FN Thomson Reuters Web of Science™ VR 1.0 PT J AU BHAT, KS GIBBS, CP BARRERA, O MORRISON, SG JAHNIG, F STERN, A KUPSCH, EM MEYER, TF SWANSON, J AF BHAT, KS GIBBS, CP BARRERA, O MORRISON, SG JAHNIG, F STERN, A KUPSCH, EM MEYER, TF SWANSON, J TI THE OPACITY PROTEINS OF NEISSERIA-GONORRHOEAE STRAIN MS11 ARE ENCODED BY A FAMILY OF 11 COMPLETE GENES SO MOLECULAR MICROBIOLOGY LA English DT Article ID GONOCOCCAL OUTER-MEMBRANE; ANTIGENIC VARIATION; ESCHERICHIA-COLI; PHASE VARIATION; DNA-SEQUENCE; EXPRESSION; VARIANTS; TRANSFORMATION; INFECTION; GENOME AB Variants of Neisseria gonorrhoeae MS11 show distinct colony morphologies because of the expression of a class of surface components called opacity (Opa, PII) proteins. Southern analyses combined with molecular cloning of genomic DNA from a single variant of MS11 has identified 11 opa genes contained in separate loci. These opa genes code for distinct opacity proteins which are distinguishable at their variable domains. The opa gene analyses were also extended to divergent variants of MS11. These studies have shown that, during in vitro and in vivo culture, 10 of the 11 opa genes did not undergo significant change in their primary sequence. However, in these variants, one gene (opaE) underwent non-reciprocal inter-opa recombinations to generate newer Opa variants. Phylogenic analysis of the opa gene sequences suggests that the opa gene family have evolved by a combination of gene duplication, gene replacement and partial inter-opa recombination events. C1 MAX PLANCK INST BIOL,INFEKT BIOL ABT,W-7400 TUBINGEN,GERMANY. RP BHAT, KS (reprint author), NIH,ROCKY MTN LABS,MICROBIAL STRUCT & FUNCT LAB,HAMILTON,MT 59840, USA. RI Meyer, Thomas F./J-2485-2013 OI Meyer, Thomas F./0000-0002-6120-8679 NR 33 TC 127 Z9 133 U1 0 U2 5 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD AUG PY 1991 VL 5 IS 8 BP 1889 EP 1901 DI 10.1111/j.1365-2958.1991.tb00813.x PG 13 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA GC394 UT WOS:A1991GC39400009 PM 1815562 ER PT J AU WANG, CD BUCK, MA FRASER, CM AF WANG, CD BUCK, MA FRASER, CM TI SITE-DIRECTED MUTAGENESIS OF ALPHA-2A-ADRENERGIC RECEPTORS - IDENTIFICATION OF AMINO-ACIDS INVOLVED IN LIGAND-BINDING AND RECEPTOR ACTIVATION BY AGONISTS SO MOLECULAR PHARMACOLOGY LA English DT Article ID BETA-ADRENERGIC-RECEPTOR; PLATELET ALPHA-2-ADRENERGIC RECEPTOR; MUSCARINIC ACETYLCHOLINE-RECEPTORS; ADENYLATE-CYCLASE; SEQUENCE-ANALYSIS; EXPRESSION; CLONING; CDNA; RESIDUES; PROTEIN AB Molecular cloning of the alpha-2A-adrenergic receptor has shown that this receptor is a member of the gene superfamily of guanine nucleotide-binding protein (G protein)-coupled receptors. The alpha-2A-adrenergic receptor expressed in Chinese hamster ovary (CHO) cells attenuates and potentiates forskolin-stimulated cAMP production through independent signaling pathways. To examine the role of three conserved aspartic acid and two conserved serine residues in alpha-2A-adrenergic receptor function, we substituted asparagine for aspartic acid or alanine for serine and characterized the mutant receptors in stably transfected CHO cells. Asn113 mutant alpha-2-adrenergic receptors display no [H-3] yohimbine specific binding, at concentrations up to 1000 nm. In transfected cells expressing the Asn113 mutant receptor, agonists, at concentrations up to 0.1 mM, produce small decreases (approximately 10% of wild-type values) in forskolin-stimulated cAMP and potentiate forskolin-stimulated cAMP concentrations in a dose-dependent manner, with EC50 values approximately 500-fold higher than those for the wild-type receptor. These findings suggest that Asp113 may be involved in high affinity binding of agonists and antagonists, as has been previously reported for beta-2-adrenergic and m 1 muscarinic acetylcholine receptors. Asn79 mutant alpha-2-adrenergic receptors display high affinity agonist binding that is insensitive to guanine nucleotides, suggesting an altered receptor-G protein coupling. Furthermore, agonist binding to Asn79 mutant receptors elicits no change in forskolin-stimulated cAMP concentrations, similar to earlier findings that the corresponding residue in beta-2-adrenergic and muscarinic receptors is required for effector stimulation. Asp130 appears to influence receptor-G protein coupling. Mutation of this residue eliminates high affinity, guanine nucleotide-sensitive, agonist binding and produces a rightward shift in the dose-response curves for agonist-mediated inhibition of forskolin-stimulated cAMP production, compared with the wild-type receptor. Moreover, agonist potentiation of forskolin-stimulated cAMP levels is abolished if Asp130 is replaced by Asn, supporting the hypothesis that inhibition and potentiation of forskolin-stimulated cAMP production in CHO cells proceed through distinct signaling pathways. Characterization of Ala204 mutant alpha-2A-adrenergic receptors suggests a possible role for Ser204 in hydrogen bond interactions with the para-hydroxyl group of the phenyl ring of the catecholamines, as has been previously described for the corresponding serine in beta-2-adrenergic receptors. Analysis of Ala200 mutant alpha-2A receptors suggests that this residue does not directly participate in receptor-agonist interactions, in contrast to the corresponding serine residue in the beta-2-adrenergic receptor, which has been postulated to interact with the meta-hydroxyl group of catecholamines. Data in this study, together with earlier reports on the mutagenesis of the beta-2-adrenergic receptor, suggest that the molecular interactions between catecholamines and alpha-adrenergic and beta-adrenergic receptors may be subtly different. C1 NIAAA,PHYSIOL & PHARMACOL STUDIES LAB,MOLEC NEUROBIOL SECT,BLDG DNAC 4,ROCKVILLE,MD 20852. OI Fraser, Claire/0000-0003-1462-2428 NR 43 TC 228 Z9 231 U1 0 U2 4 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD AUG PY 1991 VL 40 IS 2 BP 168 EP 179 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GA999 UT WOS:A1991GA99900004 PM 1678850 ER PT J AU HUGHES, AR BIRD, GSJ OBIE, JF THASTRUP, O PUTNEY, JW AF HUGHES, AR BIRD, GSJ OBIE, JF THASTRUP, O PUTNEY, JW TI ROLE OF INOSITOL (1,4,5)TRISPHOSPHATE IN EPIDERMAL GROWTH FACTOR-INDUCED CA2+ SIGNALING IN A431-CELLS SO MOLECULAR PHARMACOLOGY LA English DT Article ID PAROTID ACINAR-CELLS; PHOSPHOLIPASE-C-II; PHORBOL 12-MYRISTATE 13-ACETATE; CYTOSOLIC FREE CALCIUM; PROTEIN-KINASE-C; A431 CELLS; EGF RECEPTOR; TYROSINE PHOSPHORYLATION; TUMOR PROMOTER; INTRACELLULAR STORES AB The effects of epidermal growth factor on Ca2+ signaling in A431 cells were investigated. Epidermal growth factor induced a transient Ca2+ signal in the absence of external Ca2+ and a sustained response in the presence of extracellular Ca2+, indicating an ability to mobilize intracellular Ca2+ as well as the ability to increase Ca2+ entry from the extracellular space. The Ca2+-ATPase inhibitor thapsigargin also activated Ca2+ entry, and neither epidermal growth factor nor the guanine nucleotide-dependent protein-linked receptor agonist bradykinin activated additional Ca2+ entry over that due to thapsigargin. In nominally Ca2+-free medium, the addition of bradykinin to A431 cells rapidly but transiently increased inositol 1,4,5-trisphosphate and, in parallel fashion, transiently increased cytosolic Ca2+. Unexpectedly, under these experimental conditions, epidermal growth factor elicited a small but significant Ca2+ signal after the addition of bradykinin. Experiments were designed to determine whether the Ca2+ response to epidermal growth factor after bradykinin results from mobilization of Ca2+ by an inositol 1,4,5-trisphosphate-independent mechanism. Epidermal growth factor stimulated additional inositol 1,4,5-trisphosphate formation in bradykinin-treated cells. Furthermore, the Ca2+ signals elicited by both bradykinin and epidermal growth factor were blocked in cells microinjected with the inositol 1,4,5-trisphosphate receptor antagonist heparin, whereas the intracellular Ca2+-ATPase inhibitor thapsigargin still mobilized Ca2+. Finally, histamine, a less efficacious guanine nucleotide-dependent protein-linked receptor agonist, as well as photolyzed, microinjected, caged inositol 1,4,5-trisphosphate, also mobilized Ca2+ after bradykinin. The results of this study show (i) that epidermal growth factor activates intracellular Ca2+ release as well as Ca2+ entry, the latter most likely resulting from an indirect effect due to the depletion of intracellular Ca2+ pools, (ii) that the actions of epidermal growth factor on Ca2+ homeostasis can be fully accounted for by inositol 1,4,5-trisphosphate formation, and (iii) that the ability of A431 cells to produce Ca2+ signals when epidermal growth factor is applied after bradykinin can be explained by the rapid and complete desensitization of the bradykinin stimulated phospholipase C activity. C1 NIEHS,CELLULAR & MOLEC BIOL LAB,POB 12233,RES TRIANGLE PK,NC 27709. UNIV COPENHAGEN HOSP,RIGSHOSP,DEPT CLIN CHEM,DK-2100 COPENHAGEN,DENMARK. SYMBION,THROMBOSIS GRP,DK-2100 COPENHAGEN,DENMARK. NR 47 TC 36 Z9 36 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD AUG PY 1991 VL 40 IS 2 BP 254 EP 262 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GA999 UT WOS:A1991GA99900015 PM 1875911 ER PT J AU LOVINGER, DM WHITE, G AF LOVINGER, DM WHITE, G TI ETHANOL POTENTIATION OF 5-HYDROXYTRYPTAMINE3 RECEPTOR-MEDIATED ION CURRENT IN NEUROBLASTOMA-CELLS AND ISOLATED ADULT MAMMALIAN NEURONS SO MOLECULAR PHARMACOLOGY LA English DT Article ID 5-HT3 RECEPTORS; RAT; HIPPOCAMPAL; GANGLION; INHIBITION; RESPONSES; CHANNELS; DOPAMINE; RELEASE; CA-2+ AB Recent studies indicate that ethanol (EtOH) potentiates ion current through the channel associated with the 5-hydroxytryptamine3(5-HT3)-type serotonin receptor. The present study was designed to determine 1) whether such potentiation occurs in adult mammalian neurons expressing 5-HT3 receptors; 2) whether potentiation is selective for the 5-HT3 receptor, relative to other ligand-gated ion channels; and 3) possible mechanisms by which EtOH potentiates this response. EtOH potentiated 5-HT3 receptor-mediated ion current in freshly isolated nodose ganglion neurons at concentrations similar to those previously reported to be effective in neuroblastoma cells (25-100 mM). Current was blocked by the selective 5-HT3 antagonist ICS 205-930 even in the presence of EtOH, and current activated by a 5-HT3 agonist (2-methyl-5-HT) was potentiated by EtOH. Thus, EtOH appears to produce potentiation via an alteration in the function of 5-HT3 receptors and not through an independent effect. gamma-Aminobutyric acid(A) receptor-mediated Cl- current was not potentiated by EtOH in neurons in which potentiation of responses to 5-HT was observed. Methanol potentiated 5-HT3 receptor-mediated current with a potency lower than that of EtOH. Potentiation by EtOH decreased with increasing 5-HT concentration. In addition, EtOH increased the decay rate of current. EtOH did not alter the reversal potential of the 5-HT3 receptor-mediated current. These observations indicate that intoxicating concentrations of EtOH selectively potentiate 5-HT3 receptor-mediated responses by increasing the apparent potency of 5-HT for activating ion current. C1 NIAAA,PHYSIOL & PHARMACOL STUDIES LAB,ELECTROPHYSIOL SECT,ROCKVILLE,MD 20852. NR 34 TC 163 Z9 164 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD AUG PY 1991 VL 40 IS 2 BP 263 EP 270 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GA999 UT WOS:A1991GA99900016 PM 1715016 ER PT J AU POLITI, DMT ROGAWSKI, MA AF POLITI, DMT ROGAWSKI, MA TI GLYBURIDE-SENSITIVE K+-CHANNELS IN CULTURED RAT HIPPOCAMPAL-NEURONS - ACTIVATION BY CROMAKALIM AND ENERGY-DEPLETING CONDITIONS SO MOLECULAR PHARMACOLOGY LA English DT Article ID VASCULAR SMOOTH-MUSCLE; PANCREATIC BETA-CELLS; POTASSIUM CHANNELS; BRL-34915 CROMAKALIM; SKELETAL-MUSCLE; HYPOTHALAMIC NEURONS; CARDIAC MYOCYTES; BINDING PROTEIN; ION CHANNELS; RABBIT AORTA AB Previous studies in our laboratory have shown that cromakalim activates a tetraethylammonium-sensitive K+ current in cultured embryonic rat hippocampal neurons. This phenomenon was further characterized using whole-cell voltage-clamp and single-channel recording techniques. Glyburide (1-25-mu-M), an antagonist of ATP-sensitive K+ channels, produced a concentration-dependent depression of the cromakalim-activated current. In contrast, charybdotoxin (100 nM), an antagonist of some Ca2+-dependent and other K+ channels, not only failed to block the effect of cromakalim but actually produced a moderate enhancement of the cromakalim-activated K+ current. Neither glyburide nor charybdotoxin affected resting or voltage-activated K+ currents in the absence of cromakalim. Exposure of the cells to energy-depleting conditions (0.24-mu-g/ml oligomycin and 10 mM 2-deoxy-D-glucose) also activated an outward current. Single-channel recordings in the cell-attached configuration showed that cromakalim (100-mu-M) stimulated the opening of flickery single channels having a unitary conductance of approximately 26 pS and a prolonged burst duration (mean open time, approximately 131 msec); similar channel openings were observed in patches from cells exposed to energy-depleting conditions. In patches containing a single K+ channel, the open probability in the presence of cromakalim was approximately 0.6 and in the presence of energy-depleting conditions was approximately 0.8; in the absence of either of these treatments, channel openings were not observed. Glyburide produced a reversible inhibition of the channels activated by cromakalim and energy-depleting conditions. These data provide additional support for the existence of ATP-sensitive K+ channels in central neurons and indicate that the K+ channels whose opening is stimulated by cromakalim are likely to be of the ATP-sensitive type. C1 NINCDS,MED NEUROL BRANCH,NEURONAL EXCITABIL SECT,BLDG 10,ROOM 5N-248,BETHESDA,MD 20892. RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 NR 53 TC 51 Z9 52 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD AUG PY 1991 VL 40 IS 2 BP 308 EP 315 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GA999 UT WOS:A1991GA99900021 PM 1715018 ER PT J AU SHELBY, MD TICE, RR AF SHELBY, MD TICE, RR TI CURRENT ISSUES IN MUTAGENESIS AND CARCINOGENESIS .28. METHYL CARBAMATE - NEGATIVE RESULTS IN MOUSE BONE-MARROW MICRONUCLEUS TEST SO MUTATION RESEARCH LA English DT Article DE MICRONUCLEUS; SHORT-TERM TEST; CYTOGENETICS, INVIVO C1 NIEHS,NATL TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709. INTEGRATED LAB SYST INC,RES TRIANGLE PK,NC 27709. NR 2 TC 10 Z9 10 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 AUG PY 1991 VL 260 IS 4 BP 311 EP 311 DI 10.1016/0165-1218(91)90015-E PG 1 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA GB570 UT WOS:A1991GB57000003 PM 1870620 ER PT J AU ABUSHAKRA, A JOHNSON, L EARLEY, K JAMESON, CW KARI, FW GUPTA, R LANGENBACH, R AF ABUSHAKRA, A JOHNSON, L EARLEY, K JAMESON, CW KARI, FW GUPTA, R LANGENBACH, R TI ISOLATION OF THE MUTAGENIC AND DNA ADDUCT-INDUCING COMPONENTS FROM A COMMERCIAL PREPARATION OF HC BLUE-1 USING SALMONELLA (TA98) BIOASSAY-DIRECTED HPLC FRACTIONATION SO MUTATION RESEARCH LA English DT Article DE DNA ADDUCTS; HAIR DYE HC BLUE-1; NITROPHENYLENEDIAMINE; HPLC FRACTIONATION ID HAIR-DYES; NO-1; MOUSE; CARCINOGENICITY; RAT; GENOTOXICITY; HEPATOCYTES; CHEMICALS; INDUCTION; HAMSTER AB In the present study we report the separation of the mutagenic impurities from the nitrophenylenediamine hair dye HC Blue 1. This was accomplished by bioassay-directed HPLC fractionation, using Salmonella strain TA98 and reverse phase HPLC analysis. The mutagenic fraction eluted between 80 and 90% methanol, whereas the HPLC fraction containing the parent compound HC Blue 1 eluted with 30% methanol and was non-mutagenic. 100% of the mutagenic activity applied to the column was recovered in fractions that did not possess the blue color of HC Blue 1. Also, HPLC-purified HC Blue 1 did not form DNa adducts (P-32-postlabeling) in Salmonella strain TA98. On the other hand, commercial HC Blue 1 and the mutagenic fraction derived from commercial HC Blue 1 (HPLC-isolated) gave similar DNA-adduct profiles that consisted of 7 adducts. DNA adduction was examined concomitantly with mutagenicity and toxicity studies on the HC Blue 1 samples in TA98. The data indicated that, in Salmonella, both the mutagenicity and DNA adduction of commercial HC Blue 1 are due to impurities and not the parent compound. C1 NIEHS,RES TRIANGLE PK,NC 27709. UNIV KENTUCKY,GRAD CTR TOXICOL,LEXINGTON,KY 40506. NR 19 TC 2 Z9 2 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8262 J9 MUTAT RES PD AUG PY 1991 VL 260 IS 4 BP 377 EP 385 DI 10.1016/0165-1218(91)90023-F PG 9 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA GB570 UT WOS:A1991GB57000011 PM 1870626 ER PT J AU DESERRES, FJ HOEL, DG AF DESERRES, FJ HOEL, DG TI OBJECTIVES OF THE COLLABORATIVE STUDY ON THE GENETIC TOXICOLOGY OF 2-AMINO-N6-HYDROXYADENINE - AN EXERCISE IN GENETIC RISK ASSESSMENT SO MUTATION RESEARCH LA English DT Article DE 2-AMINO-N6-HYDROXYADENINE; GENETIC TOXICOLOGY; COLLABORATIVE STUDY; OBJECTIVES ID 2 N-HYDROXYLAMINOPURINES; FORWARD-MUTATION TEST; NEUROSPORA-CRASSA; 2-AMINOPURINE; ANALOGS C1 NIEHS,DIV BIOMETRY & RISK ASSESSMENT,RES TRIANGLE PK,NC 27709. RP DESERRES, FJ (reprint author), RES TRIANGLE INST,CTR LIFE SCI & TOXICOL,POB 12194,RES TRIANGLE PK,NC 27709, USA. NR 16 TC 1 Z9 1 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 AUG PY 1991 VL 253 IS 1 BP 1 EP 3 DI 10.1016/0165-1161(91)90339-A PG 3 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA GB862 UT WOS:A1991GB86200001 PM 1870606 ER PT J AU LEWIS, SE BARNETT, LB SADLER, BM SHELBY, MD AF LEWIS, SE BARNETT, LB SADLER, BM SHELBY, MD TI ENU MUTAGENESIS IN THE MOUSE ELECTROPHORETIC SPECIFIC-LOCUS TEST .1. DOSE-RESPONSE RELATIONSHIP OF ELECTROPHORETICALLY-DETECTED MUTATIONS ARISING FROM MOUSE SPERMATOGONIA TREATED WITH ETHYLNITROSOUREA SO MUTATION RESEARCH LA English DT Article DE ETHYLNITROSOUREA, DOSE RESPONSE; SPERMATOGONIA; ELECTROPHORETIC MUTATION-SCREENING SYSTEM; GERM CELL; ENU MUTAGENESIS ID ETHYL-N-NITROSOUREA; MICE; INDUCTION; PROCARBAZINE; FREQUENCY; MUTANTS; MODEL AB The mouse electrophoretic specific-locus test for induced germ-cell mutations, was used to determine the response of spermatogonial stem cells to a series of doses of the germ cell mutagen N-ethyl-N-nitrosourea (ENU). Male DBA/2J and C57B1/6J mice were treated with doses of 50, 100, 200 or 250 mg/kg ENU and their progeny screened for electrophoretically-detectable mutations at 32 separate loci. As expected, increasing doses of ENU led to increasing mutant frequencies. The differences in mutant frequencies between treated DBA/2J and C57B1/6J males were not statistically significant. C1 NIEHS,RES TRIANGLE PK,NC 27709. RP LEWIS, SE (reprint author), RES TRIANGLE INST,POB 12194,RES TRIANGLE PK,NC 27709, USA. FU NIEHS NIH HHS [N01-ES-2-5012] NR 24 TC 21 Z9 22 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 AUG PY 1991 VL 249 IS 2 BP 311 EP 315 DI 10.1016/0027-5107(91)90005-9 PG 5 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA FZ987 UT WOS:A1991FZ98700005 PM 2072974 ER PT J AU HSU, VW YUAN, LC NUCHTERN, JG LIPPINCOTTSCHWARTZ, J HAMMERLING, GJ KLAUSNER, RD AF HSU, VW YUAN, LC NUCHTERN, JG LIPPINCOTTSCHWARTZ, J HAMMERLING, GJ KLAUSNER, RD TI A RECYCLING PATHWAY BETWEEN THE ENDOPLASMIC-RETICULUM AND THE GOLGI-APPARATUS FOR RETENTION OF UNASSEMBLED MHC CLASS-I MOLECULES SO NATURE LA English DT Article ID HEAVY-CHAINS; BREFELDIN-A; PROTEINS; ER; ANTIBODIES; RECEPTOR; COMPLEX AB ASSEMBLY of Class I major histocompatibility complex (MHC) molecules involves the interaction of two distinct polypeptides (the heavy and light chains) with peptide antigen. Cell lines synthesizing both chains but expressing low levels of MHC class I molecules on their surface as a result of a failure in assembly and transport have been identified 1. We now report that although the apparent steady-state distribution in these cells of class I molecules is in the endoplasmic reticulum (ER), the molecules in fact are recycled between the ER and Golgi, rather than retained in the ER. This explains the failure of class I molecules to negotiate the secretory pathway. Class I molecules do not seem to be modified by Golgi enzymes, suggesting that the proteins do not reach the Golgi apparatus during recycling. But morphological and subcellular fractionation evidence indicates that they pass through the cis Golgi or a Golgi-associated organelle, which we postulate to be the recycling organelle. This compartment, which we call the 'cis-Golgi network', would thereby be a sorting organelle that selects proteins for return to the ER. C1 GERMAN CANC RES CTR,INST IMMUNOL & GENET,W-6900 HEIDELBERG,GERMANY. RP HSU, VW (reprint author), NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892, USA. NR 14 TC 151 Z9 151 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD AUG 1 PY 1991 VL 352 IS 6334 BP 441 EP 444 DI 10.1038/352441a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FZ346 UT WOS:A1991FZ34600069 PM 1861723 ER PT J AU DURCAN, MJ LISTER, RG MORGAN, PF LINNOILA, M AF DURCAN, MJ LISTER, RG MORGAN, PF LINNOILA, M TI INTERACTIONS OF INTRACEREBROVENTRICULAR PERTUSSIS TOXIN TREATMENT WITH THE ATAXIC AND HYPOTHERMIC EFFECTS OF ETHANOL SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Article DE PERTUSSIS TOXIN; PERTUSSIS TOXIN-B-OLIGOMER; G-PROTEINS; ETHANOL; ATAXIA; HYPOTHERMIA ID ALPHA-2 ADRENOCEPTOR ANTAGONISTS; ADENYLATE-CYCLASE SYSTEM; BINDING-PROTEIN; RAT-BRAIN; RECEPTORS; ATTENUATION; ADENOSINE-A1; INHIBITION; BEHAVIOR; DOPAMINE AB Pretreatment with pertussis toxin (0.5 and 1.0-mu-g/animal, i.c.v., seven days prior to testing) reversed the reduction in locomotor activity in the holeboard test caused by administration of the alpha2-adrenoceptor agonist, medetomidine (0.1 mg/kg, i.p.). Intrinsic behavioral effects of pertussis toxin treatment were also observed, these included a reduction in exploratory head-dipping and an increase in locomotor activity. These doses of pertussis toxin also reduced the ataxia induced by a 2.4 g/kg dose of ethanol. Pertussis toxin treated animals also exhibited a diminished hypothermic response to ethanol (2 g/kg), although the pertussis toxin treated animals had lower body temperatures prior to ethanol administration compared to sham treated animals. Neither the behavioral effect of pertussis holotoxin in the holeboard nor its effects on reversing medetomidine hypolocomotion or ethanol-induced ataxia were seen following administration of the binding oligomer of pertussis toxin which binds to the cell membrane but does not possess the enzymatically active subunit. These findings implicate mechanisms involving pertussis toxin sensitive G-proteins in modulating some behavioral and physiological effects of ethanol. RP DURCAN, MJ (reprint author), NIAAA,DICBR,CLIN STUDIES LAB,BLDG 10,RM 3C102,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 31 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD AUG PY 1991 VL 344 IS 2 BP 252 EP 258 DI 10.1007/BF00167227 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GC373 UT WOS:A1991GC37300018 PM 1944614 ER PT J AU GILDEN, DH DUELAND, AN COHRS, R MARTIN, JR KLEINSCHMIDTDEMASTERS, BK MAHALINGAM, R AF GILDEN, DH DUELAND, AN COHRS, R MARTIN, JR KLEINSCHMIDTDEMASTERS, BK MAHALINGAM, R TI PREHERPETIC NEURALGIA SO NEUROLOGY LA English DT Article AB We have encountered six zoster patients whose pain preceded rash by 7 to more than 100 days. Pain was severe, burning, and radicular, and located both in dermatomes different from, as well as in, the area of eventual rash. Two patients ultimately developed disseminated zoster with neurologic complications, one of zoster paresis, and the other, a fatal zoster encephalitis; both had been taking long-term, low-dose steroids. A third case of preherpetic neuralgia developed in a patient with prior metastatic carcinoma, and another case in a patient with an earlier episode of brachial neuritis. The final two cases of preherpetic neuralgia developed in individuals with no underlying disease. An extended period of pain before the onset of zoster rash has gone largely unrecognized. C1 UNIV COLORADO,SCH MED,DEPT MICROBIOL & IMMUNOL,DENVER,CO 80262. UNIV COLORADO,SCH MED,DEPT PATHOL,DENVER,CO 80262. NIH,EXPTL NEUROPATHOL LAB,BETHESDA,MD 20892. RP GILDEN, DH (reprint author), UNIV COLORADO,SCH MED,DEPT NEUROL,4200 E 9TH AVE,CAMPUS BOX B-182,DENVER,CO 80262, USA. FU NIA NIH HHS [AG-07347, AG-06127]; NINDS NIH HHS [NS-07321] NR 4 TC 60 Z9 62 U1 1 U2 2 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG PY 1991 VL 41 IS 8 BP 1215 EP 1218 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA GA850 UT WOS:A1991GA85000013 PM 1866008 ER PT J AU JOHNSON, R LITVAN, I GRAFMAN, J AF JOHNSON, R LITVAN, I GRAFMAN, J TI PROGRESSIVE SUPRANUCLEAR PALSY - ALTERED SENSORY PROCESSING LEADS TO DEGRADED COGNITION SO NEUROLOGY LA English DT Article ID EVENT-RELATED POTENTIALS; PARKINSONS-DISEASE; ELECTROPHYSIOLOGICAL DIFFERENCES; HUNTINGTONS-DISEASE; P300 AMPLITUDE; DEMENTIA; LATENCY; GENERATORS; DIAGNOSIS; ATTENTION AB We studied the latencies, amplitudes, and scalp distributions of the early and late components of the event-related brain potential (ERP) in patients with progressive supranuclear palsy (PSP) and matched normal controls. In separate choice reaction time (RT) tasks, the subjects pressed buttons to visual stimuli presented randomly at probabilities of either 20/80 or 50/50. Compared with normal controls, PSP patients had significantly reduced amplitudes and increased latencies for both the visual P2 and P300 components at all levels of probability. RTs and percent errors were significantly greater in the patients compared with controls. Neither the amplitude nor latency of the visual N1 component was significantly altered in these patients. There were no significant group differences in the distribution of electrical activity over the scalp for any of these ERP components, a finding which suggests that the neural structures responsible for generating these potentials were intact in these patients. The decreased ERP component amplitudes and increased ERP component latencies, combined with intact scalp distributions and increased RTs and error rates, present a pattern of results suggesting that the stimulus identification or categorization processes in these patients are significantly degraded. C1 NINCDS,EXPTL THERAPEUT BRANCH,BETHESDA,MD 20892. RP JOHNSON, R (reprint author), NINCDS,MED NEUROL BRANCH,COGNIT NEUROSCI SECT,BLDG 10,ROOM 5C422,BETHESDA,MD 20892, USA. OI Grafman, Jordan H./0000-0001-8645-4457; Litvan, Irene/0000-0002-3485-3445 NR 35 TC 31 Z9 32 U1 1 U2 2 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG PY 1991 VL 41 IS 8 BP 1257 EP 1262 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA GA850 UT WOS:A1991GA85000021 PM 1866015 ER PT J AU TOPKA, H COHEN, LG COLE, RA HALLETT, M AF TOPKA, H COHEN, LG COLE, RA HALLETT, M TI REORGANIZATION OF CORTICOSPINAL PATHWAYS FOLLOWING SPINAL-CORD INJURY SO NEUROLOGY LA English DT Article ID MAGNETIC STIMULATION; CORTEX; RAT; REPRESENTATION; PROJECTIONS; HEMISECTION; MUSCLES; BRAIN; AXONS; HAND AB To assess changes in the relationship between cortical motor representation areas and their target muscles following spinal cord lesions, we studied motor evoked potentials (MEPs) to transcranial magnetic stimulation in six patients with complete spinal cord injuries at low thoracic levels and eight healthy subjects. Magnetic stimulation at rest activated a larger fraction of the motoneuron pool and evoked MEPs with shorter latencies from a larger number of scalp positions in muscles immediately rostral to the level of a spinal cord injury than in corresponding muscles in controls. The MEPs associated with maximal voluntary activation were not significant different in the two groups. These results suggest enhanced excitability of motor pathways targeting muscles rostral to the level of a spinal transection, reflecting reorganization of motor pathways either within cortical motor representation areas or at the level of the spinal cord. The data do not allow the determination of the contribution of spinal or cortical mechanisms. However, they support the notion of a limited flexible relationship between primary motor cortex and its target muscles following alterations of normal input-output patterns. C1 NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,HUMAN CORTICAL PHYSIOL UNIT,BLDG 10,BETHESDA,MD 20892. NR 27 TC 178 Z9 178 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 AUG PY 1991 VL 41 IS 8 BP 1276 EP 1283 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA GA850 UT WOS:A1991GA85000025 PM 1866018 ER PT J AU COHEN, LG TOPKA, H COLE, RA HALLETT, M AF COHEN, LG TOPKA, H COLE, RA HALLETT, M TI LEG PARESTHESIAS INDUCED BY MAGNETIC BRAIN-STIMULATION IN PATIENTS WITH THORACIC SPINAL-CORD INJURY SO NEUROLOGY LA English DT Article ID COIL STIMULATION; MONKEYS; CORTEX; HUMANS AB We studied the induction of leg paresthesias by magnetic stimulation of the brain in seven patients with thoracic T9-12 spinal cord injury and in four normal volunteers by delivering transcranial magnetic stimulation over scalp positions 1 cm apart with a Cadwell MES-10 magnetic stimulator and an 8-shaped magnetic coil at 100% stimulus intensity. We asked subjects to report sensations felt after each stimulus. In all normal subjects, magnetic stimulation evoked sensations described as tingling or a wave descending along the leg, usually accompanied by EMG responses in leg muscles. In three of the seven patients, stimulation evoked sensations of tingling, numbness, touch, or a wave descending along the leg, lasting up to 10 seconds and referred to different parts of the legs and toes. In the patients, sensations were felt more distally the closer the site of stimulation was to the midline. Patients with leg paresthesias had less motor reorganization in abdominal muscles than those without paresthesias. These findings suggest that portions of the cortical representation areas for body parts deafferented by a complete spinal cord injury can remain related to those body parts for up to several years. A central origin of these paresthesias is probable. RP COHEN, LG (reprint author), NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,HUMAN CORTICAL PHYSIOL UNIT,BLDG 10,BETHESDA,MD 20892, USA. NR 21 TC 41 Z9 41 U1 2 U2 2 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG PY 1991 VL 41 IS 8 BP 1283 EP 1288 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA GA850 UT WOS:A1991GA85000026 PM 1866019 ER PT J AU GODEC, MS ASHER, DM MASTERS, CL KOZACHUK, WE FRIEDLAND, RP GIBBS, CJ GAJDUSEK, DC RAPOPORT, SI SCHAPIRO, MB AF GODEC, MS ASHER, DM MASTERS, CL KOZACHUK, WE FRIEDLAND, RP GIBBS, CJ GAJDUSEK, DC RAPOPORT, SI SCHAPIRO, MB TI EVIDENCE AGAINST THE TRANSMISSIBILITY OF ALZHEIMERS-DISEASE SO NEUROLOGY LA English DT Note C1 NIA,NEUROSCI LAB,BETHESDA,MD 20892. UNIV MELBOURNE,DEPT PATHOL,PARKVILLE,VIC 3052,AUSTRALIA. RP GODEC, MS (reprint author), NINCDS,CENT NERVOUS SYST STUDIES LAB,RM 5B21,BLDG 36,BETHESDA,MD 20892, USA. RI Friedland, Robert/A-2834-2010 OI Friedland, Robert/0000-0001-5721-1843 NR 6 TC 13 Z9 13 U1 1 U2 3 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG PY 1991 VL 41 IS 8 BP 1320 EP 1320 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA GA850 UT WOS:A1991GA85000039 PM 1866028 ER PT J AU STANFIELD, BB AF STANFIELD, BB TI THE CORTICOSPINAL TRACT ATTAINS A NORMAL CONFIGURATION IN THE ABSENCE OF MYELIN - OBSERVATIONS IN JIMPY MUTANT MICE SO NEURON LA English DT Article ID RAT SPINAL-CORD; NEURITE GROWTH; PYRAMIDAL TRACT; NERVOUS-SYSTEM; CELL-ADHESION; WHITE MATTER; GRAY-MATTER; CNS MYELIN; PROTEIN; INHIBITORS AB The corticospinal projection was examined in dysmyelinated, jimpy mice and in unaffected littermates following cortical injections of either wheat germ agglutinin conjugated to horseradish peroxidase or biocytin. Corticospinal axons in both phenotypes traverse the medulla within a well-defined pyramidal tract, decussate within several fascicles at the spinomedullary junction, and extend down the spinal cord in a compact bundle in the ventral-most part of the dorsal funiculus. Very few labeled fibers are seen separated from the main bundle. This normal configuration of the corticospinal tract is attained despite the virtual absence of CNS myelin in jimpy mice. It seems unlikely then that the myelin normally present in fiber bundles adjacent to this relatively late emerging projection can significantly influence pathway selection during its development. RP STANFIELD, BB (reprint author), NIMH,CTR ANM,NEUROPHYSIOL LAB,POOLESVILLE,MD 20837, USA. NR 41 TC 18 Z9 18 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0896-6273 J9 NEURON JI Neuron PD AUG PY 1991 VL 7 IS 2 BP 249 EP 256 DI 10.1016/0896-6273(91)90263-Y PG 8 WC Neurosciences SC Neurosciences & Neurology GA GB933 UT WOS:A1991GB93300008 PM 1908251 ER PT J AU FERRARESE, C GUIDOTTI, A COSTA, E MILETICH, RS RICE, KC DECOSTA, BR FULHAM, MJ DICHIRO, G AF FERRARESE, C GUIDOTTI, A COSTA, E MILETICH, RS RICE, KC DECOSTA, BR FULHAM, MJ DICHIRO, G TI INVIVO STUDY OF NMDA-SENSITIVE GLUTAMATE RECEPTOR BY FLUOROTHIENYLCYCLOEXYLPIPERIDINE, A POSSIBLE LIGAND FOR POSITRON EMISSION TOMOGRAPHY SO NEUROPHARMACOLOGY LA English DT Article DE EXCITATORY AMINO ACIDS; EXCITOTOXICITY; NMDA; POSITRON EMISSION TOMOGRAPHY ID RAT-BRAIN MEMBRANES; SYNAPTIC-MEMBRANES; CHANNEL COMPLEX; ASPARTATE; BINDING; ACID; PHENCYCLIDINE; MK-801; ANTAGONIST; GLYCINE AB As a preliminary to positron emission tomography (PET) studies of excitatory amino acid neurotransmission, N-methyl-D-aspartate (NMDA)-sensitive glutamate receptors of mice and rats were labelled in vivo with [H-3]fluorothienylcycloexylpiperidine (FTCP), which binds to the phencyclidine site of the NMDA receptor. After intravenous injection, the half-life of clearance of authentic FTCP from blood was 4.2 min in mice, 12 min in rats and 45 min in a rhesus monkey. In rodent brain, the specific binding of [H-3]FTCP, 10 min after intravenous injection, was 10-20% of the total binding and no regional differences were observed. However, if animals were treated with NMDA intraperitoneally (0.68 mmol/kg), 10 min before injection of [H-3]FTCP, a three- to five-fold increase in specific binding was observed in hippocampus, cerebral cortex and striatum but not in cerebellum. Thus, specific binding of [H-3]FTCP in vivo revealed the physiological status of the NMDA receptor; in fact, preliminary PET studies with [F-18]FTCP in monkeys indicated increased binding after activation of NMDA receptors. These data suggest that PET with [F-18]FTCP can be a tool to evaluate physiological or pathological modifications of the function of NMDA receptors. C1 NINCDS,NEUROIMAGING SECT,BETHESDA,MD 20892. GEORGETOWN UNIV,FIDIA GEORGETOWN INST NEUROSCI,WASHINGTON,DC 20057. NIDDKD,MED CHEM LAB,BETHESDA,MD 20892. NR 25 TC 13 Z9 13 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD AUG PY 1991 VL 30 IS 8 BP 899 EP 905 DI 10.1016/0028-3908(91)90125-U PG 7 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA GB119 UT WOS:A1991GB11900010 PM 1685770 ER PT J AU RAPOPORT, JL AF RAPOPORT, JL TI RECENT ADVANCES IN OBSESSIVE-COMPULSIVE DISORDER SO NEUROPSYCHOPHARMACOLOGY LA English DT Review DE OBSESSIVE-COMPULSIVE DISORDER; ETHOLOGY; BASAL GANGLIA; ANIMAL MODELS; CLOMIPRAMINE; TRICHOTILLOMANIA ID GLUCOSE METABOLIC RATES; LA-TOURETTES SYNDROME; MAGNETIC-RESONANCE; ADOLESCENTS; TOMOGRAPHY; ABNORMALITIES; CLOMIPRAMINE; DESIPRAMINE; SYMPTOMS; NEUROSIS AB A growing body of evidence from clinical phenomenology, including associated disorders, brain imaging, and neuropharmacologic studies, links the classic psychiatric syndrome of obsessive-compulsive disorder (OCD) to basal ganglia dysfunction and to the serotonin system. At present, OCD is the psychiatric syndrome for which a specific neurologic dysfunction is most strongly suggested, and for which a particularly compelling animal model has been found. It is proposed that dysfunction of basal ganglia-thalamic frontal cortical loops produce "positive" symptoms of excessive grooming, checking, and doubt most common in OCD. Perhaps most intriguing are preliminary data from clinical trials that a spectrum of other abnormal behaviors resembling excessive grooming in both animals and humans may be related to OCD. An ethologic perspective is suggested. RP RAPOPORT, JL (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,ROOM 6N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 64 TC 77 Z9 77 U1 2 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD AUG PY 1991 VL 5 IS 1 BP 1 EP 10 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA FW213 UT WOS:A1991FW21300001 PM 1930606 ER PT J AU MURPHY, DL AF MURPHY, DL TI THE SEROTONIN CONNECTION IN OCD - COMMENTS ON RECENT ADVANCES IN OBSESSIVE-COMPULSIVE DISORDER SO NEUROPSYCHOPHARMACOLOGY LA English DT Article ID RECEPTOR AGONISTS; ANIMAL-MODELS; RAT PUPS; MCPP; CHLOROPHENYLPIPERAZINE; RESPONSIVITY; SENSITIVITY; ANTAGONISTS; BEHAVIOR RP MURPHY, DL (reprint author), NIMH,CTR CLIN,CLIN SCI LAB,10-3D41,BETHESDA,MD 20892, USA. NR 25 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD AUG PY 1991 VL 5 IS 1 BP 11 EP 12 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA FW213 UT WOS:A1991FW21300002 PM 1834072 ER PT J AU INSEL, TR AF INSEL, TR TI HAS OCD RESEARCH GONE TO THE DOGS - COMMENTS ON RECENT ADVANCES IN OBSESSIVE-COMPULSIVE DISORDER SO NEUROPSYCHOPHARMACOLOGY LA English DT Article ID GLUCOSE METABOLIC RATES; 3,4-METHYLENEDIOXYMETHAMPHETAMINE C1 NIMH,CLIN SCI LAB,BETHESDA,MD 20892. NR 23 TC 4 Z9 4 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD AUG PY 1991 VL 5 IS 1 BP 13 EP 17 PG 5 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA FW213 UT WOS:A1991FW21300003 PM 1930607 ER PT J AU RAPOPORT, JL AF RAPOPORT, JL TI RECENT ADVANCES IN OBSESSIVE-COMPULSIVE DISORDER - REPLY SO NEUROPSYCHOPHARMACOLOGY LA English DT Letter ID TOURETTES SYNDROME RP RAPOPORT, JL (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,ROOM 6N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 8 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 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD AUG PY 1991 VL 5 IS 1 BP 21 EP 22 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA FW213 UT WOS:A1991FW21300005 ER PT J AU YUSUF, S AF YUSUF, S TI EFFECT OF ENALAPRIL ON SURVIVAL IN PATIENTS WITH REDUCED LEFT-VENTRICULAR EJECTION FRACTIONS AND CONGESTIVE-HEART-FAILURE SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CLINICAL-TRIALS; THERAPY AB Background. Patients with congestive heart failure have a high mortality rate and are also hospitalized frequently. We studied the effect of an angiotensin-converting-enzyme inhibitor, enalapril, on mortality and hospitalization in patients with chronic heart failure and ejection fractions less-than-or-equal-to 0.35. Methods. Patients receiving conventional treatment for heart failure were randomly assigned to receive either placebo (n = 1284) or enalapril (n = 1285) at doses of 2.5 to 20 mg per day in a double-blind trial. Approximately 90 percent of the patients were in New York Heart Association functional classes II and III. The follow-up averaged 41.4 months. Results. There were 510 deaths in the placebo group (39.7 percent), as compared with 452 in the enalapril group (35.2 percent) (reduction in risk, 16 percent; 95 percent confidence interval, 5 to 26 percent; P = 0.0036). Although reductions in mortality were observed in several categories of cardiac deaths, the largest reduction occurred among the deaths attributed to progressive heart failure (251 in the placebo group vs. 209 in the enalapril group; reduction in risk, 22 percent; 95 percent confidence interval, 6 to 35 percent). There was little apparent effect of treatment on deaths classified as due to arrhythmia without pump failure. Fewer patients died or were hospitalized for worsening heart failure (736 in the placebo group and 613 in the enalapril group; risk reduction, 26 percent; 95 percent confidence interval, 18 to 34 percent; P < 0.0001). Conclusions. The addition of enalapril to conventional therapy significantly reduced mortality and hospitalizations for heart failure in patients with chronic congestive heart failure and low ejection fractions. RP YUSUF, S (reprint author), NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,CLIN TRIALS BRANCH,FED BLDG,RM 5C08,BETHESDA,MD 20892, USA. NR 15 TC 3269 Z9 3356 U1 4 U2 49 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 AUG 1 PY 1991 VL 325 IS 5 BP 293 EP 302 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA FY715 UT WOS:A1991FY71500001 ER PT J AU MITSUDOMI, T VIALLET, J MULSHINE, JL LINNOILA, RI MINNA, JD GAZDAR, AF AF MITSUDOMI, T VIALLET, J MULSHINE, JL LINNOILA, RI MINNA, JD GAZDAR, AF TI MUTATIONS OF RAS GENES DISTINGUISH A SUBSET OF NON-SMALL-CELL LUNG-CANCER CELL-LINES FROM SMALL-CELL LUNG-CANCER CELL-LINES SO ONCOGENE LA English DT Article ID BLADDER-CARCINOMA ONCOGENE; POINT MUTATION; TUMOR PROGRESSION; P53 GENE; ACTIVATION; ADENOCARCINOMA; CARCINOGENESIS; AMPLIFICATION; INITIATION; EXPRESSION AB We screened a panel of 103 human lung cancer cell lines for the presence of point mutations at codons 12, 13 or 61 of the human K-, H- and N-ras genes, using restriction fragment length polymorphisms (RFLP), created through mismatched primers during polymerase chain reaction (PCR) of genomic DNA. We found ras mutations in 22/61 (36%) non-small-cell lung cancer (NSCLC) cell lines, predominantly in K-ras codon 12. Identical mutations were present in uncultured tumor materials corresponding to 11 cell lines containing mutated ras genes. ras mutations were found not only in adenocarcinoma cell lines (9/32, 28%), but also in cell lines derived from other types of NSCLC (13/29, 45%). In contrast, none of 37 small-cell lung cancer (SCLC) cell lines and five extrapulmonary small-cell cancer cell lines had ras mutations. ras mutations were not correlated with sex of the patients, tumor extent, prior therapy status or in vitro culture time. G to T or A to T transversions were the most common base substitutions, occurring in codons 12 and 61 respectively. We conclude that ras mutations play a role in the pathogenesis of a subset of NSCLC but are not involved in SCLC. C1 NATL NAVAL MED CTR, NCI NAVY MED ONCOL BRANCH, BDG 8, RM 5101, BETHESDA, MD 20889 USA. NCI, NAVY MED ONCOL BRANCH, BETHESDA, MD 20892 USA. OI Mitsudomi, Tetsuya/0000-0001-9860-8505 NR 47 TC 284 Z9 285 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG PY 1991 VL 6 IS 8 BP 1353 EP 1362 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA GX272 UT WOS:A1991GX27200010 PM 1679529 ER PT J AU CHAN, CC PALESTINE, AG DAVIS, JL DESMET, MD MCLEAN, IW BURNIER, M DROUILHET, JH NUSSENBLATT, RB AF CHAN, CC PALESTINE, AG DAVIS, JL DESMET, MD MCLEAN, IW BURNIER, M DROUILHET, JH NUSSENBLATT, RB TI ROLE OF CHORIORETINAL BIOPSY IN INFLAMMATORY EYE DISEASE SO OPHTHALMOLOGY LA English DT Article ID THERAPEUTIC SURGERY; UVEITIS; DIAGNOSIS; UVEA AB Two patients who had similar clinical presentations of bilateral multiple chorioretinal lesions and needed a correct diagnosis underwent chorioretinal biopsy. The biopsy from one patient demonstrated mainly a B cell infiltrate in choroidal and subretinal nodules, while the biopsy from the second patient showed mainly macrophages in the retina. These findings directed the therapeutic approach taken in each patient. Although chorioretinal biopsy is an invasive procedure with the potential for serious complications, the resultant finding may aid in the diagnosis and guide the subsequent management of certain patients presenting with serious ocular findings of undefined etiology. C1 GEORGETOWN UNIV,DEPT OPHTHALMOL,WASHINGTON,DC 20057. STRAUB CLIN,HONOLULU,HI. ARMED FORCES INST PATHOL,WASHINGTON,DC 20306. RP CHAN, CC (reprint author), NEI,IMMUNOL LAB,BLDG 10,RM 10N-206,BETHESDA,MD 20892, USA. OI de Smet, Marc/0000-0002-9217-5603 NR 17 TC 11 Z9 12 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD AUG PY 1991 VL 98 IS 8 BP 1281 EP 1286 PG 6 WC Ophthalmology SC Ophthalmology GA GA478 UT WOS:A1991GA47800026 PM 1923367 ER PT J AU HAYTHORNTHWAITE, JA SIEBER, WJ KERNS, RD AF HAYTHORNTHWAITE, JA SIEBER, WJ KERNS, RD TI DEPRESSION AND THE CHRONIC PAIN EXPERIENCE SO PAIN LA English DT Article DE CHRONIC PAIN; DEPRESSION; DEPRESSION DIAGNOSIS; PAIN INTENSITY; ACTIVITY; PAIN BEHAVIORS ID RESEARCH DIAGNOSTIC CRITERIA; RHEUMATOID-ARTHRITIS; AFFECTIVE-DISORDERS; PREVALENCE; INVENTORY; BEHAVIOR; SCHIZOPHRENIA; QUESTIONNAIRE; POPULATION; ANHEDONIA AB The present study examined the relationship between depression and a constellation of pain-related variables that describe the experience of chronic pain patients. Thirty-seven depressed and 32 non-depressed heterogeneous chronic pain patients were identified through structured interviews, use of standardized criteria and scores on the Beck Depression Inventory (BDI). The 2 groups were compared on demographic variables and scores on the Marlowe-Crowne Social Desirability scale (MC), as well as measures of disability and medication use, pain severity, interference due to pain and reported pain behaviors. The depressed group was found to be younger and to score lower on the MC than the non-depressed group. Multivariate analyses of covariance (MANCOVA), using age and MC as covariates, revealed that depressed chronic pain patients, relative to their non-depressed counterparts, reported greater pain intensity, greater interference due to pain and more pain behaviors. There were no group differences on the measures of disability and use of medications. The results provide further support for the importance of incorporating depression into clinical and theoretical formulations of chronic pain. Future use of structured interviews and standardized criteria for diagnosing depression may clarify some of the inconsistencies found in the literature. C1 YALE UNIV,NEW HAVEN,CT 06520. YALE UNIV,SCH MED,W HAVEN,CT 06516. W HAVEN VET AFFAIRS MED CTR,PSYCHOL SERV,W HAVEN,CT 06516. RP HAYTHORNTHWAITE, JA (reprint author), NIA,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 50 TC 127 Z9 131 U1 3 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD AUG PY 1991 VL 46 IS 2 BP 177 EP 184 DI 10.1016/0304-3959(91)90073-7 PG 8 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA GD015 UT WOS:A1991GD01500010 PM 1749640 ER PT J AU CLAESSON, BA SCHNEERSON, R LAGERGARD, T TROLLFORS, B TARANGER, J JOHANSSON, J BRYLA, D ROBBINS, JB AF CLAESSON, BA SCHNEERSON, R LAGERGARD, T TROLLFORS, B TARANGER, J JOHANSSON, J BRYLA, D ROBBINS, JB TI PERSISTENCE OF SERUM ANTIBODIES ELICITED BY HAEMOPHILUS-INFLUENZAE TYPE B-TETANUS TOXOID CONJUGATE VACCINE IN INFANTS VACCINATED AT 3, 5 AND 12 MONTHS OF AGE SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE HAEMOPHILUS-INFLUENZAE TYPE-B; TETANUS TOXOID; CONJUGATE VACCINE; CAPSULAR POLYSACCHARIDE; ANTIBODY CLASSES; IGG SUBCLASSES ID CAPSULAR POLYSACCHARIDE; 23-MONTH-OLD CHILDREN; YOUNG-CHILDREN; IMMUNIZATION; IMMUNOGENICITY; DISEASE; 18-MONTH-OLD; SPECIFICITY; INFECTIONS; SUBCLASSES AB Eighty-five children received three injections of a vaccine consisting of Haemophilus influenzae type b (Hib) capsular polysaccharide (CPS) conjugated to tetanus toxoid (TT) (Hib-TT) at 3, 5 and 12 months of age according to the vaccination schedule for Swedish children. Diphtheria-tetanus toxoid vaccine was concurrently injected at another site. Two dosages, 7.5 and 15 mu-g, of Hib CPS were studied. No serious reactions occurred. Hib-TT elicited fewer local reactions than diphtheria-tetanus toxoid vaccine. Significant increases in Hib CPS serum antibodies occurred after all injections in both dosage groups with virtually no differences between the two groups. After the first and second injections geometric mean serum antibody concentrations of both dosage groups combined increased to 0.49 and 3.71-mu-g/ml and 81 and 99% of the vaccinees, respectively, had concentrations > 0.15-mu-g/ml. After the third dose geometric mean concentrations increased to 13.7-mu-g/ml and all had concentrations > 0.15-mu-g/ml. The geometric mean Hib CPS antibody concentrations decreased to 1.24-mu-g/ml 18 months after the third injection, but 97% still had concentrations > 0.15-mu-g/ml. The rise of Hib CPS antibodies was mostly in the IgG class. The most pronounced increase was seen in the IgG1 subclass but there were also increases in IgG2 and IgG3. Protective concentrations of TT antibodies were found in all postimmunization sera. In conclusion Hib-TT is safe and immunogenic in infants and should be protective from 6 to 30 months and probably longer thereafter. C1 NICHHD,DEV & MOLEC IMMUNITY LAB,BETHESDA,MD 20892. NICHHD,BIOMETRY BRANCH,BETHESDA,MD 20892. NICHHD,MATH BRANCH,BETHESDA,MD 20892. GOTHENBURG UNIV,DEPT INFECT DIS,S-41124 GOTHENBURG,SWEDEN. GOTHENBURG UNIV,DEPT PEDIAT,S-41124 GOTHENBURG,SWEDEN. GOTHENBURG UNIV,DEPT MED MICROBIOL & IMMUNOL,S-41124 GOTHENBURG,SWEDEN. BORAS HOSP,DEPT PEDIAT,BORAS,SWEDEN. VASTRA FROLUNDA,PEDIAT OUTPATIENT CLIN,VASTRA FROLUNDA,SWEDEN. NR 32 TC 28 Z9 28 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 AUG PY 1991 VL 10 IS 8 BP 560 EP 564 DI 10.1097/00006454-199108000-00002 PG 5 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA GA463 UT WOS:A1991GA46300002 PM 1891286 ER PT J AU FRANCIS, GL JELINEK, JJ MCHALE, K ADAMSON, M LEVIN, SW AF FRANCIS, GL JELINEK, JJ MCHALE, K ADAMSON, M LEVIN, SW TI THE WEISMANN-NETTER SYNDROME - A CAUSE OF BOWED LEGS IN CHILDHOOD SO PEDIATRICS LA English DT Note C1 WALTER REED ARMY MED CTR,DEPT RADIOL,WASHINGTON,DC 20307. WALTER REED ARMY MED CTR,DEPT ORTHOPED,WASHINGTON,DC 20307. NICHHD,HUMAN GENET BRANCH,BETHESDA,MD 20892. RP FRANCIS, GL (reprint author), WALTER REED ARMY MED CTR,DEPT PEDIAT,WASHINGTON,DC 20307, USA. NR 10 TC 5 Z9 5 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD AUG PY 1991 VL 88 IS 2 BP 334 EP 337 PG 4 WC Pediatrics SC Pediatrics GA GA164 UT WOS:A1991GA16400023 PM 1861935 ER PT J AU DESOUZA, EB ZACZEK, R CULP, S APPEL, NM CONTRERA, JF AF DESOUZA, EB ZACZEK, R CULP, S APPEL, NM CONTRERA, JF TI COMPARISON OF THE EFFECTS OF REPEATED ORAL VERSUS SUBCUTANEOUS FENFLURAMINE ADMINISTRATION ON RAT-BRAIN MONOAMINE NEURONS - PHARMACOKINETIC AND DOSE-RESPONSE DATA SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE AMPHETAMINE; ANOREXIA; DOPAMINE; CATECHOLAMINES; NEUROTOXICITY; NOREPINEPHRINE; OBESITY; SEROTONIN ID SEROTONERGIC PROJECTIONS; PARA-CHLOROAMPHETAMINE; D-NORFENFLURAMINE; ANORECTIC DRUG; UPTAKE SITES; NEUROTOXICITY; MECHANISMS; TERMINALS; AMPHETAMINES; METABOLITES AB The importance of the route of drug administration (oral vs. subcutaneous) on the neurochemical effects and pharmacokinetics of repeated d,1-fenfluramine administration in rats (1-24 mg/kg b.i.d., i.e., 2-48 mg/kg/day for 4 days) was examined. Overall, comparable dose-dependent alterations in brain monoamine markers were observed following repeated oral (PO) and subcutaneous (SC) administration of fenfluramine. Doses of 1 and 2 mg/kg fenfluramine were without significant effects on the density of H-3-paroxetine-labeled serotonin (5-HT) uptake sites. Higher doses of fenfluramine (4, 12 and 24 mg/kg) produced dose-dependent decreases in 5-HT, 5-hydroxyindoleacetic acid and 5-HT uptake sites with maximal decreases (80-90%) occurring at the 12 mg/kg dose. Fenfluramine administration produced dose-dependent and biphasic effects on brain dopamine markers with increases in homovanillic acid (HVA) observed at 2 hours, whereas decreases in the levels of dopamine, HVA and dihydroxyphenylacetic acid were evident at 18 hours posttreatment. Norepinephrine levels were only decreased at the highest dose of fenfluramine. Significantly higher levels of brain fenfluramine were observed following SC than following PO administration of the drug. On the other hand, comparable levels of its active metabolite norfenfluramine were present in the brain following the two routes of fenfluramine administration. These data suggest that the importance of norefenfluramine levels in the brain in determining the high-dose neurotoxic effects of fenfluramine on brain 5-HT neurons in rats. C1 NIDA,ADDICT RES CTR,NEUROBIOL LAB,BALTIMORE,MD 21224. US FDA,CTR DRUGS & BIOL,DIV NEUROPHARMACOL DRUG PROD,ROCKVILLE,MD 20857. NR 32 TC 6 Z9 6 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD AUG PY 1991 VL 39 IS 4 BP 963 EP 969 DI 10.1016/0091-3057(91)90060-F PG 7 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA GK692 UT WOS:A1991GK69200022 PM 1763116 ER PT J AU HALL, RD BUETTNER, GR CHIGNELL, CF AF HALL, RD BUETTNER, GR CHIGNELL, CF TI THE BIPHOTONIC PHOTOIONIZATION OF CHLORPROMAZINE DURING CONVENTIONAL FLASH-PHOTOLYSIS - SPIN TRAPPING RESULTS WITH 5,5-DIMETHYL-1-PYRROLINE-N-OXIDE SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID PROMAZINE; RADICALS; PHENOTHIAZINE; TRYPTOPHAN; DEPENDENCE AB A novel combination of conventional flash photolysis and electron spin resonance (ESR) spin-trapping has been used to demonstrate that photoionization of chlorpromazine (CPZ), and the concomitant production of hydrated electron, occurs through a stepwise biphotonic mechanism during conventional flash photolysis at wavelengths above 290 nm. The production of hydrated electron in the flash photolysis experiment has been monitored and quantified through the use of the spin trapping agent 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). The effects of nitrous oxide, varying concentrations of CPZ and DMPO, and a range of flash intensities on the ESR spectra of the observed spin adducts of DMPO are discussed. The use of ESR spin trapping to monitor hydrated electron yields in flash photolysis experiments has the potential to permit the use of a much wider range of flash intensities than is typically possible with conventional optical experiments. Thus, there is a greater possiblity of distinguishing between monophotonic and biphotonic processes. C1 NIEHS,MOLEC BIOPHYS LAB,POB 12233,RES TRIANGLE PK,NC 27709. OI Buettner, Garry/0000-0002-5594-1903 NR 24 TC 17 Z9 18 U1 0 U2 0 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD AUG PY 1991 VL 54 IS 2 BP 167 EP 173 DI 10.1111/j.1751-1097.1991.tb02003.x PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA FZ590 UT WOS:A1991FZ59000003 PM 1664109 ER PT J AU DEPABLO, F ROBCIS, HL CALDES, T ALEMANY, J SCAVO, L SERRANO, J AF DEPABLO, F ROBCIS, HL CALDES, T ALEMANY, J SCAVO, L SERRANO, J TI INSULIN-LIKE GROWTH FACTOR-I AND INSULIN AS GROWTH AND DIFFERENTIATION FACTORS IN CHICKEN EMBRYOGENESIS SO POULTRY SCIENCE LA English DT Article DE INSULIN-LIKE GROWTH FACTOR-I; INSULIN; RECEPTORS; DEVELOPMENT; CHICKEN EMBRYO ID ANTIBODIES RETARD; GENE-EXPRESSION; RECEPTORS; EMBRYOS; LENS AB The avian embryo has been a useful model system for studies on the role of insulin and its close relative insulin-like growth factor-I (IGF-I) in development. The unfertilized chicken egg contains both peptides from maternal origin, and the embryo expresses insulin and IGF-I before the major organs are formed. Insulin receptors and IGF-I receptors are found in the blastoderm and in all tissues examined during organogenesis. When exogenous insulin or IGF-I are added to the embryo, growth and differentiation events are stimulated. By contrast, insulin antibodies and insulin receptor antibodies retard embryo development. In embryos cultured ex ovo, in which growth is impaired, the levels of serum IGF-I are decreased. C1 NIH,NATL CTR RES RESOURCES,VET RESOURCES PROGRAM,BETHESDA,MD 20892. RP DEPABLO, F (reprint author), NIH,NATL CTR RES RESOURCES,RECEPTORS & HORMONE ACT SECT,DIABET BRANCH,BETHESDA,MD 20892, USA. NR 17 TC 20 Z9 20 U1 0 U2 1 PU POULTRY SCIENCE ASSN INC PI CHAMPAIGN PA 309 W CLARK ST, CHAMPAIGN, IL 61802 SN 0032-5791 J9 POULTRY SCI JI Poult. Sci. PD AUG PY 1991 VL 70 IS 8 BP 1790 EP 1796 PG 7 WC Agriculture, Dairy & Animal Science SC Agriculture GA FZ113 UT WOS:A1991FZ11300019 PM 1656419 ER PT J AU SIMPSON, JL MILLS, JL RHOADS, GG CUNNINGHAM, GC HOFFMAN, HJ CONLEY, MR AF SIMPSON, JL MILLS, JL RHOADS, GG CUNNINGHAM, GC HOFFMAN, HJ CONLEY, MR TI VITAMINS, FOLIC-ACID AND NEURAL-TUBE DEFECTS - COMMENTS ON INVESTIGATIONS IN THE UNITED-STATES SO PRENATAL DIAGNOSIS LA English DT Article; Proceedings Paper CT 5TH INTERNATIONAL CONGRESS ON EARLY FETAL DIAGNOSIS : RECENT PROGRESS AND PUBLIC HEALTH CY JUL 08-14, 1990 CL PRAGUE, CZECHOSLOVAKIA SP ASSOC CZECHOSLOVAK MED SOC, SOC MED GENET OBSTET & GYNAECOL & PAEDIAT, CTR MED GENET CZECH REPUBL, CZECHOSLOVAK ACAD SCI, BIOL SOC, CYTOGENET SECT DE NEURAL TUBE DEFECTS; MULTIVITAMINS; FOLIC ACID ID PERICONCEPTIONAL USE; SUPPLEMENTATION; PREVENTION; TRIAL AB No clear answer concerning whether multivitamin/folate supplementation prevents neural tube defects (NTDs) is provided by three studies in the United States. All these studies are occurrence in nature, no recurrence studies having been conducted. The Atlanta Birth Defects Study is subject to pronounced memory and recall biases, the length between event and interview being as long as 16 years. In a second study (Boston University), objections can be raised to certain aspects of the experimental design, and the claim that 22 per cent of women started vitamins sufficiently early after pregnancy diagnosis to influence NTD formation is suspicious. Our NICHD case control study of 541 women in California and Illinois revealed no evidence for multivitamins or folic acid preventing NTDs. U.S. public policy-makers face difficulties in applying results of recurrence or occurrence studies in high-risk areas to low-risk areas in the U.S. C1 NICHHD,BETHESDA,MD. ROBERT WOOD JOHNSON MED SCH,PISCATAWAY,NJ. CALIF PUBL HLTH FDN,BERKELEY,CA. RP SIMPSON, JL (reprint author), UNIV TENNESSEE,CTR HLTH SCI,MEMPHIS,TN 38163, USA. NR 17 TC 9 Z9 9 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0197-3851 J9 PRENATAL DIAG JI Prenat. Diagn. PD AUG PY 1991 VL 11 IS 8 BP 641 EP 648 DI 10.1002/pd.1970110823 PG 8 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA GE669 UT WOS:A1991GE66900022 PM 1766937 ER PT J AU FELDER, CC WILLIAMS, HL AXELROD, J AF FELDER, CC WILLIAMS, HL AXELROD, J TI A TRANSDUCTION PATHWAY ASSOCIATED WITH RECEPTORS COUPLED TO THE INHIBITORY GUANINE-NUCLEOTIDE BINDING PROTEIN-GI THAT AMPLIFIES ATP-MEDIATED ARACHIDONIC-ACID RELEASE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE PHOSPHOLIPASE-A2; PHORBOL ESTER; PERTUSSIS TOXIN; CAMP; PROTEIN KINASE-C ID MUSCARINIC ACETYLCHOLINE-RECEPTOR; PHOSPHOLIPASE-C; ACTIVATION; CELLS; METABOLITES; STIMULATION; HYDROLYSIS; DOPAMINE; CYCLASE; CAMP AB ATP is copackaged and coreleased with adrenergic, serotonergic, and cholinergic neurotransmitters, suggesting a possible interaction between the signaling pathways for ATP and these coreleased neurotransmitters. Muscarinic m2 and m4, alpha-2-adrenergic, and D2-dopaminergic neurotransmitter receptors, which have in common their ability to inhibit adenylate cyclase through the inhibitory guanine nucleotide binding protein G(i), were transfected and expressed in Chinese hamster ovary (CHO) cells that contain endogenous ATP receptors coupled to the release of arachidonic acid. Normal functional coupling of m2, m4, alpha-2, and D2 receptors was demonstrated by their ability to inhibit forskolin-stimulated cAMP accumulation with dose-response activities consistent with previous reports for these G(i)-coupled receptors. Stimulation of m2, m4, alpha-2, and D2 receptors resulted in an augmentation of ATP-stimulated arachidonic acid release. With the exception of the m4 receptor, none of the receptors tested was able to stimulate arachidonic acid release in the absence of ATP. Potentiation of ATP-stimulated arachidonic acid release was independent of changes in cAMP. The augmentation of ATP-stimulated arachidonic acid release and the inhibition of cAMP accumulation were both blocked by pertussis toxin, an inhibitor of G(i), but with different dose-response characteristics. Inhibition of protein kinase C with staurosporine or long-term pretreatment of the cells with the phorbol ester phorbol 12-myristate 13-acetate blocked the augmentation response. This demonstrates that G(i)-coupled inhibitory receptors can amplify ATP-receptor-stimulated arachidonic acid release through a pertussis-toxin-sensitive G protein, independent of their ability to inhibit adenylate cyclase activity. C1 NIH,HOWARD HUGHES MED INST,RES SCHOLARS PROGRAM,BETHESDA,MD 20892. RP FELDER, CC (reprint author), NIMH,CELL BIOL LAB,BLDG 36,ROOM 3A-15,BETHESDA,MD 20892, USA. NR 25 TC 88 Z9 90 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 AUG PY 1991 VL 88 IS 15 BP 6477 EP 6480 DI 10.1073/pnas.88.15.6477 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FZ344 UT WOS:A1991FZ34400019 PM 1650470 ER PT J AU WALKER, TA WILSON, BA LEWIS, AM COOK, JL AF WALKER, TA WILSON, BA LEWIS, AM COOK, JL TI E1A ONCOGENE INDUCTION OF CYTOLYTIC SUSCEPTIBILITY ELIMINATES SARCOMA CELL TUMORIGENICITY SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE NEOPLASTIC TRANSFORMATION; ADENOVIRUS; NATURAL KILLER CELL; TUMOR IMMUNITY ID NATURAL-KILLER CELLS; TOXIC LYMPHOCYTES-T; ADENOVIRUS E1A; ACTIVATED MACROPHAGES; TRANSFORMED CELLS; NK SENSITIVITY; LYSIS; GENE; PRODUCTS; MYC AB The manner in which oncogenes influence tumorigenicity beyond their ability to immortalize cells is uncertain. We tested the hypothesis that, in addition to subverting cellular growth controls, oncogenes can actively determine tumor-inducing capacity by affecting neoplastic cell susceptibility to destruction by the host cellular immune response. The adenovirus type 5 E1A oncogene, which induces susceptibility to lysis by natural killer cells and encodes epitopes recognized by cytotoxic T lymphocytes, was transfected into highly tumorigenic sarcoma cells. E1A expression in these sarcoma cells eliminated their tumorigenicity in recipients with natural killer cell activity that was competent to lyse these E1A-positive targets. Thymus-dependent responses were not required for tumor rejection. These results indicate that oncogene-regulated cellular pathways that affect neoplastic cell susceptibility to natural killer cell lytic mechanisms may influence tumor development in the immunocompetent host. C1 NATL JEWISH CTR IMMUNOL & RESP MED,DEPT MED,ROBERT W LISLE RES LAB IMMUNOL & TUMOR CELL BIOL,DENVER,CO 80206. UNIV COLORADO,HLTH SCI CTR,DEPT MED,DENVER,CO 80262. UNIV COLORADO,HLTH SCI CTR,DEPT MICROBIOL IMMUNOL,DENVER,CO 80262. NIAID,IMMUNOPATHOL LAB,VIRAL PATHOGENESIS SECT,BETHESDA,MD 20892. FU NCI NIH HHS [CA 43187] NR 34 TC 32 Z9 32 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG PY 1991 VL 88 IS 15 BP 6491 EP 6495 DI 10.1073/pnas.88.15.6491 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FZ344 UT WOS:A1991FZ34400022 PM 1830664 ER PT J AU DEFEO, ML BARTOLINI, O ORLANDO, C MAGGI, M SERIO, M PINES, M HURWITZ, S FUJII, Y SAKAGUCHI, K AURBACH, GD BRANDI, ML AF DEFEO, ML BARTOLINI, O ORLANDO, C MAGGI, M SERIO, M PINES, M HURWITZ, S FUJII, Y SAKAGUCHI, K AURBACH, GD BRANDI, ML TI NATRIURETIC PEPTIDE RECEPTORS REGULATE ENDOTHELIN SYNTHESIS AND RELEASE FROM PARATHYROID CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ATRIAL NATRIURETIC PEPTIDE; BRAIN NATRIURETIC PEPTIDE; PEPTIDE HORMONE RECEPTOR; HYPERTENSION ID HORMONE-RELATED PROTEIN; SMOOTH-MUSCLE CELLS; CYCLIC-NUCLEOTIDES; CALCIUM-METABOLISM; HYPERTENSIVE RATS; MESSENGER-RNA; SECRETION; BRAIN; LINE; RADIOIMMUNOASSAY AB Cloned rat parathyroid cells (PTr cell line) that produce parathyroid hormone-related peptide plus endothelin 1 and primary cultures of human parathyroid cells were tested for growth and differentiation responses to atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). High- and low-affinity binding sites for ANP were found on PTr cells; BNP appeared to bind to the same receptors with similar affinities. Either ANP or BNP stimulated production of cGMP and caused a 30 % decrease in Na+-K+-Cl- cotransport. Each peptide increased synthesis and secretion of endothelin 1 by PTr cells in a dose-dependent fashion, but cell growth was not affected. Human parathyroid cells (normal and pathological) also responded to ANP or BNP with an increase in cGMP production. The finding of receptors for natriuretic hormones on parathyroid cells with consequent effects on release of endothelin 1 might be of relevance in understanding the clinical association between hyperparathyroidism and hypertension. C1 AGR RES ORG,VOLCANI CTR,INST ANIM SCI,IL-50250 BET DAGAN,ISRAEL. NIDDKD,METAB DIS BRANCH,BETHESDA,MD 20892. RP DEFEO, ML (reprint author), UNIV FLORENCE,DEPT CLIN PHYSIOPATHOL,VIALE PIERACCINI 6,I-50139 FLORENCE,ITALY. NR 52 TC 22 Z9 22 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 AUG PY 1991 VL 88 IS 15 BP 6496 EP 6500 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FZ344 UT WOS:A1991FZ34400023 PM 1650471 ER PT J AU LEVINE, A CANTONI, GL RAZIN, A AF LEVINE, A CANTONI, GL RAZIN, A TI INHIBITION OF PROMOTER ACTIVITY BY METHYLATION - POSSIBLE INVOLVEMENT OF PROTEIN MEDIATORS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DNA METHYLATION; TRANSCRIPTIONAL ACTIVATION; CYTOSINE METHYLATION; FACTOR BINDING; GENE; EXPRESSION; DEMETHYLATION; CHROMATIN; NUCLEI; CPGS AB To study the relationship between DNA methylation and promoter activity we have methylated in vitro the promoters of the mouse metallothionein I gene and the herpes simplex virus thymidine kinase gene. We have transiently transfected these promoters fused to the human growth hormone in their methylated or unmethylated state into mouse L or F9 cells. Promoters methylated by methylase (M.) Hpa II and M.Hha I caused inhibition of reporter gene expression in L cells but not in F9 cells, while methylation of all CpGs by M.Sss I caused inhibition in both cell lines. Repression of promoter activity by M.Hpa II and M.Hha I methylation, but not by M.Sss I methylation, could be alleviated by cotransfection with an excess of untranscribable DNA methylated with M.Sss I. The methylated sites in nuclei isolated from the transfected L cells, but not F9 cells, were found to be protected from Msp I digestion. Taken together these results suggest that a factor present in L cells and missing in F9 cells mediates the methylation-directed inhibition of promoter activity. The ability of methylated DNA to overcome the inhibition seems to reflect competition for the mediator factor. Interestingly, treatment with Zn2+ ions brought about activation of the methylated promoter of the metallothionein gene. Similarly, butyrate could override the repression of the thymidine kinase methylated promoter. These activations were not accompanied by demethylation of the promoter or displacement of the mediator factor. C1 NIMH,GEN & COMPARAT BIOCHEM LAB,BETHESDA,MD 20892. RP LEVINE, A (reprint author), HEBREW UNIV JERUSALEM,HADASSAH MED SCH,DEPT CELLULAR BIOCHEM,IL-91010 JERUSALEM,ISRAEL. NR 23 TC 78 Z9 78 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 AUG PY 1991 VL 88 IS 15 BP 6515 EP 6518 DI 10.1073/pnas.88.15.6515 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FZ344 UT WOS:A1991FZ34400027 PM 1650472 ER PT J AU TRAPNELL, BC CHU, CS PAAKKO, PK BANKS, TC YOSHIMURA, K FERRANS, VJ CHERNICK, MS CRYSTAL, RG AF TRAPNELL, BC CHU, CS PAAKKO, PK BANKS, TC YOSHIMURA, K FERRANS, VJ CHERNICK, MS CRYSTAL, RG TI EXPRESSION OF THE CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR GENE IN THE RESPIRATORY-TRACT OF NORMAL INDIVIDUALS AND INDIVIDUALS WITH CYSTIC-FIBROSIS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE MESSENGER RNA; QUANTITATIVE POLYMERASE CHAIN REACTION; EPITHELIAL CELLS ID POLYMERASE CHAIN-REACTION; MESSENGER-RNA; REVERSE-TRANSCRIPTASE; IDENTIFICATION; DNA; RIBONUCLEASE; ACID AB The most common mutation of the cystic fibrosis transmembrane conductance regulator gene, CFTR, associated with the clinical disorder cystic fibrosis (CF) is called "DELTA-Phe508," a triple-base deletion resulting in loss of phenylalanine at residue 508 of the predicted 1480-amino acid CFTR protein. In the context that the lung is the major site of morbidity and mortality in CF, we evaluated airway epithelial cells for CFTR mRNA transcripts in normal individuals, normal-DELTA-Phe508 heterozygotes, and DELTA-Phe508 homozygotes to determine if the normal and DELTA-Phe508 CFTR alleles are expressed in the respiratory epithelium, to what extent they are expressed, and whether there are relative differences in the expression of the normal and abnormal alleles at the mRNA level. Respiratory tract epithelial cells recovered by fiberoptic bronchoscopy with a cytology brush demonstrated CFTR mRNA transcripts with sequences appropriately reflecting the normal and DELTA-Phe508 CFTR alleles of the various study groups. CFTR gene expression quantified by limited polymerase chain reaction amplification showed that in normal individuals, CFTR mRNA transcripts are expressed in nasal, tracheal, and bronchial epithelial cells at almost-equal-to 1-2 copies per cell, more than 100-fold greater than in pharyngeal epithelium. Importantly, allele-specific hybridization studies demonstrated that the normal and DELTA-Phe508 CFTR alleles are expressed in the respiratory epithelium in similar amounts. C1 NHLBI,PATHOL BRANCH,BETHESDA,MD 20892. NIDDKD,PEDIAT METAB BRANCH,BETHESDA,MD 20892. RP TRAPNELL, BC (reprint author), NHLBI,PULM BRANCH,BLDG 10,ROOM 6D03,BETHESDA,MD 20892, USA. NR 19 TC 212 Z9 212 U1 1 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG PY 1991 VL 88 IS 15 BP 6565 EP 6569 DI 10.1073/pnas.88.15.6565 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FZ344 UT WOS:A1991FZ34400038 PM 1713683 ER PT J AU LEEHUANG, S HUANG, PL KUNG, HF LI, BQ HUANG, PL HUANG, P HUANG, HI CHEN, HC AF LEEHUANG, S HUANG, PL KUNG, HF LI, BQ HUANG, PL HUANG, P HUANG, HI CHEN, HC TI TAP-29 - AN ANTI-HUMAN-IMMUNODEFICIENCY-VIRUS PROTEIN FROM TRICHOSANTHES-KIRILOWII THAT IS NONTOXIC TO INTACT-CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ANTIVIRAL AGENT; AIDS; PLANT PROTEIN ID RICIN-A-CHAIN; PHYTOLACCA-AMERICANA; ANTIVIRAL PROTEIN; EUKARYOTIC RIBOSOMES; ALPHA-TRICHOSANTHIN; PURIFICATION; REPLICATION; INHIBITION; MECHANISM; HOMOLOGY AB An anti-human immunodeficiency virus (anti-HIV) protein capable of inhibiting HIV-1 infection and replication has been isolated and purified to homogeneity from Trichosanthes kirilowii. This protein, TAP 29 (Trichosanthes anti-HIV protein, 29 kDa), is distinct from trichosanthin [also known as GLQ 223 (26 kDa)] in size, N-terminal amino acid sequence, and cytotoxicity. In addition to three conservative substitutions - namely, Arg-29 to Lys, Ile-37 to Val, and Pro-42 to Ser - a total difference of residues 12-16 was found. TAP 29 yielded -Lys-Lys-Lys-Val-Tyr-, whereas trichosanthin has -Ser-Ser-Tyr-Gly-Val-. Although the two proteins exhibit similar anti-HIV activity, as measured by syncytium formation, p24 expression, and HIV reverse transcriptase activity, they differ significantly in cytotoxicity, as measured by their effects on cellular DNA and protein syntheses. At the dose level of the bioassays, 0.34-340 nM, trichosanthin demonstrates a dose-dependent toxic effect on host cells. TAP 29 displays no toxic effect, even at 100 x ID50, whereas trichosanthin demonstrates 38% and 44% inhibition on cellular DNA and protein synthesis, respectively. These results indicate that the therapeutic index of TAP 29 is at least two orders of magnitude higher than that of trichosanthin. Thus TAP 29 may offer a broader safe dose range in the treatment of AIDS. C1 AMER BIOSCI,NEW YORK,NY 10021. NCI,FREDERICK CANC RES FACIL,BIOCHEM PHYSIOL LAB,FREDERICK,MD 21701. NCI,FREDERICK CANC RES FACIL,PROGRAM RESOURCE INC,BIOL CARCINOGEN DEV PROGRAM,FREDERICK,MD 21701. NICHHD,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892. RP LEEHUANG, S (reprint author), NYU,SCH MED,DEPT BIOCHEM,NEW YORK,NY 10016, USA. FU NCRR NIH HHS [SO7 RR05399-28] NR 26 TC 106 Z9 110 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 AUG PY 1991 VL 88 IS 15 BP 6570 EP 6574 DI 10.1073/pnas.88.15.6570 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FZ344 UT WOS:A1991FZ34400039 PM 1713684 ER PT J AU URRUTIA, R MCNIVEN, MA ALBANESI, JP MURPHY, DB KACHAR, B AF URRUTIA, R MCNIVEN, MA ALBANESI, JP MURPHY, DB KACHAR, B TI PURIFIED KINESIN PROMOTES VESICLE MOTILITY AND INDUCES ACTIVE SLIDING BETWEEN MICROTUBULES INVITRO SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE MICROTUBULE MOTILITY; INTRACELLULAR TRANSPORT; MITOTIC SPINDLE DYNAMICS; ORGANELLE MOVEMENT; SECRETORY GRANULE TRANSLOCATION ID CULTURED-CELLS; ATPASE ACTIVITY; TRANSPORT; PROTEIN; MYOSIN; IDENTIFICATION; LOCALIZATION; ANTIBODIES; DROSOPHILA; MOVEMENTS AB We examined the ability of kinesin to support the movement of adrenal medullary chromaffin granules on microtubules in a defined in vitro system. We found that kinesin and ATP are all that is required to support efficient (33% vesicle motility) and rapid (0.4-0.6-mu-m/s) translocation of secretory granule membranes on microtubules in the presence of a low-salt motility buffer. Kinesin also induced the formation of microtubule asters in this buffer, with the plus ends of microtubules located at the center of each aster. This observation indicates that kinesin is capable of promoting active sliding between microtubules toward their respective plus ends, a movement analogous to that of anaphase b in the mitotic spindle. The fact that vesicle translocation, microtubule sliding, and microtubule-dependent kinesin ATPase activities are all enhanced in low-salt buffer establishes a functional parallel between this translocator and other motility ATPases, myosin, and dynein. C1 MAYO CLIN & MAYO FDN,ROCHESTER,MN 55905. UNIV TEXAS,SW MED CTR,DALLAS,TX 75235. JOHNS HOPKINS UNIV,SCH MED,DEPT CELL BIOL & ANAT,BALTIMORE,MD 21205. RP KACHAR, B (reprint author), NIDCD,CELLULAR BIOL LAB,BETHESDA,MD 20892, USA. NR 35 TC 106 Z9 107 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 AUG PY 1991 VL 88 IS 15 BP 6701 EP 6705 DI 10.1073/pnas.88.15.6701 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FZ344 UT WOS:A1991FZ34400067 PM 1830666 ER PT J AU BADER, JP MCMAHON, JB SCHULTZ, RJ NARAYANAN, VL PIERCE, JB HARRISON, WA WEISLOW, OS MIDELFORT, CF STINSON, SF BOYD, MR AF BADER, JP MCMAHON, JB SCHULTZ, RJ NARAYANAN, VL PIERCE, JB HARRISON, WA WEISLOW, OS MIDELFORT, CF STINSON, SF BOYD, MR TI OXATHIIN CARBOXANILIDE, A POTENT INHIBITOR OF HUMAN-IMMUNODEFICIENCY-VIRUS REPRODUCTION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ACQUIRED IMMUNODEFICIENCY SYNDROME; LYMPHOCYTES-T; CHEMOTHERAPY ID PLACEBO-CONTROLLED TRIAL; AIDS-RELATED COMPLEX; AZIDOTHYMIDINE AZT; ANTIVIRAL ACTIVITY; ESCHERICHIA-COLI; ZIDOVUDINE AZT; DOUBLE-BLIND; HIV; INFECTIVITY; EXPRESSION AB Oxathiin carboxanilide (OC), NSC 615985, a compound originally synthesized as a potential fungicide, was demonstrated to be highly active in preventing human immunodeficiency virus (HIV)-induced cell killing and in inhibiting HIV reproduction. Virus-infected CD4+ lymphocytes were completely protected by 0.5-mu-M OC, whereas no toxicity was observed at concentrations below 50-mu-M OC. Production of infectious virus, viral p24 antigen, and virion reverse transcriptase were reduced by OC at concentrations that prevented viral cell killing. A variety of CD4+ T-cell lines were protected by OC from HIV cytopathicity, and OC inhibited two distinct strains of HIV-1. However, HIV-2 infections were unaffected by OC. OC had no direct effect on virions of HIV or on the enzymatic activities of HIV reverse transcriptase or HIV protease. Time-limited treatments of cells with OC before, during, or after exposure of cells to virus failed to protect cells from the eventual cytopathic effects of HIV, and OC failed to inhibit the production of virus from cells in which infection was established or from chronically infected cells. We conclude that the highly active OC has a reversible effect on some early stage of HIV-1 reproduction and cytopathicity. Pilot in vivo experiments showed that circulating concentrations of OC exceeding 1-mu-M could be achieved and sustained in hamsters for at least a week with no remarkable toxicological sequelae. OC represents a new class of anti-HIV agents that are promising candidates for drug development. C1 PROGRAM RESOURCES INC,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. UNIROYAL CHEM CO INC,MIDDLEBURY,CT 06749. UNIROYAL CHEM LTD,GUELPH NIH 6N3,ONTARIO,CANADA. RP BADER, JP (reprint author), NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892, USA. NR 19 TC 65 Z9 65 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 AUG PY 1991 VL 88 IS 15 BP 6740 EP 6744 DI 10.1073/pnas.88.15.6740 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FZ344 UT WOS:A1991FZ34400075 PM 1713689 ER PT J AU SANDER, M LOWENHAUPT, K RICH, A AF SANDER, M LOWENHAUPT, K RICH, A TI DROSOPHILA RRP1 PROTEIN - AN APURINIC ENDONUCLEASE WITH HOMOLOGOUS RECOMBINATION ACTIVITIES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE STRAND TRANSFER; EXODEOXYRIBONUCLEASE; DNA REPAIR ID ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; HUMAN-CELLS; APYRIMIDINIC ENDONUCLEASES; STRAND TRANSFERASE; MEIOTIC CELLS; RECA PROTEIN; DNA; REPAIR; PURIFICATION AB A protein previously purified from Drosophila embryo extracts by a DNA strand transfer assay, Rrp1 (recombination repair protein 1), has an N-terminal 427-amino acid region unrelated to known proteins, and a 252-amino acid C-terminal region with sequence homology to two DNA repair nucleases, Escherichia coli exonuclease III and Streptococcus pneumoniae exonuclease A, which are known to be active as apurinic endonucleases and as double-stranded DNA 3' exonucleases. We demonstrate here that purified Rrp1 has apurinic endonuclease and double-stranded DNA 3' exonuclease activities and carries out single-stranded DNA renaturation in a Mg2+-dependent manner. Strand transfer, 3' exonuclease, and single-stranded DNA renaturation activities comigrate during column chromatography. The properties of Rrp1 suggest that it could promote homologous recombination at sites of DNA damage. C1 MIT,DEPT BIOL,CAMBRIDGE,MA 02139. RP SANDER, M (reprint author), NIEHS,GENET LAB D304,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 40 TC 66 Z9 68 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 AUG PY 1991 VL 88 IS 15 BP 6780 EP 6784 DI 10.1073/pnas.88.15.6780 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FZ344 UT WOS:A1991FZ34400083 PM 1713691 ER PT J AU HAYES, JJ CLARK, DJ WOLFFE, AP AF HAYES, JJ CLARK, DJ WOLFFE, AP TI HISTONE CONTRIBUTIONS TO THE STRUCTURE OF DNA IN THE NUCLEOSOME SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RNA POLYMERASE-II; CORE PARTICLE; CHROMATIN STRUCTURE; PAIR DNA; 5S RNA; TRANSCRIPTION; GENE; RESOLUTION; SEQUENCE; INVITRO AB We describe the application of the hydroxyl radical footprinting technique to examine the contribution of the core histone tails and of histones H-3 and H-4 to the structure of DNA in the nucleosome. We first establish that, as was previously determined for a nucleosome containing a unique sequence of DNA, mixed-sequence nucleosomes contain two distinct regions of DNA structure. The central three turns of DNA in the nucleosome have a helical periodicity of almost-equal-to 10.7 base pairs per turn, while nanking regions have a periodicity of almost-equal-to 10.0 base pairs per turn. Removal of the histone tails does not change the hydroxyl radical cleavage pattern in either mixed- or unique-sequence nucleosome samples. A tetramer of histones H3 and H4, (H3/H4)2, organizes the central 120 base pairs of DNA identically to that found in the nucleosome. Moreover, "tailless" octamers and the (H3/H4)2 tetramer recognize the same nucleosome positioning signals as the intact octamer. RP HAYES, JJ (reprint author), NIDDKD,MOLEC BIOL LAB,BLDG 6,ROOM 131,BETHESDA,MD 20892, USA. NR 48 TC 241 Z9 242 U1 2 U2 10 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 AUG PY 1991 VL 88 IS 15 BP 6829 EP 6833 DI 10.1073/pnas.88.15.6829 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FZ344 UT WOS:A1991FZ34400093 PM 1650485 ER PT J AU RABINDRAN, SK GIORGI, G CLOS, J WU, C AF RABINDRAN, SK GIORGI, G CLOS, J WU, C TI MOLECULAR-CLONING AND EXPRESSION OF A HUMAN HEAT-SHOCK FACTOR, HSF1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE HUMAN TRANSCRIPTION FACTOR; LEUCINE ZIPPERS; POLYMERASE CHAIN REACTION ID ESCHERICHIA-COLI; BINDING-PROTEIN; SIGMA-FACTORS; DNA-BINDING; YEAST; GENE; TRANSCRIPTION; ACTIVATION; PROMOTER; INVITRO AB Human cells respond to heat stress by inducing the binding of a preexisting transcriptional activator (heat shock factor, HSF) to DNA. We have isolated recombinant DNA clones for a human HSF (HSF1) by screening cDNA libraries with a human cDNA fragment. The human HSF1 probe was produced by the PCR with primers deduced from conserved amino acids in the Drosophila and yeast HSF sequences. The human HSF1 mRNA is constitutively expressed in HeLa cells under nonshock conditions and encodes a protein with four conserved leucine zipper motifs. Like its counterpart in Drosophila, human HSF1 produced in Escherichia coli in the absence of heat shock is active as a DNA binding transcription factor, suggesting that the intrinsic activity of HSF is under negative control in human cells. Surprisingly, an independently isolated human HSF clone, HSF2, is related to but significantly different from HSF1 [Schuetz, T. J., Gallo, G. J., Sheldon, L., Tempst, P. & Kingston, R. E. (1991) Proc. Natl. Acad. Sci. USA 88, 6911-69151. RP RABINDRAN, SK (reprint author), NCI,BIOCHEM LAB,BLDG 37,ROOM 4C-09,BETHESDA,MD 20892, USA. NR 33 TC 378 Z9 390 U1 0 U2 15 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 AUG PY 1991 VL 88 IS 16 BP 6906 EP 6910 DI 10.1073/pnas.88.16.6906 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GB701 UT WOS:A1991GB70100002 PM 1871105 ER PT J AU ZHURKIN, VB ULYANOV, NB GORIN, AA JERNIGAN, RL AF ZHURKIN, VB ULYANOV, NB GORIN, AA JERNIGAN, RL TI STATIC AND STATISTICAL BENDING OF DNA EVALUATED BY MONTE-CARLO SIMULATIONS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE DNA CURVATURE; ANISOTROPY OF DNA BENDING; FLUCTUATIONS IN B-DNA; CONFORMATIONAL ENERGY CALCULATIONS ID CURVED DNA; B-DNA; FLEXIBILITY; CURVATURE; ADENINE; TRACTS; RIGIDITY; BINDING; HELIX AB To investigate the influence of thermal fluctuations on DNA curvature the Metropolis procedure at 300 K was applied to B-DNA decamers containing A5.T5 and A4.T4 blocks. Monte Carlo simulations have confirmed the DNA bending anisotropy: B-DNA bends most easily in a groove direction (roll). The A5.T5 block is more rigid than the other sequences; the pyrimidine-purine dimers are found to be the most flexible. For A5TCTCT, A5CTCTC, and A5GAGAG, the average bend angle per decamer is 20-25-degrees in a direction toward the minor groove in the center of the A5.T5 tract, which is consistent with both the "junction" and "wedge AA" models. However, in A5T5, A4T4CG, and T4A4GC, bending is directed into the grooves at the 5' and 3' ends of purine tracts. Thus, directionality of bending caused by A(n).T(n) blocks strongly depends on their neighboring sequences. These calculations demonstrate that the sequence-dependent variation of the minor-groove width mimics the observed hydroxyl radical cleavage pattern. To estimate the effect of fluctuations on the overall shape of curved DNA fragments, longer pieces of DNA (up to 200 base pairs) were generated. For sequences with strong curvature (A5X5 and A4T4CG), the static model and Monte Carlo ensemble give similar results but, for moderately and slightly curved sequences (A5T5 or T4A4GC), the static model predicts a much smaller degree of bending than does the statistical representation. Considering fluctuations is important for quantitative interpretation of the gel electrophoresis measurements of DNA curvature, where both the static and statistical bends are operative. C1 ENGELHARDT MOLEC BIOL INST,MOSCOW 117984,USSR. RP ZHURKIN, VB (reprint author), NCI,MATH BIOL LAB,BLDG 10,ROOM 4B-56,BETHESDA,MD 20892, USA. RI Jernigan, Robert/A-5421-2012; Gorin, Andrey/B-1545-2014; Ulyanov, Nikolai/G-6998-2014 FU NCI NIH HHS [N01-CO-74102] NR 44 TC 141 Z9 143 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG PY 1991 VL 88 IS 16 BP 7046 EP 7050 DI 10.1073/pnas.88.16.7046 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GB701 UT WOS:A1991GB70100030 PM 1871119 ER PT J AU OSAWA, Y KORZEKWA, K AF OSAWA, Y KORZEKWA, K TI OXIDATIVE MODIFICATION BY LOW-LEVELS OF HOOH CAN TRANSFORM MYOGLOBIN TO AN OXIDASE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE HEMOPROTEIN; HEME MODIFICATION ID PROSTAGLANDIN-H-SYNTHASE; HYDROGEN-PEROXIDE; LIPID-PEROXIDATION; CYTOCHROME-P-450 HEME; SUICIDE INACTIVATION; HYDROXYL RADICALS; COVALENT BINDING; CARBON-MONOXIDE; IRON RELEASE; PROTEIN AB It is generally thought that the oxidative modification of hemoproteins leads to their inactivation. In the current study, however, a transiently activated form of myoglobin was shown to be formed when the prosthetic heme group became covalently bound to the polypeptide during the reaction of myoglobin with low levels of HOOH. In the presence of an enzymatic metmyoglobin reducing system containing diaphorase and methylene blue with excess NADH, this HOOH-altered myoglobin catalyzed NADH oxidation and oxygen consumption; the overall stoichiometry indicated a two-electron reduction of oxygen to HOOH. This reaction was not catalyzed by iron released from heme, as desferrioxamine had no effect on the activity. Stoichiometric amounts of HOOH were sufficient to produce the activated oxidase state of myoglobin, whereas larger amounts of HOOH lead to heme destruction, iron release, and inactivation of the oxidase activity. The alteration of myoglobin to an enzyme that can form toxic oxygen metabolites may have pathological importance, especially in myocardial injury caused by ischemia and reperfusion, where myoglobin is present in large amounts and HOOH is formed. Furthermore, the oxidase form may be involved in the mechanism of destruction of the heme seen with oxidative treatment of myoglobin. RP OSAWA, Y (reprint author), NHLBI,CHEM PHARMACOL LAB,BETHESDA,MD 20892, USA. NR 49 TC 73 Z9 73 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG PY 1991 VL 88 IS 16 BP 7081 EP 7085 DI 10.1073/pnas.88.16.7081 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GB701 UT WOS:A1991GB70100037 PM 1871123 ER PT J AU GIOVANELLI, J CAMPOS, KL KAUFMAN, S AF GIOVANELLI, J CAMPOS, KL KAUFMAN, S TI TETRAHYDROBIOPTERIN, A COFACTOR FOR RAT CEREBELLAR NITRIC-OXIDE SYNTHASE, DOES NOT FUNCTION AS A REACTANT IN THE OXYGENATION OF ARGININE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ARGININE MONOOXYGENASE; CYCLIC GMP; METHOTREXATE; DIHYDROFOLATE REDUCTASE/DIHYDROPTERIDINE REDUCTASE ID DIHYDROPTERIDINE REDUCTASE; PHENYLALANINE-HYDROXYLASE; OXIDATION; LIVER; ENZYME; SYNTHETASE; ASCORBATE AB Studies with purified nitric oxide synthase from rat cerebellum have confirmed previous reports that product formation is enhanced by tetrahydrobiopterin [H4B; 6-(L-erythro- 1,2-dihydroxypropyl)-5,6,7,8-tetrahydropterin]. The effect of the natural isomer, (6R)-H4B, is observed at extremely low (< 0.1-mu-M) concentrations and is remarkably selective. At these concentrations, only the diastereoisomer (6S)-H4B, the structural isomer 7-(L-erythro-1,2-dihydroxypropyl)5,6,7,8-tetrahydropterin, and 7,8-dihydrobiopterin showed detectable effects. Our observations are inconsistent with a stoichiometric role for H4B in the oxygenation of arginine [e.g., Stuehr, D. J., Kwon, N. S., Nathan, C. F., Griffith, O. W., Feldman, P. L. & Wiseman, J. (1991) J. Biol. Chem. 266, 6259-6263]. Activity is initially independent of added H4B; enhanced product formation with H4B is observed only as incubation progresses. The effect of H4B is catalytic, with each mole of added H4B supporting the formation of > 15 mol of product. Recycling of H4B was excluded by direct measurement during nitric oxide synthesis and by the demonstration that nitric oxide synthase is not inhibited by methotrexate. These combined results exclude H4B as a stoichiometric reactant and suggest that H4B enhances product formation by protecting enzyme activity against progressive loss. Preliminary studies indicate that the decreased activity in the absence of added H4B does not depend on catalytic turnover of the enzyme. The role of H4B may be allosteric or it may function to maintain some group(s) on the enzyme in a reduced state required for activity. RP GIOVANELLI, J (reprint author), NIMH,NEUROCHEM LAB,BETHESDA,MD 20892, USA. NR 35 TC 162 Z9 162 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 AUG PY 1991 VL 88 IS 16 BP 7091 EP 7095 DI 10.1073/pnas.88.16.7091 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GB701 UT WOS:A1991GB70100039 PM 1714584 ER PT J AU MCBRIDE, K RHEE, SG JAKEN, S AF MCBRIDE, K RHEE, SG JAKEN, S TI IMMUNOCYTOCHEMICAL LOCALIZATION OF PHOSPHOLIPASE C-GAMMA IN RAT EMBRYO FIBROBLASTS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE PROTEIN KINASE-C; SIGNAL TRANSDUCTION; CYTOSKELETON ID PROTEIN-KINASE-C; EPIDERMAL GROWTH-FACTOR; TYROSINE PHOSPHORYLATION; 2ND MESSENGERS; BOVINE BRAIN; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; IMMUNOHISTOCHEMICAL LOCALIZATION; INOSITOL TRISPHOSPHATE; MONOCLONAL-ANTIBODIES; SIGNAL TRANSDUCTION AB Rat embryo fibroblasts (REF52) exhibit a distinctive, transformation-sensitive distribution of alpha-protein kinase C (alpha-PKC). Receptor-mediated activation of phospholipase C (PLC)-gamma generates diacylglycerol, the major cellular activator of PKC. Immunofluorescence techniques were used to investigate the subcellular localization of two PLC isozymes (PLC-gamma and PLC-delta) in normal and simian virus 40-transformed REF52 cells to determine (i) if PLC colocalizes with alpha-PKC and (ii) if PLC isozyme distribution is sensitive to transformation. PLC-delta was not detected in either cell type. In REF52 cells, PLC-gamma was associated with the actin cytoskeleton and was evenly distributed along the length of the actin microfilaments. PLC-gamma was coincident with alpha-PKC at the points where the filaments are anchored to the membrane (i.e., the focal contacts). Cytoskeletal association of PLC-gamma was not transformation sensitive, although the actin cytoskeleton was more disordered in simian virus 40-transformed cells. In REF52 cells, platelet-derived growth factor induced tyrosine phosphorylation of both soluble and cytoskeletal PLC-gamma. Tyrosine phosphorylation of PLC-gamma did not seem to be a determinant of its subcellular localization, but there was a detectable increase in cytoskeleton-associated PLC-gamma in response to platelet-derived growth factor treatment. C1 W ALTON JONES CELL SCI CTR INC,LAKE PLACID,NY 12946. NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA37589, CA46530] NR 44 TC 79 Z9 79 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 AUG PY 1991 VL 88 IS 16 BP 7111 EP 7115 DI 10.1073/pnas.88.16.7111 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GB701 UT WOS:A1991GB70100043 PM 1651494 ER PT J AU SHAFFERMAN, A JAHRLING, PB BENVENISTE, RE LEWIS, MG PHIPPS, TJ EDENMCCUTCHAN, F SADOFF, J EDDY, GA BURKE, DS AF SHAFFERMAN, A JAHRLING, PB BENVENISTE, RE LEWIS, MG PHIPPS, TJ EDENMCCUTCHAN, F SADOFF, J EDDY, GA BURKE, DS TI PROTECTION OF MACAQUES WITH A SIMIAN IMMUNODEFICIENCY VIRUS ENVELOPE PEPTIDE VACCINE BASED ON CONSERVED HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SEQUENCES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ENVELOPE EPITOPES; AIDS; IMMUNITY ID HTLV-III; ANTIBODY RECOGNITION; GLYCOPROTEIN GP120; HIV INFECTION; CHIMPANZEES; RETROVIRUS; RECOMBINANT; LENTIVIRUS; CHALLENGE; MANGABEYS AB This report describes the vaccination of rhesus macaques with peptides selected from regions of the simian immunodeficiency virus (SIV) envelope that are hydrophilic, immunoreactive, and highly homologous with corresponding conserved envelope sequences of the human immunodeficiency virus (HIV). The peptides, produced as beta-galactosidase fusion proteins, induced virus-neutralizing and peptide-specific antibodies. After challenge with virulent virus, controls became virus positive and developed gradually rising antibody titers to SIV over 63 weeks. Immunized macaques developed a postchallenge anamnestic response to SIVenv antigens within 3-6 weeks followed by a gradual, fluctuating decline in SIV antibody titers and partial or total suppression of detectable SIV. Virus suppression correlated with prechallenge neutralizing antibody titers. Although the average CD4+ cell count in the blood of immunized macaques remained constant, the control macaques exhibited a progressive decrease developing about week 55 after challenge. The conserved nature of the HIV and SIV peptides and the similar humoral immunoreactivity in the respective hosts suggest that homologous HIV peptides may be important components of a successful immunization strategy. C1 USA,MED RES INST INFECT DIS,DIV DIS ASSESSMENT,FREDERICK,MD 21701. FREDERICK RES CTR,SO RES INST,FREDERICK,MD 21701. NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. HENRY M JACKSON FDN,RES LAB,ROCKVILLE,MD 20850. WALTER REED ARMY MED CTR,DEPT RETROVIROL,WASHINGTON,DC 20307. RP SHAFFERMAN, A (reprint author), ISRAEL INST BIOL RES,DEPT BIOCHEM,IL-70450 NESS ZIONA,ISRAEL. OI /0000-0002-5704-8094 NR 25 TC 104 Z9 104 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 AUG PY 1991 VL 88 IS 16 BP 7126 EP 7130 DI 10.1073/pnas.88.16.7126 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GB701 UT WOS:A1991GB70100046 PM 1871125 ER PT J AU UNGE, T SOLOMIN, L MELLINI, M DERSE, D FELBER, BK PAVLAKIS, GN AF UNGE, T SOLOMIN, L MELLINI, M DERSE, D FELBER, BK PAVLAKIS, GN TI THE REX REGULATORY PROTEIN OF HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE-I BINDS SPECIFICALLY TO ITS TARGET SITE WITHIN THE VIRAL-RNA SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE POSTTRANSCRIPTIONAL GENE REGULATION; AIDS; RNA TRANSPORT ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-1 GENE-EXPRESSION; ENV MESSENGER-RNA; LEUKEMIA-VIRUS; RESPONSIVE ELEMENT; HTLV-I; SECONDARY STRUCTURE; ESCHERICHIA-COLI; TRANS-ACTIVATOR; FUNCTIONAL-ANALYSIS AB The Rex protein of human T-cell leukemia virus type I (HTLV-I) was expressed in bacteria and partially purified. Rex was shown to bind in vitro specifically to an RNA sequence located in the 3' long terminal repeat of HTLV-I, named Rex-responsive element (RXRE). Rex also bound in vitro to the human immunodeficiency virus type 1 (HIV-1) Rev-responsive element (RRE), while purified HIV-1 Rev protein did not bind to the RXRE. The binding results obtained in vitro are therefore in agreement with the nonreciprocal function of Rev and Rex in vivo. Rex binds specifically to both RRE and RXRE and activates expression in both HIV-1 and HTLV-I, while Rev binds to RRE and activates only HIV-1. Binding of Rex to RRE deletion mutants previously shown to lack either the Rev-responsive or the Rex-responsive portion suggested preferential binding of Rex to a distinct target within the RRE. These results demonstrated that Rex, like Rev, acts by binding to a specific RNA target. C1 NCI,FREDERICK CANC RES & DEV CTR,HUMAN RETROVIRUS SECT,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,HUMAN RETROVIRUS PATHOGENESIS GRP,ADV BIOSCI LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101] NR 51 TC 45 Z9 45 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 AUG PY 1991 VL 88 IS 16 BP 7145 EP 7149 DI 10.1073/pnas.88.16.7145 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GB701 UT WOS:A1991GB70100050 PM 1871127 ER PT J AU NAKAMURA, SI RODBELL, M AF NAKAMURA, SI RODBELL, M TI GLUCAGON INDUCES DISAGGREGATION OF POLYMER-LIKE STRUCTURES OF THE ALPHA-SUBUNIT OF THE STIMULATORY G-PROTEIN IN LIVER MEMBRANES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE GLUCAGON RECEPTOR; SIGNAL TRANSDUCTION ID REGULATORY PROTEINS; PLASMA-MEMBRANES; CHOLERA-TOXIN; RAT-LIVER; TRANSDUCTION; NUCLEOTIDES; ACTIVATION; COMPLEXES; CYCLASE AB The hydrodynamic behavior of G-alpha-s, the alpha-subunit of the stimulatory guanine nucleotide-binding regulatory protein (G protein), in octyl glucoside extracts of rat liver membranes was investigated. As was previously shown for G proteins similarly extracted from brain synaptoneurosomes, G-alpha-s behaved as polydisperse structures with S values higher than that of heterotrimeric G proteins. At concentrations of guanosine 5'-[gamma-thio]triphosphate (GTP[gamma-S]) > 100-mu-M, incubation with membranes led to smaller structures having S values in the range of 4-5 S. Incubation of liver membranes with glucagon also caused a marked increase in structures having these S values; glucagon action required the presence of low concentrations of GTP[gamma-S] (maximal, 10-mu-M), was rapid (within 10 sec), and was not observed with vasopressin, angiotensin II, or glucagon-(19-29). When G-alpha-s in its membrane-bound form was [P-32]ADP-ribosylated by cholera toxin and the treated membranes were extracted with octyl glucoside, > 35% of the labeled G-alpha-s was found in material that sedimented through sucrose gradients and contained relatively low levels of immunoreactive G-alpha-s. Glucagon selectively converted the apparently large molecular weight structures to the 4-5 S structures in the presence of GTP[gamma-S], even at 1 mM (the maximal effect of the nucleotide alone), when incubated with the toxin-treated membranes. These findings suggest that the glucagon receptor selectively interacts with polymer-like structures of G-alpha-s and that activation by GTP[gamma-S] results in disaggregation. The role of the beta and gamma-subunits of G proteins in the hormone-induced process is not clear since the polymer-like structures extracted with octyl glucoside are devoid of beta and gamma-subunits. C1 NIEHS,SIGNAL TRANSDUCT SECT,RES TRIANGLE PK,NC 27709. NR 17 TC 33 Z9 33 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 AUG PY 1991 VL 88 IS 16 BP 7150 EP 7154 DI 10.1073/pnas.88.16.7150 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GB701 UT WOS:A1991GB70100051 PM 1908089 ER PT J AU DRAKE, JW AF DRAKE, JW TI A CONSTANT RATE OF SPONTANEOUS MUTATION IN DNA-BASED MICROBES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CHROMOSOME-I DNA; SACCHAROMYCES-CEREVISIAE; ESCHERICHIA-COLI; CAN1 LOCUS; NUCLEOTIDE-SEQUENCE; MOLECULAR-CLONING; LAMBDA PHAGE; LACI GENE; BACTERIOPHAGE-T4; SUBSTITUTION AB In terms of evolution and fitness, the most significant spontaneous mutation rate is likely to be that for the entire genome (or its nonfrivolous fraction). Information is now available to calculate this rate for several DNA-based haploid microbes, including bacteriophages with single- or double-stranded DNA, a bacterium, a yeast, and a filamentous fungus. Their genome sizes vary by almost-equal-to 6500-fold. Their average mutation rates per base pair vary by almost-equal-to 16,000-fold, whereas their mutation rates per genome vary by only almost-equal-to 2.5-fold, apparently randomly, around a mean value of 0.0033 per DNA replication. The average mutation rate per base pair is inversely proportional to genome size. Therefore, a nearly invariant microbial mutation rate appears to have evolved. Because this rate is uniform in such diverse organisms, it is likely to be determined by deep general forces, perhaps by a balance between the usually deleterious effects of mutation and the physiological costs of further reducing mutation rates. RP DRAKE, JW (reprint author), NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709, USA. NR 64 TC 678 Z9 694 U1 9 U2 54 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 AUG PY 1991 VL 88 IS 16 BP 7160 EP 7164 DI 10.1073/pnas.88.16.7160 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GB701 UT WOS:A1991GB70100053 PM 1831267 ER PT J AU DEVI, SJN ROBBINS, JB SCHNEERSON, R AF DEVI, SJN ROBBINS, JB SCHNEERSON, R TI ANTIBODIES TO POLY[(2-]8)-ALPHA-N-ACETYLNEURAMINIC ACID] AND POLY[(2-]9)-ALPHA-N-ACETYLNEURAMINIC ACID] ARE ELICITED BY IMMUNIZATION OF MICE WITH ESCHERICHIA-COLI K92 CONJUGATES - POTENTIAL VACCINES FOR GROUP-B AND GROUP-C MENINGOCOCCI AND ESCHERICHIA-COLI K1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID INFLUENZAE TYPE-B; TETANUS TOXOID CONJUGATE; MENINGITIDIS GROUP-B; NEISSERIA-MENINGITIDIS; CAPSULAR POLYSACCHARIDE; NEONATAL MENINGITIS; MONOCLONAL-ANTIBODY; SEROGROUP-B; ANTIGENS; IMMUNOGENICITY AB Meningitis and other systemic infections caused by group B Neisseria meningitidis and Escherichia coli K1 remain important problems. The capsular polysaccharides (CPs) of these pathogens {poly[(2 --> 8)-alpha-N-acetylneuraminic acid] or poly(alpha-2-8NeuNAc)} are identical and are virulence factors and protective antigens for both. CP vaccines for these pathogens are not available because poly(alpha-2-8NeuNAc) alone, as a complex or a conjugate, is poorly immunogenic. Because oligomers of poly(alpha-2-8NeuNAc) in fetal brain and other tissues bind antibodies in vitro, it has been suggested that antibodies to this CP might be pathologic. We synthesized conjugates of this CP with tetanus toxoid under conditions that avoid lactone formation. Using this scheme, we also synthesized conjugates of group C meningococcal CP {poly[(2 --> 9)-alpha-N-acetylneuraminic acid] or poly(alpha-2-9NeuNAc)} and of E. coli K92 CP [poly(alpha-2-8, alpha-2-9NeuNAc)]. When injected s.c. in saline into mice, conjugates of poly(alpha-2-8NeuNAc) or poly(alpha-2-9NeuNAc) elicited homologous antibodies. E. coli K92 conjugates elicited both poly(alpha-2-8NeuNAc) and poly(alpha-2-9NeuNAc) antibodies. Both components of the conjugates expressed T-dependent immunologic properties under conditions and dosages acceptable for clinical evaluation. Poly(alpha-2-8NeuNAc) antibodies elicited by the homologous or the K92 conjugates had lower binding activities at 37-degrees-C than at 22-degrees-C. "Natural" poly(alpha-2-8NeuNAc) antibodies were present in almost all matched pairs of human maternal and cord sera; most cord levels were higher than in corresponding maternal sera. These findings suggest that increased levels of poly(alpha-2-8NeuNAc) IgG antibodies elicited by our conjugates will confer protective immunity to group B meningococci and E. coli K1 and will not be pathologic. RP DEVI, SJN (reprint author), NICHHD,DEV & MOLEC IMMUN LAB,BETHESDA,MD 20892, USA. NR 56 TC 70 Z9 72 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 AUG PY 1991 VL 88 IS 16 BP 7175 EP 7179 DI 10.1073/pnas.88.16.7175 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GB701 UT WOS:A1991GB70100056 PM 1908091 ER PT J AU KELLER, JR JACOBSEN, SEW SILL, KT ELLINGSWORTH, LR RUSCETTI, FW AF KELLER, JR JACOBSEN, SEW SILL, KT ELLINGSWORTH, LR RUSCETTI, FW TI STIMULATION OF GRANULOPOIESIS BY TRANSFORMING GROWTH-FACTOR-BETA - SYNERGY WITH GRANULOCYTE MACROPHAGE-COLONY-STIMULATING FACTOR SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE RECEPTOR REGULATION; GRANULOCYTE BURST-FORMING UNIT ID HEMATOPOIETIC PROGENITOR CELLS; FACTOR-BETA-1; PROLIFERATION; PURIFICATION; ANTIBODIES; RECEPTORS; INVITRO AB Transforming growth factor beta-1 (TGF-beta-1) is known to inhibit the growth of immature hematopoietic progenitor cells, whereas more mature, lineage-restricted progenitors are not inhibited. In contrast, in the presence of saturating concentrations of granulocyte/macrophage-colony-stimulating factor (GM-CSF), TGF-beta promoted a 3- to 5-fold increase in the number and size (> 0.5 mm) of bone marrow colonies in a dose-dependent manner with an ED50 Of 10-20 pM; TGF-beta-1 alone had no effect. Morphological examination showed an increase in granulocyte colonies. In suspension cultures, TGF-beta-1 and GM-CSF stimulated an increase in total viable cells with markedly enhanced neutrophilic differentiation and a concomitant decrease in the number of monocytes/macrophages by day 6 in culture. Limiting dilution analysis demonstrated a 2- to 5-fold increase in the frequency of progenitor cells that responded to GM-CSF plus TGF-beta-1 vs. GM-CSF alone. Bone marrow progenitors obtained from mice 3 days after treatment with 5-fluorouracil responded to a combination of GM-CSF and TGF-beta-1, whereas either factor alone had no effect. A single-cell assay identified a progenitor cell that directly responded to TGF-beta and GM-CSF. TGF-beta increased the number of GM-CSF receptors on bone marrow cells. Thus, TGF-beta-1 can act as a bifunctional mediator of hematopoietic cell growth, and TGF-beta-1 and GM-CSF act together to stimulate granulopoiesis as measured by large granulocyte colony formation; the progenitor cell is tentatively designated granulocyte burst-forming unit. C1 NCI,FREDERICK CANC RES & DEV CTR,MOLEC IMMUNOREGULAT LAB,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. COLLAGEN CORP,PALO ALTO,CA 94303. RP KELLER, JR (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102] NR 24 TC 113 Z9 113 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 AUG PY 1991 VL 88 IS 16 BP 7190 EP 7194 DI 10.1073/pnas.88.16.7190 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GB701 UT WOS:A1991GB70100059 PM 1831268 ER PT J AU ETINGIN, OR SILVERSTEIN, RL HAJJAR, DP AF ETINGIN, OR SILVERSTEIN, RL HAJJAR, DP TI IDENTIFICATION OF A MONOCYTE RECEPTOR ON HERPESVIRUS-INFECTED ENDOTHELIAL-CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CELL ADHESION MOLECULE GMP140; HERPES SIMPLEX VIRUS-1; ATHEROSCLEROSIS; INFLAMMATION ID GRANULE MEMBRANE-PROTEIN; SMOOTH-MUSCLE CELLS; VIRUS-INFECTION; ARTERIAL CELLS; ADHESION; GMP-140; ATHEROSCLEROSIS; ACCUMULATION; NEUTROPHILS; EXPRESSION AB The adhesion of circulating blood cells to vascular endothelium may be an initial step in atherosclerosis, inflammation, and wound healing. One mechanism for promoting cell-cell adhesion involves the expression of adhesion molecules on the surface of the target cell. Herpes simplex virus infection of endothelium induces arterial injury and has been implicated in the development of human atherosclerosis. We now demonstrate that HSV-infected endothelial cells express the adhesion molecule GMP140 and that this requires cell surface expression of HSV glycoprotein C and local thrombin generation. Monocyte adhesion to HSV-infected endothelial cells was completely inhibited by anti-GMP140 antibodies but not by antibodies to other adhesion molecules such as VCAM and ELAM-1. The induction of GMP140 expression on HSV-infected endothelium may be an important pathophysiological mechanism in virus-induced cell injury and inflammation. C1 CORNELL UNIV,MED CTR,COLL MED,DEPT BIOCHEM,NEW YORK,NY 10021. CORNELL UNIV,MED CTR,COLL MED,DEPT PATHOL,NEW YORK,NY 10021. CORNELL UNIV,MED CTR,COLL MED,SPECIALIZED CTR THROMBOSIS RES,NIH,NEW YORK,NY 10021. RP ETINGIN, OR (reprint author), CORNELL UNIV,MED CTR,COLL MED,DEPT MED,NEW YORK,NY 10021, USA. FU NHLBI NIH HHS [HL18828, HL01687, HL46403] NR 25 TC 64 Z9 66 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 AUG PY 1991 VL 88 IS 16 BP 7200 EP 7203 DI 10.1073/pnas.88.16.7200 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GB701 UT WOS:A1991GB70100061 PM 1714592 ER PT J AU HIGLEY, JD HASERT, MF SUOMI, SJ LINNOILA, M AF HIGLEY, JD HASERT, MF SUOMI, SJ LINNOILA, M TI NONHUMAN PRIMATE MODEL OF ALCOHOL-ABUSE - EFFECTS OF EARLY EXPERIENCE, PERSONALITY, AND STRESS ON ALCOHOL-CONSUMPTION SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ALCOHOLISM; HYPOTHALAMIC PITUITARY ADRENOCORTICAL AXIS; RHESUS MONKEY CEREBROSPINAL FLUID; MONOAMINE METABOLITES ID RHESUS-MONKEYS; INDIVIDUAL-DIFFERENCES; ENVIRONMENTAL-FACTORS; CEREBROSPINAL-FLUID; DRINKING PATTERNS; ETHANOL; RATS; BEHAVIOR; RISK; MEN AB Twenty-two 50-month-old rhesus monkeys were provided concurrent free access to an aspartame-sweetened 7% ethanol solution and an aspartame-sweetened vehicle before, during, and after social separation. Subjects had been reared for their first 6 months of life either without access to adults but with constant access to age mates (peer reared), a condition producing reduced exploration and increased fear-related behaviors, or as controls with their mothers; thereafter, all subjects received identical treatment. During home-cage periods, for 1 hr each day, 4 days a week, when the ethanol solution and vehicle were freely available, peer-reared subjects consumed significantly more alcohol than mother-reared subjects. When stress was increased via social separation, mother-reared animals increased their alcohol consumption to a level nearly as high as that of peer-reared monkeys. Average individual differences in alcohol consumption were markedly stable over time. In addition, there were strong positive correlations between alcohol consumption and distress behaviors. Biological indices of increased stress, such as plasma cortisol and corticotropin, were higher in peer-reared subjects. Within the peer- and mother-reared groups, these indices were positively correlated with alcohol consumption. The results suggest that early rearing experiences that predispose monkeys to increased fear-related behaviors produce excessive alcohol consumption under normal living conditions. Furthermore, a major challenge such as social separation increases alcohol consumption to levels producing intoxication even in monkeys not particularly vulnerable to stress. C1 NIAAA,DIV INTRAMURAL CLIN & BIOL RES,CLIN STUDIES LAB,BETHESDA,MD 20892. NICHHD,COMPARAT ETHOL LAB,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,DEPT PSYCHOL,WASHINGTON,DC 20052. NR 59 TC 218 Z9 219 U1 4 U2 19 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 AUG PY 1991 VL 88 IS 16 BP 7261 EP 7265 DI 10.1073/pnas.88.16.7261 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GB701 UT WOS:A1991GB70100074 PM 1871131 ER PT J AU BURKHARDT, AL BRUNSWICK, M BOLEN, JB MOND, JJ AF BURKHARDT, AL BRUNSWICK, M BOLEN, JB MOND, JJ TI ANTIIMMUNOGLOBULIN STIMULATION OF LYMPHOCYTES-B ACTIVATES SRC-RELATED PROTEIN-TYROSINE KINASES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE B-CELL ANTIGEN RECEPTOR; TYROSINE PHOSPHORYLATION; BLK GENE; FYN GENE; LYN GENE ID SIGNAL TRANSDUCTION; CD4 RECEPTOR; CELLS; ASSOCIATION; COMPLEX; IGM; PHOSPHORYLATION; EXPRESSION; ANTIBODIES; P56LCK AB Stimulation of resting B lymphocytes with antibodies to surface immunoglobulin (sIgD or sIgM) induces protein tyrosine phosphorylation, implicating one or more B-cell protein-tyrosine kinases (PTKs) in sIg signal transduction. We have evaluated whether members of the src family of PTKs are involved in this process. Our results show that addition of antibodies to IgD or to IgM can stimulate the PTK activity of the blk, fyn, and lyn gene products. Additionally, all three PTKs were found to coimmunoprecipitate with sIg in digitonin lysates from resting B cells. In all stimulatory conditions, whether initiated through sIgD or sIgM, the blk gene product p56blk displayed the strongest activation index. The kinetics of activation of these kinases, particularly that of p56blk, paralleled the early appearance of newly tyrosine-phosphorylated B-cell proteins, suggesting that this group of kinases may account for some portion of the tyrosine kinase activity in sIg-activated B cells. These observations demonstrate a functional and possible physical association between the members of the src family of PTKs and the B-cell antigen receptor. