANCH,BETHESDA,MD 20892. UNIV TEXAS,SW MED CTR,SIMMONS COMPREHENS CANC RES CTR,DALLAS,TX. TEXAS CHILDRENS HOSP,BAYLOR COLL MED,HEMATOL ONCOL SERV,HOUSTON,TX 77030. RP FELIX, CA (reprint author), CHILDRENS HOSP,DEPT PEDIAT,DIV ONCOL,ROOM 9093,34TH ST & CIV CTR BLVD,PHILADELPHIA,PA 19104, USA. FU NCI NIH HHS [P01 CA 47983] NR 28 TC 10 Z9 10 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 1994 VL 8 IS 6 BP 963 EP 967 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA NU502 UT WOS:A1994NU50200010 PM 8207991 ER PT J AU TRAVIS, LB LI, CY ZHANG, ZN LI, DG YIN, SN CHOW, WH LI, GL DOSEMECI, M BLOT, W FRAUMENI, JF HAYES, RB LINET, MS AF TRAVIS, LB LI, CY ZHANG, ZN LI, DG YIN, SN CHOW, WH LI, GL DOSEMECI, M BLOT, W FRAUMENI, JF HAYES, RB LINET, MS TI HEMATOPOIETIC MALIGNANCIES AND RELATED DISORDERS AMONG BENZENE-EXPOSED WORKERS IN CHINA SO LEUKEMIA & LYMPHOMA LA English DT Article DE BENZENE; LEUKEMIA; DYSPLASIA AB Although the relationship between benzene and acute nonlymphocytic leukemia (ANLL) is well established, most of the analytic cohort investigations examining the relationship between benzene and hematologic neoplasms have evaluated only death certificates to validate diagnoses. In a follow-up study of 74,828 benzene-exposed and 35,805 non-exposed workers in China, pathology reports, medical records, and/or histopathologic material were reviewed for all patients with hematopoietic malignancies to ensure correct classification and to provide clinicopathologic descriptions. Eighty-two patients with hematopoietic neoplasms and related disorders were identified among benzene-exposed workers, including 32 cases of acute leukemia, 7-myelodysplastic syndrome (MDS), 9-chronic granulocytic leukemia (CGL), 20-malignant lymphoma or related disorder (ML), 9-aplastic anemia, and 5 others. Among the comparison group, 13 hematologic malignancies were observed, including 6 patients with acute leukemia, 2-CGL, 3-ML, and 2 others. The hematopathologic characteristics of the benzene-exposed ANLL cases resembled those following chemotherapy or radiotherapy. ANLL in workers exposed to benzene may represent a distinct clinicopathologic entity, with characteristics similar to treatment-related ANLL, including a preceding preleukemic phase in some patients. Results in our series, one of the largest to date, al-so indicate that a greater diversity of hematalogic neoplasms is evident among benzene-exposed workers than previously described. RP TRAVIS, LB (reprint author), NCI,EXECUT PLAZA N,SUITE 408,BETHESDA,MD 20892, USA. NR 0 TC 52 Z9 52 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 1994 VL 14 IS 1-2 BP 91 EP 102 DI 10.3109/10428199409049654 PG 12 WC Oncology; Hematology SC Oncology; Hematology GA NR631 UT WOS:A1994NR63100010 PM 7920231 ER PT J AU LOUGHRAN, TP SHERMAN, MP RUSCETTI, FW FREY, S COYLE, T MONTAGNA, RA JONES, B STARKEBAUM, G POIESZ, BJ AF LOUGHRAN, TP SHERMAN, MP RUSCETTI, FW FREY, S COYLE, T MONTAGNA, RA JONES, B STARKEBAUM, G POIESZ, BJ TI PROTOTYPICAL HTLV-I/II INFECTION IS RARE IN LGL LEUKEMIA SO LEUKEMIA RESEARCH LA English DT Article DE LGL LEUKEMIA; HTLV-I/II; GAG P24; ENV P21E; PCR; ELISA ID VIRUS TYPE-I; GRANULAR LYMPHOCYTE LEUKEMIA; HAIRY-CELL LEUKEMIA; STATES BLOOD-DONORS; CHRONIC MATURE B; T-CELL; LYMPHOPROLIFERATIVE DISEASE; PATIENT; CLASSIFICATION; REACTIVITY AB The etiology of LGL leukemia is not known; however, we recently detected HTLV-II in a patient with LGL leukemia. In this study, we found that sera from 6 of 28 patients with LGL leukemia were positive for HTLV-I/II using a whole virus ELISA; moreover, the ELISA-negative sera were near the positive cut-off value. Therefore, we performed additional studies on these sera using commercially available assays which can confirm and distinguish HTLV-I from HTLV-II infection. Serum from on ly one patient was confirmed positive using conventional criteria (HTLV-II+). Sera from 25 patients (89%) had indeterminate reactivity on Western blot assays. Of these, sera from 21 (84%) reacted to gag protein p24; 12 (48%) reacted with recombinant env protein p21e, and 10 (40%) reacted with both. We could not detect HTLV-I/ II pol or pX gene sequences in these patients using polymerase chain reaction analyses, with the exception of the HTLV-II-infected patient described previously. These data show that most patients with LGL leukemia are not infected with prototypical HTLV-I or HTLV-II. The frequent reactivity of patient sera to HTLV-I/II gag protein p24 and to env protein p21e, however, suggests that a deleted or variant farm of HTLV-I/II may be associated with LGL leukemia. C1 SUNY HLTH SCI CTR,DEPT MED,SYRACUSE,NY. SUNY HLTH SCI CTR,DEPT MICROBIOL,SYRACUSE,NY. SUNY HLTH SCI CTR,DEPT IMMUNOL,SYRACUSE,NY. UNIV WASHINGTON,SCH MED,VET AFFAIRS MED CTR,SEATTLE,WA. UNIV WASHINGTON,SCH MED,DEPT MED,SEATTLE,WA. CELLULAR PROD INC,BUFFALO,NY. FREDERICK CANC RES FACIL,FREDERICK,MD. RP LOUGHRAN, TP (reprint author), SUNY HLTH SCI CTR,VET AFFAIRS MED CTR,800 IRVING AVE,SYRACUSE,NY 13210, USA. FU NCI NIH HHS [CA 46903, CA 54552]; NIAID NIH HHS [AI127658] NR 30 TC 35 Z9 36 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD JUN PY 1994 VL 18 IS 6 BP 423 EP 429 DI 10.1016/0145-2126(94)90078-7 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA NQ865 UT WOS:A1994NQ86500005 PM 8207960 ER PT J AU ZHOU, XH MARONPOT, RR COFER, GP HEDLUND, LW JOHNSON, GA AF ZHOU, XH MARONPOT, RR COFER, GP HEDLUND, LW JOHNSON, GA TI STUDIES ON BROMOBENZENE-INDUCED HEPATOTOXICITY USING IN-VIVO MR MICROSCOPY WITH SURGICALLY IMPLANTED RF COILS SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE IN VIVO MAGNETIC RESONANCE MICROSCOPY; HEPATOTOXICITY; IMPLANTED RF COILS; INDUCTIVE COUPLING ID MAGNETIC-RESONANCE MICROSCOPY; INDUCED LIVER-DAMAGE; PLANE ROTATIONS; INVIVO NMR; SPECTROSCOPY; DIFFUSION; PULSES; FIELDS; RAT; SUSCEPTIBILITY AB Using surgically implanted RF coils at 300 MHz, three-dimensional microscopic MR images of rat liver were obtained in vivo to follow the development of pathology induced by bromobenzene exposure. Formalin fixed specimens of liver from these animals were also imaged using in vitro MR microscopy, followed by conventional optical microscopy. All MR images were acquired using a spin-warp pulse sequence with TR = 950 ms and TE = 23 ms. The in vivo images were reconstructed as 256(2) x 32 arrays with a voxel size of (50 mu m)(2) x 219 mu m, while the in vitro images were reconstructed as 256(2) x 128 arrays, giving an isotropic resolution at (39 mu m)(3). Based on results from six animals, we have found in all animals exposed to bromobenzene, image intensity decreased in specific hepatic tissue regions. These regions were well correlated to low signal intensity areas observed in in vitro MR images at higher resolution. Conventional optical microscopy indicated that the low signal intensity regions corresponded to areas of necrosis. The decrease in signal intensity is consistent with increased local diffusion coefficients as a result of necrosis. This study demonstrates that MR microscopy with implanted RF coils can be successfully used to follow tissue pathological changes in living tissues. C1 DUKE UNIV,MED CTR,CTR IN VIVO MICROSCOPY,DEPT RADIOL,DURHAM,NC 27710. NIEHS,RES TRIANGLE PK,NC. OI Hedlund, Laurence/0000-0001-5275-0397; Johnson, G.Allan/0000-0002-7606-5447 FU NCRR NIH HHS [P41-RR-05959-02]; NIEHS NIH HHS [R01-ES04187-04A1] NR 37 TC 15 Z9 15 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD JUN PY 1994 VL 31 IS 6 BP 619 EP 627 DI 10.1002/mrm.1910310607 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NN571 UT WOS:A1994NN57100006 PM 8057814 ER PT J AU WINNING, RS SARGENT, TD AF WINNING, RS SARGENT, TD TI PAGLIACCIO, A MEMBER OF THE EPH FAMILY OF RECEPTOR TYROSINE KINASE GENES, HAS LOCALIZED EXPRESSION IN A SUBSET OF NEURAL CREST AND NEURAL TISSUES IN XENOPUS-LAEVIS EMBRYOS SO MECHANISMS OF DEVELOPMENT LA English DT Article DE NEURAL CREST; RECEPTOR TYROSINE KINASE; XENOPUS EMBRYOGENESIS; CENTRAL NERVOUS SYSTEM ID GROWTH-FACTOR-ALPHA; CDNA CLONING; MESODERM INDUCTION; NERVOUS-SYSTEM; HINDBRAIN; CELLS; MIGRATION; MOUSE; DROSOPHILA; PATTERN AB Cranial neural crest cells arise from neural folds in the embryonic head and differentiate to produce most of the cartilages and bones of the skull and the somatosensory ganglia of several cranial nerves, among other tissues. Since the molecular basis of the determination of these cells is poorly understood, we have begun a search for molecules involved in signal transduction in cranial neural crest. From a Xenopus laevis cranial neural crest cDNA bank, we have cloned a cDNA encoding a putative receptor tyrosine kinase, which we call Pagliaccio (Pag). Pag RNA is present transiently in visceral arch 3, probably representing neural crest cells in this tissue. Pag is also expressed in the forebrain, rhombomeres r3 and r5 of the hindbrain and in the pronephros. Based on this localized expression, we propose that Pag may play a role in the differentiation of cranial neural crest and other tissues. C1 NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892. NR 45 TC 50 Z9 53 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD JUN PY 1994 VL 46 IS 3 BP 219 EP 229 DI 10.1016/0925-4773(94)90072-8 PG 11 WC Developmental Biology SC Developmental Biology GA NT630 UT WOS:A1994NT63000005 PM 7918105 ER PT J AU UNNI, LK RADCLIFFE, J LATHAM, G SUNDERLAND, T MARTINEZ, R POTTER, W BECKER, RE AF UNNI, LK RADCLIFFE, J LATHAM, G SUNDERLAND, T MARTINEZ, R POTTER, W BECKER, RE TI ORAL-ADMINISTRATION OF HEPTYLPHYSOSTIGMINE IN HEALTHY-VOLUNTEERS - A PRELIMINARY-STUDY SO METHODS AND FINDINGS IN EXPERIMENTAL AND CLINICAL PHARMACOLOGY LA English DT Article DE ALZHEIMERS DISEASE; CLINICAL TRIAL; PHARMACODYNAMICS; CHOLINESTERASE INHIBITOR; HEPTYLPHYSOSTIGMINE; PHYSOSTIGMINE ID CHOLINESTERASE INHIBITOR; ALZHEIMERS-DISEASE; PHYSOSTIGMINE; DEMENTIA AB Heptylphysostigmine (HP) is a reversible cholinesterase (ChE) inhibitor with greater lipophilicity and longer inhibitory action than the parent compound physostigmine (Phy). Single (0.1-0.6 mg/kg) and multiple 5-day (0.1-0.3 mg/kg) doses of HP were administered to 21 young normal volunteers. The relationship between logarithmic dose (mg/kg) and peak inhibition of red blood cell (RBC) ChE was linear with dose. In one subject given 0.6 mg/kg of HP concentration in plasma was 0.68 ng/ml at 2 h and gradually declined to below the detection limit by 4 h. Peak plasma and RBC ChE inhibitions of 31.2% and 55.8% were achieved at 2 h for both with a 0.6 mg/kg dose. Chronic studies did not result in any accumulation of ChE inhibition up to 0.2 mg/kg b.i.d., whereas at 0.3 mg/kg b.i.d. 10-15% RBC ChE inhibition was maintained. Higher levels of ChE inhibition can be achieved with HP than with its parent compound, Phy, Red blood cell ChE inhibition recovered more slowly than plasma even though the maximum inhibition was similar for both enzymes. C1 NIMH,CLIN SCI LAB,BETHESDA,MD. RP UNNI, LK (reprint author), SO ILLINOIS UNIV,SCH MED,DEPT PSYCHIAT,NEUROCHEM LAB,801 N RUTLEDGE 4TH FLOOR,SPRINGFIELD,IL 62702, USA. NR 11 TC 11 Z9 11 U1 0 U2 0 PU J R PROUS SA PI BARCELONA PA APARTADO DE CORREOS 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0379-0355 J9 METHOD FIND EXP CLIN JI Methods Find. Exp. Clin. Pharmacol. PD JUN PY 1994 VL 16 IS 5 BP 373 EP 376 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NT621 UT WOS:A1994NT62100010 PM 7934317 ER PT J AU SHERMAN, ME MANGO, LJ KELLY, D PAULL, G LUDIN, V COPELAND, C SOLOMON, D SCHIFFMAN, MH AF SHERMAN, ME MANGO, LJ KELLY, D PAULL, G LUDIN, V COPELAND, C SOLOMON, D SCHIFFMAN, MH TI PAPNET ANALYSIS OF REPORTEDLY NEGATIVE SMEARS PRECEDING THE DIAGNOSIS OF A HIGH-GRADE SQUAMOUS INTRAEPITHELIAL LESION OR CARCINOMA SO MODERN PATHOLOGY LA English DT Article DE THE BETHESDA SYSTEM; SQUAMOUS INTRAEPITHELIAL LESIONS; CERVICAL CARCINOMA; QUALITY ASSURANCE; DYSPLASIA; CERVICAL INTRAEPITHELIAL NEOPLASIA ID PAPANICOLAOU AB One hundred fourteen cervical smears obtained from 18 women developing biopsy-proven high-grade squamous intraepithelial lesions and two with invasive squamous carcinomas were analyzed by two pathologists using the PAPNET neural network-based automated screening system (PAPNET Analyses A and B). The smears were originally reported as negative and had been previously rescreened and reclassified according to The Bethesda System. Using the PAPNET video displays of 128 potentially abnormal cellular images per smear, each reviewer (PAPNET A and B) determined whether a smear required conventional rescreening. Results of the PAPNET triage were compared with the reclassification diagnoses of the smears by conventional microscopy. PAPNET Analysis A selected eight (14%) smears reclassified as negative, 25 (69%) as atypical squamous cells of undetermined significance, and 15 (71%) as squamous intraepithelial lesions (SIL) for rescreening. In PAPNET Analysis A, two (10%) SILs were not selected for rescreening, and four (19%) were considered unsatisfactory for analysis. PAPNET Analysis B selected 21 (37%) smears reclassified as negative, 25 (69%) as atypical squamous cells of undetermined significance, and 18 (86%) as SIL for review. In PAPNET Analysis B, two (10%) SILs were missed, and one (5%) smear was unsatisfactory for analysis. Each PAPNET analysis selected smears for rescreening in 19 (95%) of 20 patients and detected SILs in 10 patients that were missed in the original screeening. Using PAPNET, SILs would have been detected a median of 56 months (PAPNET A) and 62 months (PAPNET B) before their actual discovery. These preliminary data suggest that PAPNET may help detect SILs missed in routine cytologic screening. The specificity and clinical utility of PAPNET are being assessed in larger studies. C1 JOHNS HOPKINS MED INST,BALTIMORE,MD 21205. NEUROMED SYST INC,SUFFERN,NY. EMORY UNIV,SCH MED,ATLANTA,GA. NCI,BETHESDA,MD 20892. NR 7 TC 44 Z9 44 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JUN PY 1994 VL 7 IS 5 BP 578 EP 581 PG 4 WC Pathology SC Pathology GA NW310 UT WOS:A1994NW31000013 PM 7937724 ER PT J AU LI, J WIRTZ, RA MCCONKEY, GA SATTABONGKOT, J MCCUTCHAN, TF AF LI, J WIRTZ, RA MCCONKEY, GA SATTABONGKOT, J MCCUTCHAN, TF TI TRANSITION OF PLASMODIUM-VIVAX RIBOSOME TYPES CORRESPONDS TO SPOROZOITE DIFFERENTIATION IN THE MOSQUITO SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE PLASMODIUM VIVAX; SSURRNA; 18S RIBOSOMAL-RNA; DEVELOPMENTAL DIAGNOSTICS ID RNA GENES; FALCIPARUM; SEQUENCE; EVOLUTION; BERGHEI; NUMBER AB Two distinct small subunit ribosomal RNA (SSUrRNA) genes were amplified from the genomic DNA of Plasmodium vivax. Comparison of the two coding sequences reveals an overall divergence of 14.5% and most differences are clustered into the regions known to diverge rapidly in all eukaryotic SSUrRNAs. Oligonucleotides complementary to unique sequences of each gene have been used to distinguish the transcripts expressed either at schizogony in human blood (A gene) or at sporogony in the mosquito (C gene). These oligonucleotides were also used to monitor turnover of ribosomes during parasite development in mosquitoes. Transcripts of the A gene were predominant in the infected human blood and engorged mosquitoes but disappeared within 24 h after feeding. Expression of the C gene in mosquitoes was not detected until day 6 after the blood meal. A period of rapid accumulation of the C type rRNA from day 6 to day 8 corresponds to differentiation of individual sporozoites within the oocyst. Possible functional implications relating to the timing of this transition are discussed. C1 NIAID,MALARIA RES LAB,MOLEC BIOL SECT,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,DEPT PREVENT MED & BIOMETR,BETHESDA,MD 20814. WALTER REED ARMY INST RES,DEPT ENTOMOL,DIV COMMUN DIS & IMMUNOL,WASHINGTON,DC 20307. USA,MED COMPONENT,DEPT ENTOMOL,BANGKOK,THAILAND. NR 21 TC 32 Z9 38 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD JUN PY 1994 VL 65 IS 2 BP 283 EP 289 DI 10.1016/0166-6851(94)90079-5 PG 7 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA NX674 UT WOS:A1994NX67400009 PM 7969269 ER PT J AU MIYAHIRA, Y DVORAK, JA AF MIYAHIRA, Y DVORAK, JA TI KINETOPLASTIDAE DISPLAY NATURALLY-OCCURRING ANCILLARY DNA-CONTAINING STRUCTURES SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE KINETOPLASTIDA; DNA; NUCLEUS; KINETOPLAST; FLUORESCENCE MICROSCOPY; FLUORESCENT IN SITU HYBRIDIZATION ID FLOW CYTOMETRIC ANALYSIS; TRYPANOSOMA-CRUZI; MINICIRCLE DNA; GUIDE RNAS; ORGANIZATION; REPLICATION; AMPLIFICATION; GENES; IDENTIFICATION; EQUIPERDUM AB Kinetoplast-derived, DNA-containing structures were found in several members of the order Kinetoplastida. The structures, for which we propose the name ancillary DNA-containing structures (aDNA), were discovered during the course of low-light-level video fluorescence microscopy studies using several nucleic acid-specific fluorescent reagents. DNase treatment and supravital stain with Hoechst 33342 confirmed that aDNA is not an artifact of specimen preparation. Fluorescent in situ hybridization using either a 122-bp kinetoplast DNA-specific probe derived from a conserved region of minicircle DNA or a 188-bp nuclear DNA-specific probe derived from highly repetitive nuclear DNA demonstrated that aDNA is derived from the kinetoplast and not the nucleus. However, the structures do not contain minicircle DNA replication intermediates. Immunofluorescence assays using an anti-mitochondrial protein antibody, anti-mtp70, demonstrated that the structures contain mitochondrial protein and confirmed their kinetoplast origin. The frequency of occurrence of aDNA varies markedly between members of the Kinetoplastida. In the case of Trypanosoma cruzi stocks, the percentage of cells with aDNA was positively correlated to the population doubling time of the stock. However, there is no statistically significant relationship between the developmental or replicative stage of the parasite and the frequency of aDNA. An inhibitor of DNA topoisomerase I had no effect upon the frequency of aDNA. An inhibitor of DNA topoisomerase II gave equivocal results depending upon the parasite stock used. We speculate that aDNA may be the morphological consequence of a yet-to-be-determined biological process intrinsic to but variable within the Kinetoplastida. C1 NIAID,PARASIT DIS LAB,ROCKVILLE,MD 20852. NR 36 TC 16 Z9 17 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD JUN PY 1994 VL 65 IS 2 BP 339 EP 349 DI 10.1016/0166-6851(94)90084-1 PG 11 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA NX674 UT WOS:A1994NX67400014 PM 7969274 ER PT J AU MYERS, MG WANG, LM SUN, XJ ZHANG, YT YENUSH, L SCHLESSINGER, J PIERCE, JH WHITE, MF AF MYERS, MG WANG, LM SUN, XJ ZHANG, YT YENUSH, L SCHLESSINGER, J PIERCE, JH WHITE, MF TI ROLE OF IRS-1-GRB-2 COMPLEXES IN INSULIN SIGNALING SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID AFFINITY PHOSPHOTYROSYL PEPTIDE; RECEPTOR TYROSINE KINASES; PHOSPHATIDYLINOSITOL 3'-KINASE; NUCLEOTIDE EXCHANGE; HEMATOPOIETIC-CELLS; PROTEIN-KINASES; SH3 DOMAINS; RAS; IRS-1; GRB2 AB GRB-2 is a small SH2- and SH3 domain-containing adapter protein that associates with the mammalian SOS homolog to regulate p21(ras) during growth factor signaling. During insulin stimulation, GRB-2 binds to the phosphorylated Y-895 VNI motif of IRS-1. Substitution of Tyr-845 with phenylalanine (IRS-1(F-895)) prevented the IRS-1-GRB-2 association in vivo and in vitro. The myeloid progenitor cell line, 32-D, is insensitive to insulin because it contains few insulin receptors and no IRS-1. Coexpression of IRS-1 or IRS-1(F-895) with the insulin receptor was required for insulin-stimulated mitogenesis in 32-D cells, while expression of the insulin receptor alone was sufficient to mediate insulin-stimulated tyrosine phosphorylation of She and activation of p21(ras) and mitogen-activated protein (MAP) kinase. The Shc-GRB-2 complex formed during insulin stimulation is a possible mediator of p21(ras) and MAP kinase activation in IRS-1-deficient 32-D cells. Interestingly, IRS-1, but not IRS-1(F-895), enhanced the stimulation of MAP kinase by insulin in 32-D cells expressing insulin receptors. Thus, IRS-1 contributes to the stimulation of MAP kinase by insulin, probably through formation of the IRS-1-GRB-2 complex at Tyr-895. Our results suggest that the Shc-GRB-2 complex and the activation of p21(ras)-dependent signaling pathways, including MAP kinase, are insufficient for insulin-stimulated mitogenesis and that the essential function(s) of IRS-1 in proliferative signaling is largely unrelated to IRS-1-GRB-2 complex formation. C1 JOSLIN DIABET CTR,DIV RES,BOSTON,MA 02215. HARVARD UNIV,SCH MED,BOSTON,MA 02215. NYU,SCH MED,NEW YORK,NY 10016. NIH,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. RI Yenush, Lynne/J-8815-2014 OI Yenush, Lynne/0000-0001-8589-7002 FU NIDDK NIH HHS [DK 33201, DK 38712, DK 43808] NR 48 TC 180 Z9 182 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUN PY 1994 VL 14 IS 6 BP 3577 EP 3587 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NM741 UT WOS:A1994NM74100005 PM 8196603 ER PT J AU GAUEN, LKT ZHU, YX LETOURNEUR, F HU, Q BOLEN, JB MATIS, LA KLAUSNER, RD SHAW, AS AF GAUEN, LKT ZHU, YX LETOURNEUR, F HU, Q BOLEN, JB MATIS, LA KLAUSNER, RD SHAW, AS TI INTERACTIONS OF P59(FYN) AND ZAP-70 WITH T-CELL RECEPTOR ACTIVATION MOTIFS - DEFINING THE NATURE OF A SIGNALING MOTIF SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PROTEIN-TYROSINE KINASE; ANTIGEN RECEPTOR; ZETA-CHAIN; MONOCLONAL-ANTIBODIES; EFFECTOR FUNCTION; CYTOPLASMIC TAIL; CROSS-LINKING; PHOSPHORYLATION; TRANSDUCTION; ASSOCIATION AB The tyrosine-based activation motif is a 20- to 25-amino-acid sequence contained in the cytoplasmic domains of many hematopoietic receptors which is sufficient by itself to reconstitute signalling. This motif is characterized by two YXXL/I sequences separated by approximately 10 residues. The molecular basis of signalling by this motif is unknown. Here we demonstrate that the tyrosine-based activation motif is required and sufficient for association with the tyrosine kinases p59(fyn) and ZAP-70, suggesting that association with these kinases is a general feature of this motif. Focusing on the single activation motif present in epsilon, we analyzed which residues of the motif were critical for binding of p59(fyn) and ZAP-70. Surprisingly, we found that no single mutation of any residue of epsilon resulted in the loss of p59(fyn) association. In contrast, single mutations at five residues of the epsilon activating motif abrogated ZAP-70 binding. Both of the tyrosines and the leucine or isoleucine residues that follow them were critical. The spacing between the tyrosines was also important, as deletion of two residues disrupted binding of ZAP-70, although p59(fyn) binding was not disrupted. Most of the defined features of the tyrosine activation motif are therefore requirements for ZAP-70 binding. Interestingly, the interaction of ZAP-70 with the motif was dependent on the presence of both ZAP-70 SH2 domains and both of the tyrosine residues in the moth, suggesting that ZAP-70 interacts with two phosphotyrosine residues and that the binding of the two SH2 domains is cooperative. In addition, we demonstrate that the interaction between the tyrosine activation moth is direct and requires prior tyrosine phosphorylation of the motif. We propose that the activation of cells by the tyrosine activating motif occurs in four discrete steps: binding of p59(fyn), phosphorylation of the motif, binding of ZAP-70, and activation of ZAP-70 kinase activity. C1 WASHINGTON UNIV,SCH MED,DEPT PATHOL,ST LOUIS,MO 63110. BASEL INST IMMUNOL,CH-4005 BASEL,SWITZERLAND. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. NICHHD,BETHESDA,MD 20892. ALEXION PHARMACEUT,NEW HAVEN,CT 06511. BRISTOL MYERS SQUIBB,DEPT MOLEC BIOL,PRINCETON,NJ 08543. NR 53 TC 111 Z9 114 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 1994 VL 14 IS 6 BP 3729 EP 3741 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NM741 UT WOS:A1994NM74100020 PM 8196616 ER PT J AU CHANG, DY NELSON, B BILYEU, T HSU, K DARLINGTON, GJ MARAIA, RJ AF CHANG, DY NELSON, B BILYEU, T HSU, K DARLINGTON, GJ MARAIA, RJ TI A HUMAN ALU RNA-BINDING PROTEIN WHOSE EXPRESSION IS ASSOCIATED WITH ACCUMULATION OF SMALL CYTOPLASMIC ALU RNA SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SIGNAL RECOGNITION PARTICLE; HUMAN GENOME; 7SL RNA; REVERSE TRANSCRIPTION; ENDOPLASMIC-RETICULUM; SECONDARY STRUCTURE; REPEATED SEQUENCES; 7SL-RNA COMPONENT; POLYMERASE-III; SOURCE GENES AB Human Alu sequences are short interspersed DNA elements which have been greatly amplified by retrotransposition. Although initially derived from the 7SL RNA component of signal recognition particle (SRP), the Alu sequence has evolved into a dominant transposon while retaining a specific secondary structure found in 7SL RNA. We previously characterized a set of Alu sequences which are expressed as small cytoplasmic RNAs and isolated a protein that binds to these transcripts. Here we report that biochemical purification of this protein revealed it as the human homolog of the SRP 14 polypeptide which binds the Alu-homologous region of 7SL RNA. The human cDNA predicts an alanine-rich C-terminal tail translated from a trinucleotide repeat not found in the rodent homolog, which accounts for why the human protein-RNA complex migrates more slowly than its rodent counterpart in RNA mobility shift assays. The human Alu RNA-binding protein (RBP) is expressed after transfection of this cDNA into mouse cells. Expression of human RBP in rodent x human Somatic cell hybrids is associated with substantial increase in endogenous small cytoplasmic Alu and scB1 transcripts but not other small RNAs. These studies provide evidence that this RBP associates with Ala transcripts in vivo and affects their metabolism and suggests a role for Alu transcripts in translation in an SRP-like manner. Analysis of hybrid lines indicated that the Alu RBP gene maps to human chromosome 15q22, which was confirmed by Southern blotting. The possibility that the primate-specific structure of this protein may have contributed to Alu evolution is considered. C1 NICHHD,MOLEC GROWTH REGULAT LAB,BETHESDA,MD 20892. TEXAS CHILDRENS HOSP,DEPT PATHOL,HOUSTON,TX 77030. FU NIDDK NIH HHS [DK44080, DK45285] NR 75 TC 34 Z9 35 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 1994 VL 14 IS 6 BP 3949 EP 3959 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NM741 UT WOS:A1994NM74100041 PM 8196634 ER PT J AU PATTERSON, HG SIMPSON, RT AF PATTERSON, HG SIMPSON, RT TI NUCLEOSOMAL LOCATION OF THE STE6 TATA BOX AND MAT-ALPHA-2P-MEDIATED REPRESSION SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID YEAST ALPHA-2 REPRESSOR; RNA POLYMERASE-II; SACCHAROMYCES-CEREVISIAE; CRYSTAL-STRUCTURE; MINOR-GROOVE; MCM1 PROTEIN; MAJOR LATE; TRANSCRIPTION; DNA; GENE AB It has been proposed that yeast MATa cell-specific genes are repressed in MAT alpha cells by the Mat alpha 2p repressor-directed placement of a nucleosome in a position that incorporates the TATA box of the MATa-specific gene close to the nucleosomal pseudodyad. In this study, we address this proposal directly with a series of plasmids designed to place the MATa-specific STE6 TATA box at different locations in a nucleosome and in the internucleosomal linker. These plasmids contain different lengths of synthetic random DNA between the Mat alpha 2p operator and the TATA box of the STE6 promoter, which is located upstream of a lacZ reporter gene in a multicopy plasmid. We show that in MAT alpha cells, a nucleosome is retained in an identical translational frame relative to the Mat alpha 2p operator in all the constructs investigated, irrespective of the sequence of the DNA wrapped onto the histone octamer. This result shows that the nucleosomal organization of the STE6 promoter in MAT alpha cells is not conferred by the sequence of the promoter itself. No expression of the lacZ reporter gene was detectable in MAT alpha cells in any of the constructs, even with the TATA box located in a short internucleosomal linker. These data indicate that repression of MATa-specific genes in MAT alpha cells does not require the precise translational placement of the TATA box close to the nucleosomal pseudodyad; the gene remains repressed when the TATA box is located within the investigated 250-bp region in the organized chromatin domain abutting the Mat alpha 2p operator in MAT alpha cells and may remain repressed with the TATA box located anywhere within this organized repression domain. C1 NIDDKD,CELLULAR & DEV BIOL LAB,BETHESDA,MD 20892. OI Patterton, Hugh-George/0000-0003-2550-0493 NR 62 TC 36 Z9 36 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 1994 VL 14 IS 6 BP 4002 EP 4010 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA NM741 UT WOS:A1994NM74100046 PM 8196639 ER PT J AU ROMAGNOLO, D AKERS, RM BYATT, JC WONG, EA TURNER, JD AF ROMAGNOLO, D AKERS, RM BYATT, JC WONG, EA TURNER, JD TI IGF-I-INDUCED IGFBP-3 POTENTIATES THE MITOGENIC ACTIONS OF IGF-I IN MAMMARY EPITHELIAL MD-IGF-I CELLS SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE INSULIN GROWTH FACTOR I; MITOGENIC ACTION; BINDING PROTEIN ID GROWTH-FACTOR-I; FACTOR-BINDING-PROTEINS; BREAST-CANCER CELLS; GENE-EXPRESSION; LACTOGENIC HORMONES; INSULIN; FIBROBLASTS; RECEPTOR; INVITRO; SECRETION AB Limited information is available concerning the molecular and cellular mechanisms that regulate expression of insulin-like growth factor-I (IGF-I) binding proteins (IGFBPs) in bovine mammary epithelial cells. Here, we report on the autocrine mechanisms of action of IGF-I and hormonal regulation of expression of IGFBPs in bovine mammary epithelial MD-IGF-I cells which express recombinant IGF-I under the control of the glucocorticoid-inducible mouse mammary tumor virus-long terminal repeat (MMTV-LTR). Levels of IGFBP-3 mRNA and secretion of IGFBP-3 by MD-IGF-I cells were stimulated by IGF-I, insulin (INS), and IGF-I analogs but not prolactin (PRL). Conversely, parental MAC-T cells expressed little IGF-I and secreted primarily IGFBP-2 (29-32 kDa) in response to stimulation with INS, dexamethasone (DEX), or IGF-I analogs. Secretion of recombinant IGF-I caused a 26.5-fold increase in secretion of IGFBP-3, as measured by densitometric analysis of ligand blots, which was associated with a 1.7-fold increase in total DNA. Conditioned media (CM) from MD-IGF-I cells induced with DEX stimulated a 2.8-fold increase in [H-3]thymidine incorporation into DNA of parental MAC-T cells, compared with uninduced cells. Moreover, inclusion of exogenous IGF-I with CM from MD-IGF-I cells triggered an additional 3.0-fold increase in label incorporation, but only a 1.6-fold increase in the presence of IGFBP-2-containing media conditioned by MAC-T cells. Des(1-3)IGF-I added to CM from both MAC-T and MD-IGF-I cells respectively, stimulated a 10.2 and 6.9-fold increase in [H-3]thymidine incorporation into DNA of MAC-T cells. We suggest that expression of IGF-I-induced IGFBP-3 is an important component of an autocrine loop which potentiates the local mitogenic actions of IGF-I in bovine mammary epithelial cells. C1 VIRGINIA POLYTECH INST & STATE UNIV,DEPT DAIRY SCI,LACTAT PHYSIOL LAB,BLACKSBURG,VA 24061. VIRGINIA POLYTECH INST & STATE UNIV,DEPT ANIM SCI,BIOTECHNOL LAB,BLACKSBURG,VA 24061. MONSANTO AGR CO,ST LOUIS,MO 63198. MCGILL UNIV,DEPT ANIM SCI,MONTREAL 9X 1C0,PQ,CANADA. NIEHS,RES TRIANGLE PK,NC 27709. NR 41 TC 15 Z9 15 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD JUN PY 1994 VL 102 IS 1-2 BP 131 EP 139 DI 10.1016/0303-7207(94)90106-6 PG 9 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA NQ369 UT WOS:A1994NQ36900017 ER PT J AU MESSERSMITH, DJ GU, J DUBNER, R DOUGLASS, J IADAROLA, MJ AF MESSERSMITH, DJ GU, J DUBNER, R DOUGLASS, J IADAROLA, MJ TI BASAL AND INDUCIBLE TRANSCRIPTIONAL ACTIVITY OF AN UPSTREAM AP-1/CRE ELEMENT (DYNCRE3) IN THE PRODYNORPHIN PROMOTER SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article ID AMP RESPONSE ELEMENT; SPINAL-CORD NEURONS; CYCLIC-AMP; GENE-EXPRESSION; C-FOS; BINDING; DYNORPHIN; CELLS; INFLAMMATION; SEQUENCE AB During chronic pain and inflammation, prodynorphin gene expression is elevated in the spinal cord. To characterize the molecular regulation of prodynorphin gene expression, we examined an AP-1/CRE-like element, TGCGTCA, located at -1545 in the prodynorphin gene (the DYNCRE3 site). Previous work in our laboratory demonstrated by gel shift analysis that Fos and non-Fos-containing complexes formed with oligonucleotides containing this element. To examine the functional significance of this site, constructs containing variable length regions of the prodynorphin promoter were transiently transfected into PC12 or HeLa cells. Constructs containing the DYNCRE3 site consistently permitted higher levels of transcriptional activity than those lacking this site. Furthermore, placement of upstream regions containing the DYNCRE3 site adjacent to the minimal promoter yielded transcriptional activity much greater than that in the presence of the native constructs. PC12 cells transfected with constructs containing the DYNCRE3 site responded to a far greater degree to forskolin stimulation than those transfected with constructs that did not contain this site. Mutation of the DYNCRE3 site (CTcgtca) markedly reduced forskolin-induced increases in transcriptional activity. The phorbol ester 12-O-tetradecanoylphorbol 13-acetate produced little or no change in transcriptional activity. By examining successively more isolated fragments of prodynorphin promoter and by mutational analysis, we identify and characterize a 7-bp site, DYNCRE3, which, though largely unaffected by stimulations of the PKC pathway, dramatically responds to stimulations via the PKA second messenger pathway. (C) 1994 Academic Press, Inc. C1 OREGON HLTH SCI UNIV,VOLLUM INST,PORTLAND,OR 97201. RP MESSERSMITH, DJ (reprint author), NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD 20892, USA. NR 31 TC 35 Z9 35 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 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell Neurosci. PD JUN PY 1994 VL 5 IS 3 BP 238 EP 245 DI 10.1006/mcne.1994.1028 PG 8 WC Neurosciences SC Neurosciences & Neurology GA NL735 UT WOS:A1994NL73500005 PM 8087422 ER PT J AU MIYAMOTO, S NISHIDA, M MIWA, K KATO, H IMAMURA, T BARRETT, JC SHIMIZU, M OSHIMURA, M WAKE, N AF MIYAMOTO, S NISHIDA, M MIWA, K KATO, H IMAMURA, T BARRETT, JC SHIMIZU, M OSHIMURA, M WAKE, N TI INCREASED ACTIN CABLE ORGANIZATION AFTER SINGLE CHROMOSOME INTRODUCTION - ASSOCIATION WITH SUPPRESSION OF IN-VITRO CELL-GROWTH RATHER THAN TUMORIGENIC SUPPRESSION SO MOLECULAR CARCINOGENESIS LA English DT Article DE MICROCELL FUSION; HUMAN CHROMOSOME 1; TUMOR SUPPRESSOR GENE; ACTIN STRESS FIBERS; HUMAN ENDOMETRIAL CARCINOMA ID GENE; LINE; TRANSFORMATION AB We previously showed that introduction of a single human chromosome 1, 6, or 9 derived from normal fibroblasts into HHUA endometrial carcinoma cells resulted in suppression of tumorigenicity. The tumorigenic suppression was accompanied by remarkable morphological changes in the microcell hybrids containing an extra copy of chromosome 1. The study presented here was undertaken to search for target cytoskeletal components affected by chromosome 1 transfer into endometrial carcinoma cells. We found that the microcell hybrids containing an extra copy of chromosome 1 were characterized by intracellular actin bundle formation and an excessive accumulation of actin and vinculin. The latter was a result of increased stabilization of the proteins. Additionally, chromosome 3 introduction into RCC23 human renal carcinoma cells resulted in prolongation of cell division and in senescence of a significant proportion of the microcell hybrids. In these microcell hybrids, the intracellular actin network was also reorganized, but the amounts of actin and vinculin protein were not increased. These findings suggest that the increased actin organization, which appeared not to cause tumorigenic suppression in the microcell hybrids, is associated with complementation of tumor suppressor genes and senescence by multiple mechanisms. (C) 1994 Wiley-Liss, Inc. C1 KYUSHU UNIV,MED INST BIOREGULAT,DEPT REPROD PHYSIOL & ENDOCRINOL,BEPPU,OITA 874,JAPAN. NIEHS,DEPT MOLEC CARCINOGENESIS,RES TRIANGLE PK,NC 27709. TOTTORI UNIV,FAC MED,MOLEC & CELL GENET LAB,YONAGO,TOTTORI 683,JAPAN. NR 21 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 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD JUN PY 1994 VL 10 IS 2 BP 88 EP 96 DI 10.1002/mc.2940100206 PG 9 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA NV252 UT WOS:A1994NV25200005 PM 8031469 ER PT J AU SUH, DS OOI, GT RECHLER, MM AF SUH, DS OOI, GT RECHLER, MM TI IDENTIFICATION OF CIS-ELEMENTS MEDIATING THE STIMULATION OF RAT INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN-1 PROMOTER ACTIVITY BY DEXAMETHASONE, CYCLIC ADENOSINE-3',5'-MONOPHOSPHATE, AND PHORBOL ESTERS, AND INHIBITION BY INSULIN SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID STREPTOZOTOCIN-DIABETIC RATS; H4IIE HEPATOMA-CELLS; GENE-EXPRESSION; TRANSCRIPTIONAL REGULATION; GLUCOCORTICOID RECEPTOR; DEOXYRIBONUCLEIC-ACID; RESPONSIVE ELEMENT; MESSENGER-RNA; AMYLASE GENE; DNA ELEMENT AB Insulin-like growth factor-binding protein-1 (IGFBP-1) modulates the action of IGFs on target cells. IGFBP-1 transcription is highly regulated by hormonal and metabolic factors. In rat H4-II-E hepatoma cells, IGFBP-1 messenger RNA is stimulated by dexamethasone, cAMP, and phorbol esters, and dominantly inhibited by insulin. To identify the cis-elements that determine transcriptional regulation by these agents, we have coupled rat IGFBP-1 promoter fragments to a luciferase reporter gene and transfected H4-II-E cells using the cationic liposome procedure. Promoter fragments whose 5'-end was at nucleotide (nt) -925 or -327 (with respect to the transcription initiation site, I)conferred positive regulation of promoter activity by dexamethasone, cAMP, and phorbol esters. Insulin inhibited promoter activity in the presence of any of the three stimulatory agents. Stimulation by cAMP or phorbol esters was abolished when the region between nt -327 and -235 was deleted. Although this region contains potential activating protein-2 and activating protein-1 sites, the sites responsible for this regulation have not yet been identified. By contrast, stimulation by dexamethasone was retained in deletion constructs whose 5'-end was at nt -92, but was abolished by site mutagenesis of either the left or right half-sites of a potential glucocorticoid response element (GRE) located between nt -91 and -77. Surprisingly, substitution mutations in an up-stream region, -108 to -99 (M4), also decreased dexamethasone-stimulated promoter activity despite the presence of an intact GRE. We postulate that a positive factor that binds to the wild-type M4 region neutralizes factors that inhibit interaction of the glucocorticoid receptor with the GRE. The M4 region also is involved in inhibition by insulin. Insulin inhibition of dexamethasone-stimulated promoter activity was lost after deletion of nt -135 to -92 or mutation of the region between nt -108 and -99. This insulin response element is conserved in the human IGFBP-1 promoter and is homologous to the insulin response element of the phosphoenolpyruvate carboxykinase gene, which also is rapidly inhibited by insulin in H4-II-E cells. The rat IGFBP-1 promoter provides a valuable model system for studying the multihormonal regulation of transcription. RP SUH, DS (reprint author), NIDDKD, MOLEC & CELLULAR ENDOCRINOL BRANCH, GROWTH & DEV SECT, BLDG 10, ROOM 8D-14, BETHESDA, MD 20892 USA. NR 54 TC 46 Z9 46 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 1994 VL 8 IS 6 BP 794 EP 805 DI 10.1210/me.8.6.794 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA NR066 UT WOS:A1994NR06600014 PM 7523864 ER PT J AU PALMER, TM GETTYS, TW JACOBSON, KA STILES, GL AF PALMER, TM GETTYS, TW JACOBSON, KA STILES, GL TI DESENSITIZATION OF THE CANINE A(2A)-ADENOSINE RECEPTOR - DELINEATION OF MULTIPLE PROCESSES SO MOLECULAR PHARMACOLOGY LA English DT Article ID BETA-ADRENERGIC-RECEPTOR; AGONIST-PROMOTED DESENSITIZATION; PROTEIN-MEDIATED PATHWAYS; ADENYLATE-CYCLASE SYSTEM; INHIBITORY G-PROTEIN; GLIOMA HYBRID-CELLS; BETA-2-ADRENERGIC RECEPTOR; ALPHA-2-ADRENERGIC RECEPTORS; RADIOLIGAND BINDING; MOLECULAR-CLONING AB Stable cell lines that express the canine-derived A?a adenosine receptor (AP(2a)AR) have been generated. Using a previously characterized anti-A(2a)AR antibody probe, we have identified the recombinant receptor protein and examined the desensitization process of this G protein-coupled receptor. Agonist exposure induced a rapid desensitization of A(2a)AR-stimulated adenylyl cyclase activity. This was associated with reduced affinity of the receptor for the A(2a)AR-selective agonist [H-3]CGS21680 and agonist-stimulated phosphorylation of the receptor protein. Agonist-stimulated A(2a)AR sequestration into a light membrane fraction was also detected over the same time frame but, whereas inhibition of this process did not affect the extent of desensitization, the rapid recovery normally observed after short term agonist exposure was dramatically reduced. Long term agonist treatment resulted in the down-regulation of A(2a)ARs and upregulation of G(i alpha 2) and G(i) alpha(3), as determined by immunoblotting. Recovery of A(2a)AR function after agonist removal required several hours and was associated with the return of receptor levels to control values. In contrast, inactivation of G(i) proteins by pertussis toxin treatment did not alter the extent of agonist-induced desensitization observed. Neither short nor long term desensitization could be mimicked by elevation of intracellular cAMP levels alone. Therefore, these data suggest that A(2a)AR desensitization is mediated by multiple, temporally distinct, agonist-dependent processes. Agonist-stimulated phosphorylation of the receptor may induce short term desensitization by impairing receptor-G(s) coupling, whereas long term down-regulation of receptor number and up-regulation of inhibitory G proteins mediate long term adaptation. C1 DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT CELL BIOL,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT PHARMACOL,DURHAM,NC 27710. NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892. RI Palmer, Timothy/C-4975-2009; Jacobson, Kenneth/A-1530-2009; Palmer, Timothy/E-7290-2013; OI Jacobson, Kenneth/0000-0001-8104-1493; Palmer, Timothy/0000-0002-9803-7164; Gettys, Thomas/0000-0001-7125-7995 FU Intramural NIH HHS [Z99 DK999999, Z01 DK031117-20]; NHLBI NIH HHS [P50-HL17670, R01-HL35134]; NIDDK NIH HHS [DK42486] NR 50 TC 76 Z9 77 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JUN PY 1994 VL 45 IS 6 BP 1082 EP 1094 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NV485 UT WOS:A1994NV48500003 PM 8022402 ER PT J AU VANGALEN, PJM VANBERGEN, AH GALLORODRIQUEZ, C MELMAN, N OLAH, ME IJZERMAN, AP STILES, GL JACOBSON, KA AF VANGALEN, PJM VANBERGEN, AH GALLORODRIQUEZ, C MELMAN, N OLAH, ME IJZERMAN, AP STILES, GL JACOBSON, KA TI A BINDING-SITE MODEL AND STRUCTURE-ACTIVITY-RELATIONSHIPS FOR THE RAT A(3)-ADENOSINE RECEPTOR SO MOLECULAR PHARMACOLOGY LA English DT Article ID PROTEIN-COUPLED RECEPTOR; MOLECULAR-CLONING; ANTI-MODE; ANTAGONISTS; AGONISTS; ANALOGS; DERIVATIVES; A1; ADENOSINE-A1-RECEPTOR; XANTHINE-7-RIBOSIDES AB A novel adenosine receptor, the A(3) receptor, has recently been cloned. We have systematically investigated the hitherto largely unexplored structure-activity relationships (SARs) for binding at A(3) receptors, using (125)l-N-6-2-(4-aminophenyl)ethyladenosine as a radioligand and membranes from Chinese hamster ovary cells stably transfected with the rat A(3)-cDNA. As is the case for A(1) and A(2A) receptors, substitutions at the N-6 and 5' positions of adenosine, the prototypic agonist ligand, may yield fairly potent compounds. However, the highest affinity and A(3) selectivity is found for N-6,5'-disubstituted compounds, in contrast to A(1) and A(2a) receptors. Thus, N-6-benzyladenosine-5'-N-ethylcarboxamide is highly potent (K-I, 6.8 nM) and moderately selective (13- and 14-fold versus A(1) and A(2a)) The N-6 region of the A(3) receptor also appears to tolerate hydrophilic substitutions, in sharp contrast to the other subtypes. Potencies of N-6,5'-disubstituted compounds in inhibition of adenylate cyclase via A(3) receptors parallel their high affinity in the binding assay. None of the typical xanthine or nonxanthine (A(1)/A(2)) antagonists tested show any appreciable affinity for rat A(3) receptors. 1,3-Dialkylxanthines did not antagonize the A(3) agonist-induced inhibition of adenylate cyclase. A His residue in helix 6 that is absent in A(3) receptors but present in A(1)/A(2) receptors may be causal in this respect. In a molecular model for the rat A(3) receptor, this mutation, together with an increased bulkiness of residues surrounding the ligand, make antagonist binding unfavorable when compared with a previously developed A(1) receptor model. Second, this A(3) receptor model predicted similarities with A(1) and A(2) receptors in the binding requirements for the ribose moiety and that xanthine-7-ribosides would bind to rat A(3) receptors. This hypothesis was supported experimentally by the moderate affinity (K-l 6 mu M) of 7-riboside of 1,3-dibutylxanthine, which appears to be a partial agonist at rat A(3) receptors. The model presented here, which is consistent with the detailed SAR found in this study, may serve to suggest future chemical modification, site-directed mutagenesis, and SAR studies to further define essential characteristics of the ligand-receptor interaction and to develop even more potent and selective A(3) receptor ligands. C1 NIDDK,BIOORGAN CHEM LAB,MOLEC RECOGNIT SECT,BETHESDA,MD 20892. DUKE UNIV,MED CTR,DEPT MED,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT PHARMACOL,DURHAM,NC 27710. CTR BIOPHARMACEUT SCI,DIV MED CHEM,2300 RA LEIDEN,NETHERLANDS. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999] NR 48 TC 168 Z9 170 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JUN PY 1994 VL 45 IS 6 BP 1101 EP 1111 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NV485 UT WOS:A1994NV48500005 PM 8022403 ER PT J AU SEYNAEVE, CM KAZANIETZ, MG BLUMBERG, PM SAUSVILLE, EA WORLAND, PJ AF SEYNAEVE, CM KAZANIETZ, MG BLUMBERG, PM SAUSVILLE, EA WORLAND, PJ TI DIFFERENTIAL INHIBITION OF PROTEIN-KINASE-C ISOZYMES BY UCN-01, A STAUROSPORINE ANALOG SO MOLECULAR PHARMACOLOGY LA English DT Article ID MYELIN BASIC-PROTEIN; KINETIC-ANALYSIS; SELECTIVE-INHIBITION; SIGNAL-TRANSDUCTION; RAT FIBROBLASTS; GROWTH-CONTROL; PHOSPHORYLATION; EXPRESSION; POTENT; CELLS AB UCN-01 (7-hydroxystaurosporine) has been demonstrated to be a potent inhibitor of tumor cell growth both in cell culture and with in vivo xenograft models. The ability of UCN-01 to inhibit the kinase activity of recombinant protein kinase C (PKC) isozymes alpha, beta, gamma, delta, epsilon, and zeta was characterized using an in vitro kinase assay. Two distinct groups of isozymes could be defined on the basis of relative potency of kinase inhibition. UCN-01 was 15-20-fold more potent for inhibition of the Ca2+-dependent isozymes, compared with the Ca2+-independent isozymes. In contrast, UCN-02 (the diastereomer of UCN-01) and staurosporine exhibited less ability to discriminate between Ca2+-dependent and -independent isozymes. PKC-zeta was not inhibited by UCN01, UCN-02, or staurosporine. IC50 values for UCN-01 inhibition of the Ca2+-dependent PKC-alpha, -beta, and -gamma were 29, 34, and 30 nM, respectively, and for the Ca2+-independent PKC-delta and -epsilon were 530 and 590 nM, respectively. IC50 values for staurosporine inhibition of the isozymes alpha, beta, and gamma were 58, 65, and 49 nM, respectively, and for the isozymes delta and epsilon were 325 and 160 nM, respectively. UCN-02 was significantly less potent for the inhibition of PKC-alpha, -beta, -gamma, -delta, and -epsilon (IC50 values of 530, 700, 385, 2800, and 1200 nM, respectively). An analysis of the inhibition by UCN-01 and staurosporine of the kinase activity of PKC-alpha and -delta indicated mixed inhibition kinetics. Increasing the ATP concentration resulted in decreased potency, as shown by increased IC50 values. In contrast, increasing the peptide substrate concentration resulted in increased potency, as shown by decreased IC50 values. Increasing concentrations of myelin basic protein as a PKC-alpha or -delta substrate also caused increased potency of inhibition by UCN-01. Because of the competitive nature of inhibition with respect to ATP and the uncompetitive nature with respect to substrate, the concentrations of these substrates can have dramatically different effects on the degree of inhibition observed. These data also suggest that UCN-01 may be an important tool for the dissection of PKC isozyme contributions to signal transduction pathways. C1 NCI, BIOL CHEM LAB, MOLEC THERAPEUT SECT, BETHESDA, MD 20892 USA. NCI, MOLEC MECH TUMOR PROMOT SECT, CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB, BETHESDA, MD 20892 USA. NR 38 TC 150 Z9 151 U1 0 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X EI 1521-0111 J9 MOL PHARMACOL JI Mol. Pharmacol. PD JUN PY 1994 VL 45 IS 6 BP 1207 EP 1214 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NV485 UT WOS:A1994NV48500019 PM 8022414 ER PT J AU GATEHOUSE, D HAWORTH, S CEBULA, T GOCKE, E KIER, L MATSUSHIMA, T MELCION, C NOHMI, T OHTA, T VENITT, S ZEIGER, E AF GATEHOUSE, D HAWORTH, S CEBULA, T GOCKE, E KIER, L MATSUSHIMA, T MELCION, C NOHMI, T OHTA, T VENITT, S ZEIGER, E TI RECOMMENDATIONS FOR THE PERFORMANCE OF BACTERIAL MUTATION ASSAYS SO MUTATION RESEARCH LA English DT Article DE BACTERIAL MUTATION ASSAYS; RECOMMENDATIONS; STANDARDIZATION; GENOTOXICITY TEST PROCEDURES ID SALMONELLA-TYPHIMURIUM TA97A; MAMMALIAN-MICROSOME TEST; RODENT CARCINOGENICITY; 300 CHEMICALS; AMES TEST; MUTAGENICITY; TA102; REVERSION; NITROSAMINES; STRAINS AB At the International Workshop on the Standardisation of Genotoxicity Test Procedures, in Melbourne (27-28 February 1993), the current international guidelines for the correct conduct of bacterial mutation assays were considered, and the major differences between them were examined. An attempt was made to construct a scientifically based, internationally harmonised protocol. The main points of agreement were as follows. The consensus opinion was that there are currently insufficient data to justify a preference for either the preincubation or plate-incorporation methodologies as the initial test. Whichever method is used there was consensus agreement that the bacterial test battery should consist of S. typhimurium TA1537, TA1535, TA98 and TA100. There was also consensus that the 3 strains TA97a, TA97 and TA1537 could be used interchangeably. Although it was not possible to achieve a consensus, the majority of the working group members agreed that strains for the detection of mutagens acting specifically on AT base pairs should be routinely included within the test battery. These strains may be S. typhimurium TA102 or E. coli WP2 strains (WP2 pKM101 and WP2 uvrA or WP2 uvrA pkM101). With regard to study design it was universally agreed that 5 doses of test compound should be used in each experiment, and a majority agreement was obtained for 3 plates per dose. The use of 2 plates per dose is acceptable ONLY if the experiment is repeated. It is recommended that the negative controls may consist of solvent control alone provided that historical data are available to demonstrate lack of effect of the solvent in question. Positive control compounds should be included in all experiments, although the nature of these control compounds need not be specified in the guidelines. There was consensus agreement that for non-toxic freely soluble test agents, an upper limit of 5 mg/plate should be tested (5 mu l per plate for liquids). For insoluble or toxic compounds, the recommendations were the same as those for other in vitro tests (see appropriate paper). A consensus agreement was reached on the need to carry out further tests if equivocal results are obtained in the initial test, although it was generally agreed that the design of the repeat study should be left flexible. As there are little or no data to support the use of an exact repeat assay, a majority of the group recommended that negative results in the first test should be further investigated by either conducting a modified repeat (e.g. S9 titration) or by conducting the alternative methodology. If a preincubation assay is carried out, an incubation time within the range 20-60 min is recommended, usually at a temperature of 37 degrees C. Lastly, a consensus agreement on the acceptable criteria for a positive or negative result could not be reached. There was majority agreement that a reproducible dose-response was necessary for a chemical to be classified as positive. A number of limitations of the proposed test methodology were recognised and included the adequate testing of specific chemical classes or groups, (i.e. ate-dyes and diazo compounds, gases, volatile chemicals and glycosides). Such 'special cases' should be evaluated using alternative published procedures. C1 BIOTRACE LABS, SALT LAKE CITY, UT 84119 USA. US FDA, HFF 235, MOLEC BIOL BRANCH, WASHINGTON, DC 20204 USA. F HOFFMANN LA ROCHE & CO LTD, CH-4002 BASEL, SWITZERLAND. MONSANTO CO, ENVIRONM HLTH LAB, ST LOUIS, MO 63110 USA. JAPAN BIOASSAY LAB, KANAGAWA 257, JAPAN. RHONE POULENC RORER, F-92165 ANTONY, FRANCE. NATL INST HYG SCI, TOKYO 158, JAPAN. INST CANC RES, HADDOW LABS, SUTTON, SURREY, ENGLAND. NIEHS, ENVIRONM TOXICOL PROGRAM, RES TRIANGLE PK, NC 27709 USA. RP GATEHOUSE, D (reprint author), GLAXO GRP RES LTD, DEPT GENET & REPROD TOXICOL, PARK RD, WARE SG12 0DP, HERTS, ENGLAND. NR 43 TC 120 Z9 129 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8262 J9 MUTAT RES JI Mutat. Res. PD JUN PY 1994 VL 312 IS 3 BP 217 EP 233 DI 10.1016/0165-1161(94)90037-X PG 17 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA NQ875 UT WOS:A1994NQ87500005 PM 7514736 ER PT J AU TICE, RR SHELBY, MD AF TICE, RR SHELBY, MD TI REPORT OF IN-VIVO SUBGROUP SO MUTATION RESEARCH LA English DT Article; Proceedings Paper CT International Workshop on Standardisation of Genotoxicity Test Procedures CY FEB, 1993 CL MELBOURNE, AUSTRALIA DE IN VIVO GENOTOXICITY TESTING; STANDARDIZATION ID CORN-OIL; MICRONUCLEUS; HEPATOCYTES; ASSAYS; INVIVO; MOUSE C1 NIEHS,RES TRIANGLE PK,NC 27709. RP TICE, RR (reprint author), INTEGRATED LAB SYST,RES TRIANGLE PK,NC 27709, USA. NR 11 TC 12 Z9 12 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 1994 VL 312 IS 3 BP 287 EP 292 DI 10.1016/0165-1161(94)00014-X PG 6 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA NQ875 UT WOS:A1994NQ87500009 PM 7514740 ER PT J AU ADLER, ID SHELBY, MD BOOTMAN, J FAVOR, J GENEROSO, W PACCHIEROTTI, F SHIBUYA, T TANAKA, N AF ADLER, ID SHELBY, MD BOOTMAN, J FAVOR, J GENEROSO, W PACCHIEROTTI, F SHIBUYA, T TANAKA, N TI SUMMARY REPORT OF THE WORKING-GROUP-ON-MAMMALIAN-GERM-CELL-TESTS SO MUTATION RESEARCH LA English DT Article; Proceedings Paper CT International Workshop on Standardisation of Genotoxicity Test Procedures CY FEB, 1993 CL MELBOURNE, AUSTRALIA DE MAMMALIAN GERM CELL CYTOGENETIC ASSAY; RODENT DOMINANT LETHAL TEST ID DOMINANT LETHAL MUTATIONS; MALE-MICE; INDUCTION AB The two tests considered by the Working Group were the mammalian germ cell cytogenetic assay and the rodent dominant lethal test. It was agreed that both tests were mainly used for identification of germ cell hazards, however, that the commonly applied protocol of the dominant lethal assay often supplied information for hazard characterization such as sensitivity of particular developmental stages of male germ cells. No particular species or strains were indicated. Concurrent solvent controls were regarded as indispensable for both tests. In the discussion of the mammalian germ cell cytogenetic assay, harmonization was obtained to a large extent with the cytogenetic bone marrow assay regarding the number of animals (5), the number of cells analyzed per animal (200), the highest exposure dose (MTD) and sampling times (twice within 24 and 48 h after dosing). However, it was pointed out that only the single acute exposure was adequate for the mammalian germ cell cytogenetic assay. Furthermore, it was stated that only structural chromosome aberrations could be analyzed and that it was not informative to score polyploidies or aneuploidies. In the discussion of the rodent dominant lethal test, it was stated that the assay was generally performed with treated males, however, increasing concern about female specific effects required that a protocol for female dominant lethal testing should be developed and validated. Acute and subacute treatment schedules were considered equally acceptable. It was regarded as highly important that the entire male germ cell development from meiosis to mature sperm was covered in the test protocol either by the appropriate mating schedules after single dosing or by subchronic dosing during the respective period. Postimplantation loss, preimplantation loss and fertility rate were the main parameters to be assessed in the rodent dominant lethal tests. It was agreed that the size of the experiment depended on the spontaneous frequency of dead implants, the mating scheme and the statistical design of the experiment. C1 NIEHS,RES TRIANGLE PK,NC 27709. LIFE SCI RES,SUFFOLK,ENGLAND. ORNL,DIV BIOL,OAK RIDGE,TN. CTR RIC ENERGIA CASACCIA,ENEA,ROME,ITALY. HATANO RES INST,KANAGAWA,JAPAN. RP ADLER, ID (reprint author), GSF,INST SAUGETIERGENET,OBERSCHLEISSHEIM,GERMANY. NR 19 TC 14 Z9 14 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8262 J9 MUTAT RES PD JUN PY 1994 VL 312 IS 3 BP 313 EP 318 DI 10.1016/0165-1161(94)00017-4 PG 6 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA NQ875 UT WOS:A1994NQ87500012 PM 7514743 ER PT J AU TENNANT, RW AF TENNANT, RW TI TRANSGENIC SYSTEMS IN MUTAGENESIS AND CARCINOGENESIS - INTRODUCTION SO MUTATION RESEARCH LA English DT Editorial Material DE ORIGINS, GENETIC TOXICOLOGY; GENETIC ENGINEERING; TRANSGENIC LINES; SHUTTLE-VECTOR CONSTRUCTS; TRANSGENICS RP TENNANT, RW (reprint author), NIEHS,ENVIRONM CARCINOGENESIS & MUTAGENESIS LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8262 J9 MUTAT RES PD JUN 1 PY 1994 VL 307 IS 2 BP 427 EP 428 DI 10.1016/0027-5107(94)90253-4 PG 2 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA NQ016 UT WOS:A1994NQ01600001 ER PT J AU WATANABE, H KIMATA, K LINE, S STRONG, D GAO, LY KOZAK, CA YAMADA, Y AF WATANABE, H KIMATA, K LINE, S STRONG, D GAO, LY KOZAK, CA YAMADA, Y TI MOUSE CARTILAGE MATRIX DEFICIENCY (CMD) CAUSED BY A 7 BP DELETION IN THE AGGRECAN GENE SO NATURE GENETICS LA English DT Article ID PROTEOGLYCAN CORE PROTEIN; STICKLER SYNDROME ARTHROOPHTHALMOPATHY; STOP CODON; CHONDROCYTES; NANOMELIA; IDENTIFICATION; SYNTHESIZE; MUTATION; RECEPTOR; ABSENCE AB Mouse cartilage matrix deficiency (cmd) is an autosomal recessive mutation characterized by cleft palate, short limbs, tail and snout. Heterozygous mice show normal size and phenotype, while homozygous mice die just after birth due to respiratory failure. Biochemical and immunohistochemical characterization of cmd cartilage reveals normal levels of type II collagen and link protein, but an absence of the large cartilage proteoglycan, aggrecan. Here, we have mapped the aggrecan gene to a region of mouse chromosome 7 near the cmd locus. DNA sequencing of the aggrecan gene identified a 7 bp deletion in exon 5 resulting in a severely truncated molecule. The finding of an aggrecan mutation in the cmd mouse confirms the critical role of aggrecan in cartilage formation. C1 NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. AICHI MED UNIV,INST MOLEC SCI MED,NAGAKUTE,AICHI 48011,JAPAN. RP WATANABE, H (reprint author), NIDR,DEV BIOL LAB,BETHESDA,MD 20892, USA. RI Line, Sergio/H-5272-2012 OI Line, Sergio/0000-0002-6574-9464 NR 27 TC 163 Z9 169 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUN PY 1994 VL 7 IS 2 BP 154 EP 157 DI 10.1038/ng0694-154 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA NQ037 UT WOS:A1994NQ03700014 PM 7920633 ER PT J AU CRISTALLI, G VITTORI, S THOMPSON, RD PADGETT, WL SHI, D DALY, JW OLSSON, RA AF CRISTALLI, G VITTORI, S THOMPSON, RD PADGETT, WL SHI, D DALY, JW OLSSON, RA TI INHIBITION OF PLATELET-AGGREGATION BY ADENOSINE RECEPTOR AGONISTS SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Article DE PLATELET AGGREGATION; 2-ARALKOXYADENOSINES; PLATELET ADENOSINE RECEPTOR ID SELECTIVE AGONISTS; PURINE NUCLEOSIDES; ADENYLATE-CYCLASE; GUINEA-PIG; DERIVATIVES; ANALOGS; RAT; A1; FIBROBLASTS; SUBCLASSES AB 2-(Ar)alkoxyadenosines, which are agonists selective for the A(2A)AR in PC12 cell and rat striatum membranes, are also agonists at the A(2)AR coupled to adenylate cyclase (AC) that mediates the inhibition of platelet aggregation. A panel of twelve well-characterized adenosine analogues stimulated human platelet AC and inhibited ADP-induced platelet aggregation at sub- to low-micromolar concentrations with a potency ranking CGS 21680 > adenosine > R-PIA. There were significant correlations between the EC(50) Of anti-aggregatory activity and either the EC(50) Of stimulation of platelet and PC12 cell AC (r(2) = 0.66 and 0.67, respectively) or the K-i of inhibition of [H-3]NECA binding to the rat striatum membranes (r(2) = 0.75). Likewise, platelet AC stimulation correlated well with stimulation of PC12 cell AC and with [H-3]NECA binding (r(2) = 0.94 and 0.91, respectively). Ten 2-(ar)alkoxyadenosines stimulated platelet AC at EC(50)s ranging between 0.16 and 2.3 mu M and inhibited platelet aggregation at EC(50)s ranging between 2 and 30 mu M. There were no correlations between the EC(50)s of anti-aggregatory activity and either the EC(50)s of the stimulation of platelet or PC12 AC (r(2) = 0.08 and 0.06, respectively) or with the K-i of the inhibition of [H-3]NECA binding to the A(2a)AR in rat striatum (r(2) = 0.02). The EC(50)s Of the stimulation of platelet AC correlated with those of the stimulation of PC 12 C (r(2) = 0.48), and also with the K-i of [H-3]NECA binding (r(2) = 0.71). Each of the 23 adenosines completely inhibited platelet aggregation and thus, functionally, all behaved as full agonists. As stimulants of PC12 cell AC, Group A and B analogues were equally efficacious. As stimulants of platelet AC, however, the efficacy relative to NECA (=1.0) of Group B analogues was significantly less than that of Group A analogues, 0.49+/-0.2 vs. 0.72+/-0.05, P<0.01. The partial agonist activity of Group B analogues at the platelet A(2)AR but full agonist activity at the PC12 cell A(2),AR, as well as the relatively low correlations between platelet AC stimulation and other indices of A(2a)AR agonist activity, suggest the platelet receptor is not a typical A(2a)AR. Further, the lack of a correlation between the platelet anti-aggregatory and AC stimulatory activity suggests that (a) the 2-(ar)alkoxyadenosines might affect platelet aggregation by mechanisms other than AC stimulation or (b) that the stimulation of the platelet membrane AC by 2-(ar)alkoxy-adenosines does not correspond to the accumulation of cyclic AMP in intact platelets. C1 UNIV S FLORIDA,DEPT INTERNAL MED,TAMPA,FL 33612. UNIV CAMERINO,DIPARTIMENTO SCI CHIM,I-62032 CAMERINO,ITALY. UNIV S FLORIDA,DEPT BIOCHEM & MOLEC BIOL,TAMPA,FL 33612. NIDDK,BIOORGAN CHEM LAB,BETHESDA,MD 20892. NR 36 TC 54 Z9 55 U1 0 U2 1 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 1994 VL 349 IS 6 BP 644 EP 650 DI 10.1007/PL00004904 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NR676 UT WOS:A1994NR67600015 PM 7969516 ER PT J AU LI, R CHUANG, DM WYATT, RJ KIRCH, DG AF LI, R CHUANG, DM WYATT, RJ KIRCH, DG TI EFFECT OF CHRONIC HALOPERIDOL TREATMENT ON DOPAMINE-INDUCED INOSITOL PHOSPHATE FORMATION IN RAT-BRAIN SLICES SO NEUROCHEMICAL RESEARCH LA English DT Article DE DOPAMINE RECEPTORS; PHOSPHOINOSITIDE HYDROLYSIS; HALOPERIDOL; 2ND MESSENGERS ID ANTERIOR-PITUITARY CELLS; MEDIATED PHOSPHOINOSITIDE TURNOVER; RECEPTOR STIMULATION; STRIATAL SLICES; INHIBITION; CLONING; PHOSPHATIDYLINOSITOL; CHLORPROMAZINE; NEUROLEPTICS; HYDROLYSIS AB The effects of chronic haloperidol administration on the accumulation of inositol phosphates were examined in rat brain slices pre-labeled with [H-3]myo-inositol and incubated with various dopaminergic drugs. Rats were treated with haloperidol-decanoate or its vehicle (sesame oil) for two, four or six weeks. Dopamine and the selective D-1 agonist, SKF38393, induced a significant increase in lithium-dependent accumulation of [H-3]inositol monophosphate (IP1) in the frontal cortex, hippocampus and striatum of vehicle-treated animals, while the selective D-2 agonist quinpirole did not show any effect on IP1 accumulation. The actions of dopamine and SKF38393 were blocked by the D-1 antagonist, SCH23390, but not by the D-2 antagonist, spiperone, in all three brain regions. Haloperidol treatment did not affect basal phosphoinositide turnover in the three brain regions. Four or six weeks of haloperidol treatment significantly decreased dopamine-induced IP1 accumulation in the striatum (by 30% and 25%, respectively), but not in the frontal cortex and the hippocampus. Four weeks of treatment with haloperidol significantly decreased IP1 levels in the striatal slices when measured in the presence of quinpirole. However, the accumulation of IP1 measured in the presence of SKF38393 was not significantly altered after haloperidol treatment. The loss of dopamine-sensitive IP accumulation was not observed in the presence of spiperone after haloperidol treatment. The number, but not the affinity, of [H-3]sulpiride binding sites in the striatum was significantly increased (by 34-46%) after chronic haloperidol treatment. A time-course study suggests that the inhibition by chronic haloperidol treatment of dopamine-induced phosphoinositide hydrolysis may involve an effect secondary to an increase in the number of dopamine D-2 receptors in the striatum. C1 NIMH,ST ELIZABETHS HOSP,CTR NEUROSCI,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032. NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. NIMH,DIV INTRAMURAL RES PROGRAMS,BETHESDA,MD 20892. NR 29 TC 5 Z9 5 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 1994 VL 19 IS 6 BP 673 EP 678 DI 10.1007/BF00967705 PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA NK710 UT WOS:A1994NK71000005 PM 8065524 ER PT J AU ARGOV, Z BARASH, V SOFFER, D SHERMAN, J RABEN, N AF ARGOV, Z BARASH, V SOFFER, D SHERMAN, J RABEN, N TI LATE-ONSET MUSCULAR WEAKNESS IN PHOSPHOFRUCTOKINASE DEFICIENCY DUE TO EXON-5/INTRON-5 JUNCTION POINT MUTATION - A UNIQUE DISORDER OR THE NATURAL COURSE OF THIS GLYCOLYTIC DISORDER SO NEUROLOGY LA English DT Article ID GRADIENT GEL-ELECTROPHORESIS; TARUI DISEASE; GENE; ATTACHMENT; MYOPATHY; SEQUENCE; DEFECT; VII; DNA AB Late-onset muscle weakness is rare in glycolytic disorders. There are two reports in the literature of phosphofructokinase (PFK)-deficient Ashkenazi Jews with severe vacuolar myopathy manifesting in late adulthood. The genetic abnormality in these patients is unknown. We report a third patient with a similar syndrome: early-onset exercise intolerance in young childhood and progressive weakness in a limb-girdle distribution appearing at 57 years of age, leading to severe incapacity. Muscle histology showed diffuse vacuolar changes, and muscle fibers contained excess glycogen-like material. Muscle biochemistry was diagnostic for PFK deficiency. DNA analysis from the patient and his family showed that he was homozygous for a recently identified point mutation at the exon 5/intron 5 junction (a G-to-A change); two other family members were heterozygous for this mutation. it is not clear whether late-onset weakness is the natural course for all PFK-deficient patients or whether the exon 5 mutation carries increased risk for this severe myopathy. C1 HEBREW UNIV JERUSALEM,HADASSAH MED SCH,DEPT NEUROL,IL-91010 JERUSALEM,ISRAEL. HEBREW UNIV JERUSALEM,HADASSAH MED SCH,DEPT CLIN BIOCHEM,IL-91010 JERUSALEM,ISRAEL. HEBREW UNIV JERUSALEM,HADASSAH MED SCH,DEPT PATHOL,IL-91010 JERUSALEM,ISRAEL. NIAMS,ARTHRITIS & RHEUMATISM BRANCH,BETHESDA,MD. NR 17 TC 15 Z9 15 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN PY 1994 VL 44 IS 6 BP 1097 EP 1100 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA NR468 UT WOS:A1994NR46800022 PM 8208408 ER PT J AU GODEC, MS ASHER, DM KOZACHUK, WE MASTERS, CL RUBI, JU PAYNE, JA RUBIVILLA, DJ WAGNER, EE RAPOPORT, SI SCHAPIRO, MB AF GODEC, MS ASHER, DM KOZACHUK, WE MASTERS, CL RUBI, JU PAYNE, JA RUBIVILLA, DJ WAGNER, EE RAPOPORT, SI SCHAPIRO, MB TI BLOOD BUFFY COAT FROM ALZHEIMERS-DISEASE PATIENTS AND THEIR RELATIVES DOES NOT TRANSMIT SPONGIFORM ENCEPHALOPATHY TO HAMSTERS SO NEUROLOGY LA English DT Article ID CREUTZFELDT-JAKOB DISEASE; TRANSMISSIBILITY; SCRAPIE; AGENT AB There was a report of spongiform encephalopathy transmitted to Syrian hamsters by intracerebral inoculation with the blood buffy coat of patients with Alzheimer's disease (AD) and their unaffected first-degree relatives. We attempted to verify that report, taking measures to reduce the risk of contaminating samples with agents causing spongiform encephalopathies. We obtained blood from 50 subjects, including six patients with familial AD, 21 unaffected first-degree relatives (siblings and offspring) of patients with familial AD, and 20 control subjects. We inoculated the huffy coats intracerebrally into Syrian LVG hamsters, observed them for signs of neurologic disease, examined their brains for neuropathologic changes at time of death, and performed serial (blind) passages by inoculating suspensions of all recovered brains into fresh LVG hamsters. We discerned no clinical illness or histopathologic changes resembling experimental spongiform encephalopathy in any hamster inoculated with human buffy coat nor in blind-passage hamsters, nor were the Life spans of those hamsters shortened. We conclude that AD is not caused by an agent that transmits spongiform encephalopathy to hamsters. C1 NINCDS,CENT NERVOUS SYST STUDIES LAB,BETHESDA,MD 20892. NIA,NEUROSCI LAB,BETHESDA,MD 20892. UNIV MELBOURNE,DEPT PATHOL,PARKVILLE,VIC 3052,AUSTRALIA. NR 18 TC 15 Z9 15 U1 0 U2 3 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN PY 1994 VL 44 IS 6 BP 1111 EP 1115 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA NR468 UT WOS:A1994NR46800024 PM 8208410 ER PT J AU TAKESHIMA, T SHIMODA, K SAUVE, Y COMMISSIONG, JW AF TAKESHIMA, T SHIMODA, K SAUVE, Y COMMISSIONG, JW TI ASTROCYTE-DEPENDENT AND ASTROCYTE-INDEPENDENT PHASES OF THE DEVELOPMENT AND SURVIVAL OF RAT EMBRYONIC DAY 14 MESENCEPHALIC, DOPAMINERGIC-NEURONS IN CULTURE SO NEUROSCIENCE LA English DT Article ID NERVE GROWTH-FACTOR; SEPTAL CHOLINERGIC NEURONS; ORGANOTYPIC SLICE CULTURES; TRANSECTED SPINAL-CORD; VENTRAL TEGMENTAL AREA; NEUROTROPHIC FACTOR; SUBSTANTIA-NIGRA; ADULT-RAT; NONDOPAMINERGIC NEURONS; INVITRO MATURATION AB A primary neuronal culture was prepared from the ventral mesencephalon, centered on the A8, A9 and A10 dopaminergic nuclei of the embryonic day 14 rat, and studied from 12 h to 28 days. At 12 h after plating, and before cell death ensued, 95% of the cells stained positive for neuron specific enolase; 20% for tyrosine hydroxylase; 5% for vimentin and <0.1% for glial fibrillary acidic protein. In the presence of the mitotic inhibitor cytosine arabinoside (2.0 mu M), neuronal growth and survival were surprisingly normal up to the ninth day in culture, but deteriorated rapidly thereafter. In the absence of a mitotic inhibitor, and in the presence of proliferating but non-confluent glia, the tyrosine hydroxylase positive neurons that survived to the 10th day, had retracted neurites and a rounded soma, suggesting an inhibition of cell development. Those tyrosine hydroxylase positive neurons that survived this adverse phase of development tended to produce elaborate neuritic profiles after the 11th day, coincident with confluence of the astrocyte monolayer at the 12th day. By the 21st day in culture, and persisting up to the 28th day, 60% (61 +/- 10, n = 20) of the surviving neurons stained positive for tyrosine hydroxylase. When plated on an established, ventral mesencephalic monolayer of astrocytes, at the seventh day in culture, neuritic growth and branching of the tyrosine hydroxylase positive neurons were greater, compared with similar neurons grown on poly-D-lysine, and the signs of arrested development (retraction of neurites and rounded soma) seen at the 10th day after plating on poly-D-lysine, were not observed. We conclude that in the primary culture studied, and under the experimental conditions used, the survival of dopaminergic neurons was independent of glia during the first nine days, and critically dependent on glia thereafter. The resurgence of growth of dopaminergic neurons after 10 days in vitro, and their subsequent selective survival in culture, suggest that confluent type-1 astrocytes produce factors that act selectively on the dopaminergic neuronal phenotype. The successful identification of these dopaminergic-specific, neurotrophic factors could lead to an increased understanding of the etiology of Parkinson's disease, and suggest new directions for therapeutic intervention. C1 NINCDS,LMCN,NTU,BETHESDA,MD 20892. ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,BIOCHEM GENET LAB,WASHINGTON,DC 20032. MCGILL UNIV,DEPT PHYSIOL,MONTREAL H3G 1Y6,PQ,CANADA. NR 60 TC 63 Z9 63 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD JUN PY 1994 VL 60 IS 3 BP 809 EP 823 DI 10.1016/0306-4522(94)90506-1 PG 15 WC Neurosciences SC Neurosciences & Neurology GA NN295 UT WOS:A1994NN29500019 PM 7936201 ER PT J AU JUCKER, M WALKER, LC SCHWARB, P HENGEMIHLE, J KUO, H SNOW, AD BAMERT, F INGRAM, DK AF JUCKER, M WALKER, LC SCHWARB, P HENGEMIHLE, J KUO, H SNOW, AD BAMERT, F INGRAM, DK TI AGE-RELATED DEPOSITION OF GLIA-ASSOCIATED FIBRILLAR MATERIAL IN BRAINS OF C57BL/6 MICE SO NEUROSCIENCE LA English DT Article ID HEPARAN-SULFATE PROTEOGLYCAN; CENTRAL-NERVOUS-SYSTEM; LAMININ-BINDING PROTEIN; AMYLOID-BETA PROTEIN; ALZHEIMERS-DISEASE; MONOCLONAL-ANTIBODIES; CELL-ADHESION; EXTRACELLULAR-MATRIX; PRECURSOR PROTEIN; NEURITIC PLAQUES AB With advancing age, clusters of unusual granules appear in the brains of C57BL/6 (B6) mice. At the light, confocal laser and electron microscopic levels, the granules represent aggregations of fibrillar material often associated with astrocytes. The fibrillar material is largely free of normal organelles and has been located within astrocytic somata and processes, although in many cases the material is found in the neuropil and is surrounded by a discontinuous membrane. The deposits occur predominantly in hippocampus, but also in piriform cortex, cerebellum and less frequently in some other brain regions. They become evident about six months of age and increase markedly in both number and size thereafter. Incidence of the deposits varies greatly among inbred mouse strains. At six to 12 months of age, granules are abundant in male and female B6, and are absent in BALB/c, CBA, DBA/2 and A mice. In hybrid strains with a B6 background the deposits are also present and thus appear to manifest dominant genetic heritability. Similar granular structures have been described in adult brains of the senescence accelerated mouse and have been noted, albeit very rarely, in aged mice from other strains. While immunostaining of the granules with several polyclonal antisera was found by preabsorption with antigens to be non-specific, immunolabeling with monoclonal antibodies to heparan sulfate proteoglycan core protein and to laminin suggest these or related molecules as components of the fibrillar material. The presence of glycosaminoglycans is supported by staining with periodic acid-Schiff and Gomori's methenamine silver methods. The functional significance of the murine deposits is not yet clear. The deposits do not represent senile plaques with beta-amyloid deposition, but they might mimic the deposition of extracellular matrix molecules that is hypothesized to be a precursor condition for plaque formation and cerebral amyloidosis. Furthermore, the genetic differences in the incidence of the fibrillar deposits has potential to model aspects of familial neurodegenerative diseases. C1 JOHNS HOPKINS UNIV,SCH MED,NEUROPATHOL LAB,BALTIMORE,MD 21205. ZEISS AG,ZURICH,SWITZERLAND. UNIV WASHINGTON,DEPT PATHOL,SEATTLE,WA 98195. ETH ZURICH,DEPT NEUROBIOL,CH-8093 ZURICH,SWITZERLAND. RP JUCKER, M (reprint author), NIA,GERONTOL RES CTR,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 74 TC 60 Z9 60 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD JUN PY 1994 VL 60 IS 4 BP 875 EP 889 DI 10.1016/0306-4522(94)90269-0 PG 15 WC Neurosciences SC Neurosciences & Neurology GA NQ822 UT WOS:A1994NQ82200004 PM 7936209 ER PT J AU NISENBAUM, LK KITAI, ST CROWLEY, WR GERFEN, CR AF NISENBAUM, LK KITAI, ST CROWLEY, WR GERFEN, CR TI TEMPORAL DISSOCIATION BETWEEN CHANGES IN STRIATAL ENKEPHALIN AND SUBSTANCE-P MESSENGER-RNAS FOLLOWING STRIATAL DOPAMINE DEPLETION SO NEUROSCIENCE LA English DT Article ID INSITU HYBRIDIZATION HISTOCHEMISTRY; ATYPICAL NEUROLEPTIC TREATMENT; TIME COURSE; RAT-BRAIN; EXTRACELLULAR DOPAMINE; NUCLEUS-ACCUMBENS; GLOBUS PALLIDUS; GENE-EXPRESSION; EFFERENT AXONS; 6-OHDA LESION AB Changes in the levels of enkephalin and substance P messenger RNA expression were examined in the striatum following dopamine depletion resulting from unilateral injection of 6-hydroxydopamine into the substantia nigra. In response to striatal dopamine depletion, the levels of enkephalin messenger RNA were elevated, whereas substance P messenger RNA was decreased within all regions of the striatum. Examination of the striatal peptide messenger RNAs between one and 21 days after the injection of 6-hydroxydopamine revealed a temporal dissociation between changes in enkephalin and substance P messenger RNAs. Within one day of the 6-hydroxydopamine injection, substance P messenger RNA was significantly decreased by 30% at all levels of the striatum. This decrease was maintained for up to 21 days after the lesion. In contrast, striatal enkephalin messenger RNA was not significantly elevated until three days following the injection of 6-hydroxydopamine, after which there was a gradual increase up to 21 days. In order to correlate alterations in peptide messenger RNA expression with 6-hydroxydopamine-induced changes in striatal dopamine innervation, tissue punches from the striatum were examined for dopamine content at one, two, three and seven days after the lesion. One day after the lesion, striatal dopamine levels were significantly increased by 47%. In contrast, within two days tissue dopamine content was reduced by 77% compared to control levels. A further decrease of 90% or more was observed at three and seven days after the lesion. Taken together, these data demonstrate a temporal dissociation between changes in enkephalin and substance P messenger RNA levels following 6-hydroxydopamine-induced striatal dopamine depletions. This temporal dissociation may reflect a differential response of enkephalin and substance P messenger RNAs to alterations in dopamine release and subsequent receptor activation. C1 UNIV TENNESSEE, COLL MED, DEPT PHARMACOL, MEMPHIS, TN 38163 USA. NIMH, NEUROANAT SECT, BETHESDA, MD 20892 USA. RP UNIV TENNESSEE, COLL MED, DEPT ANAT & NEUROBIOL, MEMPHIS, TN 38163 USA. FU NICHD NIH HHS [HD 13703]; NINDS NIH HHS [NS2702] NR 50 TC 33 Z9 33 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 EI 1873-7544 J9 NEUROSCIENCE JI Neuroscience PD JUN PY 1994 VL 60 IS 4 BP 927 EP 937 DI 10.1016/0306-4522(94)90272-0 PG 11 WC Neurosciences SC Neurosciences & Neurology GA NQ822 UT WOS:A1994NQ82200007 PM 7523989 ER PT J AU RIFKIND, BM AF RIFKIND, BM TI LOW-CHOLESTEROL LEVELS AND THE TOTAL MORTALITY ISSUE SO NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES LA English DT Editorial Material RP RIFKIND, BM (reprint author), NHLBI,LIPID METAB ATHEROGENESIS BRANCH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MEDIKAL PRESS S R L PI MILAN PA VIA LUIGI ZOJA, 30, 20153 MILAN, ITALY SN 0939-4753 J9 NUTR METAB CARDIOVAS JI Nutr. Metab. Carbiovasc. Dis. PD JUN PY 1994 VL 4 IS 2 BP 61 EP 63 PG 3 WC Cardiac & Cardiovascular Systems; Endocrinology & Metabolism; Nutrition & Dietetics SC Cardiovascular System & Cardiology; Endocrinology & Metabolism; Nutrition & Dietetics GA NX462 UT WOS:A1994NX46200002 ER PT J AU HALLFRISCH, J DRINKWATER, DT MULLER, DC FLEG, J BUSBYWHITEHEAD, MJ ANDRES, R GOLDBERG, A AF HALLFRISCH, J DRINKWATER, DT MULLER, DC FLEG, J BUSBYWHITEHEAD, MJ ANDRES, R GOLDBERG, A TI PHYSICAL CONDITIONING STATUS AND DIET INTAKE IN ACTIVE AND SEDENTARY OLDER MEN SO NUTRITION RESEARCH LA English DT Article DE EXERCISE; FITNESS; AEROBIC CAPACITY; WAIST/HIP RATIO; BODY FAT ID BODY-COMPOSITION; AEROBIC CAPACITY; AGE; VO2MAX; DECLINE; INSULIN; PEOPLE; WEIGHT; ADULTS; YOUNG AB Changes in body composition accompanied by a reduction of food intake have been reported to occur with aging, but these changes may not be an inevitable consequence of aging, if one continues a vigorous exercise program in later life. The diets and body composition of 16 endurance-trained older athletes were compared to those of 24 healthy age and BMI-matched sedentary men. Aerobic capacity was greater in athletes (p < 0.001). Percent body fat and waist/hip ratio were lower in athletes than in controls (p < 0.05). Protein and Kcal intake per kg body weight were greater in athletes (p < 0.05). The composition of the diets was different also, with athletes consuming a greater percentage of their calories as carbohydrate and less as alcohol and fat (p < 0.05). Percent body fat was inversely related to kcal/kg intake in athletes (r = -0.58, p < 0.02), but not controls (r = -0.35, p = 0.18) and to VO2 max in controls (r = -0.45, p < 0.05) but not athletes (r = -0.17, p = 0.53). These results show that older endurance-trained male athletes can maintain high levels of aerobic fitness and desirable weight and body composition despite calorie intakes comparable to levels of much younger men. C1 UNIV SASKATCHEWAN,COLL PHYS EDUC,SASKATOON S7N 0W0,SK,CANADA. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV GERIATR MED,BALTIMORE,MD 21205. UNIV MARYLAND,SCH MED,DIV GERIATR,BALTIMORE,MD 21201. RP HALLFRISCH, J (reprint author), USDA,HUMAN NUTR RES CTR,BELTSVILLE,MD 20705, USA. RI Biguzzi, Felipe/E-4724-2015 NR 32 TC 3 Z9 3 U1 2 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0271-5317 J9 NUTR RES JI Nutr. Res. PD JUN PY 1994 VL 14 IS 6 BP 817 EP 827 DI 10.1016/S0271-5317(05)80483-X PG 11 WC Nutrition & Dietetics SC Nutrition & Dietetics GA NN009 UT WOS:A1994NN00900003 ER PT J AU MAROULAKOU, IG PAPAS, TS GREEN, JE AF MAROULAKOU, IG PAPAS, TS GREEN, JE TI DIFFERENTIAL EXPRESSION OF ETS-1 AND ETS-2 PROTOONCOGENES DURING MURINE EMBRYOGENESIS SO ONCOGENE LA English DT Article ID LONG TERMINAL REPEAT; DNA-BINDING MOTIF; C-FOS; TRANSCRIPTIONAL ACTIVATION; C-ETS-1 PROTOONCOGENE; PROMOTER SEQUENCES; TRANSFORMING GENE; CELLS; DOMAIN; PROTEINS AB ets-l and ets-2 genes have previously been identified by their sequence homology to the v-ets oncogene of the avian erythroblastosis virus, E26. These cellular genes have been shown to function as transcription factors important in lymphoid differentiation and activation and cellular proliferation. In this study, we have broadly analysed the differential expression of ets-l and ets-2 during murine development using in situ hybridization. Our results indicate that these transcription factors are expressed in multiple tissues during critical stages of embryo formation and organogenesis, suggesting that these genes may serve multiple functions during mouse development. The patterns of expression of both genes are quite different as early as day 8.0 of gestation. ets-l expression is clearly observed during a narrow developmental stage in the developing nervous system, including the presumptive hindbrain regions, the neural tube, as well as neural crest and the first and second branchial arches. ets-2 expression is limited to the developing limb buds and distal tail. At later times, ets-l expression is observed in developing vascular structures, including the heart, arteries, capillaries and meninges, whereas ets-2 is highly expressed in developing bone, tooth buds, epithelial layers of the gut, nasal sinus and uterus, and several regions of the developing brain. Both ets-l and ets-2 are expressed in developing lung, gut and skin. High levels of expression in both genes is observed in adult lymphoid tissues, but in different tissue subsets. ets-l is expressed in the adult lung, gut mesenchyme and bone marrow. ets-2 continues to be expressed at low levels in several adult tissues, except in the differentiated brain, where substantial levels of expression are found in particular regions of the mature brain. These results demonstrate that ets-l and ets-2 are differentially regulated, are widely expressed in many tissues during murine embryogenesis and may play important roles in cellular proliferation and differentiation during mouse development. C1 NCI,MOLEC ONCOL LAB,FREDERICK,MD 21702. NR 48 TC 176 Z9 179 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN PY 1994 VL 9 IS 6 BP 1551 EP 1565 PG 15 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA NL815 UT WOS:A1994NL81500005 PM 8183549 ER PT J AU WONG, WT KRAUS, MH CARLOMAGNO, F ZELANO, A DRUCK, T CROCE, CM HUEBNER, K DIFIORE, PP AF WONG, WT KRAUS, MH CARLOMAGNO, F ZELANO, A DRUCK, T CROCE, CM HUEBNER, K DIFIORE, PP TI THE HUMAN EPS15 GENE, ENCODING A TYROSINE KINASE SUBSTRATE, IS CONSERVED IN EVOLUTION AND MAPS TO 1P31-P-32 SO ONCOGENE LA English DT Article ID GUANINE-NUCLEOTIDE EXCHANGE; FACTOR RECEPTOR KINASE; GROWTH-FACTOR; SIGNAL-TRANSDUCTION; ADAPTER PROTEIN; SH3 DOMAINS; RAS; GRB2; CLONING; SOS AB Employing an expression cloning approach for tyrosine kinase substrates, we have previously isolated the coding sequence for a novel putative EGFR substrate, eps15, from NIH3T3 fibroblasts. Eps15 displayed a receptor-specific pattern of tyrosine phosphorylation in vivo and was able to transform NIH3T3 cells upon overexpression. To gain understanding of eps15 function as well as its role in normal and neoplastic proliferation, we cloned the human eps15 coding sequence and studied expression of the human RNA and protein, evolutionary conservation, and chromosomal location. The close structural similarity of human eps15 with the murine homologue is indicated by 89% and 90% identity of nucleotide and predicted amino acid sequences, respectively. Using the human eps15 coding sequence as probe, we demonstrate that eps15 is member of a gene family that is highly conserved during evolution. An essential function of eps15 in cell growth regulation is underscored by our observation of ubiquitous expression at the transcript and the protein level in normal and malignant human cells. The human EPS15 locus maps to chromosome 1p31-p32, a region involved in deletion in neuroblastoma, translocations in acute lymphoblastic leukemia, and exhibiting a fragile site. C1 NCI, CELLULAR & MOLEC BIOL LAB, BETHESDA, MD 20892 USA. THOMAS JEFFERSON UNIV, JEFFERSON MED COLL, JEFFERSON INST MOLEC MED, PHILADELPHIA, PA 19107 USA. RI Di Fiore, Pier Paolo/K-2130-2012 OI Di Fiore, Pier Paolo/0000-0002-2252-0950 FU NCI NIH HHS [CA51083] NR 49 TC 43 Z9 44 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 EI 1476-5594 J9 ONCOGENE JI Oncogene PD JUN PY 1994 VL 9 IS 6 BP 1591 EP 1597 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA NL815 UT WOS:A1994NL81500009 PM 8183552 ER PT J AU SEKIDO, Y BADER, S LATIF, F GNARRA, JR GAZDAR, AF LINEHAN, WM ZBAR, B LERMAN, MI MINNA, LD AF SEKIDO, Y BADER, S LATIF, F GNARRA, JR GAZDAR, AF LINEHAN, WM ZBAR, B LERMAN, MI MINNA, LD TI MOLECULAR ANALYSIS OF THE VON HIPPEL-LINDAU DISEASE TUMOR-SUPPRESSOR GENE IN HUMAN LUNG-CANCER CELL-LINES SO ONCOGENE LA English DT Article ID CLONAL CHROMOSOME-ABNORMALITIES; HUMAN BREAST CARCINOMAS; FREE DEFINED MEDIUM; SHORT ARM; HOMOZYGOUS DELETION; CLINICAL SPECIMENS; SMALL REGION; P53 GENE; HETEROZYGOSITY; 3P AB The deletion of the short arm of chromosome 3 is frequently observed in lung cancer. To determine whether the von Hippel-Lindau (VHL) disease tumor suppressor gene located at 3p25 is responsible for oncogenesis in lung cancer, we searched the known open reading frame using the single-strand conformation polymorphism (SSCP) technique for mutations in the VHL gene in 72 cancer cell lines including small cell (SCLC) and nonsmall cell (NSCLC) lung cancers, carcinoids, and mesotheliomas. SSCP analysis showed that four cell lines have altered SSCP patterns within the coding region and one in an intron of the VHL gene. SCLC line NCI-H1672 had a somatic mutation, G to A at nucleotide (nt) 530, leading to amino acid substitution (glycine to aspartic acid) compared to normal DNA from the same patient. Mesothelioma line NCI-H28 had T to A mutation at nt 479 leading to leucine to histidine amino acid change. We found one frequent polymorphism A (0.72) or G (0.28) at nt 19 resulting in either serine or glycine at this position, changes also found in normal peripheral blood cell DNA, often in a heterozygous state. In addition, we found single rare polymorphisms which did not alter the coding region including: C to G at mt 396, G to T at nt 843, and C to T change in an intron. These results suggest that the VHL gene is only rarely mutated in thoracic malignancies. C1 UNIV TEXAS,SOUTHWESTERN MED CTR,SIMMONS CANC CTR,DALLAS,TX 75235. NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,FREDERICK,MD 21702. NCI,SURG BRANCH,UROL ONCOL SECT,BETHESDA,MD 20892. RI Sekido, Yoshitaka/P-9756-2015 FU NCI NIH HHS [NCI CA58220-01] NR 47 TC 84 Z9 87 U1 0 U2 8 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN PY 1994 VL 9 IS 6 BP 1599 EP 1604 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA NL815 UT WOS:A1994NL81500010 PM 8183553 ER PT J AU BOURS, V AZARENKO, V DEJARDIN, E SIEBENLIST, U AF BOURS, V AZARENKO, V DEJARDIN, E SIEBENLIST, U TI HUMAN RELB (I-REL) FUNCTIONS AS A KAPPA-B SITE-DEPENDENT TRANSACTIVATING MEMBER OF THE FAMILY OF REL-RELATED PROTEINS SO ONCOGENE LA English DT Article ID DNA-BINDING SUBUNIT; V-REL; TRANSCRIPTION ACTIVATOR; ONCOPROTEIN BCL-3; PROTO-ONCOGENE; CLONING; P50; GENE; EXPRESSION; HOMOLOGY AB RelB belongs to the family of Rel-related proteins, dimers of which determine NF-kappa B activity. The murine RelB protein has been reported to be a dimerizing partner in kappa B-binding complexes which are capable of transactivation. On the other hand, the I-Rel protein, the presumed human homolog of RelB, was proposed to be an inhibitor whose presence in dimeric complexes interfered with their kappa B binding and therefore interfered also with transactivation. We demonstrate that human RelB (I-Rel) forms with p50 and p52 (p50B) kappa B-binding heterodimeric complexes which potently transactivate kappa B-dependent constructs in transfection studies. It is concluded that human RelB (I-Rel) and murine RelB can both function as transactivators and that no significant species-specific differences exist. C1 UNIV LIEGE,METASTASIS RES LAB,B-4000 LIEGE,BELGIUM. RP BOURS, V (reprint author), NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892, USA. NR 30 TC 23 Z9 23 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 1994 VL 9 IS 6 BP 1699 EP 1702 PG 4 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA NL815 UT WOS:A1994NL81500022 PM 8183565 ER PT J AU CARBONE, M PASS, HI RIZZO, P MARINETTI, MR DIMUZIO, M MEW, DJY LEVINE, AS PROCOPIO, A AF CARBONE, M PASS, HI RIZZO, P MARINETTI, MR DIMUZIO, M MEW, DJY LEVINE, AS PROCOPIO, A TI SIMIAN-VIRUS 40-LIKE DNA-SEQUENCES IN HUMAN PLEURAL MESOTHELIOMA SO ONCOGENE LA English DT Article ID T-DELETION MUTANTS; GROWTH FACTOR-I; MALIGNANT MESOTHELIOMA; PROTEIN PHOSPHATASE-2A; ASBESTOS EXPOSURE; MINERAL FIBERS; TUMOR-ANTIGEN; SV40; CELLS; MECHANISMS AB Mesotheliomas are pleural, pericardial, or peritoneal neoplasms frequently associated with asbestos exposure, and it is estimated that over the next twenty years up to 80,000 new cases are expected in the USA alone. We found simian virus 40-like DNA sequences in 29 of 48 mesotheliomas studied (60%) and demonstrated simian virus large-T antigen expression in 13 of 16 specimens. The matching lung samples did not contain simian virus 40-like sequences; however, they contained asbestos. These findings are to our knowledge the first demonstration of a physical link between DNA viruslike sequences and human mesothelioma. We suggest that a simian virus 40-like virus may act independently or as a co-carcinogen with asbestos. Moreover, the selective large T antigen expression by mesothelioma and not by the surrounding pulmonary parenchyma may have both diagnostic and therapeutic implications. C1 NCI,SURG BRANCH,THORAC ONCOL SECT,BETHESDA,MD 20892. UNIV G DANNUNZIO,FAC MED,IST PATOL UMANA & MED SOCIALE,FISIOPATOL MOLEC LAB,I-66013 CHIETI,ITALY. RP CARBONE, M (reprint author), NICHHD,DNA REPLICAT REPAIR & MUTAGENESIS SECT,BLDG 6,ROOM 1A11,BETHESDA,MD 20892, USA. NR 68 TC 361 Z9 363 U1 1 U2 7 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN PY 1994 VL 9 IS 6 BP 1781 EP 1790 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA NL815 UT WOS:A1994NL81500034 PM 8183577 ER PT J AU REID, KI DIONNE, RA SICARDROSENBAUM, L LORD, D DUBNER, RA AF REID, KI DIONNE, RA SICARDROSENBAUM, L LORD, D DUBNER, RA TI EVALUATION OF IONTOPHORETICALLY APPLIED DEXAMETHASONE FOR PAINFUL PATHOLOGICAL TEMPOROMANDIBULAR JOINTS SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Article ID STIMULATION; DISORDERS; DIAGNOSIS; TRISMUS; PLACEBO AB The effects of iontophoretically applied dexamethasone in a lidocaine vehicle were compared with those of saline placebo in 53 patients with one of three diagnoses of painful temporomandibular joint pathologic conditions: disk displacement with reduction, disk displacement without reduction, and osteoarthritis. Both dexamethasone and the saline placebo produced a significant reduction in pain scores from baseline levels after the first two of three treatments. There were no observed differences, however, in pain report or mandibular range of motion between the dexamethasone and placebo groups. A trend for pain relief was noted in the subgroup that received dexamethasone with a diagnosis of osteoarthritis. Results may reflect varying degrees of inflammation or central nervous system hyperexcitability, or both, in this heterogeneous study sample. Potential confounding variables were lack of knowledge of actual drug penetration, the effects of electric current transmitted by the iontophoresor, and pain reduction caused by cyclic fluctuations in symptoms. These data suggest that iontophoretically applied dexamethasone is no more effective than saline placebo in providing pain relief in patients with temporomandibular joint pain. C1 NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD 20892. NIH,DEPT REHABIL MED,BETHESDA,MD 20892. NR 36 TC 17 Z9 17 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD JUN PY 1994 VL 77 IS 6 BP 605 EP 609 DI 10.1016/0030-4220(94)90319-0 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA NR700 UT WOS:A1994NR70000013 PM 8065724 ER PT J AU STRECKFUS, CF WU, AJ SHIP, JA BROWN, LJ AF STRECKFUS, CF WU, AJ SHIP, JA BROWN, LJ TI COMPARISON OF STIMULATED PAROTID SALIVARY-GLAND FLOW-RATES IN NORMOTENSIVE AND HYPERTENSIVE PERSONS SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Article ID MOUTH AB Although hypertension is a prevalent condition among the elderly, little is known with respect to the influence of hypertension on oral health and function. Therefore a study was conducted that compared stimulated parotid salivary flow rates in elderly persons (65 years and older) from two diverse populations who are normotensive, mild, and severe hypertensive. The normotensive group consisted of 45 healthy subjects with systolic blood pressures of less than 140 mm Hg and diastolic pressures less than 90 mm Hg. The mildly hypertensive group consisted of 14 otherwise healthy subjects with either systolic pressures greater than 140 mm Hg or diastolic pressures greater than 90 mm Hg. The severely hypertensive group consisted of 10 otherwise healthy subjects with either systolic pressures greater than 180 mm Hg and/or diastolic pressures greater than 100 mm Hg. All three groups were not taking any prescription or nonprescription medications. Samples of 2% citrate-stimulated parotid saliva were collected from each subject. The results showed no significant differences in stimulated parotid flow between normotensive, mildly hypertensive, and severely hypertensive subjects. These results suggest that hypertension per se has no influence on stimulated parotid salivary gland flow rates in otherwise healthy, elderly unmedicated white and African-American persons. C1 UNIV MICHIGAN,SCH DENT,ANN ARBOR,MI 48109. RP STRECKFUS, CF (reprint author), NIDR,EPIDEMIOL ORAL DIS PREVENT PROGRAM,WESTWOOD BLDG,ROOM 718C,BETHESDA,MD 20892, USA. NR 25 TC 12 Z9 13 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD JUN PY 1994 VL 77 IS 6 BP 615 EP 619 DI 10.1016/0030-4220(94)90321-2 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA NR700 UT WOS:A1994NR70000015 PM 8065725 ER PT J AU SNOW, JB AF SNOW, JB TI FROM THE NATIONAL-INSTITUTE-ON-DEAFNESS-AND-OTHER-COMMUNICATION-DISORDERS SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Editorial Material RP SNOW, JB (reprint author), NIDCD,BLDG 31,ROOM 3C02,BETHESDA,MD 20892, USA. NR 0 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 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD JUN PY 1994 VL 110 IS 6 BP 607 EP 609 PG 3 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA NT251 UT WOS:A1994NT25100026 PM 8208584 ER PT J AU TAL, M BENNETT, GJ AF TAL, M BENNETT, GJ TI EXTRA-TERRITORIAL PAIN IN RATS WITH A PERIPHERAL MONONEUROPATHY - MECHANO-HYPERALGESIA AND MECHANO-ALLODYNIA IN THE TERRITORY OF AN UNINJURED NERVE SO PAIN LA English DT Article DE ALLODYNIA; CAUSALGIA; HYPERALGESIA; PAINFUL PERIPHERAL NEUROPATHY; REFLEX SYMPATHETIC DYSTROPHY; SOMATOFORM PAIN DISORDER ID SCIATIC-NERVE; NEONATAL RATS; DORSAL HORN; ADULT-RAT; NEUROPATHY; MODEL; DISORDERS; EXPANSION; INJURY; FIBERS AB The abnormal pain sensations that accompany peripheral neuropathies are sometimes found in a distribution that does not coincide with the territories of nerves or posterior roots. This 'extra-territorial' pain is one of the lines of evidence that has been advanced to support the proposal that these patients suffer from a psychogenic disorder. In the present experiments, rats were prepared with a unilateral chronic constriction injury (CCI) to the sciatic nerve. Beginning on the first postoperative day and continuing for at least 18 days, exaggerated withdrawal reflexes to pinprick stimulation, indicative of mechano-hyperalgesia, were seen on the side of nerve injury in the hindpaw territories of both the injured sciatic nerve and the uninjured saphenous nerve. Beginning on postoperative day 4 and continuing for at least the next 3 weeks, the withdrawal responses to von Prey hair stimulation on the nerve-injured side occurred at a significantly Lower threshold, indicating the presence of mechano-allodynia. The severity and time course of the mechano-allodynia were similar in both nerve territories. When tested 18 days after the CCI, mechano-allodynia in the saphenous territory was abolished by an acute saphenous transection, but unaffected by sciatic transection. Conversely, mechano-allodynia evoked from the mid-plantar sciatic territory was abolished by acute sciatic transection, but unaffected by saphenous transection. These results show that rats with an experimental painful peripheral mononeuropathy have extra-territorial pain like that seen in man. Extra-territorial pain may be partly or entirely due to a peripheral nerve injury-evoked dysfunction of pain processing neurons in the central nervous system. C1 NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD 20892. HEBREW UNIV JERUSALEM,HADASSAH SCH DENT MED,HADASSAH DENT & MED SCH,DEPT ANAT,JERUSALEM,ISRAEL. NR 31 TC 289 Z9 305 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD JUN PY 1994 VL 57 IS 3 BP 375 EP 382 DI 10.1016/0304-3959(94)90013-2 PG 8 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA NV533 UT WOS:A1994NV53300013 PM 7936715 ER PT J AU NUTMAN, TB ZIMMERMAN, PA KUBOFCIK, J KOSTYU, DD AF NUTMAN, TB ZIMMERMAN, PA KUBOFCIK, J KOSTYU, DD TI A UNIVERSALLY APPLICABLE DIAGNOSTIC-APPROACH TO FILARIAL AND OTHER INFECTIONS SO PARASITOLOGY TODAY LA English DT Article ID ONCHOCERCA-VOLVULUS; DNA-SEQUENCE; CLONING AB Antibody-based assays for the diagnosis of filarial and other infections cannot reliably distinguish between past and current infection, nor con they be used to assess the efficacy of chemotherapy. In this article, Thomas Nutman, Peter Zimmerman, Joseph Kubofcik and Donna Kostyu discuss how the detection of parasite-specific PCR products using on ELISA-based assay may overcome these problems. C1 DUKE UNIV,MED CTR,DEPT IMMUNOL,DURHAM,NC 27710. RP NUTMAN, TB (reprint author), NIAID,PARASIT DIS LAB,BETHESDA,MD 20892, USA. NR 15 TC 51 Z9 52 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0169-4758 J9 PARASITOL TODAY JI Parasitol. Today PD JUN PY 1994 VL 10 IS 6 BP 239 EP 243 DI 10.1016/0169-4758(94)90127-9 PG 5 WC Parasitology SC Parasitology GA NM215 UT WOS:A1994NM21500015 PM 15275461 ER PT J AU NATARAJAN, V PLISHKA, RJ SCOTT, EW LANE, HC SALZMAN, NP AF NATARAJAN, V PLISHKA, RJ SCOTT, EW LANE, HC SALZMAN, NP TI AN INTERNALLY CONTROLLED VIRION PCR FOR THE MEASUREMENT OF HIV-1 RNA IN PLASMA SO PCR-METHODS AND APPLICATIONS LA English DT Article ID POLYMERASE CHAIN-REACTION; IMMUNODEFICIENCY-VIRUS TYPE-1; MESSENGER-RNA; REVERSE-TRANSCRIPTION; COMPETITIVE PCR; QUANTITATION; DNA; INFECTION; CELLS; GENE AB We have developed an assay to measure the HIV-1 RNA in patients' plasma or sera using an infectious mutant virus as an internal control. The mutant virus VX-46 has a 25-bp insert in a conserved region between the primer-binding and major splice donor sites. To utilize this virus as an internal control, different dilutions of this virus were added to aliquots of plasma sample to be measured, RNA was isolated and reverse-transcribed to cDNA. PCR was performed with primers selected to include the sequences on either side of the insert contained in the externally added virus. The DNA product from the control virus is 25 bp longer than that from the virus present in plasma. The amount of viral RNA present in a plasma sample is calculated after the PCR-amplified products are separated by gel electrophoresis. Unlike other quantitative PCR assays, this Internally controlled virion PCR (ICVPCR) assay eliminates errors introduced by variable recovery during the RNA purification step, therefore, enhancing the accuracy of the assay. C1 NIAID,BETHESDA,MD 20892. RP NATARAJAN, V (reprint author), GEORGETOWN UNIV,DEPT MICROBIOL,MOLEC RETROVIROL LAB,WASHINGTON,DC 20007, USA. FU NIAID NIH HHS [NIAID NO1-A1-05058] NR 30 TC 15 Z9 15 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 1054-9803 J9 PCR METH APPL JI PCR-Methods Appl. PD JUN PY 1994 VL 3 IS 6 BP 346 EP 350 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA NV103 UT WOS:A1994NV10300005 PM 7920239 ER PT J AU SALLIE, R AF SALLIE, R TI SELECTIVE DETECTION OF HEPATITIS-B VIRUS-RNA BY PCR SO PCR-METHODS AND APPLICATIONS LA English DT Note ID POLYMERASE CHAIN-REACTION; VIRUS; PRIMER; AMPLIFICATION RP SALLIE, R (reprint author), NIDDKD,LIVER DIS SECT,BETHESDA,MD 20892, USA. NR 8 TC 8 Z9 8 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 1054-9803 J9 PCR METH APPL JI PCR-Methods Appl. PD JUN PY 1994 VL 3 IS 6 BP 376 EP 377 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA NV103 UT WOS:A1994NV10300012 PM 7920246 ER PT J AU MUELLER, BU JACOBSEN, F JAROSINSKI, P LEWIS, LL PIZZO, PA AF MUELLER, BU JACOBSEN, F JAROSINSKI, P LEWIS, LL PIZZO, PA TI ERYTHROPOIETIN FOR ZIDOVUDINE-ASSOCIATED ANEMIA IN CHILDREN WITH HIV-INFECTION SO PEDIATRIC AIDS AND HIV INFECTION-FETUS TO ADOLESCENT LA English DT Article AB In a pilot study we evaluated the effect of subcutaneously or intravenously administered erythropoietin in pediatric patients who developed anemia (hemoglobin < 8 g/dl) or transfusion dependency while on zidovudine, in spite of dosage reductions to 120 mg/m2 q 6h, in order to determine whether tolerance of zidovudine could be improved. Between April 1990 and February 1993 12 patients between 8 months and 17.4 years old, all Center for Disease Control and Prevention (CDC) class P2, were enrolled, 8 of whom were available. Endogenous erythropoietin. levels were under 200 IU/L in all but one patient. We used a sliding dosing schedule of erythropoietin in order to maintain the hemoglobin between 11-13 g/dl. Patients were on study for a mean of 31.5 weeks (range 14-85 weeks); six patients died of progressive HIV disease, and two were switched to other antiretroviral regimens. Erythropoietin was very well tolerated in all children. With doses of erythropoietin ranging between 150-400 U/kg subcutaneously or intravenously every Monday, Wednesday, and Friday, all patients were able to tolerate and be maintained on doses of zidovudine between 120-180 mg/m2 every 6 hours (480-720 mg/m2 per day). Transfusion requirement for packed red blood cells diminished markedly in four patients, and moderately in the other four. Erythropoietin appears to be beneficial in a selected group of HIV-positive children with zidovudine-related bone marrow suppression and enables them to continue receiving therapeutic doses of zidovudine. RP MUELLER, BU (reprint author), NCI,PEDIAT BRANCH,BETHESDA,MD 20892, USA. NR 0 TC 9 Z9 9 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1045-5418 J9 PEDIATR AIDS HIV INF JI Pediatr. AIDS HIV Infect.-Fetus Adolesc. PD JUN PY 1994 VL 5 IS 3 BP 169 EP 173 PG 5 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA NW626 UT WOS:A1994NW62600003 ER PT J AU MOFENSON, LM MOYE, J KORELITZ, J BETHEL, J HIRSCHHORN, R NUGENT, R AF MOFENSON, LM MOYE, J KORELITZ, J BETHEL, J HIRSCHHORN, R NUGENT, R TI CROSSOVER OF PLACEBO PATIENTS TO INTRAVENOUS IMMUNOGLOBULIN CONFIRMS EFFICACY FOR PROPHYLAXIS OF BACTERIAL-INFECTIONS AND REDUCTION OF HOSPITALIZATIONS IN HUMAN IMMUNODEFICIENCY VIRUS-INFECTED CHILDREN SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE INTRAVENOUS IMMUNOGLOBULIN; INFECTION PROPHYLAXIS; PEDIATRIC HUMAN IMMUNODEFICIENCY VIRUS INFECTION AB After completion of a placebo-controlled trial of intravenous immunoglobulin (IVIG) infection prophylaxis, patients were offered open label IVIG and optional participation in a follow-up study. The purpose of the follow-up study was to evaluate the IVIG effect in original placebo recipients and longevity of IVIG benefit in original IVIG recipients. Of 212 human immunodeficiency virus-infected children on study at trial closure, 148 (67 of 98 (68%) placebo and 81 of 114 (71%) IVIG patients) received open label IVIG for a mean of 16 months. When open label IVIG was begun, 45% were receiving trimethoprim-sulfamethoxazole prophylaxis for Pneumocystis carinii pneumonia (43% of placebo and 47% of IVIG patients) and 54% were receiving zidovudine (55% of placebo and 53% of IVIG patients). In patients who received placebo during the original study, the rate of serious bacterial infections was significantly lower after change to open label IVIG (estimated 15.8 fewer episodes/100 patient years; 95% confidence interval, 3.2 to 28.5; P = 0.014). Similar findings were observed for minor bacterial infections (estimated 61.2 fewer/100 patient years; 95% confidence interval, 29.2 to 93.3; P < 0.001) and hospitalizations (estimated 43.7 fewer/100 patient years; 95% confidence interval, 27.7 to 59.6; P < 0.001). Decreases were observed whether or not trimethoprim-sulfamethoxazole prophylaxis was being given at the time open label IVIG was begun. In patients who received IVIG during the original study, no significant difference was seen in infections or hospitalizations after change to open label IVIG. These results confirm IVIG effectiveness for reduction of bacterial infections and hospitalizations in human immunodeficiency virus-infected children and indicate that benefit is maintained for at least 3 years. In this patient cohort decrease in infections and hospitalizations with IVIG was independent of trimethoprim-sulfamethoxazole P. carinii pneumonia prophylaxis. C1 WESTAT CORP,ROCKVILLE,MD 20850. RP MOFENSON, LM (reprint author), NICHHD,CTR RES MOTHERS & CHILDREN,PEDIAT ADOLESCENT & MATERNAL AIDS BRANCH,6100 EXECUT BLVD,ROCKVILLE,MD 20852, USA. OI Mofenson, Lynne/0000-0002-2818-9808; moye, john/0000-0001-9976-8586 NR 11 TC 34 Z9 34 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD JUN PY 1994 VL 13 IS 6 BP 477 EP 484 PG 8 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA NR183 UT WOS:A1994NR18300002 PM 8078734 ER PT J AU ALWAY, D SHOTLAND, LI NICHELLI, P APPOLLONIO, I GRAFMAN, J AF ALWAY, D SHOTLAND, LI NICHELLI, P APPOLLONIO, I GRAFMAN, J TI NO SPECIFIC EFFECTS OF CALORIC STIMULATION ON THE VISUAL-IMAGERY PROCESSES OF NORMAL SUBJECTS SO PERCEPTUAL AND MOTOR SKILLS LA English DT Article ID VESTIBULAR STIMULATION; REMISSION; NEGLECT; HEMINEGLECT AB Recent research indicates that neglect can be temporarily, but only partially, ameliorated by activating the contralateral hemisphere via caloric stimulation and other techniques. In this study, we evaluated whether caloric stimulation could be used to manipulate visual-imagery processes in normal subjects. 11 normal subjects participated in a quantitative visual-imagery task while undergoing caloric stimulation. Neither side of report nor ear of caloric stimulation affected performance. Possible reasons for this negative result are reviewed. C1 NINCDS,MED NEUROL BRANCH,COGNIT NEUROSCI SECT,BLDG 10,ROOM 55209,BETHESDA,MD 20892. UNIV MILAN,PATHOL 2 CLIN,I-20122 MILAN,ITALY. RI Nichelli, Paolo/F-7336-2015; OI Nichelli, Paolo/0000-0001-9756-6796; Grafman, Jordan H./0000-0001-8645-4457 NR 11 TC 3 Z9 3 U1 0 U2 1 PU PERCEPTUAL MOTOR SKILLS PI MISSOULA PA PO BOX 9229, MISSOULA, MT 59807 SN 0031-5125 J9 PERCEPT MOTOR SKILL JI Percept. Mot. Skills PD JUN PY 1994 VL 78 IS 3 BP 1147 EP 1152 PN 2 PG 6 WC Psychology, Experimental SC Psychology GA NX698 UT WOS:A1994NX69800018 PM 7936937 ER PT J AU FREDHOLM, BB ABBRACCHIO, MP BURNSTOCK, G DALY, JW HARDEN, TK JACOBSON, KA LEFF, P WILLIAMS, M AF FREDHOLM, BB ABBRACCHIO, MP BURNSTOCK, G DALY, JW HARDEN, TK JACOBSON, KA LEFF, P WILLIAMS, M TI NOMENCLATURE AND CLASSIFICATION OF PURINOCEPTORS SO PHARMACOLOGICAL REVIEWS LA English DT Review ID A1 ADENOSINE RECEPTOR; BRAIN SYNAPTIC TERMINALS; FIBROBLAST GROWTH-FACTOR; ANTAGONIST BINDING-SITE; PIG URINARY-BLADDER; ISOLATED EAR ARTERY; GUINEA-PIG; MOLECULAR-CLONING; HUMAN-PLATELETS; G-PROTEIN C1 UNIV LONDON UNIV COLL,LONDON WC1E 6BT,ENGLAND. NIDDK,BIOORGAN CHEM LAB,BETHESDA,MD. FISONS PLC,DIV PHARMACEUT,RES & DEV LABS,LOUGHBOROUGH LE11 0RH,LEICS,ENGLAND. UNIV N CAROLINA,SCH MED,DEPT PHARMACOL,CHAPEL HILL,NC. ABBOTT LABS,NEUROSCI RES,ABBOTT PK,IL 60064. RP FREDHOLM, BB (reprint author), KAROLINSKA INST,DEPT PHYSIOL & PHARMACOL,MOLEC NEUROPHARMACOL SECT,S-17177 STOCKHOLM,SWEDEN. RI Jacobson, Kenneth/A-1530-2009; Abbracchio, Maria Pia/B-9342-2014 OI Jacobson, Kenneth/0000-0001-8104-1493; Abbracchio, Maria Pia/0000-0002-7833-3388 FU Intramural NIH HHS [Z01 DK031116-20, Z01 DK031117-20, Z99 DK999999] NR 159 TC 1494 Z9 1508 U1 3 U2 22 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-6997 J9 PHARMACOL REV JI Pharmacol. Rev. PD JUN PY 1994 VL 46 IS 2 BP 143 EP 156 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NR154 UT WOS:A1994NR15400004 PM 7938164 ER PT J AU DOUGLAS, JF ZHOU, HX HUBBARD, JB AF DOUGLAS, JF ZHOU, HX HUBBARD, JB TI HYDRODYNAMIC FRICTION AND THE CAPACITANCE OF ARBITRARILY-SHAPED OBJECTS SO PHYSICAL REVIEW E LA English DT Article ID MONTE-CARLO CALCULATION; MARKOV PROCESS EXPECTATIONS; CONTROLLED LIGAND-BINDING; KIRKWOOD-RISEMAN MODEL; EXCLUDED-VOLUME; WIENER SAUSAGE; THETA-POINT; TRANSLATIONAL DIFFUSION; RESIDUAL INTERACTIONS; ASYMPTOTIC EVALUATION AB The translational friction coefficient and the capacitance of a variety of objects are calculated with a probabilistic method involving hitting the ''probed'' objects with random walks launched from an enclosing spherical surface. This method is applied to exactly solvable examples to test the program accuracy and to physically important and analytically intractable examples (cube, chain of spheres at the vertices of self-avoiding and random walks, etc.). Large fluctuations in the friction of polymer chains with a random coil structure are found to give large deviations from the mean-field Kirkwood-Riseman theory and ''hydrodynamic fluctuation'' effects are found to diminish with the chain swelling accompanying excluded volume interaction. Capacity applications are reviewed and our probabilistic estimates of polymer friction are compared with previous calculations using alternative methods. Transients to the capacity and related properties are expressed in terms of fluctuations in the ''Wiener sausage'' volume (volume swept out by a Brownian particle where a repeated visit to a spatial region does not contribute to the volume increase in time). C1 NATL INST STAND & TECHNOL,DIV POLYMERS,GAITHERSBURG,MD. NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. NATL INST STAND & TECHNOL,DIV BIOTECHNOL,GAITHERSBURG,MD 20899. RI Zhou, Huan-Xiang/M-5170-2016 OI Zhou, Huan-Xiang/0000-0001-9020-0302 NR 157 TC 66 Z9 66 U1 2 U2 12 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1063-651X J9 PHYS REV E JI Phys. Rev. E PD JUN PY 1994 VL 49 IS 6 BP 5319 EP 5337 DI 10.1103/PhysRevE.49.5319 PN A PG 19 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA NW029 UT WOS:A1994NW02900076 ER PT J AU WADHWANI, KC RAPOPORT, SI AF WADHWANI, KC RAPOPORT, SI TI TRANSPORT-PROPERTIES OF VERTEBRATE BLOOD-NERVE BARRIER - COMPARISON WITH BLOOD-BRAIN-BARRIER SO PROGRESS IN NEUROBIOLOGY LA English DT Review ID FROG SCIATIC-NERVE; AMINO-ACID-TRANSPORT; RAT PERIPHERAL-NERVE; HUMAN DIABETIC NEUROPATHY; AGE-RELATED-CHANGES; ENDONEURIAL CAPILLARY-PERMEABILITY; PARA-NITRO-PHENYLPHOSPHATASE; NA+-K+-ATPASE; ANIONIC SITES; WALLERIAN DEGENERATION RP WADHWANI, KC (reprint author), NIA,NEUROSCI LAB,BLDG 10,RM 6C103,BETHESDA,MD 20892, USA. NR 366 TC 19 Z9 19 U1 3 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0301-0082 J9 PROG NEUROBIOL JI Prog. Neurobiol. PD JUN PY 1994 VL 43 IS 3 BP 235 EP & DI 10.1016/0301-0082(94)90002-7 PG 0 WC Neurosciences SC Neurosciences & Neurology GA PF695 UT WOS:A1994PF69500002 PM 7816928 ER PT J AU ISSA, F GERHARDT, GA BARTKO, JJ SUDDATH, RL LYNCH, M GAMACHE, PH FREEDMAN, R WYATT, RJ KIRCH, DG AF ISSA, F GERHARDT, GA BARTKO, JJ SUDDATH, RL LYNCH, M GAMACHE, PH FREEDMAN, R WYATT, RJ KIRCH, DG TI A MULTIDIMENSIONAL APPROACH TO ANALYSIS OF CEREBROSPINAL-FLUID BIOGENIC-AMINES IN SCHIZOPHRENIA .1. COMPARISONS WITH HEALTHY CONTROL SUBJECTS AND NEUROLEPTIC-TREATED/UNMEDICATED PAIRS ANALYSES SO PSYCHIATRY RESEARCH LA English DT Article DE DOPAMINE; SEROTONIN; NOREPINEPHRINE; KYNURENINE; COULOMETRIC ELECTROCHEMICAL ARRAY SYSTEM; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY ID PERFORMANCE LIQUID-CHROMATOGRAPHY; MONOAMINE METABOLITES; MAMMALIAN BRAIN; ELECTROCHEMICAL DETECTION; KYNURENIC ACID; DRUG-FREE; CSF; NEUROTRANSMITTER; VOLUNTEERS; GLUTAMATE AB Recent hypotheses and findings indicate that measurements of interactions between cerebrospinal fluid (CSF) biogenic amine systems, rather than measurement of CSF biogenic amine metabolites, better correlate with clinically important findings in schizophrenia. To test these hypotheses, we used a recent technological advance in high performance liquid chromatography with electrochemical detection and combined it with multivariate statistical analyses to study biogenic amine concentrations in CSF in schizophrenia. This approach enabled the study of the interactions of several metabolites of each of the three major neurotransmitter pathways (dopaminergic, noradrenergic, and serotonergic) to test existing hypotheses regarding the neurobiochemical basis of schizophrenia. Twenty biogenic amines, their metabolites, and other compounds from 24 medication-free schizophrenic patients and 12 normal control subjects were simultaneously measured using a recently developed technique of gradient high performance liquid chromatography coupled with a 16-channel electrochemical array detector. After covariation for storage time, results of a stepwise discriminant function analysis comparing the control and patient groups identified tryptophan, tryptophol, and epinephrine as discriminating variables. Hotelling's paired T-2 test from a subgroup of schizophrenic patients studied while they were and were not receiving neuroleptic treatment did not yield any significant differences between subgroups. A discussion of the findings and a comparison with previous studies of CSF biogenic amines in schizophrenia are presented. C1 UNIV COLORADO,HLTH SCI CTR,ROCKY MT CTR SENSOR TECHNOL,DENVER,CO. NIMH,DIV EPIDEMIOL & SERV RES,BETHESDA,MD 20892. ESA INC,BEDFORD,MA. UNIV COLORADO,HLTH SCI CTR,DEPT PSYCHIAT,DENVER,CO 80262. UNIV COLORADO,HLTH SCI CTR,CTR NEUROSCI & SCHIZOPHRENIA,DENVER,CO. MED COLL GEORGIA,SCH MED,AUGUSTA,GA 30912. RP ISSA, F (reprint author), ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,NEUROPSYCHIAT BRANCH,2700 MARTIN LUTHER KING JR AVE SE,WASHINGTON,DC 20032, USA. FU NIA NIH HHS [AG06434]; NINDS NIH HHS [NS09199] NR 42 TC 21 Z9 21 U1 1 U2 3 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 1994 VL 52 IS 3 BP 237 EP 249 DI 10.1016/0165-1781(94)90069-8 PG 13 WC Psychiatry SC Psychiatry GA PD739 UT WOS:A1994PD73900001 PM 7991718 ER PT J AU ISSA, F KIRCH, DG GERHARDT, GA BARTKO, JJ SUDDATH, RL FREEDMAN, R WYATT, RJ AF ISSA, F KIRCH, DG GERHARDT, GA BARTKO, JJ SUDDATH, RL FREEDMAN, R WYATT, RJ TI A MULTIDIMENSIONAL APPROACH TO ANALYSIS OF CEREBROSPINAL-FLUID BIOGENIC-AMINES IN SCHIZOPHRENIA .2. CORRELATIONS WITH PSYCHOPATHOLOGY SO PSYCHIATRY RESEARCH LA English DT Article DE DOPAMINE; SEROTONIN; NOREPINEPHRINE; KYNURENINE; PSYCHIATRIC SYMPTOM ASSESSMENT SCALE ID QUINOLINIC ACID; MONOAMINE METABOLITES; ENDOGENOUS EXCITANT; KYNURENIC ACID; DRUG-FREE; RECEPTORS; DISEASE; 5HIAA; HVA AB As part of a multidimensional study of cerebrospinal fluid biogenic amine metabolites in schizophrenia, the relationship between neurochemical measures and psychopathology assessed using the Psychiatric Symptom Assessment Scale (PSAS) was analyzed. In a group of 20 unmedicated patients, 3,4-dihydroxyphenylacetic acid (DOPAC) was a predictor of symptom severity in a stepwise multiple regression model. Values of 3-hydroxykynurenine and metanephrine in the unmedicated state predicted clinical response in a stepwise multiple regression model, as measured by improvement in PSAS mean item score following 6 weeks on a standard dose of neuroleptic. In a subgroup of 14 patients in whom both off- and on-medication concentrations of cerebrospinal fluid biogenic amines and metabolites were measured, change in 3-hydroxykynurenine predicted clinical outcome in a multiple regression model. These findings point toward the need to examine the role of the kynurenine pathway of tryptophan metabolism in the pathophysiology of schizophrenia. C1 MED COLL GEORGIA,SCH MED,AUGUSTA,GA 30912. UNIV COLORADO,HLTH SCI CTR,ROCKY MT CTR SENSOR TECHNOL,DENVER,CO. NIMH,DIV EPIDEMIOL & SERV RES,BETHESDA,MD. UNIV COLORADO,HLTH SCI CTR,DEPT PSYCHIAT,DENVER,CO 80262. UNIV COLORADO,HLTH SCI CTR,CTR NEUROSCI & SCHIZOPHRENIA,DENVER,CO. RP ISSA, F (reprint author), NIMH,NEUROSCI CTR ST ELIZABETHS,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032, USA. FU NIA NIH HHS [AG06434]; NINDS NIH HHS [NS09199] NR 27 TC 12 Z9 13 U1 1 U2 3 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 1994 VL 52 IS 3 BP 251 EP 258 DI 10.1016/0165-1781(94)90070-1 PG 8 WC Psychiatry SC Psychiatry GA PD739 UT WOS:A1994PD73900002 PM 7991719 ER PT J AU CASTELLANOS, FX ELIA, J KRUESI, MJP GULOTTA, CS MEFFORD, IN POTTER, WZ RITCHIE, GF RAPOPORT, JL AF CASTELLANOS, FX ELIA, J KRUESI, MJP GULOTTA, CS MEFFORD, IN POTTER, WZ RITCHIE, GF RAPOPORT, JL TI CEREBROSPINAL-FLUID MONOAMINE METABOLITES IN BOYS WITH ATTENTION-DEFICIT HYPERACTIVITY DISORDER SO PSYCHIATRY RESEARCH LA English DT Article DE LUMBAR PUNCTURE; CHILD PSYCHIATRY; AGGRESSION; HOMOVANILLIC ACID; 5-HYDROXYINDOLEACETIC ACID; 3-METHOXY-4-HYDROXYPHENYLGLYCOL ID DISRUPTIVE BEHAVIOR DISORDERS; 5-HYDROXYINDOLEACETIC ACID; AMINE METABOLITES; HOMOVANILLIC-ACID; PSYCHOMOTOR ACTIVITY; PLASMA-CORTISOL; RHESUS-MONKEYS; CHILDREN; ADOLESCENTS; AGGRESSION AB Cerebrospinal fluid (CSF), plasma, and urinary monoamine metabolites were determined for 29 boys, aged 6-12, with attention-deficit hyperactivity disorder (ADHD). Levels of CSF 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG), the metabolites of serotonin, dopamine, and norepinephrine, respectively, correlated significantly with behavioral measures of aggression and impulsivity/hyperactivity. However, these correlations were in the unexpected direction; for example, CSF 5-HIAA correlated positively with the Brown-Goodwin Lifetime History of Aggression Scale. HVA in CSF was positively correlated with several measures of hyperactivity. The replicability of these findings, as well as possible socioenvironmental effects, and the predictive value of CSF monoamines in prepubertal hyperactivity are the subjects of ongoing study. C1 MED COLL PENN,PHILADELPHIA,PA 19129. UNIV ILLINOIS,INST JUVENILE RES,CHICAGO,IL. VIRGINIA POLYTECH INST & STATE UNIV,DEPT PSYCHOL,BLACKSBURG,VA 24061. DUKE UNIV,SCH MED,DURHAM,NC. NIMH,EXPTL THERAPEUT BRANCH,CLIN PHARMACOL SECT,BETHESDA,MD 20892. RP CASTELLANOS, FX (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,RM 6N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 45 TC 124 Z9 130 U1 1 U2 3 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 1994 VL 52 IS 3 BP 305 EP 316 DI 10.1016/0165-1781(94)90076-0 PG 12 WC Psychiatry SC Psychiatry GA PD739 UT WOS:A1994PD73900008 PM 7527565 ER PT J AU MUMFORD, GK EVAN, SM KAMINSKI, BJ PRESTON, KL SANNERUD, CA SILVERMAN, K GRIFFITHS, RR AF MUMFORD, GK EVAN, SM KAMINSKI, BJ PRESTON, KL SANNERUD, CA SILVERMAN, K GRIFFITHS, RR TI DISCRIMINATIVE STIMULUS AND SUBJECTIVE EFFECTS OF THEOBROMINE AND CAFFEINE IN HUMANS SO PSYCHOPHARMACOLOGY LA English DT Article DE THEOBROMINE; CAFFEINE; METHYLXANTHINE; COCOA; CHOCOLATE; DRUG DISCRIMINATION; SUBJECTIVE EFFECTS; HUMANS ID METHYLXANTHINES; ADENOSINE; MIGRAINE; RATS AB Theobromine versus placebo discrimination and caffeine versus placebo discrimination were studied in two consecutive experiments in seven volunteers who abstained from methylxanthines. Daily sessions involved PO double-blind ingestion of two sets of capsules sequentially, one of which contained drug and the other placebo. Subjects attempted to identify, and were later informed, which set of capsules contained the drug. In each experiment subjects were exposed to progressively lower doses. Five subjects acquired the theobromine discrimination; the lowest dose discriminated ranged from 100 to 560 mg. All seven subjects acquired the caffeine discrimination; the lowest dose discriminated ranged from 1.8 to 178 mg. A final experiment evaluated subjective effect ratings following 560 mg theobromine, 178 mg caffeine and placebo, which were administered double-blind in capsules once daily, five times each in mixed sequence. Caffeine produced changes in both group and individual ratings (e.g. increased well-being, energy, social disposition and alert). Theobromine did not produce changes in group ratings but changed ratings in some subjects. Across subjects, sensitivity to caffeine discriminative effects in the discrimination experiment correlated significantly with the number and magnitude of caffeine subjective effects in the final experiment. This study documents modest discriminative effects of theobromine in humans, but the basis of the discrimination is unclear. This study suggests that commonly consumed cocoa products contain behaviorally active doses of caffeine and possibly theobromine. C1 JOHNS HOPKINS UNIV,SCH MED,BEHAV BIOL RES CTR,DEPT PSYCHIAT & BEHAV SCI,BALTIMORE,MD 21224. NIDA,ADDICT RES CTR,TREATMENT BRANCH,BALTIMORE,MD 21224. NIDA,ADDICT RES CTR,PRECLIN PHARMACOL BRANCH,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,BEHAV BIOL RES CTR,DEPT NEUROSCI,BALTIMORE,MD 21224. RI Preston, Kenzie/J-5830-2013; OI Preston, Kenzie/0000-0003-0603-2479; Silverman, Kenneth/0000-0003-2724-1413 FU NIDA NIH HHS [R01 DA03890] NR 38 TC 69 Z9 70 U1 1 U2 7 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JUN PY 1994 VL 115 IS 1-2 BP 1 EP 8 DI 10.1007/BF02244744 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA NR464 UT WOS:A1994NR46400001 PM 7862879 ER PT J AU PICKWORTH, WB BUNKER, EB HENNINGFIELD, JE AF PICKWORTH, WB BUNKER, EB HENNINGFIELD, JE TI TRANSDERMAL NICOTINE - REDUCTION OF SMOKING WITH MINIMAL ABUSE LIABILITY SO PSYCHOPHARMACOLOGY LA English DT Article DE TRANSDERMAL NICOTINE; SMOKING ID CIGARETTE-SMOKING; PHARMACOKINETIC PROPERTIES; CHEWING GUM; BEHAVIOR; PATCH; AID AB Cigarette consumption as well as the physiologic, performance and subjective effects of the nicotine patch were evaluated in ten subjects who smoked ad libitum while residing on a residential research ward for 30 days. Nicotine transdermal systems (''patches'') delivering a total of 0, 22 or 44 mg per 24 h were applied daily at a constant dose during each 7-day condition; the order of dosing conditions was varied according to a randomized, double-blind, crossover design. Nicotine patches significantly but modestly reduced spontaneous smoking and significantly increased venous plasma nicotine levels. Self ratings of patch liking, satisfaction with cigarettes and the ability to identify the patch condition did not change as a function of the nicotine dose, indicating minimal abuse liability. There were no consistent changes in the puffing pattern measures; however, in all patch conditions, subjects with extensive histories of illicit drug use smoked cigarettes faster than subjects with histories of occasional drug use. Small changes in resting heart rate, pulse and blood pressure occurred when the nicotine patch was worn. Thus large changes in venous plasma nicotine levels engender only modest changes in ad libitum cigarette consumption, measures of abuse liability and cardiovascular effects. These findings are consistent with the notion that the addictive and toxic effects of nicotine are partially determined by the rate of drug administration. RP PICKWORTH, WB (reprint author), NIDA,ADDICT RES CTR,POB 5180,BALTIMORE,MD 21224, USA. NR 25 TC 48 Z9 48 U1 0 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 1994 VL 115 IS 1-2 BP 9 EP 14 DI 10.1007/BF02244745 PG 6 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA NR464 UT WOS:A1994NR46400002 PM 7862918 ER PT J AU SPANAGEL, R ALMEIDA, OFX BARTL, C SHIPPENBERG, TS AF SPANAGEL, R ALMEIDA, OFX BARTL, C SHIPPENBERG, TS TI ENDOGENOUS K-OPIOID SYSTEMS IN OPIATE WITHDRAWAL - ROLE IN AVERSION AND ACCOMPANYING CHANGES IN MESOLIMBIC DOPAMINE RELEASE SO PSYCHOPHARMACOLOGY LA English DT Article DE OPIATE WITHDRAWAL; ENDOGENOUS OPIOID SYSTEMS; MESOLIMBIC SYSTEM; MICRODIALYSIS; PLACE PREFERENCE CONDITIONING ID MORPHINE-DEPENDENT RATS; NOR-BINALTORPHIMINE; NUCLEUS-ACCUMBENS; RECEPTOR ANTAGONISTS; PRECIPITATED WITHDRAWAL; MOTIVATIONAL PROPERTIES; PHYSICAL-DEPENDENCE; KAPPA-AGONIST; MU-AGONIST; TOLERANCE AB The kappa-opioid receptor antagonist nor-binaltorphimine (nor-BNI) was recently shown to potentiate certain overt withdrawal signs in morphine-dependent rats. The present study sought to further assess this phenomenon by examining the influence of nor-BNI treatment upon the conditioned place aversion associated with the naloxone-precipitated withdrawal syndrome. In addition, in vivo microdialysis studies were conducted in morphine-dependent rats to determine whether nor-BNI treatment can modify withdrawal-induced changes in basal dopamine (DA) release within the mesolimbic system. Rats were pretreated with either saline or a single dose of nor-BNI and then received ascending doses of morphine for 10 days. A withdrawal syndrome was then precipitated by the administration of naloxone (1 mg/kg SC). In rats which received chronic morphine injections, administration of naloxone produced a characteristic withdrawal syndrome and a marked aversion for an environment previously associated with naloxone-precipitated withdrawal. Nor-BNI treatment potentiated most overt signs of physical dependence. This treatment also resulted in a greater withdrawal-induced place aversion. Morphine-dependent rats exhibited a marked reduction in basal mesolimbic DA release. An even greater decrease in basal DA release was observed in nor-BNI treated rats. These results suggest that endogenous kappa-systems are important in the modulation of mesolimbic DA release and the accompanying place aversion which occurs during opiate withdrawal. C1 MAX PLANCK INST PSYCHIAT,DEPT NEUROPHARMACOL,D-82152 MARTINSRIED,GERMANY. NIDA,ADDICT RES CTR,PRECLIN PHARMACOL LAB,BEHAV PHARMACOL & GENET SECT,BALTIMORE,MD 21224. RP SPANAGEL, R (reprint author), MAX PLANCK INST PSYCHIAT,INST CLIN,DEPT NEUROENDOCRINOL,KRAPELINSTR 2,D-80804 MUNICH,GERMANY. RI Almeida, Osborne/E-8402-2010 OI Almeida, Osborne/0000-0001-7331-6928 NR 47 TC 83 Z9 83 U1 0 U2 4 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JUN PY 1994 VL 115 IS 1-2 BP 121 EP 127 DI 10.1007/BF02244761 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA NR464 UT WOS:A1994NR46400018 PM 7862883 ER PT J AU BENOWITZ, SC AF BENOWITZ, SC TI NEW-AGE PERSONNEL - QUALITY SERVICE DELIVERY IN CHANGING TIMES SO PUBLIC PERSONNEL MANAGEMENT LA English DT Article AB Many organizations must re-evaluate the manner in which personnel services are delivered to customers. Growing demands and increasing responsibilities placed on personnel offices have changed the nature of their work. Fiscal constraints have led to cutbacks in available staff to meet these needs. Larger organizations may have to re-evaluate the structure and responsibilities of centralized vs. decentralized systems. The National institutes of Health (NIH) is a large organization (19,000 employees) with a decentralized personnel services program. New responsibilities placed on the program (e.g., ethics, federal government recruitment and hiring regulations) and reduced resources have led to a re-examination of the services that customers need most, and of the level of the organization that is most effective in providing the service. Using focus groups, NIH identified a number of critical areas of personnel service delivery; the ten most critical are being reviewed by TQM teams. Each team will recommend the most appropriate organizational level to provide the service and will identify ways to simplify procedures (including automation) for both personnel offices and customers. This article will discuss the approach used at NIH and provide information on the results that have been accomplished to date. RP BENOWITZ, SC (reprint author), NIH,DIV PERSONNEL MANAGEMENT,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 2 U2 6 PU INT PERSONNEL MANAGEMENT ASSN PI ALEXANDRIA PA 1617 DUKE ST, ALEXANDRIA, VA 22314 SN 0091-0260 J9 PUBLIC PERS MANAGE JI Public Personnel Manage. PD SUM PY 1994 VL 23 IS 2 BP 181 EP 185 PG 5 WC Industrial Relations & Labor; Public Administration SC Business & Economics; Public Administration GA NT551 UT WOS:A1994NT55100001 ER PT J AU YAO, SX LUBIN, JH QIAO, YL BOICE, JD LI, JY CAI, SK ZHANG, FM BLOT, WJ AF YAO, SX LUBIN, JH QIAO, YL BOICE, JD LI, JY CAI, SK ZHANG, FM BLOT, WJ TI EXPOSURE TO RADON PROGENY, TOBACCO USE AND LUNG-CANCER IN A CASE-CONTROL STUDY IN SOUTHERN CHINA SO RADIATION RESEARCH LA English DT Article ID STATES URANIUM MINERS; CIGARETTE-SMOKE; TIN MINERS; RISK; COHORT; MORTALITY; DAUGHTERS AB A case-control study of lung cancer in underground tin miners in southern China was conducted to examine the interplay between exposure to radon progeny and tobacco use. A total of 460 incident cases and 1,043 controls were evaluated. Among the exposed, mean radon progeny exposures were 600 and 427 working level months (WLM) for cases and controls, respectively. The excess relative risk per WLM (ERR/WLM) was 0.28% overall, with a 95% confidence interval of 0.1-0.6%, similar to the estimate from a cohort study in a related population of underground miners. The established patterns of lung cancer associated with radon were seen; the ERR/WLM decreased with attained age and time since last exposure. Conditional on total exposure, risk was highest for exposures delivered at a low rate. The ERR/WLM did not differ significantly among current and former smokers or within categories of time since last exposure. The relative risk relationship between exposure to radon progeny and tobacco use was consistent with a multiplicative model, but the best-fitting model was intermediate between additive and multiplicative; an additive association was rejected. Adjustment for exposure to inorganic arsenic, a known lung carcinogen, reduced the estimate of the ERR/WLM from 0.86% to 0.28%. The ERR/WLM estimate was homogeneous across subgroups defined by workers not exposed to arsenic and quartiles of cumulative arsenic exposure. Although squamous cell carcinoma was the predominant cell type, small cell and adenocarcinoma histologies appeared more strongly associated with exposure to radon progeny. The finding of a stronger trend with exposure with small cell carcinomas and adenocarcinomas, compared to squamous cell carcinomas, occurred primarily at C1 NCI,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. YUNNAN TIN CORP,INST LABOR PROTECT,GEJIU CITY,JAPAN. NCI,PROGRAM CANC PREVENT RES,BETHESDA,MD 20892. CHINESE ACAD MED SCI,BEIJING,PEOPLES R CHINA. OFF CANC PREVENT & CONTROL,GEJIU,PEOPLES R CHINA. RI Qiao, You-Lin/B-4139-2012 OI Qiao, You-Lin/0000-0001-6380-0871 NR 24 TC 40 Z9 46 U1 1 U2 3 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JUN PY 1994 VL 138 IS 3 BP 326 EP 336 DI 10.2307/3578680 PG 11 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA NP025 UT WOS:A1994NP02500004 PM 8184006 ER PT J AU MA, LD JONES, B LAZENBY, AJ DOUGLAS, T BULTE, JWM AF MA, LD JONES, B LAZENBY, AJ DOUGLAS, T BULTE, JWM TI PERSISTENT ORAL CONTRAST AGENT LINING THE INTESTINE IN SEVERE MUCOSAL DISEASE - ELUCIDATION OF RADIOGRAPHIC APPEARANCE SO RADIOLOGY LA English DT Article DE CONTRAST MEDIA, EFFECTS; CYTOMEGALOVIRUS; ENTERITIS; INTESTINES; LEUKEMIA, COMPLICATIONS ID BONE-MARROW TRANSPLANTATION; VERSUS-HOST DISEASE; GASTROINTESTINAL INFLAMMATION; GRAFT; INFECTION; FEATURES AB Plain radiographs and computed tomographic scans obtained in a severely neutropenic patient with acute lymphoblastic leukemia and cytomegalovirus-associated enterocolitis revealed a pattern of prolonged mucosal adherence of oral contrast agent to the small bowel. This pattern was seen as long as 16 weeks after administration of contrast agent and has been seen previously only in patients who have received bone marrow transplants. Two sets of intestinal biopsy specimens contained crystals that coated denuded mucosa at the site of ulceration and later were trapped within the lamina propria. Electron diffraction and energy-dispersive radiographic analysis showed that these crystals were composed of barium sulfate. C1 JOHNS HOPKINS MED INST,DEPT PATHOL,BALTIMORE,MD 21287. UNIV BATH,SCH CHEM,BATH,AVON,ENGLAND. NIH,DIAGNOST RADIOL RES LAB,BETHESDA,MD. RP MA, LD (reprint author), JOHNS HOPKINS MED INST,RUSSELL H MORGAN DEPT RADIOL & RADIOL SCI,600 N WOLFE ST,BALTIMORE,MD 21287, USA. RI Bulte, Jeff/A-3240-2008; Douglas, Trevor/F-2748-2011 OI Bulte, Jeff/0000-0003-1202-1610; NR 10 TC 4 Z9 4 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUN PY 1994 VL 191 IS 3 BP 747 EP 749 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA NM668 UT WOS:A1994NM66800026 PM 8184056 ER PT J AU COLLET, MS YOUNG, NS AF COLLET, MS YOUNG, NS TI PROSPECTS FOR A HUMAN B19 PARVOVIRUS VACCINE SO REVIEWS IN MEDICAL VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; LINKED-IMMUNOSORBENT-ASSAY; ESCHERICHIA-COLI; CELL-LINE; MONOCLONAL-ANTIBODIES; PROGENITOR CELLS; IMMUNE-RESPONSE; EMPTY CAPSIDS; BONE-MARROW; FETAL LIVER C1 MEDIMMUNE INC,GAITHERSBURG,MD 20878. NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 85 TC 2 Z9 2 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 1052-9276 J9 REV MED VIROL JI Rev. Med. Virol. PD JUN PY 1994 VL 4 IS 2 BP 91 EP 103 DI 10.1002/rmv.1980040204 PG 13 WC Virology SC Virology GA NV136 UT WOS:A1994NV13600003 ER PT J AU MARSMANN, DS BARRETT, JC AF MARSMANN, DS BARRETT, JC TI APOPTOSIS AND CHEMICAL CARCINOGENESIS SO RISK ANALYSIS LA English DT Article; Proceedings Paper CT Conference on the Risk Assessment Paradigm After Ten Years: Policy and Practice Then, Now, and in the Future CY APR 05-08, 1993 CL WRIGHT PATTERSON AFB, OH SP USAF, ARMSTRONG LAB, TOXICOL DIV, USN, NAVAL MED RES INST DETACHMENT, USA, ARMY BIOMED RES & DEV LAB, US EPA, ENVIRONM CRITERIA & ASSESSMENT OFF, NATL RES COUNCIL, COMM TOXICOL DE APOPTOSIS LIVER TUMORS ALTERED HEPATIC FOCI; PEROXISOME PROLIFERATORS; INITIATION PROMOTION; CELL GROWTH-MODELING; CELL PROLIFERATION HOMEOSTASIS ID PEROXISOME PROLIFERATOR WY-14,643; PROGRAMMED CELL-DEATH; RAT-LIVER; ALTERED FOCI; PHENOTYPIC-EXPRESSION; TUMOR PROMOTERS; DNA-SYNTHESIS; REGRESSION; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN; DIETHYLNITROSAMINE AB Long recognized as a normal component of organogenesis during development, apoptosis (programmed cell death) has recently been implicated in alterations of cell growth and differentiation. Tissue homeostasis is normally maintained by a balance between cell division and cell death, with apoptosis often functioning in complement to cell growth. Thus, antithetical parallels in chemical carcinogenesis can be drawn between apoptosis and the proliferative events more commonly addressed. While enhanced cell replication may contribute to an increased frequency of mutation, apoptosis within a tissue may counteract chemical carcinogenesis through loss of mutated cells. Many strong carcinogens act as tumor promoters, selectively expanding an initiated cell population advantageously over surrounding cells. Similarly, chemicals with a selective inhibition of apoptosis within an initiated population would offer a growth advantage. In contrast, chemicals causing selective apoptosis of initiated cells would be expected to have an anticarcinogenic effect. Selective apoptosis, in concert with cell-specific replication, may explain the unique promoting effects of different carcinogens such as the peroxisome-proliferating chemicals, phenobarbital, and 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD). Cell turnover, both cell growth and cell death, is central to the process of chemically induced carcinogenesis in animals and understanding its impact is a critical determinant of the relevance of chemically induced effects to man. C1 NIEHS,ENVIRONM CARCINOGENESIS PROGRAM,RES TRIANGLE PK,NC 27709. RP MARSMANN, DS (reprint author), NIEHS,ENVIRONM TOXICOL PROGRAM,POB 12233,MD A0-01,RES TRIANGLE PK,NC 27709, USA. NR 39 TC 20 Z9 20 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0272-4332 J9 RISK ANAL JI Risk Anal. PD JUN PY 1994 VL 14 IS 3 BP 321 EP 326 DI 10.1111/j.1539-6924.1994.tb00247.x PG 6 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA NR536 UT WOS:A1994NR53600013 PM 8029504 ER PT J AU MELLEMGAARD, A ENGHOLM, G MCLAUGHLIN, JK OLSEN, JH AF MELLEMGAARD, A ENGHOLM, G MCLAUGHLIN, JK OLSEN, JH TI OCCUPATIONAL RISK-FACTORS FOR RENAL-CELL CARCINOMA IN DENMARK SO SCANDINAVIAN JOURNAL OF WORK ENVIRONMENT & HEALTH LA English DT Article DE HYDROCARBONS ID DRY CLEANING WORKERS; KIDNEY CANCER; ASBESTOS; LAUNDRY; DEATH; ARCHITECTS; MORTALITY; GASOLINE; COHORT; SWEDEN AB OBJECTIVES - Risk factors for renal-cell carcinoma, the most frequent type of kidney cancer, remains enigmatic. Time trends in incidence and changes in the regional distribution of this cancer are suggestive of environmental risk factors. This study reports on occupational risk factors for renal-cell carcinoma in Denmark. METHODS - In a population-based study, 365 persons with histologically verified renal-cell carcinoma and 396 referents were interviewed. Information was collected on occupation, education, and occupational exposure to a number of suspected substances, including hydrocarbons, asbestos, and radiation. RESULTS - Risk of renal-cell carcinoma was found to be associated with employment as a truck driver, exposure to gasoline, other hydrocarbons, and insecticides and herbicides. The risk of renal-cell carcinoma was higher in the lower socioeconomic strata for both the men and the women. Nonsignificantly elevated risks were observed for employment in oil refineries, gasoline stations, and the iron and steel industry. No association was found for exposure to radiation or for employment in industries such as leather manufacturing and health care, which have previously been linked to an increased risk of renal-cell carcinoma. CONCLUSIONS - The risk of renal-cell carcinoma is increased in lower socioeconomic strata, and previously identified or suspected risk factors do not explain the excess in risk. This study adds additional support to the hypothesis of a link between renal-cell carcinoma and hydrocarbons and also demonstrates the need for further studies on occupational risk factors for renal-cell carcinoma. C1 NCI,DIV CANC ETIOL,BIOSTAT BRANCH,BETHESDA,MD 20892. RP MELLEMGAARD, A (reprint author), DANISH CANC REGISTRY,INST CANC EPIDEMIOL,BOX 839,DK-2100 COPENHAGEN,DENMARK. NR 35 TC 52 Z9 53 U1 0 U2 2 PU SCAND J WORK ENV HEALTH PI HELSINKI PA TOPELIUKSENKATU 41A, SF-00250 HELSINKI, FINLAND SN 0355-3140 J9 SCAND J WORK ENV HEA JI Scand. J. Work Environ. Health PD JUN PY 1994 VL 20 IS 3 BP 160 EP 165 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA NX330 UT WOS:A1994NX33000002 PM 7973487 ER PT J AU ZAHM, SH BLAIR, A AF ZAHM, SH BLAIR, A TI ROLE OF THE HERBICIDE ATRAZINE IN THE DEVELOPMENT OF NON-HODGKINS-LYMPHOMA - REPLY SO SCANDINAVIAN JOURNAL OF WORK ENVIRONMENT & HEALTH LA English DT Letter ID RISK RP ZAHM, SH (reprint author), NCI,EXECUT PLAZA N 418,BETHESDA,MD 20892, USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU SCAND J WORK ENV HEALTH PI HELSINKI PA TOPELIUKSENKATU 41A, SF-00250 HELSINKI, FINLAND SN 0355-3140 J9 SCAND J WORK ENV HEA JI Scand. J. Work Environ. Health PD JUN PY 1994 VL 20 IS 3 BP 225 EP 226 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA NX330 UT WOS:A1994NX33000012 ER PT J AU MISSAR, CD GOLD, JM GOLDBERG, TE AF MISSAR, CD GOLD, JM GOLDBERG, TE TI WAIS-R SHORT FORMS IN CHRONIC-SCHIZOPHRENIA SO SCHIZOPHRENIA RESEARCH LA English DT Article DE WAIS-R; IQ; (SCHIZOPHRENIA) ID 4-SUBTEST SHORT FORMS; INTELLIGENCE; 2-SUBTEST AB Short forms of the WAIS-R provide a relatively quick screen of an individual's general cognitive ability. This study attempted to measure the merit of three WAIS-R short forms developed by Kaufman (1990) in a group of 114 chronic schizophrenic patients. The results suggest that the four-subtest short form provided the most reliable estimation of Full Scale IQ. The implications of these findings for research screening of schizophrenic patients is discussed. C1 NIMH,NEUROSCI CTR ST ELIZABETHS,DIV INTRAMURAL RES PROGRAMS,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. NIMH,NEUROSCI CTR ST ELIZABETHS,DIV INTRAMURAL RES PROGRAMS,CLIN & RES SERV BRANCH,WASHINGTON,DC 20032. NR 11 TC 39 Z9 39 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD JUN PY 1994 VL 12 IS 3 BP 247 EP 250 DI 10.1016/0920-9964(94)90034-5 PG 4 WC Psychiatry SC Psychiatry GA NR185 UT WOS:A1994NR18500007 PM 8054316 ER PT J AU WU, AJ FOX, PC AF WU, AJ FOX, PC TI SJOGRENS-SYNDROME SO SEMINARS IN DERMATOLOGY LA English DT Article RP WU, AJ (reprint author), NIDR,CIPCB,BLDG 10,ROOM 1N-113,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 12 Z9 12 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0278-145X J9 SEMIN DERMATOL JI Semin. Dermatol. PD JUN PY 1994 VL 13 IS 2 BP 138 EP 143 PG 6 WC Dermatology SC Dermatology GA NN893 UT WOS:A1994NN89300012 PM 8060826 ER PT J AU DALAKAS, MC AF DALAKAS, MC TI NEUROIMMUNOTHERAPY - A PRACTICAL APPROACH TO THE TREATMENT OF IMMUNE-MEDIATED NEUROLOGICAL DISEASES SO SEMINARS IN NEUROLOGY LA English DT Article ID GUILLAIN-BARRE-SYNDROME; MYELIN-ASSOCIATED GLYCOPROTEIN; MULTIFOCAL MOTOR NEUROPATHY; DOSE INTRAVENOUS IMMUNOGLOBULIN; INCLUSION-BODY MYOSITIS; STIFF-MAN SYNDROME; CELL LUNG-CANCER; IGM-M-PROTEINS; CONDUCTION BLOCK; EXPERIMENTAL DEMYELINATION RP DALAKAS, MC (reprint author), NINCDS,MED NEUROL BRANCH,NEUROMUSCULAR DIS SECT,BLDG 10,ROOM 4N248,BETHESDA,MD 20892, USA. NR 89 TC 5 Z9 5 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0271-8235 J9 SEMIN NEUROL JI Semin. Neurol. PD JUN PY 1994 VL 14 IS 2 BP 97 EP 105 DI 10.1055/s-2008-1041065 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA PB358 UT WOS:A1994PB35800003 PM 7984835 ER PT J AU TORO, C JACOBWITZ, DM HALLETT, M AF TORO, C JACOBWITZ, DM HALLETT, M TI STIFF-MAN SYNDROME SO SEMINARS IN NEUROLOGY LA English DT Article ID GLUTAMIC-ACID DECARBOXYLASE; EXTEROCEPTIVE REFLEXES; DIABETES-MELLITUS; GABAERGIC NEURONS; AUTOANTIBODIES; PATIENT; HETEROGENEITY; DISORDER C1 NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,BLDG 10,ROOM SN-226,BETHESDA,MD 20892. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. NR 40 TC 25 Z9 25 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0271-8235 J9 SEMIN NEUROL JI Semin. Neurol. PD JUN PY 1994 VL 14 IS 2 BP 154 EP 158 DI 10.1055/s-2008-1041073 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA PB358 UT WOS:A1994PB35800011 PM 7984830 ER PT J AU DALAKAS, MC AF DALAKAS, MC TI IMMUNOTHERAPY OF NEUROLOGIC DISEASES - PREFACE SO SEMINARS IN NEUROLOGY LA English DT Editorial Material RP DALAKAS, MC (reprint author), NINCDS,MED NEUROL BRANCH,NEUROMUSCULAR DIS SECT,BLDG 10,ROOM 4N248,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0271-8235 J9 SEMIN NEUROL JI Semin. Neurol. PD JUN PY 1994 VL 14 IS 2 BP U98 EP U98 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA PB358 UT WOS:A1994PB35800002 ER PT J AU SPOUGE, JL AF SPOUGE, JL TI COMPUTATION OF THE GAMMA, DIGAMMA, AND TRIGAMMA FUNCTIONS SO SIAM JOURNAL ON NUMERICAL ANALYSIS LA English DT Article DE STIRLING APPROXIMATION; CALCULUS OF RESIDUES; BINET INTEGRAL; COMPLETE MONOTONICITY INEQUALITIES AB This paper gives an approximation for the gamma function that, while different, has the same form as one by Lanczos [SIAM J. Numer. Anal., B1 (1964), pp. 86-96]1. Both approximations correct Stirling's approximation with contributions from the gamma function's poles, and both require O(- log epsilon) time independent of z to calculate z! with a relative error epsilon. At comparable accuracies, this paper's approximation requires slightly more computation than Lanczos' but is clearly superior in two ways: its coefficients are given by simple formulas and the error estimates apply not only to the gamma function, but also to its derivatives. Thus approximations for the digamma and trigamma functions are also given. Let F(a,1/2)(z) = z!(z + a)-z-(1/2)e(z+a)(2pi)-(1/2) and f(a)(z) = ln F(a,1/2)(z), with z complex and a real. Several lemmas in the paper require ''Stirling inequalities,'' i.e., bounds on \F(alpha,1/2)(z)\. To this end, the classical Binet integral for f0(z) is generalized from a = 0 to all real a. Since the generalized Binet integral is a Laplace transform, the requisite Stirling inequalities follow from the complete monotonicity of such transforms. The proof of the main theorem uses the calculus of residues and presents a lemma generalizing Plana's theorem, which, like the Euler-Maclaurin sum formula, evaluates the difference between a sum and the corresponding integral. This paper also presents a factorial approximation that is both simpler and more accurate than Stirling's approximation. RP SPOUGE, JL (reprint author), NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894, USA. NR 11 TC 21 Z9 21 U1 0 U2 3 PU SIAM PUBLICATIONS PI PHILADELPHIA PA 3600 UNIV CITY SCIENCE CENTER, PHILADELPHIA, PA 19104-2688 SN 0036-1429 J9 SIAM J NUMER ANAL JI SIAM J. Numer. Anal. PD JUN PY 1994 VL 31 IS 3 BP 931 EP 944 DI 10.1137/0731050 PG 14 WC Mathematics, Applied SC Mathematics GA NN242 UT WOS:A1994NN24200018 ER PT J AU ROUMEL, TJ AF ROUMEL, TJ TI A BLUEPRINT FOR ESTABLISHING A SUCCESSFUL OFFICE OF SPONSORED PROGRAMS - THE PUBLIC-HEALTH SERVICE HISTORICALLY BLACK-COLLEGE AND UNIVERSITY CAPACITY BUILDING PROGRAM SO SRA-JOURNAL OF THE SOCIETY OF RESEARCH ADMINISTRATORS LA English DT Article AB In 1992 the U.S. Public Health Service (PHS), Department of Health and Human Services (HHS), implemented a unique demonstration project known as the PHS Historically Black College and University (HBCU) Capacity Building Program. Under the guidance of the federal project officer, the effort brought together four HBCUs, PHS funding, and the expertise of professional research administrators. These resources were then used to determine the impact of establishing infrastructure support, in the form of an office of sponsored programs, at an institution of higher education. Although targeted to respond to presidential executive orders on HBCUs, the project holds implications for many small to midsized institutions, particularly those in which sponsored programs administration is either relatively new or emerging as an important function in stimulating institutional growth. The preliminary conclusion of the initiative is that if institutions follow the blueprint formulated by this project, they should be able to develop an office of sponsored programs that will be a dynamic and beneficial asset to their infrastructure. C1 NIH,BETHESDA,MD 20892. NR 3 TC 0 Z9 0 U1 0 U2 1 PU SOC RESEARCH ADMINISTRATORS PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036 SN 1062-8142 J9 SRA-J SOC RES ADMIN JI SRA-J. Soc. Res. Admin. PD SUM PY 1994 VL 26 IS 1 BP 5 EP 15 PG 11 WC Business; Management SC Business & Economics GA PQ182 UT WOS:A1994PQ18200002 ER PT J AU KNIGHT, RA DERESKI, MO HELPERN, JA ORDIDGE, RJ CHOPP, M AF KNIGHT, RA DERESKI, MO HELPERN, JA ORDIDGE, RJ CHOPP, M TI MAGNETIC-RESONANCE-IMAGING ASSESSMENT OF EVOLVING FOCAL CEREBRAL-ISCHEMIA - COMPARISON WITH HISTOPATHOLOGY IN RATS SO STROKE LA English DT Article DE CEREBRAL ISCHEMIA; HISTOLOGY; MAGNETIC RESONANCE IMAGING; RATS ID ARTERY OCCLUSION; MONONUCLEAR PHAGOCYTES; TEMPORAL EVOLUTION; T2-WEIGHTED MRI; BRAIN ISCHEMIA; DIFFUSION; INJURY; REPERFUSION; INFARCTION; CATS AB Background and Purpose This study was performed to document the progression of ischemic brain damage after middle cerebral artery occlusion in the rat using magnetic resonance imaging and histopathologic methods. Methods Cerebral ischemia was induced through permanent tandem occlusion of ipsilateral middle cerebral and common carotid arteries. The evolution of magnetic resonance imaging and histopathologic parameter changes was studied, both short term (1.5 to 8 hours) and long term (24 to 168 hours), in five specific brain regions within the middle cerebral artery territory. Results Significant changes in proton nuclear magnetic resonance spin-lattice and spin-spin relaxation times and the ''apparent'' diffusion coefficient of water could be detected within hours after the onset of permanent focal cerebral ischemia, whereas significant alterations in proton spin-density ratios were not apparent until approximately 48 hours. Histological changes were evident within 12 hours, with a significant loss of neurons seen in the most severely damaged regions at 7 days. Diffusion-weighted imaging was the most sensitive technique for visualizing acute ischemic alterations. The water diffusion coefficient was the only magnetic resonance imaging parameter studied to indicate significant alterations within the first 4 hours after arterial occlusion in all five brain regions. Conclusions The degree of change for a particular magnetic resonance imaging parameter appeared to be related to the location and extent of neuronal injury, with the most dramatic changes occurring within the areas displaying the most severe histological damage. These results indicate that complete specification of all brain regions affected by ischemic brain injury may require a combination of imaging strategies applied over a period of days and suggest the possibility of using magnetic resonance imaging to distinguish between permanent and reversible cell damage. C1 HENRY FORD HOSP,NATL INST HLTH,CTR STROKE RES,DEPT RADIAT ONCOL,DETROIT,MI 48202. HLTH SCI CTR,DETROIT,MI. OAKLAND UNIV,DEPT PHYS,ROCHESTER,MI. RP KNIGHT, RA (reprint author), HENRY FORD HOSP,NATL INST HLTH,CTR STROKE RES,DEPT NEUROL,NMR RES FACIL,2799 W GRAND BLVD,DETROIT,MI 48202, USA. RI Ordidge, Roger/F-2755-2010; OI Ordidge, Roger/0000-0002-1005-3654 FU NINDS NIH HHS [NS-23393, NS-29463, NS-30899] NR 50 TC 217 Z9 222 U1 0 U2 3 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0039-2499 J9 STROKE JI Stroke PD JUN PY 1994 VL 25 IS 6 BP 1252 EP 1261 PG 10 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA NP142 UT WOS:A1994NP14200031 PM 8202989 ER PT J AU KUJIRAI, K CARLSON, E EPSTEIN, CJ CADET, JL AF KUJIRAI, K CARLSON, E EPSTEIN, CJ CADET, JL TI AUTORADIOGRAPHIC DISTRIBUTION OF MU-OPIOID RECEPTORS IN THE BRAINS OF CU/ZN-SUPEROXIDE DISMUTASE MICE SO SYNAPSE LA English DT Article DE TRANSGENIC MICE; FREE RADICALS; NUCLEUS ACCUMBENS; SUBSTANTIA NIGRA; VENTRAL TEGMENTAL AREA; OPIATE RECEPTORS; DRUG ADDICTION ID MOLD PHYSARUM-POLYCEPHALUM; RAT NUCLEUS-ACCUMBENS; TRANSGENIC MICE; DOWNS-SYNDROME; NITRIC-OXIDE; GLUTATHIONE-PEROXIDASE; NEUROTENSIN RECEPTORS; DOPAMINE RELEASE; OPIATE RECEPTORS; BASAL FOREBRAIN AB Superoxide dismutase (SOD) is an important free radical scavenging enzyme which dismutates the superoxide anion radical. We have evaluated the role of SOD in the regulation of opioid receptors by comparing the concentration of mu opioid receptors labeled with [H-3]DAGO (Tyr-D-Ala-Gly-NMe-Phe-Gly-ol) in SOD-transgenic (SOD-Tg) mice and their non-transgenic (Non-Tg) littermates. SOD-Tg mice had higher maximal binding capacity (Bmax) in the shell division of the nucleus accumbens (NAc-shell) in comparison to Non-Tg littermates. There were no differences in Bmax in mu receptors in the core subdivision of the nucleus accumbens (NAc-core). There were no significant differences in receptor affinity (Kd) in either the NAc-shell or in the NAc-core. Moreover, there were no significant differences in either Bmax or Kd in the matrices nor in the patches of any of the striatal subdivisions. However, in a fashion similar to the situation in the NAc-shell, [H-3]DAGO binding in the substantia nigra pars compacta (SNpc), the ventral tegmental area (VTA), and the ventral part of the central grey was significantly higher in the SOD-Tg mice in comparison to Non-Tg mice. The present results are discussed in terms of their support for a possible involvement of free radicals in the differences observed in various regions of the SOD-Tg and control mice, which differ in their ability to scavenge the superoxide anion. Moreover, because of the differences in mu-opioid receptors in the NAc-shell, these transgenic mice might provide an excellent model in which to evaluate the role of the two accumbal subdivisions in paradigms of drug addiction, which appears to depend on the functional integrity of the mesocorticolimbic system. (C) 1994 Wiley-Liss, Inc. C1 NIDA, ADDICT RES CTR, MOLEC NEUROPSYCHIAT SECT, BALTIMORE, MD 21224 USA. YAMAGATA UNIV, SCH MED, DEPT INTERNAL MED 3, YAMAGATA 99023, JAPAN. UNIV CALIF SAN FRANCISCO, DEPT PEDIAT & BIOCHEM, SAN FRANCISCO, CA 94143 USA. NR 74 TC 7 Z9 7 U1 0 U2 0 PU WILEY PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0887-4476 EI 1098-2396 J9 SYNAPSE JI Synapse PD JUN PY 1994 VL 17 IS 2 BP 76 EP 83 DI 10.1002/syn.890170203 PG 8 WC Neurosciences SC Neurosciences & Neurology GA NM198 UT WOS:A1994NM19800002 PM 8091304 ER PT J AU KURATA, Y DIWAN, BA LEHMANMCKEEMAN, L RICE, JM WARD, JM AF KURATA, Y DIWAN, BA LEHMANMCKEEMAN, L RICE, JM WARD, JM TI COMPARATIVE HYALINE DROPLET NEPHROPATHY IN MALE F344/NCR RATS INDUCED BY SODIUM BARBITAL AND DIETHYLACETYLUREA, A BREAKDOWN PRODUCT OF SODIUM BARBITAL SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID ALPHA-2U-GLOBULIN NEPHROPATHY; D-LIMONENE; PHARMACOLOGICAL AGENTS; UNLEADED GASOLINE; RENAL CARCINOGEN; LESIONS; 2,2,4-TRIMETHYLPENTANE; NEPHROTOXICITY; PROLIFERATION; INDUCTION AB Hyaline droplet nephropathy in male rats due to alpha 2u-globulin accumulation in proximal tubules is caused by chemicals from several chemical classes. We have previously shown that the well-known sedative/hypnotic barbiturate, sodium barbital, and its breakdown product, diethylacetylurea, are renal toxins and renal tumor promoters. To determine comparative induction of hyaline droplets in renal tubules by sodium barbital and diethylacetylurea, male F344/NCr rats, 6 weeks of age, were given diets containing 0, 170, 341, 500, or 1000 ppm of diethylacetylurea or containing 500, 1000, or 4000 ppm of sodium barbital for periods of 2 or 10 weeks. Rats were terminated at 2 or 10 weeks and the histology of the kidney was evaluated using light microscopy with hematoxylin and eosin staining and staining by the Heidenhain method. Quantitative analysis showed dose responses for the degree of droplet accumulation in the P2 and P3 segments of the proximal tubules. Diethylacetylurea was more potent. Immunohistochemistry and ultrastructural evaluation revealed the nature of the droplets. Western blotting confirmed the presence of alpha 2u-globulin. Renal tubular necrosis, regeneration, and increased levels of cell proliferation using proliferating cell nuclear antigen immunohistochemistry were also found. Female rats similarly exposed to each chemical did not show tubule droplet accumulations nor renal lesions. We confirm for the first time that these two chemicals can be added to the enlarging list of nephrotoxic chemicals inducing alpha 2u-globulin nephropathy and possessing tumor promoting and renal carcinogenic properties. (C) 1994 Academic Press, Inc. C1 NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC,DYN CORP,FREDERICK,MD 21701. PROCTER & GAMBLE CO,CINCINNATI,OH 45239. NR 38 TC 11 Z9 11 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD JUN PY 1994 VL 126 IS 2 BP 224 EP 232 DI 10.1006/taap.1994.1111 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA NT258 UT WOS:A1994NT25800004 PM 7516096 ER PT J AU HUNTER, ES TUGMAN, JA SULIK, KK SADLER, TW AF HUNTER, ES TUGMAN, JA SULIK, KK SADLER, TW TI EFFECTS OF SHORT-TERM EXPOSURE TO ETHANOL ON MOUSE EMBRYOS IN-VITRO SO TOXICOLOGY IN VITRO LA English DT Article ID FETAL ALCOHOL SYNDROME; RAT EMBRYOS; PROXIMATE TERATOGEN; DEVELOPING INVITRO; ACETALDEHYDE; MICE AB The adverse developmental effects of ethanol consumption have been documented in humans and in animal models. In animal models, the organ system affected by ethanol administration is dependent on the point in gestation at which the xenobiotic is administered. Previous studies have shown that an exposure of 24-48 hr beginning at the early somite stage in rodent conceptuses alters neural tube closure in vitro. However, the concentration and time dependency of this effect have not been fully defined. Whole embryo culture was therefore used to expose 3-6-somite mouse conceptuses (ICR strain) to ethanol at 300, 450, 600 and 800 mg/dl. The higher concentrations were selected to approximate the peak serum ethanol concentrations that have been shown to be teratogenic in vivo. A 24-hr exposure produced a concentration-dependent increase in neural tube defects (NTDs) and concomitant growth retardation. When shorter exposure periods were used (8, 10, 12 or 20 hr) the incidence of NTDs was dependent on the ethanol concentration and exposure period. At the 600 and 800 mg/dl concentrations an exposure of 8 hr or more produced NTDs, but shorter periods (4 and 6 hr) did not affect neural tube closure when evaluated at the end of a 24-hr culture period. At the 450 mg/dl concentration a 20-hr exposure induced NTDs, but a 12-hr exposure to this lever did not. Exposure of conceptuses to ethanol for periods similar to their half-life in vivo did not induce NTDs and the highest concentration produced only a trend towards a reduction in protein content. When the incidence of NTDs was plotted against the area under the time and concentration curve (AUC) the correlation coefficient was 0.5779. An analysis of covariance indicated that the relationships between NTDs and AUC were similar at the 300 and 450 mg/dl concentrations and also at the 600 and 800 mg/dl concentrations. In contrast, the relationships between embryonic protein content and AUC did not differ at the 300, 450 and 600 mg/dl concentrations, but all differed from that at the 800 mg/dl level. These results indicate that ethanol-induced NTDs do not appear to be due solely to embryonic growth retardation. Additionally, ethanol-induced neural tube defects are a function of duration of exposure as well as of peak serum concentration. C1 NIEHS,NATL TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,DEPT CELL BIOL & ANAT,CHAPEL HILL,NC 27516. RP HUNTER, ES (reprint author), US EPA,HLTH EFFECTS RES LAB,DIV DEV TOXICOL,MD 67,RES TRIANGLE PK,NC 27711, USA. NR 24 TC 10 Z9 10 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0887-2333 J9 TOXICOL IN VITRO JI Toxicol. Vitro PD JUN PY 1994 VL 8 IS 3 BP 413 EP & DI 10.1016/0887-2333(94)90163-5 PG 0 WC Toxicology SC Toxicology GA NU845 UT WOS:A1994NU84500013 PM 20692933 ER PT J AU MULLER, J JANZ, S AF MULLER, J JANZ, S TI IN-VITRO CYTOTOXICITY OF NEUTROPHIL-LIKE HUMAN HL-60 CELLS UNDERGOING AN OXIDATIVE BURST WITH ESCHERICHIA-COLI REPORTER STRAINS SO TOXICOLOGY IN VITRO LA English DT Article ID DNA DAMAGE; LEUKEMIA-CELLS; SOS RESPONSE; MODULATION; PROTEASES; INDUCTION; PQ300 AB Neutrophil-like human promyelocytic HL-60 cells produced substantial amounts of reactive oxygen intermediates (ROIs) after stimulation with the tumour promoter phorbol myristate acetate (TPA). Escherichia coli PQ37 and PQ300 reporter strains incurred high levels of toxicity after co-incubation with neutrophil-like HL-60 cells undergoing an oxidative burst. Toxicity was dependent on (a) the differentiation of HL-60 cells into neutrophil-like cells, (b) the stimulation of HL-60 cells with TPA and (c) the ratio of HL-60 to target cells. It is concluded that Escherichia coli PQ37 and PQ300 reporter strains can effectively be used to evaluate the cytotoxicity of neutrophils in vitro. The toxicity of HL-60 cells was, however, only marginally inhibited by the antioxidative enzymes catalase or superoxide dismutase. This indicates that, under the conditions chosen, cytotoxicity of HL-60 cells to Escherichia coli is mainly determined by factors other than ROIs and appears to be the result of complex interactions of the numerous reactive compounds that are released in addition to ROIs. C1 NCI, DIV CANC BIOL DIAG & CTR, GENET LAB, BETHESDA, MD 20892 USA. RP MULLER, J (reprint author), UNIV LEIPZIG, FAC MED, INST CLIN IMMUNOL, W-0410 LEIPZIG, GERMANY. NR 17 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-2333 J9 TOXICOL IN VITRO JI Toxicol. Vitro PD JUN PY 1994 VL 8 IS 3 BP 437 EP 440 DI 10.1016/0887-2333(94)90165-1 PG 4 WC Toxicology SC Toxicology GA NU845 UT WOS:A1994NU84500015 PM 20692935 ER PT J AU DIPAOLO, JA POPESCU, NC ABLASHI, DV LUSSO, P ZIMONJIC, DB WOODWORTH, CD AF DIPAOLO, JA POPESCU, NC ABLASHI, DV LUSSO, P ZIMONJIC, DB WOODWORTH, CD TI MULTISTAGE CARCINOGENESIS UTILIZING HUMAN GENITAL CELLS AND HUMAN PAPILLOMAVIRUSES SO TOXICOLOGY LETTERS LA English DT Article; Proceedings Paper CT 4th European Meeting of Environmental Hygiene CY JUN 09-11, 1993 CL WAGENINGEN, NETHERLANDS SP WAGENINGEN AGR UNIV, HEINRICH HEINE UNIV DUSSEL, MED INST ENVIRONM HYG, DUTCH MINIST WELF HLTH & CUTURAL AFFAIRS, ROYAL NETHERLANDS ACAD SCI, ALFRED KRUPP VONBOHLEN & HALBACH FDN ESSEN DE CERVICAL EPITHELIUM; COCARCINOGENESIS; SMOKING; HUMAN PAPILLOMAVIRUS; HUMAN HERPESVIRUS ID INVASIVE CERVICAL-CANCER; SMOKING AB The preponderance of evidence indicates that a subset of human papillomaviruses are important etiological agents for cervical cancer. However, the necessity of other agents as well as cellular events is recognized because not all women with papillomaviruses develop cancer. Therefore, the exact role of papillomaviruses in the multistage carcinogenesis process is unclear. Regulation of specific viral genes is important to the malignant process. The current study demonstrates that human herpesvirus-6, another ubiquitous virus, can infect genital epithelial cells and upregulate the expression of relevant papillomavirus genes. Thus, it can be considered a cofactor for cancer. RP DIPAOLO, JA (reprint author), NCI,BIOL LAB,BETHESDA,MD 20892, USA. NR 11 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD JUN PY 1994 VL 72 IS 1-3 BP 7 EP 11 DI 10.1016/0378-4274(94)90004-3 PG 5 WC Toxicology SC Toxicology GA NQ118 UT WOS:A1994NQ11800003 PM 8202958 ER PT J AU DALY, JW SECUNDA, SI GARRAFFO, HM SPANDE, TF WISNIESKI, A COVER, JF AF DALY, JW SECUNDA, SI GARRAFFO, HM SPANDE, TF WISNIESKI, A COVER, JF TI AN UPTAKE SYSTEM FOR DIETARY ALKALOIDS IN POISON FROGS (DENDROBATIDAE) SO TOXICON LA English DT Article ID SKIN ALKALOIDS; CLASSIFICATION AB The skin of poison frogs (Dendrobatidae) contains a wide variety of alkaloids that presumably serve a defensive role. These alkaloids persist for years in captivity, but are not present in captive-raised frogs. Alkaloids fed to poison frogs (Dendrobates, Phyllobates, Epipedobates) are readily accumulated into skin, where they remain for months. The process can be selective; an ant indolizidine is accumulated, while an ant pyrrolidine is not. Frogs (Colostethus) of the same family, which do not normally contain alkaloids, do not accumulate alkaloids. Such an alkaloid uptake system provides a means of maintaining skin alkaloids and suggests that some if not all such 'dendrobatid alkaloids' may have a dietary origin. C1 BALTIMORE ZOO,DEPT HERPETOL,BALTIMORE,MD 21217. NATL AQUARIUM,BALTIMORE,MD. RP DALY, JW (reprint author), NIH,BIOORGAN CHEM LAB,BLDG 10,BETHESDA,MD 20892, USA. NR 10 TC 91 Z9 95 U1 4 U2 24 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0041-0101 J9 TOXICON JI Toxicon PD JUN PY 1994 VL 32 IS 6 BP 657 EP 663 DI 10.1016/0041-0101(94)90335-2 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA NT953 UT WOS:A1994NT95300002 PM 7940573 ER PT J AU DONEGAN, E LEE, H OPERSKALSKI, EA SHAW, GM KLEINMAN, SH BUSCH, MP STEVENS, CE SCHIFF, ER NOWICKI, MJ HOLLINGSWORTH, CG MOSLEY, JW BUCKLEY, JD GAIENNIE, J HARRIS, M KASPER, CK PIKE, MC SUCCAR, M ZHOU, Y DIETRICH, SL TAYLOR, ME LEE, H SCHRODE, J CERNEY, M KROCHMAL, E ANDERSON, E LUSHER, JM FLETCHER, MA LIAN, ECY ALEDORT, LM HASSETT, J HILGARTNER, MW TAYLOR, PE KOERPER, MA LEWIS, BH GJERSET, GF NEMO, GJ HOAK, J AF DONEGAN, E LEE, H OPERSKALSKI, EA SHAW, GM KLEINMAN, SH BUSCH, MP STEVENS, CE SCHIFF, ER NOWICKI, MJ HOLLINGSWORTH, CG MOSLEY, JW BUCKLEY, JD GAIENNIE, J HARRIS, M KASPER, CK PIKE, MC SUCCAR, M ZHOU, Y DIETRICH, SL TAYLOR, ME LEE, H SCHRODE, J CERNEY, M KROCHMAL, E ANDERSON, E LUSHER, JM FLETCHER, MA LIAN, ECY ALEDORT, LM HASSETT, J HILGARTNER, MW TAYLOR, PE KOERPER, MA LEWIS, BH GJERSET, GF NEMO, GJ HOAK, J TI TRANSFUSION TRANSMISSION OF RETROVIRUSES - HUMAN T-LYMPHOTROPIC VIRUS TYPE-I AND TYPE-II COMPARED WITH HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SO TRANSFUSION LA English DT Article ID CELL LEUKEMIA-VIRUS; STATES BLOOD-DONORS; HTLV-I; RISK-FACTORS; INFECTION; RECIPIENTS; HIV-1; SEROCONVERSION; COMPONENTS; PREVALENCE AB Background: The incidence of transfusion transmission of human T-lymphotropic virus type I (HTLV-I) and HTLV type II (HTLV-II) has not been compared directly or to that of human immunodeficiency virus type 1 (HIV-1). The effects of refridgerator storage of the blood component on infectivity of the viruses needs definition. Study Design and Methods: The circumstances influencing the transmission of HTLV-1, HTLV-II, and HIV-1 via blood of donors whose sera were stored in a repository and who were retrospectively documented as having been infected at blood donation were examined. Confirmation and typing of anti-HTLV positivity in donors and recipients used polymerase chain reaction, supplemented by specific peptide testing. Results: Overall, 27 percent (26/95) of the recipients of blood components from anti-HTLV-I- and -II-positive donors became infected (9 with HTLV-I and 17 with HTLV-II). No recipients of acellular blood components became infected with HTLV-I or -II. There was no probable transmission by components stored >10 days. The rates of transmission for both viruses were similar: 0 to 5 days' storage, 17 (74%) of 23; 6 to 10 days, 8 (44%) of 18; and 11 to 14, 0 (0%) of 10 (trend, p = 0.0002). In comparison, 89 percent (112/126) of the recipients of anti-HIV-1-positive blood were infected regardless of component type, and no effect on transmission occurred with storage for <26 days. Conclusion: Transfusion-transmitted HTLV-I and -II are similar. The data suggest that a donor's lymphocytes become noninfectious when they lose the ability to be activated or to proliferate. C1 UNIV SO CALIF,SCH MED,TRANSFUS SAFETY STUDY COORDINATING CTR LAB,LOS ANGELES,CA 90032. ABBOTT LABS,N CHICAGO,IL 60064. UNIV ALABAMA,BIRMINGHAM,AL. IRWIN MEM BLOOD CTR,SAN FRANCISCO,CA. NEW YORK BLOOD CTR,EPIDEMIOL LAB,NEW YORK,NY 10021. UNIV MIAMI,SCH MED,DIV HEPATOL,MIAMI,FL. NHLBI,TRANSFUS MED BRANCH,BETHESDA,MD 20892. AMER RED CROSS,BLOOD SERV,LOS ANGELES,CA 90006. UNIV CALIF SAN FRANCISCO,DEPT LAB MED,SAN FRANCISCO,CA 94143. UNIV CALIF LOS ANGELES,LOS ANGELES,CA. HUNTINGTON MEM HEMOPHILIA CTR,LOS ANGELES,CA. WAYNE STATE UNIV,DETROIT,MI. MT SINAI MED CTR,NEW YORK,NY 10029. CORNELL UNIV,MED CTR,NEW YORK,NY 10021. ALTA BATES COMMUNITY HOSP,SAN FRANCISCO,CA. PUGET SOUND BLOOD CTR,SEATTLE,WA 98104. FU NHLBI NIH HHS [N01-HB-4-7003, N01-HB-9-7074, N01-HB-4-7002] NR 34 TC 89 Z9 91 U1 0 U2 3 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 1994 VL 34 IS 6 BP 478 EP 483 DI 10.1046/j.1537-2995.1994.34694295061.x PG 6 WC Hematology SC Hematology GA NV575 UT WOS:A1994NV57500005 PM 8023388 ER PT J AU KOONIN, EV BORK, P AF KOONIN, EV BORK, P TI FMN OR DNA-BINDING SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Letter ID MULTIPLE ALIGNMENT C1 EUROPEAN MOLEC BIOL LAB, D-69012 HEIDELBERG, GERMANY. RP NATL LIB MED, NATL CTR BIOTECHNOL INFORMAT, BETHESDA, MD 20894 USA. RI Bork, Peer/F-1813-2013 OI Bork, Peer/0000-0002-2627-833X NR 7 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD JUN PY 1994 VL 19 IS 6 BP 234 EP 235 DI 10.1016/0968-0004(94)90145-7 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NR111 UT WOS:A1994NR11100003 PM 8073499 ER PT J AU WOLFFE, AP AF WOLFFE, AP TI NUCLEOSOME POSITIONING AND MODIFICATION - CHROMATIN STRUCTURES THAT POTENTIATE TRANSCRIPTION SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Review ID TUMOR VIRUS PROMOTER; GLUCOCORTICOID RECEPTOR; MMTV PROMOTER; FACTOR ACCESS; DNA; ACTIVATION; PROTEINS; BINDING; ENHANCER; SEQUENCE AB The role of the nucleosome in the folding of DNA has often been thought of as purely a packaging one. However, the precise folding of regulatory sequences of genes around the histones within positioned nucleosomes is also important in controlling both the access of transcription factors to chromatin and the transcription process itself. This review highlights these functions by using specific examples of an active and regulatory role for positioned nucleosomes. RP WOLFFE, AP (reprint author), NICHHD,MOLEC EMBRYOL LAB,BETHESDA,MD 20892, USA. NR 30 TC 157 Z9 158 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD JUN PY 1994 VL 19 IS 6 BP 240 EP 244 DI 10.1016/0968-0004(94)90148-1 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NR111 UT WOS:A1994NR11100006 PM 8073501 ER PT J AU HENGEN, PN AF HENGEN, PN TI METHODS AND REAGENTS - DISPOSAL OF ETHIDIUM-BROMIDE SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Note AB Methods and reagents is a unique monthly column that highlights current discussions in the newsgroup bionet.molbio.methds-reagnts, available on the Internet. This month's column discusses the Various methods used to dispose of ethidium bromide waste. For details on how to partake in the newsgroup, see the accompanying box. RP HENGEN, PN (reprint author), NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702, USA. NR 7 TC 8 Z9 8 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD JUN PY 1994 VL 19 IS 6 BP 257 EP 258 DI 10.1016/0968-0004(94)90152-X PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NR111 UT WOS:A1994NR11100010 PM 8073504 ER PT J AU CELI, FS WALSTON, J SILVER, K SHULDINER, AR AF CELI, FS WALSTON, J SILVER, K SHULDINER, AR TI RAPID SYNTHESIS OF STANDARDS FOR ALLELE-SPECIFIC OLIGONUCLEOTIDE HYBRIDIZATION SO TRENDS IN GENETICS LA English DT Note ID INSULIN-RECEPTOR SUBSTRATE-1 C1 JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21224. NIA,BALTIMORE,MD 21224. NR 4 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD JUN PY 1994 VL 10 IS 6 BP 184 EP 185 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA NN336 UT WOS:A1994NN33600004 PM 8073530 ER PT J AU CROWE, JE BUI, PT LONDON, WT DAVIS, AR HUNG, PP CHANOCK, RM MURPHY, BR AF CROWE, JE BUI, PT LONDON, WT DAVIS, AR HUNG, PP CHANOCK, RM MURPHY, BR TI SATISFACTORILY ATTENUATED AND PROTECTIVE MUTANTS DERIVED FROM A PARTIALLY ATTENUATED COLD-PASSAGED RESPIRATORY SYNCYTIAL VIRUS MUTANT BY INTRODUCTION OF ADDITIONAL ATTENUATING MUTATIONS DURING CHEMICAL MUTAGENESIS SO VACCINE LA English DT Article DE RESPIRATORY SYNCYTIAL VIRUS; COLD-PASSAGED MUTANT; ATTENUATING MUTANTS ID TEMPERATURE-SENSITIVE PHENOTYPE; COTTON RATS; PULMONARY HISTOPATHOLOGY; SURFACE GLYCOPROTEINS; RSV CHALLENGE; T-CELLS; LIVE; VACCINES; CHILDREN; IMMUNIZATION AB A cold-passaged RSV mutant, designated cp-RSV, which acquired host range mutations during 52 passages at low temperature in bovine tissue culture, was completely attenuated for seropositive adults and children but retained the capacity to cause upper respiratory disease in seronegative infants. We sought to introduce additional attenuating mutations, such as temperature-sensitive (ts) and small-plaque (sp) mutations, into the cp-RSV mutant, which is a ts + virus, in order to generate a mutant which would be satisfactorily attenuated in seronegative infants and young children. Nine mutants of cp-RSV which had acquired either the ts or small-plaque sp phenotype, were generated by chemical mutagenesis with 5-fluorouracil. The two ts mutants with the lowest in vitro shut-off temperature, namely the cpts-248 (38 degrees C) and cpts-530 (39 degrees C) mutants, were the most restricted of the nine cp-RSV mutant progeny tested for efficiency of replication in Balb/c mice. In seronegative chimpanzees, the cpts-248 mutant replicated fourfold less efficiently in the nasopharynx and caused significantly less rhinorrhoea than its cp-RSV parent. The cpts-248 mutant virus, like its cp-RSV parent, was 1000-fold restricted in replication in the trachea compared with wild-type RSV. Previously, another candidate RSV live attenuated vaccine str ain, a mutant designated ts-l, exhibited some instability of its ts phenotype following replication in susceptible humans or chimpanzees. Hence, we sought cp-RSV ts progeny that exhibited a greater degree of stability of the ts phenotype than the prototype ts-1 mutant. The cpts-248 and cpts-530 progeny viruses exhibited a greater degree of stability of the ts phenotype in nude mice than the ts-1 virus, and in chimpanzees, the former mutant also exhibited a greater stability of its ts phenotype than ts-1. The cpts-248 mutant was immunogenic and induced a high level of resistance in chimpanzees to subsequent challenge with wild-type RSV. The cpts-248 mutant therefore exhibits a set of properties that make it a promising vaccine candidate. These desirable properties of cpts-248 suggest that the mutant should be tested in humans for its suitability in immunoprophylaxis. C1 WYETH AYERST RES,DIV MOLEC BIOL,RADNOR,PA. RP CROWE, JE (reprint author), NIAID,INFECT DIS LAB,RESP VIRUSES SECT,BETHESDA,MD 20892, USA. RI Crowe, James/B-5549-2009 OI Crowe, James/0000-0002-0049-1079 NR 36 TC 58 Z9 60 U1 0 U2 3 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 1994 VL 12 IS 8 BP 691 EP 699 DI 10.1016/0264-410X(94)90218-6 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA NN325 UT WOS:A1994NN32500004 PM 8091846 ER PT J AU KALYAN, NK LEE, SG WILHELM, J PISANO, MR HUM, WT HSIAO, CL DAVIS, AR EICHBERG, JW ROBERTGUROFF, M HUNG, PP AF KALYAN, NK LEE, SG WILHELM, J PISANO, MR HUM, WT HSIAO, CL DAVIS, AR EICHBERG, JW ROBERTGUROFF, M HUNG, PP TI IMMUNOGENICITY OF RECOMBINANT INFLUENZA-VIRUS HEMAGGLUTININ CARRYING PEPTIDES FROM THE ENVELOPE PROTEIN OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SO VACCINE LA English DT Article DE HA ANTIGENIC SITES; HIV-1 EPITOPES; VACCINE DEVELOPMENT ID B SURFACE-ANTIGEN; NEUTRALIZING ANTIBODIES; HIV-1; HEMAGGLUTININ; CHIMPANZEES; EXPRESSION; GP120; GLYCOPROTEIN; VACCINATION; PROTECTION AB Haemagglutinin (HA), the major surface glycoprotein of influenza virus, is a potent immunogen against which viral neutralizing antibodies are directed. Studies of the three-dimensional structure of HA have identified major antigenic sites on the molecule. We have exploited HA as a carrier for small antigenic regions (epitopes) of the HIV-1 envelope (env) glycoprotein. Using recombinant DNA techniques, the epitopes were inserted in-frame into a known antigenic site of HA to produce HA-epitope chimeras. Guinea-pigs and mice immunized with these chimeras in combination with adjuvant generated significant immune responses against the carrier HA and also produced epitope-specific antibodies that recognized the native whole HIV-1 env. One of the chimeras which contained a V3-loop sequence of HIV-1 env elicited neutralizing antibodies against the homologous strain of HIV-1. The antibodies against HA and the inserted epitopes remained at high levels for up to 72 weeks. Remarkably, these responses were generated with low doses of immunogens containing only nanogram quantities of the inserted epitopes. These results suggest the utility of HA as a carrier to allow selective antibody induction against foreign epitopes, and offer a new approach for vaccine development as well as for the production of monospecific antibodies useful in diagnostics and research. C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. RP KALYAN, NK (reprint author), WYETH AYERST RES,DIV BIOTECHNOL & MICROBIOL,POB 8299,PHILADELPHIA,PA 19101, USA. NR 33 TC 20 Z9 20 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 1994 VL 12 IS 8 BP 753 EP 760 DI 10.1016/0264-410X(94)90228-3 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA NN325 UT WOS:A1994NN32500014 PM 7522383 ER PT J AU YUAN, JH GOEHL, TJ MURRILL, E MOORE, R CLARK, J HONG, HL IRWIN, RD AF YUAN, JH GOEHL, TJ MURRILL, E MOORE, R CLARK, J HONG, HL IRWIN, RD TI TOXICOKINETICS OF PENTACHLOROPHENOL IN THE F344 RAT - GAVAGE AND DOSED FEED STUDIES SO XENOBIOTICA LA English DT Article ID METABOLISM; PHARMACOKINETICS; TOXICOLOGY; PHENOLS AB 1. The toxicokinetics of pentachlorophenol (PCP) were studied in the Fischer 344 rat using i.v. and oral (gavage, dosed feed) routes of exposure. 2. Only minor sex differences were observed in the elimination kinetics of PCP after i.v. administration at 5 mg/kg. 3. Absorption of PCP from the gastrointestinal tract after gavage doses of 9.5 and 38 mg/kg in aqueous methylcellulose vehicles was first order with an absorption half-life of about 1.3 h. 4. The absorption rate constant of PCP from doses feed was comparable with that obtained from aqueous methylcellulose gavage formulations. 5. Bioavailability of PCP administered in dosed feed was significantly lower than the bioavailability of PCP administered by gavage. 6. Dose proportionality was established to a dosage of at least 38 mg/kg. 7. Daily fluctuation of PCP plasma concentrations was observed during the dosed feed study with peak and trough concentrations occurring in early morning and late afternoon, respectively. 8. The time course of PCP plasma concentrations during the dosed feed study were simulated using a computer model based on linear theory. The simulations were comparable with the experimentally determined concentrations. C1 NIEHS,RES TRIANGLE PK,NC 27709. MIDWEST RES INST,KANSAS CITY,MO 64110. NR 20 TC 8 Z9 9 U1 1 U2 2 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0049-8254 J9 XENOBIOTICA JI Xenobiotica PD JUN PY 1994 VL 24 IS 6 BP 553 EP 560 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA NT839 UT WOS:A1994NT83900008 PM 7975721 ER PT J AU SHOU, M GROGAN, J MANCEWICZ, JA KRAUSZ, KW GONZALEZ, FJ GELBOIN, HV KORZEKWA, KR AF SHOU, M GROGAN, J MANCEWICZ, JA KRAUSZ, KW GONZALEZ, FJ GELBOIN, HV KORZEKWA, KR TI ACTIVATION OF CYP3A4 - EVIDENCE FOR THE SIMULTANEOUS BINDING OF 2 SUBSTRATES IN A CYTOCHROME-P450 ACTIVE-SITE SO BIOCHEMISTRY LA English DT Article ID ALPHA-NAPHTHOFLAVONE; HUMAN-LIVER; RAT-LIVER; EXPRESSION; CELLS; HYDROXYLATION; METABOLISM; MICROSOMES; RABBIT AB A unique characteristic of the CYP3A subfamily of cytochrome P450 enzymes is their ability to be activated by certain compounds. It is reported that CYP3A4-catalyzed phenanthrene metabolism is activated by 7,8-benzoflavone and that 7,8-benzoflavone serves as a substrate for CYP3A4. Kinetic analyses of these two substrates show that 7,8-benzoflavone increases the V-max of phenanthrene metabolism without changing the K-m and that phenanthrene decreases the V-max of 7,8-benzoflavone metabolism without increasing the K-m. These results suggest that both substrates (or substrate and activator) are simultaneously present in the active site. Both compounds must have access to the active oxygen, since neither phenanthrene nor 7,8-benzoflavone can competitively inhibit the other substrate. These data provide the first evidence that two different molecules can be simultaneously bound to the same P450 active site. Additionally, structure-activity relationship studies were performed with derivatives of 7,8-benzoflavone structure: The effects of 13 different compounds on the regioselectivity of phenanthrene, chrysene, and benzo[a]pyrene metabolism were determined. Of the 13 compounds studied, 6 were activators, 2 Were partial activators, and 5 were inhibitors. Analyses of the data suggest that (1) naphthalene substituted with a ketone in the 2-position can activate 3A4 and (2) the presence of an activator results in a narrower effective substrate binding site. Since the CYP3A enzymes are very important in drug metabolism, the possibility of activation, and autoactivation, must be considered when in vitro-in vivo correlations are made and when possible drug interactions ace considered. C1 NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. NR 27 TC 326 Z9 330 U1 1 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 31 PY 1994 VL 33 IS 21 BP 6450 EP 6455 DI 10.1021/bi00187a009 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NP218 UT WOS:A1994NP21800009 PM 8204577 ER PT J AU BURKE, TR SMYTH, MS OTAKA, A NOMIZU, M ROLLER, PP WOLF, G CASE, R SHOELSON, SE AF BURKE, TR SMYTH, MS OTAKA, A NOMIZU, M ROLLER, PP WOLF, G CASE, R SHOELSON, SE TI NONHYDROLYZABLE PHOSPHOTYROSYL MIMETICS FOR THE PREPARATION OF PHOSPHATASE-RESISTANT SH2 DOMAIN INHIBITORS SO BIOCHEMISTRY LA English DT Article ID TYROSINE-PHOSPHORYLATED PEPTIDES; SOLID-PHASE SYNTHESIS; SRC HOMOLOGY-2 DOMAIN; SIGNALING COMPLEXES; INSULIN-RECEPTOR; BINDING; 3-KINASE; ANALOGS; IRS-1; TRANSDUCTION AB Src homology 2 (SH2) domains participate in protein tyrosine kinase (PTK)-mediated cellular signal transduction through their ability to bind with high affinity to phosphotyrosyl (pTyr)-bearing protein sequences. Although peptides containing pTyr competitively inhibit the binding between phosphoproteins and cognate SH2 proteins in a sequence-specific manner, such peptides are rapidly dephosphorylated by cellular phosphatases. We now describe our efforts to develop SR2 inhibitory peptides containing phosphatase-resistant pTyr Surrogates. The parent compound, (phosphonomethyl)phenylalanine (Pmp),is a phosphonate-based mimetic of pTyr in which the phosphate ester oxygen (>COPO3H2) has been replaced by a methylene unit (>CCX(2)PO(3)H(2), X(2) = H-2) Pmp analogues bearing fluorine (X(2) = H, F or X(2) = F-2) or hydroxyl (X(2) = H, OH) substituents on the phosphonate alpha-methylene carbon have been prepared and incorporated into peptides for use as SH2 domain inhibitors. In an assay using the C-terminal SH2 domain of phosphatidylinositol (PI) 3-kinase, peptides having a GXVPML sequence [where X = pTyr, Pmp, hydroxy-Pmp (HPmp), monofluoro-Pmp (FPmp), and difluoro-Pmp (F(2)Pmp)] exhibited binding potency in the order HPmp < Pmp < FPmp < F(2)Pmp = pTyr. Distinct peptide sequences which bind selectively with Src and Grb2 SH2 domains were also prepared with pTyr and F(2)Pmp. The F(2)Pmp peptides bound with high (0.2- to 5-fold) relative affinity, compared to analogous pTyr peptides. We conclude that peptides containing F(2)Pmp bind to SH2 domains with high affinity and specificity and, being resistant to cellular phosphatases, should provide a generally useful tool for disrupting SH2 domain-mediated signaling pathways in intact cells. C1 HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. RP BURKE, TR (reprint author), NCI,DCT,DEV THERAPEUT PROGRAM,MED CHEM LAB,BLDG 37,ROOM 5C06,BETHESDA,MD 20892, USA. RI Burke, Terrence/N-2601-2014 FU NIDDK NIH HHS [DK08366] NR 35 TC 192 Z9 193 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 31 PY 1994 VL 33 IS 21 BP 6490 EP 6494 DI 10.1021/bi00187a015 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NP218 UT WOS:A1994NP21800015 PM 7515682 ER PT J AU KASPRZAK, KS DIWAN, BA RICE, JM AF KASPRZAK, KS DIWAN, BA RICE, JM TI IRON ACCELERATES WHILE MAGNESIUM INHIBITS NICKEL-INDUCED CARCINOGENESIS IN THE RAT-KIDNEY SO TOXICOLOGY LA English DT Article DE MAGNESIUM; IRON; NICKEL CARCINOGENESIS ID RENAL CANCERS; INTRARENAL INJECTION; SUBSULFIDE; ERYTHROCYTOSIS AB Effects of magnesium basic carbonate (MgCarb) and metallic iron powder (Fe-0) on nickel subsulfide (Ni3S3)-induced carcinogenesis were studied in kidneys of male F344/NCr rats. The rats, 20-40/group, received injections of Ni3S2 alone (62 pmol Ni) or with equimolar doses of MgCarb or Fe-0 into the renal cortex of each pole of the right kidney. Control rats were given MgCarb, Fe-0, or 0.1 mi of 50% aqueous glycerol, the injection vehicle. Final incidence of renal tumors 2 years after the injection of Ni,S, alone or mixed with Fe-0 was 60%. However, rats given Ni3S2+Fe-0 developed renal tumors much more rapidly. In contrast, the incidence of renal tumors in rats given Ni3S2+MgCarb was only 20% (P < 0.01 vs. Ni3S2 alone). No kidney tumors were observed in the control rats. Between weeks 4 and 32 post injection, Ni3S2 alone caused erythrocytosis. This effect was attenuated by Fe-0, but not by MgCarb. Hence, there is no firm correlation between carcinogenic activity of nickel and its ability to induce erythropoiesis. All kidney tumors were of mesenchymal cell origin and resembled the sarcomatous variant of the classic rat renal mesenchymal tumor. Some of them metastasized to the lungs and other organs. In 3-35 days post-injection, kidneys of rats treated with Ni3S2 alone showed moderate to extensive necrosis, inflammation, fibrosis, anddegenerative and regenerative proliferative changes in the proximal tubular epithelium at the injection site. Similar, but more severe and multifocal changes were observed in the kidneys of Ni3S2+Fe-0-treated rats. The necrosis was less severe in kidneys injected with Ni3S2+MgCarb, but fibrosis and degenerative and regenerative changes in proximal tubular epithelium were similar to those observed in other treatment groups. Ni3S2 deposits were seen inside macrophages and proximal tubular epithelial cells of Ni3S2 and Ni3S2+Fe-0-treated kidneys more frequently than in Ni3S2+MgCarb-treated kidneys. Thus, magnesium antagonizes nickel carcinogenesis in the rat kidney while iron tends to enhance it. This result may be related to respectively attenuating or enhancing effects of magnesium and iron on the inflammatory response to Ni3S2. C1 NCI,FREDERICK CANC RES & DEV CTR,DYNCORP,PROGRAM RESOURCES INC,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. RP KASPRZAK, KS (reprint author), NCI,DIV CANC ETIOL,COMPARAT CARCINOGENESIS LAB,BLDG 538,RM 205,FREDERICK,MD 21702, USA. NR 18 TC 22 Z9 23 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD MAY 31 PY 1994 VL 90 IS 1-2 BP 129 EP 140 DI 10.1016/0300-483X(94)90211-9 PG 12 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA NU242 UT WOS:A1994NU24200012 PM 8023338 ER PT J AU BATTAINI, F GARBILLO, G BERGAMASCHI, S PARENTI, M WETSEL, WC GOVONI, S TRABUCCHI, M AF BATTAINI, F GARBILLO, G BERGAMASCHI, S PARENTI, M WETSEL, WC GOVONI, S TRABUCCHI, M TI REGULATION OF PROTEIN-KINASE-C IN NG108-15 CELL-DIFFERENTIATION SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID NEURO-BLASTOMA CELLS; PHORBOL ESTER BINDING; NEUROBLASTOMA-CELLS; MESSENGER-RNAS; MORPHOLOGICAL-DIFFERENTIATION; EPSILON-ISOFORM; DOWN-REGULATION; RETINOIC ACID; HYBRID-CELLS; CYCLIC-AMP AB The involvement of PKC in NG108-15 cell differentiation was investigated. Differentiation with dBcAMP was associated with a decrease in total cellular phorbol ester binding. The histone-directed PKC activity was decreased in the soluble fraction. Northern and Western blotting revealed the presence of only PKC alpha but not PKC beta and PKC gamma among the calcium-dependent isoforms. Differentiation induced a decrease of cytosolic PKC alpha immunoreactivity, with no changes of mRNA content or appearance of PKC beta and PKC gamma isoforms. The low levels of PKC alpha in the soluble fraction suggest that the mRNA for this species is less efficiently translated in differentiated NG108-15 cells. The data suggest that downregulation of PKC alpha protein and kinase activity are associated with induction of neuronal morphology in NG108-15 cells. (C) 1994 Academic Press, Inc. C1 UNIV ROMA TOR VERGATA,DEPT EXPTL MED & BIOCHEM SCI,ROME,ITALY. UNIV MILAN,DEPT PHARMACOL CHEMOTHERAPY & MED TOXICOL,MILAN,ITALY. NIEHS,CELLULAR & MOLEC PHARMACOL LAB,RES TRIANGLE PK,NC 27709. RP BATTAINI, F (reprint author), UNIV MILAN,INST PHARMACOL SCI,VIA BALZARETTI 9,I-20133 MILAN,ITALY. RI Battaini , Fiorenzo/H-2617-2012; Govoni, Stefano/K-2965-2015 OI Govoni, Stefano/0000-0002-7243-6837 NR 34 TC 13 Z9 14 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 30 PY 1994 VL 201 IS 1 BP 135 EP 142 DI 10.1006/bbrc.1994.1679 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NN877 UT WOS:A1994NN87700019 PM 8198566 ER PT J AU DURSTIN, M GAO, JL TIFFANY, HL MCDERMOTT, D MURPHY, PM AF DURSTIN, M GAO, JL TIFFANY, HL MCDERMOTT, D MURPHY, PM TI DIFFERENTIAL EXPRESSION OF MEMBERS OF THE N-FORMYLPEPTIDE RECEPTOR GENE-CLUSTER IN HUMAN PHAGOCYTES SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID FORMYL PEPTIDE RECEPTOR; XENOPUS OOCYTES; CDNA; CLONING; C5A AB The human genes for two N-formylpeptide phagocyte chemoattractant receptors (gene symbols FPR1 and FPRL1) cross-hybridize with each other and with FPRL2, a human gene of unknown expression and function. The FPR1 product is similar to 1000-fold more sensitive than the FPRL1 product to N-formylpeptides. We now report cloning of the first cDNA for FPRL2 and the first description of the RNA distribution in normal human phagocytes for all three genes. FPR1 and FPRL1 are expressed in neutrophils and monocytes. In contrast, FPRL2 RNA is detectable in monocytes but not in neutrophils, and its product could not be activated by N-formylpeptides. Thus, the regulation of FPRL2 gene expression in vivo differs from FPR1 and FPRL1. (C) 1994 Academic Press, Inc. C1 NIAID,HOST DEFENSES LAB,BETHESDA,MD 20892. RP DURSTIN, M (reprint author), UNIV CONNECTICUT,CTR HLTH,DEPT PHYSIOL,FARMINGTON,CT, USA. OI McDermott, David/0000-0001-6978-0867 FU NIAID NIH HHS [AI-28810-02] NR 13 TC 75 Z9 77 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 30 PY 1994 VL 201 IS 1 BP 174 EP 179 DI 10.1006/bbrc.1994.1685 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NN877 UT WOS:A1994NN87700025 PM 8198572 ER PT J AU VANDENBRULE, FA PRICE, J SOBEL, ME LAMBOTTE, R CASTRONOVO, V AF VANDENBRULE, FA PRICE, J SOBEL, ME LAMBOTTE, R CASTRONOVO, V TI INVERSE EXPRESSION OF 2 LAMININ-BINDING PROTEINS, 67LR AND GALECTIN-3, CORRELATES WITH THE INVASIVE PHENOTYPE OF TROPHOBLASTIC TISSUE SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID EXTRACELLULAR-MATRIX; IV COLLAGENASE; MESSENGER-RNA; RECEPTOR; CARCINOMA; LECTIN; CELLS AB Tumor invasion of host tissues and trophoblastic penetration of the endometrium share common biological features. Both processes involve the invasion of basement membranes, an event that is initiated by adhesion of cancer or trophoblast cells to basement membrane components and particularly to laminin. Adhesion to this latter glycoprotein is mediated through a variety of cell surface receptors. We have previously shown that the 67 kD Laminin Receptor (67LR) and a 31 kD Human Laminin Binding Protein, recently renamed galectin-3, are inversely modulated as the invasive phenotype of cancer cells progresses, with up regulation of the former, and down regulation of the latter, respectively. In this study, we examined the expression of these two proteins in 27 human trophoblastic specimens at different gestational ages using Northern and Western blot techniques. Expression of the 67LR increased from 7 weeks to a maximum at 12 weeks, when invasion is maximal, and then decreased. Expression of galectin-3 was inversely modulated by the gestational age, with a minimum expression at 12 weeks. Our data demonstrate that invasive trophoblast displays the same pattern of laminin binding proteins expression than invasive cancer cells, and further demonstrates that invasion of the extracellular matrix by trophoblast and cancer cells share common molecular mechanisms. (C) 1994 Academic Press, Inc. C1 UNIV LIEGE,DEPT OBSTET & GYNECOL,LIEGE,BELGIUM. NCI,PATHOL LAB,MOLEC PATHOL LAB,BETHESDA,MD 20892. RP VANDENBRULE, FA (reprint author), UNIV LIEGE,METASTASIS RES LAB,PATHOL B23,3RD FLOOR,B-4000 LIEGE 1,BELGIUM. NR 14 TC 32 Z9 33 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 30 PY 1994 VL 201 IS 1 BP 388 EP 393 DI 10.1006/bbrc.1994.1713 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NN877 UT WOS:A1994NN87700053 PM 8198600 ER PT J AU LIU, XT STEWART, CA KING, RL DANNER, DA DELLORCO, RT MCCLUNG, JK AF LIU, XT STEWART, CA KING, RL DANNER, DA DELLORCO, RT MCCLUNG, JK TI PROHIBITIN EXPRESSION DURING CELLULAR SENESCENCE OF HUMAN-DIPLOID FIBROBLASTS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID RETINOBLASTOMA GENE-PRODUCT; DNA-SYNTHESIS; MICROINJECTION SYSTEM; MESSENGER-RNA; RAT-LIVER; PROTEIN; PHOSPHORYLATION; INHIBITORS; ASSAY; P53 AB Prohibitin is an evolutionarily conserved gene postulated to possess tumor suppressor activity and to contribute to the limited lifespan of human diploid fibroblast-like cells. Prohibitin mRNA and protein expression and its ability to become post-translationally modified were determined in human diploid fibroblast-like cells of different in vitro ages. The expression of prohibitin mRNA and protein changes little with increasing in vitro age; however, its protein product is post-synthetically modified in younger but not older cells. These results suggest that prohibitin is similar to the retinoblastoma gene product whose anti-proliferative activity remains active in older cells because it is not post-synthetically modified. (C) 1994 Academic Press, Inc. C1 NIA,GENET MOLEC LAB,BALTIMORE,MD 21224. RP LIU, XT (reprint author), OKLAHOMA MED RES FDN,NOBLE CTR BIOMED RES,OKLAHOMA CITY,OK 73104, USA. NR 36 TC 42 Z9 43 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 30 PY 1994 VL 201 IS 1 BP 409 EP 414 DI 10.1006/bbrc.1994.1716 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NN877 UT WOS:A1994NN87700056 PM 8198603 ER PT J AU ICHIKAWA, H DEGUCHI, T MITANI, S NAKAGO, T JACOBOWITZ, DM YAMAAI, T SUGIMOTO, T AF ICHIKAWA, H DEGUCHI, T MITANI, S NAKAGO, T JACOBOWITZ, DM YAMAAI, T SUGIMOTO, T TI NEURAL PARVALBUMIN AND CALRETININ IN THE TOOTH-PULP SO BRAIN RESEARCH LA English DT Article DE PARVALBUMIN; CALRETININ; TACHYKININ; SENSORY NERVE; TOOTH PULP; RAT ID CARBONIC-ANHYDRASE ACTIVITY; DORSAL-ROOT GANGLIA; PRIMARY TRIGEMINAL NEURONS; P-LIKE IMMUNOREACTIVITY; GENE-RELATED PEPTIDE; CELL-SIZE ANALYSIS; IMMUNOHISTOCHEMICAL LOCALIZATION; HORSERADISH-PEROXIDASE; CENTRAL PROJECTIONS; MANDIBULAR MOLAR AB Parvalbumin- and calretinin-immunoreactivities (CR-irs) were examined in the molar tooth pulp of the rat using immunohistochemical methods. CR-ir fibers were further classified based on the tachykinin-ir revealed by a double immunofluorescence method. The rat root pulp contained three types of nerve fibers; parvalbumin-ir smooth fibers, CR-ir (TK-negative) smooth fibers and CR-ir (TK-ir) varicose fibers. These fibers projected toward the roof of the pulp chamber and pulp horn without marked ramification. In the subodontoblastic layer at the roof of the pulp chamber and pulp horn, parvalbumin-ir smooth fibers repeatedly ramified and extended varicose terminals into the odontoblastic layer. CR-ir (TK-negative) smooth fibers reached the subodontoblastic layer without marked ramification and gave rise to varicose terminals that appeared to terminate within the subodontoblastic layer. On the other hand, CR-ir (TK-ir) varicose fibers proceeded to the subodontoblastic layer at the roof of the pulp chamber and pulp horn, where they ramified and penetrated the odontoblastic layer. The present study indicates that the rat tooth pulp contains myelinated parvalbumin-ir and CR-ir (TK-negative) fibers, and unmyelinated CR-ir (TK-ir) fibers, and that they project varicose terminals to the subodontoblastic and odontoblastic layers. The central projection sites of these sensory fibers have yet to be revealed. C1 OKAYAMA UNIV,SCH DENT,DEPT ORAL ANAT 2,OKAYAMA 700,JAPAN. OKAYAMA UNIV,SCH DENT,DEPT ORTHODONT,OKAYAMA 700,JAPAN. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. NR 34 TC 36 Z9 36 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 30 PY 1994 VL 647 IS 1 BP 124 EP 130 DI 10.1016/0006-8993(94)91406-0 PG 7 WC Neurosciences SC Neurosciences & Neurology GA NN543 UT WOS:A1994NN54300016 PM 8069694 ER PT J AU WERNER, MH CLORE, GM GRONENBORN, AM KONDOH, A FISHER, RJ AF WERNER, MH CLORE, GM GRONENBORN, AM KONDOH, A FISHER, RJ TI REFOLDING PROTEINS BY GEL-FILTRATION CHROMATOGRAPHY SO FEBS LETTERS LA English DT Article DE PROTEIN REFOLDING; GEL FILTRATION; TECHNIQUE ID DNA AB We have developed a facile means for the refolding of miligram quantities of purified proteins that employs gel filtration chromatography. We demonstrate by electrophoretic mobility shift and NMR spectroscopy that human ETS-1 protein, bovine ribonucelase A and E. coli integration host factor can be refolded into the native conformation using this technique. We have extended this strategy to the preparation of miligram quantities of macromolecular complexes suitable for structural analysis by NMR spectroscopy or X-ray crystallography. The diverse challenges to overcome in refolding these proteins illustrates the potential of this technique as a general approach for recovery of recombinant proteins produced as insoluble inclusion bodies. C1 NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. PRI DYNCORP,NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21701. RI Clore, G. Marius/A-3511-2008; Fisher, Robert/B-1431-2009 OI Clore, G. Marius/0000-0003-3809-1027; NR 7 TC 82 Z9 99 U1 6 U2 8 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 30 PY 1994 VL 345 IS 2-3 BP 125 EP 130 DI 10.1016/0014-5793(94)00401-3 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA NP563 UT WOS:A1994NP56300007 PM 8200443 ER PT J AU BRINKMANN, U PASTAN, I AF BRINKMANN, U PASTAN, I TI IMMUNOTOXINS AGAINST CANCER SO BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER LA English DT Review ID RICIN-A-CHAIN; PSEUDOMONAS EXOTOXIN-A; POKEWEED ANTIVIRAL PROTEIN; EPIDERMAL GROWTH-FACTOR; SEVERE COMBINED IMMUNODEFICIENCY; RECOMBINANT FUSION PROTEIN; CHRONIC LYMPHOCYTIC-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; RESHAPING HUMAN-ANTIBODIES; SITE-DIRECTED MUTAGENESIS C1 NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 208 TC 128 Z9 128 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-419X J9 BBA-REV CANCER JI Biochim. Biophys. Acta-Rev. Cancer PD MAY 27 PY 1994 VL 1198 IS 1 BP 27 EP 45 DI 10.1016/0304-419X(94)90004-3 PG 19 WC Biochemistry & Molecular Biology; Biophysics; Oncology SC Biochemistry & Molecular Biology; Biophysics; Oncology GA NQ917 UT WOS:A1994NQ91700003 PM 8199194 ER PT J AU MARGOLIS, N HOGAN, D CIEPLAK, W SCHWAN, TG ROSA, PA AF MARGOLIS, N HOGAN, D CIEPLAK, W SCHWAN, TG ROSA, PA TI HOMOLOGY BETWEEN BORRELIA-BURGDORFERI OSPC AND MEMBERS OF THE FAMILY OF BORRELIA-HERMSII VARIABLE MAJOR PROTEINS SO GENE LA English DT Note DE SPIROCHETE; OUTER SURFACE PROTEINS; LYME DISEASE; TICK-BORNE RELAPSING FEVER; PROMOTER ID LYME-DISEASE SPIROCHETE; ANTIGENIC VARIATION; ESCHERICHIA-COLI; EXPRESSION; GENE; TAXONOMY; PLASMID AB Synthesis of the Borrelia burgdorferi outer surface protein C (OspC) is quite variable. We have cloned and sequenced the ospC gene from B. burdorferi isolate CA-11.2A, a clone in which ospC expression varies. The 5' flanking region of the gene contains at least two consensus promoter regions, as well as two large overlapping inverted repeats. Sequence comparison to other OspC proteins indicated that the CA-11.2A OspC is as closely related to OspC from two different genospecies of Lyme disease spirochetes as it is to OspC from the prototype B. burdorferi strain, B31. Comparisons of the OspC amino acid (aa) sequence with those in aa sequence databases revealed partial identity with the variable major proteins Vmp3 and Vmp24 of B. hermsii, a causative agent of tick-borne relapsing fever. An ospC probe hybridized to B. hermsii restriction fragments and linear plasmids that also were recognized by the vmp3 and vmp24 probes. OspC and these Vmp appear to be related, but their synthesis is regulated differently in the two species of spirochetes. This represents a fascinating example of the evolution of the number, position, regulation and perhaps function of homologous genes in two related pathogens. These parameters may relate to characteristic properties of the pathogens and their separate tick vectors. C1 NIAID, ROCKY MT LABS, MICROBIAL STRUCT & FUNCT LAB, HAMILTON, MT 59840 USA. NIAID, ROCKY MT LABS, VECTORS & PATHOGENS LAB, HAMILTON, MT 59840 USA. NR 26 TC 49 Z9 49 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 EI 1879-0038 J9 GENE JI Gene PD MAY 27 PY 1994 VL 143 IS 1 BP 105 EP 110 DI 10.1016/0378-1119(94)90613-0 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA NR052 UT WOS:A1994NR05200017 PM 8200524 ER PT J AU BUBB, MR SENDEROWICZ, AMJ SAUSVILLE, EA DUNCAN, KLK KORN, ED AF BUBB, MR SENDEROWICZ, AMJ SAUSVILLE, EA DUNCAN, KLK KORN, ED TI JASPLAKINOLIDE, A CYTOTOXIC NATURAL PRODUCT, INDUCES ACTIN POLYMERIZATION AND COMPETITIVELY INHIBITS THE BINDING OF PHALLOIDIN TO F-ACTIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID SPONGE AB Jasplakinolide, a naturally occurring cyclic peptide from the marine sponge, Jaspis johnstoni, has both fungicidal and antiproliferative activity. We now report that this peptide is a potent inducer of actin polymerization in vitro. The peptide has a much greater effect on Mg2+-actin than on Ca2+-actin. Competitive binding studies using rhodamine-phalloidin suggest that jasplakinolide binds to F-actin competitively with phalloidin with a dissociation constant of approximately 15 nM. This compares favorably to the previously reported IC50 of 35 nn for the antiproliferative effect of jasplakinolide on PC3 prostate carcinoma cells. The binding curve suggests that nearest neighbor positive cooperativity influences the binding of jasplakinolide (and perhaps also phalloidin) to F actin. These results imply that jasplakinolide may exert its cytotoxic effect in vivo by inducing actin polymerization and/or stabilizing pre-existing actin filaments. C1 NHLBI, CELL BIOL LAB, BETHESDA, MD 20892 USA. NCI, DIV CANC TREATMENT, DEV THERAPEUT PROGRAM, BIOL CHEM LAB, BETHESDA, MD 20892 USA. RI Korn, Edward/F-9929-2012; Duncan, Kimberly /C-3655-2013 NR 22 TC 559 Z9 563 U1 3 U2 17 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 27 PY 1994 VL 269 IS 21 BP 14869 EP 14871 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NP738 UT WOS:A1994NP73800006 PM 8195116 ER PT J AU TAOUIS, M LEVYTOLEDANO, R ROACH, P TAYLOR, SI GORDEN, P AF TAOUIS, M LEVYTOLEDANO, R ROACH, P TAYLOR, SI GORDEN, P TI STRUCTURAL BASIS BY WHICH A RECESSIVE MUTATION IN THE ALPHA-SUBUNIT OF THE INSULIN-RECEPTOR AFFECTS INSULIN BINDING SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GROWTH FACTOR-I; HIGH-AFFINITY; BETA-SUBUNIT; PLASMA-MEMBRANE; LIGAND-BINDING; KINASE; CELLS; AUTOPHOSPHORYLATION; RESISTANCE; ANTIBODIES AB Recently, a mutation substituting Leu for Ser(323) in the alpha-subunit of the human insulin receptor has been identified in an insulin-resistant patient. The Leu(323) mutation leads to a severe impairment in insulin binding without significantly altering the processing or cell surface expression of the receptor. In order to study how alpha beta half-receptors interact to form the insulin-binding site, we cotransfected NIH-3T3 cells with two insulin receptor cDNA constructs: a truncated insulin receptor lacking the C-terminal 43 amino acids (Delta 43) and the full-length Leu(323) mutant receptor. A clonal cell line from cotransfected cells expresses a hybrid receptor consisting of a Leu(323) half-receptor and a Delta 43 half-receptor. We demonstrate that the Leu(323)-Delta 43 hybrid receptor binds insulin with high affinity. Furthermore, by cross-linking I-125-insulin to immobilized hybrid receptors, we show that only the alpha beta(Delta) half of the hybrid receptor binds insulin. Since the isolated half-insulin receptor has low affinity for insulin, this suggests that the addition of even a non-binding alpha-subunit can result in high affinity binding to the holoreceptor (alpha alpha(mut)beta(Delta)beta). Both beta and beta(Delta)-subunits of the Leu(323)-Delta 43 hybrid receptor are phosphorylated in vivo and in vitro in an insulin-dependent manner, suggesting an intramolecular transphosphorylation mechanism and that the presence of the Leu(323) mutant receptor that lacks an intrinsic high affinity binding site does not prevent the associated beta-subunit from functioning either as a tyrosine kinase or as a phosphate acceptor in the hybrid insulin receptor molecule (alpha alpha(mut)beta(Delta)beta). Furthermore, we show that the hybrid receptor can phosphorylate insulin receptor substrate-1 (IRS-1) in response to insulin and can be coimmunoprecipitated together with IRS-1 by anti-IRS-1 antibody. C1 NIDDK,DIABET BRANCH,BETHESDA,MD 20892. INRA,RECH AVICOLES STN,F-37380 NOUZILLY,FRANCE. NR 28 TC 23 Z9 23 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 27 PY 1994 VL 269 IS 21 BP 14912 EP 14918 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NP738 UT WOS:A1994NP73800013 PM 8195122 ER PT J AU KAWAMOTO, S AF KAWAMOTO, S TI EVIDENCE FOR AN INTERNAL REGULATORY REGION IN A HUMAN NONMUSCLE MYOSIN HEAVY-CHAIN GENE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DIHYDROFOLATE-REDUCTASE PROMOTER; AMINO-ACID-SEQUENCES; SMOOTH-MUSCLE; MESSENGER-RNAS; TRANSCRIPTION INITIATION; DIFFERENTIAL EXPRESSION; CELLULAR MYOSIN; NERVOUS-SYSTEM; SV40 ENHANCER; DNA-SEQUENCE AB We have isolated genomic clones which encode the promoter and flanking region of human nonmuscle myosin heavy chain (MHC)-A. The sequence of this region shows many features typical of a housekeeping gene; there is no TATA element and no functional CAAT box. The GC content is high, having an average GC content of 74% in the 600 base pairs (bp) surrounding the transcriptional start sites, and multiple GC boxes (putative Sp1 binding sites) are present. A number of nucleotide sites are utilized for the initiation of transcription. Promoter activity was monitored using luciferase as a reporter following transient transfection into NIH 3T3 cells. Analysis of 5' and 3' deletion mutants in the promoter region defines the core promoter as extending from nucleotide -112 to +61, where +1 is a major transcriptional start site. An essential sequence for core promoter activity resides in the 36-bp region from -77 to -112 which includes a single potential AP-2 binding site and a single potential Spl binding site. The region just downstream from the transcriptional start site (between +62 and +257) was found to be involved in cell type-specific activation of nonmuscle MHC-A gene expression. The increase in luciferase activity due to this proximal downstream region is approximately 15-fold in NIH 3T3 cells, but no increase was observed in C2C12 myotubes and neuroblastoma cells. This 196-bp region, which consists of 100 bp from exon 1 and 96 bp from intron 1, functions in a position- and orientation-dependent manner. Quantitation of luciferase mRNA content driven by the MHC-A promoter, using both competitive polymerase chain reaction and RNase protection assays, revealed that the increase seen in luciferase mRNA due to the 196-bp fragment is approximately 5-fold in NIH 3T3 cells. This only accounts for about one-third of the total increase seen in luciferase activity (protein amounts). Thus, this proximal downstream region appears to activate gene expression in MH 3T3 cells via both pretranslational (transcription and/or mRNA stability) and translational mechanisms. RP KAWAMOTO, S (reprint author), NHLBI,MOLEC CARDIOL LAB,BETHESDA,MD 20892, USA. NR 49 TC 18 Z9 18 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 27 PY 1994 VL 269 IS 21 BP 15101 EP 15110 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NP738 UT WOS:A1994NP73800040 PM 8195147 ER PT J AU GUMUCIO, DL SHELTON, DA BLANCHARDMCQUATE, K GRAY, T TARLE, S HEILSTEDTWILLIAMSON, H SLIGHTOM, JL COLLINS, F GOODMAN, M AF GUMUCIO, DL SHELTON, DA BLANCHARDMCQUATE, K GRAY, T TARLE, S HEILSTEDTWILLIAMSON, H SLIGHTOM, JL COLLINS, F GOODMAN, M TI DIFFERENTIAL PHYLOGENETIC FOOTPRINTING AS A MEANS TO IDENTIFY BASE CHANGES RESPONSIBLE FOR RECRUITMENT OF THE ANTHROPOID GAMMA-GENE TO A FETAL EXPRESSION PATTERN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EPSILON-GLOBIN GENE; STAGE SELECTOR ELEMENT; AMINO-ACID SEQUENCES; LOCUS-CONTROL REGION; HEREDITARY PERSISTENCE; 5'-FLANKING REGION; NUCLEAR-PROTEIN; FACTOR-BINDING; PROMOTER; HPFH AB Expression of the anthropoid (simian) gamma gene in fetal life contrasts with the exclusively embryonic expression pattern of the gamma-like genes of other eutherian mammals. To elucidate the factors responsible for this change in expression pattern, we utilized a strategy called differential phylogenetic footprinting (DPF). This strategy entails the following: (a) identification, within regulatory regions, of the gamma promoter, of individual nucleotides that differ between human (fetal expression), and galago (embryonic expression) gamma genes, (b) analysis of the effect of these nucleotide differences on the binding of nuclear proteins to human and galago sequences, and (c) assessment of the functional consequences of these binding changes in expression assays. The DPF analysis revealed several proteins that bind upstream from the CCAAT motif in the galago gamma promoter but do not bind to the corresponding region of the human gamma promoter. In transfection assays, binding of these proteins is associated with erythroid-specific repression of promoter strength. Binding sites for these proteins also occur near the CCAAT box of other embryonically expressed genes, including rabbit, mouse, and dwarf lemur gamma genes and the human epsilon globin gene. These data are consistent with the hypothesis that sequence changes near the proximal CCAAT box in the ancestral simian gamma gene may have facilitated a novel expression pattern by reducing the binding of repressors that act in the fetal stage. C1 UNIV MICHIGAN, HOWARD HUGHES MED INST, ANN ARBOR, MI 48109 USA. WAYNE STATE UNIV, SCH MED, DEPT ANAT & CELL BIOL, DETROIT, MI 48201 USA. UPJOHN CO, MOLEC BIOL UNIT 7242, KALAMAZOO, MI 49007 USA. NIH, NATL CTR HUMAN GENOME RES, BETHESDA, MD 20892 USA. RP GUMUCIO, DL (reprint author), UNIV MICHIGAN, SCH MED, DEPT ANAT & CELL BIOL, 5793A MED SCI 2, ANN ARBOR, MI 48109 USA. FU NCRR NIH HHS [MO1-RR00042]; NHLBI NIH HHS [HL-33940] NR 42 TC 39 Z9 39 U1 2 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 27 PY 1994 VL 269 IS 21 BP 15371 EP 15380 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NP738 UT WOS:A1994NP73800077 PM 7515056 ER PT J AU AGUILAR, F HARRIS, CC SUN, T HOLLSTEIN, M CERUTTI, P AF AGUILAR, F HARRIS, CC SUN, T HOLLSTEIN, M CERUTTI, P TI GEOGRAPHIC-VARIATION OF P53 MUTATIONAL PROFILE IN NONMALIGNANT HUMAN LIVER SO SCIENCE LA English DT Article ID HEPATITIS-B VIRUS; HUMAN HEPATOCELLULAR CARCINOMAS; TUMOR-SUPPRESSOR GENE; 17P ALLELIC DELETIONS; CODON 249; AFLATOXIN; CHINA; 8-HYDROXYGUANINE; ABERRATIONS; MUTAGENESIS AB Fifty-eight percent of hepatocellular carcinomas (HCCs) from Qidong, China, contain an AGG to AGT mutation at codon 249 of the p53 tumor suppressor gene, a mutation that is rarely seen in HCCs from Western countries. The population of Qidong is exposed to high levels of aflatoxin B-1 (AFB(1)), a fungal toxin that has been shown to induce the same mutation in cultured human HCC cells. To investigate the role of AFB(1) and of these p53 mutations in hepatocarcinogenesis, normal liver samples from the United States, Thailand, and Qidong (where AFB(1) exposures are negligible, low, and high, respectively) were examined for p53 mutations. The frequency of the AGG to AGT mutation at codon 249 paralleled the level of AFB(1) exposure, which supports the hypothesis that this toxin has a causative-and probably early-role in hepatocarcinogenesis. C1 SWISS INST EXPTL CANC RES,DEPT CARCINOGENESIS,CH-1066 EPALINGES,SWITZERLAND. NCI,DIV CANC ETIOL,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. CHINESE ACAD MED SCI,INST CANC,BEIJING 100021,PEOPLES R CHINA. INT AGCY RES CANC,MECH CARCINOGENESIS UNIT,F-69372 LYON 08,FRANCE. NR 36 TC 229 Z9 231 U1 0 U2 3 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD MAY 27 PY 1994 VL 264 IS 5163 BP 1317 EP 1319 DI 10.1126/science.8191284 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NN767 UT WOS:A1994NN76700042 PM 8191284 ER PT J AU SETH, A STERN, LJ OTTENHOFF, THM ENGEL, I OWEN, MJ LAMB, JR KLAUSNER, RD WILEY, DC AF SETH, A STERN, LJ OTTENHOFF, THM ENGEL, I OWEN, MJ LAMB, JR KLAUSNER, RD WILEY, DC TI BINARY AND TERNARY COMPLEXES BETWEEN T-CELL RECEPTOR, CLASS-II MHC AND SUPERANTIGEN IN-VITRO SO NATURE LA English DT Article ID ANTIGEN RECEPTOR; LYMPHOCYTES-T; ENTEROTOXIN-B; PROTEINS; PEPTIDE; RECOGNITION; AFFINITY; HETERODIMERS; SURFACE; ANERGY AB SUPERANTIGENS are proteins that in association with class II major histocompatibility complex (MHC)-bearing cells can stimulate virtually all T cells that express particular classes of the variable beta-domains of the T-cell receptor (TCR)(1). This mechanism of T-cell activation circumvents the usual requirement for peptide-specific MHC recognition. Staphylococcus aureus enterotoxin B (SEB) is a bacterial superantigen that causes food poisoning and shock(2-5). We have characterized the tertiary complex of SEB, a soluble T-cell receptor, and a soluble class II MHC molecule DR1, and the three binary complexes TCR-SEB, SEB-DR1, and the peptide-specific complex DR1-TCR. We report here that in each case the specificity of the interaction among the soluble molecules is the same as observed in biological assays. Native gel electrophoresis and plasmon resonance affinity measurements indicate that SEB-TCR complex can form in the absence of class II MHC and that SEB-TCR interaction increases the binding of DR1. The observation that a superantigen can form complexes with TCR in both the absence and presence of class II MHC may provide a mechanism for its ability to induce anergy in some circumstances and activation in others(6,7) (reviewed in ref. 8). C1 HARVARD UNIV,HOWARD HUGHES MED INST,CAMBRIDGE,MA 02138. NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. IMPERIAL CANC RES FUND,LYMPHOCYTE MOLEC BIOL LAB,LONDON WC2A 3PX,ENGLAND. UNIV LONDON IMPERIAL COLL SCI TECHNOL & MED,ST MARYS HOSP,SCH MED,DEPT IMMUNOL,LONDON W2 1PG,ENGLAND. RP SETH, A (reprint author), HARVARD UNIV,DEPT BIOCHEM & MOLEC BIOL,7 DIVIN AVE,CAMBRIDGE,MA 02138, USA. NR 26 TC 159 Z9 163 U1 0 U2 1 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 26 PY 1994 VL 369 IS 6478 BP 324 EP 327 DI 10.1038/369324a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NN109 UT WOS:A1994NN10900051 PM 8183371 ER PT J AU NAKAMURA, Y RUSSELL, SM MESS, SA FRIEDMANN, M ERDOS, M FRANCOIS, C JACQUES, Y ADELSTEIN, S LEONARD, WJ AF NAKAMURA, Y RUSSELL, SM MESS, SA FRIEDMANN, M ERDOS, M FRANCOIS, C JACQUES, Y ADELSTEIN, S LEONARD, WJ TI HETERODIMERIZATION OF THE IL-2 RECEPTOR BETA-CHAIN AND GAMMA-CHAIN CYTOPLASMIC DOMAINS IS REQUIRED FOR SIGNALING SO NATURE LA English DT Article ID HUMAN INTERLEUKIN-2 RECEPTOR; CELL GROWTH-FACTOR; FUNCTIONAL COMPONENT; DISTINCT; EXPRESSION; CLONING; BINDING; GENE; INVOLVEMENT; RESPONSES AB THE interaction of interleukin-2 (IL-2) and IL-2 receptors critically regulates the T-cell immune response following antigen activation(1,2). IL-2 can signal through high or intermediate affinity receptors which contain IL-2R alpha (refs 3, 4) + beta (refs 5-8) + gamma (ref. 9) or beta + gamma chains, respectively. IL-2R gamma is a common gamma chain, gamma(c), also shared by the IL-7 (ref. 10) and IL-4 (refs 11, 12) receptors, which when mutated results in X-linked severe combined immunodeficiency(13). Using chimaeric receptor constructs together with monoclonal or bispecific antibodies we demonstrate here that IL-2 signalling requires ligand-induced extracellular-domain-mediated heterodimerization of the beta- and gamma(c)-chain cytoplasmic domains. Anti-IL-2R alpha monoclonal antibodies trigger proliferation of cells transfected with chimaeric constructs in which the extracellular domains of IL-2R beta and gamma(c), are replaced by that of IL-2R alpha. Other experiments using chimaeric constructs indicated that IL-2 binds monomerically and monovalently to IL-2R alpha and that the beta-transmembrane domain is not required for receptor chain interactions. Finally, we provide a method for mapping residues in the gamma(c) cytoplasmic domain even in cells that constitutively express gamma(c). C1 NHLBI,PULM & MOLEC IMMUNOL SECT,BETHESDA,MD 20892. INST BIOL,INSERM,U211,F-44035 NANTES,FRANCE. RI Russell, Sarah/B-9341-2009; Adelstein, Stephen/I-7936-2016 OI Russell, Sarah/0000-0001-5826-9641; Adelstein, Stephen/0000-0001-7221-6298 NR 30 TC 278 Z9 284 U1 1 U2 5 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD MAY 26 PY 1994 VL 369 IS 6478 BP 330 EP 333 DI 10.1038/369330a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NN109 UT WOS:A1994NN10900053 PM 8183373 ER PT J AU BRENNER, RA SMITH, GS OVERPECK, MD AF BRENNER, RA SMITH, GS OVERPECK, MD TI DIVERGENT TRENDS IN CHILDHOOD DROWNING RATES, 1971 THROUGH 1988 SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Note ID 5-YEAR TOTAL POPULATION; UNITED-STATES; CHILDREN; COUNTY; PREVENTION; ACCIDENTS; BRISBANE AB Objective.