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT MED,BETHESDA,MD 20814. NCI,TUMOR VIRUS BIOL LAB,BETHESDA,MD 20892. FU NIAID NIH HHS [R01 AI24273, R01 AI27465] NR 33 TC 464 Z9 465 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG PY 1991 VL 88 IS 16 BP 7410 EP 7414 DI 10.1073/pnas.88.16.7410 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA GB701 UT WOS:A1991GB70100105 PM 1714601 ER PT J AU ROBERTS, MM COPELAND, TD OROSZLAN, S AF ROBERTS, MM COPELAND, TD OROSZLAN, S TI INSITU PROCESSING OF A RETROVIRAL NUCLEOCAPSID PROTEIN BY THE VIRAL PROTEINASE SO PROTEIN ENGINEERING LA English DT Article DE RETROVIRAL CAPSID; RETROVIRAL NUCLEOCAPSID PROTEIN; RETROVIRAL PROTEINASE ID HUMAN-IMMUNODEFICIENCY-VIRUS; MURINE LEUKEMIA-VIRUS; INFECTIOUS-ANEMIA VIRUS; SCISSILE BOND CONVERTS; ACID-BINDING-PROTEINS; CYS-HIS BOX; STRUCTURAL PROTEINS; ZINC FINGERS; SELECTIVE INHIBITOR; PEPTIDE SUBSTRATE AB The proteolytic processing pathway of the nucleocapsid protein (NC) by the viral proteinase within intact capsids of equine infectious anemia virus (EIAV) is presented. The cleavage sites are located at the carboxyl side of the first cysteine residue within the zinc-finger domains. EIAV is used as a model to predict similar NC cleavages in other retroviruses, including human immunodeficiency virus (HIV). The observed cleavages suggest a previously unrecognized function of the retroviral proteinase that may be crucial for replication during the early stages of the virus life-cycle (i.e. reverse transcription/integration). RP ROBERTS, MM (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOLEC VIROL & CARCINOGENESIS LAB,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74101] NR 47 TC 38 Z9 38 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0269-2139 J9 PROTEIN ENG JI Protein Eng. PD AUG PY 1991 VL 4 IS 6 BP 695 EP 700 DI 10.1093/protein/4.6.695 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA GC292 UT WOS:A1991GC29200010 PM 1658777 ER PT J AU KATZ, MM KOSLOW, SH MAAS, JW FRAZER, A KOCSIS, J SECUNDA, S BOWDEN, CL CASPER, RC AF KATZ, MM KOSLOW, SH MAAS, JW FRAZER, A KOCSIS, J SECUNDA, S BOWDEN, CL CASPER, RC TI IDENTIFYING THE SPECIFIC CLINICAL ACTIONS OF AMITRIPTYLINE - INTERRELATIONSHIPS OF BEHAVIOR, AFFECT AND PLASMA-LEVELS IN DEPRESSION SO PSYCHOLOGICAL MEDICINE LA English DT Article ID BRANCH COLLABORATIVE PROGRAM; DRUG RESPONSE; CEREBROSPINAL-FLUID; BIOLOGICAL COMPONENT; ANTIDEPRESSANT DRUGS; PSYCHOBIOLOGY; METABOLITES; MELANCHOLIA; IMIPRAMINE; DISORDERS AB Despite increasing knowledge of the neurochemical bases of the action of the tricyclic drugs, little is known about the sequence of psychological effects which precede recovery in drug-responsive patients. This research was aimed at identifying the specific behavioural effects associated with the therapeutic action of amitriptyline in depression. The design involved measurement (post-hoc) of weekly changes in a severely depressed placebo-resistant group who recovered with drug treatment, compared with a group of similar patients treated for the equivalent four weeks, who showed minimal to no clinical response. The research strategy, in accordance with a dose-response paradigm, was to determine which of the early changes in emotion and behaviour found in treatment responders were systematically associated with plasma concentrations of amitriptyline or its major metabolite. Amitriptyline was found to act within seven days on the components of anxiety and on hostility in the responders, and on sleep disorder in all patients. After 12 to 14 days of treatment these effects increased, with improvements in other significant components distinguishing the responders from the non-responders. At the 12th to 14th treatment days when a steady state concentration of drug in plasma was approached, reductions in anxiety and hostility and in certain somatic components correlated significantly with plasma concentrations of amitriptyline. Implications of the findings for clarifying the specificity of clinical actions of the tricyclic drugs, and for understanding the psychobiological dynamics underlying rapid drug-induced recovery in depression, were explored. C1 MICHAEL REESE HOSP & MED CTR,DEPT PSYCHIAT,CHICAGO,IL 60616. CORNELL UNIV,MED CTR,COLL MED,DEPT PSYCHIAT,NEW YORK,NY 10021. UNIV PENN,VET ADM HOSP,DEPT PSYCHIAT,PHILADELPHIA,PA 19104. SPRINGFIELD PROFESS PK,SPRINGFIELD,PA. UNIV PENN,VET ADM HOSP,DEPT PSYCHIAT,PHILADELPHIA,PA 19104. NIMH,NEUROSCI RES BRANCH,ROCKVILLE,MD 20857. UNIV TEXAS,HLTH SCI CTR,DEPT PSYCHIAT,SAN ANTONIO,TX 78284. RP KATZ, MM (reprint author), ALBERT EINSTEIN COLL MED,MONTEFIORE MED CTR,DEPT PSYCHIAT,111 E 210 ST,BRONX,NY 10467, USA. FU NIMH NIH HHS [U01 MH26976, U01 MH26977, U01 MH26975] NR 45 TC 35 Z9 35 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD AUG PY 1991 VL 21 IS 3 BP 599 EP 611 PG 13 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA GE524 UT WOS:A1991GE52400007 PM 1946849 ER PT J AU ROY, A DEJONG, J FERRARO, T AF ROY, A DEJONG, J FERRARO, T TI CSF GABA IN DEPRESSED-PATIENTS AND NORMAL CONTROLS SO PSYCHOLOGICAL MEDICINE LA English DT Article ID GAMMA-AMINOBUTYRIC-ACID; CEREBROSPINAL-FLUID; PSYCHIATRIC-DISORDERS; HOMOVANILLIC-ACID; MELANCHOLIA; PLASMA; NOREPINEPHRINE AB The inhibitory neurotransmitter gamma-aminobutyric acid (GABA) has been implicated in the pathophysiology of depression. Therefore, we examined cerebrospinal fluid (CSF) levels of GABA in depressed patients (N = 25) and normal controls (N = 20). There was no significant difference between the groups. However, among the depressed patients the subgroup of unipolar melancholic patients (N = 13) had significantly lower CSF levels of GABA than the rest of the depressed patients (N = 12). There was no significant difference for CSF levels of GABA between depressed patients who were (N = 14) or were not (N = 11) cortisol non-suppressors. It was of interest that among the controls there was a significant negative correlation between CSF levels of GABA and CSF levels of norepinephrine. C1 NIMH,BETHESDA,MD 20892. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT PHARMACOL,PHILADELPHIA,PA 19107. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT NEUROL,PHILADELPHIA,PA 19107. NR 33 TC 43 Z9 44 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD AUG PY 1991 VL 21 IS 3 BP 613 EP 618 PG 6 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA GE524 UT WOS:A1991GE52400008 PM 1719577 ER PT J AU SAKAIRI, M YERGEY, AL AF SAKAIRI, M YERGEY, AL TI COMPARISON OF INTENSITIES BETWEEN DOUBLY CHARGED IONS [M+2H]2+ AND SINGLY CHARGED IONS [M+H]+ OF GRAMICIDIN-S BY ELECTROSPRAY MASS-SPECTROMETRY SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article ID AMINO-ACIDS; EVAPORATION; PARAMETERS; MOLECULES; PEPTIDES AB The reason why the intensity of doubly charged ions [M + 2H]2+ of gramicidin S is higher than that of singly charged ions [M + H]+ in electrospray is investigated by ion evaporation theory. As a result of comparison between the total free energies of extracting [M + 2H]+ and [M + H]+ from a charged droplet to infinity, it is found that the total free energy of [M + 2H]2+ is estimated to be lower than that of [M + H]+. This clearly supports the experimental result. In addition, the importance of the electrostatic contribution in electrospray is demonstrated by showing the result that the total free energy of [M + 2H]2+ without electrostatic contribution is higher than that of [M + H]+. C1 NICHHD,BETHESDA,MD 20892. RP SAKAIRI, M (reprint author), HITACHI LTD,CENT RES LAB,KOKUBUNJI,TOKYO 185,JAPAN. NR 17 TC 3 Z9 3 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0951-4198 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PD AUG PY 1991 VL 5 IS 8 BP 349 EP 353 DI 10.1002/rcm.1290050803 PG 5 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA GA799 UT WOS:A1991GA79900002 PM 1285435 ER PT J AU SAKAIRI, M YERGEY, AL AF SAKAIRI, M YERGEY, AL TI 4 INTERFACES FOR LIQUID-CHROMATOGRAPHY ATMOSPHERIC-PRESSURE-IONIZATION MASS-SPECTROMETRY SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article AB Mixture analyses are demonstrated using the liquid chromatograph/atmospheric-pressure-ionization mass spectrometric system with four modes. These modes are atmospheric-pressure spray with electron ionization, atmospheric-pressure chemical ionization, atmospheric-pressure spray ionization, and electrospray ionization modes. This system can deal with a wide variety of compounds from hydrocarbons with low polarity to proteins with high polarity. C1 NICHHD,BETHESDA,MD 20892. RP SAKAIRI, M (reprint author), HITACHI LTD,CENT RES LAB,KOKUBUNJI,TOKYO 185,JAPAN. NR 9 TC 4 Z9 4 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0951-4198 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PD AUG PY 1991 VL 5 IS 8 BP 354 EP 356 DI 10.1002/rcm.1290050804 PG 3 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA GA799 UT WOS:A1991GA79900003 PM 1369627 ER PT J AU STEWART, PA HERRICK, RF BLAIR, A CHECKOWAY, H DROZ, P FINE, L FISCHER, L HARRIS, R KAUPPINEN, T SARACCI, R AF STEWART, PA HERRICK, RF BLAIR, A CHECKOWAY, H DROZ, P FINE, L FISCHER, L HARRIS, R KAUPPINEN, T SARACCI, R TI HIGHLIGHTS OF THE 1990 LEESBURG, VIRGINIA, INTERNATIONAL WORKSHOP ON RETROSPECTIVE EXPOSURE ASSESSMENT FOR OCCUPATIONAL EPIDEMIOLOGY STUDIES SO SCANDINAVIAN JOURNAL OF WORK ENVIRONMENT & HEALTH LA English DT Article C1 NIOSH,CINCINNATI,OH 45226. INST OCCUPAT MED,LAUSANNE,SWITZERLAND. UNIV WASHINGTON,SEATTLE,WA 98195. MICHIGAN STATE UNIV,E LANSING,MI 48824. UNIV N CAROLINA,CHAPEL HILL,NC 27514. INST OCCUPAT HLTH,SF-00290 HELSINKI 29,FINLAND. INT AGCY RES CANC,F-69372 LYONS,FRANCE. RP STEWART, PA (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,ROCKVILLE,MD, USA. NR 19 TC 10 Z9 10 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 AUG PY 1991 VL 17 IS 4 BP 281 EP 285 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA GB300 UT WOS:A1991GB30000009 PM 1925441 ER PT J AU KHALSA, JH GFROERER, J AF KHALSA, JH GFROERER, J TI EPIDEMIOLOGY AND HEALTH CONSEQUENCES OF DRUG-ABUSE AMONG PREGNANT-WOMEN SO SEMINARS IN PERINATOLOGY LA English DT Article ID MATERNAL MARIJUANA USE; COCAINE USE; FOLLOW-UP; ALCOHOL; EXPOSURE; DISTURBANCES; ASSOCIATION; PREVALENCE; CIGARETTES; HUMANS RP KHALSA, JH (reprint author), NIDA,DIV EPIDEMIOL & PREVENT RES,ROCKWALL 2 BLDG,SUITE 615,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. NR 29 TC 29 Z9 30 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0146-0005 J9 SEMIN PERINATOL JI Semin. Perinatol. PD AUG PY 1991 VL 15 IS 4 BP 265 EP 270 PG 6 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA GG156 UT WOS:A1991GG15600002 PM 1948137 ER PT J AU FINNEGAN, LP AF FINNEGAN, LP TI PERINATAL SUBSTANCE-ABUSE - COMMENTS AND PERSPECTIVES SO SEMINARS IN PERINATOLOGY LA English DT Article ID FOLLOW-UP; METHADONE; INFANTS; WITHDRAWAL; PREGNANCY; CHILDREN; MOTHERS C1 THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT PEDIAT PSYCHIAT & HUMAN BEHAV,PHILADELPHIA,PA 19107. RP FINNEGAN, LP (reprint author), NIDA,ALCOHOL DRUG ABUSE MENTAL HLTH ADM,5600 FISHERS LANE,ROCKWALL 11,SUITE 615,ROCKVILLE,MD 20857, USA. NR 39 TC 32 Z9 33 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0146-0005 J9 SEMIN PERINATOL JI Semin. Perinatol. PD AUG PY 1991 VL 15 IS 4 BP 331 EP 339 PG 9 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA GG156 UT WOS:A1991GG15600010 PM 1948145 ER PT J AU ROSENBERG, PS GAIL, MH PEE, D AF ROSENBERG, PS GAIL, MH PEE, D TI MEAN-SQUARE ERROR OF ESTIMATES OF HIV PREVALENCE AND SHORT-TERM AIDS PROJECTIONS DERIVED BY BACKCALCULATION SO STATISTICS IN MEDICINE LA English DT Article AB We simulated multinomial AIDS incidence counts from 27 'representative' AIDS epidemics that spanned a period corresponding to previous applications of backcalculation (1 January 1977 to 1 July 1987) and assessed mean square error for several back-calculated estimators of HIV prevalence and short-term AIDS projections. Estimators were based on flexible model selection procedures that chose the best-fitting non-negatively constrained model of the infection curve from a family of possible step-function models. Selection of the best-fitting model from a family of four-step models each with a long last step of width of 4 or 4.5 years offered a favourable tradeoff between bias and variance when compared with selection from families of models with three steps or from families with a short last step. Five-step models performed as well as four-step models. Three-step models had substantially larger mean square error in some epidemic situations. Percentage root mean square error (PRMSE) for estimates of cumulative HIV prevalence as of 1 January 1985 was less than 14 per cent over a range of hypothetical epidemics of N = 50,000 infected individuals. PRMSE for short-term projections was less than 18 per cent. Estimates of cumulative HIV prevalence as of 1 July 1987 were substantially more uncertain and had a PRMSE of 33 per cent in the unfavourable case of a rapidly rising HIV epidemic. Estimates of cumulative HIV prevalence as of 1 July 1987 were positively biased in HIV epidemics with a rapidly decreasing recent HIV incidence rate and negatively biased in rapidly increasing HIV epidemics. Despite these uncertainties, we obtained useful estimates even for HIV epidemics with as few as 5000 infected individuals. RP ROSENBERG, PS (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,EPIDEMIOL METHODS SECT,6130 EXECUT BLVD,EXECUT PLAZA N,ROOM 403,BETHESDA,MD 20892, USA. NR 0 TC 22 Z9 22 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 AUG PY 1991 VL 10 IS 8 BP 1167 EP 1180 DI 10.1002/sim.4780100802 PG 14 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 FY401 UT WOS:A1991FY40100001 PM 1925150 ER PT J AU GART, JJ AF GART, JJ TI SIMPLE TESTS OF HOMOGENEITY OF CONTROLS IN MATCHED STUDIES SO STATISTICS IN MEDICINE LA English DT Article AB Consider matched case-control studies with a pair of distinguishable controls, say neighbourhood and hospital, wherein one of the controls may be missing. Liang and Stewart derive an efficient test for the possible difference in controls for the complete data case. They suggest inefficient tests for the situation where some triplets are incomplete. Levin, and Risch and Tibshirani, derive efficient tests for the incomplete triplet case by the methods of maximum likelihood estimator (Wald) tests and likelihood ratio tests, respectively. All these tests require the use of compute algorithms. Using score theory, we derive a simple efficient test for complete triplets which only requires solving a quadratic equation. Furthermore, we show that the usual normal approximation to McNemar's test is equivalent to the score test and is thus fully efficient as well. For incomplete triplets, score theory leads to a fully efficient test which only requires the solution of a cubic equation. We propose a nearly efficient test which is even more simply computed. The example of Liang and Stewart illustrates application of the results. RP GART, JJ (reprint author), NCI,BIOSTAT BRANCH,MATH STAT & APPL MATH SECT,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 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 AUG PY 1991 VL 10 IS 8 BP 1257 EP 1266 DI 10.1002/sim.4780100808 PG 10 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 FY401 UT WOS:A1991FY40100007 PM 1925156 ER PT J AU DOHERTY, GM JENSEN, JC ALEXANDER, HR BURESH, CM NORTON, JA AF DOHERTY, GM JENSEN, JC ALEXANDER, HR BURESH, CM NORTON, JA TI PENTOXIFYLLINE SUPPRESSION OF TUMOR-NECROSIS-FACTOR GENE-TRANSCRIPTION SO SURGERY LA English DT Article; Proceedings Paper CT 52ND ANNUAL MEETING OF THE SOC OF UNIVERSITY SURGEONS CY FEB 07-09, 1991 CL GALVESTON, TX SP SOC UNIV SURGEONS ID ISCHEMIA REPERFUSION INJURY; FACTOR-ALPHA; PASSIVE-IMMUNIZATION; ENDOTOXIN; INFECTION; LIPOPOLYSACCHARIDE; EXPRESSION; SEPSIS; MICE; CAMP AB Pentoxifylline decreases lung injury after intravenous endotoxin; the mechanism is unknown. Tumor necrosis factor-alpha (TNF) is secreted by macrophages in response to endotoxin and mediates some of the toxicity of endotoxin. This study investigates the effects of pentoxifylline on endotoxin-stimulated TNF production in vitro and in vivo. Pentoxifylline concentrations of 100 and 1000-mu-g/ml inhibited TNF production by murine adherent peritoneal exudate cells incubated with endotoxin 1-mu-g/ml. Similarly, pentoxifylline at 100 and 1000-mu-g/ml decreased the number of available TNF messenger RNA transcripts in peritoneal exudate cells assessed by Northern blot. Pentoxifylline had no effect on TNF mRNA stability, but appeared to act by inhibiting the rate of TNF mRNA production (transcription). In murine in vivo experiments at each dose of endotoxin administered from 0.01 to 30 mg/kg, pentoxifylline treatment significantly reduced serum TNF levels, suggesting a favorable shift of the endotoxin dose-response curve. Expression of murine TNF gene in the livers of these animals showed fewer TNF transcripts in the pentoxifylline-treated animals compared to controls. Pentoxifylline inhibited endotoxin-induced TNF production both in vivo and in vitro and exerted this control by inhibiting endotoxin-induced transcription of the TNF gene. This study suggests that pentoxifylline may ameliorate endotoxic shock by decreasing macrophage TNF production. C1 NCI,SURG BRANCH,SURG METAB SECT,BLDG 10,ROOM 2B07,BETHESDA,MD 20892. NR 25 TC 281 Z9 285 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0039-6060 J9 SURGERY JI Surgery PD AUG PY 1991 VL 110 IS 2 BP 192 EP 198 PG 7 WC Surgery SC Surgery GA FZ628 UT WOS:A1991FZ62800010 PM 1858029 ER PT J AU POGREBNIAK, HW MATTHEWS, W PASS, HI AF POGREBNIAK, HW MATTHEWS, W PASS, HI TI CHEMOTHERAPY AMPLIFIES PRODUCTION OF TUMOR-NECROSIS-FACTOR SO SURGERY LA English DT Article; Proceedings Paper CT 52ND ANNUAL MEETING OF THE SOC OF UNIVERSITY SURGEONS CY FEB 07-09, 1991 CL GALVESTON, TX SP SOC UNIV SURGEONS ID MURINE MACROPHAGES INVITRO; PERITONEAL-MACROPHAGES; HYDROGEN-PEROXIDE; RADICAL FORMATION; CELLS; CISPLATIN; RELEASE; INDUCTION; TOXICITY; H2O2 AB Several chemotherapeutic agents exert cytotoxicity through the generation of reactive oxygen species (ROS), and our laboratory has shown that ROS increase tumor necrosis factor (TNF) production. Therefore, we hypothesized that cis-dichlorodiammine platinum (CDDP), mitomycin-C, and doxorubicin hydrochloride (Adriamycin), by the release of ROS, would increase macrophage TNF production. Murine macrophages were incubated for 20 hours with varying doses of the chemotherapeutic drugs and 2.5-mu-g/ml endotoxin. Both CDDP and mitomycin-C increased TNF production compared to nondrug-exposed cells. Peak TNF values occurred at 10-mu-g/ml CDDP and 62.5-mu-g/ml mitomycin-C with 377 +/- 38 and 427 +/- 54 units/ml TNF produced, respectively. These increases were significant (p2 < 0.05) compared to the nonchemotherapy; but endotoxin-exposed macrophages (CDDP 11 +/- 3 units/ml; mitomycin-C 10 +/- 3 units/ml). Only CDDP-increased production of TNF from non-endotoxin-primed macrophages (0-mu-g/ml CDDP - 0 +/- 0 unit/ml TNF; 50-mu-g/ml CDDP - 13 +/- 5 units/ml TNF; p2 < 0.038). 5-Fluorouracil, a non-ROS-generating chemotherapeutic, and Adriamycin failed to amplify TNF production. By Northern blot analysis, CDDP induced transcription of the TNF gene in non-endotoxin-primed macrophages as early as 3 hours after exposure to 50-mu-g/ml CDDP, and this preceded the increase in TNF protein in kinetic studies. Because CDDP, mitomycin-C, and Adriamycin all produce ROS, the mechanism for this selective chemotherapy-induced cytokine amplification remains unclear. This finding may explain both indirect toxic and tumoricidal properties of CDDP and mitomycin-C. C1 NCI,SURG BRANCH,THORAC ONCOL SECT,BLDG 10,ROOM 2B07,BETHESDA,MD 20892. NR 24 TC 18 Z9 18 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0039-6060 J9 SURGERY JI Surgery PD AUG PY 1991 VL 110 IS 2 BP 231 EP 237 PG 7 WC Surgery SC Surgery GA FZ628 UT WOS:A1991FZ62800015 PM 1858032 ER PT J AU BATTAGLIA, G SHARKEY, J KUHAR, MJ DESOUZA, EB AF BATTAGLIA, G SHARKEY, J KUHAR, MJ DESOUZA, EB TI NEUROANATOMICAL SPECIFICITY AND TIME COURSE OF ALTERATIONS IN RAT-BRAIN SEROTONERGIC PATHWAYS INDUCED BY MDMA (3,4-METHYLENEDIOXYMETHAMPHETAMINE) - ASSESSMENT USING QUANTITATIVE AUTORADIOGRAPHY SO SYNAPSE LA English DT Article DE AMPHETAMINE; AUTORADIOGRAPHY; MDMA; 3,4-METHYLENEDIOXYMETHAMPHETAMINE; MDA; NEUROTOXICITY; SEROTONIN; PAROXETINE; 5-HT UPTAKE SITES ID MEDIAN RAPHE NUCLEI; UPTAKE SITES; PARA-CHLOROAMPHETAMINE; NERVE-TERMINALS; AXON TERMINALS; NEURONS; METHYLENEDIOXYMETHAMPHETAMINE; NEUROTOXICITY; FOREBRAIN; IMMEDIATE AB The widely abused "designer" drug MDMA (3,4-methylenedioxymethamphetamine) has been shown to cause marked and long-lasting changes in brain serotonergic systems. The present study uses quantitative in vitro autoradiography of H-3-paroxetine labeled 5-HT uptake sites to assess the time-dependent effects of MDMA on 5-HT neurons in specific neuroanatomic loci. Following treatment with MDMA (20 mg/kg, b.i.d. for 4 days), marked decreases in 5-HT uptake sites were observed in a number of brain regions known to receive projections of 5-HT neurons. These regions included cerebral cortex, caudate nucleus, hippocampus, nucleus accumbens, olfactory tubercle, superior and inferior colliculi, geniculate nuclei, and most thalamic nuclei. In contrast, other areas such as the septal nuclei and some thalamic nuclei which also receive 5-HT projections were not substantially affected by this drug. In most regions, decreases in 5-HT uptake sites occurred within 24 hours of the last dose of MDMA and persisted at the 2 week time point. Some regions such as dorsal striatum exhibited a time-dependent reduction with greater reductions occurring at 2 weeks rather than immediately following the MDMA treatment regimen. The density of 5-HT uptake sites in other regions such as endopiriform nucleus and substantia nigra at the 2 week versus 18 hour time point indicated some degree of region-specific recovery. Regions which demonstrated no significant reduction in 5-HT uptake sites included the dorsal and median raphe nuclei, ventral tegmental area, central grey, interpeduncular nucleus, locus coerulus, pontine reticular formation and cerebellum. Likewise, regions containing 5-HT axons of passage (e.g., indusium griseum and lateral hypothalamus) appeared to be insensitive to the neurotoxic effects of MDMA on 5-HT neurons. Furthermore, the neurotoxic effects of MDMA showed specificity in that the catecholamine neurons labeled by H-3-mazindol were unaffected by the treatment regimen. These data indicate that the preferential degeneration of serotonergic neurons by MDMA is mediated primarily at 5-HT terminal regions, whereas regions containing 5-HT perikarya and axons of passage remain relatively unaffected. In addition, the observed time-dependent reductions and recovery of 5-HT uptake sites which were detected within 2 weeks of the treatment regimen in certain brain regions suggest region-specific differences in recovery of 5-HT systems from MDMA-induced lesion. C1 NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. RP BATTAGLIA, G (reprint author), LOYOLA UNIV,STRITCH SCH MED,DEPT PHARMACOL,2160 S 1ST AVE,MAYWOOD,IL 60153, USA. NR 32 TC 84 Z9 84 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-4476 J9 SYNAPSE JI Synapse PD AUG PY 1991 VL 8 IS 4 BP 249 EP 260 DI 10.1002/syn.890080403 PG 12 WC Neurosciences SC Neurosciences & Neurology GA FY389 UT WOS:A1991FY38900002 PM 1681594 ER PT J AU AKUNNE, HC REID, AA THURKAUF, A JACOBSON, AE DECOSTA, BR RICE, KC HEYES, MP ROTHMAN, RB AF AKUNNE, HC REID, AA THURKAUF, A JACOBSON, AE DECOSTA, BR RICE, KC HEYES, MP ROTHMAN, RB TI [H-3] 1-[2-(2-THIENYL)CYCLOHEXYL]PIPERIDINE LABELS 2 HIGH-AFFINITY BINDING-SITES IN HUMAN CORTEX - FURTHER EVIDENCE FOR PHENCYCLIDINE BINDING-SITES ASSOCIATED WITH THE BIOGENIC-AMINE REUPTAKE COMPLEX SO SYNAPSE LA English DT Article DE PCP; GUINEA PIG BRAIN; [H-3]TCP BINDING ID DISCRIMINATIVE STIMULUS PROPERTIES; RAT-BRAIN; DOPAMINE UPTAKE; NMDA RECEPTORS; H-3 PHENCYCLIDINE; OPIATE RECEPTOR; ANGEL DUST; MK-801; PCP; ASPARTATE AB Previous work demonstrated two high-affinity PCP binding sites in guinea pig brain labeled by [H-3]TCP (1-{1-[2-thienyl]cyclohexyl}piperidine): site 1 {N-methyl-D-aspartate [NMDA]-associated) and site 2 {dopamine-reuptake complex associated}. The present study examined brain membranes prepared from various species, including human, for the presence of site 2, defined as binding in the presence of (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate ((+)-MK801) minus binding in the presence of 10-mu-M TCP (nonspecific binding). Studies were conducted in absence of sodium which was found to be inhibitory to [H-3]TCP binding. The results demonstrated detectable levels of site 2 in brain membranes of guinea pig, rabbit, pig, mouse, sheep, and human but not in the rat or chicken. Using human cortical membranes, site 2 was the predominant binding site. Detailed studies conducted with human cortical tissue showed that high-affinity dopamine {l-[2-[bis(4-fluorophenyl)-methoxy] ethyl]-4-(3-phenylpropyl)piperazine (GBR12909)}, [1,2]benzo(b)thiophenylcyclo-hexylpiperidine (BTCP), and serotonin (fluoxetine) uptake inhibitors produced a wash-resistant inhibition of [H-3]TCP binding to site 2, but not site 1. Preincubation of guinea pig brain membranes with BTCP was shown to produce an increase in the dissociation rate of [H-3]TCP from PCP site 2. Structure activity studies with various uptake inhibitors showed that GBR12909, benztropine, fluoxetine, and BTCP have higher affinity for site 2 than for site 1. (+)-MK801, ketamine, and tiletamine were very selective for site 1, whereas dexoxadrol and TCP were moderately selective for site 1. These results suggest that human cortex possesses high-affinity PCP binding sites associated with biogenic reuptake binding sites, and that guinea pig brain, but not rat brain, may be an appropriate animal model for studying PCP site 2 in human brain. C1 NIDDK,RECEPTOR STUDIES UNIT,BETHESDA,MD. NIDDK,DRUG DESIGN & SYNTH SECT,BETHESDA,MD. NIDDK,MED CHEM LAB,BETHESDA,MD. NIMH,ANALYT BIOCHEM SECT,BETHESDA,MD 20892. NR 53 TC 19 Z9 19 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0887-4476 J9 SYNAPSE JI Synapse PD AUG PY 1991 VL 8 IS 4 BP 289 EP 300 DI 10.1002/syn.890080407 PG 12 WC Neurosciences SC Neurosciences & Neurology GA FY389 UT WOS:A1991FY38900006 PM 1833849 ER PT J AU BRUGGEMAN, LA XIE, HX BROWN, KS YAMADA, Y AF BRUGGEMAN, LA XIE, HX BROWN, KS YAMADA, Y TI DEVELOPMENTAL REGULATION FOR COLLAGEN-II GENE-EXPRESSION IN TRANSGENIC MICE SO TERATOLOGY LA English DT Article ID PROTEOGLYCAN CORE PROTEIN; INSITU HYBRIDIZATION; CARTILAGE MATRIX; TOXIN GENE; LOCALIZATION; ABLATION; MOUSE; ASSAY AB In order to evaluate the involvement of the type II collagen regulatory sequences in development, we have injected a construct containing a toxin gene under the control of the rat type II collagen promoter and enhancer. The construct, pDAS10-DTA, contained the diphtheria toxin A chain gene under the control of type II collagen sequences which had been used previously to target cartilagenous tissues in transgenics. Inspection of developing fetuses at various stages of gestation revealed a high number of aborted implants as well as abnormally developing fetuses. These abnormal fetuses were of small size, had shortened and underdeveloped limbs, cleft palates, and generally resembled a phenotype similar to chondrodystrophic mice. Histological comparisons of normal and abnormal fetuses indicated a reduced amount of extracellular matrix surrounding chondrocytes, and a disorganized appearance of the tissue. These results suggest that the expression of the toxin has occurred in chondrocytes and altered the survival and development of the transgenic mice. These results also indicate that the promoter and enhancer sequences contained in the transgene controlled the developmental expression of the type II collagen gene expression. RP BRUGGEMAN, LA (reprint author), NIDR,DEV BIOL LAB,BETHESDA,MD 20892, USA. NR 18 TC 13 Z9 13 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0040-3709 J9 TERATOLOGY JI Teratology PD AUG PY 1991 VL 44 IS 2 BP 203 EP 208 DI 10.1002/tera.1420440208 PG 6 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA GA556 UT WOS:A1991GA55600007 PM 1925979 ER PT J AU VOSTAL, JG MCCAULEY, RB AF VOSTAL, JG MCCAULEY, RB TI PROTHROMBIN PLASMA-CLEARANCE IS NOT MEDIATED BY HEPATIC ASIALOGLYCOPROTEIN RECEPTORS SO THROMBOSIS RESEARCH LA English DT Article DE PROTHROMBIN HALF LIFE; ASIALOPROTHROMBIN; ASIALOGLYCOPROTEIN RECEPTORS; GLYCOPROTEIN TURNOVER ID GLYCOPROTEINS AB The hepatic asialoglycoprotein receptor (AGPR) system can efficiently internalize and degrade circulating glycoproteins which lack terminal sialic acids on their carbohydrate chains. Since pro-thrombin is a glycosylated plasma protein, possible involvement of AGPR system in its clearance from circulation was evaluated. The half lives of bovine I-125-prothrombin and I-125-asialoprothrombin, injected intravenously into rats, were 192 and 1.8 minutes, respectively. Asialoprothrombin appeared to be cleared by the hepatic AGPRs since 33% of it accumulated in the liver at 30 minutes and its clearance was competitively blocked by simultaneous administration of increasing amounts of asialofetuin. Only 5% of prothrombin accumulated in the liver at 3 hours and injections asialofetuin in amounts capable of saturating the AGPR for the duration of four asialoprothrombin half lives had no effect on the disappearance of prothrombin. Our observations indicate that, although asialoprothrombin is readily cleared from plasma by the AGPR system, prothrombin is not. Thus these receptors do not appear to be involved in physiological processes that control prothrombin half life. C1 WAYNE STATE UNIV,SCH MED,DEPT PHARMACOL,DETROIT,MI 48201. RP VOSTAL, JG (reprint author), NIDDK,CLIN HEMATOL BRANCH,BETHESDA,MD 20892, USA. NR 28 TC 7 Z9 7 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0049-3848 J9 THROMB RES JI Thromb. Res. PD AUG 1 PY 1991 VL 63 IS 3 BP 299 EP 309 DI 10.1016/0049-3848(91)90133-H PG 11 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA GB459 UT WOS:A1991GB45900003 PM 1957274 ER PT J AU DAHL, AR SUN, JD BIRNBAUM, LS BOND, JA GRIFFITH, WC MAUDERLY, JL MUGGENBURG, BA SABOURIN, PJ HENDERSON, RF AF DAHL, AR SUN, JD BIRNBAUM, LS BOND, JA GRIFFITH, WC MAUDERLY, JL MUGGENBURG, BA SABOURIN, PJ HENDERSON, RF TI TOXICOKINETICS OF INHALED 1,3-BUTADIENE IN MONKEYS - COMPARISON TO TOXICOKINETICS IN RATS AND MICE SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID SPECIES-DIFFERENCES; B6C3F1 MICE; INHALATION PHARMACOKINETICS; METABOLISM; EXPOSURE; BUTADIENE; CARCINOGENICITY; DISPOSITION; INDUCTION; TOXICITY C1 NIEHS,NATL TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709. RP DAHL, AR (reprint author), LOVELACE BIOMED & ENVIRONM RES INST,INHALAT TOXICOL RES INST,POB 5890,ALBUQUERQUE,NM 87185, USA. FU NIEHS NIH HHS [222-Y02-ES-20092, Y01-ES-200099] NR 38 TC 46 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 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD AUG PY 1991 VL 110 IS 1 BP 9 EP 19 DI 10.1016/0041-008X(91)90285-M PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA GB473 UT WOS:A1991GB47300002 PM 1908146 ER PT J AU SIKORSKI, EE BURNS, LA STERN, ML LUSTER, MI MUNSON, AE AF SIKORSKI, EE BURNS, LA STERN, ML LUSTER, MI MUNSON, AE TI SPLENIC CELL TARGETS IN GALLIUM ARSENIDE-INDUCED SUPPRESSION OF THE PRIMARY ANTIBODY-RESPONSE SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID MACROPHAGE-MEDIATED SUPPRESSION; HUMORAL IMMUNE-RESPONSE; HEAVY-METAL MODULATION; LYMPHOCYTE ACTIVITIES; MICE; MOUSE; PROSTAGLANDINS; PROLIFERATION; ACTIVATION; INTERFERON C1 VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT PHARMACOL & TOXICOL,BOX 613 MCV STN,RICHMOND,VA 23298. NIEHS,NATL TOXICOL PROGRAM,SYST TOX BRANCH,RES TRIANGLE PK,NC 27709. FU NIEHS NIH HHS [ES07087, ES55094] NR 58 TC 53 Z9 53 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 AUG PY 1991 VL 110 IS 1 BP 129 EP 142 DI 10.1016/0041-008X(91)90296-Q PG 14 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA GB473 UT WOS:A1991GB47300013 PM 1871769 ER PT J AU RODRIGUEZ, RE MISRA, M NORTH, SL KASPRZAK, KS AF RODRIGUEZ, RE MISRA, M NORTH, SL KASPRZAK, KS TI NICKEL-INDUCED LIPID-PEROXIDATION IN THE LIVER OF DIFFERENT STRAINS OF MICE AND ITS RELATION TO NICKEL EFFECTS ON ANTIOXIDANT SYSTEMS SO TOXICOLOGY LETTERS LA English DT Article DE NICKEL; LIPID PEROXIDATION; CATALASE; SUPEROXIDE DISMUTASE; GLUTATHIONE; GLUTATHIONE PEROXIDASE; GLUTATHIONE REDUCTASE; GLUTATHIONE-S-TRANSFERASE ID INVITRO; SUPEROXIDE; RADICALS; CHLORIDE; INVIVO; RATS AB After a single intraperitoneal injection of 170-mu-mol nickel(II)acetate/kg body wt., the activity of hepatic catalase (CAT) decreased by 25-56% in a strain- and time-dependent manner, the most susceptible being C57BL/6NCr > C3H/HeNCr-MTV- > B6C3F1 greater-than-or-equal-to BALB/cAnNCr mice. The glutathione (GSH) levels in all 4 strains were inhibited by nickel with the C57BL/6NCr mice showing the biggest decrease (68%) followed by BALB/cAnNCr (46%) greater-than-or-equal-to B6C3F1 (42%) > C3H/HeNCr-MTV- (22%). The response of hepatic glutathione peroxidase (GSH-Px) to nickel was variable and included 30% enhancement in C3H/HeNCr-MTV- or lack of biologically significant effect (max. +/- 10% variations in time) in the remaining strains. The activity of glutathione reductase (GSSG-R) increased gradually by up to 30% (48 h post-injection) in B6C3F1 and C3H/HeNCr-MTV- mice or, transiently, by 15-18% (3 h), in C57BL/6NCr and BALB/cAnNCr mice. Also, in some strains, nickel significantly affected superoxide dismutase (SOD) (14-19% loss in C57BL/6NCr and B6C3F1 mice, respectively), and GSH-S-transferase (GST) (26% loss in C3H/HeNCr-MTV- mice). Lipid peroxidation (LPO) in the liver reached its highest value 24 h after nickel treatment in C57BL/6NCr (549% over the control) greater-than-or-equal-to BALB/cAnNCr (519%) > B6C3F1 (426%) >> C3H/HeNCr-MTV- (39%). In conclusion, the magnitude of nickel-induced LPO shows a reverse correlation with the extent and direction of nickel effect on GSH, GSH-Px and GSSG-R, but not on CAT, SOD or GST. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC ETIOL,COMPARAT CARCINOGENESIS LAB,BLDG 538,ROOM 205E,FREDERICK,MD 21702. NR 24 TC 35 Z9 37 U1 0 U2 1 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 AUG PY 1991 VL 57 IS 3 BP 269 EP 281 DI 10.1016/0378-4274(91)90201-G PG 13 WC Toxicology SC Toxicology GA GC028 UT WOS:A1991GC02800004 PM 1882388 ER PT J AU MONTEIRORIVIERE, NA BANKS, YB BIRNBAUM, LS AF MONTEIRORIVIERE, NA BANKS, YB BIRNBAUM, LS TI LASER DOPPLER MEASUREMENTS OF CUTANEOUS BLOOD-FLOW IN AGING MICE AND RATS SO TOXICOLOGY LETTERS LA English DT Article DE MICE; RATS; AGING; BLOOD FLOW; LASER DOPPLER; SKIN ID HUMAN-SKIN; AGED SKIN; VELOCIMETRY; FLOWMETRY; ABSORPTION; ELECTRON; BURNS; SITES AB Laser Doppler velocimetry (LDV) is a non-invasive technique that measures capillary blood perfusion parameters (blood flow, volume and velocity) and can be used non-invasively to evaluate the effects of ageing on cutaneous blood perfusion. Male Fischer-344 rats (R) of 1, 2, 3, 8, 12, 16, 20 and 24 months and C57BL/6N mice (M) 1, 2, 3, 9, 15, 19 and 22 months (n = 6/mo) were used. Animals were anesthetized with ketamine/xylazine and LDV-measured blood flow was made on the backs of all animals. Five readings for each parameter were recorded in order to obtain a mean value of the individual. Skin biopsies (4 mm) were removed after LDV for assessing epidermal and dermal thickness and number of epidermal cell layers. The number of viable epidermal layers in M remained constant while in R it decreased with age. Epidermal thickness in both M and R decreased from 2-3 months and then remained constant. Dermal thickness decreased from 3 to 22 months in M, and increased in R from 1 to 2 months and remained constant. Blood flow of M increased between 1 and 2 months, remained constant to 19 months, then increased at 22 months; flow in R was constant except at 2 months. Thus age differences in epidermal and dermal thickness, and blood flow of M and R occur and should be considered when evaluating cutaneous toxicity studies in different-aged animals. These changes may potentially alter dermal absorption and/or distribution of xenobiotics. C1 NIEHS,RES TRIANGLE PK,NC 27709. RP MONTEIRORIVIERE, NA (reprint author), N CAROLINA STATE UNIV,CTR CUTANEOUS PHARMACOL & TOXICOL,BOX 8401,4700 HILLSBOROUGH ST,RALEIGH,NC 27606, USA. FU NIEHS NIH HHS [ES 00044] NR 35 TC 17 Z9 17 U1 1 U2 2 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 AUG PY 1991 VL 57 IS 3 BP 329 EP 338 DI 10.1016/0378-4274(91)90207-M PG 10 WC Toxicology SC Toxicology GA GC028 UT WOS:A1991GC02800010 PM 1831938 ER PT J AU MULUK, SC CLERICI, M VIA, CS WEIR, MR KIMMEL, PL SHEARER, GM AF MULUK, SC CLERICI, M VIA, CS WEIR, MR KIMMEL, PL SHEARER, GM TI CORRELATION OF INVITRO CD4+ T-HELPER CELL-FUNCTION WITH CLINICAL GRAFT STATUS IN IMMUNOSUPPRESSED KIDNEY-TRANSPLANT RECIPIENTS SO TRANSPLANTATION LA English DT Article ID ALLOGRAFT RECIPIENTS; REJECTION; LYMPHOCYTES; ACTIVATION; RESPONSES; PATHWAYS AB We recently identified three distinct T helper pathways which contribute to interleukin-2 (IL-2) production by human peripheral blood lymphocytes following stimulation with HLA alloantigens. In two of these pathways, CD4+ T helper cells respond to alloantigen using either self antigen-presenting cells (sAPC)* or allogeneic antigen-presenting cells (aAPC). A third pathway involves CD8+ T helper cells using aAPC. Previous in vitro studies have shown that the T helper pathway dependent on CD4+ T helper cells and sAPC (CD4-sAPC) is the most susceptible to suppression by cyclosporine. In the present study, we measured alloantigen-stimulated IL-2 production by PBL from 42 kidney transplant recipients to characterize the strength of the three T helper-APC pathways. In 58% of patients, a loss of the CD4-sAPC pathway was identified and was correlated with cyclosporine treatment. However, several patients not receiving cyclosporine also exhibited a similar loss of T helper cell function, suggesting that cyclosporine is not the only factor involved. Of 27 patients exhibiting depressed CD4-sAPC function, none had evidence of ongoing/recent graft rejection. In contrast, of 11 patients with no defects in the three pathways of in vitro T helper cell function, 6 had evidence of chronic graft rejection. Of considerable interest are the data obtained from a separate group of 4 patients who had episodes of acute rejection during the study. In each case, at the time of the rejection episode, all exhibited an intact CD4-sAPC pathway. However, samples tested prior to the rejection episode or after successful treatment of the rejection episode showed a depressed CD4-sAPC pathway. These results suggest that depression of the CD4-sAPC pathway represents adequate immunosuppression for graft retention and that patients not exhibiting such suppression are at increased risk for both acute and chronic graft rejection. These data may have relevance for diagnosis and/or prediction of graft rejection and may provide an in vitro method of monitoring the functional degree of immunosuppression in transplant recipients. C1 VET ADM MED CTR,DEPT MED,DIV RHEUMATOL & CLIN IMMUNOL,RES SERV,BALTIMORE,MD 21218. UNIV MARYLAND,SCH MED,DEPT MED,DIV NEPHROL,BALTIMORE,MD 21201. GEORGE WASHINGTON UNIV,MED CTR,DEPT MED,WASHINGTON,DC 20037. RP MULUK, SC (reprint author), NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892, USA. FU NIDDK NIH HHS [1 RO1 DK40811-01] NR 28 TC 51 Z9 51 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD AUG PY 1991 VL 52 IS 2 BP 284 EP 291 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA GB915 UT WOS:A1991GB91500019 PM 1678559 ER PT J AU SALOMON, DR AF SALOMON, DR TI AN ALTERNATIVE VIEW MINIMIZING THE SIGNIFICANCE OF CYCLOSPORINE NEPHROTOXICITY AND IN FAVOR OF ENHANCED IMMUNOSUPPRESSION FOR LONG-TERM KIDNEY-TRANSPLANT RECIPIENTS SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT FESTSCHRIFT IN HONOR OF PAUL S RUSSELL ON THE OCCASION OF HIS RETIREMENT AS CHIEF OF THE TRANSPLANTATION UNIT AT THE MASSACHUSETTS GENERAL HOSPITAL CY NOV 30-DEC 01, 1990 CL BOSTON, MA SP SANDOZ PHARM ID RENAL-TRANSPLANTATION; CHRONIC NEPHROPATHY; FOLLOW-UP; THERAPY; TRIAL RP SALOMON, DR (reprint author), NIAID,IMMUNOL LAB,CELLULAR IMMUNOL SECT,BLDG 10,RM 11N312,BETHESDA,MD 20892, USA. RI Salomon, Daniel/E-9380-2012 NR 21 TC 18 Z9 18 U1 0 U2 0 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD AUG PY 1991 VL 23 IS 4 BP 2115 EP 2118 PG 4 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA GA818 UT WOS:A1991GA81800015 PM 1871827 ER PT J AU SMITH, CV ROSENGARD, BR GUZZETTA, PC NAKAJIMA, K SACHS, DH AF SMITH, CV ROSENGARD, BR GUZZETTA, PC NAKAJIMA, K SACHS, DH TI NEW APPROACHES TO TRANSPLANTATION TOLERANCE SO TRANSPLANTATION PROCEEDINGS LA English DT Article; Proceedings Paper CT FESTSCHRIFT IN HONOR OF PAUL S RUSSELL ON THE OCCASION OF HIS RETIREMENT AS CHIEF OF THE TRANSPLANTATION UNIT AT THE MASSACHUSETTS GENERAL HOSPITAL CY NOV 30-DEC 01, 1990 CL BOSTON, MA SP SANDOZ PHARM ID BONE-MARROW TRANSPLANTATION; CLASS-II GENES; T-CELL DEPLETION; MAJOR HISTOCOMPATIBILITY COMPLEX; VERSUS-HOST DISEASE; MINIATURE SWINE; RENAL-ALLOGRAFTS; IMMUNE-RESPONSE; LYMPHOCYTES; SURVIVAL C1 MASSACHUSETTS GEN HOSP,TRANSPLANTAT BIOL RES CTR,MGH E,BLDG 149,13TH ST,BOSTON,MA 02129. NCI,IMMUNOL BRANCH,TRANSPLANTAT BIOL SECT,BETHESDA,MD 20892. NR 27 TC 11 Z9 12 U1 0 U2 0 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 SN 0041-1345 J9 TRANSPLANT P JI Transplant. Proc. PD AUG PY 1991 VL 23 IS 4 BP 2157 EP 2161 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA GA818 UT WOS:A1991GA81800024 PM 1871834 ER PT J AU RHEE, SG AF RHEE, SG TI INOSITOL PHOSPHOLIPID-SPECIFIC PHOSPHOLIPASE-C - INTERACTION OF THE GAMMA-1 ISOFORM WITH TYROSINE KINASE SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Review ID EPIDERMAL GROWTH-FACTOR; PHOSPHOINOSITIDE HYDROLYSIS; SIGNAL TRANSDUCTION; G-PROTEIN; PHOSPHORYLATION; SEQUENCE; CLONING; BINDING; ASSOCIATION; SIMILARITY AB The generation of second messengers from inositol phospholipids is catalysed by enzymes from the phospholipase C family. Activation of phospholipase C-gamma-1 through tyrosine phosphorylation provides a link between mitogenic and inositol phospholipid signaling. RP RHEE, SG (reprint author), NHLBI,BIOCHEM LAB,BLDG 3,ROOM 122,BETHESDA,MD 20892, USA. NR 41 TC 230 Z9 231 U1 0 U2 1 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 AUG PY 1991 VL 16 IS 8 BP 297 EP 301 DI 10.1016/0968-0004(91)90122-C PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA GA130 UT WOS:A1991GA13000011 PM 1659758 ER PT J AU CATT, K ABBOTT, A AF CATT, K ABBOTT, A TI MOLECULAR-CLONING OF ANGIOTENSIN-II RECEPTORS MAY PRESAGE FURTHER RECEPTOR SUBTYPES SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Editorial Material RP CATT, K (reprint author), NICHHD,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892, USA. NR 16 TC 32 Z9 32 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD AUG PY 1991 VL 12 IS 8 BP 279 EP 281 DI 10.1016/0165-6147(91)90573-B PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GA300 UT WOS:A1991GA30000001 PM 1949193 ER PT J AU SCHWARTZ, S FELBER, BK PAVLAKIS, GN AF SCHWARTZ, S FELBER, BK PAVLAKIS, GN TI EXPRESSION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 VIF AND VPR MESSENGER-RNAS IS REV-DEPENDENT AND REGULATED BY SPLICING SO VIROLOGY LA English DT Article ID GENE-PRODUCT; HTLV-III/LAV; TRANS-ACTIVATOR; AIDS VIRUS; SOR GENE; ENZYMATIC AMPLIFICATION; NUCLEOTIDE-SEQUENCE; RESPONSIVE ELEMENT; VISNA VIRUS; PROTEIN C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,HUMAN RETROVIRUS PATHOGENESIS GRP,POB B,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,HUMAN RETROVIRUS SECT,FREDERICK,MD 21702. KAROLINSKA INST,DEPT VIROL,S-10401 STOCKHOLM 60,SWEDEN. FU NCI NIH HHS [N01-CO-74101] NR 61 TC 95 Z9 96 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 0042-6822 J9 VIROLOGY JI Virology PD AUG PY 1991 VL 183 IS 2 BP 677 EP 686 DI 10.1016/0042-6822(91)90996-O PG 10 WC Virology SC Virology GA FW361 UT WOS:A1991FW36100023 PM 1830183 ER PT J AU ADAMSON, MC SILVER, J KOZAK, CA AF ADAMSON, MC SILVER, J KOZAK, CA TI THE MOUSE HOMOLOG OF THE GIBBON APE LEUKEMIA-VIRUS RECEPTOR - GENETIC-MAPPING AND A POSSIBLE RECEPTOR FUNCTION IN RODENTS SO VIROLOGY LA English DT Note ID SUSCEPTIBILITY; INFECTION; REPLICATION; CELLS; LOCUS C1 NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. OI Silver, Jonathan/0000-0001-9231-6368 NR 19 TC 153 Z9 154 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 AUG PY 1991 VL 183 IS 2 BP 778 EP 781 PG 4 WC Virology SC Virology GA FW361 UT WOS:A1991FW36100037 PM 1649508 ER PT J AU KALINSKI, H YANIV, A MASHIAH, P MIKI, T TRONICK, SR GAZIT, A AF KALINSKI, H YANIV, A MASHIAH, P MIKI, T TRONICK, SR GAZIT, A TI REV-LIKE TRANSCRIPTS OF CAPRINE ARTHRITIS ENCEPHALITIS-VIRUS SO VIROLOGY LA English DT Note ID INFECTIOUS-ANEMIA VIRUS; LONG TERMINAL REPEAT; SIMIAN IMMUNODEFICIENCY VIRUS; NUCLEOTIDE-SEQUENCE ANALYSIS; TRANS-ACTIVATOR GENE; AUG INITIATOR CODON; VIRAL MESSENGER-RNA; VISNA VIRUS; SUBCELLULAR-LOCALIZATION; HTLV-III C1 TEL AVIV UNIV,SACKLER SCH MED,DEPT HUMAN MICROBIOL,IL-69978 TEL AVIV,ISRAEL. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. NR 64 TC 11 Z9 13 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD AUG PY 1991 VL 183 IS 2 BP 786 EP 792 DI 10.1016/0042-6822(91)91012-6 PG 7 WC Virology SC Virology GA FW361 UT WOS:A1991FW36100039 PM 1649509 ER PT J AU TOHYA, Y TANIGUCHI, Y TAKAHASHI, E UTAGAWA, E TAKEDA, N MIYAMURA, K YAMAZAKI, S MIKAMI, T AF TOHYA, Y TANIGUCHI, Y TAKAHASHI, E UTAGAWA, E TAKEDA, N MIYAMURA, K YAMAZAKI, S MIKAMI, T TI SEQUENCE-ANALYSIS OF THE 3'-END OF FELINE CALICIVIRUS GENOME SO VIROLOGY LA English DT Note ID INFECTED-CELLS; ANIMAL PICORNAVIRUSES; RNA; VIRUS; POLYPEPTIDE; PROTEINS C1 UNIV TOKYO,FAC AGR,DEPT VET MICROBIOL,BUNKYO KU,TOKYO 113,JAPAN. NIH,CENT VIRUS DIAGNOST LAB,BETHESDA,MD 20892. NR 29 TC 51 Z9 54 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD AUG PY 1991 VL 183 IS 2 BP 810 EP 814 DI 10.1016/0042-6822(91)91016-A PG 5 WC Virology SC Virology GA FW361 UT WOS:A1991FW36100043 PM 1853578 ER PT J AU KWONCHUNG, KJ AF KWONCHUNG, KJ TI THE DISCOVERY OF CREATININE ASSIMILATION IN CRYPTOCOCCUS NEOFORMANS, AND SUBSEQUENT WORK ON THE CHARACTERIZATION OF THE 2 VARIETIES OF C-NEOFORMANS SO ZENTRALBLATT FUR BAKTERIOLOGIE-INTERNATIONAL JOURNAL OF MEDICAL MICROBIOLOGY VIROLOGY PARASITOLOGY AND INFECTIOUS DISEASES LA English DT Article ID SEROTYPE-B; VAR GATTII; FILOBASIDIELLA; BACILLISPORUS; STATE AB The discovery of creatinine assimilation in C. neoformans by Staib served as the foundation for our biochemical, genetical, ecological, epidermological and taxonomic studies on the two varieties of C. neoformans for the past 15 years. The two varietal concept is now widely accepted and the arrival of AIDS epidemic has promoted the recognition of the differences between the two varieties, especially in their epidemiology and ecology. Since the agent of cryptococcosis in AIDS patients almost always belongs to the var. neoformans even in geographical areas prevalent for var. gattii, it is important to study the possible differences in the pathogenesis of the two varieties. RP KWONCHUNG, KJ (reprint author), NIAID,CLIN MYCOL SECT,CLIN INVEST LAB,BLDG 10,ROOM 11N-104,BETHESDA,MD 20892, USA. NR 17 TC 3 Z9 3 U1 0 U2 0 PU GUSTAV FISCHER VERLAG PI STUTTGART PA WOLLGRASWEG 49, D-70599 STUTTGART, GERMANY SN 0934-8840 J9 ZBL BAKT-INT J MED M JI Zent.bl. Bakteriol.-Int. J. Med. Microbiol. Virol. Parasitol. Infect. Dis. PD AUG PY 1991 VL 275 IS 3 BP 390 EP 393 PG 4 WC Microbiology; Virology SC Microbiology; Virology GA GG854 UT WOS:A1991GG85400014 PM 1741922 ER PT J AU BURKE, EM DANNER, DB AF BURKE, EM DANNER, DB TI CHANGES IN FIBRONECTIN MESSENGER-RNA SPLICING WITH INVITRO PASSAGE SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID GENE; FIBROBLASTS; MOLECULE; EMBRYOS; CELLS; EXON; RAT C1 JOHNS HOPKINS UNIV, DEPT MED, DIV GERIATR, BALTIMORE, MD 21224 USA. RP BURKE, EM (reprint author), NIA, GERONTOL RES CTR, MOLEC GENET LAB, 4940 EASTERN AVE, BALTIMORE, MD 21224 USA. FU PHS HHS [5-T32-A600120-03] NR 22 TC 17 Z9 17 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 31 PY 1991 VL 178 IS 2 BP 620 EP 624 DI 10.1016/0006-291X(91)90153-X PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA FY310 UT WOS:A1991FY31000030 PM 1859422 ER PT J AU SAMUDZI, CT GRIBSKOV, CL BURTON, LE RUBIN, JR AF SAMUDZI, CT GRIBSKOV, CL BURTON, LE RUBIN, JR TI CRYSTALLIZATION AND PRELIMINARY-X-RAY DIFFRACTION STUDIES OF RECOMBINANT RABBIT INTERFERON-GAMMA SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID HUMAN IMMUNE INTERFERON; ESCHERICHIA-COLI C1 GENENTECH INC,DEPT PROC DEV,S SAN FRANCISCO,CA 94010. RP SAMUDZI, CT (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,POB B,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74101] NR 15 TC 4 Z9 4 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 JUL 31 PY 1991 VL 178 IS 2 BP 634 EP 640 DI 10.1016/0006-291X(91)90155-Z PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA FY310 UT WOS:A1991FY31000032 PM 1907135 ER PT J AU MARTIN, JL PUMFORD, NR LAROSA, AC MARTIN, BM GONZAGA, HMS BEAVEN, MA POHL, LR AF MARTIN, JL PUMFORD, NR LAROSA, AC MARTIN, BM GONZAGA, HMS BEAVEN, MA POHL, LR TI A METABOLITE OF HALOTHANE COVALENTLY BINDS TO AN ENDOPLASMIC-RETICULUM PROTEIN THAT IS HIGHLY HOMOLOGOUS TO PHOSPHATIDYLINOSITOL-SPECIFIC PHOSPHOLIPASE C-ALPHA BUT HAS NO ACTIVITY SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID HEPATITIS; IDENTIFICATION; PURIFICATION; ANTIBODIES; SERA C1 NIMH,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. JOHNS HOPKINS MED INST,DEPT ANESTHESIOL & CRIT CARE MED,BALTIMORE,MD 21205. RP MARTIN, JL (reprint author), NHLBI,CHEM PHARMACOL LAB,BETHESDA,MD 20892, USA. NR 16 TC 72 Z9 73 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 31 PY 1991 VL 178 IS 2 BP 679 EP 685 DI 10.1016/0006-291X(91)90161-Y PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA FY310 UT WOS:A1991FY31000038 PM 1650195 ER PT J AU TOYN, JH ARAKI, H SUGINO, A JOHNSTON, LH AF TOYN, JH ARAKI, H SUGINO, A JOHNSTON, LH TI THE CELL-CYCLE-REGULATED BUDDING YEAST GENE DBF2, ENCODING A PUTATIVE PROTEIN-KINASE, HAS A HOMOLOG THAT IS NOT UNDER CELL-CYCLE CONTROL SO GENE LA English DT Article DE RECOMBINANT DNA; GENE REGULATION; GENETIC MAPPING; MESSENGER RNA EXPRESSION; SACCHAROMYCES-CEREVISIAE; SEQUENCE HOMOLOGY ID SACCHAROMYCES-CEREVISIAE; FISSION YEAST; DNA-SYNTHESIS; PRODUCT; CDC7; TRANSFORMATION; DISRUPTION; LIGASE AB The budding yeast cell-cycle gene, DBF2, encoding a putative protein kinase, was shown to have a homologue, designated DBF20. This gene was cloned, sequenced, and confirmed to be highly homologous to DBF2, with over 80% identity in the 490 most C-terminal amino acid residues. Either gene could be deleted by itself, but deletion of both genes simultaneously was lethal, indicating that they are redundant for at least one vital function in yeast. In contrast to the DBF2 mRNA, which is expressed under cell-cycle control at or near START [Johnston et al., Mol. Cell. Biol. 10 (1990) 1358-1366], the DBF20 mRNA is expressed at a low level and not under cell-cycle control. Assuming there is no translational control, the differential expression of the mRNAs would result in a cell-cycle fluctuation of the relative levels of the gene products, which may constitute a novel form of regulation. C1 NATL INST MED RES,CELL PROPAGAT LAB,RIDGEWAY,MILL HILL,LONDON NW7 1AA,ENGLAND. NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709. NR 37 TC 56 Z9 59 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD JUL 31 PY 1991 VL 104 IS 1 BP 63 EP 70 DI 10.1016/0378-1119(91)90465-N PG 8 WC Genetics & Heredity SC Genetics & Heredity GA GK076 UT WOS:A1991GK07600009 PM 1916278 ER PT J AU CLARK, JM AF CLARK, JM TI DNA-SYNTHESIS ON DISCONTINUOUS TEMPLATES BY DNA-POLYMERASE-I OF ESCHERICHIA-COLI SO GENE LA English DT Article DE NONTEMPLATED NUCLEOTIDE ADDITION; NONHOMOLOGOUS RECOMBINATION ID THYMINE GLYCOL LESIONS; INVITRO; FRAGMENT AB DNA polymerases normally catalyze DNA synthesis in a template-directed manner. Generally, the continuity of the phosphodiester backbone of the template strand was thought to be an absolute requirement for DNA synthesis. Here, I demonstrate that a 3'-exonuclease-deficient derivative of the Klenow (large) fragment of Escherichia coli DNA polymerase I (PolIk) can carry out DNA synthesis on discontinuous templates in vitro. Addition of multiple nucleotides (nt) to the 3' end of a blunt-end duplex, templated by unlinked single-stranded oligodeoxyribonucleotides (oligos), was monitored electrophoretically. The reaction was demonstrable with either homopolymers or mixed-sequence oligos, but showed a requirement for complementarity between the first nt added to the duplex and the 3' nt of the unlinked oligo. These results demonstrate that continuity of the phosphodiester backbone of the template strand is not absolutely required for in vitro DNA synthesis by a 3'-exonuclease-deficient form of PolIk. RP CLARK, JM (reprint author), NIEHS,MOLEC GENET LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 11 TC 21 Z9 21 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD JUL 31 PY 1991 VL 104 IS 1 BP 75 EP 80 DI 10.1016/0378-1119(91)90467-P PG 6 WC Genetics & Heredity SC Genetics & Heredity GA GK076 UT WOS:A1991GK07600011 PM 1916280 ER PT J AU WINGFIELD, PT STAHL, SJ PAYTON, MA VENKATESAN, S MISRA, M STEVEN, AC AF WINGFIELD, PT STAHL, SJ PAYTON, MA VENKATESAN, S MISRA, M STEVEN, AC TI HIV-1 REV EXPRESSED IN RECOMBINANT ESCHERICHIA-COLI - PURIFICATION, POLYMERIZATION, AND CONFORMATIONAL PROPERTIES SO BIOCHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TOBACCO MOSAIC-VIRUS; SECONDARY STRUCTURE; GENE-PRODUCT; HTLV-III; VIRAL-RNA; PROTEIN; SEQUENCE; BINDING; LOCALIZATION AB The high-level expression of HIV-1 Rev in Escherichia coli is described. Protein in crude bacterial extracts was dissociated from bound nucleic acid with urea. A simple purification and renaturation protocol, monitored by circular dichroism, is described which results in high yields of pure protein. The purified protein binds with high affinity to the Rev-responsive element mRNA and has nativelike spectroscopic properties. The protein exhibits concentration-dependent self-association as judged by analytical ultracentrifugation and gel filtration measurements. Purified Rev showed reversible heat-induced aggregation over the temperature range 0-30-degrees-C. This hydrophobic-driven and nonspecific protein association was inhibited by low concentrations of sulfate ions. Rev solutions at > 80-mu-g/mL, incubated at 0-4-degrees-C, slowly polymerized to form long hollow fibers of 20-nm diameter. Filament formation occurs at a lower protein concentration and more rapidly in the presence of Rev-responsive mRNA. The nucleic acid containing filaments are about 8 nm in diameter and up to 0.4-mu-m in length. On the basis of physical properties of the purified protein, we have suggested that in the nucleus of infected cells, Rev binding to the Rev-responsive region of env mRNA may be followed by helical polymerization of the protein which results in coating of the nucleic acid. Coated nucleic acid could be protected from splicing in the nucleus and exported to the cytoplasm. C1 GLAXO INST MOLEC BIOL,GENEVA,SWITZERLAND. NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. NIAMSD,STRUCT BIOL RES LAB,BETHESDA,MD 20892. RP WINGFIELD, PT (reprint author), NIH,OFF DIRECTOR,PROT EXPRESS LAB,BETHESDA,MD 20892, USA. NR 41 TC 57 Z9 57 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUL 30 PY 1991 VL 30 IS 30 BP 7527 EP 7534 DI 10.1021/bi00244a023 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FZ108 UT WOS:A1991FZ10800023 PM 1854752 ER PT J AU KAUFMAN, H SCHLOM, J KANTOR, J AF KAUFMAN, H SCHLOM, J KANTOR, J TI A RECOMBINANT VACCINIA VIRUS EXPRESSING HUMAN CARCINOEMBRYONIC ANTIGEN (CEA) SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID NERVE GROWTH-FACTOR; ACTIVE-SPECIFIC IMMUNOTHERAPY; MONOCLONAL-ANTIBODIES; GENERAL-METHOD; FOREIGN GENES; CELLS; MELANOMA; VECTORS; DNA; SURFACE AB Carcinoembryonic antigen (CEA) is a 180-kDa glycoprotein expressed on most gastrointestinal carcinomas. A 2.4-kb cDNA clone, containing the complete coding sequence, was isolated from a human colon tumor cell library and inserted into a vaccinia virus genome. This newly developed construct was characterized by Southern blotting, DNA hybridization studies, and polymerase chain reaction analysis. The CEA gene was stably integrated into the vaccina virus thymidine kinase gene. The recombinant was efficiently replicated upon serial passages in cell cultures and in animals. The recombinant virus expresses on the surface of infected cells a protein product recognized by a monoclonal antibody (COL-1) directed against CEA. Immunization of mice with the vaccinia construct elicited a humoral immune response against CEA. Pilot studies also showed that administration of the recombinant CEA vaccinia construct was able to greatly reduce the growth in mice of a syngeneic murine colon adenocarcinoma which had been transduced with the human CEA gene. The use of this new recombinant CEA vaccinia construct may thus provide an approach in the specific active immunotherapy of human G1 cancer and other CEA expressing carcinoma types. C1 NCI,TUMOR IMMUNOL & BIOL LAB,BLDG 10,ROOM 8B-07,BETHESDA,MD 20892. NR 48 TC 70 Z9 73 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUL 30 PY 1991 VL 48 IS 6 BP 900 EP 907 DI 10.1002/ijc.2910480618 PG 8 WC Oncology SC Oncology GA FZ419 UT WOS:A1991FZ41900017 PM 1860736 ER PT J AU QUINN, JP FARINA, AR AF QUINN, JP FARINA, AR TI AUTOIMMUNE ANTIGEN-KU IS ENRICHED ON OLIGONUCLEOTIDE COLUMNS DISTINCT FROM THOSE CONTAINING THE OCTAMER BINDING-PROTEIN DNA CONSENSUS SEQUENCE SO FEBS LETTERS LA English DT Article DE AUTOIMMUNE ANTIGEN-KU; SEQUENCE SPECIFIC DNA BINDING PROTEIN ID LEUKEMIA-VIRUS ENHANCER; TRANSCRIPTION; COMPONENTS; PROMOTER AB During purification of the AP1 complex from the T cell line MLA144 we enriched for a complex which bound to an oligonucleotide column containing the AP1 DNA consensus sequence and co-eluted with a fraction required for AP1 binding activity. This complex although co-eluting with AP1 binding activity had previously been determined to be non-specific in its DNA binding properties. Further investigation determined that the complex was a heterodimer of 85 and 70 kDa which was antigenically related to the autoimmune antigen Ku. It is important to be aware of the abundance and avidity of the Ku complex to bind oligonucleotide columns when purifying sequence specific binding proteins. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. RP QUINN, JP (reprint author), ROYAL EDINBURGH & ASSOC HOSP,MRC,BRAIN METAB UNIT,EDINBURGH EH10 5HF,SCOTLAND. RI Quinn, John/A-2972-2010; OI Quinn, John/0000-0003-3551-7803; FARINA, Antonietta Rosella/0000-0003-0962-6088 NR 15 TC 21 Z9 21 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JUL 29 PY 1991 VL 286 IS 1-2 BP 225 EP 228 DI 10.1016/0014-5793(91)80979-D PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA FZ583 UT WOS:A1991FZ58300053 PM 1864373 ER PT J AU BOROK, Z BUHL, R GRIMES, GJ BOKSER, AD HUBBARD, RC HOLROYD, KJ ROUM, JH CZERSKI, DB CANTIN, AM CRYSTAL, RG AF BOROK, Z BUHL, R GRIMES, GJ BOKSER, AD HUBBARD, RC HOLROYD, KJ ROUM, JH CZERSKI, DB CANTIN, AM CRYSTAL, RG TI EFFECT OF GLUTATHIONE AEROSOL ON OXIDANT-ANTIOXIDANT IMBALANCE IN IDIOPATHIC PULMONARY FIBROSIS SO LANCET LA English DT Note ID LOWER RESPIRATORY-TRACT; INTERSTITIAL LUNG-DISEASES; CHRONIC INFLAMMATION; UNKNOWN CAUSE; DEFICIENCY; FLUID AB Idiopathic pulmonary fibrosis (IPF) is characterised by alveolar inflammation, exaggerated release of oxidants, and subnormal concentrations of the antioxidant glutathione in respiratory epithelial lining fluid (ELF). Glutathione (600 mg twice daily for 3 days) was given by aerosol to 10 patients with IPF. Total ELF glutathione rose transiently, ELF oxidised glutathione concentrations increased, and there was a decrease in spontaneous superoxide anion release by alveolar macrophages. Thus, glutathione by aerosol could be a means of reversing the oxidant-antioxidant imbalance in IPF. C1 NHLBI,PULM BRANCH,BLDG 10 ROOM 6D03,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT PHARM,BETHESDA,MD 20892. CHU SHERBROOKE,SERV PNEUMOL,SHERBROOKE J1H 5N4,QUEBEC,CANADA. NR 10 TC 144 Z9 147 U1 1 U2 4 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD JUL 27 PY 1991 VL 338 IS 8761 BP 215 EP 216 DI 10.1016/0140-6736(91)90350-X PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA FY504 UT WOS:A1991FY50400005 PM 1676780 ER PT J AU GILMORE, RD HACKSTADT, T AF GILMORE, RD HACKSTADT, T TI DNA POLYMORPHISM IN THE CONSERVED 190-KDA ANTIGEN GENE REPEAT REGION AMONG SPOTTED-FEVER GROUP RICKETTSIAE SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Note DE POLYMORPHISM; SEQUENCE DATA; REPEAT REGION; (R-RICKETTSII) ID NEAR-IDENTICAL SEQUENCES; MONOCLONAL-ANTIBODIES; SURFACE-ANTIGEN; GUINEA-PIGS; PROTEIN; VIRULENCE; STRAINS; VACCINE AB The 190 kDa protein gene of R. rickettsii (R strain) contains a large region of tandemly arranged repeats. Homologous sequences were discovered within the genomes of all but one species of spotted fever group Rickettsiae. Southern blots showed restriction fragment length polymorphisms between species of Rickettsiae indicating structural differences among repeat regions. Further analysis using polymerase chain reaction techniques indicated the repeat regions vary in size among Rickettsiae. In addition, strains of R. rickettsii that vary in virulence were found to contain polymorphisms in this region. RP GILMORE, RD (reprint author), NIAID,ROCKY MT LABS,INTRACELLULAR PARASITES LAB,HAMILTON,MT 59840, USA. NR 13 TC 38 Z9 39 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-3002 J9 BIOCHIM BIOPHYS ACTA PD JUL 26 PY 1991 VL 1097 IS 1 BP 77 EP 80 DI 10.1016/0925-4439(91)90027-7 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA GK946 UT WOS:A1991GK94600012 PM 1677592 ER PT J AU SHIBUSAWA, Y ITO, Y AF SHIBUSAWA, Y ITO, Y TI PROTEIN SEPARATION WITH AQUEOUS AQUEOUS POLYMER SYSTEMS BY 2 TYPES OF COUNTERCURRENT CHROMATOGRAPHS SO JOURNAL OF CHROMATOGRAPHY LA English DT Article ID COIL PLANET CENTRIFUGE; MULTILAYER COILS; PHASE SYSTEMS; PERFORMANCE; COLUMNS AB Two different types of counter-current chromatographs, the cross-axis coil planet centrifuge (X-axis CPC) and horizontal flow-through coil planet centrifuge (horizontal CPC), were evaluated for protein separation with an aqueous-aqueous two-phase polymer system. The sample solution, containing 10-200 mg each of cytochrome c, myoglobin, ovalbumin and hemoglobin in 2 ml of each phase was eluted with the lower phase. In both instruments, the effects of the flow-rate, revolution speed, and parameter beta-(helical diameters of the multilayer coil) on the protein separation were investigated. The best results were obtained from the X-axis CPC operated at 750 rpm and a flow-rate of 2.0 ml/min using a multilayer coil with a small helical diameter (beta = 0.25-0.60). Four protein samples were well resolved in less than 5 h. C1 NHLBI,BIOPHYS CHEM LAB,BLDG 10,ROOM 7N322,BETHESDA,MD 20892. NR 12 TC 38 Z9 40 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR PD JUL 26 PY 1991 VL 550 IS 1-2 BP 695 EP 704 DI 10.1016/S0021-9673(01)88575-7 PG 10 WC Chemistry, Analytical SC Chemistry GA GB882 UT WOS:A1991GB88200051 PM 1663507 ER PT J AU LOHSE, P KINDT, MR RADER, DJ BREWER, HB AF LOHSE, P KINDT, MR RADER, DJ BREWER, HB TI 3 GENETIC-VARIANTS OF HUMAN PLASMA APOLIPOPROTEIN-A-IV - APOA-IV-1(THR347-]SER), APOA-IV-0(LYS167-]GLU,GLN360-]HIS), AND APOA-IV-3(GLU165-]LYS) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SYNTHETIC PEPTIDE ANALOGS; LIPID-PROTEIN INTERACTIONS; HIGH-DENSITY LIPOPROTEINS; AORTIC ENDOTHELIAL-CELLS; CHOLESTEROL ACYLTRANSFERASE; SECONDARY STRUCTURE; AMPHIPATHIC HELIX; NUCLEOTIDE-SEQUENCE; POLYMORPHISM; RAT AB Human apolipoprotein (apo) A-IV is a genetically polymorphic glyco-protein of 376 residues. We have recently reported the molecular basis for the two most common isoproteins, apoA-IV-1 and apoA-IV-2(Gln360 --> His), and for two rare variants, apoA-IV-0 (4-amino acid insertion) and apoA-IV-3(Glu230 --> Lys). In this report, we present the genetic basis for three additional isoproteins of apoA-IV. Sequence analysis of the apoA-IV-1 allele revealed a common nucleotide substitution which converts threonine (ACT), residue 347 of the mature protein, into serine (TCT). In one out of the five subjects with the apoA-IV-1/0 phenotype we identified two point mutations: 1) replacing the positively charged lysine (AAG), amino acid 167, with a negatively charged glutamic acid (GAG), and 2) converting the neutral residue 360, glutamine (CAG), to a positively charged histidine (CAT). We have also characterized four additional heterozygotes for the apoA-IV-3 allele. One individual was found to have the previously described substitution of lysine for glutamic acid at amino acid 230. The three other subjects had the identical mutation but at a different position in the polypeptide chain, residue 165. These results indicate that one predominant allele codes for the isoproteins apoA-IV-2 and apoA-IV-0 and that at least two major allelic variants for the isoproteins apoA-Il-1 and apoA-IV-3 are present in the population analyzed. RP LOHSE, P (reprint author), NHLBI,MOLEC DIS BRANCH,BLDG 10,RM 7N117,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 66 TC 42 Z9 43 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 25 PY 1991 VL 266 IS 21 BP 13513 EP 13518 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FY027 UT WOS:A1991FY02700012 PM 1677358 ER PT J AU MENNITI, FS BIRD, GS TAKEMURA, H THASTRUP, O POTTER, BVL PUTNEY, JW AF MENNITI, FS BIRD, GS TAKEMURA, H THASTRUP, O POTTER, BVL PUTNEY, JW TI MOBILIZATION OF CALCIUM BY INOSITOL TRISPHOSPHATES FROM PERMEABILIZED RAT PAROTID ACINAR-CELLS - EVIDENCE FOR TRANSLOCATION OF CALCIUM FROM UPTAKE TO RELEASE SITES WITHIN THE INOSITOL 1,4,5-TRISPHOSPHATE-SENSITIVE AND THAPSIGARGIN-SENSITIVE CALCIUM POOL SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GUINEA-PIG HEPATOCYTES; ADRENAL GLOMERULOSA CELLS; 2ND MESSENGER; CA-2+ RELEASE; ENDOPLASMIC-RETICULUM; INTRACELLULAR CALCIUM; MICROSOMAL FRACTIONS; 3-KINASE ACTIVITY; RECEPTOR-BINDING; TUMOR PROMOTER AB D-myo-Inositol (1,4,5)-trisphosphate ((1,4,5)IP3)-induced Ca2+ release and subsequent Ca2+ reuptake were investigated in saponin-permeabilized rat parotid acinar cells. Following the rapid release of Ca2+ by (1,4,5)IP3, Ca2+ was resequestered. The sequential addition of submaximal concentrations of (1,4,5)IP3 resulted in sequential Ca2+ release. However, when the cells were challenged with the poorly metabolized (1,4,5)IP3 analogues, (1,4,5)IPS3 or (2,4,5)IP3, or under conditions where the metabolism of authentic (1,4,5)IP3 was reduced, Ca2+ reuptake again occurred, but sequestered Ca2+ was not released by subsequent additions of (1,4,5)IP3. The sequestered Ca2+ was, however, released by thapsigargin, an agent which inhibits active Ca2+ uptake into the (1,4,5)IP3-sensitive pool. Furthermore, the rate of thapsigargin-induced release was significantly increased in the continued presence of an (1,4.5)IP3 stimulus. Thus, Ca2+ reuptake apparently occurred into the (1,4,5)IP3- and thapsigargin-sensitive Ca2+ store and (1,4,5)IP3 continued to influence the permeability of this pool to Ca2+ during Ca2+ reuptake. In contrast to the findings in permeabilized cells, Ca2+ reuptake did not occur in the sustained presence of (1,4,5)IP3 in intact parotid cells. We conclude that cell permeabilization reveals a kinetic, and presumably structural, separation of Ca2+ uptake and release sites within the (1,4,5)IP3-regulated intracellular organelle. C1 UNIV COPENHAGEN HOSP,RIGSHOSP,DEPT CLIN CHEM,DK-2100 COPENHAGEN,DENMARK. SYMBION,THROMBOSIS GRP,DK-2100 COPENHAGEN,DENMARK. UNIV BATH,SCH PHARM & PHARMACOL,BATH BA2 7AY,AVON,ENGLAND. RP MENNITI, FS (reprint author), NIEHS,CALCIUM REGULAT SECT,CELLULAR & MOLEC PHARMACOL LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. RI Potter, Barry/A-1845-2012 NR 65 TC 47 Z9 47 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 25 PY 1991 VL 266 IS 21 BP 13646 EP 13653 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FY027 UT WOS:A1991FY02700033 PM 1906881 ER PT J AU AMEGADZIE, BY AHN, BY MOSS, B AF AMEGADZIE, BY AHN, BY MOSS, B TI IDENTIFICATION, SEQUENCE, AND EXPRESSION OF THE GENE ENCODING A MR 35,000 SUBUNIT OF THE VACCINIA VIRUS DNA-DEPENDENT RNA-POLYMERASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LATE MESSENGER-RNAS; NUCLEOTIDE-SEQUENCE; TRANSCRIPTION; GENOME; INITIATION; PROMOTERS; LEADER; ENDS AB The gene rpo35, encoding a subunit of the vaccinia virus DNA-dependent RNA polymerase, was identified, and its RNA and protein products were characterized. An M(r) 35,000 polypeptide, which bound antibody to the purified RNA polymerase, was synthesized in reticulocyte lysates programmed with viral mRNA that hybridized to a 2,300-base pair segment of the viral genome. Determination of the sequence of the DNA segment revealed four potential protein coding regions, none of which had evident similarity to any described RNA polymerase subunit of prokaryotes or eukaryotes. One open reading frame that could encode a 35,400-Da protein was identified as rpo35 on the basis of mRNA hybridization, cell-free translation, and immunoprecipitation. The identification was confirmed by sequencing tryptic peptides of the authentic M(r) 35,000 RNA polymerase subunit. Antiserum to the purified recombinant protein, expressed in bacteria, reacted specifically with a M(r) 35,000 polypeptide that was detected starting 2 h after virus infection and that co-sedimented with RNA polymerase purified from virions. RNA analyses indicated that the 5'-end of an early transcript started 25 nucleotides upstream of rpo35, which is consistent with the location of an early promoter consensus sequence. RP AMEGADZIE, BY (reprint author), NIAID,VIRAL DIS LAB,BETHESDA,MD 20892, USA. NR 34 TC 38 Z9 54 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 25 PY 1991 VL 266 IS 21 BP 13712 EP 13718 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FY027 UT WOS:A1991FY02700041 PM 1856205 ER PT J AU AXLEY, MJ GRAHAME, DA AF AXLEY, MJ GRAHAME, DA TI KINETICS FOR FORMATE DEHYDROGENASE OF ESCHERICHIA-COLI FORMATE-HYDROGENLYASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LYASE; SELENOCYSTEINE; METABOLISM; ENZYMES AB Kinetic parameters of the selenium-containing, formate dehydrogenase component of the Escherichia coli formate-hydrogenlyase complex have been determined with purified enzyme. A ping-pong Bi Bi kinetic mechanism was observed. The K(m) for formate is 26 mM, and the K(m) for the electron-accepting dye, benzyl viologen, is in the range 1-5 mm. The maximal turnover rate for the formate-dependent catalysis of benzyl viologen reduction was calculated to be 1.7 x 10(5) min-1. Isotope exchange analysis showed that the enzyme catalyzes carbon exchange between carbon dioxide and formate in the absence of other electron acceptors, confirming the ping-pong reaction mechanism. Dissociation constants for formate (12.2 mM) and CO2 (8.3 mM) were derived from analysis of the isotope exchange data. The enzyme catalyzes oxidation of the alternative substrate deuterioformate with little change in the V(max), but the K(m) for deuterioformate is approximately three times that of protioformate. This implies formate oxidation is not rate-limiting in the overall coupled reaction of formate oxidation and benzyl viologen reduction. The deuterium isotope effect on V(max)/K(m) was observed to be approximately 4.2-4.5. Sodium nitrate was found to inhibit enzyme activity in a competitive manner with respect to formate, with a K(i) of 7.1 mM. Sodium azide is a noncompetitive inhibitor with a K(i) of about 80-mu-M. RP AXLEY, MJ (reprint author), NHLBI,BIOCHEM LAB,BLD 3,RM 103,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 17 TC 33 Z9 33 U1 1 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 25 PY 1991 VL 266 IS 21 BP 13731 EP 13736 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FY027 UT WOS:A1991FY02700044 PM 1906883 ER PT J AU FORRYSCHAUDIES, S HUGHES, SH AF FORRYSCHAUDIES, S HUGHES, SH TI THE CHICKEN TROPOMYOSIN-1 GENE GENERATES 9 MESSENGER-RNAS BY ALTERNATIVE SPLICING SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID WEIGHT NONMUSCLE TROPOMYOSIN; MUSCLE ALPHA-TROPOMYOSIN; BETA-TROPOMYOSIN; EMBRYO FIBROBLASTS; INTRON SEQUENCES; SINGLE GENE; EXPRESSION; SKELETAL; ISOFORMS; SMOOTH AB Skeletal muscle beta-tropomyosin, smooth muscle alpha-tropomyosin, and a low molecular weight fibroblast tropomyosin are generated by alternatively splicing RNA transcripts of the chicken tropomyosin 1 (TM 1) gene (Forry-Schaudies, S., Maihle, N. J., and Hughes, S. H. (1990) J. Mol. Biol. 21 1; 321-330). Two novel tropomyosin cDNAs that derive from mRNAs of the TM 1 gene have been isolated from a chicken embryo brain cDNA library. Brain cDNA BRT-1 is 2.2 kilobases in length and encodes 283 amino acids. It is identical to skeletal muscle beta-tropomyosin from amino acids 1 to 258. The sequence 3' of this point is unique to BRT-1; a comparison to genomic sequence indicates that a new carboxyl-terminal exon is used to generate this sequence. 1.4-kilobase brain cDNA BRT-2 contains sequences found in both fibroblast cDNA FT-beta (5'-end) and skeletal muscle cDNA SKT-beta (3'-end). RNase and SI nuclease assays using RNA samples from leg muscle, gizzard, fibroblasts, and brain indicate that the TM 1 gene expresses four additional tropomyosin RNAs by alternately splicing previously characterized exons. These results demonstrate that the chicken TM 1 gene encodes nine tropomyosin RNAs through the use of two promoters, two internal exons that are mutually exclusive, and three 3'-exons. Implications for the regulation of alternative splicing are discussed. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,POB B,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101] NR 42 TC 28 Z9 28 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 25 PY 1991 VL 266 IS 21 BP 13821 EP 13827 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FY027 UT WOS:A1991FY02700059 PM 1856215 ER PT J AU DEGITZ, K LIANJIE, L CAUGHMAN, SW AF DEGITZ, K LIANJIE, L CAUGHMAN, SW TI CLONING AND CHARACTERIZATION OF THE 5'-TRANSCRIPTIONAL REGULATORY REGION OF THE HUMAN INTERCELLULAR-ADHESION MOLECULE-1 GENE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TUMOR NECROSIS FACTOR; DNA-BINDING PROTEINS; INTERFERON-GAMMA; MAMMALIAN-CELLS; PHORBOL ESTER; ICAM-1; EXPRESSION; RECEPTOR; IMMUNOGLOBULIN; KERATINOCYTES AB Cell-cell adhesion is critical in the generation of immunologic responses and is dependent upon expression of a variety of cell surface receptors. While intercellular adhesion molecule 1 (ICAM-1), a specific receptor for lymphocyte function-associated antigen 1, is constitutively expressed by some cell types, its de novo or increased expression by various cells has been associated with the initiation of inflammatory responses and appears to be transcriptionally regulated. The 5' region of the human ICAM-1 gene has been cloned and both structurally and functionally analyzed. A 17.3-kilobase genomic clone containing three exonal regions encoding the N-terminal third of the ICAM-1 protein was isolated. A 2.05-kilobase subclone, containing the 5' most exon, was utilized to determine an interferon-gamma-induced transcription initiation site via primer extension and S1 nuclease protection assays. Analysis of the 5'-flanking region revealed consensus sequences for appropriately located basal promoter elements, as well as numerous potential cis-acting enhancer elements. When subcloned into a reporter gene construct, the putative promoter subregion functioned as a potent promoter. However, in accord with biologically observed expression of ICAM-1 in specific cell types, when additional 5'-flanking sequences were included in reporter gene constructs, tissue appropriate repression of transcription was observed. C1 EMORY UNIV,SCH MED,DEPT DERMATOL,201 WOODRUFF MEM BLDG,ATLANTA,GA 30322. NCI,DERMATOL BRANCH,BETHESDA,MD 20892. NR 46 TC 161 Z9 165 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 25 PY 1991 VL 266 IS 21 BP 14024 EP 14030 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FY027 UT WOS:A1991FY02700089 PM 1677359 ER PT J AU BILSKI, P DABESTANI, R CHIGNELL, CF AF BILSKI, P DABESTANI, R CHIGNELL, CF TI INFLUENCE OF CATIONIC SURFACTANT ON THE PHOTOPROCESSES OF EOSIN AND ROSE-BENGAL IN AQUEOUS-SOLUTION SO JOURNAL OF PHYSICAL CHEMISTRY LA English DT Article ID SINGLET MOLECULAR-OXYGEN; MICELLAR SYSTEMS; XANTHENE DYES; QUANTUM YIELD; PICOSECOND FLUORESCENCE; LUMINESCENCE MEASUREMENTS; ABSORPTION-SPECTRA; PREMICELLAR REGION; REVERSE MICELLES; WATER AB The influence of cetylpyridinium chloride (CPC) on the photoprocesses of rose bengal (RB) and eosine has been investigated in aqueous solutions. When the molar ratio of dye to CPC is 1:2, hydrophobic ion pairs, dye(CPC)2, are formed. In water the ion pairs easily aggregate and can be extracted into benzene. Upon further addition of CPC to an aqueous solution, the ion pairs appear to be hosted individually in the hydrophobic interior of positively charged micelles formed at or above the critical micelle concentration of the surfactant. The aprotic interior of the micelles is responsible for a red shift in the absorption and fluorescence spectra of the dyes and longer singlet lifetimes, which greatly enhances fluorescence. The photochemical properties of the different forms of RB and eosine are affected by bimolecular deactivation processes between the dye molecules in the excited state and those in the ground state. When the dye molecules are separated from each other in the micelles, the dye triplet lifetime becomes longer because the contribution to triplet decay from self-quenching is diminished. As a result, copious singlet oxygen production is observed in micelles, while dye photobleaching is considerably reduced. The quantum yields of singlet oxygen formation for the micellar forms of RB and eosine in D2O are 0.75 and 0.24, respectively. The dyes in cationic micelles are also less sensitive to acidic pH and to the presence of a fluorescence quencher in the aqueous phase. On the other hand, the fluorescence of the ion-pair aggregates is decreased and their triplet state is effectively self-quenched, resulting in poor singlet oxygen formation and much faster photobleaching. Singlet oxygen does not appear to play a significant role in the photobleaching processes. RP BILSKI, P (reprint author), NIEHS,MOLEC BIOPHYS LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 59 TC 78 Z9 78 U1 0 U2 19 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-3654 J9 J PHYS CHEM-US JI J. Phys. Chem. PD JUL 25 PY 1991 VL 95 IS 15 BP 5784 EP 5791 DI 10.1021/j100168a015 PG 8 WC Chemistry, Physical SC Chemistry GA FY388 UT WOS:A1991FY38800015 ER PT J AU HEALY, B AF HEALY, B TI THE YENTL SYNDROME SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ANGINA RP HEALY, B (reprint author), NIH,BETHESDA,MD 20892, USA. NR 6 TC 287 Z9 289 U1 2 U2 3 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 25 PY 1991 VL 325 IS 4 BP 274 EP 276 DI 10.1056/NEJM199107253250408 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA FX627 UT WOS:A1991FX62700008 PM 2057027 ER PT J AU PATE, EJ WIKTOR, SZ SHAW, GM TAYLOR, ME CHAMPEGNIE, E MURPHY, EL BLATTNER, WA AF PATE, EJ WIKTOR, SZ SHAW, GM TAYLOR, ME CHAMPEGNIE, E MURPHY, EL BLATTNER, WA TI LACK OF VIRAL LATENCY OF HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE-1 SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID LEUKEMIA-VIRUS; TRANSMISSION C1 NCI,BETHESDA,MD 20892. UNIV ALABAMA,BIRMINGHAM,AL 35294. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. RP PATE, EJ (reprint author), UNIV W INDIES,KINGSTON 7,JAMAICA. NR 5 TC 15 Z9 15 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 25 PY 1991 VL 325 IS 4 BP 284 EP 284 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA FX627 UT WOS:A1991FX62700024 PM 2057031 ER PT J AU WU, J NICKERSON, JM AF WU, J NICKERSON, JM TI PCR DETECTION OF THE MSPL POLYMORPHISM IN THE HUMAN IRBP GENE (RPB3) SO NUCLEIC ACIDS RESEARCH LA English DT Note RP WU, J (reprint author), NEI,RETINAL CELL & MOLEC BIOL LAB,BLDG 6,ROOM 224,BETHESDA,MD 20892, USA. NR 3 TC 3 Z9 3 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL 25 PY 1991 VL 19 IS 14 BP 4016 EP 4016 DI 10.1093/nar/19.14.4016-a PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FY987 UT WOS:A1991FY98700055 PM 1713667 ER PT J AU POLYMEROPOULOS, MH XIAO, H RATH, DS MERRIL, CR AF POLYMEROPOULOS, MH XIAO, H RATH, DS MERRIL, CR TI DINUCLEOTIDE REPEAT POLYMORPHISM AT THE HUMAN CTLA4 GENE SO NUCLEIC ACIDS RESEARCH LA English DT Note RP POLYMEROPOULOS, MH (reprint author), ST ELIZABETH HOSP,CTR NEUROSCI,NATL INST MENTAL HLTH,ROOM 131,2700 MARTIN LUTHER KING AVE,WASHINGTON,DC 20032, USA. NR 3 TC 230 Z9 242 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL 25 PY 1991 VL 19 IS 14 BP 4018 EP 4018 DI 10.1093/nar/19.14.4018-a PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FY987 UT WOS:A1991FY98700059 PM 1862005 ER PT J AU POLYMEROPOULOS, MH RATH, DS XIAO, H MERRIL, CR AF POLYMEROPOULOS, MH RATH, DS XIAO, H MERRIL, CR TI TETRANUCLEOTIDE REPEAT POLYMORPHISM AT THE HUMAN C-FES/FPS PROTOONCOGENE (FES) SO NUCLEIC ACIDS RESEARCH LA English DT Note RP POLYMEROPOULOS, MH (reprint author), ST ELIZABETH HOSP,CTR NEUROSCI,NATL INST MENTAL HLTH,ROOM 131,2700 MARTIN LUTHER KING AVE,WASHINGTON,DC 20032, USA. NR 4 TC 230 Z9 242 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL 25 PY 1991 VL 19 IS 14 BP 4018 EP 4018 DI 10.1093/nar/19.14.4018-a PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FY987 UT WOS:A1991FY98700058 PM 1862005 ER PT J AU POLYMEROPOULOS, MH RATH, DS XIAO, H MERRIL, CR AF POLYMEROPOULOS, MH RATH, DS XIAO, H MERRIL, CR TI DINUCLEOTIDE REPEAT POLYMORPHISM AT THE HUMAN ATP SYNTHASE BETA SUBUNIT GENE (ATPSB) SO NUCLEIC ACIDS RESEARCH LA English DT Note RP POLYMEROPOULOS, MH (reprint author), ST ELIZABETH HOSP,CTR NEUROSCI,NATL INST MENTAL HLTH,ROOM 131,2700 MARTIN LUTHER KING AVE,WASHINGTON,DC 20032, USA. NR 4 TC 16 Z9 16 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL 25 PY 1991 VL 19 IS 14 BP 4019 EP 4019 DI 10.1093/nar/19.14.4019-a PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FY987 UT WOS:A1991FY98700061 PM 1862006 ER PT J AU POLYMEROPOULOS, MH XIAO, H RATH, DS MERRIL, CR AF POLYMEROPOULOS, MH XIAO, H RATH, DS MERRIL, CR TI DINUCLEOTIDE REPEAT POLYMORPHISM AT THE HUMAN CARDIAC BETA-MYOSIN GENE SO NUCLEIC ACIDS RESEARCH LA English DT Note RP POLYMEROPOULOS, MH (reprint author), ST ELIZABETH HOSP,CTR NEUROSCI,NATL INST MENTAL HLTH,ROOM 131,2700 MARTIN LUTHER KING AVE,WASHINGTON,DC 20032, USA. NR 3 TC 16 Z9 16 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL 25 PY 1991 VL 19 IS 14 BP 4019 EP 4019 DI 10.1093/nar/19.14.4019-a PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FY987 UT WOS:A1991FY98700060 PM 1862006 ER PT J AU BREWSTER, ES BRENNAN, MB VISSING, H AF BREWSTER, ES BRENNAN, MB VISSING, H TI DINUCLEOTIDE REPEAT POLYMORPHISM IN THE IL-2R-BETA GENE SO NUCLEIC ACIDS RESEARCH LA English DT Note C1 CUNY MT SINAI SCH MED,DEPT PSYCHIAT,NEW YORK,NY 10029. NIMH,GENOM UNIT,BETHESDA,MD 20892. HAGEDORN RES LAB,DK-2820 GENTOFTE,DENMARK. RP BREWSTER, ES (reprint author), CUNY MT SINAI SCH MED,BROOKDALE CTR MOLEC BIOL,1 GUSTAVE L LEVY PL,NEW YORK,NY 10029, USA. NR 1 TC 21 Z9 22 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL 25 PY 1991 VL 19 IS 14 BP 4022 EP 4022 DI 10.1093/nar/19.14.4022 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FY987 UT WOS:A1991FY98700066 PM 1862007 ER PT J AU HEALY, B AF HEALY, B TI WOMENS HEALTH, PUBLIC-WELFARE SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP HEALY, B (reprint author), NIH,9000 ROCKVILLE PIKE,BLDG 1,ROOM 126,BETHESDA,MD 20892, USA. NR 1 TC 29 Z9 29 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 24 PY 1991 VL 266 IS 4 BP 566 EP 568 DI 10.1001/jama.266.4.566 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA FX021 UT WOS:A1991FX02100035 PM 2061987 ER PT J AU ASHIZAWA, K MCPHIE, P LIN, KH CHENG, SY AF ASHIZAWA, K MCPHIE, P LIN, KH CHENG, SY TI AN INVITRO NOVEL MECHANISM OF REGULATING THE ACTIVITY OF PYRUVATE KINASE-M2 BY THYROID-HORMONE AND FRUCTOSE-1,6-BISPHOSPHATE SO BIOCHEMISTRY LA English DT Article ID BINDING-PROTEIN; NUCLEAR RECEPTOR; ISOZYMES; RAT; PURIFICATION; EXPRESSION; HEPATOMA; CELLS; GENE AB We have recently shown that the cytosolic thyroid hormone binding protein (p58-M2) in human epidermoid carcinoma A431 cells is a monomer of pyruvate kinase, subtype M2 (PKM2). To characterize further the molecular properties of p58-M2, we overexpressed p58-M2 in Escherichia coli and purified it to homogeneity. At 22-degrees-C, the monomeric p58-M2 exhibited kinase activity with an apparent V(max) of 22 +/- 9 units/mg. The Km for adenosine diphosphate (ADP) and phosphoenolpyruvate (PEP) are 3.85 +/- 2.4 and 1.55 +/- 0.73 mM, respectively. Upon activation by fructose 1,6-bisphosphate (Fru-1,6-P2), V(max) and K(m) for ADP and PEP were changed to 490 +/- 27 units/mg and 0.63 +/- 0.09 and 0.1 3 +/- 0.01 mM, respectively. These results indicated that p58-M2 has intrinsic kinase activity. Analysis of the molecular size indicated that the activation of p58-M2 by Fru-1,6-P2 resulted in the association of the monomeric p58-M2 to the tetrameric PKM2. p58-M2 bound to 3,3',5-triiodo-L-thyronine (T3) (K(a) = 1.7 X 10(7) M-1) and exhibited analogue specificity, whereas PKM2 did not bind thyroid hormone. The order of binding affinity was L-T3 > L-thyroxine > 3,3',5-triiodothyropropionic acid > 3'-isopropyl-3,5-triiodo-L-thyronine > 3',5',3-triiodo-L-thyronine. Binding of T3 and its analogues resulted in the inhibition of the kinase activity of p58-M2. The order of kinase inhibitory activity and preventing its association to tetrameric PKM2 was parallel to that of binding activity. The present study demonstrated that, in vitro, the molecular mechanism by which Fru-1,6-p2 induced activation of PK activity is by tetramer formation. Furthermore, thyroid hormone plays a role in regulating the enzymatic activity of PKM2. C1 NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. NIDDKD,BIOCHEM & METAB LAB,BETHESDA,MD 20892. NR 24 TC 53 Z9 54 U1 0 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 JUL 23 PY 1991 VL 30 IS 29 BP 7105 EP 7111 DI 10.1021/bi00243a010 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FX877 UT WOS:A1991FX87700010 PM 1854723 ER PT J AU SIEGALL, CB OGATA, M PASTAN, I FITZGERALD, DJ AF SIEGALL, CB OGATA, M PASTAN, I FITZGERALD, DJ TI ANALYSIS OF SEQUENCES IN DOMAIN-II OF PSEUDOMONAS EXOTOXIN-A WHICH MEDIATE TRANSLOCATION SO BIOCHEMISTRY LA English DT Article ID RECOMBINANT FUSION PROTEIN; CYTO-TOXIC ACTIVITY; DIPHTHERIA-TOXIN; ESCHERICHIA-COLI; AERUGINOSA; CLATHRIN; BINDING; ALPHA; CELLS; IMMUNOTOXIN AB Pseudomonas exotoxin (PE) contains 613 amino acids that are arranged into 3 structural domains. PE exerts its cell-killing effects in a series of steps initiated by binding to the cell surface and internalization into endocytic vesicles. The toxin is then cleaved within domain II near arginine-279, generating a C-terminal 37-kDa fragment that is translocated into the cytosol where it ADP-ribosylates elongation factor 2 and arrests protein synthesis. In this study, we have focused on the functions of PE which are encoded by domain II. We have used the chimeric toxin TGF-alpha-PE40 to deliver the toxin's ADP-ribosylating activity to the cell cytosol. Deletion analysis revealed that sequences from 253 to 345 were essential for toxicity but sequences from 346 to 364 were dispensable. Additional point mutants were constructed which identified amino acids 339 and 343 as important residues while amino acids 344 and 345 could be altered without loss of cytotoxic activity. Our data support the idea that domain II functions by first allowing PE to be processed to a 37-kDa fragment and then key sequences such as those identified in this study mediate the translocation of ADP-ribosylation activity to the cytosol. C1 NCI,DIV CANC BIOL DIAGN,MOLEC BIOL LAB,BLDG 37,ROOM 4E16,BETHESDA,MD 20892. NR 34 TC 26 Z9 29 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUL 23 PY 1991 VL 30 IS 29 BP 7154 EP 7159 DI 10.1021/bi00243a016 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FX877 UT WOS:A1991FX87700016 PM 1906738 ER PT J AU MACKALL, J KLEE, CB AF MACKALL, J KLEE, CB TI CALCIUM-INDUCED SENSITIZATION OF THE CENTRAL HELIX OF CALMODULIN TO PROTEOLYSIS SO BIOCHEMISTRY LA English DT Article ID NUCLEAR MAGNETIC-RESONANCE; STOPPED-FLOW FLUORESCENCE; X-RAY-SCATTERING; TROPONIN-C; TRYPTIC FRAGMENTS; CONFORMATIONAL CHANGE; BINDING SITES; PROTEIN; SEQUENCE; H-1-NMR AB The rate of proteolysis of trypsin-sensitive bonds was used to examine the nature of the structural changes accompanying Ca2+ and Mg2+ binding to calmodulin. In the Ca2+-free form, the rates of proteolysis at Arg-106 and Arg-37 are rapid (> 300 and 28 nmol min-1 mL-1, respectively), the bonds at Arg-74, Lys-75, and Lys-77, in the central helix, are cleaved more slowly (10 nmol min-1 mL-1), and a lag in the cleavage at the remaining bonds (Lys- 13, Lys-30, Arg-86, Arg-90, and Arg-126) suggests that they are not cleaved in the native protein. High concentrations of Ca2+, but not Mg2+, almost completely abolish proteolysis at Arg- 106 and drastically reduce the rate of cleavage at Arg-37. Both Ca2+ and Mg2+ exert a moderate protective effect on the proteolysis of the central helix. These results suggest that the F-helix of domains III and, to a lesser extent, the F-helix of domain I are somewhat flexible in the Ca2+-free form and are stabilized by Ca2+. Whereas full occupancy of the four Ca2+-binding sites produces little change in the susceptibility of the central helix to proteolytic attack, binding of two Ca2+ produces a 10-fold enhancement of the rate of proteolysis in this part of the molecule. We propose that at intermediate Ca2+ levels the flexibility of the central helix of calmodulin is greatly increased, resulting in the transient formation of intermediates which have not been detected by spectroscopic techniques but are trapped by the irreversible action of trypsin. C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. NR 48 TC 32 Z9 33 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUL 23 PY 1991 VL 30 IS 29 BP 7242 EP 7247 DI 10.1021/bi00243a028 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FX877 UT WOS:A1991FX87700028 PM 1854733 ER PT J AU WINSLOW, J INSEL, TR AF WINSLOW, J INSEL, TR TI VASOPRESSIN MODULATES MALE SQUIRREL-MONKEYS BEHAVIOR DURING SOCIAL SEPARATION SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE VOCAL BEHAVIOR; SCENT-MARKING BEHAVIOR; INTRACEREBROVENTRICULAR; OXYTOCIN; VASOPRESSIN; (MONKEY); (NEUROPEPTIDE) ID CORTICOTROPIN-RELEASING-FACTOR; GROOMING BEHAVIOR; ANTERIOR HYPOTHALAMUS; ARGININE VASOPRESSIN; MARKING BEHAVIOR; INFANT PRIMATES; STRESS RESPONSE; GOLDEN-HAMSTERS; SEXUAL-BEHAVIOR; SCENT MARKING AB The central administration of arginine-vasopressin (AVP) in rodents has been associated with the modulation of a number of categories of behavior including social recognition and learning, aggression, grooming, and feeding. Concentrations of AVP in brain have also been functionally related to gonadal steroid hormone manipulations. In the current experiments we investigated the behavioral effects of centrally administered AVP on the behavior of pair-housed male squirrel monkeys during brief social separations. Prior to treatment, pairs of male squirrel monkeys established reliable and persistent dominance relationships measured as different patterns of social behavior and plasma levels of testosterone. Central administration of AVP increased scent-marking and grooming behaviors during the social separation test, however these effects were not influenced by the social status of the treated monkey. The effects of AVP on these measures were not mimicked by doses of oxytocin (OT). Both AVP and OT decreased the frequency of vigilance-checking and 'isolation-peep' calls. The data are consistent with a facilitatory role for AVP in the stress response and also suggest that these particular effects are not influenced by differences in testosterone associated with social dominance. RP WINSLOW, J (reprint author), NIMH,CLIN SCI LAB,POB 289,POOLESVILLE,MD 20879, USA. NR 50 TC 27 Z9 28 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD JUL 23 PY 1991 VL 200 IS 1 BP 95 EP 101 DI 10.1016/0014-2999(91)90671-C PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA GA780 UT WOS:A1991GA78000014 PM 1769376 ER PT J AU KIM, RY LIETMAN, T PIATIGORSKY, J WISTOW, GJ AF KIM, RY LIETMAN, T PIATIGORSKY, J WISTOW, GJ TI STRUCTURE AND EXPRESSION OF THE DUCK ALPHA-ENOLASE TAU-CRYSTALLIN-ENCODING GENE SO GENE LA English DT Article DE RECOMBINANT DNA; GENE EXPRESSION; NUCLEOTIDE SEQUENCE; PROMOTER ID CHICKEN DELTA-1-CRYSTALLIN GENE; CHLORAMPHENICOL ACETYLTRANSFERASE; PROMOTER FUNCTION; MAMMALIAN-CELLS; TRANSGENIC MICE; LENS EPITHELIA; TURTLE LENS; PROTEIN; DNA; PURIFICATION AB In the duck, the glycolytic enzyme, alpha-enolase (alpha-ENO), and the lens structural protein, tau-crystallin (tau-CRY), are products of the same gene, an example of protein multi-functionality. We report that duck alpha-ENO/tau-CRY mRNA levels are developmentally regulated; alpha-ENO/tau-CRY mRNA levels in the lens increase over those in the liver by embryonic day 14 and, within the lens, are higher in the lens epithelium than in fiber cells. We determined the structure of the duck alpha-ENO/tau-CRY-encoding gene (alpha-ENO/tau-CRY), sequenced 1 kb of 5'-flanking region, and demonstrated that this region contains a functional promoter. The gene is 13 kb in size and is composed of twelve exons; the exon organization is identical to that of mammalian enolase-encoding genes. A fragment of 5'-flanking region (-803/+3) containing three CCAAT boxes and a TATA box was able to activate transcription of a heterologous reporter gene when transfected into cultured lens cells. However, in spite of greater quantities of alpha-ENO/tau-CRY mRNA and protein in the lens, the promoter was equally active in primary cultures of embryonic lens, liver and fibroblast cells. Since the cultured cells unexpectedly lost the restricted pattern of alpha-ENO/tau-CRY mRNA levels observed in vivo, evaluation of the promoter's tissue specificity was precluded. C1 NEI,MOLE & DEV BIOL LAB,BETHESDA,MD 20892. NR 34 TC 29 Z9 30 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD JUL 22 PY 1991 VL 103 IS 2 BP 193 EP 200 DI 10.1016/0378-1119(91)90273-E PG 8 WC Genetics & Heredity SC Genetics & Heredity GA GE571 UT WOS:A1991GE57100008 PM 1889745 ER PT J AU BRESSAN, A SOMMA, MP LEWIS, J SANTOLAMAZZA, C COPELAND, NG GILBERT, DJ JENKINS, NA LAVIA, P AF BRESSAN, A SOMMA, MP LEWIS, J SANTOLAMAZZA, C COPELAND, NG GILBERT, DJ JENKINS, NA LAVIA, P TI CHARACTERIZATION OF THE OPPOSITE-STRAND GENES FROM THE MOUSE BIDIRECTIONALLY TRANSCRIBED HTF9 LOCUS SO GENE LA English DT Article DE CPG ISLAND; GENE MOLECULAR ORGANIZATION; BIDIRECTIONAL TRANSCRIPTION; HOUSEKEEPING EXPRESSION; NUCLEOTIDE SEQUENCE; INTERSPECIFIC BACKCROSS MAPPING ID CPG-RICH ISLAND; HOUSEKEEPING GENE; RAS GENE; PROMOTER; MICE; IDENTIFICATION; METHYLATION; NUCLEUS; LINKAGE; INVITRO AB The mouse HTF9 locus contains two genes that are bidirectionally transcribed with opposite polarity from a shared CpG-rich island. Both genes were previously shown to be expressed in a housekeeping fashion in mouse. We have now determined the molecular organization of the genes over 12 kb surrounding the island. In addition, we show that the HTF9 locus resides in the proximal region of mouse chromosome 16. We have sequenced the cDNAs corresponding to both divergent transcripts. Both genes appear to code for novel proteins that are structurally unrelated to each other. Finally, we show that both genes are highly conserved and efficiently expressed in human cells. C1 UNIV ROME LA SAPIENZA,CNR,CTR GENET EVOLUZIONIST,DIPARTIMENTO GENET & BIOL MOLEC,I-00185 ROME,ITALY. NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. INST MOLEC PATHOL,VIENNA,AUSTRIA. OI Lavia, Patrizia/0000-0003-3310-6701 FU NCI NIH HHS [N01-CO-74101] NR 30 TC 41 Z9 44 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD JUL 22 PY 1991 VL 103 IS 2 BP 201 EP 209 DI 10.1016/0378-1119(91)90274-F PG 9 WC Genetics & Heredity SC Genetics & Heredity GA GE571 UT WOS:A1991GE57100009 PM 1889746 ER PT J AU SERNAGOR, E ODONOVAN, MJ AF SERNAGOR, E ODONOVAN, MJ TI WHOLE-CELL PATCH CLAMP RECORDINGS FROM RHYTHMICALLY ACTIVE MOTONEURONS IN THE ISOLATED SPINAL-CORD OF THE CHICK-EMBRYO SO NEUROSCIENCE LETTERS LA English DT Article DE WHOLE-CELL PATCH CLAMP; VOLTAGE CLAMP; SYNAPTIC CURRENT; MOTOR ACTIVITY; SPINAL CORD; MOTONEURON; CHICK EMBRYO ID CENTRAL NERVOUS-SYSTEM; NEURONS; CURRENTS; RETINA AB Whole-cell patch clamp recordings were obtained during motor activity from electrically identified motoneurons within the spinal cord of the chick embryo maintained in vitro. Most recordings were performed on E11-E13 motoneurons although it was also possible to record from younger cells (E7-E9). Voltage clamp recordings were used to characterize the synaptic currents expressed in femorotibialis (extensor) motoneurons during motor activity. These motoneurons exhibited rhythmic excitatory currents with reversal potentials near 0 mV. This powerful technique enables high resolution recordings from identified motoneurons in situ and allows investigation of the membrane and synaptic mechanisms involved in the development of embryonic motility. RP SERNAGOR, E (reprint author), NIH,NEURAL CONTROL LAB,BLDG 36,ROOM 5A31,BETHESDA,MD 20892, USA. NR 18 TC 29 Z9 29 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD JUL 22 PY 1991 VL 128 IS 2 BP 211 EP 216 DI 10.1016/0304-3940(91)90263-S PG 6 WC Neurosciences SC Neurosciences & Neurology GA FZ154 UT WOS:A1991FZ15400017 PM 1945040 ER PT J AU NAHIN, RL HYLDEN, JLK AF NAHIN, RL HYLDEN, JLK TI PERIPHERAL INFLAMMATION IS ASSOCIATED WITH INCREASED GLUTAMIC-ACID DECARBOXYLASE IMMUNOREACTIVITY IN THE RAT SPINAL-CORD SO NEUROSCIENCE LETTERS LA English DT Article DE COMPLETE FREUND ADJUVANT; HYPERALGESIA; PAIN; GABA; DYNORPHIN ID PRIMARY AFFERENT TERMINALS; DORSAL HORN; SPINOTHALAMIC TRACT; AMINO-ACIDS; NEURONS; GABA; ORGANIZATION; RESPONSES; NUCLEUS; MODEL AB We have examined the frequency and distribution of neuron profiles immunoreactive for glutamic acid decarboxylase, a biosynthetic enzyme for the putative inhibitory neurotransmitter, gamma aminobutyric acid, in the lumbar spinal cord of colchicine-treated rats with unilateral inflammation of a hindpaw. Ipsilateral to the inflamed hindpaw, there was an apparent increase in the levels of glutamic acid decarboxylase, as indicated by significant increases in the number of visible glutamic acid decarboxylase-like immunoreactive profiles within the superficial dorsal horn, neck of the dorsal horn and the deep gray matter at L4. An increase limited to the deep gray matter at L6 was also seen. No alteration was identified at L2. These results are the first to demonstrate that peripheral inflammation is associated with altered levels of glutamic acid decarboxylase-like immunoreactivity. RP NAHIN, RL (reprint author), NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BLDG 30,ROOM B-20,BETHESDA,MD 20892, USA. NR 28 TC 29 Z9 29 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD JUL 22 PY 1991 VL 128 IS 2 BP 226 EP 230 DI 10.1016/0304-3940(91)90266-V PG 5 WC Neurosciences SC Neurosciences & Neurology GA FZ154 UT WOS:A1991FZ15400020 PM 1682858 ER PT J AU LIPMAN, DJ WILBUR, WJ AF LIPMAN, DJ WILBUR, WJ TI MODELING NEUTRAL AND SELECTIVE EVOLUTION OF PROTEIN FOLDING SO PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES LA English DT Article ID MOLECULAR CLOCK AB We examine a model evolutionary space consisting of genotypes mapped to their corresponding phenotypes. This mapping is derived from a lattice model for proteins which, despite its highly idealized nature, has been shown to share general properties with real proteins. Large evolutionary networks are observed, with genotypes corresponding to non-lethal phenotypes linked by unit mutational steps. Neutral mutations are necessary for traversing the evolutionary networks, and even one neutral mutation in a genotype can change the phenotypes attainable by a unit mutational step. RP LIPMAN, DJ (reprint author), NIH, NATL LIB MED, NATL CTR BIOTECHNOL INFORMAT, BLDG 38A, 8N803, BETHESDA, MD 20894 USA. NR 20 TC 92 Z9 92 U1 0 U2 8 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 0962-8452 J9 P ROY SOC B-BIOL SCI JI Proc. R. Soc. B-Biol. Sci. PD JUL 22 PY 1991 VL 245 IS 1312 BP 7 EP 11 DI 10.1098/rspb.1991.0081 PG 5 WC Biology; Ecology; Evolutionary Biology SC Life Sciences & Biomedicine - Other Topics; Environmental Sciences & Ecology; Evolutionary Biology GA FY885 UT WOS:A1991FY88500002 PM 1682931 ER PT J AU FORMANKAY, JD GRONENBORN, AM WINGFIELD, PT CLORE, GM AF FORMANKAY, JD GRONENBORN, AM WINGFIELD, PT CLORE, GM TI DETERMINATION OF THE POSITIONS OF BOUND WATER-MOLECULES IN THE SOLUTION STRUCTURE OF REDUCED HUMAN THIOREDOXIN BY HETERONUCLEAR 3-DIMENSIONAL NUCLEAR-MAGNETIC-RESONANCE SPECTROSCOPY SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Note DE BOUND WATER; HUMAN THIOREDOXIN; SOLUTION STRUCTURE; 3D NMR ID INTERPROTON DISTANCE RESTRAINTS; SOLUTION CONFORMATION; PRACTICAL ASPECTS; ESCHERICHIA-COLI; ROTATING-FRAME; PROTEINS; DYNAMICS; NMR; IDENTIFICATION; CRAMBIN C1 NIDDKD,CHEM PHYS LAB,BLDG 2,BETHESDA,MD 20892. NIH,OFF DIRECTOR,PROT EXPRESS LAB,BETHESDA,MD 20892. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 24 TC 41 Z9 41 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 JUL 20 PY 1991 VL 220 IS 2 BP 209 EP 216 DI 10.1016/0022-2836(91)90004-P PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FY714 UT WOS:A1991FY71400004 PM 1856855 ER PT J AU MEZEY, E LERANTH, C ESKAY, R HORVATH, S PALKOVITS, M AF MEZEY, E LERANTH, C ESKAY, R HORVATH, S PALKOVITS, M TI THE ORIGIN OF SOMATOSTATIN-CONTAINING NERVE-FIBERS INNERVATING THE HYPOTHALAMIC SUPRAOPTIC NUCLEUS SO BRAIN RESEARCH LA English DT Article DE SOMATOSTATIN; VASOPRESSIN; SUPRAOPTIC NUCLEUS ID HORMONE-RELEASING HORMONE; CONTAINING NEURONS; RAT-BRAIN; VASOPRESSIN SECRETION; MONOCLONAL-ANTIBODIES; GROWTH-HORMONE; SYSTEM; LOCALIZATION; OXYTOCIN AB Light and electron microscopic studies were performed to study the connections between somatostatin (SOS)-containing nerve terminals and vasopressin (VP)-containing neurons in the rat supraoptic nucleus (SON). SOS-positive fibers innervate the SON in both the oxytocinergic and vasopressinergic areas. Using double immunostaining symmetric synaptic contacts were visualized between SOS immunoreactive boutons and the soma of VP immunopositive neurons. Surgical transection deafferentating the SON from all possible directions do not effect the presence of SOS immunopositive fibers. These results suggest a local origin of the SOS fibers. Somatostatin-containing perikarya can indeed be found at the dorsal border of the SON at the rostral and caudal pole of the nucleus - we suggest that these cells innervate the SON. The presence of synaptic contacts between SOS fibers and VP neurons as well as the lack of these fibers in the VP deficient Brattleboro rats indicate a role for SOS in the synthesis and/or release of vasopressin in the SON. C1 SEMMELWEIS UNIV MED,SCH MED,DEPT ANAT 1,H-1085 BUDAPEST 8,HUNGARY. YALE UNIV,DEPT OBSTET & GYNAECOL,NEW HAVEN,CT 06520. NIAAA,LCS,BETHESDA,MD. RP MEZEY, E (reprint author), NIMH,LCB,BLDG 36,3A17,BETHESDA,MD 20892, USA. RI Palkovits, Miklos/F-2707-2013; OI Palkovits, Miklos/0000-0003-0578-0387 FU NICHD NIH HHS [HD23830] NR 26 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUL 19 PY 1991 VL 554 IS 1-2 BP 293 EP 298 DI 10.1016/0006-8993(91)90203-8 PG 6 WC Neurosciences SC Neurosciences & Neurology GA FZ504 UT WOS:A1991FZ50400040 PM 1681988 ER PT J AU OBRIEN, SJ MAYR, E AF OBRIEN, SJ MAYR, E TI SPECIES HYBRIDIZATION AND PROTECTION OF ENDANGERED ANIMALS - REPLY SO SCIENCE LA English DT Letter C1 HARVARD UNIV,MUSEUM COMPARAT ZOOL,CAMBRIDGE,MA 02138. RP OBRIEN, SJ (reprint author), NCI,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702, USA. NR 10 TC 8 Z9 8 U1 1 U2 3 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUL 19 PY 1991 VL 253 IS 5017 BP 251 EP 252 DI 10.1126/science.253.5017.251 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FX224 UT WOS:A1991FX22400004 PM 17794670 ER PT J AU GERFEN, CR ENGBER, TM AF GERFEN, CR ENGBER, TM TI CONTROLS FOR LESIONS OF THE NIGROSTRIATAL DOPAMINE SYSTEM - REPLY SO SCIENCE LA English DT Article C1 NINCDS,EXPTL THERAPEUT BRANCH,BETHESDA,MD 20892. RP GERFEN, CR (reprint author), NIMH,CELL BIOL LAB,BETHESDA,MD 20892, USA. NR 1 TC 7 Z9 7 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUL 19 PY 1991 VL 253 IS 5017 BP 332 EP 332 DI 10.1126/science.253.5017.332-a PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FX224 UT WOS:A1991FX22400047 ER PT J AU LEY, C BAUER, HM REINGOLD, A SCHIFFMAN, MH CHAMBERS, JC TASHIRO, CJ MANOS, MM AF LEY, C BAUER, HM REINGOLD, A SCHIFFMAN, MH CHAMBERS, JC TASHIRO, CJ MANOS, MM TI DETERMINANTS OF GENITAL HUMAN PAPILLOMAVIRUS INFECTION IN YOUNG-WOMEN SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID INVASIVE CERVICAL-CANCER; ORAL-CONTRACEPTIVE USE; RISK-FACTORS; LATIN-AMERICA; HPV-16 DNA; NEOPLASIA; PREVALENCE; ASSOCIATION; SMOKING; UTERI AB Carcinoma of the cervix has several well-established epidemiologic risk factors, including multiple sexual partners and early age at first intercourse. Human papillomavirus (HPV) infection appears to have an etiologic role in the development of cervical neoplasia, but evidence linking HPV infection to known risk factors for cervical cancer has been inconsistent. The lack of expected correlations may be due to the inaccuracy of HPV assays previously used. A polymerase chain reaction DNA amplification method for the detection of HPV was used to investigate the determinants of genital HPV infection in a cross-sectional sample of 467 women attending a university health service. In contrast to studies using less accurate detection methods, the risk factors for HPV infection found here were consistent with those for cervical neoplasia. The risk of HPV infection was strongly and independently associated with increasing numbers of sexual partners in a lifetime, use of oral contraceptives, younger age, and black race. Age at first intercourse, smoking, and history of a prior sexually transmitted disease were correlated with, but not independently predictive of, HPV infection. These results demonstrate that the key risk factors for cervical carcinoma are strongly associated with genital HPV infection. This correlation suggests that HPV has an etiologic role in cervical neoplasia and reaffirms the sexual route of HPV transmission. C1 CETUS CORP,DEPT INFECT DIS,EMERYVILLE,CA 94608. UNIV CALIF BERKELEY,EPIDEMIOL PROGRAM,BERKELEY,CA 94720. UNIV CALIF BERKELEY,UNIV HLTH SERV,BERKELEY,CA 94720. NCI,DIV CANC ETIOL,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892. NR 46 TC 283 Z9 287 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 JUL 17 PY 1991 VL 83 IS 14 BP 997 EP 1003 DI 10.1093/jnci/83.14.997 PG 7 WC Oncology SC Oncology GA GA927 UT WOS:A1991GA92700011 PM 1649312 ER PT J AU REED, D YANO, K AF REED, D YANO, K TI PREDICTORS OF ARTERIOGRAPHICALLY DEFINED CORONARY STENOSIS IN THE HONOLULU HEART PROGRAM - COMPARISONS OF COHORT AND ARTERIOGRAPHY SERIES ANALYSES SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE ANGIOGRAPHY; ARTERIOSCLEROSIS; BIAS (EPIDEMIOLOGY); PROSPECTIVE STUDIES; RISK FACTORS ID RISK-FACTORS; ARTERY DISEASE; LIFESTYLE CHARACTERISTICS; REGRESSION-MODELS; ATHEROSCLEROSIS; PROGRESSION; DIETARY AB The purpose of this study was to determine if the major risk factors for clinical myocardial infarction also predicted coronary artery stenosis as defined by arteriography. Of a cohort of 7,591 men who were free of cardiovascular disease at entry, 357 had arteriographic studies during a 20-year follow-up period. Risk factor levels were therefore known prior to the onset of clinical symptoms and arteriographic studies. Men with arteriograms were divided into groups with and without prior clinical myocardial infarction. High blood pressure, serum cholesterol, obesity, and low alcohol intake predicted both severe coronary stenosis and incident myocardial infarction, thus indicating that these variables were associated with clinical events through the underlying process of atherosclerosis. Dietary intake of cholesterol and serum glucose also had similar but not always statistically significant patterns of association with both coronary stenosis and myocardial infarction. In contrast, serum triglyceride and cigarette smoking predicted clinical myocardial infarction, but not severe coronary stenosis. This suggests that these variables play a stronger role in the precipitation of acute clinical events than in the underlying process of atherosclerosis. The findings were quite different for several risk factors when analyzed in a case-control format using the arteriography series from this same data set. Examination of possible explanations for the differences raises questions concerning the use of arteriography series for etiologic studies of coronary atherosclerosis. C1 NHLBI,HONOLULU HEART PROGRAM,BETHESDA,MD 20892. RP REED, D (reprint author), KUAKINI MED CTR,HONOLULU HEART PROGRAM,347 N KUAKINI ST,HONOLULU,HI 96817, USA. FU NHLBI NIH HHS [N01-HC-02901] NR 16 TC 45 Z9 45 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUL 15 PY 1991 VL 134 IS 2 BP 111 EP 122 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA FZ245 UT WOS:A1991FZ24500001 PM 1862795 ER PT J AU RUBIN, BI HOLLAND, EJ DESMET, MD BELFORT, R NUSSENBLATT, RB AF RUBIN, BI HOLLAND, EJ DESMET, MD BELFORT, R NUSSENBLATT, RB TI RESPONSE OF REACTIVATED LIGNEOUS CONJUNCTIVITIS TO TOPICAL CYCLOSPORINE SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Letter C1 UNIV MINNESOTA,DEPT OPHTHALMOL,MINNEAPOLIS,MN 55455. RP RUBIN, BI (reprint author), NEI,IMMUNOL LAB,BLDG 10,RM 10N202,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Belfort Jr, Rubens/E-2252-2012 OI Belfort Jr, Rubens/0000-0002-8422-3898 NR 4 TC 15 Z9 15 U1 0 U2 0 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JUL 15 PY 1991 VL 112 IS 1 BP 95 EP 96 PG 2 WC Ophthalmology SC Ophthalmology GA FV107 UT WOS:A1991FV10700021 PM 1882932 ER PT J AU MOSELEY, MA DETERDING, LJ TOMER, KB JORGENSON, JW AF MOSELEY, MA DETERDING, LJ TOMER, KB JORGENSON, JW TI NANOSCALE PACKED-CAPILLARY LIQUID-CHROMATOGRAPHY COUPLED WITH MASS-SPECTROMETRY USING A COAXIAL CONTINUOUS-FLOW FAST-ATOM-BOMBARDMENT INTERFACE SO ANALYTICAL CHEMISTRY LA English DT Article ID COLUMN ELECTROCHEMICAL DETECTOR; BOROSILICATE GLASS-CAPILLARIES; REVERSED-PHASE COLUMNS; OPEN-TUBULAR COLUMNS; INNER DIAMETERS; VOLTAMMETRIC DETECTION; LIMITED PRESSURE; ANALYSIS TIME; FAB-MS; OPTIMIZATION AB Nanoscale packed-capillary liquid chromatography (LC) columns have been coupled with mass spectrometry (MS) using a coaxial continuous-flow fast atom bombardment interface. The combined system has been applied to the analysis of mixtures of peptides, including synthetic mixtures of bioactive peptides and tryptic digests of proteins. Nanoscale packed-capillary columns offer two principal advantages for LC/MS analysis-high chromatographic separation efficiencies and low mobile-phase flow rates. The high separation efficiencies facilitate the separation of complex mixtures, and the low mobile-phase flow rates reduce problems with coupling the LC effluent with the high-vacuum, high-voltage environment of sector MS ion sources. The columns used in this work were 50- or 75-mu-m l.d., 1-2 m long, packed with 10-mu-m C18 particles, using mobile-phase flow rates of 50-350 nL/min. C1 NIEHS,MOLEC BIOPHYS LAB,POB 12233,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,DEPT CHEM,CHAPEL HILL,NC 27514. RI Tomer, Kenneth/E-8018-2013 NR 38 TC 85 Z9 85 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD JUL 15 PY 1991 VL 63 IS 14 BP 1467 EP 1473 DI 10.1021/ac00014a023 PG 7 WC Chemistry, Analytical SC Chemistry GA FW297 UT WOS:A1991FW29700024 PM 1928722 ER PT J AU SAKAIRI, M YERGEY, AL SIU, KWM LEBLANC, JCY GUEVREMONT, R BERMAN, SS AF SAKAIRI, M YERGEY, AL SIU, KWM LEBLANC, JCY GUEVREMONT, R BERMAN, SS TI ELECTROSPRAY MASS-SPECTROMETRY - APPLICATION OF ION EVAPORATION THEORY TO AMINO-ACIDS SO ANALYTICAL CHEMISTRY LA English DT Article ID AFFINITIES; MOLECULES; PEPTIDES AB We describe the result of applying the ion evaporation theory to a series of amino acids. The very good correlation (r = 0.98) of the natural logarithms of protonated molecule intensities observed by electrospray with the difference between the hydration free energies of molecules and the gas-phase binding free energies of molecules and protons in amino acids is consistent with the ion evaporation model. It seems that the difference in the protonated molecule intensities of amino acids obtained by electrospray can be explained by a scheme in which protonated molecules in the liquid phase are extracted into the gas phase after a charged droplet is formed. C1 NICHHD,BETHESDA,MD 20892. NATL RES COUNCIL CANADA,DIV CHEM,OTTAWA K1A 0R6,ONTARIO,CANADA. RP SAKAIRI, M (reprint author), HITACHI LTD,CENT RES LAB,KOKUBUNJI,TOKYO 185,JAPAN. NR 16 TC 26 Z9 26 U1 1 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD JUL 15 PY 1991 VL 63 IS 14 BP 1488 EP 1490 DI 10.1021/ac00014a026 PG 3 WC Chemistry, Analytical SC Chemistry GA FW297 UT WOS:A1991FW29700027 PM 1928723 ER PT J AU ROBBINS, J MERINO, MJ BOICE, JD RON, E AIN, KB ALEXANDER, HR NORTON, JA REYNOLDS, J AF ROBBINS, J MERINO, MJ BOICE, JD RON, E AIN, KB ALEXANDER, HR NORTON, JA REYNOLDS, J TI THYROID-CANCER - A LETHAL ENDOCRINE NEOPLASM SO ANNALS OF INTERNAL MEDICINE LA English DT Discussion ID FACTORS INFLUENCING PROGNOSIS; SERUM THYROGLOBULIN DETERMINATION; POORLY DIFFERENTIATED CARCINOMA; CARCINOEMBRYONIC ANTIGEN LEVELS; INAPPARENT MEDULLARY CARCINOMA; DOXORUBICIN PLUS CISPLATIN; COLUMNAR-CELL CARCINOMA; MB-1 ANTI-CD37 ANTIBODY; UNIVERSITY-OF-MICHIGAN; EARLY LIVER METASTASES AB This conference focuses on the controversies about managing thyroid cancer, emphasizing the possibility that the treatment of patients with potentially fatal thyroid cancer may be improved. Although the mortality rate from thyroid cancer is low, it is the highest among cancers affecting the endocrine glands (excluding the ovary). Exposure to radiation during childhood in the 1930s and 1940s increased the incidence of but not the mortality from thyroid cancer, because these tumors are mainly papillary cancers developing in young adults. These rates may change as the exposed cohort ages. Risk factors that increase mortality include older patient age and the growth characteristics of the tumor at diagnosis, the presence of distant metastases, and cell type (for example, the tall-cell variants of papillary cancer, follicular cancer [to be distinguished from the more benign follicular variant of papillary cancer], medullary cancer, and anaplastic cancer). Local metastases in lymph nodes do not seem to increase the risk for death from papillary cancer, but they do increase the risk for death from follicular and medullary cancer. In the latter, mortality is decreased by the early detection and treatment of patients with the familial multiple endocrine neoplasia syndrome 2a. There are excellent tumor markers for differentiated cancer of the parafollicular and of the follicular cells (serum calcitonin and serum thyroglobulin levels, respectively). Measuring the calcitonin level allows early diagnosis of familial medullary cancer, whereas measuring the thyroglobulin level, although useful only after total thyroidectomy, allows early recognition of recurrence or metastases of papillary or follicular cancer. Initial surgery, protocols for follow-up, and the use of radioiodine for the ablation of any residual thyroid and the treatment of metastatic cancer are discussed. Because these tumors resist currently available chemotherapy regimens, possible ways to increase the effectiveness of radioiodine therapy are considered as are new approaches to treatment. C1 NCI,SURG BRANCH,SURG METAB SECT,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. NCI,RADIAT EPIDEMIOL BRANCH,BETHESDA,MD 20892. RP ROBBINS, J (reprint author), NIDDKD,CLIN ENDOCRINOL BRANCH,BLDG 10,ROOM 8N315,BETHESDA,MD 20892, USA. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 125 TC 159 Z9 160 U1 0 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 JUL 15 PY 1991 VL 115 IS 2 BP 133 EP 147 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA FW091 UT WOS:A1991FW09100010 PM 2058861 ER PT J AU CASSCELLS, W AF CASSCELLS, W TI AN ELEPHANT SWIMMING SO ANNALS OF INTERNAL MEDICINE LA English DT Letter RP CASSCELLS, W (reprint author), NIH,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUL 15 PY 1991 VL 115 IS 2 BP 160 EP 160 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA FW091 UT WOS:A1991FW09100030 ER PT J AU LAZARUS, LH SALVADORI, S TOMATIS, R WILSON, WE AF LAZARUS, LH SALVADORI, S TOMATIS, R WILSON, WE TI OPIOID RECEPTOR SELECTIVITY REVERSAL IN DELTORPHIN TETRAPEPTIDE ANALOGS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID CONFORMATIONAL PROPERTIES; HIGH-AFFINITY; SKIN PEPTIDE; DERMORPHIN; DERMENKEPHALIN; FEATURES; AGONIST; DESIGN; SITES C1 UNIV FERRARA,DEPT PHARMACEUT SCI,I-44100 FERRARA,ITALY. RP LAZARUS, LH (reprint author), NIEHS,LMIN,RES TRIANGLE PK,NC 27709, USA. NR 24 TC 19 Z9 19 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUL 15 PY 1991 VL 178 IS 1 BP 110 EP 115 DI 10.1016/0006-291X(91)91786-C PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA FW340 UT WOS:A1991FW34000016 PM 1648906 ER PT J AU LINDGREN, S RASCON, A ANDERSSON, KE MANGANIELLO, V DEGERMAN, E AF LINDGREN, S RASCON, A ANDERSSON, KE MANGANIELLO, V DEGERMAN, E TI SELECTIVE-INHIBITION OF CGMP-INHIBITED AND CGMP-NONINHIBITED CYCLIC-NUCLEOTIDE PHOSPHODIESTERASES AND RELAXATION OF RAT AORTA SO BIOCHEMICAL PHARMACOLOGY LA English DT Article ID VASCULAR SMOOTH-MUSCLE; CONGESTIVE HEART-FAILURE; CONTRACTILE RESPONSES; AMP PHOSPHODIESTERASE; ISOZYME INHIBITION; RELAXING FACTOR; CARDIAC-MUSCLE; MILRINONE; ENDOTHELIUM; BOVINE AB In the supernatant (50,000 g, 1 hr) fraction from rat aortic smooth muscle homogenates, approximately 50% of total cAMPE PDE activity was inhibited by OPC 3911 (3-mu-M), while approximately 20% was inhibited by rolipram (30-mu-M). A cGMP-inhibited cyclic nucleotide phosphodiesterase (cGI-PDE) was further purified using DEAE chromatography followed by affinity chromatography on the N-(2-isothiocyanato)ethyl derivative of cilostamide conjugated to aminoethyl agarose (CIT-agarose). OPC 3911, CI-930, and milrinone, but not rolipram, were potent and selective inhibitors of this enzyme. The PDE-activity in the CIT-agarose flow through fraction (RI-PDE), however, was inhibited potently by rolipram, but not by cGMP, OPC 3911, CI-930 or milrinone. Functional studies showed that OPC 3911, CI-930, and milrinone were potent relaxants of contracted rat aorta. Rolipram had little relaxant effect. When OPC 3911 or milrinone was combined with rolipram more than additive effects on aortic relaxation and cAMP content were obtained. OPC 3911 combined with milrinone had only additive effects. These results demonstrate the presence of a cGI-PDE in rat aortic smooth muscle, and that inhibition of this isozyme may be of primary importance for the relaxant effects of OPC 3911, CI-930, and milrinone. A RI-PDE activity was also found, but it appeared to be less important for modulation of vascular tone unless the cGI-PDE was already inhibited. This may explain the synergistic relaxant effects observed when both PDE-isozymes were inhibited. C1 UNIV LUND,DEPT MED & PHYSIOL CHEM,S-22101 LUND,SWEDEN. NHLBI,CELLULAR METAB LAB,BETHESDA,MD 20892. RP LINDGREN, S (reprint author), UNIV LUND HOSP,DEPT CLIN PHARMACOL,S-22185 LUND,SWEDEN. NR 32 TC 47 Z9 47 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD JUL 15 PY 1991 VL 42 IS 3 BP 545 EP 552 DI 10.1016/0006-2952(91)90317-X PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA FY958 UT WOS:A1991FY95800014 PM 1650216 ER PT J AU KIRCH, DG AF KIRCH, DG TI WHERE THERES SMOKE ... NICOTINE AND PSYCHIATRIC-DISORDERS SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material ID TARDIVE-DYSKINESIA; DEPRESSION; BRAIN RP KIRCH, DG (reprint author), NIMH,DIV CLIN RES,5600 FISHERS LANE,ROOM 10-105,ROCKVILLE,MD 20857, USA. NR 10 TC 6 Z9 6 U1 3 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 JUL 15 PY 1991 VL 30 IS 2 BP 107 EP 108 DI 10.1016/0006-3223(91)90162-F PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA FY198 UT WOS:A1991FY19800001 PM 1912102 ER PT J AU HOEHNSARIC, R MCLEOD, DR GLOWA, JR AF HOEHNSARIC, R MCLEOD, DR GLOWA, JR TI THE EFFECTS OF NMDA RECEPTOR BLOCKADE ON THE ACQUISITION OF A CONDITIONED EMOTIONAL RESPONSE SO BIOLOGICAL PSYCHIATRY LA English DT Article ID LONG-TERM POTENTIATION; RAT HIPPOCAMPAL SLICES; D-ASPARTATE RECEPTORS; PANIC DISORDER; ANTAGONISTS; MK-801; IMPAIRMENT; EXPRESSION; BEHAVIOR; ANXIETY AB Excitatory amino acids, acting at the N-methyl-d-aspartate (NMDA) receptor, have been postulated to play an important role in the acquisition of behavior (learning). Previous studies have shown that some forms of response acquisition can be impaired by drugs that block the NMDA receptor. To determine whether excitatory amino acid blockade could also affect the ability to acquire an emotional response, the effects of the noncompetitive NMDA receptor antagonist MK-801 were studied on the development of response suppression under a conditioned emotional response (CER) procedure in the rat. The CER procedure progressively suppressed responding when saline was given prior to the eight daily sessions over which animals were initially exposed. Daily treatment with MK-801 blocked the development of response suppression. Thus, these data are consistent with the notion that excitatory amino acid blockade prevents or diminishes the development of a learned emotional response. This suggests a potential role for this receptor in the development of anxiety-related disorders in humans. C1 NIMH,CLIN NEUROENDOCRINOL BRANCH,BLDG 14D,ROOM 311,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,BALTIMORE,MD 21205. NR 32 TC 26 Z9 26 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 JUL 15 PY 1991 VL 30 IS 2 BP 170 EP 176 DI 10.1016/0006-3223(91)90171-H PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA FY198 UT WOS:A1991FY19800010 PM 1832971 ER PT J AU RAFFELD, M JAFFE, ES AF RAFFELD, M JAFFE, ES TI BCL-1, T(11-14), AND MANTLE CELL-DERIVED LYMPHOMAS SO BLOOD LA English DT Editorial Material ID INTERMEDIATE LYMPHOCYTIC LYMPHOMA; ZONE LYMPHOMA; CHROMOSOME-TRANSLOCATION; CENTROCYTIC LYMPHOMA; MALIGNANT-LYMPHOMAS; MOLECULAR-CLONING; MULTIPLE-MYELOMA; LEUKEMIA; DIFFERENTIATION; LOCUS RP RAFFELD, M (reprint author), NCI,PATHOL LAB,HEMATOPATHOL SECT,BLDG 10,ROOM 2N108,BETHESDA,MD 20892, USA. NR 50 TC 268 Z9 269 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUL 15 PY 1991 VL 78 IS 2 BP 259 EP 263 PG 5 WC Hematology SC Hematology GA FW914 UT WOS:A1991FW91400002 PM 2070063 ER PT J AU BLANCHETTE, VS VORSTMAN, E SHORE, A WANG, E PETRIC, M JETT, BW ALTER, HJ AF BLANCHETTE, VS VORSTMAN, E SHORE, A WANG, E PETRIC, M JETT, BW ALTER, HJ TI HEPATITIS-C INFECTION IN CHILDREN WITH HEMOPHILIA-A AND HEMOPHILIA-B SO BLOOD LA English DT Article ID FACTOR-VIII CONCENTRATE; CHRONIC LIVER-DISEASE; HIGH-RISK; VIRUS; ANTIBODIES; TRANSFUSION C1 NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BETHESDA,MD 20892. HOSP SICK CHILDREN,DEPT MICROBIOL,DIV INFECT DIS,TORONTO M5G 1X8,ONTARIO,CANADA. RP BLANCHETTE, VS (reprint author), HOSP SICK CHILDREN,DEPT PEDIAT,DIV HEMATOL ONCOL,555 UNIV AVE,TORONTO M5G 1X8,ONTARIO,CANADA. NR 26 TC 66 Z9 66 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUL 15 PY 1991 VL 78 IS 2 BP 285 EP 289 PG 5 WC Hematology SC Hematology GA FW914 UT WOS:A1991FW91400006 PM 1712646 ER PT J AU DEGUCHI, Y KEHRL, JH AF DEGUCHI, Y KEHRL, JH TI SELECTIVE EXPRESSION OF 2 HOMEOBOX GENES IN CD34-POSITIVE CELLS FROM HUMAN BONE-MARROW SO BLOOD LA English DT Article ID HEMATOPOIETIC STEM-CELLS; PERIPHERAL-BLOOD; RNA; PROTEINS; IDENTIFICATION; GRANULOCYTES; RECOGNIZES; LEUKEMIAS; SEQUENCE; GROWTH RP DEGUCHI, Y (reprint author), NIAID,IMMUNOREGULAT LAB,BLDG 10,ROOM 11B-13,BETHESDA,MD 20892, USA. NR 30 TC 46 Z9 46 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUL 15 PY 1991 VL 78 IS 2 BP 323 EP 328 PG 6 WC Hematology SC Hematology GA FW914 UT WOS:A1991FW91400011 PM 1712647 ER PT J AU NOVOTNY, WF BROWN, SG MILETICH, JP RADER, DJ BROZE, GJ AF NOVOTNY, WF BROWN, SG MILETICH, JP RADER, DJ BROZE, GJ TI PLASMA ANTIGEN LEVELS OF THE LIPOPROTEIN-ASSOCIATED COAGULATION INHIBITOR IN PATIENT SAMPLES SO BLOOD LA English DT Article ID EXTRINSIC PATHWAY INHIBITOR; DISSEMINATED INTRAVASCULAR COAGULATION; TISSUE FACTOR COMPLEX; HEPATOCELLULAR DISEASE; FACTOR-VII; FACTOR-XA; MECHANISM; RELEASE; CANCER; CELLS C1 JEWISH HOSP ST LOUIS,216 S KINGSHIGHWAY BLVD,ST LOUIS,MO 63110. NHLBI,MOLEC DIS BRANCH,BETHESDA,MD 20892. WASHINGTON UNIV,SCH MED,DIV HEMATOL ONCOL,ST LOUIS,MO 63110. WASHINGTON UNIV,SCH MED,DIV LAB MED,ST LOUIS,MO 63110. FU NHLBI NIH HHS [HL 14147, HL 34462, KO8 HL02515-01] NR 26 TC 252 Z9 256 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUL 15 PY 1991 VL 78 IS 2 BP 387 EP 393 PG 7 WC Hematology SC Hematology GA FW914 UT WOS:A1991FW91400020 PM 2070076 ER PT J AU DEGUCHI, Y MORONEY, JF KEHRL, JH AF DEGUCHI, Y MORONEY, JF KEHRL, JH TI EXPRESSION OF THE HOX-2.3 HOMEOBOX GENE IN HUMAN-LYMPHOCYTES AND LYMPHOID-TISSUES SO BLOOD LA English DT Article ID TRANSCRIPTION FACTOR; CELL PROLIFERATION; RNA; PROTEIN; SEQUENCES; ACID; BETA C1 NIAID,IMMUNOREGULAT LAB,BLDG 10,ROOM 11B-13,BETHESDA,MD 20892. OI Kehrl, John/0000-0002-6526-159X NR 35 TC 33 Z9 33 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD JUL 15 PY 1991 VL 78 IS 2 BP 445 EP 450 PG 6 WC Hematology SC Hematology GA FW914 UT WOS:A1991FW91400027 PM 1676919 ER PT J AU ROBBINS, PF KANTOR, JA SALGALLER, M HAND, PH FERNSTEN, PD SCHLOM, J AF ROBBINS, PF KANTOR, JA SALGALLER, M HAND, PH FERNSTEN, PD SCHLOM, J TI TRANSDUCTION AND EXPRESSION OF THE HUMAN CARCINOEMBRYONIC ANTIGEN GENE IN A MURINE COLON-CARCINOMA CELL-LINE SO CANCER RESEARCH LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; MONOCLONAL-ANTIBODIES; RECOMBINANT INTERLEUKIN-2; ADOPTIVE IMMUNOTHERAPY; VIRUS; IDENTIFICATION; CONSTRUCTION; METASTASES; GENERATION; DEFINITION AB A cell line derived from the mouse colon adenocarcinoma, MC-38, has been transduced with a retroviral construct containing complementary DNA encoding the human carcinoembryonic antigen (CEA) gene. MC-38, which forms tumors in syngeneic C57BL/6 mice, has been extensively studied as a target for active immunotherapy. Individual transduced clones that express high levels of cell surface CEA were isolated, and two clones, termed MC-38-cea1 and MC-38-cea2, were extensively characterized. The levels of CEA found on the surface of these clones were considerably higher than that found in a moderately differentiated human colon carcinoma cell line (WiDr) and were comparable to those found on the human colon carcinoma cell lines GEO and CBS (among the highest CEA-expressing cells reported). Further analysis demonstrated that the CEA expressed in the MC-38-cea1 clone had a similar molecular weight to native CEA (M(r) 180,000), but the MC-38-cea2 cell line expressed a single M(r) 70,000 glycosylated immunoreactive product. Seven anti-CEA monoclonal antibodies were found to react with both clones. The CEA gene present in the MC-38-cea2 clone was partially sequenced and was found to contain a deletion of two of the three repeated domains present in CEA. These results provide a basis for future studies to map immunodominant epitopes of CEA and to develop a syngeneic model system that may aid in the design of reagents and protocols to study active and passive immunotherapy directed against a carcinoma expressing human CEA. RP ROBBINS, PF (reprint author), NCI,TUMOR IMMUNOL & BIOL LAB,BLDG 10,ROOM 5B46,BETHESDA,MD 20892, USA. NR 28 TC 127 Z9 127 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 15 PY 1991 VL 51 IS 14 BP 3657 EP 3662 PG 6 WC Oncology SC Oncology GA FW115 UT WOS:A1991FW11500005 PM 1712245 ER PT J AU FORD, H COONEY, DA AHLUWALIA, GS HAO, Z ROMMEL, ME HICKS, L DOBYNS, KA TOMASZEWSKI, JE JOHNS, DG AF FORD, H COONEY, DA AHLUWALIA, GS HAO, Z ROMMEL, ME HICKS, L DOBYNS, KA TOMASZEWSKI, JE JOHNS, DG TI CELLULAR PHARMACOLOGY OF CYCLOPENTENYL CYTOSINE IN MOLT-4 LYMPHOBLASTS SO CANCER RESEARCH LA English DT Article ID 1-BETA-D-ARABINOFURANOSYLCYTOSINE DIPHOSPHATE CHOLINE; LIQUID-CHROMATOGRAPHY; CELLS; CYTIDINE; LEUKEMIA; 2',3'-DIDEOXYCYTIDINE; TRIPHOSPHATE; NUCLEOTIDES; INHIBITORS; NUCLEOSIDE AB The toxicity, uptake, and metabolism of the oncolytic nucleoside cyclopentenyl cytosine (CPEC) have been examined in the Molt-4 line of human lymphoblasts. This compound is known to be converted to its 5'-triphosphate, which inhibits CTP synthetase and depletes the pools of cytidine nucleotides. In the Molt-4 system, the concentration of drug reducing proliferation by 50% in a 24-h incubation was between 50 and 100 nm. Cytidine, uridine, and nitrobenzylthioinosine almost fully prevented the cytotoxicity of CPEC when introduced shortly before or together with the drug, but only cytidine was effective as an antidote when added 12 h after 200 nm CPEC. Studies of the cellular entry of CPEC revealed that nitrobenzylthioinosine fully blocked this process over a 60-s interval and for as long as 2 h, suggesting that the initial interiorization was mediated by facilitated diffusion. In Molt-4 cells incubated with tritiated CPEC, 9 metabolites could be distinguished: prominent among these was cyclopentenyl uridine (CPEU), the deamination product of CPEC, other major metabolites included the 5'-mono-, di-, and triphosphates of CPEC, and of CPEU, along with two phosphodiesters provisionally identified as CPEC-diphosphate choline and CPEC-diphosphate ethanolamine. When the accumulation of CPEC-5'-triphosphate was measured as a function of concentration of the drug in the medium, the process was found not to be saturable by levels of CPEC up to 1000 nm. In cells incubated with 200 nm drug, CPEC-5'-triphosphate accumulated rapidly and linearly for approximately 4 h, the time for doubling of the concentration being 2 h. After a 16-h incubation with 100 nm CPEC, the concentration of CPEC-5'-triphosphate was 50-fold that of the parent drug in the medium and could be readily monitored spectrophotometrically in high-pressure liquid chromatography effluents without recourse to radiolabeled nucleoside. In 2-h incubations, the concentration of free CPEC required to reduce CTP by 50% was 150 nm; this corresponded to a CPEC-5'-triphosphate level of 750 nm. After washout of extracellular CPEC, CPEC-5'-triphosphate decayed with a half-life that ranged from 9 to 14 h. Twenty-four h after washout of 200 nm CPEC (the concentration of drug reducing proliferation by 80%), cells had not resumed proliferation, and CTP pools were still depressed by 90%. Cytidine, uridine, and nitrobenzylthioinosine all strongly repressed the anabolic phosphorylation of CPEC when added to Molt-4 cells along with the drug. Although crude and partially purified cytidine deaminases from several primate sources could deaminate CPEC, the affinity and velocities of these enzymes were, in general, low with this substrate. Since extracts of Molt-4 cells show low levels of CPEC-deaminating ability, the source of the CPEU metabolites found in these studies remains to be determined. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. RP FORD, H (reprint author), NCI,MED CHEM LAB,BLDG 37,ROOM 5C02,BETHESDA,MD 20892, USA. NR 22 TC 42 Z9 42 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 15 PY 1991 VL 51 IS 14 BP 3733 EP 3740 PG 8 WC Oncology SC Oncology GA FW115 UT WOS:A1991FW11500017 PM 1712247 ER PT J AU PASTAN, I LOVELACE, ET GALLO, MG RUTHERFORD, AV MAGNANI, JL WILLINGHAM, MC AF PASTAN, I LOVELACE, ET GALLO, MG RUTHERFORD, AV MAGNANI, JL WILLINGHAM, MC TI CHARACTERIZATION OF MONOCLONAL-ANTIBODIES B1 AND B3 THAT REACT WITH MUCINOUS ADENOCARCINOMAS SO CANCER RESEARCH LA English DT Article ID BLOOD-GROUP; CELL-LINES; ANTIGENS; EXPRESSION; BINDING; CANCER AB B1 and B3 are two newly isolated monoclonal antibodies that react uniformly with the surface of many mucinous carcinomas of the colon, stomach, and ovary but with a limited number of normal tissues, among which are glands of the stomach, epithelia of the trachea and bladder, differentiated epithelium of the esophagus, and small bowel mucin. They also react uniformly with many human tumor cell lines, including MCF7, MDA-MB-468, and HTB20 (breast), A431 (epidermoid), HT29 (colon), HTB33 (cervical), and DU145 (prostate). Immunoprecipitation experiments indicate that B1 and B3 react with epitopes present on a large number of glycoproteins, ranging in molecular weight from > 200,000 to < 40,000. Using a panel of 37 different carbohydrate residues attached to albumin to form neoglycoproteins, it was found that B1 reacts with Le(y) and H-type 2 and B3 reacts with Le(y), di-Le(x), and tri-Le(x) antigens. Thus, each antibody reacts with a distinct portion of a carbohydrate residue. Because of the limited reactivity of these antibodies with normal tissues, they merit evaluation in the treatment of cancer. C1 BIOCARB INC,GAITHERSBURG,MD 20879. RP PASTAN, I (reprint author), NCI,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 16 TC 148 Z9 150 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 15 PY 1991 VL 51 IS 14 BP 3781 EP 3787 PG 7 WC Oncology SC Oncology GA FW115 UT WOS:A1991FW11500024 PM 1648444 ER PT J AU PFEIFER, AMA JONES, RT BOWDEN, PE MANN, D SPILLARE, E KLEINSZANTO, AJP TRUMP, BF HARRIS, CC AF PFEIFER, AMA JONES, RT BOWDEN, PE MANN, D SPILLARE, E KLEINSZANTO, AJP TRUMP, BF HARRIS, CC TI HUMAN BRONCHIAL EPITHELIAL-CELLS TRANSFORMED BY THE C-RAF-1 AND C-MYC PROTOONCOGENES INDUCE MULTIDIFFERENTIATED CARCINOMAS IN NUDE-MICE - A MODEL FOR LUNG CARCINOGENESIS SO CANCER RESEARCH LA English DT Article ID LONGITUDINAL FOLLOW-UP; CLASS-II ANTIGENS; MIXED SMALL CELL; BIOLOGICAL CHARACTERISTICS; NEOPLASTIC TRANSFORMATION; DIFFERENTIAL EXPRESSION; MONOCLONAL-ANTIBODIES; RETINOBLASTOMA GENE; CANCER; LINES AB We have previously described the neoplastic transformation of immortalized human bronchial epithelial cells (BEAS-2B) by the combination of the c-raf-1 and c-myc protooncogenes and the concomitant induction of neuron-specific enolase mRNA expression (A. Pfeifer et al., Proc. Natl. Acad. Sci. USA, 86. 10075-10079, 1989). In this paper we describe the morphological, biochemical, and immunohistochemical characteristics of the primary c-raf-1/c-myc tumors, xenografts of these tumors, and tumors that originated from cell lines of the primary neoplasm. The tumors were morphologically characterized by the appearance of desmosomes and tonofilaments, microvilli, and dense core granules representing markers of squamous, glandular, and neuroendocrine differentiation, respectively. A total of 11 of 13 tumors were positive by immunohistochemical techniques for neuron-specific enolase, serotonin (nine of 13), and calcitonin (six of 13). Keratins were expressed in 11 of 13 tumors, and while specific keratins (K5, K7, K16/Kl7) decreased, there was an increase of vimentin in the tumor cells. Gastrin-releasing peptide immunoreactivity was detectable in a small number of tumors (five of 13). BEAS-2B cells transfected with the c-raf-1 and c-myc protooncogenes and cell lines established from the primary tumors expressed major histocompatibility Class II antigen which has been found on small cell lung carcinoma cells. The tumors induced by the c-raf-1 and c-myc protooncogenes resemble the multidifferentiated phenotype of small cell lung cancer frequently detected in vivo and present a defined model to study the relation between molecular markers, phenotypical appearance, and response to chemotherapeutic agents and radiation. C1 NCI,BIOL LAB,BETHESDA,MD 20892. UNIV MARYLAND,SCH MED,DEPT PATHOL,BALTIMORE,MD 21201. FOX CHASE CANC INST,DEPT PATHOL,PHILADELPHIA,PA 19111. RP HARRIS, CC (reprint author), NCI,HUMAN CARCINOGENESIS LAB,BLDG 37,ROOM 2C05,BETHESDA,MD 20892, USA. RI Klein-Szanto, Andres/E-6218-2010 NR 70 TC 28 Z9 29 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 15 PY 1991 VL 51 IS 14 BP 3793 EP 3801 PG 9 WC Oncology SC Oncology GA FW115 UT WOS:A1991FW11500026 PM 1712250 ER PT J AU PODGORNIK, R PARSEGIAN, VA AF PODGORNIK, R PARSEGIAN, VA TI AN ELECTROSTATIC-SURFACE STABILITY INTERPRETATION OF THE HYDROPHOBIC FORCE INFERRED TO OCCUR BETWEEN MICA PLATES IN SOLUTIONS OF SOLUBLE SURFACTANTS SO CHEMICAL PHYSICS LA English DT Article ID LONG-RANGE; REPULSIVE INTERACTIONS; HYDRATION FORCES; ELECTROLYTE; ATTRACTION; BILAYERS AB We analyse the data on the "hydrophobic" forces between mica surfaces immersed in solutions of the surfactant CTAB. For the particular regime where these "attractive" forces are not directly seen but are only inferred to exist because of a deviation from expected repulsive forces, we find that there is a strong correlation between the surface electrostatic potential that appears to be the source of electrostatic repulsion and the force at collapse that is used to infer the hypothetical attractive hydrophobic interaction. A simple phenomenological model is presented that takes note of this previously neglected internal correlation. From this model we suggest that, at least in the case of CTAB, the collapse is probably not due to the balance between electrostatic and Van der Waals or "hydrophobic" attractive forces; it is due rather to a shift in the balance between the inter- and intra-surface forces that govern surfactant deposition. Such a view, based on the critical desorption or rearrangement of lipids or other solutes, is consonant with recent reports that the earlier experimental results of Pashley and Israelachvili are not reproduced when one uses purified CTAB. Recognition of solute desorption and adsorption might provide a key to the puzzling data where very long-range net attractive forces are observed but where these forces change with the activity of solutes in the intervening solution. RP PODGORNIK, R (reprint author), NIH,MOLEC FORCES & ASSEMBLY SECT,BETHESDA,MD 20892, USA. RI Podgornik, Rudolf/C-6209-2008 OI Podgornik, Rudolf/0000-0002-3855-4637 NR 19 TC 50 Z9 50 U1 4 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0104 J9 CHEM PHYS JI Chem. Phys. PD JUL 15 PY 1991 VL 154 IS 3 BP 477 EP 483 DI 10.1016/0301-0104(91)85030-K PG 7 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA FW851 UT WOS:A1991FW85100012 ER PT J AU LOUIS, JM MCDONALD, RA NASHED, NT WONDRAK, EM JERINA, DM OROSZLAN, S MORA, PT AF LOUIS, JM MCDONALD, RA NASHED, NT WONDRAK, EM JERINA, DM OROSZLAN, S MORA, PT TI AUTOPROCESSING OF THE HIV-1 PROTEASE USING PURIFIED WILD-TYPE AND MUTATED FUSION PROTEINS EXPRESSED AT HIGH-LEVELS IN ESCHERICHIA-COLI SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article ID HUMAN IMMUNODEFICIENCY VIRUS; RETROVIRAL PROTEASES; CHEMICAL SYNTHESIS; AIDS VIRUS; MATURATION; HOMOLOGY; BINDING; ASSAY AB Various constructs of the human immunodeficiency virus, type 1 (HIV-1) protease containing flanking Pol region sequences were expressed as fusion proteins with the maltose-binding protein of the malE gene of Escherichia coli. The full-length fusion proteins did not exhibit self-processing in E. coli, thereby allowing rapid purification by affinity chromatography on cross-linked amylose columns. Denaturation of the fusion protein in 5 M urea, followed by renaturation, resulted in efficient site-specific autoprocessing to release the 11-kDa protease. Rapid purification involving two column steps gave an HIV-1 protease preparation of > 95% purity (specific activity almost-equal-to 8500 pmol . min-1 . mu-g protease-1) with an overall yield of about 1 mg/l culture. Incubation of an inactive mutant protease fusion protein with the purified wild-type protease resulted in specific trans cleavage and release of the mutant protease. Analysis of products of the HIV-1 fusion proteins containing mutations at either the N- or the C-terminal protease cleavage sites indicated that blocking one of the cleavage sites influences the cleavage at the non-mutated site. Such mutated full-length and truncated protease fusion proteins possess very low levels of proteolytic activity (almost-equal-to 5 pmol . min-1 . mu-g protein-1). C1 NCI, DIV CANC BIOL & DIAG, BETHESDA, MD 20892 USA. NCI, FREDERICK CANC RES & DEV CTR, BASIC RES PROGRAM, ABL, FREDERICK, MD 21701 USA. RP LOUIS, JM (reprint author), NIDDK, BIOORGAN CHEM LAB, BLDG 6, ROOM B1-22, BETHESDA, MD 20892 USA. FU NCI NIH HHS [N01-CO-74101] NR 28 TC 62 Z9 62 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD JUL 15 PY 1991 VL 199 IS 2 BP 361 EP 369 DI 10.1111/j.1432-1033.1991.tb16132.x PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FX288 UT WOS:A1991FX28800016 PM 2070793 ER PT J AU LAKATTA, EG AF LAKATTA, EG TI EXCITATION-CONTRACTION COUPLING IN HEART-FAILURE SO HOSPITAL PRACTICE LA English DT Article AB A central feature of the excitation-contraction cycle - myocardial Ca2+ handling - is altered in humans with cardiomyopathy. Many adaptive changes in excitation-contraction mechanisms observed in aged or hypertensive animals also supervene in the failing human heart. Heart failure may thus emerge when such changes lead to systolic or diastolic insufficiency. RP LAKATTA, EG (reprint author), NIA,GERONTOL RECH INST,CARDIOVASC SCI LAB,BALTIMORE,MD 21224, USA. NR 0 TC 5 Z9 5 U1 0 U2 1 PU MCGRAW HILL HEALTHCARE PUBLICATIONS PI MINNEAPOLIS PA 4530 WEST 77TH ST, MINNEAPOLIS, MN 55435-5000 SN 8750-2836 J9 HOSP PRACT JI Hosp. Pract. PD JUL 15 PY 1991 VL 26 IS 7 BP 85 EP & PG 0 WC Medicine, General & Internal SC General & Internal Medicine GA FX533 UT WOS:A1991FX53300008 PM 1677009 ER PT J AU YAMADA, KM AF YAMADA, KM TI ADHESIVE RECOGNITION SEQUENCES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-BINDING DOMAIN; HUMAN-PLASMA FIBRONECTIN; III CONNECTING SEGMENT; AMINO-ACID-SEQUENCE; GLY-ASP SEQUENCE; LAMININ-A CHAIN; SYNTHETIC PEPTIDES; NEURITE OUTGROWTH; IV COLLAGEN; IDENTIFICATION RP YAMADA, KM (reprint author), NIDR,DEV BIOL LAB,BETHESDA,MD 20892, USA. OI Yamada, Kenneth/0000-0003-1512-6805 NR 68 TC 511 Z9 518 U1 0 U2 16 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 15 PY 1991 VL 266 IS 20 BP 12809 EP 12812 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FX132 UT WOS:A1991FX13200001 PM 2071570 ER PT J AU DHARIWAL, KR BLACK, CDV LEVINE, M AF DHARIWAL, KR BLACK, CDV LEVINE, M TI SEMIDEHYDROASCORBIC ACID AS AN INTERMEDIATE IN NOREPINEPHRINE BIOSYNTHESIS IN CHROMAFFIN GRANULES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DOPAMINE BETA-MONOOXYGENASE; ENZYME-BOUND COPPER; ASCORBIC-ACID; ELECTRON-TRANSFER; REDUCTION; MEMBRANE; CELLS; RESONANCE; OXIDATION; ATP AB We investigated whether semidehydroascorbic acid was an intermediate in norepinephrine synthesis in chromaffin granules and in electron transfer across the chromaffin granule membrane. Semidehydroascorbic acid was measured in intact granules by electron spin resonance. In the presence of intragranular but not extragranular ascorbic acid, semidehydroascorbic acid was formed within granules in direct relationship to dopamine beta-monooxygenase activity. However, semidehydroascorbic acid was not generated when granules were incubated with epinephrine instead of the substrate dopamine, with dopamine beta-monooxygenase inhibitors, without oxygen, and when intragranular ascorbic acid was depleted. Experiments using the impermeant paramagnetic broadening agents [K3[Cr(C2O4)3].3H2O] and Ni(en)3(NO3)2 provided further evidence that semidehydroascorbic acid was generated only within granules. We also investigated semidehydroascorbic acid formation in the presence of intragranular and extragranular ascorbic acid. Under these conditions, semidehydroascorbic acid was formed on both sides of the granule membrane, and formation was coupled to dopamine beta-monooxygenase activity. These data indicate that dopamine beta-monooxygenase is reduced by single electron transfer from intragranular ascorbic acid, that transmembrane electron transfer occurs by single electron transfer, and that transmembrane electron transfer is directly coupled to formation of intragranular semidehydroascorbic acid via dopamine beta-monooxygenase activity. C1 NCI,DIV CANC TREATMENT,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. RP DHARIWAL, KR (reprint author), NIDDKD,CELL BIOL & GENET LAB,BETHESDA,MD 20892, USA. NR 35 TC 25 Z9 26 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 15 PY 1991 VL 266 IS 20 BP 12908 EP 12914 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FX132 UT WOS:A1991FX13200021 PM 1649168 ER PT J AU SMITH, CJ VASTA, V DEGERMAN, E BELFRAGE, P MANGANIELLO, VC AF SMITH, CJ VASTA, V DEGERMAN, E BELFRAGE, P MANGANIELLO, VC TI HORMONE-SENSITIVE CYCLIC GMP-INHIBITED CYCLIC-AMP PHOSPHODIESTERASE IN RAT ADIPOCYTES - REGULATION OF INSULIN-DEPENDENT AND CAMP-DEPENDENT ACTIVATION BY PHOSPHORYLATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE; GLYCOGEN-SYNTHASE; ADIPOSE-TISSUE; FAT-CELLS; LIPOLYSIS; ATP; PURIFICATION; PARTICULATE; STIMULATION; ANALOGS AB In (PO4)-P-32-labeled adipocytes, isoproterenol (ISO) or physiologically relevant concentrations of insulin rapidly increased phosphorylation of a particulate 135-kDa protein which has been identified as a cGMP-inhibited "low K(m)" cAMP phosphodiesterase (CGI-PDE) by several criteria, including selective immunoprecipitation with anti-CGI-PDE IgG (Degerman, E., Smith, C. J., Tornqvist, H., Vasta, V., Belfrage, P., and Manganiello, V. C. (1990) Proc. Natl. Acad. Sci. U. S. A. 87, 533-537). The time courses and concentration dependences for phosphorylation of CGI-PDE by ISO and insulin correlated with CGI-PDE activation in the presence of these agents; effects of ISO were somewhat more rapid than those of insulin. Adenosine deaminase, which metabolizes the adenylate cyclase inhibitor adenosine, also rapidly induced phosphorylation and activation of CGI-PDE. Phenylisopropyladenosine (an adenosine deaminase-resistant adenosine analog) prevented or reversed both adenosine deaminase-stimulated phosphorylation and activation of CGI-PDE (IC50 almost-equal-to 0.2 nM). Incubation of adipocytes with 0.1 nM insulin in the presence of ISO rapidly produced 30-200% greater activation and phosphorylation of CGI-PDE than the expected added effects of insulin and ISO individually; both effects preceded the insulin-induced decreases in protein kinase A activity and inhibition of lipolysis. These and other results indicate that CGI-PDE can be phosphorylated at distinct sites and activated by cAMP-dependent and insulin-dependent serine kinase(s), that the activation state of CGI-PDE reflects its relative phosphorylation state, and that synergistic phosphorylation/activation of CGI-PDE may be important in the antilipolytic action of insulin. C1 UNIV FLORENCE,DEPT BIOCHEM,I-50121 FLORENCE,ITALY. UNIV LUND,DEPT MED & PHYSIOL CHEM 4,S-22100 LUND,SWEDEN. RP SMITH, CJ (reprint author), NHLBI,CELLULAR METAB LAB,BLDG 10,RM 5N-307,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 28 TC 107 Z9 108 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 15 PY 1991 VL 266 IS 20 BP 13385 EP 13390 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FX132 UT WOS:A1991FX13200091 PM 1649189 ER PT J AU GOODMANSNITKOFF, G GOOD, MF BERZOFSKY, JA MANNINO, RJ AF GOODMANSNITKOFF, G GOOD, MF BERZOFSKY, JA MANNINO, RJ TI ROLE OF INTRASTRUCTURAL INTERMOLECULAR HELP IN IMMUNIZATION WITH PEPTIDE-PHOSPHOLIPID COMPLEXES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MALARIA CIRCUMSPOROZOITE PROTEIN; INFLUENZA-VIRUS NEURAMINIDASE; CELL ANTIGENIC SITES; PLASMODIUM-FALCIPARUM; T-CELLS; ANTIBODY-PRODUCTION; IMMUNOLOGICAL RESPONSE; VIRAL HEMAGGLUTININ; VACCINE DEVELOPMENT; SPOROZOITE VACCINE AB The design of effective subunit vaccines requires the inclusion of both B and T cell epitopes. The best mechanism for including both types of epitopes within an Ag is dependent upon how the Ag is processed by the APC for presentation to a responsive Th cell. If it is more efficient to process a single molecule for both helper and primary epitopes, than covalent linkage of B cells and T cell epitopes for intramolecular presentation of help would be recommended. If however, separate peptides containing either B or Th cell epitopes could be included within a single complex for the elicitation of intermolecular/intrastructural help, more antigenically diverse structures could be designed. This paper reports that it is possible to generate intermolecular/intrastructural help within an antigenic peptide-phospholipid (PL) complex. These peptide-PL complexes use well defined epitopes from Plasmodium falciparum as Ag. In addition to generating intrastructural help, we have shown that the Ir to these peptide-PL complexes is controlled by Ir genes and is similar to the Ir to the circumsporozoite protein of this pathogen. C1 NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. NCI,METAB BRANCH,BETHESDA,MD 20892. RP GOODMANSNITKOFF, G (reprint author), UNION UNIV,DEPT MICROBIOL & IMMUNOL,ALBANY,NY 12208, USA. NR 41 TC 13 Z9 13 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 1991 VL 147 IS 2 BP 410 EP 415 PG 6 WC Immunology SC Immunology GA FX131 UT WOS:A1991FX13100005 PM 1712806 ER PT J AU ZACHARCHUK, CM MERCEP, M JUNE, CH WEISSMAN, AM ASHWELL, JD AF ZACHARCHUK, CM MERCEP, M JUNE, CH WEISSMAN, AM ASHWELL, JD TI VARIATIONS IN THYMOCYTE SUSCEPTIBILITY TO CLONAL DELETION DURING ONTOGENY - IMPLICATIONS FOR NEONATAL TOLERANCE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CD3/T-CELL RECEPTOR COMPLEX; REACTIVE V-BETA-6+ CELLS; MONOCLONAL-ANTIBODY; T-CELLS; ANTIGEN PRESENTATION; CYCLOSPORINE-A; ACTIVATION; DEATH; APOPTOSIS; THYMUS AB Activation of immature thymocytes via the TCR results in programmed cell death and clonal deletion. We have examined thymocytes from mice of different ages and observed that, whereas TCR-mediated signaling caused deletion of thymocytes from newborn and 3-week-old mice, it failed to delete thymocytes from mice of 1 week of age. This could not be attributed to differences in cell surface TCR expression, TCR-mediated phosphoinositide hydrolysis or Ca2+ mobilization, or total cellular levels of TCR-zeta- and eta-chains. Moreover, thymocytes of all ages were equally susceptible to corticosteroid- and Ca2+ ionophore-induced programmed cell death. These data are consistent with the notion that fetal and neonatal thymocytes represent a relatively synchronous wave of cells passing through phases in which they are susceptible and then resistant to TCR-induced programmed cell death. They also support the notion that the classical phenomenon of neonatal tolerance is due to clonal deletion and that the inability of allogeneic cells to tolerize mice at 1 week of age is because the thymocytes are refractory to TCR-alpha-beta-mediated clonal deletion. C1 NCI,BIOL RESPONSE MODIFIERS PROGRAM,BLDG 10,ROOM 13N 268,BETHESDA,MD 20892. USN,MED RES INST,IMMUNE CELL BIOL PROGRAM,BETHESDA,MD 20889. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. NR 36 TC 19 Z9 19 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 1991 VL 147 IS 2 BP 460 EP 465 PG 6 WC Immunology SC Immunology GA FX131 UT WOS:A1991FX13100013 PM 1649219 ER PT J AU WHITE, MV IGARASHI, Y LUNDGREN, JD SHELHAMER, J KALINER, M AF WHITE, MV IGARASHI, Y LUNDGREN, JD SHELHAMER, J KALINER, M TI HYDROCORTISONE INHIBITS RAT BASOPHILIC LEUKEMIA-CELL MEDIATOR RELEASE INDUCED BY NEUTROPHIL-DERIVED HISTAMINE RELEASING ACTIVITY AS WELL AS BY ANTI-IGE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; MAST-CELLS; LATE-PHASE; ADENOSINE-RECEPTOR; MONONUCLEAR-CELLS; PHOSPHOLIPASE-C; FACTOR HRF; GLUCOCORTICOIDS; DEXAMETHASONE; ACTIVATION AB We determined the ability of hydrocortisone to inhibit rat basophilic leukemia cell mediator release induced by anti-IgE and by neutrophil-derived histamine-releasing activity (HRA-N). Serotonin release induced by HRA-N and anti-IgE was inhibited by 78 +/- 5 and 70 +/- 4%, respectively (IC50 7.5 x 10(-7) M) by hydrocortisone (10(-5) M). HRA-N does not cause arachidonic acid metabolism, however, anti-IgE induced the generation of PGD2 and leukotriene (LT)C4, and the generation of both mediators was inhibited by 10(-5) M hydrocortisone (IC50 = 4.8 x 10(-7) M, and 3.6 x 10(-9) M, respectively). Inhibition required at least 5 to 6 h of hydrocortisone exposure and was maximal after 22 h. The observed effects of hydrocortisone could be reproduced by human recombinant lipocortin-I (5 X 10(-7) M). Hydrocortisone, 10(-5) M, was a less potent inhibitor of calcium ionophore A23187-mediated serotonin release and PGD2 and LTC4 generation (inhibition of 20 +/- 2, 17 +/- 10, and 37 +/- 10%, respectively). Inasmuch as A23187-induced stimulation is not dependent on receptor coupling, the enhanced ability of hydrocortisone to inhibit IgE- and HRA-N-mediated events as compared with A23187 suggests that one possible site of action of hydrocortisone may be interruption of receptor-effector signals. In the presence of arachidonic acid, hydrocortisone-treated cells released as much LTB4 and PGD2 as control cells, however, serotonin release and LTC4 generation were inhibited 50 and 55%, respectively. Thus, these data suggest that hydrocortisone has three possible sites of action: 1) inhibition of phospholipase A2 activity, 2) inhibition of glutathione-s-transferase, and 3) inhibition of serotonin release by a third mechanism, possibly by interrupting the coupling of receptor and effector systems. C1 NIH,CTR CLIN,DEPT CRIT CARE MED,BETHESDA,MD 20892. RP WHITE, MV (reprint author), NIAID,ALLERG DIS SECT,CLIN INVEST LAB,BLDG 10,ROOM 11C207,BETHESDA,MD 20892, USA. OI Lundgren, Jens/0000-0001-8901-7850 NR 41 TC 11 Z9 11 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 JUL 15 PY 1991 VL 147 IS 2 BP 667 EP 673 PG 7 WC Immunology SC Immunology GA FX131 UT WOS:A1991FX13100043 PM 1712816 ER PT J AU KARP, CL TURCO, SJ SACKS, DL AF KARP, CL TURCO, SJ SACKS, DL TI LIPOPHOSPHOGLYCAN MASKS RECOGNITION OF THE LEISHMANIA-DONOVANI PROMASTIGOTE SURFACE BY HUMAN KALA-AZAR SERUM SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MONOCLONAL-ANTIBODIES; MAJOR PROMASTIGOTES; EXPRESSION; ANTIGENS AB Markedly elevated titers of anti-leishmanial antibodies are a hallmark of kala-azar. We investigated the role played by the lipophosphoglycan (LPG) in determining the reactivity of kala-azar serum with the surface of Leishmania donovani promastigotes. In assays performed with live parasites there was negligible agglutination or fluorescent staining of LPG-bearing promastigotes by kala-azar serum, but strong reactivity in both assays with the use of an L. donovani mutant strain (R2D2) that lacks surface expression of LPG. Immunoprecipitation of lysates of I-125 surface-labeled promastigotes indicated that kala-azar serum has reactivity with several surface proteins common to both the wild-type and R2D2 strains, and no reactivity with surface proteins unique to R2D2. Although direct ELISA showed that kala-azar serum recognizes purified promastigote LPG, inhibition ELISA suggested that such recognition is based solely upon reactivity with the normally unexposed core-anchor region of the molecule. We conclude that the poor reactivity of kala-azar serum with the surface of L. donovani promastigotes is caused by its lack of recognition of the exposed phosphodisaccharide repeat units of LPG, which in turn effectively mask the surface molecules that are recognized by kala-azar serum antibodies. C1 NIAID,IMMUNOL & CELL BIOL SECT,PARASIT DIS LAB,BETHESDA,MD 20892. UNIV KENTUCKY,MED CTR,LEXINGTON,KY 40356. FU NIAID NIH HHS [AI20941] NR 27 TC 27 Z9 27 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 1991 VL 147 IS 2 BP 680 EP 684 PG 5 WC Immunology SC Immunology GA FX131 UT WOS:A1991FX13100045 PM 2071901 ER PT J AU LUSSO, P MALNATI, M DEMARIA, A BALOTTA, C DEROCCO, SE MARKHAM, PD GALLO, RC AF LUSSO, P MALNATI, M DEMARIA, A BALOTTA, C DEROCCO, SE MARKHAM, PD GALLO, RC TI PRODUCTIVE INFECTION OF CD4+ AND CD8+ MATURE HUMAN T-CELL POPULATIONS AND CLONES BY HUMAN HERPESVIRUS-6 - TRANSCRIPTIONAL DOWN-REGULATION OF CD3 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID VIRUS HUMAN HERPESVIRUS-6; ANTIGEN RECEPTOR; EXPRESSION; COMPLEX; IDENTIFICATION; LYMPHOCYTES; SEQUENCES; LYMPHOMA; HBLV; CD3-EPSILON AB The susceptibility to infection by human herpes-virus 6 (HHV-6) of mature human T lymphocytes belonging to the two major subpopulations (i.e., CD3+ CD4+ CD8- and CD3+ CD4- CD8+) was investigated by using CD4+ or CD8+ T cell populations and clones derived from normal adult peripheral blood. Productive HHV-6 infection was observed in both CD4+ and CD8+ T cells. By days 2 to 6 after infection, increasing numbers of cells exhibited characteristic morphologic alterations, becoming enlarged, uniformly rounded and refractile as a consequence of the virus-induced cytopathic effect. During the course of HHV-6 infection, analysis of the surface membrane phenotype of the T cell populations and clones revealed a progressive decline in the expression of the CD3/TCR complex, whereas other T cell-associated markers (e.g., CD2) were unaffected. Northern blot analysis of mRNA extracted from HHV-6-infected T cells demonstrated a dramatic loss of the specific messages for the gamma-, delta-, and epsilon-chains of CD3. Infection by HHV-6, but not by HSV-1 or human CMV, elicited CD3/TCR down-regulation also in the neoplastic T cell line Jurkat. The down-regulation of CD3/TCR was dependent upon live virus infection, because previous inactivation of HHV-6 by heat (56-degrees-C for 1 h) or UV light (16 J/m2) totally abrogated the effect. Expression of the immediate early or early genes of HHV-6 was not sufficient to induce CD3/TCR modulation, as indicated by studies with the viral DNA polymerase inhibitor phosphonoformic acid. The observation that both major subsets of mature TCR-alpha-beta+ T lymphocytes are susceptible to HHV-6 infection indicates that this virus may have a broad spectrum of activity on the immune system. The transcriptional down-regulation of the CD3/TCR complex, by affecting a critical T cell recognition function, could be relevant to HHV-6 pathogenesis. C1 ADV BIOSCI LABS,DEPT CELL BIOL,KENSINGTON,MD 20895. NIAID,IMMUNE REGULAT LAB,BETHESDA,MD 20892. RP LUSSO, P (reprint author), NCI,TUMOR CELL BIOL LAB,BLDG 37,ROOM 6B10,BETHESDA,MD 20892, USA. RI de maria, andrea/F-7116-2016 OI de maria, andrea/0000-0001-5782-333X NR 39 TC 90 Z9 91 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 JUL 15 PY 1991 VL 147 IS 2 BP 685 EP 691 PG 7 WC Immunology SC Immunology GA FX131 UT WOS:A1991FX13100046 PM 1677024 ER PT J AU TAFFS, RE REDEGELD, FA SITKOVSKY, MV AF TAFFS, RE REDEGELD, FA SITKOVSKY, MV TI MODULATION OF CYTOLYTIC LYMPHOCYTE-T FUNCTIONS BY AN INHIBITOR OF SERINE THREONINE PHOSPHATASE, OKADAIC ACID - ENHANCEMENT OF CYTOLYTIC LYMPHOCYTE-T MEDIATED CYTOTOXICITY SO JOURNAL OF IMMUNOLOGY LA English DT Article ID DEPENDENT PROTEIN-KINASE; CELL ANTIGEN RECEPTOR; TUMOR-PROMOTER; EFFECTOR CELLS; TARGET-CELLS; ACTIVATION; IDENTIFICATION; ANTIBODY; LYSIS; EXPRESSION AB A specific and potent inhibitor of protein phosphatases 1 and 2A, okadaic acid (OA), and its inactive analog, tetramethyl ether (OA-TME), were tested in the cytotoxicity and granule exocytosis assays of CTL activation. At low concentrations OA enhanced. whereas at higher concentrations OA inhibited, CTL responses. The Ag-specific and retargeted cytotoxicity, granule exocytosis induced by target cell (TC), anti-TCR mAb, or PMA and A23187, and conjugate formation with TC were inhibited by pretreatment of CTL with OA as expected if protein phosphatases and protein dephosphorylation were indeed involved in the TCR-mediated signal transduction and effector responses of CTL. Cytotoxicity and granule exocytosis were unaffected by pretreatment of CTL with OA-TME. The inhibitory effect of OA on the exocytic response of CTL induced by TC and anti-TCR mAb can be dissociated from the inhibition of the response to PMA and A23187, suggesting the involvement of a serine and/or threonine protein phosphatase in the early events of transmembrane signaling. At lower concentrations, OA, but not OA-TME, was able to enhance the Ag-specific cytotoxicity and TC-induced exocytosis from CTL clones. The enhancement of these TCR-mediated responses of CTL was observed only if the activation was induced by the Ag on the TC surface, because OA did not enhance either the anti-TCR mAb-induced exocytosis of granules from the CTL clone or lysis of the Ag-nonbearing TC by CTL in a retargeting assay. The biphasic character of the effects of OA on CTL-TC interactions suggests the existence of at least two functionally distinct phosphatases in CTL. The ability of OA to enhance the Ag-specific response is unique and indicates the presence of an inhibitory phosphoprotein phosphatase that should be considered as a participant in the down-regulation of the cell-cell interactions between CTL and TC. The inhibitory effects of OA on both TC-induced and anti-TCR mAb-triggered CTL responses at higher concentrations point to the importance of yet another phosphatase in the CTL-TC interactions and in the TCR-mediated transmembrane signaling. The use of OA may help to decipher the details of biochemical changes involved in T lymphocyte effector functions. C1 NIAID,IMMUNOL LAB,BLDG 10,ROOM 11N311,BETHESDA,MD 20892. RI Redegeld, Frank/O-6534-2016 OI Redegeld, Frank/0000-0001-8830-7960 NR 40 TC 20 Z9 20 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 1991 VL 147 IS 2 BP 722 EP 728 PG 7 WC Immunology SC Immunology GA FX131 UT WOS:A1991FX13100051 PM 1649222 ER PT J AU LEIKIN, S KORNYSHEV, AA AF LEIKIN, S KORNYSHEV, AA TI MEAN-FIELD THEORY OF DEHYDRATION TRANSITIONS SO PHYSICAL REVIEW A LA English DT Article ID PHOSPHOLIPID-BILAYER MEMBRANES; HYDRATION FORCES; ELECTROSTATIC THEORY; ORIENTABLE DIPOLES; PHASE-TRANSITIONS; NEUTRAL SURFACES; WATER; MODEL; MOBILE; INTERFACE AB It has been shown in our previous paper [Phys. Rev. A 40, 6431 (1989)] that repulsive hydration forces between parallel hydrophilic surfaces separated by a thin water film are determined by the lateral distribution of solvated surface groups. This theory is now extended to include correlations in fluctuations of the solvated group distribution between the opposing surfaces. The solution is obtained in a treatment formally analogous to the "spherical model" for Ising systems. It is shown that the correlations between the opposing surfaces give an attractive contribution to the hydration forces. Conditions governing the crossover from net repulsion to net attraction are studied. Hydration attraction appears and increases gradually with a decrease in temperature below a critical value or with variation of other system parameters. Full transition to the net attractive force leads to formation of a dehydrated contact between the surfaces. The results are applied to describe dehydration transitions in multilayer lipid systems. C1 AN FRUMKIN ELECTROCHEM INST,MOSCOW 117071,USSR. RP LEIKIN, S (reprint author), NIDDKD,DIV COMP RES & TECHNOL,PHYS SCI LAB,BIOCHEM & METAB LAB,BLDG 10,ROOM 9B-07,BETHESDA,MD 20892, USA. RI Leikin, Sergey/A-5518-2008; Kornyshev, Alexei/C-3404-2008 OI Leikin, Sergey/0000-0001-7095-0739; NR 43 TC 26 Z9 26 U1 0 U2 6 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1050-2947 J9 PHYS REV A JI Phys. Rev. A PD JUL 15 PY 1991 VL 44 IS 2 BP 1156 EP 1168 DI 10.1103/PhysRevA.44.1156 PG 13 WC Optics; Physics, Atomic, Molecular & Chemical SC Optics; Physics GA FY463 UT WOS:A1991FY46300044 ER PT J AU TOKUYAMA, T TSUJITA, T SHIMADA, A GARRAFFO, HM SPANDE, TF DALY, JW AF TOKUYAMA, T TSUJITA, T SHIMADA, A GARRAFFO, HM SPANDE, TF DALY, JW TI ALKALOIDS FROM DENDROBATID POISON FROGS - FURTHER CIS-DECAHYDROQUINOLINES AND 8-METHYLINDOLIZIDINES SO TETRAHEDRON LA English DT Article ID SKIN ALKALOIDS; HISTRIONICOTOXINS; CLASSIFICATION; INDOLIZIDINE; SPECTRA; 167B AB Skin extracts from one population of the poison frog Dendrobates auratus contain a variety of alkaloids, including 2,5-disubstituted-cis-decahydroquinolines and 5-substituted-8-methylindolizidines. Three of the major alkaloids are cis-decahydroquinolines, whose structures based on NMR spectral analyses are 2,5-diallyl-cis-decahydroquinoline (cis-219A), 2-allyl-5(pent-2-en-4-ynyl)-cis-decahydroquinoline (cis-243A) and 5-methyl-2-propyl-cis-decahydroquinoline (cis-195A); the last is identical with ''pumiliotoxin C'' previously isolated from the poison frog Dendrobates pumilio. Alkaloids cis-219A and cis-243A differ from cis-195A in configuration at the C-2 position. Another poison frog, Dendrobates histrionicus, was previously shown to produce nearly exclusively trans-decahydroquinoline isomers of 219A and 243A. NMR analyses indicate that the structure of a minor alkaloid from Dendrobates auratus is 5-(pent-2-en-4-ynyl)-8-methylindolizidine (203A). Two additional 8-methylindolizidines isolated from Dendrobates pumilio are 5-(hept-4,6-dienyl)-8-methylindolizidine (233D) and 5-(hept-6-hydroxy-4-enyl)-8-methylindolizidine (251B). FTIR spectral analyses distinguish cis- and trans-decahydroquinolines and provide evidence for configurations of indolizidines. C1 NIDDKD,BETHESDA,MD 20892. OSAKA CITY UNIV,FAC SCI,OSAKA 558,JAPAN. NR 16 TC 54 Z9 54 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0040-4020 J9 TETRAHEDRON JI Tetrahedron PD JUL 15 PY 1991 VL 47 IS 29 BP 5401 EP 5414 DI 10.1016/S0040-4020(01)80974-1 PG 14 WC Chemistry, Organic SC Chemistry GA FW673 UT WOS:A1991FW67300005 ER PT J AU TOKUYAMA, T TSUJITA, T GARRAFFO, HM SPANDE, TF DALY, JW AF TOKUYAMA, T TSUJITA, T GARRAFFO, HM SPANDE, TF DALY, JW TI ALKALOIDS FROM DENDROBATID POISON FROGS - FURTHER PUMILIOTOXINS AND ALLOPUMILIOTOXINS AND A REASSIGNMENT OF THE KETO FUNCTION IN PUMILIOTOXIN-307F SO TETRAHEDRON LA English DT Article ID INDOLIZIDINE AB Skin extracts from the Panamanian poison-frog Dendrobates pumilio have afforded further trace alkaloids of the pumiliotoxin-A class (6-alkylidene-8-hydroxy-8-methylindolizidines) and an allopumiliotoxin subclass (7-hydroxy-PTX-As). Structures for pumiliotoxins 209F and 225F and allopumiliotoxin 225E, all with four carbon 6-alkylidene side chains, for allopumiliotoxins 309D, 325A' and 325A'', all with ten carbon 6-alkylidene side chains, and a reassignment of the position of the keto function in the ten carbon 6-alkylidene side chain of pumiliotoxin 307F are presented. Carbon-13 magnetic resonance assignments for these and the 15-O-methyl ether artefacts of pumiliotoxin 307A and allopumiliotoxin 323B, are tabulated. C1 NIDDKD,BETHESDA,MD 20892. OSAKA CITY UNIV,FAC SCI,OSAKA 558,JAPAN. NR 9 TC 10 Z9 10 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0040-4020 J9 TETRAHEDRON JI Tetrahedron PD JUL 15 PY 1991 VL 47 IS 29 BP 5415 EP 5424 DI 10.1016/S0040-4020(01)80975-3 PG 10 WC Chemistry, Organic SC Chemistry GA FW673 UT WOS:A1991FW67300006 ER PT J AU ROSNER, MH VIGANO, MA RIGBY, PWJ ARNHEITER, H STAUDT, LM AF ROSNER, MH VIGANO, MA RIGBY, PWJ ARNHEITER, H STAUDT, LM TI OCT-3 AND THE BEGINNING OF MAMMALIAN DEVELOPMENT SO SCIENCE LA English DT Editorial Material ID EMBRYONAL CARCINOMA-CELLS; DNA-BINDING DOMAIN; TRANSCRIPTION FACTOR; POU-DOMAIN; IMMUNOGLOBULIN GENES; NUCLEAR FACTOR; STEM-CELLS; MOUSE EMBRYOGENESIS; PROTEIN-BINDING; LEUKEMIA-VIRUS C1 NCI,METAB BRANCH,BETHESDA,MD 20892. NATL INST MED RES,EUKARYOT MOLEC GENET LAB,LONDON NW7 1AA,ENGLAND. NINCDS,VIRAL & MOLEC PATHOGENESIS LAB,BETHESDA,MD 20892. GEORGETOWN UNIV,SCH MED,DEPT PATHOL,WASHINGTON,DC 20057. NR 48 TC 10 Z9 10 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUL 12 PY 1991 VL 253 IS 5016 BP 144 EP 145 DI 10.1126/science.1853199 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FW160 UT WOS:A1991FW16000023 PM 1853199 ER PT J AU BIRD, GS ROSSIER, MF HUGHES, AR SHEARS, SB ARMSTRONG, DL PUTNEY, JW AF BIRD, GS ROSSIER, MF HUGHES, AR SHEARS, SB ARMSTRONG, DL PUTNEY, JW TI ACTIVATION OF CA2+ ENTRY INTO ACINAR-CELLS BY A NON-PHOSPHORYLATABLE INOSITOL TRISPHOSPHATE SO NATURE LA English DT Article ID RAT-LIVER CELLS; 1,4,5-TRISPHOSPHATE 3-KINASE; INTRACELLULAR CA-2+; CALCIUM RELEASE; 1,3,4,5-TETRAKISPHOSPHATE; PHOSPHATES; RECEPTOR; MEMBRANE; THAPSIGARGIN; PURIFICATION AB IN many cell types, receptor activation of phosphoinositidase C results in an initial release of intracellular Ca2+ stores followed by sustained Ca2+ entry across the plasma membrane. Inositol 1,4,5-trisphosphate is the mediator of the initial Ca2+ release 1, although its role in the mechanism underlying Ca2+ entry remains controversial 2-6. We have now used two techniques to introduce inositol phosphates into mouse lacrimal acinar cells and measure their effects on Ca2+ entry: microinjection into cells loaded with Fura-2, a fluorescent dye which allows the measurement of intracellular free calcium concentration by microspectrofluorimetry, and perfusion of patch clamp pipettes in the whole-cell configuration while monitoring the activity of Ca2+-activated K+ channels as an indicator of intracellular Ca2+. We report here that inositol 1,4,5-trisphosphate serves as a signal that is both necessary and sufficient for receptor activation of Ca2+ entry across the plasma membrane in these cells. RP BIRD, GS (reprint author), NIEHS,CELLULAR & MOLEC PHARMACOL LAB,CALCIUM REGULAT SECT,RES TRIANGLE PK,NC 27709, USA. NR 32 TC 169 Z9 170 U1 0 U2 2 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD JUL 11 PY 1991 VL 352 IS 6331 BP 162 EP 165 DI 10.1038/352162a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FW097 UT WOS:A1991FW09700059 PM 1648669 ER PT J AU MOFENSON, LM AF MOFENSON, LM TI INTRAVENOUS IMMUNE GLOBULIN FOR THE PREVENTION OF BACTERIAL-INFECTIONS IN CHILDREN WITH SYMPTOMATIC HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID LACTATE-DEHYDROGENASE LEVELS; B-CELL LYMPHOPROLIFERATION; DEFICIENCY SYNDROME AIDS; GAMMA-GLOBULIN; IMMUNOGLOBULIN THERAPY; POSSIBLE INDICATOR; DISEASE-ACTIVITY; ENZYME LEVELS; COMPLEX; EFFICACY AB Background. Serious recurrent bacterial infections are a major cause of morbidity and mortality in children infected with the human immunodeficiency virus (HIV). Because intravenous immune globulin has been shown to prevent bacterial infection in patients with primary immunodeficiency and in uncontrolled studies of HIV-infected children, we undertook a multicenter study of its safety and efficacy in children with symptomatic HIV infection. Methods. In a double-blind trial, 372 HIV-infected children (mean age, 40 months) with clinical or immunologic evidence of HIV disease were randomly assigned to receive either intravenous immune globulin (400 mg per kilogram of body weight) or placebo (0.1 percent albumin) every 28 days. The children were stratified into two groups according to CD4+ lymphocyte count at entry into the study and the clinical classification of the Centers for Disease Control. The median length of follow-up was 17 months. Results. For children in either group with CD4+ counts greater-than-or-equal-to 0.2 x 10(9) per liter (greater-than-or-equal-to 200 per cubic millimeter) at entry, treatment with intravenous immune globulin significantly increased the time free from serious infection; estimated infection-free rates after 24 months were 67 percent for children receiving immune globulin as compared with 48 percent for those receiving placebo (P = 0.01). In addition, immune globulin was associated with an overall reduction in the number of both serious and minor bacterial infections (relative risk, 0.68; P = 0.01) and in the number of hospitalizations tor acute care (relative risk, 0.65; P = 0.03). No such benefits were seen for children with CD4+ counts below 0.2 x 10(9) per liter at entry. For group 1 overall, there was a trend toward a difference in serious bacterial infection between immune globulin and placebo (24-month infection-free survival, 31 percent for intravenous immune globulin vs. 25 percent for placebo; P = 0.10). For group 2, the estimates of survival without serious infection were 73 percent with intravenous immune globulin as compared with 53 percent with placebo (P = 0.04). There was no effect of treatment on mortality for any group or CD4+ count at entry. Adverse reactions, noted for less than 1 percent of infusions, were minor. Conclusions. In symptomatic HIV-infected children the prophylactic use of intravenous immune globulin is safe, and it significantly increases the time free from serious bacterial infections for those entering treatment with CD4+ lymphocyte counts greater-than-or-equal-to 0.2 x 10(9) per liter. RP MOFENSON, LM (reprint author), NICHHD,PEDIAT ADOLESCENT & MATERNAL AIDS BRANCH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. OI Mofenson, Lynne/0000-0002-2818-9808 NR 36 TC 89 Z9 89 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 11 PY 1991 VL 325 IS 2 BP 73 EP 80 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA FV522 UT WOS:A1991FV52200001 ER PT J AU FARCI, P ALTER, HJ WONG, D MILLER, RH SHIH, JW JETT, B PURCELL, RH AF FARCI, P ALTER, HJ WONG, D MILLER, RH SHIH, JW JETT, B PURCELL, RH TI A LONG-TERM STUDY OF HEPATITIS-C VIRUS-REPLICATION IN NON-A, NON-B HEPATITIS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ANTIBODIES; GENOME; BLOOD; CDNA; CHIMPANZEES; SEQUENCE; ANTIGEN; RNA; PCR AB Background. Although antibodies to the hepatitis C virus (HCV) are known to be associated with non-A, non-B hepatitis, little is known about the pattern of HCV replication, its relation to antibody levels, and the clinical course of non-A, non-B hepatitis. Methods. We measured HCV RNA in serial serum samples from five patients with post-transfusion non-A, non-B hepatitis who were followed for 1 0 to 14 years after transfusion. We also studied four chimpanzees that were experimentally infected with serum from four of these patients. Serum HCV RNA was detected by a "nested" polymerase-chain-reaction (PCR) assay that used two sets of primers derived from the third (NS3) and fourth (NS4) nonstructural gene regions of the HCV genome. Results. HCV sequences were detected by PCR in only two of the five patients and two of the four chimpanzees with the set of primers corresponding to the NS3 region, but in all five patients (and in all four chimpanzees) with the primers from the NS4 region. Serum HCV RNA was first detected within three weeks of transfusion in all five patients and within one week in three patients. The viremia lasted less than 4 months in the patient (and two chimpanzees) with acute, self-limited hepatitis, whereas it persisted for 10 to 14 years in the four patients (and for 1 and 3 years in two chimpanzees) with chronic non-A, non-B hepatitis. Antibodies to HCV were first detected at week 12 to 14; they disappeared after nine years in the patient with self-limited disease and became borderline after five years in one of the patients with chronic disease. Conclusions. During the early phase of primary HCV infection, there is a period of several months of seronegativity during which HCV RNA is the only diagnostic marker of infection. The disappearance of HCV RNA from serum appears to correlate with the resolution of non-A, non-B hepatitis, whereas viremia persists in patients whose disease progresses to chronic hepatitis. In contrast, antibody levels do not necessarily remain elevated in patients with chronic disease. C1 NIH,BIOMED ENGN & INSTRUMENTAT BRANCH,WARREN G MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BETHESDA,MD 20892. RP FARCI, P (reprint author), NIAID,INFECT DIS LAB,HEPATITIS VIRUSES SECT,BLDG 7,RM 202,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 25 TC 479 Z9 485 U1 1 U2 5 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 11 PY 1991 VL 325 IS 2 BP 98 EP 104 DI 10.1056/NEJM199107113250205 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA FV522 UT WOS:A1991FV52200005 PM 1646962 ER PT J AU HARDING, F AF HARDING, F TI PAYBACK REQUIREMENTS OF NATIONAL RESEARCH SERVICE AWARD - REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP HARDING, F (reprint author), NHLBI,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 11 PY 1991 VL 325 IS 2 BP 135 EP 136 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA FV522 UT WOS:A1991FV52200025 ER PT J AU WINNING, RS SHEA, LJ MARCUS, SJ SARGENT, TD AF WINNING, RS SHEA, LJ MARCUS, SJ SARGENT, TD TI DEVELOPMENTAL REGULATION OF TRANSCRIPTION FACTOR AP-2 DURING XENOPUS-LAEVIS EMBRYOGENESIS SO NUCLEIC ACIDS RESEARCH LA English DT Article ID RETINOIC ACID; GENE-EXPRESSION; MIDBLASTULA TRANSITION; NERVOUS-SYSTEM; INDUCTION; PROMOTER; EMBRYOS; INVITRO; ELEMENT; HEAT AB We have isolated a cDNA clone encoding the Xenopus homologue of the transcription factor AP-2 (XAP-2). The predicted amino acid sequence derived from the Xenopus cDNA shows very strong conservation with the amino acid sequence of human AP-2, suggesting that this protein is evolutionarily conserved, at least among vertebrates. This is further substantiated by the demonstration that an in vitro translation product of XAP-2 cDNA bound specifically to an AP-2 binding site from the human MT-ll(A) gene. Northern blot analysis of Xenopus embryo RNA revealed the existence of three major XAP-2 mRNA species that were only detectable after the midblastula transition (when embryonic transcription is activated), with peak accumulation of the transcripts occurring during gastrulation. Therefore, in contrast to other Xenopus transcription factors, XAP-2 is not maternally derived but arises exclusively from zygotic transcription. Unlike the situation in cultured human teratocarcinoma (NT2) cells, retinoic acid treatment did not induce XAP-2 mRNA in Xenopus embryos, even though the treatment had a pronounced morphogenetic effect on the embryos. Our results suggest that XAP-2 may play a distinctive role during Xenopus embryogenesis. C1 NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892. NR 37 TC 69 Z9 69 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL 11 PY 1991 VL 19 IS 13 BP 3709 EP 3714 DI 10.1093/nar/19.13.3709 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FX358 UT WOS:A1991FX35800033 PM 1852613 ER PT J AU NILLER, HH HENNIGHAUSEN, L AF NILLER, HH HENNIGHAUSEN, L TI FORMATION OF SEVERAL SPECIFIC NUCLEOPROTEIN COMPLEXES ON THE HUMAN CYTOMEGALOVIRUS IMMEDIATE EARLY ENHANCER SO NUCLEIC ACIDS RESEARCH LA English DT Article ID NF-KAPPA-B; PROMOTER-REGULATORY REGION; AMP-RESPONSE ELEMENTS; DNA-BINDING PROTEINS; EARLY GENE; CYCLIC-AMP; TRANSCRIPTION FACTORS; VIRUS ENHANCER; REL ONCOGENE; STIMULATION AB The major immediate early enhancer of the human cytomegalovirus (HCMV) is composed of unique and repeated sequence motifs, which interact with different nuclear proteins, thus forming a large nucleoprotein complex. Using DNAase I protection analysis, we determined at the nucleotide level the interactions of B cell and HeLa cell nuclear proteins with transcription factor binding sites in the enhancer/promoter. In agreement with in vivo activity, protein binding to the 18 bp repeats (aleph B element) was found predominantly with B cell extract. Competition for proteins with individual transcription factor binding sites allowed us to define boundaries of closely spaced and overlapping binding sites, and to group binding proteins into several classes. Using gel mobility shift assays, we could show that proteins, which bind to the 17 bp repeat, also bind to a classical NF1 site. In addition, several novel binding sites were identified. The presence of overlapping binding sites, together with differences in the occupation of the 18 bp repeats in the two cell types, suggest that the HCMV major IE enhancer has several possibilities of forming nucleoprotein complexes. C1 NIDDKD,BIOCHEM & METAB LAB,BLDG 10,RM 9N113,BETHESDA,MD 20892. NR 32 TC 31 Z9 32 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL 11 PY 1991 VL 19 IS 13 BP 3715 EP 3721 DI 10.1093/nar/19.13.3715 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FX358 UT WOS:A1991FX35800034 PM 1649457 ER PT J AU DEGUCHI, Y KEHRL, JH AF DEGUCHI, Y KEHRL, JH TI NUCLEOTIDE-SEQUENCE OF A NOVEL DIVERGED HUMAN HOMEOBOX GENE ENCODES A DNA-BINDING PROTEIN SO NUCLEIC ACIDS RESEARCH LA English DT Note RP DEGUCHI, Y (reprint author), NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892, USA. NR 5 TC 10 Z9 10 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL 11 PY 1991 VL 19 IS 13 BP 3742 EP 3742 DI 10.1093/nar/19.13.3742 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FX358 UT WOS:A1991FX35800038 PM 1677181 ER PT J AU POLYMEROPOULOS, MH XIAO, H RATH, DS MERRIL, CR AF POLYMEROPOULOS, MH XIAO, H RATH, DS MERRIL, CR TI TETRANUCLEOTIDE REPEAT POLYMORPHISM AT THE HUMAN TYROSINE-HYDROXYLASE GENE (TH) SO NUCLEIC ACIDS RESEARCH LA English DT Note RP POLYMEROPOULOS, MH (reprint author), ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,ROOM 131,2700 MARTIN LUTHER KING AVE,WASHINGTON,DC 20032, USA. NR 4 TC 241 Z9 246 U1 1 U2 7 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL 11 PY 1991 VL 19 IS 13 BP 3753 EP 3753 DI 10.1093/nar/19.13.3753 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FX358 UT WOS:A1991FX35800049 PM 1852620 ER PT J AU POLYMEROPOULOS, MH XIAO, H RATH, DS MERRIL, CR AF POLYMEROPOULOS, MH XIAO, H RATH, DS MERRIL, CR TI DINUCLEOTIDE REPEAT POLYMORPHISM AT THE HUMAN NONHISTONE CHROMOSOMAL PROTEIN HMG14 GENE SO NUCLEIC ACIDS RESEARCH LA English DT Note RP POLYMEROPOULOS, MH (reprint author), ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,ROOM 131,2700 MARTIN LUTHER KING AVE,WASHINGTON,DC 20032, USA. NR 4 TC 241 Z9 246 U1 1 U2 7 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL 11 PY 1991 VL 19 IS 13 BP 3753 EP 3753 DI 10.1093/nar/19.13.3753 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FX358 UT WOS:A1991FX35800050 PM 1852620 ER PT J AU LAUER, MS ANDERSON, KM KANNEL, WB LEVY, D AF LAUER, MS ANDERSON, KM KANNEL, WB LEVY, D TI THE IMPACT OF OBESITY ON LEFT-VENTRICULAR MASS AND GEOMETRY - THE FRAMINGHAM-HEART-STUDY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID AORTIC REGURGITATION; GLUCOSE-INTOLERANCE; BLOOD-PRESSURE; BODY BUILD; HYPERTROPHY; HYPERTENSION; DISEASE; CARDIOMYOPATHY; REDUCTION; CRITERIA AB Objective.- To determine the relationship of varying degrees of obesity with left ventricular mass and geometry. Design.- Survey. Setting.- Population-based epidemiologic study. Participants and Methods.- M-mode echocardiograms, which were adequate for estimation of left ventricular mass, were obtained in 3922 healthy participants of the Framingham Heart Study Measured height and weight were used to calculate body-mass index, a measure of obesity. Results.- Body-mass index was strongly correlated with left ventricular mass. After adjusting for age and blood pressure, body-mass index remained a strong independent predictor of left ventricular mass, left ventricular wall thickness, and left ventricular internal dimension (P < .01 for all). Body-mass index was associated with prevalence of echocardiographic left ventricular hypertrophy, particularly in subjects with a body-mass index exceeding 30 kg/m2. Conclusions.