-To examine national age-, race-, and sex-specific trends in unintentional drowning rates among US children aged 0 through 19 years. Design.-National mortality data published by the National Center for Health Statistics and population data from the US Bureau of the Census were used in calculating age-, race-, and sex-specific drowning rates for 1971 through 1988. Time trends were analyzed using Poisson regression techniques. Setting.-United States, 1971 through 1988. Main Outcome Measure.-Rates of death due to unintentional, non-boat-related drowning. Results.-From 1971 through 1988, there were 45 680 unintentional, non-boat-related drowning deaths among 0- through 19-year-olds in the United States. Drowning rates declined sharply in older children (-5.8% per year in 10- through 14-year-olds and -5.4% per year in 15- through 19-year-olds), declined only slightly in toddlers (-1.6% per year in 1- and 2-year-olds), and actually increased in infants (+1.6% per year in those children younger than 1 year). Conclusion.-Drowning rates in toddlers have changed little over time despite the availability of effective prevention strategies such as pool fencing. In older children, drowning rates have declined dramatically despite the lack of clear preventive initiatives. Prevention interventions targeted specifically at the infant and toddler age groups should receive priority. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,CTR INJURY PREVENT,BALTIMORE,MD. RP BRENNER, RA (reprint author), NICHHD,DIV EPIDEMIOL STAT & PREVENT RES,6100 EXECUT BLVD,ROOM 7B03,BETHESDA,MD 20892, USA. OI Smith, Gordon/0000-0002-2911-3071 FU NIAAA NIH HHS [R29AA07700]; PHS HHS [R49/CCR302486-01] NR 32 TC 34 Z9 34 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 25 PY 1994 VL 271 IS 20 BP 1606 EP 1608 DI 10.1001/jama.271.20.1606 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA NL758 UT WOS:A1994NL75800030 PM 8182814 ER PT J AU POMERANTZ, LM BENNETT, J AF POMERANTZ, LM BENNETT, J TI FUNGI AS A CAUSE OF OTITIS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NIAID,BETHESDA,MD. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 25 PY 1994 VL 271 IS 20 BP 1628 EP 1628 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA NL758 UT WOS:A1994NL75800038 ER PT J AU SADOFSKY, MJ HESSE, JE GELLERT, M AF SADOFSKY, MJ HESSE, JE GELLERT, M TI DEFINITION OF A CORE REGION OF RAG-2 THAT IS FUNCTIONAL IN V(D)J RECOMBINATION SO NUCLEIC ACIDS RESEARCH LA English DT Article ID JOINING SIGNALS; B-CELLS; GENES; EXPRESSION; SEQUENCE; MICE AB The products of the RAG-1 and RAG-2 genes cooperate to allow V(D)J recombination in lymphoid and non-lymphoid cells. As one step toward understanding the role of RAG-2, we have constructed mutated RAG-2 genes and examined their ability to support recombination of plasmid substrates in a fibroblast cell line. The mutations define essential and dispensable parts of the RAG-2 gene. Mutations in the N-terminal part eliminate almost all activity. In the central region of the protein, some but not all local alterations still allow recombination. On the other hand, proteins with large deletions from the C-terminal end, including one truncated by 25%, still retain activity, even though this part of the protein is highly conserved between species. Similar results were obtained with substrates that retain either a signal joint or a coding joint, or perform an inversion. Thus all basic features of V(D)J joining are retained in a RAG-2 protein with only the first 75% of the sequence. C1 NIDDK,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 21 TC 133 Z9 134 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 1994 VL 22 IS 10 BP 1805 EP 1809 DI 10.1093/nar/22.10.1805 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NQ605 UT WOS:A1994NQ60500003 PM 8208603 ER PT J AU PARK, HS DAVIES, MV LANGLAND, JO CHANG, HW NAM, YS TARTAGLIA, J PAOLETTI, E JACOBS, BL KAUFMAN, RJ VENKATESAN, S AF PARK, HS DAVIES, MV LANGLAND, JO CHANG, HW NAM, YS TARTAGLIA, J PAOLETTI, E JACOBS, BL KAUFMAN, RJ VENKATESAN, S TI TAR RNA-BINDING PROTEIN IS AN INHIBITOR OF THE INTERFERON-INDUCED PROTEIN-KINASE PKR SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DOUBLE-STRANDED-RNA; IMMUNODEFICIENCY-VIRUS TYPE-1; INITIATION FACTOR-II; RESPONSIVE REGION RNA; TRANSLATIONAL CONTROL; MESSENGER-RNAS; ALPHA-SUBUNIT; MALIGNANT TRANSFORMATION; CELLULAR INHIBITOR; 3T3-F442A CELLS AB A cDNA encoding a double-stranded-RNA (dsRNA)-binding protein was isolated by screening a HeLa cell cDNA expression library for proteins that bind the HIV-1 Rev-responsive-element RNA. The cDNA encoded a protein that was identical to TRBP, the previously reported cellular protein that binds the transactivation response element (TAR) RNA of human immunodeficiency virus type 1. TRBP inhibited phosphorylation of the interferon-induced ribosome-associated protein kinase ERR and of the eukaryotic translation initiation factor eIF-2 alpha in a transient-expression system in which the translation of a reporter gene was inhibited by the localized activation of ERR. TRBP expression in HeLa cells complemented the growth and protein-synthesis defect of a vaccinia virus mutant lacking the expression of the dsRNA-binding protein E3L. These results implicate TRBP as a cellular regulatory protein that binds RNAs containing specific secondary structure(s) to mediate the inhibition of PKR activation and stimulate translation in a localized manner. C1 NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. GENET INST INC,DEPT MOLEC & CELLULAR GENET,CAMBRIDGE,MA 02140. ARIZONA STATE UNIV,DEPT MICROBIOL,TEMPE,AZ 85287. ARIZONA STATE UNIV,GRAD PROGRAM CELLULAR & MOLEC BIOL,TEMPE,AZ 85287. VIROGENET CORP,TROY,NY 12180. NR 52 TC 148 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 24 PY 1994 VL 91 IS 11 BP 4713 EP 4717 DI 10.1073/pnas.91.11.4713 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NN214 UT WOS:A1994NN21400023 PM 7515177 ER PT J AU GARCIACALVO, M KNAUS, HG GARCIA, ML KACZOROWSKI, GJ KEMPNER, ES AF GARCIACALVO, M KNAUS, HG GARCIA, ML KACZOROWSKI, GJ KEMPNER, ES TI FUNCTIONAL UNIT SIZE OF THE CHARYBDOTOXIN RECEPTOR IN SMOOTH-MUSCLE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ACTIVATED POTASSIUM CHANNELS; AFFINITY BINDING-SITES; CA-2+-ACTIVATED K+ CHANNEL; RAT-BRAIN; RADIATION INACTIVATION; DIRECT ASSOCIATION; HIGH-CONDUCTANCE; XENOPUS-OOCYTES; TARGET ANALYSIS; PURIFICATION AB Target inactivation analysis was used to determine the functional size of the charybdotoxin (ChTX) receptor in aortic and tracheal sarcolemmal membrane vesicles. This receptor has previously been shown to be an integral component of the high-conductance Ca2+-activated K+ (Maxi-K) channel in these smooth muscles. Exposure of either bovine aortic or bovine tracheal sarcolemma to high-energy irradiation results in disappearance of I-125-labeled ChTX binding activity as a monoexponential function of radiation dose; from these functions molecular masses of 88 +/- 10 kDa and 89 +/- 6 kDa, respectively, can be calculated. Similar results were obtained from radiation inactivation studies with the detergent-solubilized ChTX receptor from aortic sarcolemmal membranes. The effect of radiation on I-125-labeled ChTX binding is to decrease the number of functional ChTX receptors without affecting the affinity of receptors for the toxin, indicating that radiation is destroying, rather than altering, the binding site. The validity of the radiation inactivation technique in these membrane preparations is supported by data obtained in parallel experiments in which target sizes of the alpha(1) subunit of the L-type Ca2+ channel and 5'-nucleotidase were measured. The molecular masses determined for these entities are in excellent agreement with those expected from previous studies. The present data are discussed in terms of the recently determined subunit composition of the smooth muscle Maxi-K channel. In light of the target size, a single alpha beta subunit heterodimer complex could serve as the ChTX receptor. C1 MERCK & CO INC, RES LABS, DEPT MEMBRANE BIOCHEM & BIOPHYS, RAHWAY, NJ 07065 USA. NIAMSD, PHYS BIOL LAB, BETHESDA, MD 20892 USA. NR 36 TC 12 Z9 12 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 24 PY 1994 VL 91 IS 11 BP 4718 EP 4722 DI 10.1073/pnas.91.11.4718 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NN214 UT WOS:A1994NN21400024 PM 7515178 ER PT J AU CHOI, WJ SBURLATI, A CABIB, E AF CHOI, WJ SBURLATI, A CABIB, E TI CHITIN SYNTHASE-3 FROM YEAST HAS ZYMOGENIC PROPERTIES THAT DEPEND ON BOTH THE CAL1 AND THE CAL3 GENES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CHITIN; CELL WALL ID SACCHAROMYCES-CEREVISIAE; SYNTHESIS INVIVO; CELL-CYCLE; SYNTHETASE; PRODUCT; ENZYME; CSD2; WALL AB In previous studies, chitin synthase 3 (Chs3), the enzyme responsible for synthesis of most of the chitin present in the yeast cell, was found to be inactivated by incubation with trypsin, in contrast to other yeast chitin synthases (Chs1 and Chs2), which are stimulated by this treatment (chitin synthase; UDP-N-acetyl-D-glucosamine:chitin 4-beta-N-acetylglucosaminyltransferase, EC 2.4.1.16). It has now been found that the substrate UDPGlcNAc protects Chs3 against proteolytic inactivation. Treatment of Chs3-containing membranes with detergents drastically reduced the enzymatic activity. Activity could, however, be restored by subsequent incubation with trypsin or other proteases in the presence of UDPGlcNAc. Under such conditions, protease treatment stimulated activity as much as 10-fold. A change in divalent cation specificity after trypsin treatment suggests that the protease directly affects the enzyme molecule. Experiments with mutants in the three genes involved in Chs3 activity-CAL1, CAL2, and CAL3-showed that only CAL1 and CAL3 are required for the protease-elicited (zymogenic) activity. It is concluded that Chs3 is a zymogen and that the CAL2 product functions as its activator. The differences and possible similarities between Chs3 and the other chitin synthases are discussed. C1 NIDDKD, BIOCHEM & METAB LAB, BETHESDA, MD 20892 USA. NR 20 TC 70 Z9 72 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 24 PY 1994 VL 91 IS 11 BP 4727 EP 4730 DI 10.1073/pnas.91.11.4727 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NN214 UT WOS:A1994NN21400026 PM 8197125 ER PT J AU RONG, S SEGAL, S ANVER, M RESAU, JH VANDEWOUDE, GF AF RONG, S SEGAL, S ANVER, M RESAU, JH VANDEWOUDE, GF TI INVASIVENESS AND METASTASIS OF NIH 3T3 CELLS INDUCED BY MET-HEPATOCYTE GROWTH FACTOR/SCATTER FACTOR AUTOCRINE STIMULATION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID FACTOR SCATTER FACTOR; PROTOONCOGENE; EXPRESSION; GENE; LINE; TUMORIGENICITY; TRANSFECTION; FIBROBLASTS; RECEPTOR AB The met protooncogene product, Met, is the tyrosine kinase growth factor receptor for hepatocyte growth factor/scatter factor (HGF/SF). NIH 3T3 cells express HGF/SF endogenously and become tumorigenic in nude mice via an autocrine mechanism when murine Met is expressed ectopically (Met(mu) cells) or when human Met and human HGF/SF are coexpressed (HMH cells). Here, we show that Met(mu) and HMH cells are invasive in vitro and display enhanced protease activity necessary for the invasive phenotype. In experimental and spontaneous metastasis assays, Met(mu) or HMH cells metastasize to the lung, but lower numbers of subcutaneously injected Met(mu) and HMH cells produced invasive tumors in the heart, diaphragm, salivary gland, and retroperitoneum. It has been reported elsewhere that Met expression increased with tumor passage in athymic nude mice, and these tumor explants show enhanced activity in the metastasis assays. Autocrine-mediated Met-HGF/SF signal transduction in NIH 3T3 mesenchymal cells may provide an important system for understanding the biological process of metastasis. C1 NCI, FREDERICK CANC RES & DEV CTR, ADV BIOSCI LABS, BASIC RES PROGRAM, FREDERICK, MD 21702 USA. BEN GURION UNIV NEGEV, FAC HLTH SCI, DEPT MICROBIOL & IMMUNOL, IL-84105 BEER SHEVA, ISRAEL. NCI, FREDERICK CANC RES & DEV CTR, PROGRAM RESOURCES INC DYNCORP, FREDERICK, MD 21702 USA. FU NCI NIH HHS [N01-CO-74101] NR 34 TC 306 Z9 310 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 24 PY 1994 VL 91 IS 11 BP 4731 EP 4735 DI 10.1073/pnas.91.11.4731 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NN214 UT WOS:A1994NN21400027 PM 8197126 ER PT J AU BOYER, PL TANTILLO, C JACOBOMOLINA, A NANNI, RG DING, JP ARNOLD, E HUGHES, SH AF BOYER, PL TANTILLO, C JACOBOMOLINA, A NANNI, RG DING, JP ARNOLD, E HUGHES, SH TI SENSITIVITY OF WILD-TYPE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REVERSE-TRANSCRIPTASE TO DIDEOXYNUCLEOTIDES DEPENDS ON TEMPLATE LENGTH - THE SENSITIVITY OF DRUG-RESISTANT MUTANTS DOES NOT SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HIGH-LEVEL RESISTANCE; NONNUCLEOSIDE INHIBITORS; INVITRO SELECTION; REDUCED SENSITIVITY; ANGSTROM RESOLUTION; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; ZIDOVUDINE AZT; RNA-POLYMERASE; HIV-1 AB Analysis of the three dimensional structure of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase CRT) complexed with double-stranded DNA indicates that while many nucleoside-resistance mutations are not at the putative dNTP binding site, several are in positions to interact with the template-primer. Wild-type HIV-1 RT and two nucleoside-resistant variants, Leu(74) --> Val and Glu(89) --> Gly, have been analyzed to determine the basis of resistance. The ability of the wild-type enzyme to incorporate, or reject, a 2',3'-dideoxynucleoside triphosphate (ddNTP) is strongly affected by interactions that take place between the enzyme and the extended template strand 3-6 nt beyond the polymerase active site. Inspection of a model of the enzyme with an extended template suggests that this interaction involves the fingers subdomain of the p66 subunit in the vicinity of Leu(74). These data provide direct evidence that the fingers subdomain of the p66 subunit of HIV-1 RT interacts with the template strand. The wild-type enzyme is resistant to ddITP if the template extension is 3 nt or less and becomes sensitive only when the template extends more than 3 or 4 nt beyond the end of the primer strand. However, the mutant enzymes are resistant with both short and long template extensions. Taken together with the three-dimensional structure of HIV-1 RT in complex with double-stranded DNA, these data suggest that resistance to the dideoxynucleotide inhibitors results from a repositioning or change in the conformation of the template-primer that alters the ability of the enzyme to select or reject an incoming dNTP. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. RUTGERS STATE UNIV,CTR ADV BIOTECHNOL & MED,PISCATAWAY,NJ 08854. RUTGERS STATE UNIV,DEPT CHEM,PISCATAWAY,NJ 08854. FU NCI NIH HHS [N01-CO-74101]; NIAID NIH HHS [AI27690] NR 46 TC 150 Z9 150 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 24 PY 1994 VL 91 IS 11 BP 4882 EP 4886 DI 10.1073/pnas.91.11.4882 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NN214 UT WOS:A1994NN21400058 PM 7515182 ER PT J AU BURTON, JD BAMFORD, RN PETERS, C GRANT, AJ KURYS, G GOLDMAN, CK BRENNAN, J ROESSLER, E WALDMANN, TA AF BURTON, JD BAMFORD, RN PETERS, C GRANT, AJ KURYS, G GOLDMAN, CK BRENNAN, J ROESSLER, E WALDMANN, TA TI A LYMPHOKINE, PROVISIONALLY DESIGNATED INTERLEUKIN-T AND PRODUCED BY A HUMAN ADULT T-CELL LEUKEMIA LINE, STIMULATES T-CELL PROLIFERATION AND THE INDUCTION OF LYMPHOKINE-ACTIVATED KILLER-CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID I-ASSOCIATED MYELOPATHY; RECEPTOR GAMMA-CHAIN; VIRUS TYPE-I; GROWTH-FACTOR; LYMPHOCYTES AB In early phases of human T-cell lymphotropic virus I induced adult T-cell leukemia (ATL), the malignant cell proliferation is associated with an autocrine process involving coordinate expression of interleukin (IL) 2 and its receptor. However, during late-phase ATL, leukemic cells no longer produce IL-2 yet continue to express high affinity IL-2 receptors. During studies to define pathogenic mechanisms that underlie this IL-2-independent proliferation, we demonstrated that the ATL cell line HuT-102 secretes a lymphokine, provisionally designated IL-T, that stimulates T-cell proliferation and the induction of lymphokine-activated killer cells. Conditioned medium from HuT-102, when added to the IL-2-dependent CTLL-2 line, yielded a stimulation index of 230. Since CTLL-2 was purported to be IL 2-specific, we performed a number of studies to exclude IL-2 production by HuT-102. Stimulation of CTLL-2 cells by HuT-102-conditioned medium was not meaningfully inhibited by addition of an antiserum to IL-2. Furthermore, uninduced HuT-102 cells did not express mRNA encoding IL-2 as assessed by Northern blot analysis. No biological activity on CTLL-2 cells was mediated by purified IL-1, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, IL-13, or granulocyte/macrophage colony-stimulating factor, thus differentiating these factors from IL-T. Based on preliminary biochemical data, IL-T is a protein with a pI value of 4.5 and a molecular mass in SDS gels of 14 kDa. In addition to its action on CTLL-2 cells, 3200-fold-purified IL-T stimulated proliferation of the human cytokine-dependent T-cell line Kit-225. Furthermore, addition of IL-T enhanced cytotoxic activity of large granular lymphocytes (i.e., induced lymphokine-activated killer cells). Thus, IL-T is a lymphokine that plays a role in T-cell proliferation and induction of lymphokine activated killer cells. Furthermore, IL-T may contribute to IL-2-independent proliferation of select ATL cells and lines. C1 NCI,METAB BRANCH,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV CELLULAR & GENE THERAPY,CELLULAR IMMUNOL LAB,ROCKVILLE,MD 20852. NR 22 TC 283 Z9 295 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 24 PY 1994 VL 91 IS 11 BP 4935 EP 4939 DI 10.1073/pnas.91.11.4935 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NN214 UT WOS:A1994NN21400069 PM 8197160 ER PT J AU BAMFORD, RN GRANT, AJ BURTON, JD PETERS, C KURYS, G GOLDMAN, CK BRENNAN, J ROESSLER, E WALDMANN, TA AF BAMFORD, RN GRANT, AJ BURTON, JD PETERS, C KURYS, G GOLDMAN, CK BRENNAN, J ROESSLER, E WALDMANN, TA TI THE INTERLEUKIN (IL)-2 RECEPTOR-BETA CHAIN IS SHARED BY IL-2 AND A CYTOKINE, PROVISIONALLY DESIGNATED IL-T, THAT STIMULATES T-CELL PROLIFERATION AND THE INDUCTION OF LYMPHOKINE-ACTIVATED KILLER-CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GAMMA-CHAIN; MONOCLONAL-ANTIBODY; FUNCTIONAL COMPONENT; EXPRESSION; LEUKEMIA; TAC; P75; LYMPHOCYTES; COMPLEX; FIBROBLASTS AB Late-phase human T-cell lymphotropic virus I-associated adult T-cell leukemia cells express IL-2 receptors (IL-2R) but no longer produce IL-2. We have reported that the IL-2-independent adult T-cell leukemia line HuT-102 secretes a cytokine, provisionally designated IL-T, that stimulates T-cell proliferation and lymphokine-activated killer cell activity. Stimulation of proliferation of the cytokine-dependent human T-cell line Kit-225 mediated by HuT-102 conditioned medium or by 3200-fold purified IL-T was not blocked by the addition of antibodies against IL-2 or IL-2R alpha submit. However, IL-T-mediated stimulation of this human T-cell line was inhibited by addition of Mik-beta-1, an antibody that binds specifically to IL-2R beta subunit. In addition, the activation of large granular lymphocytes to lymphokine-activated killer cells mediated by IL-T-containing conditioned medium was not blocked by antibodies directed toward IL-2 or IL-2 alpha but was inhibited by an antibody to IL-2R beta, suggesting the requirement of this receptor subunit for IL-T action. This conclusion was confirmed using an IL-3-dependent murine myeloid precursor cell line, 32D, that expresses H-2R alpha and IL-2R gamma, but not IL-2R beta Neither IL-2 nor IL-T stimulated 32D cell proliferation. However, after transfection with the gene encoding human IL-2R beta, 32D beta cells proliferated on addition of either cytokine. The IL-T-mediated stimulation of 32D beta proliferation was inhibited by an anti-IL2R beta antibody but not by an anti-IL-2 antibody. Thus, the IL-T-mediated stimulation of T-cell and lymphokine-activated killer cell activation requires the expression of the IL-2R beta subunit. C1 NCI,METAB BRANCH,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,DIV CELLULAR & GENE THERAPY,CELLULAR IMMUNOL LAB,ROCKVILLE,MD 20852. NR 39 TC 326 Z9 336 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 24 PY 1994 VL 91 IS 11 BP 4940 EP 4944 DI 10.1073/pnas.91.11.4940 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NN214 UT WOS:A1994NN21400070 PM 8197161 ER PT J AU CHOW, LML JARVIS, C HU, QL NYE, SH GERVAIS, FG VEILLETTE, A MATIS, LA AF CHOW, LML JARVIS, C HU, QL NYE, SH GERVAIS, FG VEILLETTE, A MATIS, LA TI NTK - A CSK-RELATED PROTEIN-TYROSINE KINASE EXPRESSED IN BRAIN AND T-LYMPHOCYTES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NEGATIVE REGULATORY SITE; SRC FAMILY KINASES; CELL RECEPTOR; MOLECULAR-CLONING; CATALYTIC DOMAIN; GENE; P56(LCK); PHOSPHORYLATES; IDENTIFICATION; ASSOCIATION AB The activity of Src-related protein-tyrosine kinases is repressed by the phosphorylation of a conserved carboxyl-terminal tyrosine by another cytoplasmic protein-tyrosine kinase termed p50(csk). In this study, we characterize Ntk, a protein-tyrosine kinase bearing striking similarities to p50(csk). Like p50(csk), Ntk possesses Src homology 3 and Src homology 2 domains and lacks the consensus tyrosine phosphorylation and myristoylation sites found in members of the Src family. Expression of ntk transcripts was maximal in brain, and was observed at significant levels in thymus and spleen. ntk RNA levels were dramatically reduced upon mitogenic stimulation of normal T lymphocytes and were minimal in transformed T-cell populations. Firm evidence that Ntk is a Csk-related enzyme was provided by the observation that it phosphorylated a Src-related polypeptide on the inhibitory carboxyl-terminal tyrosine. These findings indicate that Ntk is a Csk-related enzyme that may play an inhibitory role in the control of T-cell proliferation. C1 MCGILL UNIV, MCGILL CANC CTR, MONTREAL H3G 1Y6, PQ, CANADA. MCGILL UNIV, DEPT BIOCHEM, MONTREAL H3G 1Y6, PQ, CANADA. MCGILL UNIV, DEPT MED, MONTREAL H3G 1Y6, PQ, CANADA. MCGILL UNIV, DEPT ONCOL, MONTREAL H3G 1Y6, PQ, CANADA. NCI, FREDERICK CANC RES & DEV CTR, BIOL RESPONSE MODIFIERS PROGRAM, MOLEC IMMUNOREGULAT LAB, FREDERICK, MD 21702 USA. ALEX PHARMACEUT, NEW HAVEN, CT 06511 USA. NR 30 TC 66 Z9 69 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 24 PY 1994 VL 91 IS 11 BP 4975 EP 4979 DI 10.1073/pnas.91.11.4975 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NN214 UT WOS:A1994NN21400077 PM 8197166 ER PT J AU BOVOLENTA, C DRIGGERS, PH MARKS, MS MEDIN, JA POLITIS, AD VOGEL, SN LEVY, DE SAKAGUCHI, K APPELLA, E COLIGAN, JE OZATO, K AF BOVOLENTA, C DRIGGERS, PH MARKS, MS MEDIN, JA POLITIS, AD VOGEL, SN LEVY, DE SAKAGUCHI, K APPELLA, E COLIGAN, JE OZATO, K TI MOLECULAR-INTERACTIONS BETWEEN INTERFERON CONSENSUS SEQUENCE BINDING-PROTEIN AND MEMBERS OF THE INTERFERON REGULATORY FACTOR FAMILY SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TRANSCRIPTIONAL ACTIVATOR; NEGATIVE REGULATOR; STIMULATED GENES; INDUCIBLE GENES; THYROID-HORMONE; RETINOIC ACID; RXR-BETA; ALPHA; ELEMENTS; EXPRESSION AB Interferon (IFN) consensus sequence binding protein (ICSBP) is a transcription factor expressed mostly in the cells of the immune system. ICSBP belongs to the IFN regulatory factor (IRF) family, which also includes IRF-1, IRF-2, and the IFN-alpha-stinulated gene factor 3 gamma(ISGF3 gamma). We show here that ICSBP forms a complex with IRF-1 or IRF-2 both in vivo and in vitro and, in the presence or absence of the target DNA, with the IFN-stimulated response element (ISRE). Further, electrophoretic mobility shift assays show that this interaction greatly enhances the otherwise very low binding affinity of ICSBP to the ISRE. We show, on the other hand, that ICSBP inhibits binding of the IFN-alpha-stinulated gene factor 3 gamma to the ISRE. Through these interactions ICSBP is likely to exert complex modulatory functions in the regulation of IFN-stimulated genes. C1 NICHHD,MOLEC GROWTH REGULAT LAB,BETHESDA,MD 20892. NCI,CELL BIOL LAB,BETHESDA,MD 20892. NIAID,BIOL RESOURCES BRANCH,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,DEPT MICROBIOL,BETHESDA,MD 20814. NYU,SCH MED,DEPT PATHOL,NEW YORK,NY 10016. NYU,SCH MED,KAPLAN COMPREHENS CANC CTR,NEW YORK,NY 10016. OI Marks, Michael/0000-0001-7435-7262 FU NIAID NIH HHS [AI-18797] NR 34 TC 137 Z9 137 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 24 PY 1994 VL 91 IS 11 BP 5046 EP 5050 DI 10.1073/pnas.91.11.5046 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NN214 UT WOS:A1994NN21400093 PM 8197182 ER PT J AU HINES, KL KULKARNI, AB MCCARTHY, JB TIAN, HS WARD, JM CHRIST, M MCCARTNEYFRANCIS, NL FURCHT, LT KARLSSON, S WAHL, SM AF HINES, KL KULKARNI, AB MCCARTHY, JB TIAN, HS WARD, JM CHRIST, M MCCARTNEYFRANCIS, NL FURCHT, LT KARLSSON, S WAHL, SM TI SYNTHETIC FIBRONECTIN PEPTIDES INTERRUPT INFLAMMATORY CELL INFILTRATION IN TRANSFORMING GROWTH-FACTOR-BETA-1 KNOCKOUT MICE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SULFATE PROTEOGLYCAN; ADHESION MOLECULE-1; INTEGRIN; EXPRESSION; BINDING; MOUSE; ARTHRITIS; ADHERENCE AB Pronounced mononuclear leukocyte (MNL) infiltration occurs in multiple organs of mice homozygous for a transforming growth factor beta 1 (TGF-beta 1) loss-of-function gene mutation [TGF-beta 1 (-/-)], followed by cachexia and eventually death. Consistent with the increased leukocyte adhesion and tissue infiltration, MNLs isolated from spleen, thymus, and peripheral blood of symptomatic TGF-beta 1 (-/-) mice, as compared to littermate controls, exhibited increased adhesion to extracellular matrix proteins and to endothelial cells in vitro. Incubation of TGF-beta 1 (-/-) MNLs with selected synthetic peptides corresponding to cell- and heparin-binding sequences of fibronectin (FN) significantly attenuated adhesion of these cells not only to FN but also to endothelial cells in vitro. Based on these observations, mice were treated with the FN peptides in an attempt to rescue them from tissue inflammation and cardiopulmonary failure. Daily injections of a combination of four synthetic FN peptides that interact with beta 1-integrins and/or cell surface proteoglycans blocked the massive infiltration of MNLs into the heart and lungs of TGF-beta 1 (-/-) mice. Peptide treatment initiated on day 8, coincident with the first evidence of increased leukocyte-endothelial cell interactions, not only blocked tissue infiltration but also moderated the lethal wasting syndrome. C1 NIDR,CELLULAR IMMUNOL SECT,BETHESDA,MD 20892. NINCDS,MOLEC & MED GENET SECT,BETHESDA,MD 20892. NCI,VET & TUMOR PATHOL SECT,FREDERICK,MD 21702. UNIV MINNESOTA,MED & PATHOL LAB,MINNEAPOLIS,MN 55455. NR 35 TC 83 Z9 83 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 24 PY 1994 VL 91 IS 11 BP 5187 EP 5191 DI 10.1073/pnas.91.11.5187 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NN214 UT WOS:A1994NN21400122 PM 8197206 ER PT J AU KNABLE, MB HYDE, TM EGAN, MF TOSAYALI, M WYATT, RJ KLEINMAN, JE AF KNABLE, MB HYDE, TM EGAN, MF TOSAYALI, M WYATT, RJ KLEINMAN, JE TI QUANTITATIVE AUTORADIOGRAPHY OF STRIATAL DOPAMINE D1, D2 AND REUPTAKE SITES IN RATS WITH VACUOUS CHEWING MOVEMENTS SO BRAIN RESEARCH LA English DT Article DE TARDIVE DYSKINESIA; VACUOUS CHEWING MOVEMENT; NEUROLEPTIC; DOPAMINE; DOPAMINE RECEPTOR; AUTORADIOGRAPHY ID RECEPTOR ANTAGONIST; TARDIVE-DYSKINESIA; PARKINSONS-DISEASE; ORAL DYSKINESIA; BASAL GANGLIA; BINDING; NEUROLEPTICS; BRAIN; SCHIZOPHRENIA; PHARMACOLOGY AB Rats treated with haloperidol that developed vacuous chewing movements (VCM), a possible animal model of tardive dyskinesia, were studied with quantitative autoradiography for dopamine type-1 (D1) and type-2 (D2) receptors as well as dopamine re-uptake sites. Haloperidol increased striatal D2 receptors, but did not affect D1 receptors or the dopamine re-uptake site. D2 receptor increases occurred in rats with and without VCMs. In so far as VCM is a model for tardive dyskinesia, haloperidol induced increases in striatal D2 receptors do not appear to be etiologic for these abnormal movements. C1 ST ELIZABETH HOSP,NIMH,NEUROSCI RES CTR,INTRAMURAL RES PROGRAM,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032. ST ELIZABETH HOSP,DIST COLUMBIA COMMISS MENTAL HLTH SERV,PSYCHIAT RESIDENCY PROGRAM,WASHINGTON,DC 20032. RP KNABLE, MB (reprint author), ST ELIZABETH HOSP,NIMH,NEUROSCI RES CTR,INTRAMURAL RES PROGRAM,CLIN BRAIN DISORDERS BRANC,WASHINGTON,DC 20032, USA. NR 34 TC 32 Z9 32 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 23 PY 1994 VL 646 IS 2 BP 217 EP 222 DI 10.1016/0006-8993(94)90081-7 PG 6 WC Neurosciences SC Neurosciences & Neurology GA NM416 UT WOS:A1994NM41600006 PM 8069667 ER PT J AU GALDZICKI, Z FUKUYAMA, R WADHWANI, KC RAPOPORT, SI EHRENSTEIN, G AF GALDZICKI, Z FUKUYAMA, R WADHWANI, KC RAPOPORT, SI EHRENSTEIN, G TI BETA-AMYLOID INCREASES CHOLINE CONDUCTANCE OF PC12 CELLS - POSSIBLE MECHANISM OF TOXICITY IN ALZHEIMERS-DISEASE SO BRAIN RESEARCH LA English DT Note DE CHOLINE; BETA-AMYLOID; ALZHEIMERS DISEASE; CARRIER; LEAKAGE; ACETYLCHOLINE; BRAIN; NEURON; PC12 CELL ID NERVE GROWTH-FACTOR; PROTEIN; NEURONS; BRAIN; ACETYLCHOLINE; CHANNELS; MOUSE AB When beta-amyloid-(1-40) is added to PC12 cells, there is an increase in choline conductance that is proportional to the beta-amyloid concentration. If a similar effect occurs in cholinergic brain cells of Alzheimer's disease patients, the intracellular choline concentration would be reduced, leading to a decrease in the production of acetylcholine. This could explain the reduced level of acetylcholine that has been found in post-mortem brain tissue of Alzheimer's disease patients. C1 NINCDS,CLIN NEUROL BRANCH,BETHESDA,MD 20892. RP GALDZICKI, Z (reprint author), NIA,NEUROSCI LAB,BETHESDA,MD 20892, USA. NR 22 TC 47 Z9 48 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 23 PY 1994 VL 646 IS 2 BP 332 EP 336 DI 10.1016/0006-8993(94)90101-5 PG 5 WC Neurosciences SC Neurosciences & Neurology GA NM416 UT WOS:A1994NM41600026 PM 8069685 ER PT J AU FAN, P AF FAN, P TI INHIBITION OF A 5-HT3 RECEPTOR-MEDIATED CURRENT BY THE SELECTIVE SEROTONIN UPTAKE INHIBITOR, FLUOXETINE SO NEUROSCIENCE LETTERS LA English DT Article DE 5-HT3 RECEPTOR; PATCH CLAMP; NODOSE GANGLION NEURON; FLUOXETINE; ANTIDEPRESSANT; SEROTONIN UPTAKE INHIBITOR ID HUMAN-BRAIN INVITRO; ANTIDEPRESSANTS; CELLS; ANTAGONISTS; SITES AB The effect of the selective serotonin uptake inhibitor, fluoxetine, on the inward current mediated by 5-HT3 receptors was investigated with the whole-cell patch-clamp technique. Fluoxetine inhibited the peak 5-HT current with an IC50 value of 1.2 mu M. During continuous application of fluoxetine at concentrations of less than or equal to 1 mu M, there was a transient decrease in the fluoxetine-induced inhibition of 5-HT current. It is suggested that fluoxetine may have a short-lived action on 5-HT current and that the 5-HT3 receptor is a possible acting site for the therapeutic use of fluoxetine. RP FAN, P (reprint author), NIAAA,MOLEC & CELLULAR NEUROBIOL LAB,12501 WASHINGTON AVE,ROCKVILLE,MD 20852, USA. NR 16 TC 32 Z9 32 U1 1 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD MAY 23 PY 1994 VL 173 IS 1-2 BP 210 EP 212 DI 10.1016/0304-3940(94)90185-6 PG 3 WC Neurosciences SC Neurosciences & Neurology GA PF448 UT WOS:A1994PF44800050 PM 7523998 ER PT J AU HUTCHINSON, KD SILVERTON, JV DALY, JW AF HUTCHINSON, KD SILVERTON, JV DALY, JW TI SYNTHESIS OF PYRROLIZIDINE OXIME-222 AND OXIME-236 - NOVEL ALKALOIDS OF A DENDROBATID POISON FROG SO TETRAHEDRON LA English DT Article AB The structures of two novel spiropentanopyrrolizidine oxime alkaloids, namely 2',3',5',6',7',7a'-hexahydro-2,2-dimethylspiro[cyclopentane-1,1'-[1H]-pyrrolizine]-7'-oxime (1) and 2',3',5',6',7',7a'-hexahydro-2,2-dimethylspiro [cyclopentane-1,1'-[1H]pyrrolizine]-7'-oxime-O-methyl ether (2) have been confirmed by synthesis. The route involved synthesis of nitropolyzonamine (4), a known millipede alkaloid, from 2,2-dimethylcyclopentanone in 6 steps. After conversion of 4 to the ketone 6, the oxime 1 and O-methyl oxime 2 were obtained. The relative stereochemistry of synthetic nitropolyzonamine was confirmed by x-ray crystallography. C1 NHLBI,BETHESDA,MD 20892. RP HUTCHINSON, KD (reprint author), NIDDKD,BETHESDA,MD 20892, USA. NR 12 TC 9 Z9 11 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0040-4020 J9 TETRAHEDRON JI Tetrahedron PD MAY 23 PY 1994 VL 50 IS 21 BP 6129 EP 6136 PG 8 WC Chemistry, Organic SC Chemistry GA NN446 UT WOS:A1994NN44600001 ER PT J AU MCCANCE, DR HANSON, RL CHARLES, MA JACOBSSON, LTH PETTITT, DJ BENNETT, PH KNOWLER, WC AF MCCANCE, DR HANSON, RL CHARLES, MA JACOBSSON, LTH PETTITT, DJ BENNETT, PH KNOWLER, WC TI COMPARISON OF TESTS FOR GLYCATED HEMOGLOBIN AND FASTING AND 2 HOUR PLASMA-GLUCOSE CONCENTRATIONS AS DIAGNOSTIC METHODS FOR DIABETES SO BRITISH MEDICAL JOURNAL LA English DT Article ID PIMA-INDIANS; GLYCOSYLATED HEMOGLOBIN; TOLERANCE TEST; SCREENING-TESTS; MELLITUS; BIMODALITY; 2-HOUR; ASSAY; HYPERGLYCEMIA; DISTRIBUTIONS AB Objective-To compare the ability of tests measuring two hour plasma glucose, fasting plasma glucose, and glycated haemoglobin concentrations in predicting the specific microvascular complications of non-insulin dependent diabetes mellitus. Design-Cross sectional and longitudinal analysis of the relation between complications and concomitant results of the three tests. Setting-Gila River Indian Community, Arizona. Subjects-Pima Indians (cross sectional, n=960), aged 25 years or above who were not receiving insulin or oral hypoglycaemic treatment at the baseline examination. Main outcome measures-Developement of retinopathy and nephropathy. Results-Cross sectionally, frequency distributions of logarithms of the three sets of results were bimodal, with the prevalence of retinopathy and nephropathy being, respectively, 12.0-26.7 and 3.9-4.2 times as high above as below cut off points which minimised overlap (two hour plasma glucose concentration 12.6mmol/l; fasting plasma glucose concentration 9.3mmol/l; glycated haemoglobin (HbA(1c)) concentration 7.8%). Longitudinally, each of the three measures of glycaemia significantly predicted the development of retinopathy (P<0.0001) and nephropathy (P<0.05). Receiver operating characteristic curves showed that two hour plasma glucose concentration was superior to fasting plasma glucose concentration (P<0.05) for prevalent cases of retinopathy, but otherwise no variable had a significant advantage for detecting incident or prevalent cases of either complication. Conclusions-These findings suggest that determination of glycated haemoglobin or fasting plasma glucose concentrations alone may be acceptable alternatives to measuring glucose concentration two hours after challenge with 75g glucose for the diagnosis of diabetes. C1 NIDDKD,PHOENIX EPIDEMIOL & CLIN RES BRANCH,DIABET & ARTHRITIS EPIDEMIOL SECT,PHOENIX,AZ 85014. NIAMSD,PHOENIX,AZ 85014. RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 NR 47 TC 328 Z9 345 U1 4 U2 13 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0959-8138 J9 BRIT MED J JI Br. Med. J. PD MAY 21 PY 1994 VL 308 IS 6940 BP 1323 EP 1328 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA NM989 UT WOS:A1994NM98900018 PM 8019217 ER PT J AU BROWN, SL SALIVE, ME HARRIS, TB SIMONSICK, EM GURALNIK, JM KOHOUT, FJ AF BROWN, SL SALIVE, ME HARRIS, TB SIMONSICK, EM GURALNIK, JM KOHOUT, FJ TI LOW-CHOLESTEROL CONCENTRATIONS AND SEVERE DEPRESSIVE SYMPTOMS IN ELDERLY PEOPLE SO BRITISH MEDICAL JOURNAL LA English DT Article ID LOW SERUM-CHOLESTEROL; PRIMARY PREVENTION; MORTALITY; MEN; PROGRESS AB Objective-To investigate the reported association between low serum cholestrol concentration and severe depressive symptoms in an elderly population. Design-Cross sectional analysis of pooled data from three communities of the established populations for epidemiologic studies of the elderly. Participants who completed their interview, including the Centers for Epidemiologic Studies' depression scale and consented to measurement of their cholesterol concentration were included in the study. Subjects-3939 men and women aged greater than or equal to 71. Methods-chi(2) analysis, t tests, and multivariate regression analysis of the association between low cholesterol concentration and severe depressive symptoms. All analyses were stratified by sex, and multivariate analyses were adjusted for age, self reported health, physical function, number of drugs used, and weight loss. Main outcome measure-Score of depressive symptoms on the Centers for Epidemiologic Studies' depression scale. Results-Depressive symptoms, cholesterol concentration, weight, and use of drugs were all associated with age in men and women. The relative odds of severe depressive symptoms (score greater than or equal to 16) for those with low cholesterol concentrations (<4.14 mmol/l) were 1.9 (95% confidence interval, 1.1 to 3.3) for the older group of men and 1.8 (1.1 to 2.9) for the older group of women. This association was also observed when depressive symptoms were analysed as a continuous rather than a categorical variable. In multivariate models that adjusted for age, self reported health, physical function, number of drugs used, and weight loss, the association was substantially weakened. Conclusions-After several factors relating to health had been controlled for, no significant association between low cholesterol concentration and severe depressive symptoms was found. C1 UNIV IOWA,COLL DENT,IOWA CITY,IA 52242. RP BROWN, SL (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,7201 WINSCONSIN AVE,SUITE 3C309,BETHESDA,MD 20892, USA. NR 20 TC 91 Z9 91 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0959-8138 J9 BRIT MED J JI Br. Med. J. PD MAY 21 PY 1994 VL 308 IS 6940 BP 1328 EP 1332 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA NM989 UT WOS:A1994NM98900019 PM 8019218 ER PT J AU POZSGAY, V PANNELL, L AF POZSGAY, V PANNELL, L TI CONVERGENT SYNTHESIS OF AN OCTASACCHARIDE FRAGMENT OF THE O-SPECIFIC POLYSACCHARIDE OF SHIGELLA-DYSENTARIAE TYPE-1 SO CARBOHYDRATE RESEARCH LA English DT Article ID DYSENTERIAE TYPE-1; ANTIGENS; LIPOPOLYSACCHARIDE; OLIGOSACCHARIDES; GLYCOSIDES; REMOVAL; REAGENT; CHAIN AB A stereocontrolled, convergent synthesis is described of the linear octasaccharide methyl glycoside alpha-L-Rha p-(1 --> 2)-alpha-D-Gal p-(1 --> 3)-alpha-Glc p NAc-(1 --> 3)-alpha-L-Rha p-(1 --> 3)-alpha-L-Rha p-(1 --> 2)-alpha-D-Gal p-(1 --> 3)-alpha-D-Glc p NAc-(1 --> 3)-alpha-L-Rha p-OMe (11), which corresponds to two contiguous repeating units of the O-specific polysaccharide of Shigella dysenteriae type 1. C1 NIDDK,MED CHEM LAB,BETHESDA,MD 20892. NIDDK,ANALYT CHEM LAB,BETHESDA,MD 20892. RP POZSGAY, V (reprint author), NICHHD,DEV & MOLEC IMMUN LAB,BLDG 6,ROOM 145,BETHESDA,MD 20892, USA. NR 30 TC 16 Z9 16 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD MAY 20 PY 1994 VL 258 BP 105 EP 122 DI 10.1016/0008-6215(94)84079-2 PG 18 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA NL363 UT WOS:A1994NL36300010 PM 7518739 ER PT J AU REUBEN, J RAO, CT PITHA, J AF REUBEN, J RAO, CT PITHA, J TI DISTRIBUTION OF SUBSTITUENTS IN CARBOXYMETHYL ETHERS OF CYCLOMALTOHEPTAOSE SO CARBOHYDRATE RESEARCH LA English DT Note C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. RP REUBEN, J (reprint author), HERCULES INC,RES CTR,WILMINGTON,DE 19808, USA. NR 9 TC 24 Z9 25 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD MAY 20 PY 1994 VL 258 BP 281 EP 285 DI 10.1016/0008-6215(94)84094-6 PG 5 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA NL363 UT WOS:A1994NL36300025 ER PT J AU UMAR, A BOYER, JC THOMAS, DC NGUYEN, DC RISINGER, JI BOYD, J IONOV, Y PERUCHO, M KUNKEL, TA AF UMAR, A BOYER, JC THOMAS, DC NGUYEN, DC RISINGER, JI BOYD, J IONOV, Y PERUCHO, M KUNKEL, TA TI DEFECTIVE MISMATCH REPAIR IN EXTRACTS OF COLORECTAL AND ENDOMETRIAL CANCER CELL-LINES EXHIBITING MICROSATELLITE INSTABILITY SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID CARCINOMA; ESTABLISHMENT; MUTATIONS AB A replication error (RER(+)) phenotype, characterized by somatic instability in simple repeated sequences, is associated with several types of cancer. To determine if a defect in DNA replication fidelity or repair of replication errors might explain this instability, we compared both processes in cell-free extracts from RER(+) endometrial and colorectal cancer cell lines to RER(-) cell lines. SV40 origin-dependent replication of a microsatellite sequence is highly accurate in cell extracts regardless of their RER phenotype. However, extracts from RER(+) cell lines are defective in mismatch repair, while extracts of RER(-) cell lines are not. Lack of repair was observed when the signal (a nick) for strand specific repair was either 3' or 5' to the mispair. One colorectal cancer cell line contained deletions in both alleles of the putative mismatch repair gene hMSH2, and one endometrial cancer cell line contained a 4-base pair duplication in one hMSH2 allele. No hMSH2 mutation was detected in the other allele or in the other five RER(+) cell lines. Repair was readily detected when each of the defective extracts was mixed with a repair-proficient extract, demonstrating that no trans-acting inhibitor is present. Attempts to complement the repair deficiencies by mixing two different defective extracts identified three combinations that restored repair. The data suggest that: (i) defective repair is associated with colorectal and endometrial cancer and, by extrapolation, with other types of cancer; (ii) mutations in the hMSH2 gene, and possibly other genes, result in defective mismatch repair; (iii) the defect(s) in these lines likely involves pre-incision events or the excision step, but not the incision, polymerization, or ligation steps; and (iv) at least four functional complementation groups for mismatch repair may be involved in human cancer. C1 NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709. NIEHS,MOLEC CARCINOGENESIS LAB,GYNECOL PATHOBIOL SECT,RES TRIANGLE PK,NC 27709. CALIF INST BIOL RES,LA JOLLA,CA 92037. NR 38 TC 311 Z9 313 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 20 PY 1994 VL 269 IS 20 BP 14367 EP 14370 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NM065 UT WOS:A1994NM06500011 PM 8182040 ER PT J AU SEKIGUCHI, M DOI, K ZHU, WS WATASE, K YOKOTANI, N WADA, K WENTHOLD, RJ AF SEKIGUCHI, M DOI, K ZHU, WS WATASE, K YOKOTANI, N WADA, K WENTHOLD, RJ TI A DELETION IN THE 2ND CYTOPLASMIC LOOP OF GLUR3 PRODUCES A DOMINANT-NEGATIVE MUTANT OF ALPHA-AMINO-3-HYDROXY-5-METHYL-4-ISOXAZOLE PROPIONIC-ACID RECEPTOR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DEPENDENT PROTEIN-KINASE; MUSCLE ACETYLCHOLINE-RECEPTOR; PUTATIVE GLUTAMATE RECEPTOR; KAINATE-BINDING SUBUNIT; CENTRAL NERVOUS-SYSTEM; NMDA RECEPTOR; FUNCTIONAL EXPRESSION; MOLECULAR-CLONING; STRUCTURAL DETERMINANTS; ENDOPLASMIC-RETICULUM AB We have characterized a GluR3 mutant (sGluR3) which has a 33-amino acid deletion in its second cytoplasmic loop (deficit from Tyr-715 to Gly-747 of GluR3-flop). Xenopus oocytes injected with cRNA transcribed from cDNA for this mutant did not respond to kainate and glutamate (each 100 mu M) at a holding potential of -70 mV. In oocytes coinjected with cRNAs for this mutant and for normal alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subunits, the current response to both kainate and glutamate was much weaker than that observed in oocytes injected with cRNA for the normal subunits alone. This inhibitory action was not accompanied by a significant change of ED(50) value and shape of the I-V curve and was AMPA receptor-specific, A comparable deletion in GluR1 produced a mutant with properties similar to those of sGluR3, while a 33-amino acid deletion elsewhere in the second cytoplasmic loop of GluR3 (Met-674 to Phe-706) gave a mutant with a weaker effect. These results suggest that sGluR3 acts as a dominant negative mutant on the functional expression of normal AMPA receptors in oocytes by assembling with the normal subunits to produce an essentially nonfunctional receptor complex. C1 NIDOCD, NEUROCHEM LAB, BETHESDA, MD 20892 USA. RP SEKIGUCHI, M (reprint author), NATL CTR NEUROL & PSYCHIAT, NATL INST NEUROSCI, DEPT DEGENERAT NEUROL DIS, 4-1-1 OGAWAHIGASHI, KODAIRA, TOKYO 187, JAPAN. NR 53 TC 13 Z9 13 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 20 PY 1994 VL 269 IS 20 BP 14559 EP 14565 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NM065 UT WOS:A1994NM06500041 PM 8182063 ER PT J AU PAK, CC KRUMBIEGEL, M BLUMENTHAL, R RAVIV, Y AF PAK, CC KRUMBIEGEL, M BLUMENTHAL, R RAVIV, Y TI DETECTION OF INFLUENZA HEMAGGLUTININ INTERACTION WITH BIOLOGICAL-MEMBRANES BY PHOTOSENSITIZED ACTIVATION OF [I-125] IODONAPHTHYLAZIDE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INDUCED CONFORMATIONAL CHANGE; HUMAN-ERYTHROCYTE-MEMBRANE; RED-BLOOD-CELL; FUSION ACTIVITY; VIRUS HEMAGGLUTININ; 5-IODONAPHTHYL 1-AZIDE; AMPHIPHILIC COMPOUNDS; ANION PERMEABILITY; DISULFIDE BONDS; PROTEINS AB Fusion of influenza virus with cells is triggered by a pH-dependent conformational change in the viral envelope protein, hemagglutinin, which results in exposure of the fusion peptide and its insertion into the target membrane. We have investigated the association of hemagglutinin with erythrocyte membranes by photosensitized labeling with [I-125]iodonaphthylazide. This technique relies on the collisional energy transfer from a photosensitizing chromophore to [I-125]iodonaphthylazide, which selectively labels proteins in the vicinity of the chromophore. Incubation of influenza virus with erythrocyte membranes containing chromophore and [I-125]iodonaphthylazide results in labeling of hemagglutinin under fusogenic conditions (pH 5 and 37 degrees C). We also examined photosensitized labeling of hemagglutinin upon incubation of the X31 strain of influenza virus with labeled erythrocyte membranes in a pre-fusion state (pH 5 and 4 degrees C). There was little hemagglutinin labeling under these conditions, although incubation of bromelain-cleaved hemagglutinin, which lacks the transmembrane region, resulted in rapid labeling. Hemagglutinin was also labeled by [I-125]iodonaphthylazide photosensitized by a fluorescent substrate transported through the erythrocyte band 3 sialoglycoprotein. Hemagglutinin labeling decreased after an initial rapid rise, suggesting that the fusion site is close to the sialoglycoprotein and that [I-125]iodonaphthylazide photosensitized labeling may be used to assay protein movement during fusion. C1 NCI, MEMBRANE STRUCT & FUNCT SECT, BETHESDA, MD 20892 USA. NIDDK, CELL BIOL & GENET LAB, BETHESDA, MD 20892 USA. NR 47 TC 35 Z9 35 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 20 PY 1994 VL 269 IS 20 BP 14614 EP 14619 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NM065 UT WOS:A1994NM06500049 PM 8182068 ER PT J AU LEE, YH ALBERTA, JA GONZALEZ, FJ WAXMAN, DJ AF LEE, YH ALBERTA, JA GONZALEZ, FJ WAXMAN, DJ TI MULTIPLE, FUNCTIONAL DBP SITES ON THE PROMOTER OF THE CHOLESTEROL 7-ALPHA-HYDROXYLASE P450 GENE, CYP7 - PROPOSED ROLE IN DIURNAL REGULATION OF LIVER GENE-EXPRESSION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ENRICHED TRANSCRIPTIONAL ACTIVATOR; BILE-ACID BIOSYNTHESIS; MESSENGER-RNA LEVELS; RAT-LIVER; CIRCADIAN-RHYTHM; BINDING-PROTEIN; ALPHA-HYDROXYLASE; MOLECULAR-CLONING; HEPATOMA-CELLS; ENZYME AB Hepatic cytochrome P450 cholesterol 7 alpha-hydroxylase, CYP7, is regulated in vivo at the protein and the mRNA level in response to multiple physiological factors, including liver cholesterol synthesis, bile acid feedback inhibition, and diurnal rhythm. In the present study we investigated whether the liver transcription factor DBP (albumin promoter D-site binding protein), which undergoes a striking diurnal rhythm in rat liver (DBP levels during evening/morning similar to 100:1), contributes to the diurnal regulation of CYP7 gene expression. DNase I footprinting analysis using bacterially expressed DEP and a cloned 5'-flanking DNA segment of the rat CYP7 gene revealed five distinct DBP-binding sites, designated A-E, distributed between nucleotides (nts) -41 and -295 relative to the CYP7 transcription start site. CYP7-directed gene transcription in HepG2 cells transfected with a 5'-CYP7 promoter-chloramphenicol acetyltransferase reporter was activated up to 12-fold upon cotransfection of a DBP expression vector, whereas an HNF-1 alpha expression vector did not stimulate CYP7 gene activity. 5'-Deletion analyses and site-specific mutagenesis revealed that this stimulating effect of DBP can in part be ascribed to its functional interaction with DBP binding sites B (nts -115/-125), C (nts -172/-195), and D (nts -214/-230). C/EBP beta (LAP), another liver enriched basic-leucine zipper transcription factor, bound to these same sites but effected a more modest increase in CYP7-directed gene transcription (up to 3-4-fold) when expressed in HepG2 cells. Competition for CYP7 promoter-binding sites between C/EBP, which undergoes less than or equal to 2-fold diurnal change in rat liver, and the diurnally regulated DBP is proposed to determine the relative rates of basal versus diurnally regulated CYP7 gene transcription and thus may be a primary mechanism for setting the 3-6-fold amplitude that characterizes the circadian rhythm of liver CYP7 expression. Moreover, since DBP is first expressed in rat liver 3-4 weeks after birth, these findings may account for both the enhanced expression and the onset of the diurnal pattern of CYP7 enzyme levels at this stage of development. C1 NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,DEPT BIOL CHEM & MOLEC PHARMACOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. FU NIDDK NIH HHS [DK33765] NR 54 TC 75 Z9 75 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 20 PY 1994 VL 269 IS 20 BP 14681 EP 14689 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NM065 UT WOS:A1994NM06500060 PM 8182075 ER PT J AU WOLFFE, AP AF WOLFFE, AP TI ARCHITECTURAL TRANSCRIPTION FACTORS SO SCIENCE LA English DT Editorial Material ID DNA; BINDING RP WOLFFE, AP (reprint author), NICHHD,MOLEC EMBRYOL LAB,BETHESDA,MD 20892, USA. NR 19 TC 163 Z9 164 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 20 PY 1994 VL 264 IS 5162 BP 1100 EP 1101 DI 10.1126/science.8178167 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NM146 UT WOS:A1994NM14600019 PM 8178167 ER PT J AU BRODER, CC NUSSBAUM, O GUTHEIL, WG BACHOVCHIN, WW BERGER, EA AF BRODER, CC NUSSBAUM, O GUTHEIL, WG BACHOVCHIN, WW BERGER, EA TI CD26 ANTIGEN AND HIV FUSION SO SCIENCE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; ENVELOPE GLYCOPROTEIN; CD4-MEDIATED FUSION; MURINE CELLS; INFECTION; SYSTEM C1 TUFTS UNIV,SCH MED,DEPT BIOCHEM,BOSTON,MA 02111. RP BRODER, CC (reprint author), NIAID,VIRAL DIS LAB,BETHESDA,MD 20892, USA. NR 24 TC 55 Z9 55 U1 0 U2 3 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD MAY 20 PY 1994 VL 264 IS 5162 BP 1156 EP 1159 DI 10.1126/science.7909959 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NM146 UT WOS:A1994NM14600035 PM 7909959 ER PT J AU RANDAD, RS PAN, WX GULNIK, SV BURT, S ERICKSON, JW AF RANDAD, RS PAN, WX GULNIK, SV BURT, S ERICKSON, JW TI DE-NOVO DESIGN OF NONPEPTIDIC HIV-1 PROTEASE INHIBITORS - INCORPORATION OF STRUCTURAL WATER SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article AB We describe the de novo structure-based design of C2 symmetric, non-peptidic HIV PR inhibitors. Cyclic ureas were chosen as synthetic targets owing to their ability to mimic key interacting elements observed in known HIV PP/inhibitor complexes. The urea carbonyl oxygen serves as a replacement for the buried, structural water that occurs in peptide-based inhibitor complexes. The conformational analysis of the six-membered pyrimidone ring suggests that N-substituted derivatives should exhibit a marked stereochemical preference for binding. RP RANDAD, RS (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PRI DYN CORP,STRUCT BIOCHEM PROGRAM,FREDERICK,MD 21702, USA. NR 14 TC 11 Z9 11 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD MAY 19 PY 1994 VL 4 IS 10 BP 1247 EP 1252 DI 10.1016/S0960-894X(01)80339-5 PG 6 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA NN884 UT WOS:A1994NN88400015 ER PT J AU OBRIEN, SJ PAN, WS LU, Z AF OBRIEN, SJ PAN, WS LU, Z TI PANDAS, PEOPLE AND POLICY SO NATURE LA English DT Editorial Material ID POPULATIONS C1 BEIJING UNIV,DEPT BIOL,BEIJING 100871,PEOPLES R CHINA. RP OBRIEN, SJ (reprint author), NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702, USA. NR 25 TC 23 Z9 33 U1 0 U2 6 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD MAY 19 PY 1994 VL 369 IS 6477 BP 179 EP 180 DI 10.1038/369179a0 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NM067 UT WOS:A1994NM06700024 PM 8183334 ER PT J AU NICHELLI, P GRAFMAN, J PIETRINI, P ALWAY, D CARTON, JC MILETICH, R AF NICHELLI, P GRAFMAN, J PIETRINI, P ALWAY, D CARTON, JC MILETICH, R TI BRAIN ACTIVITY IN CHESS PLAYING SO NATURE LA English DT Letter ID LOCALIZATION C1 NINCDS,MED NEUROL BRANCH,COGNIT NEUROSCI SECT,BETHESDA,MD 20892. NIA,BETHESDA,MD 20892. UNIV MODENA,NEUROL CLIN,I-41100 MODENA,ITALY. RI Nichelli, Paolo/F-7336-2015 OI Nichelli, Paolo/0000-0001-9756-6796 NR 10 TC 48 Z9 48 U1 2 U2 8 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 19 PY 1994 VL 369 IS 6477 BP 191 EP 191 DI 10.1038/369191a0 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NM067 UT WOS:A1994NM06700035 PM 8183339 ER PT J AU IWASA, KH MIZUTA, K LIM, DJ BENOS, DJ TACHIBANA, M AF IWASA, KH MIZUTA, K LIM, DJ BENOS, DJ TACHIBANA, M TI AMILORIDE-SENSITIVE CHANNELS IN MARGINAL CELLS IN THE STRIA VASCULARIS OF THE GUINEA-PIG COCHLEA SO NEUROSCIENCE LETTERS LA English DT Article DE AMILORIDE; STRIA VASCULARIS; SODIUM CHANNEL; ENDOLYMPH ID LOCALIZATION; POTENTIALS; MEMBRANE; OUABAIN AB We examined marginal cells in stria vascularis for the presence of amiloride-sensitive Na+ channels, a possible pathway for maintaining a low Na+ concentration in the endolymph. Whole-cell voltage-clamp experiment shows that amiloride at 1 mu M concentration reversibly reduces inward current more than outward current. Immunogold-labeling method shows that the luminal and lateral membrane have antigenic sites for these antibodies. These observations indicate the presence of amiloride-sensitive channels in the marginal cell. If amiloride-sensitive channels in the luminal membrane are highly selective to Na+, they could be an efficient pathway for Na+ uptake from the endolymph. In the basolateral membrane, amiloride-sensitive Na+ channels may make a relatively small contribution to the unusual resting potential. C1 NIDCD,CELLULAR BIOL LABS,BETHESDA,MD 20892. NIDCD,MOLEC GENET LABS,BETHESDA,MD 20892. UNIV ALABAMA,DEPT PHYSIOL & BIOPHYS,BIRMINGHAM,AL 35294. OI Iwasa, Kuni/0000-0002-9397-7704 FU NIDDK NIH HHS [DK37206] NR 17 TC 15 Z9 16 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD MAY 19 PY 1994 VL 172 IS 1-2 BP 163 EP 166 DI 10.1016/0304-3940(94)90687-4 PG 4 WC Neurosciences SC Neurosciences & Neurology GA NM241 UT WOS:A1994NM24100040 PM 8084526 ER PT J AU CANNON, RO QUYYUMI, AA MINCEMOYER, R STINE, AM GRACELY, RH SMITH, WB GERACI, MF BLACK, BC UHDE, TW WACLAWIW, MA MAHER, K BENJAMIN, SB AF CANNON, RO QUYYUMI, AA MINCEMOYER, R STINE, AM GRACELY, RH SMITH, WB GERACI, MF BLACK, BC UHDE, TW WACLAWIW, MA MAHER, K BENJAMIN, SB TI IMIPRAMINE IN PATIENTS WITH CHEST PAIN DESPITE NORMAL CORONARY ANGIOGRAMS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID FOLLOW-UP; POSTHERPETIC NEURALGIA; DIABETIC NEUROPATHY; CONTRACTION ABNORMALITIES; PSYCHIATRIC-ILLNESS; ANGINA-PECTORIS; PANIC DISORDER; FLOW RESERVE; ARTERIES; AMITRIPTYLINE AB Background. Ten to 30 percent of patients undergoing cardiac catheterization because of chest pain are found to have normal coronary angiograms. Because these patients may have a Visceral pain syndrome unrelated to myocardial ischemia, we investigated whether drugs that are useful in chronic pain syndromes might also be beneficial in such patients. Methods. Sixty consecutive patients underwent cardiac, esophageal, psychiatric, and pain-sensitivity testing and then participated in a randomized, double-blind, placebo-controlled three-week trial of clonidine at a dose of 0.1 mg twice daily (20 patients), imipramine at a dose of 50 mg nightly with a morning placebo (20 patients), or placebo twice daily (20 patients); this treatment phase was compared with an identical period of twice-daily placebo for all patients (placebo phase). Results. Thirteen (22 percent) of the 60 patients had ischemic-appearing electrocardiographic responses to exercise, 22 of the 54 tested (41 percent) had abnormal esophageal motility, 38 of 60 (63 percent) had one or more psychiatric disorders, and 52 of 60 (87 percent) had their characteristic chest pain provoked by right ventricular electrical stimulation or intracoronary infusion of adenosine. During the treatment phase, the imipramine group had a mean (+/-SD) reduction of 52+/-25 percent in episodes of chest pain, the clonidine group had a reduction of 39+/-51 percent, and the placebo group a reduction of 1+/-86 percent, all as compared with the placebo phase of the trial. Only the improvement with imipramine was statistically significant (P = 0.03). Repeat assessment of sensitivity to cardiac pain while the patients were receiving treatment showed significant improvement only in the imipramine group (P = 0.01). The response to imipramine did not depend on the results of cardiac, esophageal, or psychiatric testing at base line, or on the change in the psychiatric profile during the course of the study, which generally improved in all three study groups. Conclusions. Imipramine improved the symptoms of patients with chest pain and normal coronary angiograms, possibly through a visceral analgesic effect. C1 NHLBI,BIOSTAT RES BRANCH,BETHESDA,MD 20892. NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD 20892. NIMH,ANXIETY & AFFECT DISORDERS SECT,BETHESDA,MD 20892. GEORGETOWN UNIV HOSP,DIV GASTROENTEROL,WASHINGTON,DC 20007. RP CANNON, RO (reprint author), NHLBI,CARDIOL BRANCH,BLDG 10,RM 7B-15,BETHESDA,MD 20892, USA. NR 54 TC 267 Z9 275 U1 0 U2 1 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 19 PY 1994 VL 330 IS 20 BP 1411 EP 1417 DI 10.1056/NEJM199405193302003 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA NK972 UT WOS:A1994NK97200003 PM 8159194 ER PT J AU FISHER, B REDMOND, CK AF FISHER, B REDMOND, CK TI FRAUD IN BREAST-CANCER TRIALS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID COMPARING TOTAL MASTECTOMY; TUMORS RP FISHER, B (reprint author), NATL SURG ADJUVANT BREAST & BOWEL PROJECT,PITTSBURGH,PA 15261, USA. NR 4 TC 25 Z9 26 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 19 PY 1994 VL 330 IS 20 BP 1458 EP 1460 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA NK972 UT WOS:A1994NK97200015 PM 8159206 ER PT J AU BRODER, S AF BRODER, S TI FRAUD IN BREAST-CANCER TRIALS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID COMPARING TOTAL MASTECTOMY; TUMORS RP BRODER, S (reprint author), NCI, BETHESDA, MD 20892 USA. NR 4 TC 6 Z9 6 U1 0 U2 0 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 19 PY 1994 VL 330 IS 20 BP 1460 EP 1461 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA NK972 UT WOS:A1994NK97200017 PM 8159208 ER PT J AU WEED, DL AF WEED, DL TI BETWEEN SCIENCE AND TECHNOLOGY - THE CASE OF ANTIHISTAMINES AND CANCER SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID TUMORS RP WEED, DL (reprint author), NCI,DIV CANC PREVENT & CONTROL,PREVENT ONCOL BRANCH,EPS-T41,BETHESDA,MD 20892, USA. NR 18 TC 6 Z9 6 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 18 PY 1994 VL 86 IS 10 BP 740 EP 741 DI 10.1093/jnci/86.10.740 PG 2 WC Oncology SC Oncology GA NL682 UT WOS:A1994NL68200001 PM 8169968 ER PT J AU THEUER, C KASTURI, S PASTAN, I AF THEUER, C KASTURI, S PASTAN, I TI DOMAIN-II OF PSEUDOMONAS EXOTOXIN-A ARRESTS THE TRANSFER OF TRANSLOCATING NASCENT CHAINS INTO MAMMALIAN MICROSOMES SO BIOCHEMISTRY LA English DT Article ID SIGNAL RECOGNITION PARTICLE; STOP-TRANSFER SEQUENCE; ENDOPLASMIC-RETICULUM; PROTEIN TRANSLOCATION; PRION PROTEIN; MEMBRANE; RECEPTOR; TOXIN; AERUGINOSA; TRANSPORT AB The translocation of PE from the extracytosolic compartment to the cytosol during the intoxication of mammalian cells is mediated by domain II of the toxin. We have shown previously that within domain II amino acids 280-313 of PE promote their own export from mammalian microsomes following signal sequence-directed membrane insertion. In this study, we attempted to target full-length PE into mammalian microsomes using the preprocecropin signal sequence, but found that translocation was arrested to generate a transmembrane protein. ''Stop transfer'' required the presence of amino acids 280-313 of PE, and the first 313 amino acids of PE were sufficient to generate a transmembrane protein (N-terminus-in/ C-terminus-out). The mechanism of stop transfer appears to be different from that described previously because amino acids 280-313 of PE are not highly hydrophobic and do contain many charged residues. In addition, the transmembrane segment appeared to be influenced by the cytoplasmic domain of the transmembrane proteins. C1 NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,BETHESDA,MD 20892. UNIV CALIF LOS ANGELES,HARBOR MED CTR,DEPT SURG,TORRANCE,CA 90509. UNIV CALIF SAN FRANCISCO,GLADSTONE INST CARDIOVASC DIS,SAN FRANCISCO,CA 94141. FU NCI NIH HHS [CA-12197]; NCRR NIH HHS [RR-04869] NR 43 TC 29 Z9 30 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 17 PY 1994 VL 33 IS 19 BP 5894 EP 5900 DI 10.1021/bi00185a029 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NM269 UT WOS:A1994NM26900029 PM 8180218 ER PT J AU HARRIS, BD MOODY, EJ BASILE, AS SKOLNICK, P AF HARRIS, BD MOODY, EJ BASILE, AS SKOLNICK, P TI VOLATILE ANESTHETICS BIDIRECTIONALLY AND STEREOSPECIFICALLY MODULATE LIGAND-BINDING TO GABA RECEPTORS SO EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION LA English DT Article DE GABA (GAMMA-AMINOBUTYRIC ACID); INHALATIONAL ANESTHETICS; MUSCIMOL; STEREOSPECIFICITY; SR 95531 ID RAT-BRAIN SYNAPTONEUROSOMES; CHLORIDE CHANNEL COMPLEX; BENZODIAZEPINE RECEPTORS; INHALATIONAL ANESTHETICS; NEUROCHEMICAL ACTIONS; GENERAL-ANESTHETICS; CEREBRAL-CORTEX; ENHANCEMENT; MEMBRANES; HALOTHANE AB Pharmacologically relevant concentrations of volatile anesthetics can bidirectionally modulate radioligand binding to GABA(A) receptors. In mouse cerebral cortex, halothane (a prototypic volatile anesthetic) increased [H-3]muscimol (a GABA receptor agonist) binding while inhibiting the binding of a GABA receptor antagonist ([H-3]SR 95531). These bidirectional effects of inhalational anesthetics on ligand binding to GABA receptors are effected through changes in the B-max with no significant alterations in the K-D of these radioligands. Moreover, the concentration dependent, bidirectional modulation of radioligand binding to GABA receptors by volatile anesthetics exhibited stereoselectivity. Thus, (+)-isoflurane was about twice as potent as the (-)-enantiomer in enhancing [H-3]muscimol binding and similar to 50% more potent as an inhibitor of [H-3]SR 95531 binding, respectively. The demonstration of a bidirectional, stereospecific modulation of radioligand binding to GABA receptors by inhalational agents is consistent with the presence of specific recognition sites for inhalational anesthetics on the GABA(A) receptor complex. C1 JOHNS HOPKINS UNIV HOSP,DEPT ANESTHESIOL & CRIT CARE MED,DIV CARDIAC,BALTIMORE,MD 21205. RP HARRIS, BD (reprint author), NIDDK,NEUROSCI LAB,BLDG 8,BETHESDA,MD 20892, USA. NR 41 TC 53 Z9 53 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0922-4106 J9 EUR J PHARM-MOLEC PH JI Eur. J. Pharmacol.-Molec. Pharmacol. Sect. PD MAY 17 PY 1994 VL 267 IS 3 BP 269 EP 274 DI 10.1016/0922-4106(94)90150-3 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA NN802 UT WOS:A1994NN80200003 PM 8088365 ER PT J AU KIM, SG KWAK, JY LEE, JW NOVAK, RF PARK, SS KIM, ND AF KIM, SG KWAK, JY LEE, JW NOVAK, RF PARK, SS KIM, ND TI MALOTILATE, A HEPATOPROTECTANT, SUPPRESSES CYP2E1 EXPRESSION IN RATS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID N-NITROSODIMETHYLAMINE DEMETHYLASE; DIALLYL SULFIDE; CYTOCHROME-P-450; INDUCTION; ETHANOL; P450IIE1; METABOLISM; ACTIVATION; PYRIDINE AB The expression of CYP2E1 was examined in hepatic tissue from rats treated with malotilate (MT), a hepatoprotectant. Microsomal p-nitrophenol hydroxylase activity in MT-treated rats was decreased to 66% and 47% of control activity at day 2 and 3 post-treatment. SDS-PAGE and immunoblot analyses of hepatic microsomes prepared from MT-treated rats showed that CYP2E1 levels were decreased below the limit of detectability. In contrast, CYP2B1 levels were increased in MT-treated microsomes, as assessed by immunoblot analyses. MT, however, failed to modulate CYP1A expression. RNA hybridization analysis revealed that CYP2E1 mRNA levels failed to change significantly by day 2 or 3 post-treatment, whereas microsomal epoxide hydrolase mRNA levels were elevated similar to 3-fold at the same time points. These results demonstrate that MT effectively suppresses CYP2E1 expression in the absence of transcriptional inactivation. (C) 1994 Academic Press, Inc. C1 YUHAN CO LTD,CENT RES INST,KYONGGI DO,SOUTH KOREA. WAYNE STATE UNIV,INST CHEM TOXICOL,DETROIT,MI 48201. NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. SEOUL NATL UNIV,COLL PHARM,SEOUL 151742,SOUTH KOREA. RP KIM, SG (reprint author), DUKSUNG WOMENS UNIV,COLL PHARM,SEOUL 132714,SOUTH KOREA. NR 25 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 16 PY 1994 VL 200 IS 3 BP 1414 EP 1420 DI 10.1006/bbrc.1994.1608 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NL388 UT WOS:A1994NL38800035 PM 8185594 ER PT J AU NAKATSUKA, M OSAWA, Y AF NAKATSUKA, M OSAWA, Y TI SELECTIVE-INHIBITION OF THE 12-LIPOXYGENASE PATHWAY OF ARACHIDONIC-ACID METABOLISM BY L-ARGININE OR SODIUM-NITROPRUSSIDE IN INTACT HUMAN PLATELETS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID TUMOR TARGET-CELLS; NITRIC-OXIDE; ACTIVATED MACROPHAGES; 12S-HYDROXYEICOSATETRAENOIC ACID; PSORIATIC PATIENTS; IRON; AGGREGATION; MOLSIDOMINE; CYCLOOXYGENASE; BIOSYNTHESIS AB L-arginine (1-100 mu M) or sodium nitroprusside (1-100 mu M) caused a concentration dependent decrease in the metabolism of exogenously added arachidonic acid via the 12-lipoxygenase pathway in intact human platelets, as determined by the use of an HPLC assay. N-G-monomethyl-L-arginine, but not the D-isomer of this compound, diminished the inhibitory effect of L-arginine. The D isomer of arginine had no effect. The cyclooxygenase pathway was much less susceptible to these effects. This study indicated that nitric oxide formed in intact human platelets selectively inhibited 12-lipoxygenase over that of cyclooxygenase and suggests that such inhibition may be an important regulatory mechanism. (C) 1994 Academic Press, Inc. C1 NHLBI,CHEM PHARMACOL LAB,BETHESDA,MD 20892. NR 33 TC 44 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 16 PY 1994 VL 200 IS 3 BP 1630 EP 1634 DI 10.1006/bbrc.1994.1638 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NL388 UT WOS:A1994NL38800065 PM 8185619 ER PT J AU VISTICA, DT KENNEY, S HURSEY, ML BOYD, MR AF VISTICA, DT KENNEY, S HURSEY, ML BOYD, MR TI CELLULAR UPTAKE AS A DETERMINANT OF CYTOTOXICITY OF QUATERNIZED ELLIPTICINES TO HUMAN BRAIN-TUMOR CELLS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID BINDING AB The quaternized ellipticine derivative, 9-methoxy-N-2-methylellipticinium acetate (MMEA), is representative of a group of ellipticinium compounds found preferentially cytotoxic to human brain tumor cell lines comprising a subpanel of the U.S. National Cancer Institute (NCI)'s in vitro ''disease-oriented'' anticancer drug discovery screen. The present studies indicate that the accumulation and cytotoxicity of MMEA in these susceptible cells are mediated in part by a cellular transport process having substrate and inhibitor specificities similar to those found in glial-derived cells which presumably comprise part of the structural (non-neuronal) elements of normal brain. RP VISTICA, DT (reprint author), NCI,DIV CANC TREATMENT,DRUG DISCOVERY RES & DEV LAB,DEV THERAPEUT PROGRAM,BLDG 1052,ROOM 121,FREDERICK,MD 21702, USA. NR 13 TC 18 Z9 18 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAY 16 PY 1994 VL 200 IS 3 BP 1762 EP 1768 DI 10.1006/bbrc.1994.1657 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NL388 UT WOS:A1994NL38800084 PM 8185636 ER PT J AU BRODER, CC KENNEDY, PE MICHAELS, F BERGER, EA AF BRODER, CC KENNEDY, PE MICHAELS, F BERGER, EA TI EXPRESSION OF FOREIGN GENES IN CULTURED HUMAN PRIMARY MACROPHAGES USING RECOMBINANT VACCINIA VIRUS VECTORS SO GENE LA English DT Article DE ABORTIVE INFECTION; CYTOPATHIC EFFECT; DNA SYNTHESIS; PROTEIN SYNTHESIS; ALTERNATIVE PROMOTERS; P-GALACTOSIDASE; CD4; HIV ENVELOPE GLYCOPROTEIN ID BACTERIOPHAGE-T7 RNA-POLYMERASE; HUMAN-IMMUNODEFICIENCY-VIRUS; MAMMALIAN-CELLS; SYSTEM; TRANSCRIPTION; REPLICATION; INFECTION; MEMBRANE; PROTEINS AB Recombinant vaccinia viruses (re-VVs) provide an extremely versatile method for the expression of foreign genes in a wide range of cultured cell types of different lineages and species. In the present report, we examine the utility of re-VV vectors for re-protein production in cultured human primary macrophages obtained through in vitro differentiation of peripheral blood monocytes. Primary macrophages supported early stages of the VV infection cycle, including morphologic cytopathic effect, shut-off of host protein synthesis and activation of early viral protein synthesis; however, late stages of infection were blocked, including synthesis of late viral proteins, replication of viral DNA, and production of infectious progeny virions. Abortive infection was observed with several independent VV strains. Using re-VVs containing Escherichia coli lacZ as a reporter gene, we assayed the activities of different classes of VV promoters. Consistent with the results noted above, human primary macrophages supported reporter gene expression driven by an early or intermediate VV promoter, but not by a late promoter; expression was obtained with synthetic bifunctional promoters containing early and/or intermediate components. Primary macrophages also supported the VV/bacteriophage T7 RNA polymerase hybrid gene expression system. The utility of re-VV vectors for production of proteins of biological interest in human primary macrophages was demonstrated using re-VVs encoding human CD4 and the human immunodeficiency virus type-1 envelope glycoprotein. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. NR 19 TC 42 Z9 42 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 16 PY 1994 VL 142 IS 2 BP 167 EP 174 DI 10.1016/0378-1119(94)90257-7 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA NP201 UT WOS:A1994NP20100002 PM 8194748 ER PT J AU NAGATA, T KANNO, Y OZATO, K TAKETO, M AF NAGATA, T KANNO, Y OZATO, K TAKETO, M TI THE MOUSE RXRB GENE ENCODING RXR-BETA - GENOMIC ORGANIZATION AND 2 MESSENGER-RNA ISOFORMS GENERATED BY ALTERNATIVE SPLICING OF TRANSCRIPTS INITIATED FROM CPG ISLAND PROMOTERS SO GENE LA English DT Article DE RETINOIDS; HETERODIMERS; ZINC FINGERS; STEROID RECEPTORS; H-2RIIBP ID RETINOID-X RECEPTOR; NUCLEAR RECEPTOR; THYROID-HORMONE; GAMMA-GENE; ACID; SUPERFAMILY; ALPHA; EXPRESSION; SEQUENCE; INDUCTION AB Two major isoforms of retinoid X receptor beta (RXR beta; H-2RIIBP), encoded by the Rxrb gene, have been identified in the mouse. Northern analysis of Rxrb mRNA showed two close bands of 2.8 and 2.6 kb in many tissues and cell lines. They are designated as mRxr beta 1 and mRxr beta 2, respectively. Some rapidly growing cell lines and spleen tissue had about twofold more Rxr beta 1 mRNA than Rxr beta 2 whereas most adult tissues had similar amounts of both pi and beta 2. Amino acid (aa) sequences deduced from cDNAs show an extra N-terminal domain of 72 aa for RXR beta 1 that is well conserved between mouse and human, but not found in RXR beta 2. These isoforms are generated from separate exons transcribed from different CpG island promoters and spliced into the common acceptor site in the transactivation domain by an alternative splicing. The Rxrb gene contains an intron in the midst of the first zinc-finger coding region. This is different from the retinoic acid receptor (RAR) and other nuclear receptor superfamily genes that contain an intron between the first and the second zinc-finger coding regions. These results, together with their unique ability to form heterodimers with other members of the superfamily, suggest a distinct phylogenic position for the Rxr genes. C1 BANYU TSUKUBA RES INST MERCK,TSUKUBA 30033,IBARAKI,JAPAN. NICHHD,MOLEC GROWTH REGULAT LAB,BETHESDA,MD 20892. DUKE UNIV,MED CTR,DEPT MICROBIOL & IMMUNOL,DURHAM,NC 27710. RI Kanno, Yuka/B-5802-2013 NR 38 TC 46 Z9 47 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD MAY 16 PY 1994 VL 142 IS 2 BP 183 EP 189 DI 10.1016/0378-1119(94)90259-3 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA NP201 UT WOS:A1994NP20100004 PM 8194750 ER PT J AU KAHN, RA AF KAHN, RA TI HOT PAPERS - BIOCHEMISTRY - THE AMINO-TERMINUS OF ADP-RIBOSYLATION FACTOR (ARF) IS A CRITICAL DETERMINANT OF ARF ACTIVITIES AND IS A POTENT AND SPECIFIC INHIBITOR OF PROTEIN-TRANSPORT BY KAHN,R.A., RANDAZZO,P., SERAFINI,T., WEISS,O., RULKA,C., CLARK,J., AMHERDT,M., ROLLER,P., ORCI,L., ROTHMAN,J.E. SO SCIENTIST LA English DT Article RP KAHN, RA (reprint author), NCI,BIOL CHEM LAB,BETHESDA,MD 20892, USA. NR 4 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 16 PY 1994 VL 8 IS 10 BP 16 EP 16 PG 1 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA NL529 UT WOS:A1994NL52900013 ER PT J AU SIDDIQUI, MA MARQUEZ, VE DRISCOLL, JS BARCHI, JJ AF SIDDIQUI, MA MARQUEZ, VE DRISCOLL, JS BARCHI, JJ TI A DIASTEREOSELECTIVE SYNTHESIS OF (S,S)-ALPHA-FLUORO-2,2-DIMETHYL-1,3-DIOXOLANE-4-PROPANOIC ACID METHYL-ESTER, A KEY INTERMEDIATE FOR THE PREPARATION OF ANTI-HIV EFFECTIVE FLUORODIDEOXYNUCLEOSIDES SO TETRAHEDRON LETTERS LA English DT Article ID BENZENEDISULFONIMIDE; REAGENT AB (S,S)-alpha-fluoro-2,2-dimethyl-1,3-dioxolane-4-propanoic acid methyl ester (10), a key intermediate for the preparation of anti-HIV active 9-(2,3-dideoxy-2-fluoro-beta-D-threo-pentofuranosyl) adenine (1, FddA) and 1-(2,3-dideoxy-2-fluoro-beta-D-threo-pentofuranosyl)cytosine (2, FddC) was prepared via the diastereoselective fluorination of the chiral imide enolate obtained from 8 with N-fluorobenzenesulfonimide. The overall yield of 10 from the readily available 1,2:5,6-di-O-isopropylidene-D-mannitol was 25% (de 93%). C1 NCI,DIV CANC TREATMENT,MED CHEM LAB,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. RI Barchi Jr., Joseph/N-3784-2014 NR 13 TC 31 Z9 31 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD MAY 16 PY 1994 VL 35 IS 20 BP 3263 EP 3266 DI 10.1016/S0040-4039(00)76880-8 PG 4 WC Chemistry, Organic SC Chemistry GA NM584 UT WOS:A1994NM58400012 ER PT J AU SCHEFFKNECHT, BHB BONOW, RO DWYER, AJ MARON, BJ AF SCHEFFKNECHT, BHB BONOW, RO DWYER, AJ MARON, BJ TI FUNCTIONAL ASSESSMENT OF LEFT-VENTRICULAR EJECTION DYNAMICS BY CINE-MAGNETIC RESONANCE IMAGING IN HYPERTROPHIC CARDIOMYOPATHY SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Note ID GRADIENT C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. NIH,WARREN G MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. NR 7 TC 3 Z9 3 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 1994 VL 73 IS 13 BP 981 EP 984 DI 10.1016/0002-9149(94)90149-X PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA NL868 UT WOS:A1994NL86800015 PM 8184863 ER PT J AU RAUTAHARJU, PM MANOLIO, TA PSATY, BM BORHANI, NO FURBERG, CD AF RAUTAHARJU, PM MANOLIO, TA PSATY, BM BORHANI, NO FURBERG, CD TI CORRELATES OF QT PROLONGATION IN OLDER ADULTS (THE CARDIOVASCULAR-HEALTH-STUDY) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Note ID LEFT-VENTRICULAR MASS; INTERVAL; PREDICTION; DISEASE; SEX; AGE C1 NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. UNIV WASHINGTON,DEPT EPIDEMIOL,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT HLTH SERV,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT MED,SEATTLE,WA. UNIV WASHINGTON,DEPT BIOSTAT,SEATTLE,WA 98195. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,WINSTON SALEM,NC 27103. UNIV ALBERTA,DIV CARDIOL,CTR EPICORE,EDMONTON,AB,CANADA. FU NHLBI NIH HHS [N01-HC-85079, N01-HC-85080, N01-HC-85081] NR 17 TC 30 Z9 31 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 1994 VL 73 IS 13 BP 999 EP 1002 DI 10.1016/0002-9149(94)90156-2 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA NL868 UT WOS:A1994NL86800022 PM 8184870 ER PT J AU TELL, GS EVANS, GW FOLSOM, AR SHIMAKAWA, T CARPENTER, MA HEISS, G AF TELL, GS EVANS, GW FOLSOM, AR SHIMAKAWA, T CARPENTER, MA HEISS, G TI DIETARY-FAT INTAKE AND CAROTID-ARTERY WALL THICKNESS - THE ATHEROSCLEROSIS RISK IN COMMUNITIES (ARIC) STUDY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE ARTERIES; ATHEROSCLEROSIS; CHOLESTEROL; DIETARY FATS; ULTRASONOGRAPHY ID CORONARY HEART-DISEASE; B-MODE ULTRASOUND; SERUM-CHOLESTEROL; RHESUS-MONKEYS; REGRESSION; LESIONS; EPIDEMIOLOGY; PATHOGENESIS; PREDICTORS; LIPIDS AB Associations between atherosclerosis and dietary fat and cholesterol have been demonstrated in numerous animal experiments. The relation between these dietary components and atherosclerosis has not previously been reported in a population-based study among human beings. The associations of dietary fat and cholesterol with carotid artery wall thickness (atherosclerosis) were investigated in a population-based study, the Atherosclerosis Risk in Communities (ARIC) Study, from 1987 to 1989. Participants were 2,095 black women, 5,146 white women, 1,318 black men and 4,589 white men, aged 45-64 years, recruited from four US communities: Jackson, Mississippi; Forsyth County, North Carolina; Washington County, Maryland; and Minneapolis, Minnesota. Habitual diet was assessed with a food frequency questionnaire. Wall thickness was measured with B-mode ultrasound. After adjustment for age and energy intake, animal fat, saturated fat, monounsaturated fat, cholesterol, and Keys' score were positively related to wall thickness, while vegetable fat and polyunsaturated fat were inversely related to wall thickness. These associations persisted after further adjustment for smoking and hypertension and were consistent across the four race and sex groups. Thus, elements of habitual dietary intake were consistently associated with carotid artery wall thickness, compatible with their putatively atherogenic and antiatherogenic properties. C1 UNIV MINNESOTA,SCH PUBL HLTH,DIV EPIDEMIOL,MINNEAPOLIS,MN 55455. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. UNIV N CAROLINA,SCH PUBL HLTH,DEPT BIOSTAT,CHAPEL HILL,NC. UNIV N CAROLINA,SCH PUBL HLTH,DEPT EPIDEMIOL,CHAPEL HILL,NC. RP TELL, GS (reprint author), WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,MED CTR BLVD,WINSTON SALEM,NC 27157, USA. RI Tell, Grethe/G-5639-2015 OI Tell, Grethe/0000-0003-1386-1638 FU NHLBI NIH HHS [N01-HC-55015, N01-HC-55016, N01-HC-55018] NR 38 TC 41 Z9 42 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 15 PY 1994 VL 139 IS 10 BP 979 EP 989 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA NM178 UT WOS:A1994NM17800002 PM 8178786 ER PT J AU PARMELEE, DC HOANG, TN BENJAMIN, T SECHI, S AF PARMELEE, DC HOANG, TN BENJAMIN, T SECHI, S TI NONINTERFERING SYNTHETIC PEPTIDES AS INTERNAL CONTROLS FOR AMINO-ACID SEQUENCING OF SAMPLE UNKNOWNS SO ANALYTICAL BIOCHEMISTRY LA English DT Article AB Noninterfering synthetic peptides have been designed that may be used as internal sequencing standards (ISS-1 and ISS-2) by placing them in an amino acid sequencer with the sample. The peptides are composed of four unnatural amino acids which all yield phenylthiohydantoin derivatives having unique retention times compared with those obtained from the commonly observed natural residues. These internal standards indicate how the entire sequencing system was functioning during the actual analysis of an unknown by providing an initial yield and numerous repetitive yields. Verifying proper operation is extremely important when cycles appear blank due to the presence of modified amino acids or a blocked N-terminus. In addition, the ISS peptides can detect and identify different types of sequencing errors. This sometimes eliminates the need to rerun a sample due to blank cycles caused by mechanical malfunctions which result in failure to cleave the N-terminal residues. ISS-1 or ISS-2 may also be utilized during method development to compare different sample supports and to normalize sequencing data from proteins or peptides that have been treated differently. (C) Academic Press, Inc. C1 NIAID,MOLEC ALLERGY & IMMUNOL SECT,ROCKVILLE,MD 20852. RP PARMELEE, DC (reprint author), NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892, USA. NR 8 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD MAY 15 PY 1994 VL 219 IS 1 BP 71 EP 81 DI 10.1006/abio.1994.1233 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA NK804 UT WOS:A1994NK80400011 PM 8059958 ER PT J AU HALL, WA LUCIANO, MG DOPPMAN, JL PATRONAS, NJ OLDFIELD, EH AF HALL, WA LUCIANO, MG DOPPMAN, JL PATRONAS, NJ OLDFIELD, EH TI PITUITARY MAGNETIC-RESONANCE-IMAGING IN NORMAL HUMAN VOLUNTEERS - OCCULT ADENOMAS IN THE GENERAL-POPULATION SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE ADENOMA; PITUITARY NEOPLASMS; MAGNETIC RESONANCE IMAGING; GADOLINIUM; CUSHINGS SYNDROME ID SECRETING MICROADENOMAS; CUSHING DISEASE; GLAND; APPEARANCE; EXPERIENCE; 1.5-T; AGE AB Objective: To determine the prevalence of focal lesions of the pituitary gland that suggest the presence of a pituitary adenoma in asymptomatic persons. Design: 100 normal volunteers (70 women, 30 men; age range, 18 to 60 years old) were studied by high-resolution magnetic resonance imaging (MRI) of the pituitary gland before and after administration of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA). Setting: Occult pituitary adenomas are identified at autopsy in 3% to 27% of unselected asymptomatic patients. The frequency of incidental pituitary adenomas detected by MRI in normal persons is unknown. Measurements: The MRI scans from volunteers were randomly mixed with scans of 57 patients with Cushing disease and interpreted independently by three blinded reviewers. Results: Seven women (10%) and three men (10%) had focal areas of decreased signal intensity in the pituitary gland after administration of Gd-DTPA. The lesions ranged from 3 to 6 mm in greatest diameter and were diagnosed as pituitary adenomas by at least two of the three reviewers. When similar lesions were detected on MRI scans in patients with Cushing disease, the positive predictive value for identification of an adenoma at that site was 86%. Conclusions: About 10% of the normal adult population have pituitary abnormalities on MRI scans that are compatible with the diagnosis of asymptomatic pituitary adenomas. Most pituitary adenomas remain asymptomatic and do not require treatment. C1 NIH,CTR CLIN,SURG NEUROL BRANCH,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. NINCDS,BETHESDA,MD 20892. NR 26 TC 318 Z9 336 U1 2 U2 2 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 15 PY 1994 VL 120 IS 10 BP 817 EP 820 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA NK458 UT WOS:A1994NK45800001 PM 8154641 ER PT J AU FRIGUET, B SZWEDA, LI STADTMAN, ER AF FRIGUET, B SZWEDA, LI STADTMAN, ER TI SUSCEPTIBILITY OF GLUCOSE-6-PHOSPHATE-DEHYDROGENASE MODIFIED BY 4-HYDROXY-2-NONENAL AND METAL-CATALYZED OXIDATION TO PROTEOLYSIS BY THE MULTICATALYTIC PROTEASE SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID COLI GLUTAMINE-SYNTHETASE; LEUCONOSTOC-MESENTEROIDES; PROTEINASE COMPLEX; DEGRADATION; ENZYME AB Glucose-6-phosphate dehydrogenase from Leuconostoc mesenteroides is inactivated when exposed to metal-catalyzed oxidation or when modified by the lipid peroxidation product, 4-hydroxy-2-nonenal (HNE). Although in each case inactivation appears to be the result of the selective modification of an active site lysine residue, only the oxidized enzyme becomes more susceptible to proteolysis by purified rat liver multicatalytic protease, a multienzymatic proteolytic complex involved in the intracellular degradation of damaged proteins. The HNE-treated enzyme remains as resistant to proteolysis by the multicatalytic protease as the native enzyme. In contrast to the HNE-treated Glu-6-PDH, enzyme modified by Fe2+ and citrate is more thermolabile and exhibits increased binding of the hydrophobic probe 8-anilino-1-naphtalene sulfonic acid (ANSA). Heat inactivation is characterized, in part, by dissociation of the dimer to inactive subunits. No change in the secondary structure and only small variations in the fluorescence and circular dichroism of the aromatic residues are observed for the two modified forms of the enzyme as compared with the native enzyme. The increased heat sensitivity, ANSA binding, and proteolytic susceptibility are likely related to a decrease in the structural stability of oxidatively modified Glu-6-PDH. Conversely, modification of Glu-6-PDH with HNE has no apparent effect on its structural stability or proteolytic susceptibility. This finding may have important implications for the accumulation of altered protein in vivo, a process that is believed to be involved in age- and disease-related impairment of cellular function. (C) 1994 Academic Press, Inc. C1 NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. NR 20 TC 140 Z9 143 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 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD MAY 15 PY 1994 VL 311 IS 1 BP 168 EP 173 DI 10.1006/abbi.1994.1222 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NL760 UT WOS:A1994NL76000022 PM 8185314 ER PT J AU SMITH, SB DUNCAN, T KUTTY, G KUTTY, RK WIGGERT, B AF SMITH, SB DUNCAN, T KUTTY, G KUTTY, RK WIGGERT, B TI INCREASE IN RETINYL PALMITATE CONCENTRATION IN EYES AND LIVERS AND THE CONCENTRATION OF INTERPHOTORECEPTOR RETINOID-BINDING PROTEIN IN EYES OF VITILIGO MUTANT MICE SO BIOCHEMICAL JOURNAL LA English DT Article ID VITAMIN-A; PIGMENT-EPITHELIUM; MOUSE MODEL; RHODOPSIN; RATS; TRANSPORT; ACYLTRANSFERASE; PHOTORECEPTORS; TOXICITY; LECITHIN AB Retinyl esters play an important role in the visual cycle because they are involved in regeneration of 11-cis-retinal for use in rhodopsin formation. In the present study, retinyl ester concentrations were significantly elevated in eyes and livers of mice homozygous for the vitiligo mutation (mi(vit)/mi(vit)). Vitiligo mice demonstrate a slowly progressing retinal degeneration characterized by gradual loss of photoreceptor cells and rhodopsin as well as uneven pigmentation of the retinal pigment epithelium (RPE). Analysis of retinoids by h.p.l.c. indicated that the retinyl palmitate level was increased fivefold in eyes of affected mice at 10 weeks postnatally and was threefold higher at 22 weeks of age. Accumulation of retinyl palmitate occurred in the RPE rather than the neural retina. Furthermore, the concentration of all-trans-retinol was elevated in the RPE of vitiligo mice. Levels of interphotoreceptor retinoid binding protein (IRBP) were increased in vitiligo mice between ages 4 and 14 weeks, but returned to normal by 16 weeks. Increased IRBP levels were not due to increased protein synthesis because IRBP mRNA levels did not differ significantly between control and affected animals. To examine possible systemic involvement in vitiligo mice, retinoids were evaluated in liver and plasma. Mean hepatic total vitamin A levels in affected mice were approximately 1.7 times higher than controls. Analysis of esterified and non-esterified retinoids in liver showed that the concentration of retinyl palmitate was elevated. Plasma retinol levels were normal. This study provides the first evidence of altered systemic retinoid metabolism in vitiligo mice, which occurs, significantly, under normal dietary conditions. C1 MED COLL GEORGIA,DEPT OPHTHALMOL,AUGUSTA,GA 30912. NEI,RETINAL CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. RP SMITH, SB (reprint author), MED COLL GEORGIA,DEPT CELL BIOL & ANAT,AUGUSTA,GA 30912, USA. FU NEI NIH HHS [EY 06859, EY09682] NR 35 TC 24 Z9 24 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD MAY 15 PY 1994 VL 300 BP 63 EP 68 PN 1 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NN566 UT WOS:A1994NN56600011 PM 8198552 ER PT J AU RAPAPORT, MH SCHMIDT, ME RISINGER, R MANJI, H AF RAPAPORT, MH SCHMIDT, ME RISINGER, R MANJI, H TI THE EFFECTS OF PROLONGED LITHIUM EXPOSURE ON THE IMMUNE-SYSTEM OF NORMAL CONTROL SUBJECTS - SERIAL SERUM-SOLUBLE INTERLEUKIN-2 RECEPTOR AND ANTITHYROID ANTIBODY MEASUREMENTS SO BIOLOGICAL PSYCHIATRY LA English DT Article DE LITHIUM; AUTOANTIBODIES; IMMUNOLOGY; THYROID; SIL-2RS; BIOLOGICAL PSYCHIATRY ID ADENYLATE-CYCLASE ACTIVITY; INOSITOL PHOSPHOLIPID HYDROLYSIS; MANIC-DEPRESSIVE PATIENTS; RAT CEREBRAL-CORTEX; THYROID-FUNCTION; INVITRO; BRAIN; CARBONATE; INHIBITION; THERAPY AB The purpose of this study was to begin evaluating the effects of lithium carbonate on in vivo immune function in normal controls. We, postulated that lithium carbonate would stimulate lymphocytes but would not affect the production of antithyroid antibodies. Twenty-seven normal controls had blood samples drawn for measurements of serum soluble interleukin-2 receptors (SIL-2Rs), antithyroglobulin antibodies, and antimicrosomal antibodies prior to and after approximately 1 and 4 weeks of treatment with lithium carbonate at therapeutic blood levels. Subjects had a small brat statistically significant increase in serum SIL-2Rs after 4 weeks of lithium treatment (446.3 +/- 177.2 U/ml versus 497.6 +/- 232.3 U/ml, p = 0.033). There was no increase in the prevalence of antithyroglobulin or antimicrosomal antibodies with lithium treatment nor did lithium act as an adjuvant to increase the titers in subjects with preexisting antithyroid antibodies. C1 VET AFFAIRS MED CTR,PSYCHIAT SERV,SAN DIEGO,CA. NIMH,CLIN PHARMACOL SECT,EXPTL THERAPEUT BRANCH,BETHESDA,MD. RP RAPAPORT, MH (reprint author), UNIV CALIF SAN DIEGO,SCH MED,DEPT PSYCHIAT 0655,9500 GILLMAN DR,LA JOLLA,CA 92093, USA. RI Schmidt, Mark/I-5052-2016 OI Schmidt, Mark/0000-0003-3417-8977 FU NIMH NIH HHS [MH30914] NR 66 TC 17 Z9 18 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 15 PY 1994 VL 35 IS 10 BP 761 EP 766 DI 10.1016/0006-3223(94)91136-3 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NM161 UT WOS:A1994NM16100002 PM 8043704 ER PT J AU RAPAPORT, MH MCALLISTER, CG KIM, YS HAN, JH PICKAR, D NELSON, DL KIRCH, DG PAUL, SM AF RAPAPORT, MH MCALLISTER, CG KIM, YS HAN, JH PICKAR, D NELSON, DL KIRCH, DG PAUL, SM TI INCREASED SERUM-SOLUBLE INTERLEUKIN-2 RECEPTORS IN CAUCASIAN AND KOREAN SCHIZOPHRENIC-PATIENTS SO BIOLOGICAL PSYCHIATRY LA English DT Article DE SCHIZOPHRENIA; SIL-2RS; IMMUNOLOGY; ETHNICITY; BIOLOGICAL PSYCHIATRY; PSYCHOTROPIC MEDICATION ID ANTIBODY AB Recent studies have identified immunologic abnormalities in some schizophrenic subjects. This experiment replicates previous findings that serum soluble interleukin-2 receptors (SIL-2Rs) are elevated in schizophrenic patients, and is the first study to describe this phenomenon in non-Caucasian patients. Despite differences between Korean and Caucasian schizophrenic patients in absolute serum SIL-2R levels, both groups were significantly elevated when compared with their respective ethnic control groups (477 +/- 171 U/ml versus 354 +/- 172 U/ml and 763 +/- 347 U/ml versus 567 +/- 231 U/ml, respectively). Neither age, gender, medication status, nor duration of illness correlated with SIL-2R levels. These findings are further evidence that immune activation is present, regardless of ethnic origin, in some schizophrenic patients. C1 VET ADM MED CTR,PSYCHIAT SERV,SAN DIEGO,CA. UNIV PITTSBURGH,DEPT PSYCHIAT,PITTSBURGH,PA. UNIV PITTSBURGH,DEPT PSYCHOL,PITTSBURGH,PA 15260. SEOUL NATL UNIV,DEPT PSYCHIAT,SEOUL,SOUTH KOREA. ST MARYS HOSP,DEPT NEUROPSYCHIAT,SEOUL,SOUTH KOREA. CATHOLIC MED COLL,SEOUL,SOUTH KOREA. NIMH,CLIN THERAPEUT BRANCH,BETHESDA,MD. NCI,METAB BRANCH,BETHESDA,MD 20892. NCI,INTRAMURAL RES PROGRAM,BETHESDA,MD. RP RAPAPORT, MH (reprint author), UNIV CALIF SAN DIEGO,SCH MED,DEPT PSYCHIAT 0655,8950 VILLA LAJOLLA DR,SUITE 2243,LA JOLLA,CA 92037, USA. NR 30 TC 48 Z9 50 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 15 PY 1994 VL 35 IS 10 BP 767 EP 771 DI 10.1016/0006-3223(94)91137-1 PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NM161 UT WOS:A1994NM16100003 PM 8043705 ER PT J AU GEORGE, MS GUIDOTTI, A RUBINOW, D PAN, BS MIKALAUSKAS, K POST, RM AF GEORGE, MS GUIDOTTI, A RUBINOW, D PAN, BS MIKALAUSKAS, K POST, RM TI CSF NEUROACTIVE STEROIDS IN AFFECTIVE-DISORDERS - PREGNENOLONE, PROGESTERONE, AND DBI SO BIOLOGICAL PSYCHIATRY LA English DT Article DE AFFECTIVE DISORDER; ANXIETY; CEREBROSPINAL FLUID; DIAZEPAM BINDING INHIBITOR; PREGNENOLONE; PROGESTERONE; STEROIDS ID RECEPTOR; NEUROSTEROIDS; BRAIN AB Recently several steroid compounds have been discovered to act as neuromodulators in diverse central nervous system (CNS) functions. We wondered if neuroactive steroids might be involved in affective illness or in the mode of action of mood-regulating medications such as carbamazepine. Levels of the neuroactive steroids pregnenolone and progesterone, as well as the neuropeptide diazepam binding inhibitor (DBI) (known to promote steroidogenesis), were analyzed from cerebrospinal fluid (CSF) obtained by lumbar puncture (LP) from 27 medication-free subjects with affective illness and 10 healthy volunteers. Mood-disordered subjects who were clinically depressed at the time of the LP had lower CSF pregnenolone (n = 9, 0.16 ng/ml) compared with euthymic volunteers (n = 10, 0.35 ng/ml; p < 0.01). In addition, pregnenolone was lower in all affectively ill subjects (n = 26, 0.21 ng/ml), regardless of mood state on the LP day, than healthy volunteers (p < 0.05). No differences were found for progesterone or DBI levels by mood state or diagnosis. Progesterone, pregnenolone, and DBI did not change significantly or consistently in affectively ill subjects after treatment with carbamazepine. CSF pregnenolone is decreased in subjects with affective illness, particularly during episodes of active depression. Further research into the role of neuroactive steroids in mood regulation is warranted. C1 GEORGETOWN UNIV,MED CTR,WASHINGTON,DC 20007. RP GEORGE, MS (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,RM 3N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 17 TC 72 Z9 76 U1 0 U2 3 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 1994 VL 35 IS 10 BP 775 EP 780 DI 10.1016/0006-3223(94)91139-8 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NM161 UT WOS:A1994NM16100005 PM 8043707 ER PT J AU SWANN, AC STOKES, PE SECUNDA, SK MAAS, JW BOWDEN, CL BERMAN, N KOSLOW, SH AF SWANN, AC STOKES, PE SECUNDA, SK MAAS, JW BOWDEN, CL BERMAN, N KOSLOW, SH TI DEPRESSIVE MANIA VERSUS AGITATED DEPRESSION - BIOGENIC-AMINE AND HYPOTHALAMIC-PITUITARY-ADRENOCORTICAL FUNCTION SO BIOLOGICAL PSYCHIATRY LA English DT Article DE BIPOLAR DISORDER; MANIA; DEPRESSION; MIXED STATES; CATECHOLAMINES; CORTISOL; NOREPINEPHRINE ID DEXAMETHASONE SUPPRESSION TEST; BRANCH COLLABORATIVE PROGRAM; MIXED AFFECTIVE STATES; MONOAMINE METABOLITES; AFFECTIVE-DISORDERS; CATECHOLAMINE METABOLISM; CLINICAL CHARACTERISTICS; BIOLOGICAL COMPONENT; CEREBROSPINAL-FLUID; LITHIUM-CARBONATE AB The existence of mixed affective states challenges the idea of specific biological abnormalities in depression and mania. We compared biogenic amines and hypothalamic-pituitary-adreno-cortical (HPA) function in mixed manic (n = 8), pure manic (n = 11), agitated bipolar depressed (n = 20), and nonagitated bipolar depressed (n = 27) inpatients (Research Diagnostic Criteria). Mixed manics met Research Diagnostic Criteria for primary manic episodes and also met criteria for major depressive episodes except for duration. The norepinephrine metabolite methoxyhydroxy phenthylene glycol (MHPG) was higher in cerebrospinal fluid from mixed manic than from agitated depressed patients, consistent with differences previously reported between the overall samples of depressed and manic patients. Similarly, patients in a mixed state had higher urinary excretion of norepinephrine (NE) and elevated output of NE relative to its metabolites. HPA activity was similar in mixed manic and agitated depressed patients. These data suggest that mixed manics combine certain biological abnormalities considered to be characteristic of mania and of depression. C1 CORNELL UNIV MED COLL,ITHACA,NY. NIMH,BETHESDA,MD. UNIV TEXAS,SCH MED,SAN ANTONIO,TX. UNIV CALIF LOS ANGELES,HARBOR MED CTR,INST RES & EDUC,LOS ANGELES,CA 90024. RP SWANN, AC (reprint author), UNIV TEXAS,SCH MED,DEPT PSYCHIAT,POB 20708,HOUSTON,TX 77225, USA. FU NIMH NIH HHS [MH26975, MH26977, UO1 MH38084] NR 64 TC 38 Z9 39 U1 3 U2 4 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 1994 VL 35 IS 10 BP 803 EP 813 DI 10.1016/0006-3223(94)91143-6 PG 11 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NM161 UT WOS:A1994NM16100009 PM 7519061 ER PT J AU FUNAKOSHI, S LONGO, DL BECKWITH, M CONLEY, DK TSARFATY, G TSARFATY, I ARMITAGE, RJ FANSLOW, WC SPRIGGS, MK MURPHY, WJ AF FUNAKOSHI, S LONGO, DL BECKWITH, M CONLEY, DK TSARFATY, G TSARFATY, I ARMITAGE, RJ FANSLOW, WC SPRIGGS, MK MURPHY, WJ TI INHIBITION OF HUMAN B-CELL LYMPHOMA GROWTH BY CD40 STIMULATION SO BLOOD LA English DT Note ID SEVERE COMBINED IMMUNODEFICIENCY; ACTIVATION; ANTIBODY; RECEPTOR; LINES; ANTIGEN; LIGAND; MICE C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD. NCI,FREDERICK CANC RES & DEV CTR,BASIC RES PROGRAM,ADV BIOSCI LABS INC,FREDERICK,MD. IMMUNEX CORP,SEATTLE,WA. RP FUNAKOSHI, S (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,LEUKOCYTE BIOL LAB,FREDERICK,MD 21702, USA. NR 24 TC 194 Z9 201 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 15 PY 1994 VL 83 IS 10 BP 2787 EP 2794 PG 8 WC Hematology SC Hematology GA NL607 UT WOS:A1994NL60700003 PM 7514045 ER PT J AU CHAO, NJ SCHRIBER, JR LONG, GD NEGRIN, RS CATOLICO, M BROWN, BW MILLER, LL BLUME, KG AF CHAO, NJ SCHRIBER, JR LONG, GD NEGRIN, RS CATOLICO, M BROWN, BW MILLER, LL BLUME, KG TI A RANDOMIZED STUDY OF ERYTHROPOIETIN AND GRANULOCYTE-COLONY-STIMULATING FACTOR (G-CSF) VERSUS PLACEBO AND G-CSF FOR PATIENTS WITH HODGKINS AND NON-HODGKINS-LYMPHOMA UNDERGOING AUTOLOGOUS BONE-MARROW TRANSPLANTATION SO BLOOD LA English DT Article ID RECOMBINANT-HUMAN-ERYTHROPOIETIN; STAGE RENAL-DISEASE; CLINICAL-TRIAL; ANEMIA; BLOOD; CELL; CHEMOTHERAPY; THERAPY; INVIVO C1 STANFORD UNIV,DIV BIOSTAT,STANFORD,CA. NCI,CANC THERAPY EVALUAT PROGRAM,BETHESDA,MD. RP CHAO, NJ (reprint author), STANFORD UNIV,MED CTR,BONE MARROW TRANSPLANT PROGRAM,300 PASTEUR DR,ROOM H1353,STANFORD,CA 94305, USA. NR 33 TC 39 Z9 39 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 15 PY 1994 VL 83 IS 10 BP 2823 EP 2828 PG 6 WC Hematology SC Hematology GA NL607 UT WOS:A1994NL60700008 PM 7514046 ER PT J AU MCKEOWN, L VAIL, M WILLIAMS, S KRAMER, W HANSMANN, K GRALNICK, H AF MCKEOWN, L VAIL, M WILLIAMS, S KRAMER, W HANSMANN, K GRALNICK, H TI PLATELET-ADHESION TO COLLAGEN IN INDIVIDUALS LACKING GLYCOPROTEIN-IV SO BLOOD LA English DT Article ID PARASITIZED ERYTHROCYTES; MEDIATES CYTOADHERENCE; MONOCLONAL-ANTIBODY; MEMBRANE; RECEPTOR; CD36; IDENTIFICATION; THROMBOSPONDIN; PROTEIN; NAKA C1 NIH,SERV HEMATOL,BETHESDA,MD 20892. NR 26 TC 34 Z9 35 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 15 PY 1994 VL 83 IS 10 BP 2866 EP 2871 PG 6 WC Hematology SC Hematology GA NL607 UT WOS:A1994NL60700014 PM 7514049 ER PT J AU BOSCO, MC ESPINOZADELGADO, I SCHWABE, M GUSELLA, GL LONGO, DL SUGAMURA, K VARESIO, L AF BOSCO, MC ESPINOZADELGADO, I SCHWABE, M GUSELLA, GL LONGO, DL SUGAMURA, K VARESIO, L TI REGULATION BY INTERLEUKIN-2 (IL-2) AND INTERFERON-GAMMA OF IL-2 RECEPTOR-GAMMA CHAIN GENE-EXPRESSION IN HUMAN MONOCYTES SO BLOOD LA English DT Article ID NATURAL-KILLER-CELLS; MESSENGER-RNA EXPRESSION; BETA-CHAIN; ALPHA-CHAIN; BIOCHEMICAL-EVIDENCE; LIGAND-BINDING; GROWTH SIGNAL; IFN-GAMMA; INDUCTION; COMPLEX C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS DEV PROGRAM,FREDERICK,MD 21702. NCI,MED BRANCH,CLIN ONCOL PROGRAM,BETHESDA,MD 20892. TOHOKU UNIV,SCH MED,DEPT MICROBIOL,SENDAI 982,JAPAN. RP BOSCO, MC (reprint author), NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,OFF ASSOCIATE DIRECTOR,FREDERICK,MD 21702, USA. RI Bosco, Maria Carla/J-7928-2016; varesio, luigi/J-8261-2016 OI Bosco, Maria Carla/0000-0003-1857-7193; varesio, luigi/0000-0001-5659-2218 NR 56 TC 58 Z9 58 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 15 PY 1994 VL 83 IS 10 BP 2995 EP 3002 PG 8 WC Hematology SC Hematology GA NL607 UT WOS:A1994NL60700030 PM 8180396 ER PT J AU CROPP, CS NEVANLINNA, HA PYRHONEN, S STENMAN, UH SALMIKANGAS, P ALBERTSEN, B WHITE, R CALLAHAN, R AF CROPP, CS NEVANLINNA, HA PYRHONEN, S STENMAN, UH SALMIKANGAS, P ALBERTSEN, B WHITE, R CALLAHAN, R TI EVIDENCE FOR INVOLVEMENT OF BRCA1 IN SPORADIC BREAST CARCINOMAS SO CANCER RESEARCH LA English DT Note ID DUCHENNE MUSCULAR-DYSTROPHY; OVARIAN-CANCER; GENE; CHROMOSOME-17Q; POLYMORPHISMS AB The hereditary breast cancer gene BRCA1 previously has been localized to chromosome 17q21. We looked for evidence of involvement of this region of chromosome 17 in 130 sporadic breast cancers. Seventeen polymorphic sequence tagged site markers were examined in these tumors between the D17S250 and D17S579 loci to screen for deletions as measured by loss of heterozygosity. The smallest common region that was deleted occurred in the approximately 120-kilobase interval between the D17S846 and D175S746 loci within the BRCA1 region. Delineation of this commonly deleted area should accelerate attempts to identify the involved gene(s) and its relationship to BRCA1. C1 UNIV HELSINKI, CENT HOSP, DEPT OBSTET & GYNECOL 1, SF-00290 HELSINKI, FINLAND. UNIV HELSINKI, CENT HOSP, DEPT OBSTET & GYNECOL 2, SF-00290 HELSINKI, FINLAND. UNIV HELSINKI, CENT HOSP, DEPT RADIOTHERAPY & ONCOL, SF-00290 HELSINKI, FINLAND. UNIV UTAH, ECCLES INST HUMAN GENET, SALT LAKE CITY, UT 84112 USA. UNIV UTAH, HOWARD HUGHES MED INST, SALT LAKE CITY, UT 84112 USA. RP CROPP, CS (reprint author), NCI, TUMOR IMMUNOL & BIOL LAB, BLDG 10, BETHESDA, MD 20892 USA. NR 40 TC 84 Z9 86 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 1994 VL 54 IS 10 BP 2548 EP 2551 PG 4 WC Oncology SC Oncology GA NL318 UT WOS:A1994NL31800007 PM 8168077 ER PT J AU REITER, Y PAI, LH BRINKMANN, U WANG, QC PASTAN, I AF REITER, Y PAI, LH BRINKMANN, U WANG, QC PASTAN, I TI ANTITUMOR-ACTIVITY AND PHARMACOKINETICS IN MICE OF A RECOMBINANT IMMUNOTOXIN CONTAINING A DISULFIDE-STABILIZED FV FRAGMENT SO CANCER RESEARCH LA English DT Article ID SINGLE-CHAIN FV; PSEUDOMONAS EXOTOXIN; PROTEINS AB Disulfide-stabilized Fvs (dsFv) are recombinant Fv fragments of antibodies in which the inherently unstable V-H-V-L heterodimer is stabilized by a disulfide bond engineered between structurally conserved framework positions of V-H and V-L. We have recently described a recombinant immunotoxin, B3(dsFv)-PE38KDEL, that is composed of such a dsFv connected to a truncated form of Pseudomonas exotoxin (PE38KDEL). This disulfide-stabilized immunotoxin is indistinguishable in activity and specificity from its single-chain immunotoxin counterpart (Brinkmann et al., Proc. Natl. Acad. Sci. USA, 90: 7538-7542, 1993). We have now constructed and evaluated the stability, pharmacokinetics, and antitumor effect of a very similar disulfide-stabilized immunotoxin B3(dsFv)-PE38. This immunotoxin is specifically cytotoxic to human cancer cell lines such as A431 that express the B3 antigen on their surface. In addition, the dsFv-immunotoxin is more stable at 37 degrees C in human serum than the corresponding single-chain immunotoxin B3(Fv)-PE38. The survival of the disulfide-stabilized immunotoxin in the circulation of mice was determined by a bioassay on cultured A431 cells after administering the immunotoxin i.v. The half-life in blood was 23 min. To determine the therapeutic effects of the disulfide-stabilized immunotoxin, it was given i.v. to immunodeficient mice bearing s.c. human epidermoid carcinomas. The dsFv-immunotoxin caused complete regression of tumors with no toxic effect on mice. The antitumor effect was similar to that reported for the single-chain Fv-immunotoxin. Our data show that dsFv-immunotoxins retain full in vitro as well as in vivo activity when compared to scFv-immunotoxins. Because dsFv-immunotoxins have full activity, are more stable, and can be produced with significantly improved yields compared to scFv-immunotoxins, the dsFv-immunotoxins may be more useful for therapeutic applications than scFv-immunotoxins. RP PASTAN, I (reprint author), NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,BLDG 37,RM 4E16,BETHESDA,MD 20892, USA. NR 17 TC 58 Z9 61 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 15 PY 1994 VL 54 IS 10 BP 2714 EP 2718 PG 5 WC Oncology SC Oncology GA NL318 UT WOS:A1994NL31800036 PM 8168102 ER PT J AU ZHAN, QM BAE, I KASTAN, MB FORNACE, AJ AF ZHAN, QM BAE, I KASTAN, MB FORNACE, AJ TI THE P53-DEPENDENT GAMMA-RAY RESPONSE OF GADD45 SO CANCER RESEARCH LA English DT Article ID DNA-DAMAGING AGENTS; PROTEIN-KINASE-C; IONIZING-RADIATION; P53 PROTEIN; CELLS; GENE; GROWTH; JUN; RNA; ENHANCEMENT AB Activation of the human GADD45 gene by ionizing radiation (IR) has previously been shown to be dependent on the tumor suppressor and transcription factor p53 (M.B. Kastan, et al., Cell 71: 587-597, 1992). Unlike GADD45, the response of other DNA damage-inducible genes to IR is not dependent on p53 based on the observation that induction in a panel of cell lines did not correlate with a normal p53 status; this included human GADD153, another member of the gadd (growth arrest and DNA damage inducible) group; MyD118, a gene related to GADD45; and the protooncogenes c-jun and c-fos. This p53-dependent response of GADD45 was further investigated in human cells with halogenated pyrimidines, which act as radiosensitizers when incorporated into cellular DNA. When cellular DNA contained halogenated pyrimidines such as iododeoxyuridine (IdUrd), GADD45 gamma-ray induction, as measured by increased mRNA, was enhanced. Rapid induction could be seen with doses as low as 0.5 Gy, and substitution with IdUrd resulted in an approximately 2-fold increase in induction over a wide dose range. This level of IdUrd substitution produced a similar fold increase in cellular radiosensitivity and has been shown previously (T.M. Kinsella et al., Int. J. Radiation Oncology Biol. Phys. 13: 733-739, 1987) to produce a similar fold increase in DNA strand breaks after IR. Considering that substitution with halogenated pyrimidines would be expected to have little effect on other cellular targets after IR, these experiments indicate that actual damage to DNA, primarily strand breaks, is a major signal for the activation of this p53-dependent pathway that is required for GADD45 induction and for activation of the G(1) ''checkpoint'' cell cycle delay. C1 NCI,DIV CANC TREATMENT,MOLEC PHARMACOL LAB,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,JOHNS HOPKINS ONCOL CTR,BALTIMORE,MD 21287. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X FU NIEHS NIH HHS [ES05777] NR 32 TC 234 Z9 242 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 15 PY 1994 VL 54 IS 10 BP 2755 EP 2760 PG 6 WC Oncology SC Oncology GA NL318 UT WOS:A1994NL31800043 PM 8168107 ER PT J AU KAPPEL, CC VELEZYANGUAS, MC HIRSCHFELD, S HELMAN, LJ AF KAPPEL, CC VELEZYANGUAS, MC HIRSCHFELD, S HELMAN, LJ TI HUMAN OSTEOSARCOMA CELL-LINES ARE DEPENDENT ON INSULIN-LIKE GROWTH-FACTOR-I FOR IN-VITRO GROWTH SO CANCER RESEARCH LA English DT Article ID HUMAN OSTEOGENIC-SARCOMA; COLLAGEN-SYNTHESIS; HORMONE GH; RECEPTOR; CULTURES; IGF AB Osteogenic sarcoma is the most common bone tumor of childhood and typically occurs during the adolescent growth spurt when growth hormone and insulin-like growth factor I (IGF-I) may be at their lifetime highest levels. Since IGF-I is involved in normal bone growth and differentiation, we have evaluated the possible role of IGF-I signaling in the growth of human osteogenic sarcoma cell lines. In this study, we demonstrate that in vitro survival of cells is dependent on exogenously supplied IGF-I. Furthermore, we show that these cells display functional IGF-I receptors on their surface and that in vitro growth is inhibited by blocking these receptors either by monoclonal antibodies or by antisense oligonucleotides. These data demonstrate that human osteogenic sarcoma cell lines are dependent on signaling through the IGF-I receptor for in vitro survival and proliferation. Furthermore, they suggest that modulation of the growth hormone/IGF-I axis may affect the growth of these tumors in vivo. C1 NCI,MOLEC ONCOL SECT,PEDIAT BRANCH,BETHESDA,MD 20892. RI Hirschfeld, Steven/E-2987-2016 OI Hirschfeld, Steven/0000-0003-0627-7249 NR 25 TC 98 Z9 103 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 15 PY 1994 VL 54 IS 10 BP 2803 EP 2807 PG 5 WC Oncology SC Oncology GA NL318 UT WOS:A1994NL31800051 PM 8168113 ER PT J AU GROVER, S HAMEL, E AF GROVER, S HAMEL, E TI THE MAGNESIUM-GTP, INTERACTION IN MICROTUBULE ASSEMBLY SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article ID TUBULIN-NUCLEOTIDE INTERACTIONS; GUANINE-NUCLEOTIDE; DIVALENT-CATIONS; EXCHANGEABLE NUCLEOTIDE; POLYMERIZATION INVITRO; DIMETHYL-SULFOXIDE; ALUMINUM ION; BINDING; SITE; PROTEINS AB Microtubule-associated-protein-dependent assembly of tubulin with GDP in the exchangeable site (tubulin-GDP) can occur with minimal free Mg2+ (<3 mu M). This reaction is totally inhibited by EDTA and by GTP concentrations over 2 mM and stimulated by MgCl2. Quantitative aspects of this stimulation are affected by both the Mg2+ and GTP concentrations, but no relationship exists between reaction rates and relative amounts of different magnesium and GTP species. GTP binding to tubulin-GDP, while maximally stimulated 2-3-fold by exogenous MgCl2, was inhibited less than 50% by EDTA, and the amount of GTP bound increased as its concentration rose to levels that inhibited polymerization. Studies on the binding of Mg2+ to tubulin-GDP in the presence and absence of GTP showed that the increase in the amount of tubulin-associated Mg2+ was substoichiometric to the amount of GTP bound (maximum stoichiometry of additional Mg2+ to GTP bound, 0.7). Upon polymerization the increased Mg2+ content of tubulin was reduced, indicating its loss during GTP hydrolysis. Mg2+ thus plays a critical role in assembly distinct from its enhancement of GTP binding to the exchangeable site. If magnesium is present in trace amounts, this role must either be catalytic during polymerization or limited to nucleation. C1 NCI,DIV CANC TREATMENT,MOLEC PHARMACOL LAB,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. NR 38 TC 30 Z9 30 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD MAY 15 PY 1994 VL 222 IS 1 BP 163 EP 172 DI 10.1111/j.1432-1033.1994.tb18854.x PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NN083 UT WOS:A1994NN08300020 PM 8200341 ER PT J AU BOUVET, P DIMITROV, S WOLFFE, AP AF BOUVET, P DIMITROV, S WOLFFE, AP TI SPECIFIC REGULATION OF XENOPUS CHROMOSOMAL 5S RIBOSOMAL-RNA GENE-TRANSCRIPTION IN-VIVO BY HISTONE H1 SO GENES & DEVELOPMENT LA English DT Article DE XENOPUS; TFIIIA; HISTONE H1; CHROMATIN; TRANSCRIPTION; RIBOZYME ID URCHIN STRONGYLOCENTROTUS-PURPURATUS; RIBOSOMAL-RNA GENES; CLASS-III GENES; MINICHROMOSOMES ASSEMBLED INVITRO; MAJOR DEVELOPMENTAL TRANSITION; POLYMERASE-II; MESSENGER-RNA; H-1 HISTONE; DNA-REPLICATION; LINKER HISTONES AB The incorporation of histone H1 into chromatin during embryogenesis directs the specific repression of the Xenopus oocyte 5S rRNA genes. An increase in histone HI content specifically restricts TFIIIA-activated transcription, and a decrease in histone H1 within chromatin facilitates the activation of the oocyte 5S rRNA genes by TFIIIA. Variation in the amount of histone H1 in chromatin does not significantly influence somatic 5S rRNA gene transcription. Thus, the regulated expression of histone H1 during Xenopus development has a specific and dominant role in mediating the differential expression of the oocyte and somatic 5S rRNA genes. This example demonstrates that histones can exert dominant repressive effects on the transcription of a gene in vivo in spite of an abundance of transcription factors for that gene. RP BOUVET, P (reprint author), NICHHD,MOLEC EMBRYOL LAB,BETHESDA,MD 20892, USA. RI dimitrov, stefan/M-7697-2013 NR 98 TC 206 Z9 208 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAY 15 PY 1994 VL 8 IS 10 BP 1147 EP 1159 DI 10.1101/gad.8.10.1147 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA NN726 UT WOS:A1994NN72600002 PM 7926720 ER PT J AU CELI, FS COHEN, MM ANTONARAKIS, SE WERTHEIMER, E ROTH, J SHULDINER, AR AF CELI, FS COHEN, MM ANTONARAKIS, SE WERTHEIMER, E ROTH, J SHULDINER, AR TI DETERMINATION OF GENE DOSAGE BY A QUANTITATIVE ADAPTATION OF THE POLYMERASE CHAIN-REACTION (GD-PCR) - RAPID DETECTION OF DELETIONS AND DUPLICATIONS OF GENE-SEQUENCES SO GENOMICS LA English DT Article ID HUMAN INSULIN-RECEPTOR; INTERNAL STANDARDS; MOLECULAR-GENETICS; MUSCULAR-DYSTROPHY; DNA POLYMORPHISMS; AMPLIFIED DNA; DIAGNOSIS; AMPLIFICATION; MUTATIONS; DUCHENNE AB Screening methods based on the polymerase chain reaction (PCR), such as denaturing gradient gel electrophoresis, single-stranded conformational polymorphism, and heteroduplex analysis, are powerful tools for the detection of point mutations as well as small deletions and insertions, but are unable to detect heterozygous deletions or duplications of exons, genes, or chromosomes. We now report a PCR-based approach, designated gene dosage-PCR (gd-PCR), that allows rapid screening for heterozygous deletions and duplications of genes or exons. Gene dosage-PCR is a quantitative method in which two in vitro synthesized DNA internal standards are coamplified with the genomic DNA sample, one corresponding to the gene of interest (test sequence) and the other to a reference (disomic) gene (reference sequence). Both internal standards are designed to be amplified with the same primer pairs and with efficiencies similar to those of their genomic DNA counterparts, yielding PCR products slightly smaller than those derived from genomic DNA. Amplification of approximately equimolar amounts of the two internal standards and genomic DNA, in the presence of [P-32]dCTP, results in four radiolabeled PCR products; after electrophoresis and quantification of the products, gene dosage is easily calculated. For validation, genomic DNA from 56 subjects, 28 with cytogenetically documented Down syndrome (trisomy 21) and 28 controls that were disomic for chromosome 21, was assayed. Using the P-amyloid precursor protein gene (APP: chromosome 21q21) as the test sequence, control subjects had an adjusted mean gene dose of 2.00 +/- 0.29, while subjects with Down syndrome had a mean gene dose of 3.05 +/- 0.27. There was a clear separation of all of the samples between the two groups. We also successfully used gd-PCR to detect allelic deletions by screening pertinent regions of the insulin receptor gene (IR; chromosome 19p13.2-p13.3) in three unrelated patients with genetic syndromes of extreme insulin resistance-known heterozygotes for deletions of either exon 3, exon 14, or exons 17-22. Gene dosage-PCR is a versatile, rapid, and sensitive method for screening for duplications and deletions of exons, genes, or chromosomes, with broad application in both clinical and research settings. (C) 1994 Academic Press, Inc. C1 JOHNS HOPKINS UNIV,SCH MED,DIV GERIATR MED & GERONTOL,BALTIMORE,MD 21224. NIA,DIABET UNIT,CLIN PHYSIOL LAB,BALTIMORE,MD 21224. UNIV MARYLAND,SCH MED,DIV HUMAN GENET,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,CTR MED BIOTECHNOL,DEPT PEDIAT,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,CTR MED BIOTECHNOL,DEPT OBSTET & GYNECOL,BALTIMORE,MD 21201. JOHNS HOPKINS UNIV,SCH MED,CTR MED GENET,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21205. NIDDKD,DIABET BRANCH,BETHESDA,MD 20892. RI Antonarakis, Stylianos/N-8866-2014 OI Antonarakis, Stylianos/0000-0001-8907-5823 FU NICHD NIH HHS [HD24605] NR 48 TC 42 Z9 44 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 0888-7543 J9 GENOMICS JI Genomics PD MAY 15 PY 1994 VL 21 IS 2 BP 304 EP 310 DI 10.1006/geno.1994.1270 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA NP161 UT WOS:A1994NP16100002 PM 8088823 ER PT J AU GONZALEZ, P RAO, PV ZIGLER, JS AF GONZALEZ, P RAO, PV ZIGLER, JS TI ORGANIZATION OF THE HUMAN ZETA-CRYSTALLIN/QUINONE REDUCTASE GENE (CRYZ) SO GENOMICS LA English DT Article ID GUINEA-PIG LENS; HEREDITARY CATARACT; ENZYME CRYSTALLINS; QUINONE REDUCTASE; EYE LENS; PROTEIN; DNA; EVOLUTION; IDENTIFICATION; DEHYDROGENASE AB zeta-Crystallin is a protein highly expressed in the lens of guinea pigs and camels, where it comprises about 10% of the total soluble protein. It has recently been characterized as a novel quinone oxidoreductase present in a variety of mammalian tissues. We report here the isolation and characterization of the human zeta-crystallin gene (CRYZ) and its processed pseudogene. The functional gene is composed of nine exons and spans about 20 kb. The 5'-flanking region of the gene is rich in G and C (58%) and lacks TATA and CAAT boxes. Previous analysis of the guinea pig gene revealed the presence of two different promoters, one responsible for the high lens-specific expression and the other for expression at the enzymatic level in numerous tissues. Comparative analysis with the guinea pig gene shows that a region of similar to 2.5 kb that includes the promoter responsible for the high expression in the lens in guinea pig is not present in the human gene. (C) 1994 Academic Press, Inc. C1 NEI, MECHANISMS OCULAR DIS LAB, BETHESDA, MD 20892 USA. NR 34 TC 13 Z9 14 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 15 PY 1994 VL 21 IS 2 BP 317 EP 324 DI 10.1006/geno.1994.1272 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA NP161 UT WOS:A1994NP16100004 PM 8088825 ER PT J AU COUCH, FJ ABEL, KJ BRODY, LC BOEHNKE, M COLLINS, FS WEBER, BL AF COUCH, FJ ABEL, KJ BRODY, LC BOEHNKE, M COLLINS, FS WEBER, BL TI LOCALIZATION OF THE GENE FOR ATP CITRATE LYASE (ACLY) DISTAL TO GASTRIN (GAS) AND PROXIMAL TO D17S856 ON CHROMOSOME 17Q12-Q21 SO GENOMICS LA English DT Note ID BRCA1 REGION; CLONING; CDNA; HYBRIDS; MAP AB The gene encoding ATP-citrate lyase, designated ACLY, was mapped to human chromosome 17q12-q21 by PCR on a panel of human/rodent somatic cell hybrids and localized to 17q21.1 by PCR on a panel of radiation hybrids. The radiation hybrid panel indicates that the most likely position of ACLY on 17q21.1 is between gastrin (GAS) and D17S856 at a distance of 170-290 kb from the GAS locus. (C) 1994 Academic Press, Inc. C1 UNIV MICHIGAN,MED CTR,DEPT INTERNAL MED,ANN ARBOR,MI 48109. UNIV MICHIGAN,DEPT BIOSTAT,ANN ARBOR,MI 48109. UNIV MICHIGAN,DEPT HUMAN GENET,ANN ARBOR,MI 48109. NIH,NATL CTR HUMAN GENOME RES,GENE TRANSFER LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA57601] NR 14 TC 3 Z9 3 U1 1 U2 3 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 15 PY 1994 VL 21 IS 2 BP 444 EP 446 DI 10.1006/geno.1994.1293 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA NP161 UT WOS:A1994NP16100025 PM 8088842 ER PT J AU CHANDRASEKHARAPPA, SC FRIEDMAN, L KING, SE LEE, YH WELSCH, P BOWCOCK, AM WEBER, BL KING, MC COLLINS, FS AF CHANDRASEKHARAPPA, SC FRIEDMAN, L KING, SE LEE, YH WELSCH, P BOWCOCK, AM WEBER, BL KING, MC COLLINS, FS TI THE GENE FOR PANCREATIC-POLYPEPTIDE (PPY) AND THE ANONYMOUS MARKER D17S78 ARE WITHIN 45 KB OF EACH OTHER ON CHROMOSOME 17Q21 SO GENOMICS LA English DT Note ID BRCA1 REGION; CANCER; IDENTIFICATION; INTERVAL C1 UNIV MICHIGAN,MED CTR,MICHIGAN HUMAN GENOME CTR,ANN ARBOR,MI. UNIV MICHIGAN,MED CTR,DEPT HUMAN GENET,ANN ARBOR,MI 48109. UNIV MICHIGAN,MED CTR,DEPT INTERNAL MED,ANN ARBOR,MI 48109. UNIV CALIF BERKELEY,DEPT MOLEC & CELL BIOL,BERKELEY,CA 94720. UNIV TEXAS,SW MED CTR,DEPT PEDIAT,DALLAS,TX. RP CHANDRASEKHARAPPA, SC (reprint author), NIH,NATL CTR HUMAN GENOME RES,GENE TRANSFER LAB,BLDG 49,ROOM 3A76,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. FU NCI NIH HHS [R01 CA 57601, R01 CA 27632]; NHGRI NIH HHS [P30-HG00209] NR 14 TC 3 Z9 3 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD MAY 15 PY 1994 VL 21 IS 2 BP 458 EP 460 DI 10.1006/geno.1994.1299 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA NP161 UT WOS:A1994NP16100031 PM 8088848 ER PT J AU TUTTLE, SW HAZARD, L KOCH, CJ MITCHELL, JB COLEMAN, CN BIAGLOW, JE AF TUTTLE, SW HAZARD, L KOCH, CJ MITCHELL, JB COLEMAN, CN BIAGLOW, JE TI BIOREDUCTIVE METABOLISM OF SR-4233 (WIN-59075) BY WHOLE-CELL SUSPENSIONS UNDER AEROBIC AND HYPOXIC CONDITIONS - ROLE OF THE PENTOSE CYCLE AND IMPLICATIONS FOR THE MECHANISM OF CYTOTOXICITY OBSERVED IN AIR SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 8th International Conference on Chemical Modifiers of Cancer Treatment CY JUN 16-19, 1993 CL KYOTO, JAPAN SP BRISTOL MYERS SQUIBB CO, DAIICHI PHARM CO LTD, DAIKIN IND LTD, EISAI CO LTD, HLTH RES FDN, JAPAN CLIN LABS, JAPAN RADIOSENTIZAT RES ASSOC, NIHON SCHERING K K, OSAKA PHARM MANUFACTURERS ASSOC, POLA CHEM IND INC, ROBERTS PHARM, SHIMAZU SCI FDN, STERLING WINTHROP CORP, PHARM MANUFACTURERS ASSOC TOKYO, UEHARA MEM FDN, US BIOSCI CORP, YAMANOUCHI MED CO LTD, ZERIA PHARM CO LTD DE PENTROSE CYCLE; SR-4233; BIOREDUCTIVE METABOLISM; HYDROGEN PEROXIDE ID 3-AMINO-1,2,4-BENZOTRIAZINE-1,4-DIOXIDE SR-4233; TUMOR-CELLS; RADIATION; REDUCTION; WIN-59075; TOXICITY AB Purpose: Measurement of pentose cycle (PC) activity is shown to be a noninvasive means for monitoring the reduction of SR-4233 in whole cells. Comparing these measurements to the actual measurements of drug loss under aerobic and hypoxic conditions helps to define the mechanism for the associated aerobic toxicity. Methods and Materials: SR-4233 is activated to a toxic species by bioreductive metabolism. NADPH is required for the activation of the drug by purified enzymes, cell homogenates and whole cells. In viva the NADPH:NADP+ ratio is maintained by the oxidation of glucose via the oxidative limb of the pentose cycle. By measuring radiolabeled (CO2)-C-14 released as a product of this oxidation one can get an accurate measurement of the rate of drug metabolism in whole cells. These results are compared to measurements of drug consumption under aerobic and hypoxic conditions using an HPLC assay. Results: SR-4233 stimulates pentose cycle activity to a greater extent in air then under hypoxia, however, in the presence of added catalase, pentose cycle activity is stimulated to a similar extent under both conditions. The higher levels of PC activity observed in air are due to the production of hydrogen peroxide by the nitroxide free radical undergoing futile redox cycling. The contribution of H2O2 to the observed aerobic cytotoxicity of SR-4233 is minimal however, since toxicity is only slightly reduced in the presence of exogenous catalase and antioxidants such as vitamin E. The level of PC stimulation by SR-4233 suggests that the rate of electron addition to the drug is independent of O-2 concentration. The loss of drug from the incubation medium, i.e., conversion to a stable intermediate species, occurs approximately five times faster under nitrogen than in air for A549 cells. It is the rate of drug loss from the cell and not the rate of reduction which best correlates with the observed aerobic and hypoxic toxicity. Conclusion: Toxicity in air and in nitrogen is directly related to the rate of drug reduction, i.e., at equivalent levels of drug loss we observe equal levels of cytotoxicity. C1 NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. JOINT CTR RADIAT THERAPY,BOSTON,MA 02115. RP TUTTLE, SW (reprint author), UNIV PENN,SCH MED,195 MORGAN BLDG,37TH & HAMILTON WALK,PHILADELPHIA,PA 19104, USA. FU NCI NIH HHS [CA-09677, CA-44982] NR 20 TC 15 Z9 15 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAY 15 PY 1994 VL 29 IS 2 BP 357 EP 362 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA NN512 UT WOS:A1994NN51200024 PM 8195033 ER PT J AU PINET, V MALNATI, MS LONG, EO AF PINET, V MALNATI, MS LONG, EO TI 2 PROCESSING PATHWAYS FOR THE MHC CLASS II-RESTRICTED PRESENTATION OF EXOGENOUS INFLUENZA-VIRUS ANTIGEN SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; HLA-DR MOLECULES; INVARIANT CHAIN PEPTIDES; B-LYMPHOBLASTOID CELLS; T-CELLS; SURFACE EXPRESSION; PROTEIN-SYNTHESIS; PRESENTING CELLS; MUTANT; HEMAGGLUTININ AB The natural Ag influenza virus A was used to test the requirements for the HLA-DR1-restricted presentation of the epitopes 18-29 in the matrix protein and 307-318 in the hemagglutinin protein. CD4(+) cytotoxic T cell clones of similar efficiency were used to detect presentation of these two epitopes. Presentation of the matrix epitope by APC pulsed with either inactivated virus particles or purified soluble protein followed the classical pathway in that 1) it required invariant chain expression, 2) it was blocked by inhibition of protein synthesis, and 3) it was dependent on a function(s) encoded in the MHC class II region. These characteristics suggest that peptides corresponding to the matrix epitope can only load onto newly synthesized class II molecules that were targeted to a processing compartment by the invariant chain. In contrast, presentation of the hemagglutinin epitope processed from virus particles followed a different pathway. First, presentation of hemagglutinin was independent of invariant chain expression. Second, a human B lymphoblastoid cell line in which protein synthesis was inhibited for 9 h was still able to present hemagglutinin even at very low doses of Ag. Third, a DR1-transfected mutant B cell line missing the MHC class II region was able to present hemagglutinin. Thus, mature class II alpha beta molecules can acquire immunogenic peptides derived from intact natural Ags for presentation to CD4(+) T cells. This pathway may be useful for the binding of peptides derived from Ags that are rapidly degraded upon uptake into APC. C1 NIAID,IMMUNOGENET LAB,ROCKVILLE,MD 20852. RI Long, Eric/G-5475-2011; PINET, Valerie/G-6085-2012 OI Long, Eric/0000-0002-7793-3728; NR 64 TC 109 Z9 109 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 1994 VL 152 IS 10 BP 4852 EP 4860 PG 9 WC Immunology SC Immunology GA NK925 UT WOS:A1994NK92500013 PM 8176208 ER PT J AU SIECKMANN, DG HOLMES, K HORNBECK, P MARTIN, E GUELDE, G BONDADA, S LONGO, DL KENNY, JJ AF SIECKMANN, DG HOLMES, K HORNBECK, P MARTIN, E GUELDE, G BONDADA, S LONGO, DL KENNY, JJ TI B-CELLS FROM M167 MU-KAPPA TRANSGENIC MICE FAIL TO PROLIFERATE AFTER STIMULATION WITH SOLUBLE ANTI-IG ANTIBODIES - A MODEL FOR ANTIGEN-INDUCED B-CELL ANERGY SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNE-DEFICIENT MICE; MURINE LYMPHOCYTES-B; ENDOGENOUS IMMUNOGLOBULIN; MONOCLONAL-ANTIBODIES; MOUSE LYMPHOCYTES; MEMBRANE IGM; ACTIVATION; GENES; EXPRESSION; GROWTH AB The transgenic (TG) mouse strain 207-4, carries mu(a) + kappa transgenes ligated to the anti-phosphocholine (PC) V(H)1 and V kappa 24 V region genes from the MOPC-167 myeloma. Although B cells from mice carrying these transgenes respond both in vivo and in vitro to thymus-dependent Ags, they failed to proliferate in response to soluble goat anti-mu Ab or other soluble anti-Ig reagents. On the other hand, B cells from the Sp6 mu kappa anti-trinitrophenyl TG mouse line proliferated normally after stimulation with soluble anti-mu. However, the 207-4 anti-PC transgene positive (TG(+)) splenic B cells proliferated when stimulated with anti-mu, anti-idiotype, anti-allotype, or PC-conjugated to Sepharose beads. TG(+) B cells were also induced to proliferate when stimulated with anti-Lyb-2; thus, their defect may be restricted to signaling through sIgM. The lack of response to soluble anti-mu could not be reversed by addition of IL-4, by removal of T cells, by addition of anti-FcR Ab, or by stimulation with F(ab')(2) anti-mu. Thus, the failure to proliferate was not caused by active T cell suppression or FcR-mediated inhibition. In mixed cultures of TC+ and transgene negative (TC-) spleen cells, the TC- cells were able to proliferate normally to soluble anti-mu, indicating that suppressive factors were not involved in the unresponsiveness of the TG(+) anti-PC-specific B cells. These studies suggest that B cells in the 207-4 anti-PC TG mice exhibit a defect in activation through their sIgM receptors, and this unresponsiveness may reflect a form of Ag-induced tolerance. C1 NIAID, RESOURCES BRANCH, BETHESDA, MD 20892 USA. NIAID, IMMUNOPATHOL LAB, BETHESDA, MD 20892 USA. UNIV MARYLAND, DEPT MED, DIV RHEUMATOL, BALTIMORE, MD 21201 USA. NCI, FREDERICK CANC RES & DEV CTR, PRI DYNCORP, FREDERICK, MD 21702 USA. UNIV KENTUCKY, DEPT MICROBIOL & IMMUNOL, LEXINGTON, KY 40536 USA. UNIV KENTUCKY, CTR AGING, LEXINGTON, KY 40536 USA. NCI, FREDERICK CANC RES & DEV CTR, BIOL RESPONSE MODIFIERS PROGRAM, FREDERICK, MD 21702 USA. RP SIECKMANN, DG (reprint author), USN, MED RES INST, DEPT INFECT DIS, 8901 WISCONSIN AVE, BETHESDA, MD 20889 USA. FU NCI NIH HHS [N01-CO-74102]; NIAID NIH HHS [R29 AI30822-01A1] NR 49 TC 9 Z9 9 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 1994 VL 152 IS 10 BP 4873 EP 4883 PG 11 WC Immunology SC Immunology GA NK925 UT WOS:A1994NK92500015 PM 8176209 ER PT J AU RHEE, SS MARSH, JW AF RHEE, SS MARSH, JW TI HIV-1 NEF ACTIVITY IN MURINE T-CELLS - CD4 MODULATION AND POSITIVE ENHANCEMENT SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MONOCLONAL-ANTIBODY; MUTATIONAL ANALYSIS; GENE-EXPRESSION; PLASMA-MEMBRANE; TYPE-1; PROTEIN; LYMPHOCYTES; REPLICATION; ACTIVATION AB Immediately after infection of the targeted cell by HIV-1, proviral gene expression is limited to the three regulatory proteins, Tat, Rev, and Nef, with the nef transcript representing nearly 80% of total expression. Additionally, simian immunodeficiency virus Nef has been shown to be essential for high in vivo titer and the development of immunodeficiency. Recent findings demonstrate that the negative effects of Nef expression, as first defined in transformed T cell lines, are not present when Nef is expressed in primary human T cells or in T cells from transgenic mice, in which one sees moderate positive enhancements of HIV replication and the T cell activation process, respectively. We find that Nef expression in an Ag-specific murine T cell hybridoma results in both the down-modulation of CD4, as seen in primary cells and human T cell lines, and a positive enhancement of the TCR response to stimuli. Examination of a CD4(-) cell demonstrated that the positive enhancement is independent of CD4 expression or modulation. CD4 down-modulation is shown to be caused by a post-Golgi, acid-dependent process, which dramatically decreases the lifespan of the CD4 molecule. The TCR, Thy Ag, and CD45 remained unchanged in their surface expression. These findings suggest that Nef alters the normal routing and residencies of the CD4 molecule and that the positive effect of Nef on T cell activation is independent of this modulation. C1 NIMH,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 49 TC 54 Z9 54 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 15 PY 1994 VL 152 IS 10 BP 5128 EP 5134 PG 7 WC Immunology SC Immunology GA NK925 UT WOS:A1994NK92500044 PM 8176229 ER PT J AU WU, MC LAN, KKG CONNETT, JE AF WU, MC LAN, KKG CONNETT, JE TI USE OF SURROGATE INFORMATION TIME FOR MONITORING THE EFFECT OF TREATMENT ON THE CHANGE IN A RESPONSE VARIABLE IN CLINICAL-TRIALS SO STATISTICS IN MEDICINE LA English DT Article ID DESIGN AB We discuss the monitoring of clinical trials data and propose two surrogates for total information for use with the spending function approach where there are repeated measurements and we wish to compare the rates of change in a response variable under different treatments. These surrogates are applied to a setting similar to the Lung Health Study, Although the surrogates do not require estimation of the variance parameters, they do require some knowledge of the ratio R of the within- to the between-individual variances. The effects of overestimating and underestimating R are illustrated. In situations of uncertainty we recommend overestimating R, to provide a conservative estimate of information time at each interim analysis. C1 GEORGE WASHINGTON UNIV,DEPT STAT COMP & INFORMAT SYST,WASHINGTON,DC 20052. UNIV MINNESOTA,COORDINATING CTR BIO RES,MINNEAPOLIS,MN 55414. RP WU, MC (reprint author), NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BIOSTAT RES BRANCH,BETHESDA,MD 20892, USA. FU NCI NIH HHS [R01-CA55098] NR 13 TC 1 Z9 1 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 1994 VL 13 IS 9 BP 945 EP 953 DI 10.1002/sim.4780130905 PG 9 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 NL315 UT WOS:A1994NL31500004 PM 8047746 ER PT J AU WYSOCKA, M EISENLOHR, LC OTVOS, L HOROWITZ, D YEWDELL, JW BENNINK, JR HACKETT, CJ AF WYSOCKA, M EISENLOHR, LC OTVOS, L HOROWITZ, D YEWDELL, JW BENNINK, JR HACKETT, CJ TI IDENTIFICATION OF OVERLAPPING CLASS-I AND CLASS-II H-2(D)-RESTRICTED T-CELL DETERMINANTS OF INFLUENZA-VIRUS N1 NEURAMINIDASE THAT REQUIRE INFECTIOUS VIRUS FOR PRESENTATION SO VIROLOGY LA English DT Article ID CYTOTOXIC LYMPHOCYTES-T; RESTRICTED PRESENTATION; PROCESSING PATHWAYS; ENDOGENOUS ANTIGEN; VACCINIA VIRUSES; MHC MOLECULES; A VIRUS; PEPTIDES; RECOGNITION; HEMAGGLUTININ AB The requirement for endogenous viral protein synthesis in helper and cytotoxic T cell (CTL) recognition of influenza virus was studied at the level of individual epitopes. The viral envelope glycoprotein neuraminidase (NA) contains class I and class II major histocompatibility complex (MHC)-restricted T cell determinants that are presented by virus-infected antigen-presenting cells (APC). We had previously shown that recognition of NA by class II I-E(d)-restricted T cells required either active viral infection of APC or introduction of uv-inactivated virus to the cytosol, similar to the well-established requirements for class I-restricted responses. Detailed mapping of T cell epitopes was undertaken using vaccinia virus vectors encoding truncated segments of the influenza NA molecule and by synthetic peptides. Class I MHC-restricted CTL were found to recognize two regions of NA: residues 69-89 in the context of D-d and 191-201 presented by K-d. Analyses of T cell proliferation and T hybridoma clones revealed that class II-restricted responses recognized the same two regions as the CTL, presented by I-E(d) and I-A(d), respectively. Interestingly, both class I and class II MHC-restricted T cells showed similar requirements for endogenously synthesized antigen, responding poorly or not at all to endocytosed uv-inactivated virus. This extends previous observations that specific epitopes can be preferentially presented by class II molecules from endogenously synthesized antigens and shows that the same antigenic determinants can have access to both class I and class II antigen presentation pathways. (C) 1994 Academic Press, Inc. C1 IMMULOGIC PHARMACEUT CORP, PALO ALTO, CA 94304 USA. WISTAR INST ANAT & BIOL, PHILADELPHIA, PA 19104 USA. THOMAS JEFFERSON UNIV, PHILADELPHIA, PA 19107 USA. SMITHKLINE BEECHAM PHARMACEUT, KING OF PRUSSIA, PA 19406 USA. NIH, BETHESDA, MD 20892 USA. RI yewdell, jyewdell@nih.gov/A-1702-2012; OI Hackett, Charles/0000-0003-4586-9669 FU NIAID NIH HHS [AI 14162, AI 22961] NR 55 TC 13 Z9 15 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD MAY 15 PY 1994 VL 201 IS 1 BP 86 EP 94 DI 10.1006/viro.1994.1268 PG 9 WC Virology SC Virology GA NK296 UT WOS:A1994NK29600010 PM 7513927 ER PT J AU KASHANCHI, F THOMPSON, J SADAIE, MR DONIGER, J DUVALL, J BRADY, JN ROSENTHAL, LJ AF KASHANCHI, F THOMPSON, J SADAIE, MR DONIGER, J DUVALL, J BRADY, JN ROSENTHAL, LJ TI TRANSCRIPTIONAL ACTIVATION OF MINIMAL HIV-I PROMOTER BY ORF-I PROTEIN EXPRESSED FROM THE SA/I-L FRAGMENT OF HUMAN HERPESVIRUS-6 SO VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; LONG-TERMINAL REPEAT; HUMAN CYTOMEGALO-VIRUS; HUMAN LYMPHOCYTES-T; EPSTEIN-BARR-VIRUS; TRANS-ACTIVATION; EXANTHEM-SUBITUM; CELL-LINE; HTLV-I; TRANSACTIVATION AB The Sall-L fragment of human herpesvirus 6 (HHV-6) strain U1102 transformed rodent cells and transactivated the HIV-1 LTR 10- to 15-fold in both monkey fibroblasts and human T-lymphocytes. In this report, the Sall-L transactivator of the HIV-1 LTR was localized to ORF-I which codes for a protein of 357 amino acids. To determine if ORF-I required functional Spl binding sites or the TATA box element of HIV-1 LTR for transactivation, 5'-deletion mutants of the HIV-I LTR were employed. Plasmids pBS/Sall-L, pBS/Sall-L-SH, and pC6/ORF-1(S), a mammalian expression vector containing ORF-1, all transactivated a deletion mutant of HIV-1 LTR lacking functional Spl binding sites (CD-54). These studies demonstrate that transactivation occurred in the absence of Spl binding sites and required only a minimal HIV-1 promoter which contains the TATA box element. The specificity of the Sall-L transactivator for HIV-1 LTR was demonstrated by its inability to transactivate the human papillomavirus type 16 or 18 early promoters. The ORF-1 gene was cloned into and expressed from the pET17b bacterial expression vector. Purified ORF-I protein was obtained by ammonium sulfate precipitation, Mono-S chromatography, and anti-T7.Tag immunoaffinity chromatography. Transactivation of the HIV-l LTR by ORF-1 protein was demonstrated by electroporation studies in vivo and by transcription studies in vitro. To substantiate the putative biological role of ORF-1, pBS/Sall-L, pBS/Sall-L-SH, and pCG/ORF-1 all reactivated tat-defective HIV-1 provirus from latently infected cells expressing CD4. Thus, the data presented suggest that HHV-6 infection could have a cofactor role in the progression of AIDS. (C) 1994 Academic Press, Inc. C1 GEORGETOWN UNIV,MED CTR,DEPT MICROBIOL & IMMUNOL,WASHINGTON,DC 20007. US FDA,CTR BIOL EVALUAT & RES,DIV TRANSFUS TRANSMITTED DIS,ROCKVILLE,MD 20852. NCI,MOLEC VIROL LAB,BETHESDA,MD 20892. NR 81 TC 29 Z9 31 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD MAY 15 PY 1994 VL 201 IS 1 BP 95 EP 106 DI 10.1006/viro.1994.1269 PG 12 WC Virology SC Virology GA NK296 UT WOS:A1994NK29600011 PM 8178493 ER PT J AU SANTORO, TJ BRYANT, JL PELLICORO, J KLOTMAN, ME KOPP, JB BRUGGEMAN, LA FRANKS, RR NOTKINS, AL KLOTMAN, PE AF SANTORO, TJ BRYANT, JL PELLICORO, J KLOTMAN, ME KOPP, JB BRUGGEMAN, LA FRANKS, RR NOTKINS, AL KLOTMAN, PE TI GROWTH FAILURE AND AIDS-LIKE CACHEXIA SYNDROME IN HIV-I TRANSGENIC MICE SO VIROLOGY LA English DT Note ID VIRUS; PROTEIN; GENES; CELLS AB The mechanisms which predispose to growth failure in infants and children infected with immunodeficiency virus type-1 (HIV-I) are not fully understood. The contributions of viral replication and CD4(+) T cell depletion to growth failure in an HIV-1 transgenic mouse model were investigated. Mice homozygous for the transgene, a gag-pol deletion mutant of the HIV-1 provirus pNL4-3, exhibited marked cachexia, growth retardation, lymphoproliferation with a reduction in the percentage of CD4(+) T cells but an increase in the absolute number of splenic CD4(+) and CD8(+) T cells, thymic hypoplasia, and early death. Despite the absence of T cells, athymic nude mice, homozygous for the HIV transgene, displayed comparable growth failure. The results indicate that AIDS-like cachexia may be produced by expression of viral envelope or accessory genes, need not be accompanied by absolute depletion of CD4(+) T cells, and may occur independent of T cell function, (C) 1994 Academic Press, Inc. C1 UNIV COLORADO,HLTH SCI CTR,DEPT MED,DENVER,CO 80220. NIDR,ANIM CARE UNIT,BETHESDA,MD 20892. NIDR,DEV BIOL & ORAL MED LABS,BETHESDA,MD 20892. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. RI klotman, mary/A-1921-2016 NR 13 TC 39 Z9 39 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD MAY 15 PY 1994 VL 201 IS 1 BP 147 EP 151 DI 10.1006/viro.1994.1276 PG 5 WC Virology SC Virology GA NK296 UT WOS:A1994NK29600018 PM 7909972 ER PT J AU SUNADA, Y BERNIER, SM KOZAK, CA YAMADA, Y CAMPBELL, KP AF SUNADA, Y BERNIER, SM KOZAK, CA YAMADA, Y CAMPBELL, KP TI DEFICIENCY OF MEROSIN IN DYSTROPHIC DY MICE AND GENETIC-LINKAGE OF LAMININ M-CHAIN GENE TO DY LOCUS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID MUSCULAR-DYSTROPHY; GLYCOPROTEIN COMPLEX; SKELETAL-MUSCLE; MOUSE CHROMOSOME-10; SCHWANN-CELLS; PROTEINS; ACTIN; EXPRESSION; BINDING; DOMAIN AB Merosin is the predominant laminin isoform in the basal lamina of striated muscle and peripheral nerve, and consists of M, B1 or S, and B2 chains. Here we have demonstrated that merosin is a native ligand for alpha-dystroglycan, an extracellular component of the dystrophin-glycoprotein complex. We have also mapped the mouse M chain gene, Lamm, to the same region of mouse chromosome 10 to which the dystrophia muscularis (dy) locus has been mapped; The dy mutation represents a severe neuromuscular disease resembling human muscular dystrophy. Analysis of merosin expression of dystrophic dy mice revealed a specific deficiency of merosin in skeletal muscle, cardiac muscle, and peripheral nerve. Our results indicate that merosin deficiency may be the primary defect in dy mice and suggest that a disruption of the link between alpha-dystroglycan and merosin may be involved in the pathogenesis of muscle degeneration and peripheral neuropathy in dy mice. C1 UNIV IOWA,COLL MED,HOWARD HUGHES MED INST,DEPT PHYSIOL & BIOPHYS,IOWA CITY,IA 52242. NIDR,DEV BIOL LAB,BETHESDA,MD 20892. NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. NR 36 TC 273 Z9 273 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 13 PY 1994 VL 269 IS 19 BP 13729 EP 13732 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NL606 UT WOS:A1994NL60600002 PM 8188645 ER PT J AU WANG, MH GONIAS, SL SKEEL, A WOLF, BB YOSHIMURA, T LEONARD, EJ AF WANG, MH GONIAS, SL SKEEL, A WOLF, BB YOSHIMURA, T LEONARD, EJ TI PROTEOLYTIC ACTIVATION OF SINGLE-CHAIN PRECURSOR MACROPHAGE-STIMULATING PROTEIN BY NERVE GROWTH FACTOR-GAMMA AND EPIDERMAL GROWTH FACTOR-BINDING PROTEIN, MEMBERS OF THE KALLIKREIN FAMILY SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SCATTER FACTOR; BIOSYNTHESIS; SEQUENCE; MICE AB Promacrophage-stimulating protein (MSP) is an 80 kDa protein that acquires biological activity after cleavage at an Arg-Val bond to a disulfide-linked alpha beta heterodimer by serine proteases of the intrinsic coagulation cascade. These proteases, which include serum kallikrein, factor XIIa and factor XIa, are members of the trypsin family of serine proteases. We now report that two other members of the family, nerve growth factor -gamma (NGF-gamma) and epidermal growth factor-binding protein (EGF-BP), cleave and activate pro-MSP to the disulfide-linked alpha beta heterodimer. Cleavage of 1.5 nM pro-MSP by 1 nM NGF-gamma or EGF-BP at 37 degrees C was almost complete within 30 min. These concentrations of enzyme are about 2 orders of magnitude less than is required for cleavage by serum kalllikrein or factor XIIa. Cleavage of pro-MSP to MSP was associated with a conformational change in the protein, because the cleaved product, but not pro-MSP, was detected by a sandwich enzyme linked immunoassay. Cleavage caused the appearance of biological activity, as measured by chemotactic activity of MSP for resident peritoneal macrophages, by MSP induced macrophage shape change, and by stimulation of macrophage ingestion of C3bi-coated erythrocytes. These findings suggest the possibility of cooperative interactions between NGF-gamma or EGF-BP and pro-MSP in inflammation and wound healing. C1 UNIV VIRGINIA, HLTH SCI CTR, DEPT PATHOL, CHARLOTTESVILLE, VA 22908 USA. UNIV VIRGINIA, HLTH SCI CTR, DEPT BIOCHEM, CHARLOTTESVILLE, VA 22908 USA. RP WANG, MH (reprint author), NCI, FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB, IMMUNOPATHOL SECT,BLDG 560, RM 12-71, FREDERICK, MD 21702 USA. NR 28 TC 47 Z9 48 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 13 PY 1994 VL 269 IS 19 BP 13806 EP 13810 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NL606 UT WOS:A1994NL60600017 PM 8188657 ER PT J AU FARRES, J WANG, XP TAKAHASHI, K CUNNINGHAM, SJ WANG, TT WEINER, H AF FARRES, J WANG, XP TAKAHASHI, K CUNNINGHAM, SJ WANG, TT WEINER, H TI EFFECTS OF CHANGING GLUTAMATE-487 TO LYSINE IN RAT AND HUMAN LIVER MITOCHONDRIAL ALDEHYDE DEHYDROGENASE - A MODEL TO STUDY HUMAN (ORIENTAL TYPE) CLASS-2 ALDEHYDE DEHYDROGENASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID METHYLMALONATE-SEMIALDEHYDE DEHYDROGENASE; HORSE LIVER; ESCHERICHIA-COLI; MOLECULAR-CLONING; CYTOPLASMIC ISOENZYME; ALCOHOL-DEHYDROGENASE; CATALYTIC ACTIVITY; MESSENGER-RNA; CDNA; GENE AB Many Oriental people possess a liver mitochondrial aldehyde dehydrogenase where glutamate at position 487 has been replaced by a lysine, and they have very low levels of mitochondrial aldehyde dehydrogenase activity. To investigate the cause of the lack of activity of this aldehyde dehydrogenase, we mutated residue 487 of rat and human liver mitochondrial aldehyde dehydrogenase to a lysine and expressed the mutant and native enzyme forms in Escherichia coli. Both rat and human recombinant aldehyde dehydrogenases showed the same molecular and kinetic properties as the enzyme isolated from liver mitochondria. The E487K mutants were found to be active but possessed altered kinetic properties when compared to the glutamate enzyme. The K-m for NAD(+) at pH 7.4 increased more than 150-fold, whereas k(cat) decreased 2-10-fold with respect to the recombinant native enzymes. Detailed steady-state kinetic analysis showed that the binding of NAD(+) to the mutant enzyme was impaired, and it could be calculated that this resulted in a decreased nucleophilicity of the active site cysteine residue. The rate-limiting step for the rat E487K mutant was also different from that of the recombinant rat liver aldehyde dehydrogenase in that no pre-steady state burst of NADH formation was found with the mutant enzyme. Both the rat native enzyme and the E487K mutant oxidized chloroacetaldehyde twice as fast as acetaldehyde, indicating that the rate limiting step was not hydride transfer or coenzyme dissociation but depended upon nucleophilic attack. Each enzyme form showed a 2-fold activation upon the addition of Mg2+ ions. Substituting a glutamine for the glutamate did not grossly affect the properties of the enzyme. Glutamate 487 may interact directly with the positive nicotinamide ring of NAD(+) for the K-i of NADH was the same in the lysine enzyme as it was in the glutamate form. Because of the altered NAD(+) binding properties and k(cat) of the E487K variant, it is assumed that people possessing this form will not have a functional mitochondrial aldehyde dehydrogenase. C1 PURDUE UNIV,DEPT BIOCHEM,W LAFAYETTE,IN 47907. UNIV AUTONOMA BARCELONA,DEPT BIOQUIM & BIOL MOLEC,UNITAT CIENCIES,BARCELONA,SPAIN. OKAYAMA UNIV,SCH DENT,DEPT BIOCHEM,OKAYAMA 700,JAPAN. NCI,NUTR & MOLEC REGULAT LAB,FREDERICK,MD 21702. RI Farres, Jaume/F-8648-2016 OI Farres, Jaume/0000-0001-9069-3987 FU NIAAA NIH HHS [AA00028, AA05812] NR 66 TC 98 Z9 100 U1 0 U2 10 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 13 PY 1994 VL 269 IS 19 BP 13854 EP 13860 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NL606 UT WOS:A1994NL60600023 PM 7910607 ER PT J AU FARIA, TN BLAKESLEY, VA KATO, H STANNARD, B LEROITH, D ROBERTS, CT AF FARIA, TN BLAKESLEY, VA KATO, H STANNARD, B LEROITH, D ROBERTS, CT TI ROLE OF THE CARBOXYL-TERMINAL DOMAINS OF THE INSULIN AND INSULIN-LIKE GROWTH-FACTOR-I RECEPTORS IN RECEPTOR FUNCTION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TYROSINE AUTOPHOSPHORYLATION SITES; PROTEIN KINASE-C; FAMILY; PHOSPHORYLATION; SPECIFICITY; BINDING; MITOGENESIS; REGIONS; LIGAND; GENE AB The insulin and insulin-like growth factor I receptors (IR and IGF-IR, respectively) are heterotetrameric tyrosine kinases consisting of two extracellular ligand-binding alpha subunits and two transmembrane catalytic beta subunits. A number of lines of evidence have suggested that the IR and IGF-IR differ with respect to their ability to elicit mitogenic versus metabolic events upon activation by cognate ligands. To ascertain the contribution of the poorly conserved carboxyl-terminal domains to the differential functioning of the IR and IGF-IR, we have constructed receptor chimeras in which the carboxyl-terminal domain of one receptor was fused to the remainder of the heterologous receptor. The responses of a number of parameters after ligand stimulation were examined in stably transfected NIH-3T3 cells expressing the chimeric receptors or the analogous wild-type receptor sequence. Replacement of the IR carboxyl terminus with that of the IGF-IR severely affected insulin stimulated responses, whereas substitution of the carboxyl terminus of the IGF-IR with that of the IR had a minimal effect. These data suggest that the carboxyl-terminal domains of the IR and IGF-IR are not interchangeable and that the mitogenic activity of the IR can be influenced by sequences present in the carboxyl-terminal domain. The analogous functions of the IGF-IR, on the other hand, do not appear to be greatly affected by the presence of the IR carboxyl-terminal domain. C1 NIDDK,DIABET BRANCH,MOLEC & CELLULAR PHYSIOL SECT,BETHESDA,MD 20892. OI Roberts, Charles/0000-0003-1756-5772 NR 42 TC 49 Z9 49 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 13 PY 1994 VL 269 IS 19 BP 13922 EP 13928 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NL606 UT WOS:A1994NL60600034 PM 8188672 ER PT J AU CHEN, XS KURRE, U JENKINS, NA COPELAND, NG FUNK, CD AF CHEN, XS KURRE, U JENKINS, NA COPELAND, NG FUNK, CD TI CDNA CLONING, EXPRESSION, MUTAGENESIS OF C-TERMINAL ISOLEUCINE, GENOMIC STRUCTURE, AND CHROMOSOMAL LOCALIZATIONS OF MURINE 12-LIPOXYGENASES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-SPECIFIC 15-LIPOXYGENASE; AMINO-ACID SEQUENCE; ARACHIDONATE 12-LIPOXYGENASE; MOLECULAR-CLONING; POLYMORPHONUCLEAR LEUKOCYTES; HUMAN 5-LIPOXYGENASE; PORCINE LEUKOCYTES; MESSENGER-RNA; LIPOXYGENASE; PLATELETS AB Two types of 12-lipoxygenase that catalyze the transformation of arachidonic acid to 12(S)-hydroperoxyeicosatetraenoic acid (12-HPETE) have been previously classified into platelet-type and leukocyte-type categories. Here, we document, for the first time, a molecular characterization of both forms within the same species. The amino acid sequence of the murine platelet 12-lipoxygenase deduced from its cDNA is 58% identical to the murine spleen/leukocyte 12-lipoxygenase. Expression constructs carrying the cDNAs for the two 12-lipoxygenase forms were introduced into human embryonic kidney 293 cells. The platelet-type enzyme metabolized arachidonic acid exclusively to 12-HPETE, whereas the leukocyte-type enzyme formed both 12-HPETE and 15-hydro(pero)xyeicosatetraenoic acid in a ratio of approximate to 3:1. Linoleic acid was metabolized to a similar extent by the latter enzyme to 13-hydro(pero)xyoctadecadienoic acid but not by the platelet enzyme. Mutagenesis and deletion of the highly conserved lipoxygenase C-terminal isoleucine (Ile(663)), a residue believed to be involved in the non-heme iron atom coordination of all lipoxygenases, was performed. Deletion of Ile(663) and substitution with most amino acids abolished enzyme activity. Only a valine substitution retained significant activity. These findings would tend to indicate a stringent requirement for the proper spatial alignment and folding of the C-terminal chain back into the core of the enzyme to interact with the iron atom by analogy with the recently determined crystal structure of a soybean lipoxygenase (Boyington, J. C., Gaffney, B. J., and Amzel, L. M. (1993) Science 260, 1482-1486). The platelet-type and leukocyte-type 12-lipoxygenase genes were cloned from a murine 129 Sv genomic library. Both genes are divided into a similar 14-exon/13-intron format, with the platelet-type gene being approximately twice the size of the leukocyte-type gene (13 versus 7.5 kilobases). A segment of a third gene was also isolated and probably represents a pseudogene derivative of either of these 12-lipoxygenase genes. All three genes were mapped to the central region of mouse chromosome 11 in a region of homology with human chromosome 17. Antibodies prepared against the two forms of 12-lipoxygenase revealed the differential distribution of the two enzymes throughout the mouse. C1 VANDERBILT UNIV,DEPT PHARMACOL,NASHVILLE,TN 37232. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. RI Funk, Colin/A-9518-2010 FU NCI NIH HHS [NCI N01-CO-74101]; NHLBI NIH HHS [HL02710, HL46017] NR 60 TC 166 Z9 171 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 13 PY 1994 VL 269 IS 19 BP 13979 EP 13987 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NL606 UT WOS:A1994NL60600041 PM 8188678 ER PT J AU FLACK, MR FROEHLICH, J BENNET, AP ANASTI, J NISULA, BC AF FLACK, MR FROEHLICH, J BENNET, AP ANASTI, J NISULA, BC TI SITE-DIRECTED MUTAGENESIS DEFINES THE INDIVIDUAL ROLES OF THE GLYCOSYLATION SITES ON FOLLICLE-STIMULATING-HORMONE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN CHORIO-GONADOTROPIN; ASPARAGINE-LINKED OLIGOSACCHARIDES; PITUITARY GLYCOPROTEIN HORMONES; CELL AROMATASE BIOASSAY; BETA-SUBUNIT; RECEPTOR-BINDING; SIALYLATED OLIGOSACCHARIDES; SIGNAL TRANSDUCTION; ALPHA-SUBUNIT; FOLLITROPIN AB To determine the specific role of each follicle stimulating hormone (FSH) oligosaccharide, we mutated Asn to Gln at each glycosylation site (alpha Gln(52), alpha Gln(78), alpha Gln(52-78), beta Gln(7), beta Gln(24), and beta Gln(7-24)) to selectively inhibit oligosaccharide attachment. For wild-type and mutant FSH, we determined the binding affinity to homogenized rat Sertoli cells and the signal-transducing activity in cultured rat granulosa cells. The binding affinity of FSH lacking any one of the oligosaccharides was increased over wild-type FSH, while the signal-transducing activity of FSH lacking the oligosaccharide at alpha Asn(52) (alpha Gln(52) FSH) was markedly reduced, and that of FSH lacking either beta oligosaccharide (beta Gln(7) and beta Gln(24) FSH) was slightly reduced. At each FSH beta glycosylation site, we made a second amino acid substitution to inhibit glycosylation (beta Tyr(9) and beta Tyr(26)) and an amino acid substitution that preserved glycosylation (beta Ser(9) and beta Ser(26)). The amino acid sequence of the second p subunit glycosylation site was important for signal transduction, regardless of the presense or absence of the oligosaccharide. Thus, while each FSH oligosaccharide has a similar impact on binding affinity, the alpha(52) oligosaccharide has a disproportionate role in signal transduction, and the amino acid sequence at beta Asn(24) functions in both binding and signal transduction. RP NICHHD, DEV ENDOCRINOL BRANCH, BLDG 10, RM 10N262, 9000 ROCKVILLE PK, BETHESDA, MD 20892 USA. NR 30 TC 73 Z9 75 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 13 PY 1994 VL 269 IS 19 BP 14015 EP 14020 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NL606 UT WOS:A1994NL60600046 PM 8188681 ER PT J AU WANG, MH COX, GW YOSHIMURA, T SHEFFLER, LA SKEEL, A LEONARD, EJ AF WANG, MH COX, GW YOSHIMURA, T SHEFFLER, LA SKEEL, A LEONARD, EJ TI MACROPHAGE-STIMULATING PROTEIN INHIBITS INDUCTION OF NITRIC-OXIDE PRODUCTION BY ENDOTOXIN-STIMULATED OR CYTOKINE-STIMULATED MOUSE MACROPHAGES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PERITONEAL-MACROPHAGES; RELAXING FACTOR; L-ARGININE; IFN-GAMMA; MOLECULAR-CLONING; PLATELET-ADHESION; SUPEROXIDE ANION; ENDOTHELIUM; EXPRESSION; SYNTHASE AB Human serum macrophage-stimulating protein (MSP) is a disulfide-linked heterodimer that induces motile and phagocytic activity of mouse resident peritoneal macrophages. In this work, we found that MSP blocked the increase in macrophage nitric oxide synthase mRNA, as well as the associated increase in nitric oxide production, that occurred in response to several stimuli. These included bacterial products and mammalian cytokines: endotoxin, and interferon-gamma plus endotoxin, interleukin-2, or tumor necrosis factor-alpha. The inhibition by MSP of induction of nitric oxide synthase mRNA and; nitric oxide secretion was concentration-dependent. The concentration of MSP that caused maximal inhibition of nitric oxide production was comparable with the optimum for stimulation of macrophage motile and phagocytic activity. Time course studies showed that nitrate was first detected in culture fluid about 8 h after endotoxin stimulation, and it accumulated at a linear rate during the ensuing 16 h. Inhibition by MSP occurred during the 8-h lipopolysaccharide (LPS) induction period; inhibition was maximal when MSP and LPS were added together and decreased progressively to no inhibition as the interval between LPS and MSP addition increased to 11 h. C1 NCI,FREDERICK CANC RES & DEV CTR,EXPTL IMMUNOL LAB,FREDERICK,MD 21702. RP WANG, MH (reprint author), NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,BLDG 560,RM 12-71,FREDERICK,MD 21702, USA. NR 46 TC 87 Z9 90 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 13 PY 1994 VL 269 IS 19 BP 14027 EP 14031 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NL606 UT WOS:A1994NL60600048 PM 7514598 ER PT J AU DONG, BH XU, LL ZHOU, AM HASSEL, BA LEE, X TORRENCE, PF SILVERMAN, RH AF DONG, BH XU, LL ZHOU, AM HASSEL, BA LEE, X TORRENCE, PF SILVERMAN, RH TI INTRINSIC MOLECULAR ACTIVITIES OF THE INTERFERON-INDUCED 2-5A-DEPENDENT RNASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DOUBLE-STRANDED-RNA; FREE PROTEIN-SYNTHESIS; TREATED CELLS; PPP(A2'P)NA-DEPENDENT RNASE; JLS-V9R CELLS; 2-5A; ACTIVATION; BINDING; 2',5'-OLIGOADENYLATES; ENDORIBONUCLEASE AB 2-5A-dependent RNase (RNase L), a unique endoribonuclease that requires 5'-phosphorylated 2',5'-linked oligoadenylates (2-5A), functions in the molecular mechanism of interferon action. Because this enzyme is present at very low levels in nature, characterization and analysis have been limited. The molecular cloning of human, 2-5A-dependent RNase cDNA has facilitated its expression to high levels in insect cells by infecting with recombinant baculovirus. To determine the properties of the enzyme in the absence of other proteins, the recombinant 2-5A-dependent RNase was purified to homogeneity. The purified enzyme migrated as a monomer upon gel filtration in the absence of activator and showed highly specific, 2-5A-dependent RNase activity. The precise activator requirements were determined by stimulating the purified enzyme with a variety of 2',5'-linked oligonucleotides. The activated enzyme was capable of cleaving poly(rU) and, to a lesser extent, poly(rA), to sets of discrete products ranging from between 4 and 22 nucleotides in length. Reduced rates of 2-5A-dependent RNA cleavage were observed even after removal of ATP and chelation of divalent cations. However, optimal RNA cleavage rates required the presence of either manganese or magnesium and ATP. C1 CLEVELAND CLIN FDN,RES INST,DEPT CANC BIOL,CLEVELAND,OH 44195. NIDDK,MED CHEM LAB,BIOMED CHEM SECT,BETHESDA,MD 20892. FU NCI NIH HHS [5R01 CA44059] NR 45 TC 105 Z9 107 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 13 PY 1994 VL 269 IS 19 BP 14153 EP 14158 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NL606 UT WOS:A1994NL60600065 PM 7514601 ER PT J AU LANS, MS LI, Q LU, J MODI, WS NOTKINS, AL AF LANS, MS LI, Q LU, J MODI, WS NOTKINS, AL TI GENOMIC ORGANIZATION, 5'-UPSTREAM SEQUENCE, AND CHROMOSOMAL LOCALIZATION OF AN INSULINOMA-ASSOCIATED INTRONLESS GENE, IA-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTION FACTOR; RECEPTOR; PROMOTER; EXPRESSION; PROTEIN; REGIONS; SV40; DNA AB IA-1 is a novel cDNA originally isolated from a human insulinoma subtraction library (ISL-153). It encodes a protein containing both a zinc finger DNA-binding domain and a putative prohormone domain. IA-1 transcripts have been found thus far only in tumors of neuroendocrine origin. Clinical studies have shown that IA-1 is a sensitive marker for neuroendocrine differentiation of human lung tumors. In this study, we cloned and sequenced the entire IA-1 gene and its 5'-upstream region from a human liver genomic library. In situ hybridization localized the IA-1 gene to the short arm of human chromosome 20. Sequence analysis and restriction enzyme mapping showed that the IA-1 gene is uninterrupted and appears to be intronless. Evidence that IA-1 is an intronless gene that can translate into protein was obtained from in vitro translation studies that showed that both IA-1 cDNA and IA-1 genomic DNA yielded identical protein products of approximately 61,000 daltons. Examination of the 5'-upstream region (2090 base pairs) revealed several tissue-specific regulatory elements, including glucokinase upstream promoter elements and a Pit-1 factor binding site. The presence of several different upstream regulatory elements may account for IA-1 gene expression in different neuroendocrine tumors. C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS DEV PROGRAM,FREDERICK,MD 21702. RP LANS, MS (reprint author), NIDR,ORAL MED LAB,BLDG 30,RM 121,BETHESDA,MD 20892, USA. NR 30 TC 2 Z9 2 U1 1 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 13 PY 1994 VL 269 IS 19 BP 14170 EP 14174 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NL606 UT WOS:A1994NL60600068 ER PT J AU HOU, D CENCIARELLI, C JENSEN, JP NGUYEN, HB WEISSMAN, AM AF HOU, D CENCIARELLI, C JENSEN, JP NGUYEN, HB WEISSMAN, AM TI ACTIVATION-DEPENDENT UBIQUITINATION OF A T-CELL ANTIGEN RECEPTOR SUBUNIT ON MULTIPLE INTRACELLULAR LYSINES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SHORT-LIVED PROTEIN; ZETA-CHAIN; TYROSINE PHOSPHORYLATION; SIGNAL TRANSDUCTION; MONOCLONAL-ANTIBODY; CYTOPLASMIC TAIL; DOMAIN; KINASE; POLYPEPTIDE; DEGRADATION AB The T cell antigen receptor zeta chain and other T cell antigen receptor components are ubiquitinated on receptor occupancy. A systematic mutagenesis of the zeta subunit was undertaken to determine the sites of ubiquitination. Ubiquitination was found to occur in the cytoplasmic domain of zeta with multiple lysines serving as sites for mono- and polyubiquitination. The mutation of all potential sites of ubiquitination did not inhibit receptor tyrosine phosphorylation or the ubiquitination of other T cell antigen receptor subunits. Lysines introduced into nonnative positions in the zeta molecule were also able to serve as sites for ubiquitination. These findings demonstrate that once a T cell antigen receptor is targeted for ubiquitination, there is little specificity with regard to the lysine residues that are modified. C1 NCI,BIOL RESPONSE MODIFIERS PROGRAM,IMMUNE CELL BIOL LAB,BETHESDA,MD 20892. NR 50 TC 100 Z9 100 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 13 PY 1994 VL 269 IS 19 BP 14244 EP 14247 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NL606 UT WOS:A1994NL60600078 PM 8188707 ER PT J AU ROSALES, R HARRIS, N AHN, BY MOSS, B AF ROSALES, R HARRIS, N AHN, BY MOSS, B TI PURIFICATION AND IDENTIFICATION OF A VACCINIA VIRUS-ENCODED INTERMEDIATE STAGE PROMOTER-SPECIFIC TRANSCRIPTION FACTOR THAT HAS HOMOLOGY TO EUKARYOTIC TRANSCRIPTION FACTOR SII (TFIIS) AND AN ADDITIONAL ROLE AS A VIRAL-RNA POLYMERASE SUBUNIT SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MESSENGER-RNA; MUTATIONAL ANALYSIS; POLY(A) POLYMERASE; ELONGATION-FACTOR; DNA-REPLICATION; EARLY GENES; VIRIONS; GUANYLYLTRANSFERASE; EXPRESSION; TEMPLATE AB Enzymes and factors, required for in vitro transcription of templates regulated by vaccinia virus intermediate stage promoters, are present in HeLa cells infected with vaccinia virus in the presence of an inhibitor of DNA replication. Previous studies indicated that in vitro transcription could be reconstituted by adding a partially purified transcription factor to the viral RNA polymerase and capping enzyme. By using an independent purification procedure, we isolated two vaccinia virus intermediate transcription factors VITF-1 and VITF-2 that were necessary for transcription of several different intermediate stage promoter templates but not for early or late stage promoter templates. VITF-1 was purified to homogeneity, and the sequences of two tryptic peptides were mapped to the fourth open reading frame within the HindIII E fragment (E4L) of the vaccinia virus genome, which had previously been shown to encode an RNA polymerase subunit of 30 kDa (RPO30) with homology to eukaryotic transcription elongation factor SII. Co-chromatography of VITF-1 with the E4L-derived protein was demonstrated using specific antiserum. In addition, transcriptionally active recombinant VITF-1 was made by expressing the E4L open reading frame in Escherichia coli. Thus, E4L encodes a multifunctional protein, serving as a RNA polymerase subunit and a stage-specific transcription factor. The stepwise binding of capping enzyme, VITF-1, and VITF-2 to a DNA/viral RNA polymerase complex was demonstrated. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. NR 41 TC 42 Z9 42 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 13 PY 1994 VL 269 IS 19 BP 14260 EP 14267 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NL606 UT WOS:A1994NL60600081 PM 8188710 ER PT J AU BURNETT, VL LAWTON, MP PHILPOT, RM AF BURNETT, VL LAWTON, MP PHILPOT, RM TI CLONING AND SEQUENCING OF FLAVIN-CONTAINING MONOOXYGENASES FMO3 AND FMO4 FROM RABBIT AND CHARACTERIZATION OF FMO3 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PIG-LIVER-MICROSOMES; FUNCTION AMINE OXIDASE; MULTIPLE FORMS; GEL-ELECTROPHORESIS; COVALENT STRUCTURE; RIBONUCLEIC-ACID; MOUSE; PURIFICATION; LUNG; GENE AB The flavin-containing monooxygenases (FMO) are a family of enzymes that contain putative FAD- and NADPH-binding domains within the first 200 residues of their N termini. The cDNAs encoding these enzymes contain an area of relatively high identity over the 5' half of the coding region. Rabbit genomic DNA was probed under low stringency conditions, with a mixture of 5' cDNA fragments encoding rabbit FMO1, FMO2, or FMO5. Bands associated specifically with FMO1, FMO2, or FMO5 were resolved by analysis at high stringency with individual probes. Several bands were detected that could not be assigned to FMO1, FMO2, or FMO5. The behavior of the 5' probes at low versus high stringency was used to facilitate the isolation of cDNAs corresponding to the unknown DNA bands. A cDNA library was constructed from rabbit liver mRNA and screened under low stringency hybridization conditions (30 degrees C, 50% formamide, 1 x SSC, 0.1% SDS) with the mixture of 5' FMO1, FMO2, and FMO5 cDNA probes. A total of 157 clones was detected. Of these, 117 clones remained under high stringency hybridization conditions (65 degrees C, 50% formamide, 0.1 x SSC, 0.1% SDS) and were identified as FMO1 (95 clones) or FMO5 (22 clones). Of the 40 remaining clones, 36 were characterized by sequence analysis as encoding FMO3, previously identified at the protein level by Ozols (Ozols, J. (1991) Arch. Biochem. Biophys. 290, 103-115) as a second rabbit liver FMO. Four clones were shown to encode an FMO not previously described for the rabbit, FMO4. No clones encoding FMO2 were isolated from the liver library. Sequence analysis revealed that FMO3 and FMO4 are 56% identical, and analysis of genomic DNA indicated that each is encoded by a single gene. Message distribution was tissue-, species-, and form-specific. The properties of FMO3 cDNA expressed in Escherichia coli were found to be more similar to those of FMO1 than FMO2, but to differ significantly from both. Rabbit genomic DNA was probed under conditions of low stringency with a mixture of 5' cDNA fragments encoding all five FMO forms and produced results consistent with the possibility of one additional FMO. C1 NIEHS,CELLULAR & MOLEC PHARMACOL LAB,RES TRIANGLE PK,NC 27709. N CAROLINA STATE UNIV,DEPT TOXICOL,RALEIGH,NC 27695. NR 50 TC 47 Z9 49 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 13 PY 1994 VL 269 IS 19 BP 14314 EP 14322 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NL606 UT WOS:A1994NL60600089 PM 8188717 ER PT J AU YSERN, X FIELDS, BA BHAT, TN GOLDBAUM, FA DALLACQUA, W SCHWARZ, FP POLJAK, RJ MARIUZZA, BA AF YSERN, X FIELDS, BA BHAT, TN GOLDBAUM, FA DALLACQUA, W SCHWARZ, FP POLJAK, RJ MARIUZZA, BA TI SOLVENT REARRANGEMENT IN AN ANTIGEN-ANTIBODY INTERFACE INTRODUCED BY SITE-DIRECTED MUTAGENESIS OF THE ANTIBODY COMBINING SITE SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Note DE 3-DIMENSIONAL STRUCTURE; SITE-DIRECTED MUTAGENESIS; ANTIGEN-ANTIBODY REACTION; ENTHALPY-ENTROPY; HYDROPHOBIC EFFECT ID BINDING C1 UNIV MARYLAND,MARYLAND BIOTECHNOL INST,CTR ADV RES BIOTECHNOL,ROCKVILLE,MD 20850. NATL INST STAND & TECHNOL,ROCKVILLE,MD 20850. NCI,FREDERICK CANC RES & DEV CTR,CTR BIOMED SUPERCOMP,STRUCT BIOCHEM PROGRAM,FREDERICK,MD 21202. RP YSERN, X (reprint author), US FDA,CTR DRUG EVALUAT & RES,ROCKVILLE,MD 20857, USA. NR 17 TC 58 Z9 58 U1 0 U2 2 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 13 PY 1994 VL 238 IS 4 BP 496 EP 500 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NM066 UT WOS:A1994NM06600002 PM 8176740 ER PT J AU FREED, EO MARTIN, MA AF FREED, EO MARTIN, MA TI HIV-1 INFECTION OF NONDIVIDING CELLS SO NATURE LA English DT Letter RP FREED, EO (reprint author), NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892, USA. NR 6 TC 62 Z9 62 U1 0 U2 4 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 12 PY 1994 VL 369 IS 6476 BP 107 EP 108 DI 10.1038/369107b0 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NK971 UT WOS:A1994NK97100032 PM 8192816 ER PT J AU VINEIS, P BARTSCH, H CAPORASO, N HARRINGTON, AM KADLUBAR, FF LANDI, MT MALAVEILLE, C SHIELDS, PG SKIPPER, P TALASKA, G TANNENBAUM, SR AF VINEIS, P BARTSCH, H CAPORASO, N HARRINGTON, AM KADLUBAR, FF LANDI, MT MALAVEILLE, C SHIELDS, PG SKIPPER, P TALASKA, G TANNENBAUM, SR TI GENETICALLY BASED N-ACETYLTRANSFERASE METABOLIC POLYMORPHISM AND LOW-LEVEL ENVIRONMENTAL EXPOSURE TO CARCINOGENS SO NATURE LA English DT Article ID EXFOLIATED UROTHELIAL CELLS; HEMOGLOBIN ADDUCTS; DNA ADDUCTS; URINARY MUTAGENICITY; CIGARETTE SMOKERS; SMOKING; ACETYLATION; PHENOTYPE; CANCER AB THE metabolic activation or inactivation of carcinogens varies considerably in human populations, and is partly genetically determined(1,2). Inter-individual variability in the susceptibility to carcinogens may be particularly important at low degrees of environmental exposure. Examples of probable human carcinogens that present widespread low-dose exposures are environmental tobacco smoke and diesel exhaust(3,4). We have determined levels of DNA adducts in bladder cells and of 4-aminobiphenyl-haemoglobin adducts in 97 volunteers, together with the N-acetylation non-inducible phenotype, the corresponding genotype, and the levels of nicotine-cotinine in the urine. We find that among the slow acetylators, 4-aminobiphenyl adducts were higher than in rapid acetylators at low or null nicotine-cotinine levels, whereas the difference between slow and rapid acetylators was less evident at increasing nicotine-cotinine levels. The N-acetyltransferase genotype is highly predictive of the acetylation phenotype. Our results indicate that the clearance of low-dose carcinogens is decreased in the genetically based slow-acetylator phenotype. Such genetic modulation of low-dose environmental risks is relevant to 'risk assessment' procedures. C1 MAIN HOSP,I-10126 TURIN,ITALY. GERMAN CANC RES CTR,D-69120 HEIDELBERG,GERMANY. NCI,GENET EPIDEMIOL BRANCH,ROCKVILLE,MD 20892. NCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. NATL CTR TOXICOL RES,JEFFERSON,AR 72079. UNIV MILAN,IST MED LAVORO,I-20122 MILAN,ITALY. INT AGCY RES CANC,F-69372 LYON,FRANCE. MIT,DEPT CHEM,CAMBRIDGE,MA 02139. UNIV CINCINNATI,DEPT ENVIRONM HLTH,CINCINNATI,OH. RP VINEIS, P (reprint author), UNIV TURIN,DIPARTIMENTO SCI BIOMED & ONCOL UMANA,CANC EPIDEMIOL UNIT,I-10126 TURIN,ITALY. RI Shields, Peter/I-1644-2012; Osborne, Nicholas/N-4915-2015 OI Osborne, Nicholas/0000-0002-6700-2284 NR 15 TC 262 Z9 266 U1 0 U2 5 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD MAY 12 PY 1994 VL 369 IS 6476 BP 154 EP 156 DI 10.1038/369154a0 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NK971 UT WOS:A1994NK97100051 PM 7909916 ER PT J AU HOLLAND, SM EISENSTEIN, EM KUHNS, DB TURNER, ML FLEISHER, TA STROBER, W GALLIN, JI AF HOLLAND, SM EISENSTEIN, EM KUHNS, DB TURNER, ML FLEISHER, TA STROBER, W GALLIN, JI TI TREATMENT OF REFRACTORY DISSEMINATED NONTUBERCULOUS MYCOBACTERIAL INFECTION WITH INTERFERON-GAMMA - A PRELIMINARY-REPORT SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; AVIUM-INTRACELLULARE; LEPROMATOUS LEPROSY; TUBERCULOSIS; IMMUNODEFICIENCY; COMPLEX; SUSCEPTIBILITY; EXPRESSION AB Background. Studies conducted in vitro and in animals suggest that cytokine signals to monocytes or macrophages by interferon gamma are important in the containment and clearance of disseminated nontuberculous mycobacterial infections. Methods. We studied seven patients with refractory disseminated nontuberculous mycobacterial infections who were not infected with the human immunodeficiency virus. Three patients were from a family predisposed to the development of Mycobacterium avium complex infections; four patients had idiopathic CD4+ T-lymphocytopenia. Their infections were culture- or biopsy-proved, involved at least two organ systems, and had been treated with the maximal tolerated medical therapy. Cellular proliferation, cytokine production, and phagocyte function were assessed in peripheral-blood cells. Interferon gamma was administered subcutaneously two or three times weekly in a dose of 25 to 50 mu g per square meter of body-surface area in addition to antimycobacterial medications. Clinical effects were monitored by cultures, biopsies, radiographs, and in one patient a change in the need for paracentesis. Results. In response to phytohemagglutinin, the production of interferon gamma by mononuclear cells from the patients was lower than in normal subjects (P<0.001), whereas stimulation with ionomycin and phorbol myristate acetate led to normal production of interferon gamma in the patients. Within eight weeks of the start of interferon gamma therapy, all seven patients had marked clinical improvement, with abatement of fever, clearing of many lesions and quiescence of others, radiographic improvement, and a reduction in the need for paracentesis. Conclusions. Interferon gamma in combination with conventional therapy may be effective for some cases of refractory disseminated nontuberculous mycobacterial infection. C1 NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. NCI,DERMATOL BRANCH,BETHESDA,MD 20892. NIH,WARREN GRANT MAGNUSON CLIN CTR,BETHESDA,MD 20892. PRI DYNCORP INC,FREDERICK,MD. RP HOLLAND, SM (reprint author), NIAID,HOST DEF LAB,BLDG 10, RM 11N103,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 35 TC 248 Z9 252 U1 1 U2 4 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 12 PY 1994 VL 330 IS 19 BP 1348 EP 1355 DI 10.1056/NEJM199405123301904 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA NK753 UT WOS:A1994NK75300004 PM 7908719 ER PT J AU CASH, JM KLIPPEL, JH AF CASH, JM KLIPPEL, JH TI 2ND-LINE DRUG-THERAPY FOR RHEUMATOID-ARTHRITIS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID LOW-DOSE METHOTREXATE; PNEUMOCYSTIS-CARINII PNEUMONIA; CONTROLLED CLINICAL-TRIAL; LONG-TERM; DOUBLE-BLIND; FOLLOW-UP; LIVER BIOPSIES; ANTIRHEUMATIC DRUGS; D-PENICILLAMINE; 2ND-LINE DRUGS C1 NIAMS,ARTHRITIS & RHEUMATISM BRANCH,BETHESDA,MD 20892. CLEVELAND CLIN FDN,DEPT RHEUMAT & IMMUNOL DIS,CLEVELAND,OH 44195. NR 118 TC 133 Z9 134 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 12 PY 1994 VL 330 IS 19 BP 1368 EP 1375 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA NK753 UT WOS:A1994NK75300008 PM 8152450 ER PT J AU DALAKAS, MC AF DALAKAS, MC TI INTRAVENOUS IMMUNE GLOBULIN FOR DERMATOMYOSITIS - REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP DALAKAS, MC (reprint author), NIH,BETHESDA,MD 20892, USA. NR 5 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 12 PY 1994 VL 330 IS 19 BP 1392 EP 1393 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA NK753 UT WOS:A1994NK75300030 ER PT J AU JENSEN, RT FRAKER, DL AF JENSEN, RT FRAKER, DL TI ZOLLINGER-ELLISON SYNDROME - ADVANCES IN TREATMENT OF GASTRIC HYPERSECRETION AND THE GASTRINOMA SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID MULTIPLE ENDOCRINE NEOPLASIA; DUODENAL GASTRINOMAS; HELICOBACTER-PYLORI; COLORECTAL-CANCER; TYPE-1; TUMORS; LOCALIZATION; MANAGEMENT; OMEPRAZOLE; HYPERGASTRINEMIA C1 NCI, SURG METAB SECT, BETHESDA, MD USA. RP JENSEN, RT (reprint author), NIDDKD, DIGEST DIS BRANCH, BLDG 10, ROOM 9C-103, BETHESDA, MD 20892 USA. NR 68 TC 28 Z9 28 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 11 PY 1994 VL 271 IS 18 BP 1429 EP 1435 DI 10.1001/jama.271.18.1429 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA NJ693 UT WOS:A1994NJ69300031 PM 7513768 ER PT J AU REITER, Y BRINKMANN, U KREITMAN, RJ JUNG, SH LEE, B PASTAN, I AF REITER, Y BRINKMANN, U KREITMAN, RJ JUNG, SH LEE, B PASTAN, I TI STABILIZATION OF THE FV FRAGMENTS IN RECOMBINANT IMMUNOTOXINS BY DISULFIDE BONDS ENGINEERED INTO CONSERVED FRAMEWORK REGIONS SO BIOCHEMISTRY LA English DT Article ID SINGLE-CHAIN-FV; PSEUDOMONAS EXOTOXIN; ESCHERICHIA-COLI; PROTEINS; TOXINS AB Disulfide-stabilized Fv's (dsFv's) are recombinant Fv fragments of antibodies in which the unstable variable heavy (V-H) and variable light (V-L) heterodimers are stabilized by disulfide bonds engineered at specific sites that lie between structurally conserved framework positions of V-H and V-L We have recently described one example of a recombinant immunotoxin, B3(dsFv)-PE38KDEL, that is composed of such a dsFv connected to a truncated form of Pseudomonas exotoxin [Brinkmann, U., Reiter, Y., Jung, S.-H., Lee, B., and Pastan, I. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 7538-7542]. This disulfide-stabilized immunotoxin has the same cytotoxic activity and specificity as its single-chain immunotoxin counterpart. To determine whether the stabilization of Fv's by disulfides at these positions is generally applicable, we made and analyzed two other dsFv-containing immunotoxins. One is made from the e23 antibody, which binds to the carcinoma-associated antigen erbB2; the other is made from the anti-Tac antibody, which binds to the p55 subunit of the IL-2 receptor. Comparison of the specificity and activity of these immunotoxins with those of their scFv counterparts revealed that e23(dsFv)-PE38KDEL was considerably more active than e23(Fv)-PE38KDEL, whereas anti-Tac(dsFv)-PE38KDEL was only somewhat more active than its single-chain counterpart. These results suggest that dsFv's have at least the same binding properties as scFv's, and in some cases they may have better binding. Thus, it should be feasible to use the positions we have identified in the conserved framework region to disulfide-stabilize many different Fv's. Furthermore, we have optimized the design of the immunotoxin and the purification scheme, so that the yields of dsFv-immunotoxins are consistently higher than those of scFv-toxins and one can obtain up to 70 mg of pure active immunotoxin from 1 L of bacterial culture. This increased yield is mainly due to a decreased tendency of properly folded dsFv-immunotoxins to aggregate. Because dsFv-immunotoxins have equal or improved activity, they are easier to produce with high yields and are more stable than scFv-immunotoxins; dsFv-immunotoxins (and dsFv's alone) might be more useful than scFv's in clinical and other applications that require large amounts of stable recombinant Fv's. C1 NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,BETHESDA,MD 20892. RI Lee, Byungkook/E-4564-2011 OI Lee, Byungkook/0000-0002-3339-4582 NR 22 TC 105 Z9 110 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 10 PY 1994 VL 33 IS 18 BP 5451 EP 5459 DI 10.1021/bi00184a014 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NK973 UT WOS:A1994NK97300014 PM 7910034 ER PT J AU ROTHSTEIN, JD BRISTOL, LA HOSLER, B BROWN, RH KUNCL, RW AF ROTHSTEIN, JD BRISTOL, LA HOSLER, B BROWN, RH KUNCL, RW TI CHRONIC INHIBITION OF SUPEROXIDE-DISMUTASE PRODUCES APOPTOTIC DEATH OF SPINAL NEURONS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE AMYOTROPHIC LATERAL SCLEROSIS; ANTIOXIDANT; FREE RADICALS; MOTOR NEURON; ORGANOTYPE CULTURE ID CENTRAL-NERVOUS-SYSTEM; CHOLINE-ACETYLTRANSFERASE; POSTNATAL-DEVELOPMENT; GLUTAMATE; TOXICITY; RILUZOLE; NUCLEUS; ACID AB Mutations in the gene for Cu/Zn superoxide dismutase (SOD1) have been detected in some families with an autosomal dominant form of amyotrophic lateral sclerosis; these mutations appear to reduce the activity of this enzyme. To determine whether decreased SOD activity could contribute to motor neuron loss, SOD1 was inhibited chronically with either antisense oligodeoxynucleotides or diethyldithiocarbamate in spinal cord organotypic cultures. Chronic inhibition of SOD resulted in the apoptotic degeneration of spinal neurons, including motor neurons, over several weeks. Motor neuron loss was markedly potentiated by the inhibition of glutamate transport. In this paradigm, motor neuron toxicity could be entirely prevented by the antioxidant N-acetylcysteine and, to a lesser extent, by the non-N-methyl-D-aspartate glutamate receptor antagonist 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride. These data support the hypothesis that the loss of motor neurons in familial amyotrophic lateral sclerosis could be due to a reduction in SOD1 activity, possibly potentiated by inefficient glutamate transport. C1 NCI, EXPTL IMMUNOL BRANCH, BETHESDA, MD 20892 USA. MASSACHUSETTS GEN HOSP, DAY NEUROMUSCULAR RES LAB, BOSTON, MA 02129 USA. RP JOHNS HOPKINS UNIV, SCH MED, DEPT NEUROL, MEYER 5-119, 600 N WOLFE ST, BALTIMORE, MD 21287 USA. RI rothstein, jeffrey/C-9470-2013 NR 38 TC 284 Z9 288 U1 1 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 10 PY 1994 VL 91 IS 10 BP 4155 EP 4159 DI 10.1073/pnas.91.10.4155 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NL608 UT WOS:A1994NL60800012 PM 7910402 ER PT J AU SCHAFER, M CARTER, L STEIN, C AF SCHAFER, M CARTER, L STEIN, C TI INTERLEUKIN-1-BETA AND CORTICOTROPIN-RELEASING FACTOR INHIBIT PAIN BY RELEASING OPIOIDS FROM IMMUNE CELLS IN INFLAMED TISSUE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ANALGESIA; NOCICEPTION; CYTOKINES; NEUROPEPTIDES ID BLOOD MONONUCLEAR-CELLS; BETA-ENDORPHIN; INFLAMMATION; RECEPTORS; ANTINOCICEPTION; MACROPHAGES; EXPRESSION; PEPTIDES; INVIVO; SPLEEN AB Local analgesic effects of exogenous opioid agonists are particularly prominent in painful inflammatory conditions and are mediated by opioid receptors on peripheral sensory nerves. The endogenous ligands of these receptors, opioid peptides, have been demonstrated in resident immune cells within inflamed tissue of animals and humans. Here we examine in vivo and in vitro whether interleukin 1 beta (IL-1) or corticotropin-releasing factor (CRF) is capable of releasing these endogenous opioids and inhibiting pain. When injected into inflamed rat paws (but not intravenously), IL-1 and CRF produce antinociception, which is reversible by IL-1 receptor antagonist and alpha-helical CRF, respectively, and by the immunosuppressant cyclosporine A. In vivo administration of antibodies against opioid peptides indicates that the effects of IL-1 and CRF are mediated by beta-endorphin and, in addition, by dynorphin A and [Met]enkephalin, respectively. Correspondingly, IL-1 effects are inhibited by mu-, delta-, and kappa-opioid antagonists, whereas CRF effects are attenuated by all except a kappa-antagonist. Finally, IL-1 and CRF produce acute release of immunoreactive beta-endorphin in cell suspensions freshly prepared from inflamed lymph nodes. This effect is reversible by IL-1 receptor antagonist and alpha-helical CRF, respectively. These findings suggest that IL-1 and CRF activate their receptors on immune cells to release opioids that subsequently occupy multiple opioid receptors on sensory nerves and result in antinociception. beta-Endorphin, mu- and delta-opioid receptors play a major role, but IL-1 and CRF appear to differentially release additional opioid peptides. C1 JOHNS HOPKINS UNIV,DEPT ANESTHESIOL & CRIT CARE MED,BALTIMORE,MD 21287. NIDA,ADDICT RES CTR,BEHAV PHARMACOL & GENET SECT,BALTIMORE,MD 21224. FU NINDS NIH HHS [R01 NS 32466] NR 29 TC 211 Z9 215 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 10 PY 1994 VL 91 IS 10 BP 4219 EP 4223 DI 10.1073/pnas.91.10.4219 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NL608 UT WOS:A1994NL60800025 PM 7910403 ER PT J AU MCCONKEY, GA ITTARAT, I MESHNICK, SR MCCUTCHAN, TF AF MCCONKEY, GA ITTARAT, I MESHNICK, SR MCCUTCHAN, TF TI AUXOTROPHS OF PLASMODIUM-FALCIPARUM DEPENDENT ON P-AMINOBENZOIC ACID FOR GROWTH SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MALARIA PARASITES; RESISTANCE; MECHANISMS; CULTURE AB The isolation of auxotrophic strains of a parasite offers new opportunities for studying parasitology. We have isolated cloned lines of Plasmodium falciparum that, unlike the parent line from which they were derived, rely on exogenous p-aminobenzoic acid (PABA) for growth. Isolation involved random mutagenesis of a cloned line of P. falciparum and subsequent selection of PABA-dependent parasites. Both parent and PABA-dependent clones were analyzed for PABA uptake and synthesis. Each clone takes up comparable amounts of PABA from the medium. The parent line, clone 3D7, can synthesize PABA de novo, whereas the BABA-dependent clones cannot. The requirement of exogenous PABA for growth by the auxotrophic strains coupled with their inability to synthesize PABA indicates that normal parasite growth can be completely supported by either synthesis or salvage. This work further clarifies the relationship between the availability of PABA and success of the parasite, an issue of debate from classic studies showing reduced parasite load in individuals on milk-fed diets. C1 NIAID,MALARIA RES LAB,MOLEC BIOL SECT,BETHESDA,MD 20892. UNIV MICHIGAN,SCH PUBL HLTH,DEPT EPIDEMIOL,ANN ARBOR,MI 48109. NR 20 TC 25 Z9 26 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 10 PY 1994 VL 91 IS 10 BP 4244 EP 4248 DI 10.1073/pnas.91.10.4244 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA NL608 UT WOS:A1994NL60800030 PM 8183896 ER PT J AU FIGG, WD THIBAULT, A SARTOR, AO MAYS, D HEADLEE, D CALIS, KA COOPER, MR AF FIGG, WD THIBAULT, A SARTOR, AO MAYS, D HEADLEE, D CALIS, KA COOPER, MR TI HYPOTHYROIDISM ASSOCIATED WITH AMINOGLUTETHIMIDE IN PATIENTS WITH PROSTATE-CANCER SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article AB Objective: The administration of aminoglutethimide and hydrocortisone is a second-line hormonal maneuver commonly prescribed for the treatment of metastatic prostate cancer. We determine the incidence of aminoglutethimide-induced primary hypothyroidism in an elderly population who have prostate cancer. Design: Prospective evaluation. Patients: Twenty-nine men with stage D2 prostate cancer who were treated at the National Cancer Institute, Bethesda, Md, in 1992. Results: Clinical and biochemical evidence of hypothyroidism (thyrotropin levels greater than 10 mU/L) was noted in nine of 29 patients treated following the initiation of aminoglutethimide (250 mg four times daily). The elevation in thyrotropin and the clinical symptoms of hypothyroidism were reversed by the administration of levothyroxine (n = 4). Conclusion: Hypothyroidism should be included in the differential diagnosis of lethargy in elderly patients who are receiving aminoglutethimide for prostate cancer. Furthermore, patients who are receiving this agent at a dosage of 1000 mg/d or greater should have their serum thyrotropin levels monitored, and replacement therapy with levothyroxine should be initiated when abnormally elevated levels are noted. RP FIGG, WD (reprint author), NCI,CLIN PHARMACOL BRANCH,BLDG 10,ROOM 5A01,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Figg Sr, William/M-2411-2016 NR 10 TC 6 Z9 6 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAY 9 PY 1994 VL 154 IS 9 BP 1023 EP 1025 DI 10.1001/archinte.154.9.1023 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA NK247 UT WOS:A1994NK24700009 PM 8179445 ER PT J AU FREED, LM WAKABAYASHI, S BELL, JM RAPOPORT, SI AF FREED, LM WAKABAYASHI, S BELL, JM RAPOPORT, SI TI EFFECT OF INHIBITION OF BETA-OXIDATION ON INCORPORATION OF [U-C-14]PALMITATE AND [1-C-14]ARACHIDONATE INTO BRAIN LIPIDS SO BRAIN RESEARCH LA English DT Article DE PALMITIC ACID; ARACHIDONIC ACID; BRAIN; FATTY ACID; BETA-OXIDATION; PHOSPHOLIPID; METHYL PALMOXIRATE ID CEREBRAL PALMITATE INCORPORATION; UNANESTHETIZED RATS; ACID INCORPORATION; 2-TETRADECYLGLYCIDATE AB The purpose of the present study was to determine the effect of inhibiting the mitochondrial P-oxidation of free fatty acids on the incorporation of radiolabeled free fatty acids into brain lipids. To this end, methyl 2-tetradecylglycidate (MEP), an irreversible inhibitor of carnitine palmitoyltransferase I, was given orally to male rats 2, 4, and 6 h prior to an intravenous infusion of the saturated fatty acid [U-C-14]palmitic acid (PA) or the polyunsaturated fatty acid [1-C-14]arachidonate (AA). With [U-C-14]PA, MEP (10-25 mg/kg) increased brain organic radioactivity 2-fold and decreased brain aqueous radioactivity 3- to 5-fold relative to control values at all pretreatment times. The effect was due to prolongation of the plasma integral of [U-C-14]PA due to peripheral inhibition of beta-oxidation, and to direct inhibition of beta-oxidation of the tracer within the brain. MEP had no effect on brain organic radioactivity after infusion of [1-C-14]AA. Increasing the interval between MEP administration and [U-C-14]PA infusion from 2 to 6 h resulted in a dramatic redistribution of [U-C-14]PA within brain lipids. The percentage of radioactivity in phospholipids decreased from 65 to 33%, whereas that in the free fatty acid fraction increased from 10 to 47% and that in triglycerides was elevated 2-3 fold over control levels. These results indicate that MEP may facilitate the use of radiolabeled PA as an in vivo probe of brain lipid metabolism using quantitative autoradiography or positron emission tomography. RP FREED, LM (reprint author), NIA,NEUROSCI LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 30 TC 21 Z9 21 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAY 9 PY 1994 VL 645 IS 1-2 BP 41 EP 48 DI 10.1016/0006-8993(94)91636-5 PG 8 WC Neurosciences SC Neurosciences & Neurology GA NK540 UT WOS:A1994NK54000006 PM 8062099 ER PT J AU THOMAS, DN POST, RM PERT, A AF THOMAS, DN POST, RM PERT, A TI FOCAL AND SYSTEMIC COCAINE DIFFERENTIALLY AFFECT EXTRACELLULAR NOREPINEPHRINE IN THE LOCUS-COERULEUS, FRONTAL-CORTEX AND HIPPOCAMPUS OF THE ANESTHETIZED RAT SO BRAIN RESEARCH LA English DT Article DE NOREPINEPHRINE; MICRODIALYSIS; COCAINE; FRONTAL CORTEX; HIPPOCAMPUS; LOCUS COERULEUS ID NORADRENERGIC NEURONS; NUCLEUS-ACCUMBENS; NORADRENALINE RELEASE; INVIVO MICRODIALYSIS; DOPAMINE TRANSMISSION; ASCENDING PROJECTIONS; CERULEUS; BRAIN; AMPHETAMINE; INHIBITION AB The purpose of this study was to characterize and compare the effects of cocaine on norepinephrine (NE) overflow in the forebrain and somatodendritic regions of anaesthetized rats with microdialysis. Intraperitoneal injections of cocaine (20 mg/kg) failed to increase NE overflow in the hippocampus and the frontal cortex but did elevate NE in the region of the locus coeruleus. Focal application of cocaine (1-100 mu M) via the dialysis probe into the region of the locus coeruleus also produced a concentration dependent elevation of extracellular NE. In the terminal regions the application of focal cocaine (1-100 mu M) showed a differential effect, with a concentration dependent increase in extracellular NE in the hippocampus, whilst in the frontal cortex only the highest concentration of cocaine (100 mu M) elevated extracellular NE. The regional differences seen following focal applications in this study may be related to differences in transporter function in the three brain areas or to differences in the affinity for cocaine. The inability of systemically administered cocaine to increase hippocampal and cortical NE is probably related to its predominant actions in the somatodendritic region. RP THOMAS, DN (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,ROOM 3N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 53 TC 19 Z9 19 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 9 PY 1994 VL 645 IS 1-2 BP 135 EP 142 DI 10.1016/0006-8993(94)91646-2 PG 8 WC Neurosciences SC Neurosciences & Neurology GA NK540 UT WOS:A1994NK54000016 PM 8062076 ER PT J AU TIKTOPULO, EI BYCHKOVA, VE RICKA, J PTITSYN, OB AF TIKTOPULO, EI BYCHKOVA, VE RICKA, J PTITSYN, OB TI COOPERATIVITY OF THE COIL-GLOBULE TRANSITION IN A HOMOPOLYMER - MICROCALORIMETRIC STUDY OF POLY(N-ISOPROPYLACRYLAMIDE) SO MACROMOLECULES LA English DT Article ID PHASE-TRANSITION; POLYMER-CHAIN; DENATURATION; POLYSTYRENE; CYCLOHEXANE; STABILITY; PROTEINS; SYSTEM AB The temperature-induced intramolecular coil-globule transition in poly(N-isopropylacrylamide) has been studied by microcalorimetry to investigate the cooperativity of this transition. Measurements were performed in the presence of sodium dodecyl sulfate (SDS) which prevents the polymer from aggregation both in the coil and in the globule state. It has been shown that the effective (van't Hoff) enthalpy of transition of a cooperative unit is 120 times less than the calorimetric enthalpy of a polymer molecule. This means that a coil-globule transition in this polymer is not an ''all-or-none'' process and occurs independently in cooperative units (''domains'') which are 120 times smaller than the polymer molecule and have a molecular weight about 6 x 10(4). C1 UNIV BERN,INST APPL PHYS,CH-3012 BERN,SWITZERLAND. NCI,WSC,MATH BIOL LAB,BETHESDA,MD 20892. RP TIKTOPULO, EI (reprint author), RUSSIAN ACAD SCI,INST PROT RES,PUSHCHINO 142292,RUSSIA. NR 24 TC 197 Z9 197 U1 2 U2 21 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0024-9297 J9 MACROMOLECULES JI Macromolecules PD MAY 9 PY 1994 VL 27 IS 10 BP 2879 EP 2882 DI 10.1021/ma00088a031 PG 4 WC Polymer Science SC Polymer Science GA NL250 UT WOS:A1994NL25000031 ER PT J AU LAI, J BILSKY, EJ ROTHMAN, RB PORRECA, F AF LAI, J BILSKY, EJ ROTHMAN, RB PORRECA, F TI TREATMENT WITH ANTISENSE OLIGODEOXYNUCLEOTIDE TO THE OPIOID DELTA-RECEPTOR SELECTIVELY INHIBITS DELTA(2)-AGONIST ANTINOCICEPTION SO NEUROREPORT LA English DT Article DE OPIOID DELTA RECEPTOR SUBTYPES; ANTISENSE OLIGODEOXYNUCLEOTIDES; DPDPE; [D-ALA(2),GLU(4)]DELTORPHIN; ANTINOCICEPTION; MOUSE ID NALTRINDOLE 5'-ISOTHIOCYANATE; DIFFERENTIAL ANTAGONISM; FUNCTIONAL EXPRESSION; BINDING-SITES; HIGH-AFFINITY; SUBTYPES; CLONING; ENKEPHALIN; PEPTIDES; BRAIN AB USING approaches emphasizing differential antagonism of receptor selective agonists and cross-tolerance paradigms, evidence in vivo has suggested the existence of subtypes of opioid delta receptors, which have been termed delta(1), and delta(2). Recent work has elucidated the structure of an opioid delta receptor. The present investigation attempted to continue to test the hypothesis of subtypes of delta receptors and to correlate the cloned delta receptor with the existing pharmacological classification. Synthetic oligodeoxynucleotides (oligos) complementary to the 5' end of the cloned delta receptor coding region (antisense) or its corresponding sequence (sense) were given by intracerebroventricular (i.c.v.) administration to mice, twice-daily for 3 days and antinociceptive responses to selective agonists at putative delta(1) and delta(2) receptors were subsequently determined. Treatment with antisense, but not sense, oligo significantly inhibited the response to [D-Ala(2),Glu(4)]deltorphin (delta(2) agonist), but not to [D-Pen(2),D-Pen(5)]enkephalin (DPDPE, delta(1) agonist). Further, subsequent administration of DPDPE elicited a full antinociceptive response in the same antisense oligo treated mice which did not show a significant response to [D-Ala(2),Glu(4)]deltorphin while antisense oligo treated mice which responded to DPDPE did not show antinociception when tested subsequently with [D-Ala(2), Glu(4)]deltorphin. The data suggest that the cloned delta receptor corresponds to that pharmacologically classified as delta(2) and continue to support the concept of subtypes of opioid delta receptors. C1 UNIV ARIZONA,ARIZONA HLTH SCI CTR,DEPT PHARMACOL,TUCSON,AZ 85724. NIDA,ADDICT RES CTR,CLIN PSYCHOPHARMACOL SECT,BALTIMORE,MD 21224. NR 18 TC 75 Z9 75 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD MAY 9 PY 1994 VL 5 IS 9 BP 1049 EP 1052 DI 10.1097/00001756-199405000-00008 PG 4 WC Neurosciences SC Neurosciences & Neurology GA NN159 UT WOS:A1994NN15900008 PM 8080957 ER PT J AU GRAFMAN, J PASCUALLEONE, A ALWAY, D NICHELLI, P GOMEZTORTOSA, E HALLETT, M AF GRAFMAN, J PASCUALLEONE, A ALWAY, D NICHELLI, P GOMEZTORTOSA, E HALLETT, M TI INDUCTION OF A RECALL DEFICIT BY RAPID-RATE TRANSCRANIAL MAGNETIC STIMULATION SO NEUROREPORT LA English DT Article DE TRANSCRANIAL MAGNETIC STIMULATION; MEMORY; RECALL ID SHORT-TERM-MEMORY; VISUAL-PERCEPTION; OCCIPITAL CORTEX; SUPPRESSION AB WE used rapid-rate, repetitive transcranial magnetic stimulation (rTMS) for the noninvasive study of verbal recall. Five right-handed normal subjects were studied. Recall followed immediately after presentation of a 12-word list. Focal rTMS was applied with a figure eight coil in trains of 500 ms duration to F7, F8, T5, T6, P3, P4, or 01, 02 at latencies of 0, 250, 500, or 1000 ms during word list presentation. Recall was consistently significantly diminished only after left mid-temporal and bilateral dorsofrontal rTMS at both 0 and 250 ms latencies. We conclude that rTMS may be useful as a non-invasive tool for the study of verbal memory processes. C1 MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,HUMAN CORT PHYSIOL UNIT,VALENCIA,SPAIN. UNIV VALENCIA,UNIDAD NEUROBIOL,E-46100 VALENCIA,SPAIN. UNIV MODENA,NEUROL CLIN,I-41100 MODENA,ITALY. FDN JIMENEZ DIAZ,DEPT NEUROL,E-28040 MADRID,SPAIN. RP GRAFMAN, J (reprint author), NINCDS,MED NEUROL BRANCH,COGNIT NEUROSCI SECT,BLDG 10,ROOM 5S209,BETHESDA,MD 20892, USA. RI Pascual-Leone, Alvaro/G-6566-2011; Nichelli, Paolo/F-7336-2015; OI Nichelli, Paolo/0000-0001-9756-6796; Grafman, Jordan H./0000-0001-8645-4457 NR 25 TC 107 Z9 111 U1 2 U2 3 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD MAY 9 PY 1994 VL 5 IS 9 BP 1157 EP 1160 DI 10.1097/00001756-199405000-00034 PG 4 WC Neurosciences SC Neurosciences & Neurology GA NN159 UT WOS:A1994NN15900035 PM 8080978 ER PT J AU PETTIT, GR CICHACZ, ZA GAO, F BOYD, MR SCHMIDT, JM AF PETTIT, GR CICHACZ, ZA GAO, F BOYD, MR SCHMIDT, JM TI ISOLATION AND STRUCTURE OF THE CANCER CELL-GROWTH INHIBITOR DICTYOSTATIN-1 SO JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS LA English DT Article ID DINOFLAGELLATE AMPHIDINIUM SP; CYTOTOXIC MACROLIDES; C-13 ASSIGNMENTS; SPONGE; NMR; H-1 AB Dictyostatin 1 2, a new type of macrocyclic lactone bearing a 22-membered ring system, has been isolated (3.4 x 10(-7)% yield) from a Republic of Maldives marine sponge in the genus Spongia and found to strongly inhibit growth of the murine P388 lymphocytic leukaemia. C1 ARIZONA STATE UNIV,DEPT CHEM,TEMPE,AZ 85287. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,DRUG DISCOVERY R & D LAB,FREDERICK,MD 21702. RP PETTIT, GR (reprint author), ARIZONA STATE UNIV,CANC RES INST,TEMPE,AZ 85287, USA. NR 17 TC 98 Z9 100 U1 1 U2 7 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 1994 IS 9 BP 1111 EP 1112 DI 10.1039/c39940001111 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA NL472 UT WOS:A1994NL47200039 ER PT J AU TAYLOR, JA ANDERSON, M AF TAYLOR, JA ANDERSON, M TI 53-MUTATION HOTSPOT IN RADON-ASSOCIATED LUNG-CANCER - REPLY SO LANCET LA English DT Letter C1 ST MARYS HOSP,GRAND JCT,CO. RP TAYLOR, JA (reprint author), NIEHS,RES TRIANGLE PK,NC 27709, USA. NR 3 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 7 PY 1994 VL 343 IS 8906 BP 1158 EP 1159 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA NK730 UT WOS:A1994NK73000036 ER PT J AU LUJAN, HD MOWATT, MR HELMAN, LJ NASH, TE AF LUJAN, HD MOWATT, MR HELMAN, LJ NASH, TE TI INSULIN-LIKE GROWTH-FACTORS STIMULATE GROWTH AND L-CYSTEINE UPTAKE BY THE INTESTINAL PARASITE GIARDIA-LAMBLIA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID MANNOSE 6-PHOSPHATE RECEPTOR; COHN FRACTION-IV; II IGF-II; HUMAN-PLASMA; GASTROINTESTINAL-TRACT; PROTEIN; IDENTIFICATION; PURIFICATION; ANTIBODIES; PEPTIDES AB Giardia lamblia, a parasitic protozoan responsible for diarrhea and malabsorption in humans, grows axeni- cally only in media that contain serum and a high concentration of L-cysteine. During our attempts to grow Giardia in the absence of serum, we found that: (a) human insulin-like growth factors (especially IGF-II), but not insulin, promote the growth and L-cysteine uptake by G. lamblia trophozoites; (b) the growth stimulation was inhibited by alpha IR3, an anti-type 1 IGF receptor monoclonal antibody, but an anti-type 2 IGF receptor antibody had no effect; and (c) IGFs act on Giardia through a type 1 IGF receptor-like protein, which can bind IGF-II with higher affinity than IGF-I, and most likely possesses intrinsic phosphotyrosine kinase activity. C1 NCI,PEDIAT BRANCH,MOLEC GENET SECT,BETHESDA,MD 20892. RP LUJAN, HD (reprint author), NIAID,PARASIT DIS LAB,9000 ROCKVILLE PIKE,BLDG 4,RM B1-31,BETHESDA,MD 20892, USA. NR 39 TC 16 Z9 16 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 6 PY 1994 VL 269 IS 18 BP 13069 EP 13072 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NK184 UT WOS:A1994NK18400004 PM 8175729 ER PT J AU MIDURA, RJ EVANKO, SP HASCALL, VC AF MIDURA, RJ EVANKO, SP HASCALL, VC TI PARATHYROID-HORMONE STIMULATES HYALURONAN SYNTHESIS IN AN OSTEOBLAST-LIKE CELL-LINE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID OSTEOGENIC-SARCOMA CELLS; ISOLATED BONE-CELLS; CYCLIC-AMP; UMR 106-01; BIOCHEMICAL-CHARACTERIZATION; COLLAGEN-SYNTHESIS; EMBRYONIC CHICKEN; CULTURE SYSTEM; CALCIUM; PROTEOGLYCANS AB An osteoblast-like cell line (UMR 106-01 BSP), cloned from a transplantable osteosarcoma, was cultured in the presence of parathyroid hormone (PTH1-34) and metabolically labeled with [S-35]sulfate, [H-3]glucosamine, and [H-3]tyrosine to determine proteoglycan, glycoconjugate, and protein synthesis, respectively. The synthesis of secreted proteins was substantially increased by PTH treatment. However, the synthesis of bone sialoprotein and proteoglycans was, at best, only moderately stimulated by PTH. Hyaluronan (HA) synthesis was dramatically stimulated by PTH in this cell line. A 5-6-fold increase in HA production was observed using 10(-8) M PTH, and even a 50% increase was detected using 10(-10) M PTH. The PTH-induced stimulation of HA synthesis was rapid and transient, reaching a maximum level (similar to 560 pmol of HA disaccharide equivalents/h/10(6) cells at 10(-8) M PTH) by 4-7 h after hormone exposure and returning to control levels by 12-15 h after the initial treatment. Lastly, the majority of this HA synthesis stimulated by PTH required only a short exposure (<90 min) to the hormone. These data suggest (i) that normal osteoblasts (or a sub-population of preosteoblasts) probably synthesize HA in response to PTH treatment, and (ii) that this PTH-induced synthesis of HA most likely involves some signal transduction mechanism(s). C1 NIDR, BONE RES BRANCH, BETHESDA, MD 20892 USA. NR 61 TC 20 Z9 20 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 6 PY 1994 VL 269 IS 18 BP 13200 EP 13206 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NK184 UT WOS:A1994NK18400026 PM 8175749 ER PT J AU RAO, PV HORWITZ, J ZIGLER, JS AF RAO, PV HORWITZ, J ZIGLER, JS TI CHAPERONE-LIKE ACTIVITY OF ALPHA-CRYSTALLIN - THE EFFECT OF NADPH ON ITS INTERACTION WITH ZETA-CRYSTALLIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEAT-SHOCK PROTEINS; GUINEA-PIG LENS; B-CRYSTALLIN; ESCHERICHIA-COLI; QUATERNARY STRUCTURE; MOLECULAR CHAPERONE; EYE LENS; GROEL; EXPRESSION; TISSUES AB alpha-Crystallin, a major structural protein of the ocular lens of vertebrates, has been characterized recently as a molecular chaperone (Horwitz, J. (1992) Proc. Natl. Acad. Sci. U. S. A. 89, 10449-10453 and Jakob, U., Gaestel, M., Engel, K., and Buchner, J. (1993) J. Biol. Chem. 268, 1517-1520). While alpha-crystallins prevent the aggregation of various proteins denatured by heat or chaotropic agents, neither the mode of interaction between target proteins and alpha-crystallin nor the specific conformational requirements, if any, of the target protein are known. Here, we demonstrate that the ability of alpha-crystallin to prevent thermally induced aggregation of xi-crystallin/NADPH:quinone oxidoreductase, an abundant crystallin of guinea pigs and camelids, is strongly dependent on the presence of the obligate cofactor (NADPH) of the target enzyme. xi-crystallin in the absence of NADPH is readily aggregated at 41 degrees C, and alpha-crystallin added at a 1:1 (w/w) ratio offers very little protection. In contrast, in the presence of NADPH xi-crystallin remains stable to 45 degrees C and with the addition of alpha-crystallin (1:1 (w/w)) is protected from aggregation even at 55 degrees C. Cibacron blue 3GA a nonmetabolized pyridine nucleotide analog, which has very high binding affinity to xi-crystallin had similar effects. NADH and NAD(+), which are not bound by xi-crystallin, had no such effect. Complex formation between alpha-crystallin and non-native xi-crystallin was demonstrated in the presence of either cibacron blue 3GA or NADPB Circular dichroism spectroscopy of xi-crystallin in the presence and absence of NADPH or cibacron blue indicated that nucleotide binding was accompanied by a change in the protein's aromatic amino acid environment but that the secondary structure was unaffected. The data suggest that subtle change in the conformation of denaturing proteins can markedly affect the ability of alpha-crystallin to protect them from aggregation. C1 NEI,MECHANISMS OCULAR DIS LAB,BETHESDA,MD 20892. UNIV CALIF LOS ANGELES,SCH MED,JULES STEIN EYE INST,LOS ANGELES,CA 90024. FU NEI NIH HHS [EY03897] NR 66 TC 41 Z9 42 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 6 PY 1994 VL 269 IS 18 BP 13266 EP 13272 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NK184 UT WOS:A1994NK18400035 PM 7909806 ER PT J AU MUKAIDA, N MORITA, M ISHIKAWA, Y RICE, N OKAMOTO, S KASAHARA, T MATSUSHIMA, K AF MUKAIDA, N MORITA, M ISHIKAWA, Y RICE, N OKAMOTO, S KASAHARA, T MATSUSHIMA, K TI NOVEL MECHANISM OF GLUCOCORTICOID-MEDIATED GENE REPRESSION - NUCLEAR FACTOR-KAPPA-B IS TARGET FOR GLUCOCORTICOID-MEDIATED INTERLEUKIN-8 GENE REPRESSION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TUMOR-NECROSIS-FACTOR; TRANSCRIPTION FACTOR; MAMMALIAN-CELLS; CYCLOSPORINE-A; LYMPHOCYTES-T; MESSENGER-RNA; DNA-BINDING; C-JUN; RECEPTOR; EXPRESSION AB A glucocorticoid, dexamethasone, inhibited the production of a leukocyte chemotactic cytokine, interleukin 8 (IL-8), as well as mRNA expression by a glioblastoma cell line, T98G, stimulated with interleukin 1 (IL-1). Dexamethasone also inhibited IL-8 promoter-driven chloramphenicol acetyltransferase (CAT) activities induced by IL-1, suggesting that dexamethasone inhibited IL-8 production mainly at the transcriptional level. Moreover, CAT assay revealed that the nuclear factor-kappa B (NF-kappa B) binding site was the crucial cis-element required for conferring IL-1 responsiveness in conjunction with the CCAAT enhancer binding protein/nuclear factor-IL-6 (NF-IL6) and/or the AP-1 binding site(s). Mutation of either the AP-1 or NF-IL6 binding site did not abolish IL-8 gene repression by dexamethasone, suggesting that these sites were not targets for dexamethasone. Trimerized kappa B sequence in the IL-8 gene was enough for conferring the induction by IL-1 and inhibition by dexamethasone of CAT activity. Finally, dexamethasone diminished the IL-l-induced formation of NF-kappa B complexes, which were identified immunochemically to consist of p50 and p65, without reducing the amount of translocated factors. Collectively, dexamethasone interfered with the binding of the most essential transcription factor, NF-kappa B, to its cognate cis-element, thereby suppressing the transcription of IL-8 gene. C1 JICHI MED SCH,DEPT NEUROL,MINAMI KAWACHI,TOCHIGI 32904,JAPAN. JICHI MED SCH,DEPT MED BIOL & PARASITOL,MINAMI KAWACHI,TOCHIGI 32904,JAPAN. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. RP MUKAIDA, N (reprint author), KANAZAWA UNIV,CANC RES INST,DEPT PHARMACOL,KANAZAWA 920,JAPAN. RI Mukaida, Naofumi/D-7623-2011 OI Mukaida, Naofumi/0000-0002-4193-1851 FU NCI NIH HHS [NCI N01-CO-74101] NR 48 TC 381 Z9 390 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 6 PY 1994 VL 269 IS 18 BP 13289 EP 13295 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NK184 UT WOS:A1994NK18400038 PM 8175759 ER PT J AU FINAZZI, D CASSEL, D DONALDSON, JG KLAUSNER, RD AF FINAZZI, D CASSEL, D DONALDSON, JG KLAUSNER, RD TI ALUMINUM FLUORIDE ACTS ON THE REVERSIBILITY OF ARF1-DEPENDENT COAT PROTEIN-BINDING TO GOLGI MEMBRANES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ADP-RIBOSYLATION FACTOR; TRIMERIC-G-PROTEINS; BREFELDIN-A; GUANINE-NUCLEOTIDE; BETA-COP; GTP; TRANSPORT; VESICLES; ARF; RECONSTITUTION AB The GTP dependent interaction of ADP ribosylation factor 1 (ARF1) with Golgi membranes is required for the binding of cytosolic coatomer proteins to those membranes. Whereas both GTP and GTP gamma S can support coatomer binding to membranes, by using partially purified components, GTP driven binding is rapidly reversible (t(1/2) of 2 min) while that driven by GTP gamma S is more stable (t(1/2) of over 30 min). In the presence of GTP, aluminum fluoride, an activator of trimeric G proteins, promotes the stable ARF-dependent binding of coatomer to membranes, even though this reagent does not itself activate ARF. Aluminum fluoride appears to act, like GTP gamma S, to make the binding of coatomer relatively irreversible. It acts to inhibit ARF-GTP hydrolysis catalyzed by the membrane and thus makes the ARF-GTP active state persistent. This effect is not dependent on the presence of any cytosolic component, such as the coatomer. The number of molecules of ARF that can be protected from hydrolysis by aluminum fluoride, however, is only a fraction of the total amount of ARF that can bind to membranes in the presence of GTP gamma S. We propose that this population defines a set of binding sites that are sufficient for coat protein assembly onto the membrane. C1 NIH,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. TECHNION ISRAEL INST TECHNOL,DEPT BIOL,IL-32000 HAIFA,ISRAEL. NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. OI Finazzi, Dario/0000-0001-5176-2839 NR 41 TC 59 Z9 59 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 6 PY 1994 VL 269 IS 18 BP 13325 EP 13330 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NK184 UT WOS:A1994NK18400043 PM 8175763 ER PT J AU BENHAR, I WANG, QC FITZGERALD, D PASTAN, I AF BENHAR, I WANG, QC FITZGERALD, D PASTAN, I TI PSEUDOMONAS EXOTOXIN-A MUTANTS - REPLACEMENT OF SURFACE-EXPOSED RESIDUES IN DOMAIN-III WITH CYSTEINE RESIDUES THAT CAN BE MODIFIED WITH POLYETHYLENE-GLYCOL IN A SITE-SPECIFIC MANNER SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RECOMBINANT INTERLEUKIN-2; DIPHTHERIA-TOXIN; ACTIVE-SITE; ESCHERICHIA-COLI; ANIMAL TOXICITY; AERUGINOSA; PROTEIN; MUTAGENESIS; NAD; EXPRESSION AB Pseudomonas exotoxin A (PE) is composed of three structural and functional domains. Domain Ia is responsible for cell recognition, domain II for translocation of PE across the cell membrane, and domain III for ADP-ribosylation of elongation factor 2. To investigate the role of the amino acids exposed on the surface of domain III, we replaced 15 of these, generating 29 different mutants at positions 412, 416, 418, 490, 513, 516, 522, 551, 576, 590, 599, 604, 606, 607 and 608. Ah but one mutant retained substantial ADP-ribosylation and cytotoxic activities. Modification of proteins with monomethoxypolyethylene glycol (mPEG) prolongs their circulation in the blood stream and reduces their immunogenicity. Unlike PEGylated enzymes acting on small molecule substrates, PEGylated toxins may lose those functions that are based on macromolecular interactions. Therefore, we selectively PEGylated mutant PEs at positions 490, 513, 516, 522, 604, and 606. Most PEs modified by a 5-kDa mPEG via a disulfide or a thioether bond retained high cytotoxic activity. However, when a 20-kDa mPEG was used there was a decrease in cytotoxic activity with the disulfide-bonded molecules being more active. Positions 522 and 604 are good sites for PEGylation, but 490 is not. We also found that PEGylation of PE 522C prolonged its in vivo circulation time in mice. C1 NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 44 TC 33 Z9 34 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 6 PY 1994 VL 269 IS 18 BP 13398 EP 13404 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NK184 UT WOS:A1994NK18400053 PM 8175770 ER PT J AU LAMORTE, VJ THORBURN, J ABSHER, D SPIEGEL, A BROWN, JH CHIEN, KR FERAMISCO, JR KNOWLTON, KU AF LAMORTE, VJ THORBURN, J ABSHER, D SPIEGEL, A BROWN, JH CHIEN, KR FERAMISCO, JR KNOWLTON, KU TI G(G)-DEPENDENT AND RES-DEPENDENT PATHWAYS MEDIATE HYPERTROPHY OF NEONATAL RAT VENTRICULAR MYOCYTES FOLLOWING ALPHA(1)-ADRENERGIC STIMULATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ATRIAL-NATRIURETIC-FACTOR; MYOSIN LIGHT CHAIN-2; PROTEIN-KINASE-C; ALPHA-ADRENERGIC STIMULATION; CARDIAC GENE-TRANSCRIPTION; MYOCARDIAL-CELLS; PHOSPHOLIPASE-C; TRISPHOSPHATE FORMATION; ADENYLYL CYCLASE; GQ FAMILY AB alpha(1),-Adrenergic agonists activate a hypertrophic response in cultured neonatal ventricular myocytes, which include an increase in cell size, organization of contractile proteins into sarcomeric units, and the induction of the atrial natriuretic factor (ANF) gene. Previous findings have supported a role for ras in this signaling pathway. Utilizing microinjection techniques to deliver affinity-purified neutralizing antibodies to G alpha(q,11) into cultured ventricular myocytes, the current studies demonstrate a functional requirement for the heterotrimeric G protein, G(q), in the alpha(1)-adrenergic induction of the ANF gene, changes in cell size, organization of myofilaments, and phosphoinositide hydrolysis. Expression of a constitutively active mutant of G alpha(q) leads to the expression of ANF protein in these cells. Taken together, these data suggest that G(q)-dependent pathways are necessary and sufficient to activate defined features of the hypertrophic response. In attempts to further delineate the relative roles of ras and G(q) in this pathway, we found that G alpha(q) is required for alpha(1)-adrenergic phosphoinositide hydrolysis, though ras does not appear to be necessary for this response. In addition, we coexpressed an inhibitory ras mutant, along with the constitutively active G alpha(q). Expression of ANF protein stimulated by the G alpha(q) mutant was not inhibited. Thus, both ras- and G(q)-dependent pathways are necessary to fully transduce defined features of alpha(1)-adrenergic-stimulated hypertrophy of neonatal cardiac ventricular myocytes, but activated G(q) may be able to induce ANF expression independent of inhibitory ras. C1 UNIV CALIF SAN DIEGO,DEPT MED,LA JOLLA,CA 92093. UNIV CALIF SAN DIEGO,DEPT PHARMACOL,LA JOLLA,CA 92093. THEODORE GILDRED CANC CTR,LA JOLLA,CA 92093. AMER HEART ASSOC,BUGHER FDN CTR MOLEC BIOL,LA JOLLA,CA 92093. NIDDK,MOLEC PATHOPHYSIOL BRANCH,BETHESDA,MD 20892. FU NHLBI NIH HHS [HL-02618, HL46345]; NIGMS NIH HHS [GM36927] NR 41 TC 162 Z9 165 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 6 PY 1994 VL 269 IS 18 BP 13490 EP 13496 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NK184 UT WOS:A1994NK18400065 PM 8175782 ER PT J AU REDOWICZ, MJ MARTIN, B ZOLKIEWSKI, M GINSBURG, A KORN, ED AF REDOWICZ, MJ MARTIN, B ZOLKIEWSKI, M GINSBURG, A KORN, ED TI EFFECTS OF PHOSPHORYLATION AND NUCLEOTIDES ON THE CONFORMATION OF MYOSIN-II FROM ACANTHAMOEBA-CASTELLANII SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIN-ACTIVATED ATPASE; AMINO-ACID-SEQUENCE; HEAVY-CHAIN; ASPARTATE TRANSCARBAMOYLASE; MG2+-ATPASE ACTIVITY; FILAMENT FORMATION; SITES; SUBFRAGMENT-1; TAIL; PURIFICATION AB The actin-activated Mg2+-ATPase activity of filamentous Acanthamoeba myosin II is inactivated by phosphorylation of a short non-helical tailpiece at the C-terminal end of each heavy chain even though the catalytic sites are in the N-terminal globular head. Consistent with this effect, phosphorylation at the tip of the tail alters the conformation of the head as shown by a shift in the principal site of cleavage by endoproteinase Arg-C (Ganguly, C., Martin, B., Bubb, M., and Kern, E. D. (1992) J. Biol. Chem. 267, 20905-20908). We now show that the sedimentation coefficient of monomeric phospho-myosin II is 1.3-4.6% lower than that of dephospho-myosin II, which suggests that phosphorylation produces a less compact conformation with a small increase in frictional coefficient. As shown by changes in papain digestion patterns, bound nucleotide also affects the conformation of the head region of monomeric phospho- and dephospho-myosin II, the conformation of the head region of filamentous phospho- and dephospho-myosin II, and the conformation of the C-terminal region of the tail of filamentous phospho-myosin II, Conformational differences between the dephospho- and phospho-forms of myosin II in the presence of nucleotide, as detected by susceptibility to proteolysis, therefore, appear to be greater in filaments than in monomers. These results provide additional evidence for communication between the N-terminal heads and C-terminal tails of Acanthamoeba myosin II. C1 NHLBI,CELL BIOL LAB,BETHESDA,MD 20892. NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. NIMH,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. RI Korn, Edward/F-9929-2012; Redowicz, Maria Jolanta/R-4083-2016 NR 38 TC 12 Z9 12 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 6 PY 1994 VL 269 IS 18 BP 13558 EP 13563 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NK184 UT WOS:A1994NK18400074 PM 8175791 ER PT J AU BURNS, CM SAKAGUCHI, K APPELLA, E ASHWELL, JD AF BURNS, CM SAKAGUCHI, K APPELLA, E ASHWELL, JD TI CD45 REGULATION OF TYROSINE PHOSPHORYLATION AND ENZYME-ACTIVITY OF SRC FAMILY KINASES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL ANTIGEN RECEPTOR; LEUKOCYTE-COMMON ANTIGEN; PROTEIN-KINASE; SIGNAL TRANSDUCTION; ZETA-CHAIN; PHOSPHOTYROSINE PHOSPHATASE; CATALYTIC ACTIVITY; SURFACE-ANTIGENS; MICE LACKING; T-CELLS AB Previous analyses have suggested that the CD45 tyrosine phosphatase activates src family tyrosine kinases p56(lck) and p59(fyn) by dephosphorylating regulatory COOH-terminal residues. We have examined the status of p56(lck) and p59(fyn) in murine and human CD45(-) T cell lines. Surprisingly, despite the fact that p56(lck) and p59(fyn) were spontaneously hyperphosphorylated, the tyrosine kinase activity of both enzymes was increased in CD45(-) versus CD45(+) cells. In vitro exposure of hyperphosphorylated p56(lck) to CD45 decreased enzyme activity to near-basal levels. Lck from CD45(-) cells was hyperphosphorylated on the cyanogen bromide digestion fragment that contains the negative regulatory residue Tyr-505, and the identity of this site of phosphorylation was confirmed by trypsin digestion followed by high performance liquid chromatography. Loss of CD45 results, therefore, in a paradoxical hyperphosphorylation of the COOH-terminal tyrosine and increased src family kinase enzymatic activity. C1 NCI,CELL BIOL LAB,BETHESDA,MD 20892. RP BURNS, CM (reprint author), NCI,BIOL RESPONSE MODIFIERS PROGRAM,IMMUNE CELL BIOL LAB,BETHESDA,MD 20892, USA. NR 49 TC 94 Z9 94 U1 0 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 6 PY 1994 VL 269 IS 18 BP 13594 EP 13600 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NK184 UT WOS:A1994NK18400078 PM 8175795 ER PT J AU POZSGAY, V COXON, B AF POZSGAY, V COXON, B TI SYNTHESIS AND 2-DIMENSIONAL NUCLEAR-MAGNETIC-RESONANCE ANALYSIS OF A TETRA-SACCHARIDE AND A HEXASACCHARIDE FRAGMENT OF THE O-SPECIFIC POLYSACCHARIDE OF SHIGELLA-DYSENTERIAE TYPE-1 SO CARBOHYDRATE RESEARCH LA English DT Article ID B STREPTOCOCCAL POLYSACCHARIDES; TRI-SACCHARIDE; STEREOSELECTIVE SYNTHESIS; STRUCTURAL-ANALYSIS; COMMON ANTIGEN; DI-SACCHARIDE; ACETYL GROUPS; OLIGOSACCHARIDES; TRISACCHARIDE; SPECTROSCOPY AB The synthesis of the tetra- and hexa-saccharide methyl glycosides alpha-D-Gal p-(1 --> 3)-alpha-D-Glc p NAc-(1 --> 3)-alpha-L-Rha p-(1 --> 3)-alpha-L-Rha p-OMe (1), and alpha-L-Rha p-(1 --> 3)-alpha-L-Rha p-(1 --> 2)-alpha-D-Gal p-(1 --> 3)-alpha-D-Glc p NAc-(1 --> 3)-alpha-L-Rha p-(1 --> 3)-alpha-L-Rha p-OMe (3) is described, which represent various epitopes of the O-specific polysaccharide of Shigella dysenteriae type 1. The following monosaccharide intermediates were used: 1,3-di-O-acetyl-2- O-benzoyl-4-O-benzyl-alpha-L-rhamnopyranose (6 alpha), methyl 2,4-di-O-benzyl-alpha-L-rhamnopyranoside (7), methyl 2,4-di-O-benzoyl-1-thio-alpha-L-rhamnopyranoside (8), 2,3,4-tri-O-benzoyl-alpha-L-rhamnopyranosyl bromide (9), methyl 3,4,6-tri-O-benzyl-2-O-(4-methoxybenzyl)-1-thio-beta-D-galactopyranoside (13), methyl 2,3,4,6-tetra-O-benzyl-1-thio-beta-D-galactopyranoside (16), and 2-azido-4,6-O-benzylidene-3-O-bromoacetyl-2-deoxy-beta-D-glucopyranosyl chloride (19). A detailed analysis of the H-1 and C-13 NMR spectra of oligosaccharides I and 3 confirmed that the hexasaccharide 3 better approaches the conformation of the native polysaccharide, than either 1 or the homologous pentasaccharide 41. C1 NIDDKD,MED CHEM LAB,BETHESDA,MD 20892. NIST,DIV BIOTECHNOL,GAITHERSBURG,MD 20899. RP POZSGAY, V (reprint author), NICHHD,DEV & MOLEC IMMUN LAB,BLDG 6,RM 145,BETHESDA,MD 20892, USA. NR 47 TC 38 Z9 38 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD MAY 5 PY 1994 VL 257 IS 2 BP 189 EP 215 DI 10.1016/0008-6215(94)80035-9 PG 27 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA NL078 UT WOS:A1994NL07800003 PM 8013005 ER PT J AU LENFANT, C ERNST, N AF LENFANT, C ERNST, N TI DAILY DIETARY-FAT AND TOTAL FOOD-ENERGY INTAKES - NHANES-III, PHASE-1, 1988-91 (REPRINTED FROM MMWR, VOL 43, PG 116-117, PG 123-125, 1994) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 NHLBI,BETHESDA,MD 20892. CDC,NATL CTR HLTH STAT,DIV HLTH EXAMINAT STAT,ATLANTA,GA. NR 1 TC 13 Z9 13 U1 0 U2 2 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 4 PY 1994 VL 271 IS 17 BP 1309 EP 1309 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA NH487 UT WOS:A1994NH48700006 ER PT J AU CHAUDHARY, AG GHARPURE, MM RIMOLDI, JM CHORDIA, MD GUNATILAKA, AAL KINGSTON, DGI GROVER, S LIN, CM HAMEL, E AF CHAUDHARY, AG GHARPURE, MM RIMOLDI, JM CHORDIA, MD GUNATILAKA, AAL KINGSTON, DGI GROVER, S LIN, CM HAMEL, E TI UNEXPECTEDLY FACILE HYDROLYSIS OF THE 2-BENZOATE GROUP OF TAXOL AND SYNTHESES OF ANALOGS WITH INCREASED ACTIVITIES SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Note ID ANTITUMOR AGENTS; TAXANES C1 VIRGINIA POLYTECH INST & STATE UNIV,DEPT CHEM,BLACKSBURG,VA 24061. NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. RI Chordia, Mahendra/A-4706-2008 NR 17 TC 105 Z9 107 U1 1 U2 5 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 4 PY 1994 VL 116 IS 9 BP 4097 EP 4098 DI 10.1021/ja00088a063 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA NJ946 UT WOS:A1994NJ94600063 ER PT J AU RESZKA, KJ CHIGNELL, CF BILSKI, P AF RESZKA, KJ CHIGNELL, CF BILSKI, P TI SPIN-TRAPPING OF NITRIC-OXIDE ((NO)-N-CENTER-DOT) BY ACI-NITROMETHANE IN AQUEOUS-SOLUTIONS SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Note ID 1ST RP RESZKA, KJ (reprint author), NIEHS,MOLEC BIOPHYS LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 13 TC 17 Z9 17 U1 1 U2 1 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 4 PY 1994 VL 116 IS 9 BP 4119 EP 4120 DI 10.1021/ja00088a074 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA NJ946 UT WOS:A1994NJ94600074 ER PT J AU SONDIK, EJ AF SONDIK, EJ TI REANALYSES OF NSABP STUDIES SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Note ID NEGATIVE BREAST-CANCER; TUMORS RP SONDIK, EJ (reprint author), NIH,BLDG 31,RM 11A49,BETHESDA,MD 20892, USA. NR 4 TC 5 Z9 5 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 4 PY 1994 VL 86 IS 9 BP 655 EP 655 DI 10.1093/jnci/86.9.655 PG 1 WC Oncology SC Oncology GA NH714 UT WOS:A1994NH71400003 PM 8158692 ER PT J AU PARK, JG LEE, SK HONG, IG KIM, HS LIM, KH CHOE, KJ KIM, WH KIM, YI TSURUO, T GOTTESMAN, MM AF PARK, JG LEE, SK HONG, IG KIM, HS LIM, KH CHOE, KJ KIM, WH KIM, YI TSURUO, T GOTTESMAN, MM TI MDR1 GENE-EXPRESSION - ITS EFFECT ON DRUG-RESISTANCE TO DOXORUBICIN IN HUMAN HEPATOCELLULAR-CARCINOMA CELL-LINES SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID MULTIDRUG-RESISTANCE; P-GLYCOPROTEIN; CLINICAL-TRIALS; RAT-LIVER; VERAPAMIL; REVERSAL; CANCER; CHEMOEMBOLIZATION; OVEREXPRESSION; VINBLASTINE AB Background: Hepatic tumors are resistant to many chemotherapeutic agents. Although elevated MDR1 (also known as PGY1) gene expression has been shown in such tumors, no direct association has been established between the gene expression and multidrug resistance. Purpose: To evaluate the role of the MDR1 gene in the drug resistance of hepatoma, we tested nine human hepatoma cell lines for their expression of the MDR1 gene. Methods: We measured the MDR1 messenger RNA (mRNA) expression by RNA slot-blot analysis and by immunocytochemical staining with a P-glycoprotein-specific monoclonal antibody, MRK16. The in vitro chemosensitivity of these cell lines to fluorouracil, doxorubicin, mitomycin C, cisplatin, and etoposide (VP-16) was determined using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) colorimetric assay. For doxorubicin cytotoxicity, we also tested the potentiating effect of several multidrug resistance-reversing agents. Results: Slot-blot analysis and immunocytochemistry showed that two cell lines expressed high levels of MDR1 mRNA, one expressed an intermediate level, and all others were low expressors. The MTT assay results showed that all cell lines tested were generally resistant to chemotherapeutic agents. The assay area under the curve (AUC) was within a clinically achievable range only for VP-16 in one of nine cell lines. When the IC50 values were compared among the cell lines, the results revealed a close association with the MDR1 gene expression only for doxorubicin resistance. Verapamil and quinidine lowered the IC50 values of doxorubicin for MDR1-positive cell lines. The lowered assay AUC levels for both reversing agents, however, were still higher than the clinically achievable range. Conclusion: These results indicate that the MDR1 gene probably has a role in doxorubicin resistance in hepatocellular carcinoma and that the resistance can be overcome by some multidrug resistance-reversing agents. Implications: Some widely used anticancer agents might be ineffective for treating hepatocellular carcinoma in clinical situations even when combined with reversing agents. C1 SEOUL NATL UNIV,COLL MED,CANC RES CTR,SEOUL,SOUTH KOREA. SEOUL NATL UNIV,COLL MED,DEPT PATHOL,SEOUL,SOUTH KOREA. UNIV TOKYO,INST APPL MICROBIOL,TOKYO 113,JAPAN. NCI,CELL BIOL LAB,BETHESDA,MD. RP PARK, JG (reprint author), SEOUL NATL UNIV,COLL MED,CANC RES INST,CELL BIOL LAB,28 YONGON DONG,SEOUL 110460,SOUTH KOREA. RI Kim, Wooho/G-3703-2011; Seoul National University, Pathology/B-6702-2012; Park, Jae-Gahb/J-5494-2012 NR 37 TC 63 Z9 63 U1 0 U2 5 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 4 PY 1994 VL 86 IS 9 BP 700 EP 705 DI 10.1093/jnci/86.9.700 PG 6 WC Oncology SC Oncology GA NH714 UT WOS:A1994NH71400015 PM 7908989 ER PT J AU ANSARI, A JONES, CM HENRY, ER HOFRICHTER, J EATON, WA AF ANSARI, A JONES, CM HENRY, ER HOFRICHTER, J EATON, WA TI CONFORMATIONAL RELAXATION AND LIGAND-BINDING IN MYOGLOBIN SO BIOCHEMISTRY LA English DT Article ID NANOSECOND LASER PHOTOLYSIS; GLOBAL PROTEIN MOTION; GEMINATE RECOMBINATION; HEME-PROTEINS; CARBON-MONOXIDE; INTERSUBUNIT COMMUNICATION; OPTICAL SPECTROSCOPY; MOLECULAR-DYNAMICS; SOLVENT VISCOSITY; TEMPERATURE-RANGE AB Absorption spectroscopy with nanosecond time resolution shows that myoglobin undergoes conformational relaxation on the same time scale as geminate rebinding of carbon monoxide. Ligand rebinding following photodissociation of the heme-CO complex was measured from the amplitude of the average difference spectrum, while conformational changes were measured from changes in the detailed shape of the Soret spectra of the deoxyhemes. Experiments in which the solvent viscosity was varied between 1 and 300 cP and the temperature between 268 and 308 K were analyzed by fitting the multiwavelength kinetic data with both empirical and molecular models. Novel numerical techniques were employed in fitting the data, including the use of singular value decomposition to remove the effects of temperature and solvent on the spectra and of a Monte Carlo method to overcome the multiple minimum problem in searching parameter space. The molecular model is the minimal model that incorporates all of the major features of myoglobin kinetics at ambient temperatures, including a fast and slow rebinding conformation and two geminate states for each conformation. The results of fitting the kinetic data with this model indicate that the geminate-rebinding rates for the two conformations differ by at least a factor of 100. The differences between the spectra of the two conformations generated from the fits are similar to the differences between those of the R and T conformations of hemoglobin. In modeling the data, the dependence of the rates on temperature and viscosity was parametrized using a modification of Kramers theory which includes the contributions of both protein and solvent to the friction. The rate of the transition from the fast to the slow rebinding conformation is found to be inversely proportional to the viscosity when the viscosity exceeds about 30 cP and nearly viscosity independent at low viscosity. The viscosity dependence at high viscosities suggests that the two conformations differ by the global displacement of protein atoms on the proximal side of the heme observed by X-ray crystallography. We suggest that the conformational change observed in our experiments corresponds to the final portion of the nonexponential conformational relaxation recently observed by Anfinrud and co-workers, which begins on a picosecond time scale. Furthermore, extrapolation of our data to temperatures near that of the solvent glass transition suggests that this conformational relaxation may very well be the one postulated by Frauenfelder and co-workers to explain the decrease in the rate of geminate rebinding with increasing temperature above 180 K. C1 NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. RI Henry, Eric/J-3414-2013 OI Henry, Eric/0000-0002-5648-8696 NR 96 TC 192 Z9 194 U1 0 U2 17 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 3 PY 1994 VL 33 IS 17 BP 5128 EP 5145 DI 10.1021/bi00183a017 PG 18 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NJ859 UT WOS:A1994NJ85900017 PM 8172888 ER PT J AU EISENBERG, E HAVLIN, S WEISS, GH AF EISENBERG, E HAVLIN, S WEISS, GH TI FLUCTUATIONS OF THE PROBABILITY DENSITY OF DIFFUSING PARTICLES FOR DIFFERENT REALIZATIONS OF A RANDOM MEDIUM SO PHYSICAL REVIEW LETTERS LA English DT Article ID RANDOM RESISTOR NETWORKS; RANDOM-WALKS; ANOMALOUS DIFFUSION; DISORDERED MEDIA; RANDOM FRACTALS; SYSTEMS; SUPERLOCALIZATION; MULTIFRACTALITY; PERCOLATION; SURFACES AB We study the fluctuations of the probability density P(r,t) of diffusing particles to be at distance r at time t in the presence of random potentials, represented by random transition rates. We find an exact relation which expresses all the moments of P(r,t) in terms of its first moment, for both quenched and annealed disorder and for any dimension. From this relation follows that anomalous diffusion implies nontrivial behavior of the moments of P(r,t), such as an exponential divergence of the relative fluctuations for large r. C1 NIH,BETHESDA,MD 20892. RP EISENBERG, E (reprint author), BAR ILAN UNIV,DEPT PHYS,IL-52100 RAMAT GAN,ISRAEL. RI Eisenberg, Eli/D-2587-2009 OI Eisenberg, Eli/0000-0001-8681-3202 NR 30 TC 18 Z9 18 U1 0 U2 0 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 0031-9007 J9 PHYS REV LETT JI Phys. Rev. Lett. PD MAY 2 PY 1994 VL 72 IS 18 BP 2827 EP 2830 DI 10.1103/PhysRevLett.72.2827 PG 4 WC Physics, Multidisciplinary SC Physics GA NJ297 UT WOS:A1994NJ29700002 ER PT J AU GUIROY, DC WAKAYAMA, I LIBERSKI, PP GAJDUSEK, DC AF GUIROY, DC WAKAYAMA, I LIBERSKI, PP GAJDUSEK, DC TI RELATIONSHIP OF MICROGLIA AND SCRAPIE AMYLOID-IMMUNOREACTIVE PLAQUES IN KURU, CREUTZFELDT-JAKOB-DISEASE AND GERSTMANN-STRAUSSLER SYNDROME SO ACTA NEUROPATHOLOGICA LA English DT Note DE FERRITIN; PRP27-30; SUBACUTE SPONGIFORM ENCEPHALOPATHY ID SENILE PLAQUES; FERRITIN; FIBRILS; MARKER AB Kuru, Creutzfeldt-Jakob disease (CJD) and Gerstmann-Straussler syndrome (GSS) are transmissible dementias affecting humans characterized neuropathologically by intraneuronal vacuolation, spongiform change, astrocytic hypertrophy and hyperplasia and the variable presence of amyloid plaques. It has been suggested that microglia are amyloid-forming cells, which play an essential role in amyloid plaque formation. To study the relationship between microglia and amyloid plaques in kuru, CJD and GSS, cerebellar tissues were examined by the double-immunostaining technique using anti-ferritin antibodies as the microglial marker and anti-scrapie amyloid antibody as plaque marker. Ferritin-immunoreactive microglia were observed interdigitating with and among unicentric, multicentric and diffuse types of scrapie amyloid-immunoreactive plaques and were found to a lesser extent in the neuropil. In kuru and CJD, scrapie amyloid-immunoreactive plaques were predominantly unicentric and were observed in the granular layer. In kuru, 53 % of the amyloid plaques were associated with microglia, whereas only 30 % of plaques in CJD were. In contrast, scrapie-amyloid-immunoreactive plaques in GSS were of the multicentric type, predominantly observed in the molecular layer, and 90 % of these plaques were associated with microglia. Our data indicate that microglia are frequently associated with scrapie amyloid-immunoreactive plaques in GSS, less commonly in kuru and to a much lesser extent in CJD, suggesting that microglia may play a variable but important role in the formation of plaques in the transmissible spongiform encephalopathies. C1 UNIV DUSSELDORF,DEPT NEUROL,W-4000 DUSSELDORF,GERMANY. MED ACAD LODZ,DEPT ONCOL,ELECTRON MICROSCOPY LAB,LODZ,POLAND. RP GUIROY, DC (reprint author), NINCDS,FREDERICK CANC RES & DEV CTR,CENT NERVOUS SYST STUDIES LAB,FREDERICK,MD 21702, USA. NR 18 TC 54 Z9 58 U1 2 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD MAY PY 1994 VL 87 IS 5 BP 526 EP 530 PG 5 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA NJ773 UT WOS:A1994NJ77300012 PM 8059606 ER PT J AU STEELE, TD MCCANN, UD RICAURTE, GA AF STEELE, TD MCCANN, UD RICAURTE, GA TI 3,4-METHYLENEDIOXYMETHAMPHETAMINE (MDMA, ECSTASY) - PHARMACOLOGY AND TOXICOLOGY IN ANIMALS AND HUMANS SO ADDICTION LA English DT Review ID DISCRIMINATIVE STIMULUS PROPERTIES; CENTRAL SEROTONERGIC NEURONS; EXHIBIT DIFFERENTIAL VULNERABILITY; RAT-BRAIN; METHYLENEDIOXYMETHAMPHETAMINE MDMA; 3,4-METHYLENEDIOXYAMPHETAMINE MDA; AMPHETAMINE DERIVATIVES; INVIVO MICRODIALYSIS; RECREATIONAL USERS; NONHUMAN-PRIMATES AB (+/-)3,4-Methylenedioxymethamphetamine (MDMA, ''Ecstasy''), a ring-substituted amphetamine derivative first synthesized in 1914, has emerged as a popular recreational drug of abuse over the last decade. Pharmacological studies indicate that MDMA produces a mixture of central stimulant and psychedelic effects, many of which appear to be mediated by brain monoamines, particularly serotonin and dopamine. In addition to its pharmacologic actions, MDMA has been found to possess toxic activity toward brain serotonin neurones. Serotonergic neurotoxicity after MDMA has been demonstrated in a variety of experimental animals (including non-human primates). In monkeys, the neurotoxic dose of MDMA closely approaches that used by humans. While the possibility that MDMA is also neurotoxic in humans is under investigation, other adverse effects of MDMA in humans have been documented, including various systemic complications and a number of untoward neuropsychiatric sequelae. Notably, many of the adverse neuropsychiatric consequences noted after MDMA involve behavioral domains putatively influenced by brain serotonin (e.g., mood, cognition and anxiety). Given the restricted status of MDMA use, retrospective clinical observations from suspecting clinicians will probably continue to be a primary source of information regarding MDMA's effects in humans. As such, this article is intended to familiarize the reader with the behavioral pharmacology and toxicology of MDMA, with the hope that improved recognition of MDMA-related syndromes will provide insight into the function of serotonin in the human brain, in health as well as disease. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21205. NIMH,BIOL PSYCHIAT BRANCH,ANXIETY & AFFECT DISORDERS SECT,BETHESDA,MD 20892. NR 109 TC 222 Z9 228 U1 1 U2 14 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 1994 VL 89 IS 5 BP 539 EP 551 DI 10.1111/j.1360-0443.1994.tb03330.x PG 13 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA NM341 UT WOS:A1994NM34100015 PM 7913850 ER PT J AU HASIN, DS MUTHUEN, B WISNICKI, KS GRANT, B AF HASIN, DS MUTHUEN, B WISNICKI, KS GRANT, B TI VALIDITY OF THE BI-AXIAL DEPENDENCE CONCEPT - A TEST IN THE UNITED-STATES GENERAL-POPULATION SO ADDICTION LA English DT Article ID ALCOHOL DEPENDENCE; USE DISORDERS AB According to the ''bi-axial'' concept of alcohol dependence, the Alcohol Dependence Syndrome (ADS) constitutes an axis or dimension of alcohol difficulties, while other alcohol-related problems (social, legal, etc.) constitute one or more separate dimensions. The validity of the bi-axial distinction was investigated in a stratified probability sample of 3212 US current drinkers who were interviewed in their households. Indicators of the Alcohol Dependence Syndrome and potentially distinct alcohol-related problems were covered in a structured interview administered by carefully trained interviewers. This interview provided extensive coverage of drinking patterns and problems. Aspects of the ADS covered included narrowing, salience, tolerance, withdrawal, withdrawal relief/avoidance and compulsion/control. Other alcohol problems included difficulties with work, health, the law, general social difficulties and problems in marriage/home life. Confirmatory and exploratory factor analyses were used to determine whether a single factor (dimension) or two or more factors fit the data best. Using all methods, we found that one general factor explained the structure of the data better than a two-factor model or other models for males, females, blacks and whites. Thus, the utility of this approach to distinguishing between types of alcohol problems was challenged, raising some questions about abuse/dependence distinctions in various nomenclatures. C1 COLUMBIA UNIV,SCH PUBL HLTH,NEW YORK,NY 10027. NEW YORK STATE PSYCHIAT INST & HOSP,NEW YORK,NY 10032. UNIV CALIF LOS ANGELES,GRAD SCH EDUC,LOS ANGELES,CA 90024. NIAAA,DIV BIOMETRY & EPIDEMIOL,ROCKVILLE,MD 20852. RP HASIN, DS (reprint author), COLUMBIA UNIV COLL PHYS & SURG,NEW YORK,NY 10032, USA. NR 14 TC 78 Z9 78 U1 0 U2 0 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 1994 VL 89 IS 5 BP 573 EP 579 DI 10.1111/j.1360-0443.1994.tb03333.x PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA NM341 UT WOS:A1994NM34100018 PM 8044123 ER PT J AU BATTJES, RJ PICKENS, RW HAVERKOS, HW SLOBODA, Z AF BATTJES, RJ PICKENS, RW HAVERKOS, HW SLOBODA, Z TI HIV RISK-FACTORS AMONG INJECTING DRUG-USERS IN 5 US CITIES SO AIDS LA English DT Article DE AIDS; HIV; INJECTING DRUG USER; INTRAVENOUS DRUG USER; RISK FACTORS; FACE ETHNICITY ID HUMAN-IMMUNODEFICIENCY-VIRUS; NEW-YORK-CITY; HETEROSEXUAL TRANSMISSION; UNITED-STATES; INFECTION; BALTIMORE; BEHAVIORS; MARYLAND; ABUSERS; COCAINE AB Objectives: To examine factors associated with HIV infection in injecting drug users (IDU), the independent and interactive effects of potential risk factors, and geographic differences in risk factors. Methods: IDU entering methadone treatment in New York City, Asbury Park and Trenton in New jersey, Baltimore and Chicago between February 1987 and December 1991 were interviewed using a standard questionnaire and tested for HIV antibodies (n = 4584). Associations of HIV serostatus with race/ethnicity, other demographic characteristics, and injecting and sexual risk behaviors were assessed by logistic regression analyses. Results: African Americans were at increased risk for HIV in four of the five cities, and Puerto Ricans in two cities. Injection in shooting galleries and 'speedball' injection emerged as behavioral variables highly associated with HIV, although interaction of these variables indicates that each variable contributes to HIV risk only in the absence of the other behavior. Conclusions: Geographic differences in HIV risk factors and the interaction of 'speedball' and shooting gallery use suggest that multiple HIV risk models are needed that reflect seroprevalence rates, variation in risk behaviors, and the social context of risk behaviors. Increased risk among racial/ethnic minorities independent of risk behaviors, suggests the need to examine further potential social and environmental factors, such as the social networks in which injecting and sexual behaviors occur, HIV seroprevalence within these networks, and the locales in which risk behaviors occur. C1 NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. RP BATTJES, RJ (reprint author), NIDA,5600 FISHERS LANE,ROOM 10A-38,ROCKVILLE,MD 20857, USA. NR 25 TC 53 Z9 53 U1 1 U2 3 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD MAY PY 1994 VL 8 IS 5 BP 681 EP 687 DI 10.1097/00002030-199405000-00016 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA NH951 UT WOS:A1994NH95100016 PM 8060548 ER PT J AU REITZ, MS SAXINGER, WC POPOVIC, M HALL, L READCONNOLE, E MARKHAM, P GALLO, RC AF REITZ, MS SAXINGER, WC POPOVIC, M HALL, L READCONNOLE, E MARKHAM, P GALLO, RC TI PARTIAL ENVELOPE SEQUENCES FROM SOME OF THE EARLIEST ISOLATES OF HIV-1 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Note C1 CTR ADV LABS INC,KENSINGTON,MD 20895. RP REITZ, MS (reprint author), NCI,TUMOR CELL BIOL LAB,BLDG 37,ROOM 6A09,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 9 TC 2 Z9 2 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAY PY 1994 VL 10 IS 5 BP 621 EP 623 DI 10.1089/aid.1994.10.621 PG 3 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA NR146 UT WOS:A1994NR14600016 PM 7917524 ER PT J AU ABBOTT, RD RODRIGUEZ, BL BURCHFIEL, CM CURB, JD AF ABBOTT, RD RODRIGUEZ, BL BURCHFIEL, CM CURB, JD TI PHYSICAL-ACTIVITY IN OLDER MIDDLE-AGED MEN AND REDUCED RISK OF STROKE - THE HONOLULU-HEART-PROGRAM SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE CARDIOVASCULAR DISEASES; CEREBROVASCULAR DISORDERS; EXERCISE; MEN; MIDDLE AGE; RISK FACTORS; THROMBOEMBOLISM ID COLLEGE ALUMNI; JAPANESE MEN; DISEASE; INFARCTION; MORTALITY; HEALTH; HAWAII; DEATH AB From 1965 to 1968, the Honolulu Heart Program began following 8,006 men in a prospective study of cardiovascular disease. At the time of study enrollment, an estimate of current 24-hour habitual physical activity was collected from each subject. On the basis of a calculated physical activity index, subjects were classified as being inactive, partially active, or active. This report examines the relation between the levels of physical activity and stroke that occurred among 7,530 of the men over 22 years of follow-up. Risk of stroke was examined separately in younger (45-54 years) middle-aged men and older (55-68 years) middle-aged men. Among the older men, those who were inactive or partially active experienced a three- to fourfold excess incidence of hemorrhagic stroke as compared with active men (p < 0.01). There was a two- to threefold excess of intracerebral hemorrhage in men who were inactive or partially active as compared with those who were active (p < 0.05). An excess of subarachnoid hemorrhage was observed in inactive older men, with only one event occurring in those who were active (p < 0.05). After exclusion of subjects with hypertension, diabetes mellitus, and left ventricular hypertrophy, the relative risk of hemorrhagic stroke for inactive men versus active men was 3.7 (95% confidence interval (CI) 1.3-10.4). In older men who did not smoke cigarettes, the relative risk of thromboembolic stroke among inactive men versus active men was 2.8 (95% CI 1.2-6.7), and when partially active older men were compared with those who were active, the relative risk was 2.4 (95% CI 1.0-5.7). These findings persisted after control for the residual effects of systolic blood pressure and other risk factors for stroke. Benefits of physical activity in reducing the risk of thromboembolic stroke were not observed in men who smoked cigarettes. The authors conclude that physical activity may be important in reducing the risk of stroke, particularly among nonsmoking men in older middle age. C1 KUAKINI MED CTR,HONOLULU HEART PROGRAM,HONOLULU,HI. NHLBI,EPIDEMIOL & BIOMETRY PROGRAM,HONOLULU EPIDEMIOL RES SECT,HONOLULU,HI. RP ABBOTT, RD (reprint author), UNIV VIRGINIA,SCH MED,DEPT MED,DIV BIOSTAT,BOX 432,CHARLOTTESVILLE,VA 22908, USA. FU NCRR NIH HHS [RR-00847]; NHLBI NIH HHS [N01-HC-05102] NR 26 TC 147 Z9 149 U1 1 U2 7 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 1994 VL 139 IS 9 BP 881 EP 893 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA NM021 UT WOS:A1994NM02100003 PM 8166138 ER PT J AU WEINBERG, CR AF WEINBERG, CR TI TOWARD A CLEARER DEFINITION OF CONFOUNDING - REPLY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter RP WEINBERG, CR (reprint author), NIEHS,RES TRIANGLE PK,NC 27709, USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAY 1 PY 1994 VL 139 IS 9 BP 962 EP 963 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA NM021 UT WOS:A1994NM02100011 ER PT J AU GOLDSTEIN, AM STEWART, C BALE, AE BALE, SJ DEAN, M AF GOLDSTEIN, AM STEWART, C BALE, AE BALE, SJ DEAN, M TI LOCALIZATION OF THE GENE FOR THE NEVOID BASAL-CELL CARCINOMA SYNDROME SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID GORLIN SYNDROME; LINKAGE; DNA AB The nevoid basal cell carcinoma syndrome (NBCC) is an autosomal dominant multisystem disorder characterized by multiple basal cell carcinomas, jaw cysts, pits of the palms and/or soles, ectopic calcification, and skeletal malformations. The NBCC gene has recently been mapped to chromosome 9q22.3-9q31. In order to further define the region containing the NBCC gene, we have analyzed 137 individuals from eight families for linkage, using 11 markers from the region. Eight markers showed statistically significant evidence for linkage to NBCC. Three markers (D9S180, ALDOB, and D9S173) showed no definite recombination with the disease locus. All families showed some evidence for linkage to markers in this region. On the basis of the inspection of individual recombinants and previously published information about map location, we suggest the following order for the markers: D9S119-D9S12-D9S197-D9S196-(NBCC,D9S180-D9S173,ALDOB)-D9S109-D9S127-(D9S53,D9S29). We are currently developing YAC contigs for the most closely linked markers, to further refine the location of the NBCC gene. C1 NCI,CLIN EPIDEMIOL BRANCH,BETHESDA,MD 20892. NCI,VIRAL CARCINOGENESIS LAB,BETHESDA,MD 20892. FREDERICK CANC RES & DEV CTR,DYNCORP,PROGRAM RESOURCES INC,BCDP,FREDERICK,MD 21701. RP GOLDSTEIN, AM (reprint author), NCI,GENET EPIDEMIOL BRANCH,EXECUT PLAZA N,ROOM 439,BETHESDA,MD 20892, USA. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 NR 22 TC 47 Z9 47 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAY PY 1994 VL 54 IS 5 BP 765 EP 773 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA NH394 UT WOS:A1994NH39400005 PM 7909984 ER PT J AU BURNETT, CA SILVERMAN, DT LALICH, NR AF BURNETT, CA SILVERMAN, DT LALICH, NR TI A COMPARISON OF ANALYSES OF OCCUPATIONAL BLADDER-CANCER - DEATH CERTIFICATE VS POPULATION-BASED CASE-CONTROL INTERVIEW SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE BLADDER NEOPLASMS; CANCER REGISTRY; DEATH CERTIFICATES; OCCUPATION; PROPORTIONATE MORTALITY RATIO; SURVEILLANCE ID INDUSTRY DATA; LUNG-CANCER; MORTALITY; ACCURACY; RECORDS; WORKERS; SURVEILLANCE; INFORMATION; LEUKEMIA AB The authors examined the utility of death certificate data for occupational health surveillance by comparing the ability of the data to identify high-risk occupations for bladder cancer with that of a population-based case-control study. Death certificate data for white males from 23 states for 1979-1987 were analyzed using proportionate mortality ratios. The case-control study used cancer registry cases for 1977-1978. Results were compared for 21 a priori suspect occupations. A broad definition of agreement resulted in agreement for 62% of the occupations; the death certificate study identified eight of 15 occupations identified by the case-control study and neither study identified five of the categories. While death certificate data have many limitations, our results indicate that death certificate data can provide clues to some potential occupational health problems. With the advantages of inexpensive data, large sample size, and industrial coverage, more refined analyses of the data should prove useful for occupational mortality surveillance and hypothesis generation. (C) 1994 Wiley-Liss, Inc. C1 NCI,BETHESDA,MD 20892. RP BURNETT, CA (reprint author), NIOSH,DIV SURVEILLANCE HAZARD EVALUAT & FIELD STUDIES,4676 COLUMBIA PKWY,MAILSTOP R-18,CINCINNATI,OH 45226, USA. NR 33 TC 5 Z9 5 U1 2 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD MAY PY 1994 VL 25 IS 5 BP 677 EP 688 DI 10.1002/ajim.4700250507 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA NG239 UT WOS:A1994NG23900006 PM 8030638 ER PT J AU HNIZDO, E AF HNIZDO, E TI RISK OF SILICOSIS IN RELATION TO FRACTION OF RESPIRABLE QUARTZ SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Letter DE SILICA; SILICOSIS; RESPIRABLE QUARTZ FRACTION; COAL WORKERS; GOLD MINERS; LUNG CANCER RP HNIZDO, E (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 5 TC 4 Z9 5 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD MAY PY 1994 VL 25 IS 5 BP 771 EP 772 DI 10.1002/ajim.4700250517 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA NG239 UT WOS:A1994NG23900016 ER PT J AU OPITZ, JM DELACRUZ, F AF OPITZ, JM DELACRUZ, F TI CHOLESTEROL-METABOLISM IN THE RSH SMITH-LEMLI-OPITZ SYNDROME - SUMMARY OF AN NICHD CONFERENCE SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Editorial Material DE CHOLESTEROL; 7-DEHYDROCHOLESTEROL REDUCTASE DEFICIENCY; RSH-SMITH-LEMLI-OPITZ SYNDROME; CHOLESTEROL SYNTHESIS; DEVELOPMENT; PLACENTAL TRANSPORT OF CHOLESTEROL; PRENATAL; NEWBORN; AND CARRIER TESTING; TREATMENT; POPULATION GENETICS; PREVALENCE; MALFORMATION MR SYNDROME; HETEROGENEITY; VARIABILITY AB During the evolution of multicellularity and attendant processes of development, cholesterol played a key role in the formation of the plasma membrane and outer mitochondrial membrane of every cell in the organism. Later functions include pivotal involvement in steroid, bile acid, and vitamin D metabolism and myelination of the nervous system. In the CNS myelination does not begin until the third trimester, and subcortical myelination not until after birth. The cholesterol of the cell membrane of the ovum is maternally derived. It is not known when the zygote begins making its own cholesterol during morphogenesis and histogenesis, but it must occur early to keep up with the dramatic rate of cell division in the embryo. Thus, it is a startling surprise that human embryos and fetuses apparently able to synthesize little cholesterol (because of a presumed defect of the Delta(5,7)-sterol, Delta(7)-reductase that converts 7-dehydrocholesterol (7-DHC) into cholesterol) frequently live to term and, rarely, may be so mildly affected as to attend school with only mild MR. The discovery by G. Stephen Tint and his co-workers of the apparent 7-DHC reductase deficiency makes the RSH (Smith-Lemli-Opitz) syndrome the first true metabolic malformation syndrome. A teratological animal model which has been known for 30 years now appears applicable to the RSH/SLO syndrome. A multidisciplinary NICHD conference held on September 20-21, 1993 reviewed the numerous implications of this discovery and agreed unanimously that research in this field be given highest priority in order to better understand cholesterol synthesis in the mammalian brain, cholesterol transport from mother to embryo and fetus, pre- and postnatal metabolic compensation in structure and function for a profound block in cholesterol synthesis, the nature of the blood-brain barrier for cholesterol, treatment of affected infants, children, and adults, structure and genetic specification of a 7-DHC reductase enzyme (which has never been purified!) and its evolution, the variability of the syndrome and whether it is genetically homo- or heterogeneous, the population genetics of the RSH syndrome, possible selective advantages (or disadvantages) of heterozygotes, and means of newborn screening, carrier detection, and prenatal diagnosis. (C) 1994 Wiley-Liss, Inc. C1 SHODAIR HOSP,HELENA,MT. MONTANA STATE UNIV,BOZEMAN,MT 59717. UNIV WASHINGTON,SEATTLE,WA 98195. UNIV WISCONSIN,MADISON,WI. TOLEDO HOSP,FDN DEV & MED GENET,TOLEDO,OH. NICHHD,MENTAL RETARDAT & DEV DISABIL BRANCH,BETHESDA,MD 20892. NR 22 TC 48 Z9 51 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD MAY 1 PY 1994 VL 50 IS 4 BP 326 EP 338 DI 10.1002/ajmg.1320500406 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA NG003 UT WOS:A1994NG00300005 PM 7632194 ER PT J AU SCHIFF, E FRIEDMAN, SA BAUMANN, P SIBAI, BM ROMERO, R AF SCHIFF, E FRIEDMAN, SA BAUMANN, P SIBAI, BM ROMERO, R TI TUMOR-NECROSIS-FACTOR-ALPHA IN PREGNANCIES ASSOCIATED WITH PREECLAMPSIA OR SMALL-FOR-GESTATIONAL-AGE NEWBORNS SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE PREECLAMPSIA; SMALL FOR GESTATIONAL AGE; TUMOR NECROSIS FACTOR-ALPHA ID GROWTH-FACTOR; FETAL GROWTH; CELLS; PROSTACYCLIN; EXPRESSION; CYTOKINES; PROTEIN; WOMEN; SERUM AB OBJECTIVE: Our purpose was to determine the presence and concentration of tumor necrosis factor-alpha in maternal and fetal plasma in pregnancies associated with preeclampsia and small-for-gestational-age newborns. STUDY DESIGN: Maternal and fetal plasma tumor necrosis factor-alpha concentrations were measured in nonpregnant women (n = 12), women with normal pregnancies (n = 24), and women with pregnancies associated with severe preeclampsia (n = 23), small-for-gestational-age newborns (n = 14), or both preeclampsia and small-for-gestational-age newborns (n = 12). Tumor necrosis factor-alpha was measured with a sensitive and specific enzyme immunoassay. RESULTS: Tumor necrosis factor-alpha was detected in 89% of the samples studied. Concentrations ranged from <1.5 to 30 pg/ml. Similar levels were found in women with severe preeclampsia with or without small-for-gestational-age newborns, women who were delivered vaginally or abdominally in the control group, and nonpregnant women. Maternal and fetal tumor necrosis factor-alpha in the group with idiopathic small-for-gestational-age newborns were in general lower than those of all other groups. The route of delivery did not affect tumor necrosis factor-alpha concentrations in both the maternal and fetal plasma. There was a significant correlation between fetal venous and arterial plasma concentrations (r = 0.51, p = 0.01). CONCLUSIONS: Our study is the first to demonstrate a decrease in maternal and fetal plasma concentrations of tumor necrosis factor-alpha in pregnancies associated with idiopathic small-for-gestational-age newborns. This reduction may have endocrinologic importance or may reflect widespread paracrine and autocrine events. On the other hand, our findings do not support a fundamental endocrine role of tumor necrosis factor-alpha in preeclampsia. C1 UNIV TENNESSEE,DEPT OBSTET & GYNECOL,MEMPHIS,TN 38103. WAYNE STATE UNIV,HUTZEL HOSP,DEPT OBSTET & GYNECOL,DETROIT,MI 48202. NICHHD,PERINATOL BRANCH,BETHESDA,MD 20892. NR 24 TC 58 Z9 58 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 1994 VL 170 IS 5 BP 1224 EP 1229 PN 1 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA NM304 UT WOS:A1994NM30400002 PM 8178841 ER PT J AU SEPULVEDA, W ROMERO, R PRYDE, PG WOLFE, HM ADDIS, JR COTTON, DB AF SEPULVEDA, W ROMERO, R PRYDE, PG WOLFE, HM ADDIS, JR COTTON, DB TI PRENATAL-DIAGNOSIS OF SIRENOMELUS WITH COLOR DOPPLER ULTRASONOGRAPHY SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Note DE SIRENOMELUS; PRENATAL DIAGNOSIS; ULTRASONOGRAPHY; COLOR DOPPLER; OLIGOHYDRAMNIOS AB Sirenomelus is an invariably lethal congenital anomaly characterized by complete or nearly complete fusion of the lower extremities that occurs in 1 of 60,000 births. In about 50% of cases this condition cannot be diagnosed prenatally because of the associated oligohydramnios that precludes a detailed examination of the fetus. We present a case of sirenomelus in which prenatal diagnosis was aided by color Doppler ultrasonography; visualization of the vitelline artery as a single, large intraabdominal vessel that did not branch in the fetal pelvis but rather coursed ventrally into the umbilical cord proved to be diagnostic of this rare condition. Color Doppler flow ultrasonography is a valuable tool for the prenatal diagnosis of sirenomelus. C1 WAYNE STATE UNIV,HUTZEL HOSP,SCH MED,DEPT OBSTET & GYNECOL,DETROIT,MI 48201. NICHHD,PERINATOL BRANCH,BETHESDA,MD 20892. NR 3 TC 21 Z9 24 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 1994 VL 170 IS 5 BP 1377 EP 1379 PN 1 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA NM304 UT WOS:A1994NM30400034 PM 8178872 ER PT J AU FIDEL, PL ROMERO, R WOLF, N CUTRIGHT, J RAMIREZ, M ARANEDA, H COTTON, DB AF FIDEL, PL ROMERO, R WOLF, N CUTRIGHT, J RAMIREZ, M ARANEDA, H COTTON, DB TI SYSTEMIC AND LOCAL CYTOKINE PROFILES IN ENDOTOXIN-INDUCED PRETERM PARTURITION IN MICE SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE CYTOKINES; ENDOTOXIN; PRETERM PARTURITION; MURINE MODEL; AMNIOTIC FLUID ID TUMOR-NECROSIS-FACTOR; FACTOR-ALPHA; AMNIOTIC-FLUID; HUMAN DECIDUA; INTERLEUKIN-1; LABOR; INFECTION; PREGNANCY; INVIVO; ANTIBODIES AB OBJECTIVE: Our purpose was to determine whether endotoxin-induced preterm parturition is preceded by a change in the maternal serum and amniotic fluid concentrations of tumor necrosis factor-alpha, interleukin-6, and interleukin-1 alpha. STUDY DESIGN: C3H/HeN pregnant mice at 15 days of gestation (70% gestation) were randomized to receive an intraperitoneal injection of phosphate-buffered saline solution or lipopolysaccharide (50 mu g/mouse). Blood (n = 93) and amniotic fluid (n = 58) were collected at 1, 4, and 10 hours after lipopolysaccharide injection. Tumor necrosis factor-alpha, interleukin-6, and interleukin-1 alpha were determined with sensitive and specific enzyme-linked immunoassays. RESULTS: The injection-to-delivery interval was shorter in mice injected intraperitoneally with 50 mu g lipopolysaccharide than in phosphate-buffered saline solution-treated mice (median 15.5 hours, range: 10 to 105 hours vs median 88.5 hours, range: 53 to 105 hours; p < 0.001). In comparison with phosphate-buffered saline solution-treated mice, a distinct serum cytokine pattern was observed in lipopolysaccharide-treated mice. Concentrations of tumor necrosis factor-alpha were detectable 1 and 4 hours after lipopolysaccharide injection (median 874 pg/ml, range: < 100 to 8000 pg/ml, p < 0.001; and median 263 pg/ml, range: <100 to 927 pg/ml, p < 0.001, respectively). Concentrations of interleukin-6 were elevated at 1, 4, and 10 hours (median 11.8 ng/ml, range: 6 to 500 ng/ml, p < 0.001; median 27.1 ng/ml, range: 4.5 to 192 ng/ml, p < 0.001; median 1.95 ng/ml, range: < 0.05 to 35 ng/ml, p < 0.015, respectively). Concentrations of interleukin-1 alpha were significantly increased 4 hours after lipopolysaccharide injection (median 102 pg/ml, range: < 15 to 306 pg/ml, p < 0.001). A cytokine pattern distinct from serum was observed in amniotic fluid of lipopolysaccharide-treated mice. In comparison with controls, concentrations of interleukin-6 were significantly elevated 4 and 10 hours after treatment with lipopolysaccharide (median 0.88 ng/ml, range: 0.40 to 2.7 ng/ml, p < 0.025; and median 4 ng/ml, range: 1.9 to 33.6 ng/ml, p < 0.001, respectively). Interleukin-1 alpha was elevated 10 hours after lipopolysaccharide treatment (median 185.3 pg/ml, range: 38 to 511 pg/ml, p < 0.015). Tumor necrosis factor-alpha was not significantly increased in amniotic fluid. CONCLUSION: Preterm delivery after lipopolysaccharide administration is preceded by the appearance of dramatic increases in maternal serum concentrations of tumor necrosis factor-alpha, interleukin-6, and interleukin-1 alpha and in amniotic fluid concentrations of interleukin-6 and interleukin-1 alpha. C1 WAYNE STATE UNIV,HUTZEL HOSP,SCH MED,DEPT GYNECOL & OBSTET,DETROIT,MI 48201. NICHHD,PERINATAL RES BRANCH INTRAMURAL RES PROGRAM,BETHESDA,MD 20892. NR 28 TC 181 Z9 182 U1 1 U2 7 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 1994 VL 170 IS 5 BP 1467 EP 1475 PN 1 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA NM304 UT WOS:A1994NM30400052 PM 8178889 ER PT J AU BIALY, G HASELTINE, F ALEXANDER, NJ BURNHILL, M AF BIALY, G HASELTINE, F ALEXANDER, NJ BURNHILL, M TI PREVENTING UNINTENDED PREGNANCY - THE ROLE OF HORMONAL CONTRACEPTIVES - BETHESDA, MARYLAND APRIL 27-28, 1993 - INTRODUCTION SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material C1 NICHHD,POPULAT RES CTR,BETHESDA,MD 20892. NICHHD,CONTRACEPT DEV BRANCH,BETHESDA,MD 20892. UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,DEPT OBSTET & GYNECOL,NEW BRUNSWICK,NJ. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAY PY 1994 VL 170 IS 5 BP 1483 EP 1484 PN 2 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA NM305 UT WOS:A1994NM30500001 ER PT J AU SHERER, DM DAMICO, ML COX, C METLAY, LA WOODS, JR AF SHERER, DM DAMICO, ML COX, C METLAY, LA WOODS, JR TI ASSOCIATION OF IN-UTERO BEHAVIORAL-PATTERNS OF TWINS WITH EACH OTHER AS INDICATED BY FETAL HEART-RATE REACTIVITY AND NONREACTIVITY SO AMERICAN JOURNAL OF PERINATOLOGY LA English DT Article AB Prospective analysis of 75 pairs of nonstress tests (NSTs) obtained simultaneously from both members of 35 twin gestations was performed to quantitatively assess the incidence of simultaneous periods of fetal heart rate (FHR) reactivity and nonreactivity of twins. Comparative analysis of the paired NSTs was used to compute rates of simultaneous fetal heart rate reactivity and nonreactivity. Statistical analysis involved comparison of weighted averages of these rates, using sequence lengths as weights. Weighted standard deviations were used to describe variability between sets of NSTs. Trend analysis was performed using weighted linear regression to calculate slopes for pairs of twins with three or more repeat NSTs. Groups of twins were compared by performing a variance stabilizing transformation on the appropriate rates, and using a two sample t test to compare the means of transformed data. Analysis of this data revealed that twins exhibited similar in utero fetal heart reactivity and nonreactivity as indicated by simultaneous electronic fetal monitoring during 79.90% +/- 1.62 (SD) of the time monitored. The incidence of periods of simultaneously reactive FHR and simultaneously nonreactive FHR were 11.79% +/- 1.02 and 68.10% +/- 2.17, respectively, irrespective of gestational age. These data confirm the hypothesis that periods of FHR reactivity and nonreactivity of twins are strongly associated with each other. RP SHERER, DM (reprint author), GEORGETOWN UNIV,MED CTR,DEPT OBSTET & GYNECOL,NICHHD,PERINATOL RES BRANCH,3PHC,WASHINGTON,DC 20007, USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0735-1631 J9 AM J PERINAT JI Am. J. Perinatol. PD MAY PY 1994 VL 11 IS 3 BP 208 EP 212 DI 10.1055/s-2008-1040747 PG 5 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA NL066 UT WOS:A1994NL06600008 PM 8048987 ER PT J AU FEIGIN, AM NINOMIYA, Y BEZRUKOV, SM BRYANT, BP MOORE, PA KOMAI, M WACHOWIAK, M TEETER, JH VODYANOY, I BRAND, JG AF FEIGIN, AM NINOMIYA, Y BEZRUKOV, SM BRYANT, BP MOORE, PA KOMAI, M WACHOWIAK, M TEETER, JH VODYANOY, I BRAND, JG TI ENHANCEMENT OF GUSTATORY NERVE-FIBERS TO NACL AND FORMATION OF ION CHANNELS BY COMMERCIAL NOVOBIOCIN SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE SALT TASTE TRANSDUCTION; AMILORIDE ID ELECTRICAL TONGUE STIMULATIONS; CHORDA TYMPANI FIBERS; TASTE RECEPTOR-CELLS; AMILORIDE INHIBITION; NA+ CHANNEL; SALT TASTE; SODIUM; RESPONSES; ORGANIZATION; TRANSDUCTION AB Single fibers of the rat chorda tympani nerve were used to study the mechanism of action of the antibiotic novobiocin on salt taste transduction. In the rat, novobiocin selectively enhanced the responses of sodium-specific and amiloride-sensitive chorda tympani nerve fibers (N type) without affecting more broadly responsive cation-sensitive and amiloride-insensitive fibers (E type). In the presence of amiloride, novobiocin was ineffective at enhancing the response of N-type fibers toward sodium chloride. Novobiocin also increased the conductance of bilayers formed from neutral lipids by forming nonrectifying ion channels with low conductance (similar to 7 pS in 110 mM NaCl), long open times (several seconds and longer), and high cation selectivity. Amiloride did not alter either the conductance or kinetics of these novobiocin channels. These observations suggest that even though novobiocin is able to form cation channels in lipid bilayers, and possibly in cell membranes as well, its action on the salt-taste response is through modulation of existing amiloride-sensitive sodium channels. C1 DEPT VET AFFAIRS MED CTR,PHILADELPHIA,PA 19104. ASAHI UNIV,DEPT ORAL PHYSIOL,GIFU 50102,JAPAN. NIH,BETHESDA,MD 20892. ST PETERSBURG NUCL PHYS INST,ST PETERSBURG 188350,RUSSIA. OFF NAVAL RES,ARLINGTON,VA 22217. RP FEIGIN, AM (reprint author), UNIV PENN,MONELL CHEM SENSES CTR,3500 MARKET ST,PHILADELPHIA,PA 19104, USA. NR 33 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 1994 VL 266 IS 5 BP C1165 EP C1172 PN 1 PG 8 WC Physiology SC Physiology GA NP995 UT WOS:A1994NP99500003 ER PT J AU LONDON, RE RHEE, CK MURPHY, E GABEL, S LEVY, LA AF LONDON, RE RHEE, CK MURPHY, E GABEL, S LEVY, LA TI NMR-SENSITIVE FLUORINATED AND FLUORESCENT INTRACELLULAR CALCIUM-ION INDICATORS WITH HIGH DISSOCIATION-CONSTANTS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE PH; MAGNESIUM ION; 1,2-BIS(2-AMINOPHENOXY)ETHANE N,N,N',N'-TETRAACETIC ACID ID CYTOSOLIC FREE MAGNESIUM; F-19 NMR; CHELATORS; CA-2+; DESIGN; CELLS; LEAD AB A new series of high-dissociation constant (KD) Ca2+ indicators has been developed to reduce perturbations due to buffering of transients, to carry out measurements in cells and organelles with high basal Ca3+ concentrations, and to measure cytosolic Ca2+ levels in the presence of perturbations that may significantly increase these levels. A tetrafluorinated derivative of the chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid, 1,2-bis(2-amino-5, 6-difluorophenoxy)ethane-N, N, N', N'-tetraacetic acid (TF-BAPTA), has a K-D of 65 mu M and exhibits two fluorine nuclear magnetic resonances, one of which is insensitive to Ca2+ chelation and the second of which shifts by similar to 10 ppm upon Ca2+ binding. TF-BAPTA has pK values of similar to 5.0 and Mg2+ dissociation constants >50 mM. At a field of 8.5 T, the Ca2+-sensitive resonance is in fast-intermediate exchange. Correction factors for the effects of intermediate exchange and for the effect of protonation (pK similar to 5.0) and Mg2+ complexation are discussed. An analogous approach has been used to synthesize 2-[2-(5-carboxyoxazole)]-5-[2-(2-bis(carboxymethyl) amino-5,6-difluorophenoxy)]ethoxy-6-bis(carboxymethyl)aminobenzofuran (fura Fl, a structural analogue of fura 2, which exhibits fluorescence characteristics similar to those of fura 2, but has a K(D)of 20 mu M. C1 NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. NR 19 TC 26 Z9 27 U1 0 U2 4 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 1994 VL 266 IS 5 BP C1313 EP C1322 PN 1 PG 10 WC Physiology SC Physiology GA NP995 UT WOS:A1994NP99500020 ER PT J AU MURPHY, E STEENBERGEN, C LEVY, LA GABEL, S LONDON, RE AF MURPHY, E STEENBERGEN, C LEVY, LA GABEL, S LONDON, RE TI MEASUREMENT OF CYTOSOLIC-FREE CALCIUM IN PERFUSED RAT-HEART USING TF-BAPTA SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE ISCHEMIA; 5-FLUORO-1,2-BIS(2-AMINOPHENOXY)ETHANE-N,N,N',N'TETRAACETIC ACID; LEFT VENTRICULAR DEVELOPED PRESSURE ID F-19 NMR; MYOCARDIUM; CHELATORS; NECROSIS; ISCHEMIA; INJURY AB The feasibility and usefulness of loading 1,2-bis(2-amino-5,6-difluorophenoxy) -N,N,N',N'-tetraacetic acid (TF BAPTA), a new high-dissociation constant (K-D) (65 mu M) Ca2+ indicator, into perfused rat heart is demonstrated. TF-BAPTA-loaded perfused rat heart showed less than a 10% reduction in left ventricular developed pressure. In addition, loading perfused rat heart with TF-BAPTA had no effect on cell high-energy phosphates measured by P-31-nuclear magnetic resonance (NMR). Cytosolic free Ca2+ (Ca-i(2+)) can be monitored in TF-BAPTA-loaded perfused rat heart using F-19-NMR. TF-BAPTA has a Ca2+-insensitive resonance (6F) and a Ca2+-sensitive fluorine (5F) that responds to changes in Ca2+ binding with fast exchange kinetics at magnetic fields less than or equal to 8.5 T. Thus the shift difference between the 5F and 6F resonances is a measure of Ca-i(2+). Given the high KD and the slight differences in intra- vs, extracellular fluorine shifts, TF-BAPTA is not well suited for measuring basal Ca-i(2+), but it is useful for measuring increases in Ca-i(2+) above this level. For studies in which intracellular pH changes are significant, e.g., during ischemia, pH-dependent corrections must be made to obtain an accurate Ca-i(2+) value. Given its fast exchange kinetics, TF-BAPTA is also useful for measurement of free Ca2+ in different compartments or cells with different Ca-i(2+). We show that the rise in Ca-i(2+) is not uniform during prolonged global ischemia (60 min); several different Ca-i(2+) values are present. Thus TF-BAPTA is a useful new indicator for measuring elevations in Ca-i(2+) or compartmentation of Ca-i(2+). In addition, unlike 5-fluoro-1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (5F-BAPTA), introduction of TF-BAPTA into perfused rat heart has minimal effects on contractility. RP MURPHY, E (reprint author), NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709, USA. NR 19 TC 16 Z9 16 U1 1 U2 3 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 1994 VL 266 IS 5 BP C1323 EP C1329 PN 1 PG 7 WC Physiology SC Physiology GA NP995 UT WOS:A1994NP99500021 ER PT J AU PAREDES, A BRISCOE, DM WILLIAMS, CK GARCIAPEREZ, A WADE, JB HARRIS, HW AF PAREDES, A BRISCOE, DM WILLIAMS, CK GARCIAPEREZ, A WADE, JB HARRIS, HW TI WATER CHANNEL VESICLES FROM TOAD URINARY-BLADDER CONTAIN A FAMILY OF PROTEINS PRESENT IN OTHER TISSUES SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE ANTIDIURETIC HORMONE; IMMUNOGLOBULIN G1 MONOCLONAL ANTIBODY ID CORTICAL COLLECTING DUCT; ANTIDIURETIC-HORMONE; APICAL MEMBRANE; EPITHELIAL-CELLS; MONOCLONAL-ANTIBODIES; FROG-SKIN; PERMEABILITY; VASOPRESSIN; ENDOSOMES; RETRIEVAL AB Antidiuretic hormone (ADH) stimulation causes the fusion and subsequent retrieval of cytoplasmic vesicles containing water channels (WCV) with the apical membrane of toad bladder granular cells. Previously, we showed that purified WCV contain 12 major protein bands on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. To identify various WCV proteins, we screened a panel of mouse monoclonal antibodies and characterized an immunoglobulin G1 monoclonal antibody, 5E5, that recognizes integral membrane WCV proteins of 38, 33, and 31 kDa. Immunocytochemistry and Western blot analyses show that 5E5 binds to multivesicular body endosomes shown previously to contain ADH water channels. In addition, 5E5 recognizes these proteins in selected cells of the skin, intestine, liver, kidney, spleen, and lung. However, 5E5 does not appear to recognize components of the water channel itself. We conclude that WCV contain several membrane proteins recognized by 5E5 that are present in certain cells of the other organs. Monoclonal 5E5 provides a probe to determine the structure and function of these endosomal proteins as well. as their role in the ADH water permeability response. C1 CHILDRENS HOSP,DIV NEPHROL,BOSTON,MA 02030. NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BETHESDA,MD 20892. UNIV MARYLAND,DEPT PHYSIOL,BALTIMORE,MD 21201. NR 56 TC 3 Z9 3 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 1994 VL 266 IS 5 BP C1366 EP C1375 PN 1 PG 10 WC Physiology SC Physiology GA NP995 UT WOS:A1994NP99500026 ER PT J AU WADE, JB NIELSEN, S COLEMAN, RA KNEPPER, MA AF WADE, JB NIELSEN, S COLEMAN, RA KNEPPER, MA TI LONG-TERM REGULATION OF COLLECTING DUCT WATER PERMEABILITY - FREEZE-FRACTURE ANALYSIS OF ISOLATED-PERFUSED TUBULES SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE VASOPRESSIN; OSMOTIC WATER PERMEABILITY; PARTICLE CLUSTERS ID INTRAMEMBRANOUS PARTICLE CLUSTERS; NEPHROGENIC DIABETES-INSIPIDUS; RAT-KIDNEY; URINARY-BLADDER; TOAD BLADDER; VASOPRESSIN; MEMBRANE; UREA; TRANSPORT; CHANNEL AB Terminal inner medullary collecting duct (IMCD) segments from water-restricted rats have high osmotic permeabilities despite the absence of vasopressin (AVP). We performed freeze-fracture analysis of individual IMCD segments from such animals following measurement of their water permeability (P-f). IMCD segments from control rats did not have a high P-f in the absence of AW (88 +/- 15 mu m/s) and had a low incidence of E-face intramembrane particle (IMP) clusters (9.6 +/- 2.7 dusters/100 mu m(2)). Segments exposed to 0.1 nM AVP in vitro had enhanced P-f (1,060 +/- 210 mu m/s) and cluster incidence (122 +/- 33 clusters/100 mu m(2)). IMCD segments isolated from rats dehydrated for 48 h and perfused without AVP exposure had an elevated Pc (605 +/- 71 mu m/s) and a high incidence of clusters (166 +/- 36 clusters/100 mu m(2)). There also was an increase in the number of single particles between clusters in tubules from dehydrated rats (2.5-fold) and in AVP-treated tubules (3.6-fold). These findings indicate that LMP clusters are associated with high water permeability in tubules from dehydrated animals independent of continued AVP exposure. The increased incidence of particles between clusters suggests that water channels may also occur outside of duster domains. C1 NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BETHESDA,MD 20892. RP WADE, JB (reprint author), UNIV MARYLAND,SCH MED,DEPT PHYSIOL,655 W BALTIMORE ST,BALTIMORE,MD 21201, USA. FU NIDDK NIH HHS [DK-32839] NR 30 TC 10 Z9 10 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 1994 VL 266 IS 5 BP F723 EP F730 PN 2 PG 8 WC Physiology SC Physiology GA NP996 UT WOS:A1994NP99600109 PM 8203555 ER PT J AU FELLEY, CP ODORISIO, TM HOWE, B COY, DH MANTEY, SA PRADHAN, TK SUTLIFF, VE JENSEN, RT AF FELLEY, CP ODORISIO, TM HOWE, B COY, DH MANTEY, SA PRADHAN, TK SUTLIFF, VE JENSEN, RT TI CHIEF CELLS POSSESS SOMATOSTATIN RECEPTORS REGULATED BY SECRETAGOGUES ACTING THROUGH THE CALCIUM OR CAMP PATHWAY SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE CYTOSOLIC CALCIUM; ADENOSINE 3',5'-CYCLIC MONOPHOSPHATE; INOSITOL PHOSPHATES; GUINEA PIG ID RELEASE-INHIBITING HORMONE; GUINEA-PIG STOMACH; PEPSINOGEN SECRETION; GROWTH-HORMONE; GASTROINTESTINAL-TRACT; DISTINCT RECEPTORS; PHOSPHOLIPASE-C; RAT STOMACH; BINDING; GASTRIN AB Inhibition both in vivo and in vitro of pepsinogen secretion by somatostatin (SS) and the histological demonstration that fundic D-cells contain long cytoplasmic processes extending to chief cells suggest a possible direct effect of SS on chief cell function. The aim of the present study was to determine whether SS interacts directly with receptors on isolated gastric chief cells and, if so, how SS alters cell function. Binding of I-125-[Tyr(11)]SS14 to chief cells was saturable, time and temperature dependent, and was inhibited by both SS14 (K-i 1.6 nM) and SS28 (K-i 5.2 nM). SMS-201-995 was 1,300-fold less potent than SS14. Calcium-mobilizing secretagogues reduced binding of I-125-[Tyr(11)]SS14 With efficacies of cholecystokinin octapeptide (CCK-8) > carbachol > gastrin. Adenosine 3',5'-cyclic monophosphate (cAMP)-activating secretagogues also inhibited binding with efficacies of secretin > vasoactive intestinal polypeptide (VIP). 12-O-tetradecanoylphorbol 13-acetate (TPA) or A-23187 also decreased binding. Analyses demonstrated that CCK-8 and TPA were decreasing the affinity of SS receptors for I-125-[Tyr(11)]SS14 without affecting their binding capacity. Both SS14 and SS28 at a maximally effective concentration inhibited cAMP production caused by VIP or secretin (20-30%) but did not alter cytosolic calcium ([Ca2+](i)), inositol phosphates, or pepsinogen release. We conclude that chief cells possess SS receptors with a high affinity for both SS14 and SS28 but low affinity for SMS-201-995 and thus resemble the SSB receptors described in the rat cerebral cortex. Although occupation of these receptors by SS has no effect on pepsinogen release induced by secretagogues acting through either the calcium or the cAMP pathway, SS receptor occupation is regulated by agents activating phospholipase C, adenylate cyclase, protein kinase C, and [Ca2+](i). C1 NIDDKD,DIGEST DIS BRANCH,BETHESDA,MD 20892. TULANE UNIV,MED CTR,DEPT MED,PEPTIDE RES LABS,NEW ORLEANS,LA 70121. OHIO STATE UNIV,SCH MED,DEPT MED,COLUMBUS,OH 43210. NR 39 TC 10 Z9 10 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 1994 VL 266 IS 5 BP G789 EP G798 PN 1 PG 10 WC Physiology SC Physiology GA NP995 UT WOS:A1994NP99500064 PM 7911277 ER PT J AU GU, ZF PRADHAN, TK COY, DH JENSEN, RT AF GU, ZF PRADHAN, TK COY, DH JENSEN, RT TI SMOOTH-MUSCLE CELLS FROM GUINEA-PIG STOMACH POSSESS HIGH-AFFINITY GALANIN RECEPTORS THAT MEDIATE RELAXATION SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE SMOOTH MUSCLE CONTRACTION; MOTILITY; NEUROPEPTIDE ID CENTRAL NERVOUS-SYSTEM; SMALL-INTESTINE; CIRCULAR MUSCLE; BINDING-SITES; RAT; PEPTIDE; ILEUM; NEUROPEPTIDES; MOTILITY; VIP AB Galanin-like immunoactivity occurs in nerves and plexi in muscle layers throughout gastrointestinal tract including the stomach. Galanin can affect gastric emptying and contraction or relaxation of gastric muscle in different species. The aim of this study was to investigate the direct effect of galanin on dispersed gastric smooth muscle cells and to characterize any galanin receptors that mediated any effect. Dispersed gastric smooth muscle cells were prepared from guinea pig stomach by collagenase digestion. Porcine galanin (p-galanin; 1 mu M) did not stimulate contraction when present alone; however, p-galanin (1 mu M) inhibited carbachol-induced contraction with a half-maximal effect at 7 nM. p-Galanin (1 mu M) increased cellular adenosine 3',5'-cyclic monophosphate (cAMP) content by 10 s and caused a maximal increase of 80% over basal. I-125-galanin (porcine) bound to dispersed cells in a time- and temperature-dependent manner. Binding was saturable, reversible, and specific. Binding of I-125-galanin was inhibited almost equally by porcine and rat galanin (K-i = 6-8 nM) but was not inhibited by the galanin-associated peptide [preprogalanin-(108-123)]. The fragment galanin-(1-16) was equally potent to rat galanin; however, the fragment galanin-(9-29) was 56-fold less potent (K-i = 370 nM). Computer analysis demonstrated there were two binding sites for p-galanin on gastric smooth muscle cells, a high-affinity site (K-d = 2.6 nM) with low capacity (B-max = 175 fmol/mg protein) and a low-affinity site (Kd = 150 nM) with large capacity (B-max = 3,611 fmol/mg protein). I-125-galanin binding to gastric smooth muscle cell membrane was inhibited by 5'-guanylyl imidodiphosphate [Gpp(NH)p] in a dose-dependent manner(IC50 = 75 nM). Computer analysis demonstrated that with Gpp(NH)p the high-affinity binding site was lost. These results demonstrate that gastric smooth muscle cells possess high-affinity galanin receptors, occupation of which causes cAMP generation and muscle relaxation. The NH2-terminus of galanin determines the receptor affinity that is regulated by a guanine nucleotide-binding protein. C1 NIDDKD,DIGEST DIS BRANCH,BETHESDA,MD 20892. TULANE UNIV,MED CTR,PEPTIDE RES LABS,NEW ORLEANS,LA 70112. FU NCI NIH HHS [CA-45153] NR 43 TC 17 Z9 17 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 1994 VL 266 IS 5 BP G839 EP G845 PN 1 PG 7 WC Physiology SC Physiology GA NP995 UT WOS:A1994NP99500070 PM 7515574 ER PT J AU BROWN, ML FINTOR, L AF BROWN, ML FINTOR, L TI ACCREDITATION OF MAMMOGRAPHY FACILITIES BY THE AMERICAN-COLLEGE-OF-RADIOLOGY - RESULTS OF A NATIONAL SURVEY SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article AB Mammographic screening for the early detection of breast cancer is rapidly becoming an increasingly common practice in the United States. With mote than 20 million mammograms estimated to be performed annually by more than 11,000 units, ongoing quality assurance and evaluative programs have gained importance. Recent federal legislative and regulatory efforts augment a patchwork of state mandates establishing or encouraging specific quality control requirements for mammography facilities, personnel, equipment, and radiation exposure. Many of these requirements are based on the American College of Radiology's (ACR) voluntary accreditation program that has been offering facility certification since 1987. The ACR collects and maintains detailed data on the characteristics of accredited facilities; however, little is known about facilities not participating in the ACR program. This article describes national results from the 1992 National Mammography Facilities Survey, a representative sample of 1,057 mammography facilities. We found statistically significant (P < .05) differences between accredited and nonaccredited facilities in type of mammography practices, cost, personnel standards, variables linked to accessibility, and corollary screening practices (availability of breast self-examination instruction and breast physical examination). Other variables showed minor or little variation between accredited and nonaccredited facilities. The results of this study suggest that, although all facilities engage in various components of ''good'' quality assurance practices, ACR-accredited facilities reported conducting these programs more frequently. Further, despite the substantially increased costs associated with these programs, ACR-accredited facilities reported lower average charges for screening mammograms and were more likely to participate in reduced fee programs. RP BROWN, ML (reprint author), NCI,DIV CANC PREVENT & CONTROL,APPL RES BRANCH,SURVEILLANCE PROGRAM,BETHESDA,MD 20892, USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD MAY-JUN PY 1994 VL 10 IS 3 BP 162 EP 167 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA NV554 UT WOS:A1994NV55400008 PM 7917443 ER PT J AU MATOCHIK, JA LIEBENAUER, LL KING, AC SZYMANSKI, HV COHEN, RM ZAMETKIN, AJ AF MATOCHIK, JA LIEBENAUER, LL KING, AC SZYMANSKI, HV COHEN, RM ZAMETKIN, AJ TI CEREBRAL GLUCOSE-METABOLISM IN ADULTS WITH ATTENTION-DEFICIT HYPERACTIVITY DISORDER AFTER CHRONIC STIMULANT TREATMENT SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 22nd Annual Meeting of the Society-for-Neuroscience CY OCT 25-30, 1992 CL ANAHEIM, CA SP Soc Neurosci ID MINIMAL BRAIN-DYSFUNCTION; POSITRON EMISSION TOMOGRAPHY; BLOOD-FLOW; PSYCHIATRIC STATUS; RESIDUAL TYPE; AMPHETAMINE; CHILDREN; BOYS; DEXTROAMPHETAMINE; METHYLPHENIDATE AB Objective: The authors examined the effects of chronic stimulant treatment on cerebral glucose metabolism in adults diagnosed with attention deficit hyperactivity disorder (ADHD), who were studied by means of positron emission tomography (PET) with [F-18]fluorodeoxy-glucose as the tracer. Method: Each subject received two PET scans, the first before drug treatment and the second after treatment with daily oral doses, individually titrated for clinical effect, of either methylphenidate (N=19) or d-amphetamine (N=18) for a minimum of 6 weeks. The subjects completed behavioral self-report measures before and at the end of the medication period. Results: Neither stimulant medication changed global, or whole-brain, metabolism, although both drugs increased systolic blood pressure. Metabolism in only two of the 60 brain regions sampled was changed by methylphenidate, while d-amphetamine exhibited no effect on regional metabolism. Both drugs were associated with significant improvement in behavior, as evidenced by improved ratings for restlessness and ability to maintain attention. Conclusions: While the present study does not demonstrate any robust metabolic effects of chronic stimulant treatment, the behavioral data strongly indicate that methylphenidate and d-amphetamine are effective agents for the treatment of adults with ADHD. C1 VET ADM MED CTR,DEPT PSYCHIAT,BUFFALO,NY. RP MATOCHIK, JA (reprint author), NIMH,CEREBRAL METAB LAB,CLIN BRAIN IMAGING SECT,BLDG 10,RM 4N317,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 33 TC 90 Z9 91 U1 0 U2 3 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 1994 VL 151 IS 5 BP 658 EP 664 PG 7 WC Psychiatry SC Psychiatry GA NJ089 UT WOS:A1994NJ08900005 PM 8166305 ER PT J AU GIEDD, JN CASTELLANOS, FX CASEY, BJ KOZUCH, P KING, AC HAMBURGER, SD RAPOPORT, JL AF GIEDD, JN CASTELLANOS, FX CASEY, BJ KOZUCH, P KING, AC HAMBURGER, SD RAPOPORT, JL TI QUANTITATIVE MORPHOLOGY OF THE CORPUS-CALLOSUM IN ATTENTION-DEFICIT HYPERACTIVITY DISORDER SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID CHILDREN; PARENT; CORTEX; BRAIN; MRI AB Objective: By means of quantitative neuroanatomic imaging the authors assessed the hypothesis that there are structural brain abnormalities relevant to frontal lobe circuitry in children with attention deficit hyperactivity disorder (ADHD). Method: The midsagittal cross-sectional area of the corpus callosum, divided into seven sections, was measured from magnetic resonance images of Is boys with ADHD and 18 carefully matched normal boys. Results: Two anterior regions, the rostrum and the rostral body, were found to have significantly smaller areas in the ADHD group. These areas correlated in the expected direction with teacher and parent ratings of hrperactivity/impulsivity. Conclusions: This finding supports theories of abnormal frontal lobe development and function in ADHD. RP GIEDD, JN (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,RM 6N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015; OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978; kozuch, patricia/0000-0002-7465-9671 NR 35 TC 267 Z9 270 U1 1 U2 7 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 1994 VL 151 IS 5 BP 665 EP 669 PG 5 WC Psychiatry SC Psychiatry GA NJ089 UT WOS:A1994NJ08900006 PM 8166306 ER PT J AU MUELLER, TI LAVORI, PW KELLER, MB SWARTZ, A WARSHAW, M HASIN, D CORYELL, W ENDICOTT, J RICE, J AKISKAL, H AF MUELLER, TI LAVORI, PW KELLER, MB SWARTZ, A WARSHAW, M HASIN, D CORYELL, W ENDICOTT, J RICE, J AKISKAL, H TI PROGNOSTIC EFFECT OF THE VARIABLE COURSE OF ALCOHOLISM ON THE 10-YEAR COURSE OF DEPRESSION SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID PSYCHIATRIC-DISORDERS; DRUG-ABUSE; PREVALENCE; COMORBIDITY; PREDICTORS AB Objective: of patients' alcohol use on the course of major depressive disorder. Method: One hundred seventy-six probands with Research Diagnostic Criteria (RDC) diagnoses of both major depressive disorder and alcoholism were compared to 412 probands with major depressive disorder only by using 10 years of short-interval, prospective follow-up data collected as part of the National Institute of Mental Health Collaborative Depression Study. The course of depression was examined by using intensity analysis to represent transitions between states of major depressive disorder. The effect of patients' RDC alcoholism status on the long-term course of major depressive disorder was examined by stratifying the analyses by three levels of alcoholism-never alcoholic, not meeting criteria for current alcoholism, and current alcoholism. Results: Depressed probands who were either never alcoholic or currently nonactive alcoholic had twice the likelihood of recovery from major depressive disorder than did actively alcoholic depressed probands. The three levels of alcoholism did not differentially predict recurrence of major depressive disorder. Conclusions: These findings provide long-term, empirically derived evidence for the deleterious effect of current alcoholism on recovery from depression. The lack of a differential effect of the three levels of alcoholism on a recurrence of major depressive disorder suggests that other factors may have greater predictive value. C1 NIMH,COLLABORAT PROGRAM PSYCHOBIOL DEPRESS CLIN STUDIE,BETHESDA,MD 20892. FU NIMH NIH HHS [R01 MH025478, NIMH MH-25478] NR 30 TC 104 Z9 104 U1 3 U2 7 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 1994 VL 151 IS 5 BP 701 EP 706 PG 6 WC Psychiatry SC Psychiatry GA NJ089 UT WOS:A1994NJ08900012 PM 8166311 ER PT J AU ELKASHEF, AM BUCHANAN, RW GELLAD, F MUNSON, RC BREIER, A AF ELKASHEF, AM BUCHANAN, RW GELLAD, F MUNSON, RC BREIER, A TI BASAL GANGLIA PATHOLOGY IN SCHIZOPHRENIA AND TARDIVE-DYSKINESIA - AN MRI QUANTITATIVE STUDY SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Note ID CORTEX; ABNORMALITIES; DISORDER; PATTERNS AB Magnetic resonance imaging was used to measure the volumes of he caudate, putamen, and globus pallidus of 25 schizophrenic patients (17 men and eight women) and 26 age- and sex-matched comparison subjects (18 melt and eight women). Schizophrenic patients had significantly larger right and left globus pallidus and right putamen volumes than comparison subjects. There were no significant differences between schizophrenic patients with and without persistent tardive dyskinesia in the volume of any of the three structures. C1 MARYLAND PSYCHIAT RES CTR,DEPT PSYCHIAT,BETHESDA,MD. UNIV MARYLAND,SCH MED,DEPT RADIOL,BALTIMORE,MD 21201. NIMH,EXPTL THERAPEUT BRANCH,BETHESDA,MD 20892. RP ELKASHEF, AM (reprint author), ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,2700 MARTIN LUTHER KING JR AVE SE,WASHINGTON,DC 20032, USA. FU NIMH NIH HHS [MH-45074, NIMH MH-40279] NR 22 TC 75 Z9 75 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 1994 VL 151 IS 5 BP 752 EP 755 PG 4 WC Psychiatry SC Psychiatry GA NJ089 UT WOS:A1994NJ08900021 PM 7909412 ER PT J AU SICHIERI, R COITINHO, DC LEAO, MM RECINE, E EVERHART, JE AF SICHIERI, R COITINHO, DC LEAO, MM RECINE, E EVERHART, JE TI HIGH TEMPORAL, GEOGRAPHIC, AND INCOME VARIATION IN BODY-MASS INDEX AMONG ADULTS IN BRAZIL SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID SECULAR TRENDS; SOCIOECONOMIC-FACTORS; SKINFOLD THICKNESS; UNITED-STATES; OVERWEIGHT; POPULATION; PREVALENCE; OBESITY; DISEASE; MEN AB Objectives, Population-based data on body mass index for developing countries are scarce. Body mass index data from two Brazilian surveys were examined to determine regional and temporal variations in the prevalences of underweight, overweight, and obesity. Methods. Nationwide surveys in 1974/75 and 1989 collected anthropometric data in Brazil from 55 000 and 14 455 households, respectively. Trained interviewers used the same methods to measure weight and stature in both surveys, and survey designs were identical. Prevalences of underweight, overweight, and obesity were determined for persons 18 years of age and older. Results. In the 1989 survey, body mass index varied greatly according to region of the country, urbanization, and income. Tn the wealthier South, the prevalence of overweight/ obesity was the highest and the prevalence of underweight was the lowest; in the poorer rural Northeast, these patterns were reversed. For both surveys, overweight/obesity was more common among women than among men and peaked at age 45 to 64 years in both sexes. Over the 15 years between surveys, the prevalence of both overweight and obesity increased strikingly. Conclusions. In contrast to findings in developed countries, obesity in Brazil was positively associated with income and was much more prevalent among women than among men. For Brazilian women, the overall prevalence of overweight was nearly as high as that among women in the United States. C1 SAUDE UNIV ESTADUAL MARINGA,CTR CIENCIAS BIOL,MARINGA,PARANA,BRAZIL. SARAH HOSP MED APARELHO LOCOMOTOR,CTR NACL EPIDEMIOL & INFORMACAO,BRASILIA,DF,BRAZIL. NIDDK,BETHESDA,MD. NR 22 TC 82 Z9 93 U1 0 U2 1 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 1994 VL 84 IS 5 BP 793 EP 798 DI 10.2105/AJPH.84.5.793 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA NN151 UT WOS:A1994NN15100021 PM 8179051 ER PT J AU ZAPOL, WM RIMAR, S GILLIS, N MARLETTA, M BOSKEN, CH AF ZAPOL, WM RIMAR, S GILLIS, N MARLETTA, M BOSKEN, CH TI NITRIC-OXIDE AND THE LUNG SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material ID RESPIRATORY-DISTRESS-SYNDROME; HYPOXIC PULMONARY VASOCONSTRICTION; METHYL-L-ARGININE; RELAXING FACTOR; VASCULAR ENDOTHELIUM; HYPERTENSION; SYNTHASE; INHALATION; MECHANISM; NEWBORN C1 NHLBI, DIV LUNG DIS, BETHESDA, MD 20892 USA. NR 39 TC 199 Z9 204 U1 1 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAY PY 1994 VL 149 IS 5 BP 1375 EP 1380 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA NP839 UT WOS:A1994NP83900044 PM 8173780 ER PT J AU KLEINER, DE STETLERSTEVENSON, WG AF KLEINER, DE STETLERSTEVENSON, WG TI QUANTITATIVE ZYMOGRAPHY - DETECTION OF PICOGRAM QUANTITIES OF GELATINASES SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID IV COLLAGENASE; CELL-LINES; ACTIVATION; PROTEASES; INHIBITOR; COMPLEX AB Zymography is an electrophoretic technique used to identify proteolytic activity in enzymes separated in polyacrylamide gels under nonreducing conditions. It has been used extensively in the qualitative evaluation of proteases present in tumors and cell culture conditioned media. Using commercially available precast gels and a modern image analysis system, we have evaluated zymography as a quantitative technique. The degree of digestion of gelatin within the zymogram by purified gelatinase A, a matrix metalloprotease, is directly proportional to the amount of enzyme loaded over a 10- 20-fold range. With an overnight (18 h) digestion period, the linear range of this assay extended from 10 to 120 pg of enzyme. The initial rate of digestion is proportional to the enzyme loading and varying the incubation time results in a shift in the linear range of the assay. Active and latent forms of gelatinase A show the same degree of digestion in this assay system. These results justify the use of zymography in the quantitative assessment of gelatinase activity as well as demonstrate its usefulness as a qualitative technique for the analysis of gelatinase species present. (C) 1994 Academic Press, Inc. RP KLEINER, DE (reprint author), NCI,PATHOL LAB,BETHESDA,MD 20892, USA. RI Stetler-Stevenson, William/H-6956-2012; OI Stetler-Stevenson, William/0000-0002-5500-5808; Kleiner, David/0000-0003-3442-4453 NR 17 TC 718 Z9 800 U1 2 U2 20 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 1 PY 1994 VL 218 IS 2 BP 325 EP 329 DI 10.1006/abio.1994.1186 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA NH774 UT WOS:A1994NH77400014 PM 8074288 ER PT J AU NATANSON, C HOFFMAN, WD SUFFREDINI, AF EICHACKER, PQ DANNER, RL AF NATANSON, C HOFFMAN, WD SUFFREDINI, AF EICHACKER, PQ DANNER, RL TI SELECTED TREATMENT STRATEGIES FOR SEPTIC SHOCK BASED ON PROPOSED MECHANISMS OF PATHOGENESIS SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID TUMOR-NECROSIS-FACTOR; NITRIC-OXIDE SYNTHESIS; RESPIRATORY-DISTRESS SYNDROME; GRAM-NEGATIVE BACTEREMIA; COLONY-STIMULATING FACTOR; MONOMETHYL-L-ARGININE; ESCHERICHIA-COLI J5; METHYL-L-ARGININE; FACTOR-ALPHA; MONOCLONAL-ANTIBODIES AB Purpose: To review selected new therapies for septic shock designed to inhibit bacterial toxins or endogenous mediators of inflammation. Data Sources: Scientific journals, scientific meeting proceedings, and Food and Drug Administration advisory committee proceedings. Study Selection and Extraction: Preclinical and clinical data from trials using core-directed antiendotoxin antibodies and anticytokine therapies for sepsis and studies in animal models of sepsis from our laboratory. Results of Data Synthesis: Ten clinical trials using core-directed antiendotoxin antibodies produced inconsistent results and did not conclusively establish the safety or benefit of this approach. Both anti-interleukin-1 and anti-tumor necrosis factor (TNF) therapies have been beneficial in some animal models of sepsis, but did not clearly improve survival in initial human trials, and one anti-TNF therapy actually produced harm. Neutrophils, another target for therapeutic intervention, protect the host from infection but may also contribute to the development of tissue injury during sepsis. In a canine model of septic shock, granulocyte colony-stimulating factor increased the number of circulating neutrophils and improved survival, but an anti-integrin (CD11/18) antibody that inhibits neutrophil function worsened outcome. Nitric oxide, a vasodilator produced by the host, causes hypotension during septic shock but may also protect the endothelium and maintain organ blood flow. In dogs challenged with endotoxin, the inhibition of nitric oxide production decreased cardiac index and did not improve survival. Conclusions: No new therapy for sepsis has shown clinical efficacy. Perhaps more accurate clinical and laboratory predictors are needed to identify patients who may benefit from a given treatment strategy. On the other hand, the therapeutic premises may be flawed. Targeting a single microbial toxin such as endotoxin may not represent a viable strategy for treating a complex inflammatory response to diverse gram-negative bacteria. Similarly, the strategy of inhibiting the host inflammatory response may not be beneficial because immune cells and cytokines play both pathogenic and protective roles. Finally, our scientific knowledge of the complex timing of mediator release and balance during sepsis may be insufficient to develop successful therapeutic interventions for this syndrome. RP NATANSON, C (reprint author), NIH,CTR CLIN,DEPT CRIT CARE MED,BLDG 10,ROOM 7D43,BETHESDA,MD 20892, USA. NR 151 TC 372 Z9 379 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAY 1 PY 1994 VL 120 IS 9 BP 771 EP 783 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA NH251 UT WOS:A1994NH25100009 PM 8147551 ER PT J AU SEEFF, LB ALTER, HJ AF SEEFF, LB ALTER, HJ TI SPOUSAL TRANSMISSION OF THE HEPATITIS-C VIRUS SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID NON-B HEPATITIS; NON-A; UNITED-STATES; RISK-FACTORS; INFECTIONS; GENOME; HIV C1 NIH,BETHESDA,MD 20892. RP SEEFF, LB (reprint author), GEORGETOWN UNIV,SCH MED,DEPT VET AFFAIRS MED CTR,50 IRVING ST NW,WASHINGTON,DC 20422, USA. NR 30 TC 21 Z9 21 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 1994 VL 120 IS 9 BP 807 EP 809 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA NH251 UT WOS:A1994NH25100014 PM 8147555 ER PT J AU SIMPSON, IA CHUNDU, KR DAVIESHILL, T HONER, WG DAVIES, P AF SIMPSON, IA CHUNDU, KR DAVIESHILL, T HONER, WG DAVIES, P TI DECREASED CONCENTRATIONS OF GLUT1 AND GLUT3 GLUCOSE TRANSPORTERS IN THE BRAINS OF PATIENTS WITH ALZHEIMERS-DISEASE SO ANNALS OF NEUROLOGY LA English DT Article ID RAT-BRAIN; SYNAPTIC PATHOLOGY; SKELETAL-MUSCLE; BARRIER; LOCALIZATION; INSULIN; EXPRESSION; HEXOKINASE; SEQUENCE; PROTEINS AB Glucose metabolism is depressed in the temporal and parietal regions of the cortex in patients with Alzheimer's disease. We measured the concentrations of two glucose transporters, GLUT1 and GLUT3, in six regions of brains from both control subjects and patients with Alzheimer's disease. The concentrations of both transporters were reduced in the cerebral cortex, with larger and highly significant reductions observed for GLUT3, the putative neuronal glucose transporter. The reductions in GLUT3 were greater than the loss of synapses, and should be considered as a potential cause of the deficits in glucose metabolism. C1 ALBERT EINSTEIN COLL MED,DEPT PATHOL,BRONX,NY 10461. ALBERT EINSTEIN COLL MED,DEPT NEUROSCI,BRONX,NY 10461. NIDDKD,EXPTL DIABET METAB & NUTR SECT,BETHESDA,MD. FU NIA NIH HHS [AG06803]; NIMH NIH HHS [MH38623] NR 38 TC 202 Z9 205 U1 1 U2 12 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 1994 VL 35 IS 5 BP 546 EP 551 DI 10.1002/ana.410350507 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA NM108 UT WOS:A1994NM10800006 PM 8179300 ER PT J AU WHITAKER, JN WILLIAMS, PH LAYTON, BA MCFARLAND, HF STONE, LA SMITH, ME KACHELHOFER, RD BRADLEY, EL BURGARD, S ZHAO, GJ PATY, DW AF WHITAKER, JN WILLIAMS, PH LAYTON, BA MCFARLAND, HF STONE, LA SMITH, ME KACHELHOFER, RD BRADLEY, EL BURGARD, S ZHAO, GJ PATY, DW TI CORRELATION OF CLINICAL-FEATURES AND FINDINGS ON CRANIAL MAGNETIC-RESONANCE-IMAGING WITH URINARY MYELIN BASIC PROTEIN-LIKE MATERIAL IN PATIENTS WITH MULTIPLE-SCLEROSIS SO ANNALS OF NEUROLOGY LA English DT Article ID CEREBROSPINAL-FLUID; NATURAL-HISTORY; FOLLOW-UP; PEPTIDE; MRI; PROLIFERATION; REMYELINATION; EPITOPES; LESIONS AB Immunoreactive material that appears to be a peptide encompassing all or a portion of residues 80 to 89 of myelin basic protein is present in normal unconcentrated urine and is increased in certain patients with multiple sclerosis (MS). Compared with normal controls, urines collected randomly from 158 MS patients or in a clinical research unit from 8 patients with MS had higher mean values of urinary MBP-like material (MBPLM). The level of MBPLM in urine showed no direct relationship to MBPLM in cerebrospinal fluid and did not correlate with clinical relapses of disease. In the other neurological disease control group (26 patients), some patients with other inflammatory diseases, but not stroke or early phase Guillain-Barre syndrome, also showed elevations. Among the subtypes of MS, those with secondary chronic progressive disease had the highest values. Urinary MBPLM showed no definite correlation with or effect of treatment with glucocorticoids and immunosuppressants except that a lower level of urinary MBPLM showed a weak relationship with improvement following treatment with methylprednisoione/prednisone. In a serial study of 8 patients with unenhanced cranial magnetic resonance imaging and 20 patients with gadolinium-enhanced cranial magnetic resonance imaging, urinary MBPLM did not show a direct correlation with new or enhancing lesions. Urinary MBPLM does not parallel acute myelin damage but appears to reflect an ongoing process, possibly linked to attempted efforts at remyelination. C1 UNIV ALABAMA,DEPT CELL BIOL,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT BIOSTAT,BIRMINGHAM,AL 35294. UNIV ALABAMA,CTR NEUROIMMUNOL,BIRMINGHAM,AL. VET ADM MED CTR,NEUROL SERV,BIRMINGHAM,AL. VET ADM MED CTR,RES SERV,BIRMINGHAM,AL. NIH,NEUROIMMUNOL BRANCH,BETHESDA,MD. VANCOUVER GEN HOSP,DIV NEUROL,VANCOUVER,BC,CANADA. RP WHITAKER, JN (reprint author), UNIV ALABAMA,DEPT NEUROL,UAB STN,BIRMINGHAM,AL 35294, USA. FU NCRR NIH HHS [RR00032]; NINDS NIH HHS [NS23240] NR 38 TC 20 Z9 21 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 1994 VL 35 IS 5 BP 577 EP 585 DI 10.1002/ana.410350511 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA NM108 UT WOS:A1994NM10800010 PM 7513981 ER PT J AU UITTI, RJ SNOW, BJ SHINOTOH, H VINGERHOETS, FJG HAYWARD, M HASHIMOTO, S RICHMOND, J MARKEY, SP MARKEY, CJ CALNE, DB AF UITTI, RJ SNOW, BJ SHINOTOH, H VINGERHOETS, FJG HAYWARD, M HASHIMOTO, S RICHMOND, J MARKEY, SP MARKEY, CJ CALNE, DB TI PARKINSONISM INDUCED BY SOLVENT ABUSE SO ANNALS OF NEUROLOGY LA English DT Note ID TOLUENE AB We report the first description of a patient with parkinsonism induced by solvent abuse. Our patient developed parkinsonism acutely, following heavy abuse of lacquer thinner. Her clinical deficits were indistinguishable from idiopathic parkinsonism (Parkinson's disease) and she responded to levodopa. Parkinsonism has persisted for more than 3 months. Brain computed tomography was normal. Positron emission tomographic studies showed normal fluorodopa uptake and reduced raclopride binding, indicating an unusual disturbance of striatal dopaminergic function. This patient suggests that organic solvents may cause parkinsonism in susceptible individuals. C1 UNIV BRITISH COLUMBIA,CTR NEURODEGENERAT DISORDERS,VANCOUVER,BC,CANADA. UNIV BRITISH COLUMBIA,DEPT MED,VANCOUVER,BC,CANADA. STRATHCONA MED HLTH TEAM,VANCOUVER,BC,CANADA. NIMH,ANALYT BIOCHEM SECT,BETHESDA,MD. NR 15 TC 48 Z9 49 U1 1 U2 4 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 1994 VL 35 IS 5 BP 616 EP 619 DI 10.1002/ana.410350516 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA NM108 UT WOS:A1994NM10800015 PM 8179306 ER PT J AU MOON, RC STEELE, VE KELLOFF, GJ THOMAS, CF DETRISAC, CJ MEHTA, RG LUBET, RA AF MOON, RC STEELE, VE KELLOFF, GJ THOMAS, CF DETRISAC, CJ MEHTA, RG LUBET, RA TI CHEMOPREVENTION OF MNU-INDUCED MAMMARY TUMORIGENESIS BY HORMONE RESPONSE MODIFIERS - TOREMIFENE, RU-16117, TAMOXIFEN, AMINOGLUTETHIMIDE AND PROGESTERONE SO ANTICANCER RESEARCH LA English DT Article DE CHEMOPREVENTION; MNU-INDUCED MAMMARY TUMORIGENESIS; HORMONE RESPONSE MODIFIERS; TOREMIFENE; RU16117; TAMOXIFEN; AMINOGLUTETHIMIDE; PROGESTERONE ID METHYL-N-NITROSOUREA; ANTITUMOR ACTIONS; BREAST-CANCER; CARCINOGENESIS; ESTROGEN; TUMORS; RAT; INDUCTION; MODEL AB The effects of structurally different antiestrogens, progesterone and the aromatase inhibitor aminoglutethimide, were evaluated for chemopreventive activity in the N-methyl-N-nitrosourea (MNU)-induced mammary carcinogenesis model. Treatment with either RU 16117, progesterone or aminoglutethimide resulted in a significant decrease in cancer multiplicity [greater than or equal to 50%; P<.05] when administered individually at doses 80% of the maximally tolerated dose [MID]. Toremifene was also remarkably effective in inhibiting MNU-induced mammary tumorigenesis although this inhibition was achieved at a dose which caused a significant decrease in body weight gain, Aminoglutethimide, RU 16117 and toremifene citrate, in addition to their effects on tumor multiplicity, caused significant increases in the latency period for tumor development. Combinations of aminoglutethimide, progesterone and/or a suboptimal dose of tamoxifen citrate also proved to be effective in inhibiting the development of MNU-induced mammary cancers; however, the combination regimen was no more effective than either aminoglutethimide or progesterone administered alone. These results suggested that agents altering the hormonal environment, regardless of their mechanism of action, may provide protection against the development of hormone responsive mammary cancer. C1 IIT,RES INST,CHICAGO,IL 60616. NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. NR 25 TC 31 Z9 31 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 1994 VL 14 IS 3A BP 889 EP 893 PG 5 WC Oncology SC Oncology GA PD263 UT WOS:A1994PD26300018 PM 8074489 ER PT J AU MONTI, E SINHA, BK AF MONTI, E SINHA, BK TI ANTIPROLIFERATIVE EFFECT OF GENISTEIN AND ADRIAMYCIN AGAINST ESTROGEN-DEPENDENT AND ESTROGEN-INDEPENDENT HUMAN BREAST-CARCINOMA CELL-LINES SO ANTICANCER RESEARCH LA English DT Article DE GENISTEIN; ADRIAMYCIN; BREAST CARCINOMA; EGF RECEPTOR ID GROWTH-FACTOR RECEPTORS; TYROSINE KINASE; CANCER-CELLS; GLUTATHIONE-PEROXIDASE; TUMOR-CELLS; INHIBITOR; RESISTANCE; ACTIVATION; EXPRESSION; GENE AB The effects of the combination of genistein, a tyrosine kinase inhibitor, and adriainycin, an anthracycline anticancer drug, were studied in three human breast carcinoma cell lines (MCF-7/WT, MCF-7/ADR(R) and MDA-231) differing in estrogen receptor status and adriamycin sensitivity. Genistein inhibited cell proliferation in all three cell lines (IC50 between 7.0 and 37.0 mu M). The combination produced additive to synergistic effects; epidermal growth factor receptor modulation by adriamycin does not seem to be involved in this interaction. The possible therapeutic, advantage of this drug combination, especially on hormone-independent and multidrug resistant tumor cells, deserves further investigation. C1 NCI,CLIN PHARMACOL BRANCH,MOLEC & BIOCHEM PHARMACOL SECT,BETHESDA,MD 20892. RP MONTI, E (reprint author), UNIV MILAN,INST PHARMACOL,APPL PHARMACOL SECT,VIA VANVITELLI 32,I-20129 MILAN,ITALY. NR 26 TC 40 Z9 40 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 1994 VL 14 IS 3A BP 1221 EP 1226 PG 6 WC Oncology SC Oncology GA PD263 UT WOS:A1994PD26300072 PM 8074476 ER PT J AU HENDRIX, CW FLEXNER, C SZEBENI, J KUWAHARA, S PENNYPACKER, S WEINSTEIN, JN LIETMAN, PS AF HENDRIX, CW FLEXNER, C SZEBENI, J KUWAHARA, S PENNYPACKER, S WEINSTEIN, JN LIETMAN, PS TI EFFECT OF DIPYRIDAMOLE ON ZIDOVUDINE PHARMACOKINETICS AND SHORT-TERM TOLERANCE IN ASYMPTOMATIC HUMAN IMMUNODEFICIENCY VIRUS-INFECTED SUBJECTS SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID PLACEBO-CONTROLLED TRIAL; MONOCYTE MACROPHAGES; NUCLEOSIDE SALVAGE; HIV INFECTION; DOUBLE-BLIND; 3'-AZIDO-3'-DEOXYTHYMIDINE; INHIBITION; THERAPY; AIDS; AZT AB Zidovudine delays the progression of infection and prolongs the survival of human immunodeficiency virus (HIV)-infected patients, but these benefits are limited by dose-related toxicity and the cost of the drug. Dipyridamole, in micromolar concentrations, acts synergistically with zidovudine, reducing the anti-HIV 95% inhibitory concentration of zidovudine 5 to 10-fold in vitro. We sought to establish a well-tolerated dose of dipyridamole for use in combination with zidovudine and to detect clinically significant pharmacokinetic interactions. Both objectives are essential for planning studies of the efficacy of the zidovudine-dipyridamole combination. Eleven asymptomatic HIV-infected subjects (median CD4(+) cell count, 311 cells per mm(3)), 10 of whom had been on zidovudine at 500 mg/day for at least 6 months, were admitted to the study. Zidovudine pharmacokinetics were measured on day 1. Dipyridamole was then begun at 600 mg/day (subjects 1 to 3) or 450 mg/day (subjects 4 to 11), and zidovudine and dipyridamole pharmacokinetics were measured on day 5. All subjects given 600 mg of dipyridamole per day developed headache or nausea, or both. Six of eight subjects given dipyridamole at 450 mg/day developed headache or mild nausea that resolved after a median of 2 days. The area under the zidovudine concentration-time curve was not significantly different on day 1 in comparison with that on day 5 (P = 0.11). Symptoms were significantly correlated with the maximum zidovudine concentrations, which were achieved when dipyridamole was dosed concomitantly (p = 0.03). Total (free and protein-bound) dipyridamole trough concentrations were near those demonstrating synergy with zidovudine against PW in vitro. Dipyridamole was highly protein bound, with a median free/total dipyridamole ratio of 0.7%; the percent free/total dipyridamole ratio was inversely correlated with alpha, acid glycoprotein concentrations (r(2) = 0.66). Results of the study indicate that adjustment of the zidovudine dose was not required to achieve equivalent zidovudine concentrations when zidovudine was administered in combination with dipyridamole at the doses studied. In the short study described here, the zidovudine-dipyridamole combination was well tolerated in asymptomatic HIV-infected subjects after the occurrence of mild transient symptoms. C1 WILFORD HALL USAF MED CTR,CTR AIDS RES,DIV MED,LACKLAND AFB,TX 78236. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV CLIN PHARMACOL,BALTIMORE,MD 21287. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV INFECT DIS,BALTIMORE,MD 21287. JOHNS HOPKINS UNIV,SCH MED,DEPT PHARMACOL & MOLEC SCI,DIV CLIN PHARMACOL,BALTIMORE,MD 21287. JOHNS HOPKINS UNIV,SCH MED,DEPT PHARMACOL & MOLEC SCI,DIV INFECT DIS,BALTIMORE,MD 21287. JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,DIV CLIN PHARMACOL,BALTIMORE,MD 21287. NCI,BETHESDA,MD 20892. HENRY M JACKSON FDN ADVANCEMENT MIL MED,ROCKVILLE,MD 20850. MIL MED CONSORTIUM APPL RETROVIRAL RES,ROCKVILLE,MD 20850. RP HENDRIX, CW (reprint author), WILFORD HALL USAF MED CTR,DEPT INFECT DIS,LACKLAND AFB,TX 78236, USA. RI Hendrix, Craig/G-4182-2014 OI Hendrix, Craig/0000-0002-5696-8665 FU NIADDK NIH HHS [AM 26356] NR 20 TC 11 Z9 11 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAY PY 1994 VL 38 IS 5 BP 1036 EP 1040 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA NJ575 UT WOS:A1994NJ57500021 PM 8067734 ER PT J AU KAGEYAMA, S ANDERSON, BD HOESTEREY, BL HAYASHI, H KISO, Y FLORA, KP MITSUYA, H AF KAGEYAMA, S ANDERSON, BD HOESTEREY, BL HAYASHI, H KISO, Y FLORA, KP MITSUYA, H TI PROTEIN-BINDING OF HUMAN-IMMUNODEFICIENCY-VIRUS PROTEASE INHIBITOR KNI-272 AND ALTERATION OF ITS IN-VITRO ANTIRETROVIRAL ACTIVITY IN THE PRESENCE OF HIGH-CONCENTRATIONS OF PROTEINS SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID DEXTRAN SULFATE; RENIN INHIBITORS; INFECTION AB KNI-272 represents a peptide-based protease inhibitor having potent antiretroviral activity against human immunodeficiency virus (HIV) in vitro. The structure contains allophenylnorstatine [(2S,3S)-3-amino-2-hydroxy-4-phenylbutyric acid],vith a hydroxymethylcarbonyl isostere. We asked whether this experimental anti-HIV agent could exert its activity in vitro in the presence of relatively high concentrations of fetal calf serum (FCS) and assessed its protein-binding properties by using fresh human plasma preparations. The 50 and 75% inhibitory concentrations of KNI-272 against HIV type 1 replication in vitro were 3- to 5-fold and 5-fold higher in the presence of 50% FCS and 15- to 25-fold and 25- to 100-fold higher in the presence of 80% FCS, respectively, than those with 15% FCS, whereas the antiviral activity of 2',3'-dideoxyinosine was not significantly affected by FCS concentrations in the culture. Detailed studies of the protein binding of KNI-272 suggest that in human plasma binding occurs predominantly to alpha(1)-acid glycoprotein and that KNI-272 is probably extensively (similar to 98 to 99%) protein bound at concentrations likely to be achieved in the circulation. Thus, higher levels of KNI-272 in plasma may be required when this compound undergoes clinical trials relative to those inferred from in vitro data involving the use of 10 to 15% FCS containing culture media. The current data may have a relevance to other antiretroviral drugs that are under development and that have a high protein-binding capacity. C1 NCI,MED BRANCH,EXPTL RETROVIROL SECT,BETHESDA,MD 20892. NCI,TOXICOL BRANCH,BETHESDA,MD 20892. UNIV UTAH,DEPT PHARMACEUT & PHARMACEUT CHEM,SALT LAKE CITY,UT 84112. JAPAN ENERGY CORP,PHARMACEUT & BIOTECHNOL LAB,SAITAMA 335,JAPAN. KYOTO PHARMACEUT UNIV,DEPT MED CHEM,KYOTO 607,JAPAN. NR 27 TC 57 Z9 57 U1 0 U2 0 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 1994 VL 38 IS 5 BP 1107 EP 1111 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA NJ575 UT WOS:A1994NJ57500033 PM 8067746 ER PT J AU JACOBSON, MA POLSKY, B CAUSEY, D DAVIS, R TONG, W ODONNELL, JJ KUPPERMANN, BD HEINEMANN, MH FEINBERG, J LIZAK, P GAMBERTOGLIO, JG AWEEKA, FT AF JACOBSON, MA POLSKY, B CAUSEY, D DAVIS, R TONG, W ODONNELL, JJ KUPPERMANN, BD HEINEMANN, MH FEINBERG, J LIZAK, P GAMBERTOGLIO, JG AWEEKA, FT TI PHARMACODYNAMIC RELATIONSHIP OF PHARMACOKINETIC PARAMETERS OF MAINTENANCE DOSES OF FOSCARNET AND CLINICAL OUTCOME OF CYTOMEGALOVIRUS RETINITIS SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Note ID VIRUS; AIDS AB The pharmacodynamic relationship between a range of foscarnet exposure measurements obtained from studying nine patients receiving ongoing maintenance therapy for cytomegalovirus retinitis and a range of efficacy values (days to retinitis progression) obtained by independent examination of serial retinal photographs from the same nine patients was analyzed. In the resulting proportional hazards models, the foscarnet area under the concentration-time curve approached statistical significance (P = 0.11) as a predictor of decreased risk of retinitis progression. C1 UNIV CALIF SAN FRANCISCO,DEPT MED,SAN FRANCISCO,CA. UNIV CALIF SAN FRANCISCO,DEPT OPHTHALMOL,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DIV CLIN PHARM,SAN FRANCISCO,CA 94143. SAN FRANCISCO GEN HOSP,MED SERV,SAN FRANCISCO,CA 94110. SAN FRANCISCO GEN HOSP,OPHTHALMOL SERV,SAN FRANCISCO,CA 94110. UNIV SO CALIF,LOS ANGELES CTY MED CTR,DEPT MED,LOS ANGELES,CA 90033. UNIV SO CALIF,LOS ANGELES CTY MED CTR,DEPT OPHTHALMOL,LOS ANGELES,CA 90033. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. CORNELL UNIV,COLL MED,NEW YORK,NY. HARVARD UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BOSTON,MA 02115. NIAID,DIV AIDS,AIDS CLIN TRIALS GRP,BETHESDA,MD. FU NCRR NIH HHS [RR-00083]; NIAID NIH HHS [AI-27663] NR 12 TC 5 Z9 5 U1 0 U2 0 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 1994 VL 38 IS 5 BP 1190 EP 1193 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA NJ575 UT WOS:A1994NJ57500052 PM 8067763 ER PT J AU CENTENO, JA ISHAK, KG MULLICK, FG GAHL, WA OLEARY, TJ AF CENTENO, JA ISHAK, KG MULLICK, FG GAHL, WA OLEARY, TJ TI INFRARED MICROSPECTROSCOPY AND LASER RAMAN MICROPROBE IN THE DIAGNOSIS OF CYSTINOSIS SO APPLIED SPECTROSCOPY LA English DT Article DE CYSTINE; CYSTINOSIS; INFRARED MICROSPECTROSCOPY; RAMAN MICROPROBE ID SPECTROSCOPIC IDENTIFICATION; MICROSCOPIC IDENTIFICATION; KIDNEY-STONE; MICROSPECTROSCOPY; SECTIONS; TISSUES AB Infrared microspectroscopy and the laser Raman microprobe method have been employed for the identification of cystine crystals in human tissue specimens. Scanning electron microscopy was also employed to study the morphologic changes associated with the formation of these crystals in tissue. For the Raman microprobe experiments, unstained tissue specimens sectioned at 6 to 10-mum were mounted on an ordinary microscope glass slide and excited with the 514.5-nm line from an argon-ion laser. Cystine crystals in liver and spleen specimens were easily identified by the enhancement of Raman lines at 501 and 2916-2967 cm-1 arising from the disulfide (S-S) linkage and the C-H stretch motion, respectively. The infrared spectra, on the other hand, displayed absorptions at 1338, 1411, and 1621 - 1656 cm-1 assigned to the cystine C-C, -COO, and C=O group stretching frequencies, respectively. In contrast to previous macro-analytical applications of Raman scattering and infrared spectroscopy, the micro-analytical experimental approach developed here allows for morphologic and analytical determinations to be conducted on the same tissue specimen. In addition, because of the nondestructive nature of Raman and infrared microspectroscopy, the combination of these two techniques provides a rapid, accurate, and sensitive analysis to improve the diagnosis of these materials in tissue sections. C1 NICHHD,BETHESDA,MD 20892. ARMED FORCES INST PATHOL,DEPT HEPAT PATHOL,WASHINGTON,DC 20306. ARMED FORCES INST PATHOL,DEPT CELLULAR PATHOL,WASHINGTON,DC 20306. RP CENTENO, JA (reprint author), ARMED FORCES INST PATHOL,DEPT ENVIRONM & TOXICOL PATHOL,BLDG 54,ROOM 2051,WASHINGTON,DC 20306, USA. NR 23 TC 10 Z9 10 U1 0 U2 1 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 1994 VL 48 IS 5 BP 569 EP 572 DI 10.1366/0003702944924745 PG 4 WC Instruments & Instrumentation; Spectroscopy SC Instruments & Instrumentation; Spectroscopy GA NP999 UT WOS:A1994NP99900008 ER PT J AU CORCORAN, ML STETLERSTEVENSON, WG DEWITT, DL WAHL, LM AF CORCORAN, ML STETLERSTEVENSON, WG DEWITT, DL WAHL, LM TI EFFECT OF CHOLERA-TOXIN AND PERTUSSIS TOXIN ON PROSTAGLANDIN-H SYNTHASE-2, PROSTAGLANDIN E(2), AND MATRIX METALLOPROTEINASE PRODUCTION BY HUMAN MONOCYTES SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID MACROPHAGE COLLAGENASE PRODUCTION; HUMAN PERIPHERAL-BLOOD; CYCLOOXYGENASE EXPRESSION; INTERSTITIAL COLLAGENASE; MESSENGER-RNA; GROWTH-FACTOR; INHIBITION; INDUCTION; CELLS; SECRETION AB Activation of human monocytes induces the production of matrix metalloproteinases (MMPs) through a prostaglandin E(2) (PGE(2))-cAMP-dependent pathway. Since G-proteins have been documented to modulate adenylyl cyclase, we examined the effect of G-protein ADP-ribosylating agents, cholera toxin (CT) and pertussis toxin (PT), on the signal transduction pathway that culminates in the production of monocyte MMPs. Although CT elevated cAMP levels in both unstimulated and concanavalin A (Con A)-stimulated monocytes, it enhanced the production of prostaglandin H synthase-2 (PGH synthase-2, PGHS-2) protein, prostaglandins, interstitial collagenase, and 92-kDa type IV collagenase/gelatinase only in Con A-stimulated monocytes. Additionally the indomethacin-mediated suppression of Con A-induced monocyte interstitial collagenase and 92-kDa type IV collagenase/gelatinase production could be reversed by CT. In contrast to the actions of CT, PT treatment suppressed the levels of cAMP, PGHS-2, PGE(2), interstitial and 92-kDa type IV collagenase/gelatinase in Con A-stimulated monocytes. The regulation of MMP production by these toxins appears to be mediated primarily through their effect on adenylyl cyclase since the release of arachidonic acid was relatively unaffected by these agents. These findings provide evidence that G-proteins may be involved in either the enhancement or suppression of the eicosanoid-cAMP-dependent signal transduction pathway that results in the production of monocyte MMPs. (C) 1994 Academic Press, Inc. C1 NCI,PATHOL LAB,TUMOR INVAS & METASTASIS SECT,BETHESDA,MD 20892. MICHIGAN STATE UNIV,DEPT BIOCHEM,E LANSING,MI 48824. RP CORCORAN, ML (reprint author), NIDR,IMMUNOL LAB,CELLULAR IMMUNOL SECT,9000 ROCKVILLE PIKE,BLDG 30,ROOM 325,BETHESDA,MD 20892, USA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 39 TC 68 Z9 70 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD MAY 1 PY 1994 VL 310 IS 2 BP 481 EP 488 DI 10.1006/abbi.1994.1196 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NH392 UT WOS:A1994NH39200027 PM 8179336 ER PT J AU SHEAR, MK MASER, JD AF SHEAR, MK MASER, JD TI STANDARDIZED ASSESSMENT FOR PANIC DISORDER RESEARCH - A CONFERENCE REPORT SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Editorial Material ID ANXIETY; ATTACKS; QUESTIONNAIRE; VALIDITY; FEAR AB Lively controversies related to panic disorder are under active investigation by research groups around the world. However, publications from different laboratories are difficult to compare since there has been little consistency in measures or even in types of assessment used to characterize and follow up patients. Participants in the recently convened National Institutes of Health Consensus Development Conference on the Treatment of Panic Disorder noted this problem and recommended establishment of procedures to ensure comparability of studies. We organized a conference of clinical investigators whose objective was to develop a standard assessment package. Participants represented biological and psychosocial panic disorder treatment research sites in the United States and Canada. The 2-day conference resulted in agreement on a battery of assessments considered essential for panic disorder studies. The purposes of our report are to disseminate the conference conclusions and to encourage adoption of the proposed standards by clinical researchers, journal editors. Public Health Service peer review committees, and the Food and Drug Administration. We also identify some problematic issues that require further work. C1 UNIV PITTSBURGH,DEPT PSYCHIAT,PITTSBURGH,PA. NIMH,BETHESDA,MD. NR 31 TC 157 Z9 158 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD MAY PY 1994 VL 51 IS 5 BP 346 EP 354 PG 9 WC Psychiatry SC Psychiatry GA NM119 UT WOS:A1994NM11900001 PM 8179458 ER PT J AU CORYELL, W AKISKAL, HS LEON, AC WINOKUR, G MASER, JD MUELLER, TI KELLER, MB LAVORI, PW SHEA, MT FAWCETT, JA SCHEFTNER, WA HALEY, J ENDICOTT, J LOTH, J RICE, J REICH, T ANDREASEN, NC CLAYTON, PJ CROUGHAN, J KLERMAN, GL HIRSCHFELD, RMA KATZ, MM ROBINS, E SHAPIRO, RW SPITZER, RL WINOKUR, G YOUNG, M AF CORYELL, W AKISKAL, HS LEON, AC WINOKUR, G MASER, JD MUELLER, TI KELLER, MB LAVORI, PW SHEA, MT FAWCETT, JA SCHEFTNER, WA HALEY, J ENDICOTT, J LOTH, J RICE, J REICH, T ANDREASEN, NC CLAYTON, PJ CROUGHAN, J KLERMAN, GL HIRSCHFELD, RMA KATZ, MM ROBINS, E SHAPIRO, RW SPITZER, RL WINOKUR, G YOUNG, M TI THE TIME-COURSE OF NONCHRONIC MAJOR DEPRESSIVE DISORDER - UNIFORMITY ACROSS EPISODES AND SAMPLES SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID FOLLOW-UP; BIPOLAR-II; PREDICTORS; PLACEBO; PSYCHOPATHOLOGY; CHRONICITY; INPATIENTS; RECOVERY; RELAPSE AB Background: Most natural history studies of affective disorders have emphasized the prediction of eventual recovery. Little is known of changes over time in the immediate probability of recovery. Methods: To identify regularities in the timing of recovery from nonbipolar major depressive disorders, we considered only episodes that began during follow-up to increase the accuracy with which onsets were timed and to limit the study sample to individuals who had a demonstrably episodic course. Five participating centers conducted baseline assessments and followed probands (N=605) and nonclinical subjects (relatives, controls, and spouses, N=826) up for 6 years. During that time, 359 probands had at least one prospectively observed episode, and 181 had two episodes; corresponding numbers for the nonclinical subjects were 216 and 78, respectively. Our analyses considered the distribution of episode lengths across ascertainment source (probands vs nonclinical subjects), center, and episode number (first vs second prospectively observed episode). Results: Distribution was remarkably uniform. Regardless of ascertainment source, center, or episode number, recovery occurred within 3 months in 40% of episodes, within 6 months in 60%, and within 1 year in 80%; 20% had more protracted courses. Conclusions: Once triggered, the immediate likelihood of recovery changes over time in a predictable fashion. This has practical implications for the study of antidepressant efficacy and theoretical implications for factors involved in affective dysregulation. C1 NIMH,ROCKVILLE,MD. CORNELL UNIV,NEW YORK HOSP,MED CTR,ITHACA,NY 14853. BUTLER HOSP,DEPT PSYCHIAT,PROVIDENCE,RI. RP CORYELL, W (reprint author), UNIV IOWA,COLL MED,DEPT PSYCHIAT,1-457 MED EDUC BLDG,IOWA CITY,IA 52242, USA. FU NIMH NIH HHS [R01 MH025478] NR 30 TC 66 Z9 67 U1 0 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 1994 VL 51 IS 5 BP 405 EP 410 PG 6 WC Psychiatry SC Psychiatry GA NM119 UT WOS:A1994NM11900007 PM 8179464 ER PT J AU LANG, DS BECKER, S CLARK, GC DEVLIN, RB KOREN, HS AF LANG, DS BECKER, S CLARK, GC DEVLIN, RB KOREN, HS TI LACK OF DIRECT IMMUNOSUPPRESSIVE EFFECTS OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD) ON HUMAN PERIPHERAL-BLOOD LYMPHOCYTE SUBSETS IN-VITRO SO ARCHIVES OF TOXICOLOGY LA English DT Article DE 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD); HUMAN PERIPHERAL BLOOD LYMPHOCYTES; SURFACE ANTIGEN EXPRESSION; MITOGEN STIMULATION IN VITRO; CYTOCHROME P450 (CYP1A1) ENZYME INDUCTION ID PRIMATE CALLITHRIX-JACCHUS; DIBENZO-PARA-DIOXINS; IMMUNE-SYSTEM; POLYBROMINATED BIPHENYLS; IMMUNOLOGICAL EVALUATION; EPITHELIAL-CELLS; INVITRO MODEL; EXPOSURE; TOXICITY; MICE AB A wide variety of immunosuppressive effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in experimental animals has been documented. In contrast, the impact of dioxin on the human immune system remains controversial, although adverse health effects have been reported in humans after occupational or accidental exposure to dioxin. Recently, Neubert et al. (1991) found that a dose-dependent decrease of peripheral blood lymphocyte (PBL) subpopulations in humans and nonhuman primates, including helper-inducer/memory cells (CD4(+)CD29(+)) and B cells (CD20(+)) occurred in pokeweed mitogen (PWM) stimulated cultures at concentrations as low as 10(-2)-10(-14) M TCDD. Therefore, the direct effects of dioxin on human PBL subpopulations have been studied, in order to determine their usefulness as sensitive biomarkers for human dioxin exposure. Lymphocyte cultures from healthy individuals were treated with 10(-7) M-10(-14) M TCDD in the absence and presence of stimulation with pokeweed mitogen (PWM) or anti-CDS monoclonal antibody (moAb; OKT3) for 3 days. Cytochrome P450 (CYP1A1) enzyme induction, one of the best studied direct biological study, all stimulated lymphocyte cultures showed a dose-dependent significant increase of CYP1A1 activity at dioxin concentrations of 10(-7) and 10(-9) M. No enzyme activity could be detected at lower concentrations of TCDD. On the other hand, neither alteration in surface marker distribution nor suppression of lymphocyte proliferation could be demonstrated in mitogen-activated cells following any concentration of TCDD treatment. These data suggest that the inducibility of CYP1A1 enzyme activity is not correlated with direct immunotoxic effects in vitro in human PBL. In contrast to a previous report by Neubert et al. (1991), lymphoproliferation and phenotypes of human PBL are resistant to dioxin exposure in vitro and therefore appeared not to be useful as sensitive biomarkers in human exposure studies.effects of TCDD on numerous cell types, was assayed in parallel by ethoxyresorufin-O-deethylase (EROD) activity. Percentages of the different lymphocytes subsets, including CD2 (T cells); CD4; CD45 RA (suppressor-inducer/virgin T cells); CD4 CD29; CD8; CD19 (B cells) as well as interleukin 2 (IL-2) receptor (CD25) and class II antigen (HLA-DR) expression, were analyzed by flow cytometry. DNA synthesis was determined by H-3-thymidine uptake after 3 days of culture. In the present study, all stimulated lymphocyte cultures showed a dose-dependent significant increase of CYP1A1 activity at dioxin concentrations of 10(-7) and 10(-9) M. No enzyme activity could be detected at lower concentrations of TCDD. On the other hand, neither alteration in surface marker distribution nor suppression of lymphocyte proliferation could be demonstrated in mitogen-activated cells following any concentration of TCDD treatment. These data suggest that the inducibility of CYP1A1 enzyme activity is not correlated with direct immunotoxic effects in vitro in human PBL. In contrast to a previous report by Neubert et al. (1991), lymphoproliferation and phenotypes of human PBL are resistant to dioxin exposure in vitro and therefore appeared not to be useful as sensitive biomarkers in human exposure studies. C1 UNIV N CAROLINA,CTR ENVIRONM MED & LUNG BIOL,CHAPEL HILL,NC. TRC ENVIRONM CORP INC,CHAPEL HILL,NC. NIEHS,BIOCHEM RISK ANAL LAB,RES TRIANGLE PK,NC. US EPA,HLTH EFFECTS RES LAB,RES TRIANGLE PK,NC. NR 45 TC 25 Z9 26 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-5761 J9 ARCH TOXICOL JI Arch. Toxicol. PD MAY PY 1994 VL 68 IS 5 BP 296 EP 302 DI 10.1007/s002040050072 PG 7 WC Toxicology SC Toxicology GA NM035 UT WOS:A1994NM03500004 PM 8085940 ER PT J AU LALONDE, FM BISHOP, EF MARTON, G MARTIN, A AF LALONDE, FM BISHOP, EF MARTON, G MARTIN, A TI A CLIENT-SERVER TECHNOLOGY SOLUTION FOR A MULTICENTER RESEARCH DATABASE SO BEHAVIOR RESEARCH METHODS INSTRUMENTS & COMPUTERS LA English DT Article ID MACINTOSH SOFTWARE AB As researchers take advantage of advances in computer and related technologies, the amount of data has increased dramatically. Recent developments in database management systems (DBMS) such as client-server database technology provide the necessary tools for merging and managing data from various fields of study, as well as, various locations. This emerging technology allows the distribution of processing and data storage operations to a variety of computer platforms, thereby maximizing efficiency and flexibility. A DBMS that uses client-server technology is described. RP LALONDE, FM (reprint author), NIMH,CLIN SCI LAB,BLDG 10 ROOM 3D41,BETHESDA,MD 20892, USA. RI martin, alex/B-6176-2009 NR 13 TC 0 Z9 0 U1 0 U2 0 PU PSYCHONOMIC SOC INC PI AUSTIN PA 1710 FORTVIEW RD, AUSTIN, TX 78704 SN 0743-3808 J9 BEHAV RES METH INSTR JI Behav. Res. Methods Instr. Comput. PD MAY PY 1994 VL 26 IS 2 BP 198 EP 201 DI 10.3758/BF03204619 PG 4 WC Psychology, Mathematical; Psychology, Experimental SC Psychology GA NK980 UT WOS:A1994NK98000023 ER PT J AU KASLOW, DC SHILOACH, J AF KASLOW, DC SHILOACH, J TI PRODUCTION, PURIFICATION AND IMMUNOGENICITY OF A MALARIA TRANSMISSION-BLOCKING VACCINE CANDIDATE - TBV25H EXPRESSED IN YEAST AND PURIFIED USING NICKEL-NTA AGAROSE SO BIO-TECHNOLOGY LA English DT Note ID PLASMODIUM-FALCIPARUM; ANTIBODIES; PROTEIN AB We have constructed a second generation malaria transmission-blocking vaccine candidate based on Pfs25, the predominate surface protein of Plasmodium falciparum zygotes, to overcome potential production problems with the original construct. Four modifications were made: (1) addition of the last cysteine residue of the fourth epidermal growth factor like-domain of Pfs25; (2) mutagenesis of asparagine-linked glycosylation sites with glutamine rather than alanine; (3) addition of a six histidine tag at the carboxy-terminus for highly efficient purification of recombinant protein on nickel-NTA agarose; and (4) fermentation that combines continuous glucose fed-batch methodology with pH-controlled glucose addition and a terminal ethanol feed. The resulting product, TBV25H (Transmission-Blocking Vaccine based on Pfs25 with a Histidine tag), appears to be a more potent antigen and immunogen than the original construct, and the fermentation and post-fermentation processing methodology easily lend themselves to technology transfer to the ultimate users, newly industrialized countries. C1 NIDDKD,BIOTECHNOL UNIT,CELLULAR & DEV BIOL LAB,BETHESDA,MD 20892. RP KASLOW, DC (reprint author), NIAID,MOLEC VACCINE SECT,MALARIA RES LAB,BETHESDA,MD 20892, USA. NR 14 TC 91 Z9 94 U1 0 U2 4 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 0733-222X J9 BIO-TECHNOL JI Bio-Technology PD MAY PY 1994 VL 12 IS 5 BP 494 EP 499 DI 10.1038/nbt0594-494 PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA NJ863 UT WOS:A1994NJ86300025 PM 7764708 ER PT J AU WILSON, CM CUSHMAN, SW AF WILSON, CM CUSHMAN, SW TI INSULIN STIMULATION OF GLUCOSE-TRANSPORT ACTIVITY IN RAT SKELETAL-MUSCLE - INCREASE IN CELL-SURFACE GLUT4 AS ASSESSED BY PHOTOLABELING SO BIOCHEMICAL JOURNAL LA English DT Article ID 3T3-L1 ADIPOCYTES; ADIPOSE-CELLS; EXERCISE; LOCALIZATION; DISPOSAL; IDENTIFICATION; TRANSLOCATION; DIFFUSION; MEMBRANES; MECHANISM AB We have used a photoaffinity label to quantify cell surface GLUT4 glucose transporters in isolated rat soleus muscles. In this system, insulin stimulated an 8.6-fold increase in 3-O-methylglucose glucose transport, while photolabelled GLUT4 increased 8-fold. These results demonstrate that the insulin-stimulated increase in glucose transport activity in skeletal muscle can be accounted for by an increase in surface-accessible GLUT4 content. RP WILSON, CM (reprint author), NIDDKD,EXPTL DIABET METAB & NUTR SECT,DIABET BRANCH,BLDG 10,RM 5N102,BETHESDA,MD 20892, USA. NR 42 TC 86 Z9 87 U1 1 U2 1 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD MAY 1 PY 1994 VL 299 BP 755 EP 759 PN 3 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NK092 UT WOS:A1994NK09200024 PM 8192664 ER PT J AU WATSON, K EDWARDS, RJ PARMELEE, DC SHAUNAK, S GOODERHAM, NJ DAVIES, DS AF WATSON, K EDWARDS, RJ PARMELEE, DC SHAUNAK, S GOODERHAM, NJ DAVIES, DS TI HISTONES LOCATED ON THE PLASMA-MEMBRANE OF T-CELLS SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article; Proceedings Paper CT 649th Meeting of the Biochemical-Society CY DEC 19-21, 1993 CL IMPERIAL COLL LONDON, LONDON, ENGLAND SP BIOCHEM SOC HO IMPERIAL COLL LONDON ID PROTEINS; BINDING; ANTIGEN; SURFACE; IDENTIFICATION; AUTOANTIBODIES; EXPRESSION; SULFATE C1 ROYAL POSTGRAD MED SCH,DEPT INFECT DIS,LONDON W12 0NN,ENGLAND. NCI,BETHESDA,MD 20892. RP WATSON, K (reprint author), ROYAL POSTGRAD MED SCH,DEPT CLIN PHARMACOL,DU CANE RD,LONDON W12 0NN,ENGLAND. NR 14 TC 6 Z9 6 U1 0 U2 1 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD MAY PY 1994 VL 22 IS 2 BP S199 EP S199 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA NQ955 UT WOS:A1994NQ95500179 PM 7958262 ER PT J AU KAWCZYNSKI, W TORRENCE, PF KINJO, JE CZOCHRALSKA, B AF KAWCZYNSKI, W TORRENCE, PF KINJO, JE CZOCHRALSKA, B TI ELECTROCHEMICAL STUDY OF A PYRIDINE ANALOG OF 3'-AZIDO-3'-DEOXYTHYMIDINE (AZT) RELATED TO AIDS DEMENTIA SO BIOELECTROCHEMISTRY AND BIOENERGETICS LA English DT Article ID REDOX TRANSFORMATIONS; ZIDOVUDINE; REDUCTION; BRAIN; 3'-AZIDOTHYMIDINE; NUCLEOSIDES; SYSTEM; BLOOD; NADH AB The detailed mechanism of the electrochemical reduction in aqueous media of 5'-(1,4-dihydro-1-methyl-3-pyridinylcarbonyl)-3'- azido-3'-deoxythymidine (HPAZT) and 5'-(1-methyl-3-pyridinium-carbonyl)-3'-azido-3'-deoxythymidine (PAZT), the pyridine analogs of 3'-azido-3'-deoxythymidine (AZT), has been elucidated on the basis of a variety of electrochemical techniques as well as spectrophotometric and chromatographic analysis of the two species and their reduction products. Both compounds undergo two-electron reduction of the azido group to corresponding amino derivatives. In the pH range 2-7, PAZT undergoes additional one-electron reduction of the pyridine ring to produce a free radical followed by dimerization. Air compounds exhibit a high surface activity as confirmed by ac polarography. Application of cyclic voltammetry for monitoring the level of HPAZT in solution is reported. In addition, the photochemical transformation of HPAZT upon UV irradiation has also been examined. C1 NIDDKD,ANALYT CHEM LAB,BIOMED CHEM SECT,BETHESDA,MD 20892. RP KAWCZYNSKI, W (reprint author), UNIV WARSAW,INST PHYS EXPTL,DEPT BIOPHYS,93 ZWIRKI & WIGURY ST,PL-02089 WARSAW,POLAND. NR 30 TC 7 Z9 8 U1 0 U2 2 PU ELSEVIER SCIENCE SA LAUSANNE PI LAUSANNE 1 PA PO BOX 564, 1001 LAUSANNE 1, SWITZERLAND SN 0302-4598 J9 BIOELECTROCH BIOENER JI Bioelectrochem. Bioenerg. PD MAY PY 1994 VL 33 IS 2 BP 171 EP 179 DI 10.1016/0302-4598(94)85009-7 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA NJ827 UT WOS:A1994NJ82700009 ER PT J AU CHAE, HZ RHEE, SG AF CHAE, HZ RHEE, SG TI A THIOL-SPECIFIC ANTIOXIDANT AND SEQUENCE HOMOLOGY TO VARIOUS PROTEINS OF UNKNOWN FUNCTION SO BIOFACTORS LA English DT Article ID ALKYL HYDROPEROXIDE REDUCTASE; FREE-RADICAL METABOLITES; SALMONELLA-TYPHIMURIUM; SACCHAROMYCES-CEREVISIAE; ENTAMOEBA-HISTOLYTICA; HYDROGEN-PEROXIDE; ESCHERICHIA-COLI; GENE; GLUTATHIONE; OXIDATION AB Yeast and mammalian cells contain a 25 kDa enzyme that protects cellular components against oxidative damage from a system capable of generating reactive sulfur species, but not from a system that generates only reactive oxygen species. Yeast and rat cDNAs corresponding to this thiol-specific antioxidant (TSA) have been cloned and sequenced. Rat TSA is 65.3% identical and 76.2% similar to yeast TSA in amino acid sequence. A search of the GenBank database revealed 12 additional TSA-like proteins, which show sequence identity to rat TSA ranging from 31 to 76%. Except for the AhpC protein identified in Salmonella typhimurium, none of the TSA-like proteins is associated with known cellular functions. AhpC, which exhibits similar to 40% sequence identity to TSA, has been proposed to be a catalytic component of alkyl hydroperoxide reductase. Alignment of rat and yeast TSA with the TSA-like sequences revealed two conserved cysteine residues, one conserved in all 14 sequences and the other in 12 sequences. The most conserved cysteine is located in a well-conserved motif of (hydrophobic residue)(6)-Pro-non-conserved-residue-Asp-Phe-Thr-Phe-Val-Cys-Pro-Thr-Glu-hydrophobic residue. These results suggest that the TSA-like proteins of previously unknown function may represent a widely distributed family of antioxidants with functions similar to those of TSA and AhpC. C1 NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. NR 35 TC 64 Z9 65 U1 1 U2 1 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 1994 VL 4 IS 3-4 BP 177 EP 180 PG 4 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA NQ469 UT WOS:A1994NQ46900008 PM 7916964 ER PT J AU STADTMAN, TC AF STADTMAN, TC TI EMERGING AWARENESS OF THE CRITICAL ROLES OF S-PHOSPHOCYSTEINE AND SELENOPHOSPHATE IN BIOLOGICAL-SYSTEMS SO BIOFACTORS LA English DT Review ID DEPENDENT PHOSPHOTRANSFERASE SYSTEM; PROTEIN-TYROSINE-PHOSPHATASE; ESCHERICHIA-COLI; VIRULENCE DETERMINANT; SELENIUM METABOLISM; MANNITOL TRANSPORT; TRANSFER-RNA; PURIFICATION; EXPRESSION; YERSINIA AB S-Phosphocysteine residues in proteins are formed as key intermediates in certain enzyme-catalyzed reactions. In phosphoenolpyruvate (PEP)-dependent carbohydrate transport processes, the phosphoryl group of PEP is transferred sequentially to histidine residues of two cytoplasmic proteins, Enzyme I and HPr, common to all of the PEP-dependent carbohydrate transport systems. The phosphoryl group of HPr then is transferred to an essential histidine and an essential cysteine residue located in the cytoplasmic domains of certain substrate-specific, membrane-bound proteins, the actual transporters. Both the N-phosphohistidine and the S-phosphocysteine residues in these Enzyme ZI domains are transient catalytic intermediates in the final steps that lead to phosphorylation of the bound carbohydrate substrate. In a different type of biological system, numerous proteins involved in signal transduction pathways are phosphorylated on spec tyrosine residues by various kinases and the effects of these modifications are modulated by a family of protein tyrosine phosphate-specific phosphatases. The mechanism of action of these phosphatases involves the transfer of the phosphoryl group from a phosphotyrosine residue in the protein substrate to an essential ionized cysteine residue in the phosphatase polypeptide forming an S-phosphocysteine residue. Reaction of the latter with water and release of orthophosphate complete the phosphatase-catalyzed reaction. Selenophosphate, formed by phosphorylation of a selenol, is a key selenium donor compound in prokaryotes. This extremely oxygen-labile compound is synthesized from ATP and selenide by selenophosphate synthetase. This novel reactive selenium compound is the selenium donor for selenocysteyl-tRNA biosynthesis and for conversion of 2-thiouridine residues in tRNAs to 2-selenouridine. The selenocysteyl-tRNA is required for UGA codon-directed insertion of selenocysteine in proteins. The 2-selenouridine residues in the 'wobble position' [U(34)] of the anticodons of certain tRNAs can influence recognition of their degenerate G-ending and A-ending codons. Whereas the presence of a 2-thiouridine residue at position 34 favors base pairing with the A-ending codons, this discrimination is removed when the sulfur is replaced with selenium. RP STADTMAN, TC (reprint author), NHLBI,BIOCHEM LAB,BLDG 3,ROOM 108,BETHESDA,MD 20892, USA. NR 40 TC 11 Z9 11 U1 0 U2 2 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 1994 VL 4 IS 3-4 BP 181 EP 185 PG 5 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA NQ469 UT WOS:A1994NQ46900009 PM 7916965 ER PT J AU RUBINOW, DR SU, TP AF RUBINOW, DR SU, TP TI ANDROGENIC STEROIDS - EFFECTS ON BRAIN AND BEHAVIOR SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 619 EP 620 DI 10.1016/0006-3223(94)90675-0 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200019 ER PT J AU SCHMIDT, PJ BERMAN, KF OLLO, CA RUBINOW, DR AF SCHMIDT, PJ BERMAN, KF OLLO, CA RUBINOW, DR TI EFFECTS OF MEDICAL OOPHORECTOMY AND HORMONE REPLACEMENT ON MOOD, SEXUAL INTEREST, COGNITION - AND CEREBRAL BLOOD-FLOW SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. NIMH,CLIN BRAIN DISORDERS BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 619 EP 619 DI 10.1016/0006-3223(94)90674-2 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200018 ER PT J AU MANJI, HK AF MANJI, HK TI G-PROTEINS - MOLECULAR TARGETS FOR GONADAL-STEROIDS SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,EXPTL THERAPEUT BRANCH,CLIN PHARMACOL SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 620 EP 620 DI 10.1016/0006-3223(94)90677-7 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200021 ER PT J AU BERMAN, KF OSTREM, JL MATTAY, VS ESPOSITO, G VANHORN, JD ABI-DARGHAM, A TORREY, EF WEINBERGER, DR AF BERMAN, KF OSTREM, JL MATTAY, VS ESPOSITO, G VANHORN, JD ABI-DARGHAM, A TORREY, EF WEINBERGER, DR TI THE ROLES OF THE DORSOLATERAL PREFRONTAL CORTEX AND HIPPOCAMPUS IN WORKING-MEMORY AND SCHIZOPHRENIA SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 ST ELIZABETH HOSP, NIMH,CTR NEUROSCI,PET UNIT, CLIN BRAIN DISORDERS BRANCH,IRP, WASHINGTON, DC 20032 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 622 EP 622 DI 10.1016/0006-3223(94)90684-X PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200028 ER PT J AU KOTRLA, KJ MATTAY, VS DUYN, JH VANGELDEREN, P JONES, DW BARRIOS, FA SEXTON, RH MOONEN, CTW FRANK, JA WEINBERGER, DR AF KOTRLA, KJ MATTAY, VS DUYN, JH VANGELDEREN, P JONES, DW BARRIOS, FA SEXTON, RH MOONEN, CTW FRANK, JA WEINBERGER, DR TI 3-DIMENSIONAL FUNCTIONAL MRT IN SCHIZOPHRENICS AND NORMAL VOLUNTEERS PERFORMING THE WISCONSIN-CARD-SORTING-TEST SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,INTRAMURAL RES PROGRAM,CLIN BRAIN DISORDERS BRANC,WASHINGTON,DC 20032. RI Duyn, Jozef/F-2483-2010; Barrios, Fernando/B-4295-2012; Barrios, Fernando/D-1591-2016 OI Barrios, Fernando/0000-0002-5699-4222 NR 0 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 623 EP 623 DI 10.1016/0006-3223(94)90687-4 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200031 ER PT J AU GLOWA, JR WOJNICKI, FHE MATECKA, D RICE, KC ROTHMAN, RB AF GLOWA, JR WOJNICKI, FHE MATECKA, D RICE, KC ROTHMAN, RB TI DOPAMINE REUPTAKE BLOCKERS AND DRUG SEEKING BEHAVIOR SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIDDK,MED CHEM LAB,BETHESDA,MD 20892. NIDA,CLIN PSYCHOPHARMACOL SECT,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 625 EP 625 DI 10.1016/0006-3223(94)90695-5 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200039 ER PT J AU BERRETTINI, W FERRARO, T GOLDIN, L WEEKS, D DETERAWADLEIGH, S NURNBERGER, J GERSHON, E AF BERRETTINI, W FERRARO, T GOLDIN, L WEEKS, D DETERAWADLEIGH, S NURNBERGER, J GERSHON, E TI EVIDENCE FOR AN 18P11 BIPOLAR SUSCEPTIBILITY LOCUS SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 THOMAS JEFFERSON UNIV,PHILADELPHIA,PA 19107. NIMH,BETHESDA,MD 20892. UNIV PITTSBURGH,PITTSBURGH,PA. INDIANA UNIV,INDIANAPOLIS,IN 46204. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 626 EP 626 DI 10.1016/0006-3223(94)90700-5 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200044 ER PT J AU BAHRO, M LOW, H STADTMULLER, G LIS, S BERGER, M RIEMANN, D AF BAHRO, M LOW, H STADTMULLER, G LIS, S BERGER, M RIEMANN, D TI POLYSOMNOGRAPHIC DISTINCTION OF ALZHEIMERS-DISEASE, MAJOR DEPRESSION AND HEALTHY CONTROLS SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,BETHESDA,MD 20892. CENT INST MENTAL HLTH,D-68072 MANNHEIM,GERMANY. UNIV FREIBURG,PSYCHIAT CLIN,D-79014 FREIBURG,GERMANY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 627 EP 628 DI 10.1016/0006-3223(94)90704-8 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200048 ER PT J AU LIPSKA, BK SWERDLOW, NR JASKIW, GE GEYER, MA BRAFF, DL WEINBERGER, DR AF LIPSKA, BK SWERDLOW, NR JASKIW, GE GEYER, MA BRAFF, DL WEINBERGER, DR TI NEONATAL HIPPOCAMPAL DAMAGE DISRUPTS SENSORIMOTOR GATING IN POSTPUBERTAL RATS SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,NEUROSCI CTR ST ELIZABETHS,WASHINGTON,DC 20032. UNIV CALIF SAN DIEGO,SCH MED,LA JOLLA,CA 92093. VAMC,DEPT PSYCHIAT,BRECKSVILLE,OH 44141. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 631 EP 632 DI 10.1016/0006-3223(94)90719-6 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200063 ER PT J AU GOLD, J BLAXTON, T HERMANN, B GOLDBERG, T WYLER, A THEODORE, W WEINBERGER, D AF GOLD, J BLAXTON, T HERMANN, B GOLDBERG, T WYLER, A THEODORE, W WEINBERGER, D TI NEUROPSYCHOLOGICAL DIFFERENCES BETWEEN SCHIZOPHRENIA AND TEMPORAL-LOBE EPILEPSY SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,NEUROSCI CTR ST ELIZABETHS,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 1 PY 1994 VL 35 IS 9 BP 635 EP 635 DI 10.1016/0006-3223(94)90730-7 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200074 ER PT J AU WEINGARTNER, H SIROCCO, K ECKARDT, M HOMMER, D JOHNSON, DN AF WEINGARTNER, H SIROCCO, K ECKARDT, M HOMMER, D JOHNSON, DN TI COGNITIVE CONTROL FUNCTIONS IN MEMORY-IMPAIRED SUBJECTS - A NEUROPHARMACOLOGICAL MODEL SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIAAA,DICBR,CLIN STUDIES LAB,COGNIT NEUROSCI SECT,BETHESDA,MD 20892. NIAAA,DICBR,CLIN STUDIES LAB,BRAIN IMAGING & ELECTROPHYSIOL SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 640 EP 640 DI 10.1016/0006-3223(94)90750-1 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200093 ER PT J AU JOHNSON, DN WEINGARTNER, H AF JOHNSON, DN WEINGARTNER, H TI THE EFFECT OF TRIAZOLAM ON VISUAL-ATTENTION AND INFORMATION-PROCESSING SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIAAA,DICBR,COGNIT NEUROSCI SECT,CLIN STUDIES LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 641 EP 641 DI 10.1016/0006-3223(94)90752-8 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200095 ER PT J AU BAUMANN, MH BECKETTS, K ROTHMAN, RB AF BAUMANN, MH BECKETTS, K ROTHMAN, RB TI WITHDRAWAL FROM CHRONIC COCAINE IS ASSOCIATED WITH CHANGES IN PRESYNAPTIC SEROTONERGIC FUNCTION IN RATS SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIDA,ADDICT RES CTR,CPS,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 643 EP 643 DI 10.1016/0006-3223(94)90760-9 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200103 ER PT J AU ZHANG, L WU, M BARKER, J RUBINOW, DR AF ZHANG, L WU, M BARKER, J RUBINOW, DR TI DEVELOPMENTAL EXPRESSION OF SEROTONIN-RECEPTOR SUBTYPES IN RAT HIPPOCAMPUS SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NINCDS,NEUROPHYSIOL LAB,BETHESDA,MD 20892. NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 643 EP 643 DI 10.1016/0006-3223(94)90761-7 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200104 ER PT J AU SILVERTHOM, ML DERSCH, CM PARTILLA, JS CARROLL, FI MATECKA, DL RICE, KC ROTHMAN, RB AF SILVERTHOM, ML DERSCH, CM PARTILLA, JS CARROLL, FI MATECKA, DL RICE, KC ROTHMAN, RB TI [125I]RTI-55, A HIGH-AFFINITY COCAINE ANALOG, LABELS 2 BINDING-SITES IN HUMAN CAUDATE MEMBRANES POSSIBLY RELATED TO THE 5-HT TRANSPORTER SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. NIDDK,MED CHEM LAB,BETHESDA,MD 20892. NIDA,ADDICT RES CTR,CLIN PSYCHOPHARMACOL SECT,BALTIMORE,MD 21224. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 644 EP 644 DI 10.1016/0006-3223(94)90763-3 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200106 ER PT J AU GEORGE, MS KETTER, TA PAREKH, PI POST, RM AF GEORGE, MS KETTER, TA PAREKH, PI POST, RM TI REGIONAL BLOOD-FLOW CORRELATES OF TRANSIENT SELF-INDUCED SADNESS OR HAPPINESS SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. NR 0 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 647 EP 647 DI 10.1016/0006-3223(94)90776-5 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200119 ER PT J AU ESPOSITO, G VANHORN, JD OSTREM, JL MATTAY, VS WEINBERGER, DR BERMAN, KF AF ESPOSITO, G VANHORN, JD OSTREM, JL MATTAY, VS WEINBERGER, DR BERMAN, KF TI THE EFFECT OF SEX, AGE AND PCO2 ON CEREBRAL BLOOD-FLOW DURING COGNITIVE STIMULATION SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,CBDB,POSITRON EMISS TOMOG UNIT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 648 EP 648 DI 10.1016/0006-3223(94)90778-1 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200121 ER PT J AU KETTER, TA GEORGE, MS ANDREASON, PJ HERSCOVITCH, P POST, RM AF KETTER, TA GEORGE, MS ANDREASON, PJ HERSCOVITCH, P POST, RM TI BLUNTED PARALIMBIC RESTING AND PROCAINE-ACTIVATED RCBF IN HEALTHY FEMALES COMPARED TO MALES SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIAAA,BETHESDA,MD 20892. NIH,CTR CLIN,BETHESDA,MD 20892. NIMH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 648 EP 648 DI 10.1016/0006-3223(94)90777-3 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200120 ER PT J AU ALTEMUS, M DEUSTER, P GALLIVEN, E WOO, V CARTER, S MURPHY, DL GOLD, PW AF ALTEMUS, M DEUSTER, P GALLIVEN, E WOO, V CARTER, S MURPHY, DL GOLD, PW TI SUPPRESSION OF HPA AXIS RESPONSE TO STRESS IN LACTATING WOMEN SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,CLIN SCI LAB,BETHESDA,MD 20892. NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 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 1 PY 1994 VL 35 IS 9 BP 650 EP 650 DI 10.1016/0006-3223(94)90786-2 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200129 ER PT J AU MALHOTRA, AK SU, TP HO, D PICKAR, D BREIER, A AF MALHOTRA, AK SU, TP HO, D PICKAR, D BREIER, A TI THE EFFECTS OF KETAMINE ON BEHAVIORAL, COGNITIVE AND NEUROENDOCRINE FUNCTION IN SCHIZOPHRENIA SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,EXPTL THERAPEUT BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 651 EP 651 DI 10.1016/0006-3223(94)90789-7 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200132 ER PT J AU GEORGE, MS KETTER, TA POST, RM AF GEORGE, MS KETTER, TA POST, RM TI AN OVERVIEW OF BRAIN ACTIVATION STUDIES IN MOOD DISORDERS SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 658 EP 658 DI 10.1016/0006-3223(94)90814-1 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200156 ER PT J AU MOLCHAN, SE SCHREURS, BG MCINTOSH, AR BAHRO, M CANTILLON, M SUNDERLAND, T AF MOLCHAN, SE SCHREURS, BG MCINTOSH, AR BAHRO, M CANTILLON, M SUNDERLAND, T TI ALTERATIONS IN NEURAL ACTIVITY DURING ASSOCIATIVE LEARNING IN HUMANS SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,CLIN SCI LAB,GERIATR PSYCHIAT SECT,BETHESDA,MD 20892. NIA,CLIN SCI LAB,BETHESDA,MD 20892. NINCDS,ADAPT SYST LAB,BETHESDA,MD 20892. RI McIntosh, Anthony/G-4955-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 658 EP 659 DI 10.1016/0006-3223(94)90816-8 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200158 ER PT J AU GOLDBERG, TE GOLD, JM COPPOLA, R WEINBERGER, DR AF GOLDBERG, TE GOLD, JM COPPOLA, R WEINBERGER, DR TI THE EFFECTS OF DELAYED AUDITORY-FEEDBACK ON SPEECH IN SCHIZOPHRENIA SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 NIMH,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAY 1 PY 1994 VL 35 IS 9 BP 659 EP 659 DI 10.1016/0006-3223(94)90817-6 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA NJ172 UT WOS:A1994NJ17200159 ER EF