- Obesity is significantly correlated with left ventricular mass, even after controlling for age and blood pressure. The increase in left ventricular mass associated with increasing adiposity reflects increases in both left ventricular wall thickness and left ventricular internal dimension. C1 BETH ISRAEL HOSP,CHARLES A DANA RES INST,BOSTON,MA 02215. BOSTON UNIV,SCH MED,DIV EPIDEMIOL & PREVENT MED,BOSTON,MA 02118. HARVARD UNIV,SCH MED,BOSTON,MA 02115. BETH ISRAEL HOSP,DEPT MED,DIV CLIN EPIDEMIOL,BOSTON,MA 02215. HARVARD UNIV,BETH ISRAEL HOSP,DEPT MED,DIV CARDIOL,THORNDIKE LAB,BOSTON,MA 02215. RP LAUER, MS (reprint author), NHLBI,FRAMINGHAM HEART STUDY,5 THURBER ST,FRAMINGHAM,MA 02215, USA. RI Lauer, Michael/L-9656-2013 OI Lauer, Michael/0000-0002-9217-8177 FU NHLBI NIH HHS [HL07374, N01-HC-38038] NR 37 TC 336 Z9 351 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 10 PY 1991 VL 266 IS 2 BP 231 EP 236 DI 10.1001/jama.266.2.231 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA FU896 UT WOS:A1991FU89600031 PM 1829117 ER PT J AU WILBER, JF AF WILBER, JF TI NEUROPEPTIDES, APPETITE REGULATION, AND HUMAN OBESITY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID BODY-WEIGHT; ENERGY-EXPENDITURE; INSULIN; TWINS C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892. UNIV MARYLAND,SCH MED,DEPT MED,DIV ENDOCRINOL & METAB,BALTIMORE,MD 21201. FU NIDDK NIH HHS [DK37378] NR 16 TC 14 Z9 14 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 10 PY 1991 VL 266 IS 2 BP 257 EP 259 DI 10.1001/jama.266.2.257 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA FU896 UT WOS:A1991FU89600036 PM 2056628 ER PT J AU HOLBROOK, PG PANNELL, LK DALY, JW AF HOLBROOK, PG PANNELL, LK DALY, JW TI PHOSPHOLIPASE D-CATALYZED HYDROLYSIS OF PHOSPHATIDYLCHOLINE OCCURS WITH P-O BOND-CLEAVAGE SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Article DE PHOSPHOLIPASE D; PHOSPHODIESTER BOND; PHOSPHATIDYLCHOLINE; PHOSPHATIDIC ACID; SIGNAL-TRANSDUCTION; [O-18]OXYGEN LABELING ID PROTEIN-KINASE-C; DIACYLGLYCEROL FORMATION; PHOSPHATIDIC-ACID; D ACTIVATION; CELLS; PHOSPHATIDYLETHANOL; STIMULATION; BREAKDOWN; PATHWAY; PHOSPHATIDYLINOSITOL AB Mammalian phospholipase D has been implicated in signal-transduction mechanisms, most recently in association with stimuli that enhance phosphatidylcholine (PC) turnover. It was previously unknown whether hydrolysis of PC by phospholipase D proceeds via P-O or C-O bond cleavage. Commercially available phospholipase D isolated from Streptomyces chromofuscus was used to hydrolyse distearoyl phosphatidylcholine (PC) in a detergent-containing buffer consisting of 90% O-18-water. The product of hydrolysis, phosphatidic acid (PA), was purified by thin-layer chromatography and analyzed using californium-252 plasma desorption mass spectrometry. An increase of two mass units was observed, compared to a distearoyl PA control, consistent with a reaction mechanism involving cleavage of the P-O bond. RP HOLBROOK, PG (reprint author), NIDDKD,BIOORGAN CHEM LAB,BLDG 8 ROOM 1A-15,BETHESDA,MD 20892, USA. NR 39 TC 25 Z9 25 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-3002 J9 BIOCHIM BIOPHYS ACTA PD JUL 9 PY 1991 VL 1084 IS 2 BP 155 EP 158 DI 10.1016/0005-2760(91)90214-3 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA FY613 UT WOS:A1991FY61300006 PM 1854800 ER PT J AU BUCHER, JR HEJTMANCIK, MR TOFT, JD PERSING, RL EUSTIS, SL HASEMAN, JK AF BUCHER, JR HEJTMANCIK, MR TOFT, JD PERSING, RL EUSTIS, SL HASEMAN, JK TI RESULTS AND CONCLUSIONS OF THE NATIONAL TOXICOLOGY PROGRAMS RODENT CARCINOGENICITY STUDIES WITH SODIUM-FLUORIDE SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID SYRIAN-HAMSTER EMBRYO; MOUSE LYMPHOMA-CELLS; CHROMOSOME-ABERRATIONS; TRANSFORMATION; RATS AB The US National Toxicology Program (NTP) has conducted toxicity and carcinogenicity studies with sodium fluoride administered in the drinking water to F344/N rats and B6C3F1 mice. The drinking water concentrations used in the 2-year studies were 0, 25, 100, or 175 ppm sodium fluoride (equivalent to 0, 11, 45 or 79 ppm fluoride). Survival and weight gains of rats and mice were not affected by fluoride treatment. Animals receiving sodium fluoride developed effects typical of dental fluorosis, and female rats given 175 ppm had increased osteosclerosis. There were no increases in neoplasms in female rats or in male or female mice that were attributed to sodium fluoride administration. There was equivocal evidence of carcinogenic activity of sodium fluoride in male rats based on the occurrence of a small number of osteosarcomas in treated animals. C1 BATTELLE MEM INST,COLUMBUS,OH 43201. RP BUCHER, JR (reprint author), NIEHS,NATL TOXICOL PROGRAM,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 31 TC 29 Z9 33 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUL 9 PY 1991 VL 48 IS 5 BP 733 EP 737 DI 10.1002/ijc.2910480517 PG 5 WC Oncology SC Oncology GA FX549 UT WOS:A1991FX54900016 PM 2071234 ER PT J AU REDDEL, RR HSU, IC MASS, MJ HUKKU, B GERWIN, BI SALGHETTI, SE SOMERS, ANA GALATI, AJ GUNNING, WT HARRIS, CC STONER, GD AF REDDEL, RR HSU, IC MASS, MJ HUKKU, B GERWIN, BI SALGHETTI, SE SOMERS, ANA GALATI, AJ GUNNING, WT HARRIS, CC STONER, GD TI A HUMAN BRONCHIAL EPITHELIAL-CELL STRAIN WITH UNUSUAL INVITRO GROWTH-POTENTIAL WHICH UNDERGOES NEOPLASTIC TRANSFORMATION AFTER SV40 T-ANTIGEN GENE TRANSFECTION SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID SIMIAN-VIRUS 40; SQUAMOUS DIFFERENTIATION; HUMAN KERATINOCYTES; TYROSINE-HYDROXYLASE; NUCLEOTIDE-SEQUENCE; CLONED CDNA; RAS GENE; C-MYC; LINE; CARCINOMA AB Bronchial epithelial cells were cultured from an individual with no evidence of malignant disease. These cells, designated HB56B, had a greatly extended in vitro life-span, being able to undergo 50 passages and 200 population doublings in contrast to the usual 3 to 4 passages and 20 to 30 population doublings characteristic of normal human bronchial epithelial cells. HB56B cells had karyotypic evidence of an amplified region on the short arm of chromosome 11. Unlike normal bronchial epithelial cells, which undergo terminal squamous differentiation in vitro in response to fetal bovine serum, HB56B cells were only minimally affected by serum. These cells were readily established as an immortalized cell line, HB56B/5T, following transfection with a plasmid containing SV40 early region DNA. HB56B cells were non-tumorigenic in athymic nude mice, but HB56B/5T cells within a few passages of transfection with the SV40 plasmid formed tumors of which 28/37 regressed. HB56B cells may offer an experimental system for the study of proliferation, differentiation, and senescence control in human bronchial epithelial cells. C1 MED COLL OHIO,DEPT PATHOL,3000 ARLINGTON AVE,TOLEDO,OH 43699. CHILDRENS HOSP MICHIGAN,CELL CULTURE LAB,DETROIT,MI 48201. US EPA,DIV GENET TOXICOL,RES TRIANGLE PK,NC 27711. NCI,DIV CANC ETIOL,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. CHILDRENS MED RES FDN,CAMPERDOWN,NSW 2050,AUSTRALIA. UNIV MARYLAND,SCH MED,DEPT PATHOL,BALTIMORE,MD 21201. RI Gunning, William/E-4681-2010; Reddel, Roger/A-6635-2014 OI Reddel, Roger/0000-0002-6302-6107 FU NCI NIH HHS [CA28950, N01-CP-21017] NR 51 TC 17 Z9 17 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUL 9 PY 1991 VL 48 IS 5 BP 764 EP 773 DI 10.1002/ijc.2910480522 PG 10 WC Oncology SC Oncology GA FX549 UT WOS:A1991FX54900021 PM 1712759 ER PT J AU DAVIS, MD KAUFMAN, S AF DAVIS, MD KAUFMAN, S TI 7-TETRAHYDROBIOPTERIN IS AN UNCOUPLED COFACTOR FOR RAT HEPATIC PHENYLALANINE-HYDROXYLASE SO FEBS LETTERS LA English DT Article DE TETRAHYDROBIOPTERIN; 7-TETRAHYDROBIOPTERIN; PHENYLALANINE HYDROXYLASE; UNCOUPLED OXIDATION; PHENYLKETONURIA ID TETRAHYDROPTERIN OXIDATION; 7-SUBSTITUTED PTERINS; LIVER; HYPERPHENYLALANINEMIA; CONFIGURATION; PURIFICATION AB Rat hepatic phenylalamine hydroxylase requires both a tetrahydropterin cofactor and molecular oxygen to convert phenylalanine to tyrosine. During the physiological hydroxylation, a single mol of the natural cofactor, tetrahydrobiopterin, is oxidized for each mol of phenylalanine converted to tyrosine. Artificial conditions have been devised in which the oxidation of the tetrahydropterin is uncoupled from the hydroxylation of the aromatic amino acid substrate. Recently, an isomer of tetrahydrobiopterin, 7-tetrahydrobiopterin, has been isolated from the urine of certain mildly hyperphenylalaninemic children. We report in this communication that 7-tetrahydrobiopterin may be an inefficient cofactor for phenylalanine hydroxylase because, in vitro, the phenylalanine-dependent oxidation of 7-tetrahydrobiopterin is accompanied by the hydroxylation of the aromatic amino acid substrate only about 15% of the time, i.e. the enzymatic oxidation of 7-tetrahydrobiopterin is about 85% uncoupled from the hydroxylation of the amino acid substrate. RP DAVIS, MD (reprint author), NIMH,NEUROCHEM LAB,BETHESDA,MD 20892, USA. NR 34 TC 23 Z9 23 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JUL 8 PY 1991 VL 285 IS 1 BP 17 EP 20 DI 10.1016/0014-5793(91)80714-E PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA FW003 UT WOS:A1991FW00300004 PM 2065777 ER PT J AU LEE, NH ELFAKAHANY, EE AF LEE, NH ELFAKAHANY, EE TI ALLOSTERIC ANTAGONISTS OF THE MUSCARINIC ACETYLCHOLINE-RECEPTOR SO BIOCHEMICAL PHARMACOLOGY LA English DT Editorial Material ID BISQUATERNARY PYRIDINIUM OXIMES; 2ND MESSENGER RESPONSES; RAT-BRAIN; BINDING-PROPERTIES; M2 RECEPTORS; CHOLINERGIC RECEPTORS; DISSOCIATION KINETICS; H-3 PIRENZEPINE; SODIUM-CHANNELS; LIGAND-BINDING C1 UNIV MARYLAND,SCH PHARM,DEPT PHARMACOL & TOXICOL,20 N PINE ST,BALTIMORE,MD 21201. NIAAA,MOLEC NEUROBIOL SECT,PHYSIOL & PHARMACOL STUDIES LAB,ROCKVILLE,MD 20852. NR 85 TC 122 Z9 122 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD JUL 5 PY 1991 VL 42 IS 2 BP 199 EP 205 DI 10.1016/0006-2952(91)90703-8 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA FY082 UT WOS:A1991FY08200001 PM 1859442 ER PT J AU MIMNAUGH, EG FAIRCHILD, CR FRUEHAUF, JP SINHA, BK AF MIMNAUGH, EG FAIRCHILD, CR FRUEHAUF, JP SINHA, BK TI BIOCHEMICAL AND PHARMACOLOGICAL CHARACTERIZATION OF MCF-7 DRUG-SENSITIVE AND ADRR MULTIDRUG-RESISTANT HUMAN BREAST-TUMOR XENOGRAFTS IN ATHYMIC NUDE-MICE SO BIOCHEMICAL PHARMACOLOGY LA English DT Article ID FREE-RADICAL FORMATION; GLUTATHIONE-S-TRANSFERASE; CANCER CELL-LINE; ESTROGEN-RECEPTOR; GENE-EXPRESSION; CARCINOMA-CELLS; RAT-LIVER; ADRIAMYCIN; PEROXIDASE; SELENIUM AB The phenotypic expression of multidrug resistance by the doxorubicin-selected Adr(R) human breast tumor cell line is associated with overexpression of plasma membrane P-170 glycoprotein and increased cytosolic selenium-dependent GSH-peroxidase activity relative to the parental MCF-7 wild-type line (WT). To determine whether doxorubicin resistance by Adr(R) cells persists in vivo, and to further investigate the possibility of biochemical differences between WT and Adr(R) solid tumors, both tumor cell lines were grown as subcutaneous xenografts in athymic nude mice. Tumorigenicity depended upon cell inoculation burden, and tumor incidence was similar for both cell lines (> 80% tumor takes at 10(7) cells/mouse) at 14 days, provided 17-beta-estradiol was supplied to the animals bearing the WT tumors. However, the growth rate for the Adr(R) xenografts was only about half that of WT xenografts. Doxorubicin (2-8 mg/kg, i.p., injected weekly) significantly diminished the growth of the WT tumors, but Adr(R) solid tumors failed to respond to doxorubicin. The accumulation of C-14-labeled doxorubicin was 2-fold greater in WT xenografts that in Adr(R), although there were no differences in host organ drug levels in mice bearing either type of tumors. Membrane P-170 glycoprotein mRNA was detected by slot-blot analysis in the Adr(R) tumors, but not in WT. Electron spin resonance 5,5-dimethylpyrroline-N-oxide-spin-trapping experiments with microsomes and mitochondria from WT and Adr(R) xenographs demonstrated a 2-fold greater oxygen radical (superoxide and hydroxyl) formation from activated doxorubicin with WT xenographs compared to Adr(R). Selenium-dependent glutathione (GSH)-peroxidase, superoxide dismutase and GSH-S-aryltransferase activities in Adr(R) xenografts were elevated relative to WT. Although the activities of the latter two enzymes were similar to those measured in both tumor cell lines, GSH-peroxidase activities were elevated 70-fold (WT) and 10-fold (Adr(R)) in xenografts compared to tumor cells. In contrast, in both WT and Adr(R) solid tumors in vivo, catalase, NAD(P)H-oxidoreductases, and glutathione disulfide (GSSG)-reductase activities, and GSH and GSSG levels were not markedly different, and were essentially the same as in cells in vitro. Like the MDR cells in culture, Adr(R) tumor xenografts were extremely resistant to doxorubicin and retained most of the characteristics of the altered phenotype. These results suggest that WT and Adr(R) breast tumor xenografts provide a useful model for the study of biochemical and pharmacological mechanisms of drug resistance by solid tumors in vivo. RP MIMNAUGH, EG (reprint author), NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,CLIN PHARMACOL BRANCH,BIOCHEM & MOLEC PHARMACOL SECT,BETHESDA,MD 20892, USA. NR 49 TC 31 Z9 38 U1 1 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD JUL 5 PY 1991 VL 42 IS 2 BP 391 EP 402 DI 10.1016/0006-2952(91)90727-M PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA FY082 UT WOS:A1991FY08200025 PM 1677569 ER PT J AU GREM, JL ALLEGRA, CJ AF GREM, JL ALLEGRA, CJ TI SEQUENCE-DEPENDENT INTERACTION OF 5-FLUOROURACIL AND ARABINOSYL-5-AZACYTOSINE OR 1-BETA-D-ARABINOFURANOSYLCYTOSINE SO BIOCHEMICAL PHARMACOLOGY LA English DT Article ID HUMAN COLORECTAL-CARCINOMA; COLON CANCER-CELLS; CYTO-TOXICITY; CLINICAL-TRIALS; PHASE-I; METHOTREXATE; DNA; ARABINOFURANOSYL-5-AZACYTOSINE; FAZARABINE; METABOLISM AB We studied the cytotoxicity of arabinosyl-5-azacytosine (Ara-AC), a dCyd antagonist which inhibits DNA synthesis, in combination with 5-fluorouracil (FUra) in two human colon cancer cell lines, HCT 116 and SNU-C4. Clonogenic assays done following sequential or concurrent 24-hr exposures to Ara-AC and FUra showed that the sequence Ara-AC followed by FUra resulted in more than additive lethality in the HCT 116 cell lines and additive lethality in the SNU-C4 cells. In contrast, the reverse sequence, FUra followed by Ara-AC, was antagonistic in both cell lines. A similar interaction between FUra and 1-beta-D-arabinofuranosylcytosine (Ara-C) was evident in HCT 116 cells; at concentrations which individually diminished viability by 34 and 62%, respectively, the sequence Ara-C followed by FUra decreased viability by 97%. Pulse-labeling with [H-3]dUrd showed profound inhibition of DNA synthesis by the sequence Ara-AC followed by FUra, with over 90% inhibition lasting for up to 48 hr following Ara-AC exposure. When FUra preceded Ara-AC, however, earlier recovery from inhibition of DNA synthesis occurred. FUra pretreatment did not appreciably alter the quantity or distribution of [H-3]Ara-AC or [H-3]Ara-C nucleotides after a 4- to 6-hr exposure. Pre-exposure to FUra decreased Ara-AC incorporation into DNA by 37 and 73% at 6 hr in HCT 116 and SNU-C4, respectively. FUra pretreatment also inhibited Ara-C incorporation into DNA by over 50% at 6 and 24 hr. The antagonism of Ara-AC and Ara-C cytotoxicity by FUra pretreatment can thus be explained by diminished incorporation of the dCyd analogs into DNA resulting from inhibition of DNA synthesis by FUra-induced dTTP and dCTP depletion. In contrast, when Ara-Ac or Ara-C preceded FUra, their incorporation into DNA was not disturbed, and prolonged inhibition of DNA synthesis was observed. RP GREM, JL (reprint author), NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,MED BRANCH,GASTROINTESTINAL TUMOR SECT,BLDG 10,BETHESDA,MD 20892, USA. NR 38 TC 7 Z9 7 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD JUL 5 PY 1991 VL 42 IS 2 BP 409 EP 418 DI 10.1016/0006-2952(91)90729-O PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA FY082 UT WOS:A1991FY08200027 PM 1713459 ER PT J AU GIBSON, RE ZEEBERG, BR MELOGRANA, JM WANG, TF RUCH, J BRAUN, A REBA, RC AF GIBSON, RE ZEEBERG, BR MELOGRANA, JM WANG, TF RUCH, J BRAUN, A REBA, RC TI INVIVO DISSOCIATION KINETICS OF [H-3] QUINUCLIDINYL BENZILATE - RELATIONSHIP TO MUSCARINIC RECEPTOR CONCENTRATION AND INVITRO KINETICS SO BRAIN RESEARCH LA English DT Article DE ACETYLCHOLINE RECEPTOR; REGIONAL QUANTITATION; KINETIC MODELING ID LIVING HUMAN-BRAIN; RAT-BRAIN; CHOLINERGIC RECEPTORS; REGIONAL DISTRIBUTION; BINDING-SITES; AUTORADIOGRAPHY; HETEROGENEITY; PIRENZEPINE; SUBTYPES; QNB AB The in vivo washout kinetics of ([H-3]quinuclidinyl benzilate ([H-3]QNB) varies significantly in various structures in the rat brain. The slowest washout rates are from the hippocampus, corpus striatum, and cortex, intermediate rates are exhibited from the thalamus and colliculi, while the fastest washout rate is from the cerebellum. We have also demonstrated a difference in the in vitro dissociation rates (k-1) of [H-3]QNB from various structures. The k-1 for the hippocampus, corpus striatum and cortex, is two-fold slower than that observed in the thalamus, colliculi, and cerebellum. The differences in the in vitro dissociation kinetics are not, however, sufficient to explain the differences in the in vivo washout kinetics. We have developed a theoretical formulation which describes conditions under which the washout kinetics are a function of the concentration of receptor in a structure. Furthermore, we present a graphical method in which a plot of the reciprocal of the observed washout rate constant, 1/k(obs), vs receptor concentration is linear. Analysis of the washout kinetics of [H-3]QNB from various structures of the CNS of rat were well described by this theory when the differences in in vitro k-1 are included. C1 GEORGE WASHINGTON UNIV,MED CTR,WASHINGTON,DC 20037. ST ELIZABETH HOSP,NIMH,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. FU NINDS NIH HHS [NS22215] NR 31 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUL 5 PY 1991 VL 553 IS 1 BP 110 EP 116 DI 10.1016/0006-8993(91)90237-P PG 7 WC Neurosciences SC Neurosciences & Neurology GA FX176 UT WOS:A1991FX17600017 PM 1933268 ER PT J AU SOBUE, K SELLERS, JR AF SOBUE, K SELLERS, JR TI CALDESMON, A NOVEL REGULATORY PROTEIN IN SMOOTH-MUSCLE AND NONMUSCLE ACTOMYOSIN SYSTEMS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID CALMODULIN-BINDING PROTEIN; CHICKEN GIZZARD CALDESMON; MICROFILAMENTS LIKE TROPOMYOSIN; KILODALTON ACTIN-BINDING; CULTURED RAT-CELLS; ATPASE ACTIVITY; THIN-FILAMENTS; MOLECULAR-WEIGHT; F-ACTIN; MYOSIN INTERACTION C1 NHLBI,MOLEC CARDIOL LAB,BETHESDA,MD 20892. RP SOBUE, K (reprint author), OSAKA UNIV,SCH MED,BIOMED RES CTR,DEPT NEUROCHEM & NEUROPHARMACOL,OSAKA 530,JAPAN. NR 88 TC 310 Z9 310 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 5 PY 1991 VL 266 IS 19 BP 12115 EP 12118 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FV180 UT WOS:A1991FV18000001 PM 2061300 ER PT J AU WELLSTEIN, A DOBRENSKI, AF RADONOVICH, MN BRADY, JF RIEGEL, AT AF WELLSTEIN, A DOBRENSKI, AF RADONOVICH, MN BRADY, JF RIEGEL, AT TI PURIFICATION OF PO-B, A PROTEIN THAT HAS INCREASED AFFINITY FOR THE PROOPIOMELANOCORTIN GENE PROMOTER AFTER DEPHOSPHORYLATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-BINDING PROTEINS; RNA POLYMERASE-II; TRANSCRIPTION FACTOR; PROOPIOMELANOCORTIN GENE; TYROSINE-PHOSPHATASES; DEPENDENT PHOSPHORYLATION; INDUCIBLE ENHANCER; HUMAN-PLACENTA; FACTOR CREB; EXPRESSION AB The region -15 to -3 of the pro-opiomelanocortin (POMC) gene promoter specifically binds a transcription factor previously designated PO-B. This region of the POMC gene is involved in the control of constitutive POMC gene expression since mutation of the PO-B DNA-binding site severely reduces transcription from the POMC promoter both in vivo and in vitro (Riegel, A. T., Remenick, J., Wolford, R., Berard, D., and Hager, G. (1990) Nucleic Acids Res. 18, 4513-4521). We have now purified PO-B from HeLa cells approximately 25,000-fold to greater than 90% homogeneity by a combination of ion exchange and reversed phase chromatography. In addition we have studied post-translational modifications that alter the affinity of purified PO-B for its cognate DNA binding site. In Southwestern analysis of column fractions, two bands of apparent molecular masses of 54 and 56 kDa bound specifically to the PO-B recognition sequence. The two copurified components have indistinguishable amino acid composition, are highly hydrophobic, and are heat and acid stable. DNA-binding specificity studies suggest that PO-B does not represent any previously described transcription factor. In addition, dephosphorylation of both species with acid phosphatase induced an about 30-fold increase in DNA binding but failed to produce any significant change in electrophoretic mobility. We conclude that the purified PO-B species represent products of the same gene and suggest that the in vivo function of PO-B may be regulated by its phosphorylation status. C1 GEORGETOWN UNIV, SCH MED, DEPT PHARMACOL, WASHINGTON, DC 20007 USA. GEORGETOWN UNIV, SCH MED, VINCENT T LOMBARDI CANC CTR, WASHINGTON, DC 20007 USA. NCI, MOLEC VIROL LAB, BETHESDA, MD 20892 USA. OI Wellstein, Anton/0000-0002-0570-4950 FU NIDDK NIH HHS [DK43127-01] NR 42 TC 15 Z9 15 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 5 PY 1991 VL 266 IS 19 BP 12234 EP 12241 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FV180 UT WOS:A1991FV18000024 PM 2061309 ER PT J AU ELING, TE GLASGOW, WC CURTIS, JF HUBBARD, WC HANDLER, JA AF ELING, TE GLASGOW, WC CURTIS, JF HUBBARD, WC HANDLER, JA TI STUDIES ON THE REDUCTION OF ENDOGENOUSLY GENERATED PROSTAGLANDIN-G2 BY PROSTAGLANDIN-H SYNTHASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID VESICULAR GLAND MICROSOMES; ELECTRON-PARAMAGNETIC-RES; ENDOPEROXIDE SYNTHETASE; HUMAN-LUNG; POLYMORPHONUCLEAR LEUKOCYTES; ARACHIDONIC-ACID; BIOSYNTHESIS; PEROXIDASE; PURIFICATION; SUBSTRATE AB Prostaglandin H synthase oxidizes arachidonic acid to prostaglandin G2 (PGG2) via its cyclooxygenase activity and reduces PGG2 to prostaglandin H-2 by its peroxidase activity. The purpose of this study was to determine if endogenously generated PGG2 is the preferred substrate for the peroxidase compared with exogenous PGG2. Arachidonic acid and varying concentrations of exogenous PGG2 were incubated with ram seminal vesicle microsomes or purified prostaglandin H synthase in the presence of the reducing cosubstrate, aminopyrine. The formation of the aminopyrine cation free radical (AP.+) served as an index of peroxide reduction. The simultaneous addition of PGG2 with arachidonic acid did not alter cyclooxygenase activity of ram seminal vesicle microsomes or the formation of the AP.+. This suggests that the formation of AP.+, catalyzed by the peroxidase, was supported by endogenous endoperoxide formed from arachidonic acid oxidation rather than by the reduction of exogenous PGG2. In addition to the AP.+ assay, the reduction of exogenous versus endogenous PGG2 was studied by using [5,6,8,9,11,12,14,15-H-2]arachidonic acid and unlabeled PGG2 as substrates, with gas chromatography-mass spectrometry techniques to measure the amount of reduction of endogenous versus exogenous PGG2. Two distinct results were observed. With ram seminal vesicle microsomes, little reduction of exogenous PGG2 was observed even under conditions in which all of the endogenous PGG2 was reduced. In contrast, studies with purified prostaglandin H synthase showed complete reduction of both exogenous and endogenous PGG2 using similar experimental conditions. Our findings indicate that PGG2 formed by the oxidation of arachidonic acid by prostaglandin H synthase in microsomal membranes is reduced preferentially by prostaglandin H synthase. C1 NCI,FREDERICK CANC RES FACIL,DIV CANC TREATMENT,PROGRAM DEV RES GRP,FREDERICK,MD 21701. RP ELING, TE (reprint author), NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709, USA. NR 26 TC 22 Z9 22 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 5 PY 1991 VL 266 IS 19 BP 12348 EP 12355 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FV180 UT WOS:A1991FV18000040 PM 1905721 ER PT J AU TANAKA, T PARRY, DAD KLAUSKOVTUN, V STEINERT, PM STANLEY, JR AF TANAKA, T PARRY, DAD KLAUSKOVTUN, V STEINERT, PM STANLEY, JR TI COMPARISON OF MOLECULARLY CLONED BULLOUS PEMPHIGOID ANTIGEN TO DESMOPLAKIN-I CONFIRMS THAT THEY DEFINE A NEW FAMILY OF CELL-ADHESION JUNCTION PLAQUE PROTEINS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HELICAL COILED COILS; SECONDARY-STRUCTURE; DESMOSOMAL PLAQUE; ALPHA-TROPOMYOSIN; AMINO-ACID; SEQUENCE; LOCALIZATION; CDNA; HEMIDESMOSOMES; ANTIBODY AB Bullous pemphigoid is a subepidermal blistering disease in which patients have autoantibodies against the plaque of the hemidesmosome. Starting with a previously isolated 2-kilobase (kb) cDNA for bullous pemphigoid antigen (BPA), we used primer extension of keratinocyte mRNA to isolate overlapping cDNAs with a combined open reading frame of 6.3 kb, encoding most (243 kDa) of the BPA, but lacking the far amino terminus. Analysis of this amino acid sequence revealed a carboxyl-terminal domain containing two regions of 174 and 176 residues with high sequence identity. Most of the amino-terminal two-thirds of BPA is predicted to be in an alpha-helical conformation in which two chains would aggregate into a coiled-coil rod structure. BPA and desmoplakin I, a desmosome plaque protein, show remarkable sequence and structural homology. In its carboxyl-terminal domain, desmoplakin I also has 176 residue repeats with 40% sequence identity to those in BPA. The repeats in both molecules have a regular linear distribution of acidic and basic residues with a period of 9.5, the same as that found in the 1B segment of keratin filaments, suggesting a means of ionic interaction between keratin and these plaque proteins. Also, desmoplakin I, like BPA, is predicted to have a rod domain, which in both proteins has similar regular charge periodicities, suggesting a means of ionic self-aggregation. These findings extend those of Green et al. (Green, K. J., Parry, D. A. D., Steinert, P. S., Virata, L. A., Wagner, R. M., Angst, B. D., and Nilles, L. A. (1990) J. Biol. Chem. 265,2603-2612) which show that BPA and desmoplakin I represent the first members of a new family of adhesion junction plaque proteins. C1 NCI,DERMATOL BRANCH,BLDG 10,RM 12N238,BETHESDA,MD 20892. NIAMSK,SKIN BIOL LAB,BETHESDA,MD 20892. MASSEY UNIV,DEPT PHYS & BIOPHYS,PALMERSTON NORTH,NEW ZEALAND. NR 31 TC 149 Z9 150 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 5 PY 1991 VL 266 IS 19 BP 12555 EP 12559 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FV180 UT WOS:A1991FV18000071 PM 1712022 ER PT J AU MURPHY, PM MCDERMOTT, D AF MURPHY, PM MCDERMOTT, D TI FUNCTIONAL EXPRESSION OF THE HUMAN FORMYL PEPTIDE RECEPTOR IN XENOPUS OOCYTES REQUIRES A COMPLEMENTARY HUMAN FACTOR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MUSCARINIC ACETYLCHOLINE-RECEPTOR; PROTEIN-COUPLED RECEPTORS; HUMAN INTERFERON-GAMMA; GTP-BINDING PROTEIN; MOLECULAR-CLONING; ALPHA-SUBUNIT; ALPHA-2-ADRENERGIC RECEPTOR; BETA-2-ADRENERGIC RECEPTOR; CHEMOATTRACTANT RECEPTOR; SIGNAL-TRANSDUCTION AB Human phagocytic cells express receptors for bacterial N-formyl peptides (formyl peptide receptor or FPR) which mediate chemotaxis, degranulation, and the respiratory burst. Although cDNA encoding a human phagocyte formyl peptide-binding protein has been reported recently (Boulay, F., Tardif, M., Brouchon, L., and Vignais, P. (1990) Biochem. Biophys. Res. Commun. 168, 1103-1109), functional coupling to signal transduction processes was not demonstrated. We describe corresponding full-length cDNA clones and prove that they encode the calcium-mobilizing human formyl peptide receptor by demonstrating functional reconstitution in the Xenopus oocyte. We further demonstrate that in contrast to all other cloned guanine nucleotide-binding regulatory protein (G-protein) coupled receptors expressed in this system, microinjection of FPR transcripts is not sufficient to confer ligand responsiveness to the oocyte: co-injection of phagocyte RNA encoding a complementary human factor that is not the alpha-subunit of the heterotrimeric G-proteins G(i1), G(i2), or G(i3) is also required. Whereas a 1.4-kilobase FPR transcript is expressed exclusively in differentiated phagocytic cells, the complementary factor activity localizes to a 3.5-kilobase RNA fraction and is expressed in both differentiated and undifferentiated myeloid cells as well as in liver. The deduced human FPR protein possesses seven hydrophobic putative membrane spanning segments, three sites for N-linked glycosylation, and a short 18-amino acid predicted third cytoplasmic loop. Surprisingly, the human FPR possesses only 28% amino acid identity with the rabbit FPR reported recently by Thomas and co-workers (Thomas, K. M., Pyun, H. Y., and Navarro, J. (1990) J. Biol. Chem. 265, 20061-20065). Moreover, the rabbit FPR does not require a complementary factor for calcium mobilization in the oocyte. Structural alignment reveals at most 20% amino acid identity of the human FPR with other G-protein coupled receptors, indicating a common ancestral gene. Functional reconstitution of the recombinant FPR will now permit precise delineation of its functional and regulatory domains. Moreover, discovery of a complementary factor for oocyte expression of the human FPR establishes a novel approach to the qualification by ligand screening of cDNA encoding other suspected G-protein coupled receptors. RP MURPHY, PM (reprint author), NIAID,CLIN INVEST LAB,BACTERIAL DIS SECT,BLDG 10,RM 11N110,BETHESDA,MD 20892, USA. OI McDermott, David/0000-0001-6978-0867 NR 53 TC 49 Z9 50 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 5 PY 1991 VL 266 IS 19 BP 12560 EP 12567 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FV180 UT WOS:A1991FV18000072 PM 1712023 ER PT J AU MATSUMOTO, Y WICKNER, RB AF MATSUMOTO, Y WICKNER, RB TI YEAST 20-S RNA REPLICON - REPLICATION INTERMEDIATES AND ENCODED PUTATIVE RNA-POLYMERASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DEPENDENT PROTEIN-KINASE; SACCHAROMYCES-CEREVISIAE; SELF-CLEAVAGE; SEQUENCE; SPORULATION; EXPRESSION; HAIRPINS; GENOME; HSP26; VIRUS AB The 20 S RNA genome is a circular single-stranded replicon, present in most laboratory yeast strains, whose copy number is induced 10,000-fold by transfer of cells to acetate medium without a carbon source. We have sequenced most of the 20 S RNA genome, and the (+) strand has a long open reading frame with the potential to encode a protein with homology to viral RNA-dependent RNA polymerases. The presence of a typical cAMP-dependent phosphorylation site in the putative RNA polymerase suggests that the acetate amplification of the 20 S RNA genome might be mediated by cAMP, a signal known to transmit the same nutritional status information to the sporulation-control system. Our inability to clone across the gap in the sequence suggests either autocatalytic cleavage of the RNA in the reverse transcriptase reaction, an unusual linkage of 5' and 3' ends of a fundamentally linear molecule, or a structure unusually resistant to reverse transcription. The identity of our sequence with that of the accompanying paper (Rodriguez-Cousino, N., Esteban, L. M., and Esteban, R. (1991) J. Biol. Chem. 266, 12772-12778) for W double-stranded RNA (dsRNA) suggests that W is the replicative form of 20 S RNA. The presence of single-stranded (+) and (-) strands and greater than unit length molecules suggests a rolling circle mode of replication as has been suggested for viroids. RP MATSUMOTO, Y (reprint author), NIDDKD,BIOCHEM PHARMACOL LAB,GENET SIMPLE EUKARYOTES SECT,BETHESDA,MD 20892, USA. NR 28 TC 31 Z9 32 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 5 PY 1991 VL 266 IS 19 BP 12779 EP 12783 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FV180 UT WOS:A1991FV18000104 PM 1648104 ER PT J AU BARTH, RJ MULE, JJ ASHER, AL SANDA, MG ROSENBERG, SA AF BARTH, RJ MULE, JJ ASHER, AL SANDA, MG ROSENBERG, SA TI IDENTIFICATION OF UNIQUE MURINE TUMOR ASSOCIATED ANTIGENS BY TUMOR INFILTRATING LYMPHOCYTES USING TUMOR SPECIFIC SECRETION OF INTERFERON-GAMMA AND TUMOR-NECROSIS-FACTOR SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE TUMOR INFILTRATING LYMPHOCYTE; LYMPHOKINE SECRETION; INTERFERON-GAMMA; TUMOR NECROSIS FACTOR; ADOPTIVE IMMUNOTHERAPY; TUMOR ANTIGENS ID MACROPHAGE-ACTIVATING FACTOR; INVIVO ANTITUMOR-ACTIVITY; ADOPTIVE IMMUNOTHERAPY; T CLONES; LYMPHOKINE ACTIVITIES; LYT-2+; CELLS; INTERLEUKIN-2; HELPER; PHENOTYPE AB Stimulation of multiple CD8+ murine tumor infiltrating lymphocyte (TIL) lines and one TIL clone with the tumor of origin of the TIL induced at least three-fold more secretion of TNF and/or INF-gamma than was elicited by other syngeneic, methylcholanthrene (MCA) induced sarcomas. TIL which specifically secreted lymphokines were generated from three different sarcomas. Specific lymphokine secretion was a stable characteristic of the lines over time. IL-2 was necessary for maximal lymphokine secretion by TIL. These investigations demonstrate that lymphokine secretion by CD8+ lymphocytes derived from tumor bearing mice can be used to define unique tumor associated antigens on at least three different sarcomas and may be valuable in studies of the biologic nature of these antigens and of the adoptive immunotherapy of cancer. C1 NCI,SURG BRANCH,BLDG 10,ROOM 2B46,BETHESDA,MD 20892. RI Sanda, Martin/A-6202-2013; Sanda, Martin/B-2023-2015 NR 26 TC 19 Z9 19 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD JUL 5 PY 1991 VL 140 IS 2 BP 269 EP 279 DI 10.1016/0022-1759(91)90380-X PG 11 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA FW204 UT WOS:A1991FW20400017 PM 1906077 ER PT J AU RICH, A DAVIES, DR FELSENFELD, G AF RICH, A DAVIES, DR FELSENFELD, G TI TRIPLEX RNA SO SCIENCE LA English DT Letter C1 NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892. RP RICH, A (reprint author), MIT,DEPT BIOL,CAMBRIDGE,MA 02139, USA. NR 2 TC 1 Z9 1 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUL 5 PY 1991 VL 253 IS 5015 BP 17 EP 17 DI 10.1126/science.1712122 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FV177 UT WOS:A1991FV17700003 PM 1712122 ER PT J AU HOLLSTEIN, M SIDRANSKY, D VOGELSTEIN, B HARRIS, CC AF HOLLSTEIN, M SIDRANSKY, D VOGELSTEIN, B HARRIS, CC TI P53 MUTATIONS IN HUMAN CANCERS SO SCIENCE LA English DT Article ID TUMOR SUPPRESSOR GENE; WILD-TYPE P53; LUNG-CANCER; MUTANT P53; CELL-LINES; DNA DAMAGE; CHEMICAL CARCINOGENESIS; SV40-TRANSFORMED CELLS; SEQUENCE SPECIFICITY; STRUCTURAL ASPECTS AB Mutations in the evolutionarily conserved codons of the p53 tumor suppressor gene are common in diverse types of human cancer. The p53 mutational spectrum differs among cancers of the colon, lung, esophagus, breast, liver, brain, reticuloendothelial tissues, and hemopoietic tissues. Analysis of these mutations can provide clues to the etiology of these diverse tumors and to the function of specific regions of p53. Transitions predominate in colon, brain, and lymphoid malignancies, whereas G:C to T:A transversions are the most frequent substitutions observed in cancers of the lung and liver. Mutations at A:T base pairs are seen more frequently in esophageal carcinomas than in other solid tumors. Most transitions in colorectal carcinomas, brain tumors, leukemias, and lymphomas are at CpG dinucleotide mutational hot spots. G to T transversions in lung, breast, and esophageal carcinomas are dispersed among numerous codons. In liver tumors in persons from geographic areas in which both aflatoxin B1 and hepatitis B virus are cancer risk factors, most mutations are at one nucleotide pair of codon 249. These differences may reflect the etiological contributions of both exogenous and endogenous factors to human carcinogenesis. C1 NCI,HUMAN CARCINOGENESIS LAB,BLDG 37,ROOM 2C05,BETHESDA,MD 20892. JOHNS HOPKINS ONCOL CTR,BALTIMORE,MD 21231. FU NCI NIH HHS [CA 09071, CA 43460] NR 95 TC 6959 Z9 7078 U1 109 U2 940 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUL 5 PY 1991 VL 253 IS 5015 BP 49 EP 53 DI 10.1126/science.1905840 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FV177 UT WOS:A1991FV17700030 PM 1905840 ER PT J AU DAAR, I NEBREDA, AR YEW, N SASS, P PAULES, R SANTOS, E WIGLER, M VANDEWOUDE, GF AF DAAR, I NEBREDA, AR YEW, N SASS, P PAULES, R SANTOS, E WIGLER, M VANDEWOUDE, GF TI THE RAS ONCOPROTEIN AND M-PHASE ACTIVITY SO SCIENCE LA English DT Article ID MOS PROTO-ONCOGENE; MATURATION-PROMOTING FACTOR; MURINE SARCOMA-VIRUS; XENOPUS OOCYTES; CELL-CYCLE; MEIOTIC MATURATION; GENE-PRODUCT; ARREST; P21; EGGS AB The endogenous mos proto-oncogene product (Mos) is required for meiotic maturation In Xenopus oocytes, the ras oncogene product (Ras) can induce meiotic maturation and high levels of M-phase-promoting factor (MPF) independent of endogenous Mos, indicating that a parallel pathway to metaphase exists. In addition, Ras, like Mos and cytostatic factor, can arrest Xenopus embryonic cell cleavage in mitosis and maintain high levels of MPF. Thus, in the Xenopus oocyte and embryo systems Ras functions in the M phase of the cell cycle. The embryonic cleavage arrest assay is a rapid and sensitive test for Ras function. C1 NCI,FREDERIK CANC RES & DEV CTR,BASIC RES PROGRAM,ABL,FREDERICK,MD 21701. NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. LEDERLE LAB,PEARL RIVER,NY 10965. COLD SPRING HARBOR LAB,COLD SPRING HARBOR,NY 11724. OI Daar, Ira/0000-0003-2657-526X; Wigler, Michael/0000-0003-4396-1971 FU NCI NIH HHS [N01-CO-74101] NR 42 TC 70 Z9 70 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD JUL 5 PY 1991 VL 253 IS 5015 BP 74 EP 76 DI 10.1126/science.1829549 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FV177 UT WOS:A1991FV17700037 PM 1829549 ER PT J AU ANDERSON, LM HECHT, SS KOVATCH, RM AMIN, S HOFFMANN, D RICE, JM AF ANDERSON, LM HECHT, SS KOVATCH, RM AMIN, S HOFFMANN, D RICE, JM TI TUMORIGENICITY OF THE TOBACCO-SPECIFIC CARCINOGEN 4-(METHYL-NITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE IN INFANT MICE SO CANCER LETTERS LA English DT Article DE NEONATAL MICE; LIVER TUMORS; LUNG TUMORS; TOBACCO-SPECIFIC NITROSAMINE; 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE ID A/J MICE; 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE; LUNG; CANCER; SMOKING; RISK; NITROSAMINES; CHILDHOOD; N'-NITROSONORNICOTINE; METABOLISM AB The tobacco-specific nitrosamine, 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), is a potent carcinogen in adult rodents and variably effective transplacentally, depending on species. In pursuit of the thesis that human infants may be especially vulnerable targets for tumor initiation by tobacco smoke constituents, we tested the efficacy of NNK as a tumor initiator in infant mice. Cr:NIH(S) (NIH Swiss outbred) mice were given 50 mg/kg NNK i.p. on postnatal days 1, 4, 7, 10 and 14, with saline to controls. At an average age of 13-15 months, 57% of the NNK-exposed male off-spring had hepatocellular tumors, with a multiplicity of 1.15 +/- 1.4, including 4 with carcinoma. Liver tumors including 2 carcinomas were found in 8 (14%) of the NNK-exposed female offspring. There were no hepatocellular neoplasms in any control. A significant increase in primary lung tumors also occurred in the NNK-treated males, with an incidence of 30/55 (57%) and a multiplicity of 0.7 +/- 0.2, vs. 7/33 (21%), multiplicity 0.3 +/- 0.6, in controls (P < 0.025). An apparent increase in the incidence of lung tumors in NNK-treated females, 21/57 (37%) vs. 7/32 (22%) in controls, approached significance (P < 0.1). Thus NNK was a moderately potent neonatal carcinogen for liver and lung in infant Swiss mice and more efficacious in this regard than when received transplacentally by mice of the same strain. C1 PATHOL ASSOCIATES INC,FREDERICK,MD 21703. AMER HLTH FDN,NAYLOR DANA INST DIS PREVENT,VALHALLA,NY 10595. RP ANDERSON, LM (reprint author), NCI,DIV CANC ETIOL,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702, USA. OI Hecht, Stephen/0000-0001-7228-1356 FU PHS HHS [29580] NR 25 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD JUL 4 PY 1991 VL 58 IS 3 BP 177 EP 181 DI 10.1016/0304-3835(91)90097-2 PG 5 WC Oncology SC Oncology GA FY065 UT WOS:A1991FY06500003 PM 1855194 ER PT J AU STEEL, E HAVERKOS, HW AF STEEL, E HAVERKOS, HW TI INCREASING INCIDENCE OF REPORTED CASES OF AIDS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP STEEL, E (reprint author), NIDA,ROCKVILLE,MD 20857, USA. NR 7 TC 3 Z9 3 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 4 PY 1991 VL 325 IS 1 BP 65 EP 66 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA FU342 UT WOS:A1991FU34200026 PM 2046717 ER PT J AU HEALY, B AF HEALY, B TI GENETIC-MARKER FOR LONG QT SYNDROME IDENTIFIED SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP HEALY, B (reprint author), NIH,BETHESDA,MD 20892, USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 3 PY 1991 VL 266 IS 1 BP 19 EP 19 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA FT934 UT WOS:A1991FT93400005 PM 2046123 ER PT J AU HEALY, B AF HEALY, B TI REPLACEMENT THERAPY EFFECTIVE FOR PATIENTS WITH GAUCHERS-DISEASE SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP HEALY, B (reprint author), NIH,BETHESDA,MD 20892, USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 3 PY 1991 VL 266 IS 1 BP 19 EP 19 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA FT934 UT WOS:A1991FT93400003 PM 2046123 ER PT J AU HEALY, B AF HEALY, B TI ALLELIC LOSS CORRELATED WITH PRIMARY BREAST-CANCER SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP HEALY, B (reprint author), NIH,BETHESDA,MD 20892, USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 3 PY 1991 VL 266 IS 1 BP 19 EP 19 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA FT934 UT WOS:A1991FT93400004 PM 2046123 ER PT J AU LEVINE, AM WERNZ, JC KAPLAN, L RODMAN, N COHEN, P METROKA, C BENNETT, JM RARICK, MU WALSH, C KAHN, J MILES, S EHMANN, WC FEINBERG, J NATHWANI, B GILL, PS MITSUYASU, R AF LEVINE, AM WERNZ, JC KAPLAN, L RODMAN, N COHEN, P METROKA, C BENNETT, JM RARICK, MU WALSH, C KAHN, J MILES, S EHMANN, WC FEINBERG, J NATHWANI, B GILL, PS MITSUYASU, R TI LOW-DOSE CHEMOTHERAPY WITH CENTRAL-NERVOUS-SYSTEM PROPHYLAXIS AND ZIDOVUDINE MAINTENANCE IN AIDS-RELATED LYMPHOMA - A PROSPECTIVE MULTIINSTITUTIONAL TRIAL SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ACQUIRED IMMUNODEFICIENCY SYNDROME; NON-HODGKINS LYMPHOMA; AGENTS M-BACOD; HOMOSEXUAL MEN; MALIGNANT-LYMPHOMA; UNDIFFERENTIATED LYMPHOMA; IMPROVED PROGNOSIS; CELL LYMPHOMA; EXPERIENCE; NEOPLASIA AB Objective. - To ascertain if low-dose multiagent chemotherapy, with central nervous system prophylaxis and antiretroviral therapy, might be associated with increased efficacy and decreased risk of intercurrent infection in patients with malignant lymphoma related to the acquired immunodeficiency syndrome (AIDS). Design. - A phase 11 prospective clinical trial, with median follow-up of 33 months. Setting. - Eight university hospitals, within the context of the AIDS Clinical Trials Units, sponsored by the National institute of Allergy and Infectious Diseases. Patients. - Forty-two patients with AIDS-related malignant lymphoma. All were evaluable for toxicity assessment, and 35 for response. Intervention. - A low-dose modification of the M-BACOD regimen (day 1): cyclophosphamide, 300 mg/m2 intravenously (IV); doxorubicin, 25 mg/m2 IV; vincristine sulfate, 1.4 mg/m2 IV; bleomycin, 4 mg/m2 IV; dexamethasone, 3 mg/m2 orally on days 1 through 5; methotrexate, 500 mg/m2 IV on day 15, with leucovorin rescue. Intrathecal cytosine arabinoside (50 mg) to all on days 1, 8, 21, and 28, with radiation therapy to a helmet field to those with central nervous system involvement. Zidovudine for 12 months after completion of four to six cycles of chemotherapy. Main Outcome Measures. - Response rate and number of opportunistic infections. Results. - Response rate was 51% with a complete response of 46%. Of 16 complete responses, relapse occurred in four, none isolated to the central nervous system. Opportunistic infections occurred in 21% of those receiving treatment. Median duration of survival among all 42 patients is 5.6 months, 6.5 months in 35 patients evaluable for response, and 15 months in patients with complete response. Lower concentration of CD4 cells, history of prior AIDS, bone marrow involvement, and stage IV disease were independently associated with decreased survival. Conclusions. - Low-dose chemotherapy with central nervous system prophylaxis and zidovudine maintenance may be associated with durable remissions in AIDS-related lymphoma with fewer opportunistic infections than noted in prior reports. C1 UNIV SO CALIF,LOS ANGELES CTY MED CTR,LOS ANGELES,CA 90033. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. GEORGE WASHINGTON UNIV,WASHINGTON,DC 20052. UNIV ROCHESTER,CTR CANC,ROCHESTER,NY 14627. UNIV CALIF LOS ANGELES,LOS ANGELES,CA 90024. NYU,NEW YORK,NY 10003. SAN FRANCISCO GEN HOSP,SAN FRANCISCO,CA 94110. ST LUKES ROOSEVELT HOSP,NEW YORK,NY 10025. PENN STATE UNIV,MILTON S HERSHEY MED CTR,COLL MED,HERSHEY,PA 17033. NIAID,DIV AIDS,AIDS CLIN TRIALS UNIT,BETHESDA,MD 20892. RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. RP LEVINE, AM (reprint author), UNIV SO CALIF,SCH MED,1975 ZONAL AVE,KAM 110F,LOS ANGELES,CA 90033, USA. NR 31 TC 152 Z9 153 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 3 PY 1991 VL 266 IS 1 BP 84 EP 88 DI 10.1001/jama.266.1.84 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA FT934 UT WOS:A1991FT93400032 PM 1710673 ER PT J AU YUSUF, S WITTES, J PROBSTFIELD, J TYROLER, HA AF YUSUF, S WITTES, J PROBSTFIELD, J TYROLER, HA TI ANALYSIS AND INTERPRETATION OF TREATMENT EFFECTS IN SUBGROUPS OF PATIENTS IN RANDOMIZED CLINICAL-TRIALS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; HEART-DISEASE; MORTALITY; PREVENTION; OVERVIEWS AB A key principle for interpretation of subgroup results is that quantitative interactions (differences in degree) are much more likely than qualitative interactions (differences in kind). Quantitative interactions are likely to be truly present whether or not they are apparent, whereas apparent qualitative interactions should generally be disbelieved as they have usually not been replicated consistently. Therefore, the overall trial result is usually a better guide to the direction of effect in subgroups than the apparent effect observed within a subgroup. Failure to specify prior hypotheses, to account for multiple comparisons, or to correct P values increases the chance of finding spurious subgroup effects. Conversely, inadequate sample size, classification of patients into the wrong subgroup, and low power of tests of interaction make finding true subgroup effects difficult. We recommend examining the architecture of the entire set of subgroups within a trial, analyzing similar subgroups across independent trials, and interpreting the evidence in the context of known biologic mechanisms and patient prognosis. C1 NEW ENGLAND RES INST INC,WASHINGTON,DC. UNIV N CAROLINA,SCH PUBL HLTH,DEPT EPIDEMIOL,CHAPEL HILL,NC 27514. RP YUSUF, S (reprint author), NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,CLIN TRIALS BRANCH,BETHESDA,MD 20892, USA. NR 37 TC 571 Z9 573 U1 1 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 3 PY 1991 VL 266 IS 1 BP 93 EP 98 DI 10.1001/jama.266.1.93 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA FT934 UT WOS:A1991FT93400034 PM 2046134 ER PT J AU SPERA, S BAX, A AF SPERA, S BAX, A TI EMPIRICAL CORRELATION BETWEEN PROTEIN BACKBONE CONFORMATION AND C-ALPHA AND C-BETA C-13 NUCLEAR-MAGNETIC-RESONANCE CHEMICAL-SHIFTS SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Note ID 3-DIMENSIONAL NMR-SPECTROSCOPY; STAPHYLOCOCCAL NUCLEASE; CRYSTAL-STRUCTURE; SOLID-STATE; RESOLUTION; INTERLEUKIN-1-BETA; ASSIGNMENT; CALMODULIN; INHIBITOR; AMIDE C1 NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892. NR 15 TC 879 Z9 881 U1 1 U2 35 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD JUL 3 PY 1991 VL 113 IS 14 BP 5490 EP 5492 DI 10.1021/ja00014a071 PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA FU900 UT WOS:A1991FU90000071 ER PT J AU AEBERSOLD, P HYATT, C JOHNSON, S HINES, K KORCAK, L SANDERS, M LOTZE, M TOPALIAN, S YANG, J ROSENBERG, SA AF AEBERSOLD, P HYATT, C JOHNSON, S HINES, K KORCAK, L SANDERS, M LOTZE, M TOPALIAN, S YANG, J ROSENBERG, SA TI LYSIS OF AUTOLOGOUS MELANOMA-CELLS BY TUMOR-INFILTRATING LYMPHOCYTES - ASSOCIATION WITH CLINICAL-RESPONSE SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID HUMAN METASTATIC MELANOMAS; HIGH-DOSE INTERLEUKIN-2; ADOPTIVE IMMUNOTHERAPY; RECEPTOR EXPRESSION; ACTIVATION; CANCER AB Tumor-infiltrating lymphocytes (TILs) can be grown in vitro in medium containing interleukin-2 (IL-2). In clinical trials at the Surgery Branch of the National Cancer Institute, patients with metastatic malignant melanomas were treated with IL-2 plus the adoptive transfer of autologous TILs. At the time of treatment, TILs were assayed for in vitro lysis of fresh autologous and allogeneic melanoma cells and Daudi cells. Patients were evaluated for clinical response 4-8 weeks later. Lysis of autologous tumor cells by TILs was significantly higher for responding than for non-responding patients. Tumor cells from responding and non-responding patients were equally sensitive to lysis by allogeneic lymphokine-activated killer (LAK) cells. There was no difference between TILs from responding and non-responding patients for lysis of LAK-sensitive Daudi cells, which was low in most cases and demonstrated that TIL lysis of autologous tumor cells was not due to LAK cells. The observed association of autologous tumor cell lysis by TILs with clinical response suggests that the development of culture methods to optimize lysis of autologous tumors may lead to increased response rates using this TIL treatment regimen. RP AEBERSOLD, P (reprint author), NCI,DIV CANC TREATMENT,SURG BRANCH,BLDG 10,RM 2B12,BETHESDA,MD 20892, USA. NR 20 TC 175 Z9 176 U1 1 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUL 3 PY 1991 VL 83 IS 13 BP 932 EP 937 DI 10.1093/jnci/83.13.932 PG 6 WC Oncology SC Oncology GA FU294 UT WOS:A1991FU29400017 PM 2067036 ER PT J AU KIM, JH TAKAHASHI, T CHIBA, I PARK, JG BIRRER, MJ ROH, JK LEE, HD KIM, JP MINNA, JD GAZDAR, AF AF KIM, JH TAKAHASHI, T CHIBA, I PARK, JG BIRRER, MJ ROH, JK LEE, HD KIM, JP MINNA, JD GAZDAR, AF TI OCCURRENCE OF P53-GENE ABNORMALITIES IN GASTRIC-CARCINOMA TUMORS AND CELL-LINES SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID HUMAN COLORECTAL-CARCINOMA; P53 GENE-MUTATIONS; WILD-TYPE P53; LUNG-CANCER; POINT MUTATIONS; BLAST CRISIS; DNA; EXPRESSION; SEQUENCE; REARRANGEMENT AB We explored the state of the p53 gene in gastric cancer. Using one or more methods, we examined 15 specimens from primary carcinomas (14 tumors, one cell line), five cell lines derived from metastases, and seven paired samples of nonmalignant gastric mucosa. Sequence analyses of complementary DNA containing the entire p53 gene open reading frame demonstrated abnormalities in one of five samples from metastases. The single cell line derived from a primary carcinoma had no abnormality of the gene. The six abnormalities included four point mutations, one base-pair deletion resulting in a frame shift, and a 24 base-pair deletion caused by an intronic point mutation (as determined by sequence analysis of genomic DNA). Four of the six mutations mapped to regions highly conserved among species or involved in simian virus 40 T-antigen binding. Restriction fragment length polymorphism studies confirmed that chromosome 17p allelic deletions occur only in a minority of primary tumors, but that they may occur more frequently in metastases. Northern blotting and ribonuclease protection assays detected only a fraction of the p53 gene abnormalities detected by sequencing. Our findings indicate that mutations of the p53 gene are relatively rare in primary gastric tumors but appear to be relatively frequent in cell lines derived from metastatic lesions. Our results may help in understanding the molecular events associated with progression and metastasis in gastric carcinoma. C1 USN HOSP,NCI,DIV CANC TREATMENT,MED ONCOL BRANCH,BLDG 8,RM 5101,BETHESDA,MD 20814. RI Park, Jae-Gahb/J-5494-2012; Takahashi, Takashi/I-7262-2014 NR 35 TC 133 Z9 133 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUL 3 PY 1991 VL 83 IS 13 BP 938 EP 943 DI 10.1093/jnci/83.13.938 PG 6 WC Oncology SC Oncology GA FU294 UT WOS:A1991FU29400018 PM 1676761 ER PT J AU BUTZOW, JJ OEHRL, LL EICHHORN, GL AF BUTZOW, JJ OEHRL, LL EICHHORN, GL TI SELECTIVITY OF ESCHERICHIA-COLI RNA-POLYMERASE FOR TEMPLATE CONFORMATION SO BIOCHEMISTRY LA English DT Article ID HANDED Z-DNA; RIBONUCLEIC-ACID POLYMERASE; Z TRANSITION; INTERCALATING DRUGS; MOLECULAR-STRUCTURE; SIGMA-SUBUNIT; BINDING; TRANSCRIPTION; DAUNOMYCIN; SITE AB Escherichia coli RNA polymerase (RNAP) exhibits a strong selectivity for the secondary structure of its template DNA, as shown by the influence both of the DNA conformation on the transcription cycle and of the enzyme on the DNA conformation itself Binding, chain initiation and elongation characteristics of RNAP, and DNA conformational characteristics were examined by use of the alternating copolymer poly(dGdm5C).poly(dGdm5C) as template. Transcription is impeded when the DNA is in the Z conformation as compared with the B; the initial conformation is determined by the concentration of the conformational effectors Mg2+ and [Co(NH3)6]3+. RNAP binds to both Z and B conformers; the total binding is moderately greater when the template is in the B conformation than when it is strongly stabilized in the Z, by [Co-(NH3)6]3+ concentrations much higher than those required for B-Z transition. However, the Z conformer is much more easily displaced competitively from the bulk of its complexes with RNAP than is the B, indicating a specific binding preference for the B conformer. When the template is in the B conformation, or is moderately stabilized in the Z by Mg2+ concentrations such that the polynucleotide is just fully converted from B to Z, elongation is predicted well by chain initiation, indicating that on the Z conformer RNAP is effectively inhibited at the chain initiation or at an earlier stage. The average chain growth rates for polymeric product synthesized on B and on moderately stabilized Z are similar, even though overall RNA synthesis is considerably lowered on the Z form, again indicating that the limiting events precede elongation. When the Z conformer is strongly stabilized, chain initiation and elongation are further inhibited. Elongation is still roughly correlated with chain initiation, but some additional inhibition of elongation takes place independently. Circular dichroism analysis shows that RNAP-DNA binding affects the B-Z conformational equilibrium, leading to reformation of the B conformer from Z and interference with conversion of B to Z, under conditions that would otherwise favor the Z conformer. Thus, there is an RNAP concentration dependent shift of the B-Z transition to higher concentrations of Z-inducing cation, and there is an RNAP concentration dependent decrease in the rate of B to Z conversion. These effects were observed for poly-(dGdm5C).poly(dGdm5C), with Z stabilized by [Co(NH3)6]3+ or Mg2+. (They were observed as well for the unmethylated copolymer poly(dGdC).poly(dGdC), with Z stabilized by [Co(NH3)6]3+.) Perturbation of the Z conformer was detectable by circular dichroism at an RNAP:polynucleotide ratio down to a practical limit of approximately 1 RNAP:500 bp. Interference with B to Z conversion was readily detected at 1 RNAP:500 bp. Both of these phenomena appear to be fairly specific for the holoenzyme (alpha-2-beta-beta'sigma) form of RNAP, with the core enzyme (alpha-2-beta-beta') giving much smaller effects. RP BUTZOW, JJ (reprint author), NIA,GERONTOL RES CTR,CELLULAR & MOLEC BIOL LAB,BALTIMORE,MD 21224, USA. RI Dean, Lisa/B-1463-2015 OI Dean, Lisa/0000-0002-2407-9548 NR 37 TC 4 Z9 4 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUL 2 PY 1991 VL 30 IS 26 BP 6454 EP 6464 DI 10.1021/bi00240a016 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FU898 UT WOS:A1991FU89800016 PM 2054347 ER PT J AU ABEYGUNAWARDANA, C BUSH, CA CISAR, JO AF ABEYGUNAWARDANA, C BUSH, CA CISAR, JO TI COMPLETE STRUCTURE OF THE CELL-SURFACE POLYSACCHARIDE OF STREPTOCOCCUS-ORALIS ATCC-10557 - A RECEPTOR FOR LECTIN-MEDIATED INTERBACTERIAL ADHERENCE SO BIOCHEMISTRY LA English DT Article ID NUCLEAR MAGNETIC-RESONANCE; CORRELATED NMR-SPECTROSCOPY; ACTINOMYCES-VISCOSUS T14V; MULTIPLE QUANTUM NMR; SANGUIS ATCC 10557; CAPSULAR POLYSACCHARIDE; H-1-NMR SPECTRA; PROTON; COAGGREGATION; NAESLUNDII AB Lectin - carbohydrate binding is known to play an important role in a number of different cell-cell interactions including those between certain species of oral streptococci and actinomyces that colonize teeth. The cell wall polysaccharides of Streptococcus oralis ATCC 10557, S. oralis 34, and Streptococcus mitis J22, although not identical antigenically, each function as a receptor molecule for the galactose and N-acetylgalactosamine reactive fimbrial lectins of Actinomyces viscosus and Actinomyces naeslundii. Carbohydrate analysis of the receptor polysaccharide isolated from S. oralis ATCC 10557 shows galactose (3 mol), glucose (1 mol), GalNAc (1 mol), and rhamnose (1 mol). H-1 NMR spectra of the polysaccharide show that is is partially O-acetylated. Analysis of the H-1 NMR spectrum of the de-O-acetylated polysaccharide shows that it is composed of repeating subunits containing six monosaccharides and that the subunits are joined by a phosphodiester linkage. The H-1 and C-13 NMR spectra were completely assigned by two-dimensional homonuclear correlation methods and by H-1-detected heteronuclear multiple-quantum correlation (H-1[C-13]HMQC). The linkage of the component monosaccharides in the polymer, deduced from two-dimensional H-1-detected heteronuclear multiple-bond correlation spectra (H-1[C-13]HMBC), shows that the repeating unit of the de-O-acetylated polymer is a linear hexasaccharide with no branch points. The complete H-1 and C-13 assignment of the native polysaccharide was carried out by the same techniques augmented by a C-13 coupled hybrid HMQC-COSY method, which is shown to be especially useful for carbohydrates in which strong coupling and overlapping peaks in the H-1 spectrum pose difficulties. The fully assigned spectra of the native polymer show that each of two different positions is acetylated in one-third of the repeating subunits and that the acetylation is randomly distributed along the polymer. The exact positions of acetylation were assigned by a carbonyl-selective HMBC method that unambiguously defines the positions of O-acetylation. The complete structure of the native polysaccharide in S. oralis ATCC 10557 is [GRAPHICS] Comparison of this structure with those previously determined for the polysaccharides of strains 34 and J22 suggests that the similar lectin receptor activities of these molecules may depend on internal galactofuranose linked (beta-1 --> 6)- to Gal(beta-1 --> 3)GalNAc(alpha) or GalNAc(beta-1 --> 3) Gal(alpha). C1 UNIV MARYLAND,DEPT CHEM & BIOCHEM,CATONSVILLE,MD 21228. NIDR,MICROBIAL ECOL LAB,BETHESDA,MD 20892. FU NCRR NIH HHS [RR-02301]; NIDCR NIH HHS [DE-09445] NR 47 TC 37 Z9 37 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUL 2 PY 1991 VL 30 IS 26 BP 6528 EP 6540 DI 10.1021/bi00240a025 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FU898 UT WOS:A1991FU89800025 PM 2054351 ER PT J AU HOFRICHTER, J HENRY, ER SZABO, A MURRAY, LP ANSARI, A JONES, CM COLETTA, M FALCIONI, G BRUNORI, M EATON, WA AF HOFRICHTER, J HENRY, ER SZABO, A MURRAY, LP ANSARI, A JONES, CM COLETTA, M FALCIONI, G BRUNORI, M EATON, WA TI DYNAMICS OF THE QUATERNARY CONFORMATIONAL CHANGE IN TROUT HEMOGLOBIN SO BIOCHEMISTRY LA English DT Article ID CARBON-MONOXIDE; ABSORPTION-SPECTROSCOPY; GEMINATE RECOMBINATION; MODULATED EXCITATION; TRYPSIN-INHIBITOR; LASER PHOTOLYSIS; OPTICAL-SPECTRA; OXYGEN BINDING; EQUILIBRIUM; RESONANCE AB The kinetics of conformational changes in trout hemoglobin I have been characterized over the temperature range 2-65-degrees-C from time-resolved absorption spectra measured following photodissociation of the carbon monoxide complex. Changes in the spectra of the deoxyheme pbotoproduct were used to monitor changes in the protein conformation. Although the deoxyheme spectral changes are only about 8% of the total spectral change due to ligand rebinding, a combination of high-precision measurements and singular value decomposition of the data permits a detailed analysis of both their amplitudes and relaxation rates. Systematic variation of the degree of photolysis was used to alter the distribution of liganded tetramers, permitting the assignment of the spectral relaxation at 20-mu-s to the R --> T quaternary conformational change of the zero-liganded and singly liganded molecules and spectral relaxations at about 50 ns and 2-mu-s to tertiary conformational changes within the R structure. Analysis of the effect of photoselection by the linearly polarized excitation pulse indicates that a major contribution to the apparent geminate rebinding in the 50-ns relaxation arises from rotational diffusion of molecules containing unphotolyzed heme-CO complexes. The activation enthalpy and activation entropy for the R0 --> T0 transition are +7.4 kcal/mol and -12 cal mol-1 K-1. Using the equilibrium data, DELTA-H = +29.4 kcal/mol and DELTA-S = +84.4 cal mol-1 K-1 [Barisas, B. G., & Gill, S. J. (1979) Biophys. Chem. 9, 235-244], the activation parameters for the T0 --> R0 transition are calculated to be DELTA-H = +37 kcal/mol and DELTA-S = +73 cal mol-1 K-1. The similarity of the equilibrium and activation parameters for the T0 - R0 transition indicates that the transition state is much more R-like than T-like. This result suggests that in the path from T0 to R0 the subunits have already almost completely rearranged into the R configuration when the transition state is reached, while in the path from R0 to T0 the subunits remain in a configuration close to R in the transition state. The finding of an R-like transition state explains why the binding of ligands causes much smaller changes in the R --> T rates than in the T --> R rates. C1 UNIV ROME LA SAPIENZA,DEPT BIOCHEM SCI,I-00185 ROME,ITALY. RP HOFRICHTER, J (reprint author), NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892, USA. RI Szabo, Attila/H-3867-2012; Henry, Eric/J-3414-2013; OI Henry, Eric/0000-0002-5648-8696; Brunori, Maurizio/0000-0002-7795-1635 NR 59 TC 34 Z9 34 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUL 2 PY 1991 VL 30 IS 26 BP 6583 EP 6598 DI 10.1021/bi00240a031 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FU898 UT WOS:A1991FU89800031 PM 2054357 ER PT J AU MASYS, D AF MASYS, D TI THE NATIONAL-RESEARCH-AND-EDUCATION-NETWORK SO ACADEMIC MEDICINE LA English DT Editorial Material RP MASYS, D (reprint author), NATL LIB MED,LISTER HILL NATL CTR BIOMED COMMUN,BETHESDA,MD 20209, USA. NR 2 TC 3 Z9 3 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 1040-2446 J9 ACAD MED JI Acad. Med. PD JUL PY 1991 VL 66 IS 7 BP 397 EP 398 DI 10.1097/00001888-199107000-00005 PG 2 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA FX101 UT WOS:A1991FX10100005 PM 2059265 ER PT J AU RABINOVICH, S SHMUELI, U STEIN, Z SHASHUA, R WEISS, GH AF RABINOVICH, S SHMUELI, U STEIN, Z SHASHUA, R WEISS, GH TI EXACT RANDOM-WALK MODELS IN CRYSTALLOGRAPHIC STATISTICS .6. PDFS OF [E] FOR ALL PLANE GROUPS AND MOST SPACE-GROUPS SO ACTA CRYSTALLOGRAPHICA SECTION A LA English DT Article ID INTENSITY STATISTICS; DISTRIBUTIONS; SYMMETRY AB An exact calculation of the probability density function (p.d.f.) of (E), the magnitude of the normalized structure factor, can be developed in terms of Fourier and Fourier-Bessel series whose coefficients can be expressed in terms of the characteristic function. This article provides the formulae for atomic contributions to such characteristic functions. The results presented in this study are applicable to all the plane groups and to 206 three-dimensional space groups. Only the space groups isomorphous to the cubic point groups 432, 4BAR3m and m3BARm were omitted due to the complexity of the resulting expressions and the small deviations of the corresponding densities from the central-limit-theorem approximation, which have been observed in simulations for extreme atomic heterogeneities. Representative derivations illustrating the problems and techniques of their solution are provided. All the theoretical results have been computed numerically and compared with simulated distributions. Some results of these computations are illustrated in the accompanying paper, Part VII of this series [Rabinovich, Shmueli, Stein, Shashua & Weiss (1991). C1 NIH,DIV COMP RES & TECHNOL,PHYS SCI LAB,BETHESDA,MD 20892. RP RABINOVICH, S (reprint author), TEL AVIV UNIV,SCH CHEM,IL-69978 TEL AVIV,ISRAEL. NR 18 TC 10 Z9 10 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0108-7673 J9 ACTA CRYSTALLOGR A JI Acta Crystallogr. Sect. A PD JUL 1 PY 1991 VL 47 BP 328 EP 335 DI 10.1107/S0108767390013307 PN 4 PG 8 WC Chemistry, Multidisciplinary; Crystallography SC Chemistry; Crystallography GA FY900 UT WOS:A1991FY90000004 PM 1910632 ER PT J AU RABINOVICH, S SHMUELI, U STEIN, Z SHASHUA, R WEISS, GH AF RABINOVICH, S SHMUELI, U STEIN, Z SHASHUA, R WEISS, GH TI EXACT RANDOM-WALK MODELS IN CRYSTALLOGRAPHIC STATISTICS .7. AN ALL-SPACE-GROUP STUDY OF THE EFFECTS OF ATOMIC HETEROGENEITY ON THE PDFS OF [E] SO ACTA CRYSTALLOGRAPHICA SECTION A LA English DT Article ID GENERALIZED INTENSITY STATISTICS; DISTRIBUTIONS; DISPERSION; SYMMETRY AB Exact expressions have been found for the probability density functions (p.d.f.'s) of the magnitude of the normalized structure factor for all the two-dimensional and most three-dimensional space groups [ Part VI: Rabinovich, Shmueli, Stein, Shashua & Weiss (1991). Acta Cryst. A47, 328-335]. The results of that investigation are used in the present article to examine some effects of atomic heterogeneity, in the various space-group symmetries, on the p.d.f.'s. Some typical comparisons are made between p.d.f.'s based on the central limit theorem and p.d.f.'s computed from exact formulae. In addition, the exact results are compared to histograms of simulated values of (E). It is found that the p.d.f.'s for some space groups are influenced rather strongly by the presence of outstandingly heavy scatterers, but they are quite insensitive to the presence of such scatterers in other space groups. The often made general statement 'The presence of outstandingly heavy scatterers may invalidate the indications of Wilson's statistics' is made more precise here, insofar as it depends on the particular space group. C1 NIH,DIV COMP RES & TECHNOL,PHYS SCI LAB,BETHESDA,MD 20892. RP RABINOVICH, S (reprint author), TEL AVIV UNIV,SCH CHEM,IL-69978 TEL AVIV,ISRAEL. NR 24 TC 5 Z9 5 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0108-7673 J9 ACTA CRYSTALLOGR A JI Acta Crystallogr. Sect. A PD JUL 1 PY 1991 VL 47 BP 336 EP 340 DI 10.1107/S0108767390013319 PN 4 PG 5 WC Chemistry, Multidisciplinary; Crystallography SC Chemistry; Crystallography GA FY900 UT WOS:A1991FY90000005 PM 1910633 ER PT J AU WINDLE, C AF WINDLE, C TI RESEARCH ON SEVERE MENTAL-ILLNESS - AN AGENDA FOR THE 1990S SO ADMINISTRATION AND POLICY IN MENTAL HEALTH LA English DT Article RP WINDLE, C (reprint author), NIMH,DIV APPL & SERV RES,BETHESDA,MD 20892, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU HUMAN SCI PRESS INC PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 SN 0894-587X J9 ADM POLICY MENT HLTH JI Adm. Policy. Ment. Health PD JUL PY 1991 VL 18 IS 6 BP 469 EP 471 DI 10.1007/BF00707321 PG 3 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA FX439 UT WOS:A1991FX43900009 ER PT J AU PURI, J PIERCE, JH HOFFMAN, T AF PURI, J PIERCE, JH HOFFMAN, T TI SELECTIVE-INHIBITION OF PGE2 PRODUCTION IN CELLS TRANSFECTED WITH C-FMS ENCODED CSF-1 RECEPTOR GENES BY THE TYROSINE KINASE INHIBITOR, ST638 SO AGENTS AND ACTIONS LA English DT Article ID 4-HYDROXYCINNAMAMIDE DERIVATIVES AB In this study, we investigated the effect of ST638, a novel tyrosine kinase inhibitor, on TPA and ionomycin-stimulated PGE2 production after transfection of c-fms encoded CSF-1 receptor (CSF-1R) DNA (with or without transforming activity) into the myeloid progenitor cell line, 32D. ST638 inhibited prostaglandin E2 (PGE2) production induced after transfection of normal c-fms into 32D cell line, but failed to inhibit PGE2 production induced in 32D cells transformed with c-fms containing a point mutation at tyrosine 969 in the intracellular domain (substitution with phenylalanine) and at leucine 301 in the extracellular domain (substitution with serine). The selective effect on PGE2 production in normal c-fms-bearing cells by ST638 may indicate the presence of different induction pathways, one sensitive to ST638 and the other not. Alternatively, the phosphorylation site at tyr969 in c-fms may be a site of ST638 action, and upon its removal from the transforming c-fms, ST638 loses its inhibitory effect. C1 WEIZMANN INST SCI,IL-76100 REHOVOT,ISRAEL. NCI,CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. RP PURI, J (reprint author), US FDA,CTR BIOL EVALUAT & RES,DIV BLOOD & BLOOD PROD,CELL BIOL LAB,HFB-420,BLDG 29,ROOM 223,BETHESDA,MD 20892, USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU BIRKHAUSER VERLAG AG PI BASEL PA PO BOX 133 KLOSTERBERG 23, CH-4010 BASEL, SWITZERLAND SN 0065-4299 J9 AGENTS ACTIONS JI Agents Actions PD JUL PY 1991 VL 33 IS 3-4 BP 314 EP 317 DI 10.1007/BF01986579 PG 4 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA FX802 UT WOS:A1991FX80200014 PM 1950818 ER PT J AU AKERBLOM, L NARA, P DUNLOP, N MOREIN, B AF AKERBLOM, L NARA, P DUNLOP, N MOREIN, B TI CROSS-NEUTRALIZING ANTIBODIES TO HIV-1 IN MICE AFTER IMMUNIZATION WITH GP160 ISCOMS - DISSECTION OF THE IMMUNE-RESPONSE SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN IMMUNODEFICIENCY VIRUS; IMMUNOSTIMULATORY COMPLEXES ISCOMS; ANTIGENIC PRESENTATION; GP120; ENVELOPE; PROTEINS; CHIMPANZEES; IMMUNOASSAY; EXPRESSION; SEQUENCE AB Gp160 expressed in vaccinia and produced in vero cells was integrated into iscoms. Gp160 iscoms elicited a high serum antibody response in mice, and after two immunizations a ceiling was reached. The serum antibody response was dissected by the use of defined recombinant DNA products, representing different regions of the gp160 molecule. High antibody titers to the peptide RP135 (a.a. 296-332) correlated with induction of neutralizing serum antibodies. In some animals, gp160 (IIIB) iscoms elicited cross-neutralizing antibodies that also neutralized the distantly related RF isolate. C1 FREDERICK CANC RES CTR,FREDERICK,MD. NATL VET INST,DEPT VIROL,UPPSALA,SWEDEN. RP AKERBLOM, L (reprint author), DEPT VET MICROBIOL,VIROL SECT,BMC,BOX 585,S-75123 UPPSALA,SWEDEN. NR 38 TC 14 Z9 14 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JUL PY 1991 VL 7 IS 7 BP 621 EP 627 DI 10.1089/aid.1991.7.621 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA FZ982 UT WOS:A1991FZ98200008 PM 1768464 ER PT J AU COHEN, SG AF COHEN, SG TI ZABRISKIE ON PEACH HAIRS IN HAY-FEVER SO ALLERGY PROCEEDINGS LA English DT Note RP COHEN, SG (reprint author), NIAID,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 SN 1046-9354 J9 ALLERGY PROC JI Allergy Proc. PD JUL-AUG PY 1991 VL 12 IS 4 BP 277 EP 283 DI 10.2500/108854191778879322 PG 7 WC Allergy SC Allergy GA GC342 UT WOS:A1991GC34200014 PM 1936979 ER PT J AU MCGRATH, JC AF MCGRATH, JC TI EVALUATING NATIONAL-HEALTH COMMUNICATION CAMPAIGNS - FORMATIVE AND SUMMATIVE RESEARCH ISSUES SO AMERICAN BEHAVIORAL SCIENTIST LA English DT Article ID CHOLESTEROL; DISEASE RP MCGRATH, JC (reprint author), NHLBI,COMMUNICAT & MKT SECT,BETHESDA,MD 20892, USA. NR 24 TC 6 Z9 6 U1 0 U2 1 PU SAGE SCIENCE PRESS PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 0002-7642 J9 AM BEHAV SCI JI Am. Behav. Sci. PD JUL-AUG PY 1991 VL 34 IS 6 BP 652 EP 665 DI 10.1177/0002764291034006004 PG 14 WC Psychology, Clinical; Social Sciences, Interdisciplinary SC Psychology; Social Sciences - Other Topics GA FY963 UT WOS:A1991FY96300002 ER PT J AU HUSTEN, CG MANLEY, MW AF HUSTEN, CG MANLEY, MW TI WITHDRAWAL FROM NICOTINE GUM - REPLY SO AMERICAN FAMILY PHYSICIAN LA English DT Letter RP HUSTEN, CG (reprint author), NCI,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD FAMILY PHYSICIANS PI KANSAS CITY PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 SN 0002-838X J9 AM FAM PHYSICIAN JI Am. Fam. Physician PD JUL PY 1991 VL 44 IS 1 BP 49 EP 50 PG 2 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA FV831 UT WOS:A1991FV83100005 ER PT J AU GALDERISI, M ANDERSON, KM WILSON, PWF LEVY, D AF GALDERISI, M ANDERSON, KM WILSON, PWF LEVY, D TI ECHOCARDIOGRAPHIC EVIDENCE FOR THE EXISTENCE OF A DISTINCT DIABETIC CARDIOMYOPATHY (THE FRAMINGHAM-HEART-STUDY) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID LEFT-VENTRICULAR HYPERTROPHY; M-MODE ECHOCARDIOGRAPHY; MORPHOLOGICAL FEATURES; RISK-FACTORS; DISEASE; HYPERTENSION; MELLITUS; FAILURE; MASS AB Although several reports have described early changes of cardiac structure and function in diabetic patients, controversy persists regarding the existence of a clinically distinct diabetic cardiomyopathy. To this end, sex-specific linear regression analyses were used to examine the contribution of diabetes mellitus and glucose intolerance to age-adjusted echocardiographic parameters in 1,986 men (mean age 48 years) and 2,529 women (mean age 50 years) from the original Framingham Study cohort and the Framingham Offspring Study. Subjects with evidence of cardiovascular disease at the time of echocardiogram were excluded. Diabetics had higher heart rates than nondiabetics (67.9 vs 64.0 beats/min (p = 0.002) in men, and 73.1 vs 68.3 beats/min (p = 0.004) in women). Diabetic women had increased left ventricular (LV) wall thickness (18.7 vs 17.1 mm, p < 0.001), relative wall thickness (0.403 vs 0.377, p = 0.008), LV end-diastolic dimension (46.9 vs 45.7 mm, p = 0.03) and LV mass corrected for height (100.4 vs 82.2 g/m, p < 0.001). Women with glucose intolerance showed similar, less significant trends (p = 0.007 for wall thickness, p < 0.01 for LV mass). In diabetic men, fractional shortening was slightly reduced (0.355 vs 0.360, p < 0.05). In a multivariate model that included potentially confounding factors, diabetes remained an independent contributor to LV mass (p = 0.004) and wall thickness (p = 0.008) in women. In a separate linear regression model, which assessed the association of age with LV mass, the age-coefficient for diabetic women was much higher than that for nondiabetics (13.6 vs 6.6 g/m per 10-year increment in age). In conclusion, many echocardiographic differences in diabetics are explained by the contributions of other concomitant factors such as obesity, hypertension and smoking, but an independent association of diabetes with LV mass and LV wall thickness is evident in women. C1 NHLBI,BETHESDA,MD 20892. RP LEVY, D (reprint author), FRAMINGHAM HEART DIS EPIDEMIOL STUDY,5 THURBER ST,FRAMINGHAM,MA 01701, USA. OI Galderisi, Maurizio/0000-0003-0311-9069 NR 29 TC 360 Z9 364 U1 0 U2 6 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUL 1 PY 1991 VL 68 IS 1 BP 85 EP 89 DI 10.1016/0002-9149(91)90716-X PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA FT346 UT WOS:A1991FT34600017 PM 2058564 ER PT J AU PALMERI, ST KEMPNER, KM POWER, JA BACHARACH, SL CHOI, BW ROSING, DR BONOW, RO AF PALMERI, ST KEMPNER, KM POWER, JA BACHARACH, SL CHOI, BW ROSING, DR BONOW, RO TI EFFECTS OF PERCUTANEOUS TRANSLUMINAL CORONARY ANGIOPLASTY ON EXERCISE-INDUCED CHANGES IN R-WAVE AMPLITUDE SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Note ID ST-SEGMENT DEPRESSION; ANGIOGRAPHIC CORRELATION; ARTERY C1 NIH,DIV COMP RES & TECHNOL,COMP SYST LAB,BETHESDA,MD 20892. NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT NUCL MED,BETHESDA,MD 20892. NR 10 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUL 1 PY 1991 VL 68 IS 1 BP 114 EP 116 DI 10.1016/0002-9149(91)90723-X PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA FT346 UT WOS:A1991FT34600024 PM 2058544 ER PT J AU MARON, BJ LEON, MB SWAIN, JA CANNON, RO PELLICCIA, A AF MARON, BJ LEON, MB SWAIN, JA CANNON, RO PELLICCIA, A TI PROSPECTIVE IDENTIFICATION BY 2-DIMENSIONAL ECHOCARDIOGRAPHY OF ANOMALOUS ORIGIN OF THE LEFT MAIN CORONARY-ARTERY FROM THE RIGHT SINUS OF VALSALVA SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CARDIOVASCULAR-DISEASE; SUDDEN-DEATH C1 NHLBI,SURG BRANCH,BETHESDA,MD 20892. RP MARON, BJ (reprint author), NHLBI,CARDIOL BRANCH,BLDG 10,ROOM 7B15,BETHESDA,MD 20892, USA. NR 6 TC 33 Z9 34 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUL 1 PY 1991 VL 68 IS 1 BP 140 EP 142 DI 10.1016/0002-9149(91)90732-Z PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA FT346 UT WOS:A1991FT34600033 PM 2058554 ER PT J AU LANDS, WEM ZAKHARI, S AF LANDS, WEM ZAKHARI, S TI THE CASE OF THE MISSING CALORIES SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID OXIDOREDUCTION INVIVO; HYDROGEN TRANSFER; METABOLISM; ETHANOL; ALCOHOL RP LANDS, WEM (reprint author), NIAAA,DIV BASIC RES,5600 FISHERS LANE,ROOM 16C-06,ROCKVILLE,MD 20857, USA. NR 12 TC 59 Z9 60 U1 0 U2 0 PU AMER SOC CLIN NUTRITION INC PI BETHESDA PA 9650 ROCKVILLE PIKE SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998 SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUL PY 1991 VL 54 IS 1 BP 47 EP 48 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA FU358 UT WOS:A1991FU35800009 PM 2058586 ER PT J AU COLDITZ, GA GIOVANNUCCI, E RIMM, EB STAMPFER, MJ ROSNER, B SPEIZER, FE GORDIS, E WILLETT, WC AF COLDITZ, GA GIOVANNUCCI, E RIMM, EB STAMPFER, MJ ROSNER, B SPEIZER, FE GORDIS, E WILLETT, WC TI ALCOHOL INTAKE IN RELATION TO DIET AND OBESITY IN WOMEN AND MEN SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE ALCOHOL; DIET; BODY MASS INDEX; OBESITY; SUCROSE; CARBOHYDRATE; POPULATION STUDIES ID FOOD FREQUENCY QUESTIONNAIRE; UNITED-STATES ADULTS; NUTRIENT INTAKE; BODY-WEIGHT; CONSUMPTION; SMOKING; REPRODUCIBILITY; VALIDATION; VALIDITY; HEALTH AB We studied relations between alcohol intake, body mass index, and diet in 89 538 women and 48 493 men in two cohort studies. Total energy increased with alcohol consumption (partial r = 0.11, P < 0.001), and carbohydrate intake decreased from 153 g/d in abstainers to 131 g/d in women drinking 25.0-49.9 g alcohol/d. The decrease in carbohydrate intake was due mainly to decreased sugar consumption with higher alcohol intake (partial r = -0.05, P < 0.001), reflecting decreased energy consumption from sources excluding alcohol. In men total energy increased with alcohol consumption (partial r = 0.19, P < 0.001), from 7575.6 (abstainers) to 9821.5 kJ/d (> 50 g alcohol/d). Energy intake excluding alcohol varied little with alcohol intake (partial r = 0.003, P = 0.48) but sucrose intake decreased with higher alcohol intake. These data suggest that calories from alcohol were added to energy intake from other sources in men, and that in women, energy from alcohol intake displaced sucrose. The consumption of candy and sugar is inversely related to alcohol intake, raising the possibility that it is related to appetite for alcohol. C1 HARVARD UNIV,SCH MED,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BOSTON,MA 02115. HARVARD UNIV,SCH PUBL HLTH,DEPT NUTR,BOSTON,MA 02115. NIAAA,BETHESDA,MD. RP COLDITZ, GA (reprint author), BRIGHAM & WOMENS HOSP,DEPT MED,CHANNING LAB,180 LONGWOOD AVE,BOSTON,MA 02115, USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA90356]; NHLBI NIH HHS [HL35464]; NIDDK NIH HHS [DK36798] NR 23 TC 235 Z9 240 U1 2 U2 7 PU AMER SOC CLIN NUTRITION INC PI BETHESDA PA 9650 ROCKVILLE PIKE SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998 SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUL PY 1991 VL 54 IS 1 BP 49 EP 55 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA FU358 UT WOS:A1991FU35800010 PM 2058587 ER PT J AU DANFORD, DE HUBBARD, VS COMBS, GF HALL, CA LARSEN, LA SCHNAKENBERG, DD AF DANFORD, DE HUBBARD, VS COMBS, GF HALL, CA LARSEN, LA SCHNAKENBERG, DD TI REPORT ON THE 4TH CONFERENCE FOR FEDERALLY SUPPORTED HUMAN-NUTRITION RESEARCH UNITS AND CENTERS SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Editorial Material AB The Fourth Conference for Federally Supported Human Nutrition Research Units and Centers, sponsored by the Interagency Committee on Human Nutrition Research, addressed two topics: nutrition and function, and nutrient interactions and toxicities. This article summarizes the conference's introductory remarks and the contents of the 34 papers presented. Future meetings of federally supported nutrition research units and centers will focus on other human nutrition research topics and will be held biennially. C1 NIDDK,NUTR SCI BRANCH,BETHESDA,MD 20892. USDA ARS,BELTSVILLE AGR RES CTR,NATL PROGRAM STAFF,BELTSVILLE,MD 20705. DEPT VET AFFAIRS,NUTR LAB CLIN ASSESSMENT & RES,ALBANY,NY. US FDA,PROGRAM DEV,WASHINGTON,DC 20204. US DEPT DEF,OFF ASSISTANT SURG GEN RES & DEV,FALLS CHURCH,VA. RP DANFORD, DE (reprint author), NIDDK,DIV NUTR RES COORDINAT,BLDG 31,ROOM 4B63,BETHESDA,MD 20892, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLIN NUTRITION INC PI BETHESDA PA 9650 ROCKVILLE PIKE SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998 SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUL PY 1991 VL 54 IS 1 BP 164 EP 168 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA FU358 UT WOS:A1991FU35800027 PM 2058579 ER PT J AU GONZALEZ, CL MEDEIROS, LJ JAFFE, ES AF GONZALEZ, CL MEDEIROS, LJ JAFFE, ES TI COMPOSITE LYMPHOMA - A CLINICOPATHOLOGICAL ANALYSIS OF 9 PATIENTS WITH HODGKINS-DISEASE AND B-CELL NON-HODGKINS-LYMPHOMA SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE MALIGNANT LYMPHOMA; COMPOSITE LYMPHOMA; HODGKINS DISEASE; IMMUNOHISTOCHEMISTRY ID IMMUNOGLOBULIN GENE REARRANGEMENTS; REED-STERNBERG CELLS; NODULAR PARAGRANULOMA; PREDOMINANCE TYPE; LYMPHOCYTIC PREDOMINANCE; FEATURES; ORIGIN AB Nine patients had composite lymphoma in which Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) involved the same anatomic site. Two of these patients had relapses of their tumors. In one, the initial biopsy specimen contained follicular and diffuse large cell NHL with unclassifiable HD, but the relapse showed diffuse large cell NHL with nodular sclerosis HD. In the other patient, both biopsy specimens showed follicular mixed NHL; the HD component in the initial biopsy specimen was nodular sclerosis, whereas, at relapse, it had the appearance of interfollicular HD. In the remaining seven patients, the HD component was subclassified as nodular sclerosis (three specimens) or mixed cellularity (three specimens), or it was unclassifiable (one specimen). The NHL component was categorized as diffuse large cell (two specimens), diffuse large cell immunoblastic (two specimens), follicular and diffuse large cell (one specimen), diffuse mixed small and large cell (one specimen), and lymphocytic lymphoma of intermediate differentiation (modified Rappaport classification) (one specimen). Paraffin section immunoperoxidase studies were done on the NHL component in eight patients (nine specimens) and on the HD component in six patients (seven specimens). In each of these, the NHL component was leukocyte common antigen (LCA) positive and Leu-M1 negative. In addition, the neoplastic cells were L26 positive and UCHL-1 negative, indicating a B-cell phenotype. In five of seven immunophenotyped cases, Reed-Sternberg (RS) and Hodgkin's (H) cells from the HD areas were Leu-M1 positive and LCA negative, reflecting an immunophenotype that is typical of non-lymphocyte-predominant HD. In two specimens, the malignant cells were negative for Leu-M1 and LCA (with positive internal controls). Composite lymphomas composed of HD and NHL are unusual, and cases of coexistent HD of the non-lymphocyte-predominant subtype and NHL are even less common. The results of the current study and a review of the literature indicate that this phenomenon usually involves a B-cell NHL that coexists with HD, perhaps further suggesting a close relationship between the malignant cells of HD (RS and H cells) and B lymphocytes. C1 NCI,PATHOL LAB,HEMATOPATHOL SECT,BLDG 10,ROOM 2N202,BETHESDA,MD 20892. NR 40 TC 88 Z9 90 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD JUL PY 1991 VL 96 IS 1 BP 81 EP 89 PG 9 WC Pathology SC Pathology GA FV539 UT WOS:A1991FV53900013 PM 2069139 ER PT J AU PERLMAN, JA SPIRTAS, R KELAGHAN, J MADANS, J COX, C KLEINMAN, J AF PERLMAN, JA SPIRTAS, R KELAGHAN, J MADANS, J COX, C KLEINMAN, J TI VASECTOMY AND THE RISK OF PROSTATE-CANCER SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter C1 NATL CTR HLTH STAT,HYATTSVILLE,MD 20782. RP PERLMAN, JA (reprint author), NICHHD,BETHESDA,MD 20892, USA. NR 8 TC 18 Z9 18 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUL 1 PY 1991 VL 134 IS 1 BP 107 EP 108 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA FX669 UT WOS:A1991FX66900012 ER PT J AU WAUGH, WN TRISSEL, LA STELLA, VJ AF WAUGH, WN TRISSEL, LA STELLA, VJ TI STABILITY, COMPATIBILITY, AND PLASTICIZER EXTRACTION OF TAXOL (NSC-125973) INJECTION DILUTED IN INFUSION SOLUTIONS AND STORED IN VARIOUS CONTAINERS SO AMERICAN JOURNAL OF HOSPITAL PHARMACY LA English DT Article DE ANTINEOPLASTIC AGENTS; CONCENTRATION; CONTAINERS; CONTAMINATION; DEXTROSE; DIETHYLHEXYL PHTHALATE; GLASS; INCOMPATIBILITIES; INJECTIONS; PLASTICIZERS; POLYETHYLENE; POLYOLEFIN; POLYVINYL CHLORIDE; PRECIPITATION; SODIUM CHLORIDE; STABILITY; STORAGE; SURGICAL SUPPLIES; TAXOL; VEHICLES ID BAGS; PHTHALATE AB The stability of taxol (NSC-125973) in various diluents and containers was determined, and the extent of leaching of di(2-ethylhexyl) phthalate (DEHP) from polyvinyl chloride (PVC) bags caused by the taxol formulation was measured. A taxol formulation consisting of a 6-mg/mL solution of taxol in 50% polyoxyethylated castor oil and 50% dehydrated ethanol was added to 50- and 100-mL glass bottles, PVC infusion bags, and polyolefin containers containing 5% dextrose injection or 0.9% sodium chloride injection to give initial nominal taxol concentrations of 0.3, 0.6, 0.9, and 1.2 mg/mL. The containers were maintained at 20-23-degrees-C for 12-24 hours. Samples were assayed by stability-indicating high-performance liquid chromatography, and clarity was determined visually. An experiment was run to ascertain whether DEHP would leach from a PVC administration set during a simulated infusion. There was no substantial loss of taxol over 24 hours. Filtration through a membrane resulted in no loss of taxol. All the solutions initially appeared hazy. Solutions stored in PVC bags became more hazy with time than solutions stored in glass or polyolefin containers. The haze seen in PVC bags was traced to leaching of DEHP. Agitation had no effect on the extent of leaching. Leaching was also seen during simulated delivery through PVC administration sets. No DEHP was detected when solutions were stored in glass or polyolefin containers and infused through polyethylene-lined sets. At the dilutions studied, taxol was visually and chemically stable for up to 24 hours. To minimize patient exposure to DEHP, taxol solutions may be stored in a glass or polyolefin container and delivered through a polyethylene-lined i.v. administration set. C1 UNIV KANSAS,DEPT PHARMACEUT CHEM,MALOTT HALL,LAWRENCE,KS 66045. MD ANDERSON CANC CTR,INVEST PHARMACEUT SERV,HOUSTON,TX. NIH,PHARMACEUT RESOURCES BRANCH,BETHESDA,MD 20892. FU NCI NIH HHS [N01-CM-67912, N01-CM-97576] NR 5 TC 118 Z9 124 U1 1 U2 19 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 SN 0002-9289 J9 AM J HOSP PHARM JI Am. J. Hosp. Pharm. PD JUL PY 1991 VL 48 IS 7 BP 1520 EP 1524 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA FU188 UT WOS:A1991FU18800031 PM 1679294 ER PT J AU PODUSLO, SE DEAN, M KOLCH, U OBRIEN, SJ AF PODUSLO, SE DEAN, M KOLCH, U OBRIEN, SJ TI DETECTING HIGH-RESOLUTION POLYMORPHISMS IN HUMAN CODING LOCI BY COMBINING PCR AND SINGLE-STRAND CONFORMATION POLYMORPHISM (SSCP) ANALYSIS SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID DNA POLYMORPHISMS; CYSTIC-FIBROSIS; SEQUENCE; MUTATIONS; MULTIPLE; ONCOGENE; KINASE; GENES AB A strategy is described that allows the development of polymorphic genetic markers to be characterized in individual genes. Segments of the 3' untranslated regions are amplified, and polymorphisms are detected by digestion with frequently cutting enzymes and with the detection of single-stranded conformation polymorphisms. This allows these genes, or DNA segments, to be placed on the linkage maps of human chromosomes. Polymorphisms in two genes have been identified using this approach. A HaeIII polymorphism was detected in the KIT proto-oncogene, physically assigned to chromosome 4q11-12. This polymorphism is linked to other chromosome 4p markers and is in linkage disequilibrium with a HindIII polymorphism previously described at this locus. We have also identified in the insulin-like growth factor1 receptor gene (IGF1R) a 2-bp deletion that is present at a frequency of .25 in the Caucasian population. Pedigree analysis with this insertion/deletion polymorphism placed the IGF1R gene at the end of the current linkage map of chromosome 15q, consistent with the physical assignment of 15q2526. Thus, polymorphisms in specific genes can be used to relate the physical, genetic, and comparative maps of mammalian genomes and to simplify the testing of candidate genes for human diseases. C1 NCI,FREDERICK CANC RES & DEV CTR,INC DYNCORP,PROGRAM RESOURCES,BLDG 560,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 FU NCI NIH HHS [N01-CO-74102] NR 25 TC 52 Z9 53 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 JUL PY 1991 VL 49 IS 1 BP 106 EP 111 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA FW511 UT WOS:A1991FW51100013 PM 1676559 ER PT J AU EPSTEIN, CJ KORENBERG, JR ANNEREN, G ANTONARAKIS, SE AYME, S COURCHESNE, E EPSTEIN, LB FOWLER, A GRONER, Y HURET, JL KEMPER, TL LOTT, IT LUBIN, BH MAGENIS, E OPITZ, JM PATTERSON, D PRIEST, JH PUESCHEL, SM RAPOPORT, SI SINET, PM TANZI, RE DELACRUZ, F AF EPSTEIN, CJ KORENBERG, JR ANNEREN, G ANTONARAKIS, SE AYME, S COURCHESNE, E EPSTEIN, LB FOWLER, A GRONER, Y HURET, JL KEMPER, TL LOTT, IT LUBIN, BH MAGENIS, E OPITZ, JM PATTERSON, D PRIEST, JH PUESCHEL, SM RAPOPORT, SI SINET, PM TANZI, RE DELACRUZ, F TI PROTOCOLS TO ESTABLISH GENOTYPE-PHENOTYPE CORRELATIONS IN DOWN-SYNDROME SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID ADULT DOWNS-SYNDROME; ATLANTO-AXIAL INSTABILITY; QUANTITATIVE CT ANALYSIS; BRAIN-STEM RESPONSES; ALZHEIMERS-DISEASE; GLUCOSE-UTILIZATION; SYNDROME CHILDREN; DIFFERENT AGES; CHROMOSOME-21; REGION C1 NICHHD,MENTAL RETARDAT & DEV DISABIL BRANCH,EXECUT PLAZA N,ROOM 631,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,DEPT PEDIAT,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,CANC RES INST,SAN FRANCISCO,CA 94143. CEDARS SINAI MED CTR,DEPT PEDIAT,LOS ANGELES,CA 90048. UNIV HOSP UPPSALA,DEPT CLIN GENET,UPPSALA,SWEDEN. JOHNS HOPKINS UNIV,SCH MED,CTR MED GENET,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21205. HOP ENFANTS LA TIMONE,CTR GENET MED,F-13385 MARSEILLE 4,FRANCE. UNIV CALIF SAN DIEGO,SCH MED,DEPT NEUROSCI,LA JOLLA,CA 92093. HASKINS LABS INC,NEW HAVEN,CT 06511. WEIZMANN INST SCI,DEPT MOLEC GENET & VIROL,IL-76100 REHOVOT,ISRAEL. BOSTON CITY HOSP,DEPT NEUROL,BOSTON,MA 02118. CHR MIL,CNRS,URA 1338,PORTIERS,FRANCE. MASSACHUSETTS GEN HOSP,DEPT NEUROGENET,BOSTON,MA 02114. UNIV CALIF IRVINE,MED CTR,DEPT PEDIAT,IRVINE,CA 92717. CHILDRENS HOSP MED CTR NO CALIF,RES INST,OAKLAND,CA 94609. OREGON HLTH SCI UNIV,CTR CHILD DEV REHABIL,PORTLAND,OR 97201. SHODAIR CHILDRENS HOSP,HELENA,MT. ELEANOR ROOSEVELT INST CANC RES,DENVER,CO. EMORY UNIV,DEPT MED GENET,ATLANTA,GA 30322. RHODE ISL HOSP,CTR CHILD DEV,PROVIDENCE,RI 02902. BROWN UNIV,PROGRAM MED,PROVIDENCE,RI 02912. NIA,NEUROSCI LAB,BETHESDA,MD 20892. HOP NECKER ENFANTS MALAD,BIOCHIM GENET LAB,CNRS,URA 1335,F-75730 PARIS 15,FRANCE. RI Antonarakis, Stylianos/N-8866-2014 OI Antonarakis, Stylianos/0000-0001-8907-5823 FU NCI NIH HHS [CA-27903, CA-44446]; NIA NIH HHS [AG-08938] NR 92 TC 114 Z9 115 U1 0 U2 11 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JUL PY 1991 VL 49 IS 1 BP 207 EP 235 PG 29 WC Genetics & Heredity SC Genetics & Heredity GA FW511 UT WOS:A1991FW51100024 PM 1829580 ER PT J AU HOFFMAN, A GROSSMAN, E KEISER, HR AF HOFFMAN, A GROSSMAN, E KEISER, HR TI INCREASED PLASMA-LEVELS AND BLUNTED EFFECTS OF BRAIN NATRIURETIC PEPTIDE IN RATS WITH CONGESTIVE-HEART-FAILURE SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE BRAIN NATRIURETIC PEPTIDE; ATRIAL NATRIURETIC FACTOR; CONGESTIVE HEART FAILURE; RENAL FUNCTION; RADIOIMMUNOASSAY AB The hemodynamic and renal effects of brain natriuretic peptide (BNP) were studied in conscious rats with experimental congestive heart failure (CHF) produced by an aortocaval fistula. The peptide had potent hypotensive, diuretic, and natriuretic effects in control rats, all of which were abolished in CHF. Plasma levels of BNP increased time-dependently during the development of CHF, and were more than four-fold higher in sodium retaining rats than in control rats. The data suggest that BNP secretion from the atria is increased in CHF, and that resistance to BNP, in addition to the relative resistance to atrial natriuretic factor, may contribute to sodium retention in CHF. RP HOFFMAN, A (reprint author), NHLBI,BLDG 10,ROOM 8C103,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 22 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD JUL PY 1991 VL 4 IS 7 BP 597 EP 601 PN 1 PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA FW770 UT WOS:A1991FW77000006 PM 1831369 ER PT J AU AMANDUS, HE SHY, C WING, S BLAIR, A HEINEMAN, EF AF AMANDUS, HE SHY, C WING, S BLAIR, A HEINEMAN, EF TI SILICOSIS AND LUNG-CANCER IN NORTH-CAROLINA DUSTY TRADES WORKERS SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE SILICOSIS; LUNG CANCER; MINING; CONSTRUCTION TRADES; FOUNDRY WORKERS; QUARRY EXPOSURES; ASBESTOS PRODUCTS; COAL WORKERS PNEUMOCONIOSIS; TUBERCULOSIS; NON-WHITES ID MORTALITY; PNEUMOCONIOSIS; EXPOSURE AB Since 1940, 760 cases of silicosis have been diagnosed as part of the State of North Carolina's (NC) pneumoconiosis surveillance program for dusty trades workers. Vital status was ascertained through 1983 for 714 cases that had been diagnosed since 1940 and death certificates were obtained for 546 of the 550 deceased. Mortality from tuberculosis, cancer of the intestine and lung, pneumonia, bronchitis, emphysema, asthma, pneumoconiosis, and kidney disease was significantly increased in whites. Mortality from tuberculosis, ischemic heart disease, and pneumoconiosis was significantly increased in non-whites. The standardized mortality ratio (95% CI) for lung cancer based on U.S. rates was 2.6 (1.8-3.6) in whites, 2.3 (1.5-3.4) in those who had no exposure to other known occupational carcinogens, and 2.4 (1.5-3.6) in those who had no other exposure and who had been diagnosed for silicosis while employed in the NC dusty trades. Age-adjusted lung cancer rates in silicotics who had no exposure to other known occupational carcinogens were 1.5 (.8-2.9) times higher than that in a referent group of coal miners with coalworkers' pneumoconiosis (CWP) and 2.4 (1.5-3.9) times higher than that in a referent group of non-silicotic metal miners. Age- and smoking-adjusted rates in silicotics were 3.9 (2.4-6.4) times higher than that in metal miners. This analysis effectively controls for confounding by age, cigarette smoking, and exposure to other known occupational carcinogens, and it is unlikely that other correlates of silica exposure could explain the excess lung cancer mortality in the silicotics. C1 NCI,OCCUPAT STUDIES SECT,ROCKVILLE,MD. UNIV N CAROLINA,OCCUPAT HLTH STUDIES GRP,CHAPEL HILL,NC 27514. RP AMANDUS, HE (reprint author), NIOSH,DIV RESP DIS STUDIES,944 CHESTNUT RIDGE RD,MORGANTOWN,WV 26505, USA. NR 35 TC 41 Z9 41 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 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD JUL PY 1991 VL 20 IS 1 BP 57 EP 70 DI 10.1002/ajim.4700200106 PG 14 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA FR855 UT WOS:A1991FR85500005 PM 1867218 ER PT J AU BRUGGEMAN, LA HORIKOSHI, S BURBELO, PD YAMADA, Y KLOTMAN, PE AF BRUGGEMAN, LA HORIKOSHI, S BURBELO, PD YAMADA, Y KLOTMAN, PE TI PHYSIOLOGY AND CELL BIOLOGY UPDATE - MECHANISMS OF TYPE-IV COLLAGEN GENE-REGULATION SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Editorial Material DE TYPE-IV COLLAGEN; GENE REGULATION; PROMOTER; ENHANCER; GLOMERULOSCLEROSIS ID DNA-BINDING PROTEINS; MESSENGER-RNA; GEL-ELECTROPHORESIS; TRANSCRIPTIONAL REGULATION; SEQUENCE; EXPRESSION; METHYLATION; ALPHA-1(IV); COMPONENTS; PROMOTERS C1 NIDR,DEV BIOL & ANOMALIES LAB,BLDG 30,ROOM 433,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. RI Burbelo, Peter/B-1027-2009 NR 33 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JUL PY 1991 VL 18 IS 1 BP 134 EP 139 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA FW766 UT WOS:A1991FW76600023 PM 2063849 ER PT J AU ISHIKIRIYAMA, S SAWADA, H NAMBU, H NIIKAWA, N AF ISHIKIRIYAMA, S SAWADA, H NAMBU, H NIIKAWA, N TI CROSSED POLYDACTYLY TYPE-I IN A MOTHER AND SON - AN AUTOSOMAL DOMINANT TRAIT SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE CROSSED POLYDACTYLY; PREAXIAL POLYDACTYLY; POSTAXIAL POLYDACTYLY; FAMILIAL POLYDACTYLY; AUTOSOMAL DOMINANT INHERITANCE AB In a Japanese family, a propositus and his mother had crossed polydactyly type I. A maternal grandaunt also had preaxial polydactyly of the feet. The findings that both of the mother and son had the identical type of polydactyly are consistent with an autosomal dominant inheritance with variable expressivity. Other explanations include X-linked recessive inheritance, polygenic inheritance, and a chance occurrence of the 2 different kinds of polydactyly. C1 CHIBA CHILDRENS HOSP,DIV MED GENET,CHIBA,JAPAN. TENSHI HOSP,DIV PEDIAT,SAPPORO,JAPAN. NAGASAKI UNIV,SCH MED,DEPT HUMAN GENET,NAGASAKI 852,JAPAN. RP ISHIKIRIYAMA, S (reprint author), NIDOCD,MOLEC OTOL LAB,BLDG 36,ROOM 5D08,BETHESDA,MD 20892, USA. NR 15 TC 8 Z9 9 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 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD JUL 1 PY 1991 VL 40 IS 1 BP 41 EP 43 DI 10.1002/ajmg.1320400108 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA FU021 UT WOS:A1991FU02100007 PM 1887848 ER PT J AU BIZZI, A HILL, JM BROOKS, RA DICHIRO, G AF BIZZI, A HILL, JM BROOKS, RA DICHIRO, G TI IS PERLS STAIN SPECIFIC FOR HEMOSIDERIN SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Letter ID CEREBRAL-HEMORRHAGE; MR APPEARANCE; FERRITIN; IRON; BRAIN; RATS RP BIZZI, A (reprint author), NIH,BETHESDA,MD 20892, USA. RI Bizzi, Alberto/K-3141-2016 OI Bizzi, Alberto/0000-0002-0253-5274 NR 7 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD JUL-AUG PY 1991 VL 12 IS 4 BP 805 EP 805 PG 1 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA FU351 UT WOS:A1991FU35100047 PM 1715666 ER PT J AU RHOADS, GG MCNELLIS, DC KESSEL, SS AF RHOADS, GG MCNELLIS, DC KESSEL, SS TI HOME MONITORING OF UTERINE CONTRACTILITY SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material DE PRETERM DELIVERY; TOCODYNAMOMETRY; UTERINE MONITORING ID PROSPECTIVE RANDOM TRIAL; PRETERM LABOR; AMBULATORY PATIENTS; INCREASED RISK; PREGNANCIES AB At an interdisciplinary workshop on home monitoring of uterine activity, participants reviewed the basis of this technology and its use in the identification of women at high risk of preterm delivery and in the prevention of preterm birth. Although the guard-ring devices in current use appear capable of detecting uterine activity, they do not clearly distinguish between Braxton Hicks contractions and the contractions of early labor. There was agreement that women destined for preterm delivery have more uterine activity on average than do other women of comparable gestational age but that there is substantial overlap between the two groups. Thus it is uncertain whether this difference can be used effectively for screening purposes. Conferees agreed that there is considerable evidence that twice-daily monitoring of very-high-risk women, in conjunction with daily nursing support and high-quality obstetric care, may prevent preterm births. Available evidence does not clearly distinguish the contribution of tocodynamometry from that of nursing support. A number of areas were identified in which further research is needed. C1 NICHHD,6TH FLOOR,EPN BLDG,BETHESDA,MD 20892. NR 21 TC 14 Z9 14 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 JUL PY 1991 VL 165 IS 1 BP 2 EP 6 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA FY358 UT WOS:A1991FY35800002 PM 1677235 ER PT J AU BATISTA, MC BRISTOW, TL MATHEWS, J STOKES, WS LORIAUX, DL NIEMAN, LK AF BATISTA, MC BRISTOW, TL MATHEWS, J STOKES, WS LORIAUX, DL NIEMAN, LK TI DAILY ADMINISTRATION OF THE PROGESTERONE ANTAGONIST RU-486 PREVENTS IMPLANTATION IN THE CYCLING GUINEA-PIG SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE RU-486; GUINEA PIG; CONTRACEPTION; IMPLANTATION ID PLASMA PROGESTERONE; ESTROUS-CYCLE; CONTRAGESTION; INHIBITION; MATURATION; TRANSPORT; OVULATION; RECEPTOR; RU486; RATS AB Since progesterone is required to prepare the endometrium for implantation of an embryo, a progesterone antagonist may inhibit nidation and thus prevent pregnancy. We addressed this possibility in the guinea pig, the small laboratory animal whose reproductive physiology most resembles that of women. Daily administration of the antiprogestin RU 486 (0, 1, 2, or 3 mg/kg, subcutaneously) for 9 days after mating inhibited implantation in a dose-dependent fashion. When this compound was given daily throughout the estrous cycle, cyclic vaginal changes, ovulation, and mating were suppressed in up to 17%, 28%, and 55% of animals, respectively. Two of seven mated female animals receiving RU 486, 1 mg/kg/day, had implantation sites. Nidation was completely blocked at higher doses. Thus daily antiprogestin administration prevented pregnancy in sexually active, normally cycling guinea pigs. A similar strategy using a daily antinidatory dose of an antiprogestin may offer a novel approach to human fertility control. C1 NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NICHHD,INTRAMURAL RES PROGRAM,BETHESDA,MD 20892. NR 24 TC 21 Z9 21 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 JUL PY 1991 VL 165 IS 1 BP 82 EP 86 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA FY358 UT WOS:A1991FY35800019 PM 1853922 ER PT J AU VANKRIEKEN, JHJM ELWOOD, L ANDRADE, RE JAFFE, ES COSSMAN, J MEDEIROS, LJ AF VANKRIEKEN, JHJM ELWOOD, L ANDRADE, RE JAFFE, ES COSSMAN, J MEDEIROS, LJ TI REARRANGEMENT OF THE T-CELL RECEPTOR DELTA CHAIN GENE IN T-CELL LYMPHOMAS WITH A MATURE PHENOTYPE SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID LYMPHOPROLIFERATIVE DISORDERS; ANTIGEN RECEPTOR; HODGKINS-DISEASE; NEOPLASMS; CLONALITY; LINEAGE; MALIGNANCIES; MARKERS; EXPRESSION; DIAGNOSIS AB The configuration of the T-cell receptor (TCR) delta chain gene was assessed using restriction fragment analysis and the Southern blot technique in 39 T-cell lymphomas with a mature immunophenotype. The TCR-delta-gene was rearranged in four lymphomas although the gamma/delta-TCR was not expressed in two cases studied. The TCR-delta-gene was the only TCR gene rearranged in two cases. Each lymphoma with TCR-delta-gene rearrangement had an aberrant T-cell immunophenotype and three cases were of the large cell anaplastic type. The TCR-delta-gene was deleted in 22 cases and was in the germline configuration in 13 lymphomas. Deletion of the TCR-delta-gene was characteristic of mycosis fungoides, adult T-cell leukemia/lymphoma (human T cell leukemia-lymphoma virus positive), and Lennert's lymphoma, and was not identified in angiocentric lymphomas. In eight cases with TCR-delta deletion, however, a large number of polyclonal (presumably reactive) T cells were present and, in these lymphomas, the authors could not determine if TCR-delta-gene deletion occurred in the polyclonal T cells, the neoplastic cells, or both cell populations. The authors conclude that the TCR-delta-gene is usually deleted in mature T-cell lymphomas, as would be expected in alpha/beta-TCR T cells. However, TCR-delta-gene rearrangement is detectable in approximately 10% of cases. Analysis of this locus may be useful diagnostically, as it occasionally may be the only molecular marker of clonality in mature T-cell lymphomas. T-cell receptor delta chain gene rearrangement also is found most often in lymphomas of the large cell anaplastic type. C1 NCI,PATHOL LAB,HEMATOPATHOL SECT,BLDG 10,ROOM 2N108,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,DEPT PATHOL,WASHINGTON,DC 20007. RI van Krieken, Joannes/D-4138-2009 OI van Krieken, Joannes/0000-0001-6544-1040 NR 32 TC 19 Z9 19 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUL PY 1991 VL 139 IS 1 BP 161 EP 168 PG 8 WC Pathology SC Pathology GA FV816 UT WOS:A1991FV81600018 PM 1830192 ER PT J AU LEE, SI TURNER, RJ AF LEE, SI TURNER, RJ TI MECHANISM OF SECRETAGOGUE-INDUCED HCO3- AND CL- LOSS FROM RAT PAROTID ACINI SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE CHLORIDE CHANNEL; BICARBONATE SECRETION; FLUID SECRETION; MUSCARINIC STIMULATION; EXOCRINE GLAND; SALIVA ID MANDIBULAR SALIVARY-GLAND; ACTIVATED POTASSIUM CHANNELS; FLUID SECRETION; INTRACELLULAR PH; BICARBONATE SECRETION; CELLS; TRANSPORT; CALCIUM; MEMBRANE; RELEASE AB The Cl-- and HCO3--dependent components of muscarinic agonist (carbachol)-induced K+ loss from a rat parotid mince were studied using Rb-86+ as a K+ marker. Both components of Rb-86+ loss were blunted by K+ and Cl- channel blockers and by removal of extracellular Ca2+, consistent with the hypothesis that Rb-86+ loss occurs via a Ca2+-activated K+ channel and that this cation loss serves to electrically balance a concomitant loss of the corresponding anion via one or more conductive pathways (channels). Two tissue "pools" of Rb-86+ were observed, a carbachol-sensitive pool and a carbachol-insensitive pool (approximately 70 and approximately 30% of the total Rb-86+ content, respectively). There was no evidence for a time-dependent desensitization of the muscarinic response of the carbachol-sensitive pool. Cl--dependent Rb-86+ loss was not affected by HCO3- addition, suggesting that both Cl- and HCO3- secretion are accompanied by Rb-86+ loss from the same pool and thus occur from the same cells. HCO3--dependent Rb-86+ loss was not enhanced by lowering the extracellular Na+ concentration, indicating that the HCO3- exit pathway is not a Na+-HCO3- symport. The data are consistent with the postulate that Cl- and HCO3- are secreted by rat parotid acinar cells via the same or very similar conductive transport pathways in response to muscarinic stimulation. C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,BLDG 10,RM 1A06,BETHESDA,MD 20892. NR 40 TC 17 Z9 17 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD JUL PY 1991 VL 261 IS 1 BP G111 EP G118 PN 1 PG 8 WC Physiology SC Physiology GA FY356 UT WOS:A1991FY35600059 PM 1713414 ER PT J AU OTSUKA, T WEI, L ACUFF, VR SHIMIZU, A PETTIGREW, KD PATLAK, CS FENSTERMACHER, JD AF OTSUKA, T WEI, L ACUFF, VR SHIMIZU, A PETTIGREW, KD PATLAK, CS FENSTERMACHER, JD TI VARIATION IN LOCAL CEREBRAL BLOOD-FLOW RESPONSE TO HIGH-DOSE PENTOBARBITAL SODIUM IN THE RAT SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE BLOOD FLOW REGULATION; FOREBRAIN; HINDBRAIN; CIRCUMVENTRICULAR ORGANS ID GLUCOSE-UTILIZATION; C-14 IODOANTIPYRINE; AWAKE RAT; METABOLISM; NICOTINE AB Microvascular bed structure and functions are known to vary throughout the brain. Microvascular responses to high doses of pentobarbital sodium might therefore differ among brain areas. This possibility was examined by measuring local cerebral blood flow (LCBF) with [C-14]iodoantipyrine in 52 brain areas at 5, 10, 25, and 60 min after intraperitoneal administration of pentobarbital (50 mg/kg). From 5 to 60 min, LCBF was significantly lowered in 17 of 25 forebrain gray matter areas but in only 1 of 18 hindbrain gray matter structures, the pontine nuclei. Smaller, shorter duration lowering of LCBF was also observed in ten other brain areas. In both control and treated rats, LCBF was found to vary within individual brain structures. The pattern of these LCBF variations was columnar in the cerebral cortex and the hippocampus but was patchy in the caudate-putamen, thalamus, and inferior colliculus. These results indicate that pentobarbital anesthesia more strongly alters LCBF in the forebrain than in the hindbrain and produces different patterns of changes in LCBF than in local cerebral glucose utilization, which was measured with 2-deoxyglucose in a companion study. C1 SUNY STONY BROOK,HLTH SCI CTR,DEPT NEUROL SURG,T12-080,STONY BROOK,NY 11794. NIMH,DIV BIOMETRY & APPL SCI,BETHESDA,MD 20892. FU NINDS NIH HHS [NS-21157, NS-35791] NR 28 TC 41 Z9 41 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD JUL PY 1991 VL 261 IS 1 BP H110 EP H120 PN 2 PG 11 WC Physiology SC Physiology GA FY357 UT WOS:A1991FY35700017 PM 1858910 ER PT J AU TSUTSUMI, K SAAVEDRA, JM AF TSUTSUMI, K SAAVEDRA, JM TI CHARACTERIZATION AND DEVELOPMENT OF ANGIOTENSIN-II RECEPTOR SUBTYPES (AT1 AND AT2) IN RAT-BRAIN SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE ANGIOTENSIN RECEPTOR SUBTYPES; DUPONT 753; CGP-42112A; RENIN-ANGIOTENSIN SYSTEM; RECEPTOR DEVELOPMENT ID ATRIAL-NATRIURETIC-PEPTIDE; BINDING-SITES; PARAVENTRICULAR NUCLEUS; SUBFORNICAL ORGAN; HYPERTENSIVE RATS; AUTORADIOGRAPHY; DITHIOTHREITOL; ANTAGONISTS; CORTEX AB Angiotensin II receptor subtypes (AT1 and AT2) were characterized in rat brain by displacement with the specific angiotensin antagonists Du Pont 753 and CGP 42112A, respectively, and quantitative autoradiography. Young (2-wk-old) rats expressed AT1 receptors in selected limbic system areas, structures involved in cardiovascular and fluid regulation, parts of the hippocampal formation, and the choroid plexus. In young rats, AT2 receptors were concentrated in areas involved in control and learning of motor activity, sensory areas, and selected limbic system structures. The cingulate cortex, the molecular layer of the cerebellar cortex, and the superior colliculus contained both AT1 and AT2 receptors. The number of AT1 receptors in most areas of adult (8-wk-old) rats was similar to or even higher than that present in young rats. Conversely, AT2 receptors were always much lower in number in adult animals, and in some areas they were undetectable in adults. Their differential localization and development suggest different functions for the specific angiotensin II receptor subtypes. C1 NIMH,PHARMACOL SECT,CLIN SCI LAB,9000 ROCKVILLE PIKE,BLDG 10,ROOM 2D-45,BETHESDA,MD 20892. NR 31 TC 294 Z9 294 U1 1 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD JUL PY 1991 VL 261 IS 1 BP R209 EP R216 PN 2 PG 8 WC Physiology SC Physiology GA FY357 UT WOS:A1991FY35700067 PM 1858948 ER PT J AU SALIVE, ME AF SALIVE, ME TI PREVENTIVE MEDICINE RESIDENCY TRAINING - A RESIDENTS PERSPECTIVE SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article AB Preventive medicine as a discipline confronts considerable internal and external pressure today about society's needs for prevention specialists. Training in the field has remained static in the face of great changes. This article asserts the need to reassess the philosophy, content, and structure of graduate training in preventive medicine. The field of preventive medicine faces an identity crisis of its own making, trying to be everything to everybody. The need for funding to overcome the shortage of specialists remains a critical but difficult issue that demands innovative solutions. RP SALIVE, ME (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,9000 WISCONSIN AVE,FED BLDG,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD JUL-AUG PY 1991 VL 7 IS 4 BP 248 EP 251 PG 4 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA HG425 UT WOS:A1991HG42500012 PM 1756063 ER PT J AU SCHMIDT, PJ RUBINOW, DR AF SCHMIDT, PJ RUBINOW, DR TI MENOPAUSE-RELATED AFFECTIVE-DISORDERS - A JUSTIFICATION FOR FURTHER STUDY SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID RAT-BRAIN; INVOLUTIONAL MELANCHOLIA; PSYCHOLOGICAL SYMPTOMS; GONADAL-STEROIDS; WOMEN; ESTROGEN; PROGESTERONE; DEPRESSION; ESTRADIOL; HORMONES AB Despite descriptions dating back to the nineteenth century of menopause-related affective syndromes, recent investigations have been unable to characterize a specific disturbance of mood or behavior related to this period of life. In this article the authors identify a number of methodologic problems in earlier studies and suggest that further study is warranted and that it is premature to conclude that menopause-related affective syndromes do not exist. They then provide guidelines for examining mood and behavioral changes that take place during the climacteric and menopause, with the hope of stimulating further research which may determine whether menopause-related affective disorders exist and, if so, their characteristics. RP SCHMIDT, PJ (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,RM 3N238,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 70 TC 102 Z9 108 U1 2 U2 4 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUL PY 1991 VL 148 IS 7 BP 844 EP 852 PG 9 WC Psychiatry SC Psychiatry GA FU836 UT WOS:A1991FU83600003 PM 2053622 ER PT J AU LEVINE, SH BYSTRITSKY, A BARON, D JONES, LD AF LEVINE, SH BYSTRITSKY, A BARON, D JONES, LD TI GROUP-PSYCHOTHERAPY FOR HIV-SEROPOSITIVE PATIENTS WITH MAJOR DEPRESSION SO AMERICAN JOURNAL OF PSYCHOTHERAPY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; IMMUNE-DEFICIENCY SYNDROME; SYNDROME AIDS; 3'-AZIDO-2',3'-DIDEOXYTHYMIDINE; ZIDOVUDINE; DISORDERS AB Patients were recruited from the UCLA AIDS Research Center who had previously been referred to psychiatry for participation in an open-label pilot program that treated patients with major depression with fluoxetine. They chose to participate in group therapy to get help in coping with their HIV-seropositive status, problems at home and work, dissolution of their support system, "accepting patienthood," and being placed on an experimental medical protocol. This closed, twenty-session, homogeneous (for patient characteristics), psychoeducational, supportive and cognitively oriented psychotherapy group was successful. C1 UNIV CALIF IRVINE,PSYCHIAT,IRVINE,CA 92717. UNIV CALIF LOS ANGELES,DEPT PSYCHIAT & BEHAV SCI,LOS ANGELES,CA 90024. NIMH,INTRAMURAL RES PROGRAM,WASHINGTON,DC 20032. UNIV CALIF LOS ANGELES,SUNSET KAISER PERMANENTE MED CTR,DEPT PSYCHIAT,LOS ANGELES,CA 90024. NR 28 TC 15 Z9 16 U1 1 U2 1 PU ASSN ADVAN PSYCHOTHERAPY PI BRONX PA BELFER EDUC CENTER, ROOM 402 ALBERT EINSTEIN COLL MED 1300 MORRIS PARK AVE, BRONX, NY 10461-1602 SN 0002-9564 J9 AM J PSYCHOTHER JI Am. J. Psychother. PD JUL PY 1991 VL 45 IS 3 BP 413 EP 424 PG 12 WC Psychology, Clinical; Psychiatry; Psychology; Psychology, Psychoanalysis SC Psychology; Psychiatry GA GC137 UT WOS:A1991GC13700009 PM 1951789 ER PT J AU ZAHM, SH COCCO, P BLAIR, A AF ZAHM, SH COCCO, P BLAIR, A TI TOBACCO SMOKING AS A RISK FACTOR FOR COLON POLYPS SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID LARGE-BOWEL-CANCER; COLORECTAL POLYPS; BRITISH DOCTORS; UNITED-STATES; MORTALITY; ALCOHOL; PREVALENCE; ADENOMAS; ETIOLOGY; PATTERN AB Background: Data from a cancer screening project among pattern makers were used to evaluate the association between tobacco smoking and prevalence of colon polyps. Methods: From 1981-1983, 549 White men were examined by flexible sigmoidoscopy and completed self-administered questionnaires including smoking histories. Results: One or more colon polyps were detected in 76 men. Standardized prevalence rates (SPR) for polyps increased by smoking category (never smoked = 0.094; ex-smokers = 0.118, current smokers = 0.214) and by cigarettes per day, years of smoking, and pack-years among both current and ex-smokers. Both adenomatous and hyperplastic polyps showed an association with smoking while other types of polyps and polyps with unspecified histology did not. The risk associated with smoking was greater for polyps greater than one centimeter in diameter. An interaction with occupational exposures was suggested by a greater increase in the SPR for polyps among current smokers employed as pattern makers for more than 10 years than among current smokers similarly employed for 10 years or less. Conclusions: Since at least some colon polyps are considered precursor lesions to colon cancer, one of the most common cancers in the United States, this report suggests that the possible link between colon polyps and smoking deserves further evaluation. RP ZAHM, SH (reprint author), NCI,OCCUPAT STUDIES SECT,EXECUT PLAZA N,ROOM 418,ROCKVILLE,MD 20892, USA. RI Zahm, Shelia/B-5025-2015 NR 28 TC 48 Z9 49 U1 0 U2 2 PU AMER PUBLIC HEALTH ASSN INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUL PY 1991 VL 81 IS 7 BP 846 EP 849 DI 10.2105/AJPH.81.7.846 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA GD161 UT WOS:A1991GD16100007 PM 2053658 ER PT J AU SICHIERI, R EVERHART, JE ROTH, H AF SICHIERI, R EVERHART, JE ROTH, H TI A PROSPECTIVE-STUDY OF HOSPITALIZATION WITH GALLSTONE DISEASE AMONG WOMEN - ROLE OF DIETARY FACTORS, FASTING PERIOD, AND DIETING SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID MIDDLE-AGED WOMEN; GALLBLADDER-DISEASE; DIABETES-MELLITUS; MEAL FREQUENCY; CHOLESTEROL; WEIGHT; NUTRITION; CHOLELITHIASIS; CONSUMPTION; PREVALENCE AB Background: Dietary risk factors for the development of gallstones have not been clearly established. We analyzed data from a population-based prospective study to determine dietary risk factors for hospitalization with gallstone disease. Methods: We evaluated the role of dietary constituents, fasting, and dieting on subsequent hospitalization with gallstone disease among 4,730 women, ages 25 to 74 years, who participated in the first follow-up of the first National Health and Nutrition Examination Survey. Baseline dietary variables were established through a 24-hour dietary recall and a medical history. Proportional hazards models were used to calculate the effects of dietary variables while controlling for baseline risk factors. Results: After an average of 10 years follow-up, gallstone disease was confirmed by hospital records among 216 women who denied gallstone disease at the baseline examination. The hazard rate of hospitalization with gallstone disease increased with increasing overnight fasting period and with dieting. Intake of fiber showed a small protective effect. The effect of energy intake was significant only among women younger than age 50 years at baseline. Results were not affected by adjustment for known risk factors for gallstone disease or other dietary factors. Conclusion: A long overnight fasting period, dieting, and low fiber intake may increase the risk of hospitalization with gallstone disease. C1 NIDDKD,EPIDEMIOL & DATA SYST PROGRAM,FED BLDG,RM 106,7550 WISCONSIN AVE,BETHESDA,MD 20892. CTR CIENCIAS BIOL & SAUDE UNIV ESTADUAL MARINGA,PARANA,BRAZIL. NR 42 TC 35 Z9 35 U1 0 U2 1 PU AMER PUBLIC HEALTH ASSN INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUL PY 1991 VL 81 IS 7 BP 880 EP 884 DI 10.2105/AJPH.81.7.880 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA GD161 UT WOS:A1991GD16100014 PM 1647144 ER PT J AU HARLAN, LC BERNSTEIN, AB KESSLER, LG AF HARLAN, LC BERNSTEIN, AB KESSLER, LG TI CERVICAL-CANCER SCREENING - WHO IS NOT SCREENED AND WHY SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID WOMEN AB Background: The decline in death rates from cervical cancer in the United States has been widely attributed to the use of Papanicolaou (Pap) smears for early detection of cervical cancer. Methods: Pap smear screening rates, beliefs about appropriate screening intervals and factors affecting screening were examined using 1987 National Health Interview Survey data. Results: Results indicate that through age 69, Blacks are screened at similar or higher rates than Whites. Hispanics, particularly those speaking only or mostly Spanish, are least likely to have received a Pap smear within the last three years. Of women who had never heard of or never had a Pap smear, nearly 80 percent reported contact with a medical practitioner in the past two years, while more than 90 percent reported a contact in the past five years. Overall, the most frequently reported reason for not having a recent Pap smear was procrastinating or not believing it was necessary. Conclusions: Thus, in developing screening programs, Hispanics, particularly Spanish speakers, must be targeted. In addition, educational programs should target unscreened women who forego the test due to underestimating its importance, procrastination, or because their medical care provider did not suggest the procedure. Women must be intensively educated that Pap smears should be scheduled routinely to detect asymptomatic cervical cancer. RP HARLAN, LC (reprint author), NCI,EXECUT PLAZA N,ROOM 313,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 11 TC 230 Z9 233 U1 1 U2 10 PU AMER PUBLIC HEALTH ASSN INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUL PY 1991 VL 81 IS 7 BP 885 EP 891 DI 10.2105/AJPH.81.7.885 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA GD161 UT WOS:A1991GD16100015 PM 2053665 ER PT J AU BENFANTE, R REED, D FRANK, J AF BENFANTE, R REED, D FRANK, J TI DOES CIGARETTE-SMOKING HAVE AN INDEPENDENT EFFECT ON CORONARY HEART-DISEASE INCIDENCE IN THE ELDERLY SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Note ID RISK-FACTORS; ARTERY DISEASE; MORTALITY; OLDER; MEN; PROGRAM; HAWAII AB In order to evaluate the effects of cigarette smoking on coronary heart disease (CHD) in elderly persons in the Honolulu Heart Program, 1,394 men between ages 65 and 74 were followed during an average 12-year period for new cases of nonfatal myocardial infarction and fatal CHD. Incidence rates increased progressively in individuals classified at baseline as never, former, and current smokers, respectively. The absolute excess risk associated with cigarette smoking was nearly twice as high in elderly compared with middle-aged men. C1 NHLBI,BETHESDA,MD 20892. RP BENFANTE, R (reprint author), KUAKINI MED CTR,HONOLULU HEART PROGRAM,347 N KUAKINI,HONOLULU,HI 96817, USA. FU NHLBI NIH HHS [N01-HC-02901] NR 24 TC 24 Z9 24 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSN INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUL PY 1991 VL 81 IS 7 BP 897 EP 899 DI 10.2105/AJPH.81.7.897 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA GD161 UT WOS:A1991GD16100018 PM 2053668 ER PT J AU LOGUN, C MULLOL, J RIEVES, D HOFFMAN, A JOHNSON, C MILLER, R GOFF, J KALINER, M SHELHAMER, J AF LOGUN, C MULLOL, J RIEVES, D HOFFMAN, A JOHNSON, C MILLER, R GOFF, J KALINER, M SHELHAMER, J TI USE OF A MONOCLONAL-ANTIBODY ENZYME-LINKED-IMMUNOSORBENT-ASSAY TO MEASURE HUMAN RESPIRATORY GLYCOPROTEIN PRODUCTION INVITRO SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID TRACHEAL EPITHELIAL-CELLS; MUCOUS GLYCOPROTEINS; NEUTROPHIL ELASTASE; HUMAN AIRWAY; ANTIGENS; RELEASE; SECRETION; CULTURES; MUCINS AB High-molecular-weight glycoprotein from human airway cultures was used to generate murine monoclonal antibodies, one of which recognizes a high-molecular-weight, hyaluronidase-resistant glycoprotein localized by immunofluorescent microscopy and immunogold electron microscopy to the secretory granules of human airway submucosal gland mucous cells and goblet cells. This monoclonal antibody was used to develop an enzyme-linked immunosorbent assay (ELISA) that was adapted to the study of respiratory glycoprotein secretion from human airways in vitro. Using the assay, the effect of a known mucus secretagogue, the cholinergic agonist methacholine, was studied on explant cultures of tissue from human bronchus or from human nasal mucosa. In studies of human bronchus explants, methacholine, 100 and 10-mu-M, stimulated increased secretion of respiratory glycoprotein (RGP) by 109 +/- 8% (n = 14; P < 0.001) and 96 +/- 14% (n = 9; P < 0.001), respectively, above control values. In studies of human nasal turbinate mucosal explants, methacholine, 100 and 10-mu-M, stimulated increased secretion of RGP by 75 +/- 28% (n = 7; P < 0.01) and 70 +/- 21% (n = 4; P < 0.01) above control values. An ELISA for the measurement of RGP secretion may provide a sensitive and more specific method for the performance of in vitro studies of RGP secretion from human tissues. C1 NIAID,CLIN INVEST LAB,ALLERG DIS SECT,BETHESDA,MD 20892. RP LOGUN, C (reprint author), NIAID,CTR CLIN,DEPT CLIN CARE MED,BLDG 10,ROOM 10-D-48,BETHESDA,MD 20892, USA. NR 22 TC 30 Z9 30 U1 0 U2 1 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD JUL PY 1991 VL 5 IS 1 BP 71 EP 79 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA FW038 UT WOS:A1991FW03800012 PM 1878254 ER PT J AU TAKANO, K BOGERT, M MALAMUD, D LALLY, E HAND, AR AF TAKANO, K BOGERT, M MALAMUD, D LALLY, E HAND, AR TI DIFFERENTIAL DISTRIBUTION OF SALIVARY AGGLUTININ AND AMYLASE IN THE GOLGI-APPARATUS AND SECRETORY GRANULES OF HUMAN SALIVARY-GLAND ACINAR-CELLS SO ANATOMICAL RECORD LA English DT Article ID FREEZE-SUBSTITUTION FIXATION; IMMUNOCYTOCHEMICAL LOCALIZATION; ULTRASTRUCTURAL-LOCALIZATION; MONOCLONAL-ANTIBODIES; ENDOPLASMIC-RETICULUM; STREPTOCOCCUS-MUTANS; SUBMANDIBULAR-GLAND; VESICULAR TRANSPORT; MAMMALIAN-CELLS; FINE-STRUCTURE AB The secretory granules of salivary glands often display complex internal substructures, yet little is known of the molecular organization of their contents or the mechanisms involved in packaging of the secretory proteins. We used post-embedding immunogold labeling with antibodies to two secretory proteins, agglutinin and alpha-amylase, to determine their distribution in the Golgi apparatus and secretory granules of the human submandibular gland acinar cells. With monoclonal antibodies specific for carbohydrate epitopes of the agglutinin, reactivity was found in the trans Golgi saccules, trans Golgi network, and immature and mature secretory granules. In the granules, labeling was seen in regions of low and medium electron density, but not in the dense cores. Reactivity seen on the apical and basolateral membranes of acinar and duct cells was attributed to a shared epitope on a membrane glycoprotein. Labeling with a polyclonal antibody to amylase was found in the Golgi saccules, immature and mature secretory granules, but not in the trans Golgi network. In the granules, amylase was present in the dense cores and in areas of medium density, but not in the regions of low density. These results indicate that these two proteins are distributed differently within the secretory granules, and suggest that they follow separate pathways between the Golgi apparatus and forming secretory granules. Small vesicles and tubular structures that labeled only with the antibodies to the agglutinin were observed on both faces of the Golgi apparatus and in the vicinity of the cell membrane. These structures may represent constitutive secretion vesicles involved in transport of the putative membrane glycoprotein to the cell membrane. C1 UNIV PENN,SCH DENT MED,CTR ORAL HLTH RES,PHILADELPHIA,PA 19104. NIDR,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892. RP TAKANO, K (reprint author), NAGASAKI UNIV,SCH DENT,DEPT ORAL HISTOL,NAGASAKI 852,JAPAN. OI Malamud, Daniel/0000-0002-9094-4122 FU NCRR NIH HHS [RR01224]; NIDCR NIH HHS [DE02623] NR 62 TC 40 Z9 41 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0003-276X J9 ANAT REC JI Anat. Rec. PD JUL PY 1991 VL 230 IS 3 BP 307 EP 318 DI 10.1002/ar.1092300303 PG 12 WC Anatomy & Morphology SC Anatomy & Morphology GA FP771 UT WOS:A1991FP77100002 PM 1714258 ER PT J AU CUTLER, RG AF CUTLER, RG TI HUMAN LONGEVITY AND AGING - POSSIBLE ROLE OF REACTIVE OXYGEN SPECIES SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID SUPEROXIDE-DISMUTASE; LIFE-SPAN; METABOLIC-RATE; DROSOPHILA; EVOLUTION; EXPRESSION; OLD RP CUTLER, RG (reprint author), NATL INST AGING, GERONTOL RES CTR, 4940 EASTERN AVE, BALTIMORE, MD 21224 USA. NR 55 TC 3 Z9 3 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PD JUL 1 PY 1991 VL 621 BP 1 EP 28 PG 28 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FZ453 UT WOS:A1991FZ45300001 ER PT J AU SPECTOR, NH AF SPECTOR, NH TI CONCLUDING REMARKS - 2 DOZEN CURRENT PROBLEMS IN NEUROIMMUNOMODULATION, AGING, AND CANCER-RESEARCH - THE 2ND STROMBOLI COCKTAIL - FURTHER RAMBUNCTIOUS REMARKS SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article RP SPECTOR, NH (reprint author), NIH, DIV FUNDAMENTAL NEUROSCI, FED BLDG, ROOM 916, BETHESDA, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PD JUL 1 PY 1991 VL 621 BP 441 EP 446 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA FZ453 UT WOS:A1991FZ45300034 ER PT J AU HOLLAND, FW BROWN, PS WEINTRAUB, BD CLARK, RE AF HOLLAND, FW BROWN, PS WEINTRAUB, BD CLARK, RE TI CARDIOPULMONARY BYPASS AND THYROID-FUNCTION - A EUTHYROID SICK SYNDROME SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 37TH ANNUAL MEETING OF THE SOUTHERN THORACIC SURGICAL ASSOC CY NOV 08-10, 1990 CL DORADO, PR SP SO THORAC SURG ASSOC ID OPEN-HEART SURGERY; TRIIODOTHYRONINE; T3; ILLNESSES; TSH; T4 AB The purpose of this prospective study was to define the effect of cardiopulmonary bypass on the concentrations of thyroid hormones and metabolites. Blood samples were obtained from 14 patients preoperatively, at specific times throughout cardiopulmonary bypass, and serially to 24 hours postoperatively. Thyroid-stimulating hormone, thyroid-binding globulin, total thyroxine, triiodothyronine (T3), and reverse T3, an inactive metabolite of thyroxine, were measured by radioimmunoassay. Free T3 was assayed by equilibrium dialysis. Values of total T3 and free T3, the active hormone, were significantly depressed (75% and 50%, respectively) up to 24 hours after bypass (p < 0.05). Reverse T3 demonstrated a greater than fourfold rise at 8 and 24 hours postoperatively (p < 0.05). Thyroid-binding globulin was decreased at all sampling times (p < 0.05). Thyroid-stimulating hormone, thyroxine, and free thyroxine levels remained within normal ranges at all sampling times. These results indicate that cardiopulmonary bypass simulates the "euthyroid sick syndrome" as seen in severely burned patients and critically ill patients, which is characterized by depression of T3 and free T3 concentrations with a concomitant increase in reverse T3 levels and normal concentrations of thyroid-stimulating hormone, thyroxine, and free thyroxine. The hemodynamic effects of primary hypothyroidism are well established. These data provide further support for investigational trials of intravenous administration of T3 in the prevention or treatment of low cardiac output syndrome after cardiopulmonary bypass. C1 NHLBI,SURG BRANCH,BETHESDA,MD 20892. NATL INST DIABET DIGEST & KIDNEY DIS,MOLEC CELLULAR & NUTR ENDOCRINOL BRANCH,BETHESDA,MD. NR 24 TC 121 Z9 130 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JUL PY 1991 VL 52 IS 1 BP 46 EP 50 PG 5 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA FX266 UT WOS:A1991FX26600010 PM 2069461 ER PT J AU ULLMANN, CAD ELIOT, HM SINHA, BK AF ULLMANN, CAD ELIOT, HM SINHA, BK TI DISTRIBUTION, DNA DAMAGE AND CYTOTOXIC EFFECTS OF ETOPOSIDE IN HUMAN TUMOR XENOGRAFTS INVIVO SO ANTICANCER RESEARCH LA English DT Article DE VP-16; MULTIDRUG RESISTANCE; XENOGRAFTS; DNA DAMAGE; DISTRIBUTION ID ANTICANCER DRUG; CHEMOTHERAPEUTIC-AGENTS; STRAND BREAKS; FREE-RADICALS; CANCER-CELLS; RESISTANCE; CARCINOMA; MECHANISM; VP16-213 AB Mechanisms of resistance to VP-16 in vivo were studied using sensitive and multidrug resistant human breast tumor (MCF-7) cells, implanted bilaterally in nude mice. Administration of VP-16 (40 mg/kg, i.p.) indicated that there were no significant differences in either accumulation and retention of VP-16 or in the drug-induced bulk DNA damage in sensitive or resistant solid xenografts. Furthermore, under these conditions, no differential cytotoxic response to VP-16 was observed in solid tumors. C1 NCI,BIOCHEM & MOLEC PHARMACOL SECT,CLIN PHARMACOL BRANCH,BLDG 10,BETHESDA,MD 20892. RP SINHA, BK (reprint author), NCI,BIOCHEM & MOLEC PHARMACOL SECT,CLIN PHARMACOL BRANCH,BLDG 10,BETHESDA,MD 20892, USA. NR 23 TC 8 Z9 8 U1 0 U2 1 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD JUL-AUG PY 1991 VL 11 IS 4 BP 1379 EP 1382 PG 4 WC Oncology SC Oncology GA GT706 UT WOS:A1991GT70600002 PM 1746894 ER PT J AU GUADAGNI, F ROSELLI, M FERRONI, P AMATO, T COLCHER, D GREINER, JW SCHLOM, J AF GUADAGNI, F ROSELLI, M FERRONI, P AMATO, T COLCHER, D GREINER, JW SCHLOM, J TI CLINICAL-EVALUATION OF THE NEW TUMOR-MARKER TAG-72 SO ANTICANCER RESEARCH LA English DT Article DE TUMOR-ASSOCIATED GLYCOPROTEIN-72; CARCINOEMBRYONIC ANTIGEN; COLORECTAL CANCER; STOMACH CANCER; BODY FLUIDS; RADIOIMMUNOASSAY ID MONOCLONAL-ANTIBODY B72.3; CARCINOEMBRYONIC ANTIGEN LEVELS; METASTATIC BREAST-CANCER; GLYCOPROTEIN TAG-72; SEROUS EFFUSIONS; CA-72-4 RADIOIMMUNOASSAY; IMMUNORADIOMETRIC ASSAY; OVARIAN CARCINOMAS; COLORECTAL-CANCER; PLEURAL EFFUSIONS AB Tumor-associated glycoprotein-72 (TAG-72) is a high molecular weight glycoprotein found in the sera of patients diagnosed with gastrointestinal and other malignancies. TAG-72 was detected in the serum of a significant percentage of patients whose CEA levels were negative which underscores the possibility of exploiting the complementarity of the two tumor markers in the diagnosis of gastrointestinal (G.I.) carcinoma. Moreover, the measurement of TAG-72 may also be clinically useful in discriminating malignant from benign effusions. Serum TAG-72 and CEA levels were evaluated longitudinally in a series of patients following resecton of primary G.I. carcinomas. A consistent relationship between efficacy of the surgery and serum TAG-72 clearance was observed, and TAG-72 alone or in combination with CEA accurately predicted recurrence of malignant disease in > 90% of the patients. The results indicate that TAG-72 is a new human serum tumor marker which, measured alone or in combination with other well established markers, may improve the diagnosis and/or clinical management of malignant disease. C1 NCI,TUMOR IMMUNOL & BIOL LAB,BLDG 10,ROOM 8B-07,BETHESDA,MD 20892. REGINA ELENA INST CANC RES,ROME,ITALY. UNIV ROME 2,SCH MED,DEPT SURG,ROME,ITALY. UNIV ROME LA SAPIENZA,DEPT EXPTL MED,I-00185 ROME,ITALY. RP SCHLOM, J (reprint author), NCI,TUMOR IMMUNOL & BIOL LAB,BLDG 10,ROOM 8B-07,BETHESDA,MD 20892, USA. RI Guadagni, Fiorella/J-4432-2013; Ferroni, Patrizia/C-2705-2017 OI Guadagni, Fiorella/0000-0003-3652-0457; Ferroni, Patrizia/0000-0002-9877-8712 NR 49 TC 11 Z9 11 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 JUL-AUG PY 1991 VL 11 IS 4 BP 1389 EP 1394 PG 6 WC Oncology SC Oncology GA GT706 UT WOS:A1991GT70600004 PM 1746895 ER PT J AU KUMAR, S HAND, PH MARSDEN, HB KUMAR, P THOR, A AF KUMAR, S HAND, PH MARSDEN, HB KUMAR, P THOR, A TI QUANTITATION OF ENHANCED EXPRESSION OF RAS-ONCOGENE PRODUCT (P21) IN CHILDHOOD RENAL TUMORS SO ANTICANCER RESEARCH LA English DT Article DE RAS-ONCOGENE PRODUCT P21; CHILDHOOD RENAL TUMORS ID LIQUID COMPETITION RADIOIMMUNOASSAYS; URINARY-TRACT TUMORS; WILMS TUMOR; MONOCLONAL-ANTIBODIES; COLON CARCINOMAS; GENE-EXPRESSION; HUMAN MAMMARY; GROWTH; FIBRONECTIN; ANIRIDIA AB A monoclonal antibody, RAP-5, raised against the 21000d ras-oncogene product, p21, was used in an immunoperoxidase staining procedure to study the expression of p21 in normal children's and foetal kidneys, pre-malignant lesions and benign and malignant childhood renal tumours with good, moderate or poor prognosis. ras-p21 was expressed in both normal and foetal kidneys but its distribution in renal tumours differed markedly (p < 0.01). A quantitative liquid competition radioimmunoassay (RIA) was used to determine ras-p21 level in tissue homogenates. The results were expressed as pg of ras-p21 per mu-g protein of tissue extract. There were significant differences in the levels of ras-p21 among various renal tissue extracts (p < 0.05). Generally it emerged that the amount of ras-p21 was greater in both malignant renal tumours and foetal kidneys compared to normal kidneys, pre-malignant lesions and benign renal tumours. C1 NIH,WASHINGTON,DC. RP KUMAR, S (reprint author), CHRISTIE HOSP & HOLT RADIUM INST,WILMSLOW RD,MANCHESTER M20 9BX,LANCS,ENGLAND. NR 34 TC 3 Z9 3 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 JUL-AUG PY 1991 VL 11 IS 4 BP 1657 EP 1662 PG 6 WC Oncology SC Oncology GA GT706 UT WOS:A1991GT70600045 PM 1660693 ER PT J AU WALSH, TJ LEE, JW KELLY, P BACHER, J LECCIONES, J THOMAS, V LYMAN, C COLEMAN, D GORDEE, R PIZZO, PA AF WALSH, TJ LEE, JW KELLY, P BACHER, J LECCIONES, J THOMAS, V LYMAN, C COLEMAN, D GORDEE, R PIZZO, PA TI ANTIFUNGAL EFFECTS OF THE NONLINEAR PHARMACOKINETICS OF CILOFUNGIN, A 1,3-BETA-GLUCAN SYNTHETASE INHIBITOR, DURING CONTINUOUS AND INTERMITTENT INTRAVENOUS INFUSIONS IN TREATMENT OF EXPERIMENTAL DISSEMINATED CANDIDIASIS SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID PNEUMOCYSTIS-CARINII; INVITRO ACTIVITY; LY121019; RABBITS; ALBICANS; AGENT AB Cilofungin (LY-121019) is a fungicidal cell wall-active 1,3-beta-glucan synthetase inhibitor with a short plasma half-life and saturable nonlinear plasma pharmacokinetics. To optimize the in vivo efficacy of this compound, we studied the effects of its linear and nonlinear pharmacokinetics during continuous versus intermittent intravenous infusion of cilofungin in the treatment of experimental disseminated candidiasis in persistently granulocytopenic rabbits. Six groups of rabbits were studied, untreated controls (n = 32) and five cilofungin dosage regimen groups consisting of the following: 25 mg/kg of body weight intravenously twice daily (VLoINT) (n = 9); 50 mg/kg twice daily (LoINT) (n = 9); 90 mg/kg twice daily (HiINT) (n = 11); 5 mg/kg/h for 18 h/day (LoCI) (n = 7); and 10 mg/kg/h for 18 h/day (HiCI) (n = 7). All regimens achieved plasma concentrations exceeding the MIC for Candida albicans (0.25-mu-g/ml). In vitro timed kill assays found that the fungicidal activity and rate of kill by cilofungin above the MIC for C. albicans was concentration dependent. At the lower dosage regimes (VLoINT, LoINT, and LoCI), cilofungin followed linear plasma pharmacokinetics, whereas at higher doses (HiCI and HiINT), nonlinear kinetics consistent with a saturated elimination pathway(s) were observed. Only HiCI and HiINT produced a 10(3)- to 10(4)-fold reduction in CFU per gram in candidiasis of the brain (P less-than-or-equal-to 0.001). HiCI and HiINT also significantly reduced infection in the choroid (P less-than-or-equal-to 0.05). All regimens, except VLoInt, significantly (P less-than-or-equal-to 0.01) reduced tissue infections in lung, liver, spleen, and kidney. However, only the regimens with nonlinear saturation kinetics (HiCI and HiINT) produced a 10(6) reduction in the spleen and a > 10(5) reduction of C. albicans in the kidney and liver. A simple doubling of the dosage from LoCI to HiCI resulted in tissue concentrations that were 10 times higher and a 10(2)- to 10(4)-fold-greater antifungal effect. There was a direct correlation (r2 = 0.83) between tissue concentrations of cilofungin and antifungal activity. Thus, continuous and intermittent infusion dosage regimens that elicit nonlinear saturation plasma pharmacokinetics of cilofungin were associated with increased antifungal activity against experimental disseminated candidiasis. C1 NIH,NATL CTR RES RESOURCES,VET RESOURCES PROGRAM,BETHESDA,MD 20892. ELI LILLY & CO,LILLY RES LAB,INFECT DIS RES & BIOANALYT DEV,INDIANAPOLIS,IN 46285. RP WALSH, TJ (reprint author), NCI,PEDIAT BRANCH,INFECT DIS SECT,BETHESDA,MD 20892, USA. NR 29 TC 34 Z9 34 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JUL PY 1991 VL 35 IS 7 BP 1321 EP 1328 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA FV098 UT WOS:A1991FV09800010 PM 1929288 ER PT J AU THAKKER, DR BOEHLERT, C LEVIN, W RYAN, DE THOMAS, PE YAGI, H JERINA, DM AF THAKKER, DR BOEHLERT, C LEVIN, W RYAN, DE THOMAS, PE YAGI, H JERINA, DM TI NOVEL STEREOSELECTIVITY OF RAT-LIVER CYTOCHROME(S)-P450 TOWARD ENANTIOMERS OF THE TRANS-1,2-DIHYDRODIOL OF TRIPHENYLENE SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; RING DIOL EPOXIDES; CYTOCHROME-P-450 ISOZYMES; ANTHRACENE 1,2-OXIDES; ORTHO-QUINONES; PURIFICATION; NAPHTHALENE; MICROSOMES; HYDROLASE C1 US FDA,CTR BIOL EVALUAT & RES,DIV BIOCHEM & BIOPHYS,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. HOFFMANN LA ROCHE INC,DEPT PROT BIOCHEM,NUTLEY,NJ 07110. NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892. RP THAKKER, DR (reprint author), GLAXO INC,RES INST,DEPT DRUG METAB,RES TRIANGLE PK,NC 27709, USA. NR 30 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 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUL PY 1991 VL 288 IS 1 BP 54 EP 63 DI 10.1016/0003-9861(91)90164-E PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA FQ165 UT WOS:A1991FQ16500008 PM 1898024 ER PT J AU WOLFF, B PARK, MK KLIMA, E HANOVER, JA AF WOLFF, B PARK, MK KLIMA, E HANOVER, JA TI ANTIBODIES AGAINST THE SV40 LARGE T-ANTIGEN NUCLEAR-LOCALIZATION SEQUENCE SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID LOCATION SIGNAL; MONOCLONAL-ANTIBODIES; TRANSPORT SIGNAL; BINDING-PROTEINS; TUMOR-ANTIGEN; IDENTIFICATION; IMPORT C1 NIDDK,BIOCHEM & METAB LAB,BETHESDA,MD 20892. NR 23 TC 7 Z9 7 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUL PY 1991 VL 288 IS 1 BP 131 EP 140 DI 10.1016/0003-9861(91)90174-H PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA FQ165 UT WOS:A1991FQ16500018 PM 1654819 ER PT J AU HAHN, SM KRISHNA, CM SAMUNI, A MITCHELL, JB RUSSO, A AF HAHN, SM KRISHNA, CM SAMUNI, A MITCHELL, JB RUSSO, A TI MN(III)-DESFERRIOXAMINE SUPEROXIDE DISMUTASE-MIMIC - ALTERNATIVE MODES OF ACTION SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID TERT-BUTYL HYDROPEROXIDE; HYDROGEN-PEROXIDE; CYTO-TOXICITY; COMPLEXES; COPPER; CELLS; DESFERRIOXAMINE; PROTECTION; RADICALS; PARAQUAT C1 NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. HEBREW UNIV JERUSALEM,SCH MED,IL-91010 JERUSALEM,ISRAEL. NR 28 TC 26 Z9 27 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUL PY 1991 VL 288 IS 1 BP 215 EP 219 DI 10.1016/0003-9861(91)90186-M PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA FQ165 UT WOS:A1991FQ16500030 PM 1654823 ER PT J AU BROWN, AR TSO, POP CUTLER, RG AF BROWN, AR TSO, POP CUTLER, RG TI EXPRESSION OF THE INTRACISTERNAL-A PARTICLE ENDOGENOUS RETROVIRUS GENES OVER THE LIFETIME OF MOUSE AND SYRIAN-HAMSTER SO ARCHIVES OF GERONTOLOGY AND GERIATRICS LA English DT Article DE INTRACISTERNAL-A PARTICLE GENES; ENDOGENOUS RETROVIRUS; GENE REGULATION; (SYRIAN HAMSTER) ID LONG TERMINAL REPEAT; RIBONUCLEIC-ACID; MOLECULAR-CLONING; RNA; AGE; SEQUENCES; CELLS; GENOME; BRAIN; VIRUS AB Transcription of intracisternal A particle genes in several tissues has been examined throughout the lifespan or inbred C57BL/6J and outbred wild-type mice and golden Syrian hamster. In both rodent species, expression of the genes occurs at all ages and in all tissues. Also, in both species, RNA transcripts of heterogeneous lengths are found that correspond in size not only to the proviral genes previously characterized but also to genes larger than those reported. In hamster, the size heterogeneity is more extensive than in the mouse, where discrete size transcripts are detectable over the heterogeneous signal. Transcription of these genes throughout the lifespan is not peculiar to the hamster or inbred laboratory mouse strain (C57BL/6J) but also occurs in many tissues of outbred wild-type Mus musculus at each age examined. Lifelong transcription of intracisternal A particle retrovirus genes raises the suggestion that retrovirus proteins and cDNA are continuously produced and could facilitate cumulative genomic rearrangements. This could lead to improper gene regulation and thus contribute to the age-dependent increase of cancer and more generally to the aging process itself. C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. RP BROWN, AR (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,615 N WOLFE ST,BALTIMORE,MD 21205, USA. NR 39 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0167-4943 J9 ARCH GERONTOL GERIAT JI Arch. Gerontol. Geriatr. PD JUL-AUG PY 1991 VL 13 IS 1 BP 15 EP 30 DI 10.1016/0167-4943(91)90012-F PG 16 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA FY242 UT WOS:A1991FY24200002 PM 15374432 ER PT J AU ROCCELLA, EJ AF ROCCELLA, EJ TI NATIONAL HIGH BLOOD-PRESSURE EDUCATION-PROGRAM WORKING GROUP-REPORT ON HYPERTENSION AND CHRONIC-RENAL-FAILURE SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CONVERTING ENZYME-INHIBITORS; ARTERY-STENOSIS; CALCIUM-ANTAGONISTS; ENALAPRIL THERAPY; SOLITARY KIDNEY; CAPTOPRIL; INSUFFICIENCY; DISEASE; HEMODYNAMICS; BLOCKERS AB End-stage renal disease attributed to hypertension has increased annually for the last decade and will probably worsen through the year 2000. Patients with diabetic nephropathy and patients with hypertensive renal disease account for most new cases annually. Evidence reveals that all levels of untreated hypertension are associated with potentially declining renal function. Data from the Hypertension Detection and Follow-up Program and other studies show that antihypertensive treatment can prevent progressive renal failure. An ablation model demonstrates glomerular hyperfiltration as a possible mechanism for progressive renal failure. Human data on the renal effects of antihypertensive agents are limited and inconsistent. Despite the limitations, the Working Group on Hypertension and Chronic Renal Failure concludes that controlled hypertension to less than 140/90 mm Hg reduces the incidence of end-stage renal disease. Patients with established renal impairment may benefit from individualized treatment to 130/85 mm Hg or less. RP ROCCELLA, EJ (reprint author), NHLBI,NATL HIGH BLOOD PRESSURE EDUC PROGRAM,BETHESDA,MD 20892, USA. NR 88 TC 26 Z9 29 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUL PY 1991 VL 151 IS 7 BP 1280 EP 1287 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA FW295 UT WOS:A1991FW29500006 ER PT J AU CAPPELLO, M BERNARD, KW JONES, B FRANCIS, H VANDERVLUGT, T AF CAPPELLO, M BERNARD, KW JONES, B FRANCIS, H VANDERVLUGT, T TI HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION AMONG PEACE-CORPS VOLUNTEERS IN ZAIRE - NO EVIDENCE FOR UNUSUAL MODES OF TRANSMISSION SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID RISK-FACTORS; AIDS; AFRICA; PREVALENCE; KINSHASA; HIV AB A prospective study of US Peace Corps volunteers (PCVs) serving in Zaire, central Africa, was undertaken to determine the risk of human immunodeficiency virus (HIV) and hepatitis B virus infection in an acquired immunodeficiency syndrome-aware expatriate population living in an area of high endemicity for both diseases. Of the 338 PCVs who served in Zaire between October 1985 and May 1988, 282 (83%) were enrolled, representing 7776 volunteer-months of service. Analyses of serum samples for HIV and hepatitis B virus were performed on enrollment and at completion of service. All PCVs received extensive education and counseling regarding HIV and acquired immunodeficiency syndrome throughout their stay in Zaire. There were no documented seroconversions to HIV among 282 PCVs who lived in Zaire for periods ranging from 1 to 81 months, with a mean length of stay of 27.4 months. Of the 14 (6.20%) of 226 PCVs tested who had at least one positive serologic marker for infection with hepatitis B virus, none was documented to have seroconverted during service. During the study period, the rate of all sexually transmitted diseases among PCVs in Africa decreased from 131 to 68 per 1000 study population per year, and there were 52 cases of confirmed malaria among volunteers in Zaire. These data suggest that the risk of acquiring infection with HIV or hepatitis B virus in PCVs in Zaire is very low, and there is no evidence for unusual modes of transmission. C1 GEORGETOWN UNIV,MED CTR,DEPT INTERNAL MED,WASHINGTON,DC 20007. US PHS,OFF INT HLTH,WASHINGTON,DC. JOHNS HOPKINS UNIV HOSP,DEPT PSYCHIAT,BALTIMORE,MD 21205. NIAID,BETHESDA,MD 20892. US PEACE CORPS,OFF MED SERV,WASHINGTON,DC. NR 25 TC 10 Z9 10 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUL PY 1991 VL 151 IS 7 BP 1328 EP 1330 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA FW295 UT WOS:A1991FW29500011 PM 2064483 ER PT J AU KREGER, BE ANDERSON, KM LEVY, D AF KREGER, BE ANDERSON, KM LEVY, D TI QRS INTERVAL FAILS TO PREDICT CORONARY-DISEASE INCIDENCE - THE FRAMINGHAM-STUDY SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID BUNDLE-BRANCH BLOCK; ACUTE MYOCARDIAL-INFARCTION; NEWLY ACQUIRED LEFT; CLINICAL-SIGNIFICANCE; GENERAL-POPULATION; BYPASS AB The Framingham Study cohort of 5209 white men and women was examined to determine the long-term incidence of manifestations of new coronary heart disease as a function of QRS interval on subjects' baseline electrocardiograms (recorded at the 9th biennial examination). Over 18 years of follow-up, age-adjusted incidence of myocardial infarction, angina pectoris, and coronary death appeared unrelated to baseline QRS prolongation in both sexes, by Cox regression. Subjects with left bundle-branch block fared no worse than those with right pattern. These relations held whether or not subjects with baseline electrocardiographic abnormalities other than intraventricular block were excluded from consideration. In sum, QRS duration is an unimportant predictor of coronary disease in this Framingham population. C1 BOSTON UNIV,MED CTR,EVANS MEM DEPT CLIN RES,GEN INTERNAL MED SECT,BOSTON,MA 02215. BOSTON UNIV,MED CTR,EVANS MEM DEPT CLIN RES,PREVENT MED & EPIDEMIOL SECT,BOSTON,MA 02215. NHLBI,FRAMINGHAM,MA. FU NHLBI NIH HHS [N01-HC38038] NR 20 TC 13 Z9 13 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUL PY 1991 VL 151 IS 7 BP 1365 EP 1368 DI 10.1001/archinte.151.7.1365 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA FW295 UT WOS:A1991FW29500016 PM 2064487 ER PT J AU WHITCUP, SM BELFORT, R DESMET, MD PALESTINE, AG NUSSENBLATT, RB CHAN, CC AF WHITCUP, SM BELFORT, R DESMET, MD PALESTINE, AG NUSSENBLATT, RB CHAN, CC TI IMMUNOHISTOCHEMISTRY OF THE INFLAMMATORY RESPONSE IN PROPIONIBACTERIUM-ACNES ENDOPHTHALMITIS SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID EXTRACAPSULAR CATARACT-EXTRACTION; INTRAOCULAR-LENS IMPLANTATION; ALLERGIC CONTACT-DERMATITIS; CORYNEBACTERIUM-PARVUM; LYMPHOCYTES-T; SERUM; COMPLEMENT; ACTIVATION; MODULATION; INHIBITION AB Specimens were obtained from two patients with culture-proven Propionibacterium acnes endophthalmitis who had undergone vitrectomy. Wright's and Giemsa stains were performed using cytospin preparations of the dilute vitreous and revealed a predominance of polymorphonuclear leukocytes (80% to 90%). The remaining inflammatory cells in the vitreous were mostly macrophages (10% to 15%); very few lymphocytes were present (< 5%). Immunohistochemical studies using monoclonal antibodies confirmed the paucity of lymphocytes. Most lymphocytes were CD4+ helper/inducer T cells. Almost no CD8+ suppressor/ cytotoxic T lymphocytes or B lymphocytes were found. The inflammatory response in these two patients is most characteristic of acute inflammation and consistent with an underlying bacterial infection, despite a clinical picture of persistent, low-grade inflammation. Infection with P acnes has been shown to inhibit CD8+ T cells and may play a role in the persistent inflammation in cases of P acnes endophthalmitis. RP WHITCUP, SM (reprint author), NEI,IMMUNOL LAB,BLDG 10,ROOM 10N 202,BETHESDA,MD 20892, USA. RI Belfort Jr, Rubens/E-2252-2012; OI Belfort Jr, Rubens/0000-0002-8422-3898; de Smet, Marc/0000-0002-9217-5603 NR 13 TC 14 Z9 14 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JUL PY 1991 VL 109 IS 7 BP 978 EP 979 PG 2 WC Ophthalmology SC Ophthalmology GA FV414 UT WOS:A1991FV41400030 PM 2064579 ER PT J AU LOPEZ, JS PRICE, FW WHITCUP, SM LI, Q DESMET, M CHAN, CC AF LOPEZ, JS PRICE, FW WHITCUP, SM LI, Q DESMET, M CHAN, CC TI IMMUNOHISTOCHEMISTRY OF TERRIENS AND MOORENS CORNEAL DEGENERATION SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID PIGMENT EPITHELIAL-CELLS; HLA-DR ANTIGENS; MARGINAL DEGENERATION; ABERRANT EXPRESSION; ULCER; DISEASE; THERAPY AB Lamellar keratoplasty specimens from a patient with Terrien's marginal degeneration and a patient with Mooren's ulcer were compared using routine histopathologic and immunohistochemical staining with an avidin-biotin-peroxidase complex. Less than 25% of the resident cells in the Terrien's marginal degeneration specimen expressed major histocompatibility class II antigens compared with 75% to 100% of the resident cells in the Mooren's ulcer specimen. The ratio of CD4 cells (T-helper/inducer) to CD8 cells (T-suppressor/cytotoxic cells) in the Terrien's marginal degeneration specimen was almost 1:1 compared with 2.4:1 in the Mooren's ulcer specimen. In addition, less than 5% of the infiltrating cells from the Terrien's marginal degeneration specimen stained positive for CD22 (B cells), compared with 25% to 50% from the Mooren's ulcer specimen. These data may help explain why Terrien's marginal degeneration runs a more benign course than does Mooren's ulcer and provides a rationale for the use of immunosuppressive drugs to treat Mooren's ulcer. C1 CORNEA RES FDN AMER,INDIANAPOLIS,IN. RP LOPEZ, JS (reprint author), NEI,IMMUNOL LAB,BLDG 10,ROOM 10N 202,BETHESDA,MD 20892, USA. OI de Smet, Marc/0000-0002-9217-5603 NR 27 TC 24 Z9 31 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JUL PY 1991 VL 109 IS 7 BP 988 EP 992 PG 5 WC Ophthalmology SC Ophthalmology GA FV414 UT WOS:A1991FV41400034 PM 2064583 ER PT J AU CAMPOS, H WILLETT, WC PETERSON, RM SILES, X BAILEY, SM WILSON, PWF POSNER, BM ORDOVAS, JM SCHAEFER, EJ AF CAMPOS, H WILLETT, WC PETERSON, RM SILES, X BAILEY, SM WILSON, PWF POSNER, BM ORDOVAS, JM SCHAEFER, EJ TI NUTRIENT INTAKE COMPARISONS BETWEEN FRAMINGHAM AND RURAL AND URBAN PURISCAL, COSTA-RICA - ASSOCIATIONS WITH LIPOPROTEINS, APOLIPOPROTEINS, AND LOW-DENSITY-LIPOPROTEIN PARTICLE-SIZE SO ARTERIOSCLEROSIS AND THROMBOSIS LA English DT Article DE DIETARY INTAKE; PLASMA LIPOPROTEINS; TRIGLYCERIDES; CHOLESTEROL; APOLIPOPROTEINS; LOW DENSITY LIPOPROTEIN PARTICLE SIZE; PHYSICAL ACTIVITY; POPULATION COMPARISONS ID CORONARY HEART-DISEASE; SERUM-CHOLESTEROL RESPONSE; FOOD FREQUENCY QUESTIONNAIRE; DIETARY-CHOLESTEROL; PLASMA-LIPOPROTEINS; PHYSICAL-ACTIVITY; HIGH-CARBOHYDRATE; ARTERY DISEASE; NORMAL HUMANS; PIMA-INDIANS AB To assess cross-cultural relations between dietary intake and plasma lipoproteins, we randomly selected 222 men and 243 women from the urban and rural areas of Puriscal, Costa Rica; related their dietary composition (assessed by a food-frequency questionnaire), fitness level, and body fat to plasma lipids, apolipoproteins, and low density lipoprotein (LDL) particle size; and compared these data with those from a subsample of 280 adults from the Framingham Offspring Study. Total cholesterol and LDL cholesterol levels were significantly (p < 0.0001) higher in Framingham (207 and 137 mg/dl, respectively) than in Puriscal (184 and 114 mg/dl, respectively) residents. Elevated triglyceride and apolipoprotein (apo) B levels (25% and 16% higher), low HDL cholesterol and apo A-I levels (12% and 29% lower), and smaller LDL particles (17%) were more frequent in Puriscal than in Framingham residents. Urban Puriscal residents had a significantly lower fitness level; increased body fat, total cholesterol, and triglyceride levels; decreased HDL cholesterol in men; and higher apo B levels in women compared with rural Puriscal residents. Body fat, animal fat, and saturated fat intakes were significantly correlated with total cholesterol, LDL cholesterol, and apo B levels in both men and women in Puriscal. Intakes of protein and animal fat were higher among urban (10.7% and 14.1%, respectively) compared with rural (8.9% and 9.9%, respectively) Puriscal residents and in Framingham (16.0% and 20.8%, respectively) compared with Puriscal residents. No significant difference were found in dietary cholesterol. Saturated fat (largely from palm oil in Puriscal) intakes were significantly different among the three groups: rural Puriscal, 10.7% of calories; urban Puriscal, 11.6%; and Framingham residents, 12.9%. These data indicate that the more atherogenic plasma lipid profile among urban compared with Puriscal residents was largely explained by increased adiposity, decreased fitness level, and higher saturated fatty acid intake. Puriscal residents consumed less animal fat and more carbohydrate than did Framingham residents, and these differences were associated with a 21% lower LDL cholesterol level, a 12% lower HDL cholesterol level, a 29% lower apo A-I level, a 25% higher triglyceride level, a 16% higher apo B level, and a 17% smaller LDL particle size. Some of these cross-cultural differences may be due to differences in ethnic background and physical activity as well. C1 TUFTS UNIV,USDA,HUMAN NUTR RES CTR AGING,LIPID METAB LAB,BOSTON,MA 02111. TUFTS UNIV,SCH NUTR,MEDFORD,MA 02155. HARVARD UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL & NUTR,BOSTON,MA 02115. TUFTS UNIV,DEPT SOCIOL & ANTHROPOL,MEDFORD,MA 02155. UNIV COSTA RICA,INST INVEST SALUD,SAN PEDRO,COSTA RICA. NHLBI,FRAMINGHAM HEART STUDY,FRAMINGHAM,MA. BOSTON UNIV,SCH PUBL HLTH,BOSTON,MA 02215. BOSTON UNIV,SCH MED,BOSTON,MA 02118. OI Ordovas, Jose/0000-0002-7581-5680 FU NHLBI NIH HHS [HL-35243, HL-39144, HL-43919] NR 79 TC 83 Z9 83 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 1049-8834 J9 ARTERIOSCLER THROMB JI Arterioscler. Thromb. PD JUL-AUG PY 1991 VL 11 IS 4 BP 1089 EP 1099 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA FX248 UT WOS:A1991FX24800033 PM 2065030 ER PT J AU TERKELTAUB, R ZACHARIAE, C SANTORO, D MARTIN, J PEVERI, P MATSUSHIMA, K AF TERKELTAUB, R ZACHARIAE, C SANTORO, D MARTIN, J PEVERI, P MATSUSHIMA, K TI MONOCYTE-DERIVED NEUTROPHIL CHEMOTACTIC FACTOR INTERLEUKIN-8 IS A POTENTIAL MEDIATOR OF CRYSTAL-INDUCED INFLAMMATION SO ARTHRITIS AND RHEUMATISM LA English DT Article ID TUMOR NECROSIS FACTOR; MONOSODIUM URATE CRYSTALS; HUMAN DERMAL FIBROBLASTS; ACTIVATING PEPTIDE-1 INTERLEUKIN-8; ENDOGENOUS PYROGEN PRODUCTION; STIMULATED HUMAN MONOCYTES; MONONUCLEAR PHAGOCYTES; MESSENGER-RNA; MACROPHAGE; PROTEIN AB The physical interaction of particulates with resident mononuclear phagocytes is a consistent feature in certain forms of crystal-induced inflammation. In this study, we observed that monosodium urate crystals stimulated the rapid release of neutrophil chemotactic activity from monocytes, and that this activity steadily increased over 24 hours. Because the release of monocyte-derived neutrophil chemotactic activity was markedly diminished by pretreatment of the monocytes with cycloheximide, and was completely removed from conditioned media by adsorption to heparin-agarose, we addressed the possibility that monocyte-derived neutrophil chemotactic factor/interleukin-8 (IL-8), a heparinbinding neutrophil-activating polypeptide, might modulate these activities. Urate crystal-induced IL-8 secretion from monocytes was verified by radioimmunoassay. In addition, an IL-8-specific antibody markedly inhibited the neutrophil-activating capacity of the conditioned media from monocytes activated by urate crystals, as well as by inflammatory silica crystals. Last, IL-8 was significantly increased in gouty synovial fluids (range 3.0-16.8 ng/ml, mean 8.4 ng/ml, n = 6) relative to osteoarthritic synovial fluids (range 1.1-1.7 ng/ml, mean 1.5 ng/ml, n = 6) (P = 0.006). We conclude that microcrystal-induced secretion of IL-8 by mononuclear phagocytes may mediate a number of forms of crystal-induced inflammation. C1 UNIV CALIF SAN DIEGO,DEPT MED,SAN DIEGO,CA 92103. SCRIPPS CLIN & RES FDN,DEPT CLIN RES,LA JOLLA,CA 92037. NCI,BIOL RESPONSE MODIFIERS PROGRAM,IMMUNOREGULAT LAB,FREDERICK,MD 21701. RP TERKELTAUB, R (reprint author), VET ADM MED CTR,V-111K,3350 LA JOLLA VILLAGE DR,SAN DIEGO,CA 92161, USA. FU NIDDK NIH HHS [DK-36702] NR 56 TC 136 Z9 140 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUL PY 1991 VL 34 IS 7 BP 894 EP 903 DI 10.1002/art.1780340716 PG 10 WC Rheumatology SC Rheumatology GA FV530 UT WOS:A1991FV53000014 PM 2059236 ER PT J AU MCQUILLAN, DJ FINDLAY, DM HOCKING, AM YANAGISHITA, M MIDURA, RJ HASCALL, VC AF MCQUILLAN, DJ FINDLAY, DM HOCKING, AM YANAGISHITA, M MIDURA, RJ HASCALL, VC TI PROTEOGLYCANS SYNTHESIZED BY AN OSTEOBLAST-LIKE CELL-LINE (UMR 106-01) SO BIOCHEMICAL JOURNAL LA English DT Article ID DERMATAN SULFATE PROTEOGLYCANS; OVARIAN GRANULOSA-CELLS; PARATHYROID-HORMONE; BONE SIALOPROTEIN; RAT; CARTILAGE; PROTEINS; CULTURE; GROWTH AB The proteoglycans synthesized by an osteoblast-like cell line of rat origin (UMR 106-01) were defined after biosynthetic labelling with [S-35]sulphate and [H-3]glucosamine. Newly synthesized labelled proteoglycans were characterized by differential enzymic digestion in combination with analytical gel filtration and SDS/PAGE. UMR 106-01 cells were found to synthesize three major species of proteoglycan: a large chondroitin sulphate proteoglycan of M(r) approximately 1 x 10(6), with a core protein of M(r) approximately 350 000-400 000; a small chondroitin sulphate-containing species of M(r) approximately 120 000 with a core protein of M(r) 43 000; and a heparan sulphate proteoglycan of M(r) approximately 150 000, with a core protein of M(r) approximately 80 000. Over 70% of the newly synthesized intact proteoglycan species are associated with the cell layer of near-confluent cells; however, accessibility to trypsin digestion suggests an extracellular location. Chemical characteristics of the proteoglycans and preliminary mRNA hybridization indicate that the small chondroitin sulphate proteoglycan is probably PG II (decorin). The large chondroitin sulphate proteoglycan is most likely related to a hyaluronate-aggregating species from fibroblasts (versican), and the heparan sulphate proteoglycan bears striking similarities to cell-membrane-intercalated species described for a number of cell types. C1 ST VINCENTS HOSP,INST MED RES,MELBOURNE,VIC 3065,AUSTRALIA. NIDR,BONE RES BRANCH,BETHESDA,MD 20892. RP MCQUILLAN, DJ (reprint author), UNIV MELBOURNE,ROYAL CHILDRENS HOSP,DEPT PAEDIAT,PARKVILLE,VIC 3052,AUSTRALIA. NR 32 TC 29 Z9 29 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JUL 1 PY 1991 VL 277 BP 199 EP 206 PN 1 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA FV584 UT WOS:A1991FV58400028 PM 1906708 ER PT J AU YAN, B BAKER, PD EVANS, CH MARSH, JW AF YAN, B BAKER, PD EVANS, CH MARSH, JW TI INFLUENCE OF ENDOGENOUS THY1.1 CELLS UPON THE EFFICACY OF AN ANTI-THY1.1 ANTIBODY DIPHTHERIA-TOXIN CONJUGATE SO BIOCONJUGATE CHEMISTRY LA English DT Article ID RICIN-A-CHAIN; RIBOSOME-INACTIVATING PROTEIN; MONOCLONAL-ANTIBODIES; NONHUMAN-PRIMATES; DISULFIDE BOND; INVIVO; IMMUNOTOXIN; TUMOR; DEGLYCOSYLATION; CLEARANCE AB The chemical conjugation of antibodies to protein toxins results in cell-specific cytotoxic agents that can be defined in terms of in vitro potency and efficacy; however, it is the in vivo utilities that are largely being pursued in clinical trials. The nature of in vivo target cell depletion by toxin conjugates is largely unknown. The anti-murine Thy1.1 antibody-diphtheria toxin conjugate possesses high in vitro efficacy, and because mice are remarkably resistant to the native toxin, the conjugate possesses in vivo efficacy. When administered intravenously, the conjugate is shown to deplete peripheral blood Thy1.1+ target cells in a concentration-dependent fashion. When the log kill of Thy1.1+ tumor cells was analyzed by the life span extension method, it was determined, however, that the log kill is inversely proportional to the number of target cells. That is, the presence of an endogenous cell population, which is expressing the same surface antigen targeted by the antibody conjugate as on the pathological cell, may drastically lower the clinical efficacy of the immunotoxin. Thus, the greatest potential for antibody-toxin conjugates will be for low target cell burdens and for pathogenic cell populations expressing unique surface antigens. These are important considerations in the design of bioconjugates to insure high in vivo efficacy in elimination of intended target cells. C1 NIMH,MOLEC BIOL LAB,BLD 36,RM 1B08,BETHESDA,MD 20892. NCI,BIOL LAB,BETHESDA,MD 20892. NR 21 TC 3 Z9 3 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD JUL-AUG PY 1991 VL 2 IS 4 BP 207 EP 210 DI 10.1021/bc00010a003 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA GB086 UT WOS:A1991GB08600003 PM 1685330 ER PT J AU SUNDERLAND, T BERRETTINI, WH MOLCHAN, SE LAWLOR, BA MARTINEZ, RA VITIELLO, B TARIOT, PN COHEN, RM AF SUNDERLAND, T BERRETTINI, WH MOLCHAN, SE LAWLOR, BA MARTINEZ, RA VITIELLO, B TARIOT, PN COHEN, RM TI REDUCED CEREBROSPINAL-FLUID DYNORPHIN-A1-8 IN ALZHEIMERS-DISEASE SO BIOLOGICAL PSYCHIATRY LA English DT Article ID CSF SOMATOSTATIN; SENILE DEMENTIA; BETA-ENDORPHIN; DEPRESSED-PATIENTS; RECEPTOR-BINDING; IMMUNOREACTIVITY; NALOXONE; LUMBAR; REGIONS; MEMORY AB Cerebrospinal fluid (CSF) measures of dynorphin A1-8 were compared in three groups. Alzheimer patients (n = 9), elderly depressives (n = 9), and age-matched normal controls (n = 9). The Alzheimer patients revealed a 40% decrease in CSF dynorphin compared with controls (36 +/- 15 versus 60 +/- 21 pg/ml, p < 0.05). In contrast, other peptide measures [Neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), and galanin] remained unchanged across groups. This finding was further supported when an additional 20 Alzheimer patients with similar clinical backgrounds also showed reduced CSF dynorphin (37 +/- 13 pg/ml). CSF dynorphin did not correlate significantly with clinical variables or other CSF measures of monoamine metabolites [i.e., 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleactic acid (5-HIAA), and homovanillic acid (HVA)]. Given the previous report of increased kappa binding of Alzheimer brains at autopsy, the authors speculate about a possible up-regulation of opiate receptors in Alzheimer's disease and suggest ways to test this hypothesis in vivo. C1 CUNY MT SINAI SCH MED,DEPT PSYCHIAT,NEW YORK,NY 10029. NIMH,CEREBRAL METAB LAB,CLIN BRAIN IMAGING SECT,BETHESDA,MD 20892. THOMAS JEFFERSON UNIV,DEPT PSYCHIAT,PHILADELPHIA,PA 19107. UNIV ROCHESTER,MED CTR,DEPT PSYCHIAT,ROCHESTER,NY 14642. RP SUNDERLAND, T (reprint author), NIMH,CTR CLIN,CLIN SCI LAB,GERIATR PSYCHOPHARMACOL UNIT,10-3D41,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 33 TC 15 Z9 15 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 JUL 1 PY 1991 VL 30 IS 1 BP 81 EP 87 DI 10.1016/0006-3223(91)90073-U PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA FX216 UT WOS:A1991FX21600010 PM 1716470 ER PT J AU LEE, B AF LEE, B TI SOLVENT REORGANIZATION CONTRIBUTION TO THE TRANSFER THERMODYNAMICS OF SMALL NONPOLAR MOLECULES SO BIOPOLYMERS LA English DT Article ID HYDROPHOBIC INTERACTION; WATER; HYDROCARBONS; SOLUBILITY; SOLUTES; LIQUIDS; MODEL; GASES AB The experimental thermodynamic data for the dissolution of five simple hydrocarbon molecules in water were combined with the solute-solvent interaction energy from a computer simulation study to yield data on the enthalpy change of solvent reorganization. Similar data were generated for dissolving these same solute molecules in their respective neat solvents using the equilibrium vapor pressure and the heat of vaporization data for the pure liquid. The enthalpy and the free energy changes upon cavity formation were also estimated using the temperature dependence of the solute-solvent interaction energy. Both the enthalpy and T-DELTA-S for cavity formation rapidly increase with temperature in both solvent types, and the free energy of cavity formation can be reproduced accurately by the scaled particle theory over the entire temperature range in all cases. These results indicate that the characteristic structure formation around an inert solute molecule in water produces compensating changes in enthalpy and entropy, and that the hydrophobicity arises mainly from the difference in the excluded volume effect. RP NIMH, DIV COMP RES & TECHNOL, PHYS SCI LAB, BLDG 12A, ROOM 2007, BETHESDA, MD 20892 USA. RI Lee, Byungkook/E-4564-2011 OI Lee, Byungkook/0000-0002-3339-4582 NR 34 TC 214 Z9 217 U1 4 U2 26 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0006-3525 EI 1097-0282 J9 BIOPOLYMERS JI Biopolymers PD JUL PY 1991 VL 31 IS 8 BP 993 EP 1008 DI 10.1002/bip.360310809 PG 16 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA GE657 UT WOS:A1991GE65700008 PM 1782360 ER PT J AU RAMPINO, NJ AF RAMPINO, NJ TI INFORMATION CONCERNING THE MECHANISM OF ELECTROPHORETIC DNA SEPARATION PROVIDED BY QUANTITATIVE VIDEO-EPIFLUORESCENCE MICROSCOPY SO BIOPOLYMERS LA English DT Article ID GEL-ELECTROPHORESIS; MOLECULES; INVERSION; FIELD AB Changes in conformation, length, and mobility of individual DNA molecules during agarose gel electrophoresis were measured using video micrographs obtained by epifluorescence microscopy. Globular, V-shaped, and linear conformations of DNA are found. The mobility, upon transformation from the globular to the V-shaped conformation, decreases, suggesting a collision with a gel fiber. The duration of interaction between DNA and gel fiber is proportional to the length of DNA. Hypothetically, this proportionality underlies the size separation of DNA by agarose gel electrophoresis. DNA release from the gel fiber appears to involve the movement of the arms of the V-shaped molecule around the gel fiber. Concomitant with this movement is a length reduction the degree of which is constant for DNA of various lengths in a particular buffer milieu. The luminant densitometric profiles of DNA molecules in the V conformation show maxima at the ends and apex of the V. The unequal distribution of nucleotides along the DNA chain appears to provide the driving force for the molecular movement around the gel fiber. RP NICHHD, THEORET & PHYS BIOL LAB, MACROMOLEC ANAL SECT, BETHESDA, MD 20892 USA. NR 23 TC 37 Z9 37 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0006-3525 EI 1097-0282 J9 BIOPOLYMERS JI Biopolymers PD JUL PY 1991 VL 31 IS 8 BP 1009 EP 1016 DI 10.1002/bip.360310810 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA GE657 UT WOS:A1991GE65700009 PM 1838286 ER PT J AU FUTAMI, H PILARO, AM GRUYS, ME BACK, TC YOUNG, HA WILTROUT, RH AF FUTAMI, H PILARO, AM GRUYS, ME BACK, TC YOUNG, HA WILTROUT, RH TI INVIVO DISTRIBUTION AND CYTOKINE GENE-EXPRESSION BY ENRICHED MOUSE LAK EFFECTOR-CELLS SO BIOTHERAPY LA English DT Article DE LAK CELLS; PERCOLL FRACTIONATION; CYTOKINE GENE EXPRESSION; INVIVO LOCALIZATION ID ACTIVATED KILLER CELLS; TUMOR NECROSIS FACTOR; LARGE GRANULAR LYMPHOCYTES; MURINE RENAL-CANCER; RECOMBINANT INTERLEUKIN-2; FACTOR-ALPHA; ADOPTIVE IMMUNOTHERAPY; PRECURSOR PHENOTYPE; INTERFERON; INVITRO AB Lymphokine activated killer (LAK) cells administered in combination with interleukin 2 (IL2) can mediate antitumor activity in tumor-bearing mice and advanced cancer patients. Relatively little is known about the mechanism by which adoptively transferred LAK cells plus IL2 mediate these antitumor effects in vivo, and it remains unclear to what extent the actual LAK effector cells can accumulate in tumors. In the present study, enriched cytolytic LAK effector cells were obtained by fractionation of bulk LAK cell cultures on Percoll density gradients. About 95% of the total lytic activity was recovered from the 55% of cells isolated in fraction 2 (Fr2). The cells recovered in Fr2 are mostly large, proliferating lymphoblasts that express either the NK-associated surface markers NK 1.1 (38%) or LGL-1 (31%), or the cytotoxic T cell phenotype, Lyt2 (39%). The cytolytic lymphoblasts obtained from Fr2 were radiolabelled with either Indium-111-Oxine (In-111Ox) which labels all cells in the population, or with Iododeoxyuridine-125 (I-125UDR) which labels only proliferating cells, and injected iv into bearing murine renal cancer (Renca) In-111-Ox-labeled Fr2 cells migrated mostly to spleen (28%) and liver (35%), with approximately 5% of the injected label detectable in the Renca-bearing kidney by 24 hrs. In contrast, Fr2 cells labeled with I-125UdR, which labels only the proliferating blasts thought to include the actual effector cells, exhibited a very different localization pattern. I-125UDR-Fr2 cells were retained in the lungs at higher levels than were In-111Ox-Fr2 cells and very little label was detectable in liver (6%), spleen (3%), or tumor bearing kidney (2%) at 24 hrs. These results suggest that most of the large, proliferating lymphoblasts are cleared from the body by 24 hrs and very few localize into even large tumors. Subsequently, Northern blot analyses performed on bulk LAK cells revealed a potent induction of mRNA for TNF-alpha by 6 hrs and for IFN-gamma by 48 hrs. The intensity of gene expression for both cytokines was increased in Fr2 as compared to the unfractionated bulk LAK cells or to non-cytolytic cells obtained from Fr3. Overall, these results suggest that at least some of the antitumor effects mediated by LAK cells occur by the release of cytokines that synergize with exogenous IL2 for the activation of host effector cells. C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,EXPTL IMMUNOL LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC,BIOL CARCINOGENESIS DEV PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74102] NR 43 TC 4 Z9 4 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0921-299X J9 BIOTHERAPY JI Biotherapy PD JUL PY 1991 VL 3 IS 3 BP 219 EP 232 DI 10.1007/BF02171685 PG 14 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA FT986 UT WOS:A1991FT98600004 PM 1906724 ER PT J AU VANSCHRAVENDIJK, MR ROCK, EP MARSH, K ITO, Y AIKAWA, M NEEQUAYE, J OFORIADJEI, D RODRIGUEZ, R PATARROYO, ME HOWARD, RJ AF VANSCHRAVENDIJK, MR ROCK, EP MARSH, K ITO, Y AIKAWA, M NEEQUAYE, J OFORIADJEI, D RODRIGUEZ, R PATARROYO, ME HOWARD, RJ TI CHARACTERIZATION AND LOCALIZATION OF PLASMODIUM-FALCIPARUM SURFACE-ANTIGENS ON INFECTED ERYTHROCYTES FROM WEST AFRICAN PATIENTS SO BLOOD LA English DT Article ID HUMAN CEREBRAL MALARIA; PAPUA-NEW-GUINEA; MELANOMA-CELLS; PARASITIZED ERYTHROCYTES; MONOCLONAL-ANTIBODY; CYTOADHERENCE; MEMBRANE; EXPRESSION; PROTEINS; AGGLUTINATION C1 DNAX RES INST MOLEC & CELLULAR BIOL INC, INFECT DIS UNIT, 901 CALIF AVE, PALO ALTO, CA 94304 USA. NIAID, LPD, MALARIA SECT, BETHESDA, MD 20892 USA. HOWARD HUGHES MED INST, BETHESDA, MD USA. JOHN RADCLIFFE HOSP, NUFFIELD INST MOLEC MED, OXFORD OX3 9DU, ENGLAND. CASE WESTERN RESERVE UNIV, INST PATHOL, CLEVELAND, OH 44106 USA. UNIV GHANA, SCH MED, ACCRA, GHANA. KORLE BU HOSP, ACCRA, GHANA. UNIV NACL COLOMBIA, HOSP SAN JUAN DIOS, INST INMUNOL, SANTA FE DE BOGOTA, COLOMBIA. FU NCI NIH HHS [N01-CP-85612]; NIAID NIH HHS [AI-10645] NR 34 TC 35 Z9 35 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD JUL 1 PY 1991 VL 78 IS 1 BP 226 EP 236 PG 11 WC Hematology SC Hematology GA FU768 UT WOS:A1991FU76800031 PM 2070055 ER PT J AU LOTHROP, CD ALLEBBAN, ZS NIEMEYER, GP JONES, JB PETERSON, MG SMITH, JR BAKER, HJ MORGAN, RA EGLITIS, MA ANDERSON, WF AF LOTHROP, CD ALLEBBAN, ZS NIEMEYER, GP JONES, JB PETERSON, MG SMITH, JR BAKER, HJ MORGAN, RA EGLITIS, MA ANDERSON, WF TI EXPRESSION OF A FOREIGN GENE IN CATS RECONSTITUTED WITH RETROVIRAL VECTOR INFECTED AUTOLOGOUS BONE-MARROW SO BLOOD LA English DT Article ID HEMATOPOIETIC PROGENITOR CELLS; BETA-GLOBIN GENE; HUMAN ADENOSINE-DEAMINASE; STEM-CELLS; MEDIATED TRANSFER; AMPHOTROPIC RETROVIRUSES; SELECTABLE GENE; STROMAL CELLS; CANINE MODEL; MURINE C1 UNIV TENNESSEE,DEPT RADIAT ONCOL,KNOXVILLE,TN 37901. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT COMPARAT MED,WINSTON SALEM,NC 27103. NHLBI,MOLEC HEMATOL LAB,BETHESDA,MD 20892. RP LOTHROP, CD (reprint author), UNIV TENNESSEE,COLL VET MED,DEPT ENVIRONM PRACTICE,POB 1071,KNOXVILLE,TN 37901, USA. FU NHLBI NIH HHS [HL-15647]; NINDS NIH HHS [NS-10967] NR 44 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 JUL 1 PY 1991 VL 78 IS 1 BP 237 EP 245 PG 9 WC Hematology SC Hematology GA FU768 UT WOS:A1991FU76800032 PM 2070056 ER PT J AU KARP, JE MERZ, WG DICK, JD SARAL, R AF KARP, JE MERZ, WG DICK, JD SARAL, R TI STRATEGIES TO PREVENT OR CONTROL INFECTIONS AFTER BONE-MARROW TRANSPLANTS SO BONE MARROW TRANSPLANTATION LA English DT Review ID ORAL TRIMETHOPRIM-SULFAMETHOXAZOLE; ACUTE NONLYMPHOCYTIC LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; PLACEBO-CONTROLLED TRIAL; GRANULOCYTOPENIC PATIENTS; CANCER-PATIENTS; DOUBLE-BLIND; AMPHOTERICIN-B; INVASIVE ASPERGILLOSIS; BACTERIAL-INFECTIONS AB Patients receiving bone marrow transplants are at risk of life-threatening infections early post-transplant. This predisposition results from extensive mucosal damage and severe granulocytopenia. Common causes of infection include bacteria and fungi. Infections with opportunistic pathogens occur later and are associated with defects in cellular and/or humoral immunity. The most common sites of infections are the gastrointestinal tract, oropharynx, lung, skin and indwelling vascular catheters. Empiric approaches designed to treat common bacterial and fungal pathogens are generally effective as are measures designed to prevent dissemination of infections. These approaches are also used to prevent fungal infections. C1 JOHNS HOPKINS MED INST,BALTIMORE,MD 21205. RP KARP, JE (reprint author), NCI,9000 ROCKVILLE PIKE,BLDG 31,ROOM 11A27,BETHESDA,MD 20892, USA. NR 77 TC 17 Z9 17 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD JUL PY 1991 VL 8 IS 1 BP 1 EP 6 PG 6 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA FY099 UT WOS:A1991FY09900001 PM 1912952 ER PT J AU COMMISSIONG, JW SAUVE, Y CSONKA, K KAROUM, F TOFFANO, G AF COMMISSIONG, JW SAUVE, Y CSONKA, K KAROUM, F TOFFANO, G TI RECOVERY OF FUNCTION IN SPINALIZED, NEONATAL RATS SO BRAIN RESEARCH BULLETIN LA English DT Article DE NEONATAL RAT; CORDOTOMY; GM1 GANGLIOSIDE; FUNCTIONAL RECOVERY; MOTOR CENTRAL PATTERN GENERATOR; PROPRIOCEPTIVE AFFERENTS; NEURAL TRANSPLANTATION; SPINAL CORD INJURY ID NON-RECIPROCAL INHIBITION; RESPIRATORY ACTIVITY; CORD TRANSECTION; TRICEPS SURAE; ADULT-RAT; CAT; NEURONS; INTERNEURONES; GANGLIOSIDES; MOTONEURONES AB Neonatal rats, when spinalized on the fourteenth postnatal day, showed minimal recovery of function in their hindlimbs. Bridging the cut spinal cord with E16 fetal spinal cord tissue did not improve functional recovery. Bridging, plus treatment with GM1 ganglioside, caused a significant (p < 0.05) improvement in function, versus the bridged animals treated with saline. The E16 spinal cord transplants survived poorly, or not at all. Contact of the hindlimbs with a surface is necessary to elicit function. Regrowth of descending fibers into the caudal region of the cord is probably not involved in functional recovery. It is suggested that functional recovery is mediated by hindlimb proprioceptive afferents, which activate the lumbosacral motor central pattern generator. C1 MCGILL UNIV,DEPT PHYSIOL,MONTREAL H3G 1Y6,QUEBEC,CANADA. ST ELIZABETH HOSP,NIMH,CTR NEUROSCI,DIV NEUROPSYCHOPHARMACOL,WASHINGTON,DC 20032. FIDIA RES LABS,I-35031 ABANO TERME,ITALY. NR 23 TC 6 Z9 6 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PD JUL PY 1991 VL 27 IS 1 BP 1 EP 4 DI 10.1016/0361-9230(91)90272-L PG 4 WC Neurosciences SC Neurosciences & Neurology GA GG702 UT WOS:A1991GG70200001 PM 1933420 ER PT J AU HALL, P HOLM, LE LUNDELL, G BJELKENGREN, G LARSSON, LG LINDBERG, S TENNVALL, J WICKLUND, H BOICE, JD AF HALL, P HOLM, LE LUNDELL, G BJELKENGREN, G LARSSON, LG LINDBERG, S TENNVALL, J WICKLUND, H BOICE, JD TI CANCER RISKS IN THYROID-CANCER PATIENTS SO BRITISH JOURNAL OF CANCER LA English DT Article ID BREAST; I-131 AB Cancer risks were studied in 834 thyroid cancer patients given I-131 (4,551 MBq, average) and in 1,121 patients treated by other means in Sweden between 1950 and 1975. Record-linkage with the Swedish Cancer Register identified 99 new cancers more than 2 years after I-131 therapy [standardised incidence ratio (SIR) = 1.43; 95% confidence interval (CI) 1.17-1.75] vs 122 (SIR = 1.19; 95% CI 0.88-1.42) in patients not receiving I-131. In females treated with I-131 overall SIR was 1.45 (95% CI 1.14-1.83) and significantly elevated were noted for tumours of the salivary glands, genital organs, kidney and adrenal gland. No elevated risk of a subsequent breast cancer or leukaemia was noted. SIR did not change over time, arguing against a strong radiation effect of I-131. Organs that were estimated to have received more than 1.0 Gy had together a significantly increased risk of a subsequent cancer following I-131 treatment (SIR = 2.59; n = 18). A significant trend was seen for increasing activities of I-131 with highest risk for patients exposed to greater-than-or-equal-to 3,664 MBq (SIR = 1.80; 95% CI 1.20-2.58). No specific cancer or group of cancers could be convincingly linked to high-dose I-131 exposures since SIR did not increase after 10 years of observation. However, upper confidence intervals could not exclude levels of risk that would be predicted based on data from the study of atomic bomb survivors. We conclude that the current practice of extrapolating the effects of high-dose exposures to lower-dose situations is unlikely to seriously underestimate radiation hazards for low LET radiation. C1 KAROLINSKA HOSP,RADIUM HEMMET,DEPT CANC PREVENT,S-10401 STOCKHOLM,SWEDEN. MALMO GEN HOSP,DEPT GEN ONCOL,S-21401 MALMO,SWEDEN. UNIV HOSP UMEA,CTR ONCOL,S-90185 UMEA,SWEDEN. SAHLGRENS UNIV HOSP,DEPT GEN ONCOL,NUCL MED SECT,S-41345 GOTHENBURG,SWEDEN. UNIV LUND HOSP,DEPT GEN ONCOL,S-22185 LUND,SWEDEN. UNIV UPPSALA HOSP,DEPT GEN ONCOL,S-75014 UPPSALA,SWEDEN. NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. RP HALL, P (reprint author), KAROLINSKA HOSP,RADIUM HEMMET,DEPT GEN ONCOL,S-10401 STOCKHOLM,SWEDEN. RI Tennvall, Jan/F-8760-2014 FU NCI NIH HHS [N01-CP-51034] NR 22 TC 82 Z9 83 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JUL PY 1991 VL 64 IS 1 BP 159 EP 163 DI 10.1038/bjc.1991.261 PG 5 WC Oncology SC Oncology GA FW351 UT WOS:A1991FW35100034 PM 1854616 ER PT J AU YUAN, JH JAMESON, CW GOEHL, TJ COLLINS, BJ CORNIFFE, G KUHN, G CASTRO, C AF YUAN, JH JAMESON, CW GOEHL, TJ COLLINS, BJ CORNIFFE, G KUHN, G CASTRO, C TI EFFECTS OF PHYSICAL BINDING OF O-NITROANISOLE WITH FEED UPON ITS SYSTEMIC AVAILABILITY IN MALE F344 RATS SO BULLETIN OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY LA English DT Article C1 NIEHS,NATL TOXICOL PROGRAM,POB 12233,RES TRIANGLE PK,NC 27709. MIDWEST RES INST,KANSAS CITY,MO 64110. NR 6 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0007-4861 J9 B ENVIRON CONTAM TOX JI Bull. Environ. Contam. Toxicol. PD JUL PY 1991 VL 47 IS 1 BP 152 EP 159 PG 8 WC Environmental Sciences; Toxicology SC Environmental Sciences & Ecology; Toxicology GA FQ807 UT WOS:A1991FQ80700023 PM 1932857 ER PT J AU NISHIDA, M KIMOTO, H FUJII, S HAYAKAWA, Y COHEN, LA AF NISHIDA, M KIMOTO, H FUJII, S HAYAKAWA, Y COHEN, LA TI PHOTOCHEMICAL TRIFLUOROMETHYLATION OF 1-METHYLIMIDAZOLES AND 1-METHYLPYRROLES CONTAINING METHYLTHIO GROUPS SO BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN LA English DT Article ID HETEROAROMATIC SYSTEMS; ISOTOPE EXCHANGE; FACILE SYNTHESIS; RING HYDROGENS; IMIDAZOLES AB The title reaction was achieved by UV (254 nm) irradiation with CF3I. The methylthio group was introduced to increase electron density and to limit available reactive sites in the rings. Following trifluoromethylation, the methylthio groups were readily removed by hydrogenolysis (Raney Ni) to give the desired trifluoromethyl heterocycles. C1 NIDDKD, BIOORGAN CHEM LAB, BETHESDA, MD 20892 USA. RP NISHIDA, M (reprint author), GOVT IND RES INST, KITA KU, NAGOYA, AICHI 462, JAPAN. RI Nishida, Masakazu/I-7698-2016 OI Nishida, Masakazu/0000-0001-6588-9566 NR 28 TC 12 Z9 12 U1 2 U2 5 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 JUL PY 1991 VL 64 IS 7 BP 2255 EP 2259 DI 10.1246/bcsj.64.2255 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA FZ827 UT WOS:A1991FZ82700035 ER PT J AU ANDRZEJEWSKI, SJ MOORE, CM CORVETTE, M HERRMANN, D AF ANDRZEJEWSKI, SJ MOORE, CM CORVETTE, M HERRMANN, D TI PROSPECTIVE MEMORY SKILL SO BULLETIN OF THE PSYCHONOMIC SOCIETY LA English DT Article C1 HAMILTON COLL,CLINTON,NY 13323. NIMH,SOCIOENVIRONM STUDIES LAB,BETHESDA,MD 20892. NR 10 TC 18 Z9 18 U1 0 U2 1 PU PSYCHONOMIC SOC INC PI AUSTIN PA 1710 FORTVIEW RD, AUSTIN, TX 78704 SN 0090-5054 J9 B PSYCHONOMIC SOC PD JUL PY 1991 VL 29 IS 4 BP 304 EP 306 PG 3 WC Psychology, Mathematical SC Psychology GA FU974 UT WOS:A1991FU97400006 ER PT J AU DORR, FA FRIEDMAN, MA AF DORR, FA FRIEDMAN, MA TI THE ROLE OF CHEMOTHERAPY IN THE MANAGEMENT OF PRIMARY BREAST-CANCER SO CA-A CANCER JOURNAL FOR CLINICIANS LA English DT Article AB It is known that patients presenting with primary breast cancer may already have established micrometastases at the time of diagnosis that remain clinically undetectable by currently available methods. The precise role of adjuvant chemotherapy and endocrine therapy in controlling these micrometastases is still evolving. In this sixth article in Ca's special series on breast cancer, the authors review the current data and the implications for routine practice. RP DORR, FA (reprint author), NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,BETHESDA,MD 20892, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER CANCER SOC PI NEW YORK PA C/O JB LIPPINCOTT CO 1180 AVE OF THE AMERICAS 6TH FLOOR, NEW YORK, NY 10036 SN 0007-9235 J9 CA-CANCER J CLIN JI CA-Cancer J. Clin. PD JUL-AUG PY 1991 VL 41 IS 4 BP 231 EP 241 DI 10.3322/canjclin.41.4.231 PG 11 WC Oncology SC Oncology GA FV639 UT WOS:A1991FV63900004 PM 2049636 ER PT J AU SAUK, JJ NORRIS, K KERR, JM SOMERMAN, MJ YOUNG, MF AF SAUK, JJ NORRIS, K KERR, JM SOMERMAN, MJ YOUNG, MF TI DIVERSE FORMS OF STRESS RESULT IN CHANGES IN CELLULAR-LEVELS OF OSTEONECTIN SPARC WITHOUT ALTERING MESSENGER-RNA LEVELS IN OSTEOLIGAMENT CELLS SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE LIGAMENT; OSTEONECTIN SPARC; STRESS; HEAT SHOCK ID BASEMENT-MEMBRANE TUMOR; HEAT-SHOCK RESPONSE; POLYACRYLAMIDE GELS; ENDOTHELIAL-CELLS; PROTEIN SPARC; BONE; BINDING; GLYCOPROTEIN; EXPRESSION; INVITRO AB The osteonectin/SPARC gene has been shown to possess motifs for a heat shock element and metal responsiveness. Also, the expression of the protein has been associated with culture stress in endothelial cells. In the present study, osteoligament (OL) cells derived from the patellar ligament were subjected to diverse forms of stress that included (a) exposure to sodium arsenite, (b) heat shock, (c) cadmium ion, and (d) the amino acid analog, AZC. Osteonectin/ SPARC levels in OL cells were determined by Western blot analyses, and immunoprecipitation using antiosteonectin antibodies. Expression of osteonectin/SPARC mRNA was determined by Northern analysis using a 1.5 kb EcoRI restriction fragment of bovine osteonectin cDNA. These studies reveal that osteonectin/SPARC is produced following diverse forms of stress, however, the levels are lower than observed in unchallenged OL cells. In all instances, the mRNA levels were comparable to control cells. These studies indicate that expression of osteonectin/ SPARC mRNA is tightly controlled in OL cells and that the protein may be regulated at the level of protein translation. C1 UNIV MARYLAND,SCH DENT,DEPT PHARMACOL PERIODONT,BALTIMORE,MD 21201. NIDR,BONE RES BRANCH,BETHESDA,MD 20892. RP SAUK, JJ (reprint author), UNIV MARYLAND,SCH DENT,DEPT ORAL PATHOL,66 W BALTIMORE ST,BALTIMORE,MD 21201, USA. FU NIDCR NIH HHS [DE-08648] NR 34 TC 12 Z9 12 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD JUL PY 1991 VL 49 IS 1 BP 58 EP 62 DI 10.1007/BF02555904 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA FR177 UT WOS:A1991FR17700011 PM 1893297 ER PT J AU GREENGALLO, LA BUIVYS, DM FISHER, KL CAPORASO, N SLAWSON, RG ELIAS, EG DIDOLKAR, MS IVUSICH, WJ RESAU, JH AF GREENGALLO, LA BUIVYS, DM FISHER, KL CAPORASO, N SLAWSON, RG ELIAS, EG DIDOLKAR, MS IVUSICH, WJ RESAU, JH TI A PROTOCOL FOR THE SAFE ADMINISTRATION OF DEBRISOQUINE IN BIOCHEMICAL EPIDEMIOLOGIC RESEARCH PROTOCOLS FOR HOSPITALIZED-PATIENTS SO CANCER LA English DT Article ID LUNG-CANCER RISK; METABOLIC PHENOTYPE; HYDROXYLATION; OXIDATION AB The genetically determined ability to metabolize the antihypertensive drug debrisoquine has been proposed as a genetic risk factor for primary carcinomas of the lung. To test this hypothesis, the metabolism of the drug was evaluated in a case control study. The subjects were characterized by their ability to metabolize debrisoquine after receiving a test dose of the drug followed by the collection of an 8-hour urine sample. They were classified by laboratory analysis into one of the following three groups: extensive, intermediate, and poor metabolizers. Poor metabolizers comprise 10% of the population and are unable to hydroxylate the drug. This group was expected to be at highest risk for deleterious effects from this medication. A protocol was created that included patient education and blood pressure monitoring to administer this medication safely to a group of patients with cancer who were already compromised. Although poor metabolizers showed a small decrease in systolic and diastolic blood pressure, no significant hypotensive episodes or clinical sequelae were observed in any of the groups. These data suggest that debrisoquine can be administered safely in a controlled clinical setting and will be useful for the characterization of lung cancer patients in biochemical epidemiology studies. C1 UNIV MARYLAND,SCH MED,DEPT PATHOL,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,DEPT RADIAT ONCOL,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,DEPT SURG ONCOL,BALTIMORE,MD 21201. VET ADM MED CTR,DEPT PATHOL,BALTIMORE,MD 21218. NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892. NR 28 TC 3 Z9 3 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 JUL 1 PY 1991 VL 68 IS 1 BP 206 EP 210 DI 10.1002/1097-0142(19910701)68:1<206::AID-CNCR2820680138>3.0.CO;2-F PG 5 WC Oncology SC Oncology GA FU292 UT WOS:A1991FU29200037 PM 2049747 ER PT J AU STEEG, PS COHN, KH LEONE, A AF STEEG, PS COHN, KH LEONE, A TI TUMOR-METASTASIS AND NM23 - CURRENT CONCEPTS SO CANCER CELLS-A MONTHLY REVIEW LA English DT Review ID GENE-EXPRESSION; CELLS; TRANSFECTION; ONCOGENES; PROGRESSION; CARCINOMA; PROTEIN AB Reduced expression and/or somatic allelic deletion of nm23 is associated with high metastatic potential in several types of rodent tumors and human breast and colorectal carcinomas. Transfection of murine nm23-1 cDNA into highly metastatic murine K-1735 TK melanoma cells results in a reduced incidence of primary tumor formation, significant reduction in tumor metastatic potential, and altered responsiveness to the cytokine, transforming growth factor-beta. Here we discuss emerging concepts concerning nm23, such as its varied pattern of alteration/expression in tumor metastasis, its effect on tumorigenesis, and its possible biochemical functions. C1 SUNY HLTH SCI CTR,DEPT SURG,BROOKLYN,NY 11203. RP STEEG, PS (reprint author), NCI,PATHOL LAB,BETHESDA,MD 20892, USA. RI Leone, Alvaro/K-6410-2016 OI Leone, Alvaro/0000-0003-3815-9052 NR 27 TC 55 Z9 62 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 1042-2196 J9 CANCER CELL-MON REV PD JUL PY 1991 VL 3 IS 7 BP 257 EP 262 PG 6 WC Oncology; Medicine, Research & Experimental SC Oncology; Research & Experimental Medicine GA FZ518 UT WOS:A1991FZ51800001 PM 1911039 ER PT J AU YEWDELL, J AF YEWDELL, J TI MOLECULAR AND CELLULAR BIOLOGY OF ANTIGEN PROCESSING AND PRESENTATION SO CANCER CELLS-A MONTHLY REVIEW LA English DT Editorial Material RP YEWDELL, J (reprint author), NIAID,VIRAL DIS LAB,BETHESDA,MD 20892, USA. RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 1042-2196 J9 CANCER CELL-MON REV PD JUL PY 1991 VL 3 IS 7 BP 278 EP 282 PG 5 WC Oncology; Medicine, Research & Experimental SC Oncology; Research & Experimental Medicine GA FZ518 UT WOS:A1991FZ51800005 PM 1911041 ER PT J AU DOLAN, ME MITCHELL, RB MUMMERT, C MOSCHEL, RC PEGG, AE AF DOLAN, ME MITCHELL, RB MUMMERT, C MOSCHEL, RC PEGG, AE TI EFFECT OF O6-BENZYLGUANINE ANALOGS ON SENSITIVITY OF HUMAN TUMOR-CELLS TO THE CYTOTOXIC EFFECTS OF ALKYLATING-AGENTS SO CANCER RESEARCH LA English DT Article ID MAMMALIAN O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; BONE-MARROW TOXICITY; CROSS-LINKING; DNA ALKYLATION; REPAIR; CHLOROETHYLNITROSOUREA; METHYLTRANSFERASE; CHLOROZOTOCIN; NITROSOUREA; MUTAGENESIS AB The effect of O6-benzylguanine, O6-(p-chlorobenzyl)guanine, and O6-(p-methylbenzyl)guanine on the sensitivity of various human tumor cell lines to alkylating agents is evaluated. The sensitivity of human colon tumor cells, HT29, to the chloroethylating agents, 1,3-bis(2-chloroethyl)-1-nitrosourea, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, 2-chloroethyl(methylsulfonyl) methanesulfonate (clomesone), and chlorozotocin was increased by pretreatment for 2 h with 25-mu-M of each analogue. O6-Benzylguanine was slightly more effective as a sensitizer in HT29 cells than the p-chlorobenzyl and p-methylbenzyl analogues. However, all analogues sensitized SF767 glioma cells to the cytotoxic effects of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, 1,3-bis(2-chloroethyl)-1-nitrosourea, and clomesone to the same degree. Both cell lines were sensitized to the methylating agents streptozotocin and 5-(3-methyl-1-triazeno) imidazole-4-carboxamide, the active intermediate of 5-(3,3-dimethyl-1-triazenyl) imidazole-4-carboxamide, by pretreatment with 10-mu-M O6-benzylguanine for 2 h. The number of Raji cells surviving 50-mu-M clomesone decreased 3-fold upon pretreatment for 2 h with 1-mu-M O6-benzylguanine. The degree of enhancement was dependent on the amount of alkyltransferase protein present in cell lines. For example, HT29 cells (alkyltransferase activity, 381 fmol/mg protein) exhibited a greater degree of enhancement when treated with O6-benzylguanine than SF767 (77 fmol/mg protein) and M19-MEL melanoma (36 fmol/mg protein) cells. There was no enhancement observed in mer- cell lines, U251 (< 2 fmol/mg protein), and BE (3 fmol/mg protein), or with alkylating agents which did not produce a cytotoxic lesion at the O6 position of guanine in DNA such as cisplatin or 4-hydroperoxycyclophosphamide. Our studies suggest that O6-benzylguanine analogues may have utility in mer+ tumors as an adjuvant to a variety of alkylating agents which produce a toxic lesion at the O6 position of guanine. C1 PENN STATE UNIV,MILTON S HERSHEY MED CTR,DEPT CELLULAR & MOLEC PHYSIOL,HERSHEY,PA 17033. PENN STATE UNIV,MILTON S HERSHEY MED CTR,DEPT PHARMACOL,HERSHEY,PA 17033. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,CHEM CARCINOGENESIS LAB,FREDERICK,MD 21702. RP DOLAN, ME (reprint author), UNIV CHICAGO,MED CTR,DIV HEMATOL ONCOL,5841 S MARYLAND AVE,BOX 420,CHICAGO,IL 60637, USA. FU NCI NIH HHS [CA-47228, CA-18137, N01-CO-74101] NR 32 TC 261 Z9 262 U1 0 U2 9 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 JUL 1 PY 1991 VL 51 IS 13 BP 3367 EP 3372 PG 6 WC Oncology SC Oncology GA FT764 UT WOS:A1991FT76400006 PM 1647266 ER PT J AU POLLARD, M LUCKERT, PH SPORN, MB AF POLLARD, M LUCKERT, PH SPORN, MB TI PREVENTION OF PRIMARY PROSTATE-CANCER IN LOBUND-WISTAR RATS BY N-(4-HYDROXYPHENYL)RETINAMIDE SO CANCER RESEARCH LA English DT Note ID L-W RATS; TESTOSTERONE AB We report for the first time that a synthetic retinoid, N-(4-hydroxyphenyl) retinamide, can prevent the development of both primary and metastatic tumors in an animal model of metastasizing primary prostate cancer. Prostatic adenocarcinomas were induced in high incidence in Lobund-Wistar rats by initiation with methylnitrosourea i.v. and promotion with testosterone. Feeding of N-(4-hydroxyphenyl)retinamide to these rats during the latency period markedly diminished the final incidence of both primary and metastatic prostate carcinomas. C1 NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. RP POLLARD, M (reprint author), UNIV NOTRE DAME,LOBUND LAB,NOTRE DAME,IN 46556, USA. NR 9 TC 193 Z9 194 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 1991 VL 51 IS 13 BP 3610 EP 3611 PG 2 WC Oncology SC Oncology GA FT764 UT WOS:A1991FT76400042 PM 1829024 ER PT J AU MARTIN, GR AF MARTIN, GR TI INVASION OF RECONSTITUTED BASEMENT-MEMBRANE MATRIX IS NOT CORRELATED TO THE MALIGNANT METASTATIC CELL PHENOTYPE SO CANCER RESEARCH LA English DT Letter ID TUMOR-CELLS; INVITRO ASSAY; INVASIVENESS; MOTILITY C1 NIDR,DEV BIOL & ANOMALIES,CELL BIOL SECT,BETHESDA,MD 20892. RP MARTIN, GR (reprint author), NIA,GERONTOL RES CTR,BALTIMORE,MD 21224, USA. NR 11 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 1991 VL 51 IS 13 BP 3624 EP 3624 PG 1 WC Oncology SC Oncology GA FT764 UT WOS:A1991FT76400046 PM 2054798 ER PT J AU LI, JJ MUELLER, GC SEKELY, LI AF LI, JJ MUELLER, GC SEKELY, LI TI WORKSHOP REPORT FROM THE DIVISION OF CANCER ETIOLOGY, NATIONAL-CANCER-INSTITUTE, NATIONAL-INSTITUTES-OF-HEALTH - CURRENT PERSPECTIVES AND FUTURE-TRENDS IN HORMONAL CARCINOGENESIS SO CANCER RESEARCH LA English DT Editorial Material C1 UNIV WISCONSIN,MCARDLE LAB CANC RES,MADISON,WI 53706. NCI,DIV CANC ETIOL,BETHESDA,MD 20892. RP LI, JJ (reprint author), WASHINGTON STATE UNIV,DEPT PHARMACEUT SCI,HORMONAL CARCINOGENESIS LAB,PULLMAN,WA 99164, USA. NR 4 TC 9 Z9 11 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 1991 VL 51 IS 13 BP 3626 EP 3629 PG 4 WC Oncology SC Oncology GA FT764 UT WOS:A1991FT76400048 PM 2054799 ER PT J AU ELESPURU, RK STUPAR, LL GORDON, JA AF ELESPURU, RK STUPAR, LL GORDON, JA TI DISCRIMINATION OF MUTAGENIC INTERMEDIATES DERIVED FROM ALKYLATING-AGENTS BY MUTATIONAL PATTERNS GENERATED IN ESCHERICHIA-COLI SO CARCINOGENESIS LA English DT Article ID N-NITROSO COMPOUNDS; LACI GENE; MICROSOMAL METABOLISM; UV MUTAGENESIS; NUCLEIC-ACIDS; DNA-SEQUENCE; RAT-LIVER; SPECIFICITY; CARCINOGEN; NITROSODIMETHYLAMINE AB Reactive intermediates (ultimate mutagens/carcinogens) generated by alkylating agents are unstable and difficult to characterize by chemical means. We have used a genetic system to distinguish the in vivo interactions of eight carcinogenic methylating agents and five ethylating agents by the patterns of induced mutations at different target sites in Escherichia coli WU3610. For this multiple locus assay, target sites were an amber (TAG) and an ochre (TAA) triplet, DNA encoding five suppressor tRNA anticodons, and one unidentified locus. Most of the mutations could be classified as specific sequence changes at the target loci by suppressor analysis using T4 bacteriophage. Ratios of the slopes of dose-response curves for induced mutations were used to generate a profile of preferred sites for mutagenesis independent of mutagen potency. 'Mutational fingerprints' derived from different methylating and ethylating agents were compared, as evidence for the existence of common intermediates responsible for their biological effects. Six methylating agents thought to act via S(N)1 mechanisms were found to generate similar mutational patterns, indicative of a common mechanism, while two methylating agents reacting via S(N)2 mechanisms gave different patterns. The mutational fingerprints of S(N)1- and S(N)-type ethylating agents were also distinct. Mutational fingerprints may be useful in distinguishing the interactions of different ultimate mutagens. C1 NCI,FREDERICK CANC RES FACIL,ABL,BASIC RES PROGRAM,CHEM & PHYS CARCINOGENESIS LAB,FREDERICK,MD 21701. FU PHS HHS [N01-74101] NR 52 TC 6 Z9 6 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUL PY 1991 VL 12 IS 7 BP 1161 EP 1167 DI 10.1093/carcin/12.7.1161 PG 7 WC Oncology SC Oncology GA FW434 UT WOS:A1991FW43400002 PM 2070480 ER PT J AU CRESPI, CL PENMAN, BW GELBOIN, HV GONZALEZ, FJ AF CRESPI, CL PENMAN, BW GELBOIN, HV GONZALEZ, FJ TI A TOBACCO SMOKE-DERIVED NITROSAMINE, 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE, IS ACTIVATED BY MULTIPLE HUMAN CYTOCHROME P450S INCLUDING THE POLYMORPHIC HUMAN CYTOCHROME P4502D6 SO CARCINOGENESIS LA English DT Article ID DEBRISOQUINE METABOLIC PHENOTYPE; LUNG-CANCER; COMPARATIVE CARCINOGENICITY; CELL-LINE; F344 RATS; N'-NITROSONORNICOTINE; DNA; MICROSOMES; OXIDATION; SPARTEINE AB We have developed a human B-lymphoblastoid cell line, designated 2D6/Hol, which stably expresses human cytochrome P450 CYP2D6 cDNA. This cell line exhibits bufuralol 1'-hydroxylase activity and immunologically detectable CYP2D6 protein. The specific activity of (+)-bufuralol 1'-hydroxylase in microsomes from 2D6/Hol cells was comparable to that observed in human liver microsomes. This cell line was used to examine the mutagenicity activation of three tobacco smoke-derived nitrosamines, N-nitrosonornicotine (NNN), 1-(N-methyl-N-nitrosamino)-1-(3-pyridinyl)-4-butanal) (NNA) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), by CYP2D6. Exposure of 2D6/Hol cells to NNK concentrations of 30-90-mu-g/ml induced a concentration-dependent decrease in relative survival and increase in mutant fraction at the hypoxanthine guanine phosphoribosyl transferase (hprt) locus. In contrast, NNK was non-mutagenic and non-cytotoxic to control cells at exposure concentrations up to 150-mu-g/ml. NNK mutagenicity in 2D6/Hol cells was compared to the responses observed in isogenic cell lines expressing human CYP1A2 (1A2/Hol), human CYP2A3 (2A3/Hol) and human CYP2E1 (2E1/Hol). These three additional human cytochrome P450-expressing cell lines were also found to be sensitive to NNK-induced mutagenicity and cytotoxicity. We found no evidence for CYP2D6-mediated activation of NNN or NNA. NNN was non-cytotoxic and non-mutagenic to both control and 2D6/Hol cells. NNA was equally cytotoxic and mutagenic to control cells and 2D6/Hol cells. The activation of NNA to a mutagen may have been carried out by P450 native to the AHH-1 TK +/- cell line. The 2D6/Hol cell line, in conjunction with the control cell line and other isogenic cell lines expressing other human cytochrome P450 cDNAs provides a useful system for the examination of the role of the polymorphic CYP2D6 in human procarcinogen activation and drug metabolism. C1 NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. RP CRESPI, CL (reprint author), GENTEST CORP,6 HENSHAW ST,WOBURN,MA 01801, USA. NR 27 TC 248 Z9 254 U1 0 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUL PY 1991 VL 12 IS 7 BP 1197 EP 1201 DI 10.1093/carcin/12.7.1197 PG 5 WC Oncology SC Oncology GA FW434 UT WOS:A1991FW43400008 PM 2070484 ER PT J AU JANZ, S BREDE, O MULLER, J AF JANZ, S BREDE, O MULLER, J TI THE REACTION OF PRISTANE (2,6,10,14-TETRAMETHYLPENTADECANE) WITH RADIOLYTICALLY GENERATED REACTIVE OXYGEN INTERMEDIATES RESULTS IN A STABLE GENOTOXIC COMPOUND AS ASSESSED BY THE SOS CHROMOTEST SO CARCINOGENESIS LA English DT Article ID COLORIMETRIC BACTERIAL ASSAY; ESCHERICHIA-COLI; INDUCTION; CELLS; AGENTS; NEUTROPHILS; MACROPHAGES; PHAGOCYTES; DAMAGE; MICE AB The most widely studied model of plasmacytomagenesis is the induction of plasmacytomas in BALB/c mice by i.p. injections of the isoalkane pristane (2,6,10,14-tetramethylpentadecane). Employing a simple quantitative and well-established short-term bacterial genotoxicity assay, the SOS chromotest, as a model system, we have investigated whether pristane may potentially be involved in causing or modulating the genotoxic events thought to induce plasma cell tumorigenesis. We found that incorporation of pristane into the cell membranes enhance the SOS response in Escherichia coli PQ37 and PQ300 induced by gamma-radiation under hyperoxic conditions. Moreover, the oxidation of pristane by radiolytically generated reactive oxygen intermediates yielded a stable, genotoxic product active on E. coli PQ300, a SOS tester strain designed to detect oxidative genotoxins. We discuss these findings in relation to the tumor-promoting role of the chronic i.p. inflammation that accompanies plasmacytomagenesis and conclude that, under these specific conditions, pristane may possess a previously unrecognized genotoxic activity in its tumorigenic potential. C1 NCI,GENET LAB,BETHESDA,MD 20892. ACAD SCI GDR,CENT INST ISOTOPE & RADIAT RES,LEIPZIG,GERMANY. RP JANZ, S (reprint author), KARL MARX UNIV,FAC MED,INST CLIN IMMUNOL,O-7010 LEIPZIG,GERMANY. NR 33 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUL PY 1991 VL 12 IS 7 BP 1241 EP 1246 DI 10.1093/carcin/12.7.1241 PG 6 WC Oncology SC Oncology GA FW434 UT WOS:A1991FW43400016 PM 2070489 ER PT J AU PARKER, RJ GILL, I TARONE, R VIONNET, JA GRUNBERG, S MUGGIA, FM REED, E AF PARKER, RJ GILL, I TARONE, R VIONNET, JA GRUNBERG, S MUGGIA, FM REED, E TI PLATINUM DNA DAMAGE IN LEUKOCYTE DNA OF PATIENTS RECEIVING CARBOPLATIN AND CISPLATIN CHEMOTHERAPY, MEASURED BY ATOMIC-ABSORPTION SPECTROMETRY SO CARCINOGENESIS LA English DT Article ID OVARIAN-CANCER PATIENTS; ADDUCT LEVELS; REPAIR; QUANTITATION AB Previous studies have shown that platinum - DNA adduct level in leukocyte DNA (measured by antibody methodology) is directly related to disease response in ovarian cancer and testicular cancer. To determine if this principle could be more broadly applied, platinum - DNA damage was studied in a blinded fashion in leukocyte DNA of 21 cancer patients who received carboplatin (day 1) and cisplatin (day 3) in a phase 1 clinical trial. Fifteen different tumor types were included in this cohort. Using atomic absorption spectrometry with Zeeman background correction, DNA-bound platinum was measured during cycles 1 (C1) and 2 (C2) of therapy for most patients. For each of two cycles of therapy, most patients developed measurable levels of adduct after carboplatin, and in most patients adduct levels increased further after cisplatin, often in a supra-additive fashion. Total mg dose levels varied by < 2-fold, whereas individual patients differed by as much as 10(3) in their adduct measurements after C1 and after C2, and by 29-fold after the very first carboplatin dose. All patients had refractory disease at the initiation of therapy, and 19 patients were evaluable for disease response. Adduct determinations were made 24 h after the first dose of platinum therapy in 17 of these individuals. Mean adduct levels after the first dose of carboplatin were higher in six responders (50 fmol/mu-g DNA +/- 26) than in 11 non-responders (14 fmol/mu-g DNA +/- 10); Wilcoxon two sample test two-sided P = 0.0071. The six responders were patients with pleural mesothelioma (2), breast cancer, buccal mucosa cancer, esophageal cancer and ovarian cancer. Adduct levels were consistently higher in the group of responders on each day that adduct was measured, with a summary two-sided P value of 0.00011. We conclude that analysis of platinum - DNA adduct formation may help determine whether pharmacogenetics are important in cancer drug resistance; and may help to determine the relationship between DNA damage in the peripheral blood compartment and internal organ response to in vivo exposures to DNA-damaging agents. C1 NCI,MED BRANCH,BETHESDA,MD 20892. UNIV SO CALIF,NORRIS CANC CTR,DIV MED ONCOL,LOS ANGELES,CA 90033. NCI,DIV CANC ETIOL,BETHESDA,MD 20892. NR 20 TC 81 Z9 81 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUL PY 1991 VL 12 IS 7 BP 1253 EP 1258 DI 10.1093/carcin/12.7.1253 PG 6 WC Oncology SC Oncology GA FW434 UT WOS:A1991FW43400018 PM 2070490 ER PT J AU SHERN, RJ MIRTH, DB BARTKIEWICZ, A MONELLTORRENS, E LI, SH CHOW, LC AF SHERN, RJ MIRTH, DB BARTKIEWICZ, A MONELLTORRENS, E LI, SH CHOW, LC TI EFFECTS OF AN ACIDIC CALCIUM-PHOSPHATE SOLUTION AND THE INTRAORAL FLUORIDE-RELEASING DEVICE ON DENTAL-CARIES AND FLUORIDE UPTAKE IN RATS SO CARIES RESEARCH LA English DT Article DE CALCIUM PHOSPHATE SOLUTION; FLUORIDE-RELEASING DEVICE; RAT CARIES; FLUORIDE UPTAKE ID TOOTH ENAMEL; PLAQUE; CAHPO4.2H2O; INHIBITION; RINSES; MOLARS; PH AB This investigation comprised two studies evaluating the effects of an acidic calcium phosphate solution (CPS) on fluoride uptake in the enamel, glycolysis of dental plaque, the incidence of dental caries and urinary fluoride concentrations of rats wearing an intraoral fluoride-releasing device (IFRD). In the first study, CPS-fluoride treatment preceded the cariogenic challenge. In the second study, the cariogenic challenge preceded the treatments. In the first study, CPS treatments increased the ability of enamel to bind fluoride. However, the enamel-bound fluoride exerted a negligible effect on plaque glycolysis as measured by the pH decrease after sucrose challenge. In the second study CPS augmented the caries inhibition for both the sulcal-morsal and buccal-lingual surfaces. In both studies the IFRD significantly restricted the development of carious enamel on the sulcal-morsal surfaces and caused elevated concentrations of fluoride in the urine independent of CPS treatments. C1 NATL INST STAND & TECHNOL,PAFFENBARGER RES CTR,AMER DENT ASSOC HLTH FDN,GAITHERSBURG,MD. RP SHERN, RJ (reprint author), NIDR,CLIN INVEST & PATIENT CARE BRANCH,BLDN 10,ROOM 1N114,BETHESDA,MD 20892, USA. NR 25 TC 3 Z9 3 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6568 J9 CARIES RES JI Caries Res. PD JUL-AUG PY 1991 VL 25 IS 4 BP 268 EP 276 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA GD301 UT WOS:A1991GD30100005 PM 1913764 ER PT J AU ONO, M KUWANO, M KUNG, HF AF ONO, M KUWANO, M KUNG, HF TI MALIGNANT TRANSFORMATION OF MOUSE BALB/3T3 CELLS BY POLYOMA MIDDLE T-ANTIGEN REQUIRES EPIDERMAL GROWTH-FACTOR RECEPTOR EXPRESSION SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID EGF RECEPTOR; KINASE-ACTIVITY; PROTO-ONCOGENE; TYROSINE PHOSPHORYLATION; CHEMICAL CARCINOGENS; RAT FIBROBLASTS; FACTOR-BETA; MUTANT; BINDING; VIRUS AB The mouse cell line MO-5, which is defective in receptor-binding activity of epidermal growth factor (EGF), is very poorly transformed by polyoma middle T antigen or v-src gene, but activated c-H-ras and v-mos gene can induce the transformation (M. Ono, M. Yakushinji, K. Segawa, and M. Kuwano, Mol. Cell. Biol., 8: 4190-4196, 1988). We established clones of MO-5 expressing a functional EGF receptor (EGF-R) after introduction of the human EGF-R complementary DNA into MO-5 (MNER23 and MNER31), and we also established a clone (BNER4) expressing human EGF-R from the parental cell line, BALB/3T3. MNER23, MNER31, and BNER4 expressed EGF-R activity at about 2- to 6-fold higher levels than did control BALB/3T3 cells. A marked increase in DNA synthesis in response to EGF was observed in these BNER4, MNER23, and MNER31 cell lines compared to BALB/3T3 cells; however, there was little if any increase in DNA synthesis of MO-5 in the presence of EGF. Introduction of the polyoma middle T antigen gene into BALB/3T3, BNER4, MNER23, and MNER31 resulted in the appearance of transformation foci, but MO-5 again showed little response. We purified clones B4-mT-2, M23-mT-1, M23-mT-2, M23-mT-3, and M31-mT-13 from transformation foci of BNER4, MNER23, and MNER31 cells, which were respectively transfected with the middle T antigen. All of the middle T antigen-positive transfectants demonstrated abilities to form both colonies in soft agar and tumors in nude mice. The presence of EGF-R appears to be indispensable for malignant transformation by polyoma middle T antigen. C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,BIOCHEM PHYSIOL LAB,FREDERICK,MD 21702. RP ONO, M (reprint author), OITA MED SCH,DEPT BIOCHEM,OITA 87955,JAPAN. NR 37 TC 17 Z9 17 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD JUL PY 1991 VL 2 IS 7 BP 317 EP 322 PG 6 WC Cell Biology SC Cell Biology GA FV622 UT WOS:A1991FV62200002 PM 1782150 ER PT J AU FERRIS, DK WHITE, GA KELVIN, DJ COPELAND, TD LI, CCH LONGO, DL AF FERRIS, DK WHITE, GA KELVIN, DJ COPELAND, TD LI, CCH LONGO, DL TI P34CDC2 IS PHYSICALLY ASSOCIATED WITH AND PHOSPHORYLATED BY A CDC2-SPECIFIC TYROSINE KINASE SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID CDC2 PROTEIN-KINASE; CONTROL GENE CDC2+; CELL-CYCLE; ACTIVATION; MITOSIS; DEPHOSPHORYLATION; COMPLEMENTATION; HOMOLOG; SUBUNIT; ENTRY AB The mammalian homologue of the yeast cdc2 gene encodes a 34-kilodalton serine/threonine kinase that is a subunit of M phase-promoting factor. Recent studies have shown that p34cdc2 is also a major tyrosine-phosphorylated protein in HeLa cells and that its phosphotyrosine content is cell cycle regulated and related to its kinase activity. Here, we show that cdc2 is physically associated with and phosphorylated in vitro by a highly specific tyrosine kinase. Tyrosine phosphorylation of cdc2 in vitro occurs at tyrosine 15, the same site that is phosphorylated in vivo. The association between the two kinases takes place in the cytosolic compartment and involves cyclin B-associated cdc2. Evidence is presented that a substantial fraction of cytosolic cdc2 is hypophosphorylated, whereas nuclear cdc2 is hyperphosphorylated. Finally, we show that the tyrosine kinase associated with cdc2 may be a 67-kilodalton protein and is distinct from src, abl, fms, and other previously reported tyrosine kinases. C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,MOLEC IMMUNOREGULAT LAB,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOLEC VIROL & CARCINOGENESIS LAB,FREDERICK,MD 21702. RP FERRIS, DK (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DYNCORP,PROGRAM RESOURCES INC,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74101, N01-CO-74102] NR 21 TC 11 Z9 11 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD JUL PY 1991 VL 2 IS 7 BP 343 EP 349 PG 7 WC Cell Biology SC Cell Biology GA FV622 UT WOS:A1991FV62200005 PM 1664235 ER PT J AU JAKOWLEW, SB MEAD, JE DANIELPOUR, D WU, J ROBERTS, AB FAUSTO, N AF JAKOWLEW, SB MEAD, JE DANIELPOUR, D WU, J ROBERTS, AB FAUSTO, N TI TRANSFORMING GROWTH-FACTOR-BETA (TGF-BETA) ISOFORMS IN RAT-LIVER REGENERATION - MESSENGER-RNA EXPRESSION AND ACTIVATION OF LATENT TGF-BETA SO CELL REGULATION LA English DT Article ID ENDOTHELIAL-CELL PROLIFERATION; EPITHELIAL-CELLS; DNA-SYNTHESIS; C-MYC; PARTIAL-HEPATECTOMY; GENE-EXPRESSION; FACTOR-BETA-1; INHIBITION; HEPATOCYTES; FIBROSIS AB Expression of transforming growth factor-beta-s (TGF-beta-s) 1-3 was studied in normal liver and during liver regeneration after partial hepatectomy in the rat to determine whether each of these isoforms might be involved in hepatocyte growth in vivo. Expression of the mRNAs for all three TGF-beta isoforms increases in the regenerating liver. In addition, the levels of expression of the mRNAs for several extracellular matrix proteins, including fibronectin, vitronectin, laminin, and collagen, also increase in the regenerating liver. Immunohistochemical staining analysis shows a similar distribution of all three TGF-beta-s in normal and regenerating liver; however, in both tissues, the level of expression of TGF-beta-1 is 8- to 10-fold higher than that of TGF-beta-2 as determined by sandwich enzyme-linked immunosorbent assay. Expression of all three TGF-beta mRNAs is restricted to liver nonparenchymal cells. Although hepatocytes from normal and regenerating livers do not synthesize TGF-beta, they are sensitive to inhibition of growth by all three TGF-beta isoforms. Hepatocytes from regenerating livers are capable of activating latent TGF-beta-1 complexes in vitro, whereas normal hepatocytes are not. The different TGF-beta isoforms may function in an inhibitory paracrine mechanism that is activated during liver regeneration and may also regulate the synthesis of extracellular matrix components in the regenerating liver. C1 BROWN UNIV,DEPT PATHOL,PROVIDENCE,RI 02912. RP JAKOWLEW, SB (reprint author), NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892, USA. FU NCI NIH HHS [CA-23226, CA-35249] NR 69 TC 122 Z9 123 U1 0 U2 1 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1044-2030 J9 CELL REGUL PD JUL PY 1991 VL 2 IS 7 BP 535 EP 548 PG 14 WC Cell Biology SC Cell Biology GA FY438 UT WOS:A1991FY43800004 PM 1782214 ER PT J AU RUSS, G BENNINK, JR BACHI, T YEWDELL, JW AF RUSS, G BENNINK, JR BACHI, T YEWDELL, JW TI INFLUENZA-VIRUS HEMAGGLUTININ TRIMERS AND MONOMERS MAINTAIN DISTINCT BIOCHEMICAL MODIFICATIONS AND INTRACELLULAR-DISTRIBUTION IN BREFELDIN A-TREATED CELLS SO CELL REGULATION LA English DT Article ID VESICULAR STOMATITIS-VIRUS; ENDOPLASMIC-RETICULUM; SECRETORY PROTEINS; GOLGI-COMPLEX; ANTIGENIC STRUCTURE; SURFACE EXPRESSION; BINDING-PROTEIN; TRANSPORT; MEMBRANE; GLYCOPROTEINS AB Brefeldin A (BFA) induces the retrograde transport of proteins from the Golgi complex (GC) to the endoplasmic reticulum (ER). It is uncertain, however, whether the drug completely merges the ER with post-ER compartments, or whether some of their elements remain physically and functionally distinct. We investigated this question by the use of monoclonal antibodies specific for monomers and trimers of the influenza virus hemagglutinin (HA). In untreated influenza virus-infected cells, monomers and trimers almost exclusively partition into the ER and GC, respectively. In BFA-treated cells, both monomers and trimers are detected in the ER by immunofluorescence. Cell fractionation experiments indicate, however, that whereas HA monomers synthesized in the presence of BFA reside predominantly in vesicles with a characteristic density of the ER, HA trimers are primarily located in lighter vesicles characteristic of post-ER compartments. Biochemical experiments confirm that in BFA-treated cells, trimers are more extensively modified than monomers by GC-associated enzymes. Additional immunofluorescence experiments reveal that in BFA-treated cells, HA monomers can exist in an ER subcompartment less accessible to trimers and, conversely, that trimers are present in a vesicular compartment less accessible to monomers. These findings favor the existence of a post-ER compartment for which communication with the ER is maintained in the presence of BFA and suggest that trimers cycle between this compartment and the ER, but have access to only a portion of the ER. C1 NIAID,VIRAL DIS LAB,ROOM 209,BLDG 4,BETHESDA,MD 20892. UNIV ZURICH,CENT LAB ELECTRON MICROSCOPE,CH-8028 ZURICH,SWITZERLAND. RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 38 TC 17 Z9 17 U1 0 U2 0 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1044-2030 J9 CELL REGUL PD JUL PY 1991 VL 2 IS 7 BP 549 EP 563 PG 15 WC Cell Biology SC Cell Biology GA FY438 UT WOS:A1991FY43800005 PM 1664239 ER PT J AU TING, CC HARGROVE, ME AF TING, CC HARGROVE, ME TI ANTI-CD3 ANTIBODY-INDUCED ACTIVATED KILLER-CELLS - CYTOKINES AS THE ADDITIONAL SIGNALS FOR ACTIVATION OF KILLER-CELLS IN EFFECTOR PHASE TO MEDIATE SLOW LYSIS SO CELLULAR IMMUNOLOGY LA English DT Article ID CYTOLYTIC LYMPHOCYTES-T; TUMOR NECROSIS FACTOR; TARGET-CELLS; DIFFERENTIATION FACTOR; MONOCLONAL-ANTIBODY; CYTO-TOXICITY; FRIEND VIRUS; IMMUNE LYSIS; INDUCTION; LINES RP TING, CC (reprint author), NCI,DIV CANC BIOL & DIAG,OFF DIRECTOR,BLDG 10,ROOM 4B17,BETHESDA,MD 20892, USA. NR 40 TC 8 Z9 12 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD JUL PY 1991 VL 135 IS 2 BP 273 EP 284 DI 10.1016/0008-8749(91)90273-E PG 12 WC Cell Biology; Immunology SC Cell Biology; Immunology GA FP108 UT WOS:A1991FP10800001 PM 1828008 ER PT J AU Deutch, AY Lee, MC Gillham, MH Cameron, DA Goldstein, M Iadarola, MJ AF Deutch, Ariel Y. Lee, Maggie C. Gillham, Martha H. Cameron, Dorothy A. Goldstein, Menek Iadarola, Michael J. TI Stress Selectively Increases Fos Protein in Dopamine Neurons Innervating the Prefrontal Cortex SO CEREBRAL CORTEX LA English DT Article ID VENTRAL TEGMENTAL AREA; 3,4-DIHYDROXYPHENYLACETIC ACID DOPAC; IMMEDIATE-EARLY GENES; CAT CAUDATE-NUCLEUS; NERVE GROWTH-FACTOR; C-FOS; BETA-CARBOLINE; TYROSINE-HYDROXYLASE; SUBSTANTIA-NIGRA; CEREBRAL-CORTEX AB Stress-induced alterations in expression of c-fos protein (Fos) in mesencephalic dopamine (DA) neurons of the rat were examined in order to discern which midbrain DA neurons are metabolically activated by stress. Restraint stress for 30 min increased the number of DA neurons exhibiting Fos-like immunoreactivity in the ventral tegmental area (VTA), but not in the substantia nigra or retrorubral field. Stress elicited an increase in the number of DA neurons expressing Fos in specific nuclei within the VTA. Administration of the anxiogenic beta-carboline FG 7142 also increased the total number of VTA DA neurons expressing Fos protein, whereas pretreatment with an anxiolytic benzodiazepine (diazepam) partially prevented the stress-induced increase in Fos expression. Restraint stress for 30 min increased concentrations of the DA metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the nucleus accumbens and striatum, as well as in the prefrontal cortex. Retrograde tracer studies revealed that stress increased Fos protein expression in a distinct subset of DA neurons projecting to the prefrontal cortex. In contrast, Fos expression was not increased in any DA neurons projecting to the nucleus accumbens. The present data indicate that there are at least two functionally distinct DA systems embedded within the prefrontal cortex of the rat. C1 [Deutch, Ariel Y.] Yale Univ, Sch Med, Dept Psychiat, CMHC, New Haven, CT 06508 USA. [Deutch, Ariel Y.; Lee, Maggie C.; Gillham, Martha H.; Cameron, Dorothy A.] Dept Vet Affairs Med Ctr, West Haven, CT 06516 USA. [Goldstein, Menek] NYU, Sch Med, Dept Psychiat, New York, NY 10016 USA. [Iadarola, Michael J.] NIDR, Neurobiol & Anesthesiol Branch, NIH, Bethesda, MD 20892 USA. RP Deutch, AY (reprint author), Yale Univ, Sch Med, Dept Psychiat, CMHC, 34 Pk St, New Haven, CT 06508 USA. FU Scottish Rite Schizophrenia Research Program; National Parkinson Foundation Research Laboratories at Yale University; Post-Traumatic Stress Disorder Center; Schizophrenia Research Center of the West Haven Veteran's Administration Medical Center; [MH-45124] FX We wish to acknowledge the anonymous reviewer who suggested that the interoceptive state associated with diazepam administration might contribute to the diazepam-induced increase in Fos expression in A10 DA neurons. This work was supported by grant MH-45124 and a grant from the Scottish Rite Schizophrenia Research Program to A.Y.D., by the National Parkinson Foundation Research Laboratories at Yale University, and by the Post-Traumatic Stress Disorder Center and the Schizophrenia Research Center of the West Haven Veteran's Administration Medical Center. NR 100 TC 112 Z9 113 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD JUL PY 1991 VL 1 IS 4 BP 273 EP 292 DI 10.1093/cercor/1.4.273 PG 20 WC Neurosciences SC Neurosciences & Neurology GA V19BI UT WOS:000208047500001 PM 1668366 ER PT J AU THOMPSON, DC ELING, TE AF THOMPSON, DC ELING, TE TI REACTIVE INTERMEDIATES FORMED DURING THE PEROXIDATIVE OXIDATION OF ANISIDINE ISOMERS SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID PROSTAGLANDIN-H SYNTHASE; PARA-BENZOQUINONE IMINE; AROMATIC-AMINES; ENDOPEROXIDE SYNTHETASE; PARA-PHENETIDINE; HORSERADISH-PEROXIDASE; BINDING; ACTIVATION; METABOLISM; BENZIDINE AB The ortho isomer of anisidine (2-methoxyaniline) causes urinary bladder tumors in both mice and rats while the para isomer (4-methoxyaniline) is inactive. Since the urinary bladder contains substantial peroxidase activity, we investigated the peroxidative metabolism of both o- and p-anisidine using horseradish peroxidase as a model enzyme. Both isomers were excellent reducing cofactors for the oxidized state of horseradish peroxidase (HRP), resulting in one-electron oxidation to free radicals. Using high-pressure liquid chromatography, we observed that HRP oxidized p-anisidine to a diimine metabolite which subsequently hydrolyzed to form a quinone imine. Also observed was a dimeric metabolite with an azo bond. Both the diimine and quinone imine metabolites were reactive toward nucleophiles. The quinone imine formed a conjugate with glutathione and was also reduced by glutathione or ascorbic acid. Higher concentrations of substrate (> 1 mM) led to the formation of polymeric products (tetramer). Similar metabolites (diimine, quinone imine, azo dimer, polymers) were observed with o-anisidine. Using tritium-labeled anisidine, we observed substantial metabolism-dependent covalent binding of both isomers to protein and DNA. These results demonstrate that horseradish peroxidase dependent metabolism of anisidine isomers yields similar metabolites, although some differences in reactivity of the respective intermediates with nucleophiles were observed. C1 NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. NR 32 TC 21 Z9 22 U1 1 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JUL-AUG PY 1991 VL 4 IS 4 BP 474 EP 481 DI 10.1021/tx00022a012 PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA FX149 UT WOS:A1991FX14900012 PM 1912336 ER PT J AU SAREMBOCK, IJ GERTZ, SD GIMPLE, LW OWEN, RM POWERS, ER ROBERTS, WC AF SAREMBOCK, IJ GERTZ, SD GIMPLE, LW OWEN, RM POWERS, ER ROBERTS, WC TI EFFECTIVENESS OF RECOMBINANT DESULFATOHIRUDIN IN REDUCING RESTENOSIS AFTER BALLOON ANGIOPLASTY OF ATHEROSCLEROTIC FEMORAL ARTERIES IN RABBITS SO CIRCULATION LA English DT Article DE ANGIOPLASTY; RESTENOSES; THROMBOSIS; HIRUDIN; HEPARIN ID ACUTE MYOCARDIAL-INFARCTION; TRANS-LUMINAL ANGIOPLASTY; CORONARY ANGIOPLASTY; INTIMAL HYPERPLASIA; THROMBIN INHIBITION; ENDOTHELIAL-CELLS; GROWTH-FACTOR; INJURY; HIRUDIN; ANTICOAGULANT AB Background. The effectiveness of balloon angioplasty is limited by a restenosis rate of approximately 30%. Recombinant desulphatohirudin (r-hirudin [CGP 39393]) has been found to be highly effective in preventing acute platelet-rich thrombosis after deep arterial injury as compared with heparin. Methods and Results. This study evaluated the effect of intravenous r-hirudin, a selective inhibitor of thrombin, on restenosis after balloon angioplasty in 29 rabbits. Focal femoral atherosclerosis was induced by air desiccation endothelial injury followed by a 2% cholesterol diet for 1 month. At angioplasty (2.5-mm balloon with three 60-second, 10-atm inflations 60 seconds apart), the rabbits received heparin (150 units/kg bolus, n = 16) or r-hirudin (1 mg/kg bolus followed by infusions of 1 mg/kg for the first hour and 0.5 mg/kg for the second hour, n = 13). Angiograms performed before and after angioplasty and before death were analyzed quantitatively by a blinded observer. Rabbits were killed 2 hours (n = 14) or 28 days (n = 15) after angioplasty. Femoral arteries were fixed in situ by perfusion of 10% formaldehyde at 100 mm Hg. The mean luminal diameter of the arteries with successful angioplasty (greater-than-or-equal-to 20% increase in luminal diameter) in rabbits treated with heparin (n = 8 arteries) increased from 1.18 +/- 0.29 mm before angioplasty to 1.86 +/- 0.24 mm immediately after angioplasty (p < 0.001) and decreased to 0.94 +/- 0.69 mm (p = 0.0004) at 28 days after angioplasty. In rabbits treated with r-hirudin (n = 11 arteries), the mean luminal diameter increased from 1.14 +/- 0.17 mm before angioplasty to 1.68 +/- 0.20 mm immediately after angioplasty (p < 0.001) and decreased to 1.37 +/- 0.47 mm (p = 0.01) at 28 days after angioplasty. The mean reduction in luminal diameter by angiography was less in the r-hirudin-treated group than in the heparin-treated group (0.30 +/- 0.33 versus 0.92 +/- 0.61 mm, p = 0.01). Blinded planimetric analysis of stained histological sections of the femoral arteries also showed less cross-sectional area narrowing by plaque in rabbits treated with r-hirudin compared with those treated with heparin (22 +/- 16% versus 48 +/- 29%, p = 0.01). Both groups had similar numbers of arteries with histological evidence of balloon-induced plaque tear (12 of 13 versus 13 of 15). Conclusions. Rabbits receiving r-hirudin at the time of experimental balloon angioplasty had significantly less restenosis by angiography and by quantitative histopathology than rabbits receiving heparin. C1 NHLBI,PATHOL BRANCH,BETHESDA,MD 20892. RP SAREMBOCK, IJ (reprint author), UNIV VIRGINIA,HLTH SCI CTR,DEPT MED,DIV CARDIOL,BOX 158,CHARLOTTESVILLE,VA 22908, USA. NR 49 TC 228 Z9 230 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 JUL PY 1991 VL 84 IS 1 BP 232 EP 243 PG 12 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA FV867 UT WOS:A1991FV86700026 PM 1829399 ER PT J AU SPIRITO, P FU, YM YU, ZX EPSTEIN, SE CASSCELLS, W AF SPIRITO, P FU, YM YU, ZX EPSTEIN, SE CASSCELLS, W TI IMMUNOHISTOCHEMICAL LOCALIZATION OF BASIC AND ACIDIC FIBROBLAST GROWTH-FACTORS IN THE DEVELOPING RAT-HEART SO CIRCULATION LA English DT Article DE FIBROBLAST GROWTH FACTORS; IMMUNOHISTOCHEMISTRY; ANTIBODIES ID CARDIAC MYOCYTES; MUSCLE CELLS; FACTOR-BETA; PROLIFERATION; TISSUES; BOVINE; DIFFERENTIATION; FACTOR-BETA-1; ANTIBODIES; EMBRYO AB Background. We used biochemical and immunohistochemcial techniques to investigate the expression and distribution of immunoreactive basic and acidic fibroblast growth factors (bFGF and aFGF, respectively) in the hearts of rat embryos (11-20 days of gestation) and of postnatal rats (1-35 days after birth). Our purpose was to assess the relation between the cellular distribution of these growth factors and histogenetic and morphogenetic events in the developing heart. Methods and Results. Western-blot analysis of heparin-bound material from neonatal heart extracts identified a single band with a molecular weight of approximately 18 kD for both bFGF and aFGF. Five antibodies for bFGF and three for aFGF showed superimposable distribution of immunoreactive bFGF and aFGF in the heart at each stage examined. At the cellular level, these peptides were localized in the cytoplasm and extracellular matrix. In the myocytes, immunostaining was positive throughout the embryonic and neonatal periods. In the majority of the mesenchymal cells of the cushions and endothelial cells of endocardium and vessels, staining was also positive. In the smooth muscle cells of the aorta, other large arteries, and coronary arteries, immunostaining was intensely positive at early stages of development but became faint or negative with increasing cell differentiation. Conclusions. The wide distribution of immunoreactive bFGF and aFGF that we identified in the developing rat heart suggests that these growth factors play an important role in heart cytodifferentiation and morphogenesis. Their superimposable distribution may reflect functional interaction. The progressive changes in their distribution suggest a changing role for these peptides during organogenesis. C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. NR 35 TC 56 Z9 56 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 JUL PY 1991 VL 84 IS 1 BP 322 EP 332 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA FV867 UT WOS:A1991FV86700035 PM 1711938 ER PT J AU BANAI, S JAKLITSCH, MT CASSCELLS, W SHOU, M SHRIVASTAV, S CORREA, R EPSTEIN, SE UNGER, EF AF BANAI, S JAKLITSCH, MT CASSCELLS, W SHOU, M SHRIVASTAV, S CORREA, R EPSTEIN, SE UNGER, EF TI EFFECTS OF ACIDIC FIBROBLAST GROWTH-FACTOR ON NORMAL AND ISCHEMIC MYOCARDIUM SO CIRCULATION RESEARCH LA English DT Article DE NEOVASCULARIZATION; SMOOTH MUSCLE CELLS; ACIDIC FIBROBLAST GROWTH FACTOR; MYOCARDIAL ISCHEMIA ID SMOOTH-MUSCLE CELLS; CARDIAC MYOCYTES; HEPARIN; BINDING; PROLIFERATION; LOCALIZATION; EXPRESSION; DENSITY; CULTURE; PROTEIN AB We sought to determine the effects of acidic fibroblast growth factor (FGF) on ischemic and normal myocardium and to determine whether direct application of acidic FGF to the heart could promote angiogenesis. Eighteen dogs underwent placement of an ameroid constrictor on the left anterior descending coronary artery (LAD). Three weeks later, a left internal mammary artery (IMA) pedicle was positioned over the LAD territory, with a sponge saturated with acidic FGF (n = 12) or saline (n = 4) interposed between the pedicle and the heart. Polytetrafluoroethylene fiber or collagen I sponges were used to deliver the acidic FGF. Weekly angiography of the IMA was performed in all dogs, but significant IMA to coronary collaterals were not demonstrable in any dog. Eight dogs had histological evidence of subendocardial infarction in the LAD territory (five acidic FGF, three control, p = NS). Striking smooth muscle cell hyperplasia was present in arterioles and small arteries exclusively in areas of subendocardial infarction in all of the acidic FGF-treated dogs but in none of the control dogs (p < 0.05). Noninfarcted myocardium appeared normal in all dogs. In two additional dogs, ameroid constrictors were not placed on the LAD, such that acidic FGF-treated sponges were placed on normally perfused myocardium of the LAD territory. Histological evaluation of those hearts revealed normal myocardium, without evidence of myocardial infarction or smooth muscle cell hyperplasia. Thus, when acidic FGF is delivered to the myocardium via an epicardial sponge in dogs whose coronary flow is compromised, acidic FGF does not cause an angiogenic response in viable myocardium but causes vascular smooth muscle cell hyperplasia in areas subjected to ischemic injury. C1 NHLBI, CARDIOL BRANCH, EXPTL PHYSIOL & PHARMACOL LAB, 10-7B15, BETHESDA, MD 20892 USA. NR 32 TC 110 Z9 114 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD JUL PY 1991 VL 69 IS 1 BP 76 EP 85 PG 10 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA FV023 UT WOS:A1991FV02300010 PM 1711423 ER PT J AU HANO, O LAKATTA, EG AF HANO, O LAKATTA, EG TI DIMINISHED TOLERANCE OF PREHYPERTROPHIC, CARDIOMYOPATHIC SYRIAN-HAMSTER HEARTS TO CA2+ STRESSES SO CIRCULATION RESEARCH LA English DT Article DE SYRIAN HAMSTER CARDIOMYOPATHY; CA2+; BETA-ADRENERGIC AGONIST; ALPHA-ADRENERGIC AGONIST; CA2+ CHANNEL AGONIST ID GENETICALLY-DETERMINED CARDIOMYOPATHY; CALCIUM-ANTAGONIST RECEPTORS; RAT CARDIAC-MUSCLE; SARCOPLASMIC-RETICULUM; LIGHT FLUCTUATION; VERAPAMIL; RELEASE; ADRENOCEPTORS; OSCILLATIONS; TRANSIENTS AB Although abnormal myocardial calcium homeostasis in the cardiomyopathic hamster (CMH) has been documented in the hypertrophic stage of the disease, the Ca2+ tolerance before the hypertrophic stage has not been investigated. We studied isovolumic contractile function in response to a variety of Ca2+ stresses including increases in perfusate [Ca2+] (Ca(o)), the Ca2+ channel agonist Bay K 8644, and alpha- or beta-adrenergic agonists of isolated perfused hamster hearts from 24-45-day-old male CMH, BIO 14.6 strain, and age- and sex-matched F1B strain controls. The coronary flow at a constant perfusion pressure did not differ between two groups at baseline or after any Ca2+ stress. At a Ca(o) of 1.0 mM, neither end-diastolic pressure (EDP) nor developed pressure (DP) nor half relaxation time (RT1/2) during stimulation at 1-3 Hz differed between the two groups; as Ca(o) was increased up to 10 mM, CMH hearts showed a lower threshold for the occurrence of a Ca2+ overload profile: EDP and RT1/2 increased to a greater, and DP to a lesser, extent in CMH than in control hearts. To determine whether calcium influx via Ca2+ channels mediates the lower threshold for Ca2+ overload in CMH hearts, we measured resting pressure and scattered laser light intensity fluctuation (SLIF) in unstimulated hearts. Prior studies have shown that SLIF is generated by microscopic tissue motion caused by diastolic spontaneous sarcoplasmic reticulum Ca2+ release and that SLIF amplitude reflects the extent of cell and sarcoplasmic reticulum Ca2+ loading. The Ca2+-dependent increase in resting pressure in unstimulated hearts was highly correlated with an increase in SLIF, and this relation was steeper in CMH than in control hearts. CMH hearts also showed a reduced threshold for the occurrence of a Ca2+ overload profile in response to the adrenergic receptor agonists and the Ca2+ channel agonist during electrical stimulation in a Ca(o) of 2.0 mM: maximum DP achieved with each agonist was significantly less and the dose-response curves to each agonist were shifted leftward in CMH versus control hearts. In CMH hearts EDP began to increase at a significantly lower concentration of each agonist, and the maximum extent of increase in EDP in response to all agonists was significantly enhanced compared with control hearts. In response to beta-adrenergic or Ca2+ channel agonists, neither resting pressure nor SLIF in unstimulated hearts increased in control or in CMH hearts. In contrast, in response to alpha-adrenergic stimulation, both SLIF and resting pressure increased to a greater extent in CMH than in control hearts. These results indicate that in the prehypertrophic CMH heart contractile function is preserved, and no evidence of cellular Ca2+ overload is present during conditions requiring relatively low contractile performance. However, in response to an increase of Ca(o) or to the addition of adrenergic or Ca2+ channel agonists, CMH hearts evidenced a lower threshold for signs of Ca2+ overload than did control hearts. This indicates that this cardiomyopathy is not solely due to vascular pathology and that a latent Ca2+ intolerance of myocardial cells occurs in CMH at an early stage of the disease. That Ca2+ overload could be elicited by an increase in Ca(o) in the absence of electrical stimulation indicates that it is not mediated via Ca2+ influx via Ca2+ channels. C1 NIA,GERONTOL RES CTR,4940 EASTERN AVE,BALTIMORE,MD 21224. NR 39 TC 29 Z9 29 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD JUL PY 1991 VL 69 IS 1 BP 123 EP 133 PG 11 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA FV023 UT WOS:A1991FV02300015 PM 1711422 ER PT J AU SILVERMAN, HS NINOMIYA, M BLANK, PS HANO, O MIYATA, H SPURGEON, HA LAKATTA, EG STERN, MD AF SILVERMAN, HS NINOMIYA, M BLANK, PS HANO, O MIYATA, H SPURGEON, HA LAKATTA, EG STERN, MD TI A CELLULAR MECHANISM FOR IMPAIRED POSTHYPOXIC RELAXATION IN ISOLATED CARDIAC MYOCYTES - ALTERED MYOFILAMENT RELAXATION KINETICS AT REOXYGENATION SO CIRCULATION RESEARCH LA English DT Article DE MYOCYTES; RELAXATION; MYOFILAMENTS; CALCIUM; HYPOXIA ID INTRACELLULAR CALCIUM; MYOCARDIAL HYPOXIA; CONTRACTILE FAILURE; INORGANIC-PHOSPHATE; PH MEASUREMENT; FERRET HEART; TENSION; MUSCLE; CA-2+; PHOSPHORYLATION AB Single, isolated rat ventricular myocytes were made hypoxic for 10 minutes and then reoxygenated. During hypoxia, there was a marked abbreviation of the mechanical twitch, without a decrease in its amplitude. Immediately after reoxygenation, both the time to peak shortening and the duration of relaxation were markedly prolonged, and they remained prolonged for 10-50 minutes. The alterations in contraction and relaxation were not associated with any change in the time course of either the transmembrane action potential or the cytosolic calcium transient, as recorded with the fluorescent probe indo 1. Intracellular pH, measured with a fluorescent probe (carboxyseminaphthorhodofluor), showed an acid shift during hypoxia and an alkaline rebound immediately after reoxygenation. The time courses of intracellular pH and contraction duration were not parallel during hypoxia or reoxygenation, and simulation of the alkaline pH shift by lowering PCO2 or superfusing NH4Cl (in the absence of exposure to hypoxia) did not quantitatively reproduce the prolongation of relaxation seen after reoxygenation. The prolongation of contraction after reoxygenation could be overridden by the beta-adrenergic agonist isoproterenol or the nonenzymatic phosphatase butanedione monoxime. We conclude that delayed relaxation after reoxygenation exists at the single cell level and is due to an alteration of the properties of the myofilaments. Intracellular pH is not the primary mediator of this alteration. We speculate that alteration of intracellular inorganic phosphate or covalent modification of the myofilaments might be involved. C1 JOHNS HOPKINS MED INST,DEPT MED,DIV CARDIOL,BALTIMORE,MD 21205. NIA,GERONTOL RES CTR,CARDIOVASC SCI LAB,BETHESDA,MD 20892. FU NHLBI NIH HHS [R01 HL-42050, P50 HL-17655] NR 27 TC 29 Z9 29 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD JUL PY 1991 VL 69 IS 1 BP 196 EP 208 PG 13 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA FV023 UT WOS:A1991FV02300022 PM 2054932 ER PT J AU HEALY, BP AF HEALY, BP TI QUO-VADIS, NIH - THE NEW DIRECTOR PLOTS A COURSE SO CLEVELAND CLINIC JOURNAL OF MEDICINE LA English DT Article RP HEALY, BP (reprint author), NIH,RES INST,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CLEVELAND CLINIC PI CLEVELAND PA 9500 EUCLID AVE, CLEVELAND, OH 44106 SN 0891-1150 J9 CLEV CLIN J MED JI Clevel. Clin. J. Med. PD JUL-AUG PY 1991 VL 58 IS 4 BP 305 EP 307 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA FX163 UT WOS:A1991FX16300007 PM 1889112 ER PT J AU IZZO, AA MARMION, BP HACKSTADT, T AF IZZO, AA MARMION, BP HACKSTADT, T TI ANALYSIS OF THE CELLS INVOLVED IN THE LYMPHOPROLIFERATIVE RESPONSE TO COXIELLA-BURNETII ANTIGENS SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE Q-FEVER ANTIGENS AND FRACTIONS; LYMPHOPROLIFERATIVE RESPONSES ID Q-FEVER VACCINE; PHASE-I; LIPOPOLYSACCHARIDE; IMMUNITY; IDENTIFICATION; INTRASTRAIN; MONOCYTES; MICE AB Vaccination with an inactivated, whole cell, Q fever vaccine (Q-vax) induces lasting antibody conversion and a positive delayed-type hypersensitivity (DTH) skin reaction in about 60% of recipients but a long-lasting positive lymphoproliferative or mitogenic response to C. burnetii antigens with peripheral blood mononuclear cells (PBMC) in 85-95% of subjects. Analysis of the lymphoproliferative response to C. burnetii antigens has now been made by fractionation-reconstitution experiments with PBMC from vaccinees, from past infections, and from healthy controls. The major contributor to the response in immune subjects proved to be the T lymphocyte. T cells were stimulated by both the phase I and phase II antigens of two prototype strains of C. burnetii and responses were greately amplified by addition of IL-2. Similar T lymphocyte stimulation profiles were obtained with the 'Priscilla' strain of C. burnetii which represents a different biotype of Coxiella isolated from Q fever endocarditis; Q-vax is therefore likely to protect against endocarditis strains. Fractionation-reconstitution experiments with T and B cells from vaccinees and subjects infected in the past, using various antigenic or haptenic fractions from C. burnetii indicate that protein, nonlipopolysaccharide components of the organism are responsible for the mitogenic response of immune T cells. However, the role of the lipopolysaccharide in the protective immunogen has still to be defined. C1 UNIV ADELAIDE,DEPT PATHOL,GPO BOX 498,ADELAIDE,SA 5000,AUSTRALIA. NIAID,ROCKY MT LAB,HAMILTON,MT 59840. RI Izzo, Angelo/F-1229-2017 OI Izzo, Angelo/0000-0003-3208-2330 NR 46 TC 15 Z9 16 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD JUL PY 1991 VL 85 IS 1 BP 98 EP 108 PG 11 WC Immunology SC Immunology GA FU469 UT WOS:A1991FU46900018 PM 2070564 ER PT J AU BOUMPAS, DT PALIOGIANNI, F ANASTASSIOU, ED BALOW, JE AF BOUMPAS, DT PALIOGIANNI, F ANASTASSIOU, ED BALOW, JE TI GLUCOCORTICOSTEROID ACTION ON THE IMMUNE-SYSTEM - MOLECULAR AND CELLULAR ASPECTS SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Review DE GLUCOCORTICOSTEROIDS; GENE TRANSCRIPTION; LIPOCORTINS; MONOCYTES; LYMPHOCYTES; TRANSCRIPTION FACTOR ID NITRIC-OXIDE SYNTHASE; HUMAN-LYMPHOCYTES; GROWTH-FACTOR; PHOSPHOLIPASE-A2 INHIBITOR; PROTEIN-DEGRADATION; ENDOTHELIAL-CELLS; RESPONSE ELEMENT; GENE-REGULATION; B-CELLS; DEXAMETHASONE AB The history of glucocorticosteroid therapy and modern rheumatology are inseparable. Glucocorticosteroids exert profound effects on the inflammatory and immune responses. They affect the growth, differentiation and function of monocytes and lymphocytes, the distribution of cellular subsets, and the production of cytokines. Glucocorticosteroid-induced lipocortins inhibit eicosanoid production and release by suppressing phospholipase A2. The principal mechanism whereby they exert their powerful effects is through modulation of the transcription of specific sets of genes. Recently, post-transcriptional mechanisms have also been recognized to be affected by glucocorticosteroids. In this review we discuss the molecular and cellular aspects of glucocorticosteroid action on the immune system. RP BOUMPAS, DT (reprint author), NIDDKD,KIDNEY DIS SECT,BLDG 10,ROOM 3N116,BETHESDA,MD 20892, USA. NR 81 TC 142 Z9 146 U1 0 U2 1 PU CLINICAL & EXPER RHEUMATOLOGY PI PISA PA VIA SANTA MARIA 31, 56126 PISA, ITALY SN 0392-856X J9 CLIN EXP RHEUMATOL JI Clin. Exp. Rheumatol. PD JUL-AUG PY 1991 VL 9 IS 4 BP 413 EP 423 PG 11 WC Rheumatology SC Rheumatology GA FZ706 UT WOS:A1991FZ70600015 PM 1934694 ER PT J AU NUSSINOV, R AF NUSSINOV, R TI COMPOSITIONAL VARIATIONS IN DNA-SEQUENCES SO COMPUTER APPLICATIONS IN THE BIOSCIENCES LA English DT Article ID REGULATORY SITES; MOLECULAR-BIOLOGY; EUKARYOTIC DNA; PATTERNS; NUCLEOTIDES; PERIODICITY; PROTEIN; CONTEXT; ORIGIN; TRACTS AB Biologically occurring nucleotide sequences differ from randomly generated ones. Here we describe general patterns found in prokaryotic and in eukaryotic DNA. In the accompanying paper (Nussinov, 1991) we also describe DNA signals recognized by their corresponding protein factors. In particular, we focus on modes of searches for such patterns and signals and on the potential properties such sequences may possess. C1 TEL AVIV UNIV,FAC MED,SACKLER INST MOLEC MED,IL-69978 TEL AVIV,ISRAEL. RP NUSSINOV, R (reprint author), NCI,MATH BIOL LAB,BLDG 10,RM 4B-56,BETHESDA,MD 20892, USA. NR 25 TC 18 Z9 18 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0266-7061 J9 COMPUT APPL BIOSCI JI Comput. Appl. Biosci. PD JUL PY 1991 VL 7 IS 3 BP 287 EP 293 PG 7 WC Computer Science, Interdisciplinary Applications SC Computer Science GA FY071 UT WOS:A1991FY07100001 PM 1913208 ER PT J AU NUSSINOV, R AF NUSSINOV, R TI SIGNALS IN DNA-SEQUENCES AND THEIR POTENTIAL PROPERTIES SO COMPUTER APPLICATIONS IN THE BIOSCIENCES LA English DT Article ID REPRESSOR OPERATOR COMPLEX; DOUBLE-HELICAL DNA; BASE SEQUENCE; REGULATORY SITES; INITIATION SITES; TRANSCRIPTION; PROTEIN; REGIONS; EUKARYOTES; RESOLUTION AB DNA and RNA molecules contain signals which are recognized by regulatory proteins or enzymes either directly, through their nucleotide sequences or indirectly, through induced structural changes on their neighboring sequences. To date, most signal searches have been focused on specific recurrences of nucleotide sequences. Much less attention has been directed towards the structure, flexibility and hydrogen-bonding patterns that recognition elements may possess. Here we review the various methods involved in such searches, In particular, however, we also address the searches for potential properties. In this regard it is of interest to inspect the asymmetry in the distributions of complementary oligomers near biological features. Upstream of transcription initiation the frequencies of G-rich oligomers are particularly high (Nussinov, 1987a; 1990). The frequencies of C-rich oligomers are lower. A-tracts are also very frequent in these regions. This may correlate with the recent finding that guanine, but not cytosine, tracts enhance A-tract directed bends (Milton et al., 1990). Presumably A-tracts near G-tracts on the same strand may induce a structural change in the G-tracts which may enhance the bend. G-tracts may have the potential for participating in a DNA bend due to their compression of the major groove. Thus, proteins may not always be necessary to induce DNA conformational changes. This example illustrates the importance of studies of the properties of DNA oligomers in regulatory regions, and of algorithms for their detection. C1 TEL AVIV UNIV,FAC MED,SACKLER INST MOLEC MED,IL-69978 TEL AVIV,ISRAEL. RP NUSSINOV, R (reprint author), NCI,MATH BIOL LAB,BLDG 10,ROOM 4B-56,BETHESDA,MD 20892, USA. NR 45 TC 11 Z9 11 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0266-7061 J9 COMPUT APPL BIOSCI JI Comput. Appl. Biosci. PD JUL PY 1991 VL 7 IS 3 BP 295 EP 299 PG 5 WC Computer Science, Interdisciplinary Applications SC Computer Science GA FY071 UT WOS:A1991FY07100002 PM 1913209 ER PT J AU ROCK, DL AF ROCK, DL TI THE DEVELOPMENT OF THE EGO - IMPLICATIONS FOR PERSONALITY THEORY, PSYCHOPATHOLOGY, AND THE PSYCHOTHERAPEUTIC PROCESS - GREENSPAN,SI SO CONTEMPORARY PSYCHOLOGY LA English DT Book Review C1 VANDERBILT UNIV,PSYCHOL,NASHVILLE,TN 37240. RP ROCK, DL (reprint author), NIMH,CTR PSYCHOTHERAPY RES,WASHINGTON,DC 20032, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0010-7549 J9 CONTEMP PSYCHOL JI Comtemp. Psychol. PD JUL PY 1991 VL 36 IS 7 BP 593 EP 594 PG 2 WC Psychology, Multidisciplinary SC Psychology GA FU150 UT WOS:A1991FU15000031 ER PT J AU INSEL, TR AF INSEL, TR TI PSYCHOENDOCRINOLOGY - BRUSH,FR, LEVINE,S SO CONTEMPORARY PSYCHOLOGY LA English DT Book Review RP INSEL, TR (reprint author), NIMH,COMPARAT STUDIES BRAIN & BEHAV SECT,POOLESVILLE,MD, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0010-7549 J9 CONTEMP PSYCHOL JI Comtemp. Psychol. PD JUL PY 1991 VL 36 IS 7 BP 599 EP 600 PG 2 WC Psychology, Multidisciplinary SC Psychology GA FU150 UT WOS:A1991FU15000036 ER PT J AU CRAWLEY, JN AF CRAWLEY, JN TI ANIMAL-MODELS OF DEPRESSION - KOOB,GF, EHLERS,CL, KUPFER,DJ SO CONTEMPORARY PSYCHOLOGY LA English DT Book Review RP CRAWLEY, JN (reprint author), NIMH,EXPTL THERAPEUT BRANCH,BEHAV NEUROPHARMACOL UNIT,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0010-7549 J9 CONTEMP PSYCHOL JI Comtemp. Psychol. PD JUL PY 1991 VL 36 IS 7 BP 613 EP 614 PG 2 WC Psychology, Multidisciplinary SC Psychology GA FU150 UT WOS:A1991FU15000049 ER PT J AU FUJINO, Y MOCHIZUKI, M CHAN, CC RABER, J KOTAKE, S GERY, I NUSSENBLATT, RB AF FUJINO, Y MOCHIZUKI, M CHAN, CC RABER, J KOTAKE, S GERY, I NUSSENBLATT, RB TI FK506 TREATMENT OF S-ANTIGEN INDUCED UVEITIS IN PRIMATES SO CURRENT EYE RESEARCH LA English DT Article ID PEPTIDYL-PROLYL ISOMERASE; IMMUNOSUPPRESSIVE AGENT; RENAL-TRANSPLANTATION; FK-506; INVITRO; STREPTOMYCES; CYCLOSPORINE; ACTIVATION; BABOONS; DISEASE AB FK506 is a new immunosuppressive agent which has been found more potent than cyclosporine based on the dosage. FK506 was examined here for its effect on the development of uveitis in primates immunized with S-antigen. FK506 successfully inhibited uveitis in monkeys, even when administered three weeks after the first immunization, at the time when the immunopathogenic mechanism of uveitis is assumed to be developed. All four monkeys injected with 0.5 mg/kg/day of FK506 did not develop uveitis, 2 out of 4 treated with the 0.25 mg and 3 out of 4 of those receiving the 0.125 mg also did not develop disease. FK506 suppressed to some extent the cellular and humoral immune responses to S-antigen. The main side effect of FK506 was weight loss. We consider that this drug may be considered as a new potential therapeutic agent for immune-mediated ocular disease in humans. C1 NEI,IMMUNOL LAB,BLDG 10,ROOM 10N202,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. KURUME UNIV,DEPT OPHTHALMOL,KURUME,FUKUOKA 830,JAPAN. NR 28 TC 23 Z9 24 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD JUL PY 1991 VL 10 IS 7 BP 679 EP 690 DI 10.3109/02713689109013859 PG 12 WC Ophthalmology SC Ophthalmology GA FZ295 UT WOS:A1991FZ29500010 PM 1717199 ER PT J AU SATO, SM SARGENT, TD AF SATO, SM SARGENT, TD TI LOCALIZED AND INDUCIBLE EXPRESSION OF XENOPUS-POSTERIOR (XPO), A NOVEL GENE ACTIVE IN EARLY FROG EMBRYOS, ENCODING A PROTEIN WITH A CCHC FINGER DOMAIN SO DEVELOPMENT LA English DT Article DE XENOPUS; POSTERIOR (XPO); GENE ACTIVITY; PROTEIN ID COMPLETE NUCLEOTIDE-SEQUENCE; MURINE LEUKEMIA-VIRUS; HOMEOBOX GENE; MESODERM INDUCTION; GROWTH-FACTORS; CELL-LINE; LAEVIS; RNA; ANTERIOR; IDENTIFICATION AB Xenopus-posterior (Xpo) is a gene that is activated at or shortly after the midblastula transition (MBT). The RNA accumulates to a relatively low level, which remains constant until gastrulation, then rapidly and transiently increases in posterior ectoderm and mesoderm. A single copy of a putative finger motif, of the 'CCHC' type, is located near the carboxyl terminus. One or two copies of similar sequence motifs are found in the nucleocapsid protein of retroviruses where they are involved in protein-RNA interactions, and in cellular nucleic acid binding protein (CNBP), a protein that binds to the sterol regulatory element. Xpo expression is induced in ectodermal explants by treatment with basic fibroblast growth factor (bFGF) and with polypeptide growth factors found in medium conditioned by the Xenopus XTC cell line (XTC-CM). Taken together, these properties suggest a possible role for Xpo in the organization of the anteroposterior axis during development. C1 NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892. RP SATO, SM (reprint author), NIDDK,CLIN ENDOCRINOL BRANCH,BETHESDA,MD 20892, USA. NR 44 TC 67 Z9 68 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD JUL PY 1991 VL 112 IS 3 BP 747 EP 753 PG 7 WC Developmental Biology SC Developmental Biology GA FX582 UT WOS:A1991FX58200007 PM 1718676 ER PT J AU MACKEM, S MAHON, KA AF MACKEM, S MAHON, KA TI GHOX 4.7 - A CHICK HOMEOBOX GENE EXPRESSED PRIMARILY IN LIMB BUDS WITH LIMB-TYPE DIFFERENCES IN EXPRESSION SO DEVELOPMENT LA English DT Article DE HOMEOBOX GENES; CHICK EMBRYO; LIMB MORPHOGENESIS; PATTERN FORMATION; INSITU HYBRIDIZATION ID BOX-CONTAINING GENES; MOUSE HOMEOBOX; RETINOIC ACID; DEVELOPMENTAL EXPRESSION; QUANTITATIVE-ANALYSIS; HOMEODOMAIN PROTEINS; CHROMOSOMAL LOCATION; POLARIZING REGION; PATTERN-FORMATION; LOCAL APPLICATION AB Homeobox genes play a key role in specifying the segmented body plan of Drosophila, and recent work suggests that at least several homeobox genes may play a regulatory role during vertebrate limb morphogenesis. We have used degenerate oligonucleotide primers from highly conserved domains in the homeobox motif to amplify homeobox gene segments from chick embryo limb bud cDNAs using the polymerase chain reaction. Expression of a large number of homeobox genes (at least 17) is detected using this approach. One of these genes contains a novel homeobox loosely related to the Drosophila Abdominal B class, and was further analyzed by determining its complete coding sequence and evaluating its expression during embryogenesis by in situ hybridization. Based on sequence and expression patterns, we have designated this gene as Ghox 4.7 and believe that it is the chick homologue of the murine Hox 4.7 gene (formerly Hox 5.6). Ghox 4.7 is expressed primarily in limb buds during development and shows a striking spatial restriction to the posterior zone of the limb bud, suggesting a role in specifying anterior-posterior pattern formation. In chick, this gene also displays differences in expression between wing and leg buds, raising the possibility that it may participate in specifying limb-type identity. C1 NICHHD,MAMMALIAN GENES & DEV LAB,BETHESDA,MD 20892. RP MACKEM, S (reprint author), NCI,PATHOL LAB,BETHESDA,MD 20892, USA. NR 79 TC 47 Z9 48 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD JUL PY 1991 VL 112 IS 3 BP 791 EP 806 PG 16 WC Developmental Biology SC Developmental Biology GA FX582 UT WOS:A1991FX58200011 PM 1682126 ER PT J AU MCGUIRE, MC FIELDS, RM NYOMBA, BL RAZ, I BOGARDUS, C TONKS, NK SOMMERCORN, J AF MCGUIRE, MC FIELDS, RM NYOMBA, BL RAZ, I BOGARDUS, C TONKS, NK SOMMERCORN, J TI ABNORMAL REGULATION OF PROTEIN TYROSINE PHOSPHATASE-ACTIVITIES IN SKELETAL-MUSCLE OF INSULIN-RESISTANT HUMANS SO DIABETES LA English DT Note ID XENOPUS OOCYTES; KINASE-ACTIVITY; HUMAN-PLACENTA; RECEPTOR; MICROINJECTION; SEQUENCE; INVIVO; CELLS AB Insulin resistance in skeletal muscle may be an expression of the genetic basis of a common form of non-insulin-dependent diabetes mellitus (NIDDM) in humans. Impaired insulin action results from an apparent postreceptor defect in insulin signal transduction that limits the influence of the hormone on various protein serine/threonine kinases and phosphatases that are thought to contribute to the mechanism by which insulin affects intracellular events. The fact that numerous responses to insulin are affected suggests that the cause of insulin resistance involves an early step in insulin action. Therefore, we examined the influence of insulin on protein tyrosine phosphatase (PTPase) activities, which may counteract the protein tyrosine kinase activity of the insulin receptor in skeletal muscle of insulin-sensitive and insulin-resistant humans. Insulin infusion in vivo produced a rapid 25% suppression of soluble-PTPase activity in muscle of insulin-sensitive subjects, but this response was severely impaired in subjects who were insulin resistant. Insulin did not affect PTPase activity in the particulate fraction of muscle from either group, but basal particulate activity was 33% higher in resistant subjects than in sensitive subjects. Either or both of these abnormal characteristics of PTPase activities could be central to the causes of insulin resistance and NIDDM. C1 NIDDKD,CLIN DIABET & NUTR SECT,4212 N 16TH ST,PHOENIX,AZ 85016. COLD SPRING HARBOR LAB,COLD SPRING HARBOR,NY 11724. NR 24 TC 93 Z9 95 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 1991 VL 40 IS 7 BP 939 EP 942 DI 10.2337/diabetes.40.7.939 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA FU962 UT WOS:A1991FU96200022 PM 1647997 ER PT J AU FLEGAL, KM EZZATI, TM HARRIS, MI HAYNES, SG JUAREZ, RZ KNOWLER, WC PEREZSTABLE, EJ STERN, MP AF FLEGAL, KM EZZATI, TM HARRIS, MI HAYNES, SG JUAREZ, RZ KNOWLER, WC PEREZSTABLE, EJ STERN, MP TI PREVALENCE OF DIABETES IN MEXICAN-AMERICANS, CUBANS, AND PUERTO-RICANS FROM THE HISPANIC HEALTH AND NUTRITION EXAMINATION SURVEY, 1982-1984 SO DIABETES CARE LA English DT Article; Proceedings Paper CT WORKSHOP ON DIABETES IN HISPANIC AMERICANS CY MAY, 1988 CL NIH, MARY WOODWARD LASKAR CTR, BETHESDA, MD SP NIDDKD, NATL COALIT HISPAN MENTAL HLTH & HUMAN SERV HO NIH, MARY WOODWARD LASKAR CTR ID CARDIOVASCULAR RISK-FACTORS; IMPAIRED GLUCOSE-TOLERANCE; SAN-ANTONIO; HEART-DISEASE; UNITED-STATES; MELLITUS; TEXAS; POPULATION; MORTALITY; PROGRAM AB The purpose of this study was to estimate the prevalence of diagnosed and undiagnosed diabetes among Mexican Americans, Cubans, and Puerto Ricans in the United States and compare these estimates to data from prior surveys for U.S. non-Hispanic whites and blacks. Data for this study are from the Hispanic Health and Nutrition Examination Survey, a multipurpose cross-sectional survey of three U.S. Hispanic populations conducted in 1982-1984. The interviewed sample of people aged 20-74 yr included 3935 Mexican Americans in the southwest, 1134 Cubans in Florida, and 1519 Puerto Ricans in the New York City area. The diabetes component consisted of interview questions on diabetes diagnosis and treatment and an oral glucose tolerance test administered to a subsample. The prevalence of diabetes was two to three times greater for Mexican Americans and Puerto Ricans than for non-Hispanic whites surveyed in 1976-1980. In Cubans, the prevalence was similar to that for non-Hispanic whites. In men and women 45-74 yr of age, the prevalence of diabetes was extremely high for both Mexican Americans (23.9%) and Puerto Ricans (26.1%) compared with Cubans (15.8%) or non-Hispanic whites (12%). The total prevalence of diabetes was not significantly different for Mexican Americans and Puerto Ricans but was significantly lower for Cubans. The relatively lower prevalence of diabetes among Cubans and the high prevalence in both Mexican Americans and Puerto Ricans may be related to socioeconomic, genetic, behavioral, or environmental factors. C1 NATL INST DIABET & DIGEST & KIDNEY DIS,BETHESDA,MD. NATL INST DIABET & DIGEST & KIDNEY DIS,PHOENIX,AZ. PAN AMER UNIV,EDINBURG,TX 78539. UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX 78284. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. RP FLEGAL, KM (reprint author), NATL CTR HLTH STAT,DIV HLTH EXAMINAT STAT,ROOM 900,6525 BELCREST RD,HYATTSVILLE,MD 20782, USA. RI Flegal, Katherine/A-4608-2013; OI Flegal, Katherine/0000-0002-0838-469X NR 29 TC 226 Z9 232 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUL PY 1991 VL 14 IS 7 SU 3 BP 628 EP 638 DI 10.2337/diacare.14.7.628 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA FU311 UT WOS:A1991FU31100022 PM 1914812 ER PT J AU HARRIS, MI AF HARRIS, MI TI EPIDEMIOLOGIC CORRELATES OF NIDDM IN HISPANICS, WHITES, AND BLACKS IN THE UNITED-STATES POPULATION SO DIABETES CARE LA English DT Article; Proceedings Paper CT WORKSHOP ON DIABETES IN HISPANIC AMERICANS CY MAY, 1988 CL NIH, MARY WOODWARD LASKAR CTR, BETHESDA, MD SP NIDDKD, NATL COALIT HISPAN MENTAL HLTH & HUMAN SERV HO NIH, MARY WOODWARD LASKAR CTR ID IMPAIRED GLUCOSE-TOLERANCE; DEPENDENT DIABETES-MELLITUS; CARDIOVASCULAR RISK-FACTORS; 10-YEAR FOLLOW-UP; MEXICAN-AMERICANS; SAN-ANTONIO; SOCIOECONOMIC-STATUS; FAT DISTRIBUTION; NATURAL-HISTORY; STARR COUNTY AB Characteristics, prevalence, and risk factors for non-insulin-dependent diabetes mellitus (NIDDM) among Hispanics, blacks, and whites aged 20-74 yr in the United States population were investigated with two national surveys that used a household interview to ascertain diagnosed diabetes and a 75-g 2-h oral glucose tolerance test to measure undiagnosed diabetes. The Hispanic Health and Nutrition Examination Survey of 1982-1984 studied Mexican Americans in the southwest U.S., Cuban Americans in the Miami, Florida, area, and Puerto Ricans in the New York City area. The National Health and Nutrition Examination Survey of 1976-1980 examined a national sample of U.S. residents, of whom data on blacks and whites were analyzed. People with diagnosed diabetes in the five populations were similar with respect to mean age (53-57 yr), age at diagnosis (45-48 yr), duration of diabetes (6.9-8.7 yr), and diabetes therapies (58-67% using pharmacological treatment). Mean age of people with undiagnosed diabetes (51-59 yr) was comparable to that of diagnosed cases, and mean fasting (7 1-7.8 mM) and 2-h postchallenge plasma glucose (14.1-15.5 mM) values for people with undiagnosed diabetes were similar among the five populations. However, obesity levels varied by race, sex, and whether diabetes was diagnosed or undiagnosed. Age-standardized prevalence of diabetes (sum of diagnosed and undiagnosed cases) was 6.2% in whites, 9.3% in Cubans, 10.2% in blacks, 13% in Mexican Americans, and 13.4% in Puerto Ricans. Thus, compared to whites, diabetes rates were 50-60% higher among Cubans and blacks and 110-120% higher among Mexican Americans and Puerto Ricans. Age-standardized rates of impaired glucose tolerance were similar among the five populations (10.3-13.8%). Increasing age, obesity, and family history of diabetes were associated with higher rates of diabetes but sex, physical activity, education, income, and acculturation were not risk factors or were only weakly associated with diabetes prevalence. RP HARRIS, MI (reprint author), NATL INST DIABET & DIGEST & KIDNEY DIS,NATL DIABET DATA GRP,WESTWOOD 620,BETHESDA,MD 20892, USA. NR 44 TC 139 Z9 143 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUL PY 1991 VL 14 IS 7 SU 3 BP 639 EP 648 DI 10.2337/diacare.14.7.639 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA FU311 UT WOS:A1991FU31100023 PM 1914813 ER PT J AU BOGARDUS, C AF BOGARDUS, C TI PATHOGENESIS OF NIDDM IN PIMA-INDIANS SO DIABETES CARE LA English DT Article; Proceedings Paper CT WORKSHOP ON DIABETES IN HISPANIC AMERICANS CY MAY, 1988 CL NIH, MARY WOODWARD LASKAR CTR, BETHESDA, MD SP NIDDKD, NATL COALIT HISPAN MENTAL HLTH & HUMAN SERV HO NIH, MARY WOODWARD LASKAR CTR ID INVIVO INSULIN ACTION; OBESITY AB The Pima Indians of Arizona have the highest reported prevalence and incidence of non-insulin-dependent diabetes mellitus (NIDDM) of any population in the world. A cross-sectional and longitudinal study was begun in 1982 to determine the metabolic characteristic(s) that is (are) predictive of the development of NIDDM and to document the sequence of metabolic events that occur with the transition from normal to impaired glucose tolerance and then to diabetes. Preliminary analyses suggest that insulin resistance is a primary abnormality predisposing Pima Indians to develop impaired glucose tolerance, and that the development of diabetes occurs with subsequent pancreatic failure. C1 NATL INST DIABET & DIGEST & KIDNEY DIS,CLIN DIABET & NUTR SECT,PHOENIX,AZ. RI Lillioja, Stephen/A-8185-2012; OI Lillioja, Stephen/0000-0001-5333-5240 NR 15 TC 26 Z9 26 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 JUL PY 1991 VL 14 IS 7 SU 3 BP 685 EP 690 DI 10.2337/diacare.14.7.685 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA FU311 UT WOS:A1991FU31100029 PM 1914819 ER PT J AU GOLDSPIEL, BR KOHLER, DR AF GOLDSPIEL, BR KOHLER, DR TI GOSERELIN ACETATE IMPLANT - A DEPOT LUTEINIZING-HORMONE-RELEASING HORMONE ANALOG FOR ADVANCED PROSTATE-CANCER SO DICP-THE ANNALS OF PHARMACOTHERAPY LA English DT Article ID PHASE-III; CARCINOMA; ZOLADEX; DIETHYLSTILBESTROL; ORCHIECTOMY; LEUPROLIDE; ICI-118630; FLUTAMIDE; EFFICACY; AGONIST AB Goserelin acetate implant is a newly approved depot formulation of a luteinizing hormone-releasing hormone (LHRH) agonist indicated for palliation of advanced prostate cancer. LHRH superagonists suppress gonadotropin release from the pituitary gland by causing down-regulation of receptors. The sustained-release dosage form contains goserelin acetate dispersed in a biodegradable copolymer matrix and is designed to release active drug over 28 days. Pharmacokinetic studies have demonstrated that, despite nonzero order release of goserelin from the matrix, goserelin acetate implant maintains serum concentrations of testosterone in the range normally found in castrated men (< 2 nmol/L) throughout the recommended 28-day dosing interval. Response rates similar to those for orchiectomy and estrogen administration have been demonstrated. Combination therapy with either diethylstibestrol or flutamide has produced favorable results, although the major advantage appears to be a reduction in the tumor flare seen during the first week of LHRH agonist therapy rather than an increase in response rate or survival. Adverse effects are similar to other LHRH agonists and include tumor flare during the first week of therapy, decreased libido, decreased erectile potency, hot flashes, and gynecomastia. In combination with flutamide, additional adverse effects include diarrhea, nausea, vomiting, and elevated hepatic aminotransferases, all of which can be attributed to flutamide administration. Local reactions are minimal; however, some patients require a local anesthetic before goserelin acetate implant injection. The recommended dose is 3.6 mg administered subcutaneously into the upper abdominal wall every 28 days. The average wholesale cost is approximately $320 per month. Formulary addition is recommended. RP GOLDSPIEL, BR (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT PHARM,BLDG 10,ROOM 1N-257,BETHESDA,MD 20892, USA. NR 47 TC 8 Z9 8 U1 1 U2 5 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 SN 0012-6578 J9 DICP ANN PHARMAC PD JUL-AUG PY 1991 VL 25 IS 7-8 BP 796 EP 804 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA FX646 UT WOS:A1991FX64600019 PM 1835221 ER PT J AU VALDEZ, IH FOX, PC AF VALDEZ, IH FOX, PC TI INTERACTIONS OF THE SALIVARY AND GASTROINTESTINAL SYSTEMS .2. EFFECTS OF SALIVARY-GLAND DYSFUNCTION ON THE GASTROINTESTINAL-TRACT SO DIGESTIVE DISEASES LA English DT Article AB Salivary gland dysfunction is uniformly detrimental to the oral cavity. Its effects on the GI tract have begun to be explored. Dry mouth is a common complaint among older adults, probably due to systemic disease and its therapy rather than the aging process per se. Evaluation of complaints of dry mouth should include medical history, sialometry and physical examination. Numerous medications can elicit drug-induced xerostomia. Patients who have received radiation therapy to the head and neck region often have permanent radiation-induced xerostomia, which has been linked to esophagitis. SS is an autoimmune systemic exocrinopathy resulting in irreversible salivary gland dysfunction. SS has numerous GI manifestations, including dysphagia, temporal defects of deglutition, esophageal dysmotility, gastritis, pancreatitis and liver disease. Management of salivary hypofunction is directed toward preserving the dentition and improving patient comfort. Drug-induced xerostomia is often correctable by altering the therapeutic modality. RP VALDEZ, IH (reprint author), NIDR,CLIN INVEST & PATIENT CARE BRANCH,BLDG 10,RM 1N-113,BETHESDA,MD 20892, USA. NR 0 TC 20 Z9 20 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0257-2753 J9 DIGEST DIS JI Dig. Dis. PD JUL-AUG PY 1991 VL 9 IS 4 BP 210 EP 218 DI 10.1159/000171305 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA GA697 UT WOS:A1991GA69700002 PM 1914220 ER PT J AU THOMASSEN, D AF THOMASSEN, D TI EFFECT OF STRESS ON DRUG HYPERSENSITIVITY SO DRUG SAFETY LA English DT Article RP THOMASSEN, D (reprint author), NHLBI,CHEM PHARMACOL LAB,BLDG 10,ROOM 8N110,BETHESDA,MD 20892, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0114-5916 J9 DRUG SAFETY JI Drug Saf. PD JUL-AUG PY 1991 VL 6 IS 4 BP 235 EP 240 DI 10.2165/00002018-199106040-00001 PG 6 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA FX269 UT WOS:A1991FX26900001 PM 1888439 ER PT J AU MANOLIOS, N LETOURNEUR, F BONIFACINO, JS KLAUSNER, RD AF MANOLIOS, N LETOURNEUR, F BONIFACINO, JS KLAUSNER, RD TI PAIRWISE, COOPERATIVE AND INHIBITORY INTERACTIONS DESCRIBE THE ASSEMBLY AND PROBABLE STRUCTURE OF THE T-CELL ANTIGEN RECEPTOR SO EMBO JOURNAL LA English DT Article DE ASSEMBLY; COS CELLS; PARTIAL COMPLEXES; T-CELL ANTIGEN RECEPTOR; TRANSFECTION ID NATURAL-KILLER CELLS; MOLECULAR-CLONING; CD3 COMPLEX; ZETA-CHAIN; ETA-CHAIN; SUBUNIT INTERACTIONS; MAMMALIAN-CELLS; DELTA-CHAIN; PROTEIN; GENE AB The T-cell antigen receptor (TCR) is a multi-subunit complex consisting of clonotypic heterodimers (TCR-alpha-beta or TCR-gamma-delta) that are non-covalently linked to at least four invariant chains (CD3-delta,-epsilon,-gamma; and zeta or eta). The ordered process of assembly and the final number of individual chains that comprise the TCR is unclear. In this study, we examined the molecular basis of subunit interactions and the component requirements leading to the formation of a complete TCR. Analysis of transient cotransfections in monkey kidney fibroblasts (COS cells) showed assembly between selective chain pairs. Multiple chain cotransfections demonstrated the formation of stable higher order partial complexes. Assembly of such subcomplexes was facilitated by cooperative interactions between clonotypic and invariant CD3 chains. When zeta was cotransfected with any TCR component, no pairwise interaction was detected. Only when there was coexpression of all of the other TCR chains (TCR-alpha,-beta, CD3-epsilon,-gamma,-delta) did zeta-assemble with the TCR complex. Not all chain pairs formed stable heterodimers. For one such pair, lack of assembly is due to the inhibitory effects of negatively charged residues within their transmembrane domains. The combined effects of these interactions probably determine the assembly and the quaternary structure of the TCR complex. RP MANOLIOS, N (reprint author), NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892, USA. OI Bonifacino, Juan S./0000-0002-5673-6370 NR 46 TC 165 Z9 165 U1 0 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD JUL PY 1991 VL 10 IS 7 BP 1643 EP 1651 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA FR684 UT WOS:A1991FR68400005 PM 1828760 ER PT J AU MULHERON, GW DANIELPOUR, D SCHOMBERG, DW AF MULHERON, GW DANIELPOUR, D SCHOMBERG, DW TI RAT THECAL INTERSTITIAL-CELLS EXPRESS TRANSFORMING GROWTH-FACTOR-BETA TYPE-1 AND TYPE-2, BUT ONLY TYPE-2 IS REGULATED BY GONADOTROPIN INVITRO SO ENDOCRINOLOGY LA English DT Article ID PORCINE GRANULOSA-CELLS; ANDROGEN PRODUCTION; CDNA CLONING; FACTOR-BETA-1; PROTEINS; CULTURES; SEQUENCE; TISSUES; ADULT; ACID AB We previously demonstrated that granulosa cells from diethylstilbestrol-primed immature rats expressed transforming growth factor-beta-2 (TGF-beta-2), but not TGF-beta-1, mRNA and that its expression was regulated by FSH in vitro. The present studies were designed, therefore, to establish whether thecal/interstitial cells (TIC) from diethylstilbestrol-primed immature rats express more than one subtype of TGF-beta-mRNA and gene product and whether the levels of expression/production in vitro were regulated by LH/hCG. Reverse transcription-polymerase chain reaction (RT-PCR) analysis of total RNA indicated that TIC expressed both TGF-beta-1 and TGF-beta-2 mRNA. In response to hCG (200 ng/ml), TIC expressed TGF-beta-2 mRNA levels that were 51% of control levels; TGF-beta-1 mRNA levels were not altered. In response to cholera toxin (10(-9) M), TIC expression of TGF-beta-2 and TGF-beta-1 mRNA levels was 10% and 55% of control values, respectively. Western blot analysis established that both TGF-beta-1 and TGF-beta-2 were secreted in vitro. hCG and cholera toxin reduced secretion of TGF-beta-bioactivity by 55% and 90%, respectively. In summary, these results indicate: 1) TIC express both TGF-beta-1 and TGF-beta-2 mRNA; 2) TIC expression of TGF-beta-2, but not TGF-beta-1, mRNA is regulated by hCG in vitro; 3) TIC secrete both TGF-beta-1 and TGF-beta-2; and 4) TIC secretion in vitro of TGF-beta-activity is gonadotropin regulated. C1 DUKE UNIV,MED CTR,DEPT OBSTET & GYNECOL,BOX 3323,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT CELL BIOL,DURHAM,NC 27710. DUKE UNIV,MED CTR,CTR COMPREHENS CANC,DURHAM,NC 27710. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. FU NICHD NIH HHS [HD-11827, HD-07315] NR 30 TC 47 Z9 47 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 JUL PY 1991 VL 129 IS 1 BP 368 EP 374 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA FT966 UT WOS:A1991FT96600050 PM 1711465 ER PT J AU MEDHAMURTHY, R CULLER, MD GAY, VL NEGROVILAR, A PLANT, TM AF MEDHAMURTHY, R CULLER, MD GAY, VL NEGROVILAR, A PLANT, TM TI EVIDENCE THAT INHIBIN PLAYS A MAJOR ROLE IN THE REGULATION OF FOLLICLE-STIMULATING-HORMONE SECRETION IN THE FULLY ADULT MALE RHESUS-MONKEY (MACACA-MULATTA) SO ENDOCRINOLOGY LA English DT Article ID GONADOTROPIN-SECRETION; CIRCULATING INHIBIN; ALPHA-SUBUNIT; SERUM; IMMUNONEUTRALIZATION; TESTOSTERONE; PUBERTY; RELEASE; BLOOD; MEN AB In the juvenile male rhesus monkey in which an adult-like pattern of endocrine activity in the pituitary-testicular axis is imposed by pulsatile stimulation with exogenous GnRH, administration of inhibin antiserum elicits a marked and selective hypersecretion of FSH. This finding suggests that in the monkey, testicular inhibin plays a major role in the postpubertal regulation of this gonadotropin. The purpose of the present study was to confirm this view more directly. To this end, 10 adult male rhesus monkeys were implanted with indwelling venous catheters and housed in specialized cages that permit continuous access to the venous circulation with minimal restraint and without tranquilization. Six of the males received a continuous infusion of an ovine antiserum to the alpha-subunit of human inhibin (iv bolus injection of 2.22 ml/kg BW, followed by a continuous infusion of serum at 0.62 ml/kg BW .24 h), and 4 animals received a similar infusion of control ovine immune serum. The duration of the infusion of the inhibin antiserum ranged from 2.5-7.5 days, and that for the control serum was 7.5 days. The FSH response to immunoneutralization of circulating inhibin was determined by measuring concentrations of this gonadotropin in sequential plasma samples collected between 1900-2300 h on the day before initiation of the anti-serum infusion and, depending on the duration of the infusion, on days 0.5, 1.5, 2.5, 4.5, and 6.5 of antiserum administration. In 5 of the 6 animals that received the inhibin antiserum, a progressive hypersecretion of FSH was observed during the initial 2.5 days of the infusion. This increase in circulating FSH concentration, which reached, by day 2.5 of treatment, a value 2- to 3-fold greater (P < 0.05) than the pretreatment control level, was not associated with changes in either LH or testosterone levels. Continuation of the infusion of the inhibin antiserum beyond 2.5 days invariably resulted in a marked decline in LH and testosterone secretion, suggesting that the hypophysiotropic drive to the pituitary-testicular axis may have been compromised, presumably by a mechanism related to the infusion of heterologous serum. Infusion of the control immune serum for 2.5 days was not associated with an elevation of circulating FSH concentrations, and changes in circulating concentrations of plasma LH and testosterone were, as expected, unremarkable. Continuation of the infusion of control serum, like that of antiserum, generally resulted in a temporary but precipitous decline in LH and testosterone secretion. Although the nonspecific effects of prolonged infusions of ovine serum on the hypothalamic-pituitary unit partially compromise the present study, the finding of a selective and marked hypersecretion of FSH during the first 2.5 days of infusion of inhibin antiserum provides substantial evidence in confirmation of the view that testicular inhibin plays a major role in the regulation of FSH secretion in the adult male monkey. C1 UNIV PITTSBURGH,SCH MED,DEPT PHYSIOL,W1451 BIOMED SCI TOWER,PITTSBURGH,PA 15261. NIEHS,MOLEC & INTEGRAT NEUROSCI LAB,RES TRIANGLE PK,NC 27709. RI medhamurthy, rudraiah/A-9067-2009 FU NICHD NIH HHS [HD-08610, HD-16851] NR 22 TC 47 Z9 47 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 1991 VL 129 IS 1 BP 389 EP 395 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA FT966 UT WOS:A1991FT96600053 PM 1905228 ER PT J AU LICINIO, J WONG, ML GOLD, PW AF LICINIO, J WONG, ML GOLD, PW TI LOCALIZATION OF INTERLEUKIN-1 RECEPTOR ANTAGONIST MESSENGER-RNA IN RAT-BRAIN SO ENDOCRINOLOGY LA English DT Note ID CORTICOTROPIN-RELEASING FACTOR; EXPRESSION; SECRETION; HORMONES; INHIBIT AB Interleukin-1 (IL-1) is an inflammatory peptide hormone, with potent neuroendocrine effects. IL-1 stimulates the central nervous system production of corticotropin-releasing hormone (CRH), growth hormone (GH), thyroid-stimulating hormone (TSH), and somatostatin, and inhibits the secretion of prolactin and luteinizing hormone (LH). Interleukin-1 receptor antagonist (IL-1ra) is a novel cytokine, recently purified, characterized, and cloned. IL-1ra is a pure endogenous antagonist of IL-1:IL-1 function is modulated not only by local levels of IL-1, but also by the levels of IL-1ra. We have localized by in situ hybridization histochemistry IL-1ra mRNA in rat brain, in areas of importance to neuroendocrine function, such as the paraventricular nucleus (PVN) of the hypothalamus, hippocampus, as well as cerebellum. These findings indicate that IL-1ra is produced in brain in areas of relevance to the regulation of neuroendocrine function and suggest that IL-1ra may modulate the neuroendocrine effects of IL-1. C1 W HAVEN VET AFFAIRS MED CTR 116A,W HAVEN,CT 06516. NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. RP LICINIO, J (reprint author), YALE UNIV,SCH MED,DEPT PSYCHIAT,NEW HAVEN,CT 06510, USA. RI Wong, Ma-Li/D-7903-2011; Licinio, Julio/L-4244-2013 OI Licinio, Julio/0000-0001-6905-5884 NR 26 TC 100 Z9 102 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 JUL PY 1991 VL 129 IS 1 BP 562 EP 564 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA FT966 UT WOS:A1991FT96600076 PM 1829036 ER PT J AU SHORES, EW VANEWIJK, W SINGER, A AF SHORES, EW VANEWIJK, W SINGER, A TI DISORGANIZATION AND RESTORATION OF THYMIC MEDULLARY EPITHELIAL-CELLS IN T-CELL RECEPTOR-NEGATIVE SCID MICE - EVIDENCE THAT RECEPTOR-BEARING LYMPHOCYTES INFLUENCE MATURATION OF THE THYMIC MICROENVIRONMENT SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article ID COMBINED IMMUNE-DEFICIENCY; MONOCLONAL-ANTIBODIES; ANTIGEN EXPRESSION; INTERFERON-GAMMA; FETAL THYMUS; DIFFERENTIATION; MOUSE; ACTIVATION; EVENTS; THYMOCYTES AB In order to assess the possible role of lymphoid cells in the development of thymic epithelium, we compared the organization and maturation of thymic epithelium in scid mice lacking T cell receptor (TcR)-positive cells with that in scid mice containing TcR+ cells. Immunohistologic examination revealed that thymi from TcR- scid mice were deficient in thymic medullary epithelial cells recognized by the monoclonal antibody ER-TR5, and that the few thymic medullary epithelial cells present were not organized into discrete medullary areas. In contrast, thymi from scid mice containing TcR+ cells possessed ER-TR5+ thymic medullary epithelial cells and these cells were organized normally into discrete medullary regions. Thus, normal organization and maturation of thymic medullary epithelial cells did not occur in the absence of TcR+ cells, but did occur upon introduction of TcR+ cells. We conclude that lympho-stromal cell interactions in the thymus are not unidirectional, and that a symbiotic relationship exists between maturing epithelial cells and developing lymphocytes. C1 ERASMUS UNIV,DEPT IMMUNOL,3000 DR ROTTERDAM,NETHERLANDS. RP SHORES, EW (reprint author), NCI,EXPTL IMMUNOL BRANCH,BLDG 10,RM 4B17,BETHESDA,MD 20892, USA. NR 29 TC 161 Z9 162 U1 2 U2 3 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JUL PY 1991 VL 21 IS 7 BP 1657 EP 1661 DI 10.1002/eji.1830210711 PG 5 WC Immunology SC Immunology GA FW387 UT WOS:A1991FW38700010 PM 2060577 ER PT J AU COULIE, PG UYTTENHOVE, C WAUTERS, P MANOLIOS, N KLAUSNER, RD SAMELSON, LE VANSNICK, J AF COULIE, PG UYTTENHOVE, C WAUTERS, P MANOLIOS, N KLAUSNER, RD SAMELSON, LE VANSNICK, J TI IDENTIFICATION OF A MURINE MONOCLONAL-ANTIBODY SPECIFIC FOR AN ALLOTYPIC DETERMINANT ON MOUSE CD3 SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article ID CELL ANTIGEN RECEPTOR; SUBUNIT INTERACTIONS; COMPLEX; DEGRADATION AB A murine monoclonal antibody (mAb; 7D6) that was mitogenic for T cells was derived from 129/Sv animals immunized with a T helper clone from C57BL/6 origin. Fluoresceinated 7D6 labeled T cells from most common mouse strains but not from 129/Sv and LP/J animals, and this labelling was inhibited by the anti-CD3 epsilon mAb 145-2C11. The mitogenicity of 7D6 for T cells had a similar strain specificity. The antibody immunoprecipitated the T cell receptor (TcR) complex from a T cell hybridoma. After dissociation of this immunoprecipitate with detergents, the CD3 gamma and epsilon chains were retained by the 7D6 antibody. Immunoprecipitation data were also obtained with COS cells transfected with the CD3 gamma, delta or epsilon chains alone, in pairs or together. They confirmed that 7D6 bound the CD3 gamma-epsilon pair, suggesting that the antibody recognizes a conformational epitope formed by gamma-epsilon pairing, whereas 145-2C11 bound both gamma-epsilon and delta-epsilon pairs. These results, therefore, add to current information about TcR structure and subunit stoichiometry. We have demonstrated that the 7D6 mAb specifically binds to a CD3 dimer comprised of gamma and epsilon chains. We thus provide additional evidence that indicates that two CD3 epsilon chains are found within the receptor, one linked to CD3 gamma and the other to CD3 delta. C1 CATHOLIC UNIV LOUVAIN,CELLULAR GENET UNIT,B-1348 LOUVAIN,BELGIUM. NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. RP COULIE, PG (reprint author), LUDWIG INST CANC RES,7459 AVE HIPPOCRATE,B-1200 BRUSSELS,BELGIUM. NR 28 TC 34 Z9 34 U1 0 U2 2 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JUL PY 1991 VL 21 IS 7 BP 1703 EP 1709 DI 10.1002/eji.1830210718 PG 7 WC Immunology SC Immunology GA FW387 UT WOS:A1991FW38700017 PM 1711976 ER PT J AU VANSEVENTER, GA SHIMIZU, Y HORGAN, KJ LUCE, GEG WEBB, D SHAW, S AF VANSEVENTER, GA SHIMIZU, Y HORGAN, KJ LUCE, GEG WEBB, D SHAW, S TI REMOTE T-CELL CO-STIMULATION VIA LFA-1/ICAM-1 AND CD2/LFA-3 - DEMONSTRATION WITH IMMOBILIZED LIGAND/MAB AND IMPLICATION IN MONOCYTE-MEDIATED CO-STIMULATION SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article ID FUNCTION-ASSOCIATED ANTIGEN-1; ADHESION MOLECULE-1 ICAM-1; B-CELLS; MONOCLONAL-ANTIBODY; RECEPTOR OCCUPANCY; ACCESSORY CELLS; LYMPHOCYTES-T; IMMUNE-SYSTEM; ACTIVATION; CD2 AB Proliferative response of resting T cells generally requires not only cross-linking of the Tcell receptor (TcR) but also co-stimulatory signals from accessory molecules. We here have used a "three-cell" model consisting of: (a) resting human CD4+ T cells as responders; (b) CD3 monoclonal antibody (mAb) OKT3 on latex beads as surrogate stimulators; (c) autologous monocytes as source of co-stimulation. As described by Kawakami et al. (J. Immunol. 1989. 142: 1818), T cell proliferation in this system is observed with paraformaldehyde-fixed monocytes if they have been activated and interleukin (IL) 1-beta/IL 6 is supplied. Since this three-cell system provides TcR cross-linking at a site spatially "remote" from co-stimulation, they help distinguish adhesion from signal transduction but the molecules that mediate co-stimulation in this system have not been identified. Our studies now demonstrate that co-stimulation by the monocytes is dependent on each of two receptor/ligand pathways CD2/LFA-3 and LFA-1/ICAM-1 since it is inhibited by each relevant mAb but not a variety of control mAb. The hypotheses that CD2 and LFA-1 could each mediate co-stimulation was tested in simplified model systems in which the monocyte was replaced with immobilized CD2 mAb or purified ICAM-1 presented on a separate surface from the CD3 mAb. The results in these simplified models demonstrate that on resting T cells either CD2 or LFA-1 molecules alone can mediate "remote" co-stimulation unlike most other T cell surface molecules. Co-stimulation requires IL 1-beta/IL6 both in thw weaker LFA-1 ligand-mediated co-stimulation and at lower CD2 mAb concentrations in the stronger CD2 mAb-mediated co-stimulation. Thus: (a) the accessory cell function of stimulated fixed monocytes in T cell proliferation requires both the LFA-1/ICAM-1 and CD2/LFA-3 pathways; and (b) the T cell molecules CD2 and LFA-1 can give co-stimulatory signals that can act in a "remote" fashion. C1 UNIV MICHIGAN,SCH MED,DEPT MICROBIOL & IMMUNOL,ANN ARBOR,MI 48104. US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,BETHESDA,MD 20205. RP VANSEVENTER, GA (reprint author), NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892, USA. OI Shimizu, Yoji/0000-0001-9760-0288 NR 61 TC 90 Z9 90 U1 0 U2 1 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JUL PY 1991 VL 21 IS 7 BP 1711 EP 1718 DI 10.1002/eji.1830210719 PG 8 WC Immunology SC Immunology GA FW387 UT WOS:A1991FW38700018 PM 1711977 ER PT J AU CERNY, A MERINO, R MAKINO, M WALDVOGEL, FA MORSE, HC IZUI, S AF CERNY, A MERINO, R MAKINO, M WALDVOGEL, FA MORSE, HC IZUI, S TI PROTECTIVE EFFECT OF CYCLOSPORINE-A ON IMMUNE ABNORMALITIES OBSERVED IN THE MURINE ACQUIRED-IMMUNODEFICIENCY-SYNDROME SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL SUBSETS; IFN-GAMMA; INDUCTION; VIRUS; MAIDS; ACTIVATION; DISEASE; MICE; AIDS AB The murine leukemia viruses (MuLV) designated LP-BM5 induce an immunodeficiency disease in susceptible strains of mice with many features in common to human acquired immunodeficiency syndrome (AIDS), including lymphadenopathy and profound immunodeficiency associated with enhanced susceptibility to infection and terminal B cell lymphomas. The disease, termed murine AIDS (MAIDS), crucially depends on the presence of B cells and CD4+ T cells, suggesting that mutual activation of these two cell types is central in the pathogenesis of the immunodeficiency syndrome. Cyclosporin A (CsA), whose immunosuppressive effect is attributed mainly to inhibition of interleukin 2 and interferon-gamma expression, interferes in T-B cell interactions. Here we show that chronic treatment with CsA (40 or 60 mg/kg/day) before and after infection with LP-BM5 MuLV protects against the development of immunodeficiency disease as assessed by functional, serological and histopathological criteria. The protection was not complete, suggesting both CsA-sensitive and CsA-resistant components to the pathogenesis of this syndrome, and was found to be independent of ecotropic MuLV expression. These results underline immunopathological mechanisms in the progression of immune abnormalities in MAIDS that are susceptible to inhibition of CsA and may serve as an experimental basis for developing a treatment of the human disorder with immunomodulators. C1 CTR MED UNIV GENEVA,DEPT PATHOL,GENEVA,SWITZERLAND. NIAID,IMMUNOPATHOL LAB,BETHESDA,MD 20892. RP CERNY, A (reprint author), HOP CANTONAL GENEVA,MED THERAPEUT CLIN,24 RUE MICHELI DU CREST,CH-1211 GENEVA 4,SWITZERLAND. RI Merino, Ramon/L-1310-2014 OI Merino, Ramon/0000-0002-5306-0635 FU NIAID NIH HHS [N01-AI-72622] NR 17 TC 21 Z9 21 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JUL PY 1991 VL 21 IS 7 BP 1747 EP 1750 DI 10.1002/eji.1830210724 PG 4 WC Immunology SC Immunology GA FW387 UT WOS:A1991FW38700023 PM 1647958 ER PT J AU PANTALEO, G POLI, G BUTINI, L FOX, C DAYTON, AI FAUCI, AS AF PANTALEO, G POLI, G BUTINI, L FOX, C DAYTON, AI FAUCI, AS TI DISSOCIATION BETWEEN SYNCYTIA FORMATION AND HIV SPREADING - SUPPRESSION OF SYNCYTIA FORMATION DOES NOT NECESSARILY REFLECT INHIBITION OF HIV-INFECTION SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN IMMUNODEFICIENCY VIRUS; AIDS RETROVIRUS; RECEPTOR; ANTIGEN; INVOLVEMENT AB In this study, we have observed that a dissociation may occur in vitro between syncytia formation and HIV spreading. Efficient HIV spreading and virus replication occurred either in HIV-infected LFA-1+ lymphocytes treated with anti-LFA-1 mAb or in HIV-infected lymphocytes genetically deficient in LFA-1, despite the fact that syncytia formation was completely suppressed. Therefore, these results indicate that syncytia formation cannot be used as the sole parameter to evaluate the spread of HIV in vitro. RP PANTALEO, G (reprint author), NIAID,IMMUNOREGULAT LAB,BLDG 10,RM 11B-13,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Pantaleo, Giuseppe/K-6163-2016 NR 16 TC 29 Z9 29 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JUL PY 1991 VL 21 IS 7 BP 1771 EP 1774 DI 10.1002/eji.1830210730 PG 4 WC Immunology SC Immunology GA FW387 UT WOS:A1991FW38700029 PM 2060584 ER PT J AU KAPLAN, D ZIMMERBERG, J PURI, A SARKAR, DP BLUMENTHAL, R AF KAPLAN, D ZIMMERBERG, J PURI, A SARKAR, DP BLUMENTHAL, R TI SINGLE CELL-FUSION EVENTS INDUCED BY INFLUENZA HEMAGGLUTININ - STUDIES WITH RAPID-FLOW, QUANTITATIVE FLUORESCENCE MICROSCOPY SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID MEMBRANE-FUSION; MAST-CELLS; KINETICS; REDISTRIBUTION; EXOCYTOSIS C1 NCI,MEMBRANE STRUCT & FUNCT SECT,LMMB,BETHESDA,MD 20892. NATL INST CHILD HLTH & DEV,THEORET & PHYS BIOL LAB,BETHESDA,MD 20892. NR 15 TC 29 Z9 29 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 JUL PY 1991 VL 195 IS 1 BP 137 EP 144 DI 10.1016/0014-4827(91)90509-S PG 8 WC Oncology; Cell Biology SC Oncology; Cell Biology GA FR949 UT WOS:A1991FR94900018 PM 2055263 ER PT J AU NERVI, C VOLLBERG, TM GEORGE, MD ZELENT, A CHAMBON, P JETTEN, AM AF NERVI, C VOLLBERG, TM GEORGE, MD ZELENT, A CHAMBON, P JETTEN, AM TI EXPRESSION OF NUCLEAR RETINOIC ACID RECEPTORS IN NORMAL TRACHEOBRONCHIAL CELLS AND IN LUNG-CARCINOMA CELLS SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID TRACHEAL EPITHELIAL-CELLS; INVITRO SQUAMOUS DIFFERENTIATION; VITAMIN-A; MECHANICAL INJURY; DNA-SEQUENCE; CYCLIC-AMP; BETA-GENE; IDENTIFICATION; GAMMA; METAPLASIA C1 NIEHS,PULM PATHOBIOL LAB,CELL BIOL GRP,POB 12233,RES TRIANGLE PK,NC 27709. FAC MED STRASBOURG,INST CHIM BIOL,GENET MOLEC EUCARYOTES LAB,F-67085 STRASBOURG,FRANCE. RI Zelent, Arthur/B-3532-2009; OI Jetten, Anton/0000-0003-0954-4445; NERVI, Clara/0000-0001-9341-0188 NR 50 TC 114 Z9 114 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD JUL PY 1991 VL 195 IS 1 BP 163 EP 170 DI 10.1016/0014-4827(91)90512-S PG 8 WC Oncology; Cell Biology SC Oncology; Cell Biology GA FR949 UT WOS:A1991FR94900021 PM 1675998 ER PT J AU WALDBILLIG, RJ ARNOLD, DR FLETCHER, RT CHADER, GJ AF WALDBILLIG, RJ ARNOLD, DR FLETCHER, RT CHADER, GJ TI INSULIN AND IGF-I BINDING IN DEVELOPING CHICK NEURAL RETINA AND PIGMENT-EPITHELIUM - A CHARACTERIZATION OF BINDING AND STRUCTURAL DIFFERENCES SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE INSULIN RECEPTOR; IGF-I RECEPTOR; CHICKEN; DEVELOPMENTAL; RETINA; PIGMENT EPITHELIUM; BRAIN; GLYCOSYLATION ID GROWTH FACTOR-I; ROD OUTER SEGMENTS; SUBUNIT STRUCTURE; KINASE-ACTIVITY; ALPHA-SUBUNIT; RECEPTORS; LOCALIZATION; BRAIN; LIVER; TISSUES RP WALDBILLIG, RJ (reprint author), NEI,RETINAL CELL & MOLEC BIOL LAB,BLDG 6,ROOM B1A-11,BETHESDA,MD 20892, USA. NR 30 TC 45 Z9 47 U1 0 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD JUL PY 1991 VL 53 IS 1 BP 13 EP 22 DI 10.1016/0014-4835(91)90139-6 PG 10 WC Ophthalmology SC Ophthalmology GA FX285 UT WOS:A1991FX28500003 PM 1879497 ER PT J AU BARRETT, JC RICHTER, H ANNAB, L BURKHART, B AFSHARI, C FUTREAL, A BOYD, J AF BARRETT, JC RICHTER, H ANNAB, L BURKHART, B AFSHARI, C FUTREAL, A BOYD, J TI TUMOR SUPPRESSOR GENES AS NEGATIVE REGULATORS OF GROWTH-FACTOR RESPONSES SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 1991 VL 19 IS 6 BP 459 EP 459 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA FQ310 UT WOS:A1991FQ31000012 ER PT J AU WALDMANN, TA AF WALDMANN, TA TI THE MULTISUBUNIT IL-2 RECEPTOR - A TARGET FOR IMMUNOTHERAPY IN LEUKEMIA LYMPHOMA, AUTOIMMUNE-DISEASES, AND GRAFT-VERSUS-HOST DISEASE SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 1991 VL 19 IS 6 BP 462 EP 462 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA FQ310 UT WOS:A1991FQ31000022 ER PT J AU MCNIECE, I BERTONCELLO, I KELLER, J RUSCETTI, F HARTLEY, C ZSEBO, K AF MCNIECE, I BERTONCELLO, I KELLER, J RUSCETTI, F HARTLEY, C ZSEBO, K TI TRANSFORMING GROWTH-FACTOR-BETA INHIBITS THE ACTION OF STEM-CELL FACTOR ON MOUSE AND HUMAN PROGENITOR CELLS SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 AMGEN INC,THOUSAND OAKS,CA. CANC INST,MELBOURNE,VIC 3000,AUSTRALIA. FREDERICK CANC RES FACIL,FREDERICK,MD 21701. NR 0 TC 1 Z9 1 U1 0 U2 1 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 1991 VL 19 IS 6 BP 508 EP 508 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA FQ310 UT WOS:A1991FQ31000194 ER PT J AU YONG, KY SALOOJA, N HEGDE, UM DONAHUE, RE LINCH, DC AF YONG, KY SALOOJA, N HEGDE, UM DONAHUE, RE LINCH, DC TI MACROPHAGE COLONY-STIMULATING FACTOR LEVELS IN IMMUNE THROMBOCYTOPENIC PURPURA (ITP) AND PREGNANCY SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 UNIV COLL & MIDDLESEX SCH MED,DEPT HAEMATOL,LONDON,ENGLAND. EALING GEN HOSP,DEPT HAEMATOL,LONDON,ENGLAND. NIH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 1991 VL 19 IS 6 BP 519 EP 519 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA FQ310 UT WOS:A1991FQ31000236 ER PT J AU LU, L WU, B XIAO, M ZHEN, Z SHEN, RN WILLIAMS, DE KIM, YJ KWON, BS RUSCETTI, S BROXMEYER, HE AF LU, L WU, B XIAO, M ZHEN, Z SHEN, RN WILLIAMS, DE KIM, YJ KWON, BS RUSCETTI, S BROXMEYER, HE TI THERAPEUTIC EFFECT OF RECOMBINANT HUMAN INTERLEUKIN (IL)-7 ON DISEASE PROGRESSION IN MICE INFECTED WITH FRIEND-VIRUS COMPLEX SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 INDIANA UNIV,INDIANAPOLIS,IN 46204. IMMUNEX CORP,SEATTLE,WA. NCI,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 1 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 1991 VL 19 IS 6 BP 528 EP 528 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA FQ310 UT WOS:A1991FQ31000268 ER PT J AU PEARCE, EJ SHER, A AF PEARCE, EJ SHER, A TI FUNCTIONAL DICHOTOMY IN THE CD4+T CELL RESPONSE TO SCHISTOSOMA-MANSONI SO EXPERIMENTAL PARASITOLOGY LA English DT Review ID DELAYED-TYPE HYPERSENSITIVITY; TH1 CLONES; IFN-GAMMA; T-CELLS; IMMUNITY; MOUSE; MICE; INTERLEUKIN-5; EOSINOPHILIA; CYTOKINES C1 NIAID,PARASIT DIS LAB,IMMUNOL & CELL BIOL SECT,BETHESDA,MD 20892. RP PEARCE, EJ (reprint author), CORNELL UNIV,NEW YORK STATE COLL VET MED,DEPT MICROBIOL IMMUNOL & PARASITOL,ITHACA,NY 14853, USA. NR 30 TC 38 Z9 40 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 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD JUL PY 1991 VL 73 IS 1 BP 110 EP 116 DI 10.1016/0014-4894(91)90014-N PG 7 WC Parasitology SC Parasitology GA FW118 UT WOS:A1991FW11800013 PM 1711476 ER PT J AU BLATTNER, WA AF BLATTNER, WA TI HIV EPIDEMIOLOGY - PAST, PRESENT, AND FUTURE SO FASEB JOURNAL LA English DT Review DE HIGH-RISK INDIVIDUAL; T-CELL LEUKEMIA VIRUS; LIFE-STYLE ID HUMAN-IMMUNODEFICIENCY-VIRUS; HOMOSEXUAL MEN; TYPE-1 INFECTION; AIDS; RETROVIRUS; TRANSMISSION; LYMPHOCYTES; PROSTITUTES; LYMPHOMA; CHILDREN AB The worldwide pandemic of acquired immunodeficiency syndrome (AIDS) has the potential to cause catastrophic medical and social effects that will influence world health well into the 21st century. The causative agent, a lentiretrovirus called human immunodeficiency virus (HIV-1), is spread by intimate exposure to blood and bodily fluids through sexual, parenteral, and mother-to-infant exposure. The natural history from exposure to disease has a median incubation period of 8-10 years and is characterized by progressive depletion of CD-4 positive T lymphocytes as well as effects on other immune and central nervous system cell populations. The World Health Organization (WHO) estimates that between 8 and 10 million persons are currently infected with the virus worldwide, with 8 to 10 times this level projected by some estimates into the 21st century. Recent leveling off of AIDS incidence in the U.S. appears to represent the positive benefits of antiretroviral therapy, and considerable benefit could be seen if such therapies were made more widely available to medically underserved populations. With prolonged survival, however, other long-term sequelae such as cancer and lymphoma may emerge as significant complications of prolonged immunodeficiency. Furthermore, the large pool of already infected persons and continued spread of the virus make the development of additional therapies and an effective anti-HIV vaccine priorities of medical research. RP BLATTNER, WA (reprint author), NCI,VIRAL EPIDEMIOL SECT,BETHESDA,MD 20892, USA. NR 54 TC 43 Z9 43 U1 2 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL PY 1991 VL 5 IS 10 BP 2340 EP 2348 PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA FW087 UT WOS:A1991FW08700004 PM 2065886 ER PT J AU MITSUYA, H YARCHOAN, R KAGEYAMA, S BRODER, S AF MITSUYA, H YARCHOAN, R KAGEYAMA, S BRODER, S TI TARGETED THERAPY OF HUMAN IMMUNODEFICIENCY VIRUS-RELATED DISEASE SO FASEB JOURNAL LA English DT Review DE AZT; REVERSE TRANSCRIPTASE INHIBITORS; DDI; DDC; PROTEASE INHIBITORS ID AIDS-RELATED COMPLEX; RECOMBINANT SOLUBLE CD4; HIV-1 REPLICATION INVITRO; PLACEBO-CONTROLLED TRIAL; PHASE-I TRIAL; DEXTRAN SULFATE; REVERSE-TRANSCRIPTASE; ZIDOVUDINE AZT; 2',3'-DIDEOXYINOSINE DDI; TYPE-1 INFECTION AB Since the discovery of human immunodeficiency virus (HIV) as a pathogenic retrovirus linked to acquired immunodeficiency syndrome (AIDS), a number of potentially useful strategies for antiretroviral therapy of AIDS and its related diseases have emerged. One such strategy involves use of the broad family of 2',3'-dideoxynucleosides, to which 3'-azido-2',3'-dideoxythymidine (AZT) belongs. AZT has been shown to reduce the replication of HIV in vivo and to confer significant clinical benefits in patients in both early and advanced stages of infection. Other members of the family, 2',3'-dideoxycytidine (ddC), 2',3'-dideoxyinosine (ddI), and 2',3'-didehydro-2',3'-dideoxythymidine (d4T), have also been reported to be active against HIV in short-term clinical trials. The armamentarium of antiretroviral agents is rapidly growing. Various nonnucleoside agents have recently been identified to be active against HIV in vitro. HIV-1 protease inhibitors are notable as possible new therapies for HIV-1-related diseases. However, we have faced several new challenges in the antiretroviral therapy in AIDS. These include long-term drug-related toxicities; emergence of drug-resistant HIV variants; and development of various cancers, particularly as effective therapies prolong survival. Progress in understanding structure-activity relations and clinical effectiveness will continue with dideoxynucleoside analogs. However, it seems certain that a variety of nonnucleoside analogs affecting multiple steps in viral replication will become available before long, and combination therapies using multiple antiretroviral drugs will be available. Such therapies will exert major effects against the moribidity and mortality caused by HIV. RP MITSUYA, H (reprint author), NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,BETHESDA,MD 20892, USA. NR 99 TC 78 Z9 78 U1 1 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL PY 1991 VL 5 IS 10 BP 2369 EP 2381 PG 13 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA FW087 UT WOS:A1991FW08700007 PM 1712326 ER PT J AU ROSENBERG, ZF FAUCI, AS AF ROSENBERG, ZF FAUCI, AS TI IMMUNOPATHOGENESIS OF HIV-INFECTION SO FASEB JOURNAL LA English DT Review DE CD4+ LYMPHOCYTE-T; HIV PATHOGENESIS; VIRAL ACTIVATION ID HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR-NECROSIS-FACTOR; LONG TERMINAL REPEAT; HUMAN CELL-LINES; MEMORY T-CELLS; PERIPHERAL-BLOOD; CD4+ LYMPHOCYTES; MONONUCLEAR PHAGOCYTES; TYPE-1 INFECTION; PROGENITOR CELLS AB The ultimate consequence of infection with HIV is profound immunosuppression that is the result of both quantitative and qualitative abnormalities of the helper/inducer subset of T lymphocytes. The initial pathogenic event in HIV infection is binding of the envelope glycoprotein of HIV to the CD4 receptor molecule present on the surface of CD4+ T lymphocytes and monocyte/macrophages. In vivo the reservoir for HIV infection in the peripheral blood is the CD4+ T cell, whereas in other tissues the monocyte/macrophage may play a substantial role. As disease progresses in HIV-infected individuals, the viral burden in the peripheral blood CD4+ T cells increases. An understanding of the mechanisms involved in the transition from an initially low viral burden during the asymptomatic phase of HIV infection to the higher levels of virus expression detected iii late stage disease is being investigated intensively. A number of potential agents that may influence regulation of HIV expression have been identified including mitogens, antigens, heterologous viruses, cytokines, and physical factors. The pathogenic mechanisms of HIV-induced neurologic abnormalities and the potential role of HIV in a number of other clinical manifestations of HIV infection are also discussed. RP ROSENBERG, ZF (reprint author), NIAID,BETHESDA,MD 20892, USA. NR 101 TC 195 Z9 197 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL PY 1991 VL 5 IS 10 BP 2382 EP 2390 PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA FW087 UT WOS:A1991FW08700008 PM 1676689 ER PT J AU BERZOFSKY, JA AF BERZOFSKY, JA TI DEVELOPMENT OF ARTIFICIAL VACCINES AGAINST HIV USING DEFINED EPITOPES SO FASEB JOURNAL LA English DT Review DE T-CELLS; CYTOTOXIC LYMPHOCYTES-T; SYNTHETIC PEPTIDES; NEUTRALIZING ANTIBODIES; ANTIGENIC DETERMINANTS ID HUMAN-IMMUNODEFICIENCY-VIRUS; TOXIC LYMPHOCYTES-T; MAJOR HISTOCOMPATIBILITY COMPLEX; CELL ANTIGENIC SITES; SYNTHETIC PEPTIDES; NEUTRALIZING ANTIBODIES; INFLUENZA NUCLEOPROTEIN; INFECTION INVITRO; ENVELOPE PROTEIN; SEROPOSITIVE INDIVIDUALS AB HIV may not follow the paradigm that has been used successfully for developing most viral vaccines, namely, that the best vaccine is the one that most closely mimics natural infection. This approach is based on the premise that natural infection leads to long-lasting protective immunity, which may not be applicable to HIV. Also, some immune responses elicited by infection with HIV may enhance infection or contribute to the development of immune deficiency. To overcome these problems, an artificial vaccine could be constructed using only antigenic epitopes that elicit neutralizing antibodies, helper T cells, and CD8+ cytotoxic T cells, and avoiding epitopes that elicit deleterious responses. Progress has been made in identifying all three of these types of epitopes, in characterizing their activity in animals, and in demonstrating that at least two of these can be linked to induce neutralizing antibodies without a carrier. Methods have also been developed to induce cytotoxic T cells. It is therefore feasible to construct an artificial vaccine for HIV that should be safer and more effective than a natural whole viral or subunit vaccine. RP BERZOFSKY, JA (reprint author), NCI, METAB BRANCH, MOLEC IMMUNOGENET & VACCINE RES SECT, BETHESDA, MD 20892 USA. NR 86 TC 54 Z9 55 U1 1 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL PY 1991 VL 5 IS 10 BP 2412 EP 2418 PG 7 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA FW087 UT WOS:A1991FW08700012 PM 1712327 ER PT J AU GOUDSMIT, J BACK, NKT NARA, PL AF GOUDSMIT, J BACK, NKT NARA, PL TI GENOMIC DIVERSITY AND ANTIGENIC VARIATION OF HIV-1 - LINKS BETWEEN PATHOGENESIS, EPIDEMIOLOGY AND VACCINE DEVELOPMENT SO FASEB JOURNAL LA English DT Review DE AIDS VIRUS EVOLUTION; CYTOPATHICITY DETERMINANTS; V3 DOMAIN; NEUTRALIZATION-RESISTANT MUTANTS; VACCINE DEVELOPMENT ID HUMAN-IMMUNODEFICIENCY-VIRUS; CYTOTOXIC LYMPHOCYTE-T; CELL-FUSION INHIBITION; MOUTH-DISEASE VIRUS; INFLUENZA-VIRUS; VISNA VIRUS; B-CELL; NUCLEOTIDE SUBSTITUTION; NEUTRALIZATION EPITOPE; ACID SEQUENCE AB Recent analysis of primate lentivirus genomes (1) indicates that lentiviruses have infected primates for hundreds of years. The pathogenicity of such viruses may fluctuate due to the high evolution rate of some parts of the viral genome. Fixed nucleic acid substitutions in the gag gene appear to be caused by random fixation of selectively neutral mutants, whereas nonrandom fixation of selectively advantageous mutants, as has been observed for MHC molecules and serine protease inhibitors, appears to be operational for some hypervariable env gene regions. The former is characterized by an excess of silent mutations independent of the rate of change, the latter by an excess of nonsilent mutations. This latter type of selection may especially characterize the third variable region of the external HIV envelope (V3), which contains the principal neutralization domain. C1 FREDERICK CANC RES DEV CTR,VIRUS BIOL SECT,FREDERICK,MD. RP GOUDSMIT, J (reprint author), UNIV AMSTERDAM,ACAD MED CTR,HUMAN RETROVIRUS LAB,MEIBERGDREEF 15,1105 AZ AMSTERDAM,NETHERLANDS. RI Back, Nicole/K-3884-2013 NR 53 TC 72 Z9 72 U1 1 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL PY 1991 VL 5 IS 10 BP 2427 EP 2436 PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA FW087 UT WOS:A1991FW08700014 PM 2065891 ER PT J AU NARA, PL GARRITY, RR GOUDSMIT, J AF NARA, PL GARRITY, RR GOUDSMIT, J TI NEUTRALIZATION OF HIV-1 - A PARADOX OF HUMORAL PROPORTIONS SO FASEB JOURNAL LA English DT Review DE ENVELOPE PLASTICITY; IMMUNOGENICITY; V3 EPITOPE; ONTOGENY OF B-CELLS; ANTIGENIC VARIATION; CLONAL DOMINANCE; CROSS REACTIVITY; LAW OF MASS ACTION ID HUMAN-IMMUNODEFICIENCY-VIRUS; INFECTIOUS-ANEMIA VIRUS; PURIFIED ENVELOPE GLYCOPROTEINS; ENCODED SYNTHETIC PEPTIDES; RETROVIRUSES HTLV-III; MOUTH-DISEASE VIRUS; IMMUNE-RESPONSE; MONOCLONAL-ANTIBODIES; PERSISTENT INFECTION; OLIGOMERIC STRUCTURE AB The production of immunoglobulin capable of neutralizing the infectivity of a virus represents one of the most remarkable molecular accomplishments of the host's available immune defenses. It should be no surprise that a virus that has existed in the parenchyma of the immune system has evolved as an equally dynamic molecule (i.e., viral envelope) for survival. Neutralizing immunoglobulin (Ig) can best serve the host under conditions where the invading pathogen requires a well-defined cell-free state for establishing an infection or transmission. Evidence for a controlling and therefore protective role of neutralizing Ig against lentiviruses has been defined in natural and experimental infections with equine infectious anemia virus of ungulate members in the family equidae. Rapid replication of the virus immediately after infection and its release in a cell-free state leads to the production of neutralizing Ig and subsequent control of the primary viremia. A similar cause-effect relationship exists in humans between the high-titered viremia, observed shortly after HIV-1 infection, and the subsequent production of neutralizing Ig. Partially controlling this acute stage of viral replication by neutralizing Ig and thus preventing an otherwise acute form of immunosuppression or immune complex disease may be viewed paradoxically as a survival property of the virus. Immunologically mediated control, in a Darwinian sense, selects for viruses that have optimized the parameters of longevity and transmission from host to host. This paradox of neutralization in HIV-1 infection appears to be mediated by the convergence of structural and functional roles of the third variable domain (V3) of the external envelope glycoprotein. During infection or envelope-based vaccination, antibody to this cross-reactive, immunodominant epitope dominates the antigenic repertoire. Once this occurs, the host is less able to respond to emerging viruses containing closely related V3 structures. Thus a relatively restricted clonal-dominance of the neutralization response results. The V3 domain, apparently in concert with the rest of the molecule, provides an epitope that can tolerate and utilize its conformational flexibility to allow immune escape while maintaining its functional role in infectivity. Sixteen other putative epitopes have been described as being involved in the induction of neutralizing Ig. Currently the biologically functional role of neutralizing Ig to these other epitopes are complicated by a prior lack of knowledge and appreciation of the in vitro variables affecting their measurements. Thus it appears that the mechanisms of neutralization, the immunologic complexities of the viral envelope, and the design of in vitro assays to more accurately reflect in vivo conditions should greatly improve our future chances of designing, identifying, and eliciting protective immune responses through vaccination. C1 UNIV AMSTERDAM,ACAD MED CTR,HUMAN RETROVIRUS LAB,1105 AZ AMSTERDAM,NETHERLANDS. RP NARA, PL (reprint author), NCI,FREDERICK CANC RES & DEV CTR,VIRUS BIOL SECT,TUMOR CELL BIOL LAB,BLDG 560,ROOM 12-92,FREDERICK,MD 21702, USA. NR 109 TC 172 Z9 173 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL PY 1991 VL 5 IS 10 BP 2437 EP 2455 PG 19 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA FW087 UT WOS:A1991FW08700015 PM 1712328 ER PT J AU VISHWANATH, S AF VISHWANATH, S TI ANTIGENIC RELATIONSHIPS AMONG THE RICKETTSIAE OF THE SPOTTED-FEVER AND TYPHUS GROUPS SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE RICKETTSIAE; SPOTTED FEVER; TYPHUS ID MONOCLONAL-ANTIBODIES; PROTEINS; VACCINE; GENE AB Using immunoblots to analyze antigenic relationships among the pathogenic spotted fever and typhus group rickettsiae, I found that the rickettsial lipopolysaccharide (LPS) was a group-specific antigen. All the rickettsiae examined had 135-kDa and 58-kDa protein antigens. The spotted fever rickettsiae and Rickettsia canada had, in addition, 190-kDa protein antigens which were antigenic analogs of previously described protective antigens of R. conorii and R. rickettsii. C1 NIAID,ROCKY MT LABS,INTRACELLULAR PARASITES LAB,HAMILTON,MT 59840. RP VISHWANATH, S (reprint author), CTR DIS CONTROL,CTR INFECT DIS,DIV HIV AIDS,LAB INVESTIGAT BRANCH,MAIL STOP G-15,1600 CLIFTON RD,ATLANTA,GA 30333, USA. NR 17 TC 33 Z9 34 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1097 J9 FEMS MICROBIOL LETT JI FEMS Microbiol. Lett. PD JUL 1 PY 1991 VL 81 IS 3 BP 341 EP 344 DI 10.1111/j.1574-6968.1991.tb04783.x PG 4 WC Microbiology SC Microbiology GA FY750 UT WOS:A1991FY75000019 PM 1916232 ER PT J AU THOMPSON, MB DUNNICK, JK SUTPHIN, ME GILES, HD IRWIN, RD PREJEAN, JD AF THOMPSON, MB DUNNICK, JK SUTPHIN, ME GILES, HD IRWIN, RD PREJEAN, JD TI HEMATOLOGIC TOXICITY OF AZT AND DDC ADMINISTERED AS SINGLE AGENTS AND IN COMBINATION TO RATS AND MICE SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID AIDS; 3'-AZIDO-3'-DEOXYTHYMIDINE; ZIDOVUDINE; INVITRO; CELLS; 3'-AZIDO-2',3'-DIDEOXYTHYMIDINE; DIDEOXYNUCLEOSIDES; AZIDOTHYMIDINE; PHARMACOLOGY C1 EXPTL PATHOL LABS,RES TRIANGLE PK,NC 27709. SO RES INST,BIRMINGHAM,AL 35255. RP THOMPSON, MB (reprint author), NIEHS,RES TRIANGLE PK,NC 27709, USA. NR 16 TC 25 Z9 25 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD JUL PY 1991 VL 17 IS 1 BP 159 EP 176 DI 10.1016/0272-0590(91)90248-3 PG 18 WC Toxicology SC Toxicology GA FV600 UT WOS:A1991FV60000016 PM 1655546 ER PT J AU BERG, M MURAKAWA, Y CAMERINI, D JAMES, SP AF BERG, M MURAKAWA, Y CAMERINI, D JAMES, SP TI LAMINA PROPRIA LYMPHOCYTES ARE DERIVED FROM CIRCULATING CELLS THAT LACK THE LEU-8 LYMPH-NODE HOMING RECEPTOR SO GASTROENTEROLOGY LA English DT Article ID HIGH-ENDOTHELIAL VENULES; NORMAL NONHUMAN-PRIMATES; SUPPRESSOR T-CELLS; DIFFERENTIATION ANTIGENS; ADHESION MOLECULE; SURFACE MOLECULE; HELPER-INDUCER; EXPRESSION; MUCOSAL; ACTIVATION C1 MASSACHUSETTS GEN HOSP,DEPT MOLEC BIOL,BOSTON,MA 02114. NIAID,CLIN INVEST LAB,MUCOSAL IMMUN SECT,BETHESDA,MD 20892. NR 47 TC 38 Z9 38 U1 0 U2 0 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 JUL PY 1991 VL 101 IS 1 BP 90 EP 99 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA FQ871 UT WOS:A1991FQ87100012 PM 2044931 ER PT J AU VINAYEK, R AMANTEA, MA MATON, PN FRUCHT, H GARDNER, JD JENSEN, RT AF VINAYEK, R AMANTEA, MA MATON, PN FRUCHT, H GARDNER, JD JENSEN, RT TI PHARMACOKINETICS OF ORAL AND INTRAVENOUS OMEPRAZOLE IN PATIENTS WITH THE ZOLLINGER-ELLISON SYNDROME SO GASTROENTEROLOGY LA English DT Article ID GASTRIC-ACID SECRETION; BLIND COMPARATIVE TRIAL; REFLUX ESOPHAGITIS; DUODENAL-ULCER; SUBSTITUTED BENZIMIDAZOLES; INTRAGASTRIC PH; CIMETIDINE; MANAGEMENT; RANITIDINE; THERAPY C1 NIDDKD,DIGEST DIS BRANCH,BLDG 10,ROOM 9C103,BETHESDA,MD 20892. NIH,CTR CLIN,CLIN DEPT PHARM,BETHESDA,MD 20892. NR 51 TC 30 Z9 30 U1 0 U2 3 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 JUL PY 1991 VL 101 IS 1 BP 138 EP 147 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA FQ871 UT WOS:A1991FQ87100018 PM 2044903 ER PT J AU KOVACS, G FUZESI, L EMANUEL, A KUNG, HF AF KOVACS, G FUZESI, L EMANUEL, A KUNG, HF TI CYTOGENETICS OF PAPILLARY RENAL-CELL TUMORS SO GENES CHROMOSOMES & CANCER LA English DT Article ID CHROMOSOME-ABNORMALITIES; CARCINOMA; PROGRESSION; RECEPTOR; HETEROZYGOSITY; GENES AB Chromosome aberrations were determined in short-term cultures of 18 papillary renal cell tumors, as well as in the cell line ACHN, and the results were evaluated together with 20 previously published cases. We found that chromosomes 7, 17, and 16 and the Y chromosome were specifically involved in the karyotype changes in this tumor type. A combination of tri- or tetrasomy 7 and trisomy 17, as the only autosomal karyotype changes, marks benign papillary renal cell adenomas (ten cases). Malignant papillary renal cell carcinomas (29 cases) were characterized by additional trisomies: trisomy 16 occurred in 20 tumors, and trisomy 12 and 20 in 8 tumors each. Loss of the Y chromosome was observed in 7 of 9 benign and in 23 of 25 malignant tumors that developed in males. None of the papillary renal cell adenomas or carcinomas showed a loss of 3p or gain of a 5q segment, both of which are characteristic of common non-papillary renal cell carcinomas. C1 PROGRAM RESOURCE INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD. UNIV FREIBURG,INST PATHOL,W-7800 FREIBURG,GERMANY. RP KOVACS, G (reprint author), NCI,FREDERICK CANC RES & DEV CTR,BIOCHEM PHYSIOL LAB,POB B,BLDG 560,RM 31-76,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102] NR 33 TC 243 Z9 247 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 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD JUL PY 1991 VL 3 IS 4 BP 249 EP 255 DI 10.1002/gcc.2870030403 PG 7 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA GB549 UT WOS:A1991GB54900002 PM 1958590 ER PT J AU KOVACS, G EMANUEL, A NEUMANN, HPH KUNG, HF AF KOVACS, G EMANUEL, A NEUMANN, HPH KUNG, HF TI CYTOGENETICS OF RENAL-CELL CARCINOMAS ASSOCIATED WITH VONHIPPEL-LINDAU DISEASE SO GENES CHROMOSOMES & CANCER LA English DT Article ID ABNORMALITIES; DELETION; REGION; CHROMOSOME-3; TUMORS; TISSUE AB To establish the chromosome pattern, we have analyzed short-term cultures of 24 renal cell carcinomas (RCC) from four patients with von Hippel-Lindau disease (VHL). We evaluated the results together with those for 16 RCCs from two VHL patients karyotyped previously in our laboratory and those of 6 tumors published by others. In all 46 RCCs, the cells had lost the shortest overlapping region of the 3p13-pter chromosome segment. The rearrangement of 3p was the only karyotype change in 20 tumors. In more than 50% of the tumors, a gain of the shortest overlapping region of the 5q22-qter segment was detected. Comparative analysis showed that the chromosome aberrations in RCCs associated with VHL are similar to those found in sporadic RCCs. These results indicate that non-papillary sporadic and VHL-RCCs have common genetic mechanisms that result in the loss of the 3p13-pter region containing one or more putative suppressor genes. C1 PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD. UNIV FREIBURG,INST PATHOL,W-7800 FREIBURG,GERMANY. RP KOVACS, G (reprint author), NCI,FREDERICK CANC RES & DEV CTR,BIOCHEM PHYSIOL LAB,POB B,BLDG 560,RM 31-76,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102] NR 20 TC 47 Z9 47 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD JUL PY 1991 VL 3 IS 4 BP 256 EP 262 DI 10.1002/gcc.2870030404 PG 7 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA GB549 UT WOS:A1991GB54900003 PM 1958591 ER PT J AU GRAZIANO, SL PFEIFER, AM TESTA, JR MARK, GE JOHNSON, BE HALLINAN, EJ PETTENGILL, OS SORENSON, GD TATUM, AH BRAUCH, H ZBAR, B FLEJTER, WL EHRLICH, GD POIESZ, BJ AF GRAZIANO, SL PFEIFER, AM TESTA, JR MARK, GE JOHNSON, BE HALLINAN, EJ PETTENGILL, OS SORENSON, GD TATUM, AH BRAUCH, H ZBAR, B FLEJTER, WL EHRLICH, GD POIESZ, BJ TI INVOLVEMENT OF THE RAFI LOCUS, AT BAND 3P25, IN THE 3P DELETION OF SMALL-CELL LUNG-CANCER SO GENES CHROMOSOMES & CANCER LA English DT Article ID BRONCHIAL EPITHELIAL-CELLS; L-DOPA DECARBOXYLASE; C-MYC; CHROMOSOMAL-ABNORMALITIES; CHEMOTHERAPY SENSITIVITY; MORPHOLOGICAL VARIANTS; INVITRO RADIATION; GROWTH-PROPERTIES; KINASE-ACTIVITY; SHORT ARM AB The ability to establish long-term cell lines of small-cell lung cancer (SCLC) has provided an in vitro model for the disease. We report on the characterization of 10 new human SCLC cell lines established from 34 cytopathologically positive specimens. Based on morphologic and biochemical characterization, growth properties, and expression of MYC and neuroendocrine properties, eight cell lines were categorized as "classic" and two cell lines as "variant." Cytogenetic examination revealed loss of all or part of 3p in all nine SCLC cell lines analyzed. The smallest deletion in common was found at 3p21-3p25. Restriction fragment length polymorphism (RFLP) analyses with probes for 3p were performed for correlation with karyotypic data and supported the cytogenetic findings. In 21 SCLC specimens (cell lines and tumor tissue) with normal DNA, used for comparison, we observed loss of heterozygosity at RAFI (3p25) in ten of ten informative pairs by using two RFLPs from the RAFI locus. In addition, loss of heterozygosity was noted in nine of 10 pairs examined with DNF15S2 (3p21) and four of four with D3S3 (3p14). Analysis of cell lines and tumor specimens that lacked paired normal tissue showed a homozygous pattern with the RAFI probes in all 18 cases. Northern blots revealed significant expression of RAFI in all cell lines tested. The transcript size was normal. The cytogenetic and RFLP data suggest that the RAFI locus at 3p25 is involved in the chromosomal deletion of SCLC. C1 VET ADM MED CTR,DEPT MICROBIOL,SYRACUSE,NY 13210. VET ADM MED CTR,DEPT PATHOL,SYRACUSE,NY 13210. SUNY HLTH SCI CTR,DEPT MED,SYRACUSE,NY. SUNY HLTH SCI CTR,DEPT MICROBIOL,SYRACUSE,NY. SUNY HLTH SCI CTR,DEPT PATHOL,SYRACUSE,NY. NCI,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892. NCI,NAVY MED ONCOL BRANCH,BETHESDA,MD 20892. FOX CHASE CANC INST,DEPT MED ONCOL,PHILADELPHIA,PA 19111. DARTMOUTH COLL,HITCHCOCK MED CTR,DARTMOUTH MED SCH,DEPT PATHOL,HANOVER,NH 03756. NCI,FREDERICK CANC RES FACIL,IMMUNOBIOL LAB,FREDERICK,MD 21701. UNIV MARYLAND,DEPT HUMAN GENET,BALTIMORE,MD 21201. RP GRAZIANO, SL (reprint author), VET ADM MED CTR,DEPT MED,800 IRVING AVE,SYRACUSE,NY 13210, USA. FU NCI NIH HHS [CA 45745] NR 73 TC 29 Z9 29 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 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD JUL PY 1991 VL 3 IS 4 BP 283 EP 293 DI 10.1002/gcc.2870030407 PG 11 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA GB549 UT WOS:A1991GB54900006 PM 1683566 ER PT J AU LAROCHELLE, WJ MAYSIROFF, M ROBBINS, KC AARONSON, SA AF LAROCHELLE, WJ MAYSIROFF, M ROBBINS, KC AARONSON, SA TI A NOVEL MECHANISM REGULATING GROWTH-FACTOR ASSOCIATION WITH THE CELL-SURFACE - IDENTIFICATION OF A PDGF RETENTION DOMAIN SO GENES & DEVELOPMENT LA English DT Article DE PLATELET-DERIVED GROWTH FACTOR; DEVELOPMENT; CELL SURFACE ASSOCIATION; RETENTION SEQUENCE; PROTEIN STRUCTURE ID SIMIAN SARCOMA-VIRUS; TRANSFORMING GENE-PRODUCT; NUCLEOTIDE-SEQUENCE; V-SIS; TRANSMEMBRANE PROTEINS; ENDOPLASMIC-RETICULUM; MAMMARY ONCOGENE; MUTAGENESIS; INT-1; LOCALIZATION AB Platelet-derived growth factor (PDGF) chimeras were used to map a domain responsible for either efficient secretion of PDGF-A or the tight cell association of PDGF-B to their carboxy-terminal domains. Introduction of stop codons within PDGF-A or PDGF-B further dissected their respective carboxy-terminal domains. Although successive deletions of the PDGF-A carboxyl terminus did not impair its secretion, incremental deletions from the carboxyl terminus of PDGF-B abrogated its membrane retention properties and promoted secretion. By this approach, PDGF-B retention properties could be localized to PDGF-B residues 212-226. A processed form of PDGF-B, which contained this domain, was expressed at the cell surface but not released. Comparison of PDGF-B with PDGF-A revealed an analogous sequence located at the PDGF-A carboxyl terminus. We demonstrated that this PDGF-A domain also acts as a retention sequence under conditions that inhibit its proteolytic cleavage. Thus, differences in PDGF-A and PDGF-B secretion relate to differential proteolytic processing of analogous retention domains. All of these findings establish a new mechanism for stable growth factor presentation at the cell surface. C1 NIDR,CELLULAR DEV & ONCOL LAB,BETHESDA,MD 20892. RP LAROCHELLE, WJ (reprint author), NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 33 TC 99 Z9 99 U1 1 U2 2 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 JUL PY 1991 VL 5 IS 7 BP 1191 EP 1199 DI 10.1101/gad.5.7.1191 PG 9 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA FV521 UT WOS:A1991FV52100008 PM 2065974 ER PT J AU ROBBINS, J ROBBINS, PF KOZAK, CA CALLAHAN, R AF ROBBINS, J ROBBINS, PF KOZAK, CA CALLAHAN, R TI THE MOUSE BILIARY GLYCOPROTEIN GENE (BGP) - PARTIAL NUCLEOTIDE-SEQUENCE, EXPRESSION, AND CHROMOSOMAL ASSIGNMENT SO GENOMICS LA English DT Article ID HUMAN CARCINOEMBRYONIC ANTIGEN; MONOCLONAL-ANTIBODIES; MAMMARY TUMORIGENESIS; CDNA CLONES; FAMILY; TUMORS; CEA; IDENTIFICATION; CHROMATOGRAPHY; LOCALIZATION C1 NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. RP ROBBINS, J (reprint author), NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892, USA. NR 27 TC 17 Z9 17 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JUL PY 1991 VL 10 IS 3 BP 583 EP 587 DI 10.1016/0888-7543(91)90439-L PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA FQ640 UT WOS:A1991FQ64000010 PM 1653760 ER PT J AU DODGE, GR KOVALSZKY, I CHU, ML HASSELL, JR MCBRIDE, OW YI, HF IOZZO, RV AF DODGE, GR KOVALSZKY, I CHU, ML HASSELL, JR MCBRIDE, OW YI, HF IOZZO, RV TI HEPARAN-SULFATE PROTEOGLYCAN OF HUMAN COLON - PARTIAL MOLECULAR-CLONING, CELLULAR EXPRESSION, AND MAPPING OF THE GENE (HSPG2) TO THE SHORT ARM OF HUMAN CHROMOSOME-1 SO GENOMICS LA English DT Article ID CARCINOMA-CELLS; BASEMENT-MEMBRANE; MESSENGER-RNA; CDNA CLONING; HUMAN-LUNG; DNA; LOCALIZATION; IDENTIFICATION; BIOSYNTHESIS; PROTEIN C1 THOMAS JEFFERSON UNIV,DEPT PATHOL & CELL BIOL,JEFFERSON ALUMNI HALL,ROOM 249,PHILADELPHIA,PA 19107. THOMAS JEFFERSON UNIV,DEPT DERMATOL,PHILADELPHIA,PA 19107. THOMAS JEFFERSON UNIV,DEPT BIOCHEM & MOLEC BIOL,PHILADELPHIA,PA 19107. UNIV PITTSBURGH,INST EYE & EAR,PITTSBURGH,PA 15213. NCI,BIOCHEM LAB,BETHESDA,MD 20205. OI Iozzo, Renato/0000-0002-5908-5112 FU NCI NIH HHS [CA-47282, CA-39481] NR 37 TC 51 Z9 52 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD JUL PY 1991 VL 10 IS 3 BP 673 EP 680 DI 10.1016/0888-7543(91)90451-J PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA FQ640 UT WOS:A1991FQ64000022 PM 1679749 ER PT J AU PRITCHARD, MA BAKER, E WHITMORE, SA SUTHERLAND, GR IDZERDA, RL PARK, LS COSMAN, D JENKINS, NA GILBERT, DJ COPELAND, NG BECKMANN, MP AF PRITCHARD, MA BAKER, E WHITMORE, SA SUTHERLAND, GR IDZERDA, RL PARK, LS COSMAN, D JENKINS, NA GILBERT, DJ COPELAND, NG BECKMANN, MP TI THE INTERLEUKIN-4 RECEPTOR GENE (IL4R) MAPS TO 16P11.2-16P12.1 IN HUMAN AND TO THE DISTAL REGION OF MOUSE CHROMOSOME-7 SO GENOMICS LA English DT Article ID ERYTHROPOIETIN RECEPTOR; LOCALIZATION; SUPERFAMILY; ORGANIZATION; EXPRESSION; ASSIGNMENT; MULTIPLE; DISTINCT; SEQUENCE; LINKAGE C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. IMMUNEX CORP,DEPT MOLEC BIOL,SEATTLE,WA 98101. IMMUNEX CORP,DEPT BIOCHEM,SEATTLE,WA 98101. RP PRITCHARD, MA (reprint author), ADELAIDE CHILDRENS HOSP INC,DEPT CYTOGENET & MOLEC GENET,ADELAIDE,SA 5006,AUSTRALIA. RI Sutherland, Grant/D-2606-2012 FU NCI NIH HHS [N01-CO-74101] NR 28 TC 56 Z9 56 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 0888-7543 J9 GENOMICS JI Genomics PD JUL PY 1991 VL 10 IS 3 BP 801 EP 806 DI 10.1016/0888-7543(91)90466-R PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA FQ640 UT WOS:A1991FQ64000037 PM 1679753 ER PT J AU TURA, S CANELLOS, G GOLDSTONE, A LONGO, D MCMILLAN, A URBA, W ZINZANI, PL AF TURA, S CANELLOS, G GOLDSTONE, A LONGO, D MCMILLAN, A URBA, W ZINZANI, PL TI HODGKINS-DISEASE - CONTROVERSIES AND CHALLENGES FOR THE FUTURE SO HAEMATOLOGICA LA English DT Discussion ID BONE-MARROW TRANSPLANTATION; HIGH-DOSE CYCLOPHOSPHAMIDE; COMBINATION CHEMOTHERAPY; MALIGNANT NEOPLASMS; MOPP CHEMOTHERAPY; INCREASED RISK; FREE SURVIVAL; 1ST RELAPSE; FOLLOW-UP; LEUKEMIA C1 UNIV BOLOGNA,IST EMATOL LA SERAGNOLI,I-40126 BOLOGNA,ITALY. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CLIN ONCOL,BOSTON,MA 02115. UNIV COLL HOSP LONDON,DEPT HEMATOL,WC1 LONDON,ENGLAND. NCI,FREDERICK,MD 21701. RI Zinzani, Pier Luigi/J-9182-2016 OI Zinzani, Pier Luigi/0000-0002-2112-2651 NR 72 TC 7 Z9 7 U1 0 U2 0 PU PENSIERO SCIENTIFICO EDITOR PI ROME PA VIA BRADANO 3/C, 00199 ROME, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUL-AUG PY 1991 VL 76 IS 4 BP 263 EP 279 PG 17 WC Hematology SC Hematology GA GC709 UT WOS:A1991GC70900001 PM 1724436 ER PT J AU KNEBEL, AR AF KNEBEL, AR TI WEANING FROM MECHANICAL VENTILATION - CURRENT CONTROVERSIES SO HEART & LUNG LA English DT Article AB As an acute episode of respiratory failure resolves for the patient who is receiving mechanical ventilation, the sometimes difficult task of resuming spontaneous ventilation begins. The resumption of spontaneous ventilation, commonly referred to as weaning, is often difficult for the patient with preexisting lung disease. The purpose of this article is to explore the current controversies related to weaning patients from mechanical ventilation. Patients with chronic obstructive pulmonary disease are used as examples, providing the background for understanding weaning in difficult cases. Weaning is conceptualized as a process of three phases: preweaning, weaning, and extubation. Important considerations during each phase are examined. RP KNEBEL, AR (reprint author), NIA,GRC 3B06,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 0 TC 8 Z9 8 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0147-9563 J9 HEART LUNG JI Heart Lung PD JUL PY 1991 VL 20 IS 4 BP 321 EP 334 PG 14 WC Cardiac & Cardiovascular Systems; Nursing; Respiratory System SC Cardiovascular System & Cardiology; Nursing; Respiratory System GA FZ436 UT WOS:A1991FZ43600002 PM 2071425 ER PT J AU MAGRATH, I ADDE, M SANDLUND, J JAIN, V AF MAGRATH, I ADDE, M SANDLUND, J JAIN, V TI IFOSFAMIDE IN THE TREATMENT OF HIGH-GRADE RECURRENT NON-HODGKINS-LYMPHOMAS SO HEMATOLOGICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 4TH INTERNATIONAL CONF ON MALIGNANT LYMPHOMA CY JUN 06-09, 1990 CL LUGANO, SWITZERLAND DE NON-HODGKINS LYMPHOMA; SALVAGE TREATMENT; IFOSFAMIDE MONOTHERAPY; COMBINATION THERAPY ID CONTINUOUS INFUSION; EFFICACY; MESNA AB We report the results of two phase II trials of ifosfamide in very high risk patients with either partially responsive or recurrent non-Hodgkin's lymphomas. In the first study, in which patients were extremely heavily pretreated (50 per cent had received a very intensive salvage regimen containing very high dose cyclophosphamide), there were two complete responses, two partial responses and one objective (minimal) response among 14 patients treated. Toxicity was acceptable even in this end-stage patient group. We concluded that ifosfamide is an active agent even in patients with tumours resistant to cyclophosphamide. The second trial was a pilot study in 13 patients of a regimen incorporating VP16, ifosfamide/mesna, and high dose ara-C (VIPA). There were four complete responses, five partial responses and two objective responses. Two patients died in complete remission from toxic complications, while a third, with a stably regressed mediastinal mass died after completion of the protocol. While very toxic. we considered that this regimen was highly effective, and have since incorporated a slightly less intensive combination of the same drugs into the primary therapy of high risk patients. Since the primary toxicity of the VIPA combination was myelosuppression, the use of a modified protocol incorporating colony stimulating factors to ameliorate the side-effects and possibly increase dose rate is worthy of further exploration in patients with recurrent B cell tumours. RP MAGRATH, I (reprint author), NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,PEDIAT BRANCH,BETHESDA,MD 20892, USA. NR 13 TC 13 Z9 13 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0278-0232 J9 HEMATOL ONCOL JI Hematol. Oncol. PD JUL-OCT PY 1991 VL 9 IS 4-5 BP 267 EP 274 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA GT212 UT WOS:A1991GT21200011 PM 1743629 ER PT J AU GADELMAWLA, N HAMZA, MR ABDELHADI, S ELTANNIR, O HUSSEIN, MH ELHADDAD, A ADDE, M MAGRATH, I AF GADELMAWLA, N HAMZA, MR ABDELHADI, S ELTANNIR, O HUSSEIN, MH ELHADDAD, A ADDE, M MAGRATH, I TI PROLONGED DISEASE-FREE SURVIVAL IN PEDIATRIC NON-HODGKINS-LYMPHOMA USING IFOSFAMIDE-CONTAINING COMBINATION CHEMOTHERAPY SO HEMATOLOGICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 4TH INTERNATIONAL CONF ON MALIGNANT LYMPHOMA CY JUN 06-09, 1990 CL LUGANO, SWITZERLAND DE NON-HODGKINS LYMPHOMA; SURVIVAL PROLONGATION; IFOSFAMIDE; COMBINATION CHEMOTHERAPY ID CHILDREN; ADULTS AB Pediatric non-Hodgkin's lymphoma (NHL) constitutes 16 per cent of pediatric malignancies reported to the National Cancer Institute (NCI) in Cairo. The adopted treatment for these cases was, from 1982 to July 1985. a modified St Jude's regimen consisting of: vincristine, cyclophosphamide, adriamycin, prednisone and intrathecal methotrexate for the first 6 weeks for induction, followed by cranial irradiation for cranial prophylaxis. Patients in remission received maintenance therapy for 18 months. Of 32 patients complete remission (CR) was achieved in 24 patients (75 per cent); partial remission (PR) in one patient (3 per cent): five patients showed no response (15 per cent) while two patients died during the induction phase. At 60+ months follow-up, 60 per cent of cases are still alive, disease-free, and overall survival is 66 per cent. A new protocol was adopted in 1985, consisting of alternating cycles: A and B, for 4-8 cycles. Cycle A: cyclophosphamide, high dose ara-C, adriamycin, and vincristine. Cycle B: ifosfamide, methotrexate, VP 16. with intrathecal methotrexate. The response in 39 cases is: CR in 31 cases (82 per cent); PR in four cases (10 per cent); no response in three cases (8 per cent). At 60+ months, the disease-free survival is 60 per cent, and overall survival 80 per cent. This new protocol has the advantage of: short duration of therapy and so better patient compliance, no maintenance therapy or cranial irradiation with its sequelae in the future. Moreover, it has a better overall survival. C1 NATL CANC INST,BETHESDA,MD. RP GADELMAWLA, N (reprint author), NATL CANC INST,CAIRO,EGYPT. NR 12 TC 3 Z9 3 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0278-0232 J9 HEMATOL ONCOL JI Hematol. Oncol. PD JUL-OCT PY 1991 VL 9 IS 4-5 BP 281 EP 286 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA GT212 UT WOS:A1991GT21200013 PM 1743631 ER PT J AU CRISTIANO, K DIBISCEGLIE, AM HOOFNAGLE, JH FEINSTONE, SM AF CRISTIANO, K DIBISCEGLIE, AM HOOFNAGLE, JH FEINSTONE, SM TI HEPATITIS-C VIRAL-RNA IN SERUM OF PATIENTS WITH CHRONIC NON-A, NON-B HEPATITIS - DETECTION BY THE POLYMERASE CHAIN-REACTION USING MULTIPLE PRIMER SETS SO HEPATOLOGY LA English DT Article ID VIRUS; CHIMPANZEES; INACTIVATION; GENOME; AGENT AB The recently introduced antibody test for hepatitis C virus infection has already proved to be valuable in many situations such as screening blood donors and diagnosing chronically infected patients, but this antibody assay has certain limitations. Hepatitis C virus itself is usually present in clinical specimens at very low titers; therefore a useful assay for the virus must have very high sensitivity. We have developed a simple, highly sensitive assay for hepatitis C virus RNA based on the polymerase chain reaction. In this test RNA extracted from hepatitis C virus - infected serum or plasma is used as the template for double polymerase chain reaction with nested primers. Sensitivity studies demonstrate that this assay is able to detect hepatitis C virus at or beyond the sensitivity level of chimpanzee infectivity. Preliminary studies in chronic non-A, non-B hepatitis showed that 16 of 36 patients positive for antibody to hepatitis C virus and 2 of 4 patients negative for antibody to hepatitis C virus were positive in the polymerase chain reaction test. By retesting the polymerase chain reaction - negative patients with several sets of polymerase chain reaction primers, we found hepatitis C virus RNA in 35 of the 40 patients including all 4 seronegative patients. Normal human plasma and plasma from patients with hepatitis B infection did not react in this test. This assay has proved to be valuable for determining the presence of hepatitis C virus RNA in various samples. Furthermore, it offers the possibility of diagnosis of hepatitis C virus infection in patients who do not react in the presently available antibody tests. C1 US FDA,CTR BIOL EVALUAT & RES,DIV VIROL,HEPATITIS RES LAB,8800 ROCKVILLE PIKE,BLDG 29A,HFB-500,BETHESDA,MD 20892. NIDDKD,LIVER DIS SECT,BETHESDA,MD 20892. NR 15 TC 151 Z9 151 U1 0 U2 3 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 JUL PY 1991 VL 14 IS 1 BP 51 EP 55 DI 10.1002/hep.1840140109 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA FW002 UT WOS:A1991FW00200008 PM 1648539 ER PT J AU FONG, TL DIBISCEGLIE, AM WAGGONER, JG BANKS, SM HOOFNAGLE, JH AF FONG, TL DIBISCEGLIE, AM WAGGONER, JG BANKS, SM HOOFNAGLE, JH TI THE SIGNIFICANCE OF ANTIBODY TO HEPATITIS-C VIRUS IN PATIENTS WITH CHRONIC HEPATITIS-B SO HEPATOLOGY LA English DT Article ID NON-A; VIRAL-HEPATITIS; BLOOD-DONORS; EPIDEMIOLOGY; CARRIERS AB We assessed the prevalence and clinical significance of antibodies to hepatitis C virus among a cohort of 148 patients with chronic hepatitis B virus infection. Sixteen patients (11%) had anti-hepatitis C virus detectable by enzyme-linked immunoassay. The results from eight of these patients were positive by recombinant immunoblot assay. The results of recombinant immunoblot assay testing were not consistent; therefore the analysis of the patients' data was based on anti-hepatitis C virus enzyme-linked immunoassay results. Patients with chronic hepatitis B with anti-hepatitis C virus were more likely to be cirrhotic (44% vs. 21%) and to have decompensated liver disease (24% vs. 6%). Hepatitis B virus replication appeared to be suppressed in patients with both infections as measured by hepatitis B virus - associated DNA polymerase activity (mean = 2,055 vs. 2,555 cpm). Human immunodeficiency virus infection was more common in the anti-hepatitis C virus positive group (36% vs. 11%). Thus hepatitis C virus appears to suppress hepatitis B virus replication and to cause more severe liver disease in patients with chronic hepatitis B infection. C1 NIAID,OFF SCI DIRECTOR,BETHESDA,MD 20892. RP FONG, TL (reprint author), NIDDKD,LIVER DIS SECT,BLDG 10,ROOM 4D52,BETHESDA,MD 20892, USA. NR 19 TC 186 Z9 190 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JUL PY 1991 VL 14 IS 1 BP 64 EP 67 DI 10.1002/hep.1840140111 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA FW002 UT WOS:A1991FW00200010 PM 1648540 ER PT J AU LARDELLI, P SWABY, RF MEDEIROS, LJ JAFFE, ES RIZZI, R STETLERSTEVENSON, M AF LARDELLI, P SWABY, RF MEDEIROS, LJ JAFFE, ES RIZZI, R STETLERSTEVENSON, M TI DETERMINATION OF LINEAGE AND CLONALITY IN DIFFUSE LYMPHOMAS USING THE POLYMERASE CHAIN-REACTION TECHNIQUE SO HUMAN PATHOLOGY LA English DT Article DE DIFFUSE LYMPHOMA; POLYMERASE CHAIN REACTION TECHNIQUE ID NON-HODGKINS LYMPHOMAS; MALIGNANT-LYMPHOMA; LARGE-CELL; TRANSLOCATIONS; NEOPLASMS; DISEASE C1 NCI,HEMATOPATHOL LAB,BLDG 10,2A-33,BETHESDA,MD 20892. OI Rizzi, Rita/0000-0002-2557-1235 NR 23 TC 7 Z9 7 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD JUL PY 1991 VL 22 IS 7 BP 685 EP 689 DI 10.1016/0046-8177(91)90290-6 PG 5 WC Pathology SC Pathology GA GQ801 UT WOS:A1991GQ80100009 PM 2071113 ER PT J AU BURGDORFER, W AF BURGDORFER, W TI LYME BORRELIOSIS - 10 YEARS AFTER DISCOVERY OF THE ETIOLOGIC AGENT, BORRELIA-BURGDORFERI SO INFECTION LA English DT Article ID CHRONIC NEUROLOGIC MANIFESTATIONS; POLYMERASE CHAIN-REACTION; TICK-BORNE SPIROCHETOSIS; IXODES-DAMMINI TICKS; DISEASE SPIROCHETE; INFECTION; ANTIGEN; CULTIVATION; MORPHEA; GENE AB Since the recovery of its causative agent, Borrelia burgdorferi, in 1981, Lyme borreliosis has become the most prevalent tick-borne disease in the United States as well as in Europe. Its steadily increasing clinical spectrum now includes erythema migrans, acrodermatitis chronica atrophicans, lymphadenosis beniga cutis, arthritis, myocarditis, progressive meningoencephalitis, myositis, and various ocular and skin disorders. The true incidence of Lyme borreliosis in the world is unknown. In the United States, it has increased from 2,000 cases in 1987, to more than 8,000 in 1989. It occurs now in regions where the tick vectors, Ixodes dammini and Ixodes pacificus, are absent and where other species of ticks may be responsible for maintaining and distributing the spirochete. In Europe, Lyme borreliosis has been reported from 19 countries; its occurrence coincides with the distribution of the vector tick, Ixodes ricinus and possibly Ixodes hexagonus. Specific and dependable serological tests are still not available, but development of probes for specific antigens and the polymerase chain reaction appear promising in detecting ongoing infection and in identifying B. burgdorferi in ticks, animal, and human hosts. Brief reference is made to advances in the preparation of whole cell and genetically engineered vaccines. RP BURGDORFER, W (reprint author), NIAID,VECTORS & PATHOGENS LAB,HAMILTON,MT 59840, USA. NR 42 TC 18 Z9 18 U1 1 U2 6 PU MMW MEDIZIN VERLAG GMBH PI MUNICH 80 PA NEUMARKTER STRASSE 18, W-8000 MUNICH 80, GERMANY SN 0300-8126 J9 INFECTION JI Infection PD JUL-AUG PY 1991 VL 19 IS 4 BP 257 EP 262 DI 10.1007/BF01644963 PG 6 WC Infectious Diseases SC Infectious Diseases GA GD252 UT WOS:A1991GD25200017 PM 1917043 ER PT J AU WICKES, B STAUDINGER, J MAGEE, BB KWONCHUNG, KJ MAGEE, PT SCHERER, S AF WICKES, B STAUDINGER, J MAGEE, BB KWONCHUNG, KJ MAGEE, PT SCHERER, S TI PHYSICAL AND GENETIC-MAPPING OF CANDIDA-ALBICANS - SEVERAL GENES PREVIOUSLY ASSIGNED TO CHROMOSOME-1 MAP TO CHROMOSOME-R, THE RDNA-CONTAINING LINKAGE GROUP SO INFECTION AND IMMUNITY LA English DT Article ID FIELD GEL-ELECTROPHORESIS; DNA; SEPARATION AB Analysis of the karyotypes of multiple Candida albicans isolates by pulsed-field electrophoresis confirms the observation by Lasker et al. of eight chromosomes. The genes previously assigned to chromosome 1 in fact fall into two groups, one (including ADE1, SOR9, and CDC10) is linked to the ribosomal DNA genes on a chromosome called R, whereas the others are found on chromosome 1. Chromosome R varies in electrophoretic mobility among strains, usually running equal to or faster than chromosome 1 but in rare cases running slower than chromosome 1. In strain 1012A, the decreased mobility of one homolog is associated with the very large majority of the rDNA genes being on that homolog; the second homolog, with only a few copies, migrates with chromosome 2. Linkage analysis by using spheroplast fusion confirms the gene assignments made by hybridization to blots of the electrophoretic karyotype. A newly cloned gene, LYS2, hybridizes to chromosome 1. C1 UNIV MINNESOTA,DEPT GENET & CELL BIOL,ST PAUL,MN 55108. NCI,CLIN INVEST LAB,BETHESDA,MD 20892. UNIV MINNESOTA,DEPT MICROBIOL,MINNEAPOLIS,MN 55455. FU NIAID NIH HHS [AI 23850, AI 16567] NR 20 TC 65 Z9 71 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 1991 VL 59 IS 7 BP 2480 EP 2484 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA FT922 UT WOS:A1991FT92200037 PM 2050413 ER PT J AU MILEI, J PESCE, R VALERO, E MURATORE, C BEIGELMAN, R FERRANS, VJ AF MILEI, J PESCE, R VALERO, E MURATORE, C BEIGELMAN, R FERRANS, VJ TI ELECTROPHYSIOLOGICAL-STRUCTURAL CORRELATIONS IN CHAGASIC ANEURYSMS CAUSING MALIGNANT ARRHYTHMIAS SO INTERNATIONAL JOURNAL OF CARDIOLOGY LA English DT Article DE CHAGASIC ANEURYSM; ARRHYTHMIA; REFRACTORY VENTRICULAR TACHYCARDIA; EARLY DAMAGED MYOCARDIUM ID SUSTAINED VENTRICULAR-TACHYCARDIA; MYOCARDIAL-INFARCTION; HEART-DISEASE; MECHANISM; REENTRY AB We studied the structure and ultrastructure of three chagasic aneurysms, the excision of which abolished malignant arrhythmias. Chronic recurrent ventricular tachycardia often occurs in patients with chagasic aneurysms, and ventricular mapping indicates that these arrhythmias originate in regions adjacent to those aneurysms. In our patients, ventricular tachycardia had been refractory to medical treatment. During surgery, epicardial and endocardial mapping showed abnormal potentials. Sutures were placed in the areas of resection, their sizes approximating those of earliest activation so that these sites could be identified. The myocardium showed chronic inflammatory reaction, myocytolysis and fibrosis. The presence of "islets" was common (normal, "early" damaged or "established" necrotic myocytes surrounded by fibrous tissue). The 'early" lesions were predominant at the previously identified areas of arrhythmogenic activity. The ultrastructural studies showed hypertrophy of myocytes and partial or complete loss of myofibrils, swelling of mitochondria and disruption of mitochondrial cristae, accumulation of lipofuscin granules, and intracellular oedema. A most striking alteration was the thickening of the basement membranes of myocytes and vascular endothelial and smooth muscle cells. The interlaced fronts of respectively healthy (fast conducting) and "early" damaged (slow conducting) myocytes seen in serial sectioning produced an ideal configuration for reentry circuits. The final proof that the arrhythmias originated in these endocardial regions was their abolition by resection of the aneurysm. C1 FDN FAVALORO,BUENOS AIRES,ARGENTINA. NHLBI,PATHOL BRANCH,BETHESDA,MD 20892. RP MILEI, J (reprint author), HOSP JUAN A FERNANDEZ,TUCUMAN 2163 4B,RA-1050 BUENOS AIRES,ARGENTINA. OI MILEI, JOSE/0000-0003-4029-5993 NR 21 TC 11 Z9 13 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0167-5273 J9 INT J CARDIOL JI Int. J. Cardiol. PD JUL PY 1991 VL 32 IS 1 BP 65 EP 74 DI 10.1016/0167-5273(91)90045-Q PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA FU235 UT WOS:A1991FU23500009 PM 1864671 ER PT J AU ENGEL, BT AF ENGEL, BT TI AN INTEGRATIVE MODEL FOR BEHAVIORAL PHYSIOLOGY SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 NIA,BEHAV SCI LAB,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD JUL PY 1991 VL 11 IS 1 BP 26 EP 26 DI 10.1016/0167-8760(91)90117-G PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA FZ975 UT WOS:A1991FZ97500076 ER PT J AU MINOR, TR WILKINS, JN INSEL, T AF MINOR, TR WILKINS, JN INSEL, T TI EXPERIMENTAL-ANALYSIS OF THE DST AND PITUITARY-DEPENDENT OPIATE ANALGESIA IN THE LEARNED HELPLESSNESS PARADIGM SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES,LOS ANGELES,CA 90024. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD JUL PY 1991 VL 11 IS 1 BP 57 EP 57 DI 10.1016/0167-8760(91)90240-X PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA FZ975 UT WOS:A1991FZ97500199 ER PT J AU ROBINSON, TN ZAHN, TP AF ROBINSON, TN ZAHN, TP TI BILATERAL EDR AND HEART-RATE DIFFERENCES FOR INTROVERTS AND EXTROVERTS IN THE SIMPLE RT PARADIGM SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 UNIV MARYLAND,BALTIMORE,MD 21201. NIMH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD JUL PY 1991 VL 11 IS 1 BP 70 EP 70 DI 10.1016/0167-8760(91)90293-7 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA FZ975 UT WOS:A1991FZ97500252 ER PT J AU TALAN, MI AF TALAN, MI TI LEARNED ADAPTATION TO REPEATED MILD-COLD EXPOSURES IN MICE SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 NIA,BEHAV SCI LAB,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD JUL PY 1991 VL 11 IS 1 BP 79 EP 80 DI 10.1016/0167-8760(91)90334-T PG 2 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA FZ975 UT WOS:A1991FZ97500293 ER PT J AU SPERDUTO, PW DELANEY, TF THOMAS, G SMITH, P DACHOWSKI, LJ RUSSO, A BONNER, R GLATSTEIN, E AF SPERDUTO, PW DELANEY, TF THOMAS, G SMITH, P DACHOWSKI, LJ RUSSO, A BONNER, R GLATSTEIN, E TI PHOTODYNAMIC THERAPY FOR CHEST-WALL RECURRENCE IN BREAST-CANCER SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE HEMATOPORPHYRIN DERIVATIVE; BREAST CANCER; LASER; PHOTOSENSITIZER ID PHOTORADIATION THERAPY; BRONCHOSCOPIC PHOTOTHERAPY; CARCINOMA; TUMORS AB Photodynamic therapy is the use of a sensitizer (dihematoporphyrin ethers) which is preferentially retained in tumor cells and activated by subsequent light delivery resulting in a selective tumoricidal effect. Between 1986 and 1989, we treated 20 patients with photodynamic therapy for chest wall recurrence of breast cancer. Responses were seen (20% complete response, 45% partial response, 35% no response), but the duration of response was short (average 2.5 months). Complications, in decreasing frequency, included pain, ecchymoses, blistering, ulceration and necrosis in the area of tumor involvement on the chest wall. One patient required skin flap reconstruction for full thickness necrosis. A limitation to this mode of therapy is that the sensitizer currently used is activated by light at a wavelength of 630 nm. This light can penetrate to a tissue depth of only 0.5 to 1.0 cm; thus, deeper disease cannot be treated. Future research must focus on the development of a clinically useful photosensitizer that can be activated by light at longer wavelengths and thereby achieve deeper tissue penetration. This would greatly expand the patient population for which this therapy is useful. RP SPERDUTO, PW (reprint author), NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,RADIAT ONCOL BRANCH,BLDG 10,RM B3 B69,BETHESDA,MD 20892, USA. RI Bonner, Robert/C-6783-2015 NR 18 TC 44 Z9 44 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 JUL PY 1991 VL 21 IS 2 BP 441 EP 446 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA FV885 UT WOS:A1991FV88500023 PM 2061120 ER PT J AU MILLER, RW RAUBITSCHEK, AA HARRINGTON, FS VANDEGEIJN, J OVADIA, J GLATSTEIN, E AF MILLER, RW RAUBITSCHEK, AA HARRINGTON, FS VANDEGEIJN, J OVADIA, J GLATSTEIN, E TI AN ISOCENTRIC CHAIR FOR THE SIMULATION AND TREATMENT OF RADIATION-THERAPY PATIENTS SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Note DE RADIOTHERAPY; INSTRUMENTATION; CHAIR AB There are a variety of clinical situations in which patients undergoing radiation therapy can benefit from being treated in an upright position. The authors describe a new design for a treatment chair to assist in accomplishing this task. The present chair differs from previous designs in that it can be used with existing radiotherapy simulators as well as treatment units and that it permits isocentric setup and treatment of tumors either at the nominal source-to-axis distance (SAD) of a machine or at extended distance. This design permits treatment of mediastinal tumors as well as those of the head and neck using a variety of field arrangements including AP-PA, opposed laterals, and multiple obliques. The seat is designed on the "tool platform" principle. A wide variety of devices can be attached onto it to ensure accurate and reproducible, yet comfortable, patient positioning. RP MILLER, RW (reprint author), NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892, USA. NR 8 TC 6 Z9 6 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUL PY 1991 VL 21 IS 2 BP 469 EP 473 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA FV885 UT WOS:A1991FV88500028 PM 2061123 ER PT J AU COUSINS, SW MCCABE, MM DANIELPOUR, D STREILEIN, JW AF COUSINS, SW MCCABE, MM DANIELPOUR, D STREILEIN, JW TI IDENTIFICATION OF TRANSFORMING GROWTH-FACTOR-BETA AS AN IMMUNOSUPPRESSIVE FACTOR IN AQUEOUS-HUMOR SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE IMMUNOSUPPRESSIVE FACTORS; OCULAR IMMUNE RESPONSE; ACAID; AQUEOUS HUMOR; TGF-BETA ID CELL SUPPRESSOR FACTOR; IMMUNE DEVIATION; EYE; GLIOBLASTOMA; TGF-BETA-1; INDUCTION; SYSTEM; FORMS AB The anterior chamber of the eye is an immunologically privileged site. Over the past 15 years, numerous laboratories documented that the privileged status of this unique site is mediated by multifactorial immunoregulatory processes. Among the participating factors is the aqueous humor that circulates in the anterior chamber and is in contact with most of the tissues in the anterior segment of the eye. Recently, it was found that normal aqueous humor is a powerful inhibitor of antigen-driven T lymphocyte activation, but it spares other important functional properties of T cells. The spectrum of immune inhibitory properties resembles some of the activities of transforming growth factor-beta (TGF-beta), a polypeptide cytokine. Because of this similarity, the authors tried to determine if TGF-beta is present in aqueous humor and whether this cytokine could account for the lymphocyte inhibitory activity of this biologic fluid. They found TGF-beta in aqueous humor by dot-blot analysis. Using the CCL-64 mink lung epithelial cell bioassay for this compound, TGF-beta-bioactivity was shown in aqueous humor from several different species, including human. In rabbit and human aqueous humor, most of the biologic activity was due to TGF-beta-2 (80-90%). Dose-response curves generated by using purified porcine TGF-beta showed that aqueous humor contained sufficient concentrations of TGF-beta to account for the observed inhibition in several assays for T cell activation and proliferation. Partial purification of the lymphocyte inhibitor in rabbit aqueous humor by size exclusion in high-performance liquid chromatography demonstrated that several lymphocyte inhibitory fractions contained TGF-beta-bioactivity. Finally, neutralizing antisera to TGF-beta-2 were able to reverse most of the lymphocyte inhibitory activity of aqueous humor. It was concluded that TGF-beta was present in high concentration in normal aqueous humor and that this cytokine contributed to the immunosuppressive properties of aqueous humor. C1 NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. UNIV MIAMI,SCH MED,BASCOM PALMER EYE INST,MIAMI,FL 33152. RP COUSINS, SW (reprint author), UNIV MIAMI,SCH MED,DEPT MICROBIOL & IMMUNOL,MCKNIGHT VIS RES CTR,POB 016880,MIAMI,FL 33101, USA. FU NEI NIH HHS [EY 00308, EY 05678] NR 30 TC 382 Z9 392 U1 2 U2 7 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 JUL PY 1991 VL 32 IS 8 BP 2201 EP 2211 PG 11 WC Ophthalmology SC Ophthalmology GA FX406 UT WOS:A1991FX40600005 PM 2071334 ER PT J AU BERKOWITZ, BA WILSON, CA HATCHELL, DL AF BERKOWITZ, BA WILSON, CA HATCHELL, DL TI OXYGEN KINETICS IN THE VITREOUS SUBSTITUTE PERFLUOROTRIBUTYLAMINE - A F-19 NMR-STUDY INVIVO SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID CAT RETINA; CIRCULATION; CONSUMPTION; HYPEROXIA; PRESSURE; LIQUIDS; TENSION; GASES AB Perfluorocarbon (PFC) vitreous substitutes yielded promising results in the surgical management of retinal detachments. This success is due primarily to their useful physical properties. However, oxygen kinetics in PFC in vivo have not been investigated. The oxygen flux in the vitreous substitute perfluorotributylamine (FTBA) was assessed in the rabbit eye by monitoring the partial oxygen pressure (PO2) in real-time using Fluorine-19 nuclear magnetic resonance spectroscopy (F-19 NMR). The spin-lattice relaxation rate (T1)-1 of the CF, resonance of FTBA is a rapid and sensitive index of PO2. T1-derived PO2 from the FTBA-filled rabbit eye was followed at regular time intervals under different oxygenation protocols. In the first series of experiments, FTBA in the vitreous space was oxygenated by ventilating the rabbit with a mixture of 95% 02 and 5% CO2. The oxygen uptake profile could be approximated by a simple exponential function with a time constant of 159 +/- 110 min (mean +/- SD, n = 3). A more reproducible correlate was obtained by performing an initial rate analysis on the first hour of ventilation with high oxygen levels. This analysis showed that the rate of increase in FTBA PO, was 2.34 +/- 0.67 mm Hg/min (mean +/- SD, r2 = 0.99, n = 7). After the animal was removed from the 95% O2/5% CO2 gas and was ventilated with room air, the oxygen clearance profile could be approximated in all cases by a single exponential with a time constant of 59.8 +/- 9.6 min (mean +/- SD, n = 4). To assess whether or not ventilating the animal with 95% 02/5% CO2 could have influenced the O2 clearance rate, FTBA was preoxygenated with 100% 02 immediately before injecting the compound into the vitreous cavity. The animal was continuously ventilated with room air. A single exponential profile was again obtained with a time constant of 69.6 +/- 12.6 min (mean +/- SD, n = 4) which does not differ statistically from the above mean (p = 0.4). This work represents the first to characterize oxygen kinetics in a perfluorocarbon vitreous substitute in vivo. These experiments provide a basis for future investigations to determine the possible beneficial effects of oxygenated PFC when used as vitreous substitutes during vitreoretinal surgical conditions. C1 DUKE UNIV,CTR EYE,DURHAM,NC 27706. VET ADM MED CTR,DURHAM,NC 27705. RP BERKOWITZ, BA (reprint author), NIEHS,MAIL DROP 4A-01,POB 12233,RES TRIANGLE PK,NC 27709, USA. FU NEI NIH HHS [R01 EY02903] NR 21 TC 24 Z9 24 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUL PY 1991 VL 32 IS 8 BP 2382 EP 2387 PG 6 WC Ophthalmology SC Ophthalmology GA FX406 UT WOS:A1991FX40600023 PM 2071349 ER PT J AU MARAINI, G PASQUINI, P SPERDUTO, RD BONACINI, M CARRIERI, MP CORONA, R GRAZIOSI, P TOMBA, MC WILLIAMS, SL AF MARAINI, G PASQUINI, P SPERDUTO, RD BONACINI, M CARRIERI, MP CORONA, R GRAZIOSI, P TOMBA, MC WILLIAMS, SL TI THE EFFECT OF CATARACT SEVERITY AND MORPHOLOGY ON THE RELIABILITY OF THE LENS OPACITIES CLASSIFICATION SYSTEM-II (LOCS-II) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE CATARACTS, CLASSIFICATION; CLINICAL GRADING; PHOTOGRAPHIC GRADING; LOCS-II AB Data collected from 3646 eyes in the Italian-American Natural History Study of Age-Related Cataract were used to investigate whether the reliability of the Lens Opacities Classification System II (LOCS II) by the severity of the opacity that is being graded or is influenced by the presence and severity of coexisting opacities. Reliability was assessed by comparing the slit-lamp gradings of two clinical examiners (346 eyes) and the gradings performed at the slit lamp with gradings of photographs (3646 eyes). The severity of cortical and nuclear opacities did not affect the reproducibility of slit-lamp gradings, but clinical grading of posterior subcapsular opacities became more reliable as the severity of the posterior subcapsular opacities increased. More advanced coexisting opacities decreased the agreement in the slit-lamp diagnosis of nuclear, but not cortical or posterior subcapsular, opacities. Comparisons of clinical and photographic gradings showed very good to excellent agreement for nuclear and cortical opacities, regardless of the severity of the specific opacity or the severity of the coexisting opacities. Agreement in diagnosing posterior subcapsular opacities was decreased in eyes with milder posterior subcapsular opacities and in eyes with more severe coexisting nuclear and/or cortical opacities. The effect of the severity of the opacity being graded and the severity of coexisting opacities on the reliability of the LOCS II must be considered in studies that use the system to classify and grade cataracts. C1 IST SUPER SANITA,EPIDEMIOL & BIOSTAT LAB,I-00161 ROME,ITALY. NEI,BETHESDA,MD 20892. RP MARAINI, G (reprint author), UNIV PARMA,INST OPHTHALMOL,I-43100 PARMA,ITALY. FU NEI NIH HHS [1-EY-9-2108] NR 3 TC 20 Z9 20 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 JUL PY 1991 VL 32 IS 8 BP 2400 EP 2403 PG 4 WC Ophthalmology SC Ophthalmology GA FX406 UT WOS:A1991FX40600026 PM 2071351 ER PT J AU RAPHAEL, GD IGARASHI, Y WHITE, MV KALINER, MA AF RAPHAEL, GD IGARASHI, Y WHITE, MV KALINER, MA TI THE PATHOPHYSIOLOGY OF RHINITIS .5. SOURCES OF PROTEIN IN ALLERGEN-INDUCED NASAL SECRETIONS SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE ALLERGIC RHINITIS; NASAL CHALLENGE; LAVAGE; PROTEIN; ALBUMIN; LACTOFERRIN; LYSOZYME ID MEDIATOR RELEASE; ANTIGEN CHALLENGE; PATHO-PHYSIOLOGY; AIRWAY CHALLENGE; HAY-FEVER; HISTAMINE; RADIOIMMUNOASSAY; METHACHOLINE; INDIVIDUALS; PROVOCATION AB Allergic rhinitis is characterized by a profuse rhinorrhea in addition to paroxysms of sneezing, nasal congestion, and pruritus. To define better the sources of nasal secretion produced during rhinitis, nasal allergen challenges were performed on nine atopic subjects with seasonal rhinitis. A single dose of allergen was sprayed into one side of the nose, and nasal lavages were collected bilaterally for 7 hours. Nasal lavages were assayed for protein (total protein, albumin, lactoferrin, and lysozyme) and mediator (histamine and prostaglandin D2) content. Protein concentrations increased and remained elevated above baseline levels in both ipsilateral and contralateral secretions for up to 3 hours after allergen challenge. The proportion of albumin relative to total protein (the albumin percent) increased on the ipsilateral side, whereas the relative proportions of lactoferrin and lysozyme (the lactoferrin percent and lysozyme percent) increased on the contralateral side. Prostaglandin D2, but not histamine, increased selectively on the ipsilateral side. These data suggest that the ipsilateral protein secretory response is due to allergen-induced mast cell mediator release causing increased vascular permeability, whereas the contralateral protein secretory response is primarily a reflex-induced glandular secretion. RP RAPHAEL, GD (reprint author), NIAID,CLIN INVEST LAB,ALLERG DIS SECT,9000 ROCKVILLE PIKE,BLDG 10,11C207,BETHESDA,MD 20892, USA. NR 37 TC 75 Z9 76 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUL PY 1991 VL 88 IS 1 BP 33 EP 42 DI 10.1016/0091-6749(91)90298-3 PG 10 WC Allergy; Immunology SC Allergy; Immunology GA FY204 UT WOS:A1991FY20400004 PM 1712803 ER PT J AU CONE, EJ WELCH, P PAUL, BD MITCHELL, JM AF CONE, EJ WELCH, P PAUL, BD MITCHELL, JM TI FORENSIC DRUG-TESTING FOR OPIATES .3. URINARY-EXCRETION RATES OF MORPHINE AND CODEINE FOLLOWING CODEINE ADMINISTRATION SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID POPPY SEEDS; CONSUMPTION; DEMETHYLATION; HYDROXYLATION; INGESTION AB The urinary excretion profile of free and conjugated codeine and morphine was determined by GC/MS for four healthy male subjects after intramuscular administration of 60- and 120-mg doses of codeine. Codeine and metabolites were rapidly excreted with the majority of drug appearing in the first 24 h. No dose-related differences in metabolism were observed. The initial ratio of total codeine to total morphine was substantially greater than 1.0 but declined over time. For two of the four subjects, the codeine-morphine ratio declined below 1.0 late in the elimination phase. With a 300-ng/mL cutoff, one subject tested positive on more than one occasion for total morphine and negative for codeine during the terminal elimination phase. The data Indicate that urine codeine-morphine ratios are not reliable indices of the type of opiate exposure. C1 USN,DRUG SCREENING LAB,NORFOLK,VA 23511. RP CONE, EJ (reprint author), NIDA,ADDICT RES CTR,POB 5180,BALTIMORE,MD 21224, USA. NR 28 TC 61 Z9 62 U1 1 U2 8 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD JUL-AUG PY 1991 VL 15 IS 4 BP 161 EP 166 PG 6 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA FX674 UT WOS:A1991FX67400001 PM 1943064 ER PT J AU BRENDLER, T ABELES, A AUSTIN, S AF BRENDLER, T ABELES, A AUSTIN, S TI CRITICAL SEQUENCES IN THE CORE OF THE P1 PLASMID REPLICATION ORIGIN SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ESCHERICHIA-COLI; DNA-SEQUENCE; COPY NUMBER; PROTEIN; INITIATION; CLONING; REPA; GENE; MINIPLASMIDS; MAINTENANCE AB The core of the P1 plasmid replication origin consists of a series of 7-bp repeats and a G+C-rich stretch. Methylation of the GATC sequences in the repeats is essential. Forty different single-base mutations in the region were isolated and assayed for origin function. A single-base change within any 7-bp repeat could block the origin, irrespective of whether GATC bases were affected. The repeats themselves were critical, but the short intervals between them were not. Mutations in the G+C-rich region showed it to be a spacer whose exact length is important but whose sequence can vary considerably. It maintains a precise distance between the 7-bp repeats and binding sites for the P1 RepA initiator protein. It may also serve as a clamp to limit strand separation during initiation. RP BRENDLER, T (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,CHROMOSOME BIOL LAB,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74101] NR 39 TC 22 Z9 22 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JUL PY 1991 VL 173 IS 13 BP 3935 EP 3942 PG 8 WC Microbiology SC Microbiology GA FV039 UT WOS:A1991FV03900001 PM 2061278 ER PT J AU KUMAGAI, H SACKTOR, B FILBURN, CR AF KUMAGAI, H SACKTOR, B FILBURN, CR TI PURINERGIC REGULATION OF CYTOSOLIC CALCIUM AND PHOSPHOINOSITIDE METABOLISM IN RAT OSTEOBLAST-LIKE OSTEOSARCOMA CELLS SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID PARATHYROID-HORMONE; BONE-RESORPTION; INOSITOL PHOSPHATES; EXTRACELLULAR ATP; PROTEIN-KINASE; ADENINE-NUCLEOTIDES; LINE UMR-106; CA-2+; PROSTAGLANDIN-E2; FORSKOLIN AB We have shown that ATP increases cytosolic Ca2+ in UMR-106 cells through P2-purinergic receptor stimulation (Calcif Tissue Int 45:251-254). This response was further characterized using cells loaded with indo-1/AM or prelabeled with [H-3]inositol. ATP elicited a rapid transient increase in Ca2+ from 148 to 540 nM, followed by a biphasic decline (first rapid and then slower) to basal within 1 minute and then a late slow rise to 200 nM by 4 minutes. ADP also elicited a rapid transient increase, but this was followed by a second smaller transient and a later, slow increase above basal Ca2+. These transient increases in Ca2+ induced by ATP and ADP were dose dependent, detected at 10(-6) M ATP and 10(-7) M ADP, and saturated at 10(-4) M with both nucleotides. The maximum increase in Ca2+ was 20% greater with ATP than ADP. EGTA chelation of extracellular Ca2+ abolished the biphasicity of the ATP-induced Ca2+ transient, the second ADP-induced transient, and all late slower increases in Ca2+. Desmethoxyverapamil pretreatment attenuated the biphasicity of the ATP-induced transient and the second peak elicited by ADP. Elevated extracellular Ca2+ (5 mM) prevented the return to the basal level that normally follows the ATP-induced Ca2+ transient and amplified the sustained increase in Ca2+ but had little effect on the response to ADP. IP3 and IP4 increased rapidly after addition of ATP, with I(1,4,5)P3 increasing before I(1,3,4)P3. These data indicate that P2-purinergic stimulation of UMR-106 cells causes three consecutive responses in cytosolic Ca2+: (1) a transient increase due to IP3-mediated mobilization of intracellular Ca2+; (2) a transient increase due in part to influx, probably associated with a Ca2+ channel; and (3) a later sustained increase that requires extracellular calcium. C1 NIA,GERONTOL RES CTR,BIOL CHEM LAB,4940 EASTERN AVE,BALTIMORE,MD 21224. NR 52 TC 50 Z9 50 U1 0 U2 1 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 JUL PY 1991 VL 6 IS 7 BP 697 EP 708 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA GN789 UT WOS:A1991GN78900006 PM 1659120 ER PT J AU VALDIVIESO, MH MOL, PC SHAW, JA CABIB, E DURAN, A AF VALDIVIESO, MH MOL, PC SHAW, JA CABIB, E DURAN, A TI CAL1, A GENE REQUIRED FOR ACTIVITY OF CHITIN SYNTHASE-3 IN SACCHAROMYCES-CEREVISIAE SO JOURNAL OF CELL BIOLOGY LA English DT Article ID CALCOFLUOR WHITE; ESCHERICHIA-COLI; SYNTHESIS INVIVO; S-CEREVISIAE; YEAST; DNA; TRANSFORMATION; SEQUENCE; ACTIVATION; EXPRESSION AB The CAL1 gene was cloned by complementation of the defect in Calcofluor-resistant cal(R)1 mutants of Saccharomyces cerevisiae. Transformation of the mutants with a plasmid carrying the appropriate insert restored Calcofluor sensitivity, wild-type chitin levels and normal spore maturation. Southern blots using the DNA fragment as a probe showed hybridization to a single locus. Allelic tests indicated that the cloned gene corresponded to the cal(R)1 locus. The DNA insert contains a single open-reading frame encoding a protein of 1,099 amino acids with a molecular mass of 124 kD. The predicted amino acid sequence shows several regions of homology with those of chitin synthases 1 and 2 from S. cerevisiae and chitin synthase 1 from Candida albicans. cal(R)1 mutants have been found to be defective in chitin synthase 3, a trypsin-independent synthase. Transformation of the mutants with a plasmid carrying CAL1 restored chitin synthase 3 activity; however, overexpression of the enzyme was not achieved even with a high copy number plasmid. Since Calcofluor-resistance mutations different from cal(R)1 also result in reduced levels of chitin synthase 3, it is postulated that the products of some of these CAL genes may be limiting for expression of the enzymatic activity. Disruption of the CAL1 gene was not lethal, indicating that chitin synthase 3 is not an essential enzyme for S. cerevisiae. C1 NIDDKD,BIOCHEM & METAB LAB,BETHESDA,MD 20892. CSIC,FAC BIOL,INST MICROBIOL BIOQUIM,SALAMANCA,SPAIN. UNIV SALAMANCA,SALAMANCA,SPAIN. OI Valdivieso, M.-Henar/0000-0002-6857-7493 NR 47 TC 143 Z9 145 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JUL PY 1991 VL 114 IS 1 BP 101 EP 109 DI 10.1083/jcb.114.1.101 PG 9 WC Cell Biology SC Cell Biology GA FT938 UT WOS:A1991FT93800010 PM 2050737 ER PT J AU SHAW, JA MOL, PC BOWERS, B SILVERMAN, SJ VALDIVIESO, MH DURAN, A CABIB, E AF SHAW, JA MOL, PC BOWERS, B SILVERMAN, SJ VALDIVIESO, MH DURAN, A CABIB, E TI THE FUNCTION OF CHITIN SYNTHASE-2 AND SYNTHASE-3 IN THE SACCHAROMYCES-CEREVISIAE CELL-CYCLE SO JOURNAL OF CELL BIOLOGY LA English DT Article ID CYTOKINESIS-DEFECTIVE MUTANTS; CALCOFLUOR WHITE; SEPTUM FORMATION; SYNTHESIS INVIVO; YEAST CHITINASE; SHUTTLE VECTORS; S-CEREVISIAE; SUBUNIT-II; POLYOXIN-D; WALL AB The morphology of three Saccharomyces cerevisiae strains, all lacking chitin synthase 1 (Chs1) and two of them deficient in either Chs3 (cal(R)1 mutation) or Chs2 was observed by light and electron microscopy. Cells deficient in Chs2 showed clumpy growth and aberrant shape and size. Their septa were very thick; the primary septum was absent. Staining with WGA-gold complexes revealed a diffuse distribution of chitin in the septum, whereas chitin was normally located at the neck between mother cell and bud and in the wall of mother cells. Strains deficient in Chs3 exhibited minor abnormalities in budding pattern and shape. Their septa were thin and trilaminar. Staining for chitin revealed a thin line of the polysaccharide along the primary septum; no chitin was present elsewhere in the wall. Therefore, Chs2 is specific for primary septum formation, whereas Chs3 is responsible for chitin in the ring at bud emergence and in the cell wall. Chs3 is also required for chitin synthesized in the presence of alpha-pheromone or deposited in the cell wall of cdc mutants at nonpermissive temperature, and for chitosan in spore walls. Genetic evidence indicated that a mutant lacking all three chitin synthases was inviable; this was confirmed by constructing a triple mutant rescued by a plasmid carrying a CHS2 gene under control of a GAL1 promoter. Transfer of the mutant from galactose to glucose resulted in cell division arrest followed by cell death. We conclude that some chitin synthesis is essential for viability of yeast cells. C1 NIDDKD,BIOCHEM & METAB LAB,BLDG 10,ROOM 9N-115,BETHESDA,MD 20892. CSIC,FAC BIOL,INST MICROBIOL BIOQUIM,SALAMANCA,SPAIN. NHLBI,CELL BIOL LAB,BETHESDA,MD 20892. UNIV SALAMANCA,SALAMANCA,SPAIN. OI Valdivieso, M.-Henar/0000-0002-6857-7493 NR 44 TC 283 Z9 286 U1 0 U2 7 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JUL PY 1991 VL 114 IS 1 BP 111 EP 123 DI 10.1083/jcb.114.1.111 PG 13 WC Cell Biology SC Cell Biology GA FT938 UT WOS:A1991FT93800011 PM 2050738 ER PT J AU SUZUKI, CK BONIFACINO, JS LIN, AY DAVIS, MM KLAUSNER, RD AF SUZUKI, CK BONIFACINO, JS LIN, AY DAVIS, MM KLAUSNER, RD TI REGULATING THE RETENTION OF T-CELL RECEPTOR ALPHA-CHAIN VARIANTS WITHIN THE ENDOPLASMIC-RETICULUM - CA2+-DEPENDENT ASSOCIATION WITH BIP SO JOURNAL OF CELL BIOLOGY LA English DT Article ID IMMUNOGLOBULIN HEAVY-CHAIN; LUMINAL ER PROTEINS; BINDING-PROTEIN; ANTIGEN RECEPTOR; INFLUENZA HEMAGGLUTININ; INTRACELLULAR-TRANSPORT; SECRETORY PROTEINS; LIGHT CHAIN; CALCIUM; DEGRADATION AB Immunoglobulin heavy chain binding protein (BiP, GRP 78) coprecipitates with soluble and membrane-associated variants of the T-cell antigen receptor alpha-chain (TCR-alpha) which are stably retained within the ER. Chelation of Ca2+ during solubilization of cells leads to the dissociation of BiP from the TCR-alpha-variants, which is dependent upon the availability of Mg2+ and hydrolyzable ATP; this suggests that Ca2+ levels can serve to modulate the association/ dissociation of these proteins with BiP. In vivo treatment of cells expressing either the soluble or membrane-anchored TCR-alpha-variants with the Ca2+ ionophore, A23187, or an inhibitor of an ER Ca2+- ATPase, thapsigargin, or the membrane-permeant Ca2+ chelator BAPTA-AM, results in the redistribution of these proteins out of the ER and their subsequent secretion or cell surface expression. Under the same assay conditions, no movement of BiP out of the ER is observed. Taken together, these observations indicate that decreased Ca2+ levels result in the dissociation of a protein bound to BiP, leading to its release from ER retention. These data suggest that the intracellular fate of newly synthesized proteins stably associated with BiP can be regulated by Ca2+ levels in the ER. C1 STANFORD UNIV,MED CTR,SCH MED,DEPT MICROBIOL & IMMUNOL,STANFORD,CA 94305. STANFORD UNIV,MED CTR,SCH MED,HOWARD HUGHES MED INST,STANFORD,CA 94305. RP SUZUKI, CK (reprint author), NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892, USA. NR 65 TC 165 Z9 166 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JUL PY 1991 VL 114 IS 2 BP 189 EP 205 DI 10.1083/jcb.114.2.189 PG 17 WC Cell Biology SC Cell Biology GA FW739 UT WOS:A1991FW73900001 PM 1649196 ER PT J AU DAAR, I PAULES, RS VANDEWOUDE, GF AF DAAR, I PAULES, RS VANDEWOUDE, GF TI A CHARACTERIZATION OF CYTOSTATIC FACTOR ACTIVITY FROM XENOPUS EGGS AND C-MOS-TRANSFORMED CELLS SO JOURNAL OF CELL BIOLOGY LA English DT Article ID MATURATION-PROMOTING FACTOR; PROTEIN-KINASE ACTIVITY; MEIOTIC MATURATION; OOCYTE MATURATION; CYTOPLASMIC FACTOR; ONCOGENE PRODUCT; SARCOMA-VIRUS; CDC2 PROTEIN; V-MOS; CYCLE AB In Xenopus oocytes, the mos protooncogene product is required during meiosis I for the activation of maturation promoting factor (MPF) and the subsequent breakdown of the germinal vesicle (GVBD). In addition, the mos product has been shown to be a candidate 'initiator" of meiotic maturation and is an active component of cytostatic factor (CSF), an activity responsible for metaphase II arrest. Here we demonstrate that pp39mos is required throughout oocyte maturation. We found that in progesterone stimulated oocytes, depletion of mos RNA immediately before GVBD terminally decreased MPF. Likewise, oocytes depleted of mos RNA and induced to mature with crude MPF proceeded through GVBD, but lacked the MPF activity required to arrest mature oocytes at metaphase II. Thus, during maturation the mos product is required, directly or indirectly, to sustain MPF activity. On the other hand, mouse NIH/3T3 cells transformed by the constitutive expression of pp39mosxe possessed CSF activity but lacked constitutive levels of MPF or its associated histone H-1 kinase activity. Moreover, cytosols prepared from transformed NIH/ 3T3 cells or Xenopus eggs had similar levels of CSF activity, but pp39mos levels were > 40-fold higher in the transformed cell extract. These analyses show that maintenance of CSF during interphase does not result in the maintenance of MPF. RP DAAR, I (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702, USA. OI Daar, Ira/0000-0003-2657-526X FU NCI NIH HHS [N01-CO-74101] NR 40 TC 70 Z9 70 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JUL PY 1991 VL 114 IS 2 BP 329 EP 335 DI 10.1083/jcb.114.2.329 PG 7 WC Cell Biology SC Cell Biology GA FW739 UT WOS:A1991FW73900014 PM 1830055 ER PT J AU LEE, E YUSPA, SH AF LEE, E YUSPA, SH TI ALUMINUM FLUORIDE STIMULATES INOSITOL PHOSPHATE-METABOLISM AND INHIBITS EXPRESSION OF DIFFERENTIATION MARKERS IN MOUSE KERATINOCYTES SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID CULTURED HUMAN KERATINOCYTES; POLYPHOSPHOINOSITIDE PHOSPHOLIPASE-C; BOVINE PARATHYROID CELLS; PROTEIN KINASE-C; EPIDERMAL-CELLS; TERMINAL DIFFERENTIATION; QUANTITATIVE MEASUREMENT; SIGNAL TRANSDUCTION; CALCIUM REGULATION; ACTIVATION AB Mouse keratinocytes are induced to differentiate in vitro by elevating the level of extracellular calcium from 0.05 mM, where keratinocytes express a basal cell phenotype, to > 0.10 mM, where they express the differentiated phenotype. This process has been associated with a rapid, sustained increase in inositol phosphate (InsP) turnover, which precedes the expression of differentiation-specific proteins. In 0.05 mM Ca2+ medium, aluminum and fluoride salts (AlF4-), which combine to activate nonspecifically heterotrimeric guanine nucleotide-binding (G) proteins, cause a concentration-dependent increase in InsP metabolism in keratinocytes and generate elevated intracellular diacylglycerol levels. This is associated with an inhibition of cell growth. Treatment with both AlF4- and Ca2+ > 0.10 mM resulted in an additive increase in InsP turnover, implying the presence of at least two responsive InsP pools. AlF4- inhibited the expression of differentiation markers induced by Ca2+ > 0.10 mM and altered the morphology of keratinocytes from squamous to dendritic, which was reversible upon withdrawal of AlF4-. Neoplastic keratinocytes, in which basal levels of InsP metabolism are higher than in normal cells, do not differentiate in response to Ca2+. Neoplastic keratinocytes responded to AlF4- treatment with an even greater rise in InsP metabolism. AlF4- also inhibited cell growth and reversibly altered morphology in neoplastic keratinocytes. These data suggest that InsP metabolism in keratinocytes is at least partially regulated by a G protein mechanism. Furthermore, an increase in InsP metabolism is not sufficient to stimulate differentiation and may be inhibitory to differentiation if exceeding limited increases. However, these observations cannot exclude the possibility that other AlF4--stimulated pathways involving G or non-G proteins can also influence keratinocyte biology. C1 NCI, CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB, BETHESDA, MD 20892 USA. NR 44 TC 20 Z9 20 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9541 EI 1097-4652 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD JUL PY 1991 VL 148 IS 1 BP 106 EP 115 DI 10.1002/jcp.1041480113 PG 10 WC Cell Biology; Physiology SC Cell Biology; Physiology GA GA081 UT WOS:A1991GA08100012 PM 1860890 ER PT J AU KAWAI, R CARSON, RE DUNN, B NEWMAN, AH RICE, KC BLASBERG, RG AF KAWAI, R CARSON, RE DUNN, B NEWMAN, AH RICE, KC BLASBERG, RG TI REGIONAL BRAIN MEASUREMENT OF BMAX AND KD WITH THE OPIATE ANTAGONIST CYCLOFOXY - EQUILIBRIUM STUDIES IN THE CONSCIOUS RAT SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE CYCLOFOXY; OPIATE ANTAGONIST; ENANTIOMERS; OPIATE RECEPTOR; PET; NONSPECIFIC BINDING; KD; BMAX; BRAIN ID POSITRON EMISSION TOMOGRAPHY; LIVING HUMAN-BRAIN; ALPHA-AMINOISOBUTYRIC-ACID; C-11 CARFENTANIL BINDING; KINETIC-ANALYSIS; INACTIVE ENANTIOMERS; CELLULAR MEMBRANES; RECEPTOR-BINDING; INVIVO; TRANSPORT AB Brain distribution of the opiate receptor antagonist, cyclofoxy (CF), was evaluated at equilibrium in rats. A combination of i.v. injection and constant i.v. infusion was used to administer CF over a wide dose range (2.4-450 nmol/rat). Kinetic simulations and experimental results showed that this administration schedule accomplishes "true" tissue-blood equilibrium of CF within 60 min. To estimate the receptor-ligand binding parameters, we assumed that the CF concentration at the receptor site is identical to that in plasma water at equilibrium, and can be calculated from measured blood data after corrections for radiolabeled metabolites and plasma protein binding. This assumption was supported by CSF and plasma water measurements at equilibrium. Regional K(D), B(max), and a nonspecific tissue binding equilibrium constant (K(eq)) were estimated by fitting the tissue and plasma water concentrations to a single receptor model; the estimated values were 1.4-2.9 nM, 15-74 pmol/g of tissue, and 5.2-8.0, respectively. They are in good agreement with previous in vitro measurements (Rothman and McLean, 1988) as well as in vivo estimates from i.v. injection experiments (Sawada et al., 1990c). The conventional method to estimate the receptor-ligand binding parameters using data from cerebellum to approximate nonspecific tissue binding was found to be unacceptable. Although cerebellum is a brain region with no opiate receptors in rats, small differences in nonspecific tissue binding in different brain regions resulted in significant overestimations of K(D) and B(max) with this method. Receptor-active and -inactive enantiomers [[18F](-)-CF and [H-3](+)-CF)] were simultaneously administered to the same animal and the receptor-bound CF concentration could be accurately measured; this method was used to estimate B(max) from a single study in a single animal and has potential for direct application in human studies using positron emission tomography. C1 MEM SLOAN KETTERING CANC CTR,DEPT NEUROL,ROOM C 799,1275 YORK AVE,NEW YORK,NY 10021. NIDDK,CTR CLIN,NUCL MED PET PROGRAM,BETHESDA,MD. NIDDK,MED CHEM LAB,BETHESDA,MD. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 40 TC 47 Z9 47 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUL PY 1991 VL 11 IS 4 BP 529 EP 544 PG 16 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA FT182 UT WOS:A1991FT18200001 PM 1646826 ER PT J AU HIBBS, ED HAMBURGER, SD LENANE, M RAPOPORT, JL KRUESI, MJP KEYSOR, CS GOLDSTEIN, MJ AF HIBBS, ED HAMBURGER, SD LENANE, M RAPOPORT, JL KRUESI, MJP KEYSOR, CS GOLDSTEIN, MJ TI DETERMINANTS OF EXPRESSED EMOTION IN FAMILIES OF DISTURBED AND NORMAL-CHILDREN SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES LA English DT Article DE DISRUPTIVE BEHAVIOR DISORDERS; OBSESSIVE COMPULSIVE DISORDER; PSYCHOPATHOLOGY; EXPRESSED EMOTION ID OBSESSIVE-COMPULSIVE DISORDER; BIOLOGICAL REFERENCE VALUES; PSYCHIATRIC-DISORDERS; AFFECTIVE STYLE; SCHIZOPHRENIA; RELAPSE; ADOLESCENTS; RELATIVES; AGREEMENT C1 UNIV CALIF LOS ANGELES,DEPT PSYCHOL,LOS ANGELES,CA 90024. RP HIBBS, ED (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,ROOM 6N240,BETHESDA,MD 20892, USA. NR 50 TC 144 Z9 146 U1 2 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0021-9630 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry Allied Discip. PD JUL PY 1991 VL 32 IS 5 BP 757 EP 770 DI 10.1111/j.1469-7610.1991.tb01900.x PG 14 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA GA946 UT WOS:A1991GA94600003 PM 1918226 ER PT J AU BATES, SE SHIEH, CY MICKLEY, LA DICHEK, HL GAZDAR, A LORIAUX, DL FOJO, AT AF BATES, SE SHIEH, CY MICKLEY, LA DICHEK, HL GAZDAR, A LORIAUX, DL FOJO, AT TI MITOTANE ENHANCES CYTOTOXICITY OF CHEMOTHERAPY IN CELL-LINES EXPRESSING A MULTIDRUG RESISTANCE GENE (MDR-1/P-GLYCOPROTEIN) WHICH IS ALSO EXPRESSED BY ADRENOCORTICAL CARCINOMAS SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ADRENAL-CORTICAL CARCINOMA; BACTERIAL TRANSPORT PROTEINS; HUMAN-LEUKEMIC LYMPHOBLASTS; CALCIUM-CHANNEL BLOCKERS; P-GLYCOPROTEIN GENE; HUMAN CANCER-CELLS; MEMBRANE-VESICLES; DRUG-RESISTANCE; ADRIAMYCIN; MECHANISM AB P-Glycoprotein (Pgp), product of the mdr-1 gene, is a 130- to 180-kDa plasma membrane phosphoglycoprotein which mediates multidrug resistance in cell culture by increasing efflux of the natural product chemotherapeutic agents. High levels of expression of mdr-1/Pgp are found in both the normal adrenal and adrenocortical cancers. By RNA in situ hybridization the expression in adrenocortical cancer is shown to be widely distributed. The present study demonstrates that decreased drug accumulation mediated by mdr-1/Pgp can be overcome by clinically achieveable concentrations of mitotane (o,p'-DDD). The increase in drug accumulation with the addition of mitotane is due at least in part to a decrease in drug efflux and results in an increase in cytotoxicity when agents of the natural product class are used. This effect is observed in cells with a broad range of mdr-1/Pgp expression, including levels comparable to those found in most adrenocortical cancers. Similar increases in drug accumulation can be demonstrated in an unselected adrenocortical cancer cell line that expresses mdr-1/Pgp. The finding that multidrug resistance mediated by mdr-1/Pgp can be reversed by mitotane provides a rational basis for exploring the use of mitotane in combination with natural product chemotherapeutic agents in adrenocortical cancer. C1 NCI, USN, MED ONCOL BRANCH, BETHESDA, MD 20892 USA. NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. RP BATES, SE (reprint author), NCI, MED BRANCH, BLDG 10, ROOM 12N226, BETHESDA, MD 20892 USA. NR 48 TC 61 Z9 64 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 1991 VL 73 IS 1 BP 18 EP 29 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA FR758 UT WOS:A1991FR75800004 PM 1675220 ER PT J AU SWINBURN, BA BOYCE, VL BERGMAN, RN HOWARD, BV BOGARDUS, C AF SWINBURN, BA BOYCE, VL BERGMAN, RN HOWARD, BV BOGARDUS, C TI DETERIORATION IN CARBOHYDRATE-METABOLISM AND LIPOPROTEIN CHANGES INDUCED BY MODERN, HIGH-FAT DIET IN PIMA-INDIANS AND CAUCASIANS SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CELL SECRETORY CAPACITY; INSULIN SENSITIVITY; DENSITY LIPOPROTEIN; DIABETES-MELLITUS; GLUCOSE-TOLERANCE; PLASMA-GLUCOSE; APOLIPOPROTEIN; CHOLESTEROL; RESISTANCE; RESPONSES AB The transition from a high carbohydrate to a high fat diet may explain in part the dramatic increase in the prevalence of noninsulin-dependent diabetes mellitus among Pima Indians over the last century. In this study, 12 Pimas and 12 caucasians, all nondiabetic, were admitted to a metabolic ward and, in random order, fed 2 14-day weight-maintaining diets: a traditional Pima diet (percentage of calories: carbohydrate, 70%; fat, 15%; protein, 15%) and a high fat modern diet (carbohydrate, 30%; fat, 50%; protein, 20%). Carbohydrate metabolism was characterized using the modified iv glucose tolerance test (minimal model), the acute insulin responses to arginine during a 3-step glycemic clamp, and the oral glucose tolerance test. Compared with the traditional diet, the modern diet was associated with a decrease in oral glucose tolerance (P < 0.01) and higher plasma cholesterol concentrations (P < 0.02). The decline in glucose tolerance was associated with similar insulin-mediated, but 23% lower glucose-mediated (P < 0.001), glucose disposal, a 17% lower acute insulin response to glucose (P < 0.03), a 9% lower beta-cell sensitivity to glucose (P < 0.02), and similar beta-cell capacities. Pimas and caucasians responded similarly, except for larger changes in plasma lipids among the Pimas. Since glucose-mediated glucose disposal, beta-cell function, and glucose tolerance deteriorated on the modern diet, it is likely that diet composition affects the prevalence of noninsulin-dependent diabetes mellitus in both Pimas and caucasians. C1 NIDDKD, CLIN DIABET & NUTR SECT, 4212 N 16TH ST, ROOM 541, PHOENIX, AZ 85016 USA. NR 39 TC 127 Z9 129 U1 1 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 1991 VL 73 IS 1 BP 156 EP 165 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA FR758 UT WOS:A1991FR75800025 PM 2045466 ER PT J AU MOVSESIAN, MA SMITH, CJ KRALL, J BRISTOW, MR MANGANIELLO, VC AF MOVSESIAN, MA SMITH, CJ KRALL, J BRISTOW, MR MANGANIELLO, VC TI SARCOPLASMIC RETICULUM-ASSOCIATED CYCLIC ADENOSINE 5'-MONOPHOSPHATE PHOSPHODIESTERASE ACTIVITY IN NORMAL AND FAILING HUMAN HEARTS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE PHOSPHODIESTERASE INHIBITORS; CYCLIC GUANOSINE 5'-MONOPHOSPHATE; CILOSTAMIDE; ROLIPRAM; CA2+ TRANSPORT ID HUMAN VENTRICULAR MYOCARDIUM; NUCLEOTIDE PHOSPHODIESTERASE; CAMP PHOSPHODIESTERASE; AMP PHOSPHODIESTERASE; CARDIOTONIC ACTIVITY; DOWN-REGULATION; CARDIAC-MUSCLE; CA-2+ UPTAKE; MECHANISM; MILRINONE AB Sarcoplasmic reticulum-associated cAMP phosphodiesterase activity was examined in microsomes prepared from the left ventricular myocardium of eight heart transplant recipients with end-stage idiopathic dilated cardiomyopathy and six unmatched organ donors with normal cardiac function. At cAMP concentrations less-than-or-equal-to 1.0-mu-M, sarcoplasmic reticulum-associated cAMP phosphodiesterase activity was functionally homogeneous. cAMP phosphodiesterase activity was inhibited competitively by cGMP (K(i) = 0.031 +/- 0.008-mu-M) and the cilostamide derivative OPC 3911 (K(i) = 0.018 +/- 0.004-mu-M), but was essentially insensitive to rolipram. V(max) and K(m) were 781.7 +/- 109.2 nmol/mg per min and 0.188 +/- 0.031-mu-M, respectively, in microsomes prepared from nonfailing hearts and 793.9 +/- 68.9 nmol/mg per min and 0.150 +/- 0.027-mu-M in microsomes prepared from failing hearts. Microsomes prepared from nonfailing and failing hearts did not differ with respect to either the ratio of cAMP phosphodiesterase activity to ATP-dependent Ca2+ accumulation activity or the sensitivity of cAMP phosphodiesterase activity to inhibition by OPC 3911. These data suggest that the diminished inotropic efficacy of phosphodiesterase inhibitors in failing human hearts does not result from changes in the level, kinetic properties, or pharmacologic sensitivity of sarcoplasmic reticulum-associated cAMP phosphodiesterase activity. C1 NHLBI, CELLULAR METAB LAB, BETHESDA, MD 20892 USA. RP UNIV UTAH, MED CTR,HLTH SCI CTR,DIV CARDIOL,ROOM 4A-100, SO N MED DR, SALT LAKE CITY, UT 84132 USA. NR 30 TC 72 Z9 72 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 1991 VL 88 IS 1 BP 15 EP 19 DI 10.1172/JCI115272 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA FU443 UT WOS:A1991FU44300003 PM 1647414 ER PT J AU ALEXANDER, HR SHEPPARD, BC JENSEN, JC LANGSTEIN, HN BURESH, CM VENZON, D WALKER, EC FRAKER, DL STOVROFF, MC NORTON, JA AF ALEXANDER, HR SHEPPARD, BC JENSEN, JC LANGSTEIN, HN BURESH, CM VENZON, D WALKER, EC FRAKER, DL STOVROFF, MC NORTON, JA TI TREATMENT WITH RECOMBINANT HUMAN TUMOR-NECROSIS-FACTOR-ALPHA PROTECTS RATS AGAINST THE LETHALITY, HYPOTENSION, AND HYPOTHERMIA OF GRAM-NEGATIVE SEPSIS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE CACHECTIN; CYTOKINE; TOLERANCE ID MANGANOUS SUPEROXIDE-DISMUTASE; SEPTIC SHOCK; CACHECTIN; ENDOTOXIN; INDUCTION; INTERLEUKIN-1; TOXICITY; ENHANCEMENT; TOLERANCE; MODELS AB Tumor necrosis factor (TNF) is a peptide secreted by macrophages in response to endotoxin that can produce many of the changes seen in septic shock. After cecal ligation and puncture (CLP) rats gradually develop tachycardia, hypotension, tachypnea, and hypothermia. At 5 h post-CLP, rats have a peak in serum levels of endotoxin and 60% of rats have blood cultures that grow Gram-negative rods (Escherichia coli and Klebsiella pneumonia). At 20 h post-CLP all rats develop positive blood cultures. Serum levels of TNF are not reproducibly measurable in rats following CLP. Rats undergoing CLP have a 50-80% mortality with deaths usually occurring 24-72 h postinjury. Repetitive (twice daily x 6 d) i.p. injection of sublethal doses of recombinant human TNF-alpha (100-mu-g/kg) to rats undergoing CLP 1 d after the treatment period resulted in a significant reduction in mortality compared to control rats previously unexposed to rTNF (P < 0.03). Animals treated with rTNF had no hypotension or hypothermia after CLP and regained normal food intake faster than control rats. 12 h after CLP the gene expression for manganous superoxide dismutase (MnSOD), an inducible mitochondrial metalloenzyme responsible for cellular resistance to injury from toxic reactive oxygen species, was higher in livers of rats treated with rTNF suggesting that the TNF treatment augmented expression of this protective enzyme. Unlike MnSOD, expression of the gene for copper-zinc SOD was not affected by CLP or rTNF treatment. The results suggest that prior treatment with recombinant TNF can ameliorate the lethality, hypotension, hypothermia, and anorexia of Gram-negative sepsis in rats and that the mechanism may be related to enhanced hepatic expression of the gene for MnSOD. Repeated administration of recombinant TNF may be a strategy to minimize mortality and morbidity of Gram-negative sepsis. C1 NCI,SURG BRANCH,SURG METAB SECT,BLDG 10,ROOM 2B07,BETHESDA,MD 20892. NCI,CLIN ONCOL PROGRAM,BIOSTAT & DATA MANAGEMENT BRANCH,BETHESDA,MD 20892. NIH,BIOMED ENGN & INSTRUMENTAT BRANCH,BETHESDA,MD 20892. NIH,DIV RES RESOURCES,BETHESDA,MD 20892. RI Venzon, David/B-3078-2008 NR 37 TC 150 Z9 151 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 1991 VL 88 IS 1 BP 34 EP 39 DI 10.1172/JCI115298 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA FU443 UT WOS:A1991FU44300006 PM 2056127 ER PT J AU SWINBURN, BA NYOMBA, BL SAAD, MF ZURLO, F RAZ, I KNOWLER, WC LILLIOJA, S BOGARDUS, C RAVUSSIN, E AF SWINBURN, BA NYOMBA, BL SAAD, MF ZURLO, F RAZ, I KNOWLER, WC LILLIOJA, S BOGARDUS, C RAVUSSIN, E TI INSULIN RESISTANCE ASSOCIATED WITH LOWER RATES OF WEIGHT-GAIN IN PIMA-INDIANS SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE OBESITY; INSULIN RESISTANCE; GLUCOSE OXIDATION; WEIGHT GAIN; NONINSULIN-DEPENDENT DIABETES-MELLITUS ID BODY-WEIGHT; FOOD-INTAKE; ENERGY-EXPENDITURE; FAT BALANCES; OBESITY; GLUCOSE; PATHOGENESIS; CARBOHYDRATE; OXIDATION; INVIVO AB Insulin resistance is commonly associated with obesity and noninsulin-dependent diabetes. Whereas it predicts the development of diabetes, its effect on body weight change is unknown. We measured glucose disposal rates at submaximally- and maximally-stimulating insulin concentrations in 192 nondiabetic Pima Indians and followed their weight change over 3.5 +/- 1.8 y (mean +/- SD). Results: (a) Insulin-resistant subjects gained less weight than insulin-sensitive subjects (3.1 vs. 7.6 kg, P < 0.0001). (b) The percent weight change per year correlated with glucose disposal at submaximally- (r = 0.19, P < 0.01) and maximally-stimulating (r = 0.34, P < 0.0001) insulin concentrations independent of sex, age, initial weight, and 24-h energy expenditure; the correlations were stronger for glucose oxidation than for glucose storage. (c) Weight gain was associated with an increase in insulin resistance more than four times that predicted from the cross-sectional data. We conclude that insulin resistance is associated with a reduced risk of weight gain in nondiabetic Pima Indians. C1 NIDDKD,PHOENIX EPIDEMIOL & CLIN RES BRANCH,CLIN DIABET & NUTR SECT,4212 N 16TH ST,PHOENIX,AZ 85016. NIDDKD,PHOENIX EPIDEMIOL & CLIN RES BRANCH,ARTHRITIS & EPIDEMIOL SECT,PHOENIX,AZ 85016. RI Lillioja, Stephen/A-8185-2012; OI Lillioja, Stephen/0000-0001-5333-5240 NR 32 TC 294 Z9 295 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 1991 VL 88 IS 1 BP 168 EP 173 DI 10.1172/JCI115274 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA FU443 UT WOS:A1991FU44300024 PM 2056116 ER PT J AU FREEDMAN, DO LUJANTRANGAY, A STEEL, C GONZALEZPERALTA, C NUTMAN, TB AF FREEDMAN, DO LUJANTRANGAY, A STEEL, C GONZALEZPERALTA, C NUTMAN, TB TI IMMUNOREGULATION IN ONCHOCERCIASIS - FUNCTIONAL AND PHENOTYPIC ABNORMALITIES OF LYMPHOCYTE SUBSETS AND CHANGES WITH THERAPY SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE CD45RA; FLOW CYTOMETRY; INTERLEUKINS; IVERMECTIN ID T-CELL SUBSET; IMMUNE-RESPONSES; RHEUMATOID-ARTHRITIS; VOLVULUS INFECTION; PARASITE ANTIGEN; PERIPHERAL-BLOOD; INDUCER; INTERLEUKIN-4; HYPERSENSITIVITY; IMMUNIZATION AB To help define the immunoregulatory defects in patients with onchocerciasis, flow cytometric analysis of circulating lymphocyte subpopulations was performed in parallel with functional assays. No significant differences in CD4/CD8 ratios were seen when microfilariae-positive individuals from Guatemala were compared with Guatemalan controls. However, the infected individuals had significantly increased numbers of circulating CD4+CD45RA+ lymphocytes (mean 38.3%) when compared with controls (mean 16.0%). Coexpression of the activation marker HLA-DR was significantly increased on CD4+ cells from infected individuals. In contrast, no up-regulation of HLA-DR was seen on CD8+ or CD19+ cells. At 1 year after initiation of treatment with semiannual doses of the microfilaricide ivermectin, there were significant increases (P < 0.05) in the percentage of CD4+CD45RA- cells, the percentage of CD4+HLA-DR+ cells, and mitogen-induced lymphokine production (IL-2, IL-4). Despite these changes, parasite-specific IL-2 and IL-4 production which had been undetectable before treatment did not manifest itself even by the 2-yr follow-up. Defects in the T-cell activation pathway in Onchocerca volvulus-infected individuals may thus exist at several independent points; a state of parasite antigen-specific tolerance appears to remain even after the relative reversal of other generalized immunoregulatory defects. C1 NIAID,PARASIT DIS LAB,CLIN PARASITOL SECT,BETHESDA,MD 20892. MINIST PUBL HLTH,DEPT ONCHOCERCIASIS,SOC NACL ENDIACIAN MALARIA,GUATEMALA CITY,GUATEMALA. UNIV ARIZONA,DEPT ENTOMOL,TUCSON,AZ 85721. NR 37 TC 28 Z9 28 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 1991 VL 88 IS 1 BP 231 EP 238 DI 10.1172/JCI115282 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA FU443 UT WOS:A1991FU44300031 PM 1829096 ER PT J AU JAFFE, HA BUHL, R MASTRANGELI, A HOLROYD, KJ SALTINI, C CZERSKI, D JAFFE, HS KRAMER, S SHERWIN, S CRYSTAL, RG AF JAFFE, HA BUHL, R MASTRANGELI, A HOLROYD, KJ SALTINI, C CZERSKI, D JAFFE, HS KRAMER, S SHERWIN, S CRYSTAL, RG TI ORGAN SPECIFIC CYTOKINE THERAPY - LOCAL ACTIVATION OF MONONUCLEAR PHAGOCYTES BY DELIVERY OF AN AEROSOL OF RECOMBINANT INTERFERON-GAMMA TO THE HUMAN LUNG SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE BRONCHOALVEOLAR LAVAGE; MACROPHAGE; IMMUNE DEFENSE; IP-10; GENE ID CHRONIC GRANULOMATOUS-DISEASE; INDUCED PROTEIN IP-10; ALVEOLAR MACROPHAGES; IFN-GAMMA; BIOCHEMICAL-CHARACTERIZATION; BRONCHOALVEOLAR LAVAGE; HYDROGEN-PEROXIDE; BLOOD MONOCYTES; CANCER-PATIENTS; MESSENGER-RNA AB In the context of the central role of the alveolar macrophage in host defense of the respiratory epithelial surface, and the ability of IFN-gamma to activate mononuclear phagocytes, we have evaluated strategies to use rIFN-gamma to activate human alveolar macrophages in vivo. To accomplish this, rIFN-gamma was administered to nonsmoking normals, the amounts of IFN-gamma quantified in serum and respiratory epithelial lining fluid (ELF) and the status of IFN-gamma related activation of blood monocytes and alveolar macrophages was evaluated by quantifying the expression of mRNA transcripts of IP-10, a gene induced specifically by IFN-gamma. Systemic administration (subcutaneous) of maximally tolerated amounts of rIFN-gamma (250-mu-g) was followed by detectable levels of IFN-gamma in serum but not ELF, the expression of IP-10 transcripts in blood monocytes but not alveolar macrophages, and multiple systemic adverse effects. To circumvent the inability of systemic administration to reach respiratory ELF and activate alveolar macrophages, rIFN-gamma (250-1,000-mu-g) was inhaled as an aerosol once daily for 3 d. Strikingly, while IFN-gamma was not detected in serum it was detectable in respiratory ELF in a dose-dependent fashion. Further, alveolar macrophages, but not blood monocytes, expressed IP-10 mRNA transcripts and, importantly, inhalation of aerosolized rIFN-gamma was not associated with local or systemic adverse effects. Thus, it is feasible to use rIFN-gamma to activate alveolar macrophages by targeting the cytokine directly to the lung. These data suggest a potential strategy for targeted cytokine therapy, without systemic side effects, to augment respiratory tract defenses in individuals at risk for or with lung infection. C1 NHLBI,PULM BRANCH,BLDG 10,ROOM 6D03,BETHESDA,MD 20892. GENENTECH INC,SAN FRANCISCO,CA 94080. NR 54 TC 111 Z9 111 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 1991 VL 88 IS 1 BP 297 EP 302 DI 10.1172/JCI115291 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA FU443 UT WOS:A1991FU44300039 PM 1905329 ER PT J AU TARKKA, IM HALLETT, M AF TARKKA, IM HALLETT, M TI TOPOGRAPHY OF SCALP-RECORDED MOTOR POTENTIALS IN HUMAN FINGER MOVEMENTS SO JOURNAL OF CLINICAL NEUROPHYSIOLOGY LA English DT Article DE MOVEMENT-RELATED CORTICAL POTENTIALS; MOTOR CORTEX; EEG; BEREITSCHAFTSPOTENTIAL; SUPPLEMENTARY MOTOR AREA; VOLUNTARY MOVEMENT; EVOKED POTENTIALS ID SOMATOSENSORY EVOKED-POTENTIALS; CONTRASTING NEURONAL-ACTIVITY; CEREBRAL BLOOD-FLOW; CORTICAL POTENTIALS; VOLUNTARY MOVEMENT; SUPPLEMENTARY; AREA; CORTEX; STIMULATION; COMPONENTS AB Four distinct negative events were identified in the averaged, scalp-recorded EEGs of normal subjects before and after the onset of self-paced, voluntary finger movements; reaction-time movements and passive movements were also studied. These events are the peak of the negative slope (NS'), the initial slope of motor potential (isMP), the parietal peak of motor potential (ppMP), and the frontal peak of motor potential (fpMP). For self-paced movements, NS' and isMP occurred before the onset of electromyographic (EMG) activity, and ppMP and fpMP occurred after the onset of EMG activity. NS' had a wide distribution, covering the parietal region with slight contralateral predominance. The isMP mapped focally over the contralateral hand motor area on the scalp. The location of ppMP was similar to that of isMP. The fpMP was localized anterior and medial to motor cortex with a contralateral preponderance and possible location over the supplementary motor area. The isMP and fpMP also were identified in the recordings of reaction-time movements, but only the fpMP persisted in the recordings of passive movements. The isMP appears to reflect activation of the cortical cells in the hand area of motor cortex for the execution of voluntary movement, and the fpMP appears to reflect proprioceptive feed-back from the periphery. C1 NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,BLDG 10,ROOM 5N226,BETHESDA,MD 20892. NR 36 TC 62 Z9 62 U1 2 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0736-0258 J9 J CLIN NEUROPHYSIOL JI J. Clin. Neurophysiol. PD JUL PY 1991 VL 8 IS 3 BP 331 EP 341 DI 10.1097/00004691-199107010-00009 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA GB559 UT WOS:A1991GB55900009 PM 1918338 ER PT J AU BROADHEAD, WE LARSON, DB YARNALL, KSH BLAZER, DG TSE, CKJ AF BROADHEAD, WE LARSON, DB YARNALL, KSH BLAZER, DG TSE, CKJ TI TRICYCLIC ANTIDEPRESSANT PRESCRIBING FOR NONPSYCHIATRIC DISORDERS - AN ANALYSIS BASED ON DATA FROM THE 1985 NATIONAL AMBULATORY MEDICAL-CARE SURVEY SO JOURNAL OF FAMILY PRACTICE LA English DT Article DE PRIMARY HEALTH CARE; ANTIDEPRESSIVE AGENTS, TRICYCLIC; COMPARATIVE STUDY; FAMILY PRACTICE; INTERNAL MEDICINE ID LOW-BACK-PAIN; RHEUMATOID-ARTHRITIS; PARKINSONS-DISEASE; AMITRIPTYLINE; PLACEBO; DEPRESSION; IMIPRAMINE; DOXEPIN; DESIPRAMINE; MECHANISMS AB Background. Primary care physicians often do not document a psychiatric diagnosis when prescribing psychotropic medications. Recent literature suggests the potential benefit of tricyclic antidepressants (TCAs) in a number of nonpsychiatric conditions (low back pain, peptic disease, fibrositis, headache, peripheral neuropathy, rheumatoid disease, and irritable colon). Methods. Data from the 1985 National Ambulatory Medical Care Survey (NAMCS) were used to categorize the primary diagnoses given during office visits in which tricyclic antidepressants were prescribed. Comparisons were made across specialties. Results. Primary care physicians prescribed tricyclic antidepressants in 1% of all visits (an estimated 2,892,000 visits per year). Whereas 50% of these visits at which TCAs were prescribed were for documented psychiatric illnesses or conditions, 15% were for nonpsychiatric TCA-responsive conditions. The majority of visits by patients with these disorders were to primary care physicians. The pattern of TCA prescribing for these disorders by primary care physicians parallels that of other medical specialties except that primary care physicians prescribed TCAs for nonpsychiatric TCA-responsive disorders less frequently than did other medical specialists. Conclusions. When nonpsychiatric TCA-responsive disorders are included, primary care physicians document with appropriate diagnoses 15% more of their TCA prescriptions than previous studies have indicated. An understanding of the 35% of TCA prescriptions that do not show proper documentation will require further study and information not available from the NAMCS. C1 DUKE UNIV,MED CTR,DEPT PSYCHIAT,DURHAM,NC 27710. NIMH,DIV APPL & SERV RES,PRIMARY CARE RES PROGRAM,ROCKVILLE,MD 20857. RP BROADHEAD, WE (reprint author), DUKE UNIV,MED CTR,DEPT COMMUNITY & FAMILY MED,BOX 2914,DURHAM,NC 27710, USA. NR 54 TC 28 Z9 28 U1 1 U2 1 PU APPLETON & LANGE PI E NORWALK PA 25 VAN ZANT ST, E NORWALK, CT 06855 SN 0094-3509 J9 J FAM PRACTICE JI J. Fam. Pract. PD JUL PY 1991 VL 33 IS 1 BP 24 EP 32 PG 9 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA FW757 UT WOS:A1991FW75700006 PM 2056287 ER PT J AU TSAREV, SA EMERSON, SU BALAYAN, MS TICEHURST, J PURCELL, RH AF TSAREV, SA EMERSON, SU BALAYAN, MS TICEHURST, J PURCELL, RH TI SIMIAN HEPATITIS-A VIRUS (HAV) STRAIN AGM-27 - COMPARISON OF GENOME STRUCTURE AND GROWTH IN CELL-CULTURE WITH OTHER HAV STRAINS SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID COMPLETE NUCLEOTIDE-SEQUENCE; POLYMERASE CHAIN-REACTION; MOLECULAR-CLONING; WILD-TYPE; EXPERIMENTAL-INFECTION; GENE ORGANIZATION; ACID-SEQUENCES; DNA-POLYMERASE; RNA; IDENTIFICATION AB Fragments of cDNA representing greater than 99% of the entire genome of wild-type hepatitis A virus (HAV) strain AGM-27, isolated from an African green monkey, were obtained by the polymerase chain reaction and sequenced. Comparison with other HAV isolates revealed differences in the predicted amino acid sequence in functionally critical parts of the genome. Comparison of the biological properties of AGM-27 with those of human wild-type and cell culture-adapted HM-175 strains revealed that AGM-27 grew in cell culture significantly better than did wild-type HM-175, but not as well as cell culture-adapted HM-175. AGM-27 and cell culture-adapted HM-175 were distinguishable by their differential growth in CV-1, FRhK-4 and primary AGMK cells. C1 MOSCOW POLIOMYELITIS & VIRAL ENCEPHALITIDES INST,MOSCOW,USSR. WALTER REED ARMY MED CTR,DEPT VIRUS DIS,WASHINGTON,DC 20307. SHEMYAKIN INST BIOORGAN CHEM,MOSCOW 117871,USSR. RP TSAREV, SA (reprint author), NIAID,HEPATITUS VIRUSES SECT,INFECT DIS LAB,BETHESDA,MD 20892, USA. RI Ticehurst, John/I-7532-2012 NR 36 TC 51 Z9 53 U1 0 U2 0 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 JUL PY 1991 VL 72 BP 1677 EP 1683 DI 10.1099/0022-1317-72-7-1677 PN 7 PG 7 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA FW644 UT WOS:A1991FW64400022 PM 1649901 ER PT J AU MATSUURA, S HAND, AR AF MATSUURA, S HAND, AR TI QUANTITATIVE IMMUNOCYTOCHEMISTRY OF RAT SUBMANDIBULAR SECRETORY PROTEINS DURING CHRONIC ISOPROTERENOL ADMINISTRATION AND RECOVERY SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE ISOPROTERENOL; RAT; SUBMANDIBULAR GLAND; SECRETORY PROTEINS; IMMUNOGOLD LABELING; SECRETORY GRANULES; ACINAR CELLS; INTERCALATED DUCT CELLS; MORPHOMETRIC ANALYSIS ID PROLINE-RICH PROTEIN; BETA-ADRENERGIC STIMULATION; MOUSE PAROTID-GLANDS; TREATED RATS; MESSENGER-RNAS; LIQUID DIET; LOCALIZATION; INDUCTION; RECEPTORS; CELLS AB We utilized quantitative electron microscopic immunogold labeling procedures to follow changes in the intragranular content of five secretory proteins of the rat submandibular gland (SMG) during and after chronic treatment with the beta-adrenergic agonist isoproterenol (IPR). Labeling intensities (gold particles/mu-m2) of acinar cell secretory granules for mucin and glutamine/glutamic acid-rich proteins, major secretory proteins of the normal SMG, showed opposite responses to IPR. Labeling intensities increased for mucin and decreased for glutamine/glutamic acid-rich proteins immediately after IPR injections began, then rapidly returned to control levels after cessation of IPR treatment. SMG Protein C immunoreactivity, found in both acinar and intercalated duct granules, was less affected by IPR. However, opposite changes in labeling intensity were observed between acinar and intercalated duct granules. Labeling intensities for proline-rich proteins, IPR-inducible secretory proteins, increased only after 10 days of stimulation and maintained a high level even after cessation of drug treatment. Type 2 cystatin, another IPR-inducible protein, increased gradually with chronic IPR treatment and decreased slowly during the recovery phase. These results suggest that chronic beta-adrenergic stimulation affects the expression of genes for several rat SMG secretory proteins in a different manner. C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892. NR 53 TC 17 Z9 17 U1 0 U2 0 PU HISTOCHEMICAL SOC INC PI NEW YORK PA MT SINAI MEDICAL CENTER 19 EAST 98TH ST SUTIE 9G, NEW YORK, NY 10029 SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD JUL PY 1991 VL 39 IS 7 BP 945 EP 954 PG 10 WC Cell Biology SC Cell Biology GA FT146 UT WOS:A1991FT14600008 PM 1865112 ER PT J AU HESTDAL, K RUSCETTI, FW IHLE, JN JACOBSEN, SEW DUBOIS, CM KOPP, WC LONGO, DL KELLER, JR AF HESTDAL, K RUSCETTI, FW IHLE, JN JACOBSEN, SEW DUBOIS, CM KOPP, WC LONGO, DL KELLER, JR TI CHARACTERIZATION AND REGULATION OF RB6-8C5 ANTIGEN EXPRESSION ON MURINE BONE-MARROW CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; MONOCLONAL-ANTIBODIES; MAC-1; NEUTROPHILS; MACROPHAGE; RECEPTORS; BINDING; LFA-1; MOUSE; GLYCOPROTEINS AB Murine bone marrow cells expressing the cell surface Ag RB6-8C5 were identified by fluorescence-activated cell-sorting analysis using a rat IgG mAb. The fluorescent intensity of RB6-8C5 was variable on bone marrow cells. This made it possible to separate bone marrow cells into distinct subpopulations, RB6-8C5neg, RB6-8C5lo, and RB6-8C5hi cells. Morphologic analysis of the sorted populations demonstrated that the Ag was expressed on myeloid cells. The expression of RB6-8C5 increases with granulocyte maturation, whereas expression is transient on cells in the monocytic lineage. The RB6-8C5hi sorted cells were enriched for end-stage neutrophils (75%), whereas the RB6-8C5lo sorted cells contained more immature myeloid cells and myelocytes (75%). Lymphocytes and macrophages were < 5% in any RB6-8C5+ population, whereas the erythroid precursors were RB6-8C5neg. The colony forming unit culture (CFU-C) (> 90%) were found in the RB6-8C5neg and RB6-8C5lo populations, and all the CFU-granulocyte, erythroid, megakaryocyte, and macrophage (CFU-GEMM) and burst-forming units-erythroid (BFU-E) were in the RB6-8C5neg population. Granulocyte-macrophage-CSFR (GM-CSFR) and IL-1-alpha-R were expressed on RB6-8C5hi bone marrow cells, whereas no receptors could be detected on RB6-8C5neg and RB6-8C5lo cells. The expression of the RB6-8C5 Ag can be induced on RB6-8C5neg cells in liquid culture by IL-3 and granulocyte-macrophage CSF. Thus, RB6-8C5 is a myeloid differentiation Ag whose expression can be regulated by cytokines. C1 NCI, FREDERICK CANC RES & DEV CTR, DYNCORP, PROGRAM RESOURCES INC, FREDERICK, MD 21702 USA. ST JUDE CHILDRENS RES HOSP, DEPT BIOCHIM & GENET MICROBIENNE, MEMPHIS, TN 38101 USA. RP HESTDAL, K (reprint author), NCI, FREDERICK CANC RES & DEV CTR, BIOL RESPONSE MODIFIERS PROGRAM, PRECLIN EVALUAT LAB, POB B, FREDERICK, MD 21702 USA. FU NCI NIH HHS [N01-CO-74102] NR 20 TC 400 Z9 405 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 1991 VL 147 IS 1 BP 22 EP 28 PG 7 WC Immunology SC Immunology GA FT763 UT WOS:A1991FT76300004 PM 1711076 ER PT J AU AKSENTIJEVICH, I SACHS, DH SYKES, M AF AKSENTIJEVICH, I SACHS, DH SYKES, M TI NATURAL ANTIBODIES AGAINST BONE-MARROW CELLS OF A CONCORDANT XENOGENEIC SPECIES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NONLETHAL PREPARATIVE REGIMEN; MONOCLONAL-ANTIBODIES; MOUSE; XENOGRAFTS; TRANSPLANTATION; ANTIGENS; MICE; MACROPHAGE; RECEPTORS; INVIVO AB Hyperacute rejection does not occur when vascularized organs are transplanted between rat and mouse, and this species combination is considered to be concordant. Since hyperacute rejection is believed to reflect the presence of pre-existing antibodies (usually of the IgM class), and lymphocytotoxic antibodies against rat cells have not been detected in normal mouse sera, it has previously been concluded that mouse anti-rat natural antibody (NAb) does not exist. However, studies have not been reported in which rat bone marrow cells (BMC) were used as targets for evaluation of normal mouse sera. Because previous work from our and other laboratories has shown that bone marrow chimerism in the rat into mouse species combination can be achieved only by transplanting large numbers of rat BMC, we have evaluated normal mouse sera for the presence of NAb against rat BMC that might explain these in vivo results. Fisher 344 rat BMC and spleen cells were incubated with serum from nonimmunized mice, then stained with fluoresceinated rat anti-mouse subclass-specific secondary reagents and analyzed using flow cytometry. NAb of the IgM and IgG3 classes were found that bound strongly to rat BMC but showed weak or absent binding to spleen cells. A low level of IgG2b binding was observed to both BMC and spleen cells. Cytotoxic activity was detected against rat BMC but not against spleen cells. The environment in which the animals were maintained played a significant role in determining the level of cytotoxic NAb in normal mouse sera. Our results are consistent with the possibility that bone marrow-specific NAb play a role in resisting engraftment of BMC across this species barrier. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,SURG SERV,TRANSPLANTAT RES BIOL CTR,MGH-E,BLDG 149,BOSTON,MA 02129. NCI,IMMUNOL BRANCH,BETHESDA,MD 20892. NR 33 TC 36 Z9 36 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 1991 VL 147 IS 1 BP 79 EP 85 PG 7 WC Immunology SC Immunology GA FT763 UT WOS:A1991FT76300012 PM 2051029 ER PT J AU DHAWAN, S STREICHER, HZ WAHL, LM MILLER, N LOUIE, AT GOLDFARB, IS JACKSON, WL CASALI, P NOTKINS, AL AF DHAWAN, S STREICHER, HZ WAHL, LM MILLER, N LOUIE, AT GOLDFARB, IS JACKSON, WL CASALI, P NOTKINS, AL TI MODEL FOR STUDYING VIRUS ATTACHMENT .2. BINDING OF BIOTINYLATED HUMAN T-CELL LEUKEMIA-VIRUS TYPE-I TO HUMAN BLOOD MONONUCLEAR-CELLS POTENTIAL TARGETS FOR HUMAN T-CELL LEUKEMIA-VIRUS TYPE-I INFECTION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EPSTEIN-BARR VIRUS; B-LYMPHOID CELLS; LYMPHOCYTES; RETROVIRUS; ANTIBODIES; FREQUENCY; PATIENT; DISEASE; RATS AB Purified human T cell leukemia virus type I (HTLV-1) was biotinylated and used to study its attachment to human PBMC. The use of biotinylated HTLV-I (biot-HTLV-I) in conjunction with mouse mAb specific for selected cell-surface molecules and flow cytometric analysis allowed us to positively identify virus-binding cells among a heterogeneous blood mononuclear cell population. Biot-HTLV-I efficiently bound not only to T cells, but also to B cells and monocytes. Preincubation of monocytes with excess of unlabeled HTLV-L significantly reduced the attachment of biot-HTLV-I. HTLV-l not only bound to, but also infected, B cells, as suggested by: i) in situ hybridization of a S-35-labeled full length HTLV-I DNA probe with EBV-transformed B cells, previously cocultured with HTLV-I-producing (G11MJ) T cells, and ii) hybridization of the same nick-translated P-32-labeled DNA probe with blotted DNA from similar HTLV-I-infected EBV-transformed B cells. HTLV-I infection did not affect the ability of B cells to secrete IgG. These findings suggest that HTLV-I cannot only infect cells of the T lineage, but can also infect B cells. C1 NIDR,ORAL MED LAB,BETHESDA,MD 20892. NIDR,IMMUNOL LAB,BETHESDA,MD 20892. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. NYU,SCH MED,DEPT PATHOL,NEW YORK,NY 10016. NYU,SCH MED,KAPLAN CANC CTR,NEW YORK,NY 10016. RI Casali, Paolo/F-6579-2010 NR 31 TC 18 Z9 18 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 1991 VL 147 IS 1 BP 102 EP 108 PG 7 WC Immunology SC Immunology GA FT763 UT WOS:A1991FT76300015 PM 1646840 ER PT J AU KANOF, ME STROBER, W KWAN, WC OCONNELL, NA JAMES, SP AF KANOF, ME STROBER, W KWAN, WC OCONNELL, NA JAMES, SP TI CD4+ LEU-8+ T-CELL SUPERNATANT ACTIVITY THAT INHIBITS IG PRODUCTION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NODE HOMING RECEPTOR; IMMUNOGLOBULIN PRODUCTION; SUPPRESSOR CELLS; LYMPHOCYTES-T; GROWTH-FACTOR; SOLUBLE SUPPRESSOR; INTERFERON-GAMMA; HUMAN EQUIVALENT; B-CELLS; SUBSETS AB The subpopulation of CD4+ T cells that expresses the Leu-8 peripheral lymph node homing receptor suppresses PWM-stimulated Ig synthesis. To determine the mechanism of this suppression, the immunoregulatory activity of culture supernatants obtained from peripheral blood CD4+ Leu-8+ T cells cultured with anti-CD3 mAb and PMA (Leu-8+ supernatant) was determined. Leu-8+ supernatant suppressed PWM-stimulated Ig synthesis in cultures containing non-T cells and CD4+ Leu-8- T cells. In contrast, the supernatant from CD4+ Leu-8- T cells did not suppress Ig synthesis. The inhibitory activity of CD4+ Leu-8+ T cell supernatants could not be accounted for by a deficiency or excess of IL-2, IL-4, IFN-gamma, IL-6, or PGE2. In studies examining the effect of CD4+ Leu-8+ supernatant on T cells, the supernatant did not alter either mitogen-induced proliferation or the helper function of CD4+ Leu-8-T cells. In studies examining the effect of CD4+ Leu-8+ supernatant on B cells, the supernatant inhibited Staphylococcus aureus Cowan I strain-induced B cell Ig secretion but not B cell proliferation. The suppressor activity of Leu-8+ supernatant was eliminated by protease treatment and was eluted by HPLC in two main peaks, with molecular sizes of 44 and 12 kDa. In summary, these studies indicate that supernatants from activated CD4+ Leu-8+ T cells directly suppress B cell Ig production. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,COMBINED PROGRAM PEDIAT GASTROENTEROL & NUTR,BOSTON,MA 02114. NIAID,CLIN INVEST LAB,MUCOSAL IMMUN SECT,BETHESDA,MD 20892. FU NIAID NIH HHS [AI-07439]; NIDDK NIH HHS [DK-40918] NR 48 TC 11 Z9 11 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 1991 VL 147 IS 1 BP 155 EP 161 PG 7 WC Immunology SC Immunology GA FT763 UT WOS:A1991FT76300023 PM 1711071 ER PT J AU LEIGHTON, J SETTE, A SIDNEY, J APPELLA, E EHRHARDT, C FUCHS, S ADORINI, L AF LEIGHTON, J SETTE, A SIDNEY, J APPELLA, E EHRHARDT, C FUCHS, S ADORINI, L TI COMPARISON OF STRUCTURAL REQUIREMENTS FOR INTERACTION OF THE SAME PEPTIDE WITH I-EK AND I-ED MOLECULES IN THE ACTIVATION OF MHC CLASS II-RESTRICTED T-CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HISTOCOMPATIBILITY MOLECULES; IMMUNOGENIC PEPTIDES; FINE SPECIFICITY; RECOGNITION; ANTIGEN; BINDING; PROTEIN; EPITOPE; DETERMINANTS; ASSOCIATION AB We have analyzed the interaction of the hen egg-white lysozyme (HEL) peptide 107-116 with the MHC class II molecule I-E(k), using truncated and single residue substitution analogues to measure activation of I-E(k)-restricted, 107-116-specific T cell hybridomas and competition for Ag presentation by I-E(k) molecules. These results have been compared with previous findings on the interaction of the same peptide with the I-E(d) molecule. Stimulation of T cell hybridomas by truncated peptides defines the sequence 108-116 as the minimum epitope necessary for activation of both I-E(k)- and I-E(d)-restricted T cell hybridomas. Substitution analysis pinpoints three residues (V109, A110, and K116) in the sequence 108-116 as being critical for binding to I-E(k) molecules and demonstrates the involvement of most other residues in recognition by T cells. Results previously obtained for binding of HEL 107-116 to I-E(d) molecules indicated that peptide residues R112, R114, and K116 were critical for interaction with I-E(d). Comparison of these results indicates a difference in the likely MHC contact residues between the HEL sequence 108-116 and I-E(d) or I-E(k) molecules, suggesting that the same HEL peptide assumes a different conformation in the binding site of these two MHC molecules. This in turn affects residues interacting with the specific T cell receptor. According to the hypothetical tridimensional structure predicted for class II molecules, the difference in MHC contact residues observed within the sequence 108-116 can be related to polymorphic amino acids in the binding site of I-E(k) and I-E(d) molecules. A search through published binding data for a common pattern in this and other I-E(k)-binding peptides has permitted us to derive a possible motif for predicting peptide binding to I-E(k) molecules. This putative motif was tested by determining binding to I-E(k) of an unbiased panel of about 150 synthetic peptides. Binding data indeed demonstrate the presence of this motif in the majority of good binders to I-E(k) molecules. C1 SANDOZ PHARMA LTD,PRECLIN RES 386101,CH-4002 BASEL,SWITZERLAND. CYTEL,LA JOLLA,CA 92037. NCI,CELL BIOL LAB,BETHESDA,MD 20892. FU NIAID NIH HHS [AI18634] NR 25 TC 53 Z9 53 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 1991 VL 147 IS 1 BP 198 EP 204 PG 7 WC Immunology SC Immunology GA FT763 UT WOS:A1991FT76300029 PM 1711074 ER PT J AU THYPHRONITIS, G KINOSHITA, T INOUE, K SCHWEINLE, JE TSOKOS, GC METCALF, ES FINKELMAN, FD BALOW, JE AF THYPHRONITIS, G KINOSHITA, T INOUE, K SCHWEINLE, JE TSOKOS, GC METCALF, ES FINKELMAN, FD BALOW, JE TI MODULATION OF MOUSE COMPLEMENT RECEPTOR-1 AND RECEPTOR-2 SUPPRESSES ANTIBODY-RESPONSES INVIVO SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MURINE LYMPHOCYTES-B; MONOCLONAL-ANTIBODIES; IMMUNE-RESPONSE; TYPE-1 CR-1; C3B; CELLS; ACTIVATION; SURFACE; ANTIGEN; LIPOPOLYSACCHARIDE AB A mAb, 7G6, that binds to mouse CR1 and CR2 and down-modulates their expression on splenic B cells in vivo, was used to determine whether a decrease in CR1 and CR2 expression affects antibody responses to different T-dependent and T-independent Ag. Injection of mice with the mAb 7G6 prior to immunization with FITC haptenated Salmonella typhimurium (SH5771), Salmonella montevideo (SH5770), SRBC, or Ficoll dramatically decreased subsequent antibody responses to FITC. Although both IgM and IgG primary antibody responses were affected similarly, the antibody levels were most inhibited during early phases of the response. In contrast, down-modulation of the CR did not affect memory antibody responses, because injection of mice with 7G6 before a second immunization with FITC-SH5771 had no effect on subsequent anti-FITC antibody production. Moreover, polyclonal in vivo activation of the mouse immune system by antimouse IgD antibodies was not affected by previous administration of 7G6, because anti-IgD-induced increases in Ia expression and serum IgG1 levels were not affected. Taken together, these observations suggest that CRI and CR2 may play an important role in enhancing primary antibody responses to many T-dependent and T-independent Ag and may contribute to a host's response to naturally occurring antigens such as bacteria. C1 OSAKA UNIV,SCH MED,DEPT BACTERIOL,OSAKA 565,JAPAN. NIDDKD,KIDNEY DIS SECT,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,DEPT MICROBIOL,BETHESDA,MD 20814. YALE UNIV,SCH MED,DEPT INTERNAL MED,NEW HAVEN,CT 06510. RP THYPHRONITIS, G (reprint author), UNIFORMED SERV UNIV HLTH SCI,DEPT MED,ROOM A3060,4301 JONES BRIDGE RD,BETHESDA,MD 20814, USA. RI Kinoshita, Taroh/C-7353-2009 FU NIAID NIH HHS [AI21328, AI22436] NR 43 TC 102 Z9 102 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 1991 VL 147 IS 1 BP 224 EP 230 PG 7 WC Immunology SC Immunology GA FT763 UT WOS:A1991FT76300033 PM 1828822 ER PT J AU SIMMS, HH GAITHER, TA FRIES, LF FRANK, MM AF SIMMS, HH GAITHER, TA FRIES, LF FRANK, MM TI MONOKINES RELEASED DURING SHORT-TERM FC-GAMMA RECEPTOR PHAGOCYTOSIS UP-REGULATE POLYMORPHONUCLEAR LEUKOCYTES AND MONOCYTE-PHAGOCYTIC FUNCTION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR NECROSIS FACTOR; HUMAN INTERLEUKIN-1; BLOOD MONOCYTES; IGG; INDUCTION; BINDING; NEUTROPHILS; STIMULATION; EXPRESSION; COMPLEMENT AB Freshly explanted monocytes phagocytosing IgG antibody-coated erythrocyte targets (EIgG) release a factor(s) that stimulates phagocytosis by neighboring monocytes and polymorphonuclear leukocytes (PMN). Culture supernatants obtained after 30-min incubation of adherent monocytes with EIgG, but not unopsonized sheep erythrocytes, markedly up-regulated the extent of PMN phagocytosis and enhanced the rate at which monocytes ingested EIgG. The presence of this factor(s) was first evident in phagocytic studies in which monocytes were prepared by a colloidal silica-based continuous gradient technique (Sepracell-Mn). After introduction of erythrocyte targets, there was a 20- to 30-min delay before initiation of phagocytosis that was not observed with monocytes prepared by the standard Percoll-gradient technique. Experiments suggest that, when compared with monocytes prepared by the Percoll-gradient method, Sepracell-Mn monocytes are closer to a base line state of activation with regard to the expression of Fc-gamma-RI and the ability to ingest EIgG. The mechanism of PMN upregulation by the monocyte factor(s) was explored. Monocyte supernatants did not induce an increase in the surface expression of PMN Fc-gamma-RI, 11, or III. Neither anti-TNF, anti-IL-2, nor anti-GM-CSF had any significant effect on monocyte supernatant activity. Neutrophil activating protein-1 Was not detected by ELISA. In contrast, anti-IL-1 completely blocked the effect of the supernatant on subsequent monocyte phagocytosis, and partially inhibited its effect on PMN phagocytosis. Furthermore, it was shown that RIL-1 as well as TNF markedly enhanced monocyte and PMN ingestion of EIgG. These results suggest that monocytes, after Fc-gamma-R-mediated phagocytosis, release monokines, including at least IL-1, which enhance the phagocytic function of neighboring PMN and monocytes to augment the host defense process. C1 NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. RP SIMMS, HH (reprint author), RHODE ISL HOSP,DEPT SURG,593 EDDY ST,PROVIDENCE,RI 02905, USA. NR 39 TC 39 Z9 39 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 1991 VL 147 IS 1 BP 265 EP 272 PG 8 WC Immunology SC Immunology GA FT763 UT WOS:A1991FT76300040 PM 1828823 ER PT J AU MUELENAER, PM HENDERSON, FW HEMMING, VG WALSH, EE ANDERSON, LJ PRINCE, GA MURPHY, BR AF MUELENAER, PM HENDERSON, FW HEMMING, VG WALSH, EE ANDERSON, LJ PRINCE, GA MURPHY, BR TI GROUP-SPECIFIC SERUM ANTIBODY-RESPONSES IN CHILDREN WITH PRIMARY AND RECURRENT RESPIRATORY SYNCYTIAL VIRUS-INFECTIONS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID LARGE G GLYCOPROTEINS; SUBGROUP-B; MONOCLONAL-ANTIBODIES; FUSION PROTEIN; F-GLYCOPROTEIN; ANTIGENIC RELATEDNESS; STRAINS; INFANTS; NEUTRALIZATION; PURIFICATION AB Antigenic group-specific serum antibody responses to first and second respiratory syncytial virus (RSV) infections were studied in children who had been followed longitudinally from early infancy in a research day-care center. Plaque-reduction neutralizing (PRN) antibody assays and ELISAs for the fusion (F) and attachment (G) glycoproteins were done using antigens of prototype RSV strains from groups A and B. Responses to antigens of viruses homologous and heterologous to the antigenic group of the infecting viral strain were compared. Primary group A infection elicited antibodies cross-reactive with group B virus in the PRN(B) and the ELISAs for G(B) and F(B). In contrast, primary group B infection induced significant increases in mean concentrations of antibody cross-reactive with group A virus only in the F(A) ELISA. Second RSV infections caused by group B viruses in children with histories of primary group A infection induced heterologous rises in the PRN(A) and G(A) assays, suggesting that prior group A infection had primed for a more extensive cross-reacting antibody response at the time of second RSV infections with group B viruses. C1 UNIV N CAROLINA,SCH MED,FRANK PORTER GRAHAM CHILD DEV CTR,CB 8180,105 SMITH LEVEL RD,CHAPEL HILL,NC 27599. UNIV N CAROLINA,SCH MED,DEPT PEDIAT,CHAPEL HILL,NC 27514. UNIFORMED SERV UNIV HLTH SCI,DEPT PEDIAT,BETHESDA,MD 20814. NIAID,INFECT DIS LAB,BETHESDA,MD 20892. UNIV ROCHESTER,ROCHESTER GEN HOSP,SCH MED,DEPT MED,ROCHESTER,NY 14621. CTR DIS CONTROL,CTR INFECT DIS,DIV VIRAL & RICKETTSIAL DIS,ATLANTA,GA 30333. FU NHLBI NIH HHS [HL-19171] NR 30 TC 37 Z9 39 U1 0 U2 4 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 JUL PY 1991 VL 164 IS 1 BP 15 EP 21 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA FT630 UT WOS:A1991FT63000003 PM 2056202 ER PT J AU FEIGAL, E MURPHY, E VRANIZAN, K BACCHETTI, P CHAISSON, R DRUMMOND, JE BLATTNER, W MCGRATH, M GREENSPAN, J MOSS, A AF FEIGAL, E MURPHY, E VRANIZAN, K BACCHETTI, P CHAISSON, R DRUMMOND, JE BLATTNER, W MCGRATH, M GREENSPAN, J MOSS, A TI HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE-I AND TYPE-II IN INTRAVENOUS-DRUG-USERS IN SAN-FRANCISCO - RISK-FACTORS ASSOCIATED WITH SEROPOSITIVITY SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HTLV-I; UNITED-STATES; HOMOSEXUAL MEN; LEUKEMIA-VIRUS; INFECTION; ANTIBODY; IMMUNOFLUORESCENCE; ABUSERS; AIDS; HIV AB Serologic assays for human T cell lymphotropic virus types I and II (HTLV I/II) infection were done in 676 intravenous drug users (IVDUs) in San Francisco between 1985 and 1987: 150 in 1985, 44 in 1986, and 482 in 1987. All sera were tested by Western blot, ELISA, and p24 RIA. A total of 111 participants were seropositive in a minimum of two assays. Duration of intravenous heroin use was strongly associated with the risk of HTLV I/II seropositivity: greater-than-or-equal-to 21 years odds ratio, 6.1 (95% confidence interval [CI], 2.2-17.5), compared with less-than-or-equal-to 10 years of heroin use. Additional independent risk factors included black or Hispanic race, female sex, and the use of drugs in a shooting gallery. Coinfection of HTLV I/II and human immunodeficiency virus was less frequent than expected by chance (P < .02). Longitudinal specimens were available in 154 participants. The age- and race-adjusted seroconversion rate was 3.4% (95% CI, 1.3-8.9) per person per year. Of the 349 homosexual men tested, none were HTLV I/II-seropositive. C1 UNIV CALIF SAN FRANCISCO,DEPT LAB MED,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT EPIDEMIOL & BIOSTAT,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,CTR ORAL AIDS,SAN FRANCISCO,CA 94143. SAN FRANCISCO GEN HOSP,DIV AIDS ONCOL,SAN FRANCISCO,CA 94110. JOHNS HOPKINS UNIV,DIV INFECT DIS,BALTIMORE,MD 21218. NCI,FREDERICK CANC RES FACIL,PROGRAM RESOURCES INC,BETHESDA,MD 20892. RP FEIGAL, E (reprint author), UNIV CALIF SAN DIEGO,DEPT INTERNAL MED,DIV HEMATOL ONCOL,SAN DIEGO,CA 92103, USA. FU NCI NIH HHS [CO-74102]; NIDA NIH HHS [DA-04363] NR 32 TC 52 Z9 53 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 JUL PY 1991 VL 164 IS 1 BP 36 EP 42 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA FT630 UT WOS:A1991FT63000006 PM 2056217 ER PT J AU DAVEY, RT DAVEY, VJ METCALF, JA ZURLO, JJ KOVACS, JA FALLOON, J POLIS, MA ZUNICH, KM MASUR, H LANE, HC AF DAVEY, RT DAVEY, VJ METCALF, JA ZURLO, JJ KOVACS, JA FALLOON, J POLIS, MA ZUNICH, KM MASUR, H LANE, HC TI A PHASE-I/II TRIAL OF ZIDOVUDINE, INTERFERON-ALPHA, AND GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR IN THE TREATMENT OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID PLACEBO-CONTROLLED TRIAL; AIDS-RELATED COMPLEX; MYELODYSPLASTIC SYNDROMES; SYNERGISTIC INHIBITION; REPLICATION INVITRO; AZIDOTHYMIDINE AZT; KAPOSI-SARCOMA; DOUBLE-BLIND; HIV-1; CHEMOTHERAPY AB Twenty-four patients infected with human immunodeficiency virus type 1 (HIV-1) who had CD4+ counts of 0.2-0.5 x 10(9) cells/l received granulocyte-macrophage colony-stimulating factor (GM-CSF) in combination with zidovudine plus escalating doses of daily subcutaneous interferon-alpha. Mean neutropenia-inducing doses of interferon-alpha were 9.4 x 10(6) and 10.6 x 10(6) IU/day for groups receiving 100 or 200 mg zidovudine every 4 h, respectively. Mean GM-CSF doses used to reverse neutropenia were 0.64 and 0.63-mu-g/kg/day for these two groups, respectively, although the mean minimum effective GM-CSF dose for both was only 0.30-mu-g/kg/day. Serum p24 antigen declined > 70% in all 5 antigenemic patients. Toxicities included a dose-dependent increase in lymphokine-like side effects (100%), anorexia and weight loss (42%), fatigue (42%), and anemia (50%). While toxicities of the combination can be significant, low-dose GM-CSF readily ameliorated neutropenia associated with zidovudine and interferon-alpha therapy without adversely affecting the antiviral properties of the combination. C1 NIH,DEPT CRIT CARE MED,BETHESDA,MD 20892. RP DAVEY, RT (reprint author), NIAID,BLDG 10 ROOM 11B13,BETHESDA,MD 20892, USA. OI Polis, Michael/0000-0002-9151-2268 NR 38 TC 63 Z9 63 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 JUL PY 1991 VL 164 IS 1 BP 43 EP 52 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA FT630 UT WOS:A1991FT63000007 PM 1676045 ER PT J AU OCKENHOUSE, CF HO, M TANDON, NN VANSEVENTER, GA SHAW, S WHITE, NJ JAMIESON, GA CHULAY, JD WEBSTER, HK AF OCKENHOUSE, CF HO, M TANDON, NN VANSEVENTER, GA SHAW, S WHITE, NJ JAMIESON, GA CHULAY, JD WEBSTER, HK TI MOLECULAR-BASIS OF SEQUESTRATION IN SEVERE AND UNCOMPLICATED PLASMODIUM-FALCIPARUM MALARIA - DIFFERENTIAL ADHESION OF INFECTED ERYTHROCYTES TO CD36 AND ICAM-1 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID GLYCOPROTEIN-IV CD36; PARASITIZED ERYTHROCYTES; MEDIATES CYTOADHERENCE; MEMBRANE GLYCOPROTEIN; CEREBRAL MALARIA; T-CELLS; RECEPTOR; LIGAND; LFA-1; IDENTIFICATION AB The CD36 and ICAM-1 glycoproteins on vascular endothelial cells have been implicated as cytoadherence receptors for Plasmodium falciparum-infected erythrocytes (IRBC). Adhesion of IRBC from Thai patients with uncomplicated and severe falciparum malaria to purified CD36 or ICAM-1 and to C32 melanoma cells was compared. All malaria isolates bound to solid phase-adsorbed CD36 and to fluid-phase I-125-labeled CD36. IRBC adhesion to purified ICAM-1 varied widely, and no correlation with clinical severity of disease was observed. The cytoadherent phenotype of IRBC was modulated by selective panning on plates coated with purified CD36 or ICAM-1. IRBC selected by panning on CD36+, ICAM-1+ melanoma cells bound to cells that express surface CD36 but not to CD36-deficient cells, indicating that CD36 exerts a strong selective pressure on the IRBC cytoadherent phenotype. IRBC adhesion to CD36 and ICAM-1 suggests that P. falciparum parasites may use these receptors in vivo to promote parasite survival and immune evasion. C1 WALTER REED ARMY MED CTR,IMMUNOL BRANCH,WASHINGTON,DC 20307. AMER RED CROSS,CELL BIOL LAB,ROCKVILLE,MD. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. USA,MED RES INST INFECT DIS,DIV VIROL,FREDERICK,MD 21701. UNIV CALGARY,DEPT MICROBIOL & INFECT DIS,CALGARY T2N 1N4,ALBERTA,CANADA. MAHIDOL UNIV,HOSP TROP DIS,FAC TROP MED,BANGKOK 10700,THAILAND. USA,MED COMPONENT,ARMED FORCES RES INST MED SCI,BANGKOK,THAILAND. RP OCKENHOUSE, CF (reprint author), WALTER REED ARMY MED CTR,DEPT MED,WASHINGTON,DC 20307, USA. RI White, Nicholas/I-4629-2012 NR 31 TC 188 Z9 188 U1 0 U2 4 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 JUL PY 1991 VL 164 IS 1 BP 163 EP 169 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA FT630 UT WOS:A1991FT63000024 PM 1711552 ER PT J AU CLERICI, M BERZOFSKY, JA SHEARER, GM TACKET, CO AF CLERICI, M BERZOFSKY, JA SHEARER, GM TACKET, CO TI EXPOSURE TO HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1-SPECIFIC T-HELPER CELL RESPONSES BEFORE DETECTION OF INFECTION BY POLYMERASE CHAIN-REACTION AND SERUM ANTIBODIES SO JOURNAL OF INFECTIOUS DISEASES LA English DT Note ID TYPE-1 HIV-1; INDIVIDUALS; TRIAL AB A healthy individual at risk for human immunodeficiency virus type 1 (HIV-1) infection was studied longitudinally for 19 months for evidence of exposure to and infection with HIV. Peripheral blood mononuclear cells (PBMC) were tested at 1, 5, 13, 16, and 19 months for T helper (Th) cell function by in vitro-generated proliferation and interleukin-2 production in response to four synthetic peptides corresponding to env of HIV. PBMC were also tested for proviral DNA using gag primers by the polymerase chain reaction (PCR) at 0, 5, 10, 13, 16, and 19 months. HIV serology by ELISA and p24 antigen and Western blot analyses were done on samples taken at 0, 1, 5, 10, 13, 16, and 19 months. The results indicated that both Th cell tests were positive during months 5-19. In contrast, the PCR and all serologic assays were negative except for month 19, when the assays became positive. These results, based on the longitudinal study of one individual, showed that the Th cell tests can reveal exposure to HIV-1 antigens several months before evidence of viral infection is detected, even by PCR. C1 UNIV MARYLAND,SCH MED,DEPT MED,DIV GEOG MED,CTR VACCINE DEV,10 S PINE ST,BALTIMORE,MD 21201. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. NCI,METAB BRANCH,BETHESDA,MD 20892. FU NIAID NIH HHS [AI-62528] NR 17 TC 98 Z9 98 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 JUL PY 1991 VL 164 IS 1 BP 178 EP 182 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA FT630 UT WOS:A1991FT63000026 PM 1829105 ER PT J AU CECKLER, TL BALABAN, RS AF CECKLER, TL BALABAN, RS TI TRITIUM PROTON MAGNETIZATION TRANSFER AS A PROBE OF CROSS RELAXATION IN AQUEOUS LIPID BILAYER SUSPENSIONS SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article ID PROTEIN SOLUTIONS; SPIN DIFFUSION; MODEL MEMBRANES; SOLVENT H-1; WATER; NMR; CHOLESTEROL; EXCHANGE; SYSTEMS; DISPERSION RP CECKLER, TL (reprint author), NHLBI,BLDG 1,ROOM B307,BETHESDA,MD 20892, USA. NR 39 TC 34 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 0022-2364 J9 J MAGN RESON PD JUL PY 1991 VL 93 IS 3 BP 572 EP 588 DI 10.1016/0022-2364(91)90084-7 PG 17 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA FT605 UT WOS:A1991FT60500011 ER PT J AU LANFORD, RE NOTVALL, L BARBOSA, LH EICHBERG, JW AF LANFORD, RE NOTVALL, L BARBOSA, LH EICHBERG, JW TI EVALUATION OF A CHIMPANZEE COLONY FOR ANTIBODIES TO HEPATITIS-C VIRUS SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE VIRAL HEPATITIS; HEPATITIS-C VIRUS; IMMUNOASSAY; CHIMPANZEE ID NON-B-HEPATITIS; NON-A; HEPATOCELLULAR-CARCINOMA; BLOOD-DONORS; VIRAL SEQUENCES; CDNA; PREVALENCE AB The chimpanzee is the only species other than man that is generally susceptible to infection by hepatitis C virus (HCV). Aspects of future studies on vaccines and therapeutics for HCV may continue to depend on the chimpanzee. In an attempt to determine the HCV status of the animals in a chimpanzee colony, the recently developed enzyme immunoassay (EIA) for antibodies to HCV was used. The results of the assay indicated that only 31.3% of the animals that had previously been inoculated with a non-A, non-B hepatitis agent were currently positive in the assay. A retrospective analysis suggested that an additional 20% of the chimpanzees had been positive at some time following infection. Seroconversion to an anti-HCV antibody response using this assay did not appear to correlate with the severity of the initial disease or the development of chronic liver damage. Examination of the EIA-positive samples using the second generation recombinant immunoblot assay (RIBA) containing four HCV antigens suggested that chimpanzees responded differentially to these antigens. Examination of serum samples from 139 uninoculated animals by EIA revealed seven positive samples and ten samples with borderline values. The nature of the reactivities in most of the positive samples could not be resolved, but analysis by RIBA indicated that at least one animal in the breeder colony had been exposed to HCV. Due to the low seroconversion rate and the uncertainties surrounding many of the positive reactions, this assay cannot be used to determine the initial source or extent of spread of HCV infections in the uninoculated animals. C1 NHLBI,BETHESDA,MD 20892. RP LANFORD, RE (reprint author), SW FDN BIOMED RES,DEPT VIROL IMMUNOL,POB 28147,SAN ANTONIO,TX 78228, USA. FU NHLBI NIH HHS [N01-HB-7-7029] NR 20 TC 13 Z9 13 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD JUL PY 1991 VL 34 IS 3 BP 148 EP 153 DI 10.1002/jmv.1890340303 PG 6 WC Virology SC Virology GA FZ478 UT WOS:A1991FZ47800002 PM 1717646 ER PT J AU KARTON, Y BRADBURY, BJ BAUMGOLD, J PAEK, R JACOBSON, KA AF KARTON, Y BRADBURY, BJ BAUMGOLD, J PAEK, R JACOBSON, KA TI FUNCTIONALIZED CONGENER APPROACH TO MUSCARINIC ANTAGONISTS - ANALOGS OF PIRENZEPINE SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ACETYLCHOLINE-RECEPTOR GENES; TRICYCLIC COMPOUNDS; SELECTIVE ANTIMUSCARINICS; ADENOSINE RECEPTOR; SUBTYPES; IDENTIFICATION; INHIBITION; RESPONSES; SUBUNIT; MUSTARD AB The M1-selective muscarinic receptor antagonist pirenzepine (5,11-dihydro-11-[(4-methyl-1-piperazinyl)acetyl]-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one) was derivatized to explore points of attachment of functionalized side chains for the synthesis of receptor probes and ligands for affinity chromatography. The analogues prepared were evaluated in competitive binding assays versus [H-3]-N-methylscopolamine at four muscarinic receptor subtypes (m1AChR-m4AChR) in membranes from rat heart tissue and transfected A9L cells. 9-(Hydroxymethyl)pirenzepine, 8-(methylthio)pirenzepine, and a series of 8-aminosulfonyl derivatives were synthesized. Several 5-substituted analogues of pirenzepine also were prepared. An alternate series of analogues substituted on the 4-position of the piperazine ring was prepared by reaction of 4-desmethylpirenzepine with various electrophiles. An N-chloroethyl analogue of pirenzepine was shown to form a reactive aziridine species in aqueous buffer yet failed to affinity label muscarinic receptors. Within a series of aminoalkyl analogues, the affinity increased as the length of the alkyl chain increased. Shorter chain analogues were generally much less potent than pirenzepine, and longer analogues (7-10 carbons) were roughly as potent as pirenzepine at m1 receptors, but were nonselective. Depending on the methylene chain length, acylation or alkyl substitution of the terminal amine also influenced the affinity at muscarinic receptors. C1 NIDDK, BIOORGAN CHEM LAB, BETHESDA, MD 20892 USA. GEORGE WASHINGTON UNIV, DEPT RADIOL, WASHINGTON, DC 20037 USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031115-24, Z99 DK999999] NR 45 TC 28 Z9 28 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 EI 1520-4804 J9 J MED CHEM JI J. Med. Chem. PD JUL PY 1991 VL 34 IS 7 BP 2133 EP 2145 DI 10.1021/jm00111a032 PG 13 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA FW170 UT WOS:A1991FW17000032 PM 2066986 ER PT J AU MORRISON, PF BUNGAY, PM HSIAO, JK BALL, BA MEFFORD, IN DEDRICK, RL AF MORRISON, PF BUNGAY, PM HSIAO, JK BALL, BA MEFFORD, IN DEDRICK, RL TI QUANTITATIVE MICRODIALYSIS - ANALYSIS OF TRANSIENTS AND APPLICATION TO PHARMACOKINETICS IN BRAIN SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE MICRODIALYSIS; BRAIN; PHARMACOKINETICS; ACETAMINOPHEN ID AMINO-ACIDS; INTRACEREBRAL MICRODIALYSIS; DIFFUSION KINETICS; INVIVO; ACETAMINOPHEN; DIALYSIS; RAT; MEMBRANES; INVITRO; PROBES AB The behavior of a microdialysis probe in vivo is mathematically described. A diffusion-reaction model is developed that not only accounts for transport of substances through tissues and probe membranes but also accounts for transport across the microvasculature and metabolism. Time-dependent equations are presented both for the effluent microdialysate concentration and for concentration profiles about the probe. The analysis applies either to measuring the tissue pharmacokinetics of drugs administered systemically, or for sampling of endogenously produced substances from tissue. In addition, an expression is developed for the transient concentration about the probe when it is used as an infusion device. All mathematical expressions are found to be a sum of an algebraic and an integral term. Theoretical prediction of time-dependent probe behavior in brain has been compared with experimental data for acetaminophen administered at 15 mg/kg to rats by intravenous bolus. Plasma and whole striatal tissue samples were used to describe plasma kinetics and to estimate a capillary permeability-area product of 0.07 min-1. Theoretical prediction of transient effluent dialysate concentrations exhibited close agreement with experimental data over 60 min. Terminal decline of the dialysate effluent concentration was slightly overestimated but theoretical concentrations still lay within the 95% confidence interval of the experimental data at 112 min. Microvasculature transport and metabolism play major roles in determining microdialysate transient responses. Extraction fraction (recovery) has been shown to be a declining function in time for five probe operating conditions. High rates of metabolism and/or capillary transport affect the time required to approach steady-state extraction, shortening the time as the rates increase. Conversely, for substances characterized by low permeabilities and negligible metabolism, experimental situations exist that are predicted to have very slow approaches to microdialysis steady state. C1 NIMH,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. RP MORRISON, PF (reprint author), NCRR,BIOMED ENGN & INSTRUMENTAT PROGRAM,BLDG 13,ROOM 3W13,BETHESDA,MD 20892, USA. NR 37 TC 130 Z9 130 U1 0 U2 5 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUL PY 1991 VL 57 IS 1 BP 103 EP 119 DI 10.1111/j.1471-4159.1991.tb02105.x PG 17 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA FR859 UT WOS:A1991FR85900015 PM 2051160 ER PT J AU PERRY, LL BARZAGAGILBERT, E TROTTER, JL AF PERRY, LL BARZAGAGILBERT, E TROTTER, JL TI T-CELL SENSITIZATION TO PROTEOLIPID PROTEIN IN MYELIN BASIC PROTEIN-INDUCED RELAPSING EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE ENCEPHALOMYELITIS; MYELIN BASIC PROTEIN; PROTEOLIPID PROTEIN; MULTIPLE SCLEROSIS; (MOUSE) ID MULTIPLE-SCLEROSIS PATIENTS; AUTOIMMUNE ENCEPHALOMYELITIS; LYMPHOCYTE-T; ENCEPHALITOGENIC EPITOPES; CEREBROSPINAL-FLUID; ANTIBODY-SYNTHESIS; HLA RESTRICTION; SJL/J MICE; SPECIFICITY; APOPROTEIN AB (SJL/J x PL/J)F1 mice immunized with myelin basic protein (MBP) develop an autoimmune demyelinating disease termed relapsing experimental allergic encephalomyelitis (rEAE). The acute stage of disease is mediated by CD4+ T cells specific for MBP amino acids 1-9. To determine the immunologic bases for disease relapse, host sensitization to additional autoantigens of the central nervous system was measured. Results indicate that most animals develop T cell reactivity to endogenous myelin proteolipid protein (PLP) during rEAE. However, PLP-specific immunity does not appear to account for expression of relapse episodes of demyelination. C1 UNIV VIRGINIA,DEPT MICROBIOL,CHARLOTTESVILLE,VA 22908. WASHINGTON UNIV,DEPT NEUROL & NEUROL SURG,ST LOUIS,MO 63110. RP PERRY, LL (reprint author), NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840, USA. NR 64 TC 84 Z9 84 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD JUL PY 1991 VL 33 IS 1 BP 7 EP 15 DI 10.1016/0165-5728(91)90029-7 PG 9 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA FU399 UT WOS:A1991FU39900002 PM 1711539 ER PT J AU DANIEL, DG WEINBERGER, DR JONES, DW ZIGUN, JR COPPOLA, R HANDEL, S BIGELOW, LB GOLDBERG, TE BERMAN, KF KLEINMAN, JE AF DANIEL, DG WEINBERGER, DR JONES, DW ZIGUN, JR COPPOLA, R HANDEL, S BIGELOW, LB GOLDBERG, TE BERMAN, KF KLEINMAN, JE TI THE EFFECT OF AMPHETAMINE ON REGIONAL CEREBRAL BLOOD-FLOW DURING COGNITIVE ACTIVATION IN SCHIZOPHRENIA SO JOURNAL OF NEUROSCIENCE LA English DT Review ID DORSOLATERAL PREFRONTAL CORTEX; EMISSION COMPUTED-TOMOGRAPHY; INERT-GAS CONCENTRATIONS; L-DOPA; PHYSIOLOGICAL DYSFUNCTION; PARKINSONS-DISEASE; RAT-BRAIN; METABOLISM; RECEPTORS; NEURONS AB To explore the role of monoamines on cerebral function during specific prefrontal cognitive activation, we conducted a double-blind placebo-controlled crossover study of the effects of 0.25 mg/kg oral dextroamphetamine on regional cerebral blood flow (rCBF) as determined by Xe-133 dynamic single-photon emission-computed tomography (SPECT) during performance of the Wisconsin Card Sorting Test (WCST) and a sensorimotor control task. Ten patients with chronic schizophrenia who had been stabilized for at least 6 weeks on 0.4 mg/kg haloperidol participated. Amphetamine produced a modest, nonsignificant, task-independent, global reduction in rCBF. However, the effect of amphetamine on task-dependent activation of rCBF (i.e., WCST minus control task) was striking. Whereas on placebo no significant activation of rCBF was seen during the WCST compared with the control task, on amphetamine significant activation of the left dorsolateral prefrontal cortex (DLPFC) occurred (p = 0.0006). Both the mean number of correct responses and the mean conceptual level increased (p < 0.05) with amphetamine relative to placebo. In addition, with amphetamine, but not with placebo, a significant correlation (rho = -0.71; p < 0.05) emerged between activation of DLPFC rCBF and performance of the WCST task. These findings are consistent with animal models in which mesocortical catecholaminergic activity modulates and enhances the signal-to-noise ratio of evoked cortical activity. C1 NIMH,NEUROSCI CTR ST ELIZABETHS,INTRAMURAL RES PROGRAM,WASHINGTON,DC 20032. RP DANIEL, DG (reprint author), NIMH,NEUROPSYCHIAT RES HOSP,WILLIAM A WHITE BLDG,WASHINGTON,DC 20032, USA. NR 100 TC 228 Z9 229 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUL PY 1991 VL 11 IS 7 BP 1907 EP 1917 PG 11 WC Neurosciences SC Neurosciences & Neurology GA FW523 UT WOS:A1991FW52300003 PM 2066768 ER PT J AU WINSLOW, JT INSEL, TR AF WINSLOW, JT INSEL, TR TI SOCIAL-STATUS IN PAIRS OF MALE SQUIRREL-MONKEYS DETERMINES THE BEHAVIORAL-RESPONSE TO CENTRAL OXYTOCIN ADMINISTRATION SO JOURNAL OF NEUROSCIENCE LA English DT Article ID SEXUAL-BEHAVIOR; FEMALE RATS; AGGRESSIVE-BEHAVIOR; MATERNAL-BEHAVIOR; MARKING BEHAVIOR; SAIMIRI-SCIUREUS; GOLDEN-HAMSTERS; SCENT MARKING; VASOPRESSIN; HYPOTHALAMUS AB Oxytocin, when administered centrally, has been associated with the modulation of various social initiatives including maternal and sexual behaviors. The nature of these effects depends on gonadal hormone status. In the present experiments, we investigated the effects of centrally administered oxytocin on the behavior of pair-housed male squirrel monkeys during interactions with a familiar female monkey. Pairs of male squirrel monkeys established reliable and persistent dominance relationships with dominant males showing increased sexual and aggressive behavior as well as higher plasma concentrations of testosterone. Oxytocin (0.1, 1.0-mu-g) increased the sexual and aggressive behavior of dominant monkeys without affecting these measures in the sub-ordinate monkeys. In contrast to these effects in the dominant monkeys, oxytocin increased associative and marking behaviors only in subordinate monkeys. Central administration of the oxytocin receptor antagonist d(CH2)5[Tyr(Me)2, Thr4,Tyr-NH2(9)] OVT (OTA; 0.05-mu-g) had no intrinsic effect on behavior but blocked the effects of exogenous oxytocin. To investigate further the specificity of oxytocin's effects on social behavior, we administered the structurally related peptide arginine vasopressin under identical conditions. Vasopressin (0.5, 5.0-mu-g) decreased social behaviors and increased motor activity in both dominant and subordinate monkeys. Previous studies in rodents have demonstrated that oxytocin receptors are induced by gonadal steroids in a regionally specific fashion. The status-related behavioral effects of oxytocin in the squirrel monkey may reflect differences in brain oxytocin receptor density associated with the higher concentrations of testosterone in the dominant animal. Alternatively, the status-related effects may depend on the conditioned behavioral differences associated with social organization. RP WINSLOW, JT (reprint author), NIMH,NIHAC,CLIN SCI LAB,POB 289,POOLESVILLE,MD 20837, USA. NR 47 TC 93 Z9 93 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUL PY 1991 VL 11 IS 7 BP 2032 EP 2038 PG 7 WC Neurosciences SC Neurosciences & Neurology GA FW523 UT WOS:A1991FW52300013 PM 1648603 ER PT J AU DICHIRO, C AF DICHIRO, C TI WHICH PET RADIOPHARMACEUTICAL FOR BRAIN-TUMORS SO JOURNAL OF NUCLEAR MEDICINE LA English DT Editorial Material RP DICHIRO, C (reprint author), NIH,TOMOG SECT,BLDG 10,RM 3010,BETHESDA,MD 20205, USA. NR 12 TC 18 Z9 18 U1 0 U2 2 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD JUL PY 1991 VL 32 IS 7 BP 1346 EP 1348 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA FV990 UT WOS:A1991FV99000010 ER PT J AU DOUDET, DJ MCLELLAN, CA AIGNER, TG WYATT, R ADAMS, HR MIYAKE, H FINN, RT COHEN, RM AF DOUDET, DJ MCLELLAN, CA AIGNER, TG WYATT, R ADAMS, HR MIYAKE, H FINN, RT COHEN, RM TI POSTINJECTION L-PHENYLALANINE INCREASES BASAL GANGLIA CONTRAST IN PET SCANS OF 6-F-18-DOPA SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; CATECHOL-O-METHYLTRANSFERASE; CEREBRAL METABOLISM; PARKINSONS-DISEASE; HOODED RAT; BRAIN; -6-FLUORODOPA; INHIBITION; MONKEYS; MPTP AB The sensitivity of F-18-DOPA positron emission tomography for imaging presynaptic dopamine systems is limited by the amount of specific-to-nonspecific accumulation of radioactivity in brain. In rhesus monkeys, we have been able to increase this ratio by taking advantage of the lag time between F-18-DOPA injection and the formation of its main metabolite, the amino acid F-18-fluoromethoxydopa, the entrance of which into brain is responsible for most of the brain's nonspecific radioactivity. By infusing an unlabeled amino acid, L-phenylalanine, starting 15 min after F-18-DOPA administration, we preferentially blocked the accumulation of F-18-fluoromethoxydopa by preventing its entrance into brain through competition at the large neutral amino acid transport system of the blood-brain barrier. This method appears as reliable as the original and more sensitive, as demonstrated by the comparison of normal and MPTP-treated animals under both conditions. C1 NIMH,NEUROPSYCHIAT BRANCH,BETHESDA,MD 20892. NIH,CC,NMD,BETHESDA,MD 20892. RP DOUDET, DJ (reprint author), NIMH,NEUROPSYCHOL LAB,IRP,LCM,CLIN BRAIN IMAGING SECT,BLDG 10 4N317,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 23 TC 8 Z9 8 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD JUL PY 1991 VL 32 IS 7 BP 1408 EP 1413 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA FV990 UT WOS:A1991FV99000025 PM 1906094 ER PT J AU GLADEN, BC ROGAN, WJ AF GLADEN, BC ROGAN, WJ TI EFFECTS OF PERINATAL POLYCHLORINATED-BIPHENYLS AND DICHLORODIPHENYL DICHLOROETHENE ON LATER DEVELOPMENT SO JOURNAL OF PEDIATRICS LA English DT Article ID MCCARTHY-SCALES; HUMAN-MILK; CHILDRENS ABILITIES; YOUNG-CHILDREN; PCBS; CONTAMINANTS; ACHIEVEMENT; MOTHERS; DDE; LACTATION AB Objective: Determining whether early developmental effects of perinatal exposure to polychlorinated biphenyls (PCBs) or dichlorodiphenyl dichloroethene (DDE) persist. Design: Cohort followed from birth; ages now 5 1/2 to 10 1/2 years. Setting: General community. Participants: Volunteer sample of 859 children, of whom 712 had been examined with the McCarthy Scales of Children's Abilities at 3, 4, or 5 years; 506 sent report cards. Interventions: None. Measurements and results: Neither transplacental nor breast-feeding exposure to PCBs or DDE affected McCarthy scores at 3, 4, or 5 years. There was no statistically significant relationship between poorer grades and PCB or DDE exposure by either route. Conclusions: The deficits seen in these children on the Bayley Scales of Infant Development through 2 years of age are no longer apparent. C1 NIEHS, EPIDEMIOL BRANCH, RES TRIANGLE PK, NC 27709 USA. RP GLADEN, BC (reprint author), NIEHS, STAT & BIOMATH BRANCH, MAIL DROP B3-02, POB 12233, RES TRIANGLE PK, NC 27709 USA. RI Rogan, Walter/I-6034-2012 OI Rogan, Walter/0000-0002-9302-0160 NR 19 TC 200 Z9 205 U1 0 U2 5 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 JUL PY 1991 VL 119 IS 1 BP 58 EP 63 DI 10.1016/S0022-3476(05)81039-X PN 1 PG 6 WC Pediatrics SC Pediatrics GA FV330 UT WOS:A1991FV33000010 PM 1906100 ER PT J AU CASSORLA, F LORIAUX, DL AF CASSORLA, F LORIAUX, DL TI REPLACEMENT DOSES OF GLUCOCORTICOIDS - REPLY SO JOURNAL OF PEDIATRICS LA English DT Letter C1 UNIV OREGON, MED, PORTLAND, OR 97201 USA. RP CASSORLA, F (reprint author), NICHHD, BETHESDA, MD 20892 USA. NR 5 TC 0 Z9 0 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 JUL PY 1991 VL 119 IS 1 BP 161 EP 161 DI 10.1016/S0022-3476(05)81065-0 PN 1 PG 1 WC Pediatrics SC Pediatrics GA FV330 UT WOS:A1991FV33000035 ER PT J AU DUNCAN, MW VILLACRESES, NE PEARSON, PG WYATT, L RAPOPORT, SI KOPIN, IJ MARKEY, SP SMITH, QR AF DUNCAN, MW VILLACRESES, NE PEARSON, PG WYATT, L RAPOPORT, SI KOPIN, IJ MARKEY, SP SMITH, QR TI 2-AMINO-3-(METHYLAMINO)-PROPANOIC ACID (BMAA) PHARMACOKINETICS AND BLOOD-BRAIN-BARRIER PERMEABILITY IN THE RAT SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID AMYOTROPHIC LATERAL SCLEROSIS; METHYLAMINO-L-ALANINE; ALPHA-AMINOISOBUTYRIC-ACID; OXALYLAMINO-L-ALANINE; MOTOR NEURON DISEASE; PARKINSONISM-DEMENTIA; CEREBROVASCULAR PERMEABILITY; CEREBROSPINAL-FLUID; CORTICAL-NEURONS; UNLIKELY CAUSE AB 2-Amino-3-(methylamino)-propanoic acid (BMAA) is a neurotoxic, excitatory amino acid which has been linked through cycad use and consumption with the onset of a variant of amyotrophic lateral sclerosis occurring with high incidence in the western Pacific region. We have studied BMAA pharmacokinetics, oral bioavailability and blood-brain barrier permeability in the rat in an attempt to better define the possible role for BMAA in this disease. To evaluate its kinetics and uptake, BMAA (25-400 mg/kg) was administered to rats, either acutely or chronically, and then plasma and brain concentrations were determined at various times thereafter by combined gas chromatography mass spectrometry. After single dose i.v. injection, BMAA was cleared from plasma in a rapid distribution phase (V(d) almost-equal-to 16 liters/kg) followed by a slower elimination phase (t1/2 almost-equal-to 1 day). Brain uptake was limited by a low blood-brain barrier permeability-surface area product of 2 to 5 x 10(-5) ml/sec/g. Brain BMAA levels peaked within 8 hr after injection, and then declined with a t1/2 similar to that of plasma. After two weeks of continuous infusion (100 mg/kg/day), steady-state brain concentrations equalled 10 to 30-mu-g/g, and only moderately exceeded those in plasma. The results suggest that BMAA may reach potentially toxic levels in brain (i.e., > 250-mu-M) after large doses (> 100 mg/kg). However, such doses are orders of magnitude greater than those available from dietary or medicinal use of cycads. C1 NINCDS,INTRAMURAL RES PROGRAM,BETHESDA,MD 20892. NIA,NEUROSCI LAB,NEUROCHEM & BRAIN TRANSPORT SECT,BETHESDA,MD 20892. NIMH,ANALYT BIOCHEM SECT,BETHESDA,MD 20892. NR 42 TC 39 Z9 39 U1 0 U2 8 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 JUL PY 1991 VL 258 IS 1 BP 27 EP 35 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA FZ156 UT WOS:A1991FZ15600005 PM 2072299 ER PT J AU STONE, M AF STONE, M TI TOWARD A MODEL OF 3-DIMENSIONAL TONGUE MOVEMENT SO JOURNAL OF PHONETICS LA English DT Article; Proceedings Paper CT 2ND INTERNATIONAL SEMINAR ON SPEECH PRODUCTION : MODELS AND DATA CY MAY 13-15, 1990 CL LEEDS, ENGLAND ID VOWELS; SHAPE; TENTACLES; TRUNKS RP STONE, M (reprint author), NIH,DEPT REHABIL MED,BLDG 10,ROOM 65235,BETHESDA,MD 20892, USA. NR 21 TC 34 Z9 36 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0095-4470 J9 J PHONETICS JI J. Phon. PD JUL-OCT PY 1991 VL 19 IS 3-4 BP 309 EP 320 PG 12 WC Linguistics; Language & Linguistics SC Linguistics GA FZ817 UT WOS:A1991FZ81700006 ER PT J AU HARDCASTLE, WJ GIBBON, F NICOLAIDIS, K RECASENS, D WOOD, SAS MUNHALL, KG OSTRY, DJ FLANAGAN, JR STONE, M AF HARDCASTLE, WJ GIBBON, F NICOLAIDIS, K RECASENS, D WOOD, SAS MUNHALL, KG OSTRY, DJ FLANAGAN, JR STONE, M TI VOCAL-TRACT ARTICULATION SO JOURNAL OF PHONETICS LA English DT Discussion C1 MCGILL UNIV,DEPT PSYCHOL,MONTREAL H3A 2T5,QUEBEC,CANADA. UNIV AUTONOMA BARCELONA,DEPT FILOL CATALANA,BARCELONA,SPAIN. INST ESTUDIS CATALANS,CEDI,E-08001 BARCELONA,SPAIN. UMEA UNIV,DEPT LINGUIST,S-90187 UMEA,SWEDEN. NIH,DEPT REHABIL MED,BETHESDA,MD 20892. QUEENS UNIV,DEPT PSYCHOL,KINGSTON K7L 3N6,ONTARIO,CANADA. RP HARDCASTLE, WJ (reprint author), UNIV READING,DEPT LINGUIST SCI,SPEECH RES LAB,READING RG6 2AH,BERKS,ENGLAND. RI Gibbon, Fiona/J-8255-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0095-4470 J9 J PHONETICS JI J. Phon. PD JUL-OCT PY 1991 VL 19 IS 3-4 BP 485 EP 486 PG 2 WC Linguistics; Language & Linguistics SC Linguistics GA FZ817 UT WOS:A1991FZ81700022 ER PT J AU JOHNSTON, LA DONOGHUE, AM OBRIEN, SJ WILDT, DE AF JOHNSTON, LA DONOGHUE, AM OBRIEN, SJ WILDT, DE TI INFLUENCE OF TEMPERATURE AND GAS ATMOSPHERE ON INVITRO FERTILIZATION AND EMBRYO DEVELOPMENT IN DOMESTIC CATS SO JOURNAL OF REPRODUCTION AND FERTILITY LA English DT Article DE CAT; FERTILIZATION; EMBRYO; INVITRO CULTURE; INCUBATION; TEMPERATURE; GAS ATMOSPHERE ID FOLLICULAR OOCYTES; MATURATION; CULTURE; SHEEP AB The influence of culture temperature and gas atmosphere on in-vitro fertilization and embryo development was examined in the domestic cat. In Exp. 1, eggs were fertilized and cultured in 5% CO2 in air at 37, 38 or 39-degrees-C. Experiment 2 evaluated the effects of 5% CO2 in air; 5% CO2, 5% O2 and 90% N2; and 10% CO2 in air. Fertilization (cleavage) and development to the morula/blastocyst stage were not influenced (P > 0.05) by variations in temperature and gas composition. Despite changing these culture conditions, egg cleavage averaged approximately 75% and > 80% of the 2-cell embryos proceeded to morulae in vitro. However, the partial in-vitro morula-to-blastocyst developmental block normally observed in this species was not removed. C1 SMITHSONIAN INST,NATL ZOOL PK,WASHINGTON,DC 20008. NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. FU NICHD NIH HHS [HD 23583] NR 28 TC 55 Z9 56 U1 1 U2 2 PU J REPROD FERTIL INC PI CAMBRIDGE PA 22 NEWMARKET RD, CAMBRIDGE, ENGLAND CB5 8DT SN 0022-4251 J9 J REPROD FERTIL JI J. Reprod. Fertil. PD JUL PY 1991 VL 92 IS 2 BP 377 EP 382 PG 6 WC Reproductive Biology SC Reproductive Biology GA FY689 UT WOS:A1991FY68900013 PM 1909365 ER PT J AU IGNARTROWBRIDGE, DM NELSON, KG ROSS, KA WASHBURN, TF KORACH, KS MCLACHLAN, JA AF IGNARTROWBRIDGE, DM NELSON, KG ROSS, KA WASHBURN, TF KORACH, KS MCLACHLAN, JA TI LOCALIZATION OF THE ESTROGEN-RECEPTOR IN UTERINE CELLS BY AFFINITY LABELING WITH [H-3] TAMOXIFEN AZIRIDINE SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Note ID PLASMA-MEMBRANE; BINDING; ESTRADIOL AB The possibility that estrogen receptors may exist in uterine plasma membranes was investigated by covalent labeling of estrogen receptors in mouse uterine cells with [H-3]tamoxifen aziridine (TA). Isolated epithelial and stromal cells of immature mice were incubated with [H-3]TA in the presence or absence of unlabeled tamoxifen, homogenized and separated into nuclear, cytosolic and microsomal fractions by differential centrifugation. These fractions were subjected to SDS-polyacrylamide gel electrophoresis and the proteins labeled covalently with TA were visualized by autoradiography. Proteins labeled specifically with [H-3]TA were observed almost exclusively in the nuclear fraction of both epithelial and stromal cells. In contrast, very little labeled protein was detected in the cytosolic or microsomal fraction. Although these data do not preclude the possibility that estrogen binding sites are present in plasma membranes of uterine cells, this cellular fraction is definitely not labeled to a significant extent by [H-3]TA. Thus, if membrane estrogen binding sites exist, their structural conformations may be different from that of nuclear estrogen receptors. C1 NIEHS,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC 27709. NR 10 TC 4 Z9 4 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-0760 J9 J STEROID BIOCHEM JI J. Steroid Biochem. Mol. Biol. PD JUL PY 1991 VL 39 IS 1 BP 131 EP 132 DI 10.1016/0960-0760(91)90021-V PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA FW528 UT WOS:A1991FW52800018 PM 2069860 ER PT J AU FISHER, ER LEEMING, R ANDERSON, S REDMOND, C FISHER, B AF FISHER, ER LEEMING, R ANDERSON, S REDMOND, C FISHER, B TI CONSERVATIVE MANAGEMENT OF INTRADUCTAL CARCINOMA (DCIS) OF THE BREAST SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article DE BREAST RECURRENCE; LUMPECTOMY; MULTICENTRICITY; COMEDO-NECROSIS; BREAST IRRADIATION ID COMPARING TOTAL MASTECTOMY; INSITU DUCTAL CARCINOMA; PATHOLOGIC FINDINGS; INVASIVE-CARCINOMA; PROJECT PROTOCOL-6; EXCISIONAL BIOPSY; RADIATION-THERAPY; FEMALE BREAST; FOLLOW-UP; CANCER AB Seventy-six patients with intraductal carcinoma (DCIS) of the breast have been observed for 83 months (range 50-141) following treatment by lumpectomy (L) only (21), L and breast irradiation (XRT) (27), or mastectomy (28). All represented examples of DCIS retrieved after pathologic examination of a much larger cohort of patients with stage I and II invasive breast cancer enrolled in NSABP protocol 6. Local breast recurrences were similar for women with DCIS and those from this cohort at a similar period of follow-up with invasive cancer treated by L only (43% vs. 39%) and L + XRT (7% vs. 10%). The presence of moderate/marked comedonecrosis was suggestively related to local breast recurrence (P = .07). This latter was significantly reduced for patients receiving post L XRT (P = .01). All local breast recurrences in this study and 29 of 31 recorded by others occurred at or close to the site of extirpation of the index cancer minimizing multicentricity as a contraindication for the conservative surgical treatment of DCIS. Survival rates which were similar for patients with DCIS regardless of form of local treatment were better than that observed for negative node patients with invasive cancer enrolled in protocol 6. Thus, DCIS is a less, not more, ominous disease than invasive cancer. This and other features of its natural history indicate that it would be a contradiction to treat invasive cancer but not DCIS conservatively. C1 NATL SURG ADJUVANT BREAST & BOWEL PROJECTS,PITTSBURGH,PA. UNIV PITTSBURGH,SCH MED,DEPT SURG,PITTSBURGH,PA 15261. UNIV PITTSBURGH,SCH PUBL HLTH,DEPT BIOSTAT,PITTSBURGH,PA 15260. MT SINAI HOSP,DEPT SURG,PITTSBURGH,PA. RP FISHER, ER (reprint author), SHADYSIDE HOSP,INST PATHOL,5230 CTR AVE,PITTSBURGH,PA 15232, USA. FU NCI NIH HHS [NCI-410-CA-120270] NR 35 TC 98 Z9 99 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 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD JUL PY 1991 VL 47 IS 3 BP 139 EP 147 DI 10.1002/jso.2930470302 PG 9 WC Oncology; Surgery SC Oncology; Surgery GA FZ183 UT WOS:A1991FZ18300001 PM 1649353 ER PT J AU CARTY, SE BURESH, CM NORTON, JA AF CARTY, SE BURESH, CM NORTON, JA TI DECREASED IL-6 SECRETION BY FIBROBLASTS FOLLOWING REPEATED DOSES OF TNF-ALPHA OR IL-1-ALPHA - POSTTRANSCRIPTIONAL GENE-REGULATION SO JOURNAL OF SURGICAL RESEARCH LA English DT Article; Proceedings Paper CT 1990 ANNUAL MEETING OF THE ASSOC FOR ACADEMIC SURGERY CY NOV 14-17, 1990 CL HOUSTON, TX SP ASSOC ACAD SURG ID TUMOR-NECROSIS-FACTOR; GROWTH-FACTOR; RECOMBINANT INTERLEUKIN-1; DERMAL FIBROBLASTS; MESSENGER-RNA; CYTOKINES; CACHECTIN; INDUCTION; CELLS; STIMULATION RP CARTY, SE (reprint author), NCI,SURG BRANCH,BETHESDA,MD 20892, USA. NR 47 TC 7 Z9 7 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD JUL PY 1991 VL 51 IS 1 BP 24 EP 32 DI 10.1016/0022-4804(91)90065-T PG 9 WC Surgery SC Surgery GA FW324 UT WOS:A1991FW32400005 PM 2067355 ER PT J AU PECK, GL DIGIOVANNA, JJ RUBINOW, DR AF PECK, GL DIGIOVANNA, JJ RUBINOW, DR TI ACUTE DEPRESSION FROM ISOTRETINOIN - REPLY SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Letter ID DARIERS DISEASE C1 NIMH,BETHESDA,MD 20892. RP PECK, GL (reprint author), NCI,DERMATOL BRANCH,BETHESDA,MD 20892, USA. NR 3 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JUL PY 1991 VL 25 IS 1 BP 132 EP 132 DI 10.1016/S0190-9622(08)80510-5 PN 1 PG 1 WC Dermatology SC Dermatology GA FV333 UT WOS:A1991FV33300026 ER PT J AU SWANGO, PA KLEINMAN, DV KONZELMAN, JL AF SWANGO, PA KLEINMAN, DV KONZELMAN, JL TI HIV AND PERIODONTAL HEALTH - A STUDY OF MILITARY PERSONNEL WITH HIV SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID ACQUIRED IMMUNODEFICIENCY SYNDROME; ORAL FINDINGS; HIGH-RISK; VIRUS; AIDS AB In 230 military personnel who were seropositive for the human immunodeficiency virus, the prevalence of viral and fungal infections in the mouth was clearly related to the degree of immune dysfunction as measured by T4-lymphocyte counts. The relation between periodontal health and T4 counts was less clear. Tobacco use was related to the increased occurrence of both mucosal lesions and periodontal diseases. C1 NIDR,EPIDEMIOL & ORAL DIS PREVENT PROGRAM,BETHESDA,MD 20892. RP SWANGO, PA (reprint author), NIDR,DEPT HLTH & HUMAN SERV,BETHESDA,MD 20892, USA. NR 18 TC 57 Z9 58 U1 0 U2 1 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD JUL PY 1991 VL 122 IS 8 BP 49 EP 54 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA FW383 UT WOS:A1991FW38300008 PM 1677647 ER PT J AU MESSINA, M MESSINA, V AF MESSINA, M MESSINA, V TI INCREASING USE OF SOYFOODS AND THEIR POTENTIAL ROLE IN CANCER PREVENTION SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID BIRK PROTEASE INHIBITOR; BREAST-CANCER; DIETARY HABITS; NIH-3T3 CELLS; MOUSE COLON; GENISTEIN; ESTROGENS; GROWTH; TUMORS; FOODS AB The United States produces approximately half of the world's soybeans. Although most of what is produced is used as animal feed, soy-protein products (eg, soy-protein flour, concentrates, and isolates) are used extensively by the food industry, primarily for their functional characteristics, such as emulsification. During the past decade, however, there has been a marked increase in the use of both traditional soyfoods, such as tofu and soymilk, and second-generation soyfoods, products which generally simulate familiar American dishes. Recently, attention has focused on the possible role of soybean consumption in reducing cancer risk. Soybeans contain, in relatively high concentrations, several compounds with demonstrated anticarcinogenic activity. Two of these compounds-protease inhibitors and phytic acid-have traditionally been viewed as antinutrients. The scientific community has begun to appreciate the potential importance of nonnutritive dietary compounds (phytochemicals) in foods such as soybeans. Dietitians need to become more aware of the phytochemical content of foods and the possible effect of phytochemicals on health and disease. RP MESSINA, M (reprint author), NCI,DIV CANC PREVENT & CONTROL,DIET & CANCER BRANCH,BETHESDA,MD 20892, USA. NR 55 TC 101 Z9 103 U1 0 U2 6 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 JUL PY 1991 VL 91 IS 7 BP 836 EP 840 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA FW388 UT WOS:A1991FW38800016 PM 2071799 ER PT J AU PACKER, RK DESAI, SS HORNBUCKLE, K KNEPPER, MA AF PACKER, RK DESAI, SS HORNBUCKLE, K KNEPPER, MA TI ROLE OF COUNTERCURRENT MULTIPLICATION IN RENAL AMMONIUM HANDLING - REGULATION OF MEDULLARY AMMONIUM ACCUMULATION SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article DE AMMONIA EXCRETION; COUNTERCURRENT MECHANISM; RENAL ACID-BASE BALANCE; RENAL MEDULLARY AMMONIA GRADIENT ID THICK ASCENDING LIMB; RAT; TRANSPORT; KIDNEY; ABSORPTION; INHIBITION; POTASSIUM AB Ammonium (NH3 plus NH4+), produced predominantly in the proximal tubule, is transferred to the final urine by a process involving countercurrent multiplication of ammonium which generates an ammonium concentration gradient in the renal medulla. It was hypothesized that if urinary ammonium excretion rates are controlled in part by the medullary ammonium gradient, changes in hydration and acid-base state should cause changes in the medullary ammonium gradient consistent with expected changes in urinary ammonium concentrations. To test that hypothesis, rats were subjected to water diruesis, water deprivation, water deprivation plus furosemide, and dietary acid and base loads and corticomedullary ammonium gradients in their kidneys were then measured. Sections were cut along the corticomedullary axis to yield slices of cortex, outer stripe of outer medulla, inner stripe of outer medulla, and three levels of the inner medulla. The total ammonia content of homogenized slices was measured by either a membrane ammonia electrode or an enzymatic technique. Kidneys from water-deprived animals showed a distinct ammonium gradient along the corticomedullary axis, with the highest contents found at the tip of the papilla. The gradient was attenuated by water diuresis and abolished by furosemide. Acid loading enhanced the gradient, and base loading abolished it. These results indicate that the corticomedullary ammonium gradient is regulated in response to changes in hydration and acid-base state. C1 NHLBI,KIDNEY & ELECTROLYTE METAB,BETHESDA,MD 20892. RP PACKER, RK (reprint author), GEORGE WASHINGTON UNIV,DEPT BIOL SCI,307 LISNER HALL,WASHINGTON,DC 20052, USA. NR 15 TC 32 Z9 32 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JUL PY 1991 VL 2 IS 1 BP 77 EP 83 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA FZ094 UT WOS:A1991FZ09400009 PM 1912412 ER PT J AU SWAIN, JA MCDONALD, TJ GRIFFITH, PK BALABAN, RS CLARK, RE CECKLER, T AF SWAIN, JA MCDONALD, TJ GRIFFITH, PK BALABAN, RS CLARK, RE CECKLER, T TI LOW-FLOW HYPOTHERMIC CARDIOPULMONARY BYPASS PROTECTS THE BRAIN SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 70TH ANNUAL MEETING OF THE AMERICAN ASSOC FOR THORACIC SURGERY CY MAY 07-09, 1990 CL TORONTO, CANADA SP AMER ASSOC THORAC SURG ID NUCLEAR-MAGNETIC-RESONANCE; CIRCULATORY ARREST; PROFOUND HYPOTHERMIA; RAT-BRAIN; INTRACELLULAR PH; DEEP HYPOTHERMIA; BLOOD-FLOW; PERFUSION; CHILDREN; METABOLISM AB Cerebral protection during surgical procedures necessitating circulatory arrest or low flow remains the factor that most limits the critical time for repair of lesions. In vivo phosphorus-31 nuclear magnetic resonance spectroscopy was used to assess the metabolic state of the brain during circulatory arrest by measuring the concentration of high-energy phosphate compounds and the intracellular pH. The degree of cerebral protection during deep hypothermic cardiopulmonary bypass at low flow rates was compared with that obtained with a period of circulatory arrest interrupted by intermittent systemic perfusion. Sheep were instrumented with cannulas for cardiopulmonary bypass, and a radiofrequency coil was positioned on the skull. Animals were placed in the bore of a 4.7 Tesla magnet, cooled with the aid of cardiopulmonary bypass to 15-degrees-C, and had either circulatory arrest (n = 5) or continuous low flow rates of 5 ml/kg/min (n = 6) or 10 ml/kg/min (n = 7) for 2 hours. A fourth group (n = 5) underwent 1 hour of circulatory arrest, systemic reperfusion for 30 minutes, then another hour of circulatory arrest. Both circulatory arrest and a flow rate of 5 ml/kg/min resulted in severe intracellular acidosis and depletion of high-energy phosphates. A flow of 10 ml/kg/min preserved high-energy phosphates and intracellular pH. Therefore deep hypothermia with cardiopulmonary bypass flows as low as 10 ml/kg/min can maintain brain high-energy phosphate concentrations and intracellular pH for 2 hours in sheep, whereas flows of 5 ml/kg/min or intermittent full-flow systemic perfusion between periods of circulatory arrest offers less protection. Previous studies from our laboratory have shown that improvement in nuclear magnetic resonance parameters positively correlates with improved survival and preservation of neurologic function. C1 NHLBI,SURG BRANCH,BETHESDA,MD 20892. NR 34 TC 108 Z9 111 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD JUL PY 1991 VL 102 IS 1 BP 76 EP 84 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA FW773 UT WOS:A1991FW77300010 PM 2072731 ER PT J AU PERRY, LL LODMELL, DL AF PERRY, LL LODMELL, DL TI ROLE OF CD4+ AND CD8+ T-CELLS IN MURINE RESISTANCE TO STREET RABIES VIRUS SO JOURNAL OF VIROLOGY LA English DT Article ID EXPERIMENTAL AUTOIMMUNE-THYROIDITIS; MONOCLONAL-ANTIBODIES; NERVOUS-SYSTEM; MICE; GLYCOPROTEIN; IMMUNITY; PROTECTION; INDUCTION; DEPLETION; L3T4+ AB Mice of the SJL/J and BALB/cByJ inbred strains are naturally resistant to street rabies virus (SRV) injected via the intraperitoneal route. To determine the cellular mechanism of resistance, monoclonal antibodies specific for CD4+ or CD8+ subsets of T cells were used to deplete the respective cell population in SRV-infected animals. Elimination of CD4+ T-helper cells abrogated the production of immunoglobulin G (IgG) neutralizing antibodies in response to rabies virus infection and reversed the resistant status of SJL/J and BALB/cByJ mice. In contrast, in vivo depletion of CD8+ cytotoxic T cells had no measurable effect on host resistance to SRV. These results indicate that serum neutralizing antibodies of the IgG class are a primary immunological mechanism of defense against rabies virus infection in this murine model of disease. CD8+ cytotoxic T lymphocytes, which have been shown to transfer protection in other rabies virus systems, appear to have no role in protecting mice against intraperitoneally injected SRV. C1 NIAID,ROCKY MT LABS,PERISTENT VIRAL DIS LAB,HAMILTON,MT 59840. NR 39 TC 55 Z9 58 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 JUL PY 1991 VL 65 IS 7 BP 3429 EP 3434 PG 6 WC Virology SC Virology GA FQ940 UT WOS:A1991FQ94000003 PM 1674967 ER PT J AU CARROLL, R MARTARANO, L DERSE, D AF CARROLL, R MARTARANO, L DERSE, D TI IDENTIFICATION OF LENTIVIRUS TAT FUNCTIONAL DOMAINS THROUGH GENERATION OF EQUINE INFECTIOUS-ANEMIA VIRUS HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 TAT GENE CHIMERAS SO JOURNAL OF VIROLOGY LA English DT Article ID LONG TERMINAL REPEAT; ACTIVATION-RESPONSIVE REGION; III HTLV-III; TRANS-ACTIVATION; HIV-1 TAT; MUTATIONAL ANALYSIS; TRANSCRIPTIONAL REGULATION; MESSENGER-RNA; NUCLEOTIDE-SEQUENCE; GENOME ORGANIZATION AB The structural regions that comprise the functional domains of lentivirus Tat proteins were examined. Chimeric tat genes and chimeric viral promoters were constructed between the distantly related human immunodeficiency virus type 1 (HIV-1) and equine infectious anemia virus (EIAV). These exchange experiments revealed that the EIAV Tat-responsive element recognition domain is formed by two distinct structural regions. Activation domains of both HIV-1 and EIAV Tat contain a conserved core element, but at least HIV-1 Tat requires the presence of additional structural regions. The interchangeable nature of Tat activation domains suggests that these domains act through a common or ubiquitous cellular transcription factor. C1 NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. NCI,PRIDYN CORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD. FU NCI NIH HHS [N01-CO-74102] NR 65 TC 82 Z9 83 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 1991 VL 65 IS 7 BP 3460 EP 3467 PG 8 WC Virology SC Virology GA FQ940 UT WOS:A1991FQ94000007 PM 1645777 ER PT J AU CARVALHO, M DERSE, D AF CARVALHO, M DERSE, D TI MUTATIONAL ANALYSIS OF THE EQUINE INFECTIOUS-ANEMIA VIRUS TAT-RESPONSIVE ELEMENT SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; LONG TERMINAL REPEAT; TRANS-ACTIVATION; HIV-1 TAT; GENE-EXPRESSION; NUCLEAR-PROTEIN; LOOP SEQUENCE; RNA; REGION; TYPE-1 AB A hairpinlike structure is predicted to exist at the 5' end of equine infectious anemia virus (EIAV) RNA which is similar in many ways to the human immunodeficiency type 1 (HIV-1) Tat-responsive element (TAR). In EIAV, this structure has a shorter stem than in HIV-1 and lacks the uridine bulge. Primer extension analysis of EIAV RNA was used to identify the transcriptional start site in the viral long terminal repeat. Premature termination of primer elongation at the predicted double-stranded RNA region was frequently observed and suggests that the inferred hairpin structure exists under these conditions. We have functionally characterized EIAV TAR by site-directed mutagenesis and transient gene expression analysis. It is demonstrated here that the secondary structure of this element is essential for Tat action. Mutations that disrupted base pairing abolished TAR function, and compensatory mutations that restored the stem structure resulted in Tat activation. The TAR loop appears to be closed by two U . G base pairs that are likely to provide a unique structural motif recognized by the Tat protein. With one exception, substitutions of nucleotides within the EIAV loop sequence decreased TAR function. All nucleotide substitutions of the cytidine at position +14 increased EIAV Tat responsiveness; however, its deletion abolished trans activation. Our results lead us to propose that the EIAV and HIV-1 Tat systems employ closely related cis- and trans-acting components that probably act by the same mechanism. C1 NCI,FREDERICK CANC RES FACIL,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21701. NR 39 TC 51 Z9 56 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 JUL PY 1991 VL 65 IS 7 BP 3468 EP 3474 PG 7 WC Virology SC Virology GA FQ940 UT WOS:A1991FQ94000008 PM 1645778 ER PT J AU WOLFF, L KOLLER, R DAVIDSON, W AF WOLFF, L KOLLER, R DAVIDSON, W TI ACUTE MYELOID-LEUKEMIA INDUCTION BY AMPHOTROPIC MURINE RETROVIRUS (4070A) - CLONAL INTEGRATIONS INVOLVE C-MYB IN SOME BUT NOT ALL LEUKEMIAS SO JOURNAL OF VIROLOGY LA English DT Article ID LONG TERMINAL REPEAT; FOCUS-INDUCING VIRUSES; B-CELL LYMPHOMAS; NUCLEOTIDE-SEQUENCE; INSERTIONAL MUTAGENESIS; HEMATOPOIETIC-CELLS; MESSENGER-RNA; BALB/C MICE; V-MYB; ACTIVATION AB Amphotropic murine retrovirus 4070A was demonstrated to be highly leukemogenic when inoculated intravenously into adult DBA/2 mice that were undergoing an intense chronic inflammatory response, but was nonleukemogenic in the absence of inflammation. The virus-induced promonocytic leukemias, designated AMPH-ML, are similar morphologically and in cell surface marker expression to monocytic leukemias, called MML and MF-ML, previously shown to be induced by Moloney murine leukemia virus and MF-3 virus (a recombinant between Friend murine leukemia virus and Moloney murine leukemia virus) and resemble certain mature acute monocytic leukemias in humans (AML subtype M5). Approximately two-thirds of the AMPH-MLs (subgroup I) were demonstrated to have alterations in the 5' end of the c-myb locus, an event which occurs in 100% of MML and MF-ML. Data indicate that proviral insertions in AMPH-ML subgroup I resulted in aberrant c-myb mRNA expression and truncation of its translation product at the amino terminus. Approximately one-third of the AMPH-MLs (subgroup II) had not undergone any DNA rearrangements at the c-myb locus. In addition, their transcripts and protein products were of normal size. These latter leukemias also had not undergone DNA rearrangements in c-myc, although retroviruses expressing myc have previously been shown to induce monocyte-macrophage tumors in mice undergoing a chronic inflammation. That subgroup II luekemias had at least one clonal viral insertion suggests that there may be other sites in the cellular genome that can be activated by insertional mutagenesis in these murine acute monocytic leukemias. RP WOLFF, L (reprint author), NCI, GENET LAB, BETHESDA, MD 20892 USA. NR 43 TC 38 Z9 38 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 1991 VL 65 IS 7 BP 3607 EP 3616 PG 10 WC Virology SC Virology GA FQ940 UT WOS:A1991FQ94000026 PM 1645785 ER PT J AU WRIGHT, CF KECK, JG TSAI, MM MOSS, B AF WRIGHT, CF KECK, JG TSAI, MM MOSS, B TI A TRANSCRIPTION FACTOR FOR EXPRESSION OF VACCINIA VIRUS LATE GENES IS ENCODED BY AN INTERMEDIATE GENE SO JOURNAL OF VIROLOGY LA English DT Article ID DNA-REPLICATION; INVITRO; HEAD; RNA AB A factor, designated VLTF-1, that is required in vitro for specific transcription of vaccinia virus late genes was previously isolated from vaccinia virus-infected cells. Subsequent genetic experiments identified three vaccinia virus genes, encoding proteins of 17, 26, and 30 kDa, that together trans activate late gene expression in vivo. The purpose of this study was to determine whether VLTF-1 corresponded to one of the three trans activators. Toward this end, VLTF-1 was further purified, the trans-activator genes were expressed in Escherichia coli, and antisera were made to the native and recombinant proteins. Antibody to the 30-kDa recombinant protein reacted on Western immunoblots with a protein of approximately M(r) 30,000 that cochromatographed and cosedimented with VLTF-1 activity from virus-infected cells. Conversely, antibody to purified VLTF-1 bound to products produced by in vitro transcription and translation of the open reading frame encoding the 30-kDa trans-activator protein. Both antisera depleted VLTF-1 activity and blocked late gene transcription by partially purified extracts of vaccinia virus-infected cells. Taken together, these data demonstrate that the 30-kDa trans activator comprises part, if not all, of VLTF-1 activity. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. RP WRIGHT, CF (reprint author), ARMED FORCES INST PATHOL,DEPT CELLULAR PATHOL,AMER REGISTRY PATHOL,WASHINGTON,DC 20306, USA. FU NIAID NIH HHS [AI31220-01] NR 13 TC 35 Z9 36 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 JUL PY 1991 VL 65 IS 7 BP 3715 EP 3720 PG 6 WC Virology SC Virology GA FQ940 UT WOS:A1991FQ94000038 PM 2041091 ER PT J AU PETROPOULOS, CJ HUGHES, SH AF PETROPOULOS, CJ HUGHES, SH TI REPLICATION-COMPETENT RETROVIRUS VECTORS FOR THE TRANSFER AND EXPRESSION OF GENE CASSETTES IN AVIAN CELLS SO JOURNAL OF VIROLOGY LA English DT Article ID LONG TERMINAL REPEATS; ROUS-SARCOMA VIRUS; CHICKEN GERM LINE; ENHANCER ACTIVITY; FPS-GENE; TRANSFORMATION; SEQUENCES; INSERTION; PROMOTER; TUMORS AB We have constructed a series of replication-competent retrovirus vectors to introduce and express gene cassettes in avian cells. To characterize these vectors, we inserted the coding sequences for the bacterial chloramphenicol acetyltransferase (CAT) gene linked to the chicken beta-actin gene promoter or the mouse metallothionein 1 gene promoter. In all cases, we found the structure of integrated proviruses to be stable during serial cell passage in vitro. Chloramphenicol acetyltransferase activity was detected biochemically and immunocytochemically in infected cells. Cassettes were inserted in the vectors in the same or in the opposite orientation with respect to viral transcription. Although both orientations were functional, the cassettes inserted in the forward orientation were usually expressed at higher levels than the corresponding backward constructions. The level of expression was strongly influenced by surrounding proviral sequences, particularly by the transcriptional enhancer elements within the retrovirus long terminal repeat sequences. Expression was higher with vectors that contained the polymerase (pol) region of the Bryan high-titer strain of Rous sarcoma virus. Inclusion of the Bryan pol region also improved vector replication in the chemically transformed quail fibroblast line QT6. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,POB B,FREDERICK,MD 21702. FU PHS HHS [N01-C0-74101] NR 38 TC 149 Z9 152 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 1991 VL 65 IS 7 BP 3728 EP 3737 PG 10 WC Virology SC Virology GA FQ940 UT WOS:A1991FQ94000040 PM 2041092 ER PT J AU THOMAS, DJ WALL, JS HAINFELD, JF KACZOREK, M BOOY, FP TRUS, BL EISERLING, FA STEVEN, AC AF THOMAS, DJ WALL, JS HAINFELD, JF KACZOREK, M BOOY, FP TRUS, BL EISERLING, FA STEVEN, AC TI GP160, THE ENVELOPE GLYCOPROTEIN OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1, IS A DIMER OF 125-KILODALTON SUBUNITS STABILIZED THROUGH INTERACTIONS BETWEEN THEIR GP41 DOMAINS SO JOURNAL OF VIROLOGY LA English DT Article ID TRANSMISSION ELECTRON-MICROSCOPE; HAMSTER OVARY CELLS; OLIGOMERIC STRUCTURE; GLUTAMINE-SYNTHETASE; NUCLEOTIDE-SEQUENCE; AIDS PATIENTS; HTLV-III; HIV; PROTEIN; ANTIBODIES AB The molecular masses, carbohydrate contents, oligomeric status, and overall molecular structure of the env glycoproteins of human immunodeficiency virus type 1-gp120, gp160, and gp41-have been determined by quantitative electron microscopy. Using purified gp160s, a water-soluble form of env purified from a recombinant vaccinia virus expression system, we have measured the masses of several hundred individual molecules by dark-field scanning transmission electron microscopy. When combined with sequence-based information, these mass measurements establish that gp160s is a dimer of subunits with an average monomer mass of 123 kDa, of which approximately 32 kDa is carbohydrate and 91 kDa is protein. Similarly, gp120 was found to be a monomer of 89 kDa and to contain virtually all of env's glycosylation. gp41 is glycosylated only slightly, if at all, and is responsible for the interactions that stabilize the gp160s dimer. A molecular mass map of gp160s derived by image processing depicts an asymmetric dumbbell whose two domains have masses of approximately 173 and approximately 73 kDa, corresponding to a gp120 dimer and a gp41 dimer, respectively. We infer that the average monomer mass of native gp160 is 125 kDa and that in situ, env is either a dimer or a tetramer but is most unlikely to be a trimer. C1 NIAMSD,STRUCT BIOL RES LAB,BLDG 6,ROOM 114,BETHESDA,MD 20892. NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. UNIV RENNES 1,BIOL CELLULAIRE LAB,CNRS,URA 256,F-35042 RENNES,FRANCE. PASTEUR MERIEUX,RES & DEV,F-27101 VAL DE REUIL,FRANCE. BROOKHAVEN NATL LAB,DEPT BIOL,UPTON,NY 11973. UNIV CALIF LOS ANGELES,DEPT MOLEC BIOL,LOS ANGELES,CA 90024. FU NCRR NIH HHS [RR01777]; NIAID NIH HHS [AI25319] NR 46 TC 70 Z9 70 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 JUL PY 1991 VL 65 IS 7 BP 3797 EP 3803 PG 7 WC Virology SC Virology GA FQ940 UT WOS:A1991FQ94000047 PM 2041094 ER PT J AU GENDELMAN, HE EHRLICH, GD BACA, LM CONLEY, S RIBAS, J KALTER, DC MELTZER, MS POIESZ, BJ NARA, P AF GENDELMAN, HE EHRLICH, GD BACA, LM CONLEY, S RIBAS, J KALTER, DC MELTZER, MS POIESZ, BJ NARA, P TI THE INABILITY OF HUMAN-IMMUNODEFICIENCY-VIRUS TO INFECT CHIMPANZEE MONOCYTES CAN BE OVERCOME BY SERIAL VIRAL PASSAGE INVIVO SO JOURNAL OF VIROLOGY LA English DT Article ID LYMPHADENOPATHY-ASSOCIATED VIRUS; T-LYMPHOTROPIC RETROVIRUSES; SEROLOGICAL RESPONSES; PERSISTENT INFECTION; AIDS; PATHOGENESIS; MACROPHAGES; ENVELOPE; TRANSMISSION; REPLICATION AB Studies of lentivirus infection in ruminants, nonhuman primates, and humans suggest that virus infection of macrophages plays a central role in the disease process. To investigate whether human immunodeficiency virus type 1 (HIV-1) can infect chimpanzee macrophages, we recovered monocytes from peripheral blood mononuclear cells of HIV-1-negative animals and inoculated these and control human monocytes with a panel of four human-passaged monocytotropic virus strains and one chimpanzee-passaged isolate. HIV-1-infected human monocytes synthesized proviral DNA, viral mRNA, p24 antigen, and progeny virions. In contrast, except for the chimpanzee-passaged HIV-1 isolate, chimpanzee monocytes failed to support HIV-1 replication when cultured under both identical and a variety of other conditions. Proviral DNA was demonstrated only at background levels in these cell cultures by polymerase chain reaction for gag- and env-related sequences. Interestingly, the chimpanzee-passaged HIV-1 isolate did not replicate in human monocytes; viral p24 antigens and progeny virions were not detected. The same monocytotropic panel of HIV-1 strains replicated in both human and chimpanzee CD4+ T lymphoblasts treated with phytohemagglutinin and interleukin-2. The failure of HIV-1 to infect chimpanzee monocytes, which can be overcome by serial in vivo viral passage, occurs through a block early in the viral life cycle. C1 NCI,FREDERICK CANC RES DEV CTR,TUMOR CELL BIOL LAB,VIRUS BIOL SECT,FREDERICK,MD 21701. HENRY M JACKSON FDN ADV MIL MED,ROCKVILLE,MD 20852. WALTER REED ARMY MED CTR,DEPT CELLULAR IMMUNOL,HIV IMMUNOPATHOGENESIS PROGRAM,WASHINGTON,DC 20307. ARMED FORCES INST PATHOL,WASHINGTON,DC 20306. SUNY HLTH SCI CTR,DIV HEMATOL & ONCOL,SYRACUSE,NY 13210. NCI,PROGRAM RESOURCES INC,FREDERICK,MD 21701. FU NCI NIH HHS [N01-CO-74102]; NHLBI NIH HHS [N01-HB-67021] NR 37 TC 36 Z9 36 U1 2 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 1991 VL 65 IS 7 BP 3853 EP 3863 PG 11 WC Virology SC Virology GA FQ940 UT WOS:A1991FQ94000053 PM 1674968 ER PT J AU WHITCOMB, JM HUGHES, SH AF WHITCOMB, JM HUGHES, SH TI THE SEQUENCE OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-2 CIRCLE JUNCTION SUGGESTS THAT INTEGRATION PROTEIN CLEAVES THE ENDS OF LINEAR DNA ASYMMETRICALLY SO JOURNAL OF VIROLOGY LA English DT Note ID MURINE LEUKEMIA-VIRUS; RETROVIRAL DNA; NUCLEOTIDE-SEQUENCE; VIRAL-DNA; TERMINAL NUCLEOTIDES; AIDS VIRUS; INVITRO; SITE; CELL; RECOMBINATION AB The sequence of the human immunodeficiency virus type 2 circle junction was determined. The most common sequence found between the conserved CA and TG dinucleotides at the ends of the integrated provirus was five bases long (GGTAC). This suggests that the integration of human immunodeficiency virus type 2 DNA is accompanied by the asymmetric loss of two and three bases, respectively, from the U3 and U5 ends of the linear double-stranded DNA prior to integration. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,POB B,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101] NR 34 TC 18 Z9 18 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 1991 VL 65 IS 7 BP 3906 EP 3910 PG 5 WC Virology SC Virology GA FQ940 UT WOS:A1991FQ94000063 PM 2041100 ER PT J AU OBERSTE, MS GREENWOOD, JD GONDA, MA AF OBERSTE, MS GREENWOOD, JD GONDA, MA TI ANALYSIS OF THE TRANSCRIPTION PATTERN AND MAPPING OF THE PUTATIVE REV AND ENV SPLICE JUNCTIONS OF BOVINE IMMUNODEFICIENCY-LIKE VIRUS SO JOURNAL OF VIROLOGY LA English DT Note ID BIOLOGICALLY-ACTIVE PROVIRUSES; T-LYMPHOTROPIC RETROVIRUS; INFECTIOUS-ANEMIA VIRUS; VIRAL MESSENGER-RNA; METAL-LINKED DIMER; VISNA VIRUS; TAT PROTEIN; GENE-PRODUCT; MOLECULAR-CLONING; HTLV-III AB The bovine immunodeficiency-like virus (BIV) genome contains the obligatory structural genes of all retroviruses and, in addition, the complex central region of lentiviruses; this novel region may code for at least five nonstructural/regulatory genes in BIV (K. J. Garvey, M.S. Oberste, J. E. Elser, M. J. Braun, and M. A. Gonda, Virology 175:391-409, 1990). As a prelude to determining the function of these novel open reading frames, the transcriptional pattern of BIV was studied by Northern analysis of RNA from BIV-infected cells. Five size classes of BIV-specific RNAs of 8.5, 4.1, 3.8, 1.7, and 1.4 kb were detected. The 8.5-kb RNA contains sequences from all regions of the genome; it is the virion RNA and probably serves as the gag-pol transcript as well. By using gene-specific probes, subgenomic viral RNAs of 3.8, 1.7, and 1.4 kb were tentatively identified as the env, tat, and rev spliced messages, respectively. The 4.1-kb RNA could not be unambiguously identified but may encode vif. The hybridization patterns of the putative tat and rev mRNAs suggest that they are the products of multiple splicing events. Discrete transcripts for the BIV W and Y central region open reading frames were not defined. The characterization of partial cDNA clones has permitted the mapping of the env and putative rev splice junctions. C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC,CELL & MOLEC STRUCT LAB,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74102] NR 47 TC 40 Z9 43 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 JUL PY 1991 VL 65 IS 7 BP 3932 EP 3937 PG 6 WC Virology SC Virology GA FQ940 UT WOS:A1991FQ94000069 PM 1645801 ER PT J AU MARCON, L MICHAELS, F HATTORI, N FARGNOLI, K GALLO, RC FRANCHINI, G AF MARCON, L MICHAELS, F HATTORI, N FARGNOLI, K GALLO, RC FRANCHINI, G TI DISPENSABLE ROLE OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-2 VPX PROTEIN IN VIRAL REPLICATION SO JOURNAL OF VIROLOGY LA English DT Note ID T-LYMPHOTROPIC RETROVIRUS; HTLV-III; PERSISTENT INFECTION; RHESUS-MONKEYS; HIV-2; AIDS; GENE; MACAQUES; SIV; SEQUENCE AB Human immunodeficiency virus type 2 (HIV-2) is similar in genetic organization to HIV-1 but contains a unique gene (vpx) that encodes a 16-kDa protein. A replication-competent molecular clone of HIV-2 (HIV-2sbl/isy) that infects human primary cells in vitro and rhesus monkeys was used to generate three mutations in the vpx gene. In the first mutant, the vpx open reading frame was truncated at amino acid 20; the second mutant was tailored to eliminate the proline-rich carboxyl terminus of the protein; and the third mutant was obtained by addition of four amino acids (KDEL) to the carboxyl terminus of the protein to provide a retention signal in the endoplasmic reticulum. The viral infection kinetics of the three mutant viruses and isogeneic HIV-2sbl/isy in the SupT1 cell line were similar. Slight impairment in the early phases of viral replication was observed during infection of primary human peripheral blood mononuclear cells with the vpx mutant viruses. All of the vpx mutant viruses readily infected macrophages, indicating that vpx expression is dispensable for HIV-2 infection and replication in human macrophages. C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. NR 33 TC 29 Z9 29 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 JUL PY 1991 VL 65 IS 7 BP 3938 EP 3942 PG 5 WC Virology SC Virology GA FQ940 UT WOS:A1991FQ94000070 PM 2041103 ER PT J AU MUNGER, K YEE, CL PHELPS, WC PIETENPOL, JA MOSES, HL HOWLEY, PM AF MUNGER, K YEE, CL PHELPS, WC PIETENPOL, JA MOSES, HL HOWLEY, PM TI BIOCHEMICAL AND BIOLOGICAL DIFFERENCES BETWEEN E7 ONCOPROTEINS OF THE HIGH-RISK AND LOW-RISK HUMAN PAPILLOMAVIRUS TYPES ARE DETERMINED BY AMINO-TERMINAL SEQUENCES SO JOURNAL OF VIROLOGY LA English DT Note ID RETINOBLASTOMA GENE-PRODUCT; ADENOVIRUS E1A PROTEINS; CERVICAL-CARCINOMA; MUTATIONAL ANALYSIS; HUMAN KERATINOCYTES; TRANSFORMING GENE; BINDING; SV40; CELLS; DNA AB Differences in the biological characteristics of the high-risk human papillomavirus type 16 (HPV-16) and the low-risk HPV-6 E7 proteins were analyzed and shown to correlate with certain biochemical properties. To ascertain which region of E7 conferred these properties, chimeric E7 genes were constructed by the exchange of the amino and carboxyl coding halves of the HPV-6 and HPV-16 E7 genes. The amino-terminal half of E7 determined the affinity for binding to the retinoblastoma protein pRB, the transformation properties, and the ability to abrogate transforming growth factor beta-mediated repression of the c-myc promoter. This region of E7 is therefore responsible for the biological and biochemical differences between the E7 proteins of the low-risk and the high-risk HPVs and consequently is one of the critical determinants distinguishing these two groups of viruses. Transcriptional transactivation of the adenovirus E2 promoter, in contrast, was a property shared by E7 proteins of both low-risk and high-risk HPVs. C1 BURROUGHS WELLCOME CO,DIV VIROL,RES TRIANGLE PK,NC 27709. VANDERBILT UNIV,MED CTR,SCH MED,DEPT CELL BIOL,NASHVILLE,TN 37232. RP MUNGER, K (reprint author), NCI,TUMOR VIRUS BIOL LAB,BETHESDA,MD 20892, USA. OI Munger, Karl/0000-0003-3288-9935 FU NCI NIH HHS [CA-42572] NR 40 TC 104 Z9 106 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 1991 VL 65 IS 7 BP 3943 EP 3948 PG 6 WC Virology SC Virology GA FQ940 UT WOS:A1991FQ94000071 PM 1645802 ER PT J AU FERNIE, BF POLI, G FAUCI, AS AF FERNIE, BF POLI, G FAUCI, AS TI ALPHA-INTERFERON SUPPRESSES VIRION BUT NOT SOLUBLE HUMAN-IMMUNODEFICIENCY-VIRUS ANTIGEN PRODUCTION IN CHRONICALLY INFECTED T-LYMPHOCYTIC CELLS SO JOURNAL OF VIROLOGY LA English DT Note ID ENVELOPE GLYCOPROTEIN; HTLV-III; EXPRESSION; HIV; REPLICATION; CLONE; AIDS; MACROPHAGES; INVITRO; SURFACE AB Alpha interferon (IFN-alpha) is effective in preventing the release of human immunodeficiency virus (HIV) from chronically infected T-lymphocytic (ACH-2) and promonocytic (U1) cell lines stimulated with the phorbol ester phorbol-12-myristate-13 acetate (PMA). In the present study, we observed that together with particle production, shedding of HIV antigen (p24gag) occurs in the T-cell line ACH-2 both constitutively and after stimulation with PMA. IFN-alpha, although effective in suppressing the release of HIV particles, did not inhibit shedding of p24gag into the culture supernatants of either unstimulated or PMA-stimulated cells. These observations may be of relevance in the evaluation of the in vivo efficacy of IFN-alpha-treatment of HIV-infected individuals as determined by levels of p24 antigen in plasma. C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. GEORGETOWN UNIV,DEPT MICROBIOL,DIV MOLEC VIROL & IMMUNOL,ROCKVILLE,MD 20852. FU NIAID NIH HHS [N01-AI-72623] NR 28 TC 56 Z9 58 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 JUL PY 1991 VL 65 IS 7 BP 3968 EP 3971 PG 4 WC Virology SC Virology GA FQ940 UT WOS:A1991FQ94000076 PM 1710293 ER PT J AU EFFROS, RB WALFORD, RL WEINDRUCH, R MITCHELTREE, C AF EFFROS, RB WALFORD, RL WEINDRUCH, R MITCHELTREE, C TI INFLUENCES OF DIETARY RESTRICTION ON IMMUNITY TO INFLUENZA IN AGED MICE SO JOURNALS OF GERONTOLOGY LA English DT Article ID MIXED LYMPHOCYTE-REACTION; CELLS; MACROPHAGES; EXPRESSION; EXTENSION; DECLINE AB Our previous studies of the immune response of aged mice inoculated with influenza A virus revealed age-related decreases in antigen-specific cytotoxic T-lymphocyte function (CTL), T-cell proliferation, IL-2 production, antigen presentation, and antibody production. Because dietary restriction (DR) of rodents has been shown to extend maximum life span, delay the onset of tumors, and improve many immunologic parameters in aged animals, we tested the effect of such a regimen on the immune response to the influenza virus. We report that DR significantly inhibited the age-related decline in antigen presentation and T-cell proliferation. It also reduced the decline in antibody production to the virus. This is the first demonstration of improved immunity to an actual infectious agent resulting from DR. The improvement appears to be on a number of levels and to reflect more than one operative mechanism. C1 NIA,BIOMED RES & CLIN MED PROGRAM,BETHESDA,MD 20892. RP EFFROS, RB (reprint author), UNIV CALIF LOS ANGELES,SCH MED,DEPT PATHOL,LOS ANGELES,CA 90024, USA. FU NIA NIH HHS [K04 AG00427, R01 AG00424] NR 34 TC 58 Z9 61 U1 0 U2 1 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 0022-1422 J9 J GERONTOL JI J. Gerontol. PD JUL PY 1991 VL 46 IS 4 BP B142 EP B147 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA FW033 UT WOS:A1991FW03300019 PM 2071828 ER PT J AU BRANCH, LG GURALNIK, JM FOLEY, DJ KOHOUT, FJ WETLE, TT OSTFELD, A KATZ, S AF BRANCH, LG GURALNIK, JM FOLEY, DJ KOHOUT, FJ WETLE, TT OSTFELD, A KATZ, S TI ACTIVE LIFE EXPECTANCY FOR 10,000 CAUCASIAN MEN AND WOMEN IN 3 COMMUNITIES SO JOURNALS OF GERONTOLOGY LA English DT Article ID MORTALITY AB Active life expectancies (ALEs) were calculated using increment-decrement life table techniques for 10,000 Caucasian men and women from three geographic areas. This technique is more appropriate than the single decrement model originally used, and resulting ALE was substantially greater among initially independent men and women aged 65 years: from 9.3 for men and 10.6 for women to 11.3 to 13.0 for men and 15.5 to 17.1 for women. These increases may be attributable to factors other than the change of method, however, including the change in time from 1975 to 1982 and the change from one state to three communities. The six differences suggest that the added years of life that women have enjoyed over men are neither solely added years of vigor nor solely added years of disability, but added years with the same mix of independence/dependence that the shorter-lived males experience. The age patterns suggest that at any age the future presents a relatively constant expectation of the total duration of dependency, and concordantly, as one ages, there is a relatively uniform decrease in the proportion of active life to remaining years. C1 NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,BETHESDA,MD 20892. INST LIVING,BRACELAND CTR MENTAL HLTH & AGING,HARTFORD,CT 06106. YALE UNIV,SCH MED,NEW HAVEN,CT 06510. COLUMBIA UNIV,NEW YORK,NY 10027. RP BRANCH, LG (reprint author), BOSTON UNIV,SCH MED,80 E CONCORD ST,M-936,BOSTON,MA 02118, USA. NR 16 TC 56 Z9 56 U1 1 U2 1 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 0022-1422 J9 J GERONTOL JI J. Gerontol. PD JUL PY 1991 VL 46 IS 4 BP M145 EP M150 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA FW033 UT WOS:A1991FW03300028 PM 2071836 ER PT J AU KNEPPER, MA AF KNEPPER, MA TI NH4+ TRANSPORT IN THE KIDNEY SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT SATELLITE SYMP TO THE 11TH INTERNATIONAL CONGRESS OF NEPHROLOGY : PROTON, BICARBONATE AND CHLORIDE TRANSPORT IN THE KIDNEY CY JUL 22-24, 1990 CL NARA, JAPAN ID THICK ASCENDING LIMB; CHRONIC METABOLIC-ACIDOSIS; MEDULLARY COLLECTING DUCT; AMMONIA TRANSPORT; BICARBONATE TRANSPORT; CARBONIC-ANHYDRASE; DISEQUILIBRIUM PH; NEPHRON SEGMENTS; RAT-KIDNEY; PROXIMAL TUBULES RP KNEPPER, MA (reprint author), NHLBI,KIDNEY & ELECTROLYTE METAB LAB,BLDG 10,ROOM 6N307,BETHESDA,MD 20892, USA. NR 67 TC 58 Z9 59 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JUL PY 1991 VL 40 SU 33 BP S95 EP S102 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA FT574 UT WOS:A1991FT57400019 ER PT J AU SPRING, KR AF SPRING, KR TI ILLUMINATION, WAVELENGTH SELECTION, AND DETECTION IN FLUORESCENCE MICROSCOPY SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT SATELLITE SYMP TO THE 11TH INTERNATIONAL CONGRESS OF NEPHROLOGY : PROTON, BICARBONATE AND CHLORIDE TRANSPORT IN THE KIDNEY CY JUL 22-24, 1990 CL NARA, JAPAN ID DIGITAL IMAGING MICROSCOPY; CYTOPLASMIC PH; CELLS; SPECTROSCOPY; INDICATOR RP SPRING, KR (reprint author), NIH,KIDNEY & ELECTROLYTE METAB LAB,BLDG 10-6N309,BETHESDA,MD 20892, USA. NR 30 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JUL PY 1991 VL 40 SU 33 BP S18 EP S22 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA FT574 UT WOS:A1991FT57400005 ER PT J AU BAKEWELL, WE VIVIANO, CJ DIXON, D SMITH, GJ HOOK, GER AF BAKEWELL, WE VIVIANO, CJ DIXON, D SMITH, GJ HOOK, GER TI CONFOCAL LASER SCANNING IMMUNOFLUORESCENCE MICROSCOPY OF LAMELLAR BODIES AND PULMONARY SURFACTANT PROTEIN-A IN ISOLATED ALVEOLAR TYPE-II CELLS SO LABORATORY INVESTIGATION LA English DT Article ID POST-TRANSLATIONAL MODIFICATION; RAT LUNG; GLYCOPROTEIN-A; LOCALIZATION; APOPROTEINS; MACROPHAGES; SECRETION; PRODUCTS AB We have determined the distribution of surfactant protein A (SP-A) in isolated type II cells from the lungs of rats by using immunofluorescence in conjunction with a laser scanning microscope fitted with a confocal aperture. Because of the very narrow depth of field of this microscope (< 0.4-mu-m) in the confocal format, we were able to optically section type II cells and determine both the distribution of SP-A in the type II cell and the distribution of the lamellar bodies. The location of SP-A was determined by using fluorescein isothiocyanate-labeled secondary antibodies and the lamellar body distribution by using the lipid soluble fluorescent stain Phosphine 3R. SP-A was detected in the cytoplasm of type II cells as asymmetrically distributed punctate fluorescent bodies that resembled lamellar bodies in terms of size, number, and distribution within the cytoplasm of the cell. Most of the SP-A was located within bodies of the type II cell. Diffuse patches of fluorescence were seen in other cytoplasmic regions as well as the nucleus of the cell. We conclude that SP-A is localized primarily, but not exclusively, in lamellar bodies of type II cells and that laser scanning microscopy is a much superior technique for the localization of SP-A than conventional microscopy in terms of both sensitivity and resolution. C1 NIEHS,PULM PATHOBIOL LAB,POB 12233,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,CURRICULUM TOXICOL,CHAPEL HILL,NC 27514. UNIV N CAROLINA,DEPT PATHOL,CHAPEL HILL,NC 27514. FU NCI NIH HHS [CA-24144]; NIEHS NIH HHS [ES-07126-07, ES-07126-08] NR 33 TC 13 Z9 13 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JUL PY 1991 VL 65 IS 1 BP 87 EP 95 PG 9 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA FX346 UT WOS:A1991FX34600011 PM 2072667 ER PT J AU FERRETTI, A JUDD, JT BALLARDBARBASH, R NAIR, PP TAYLOR, PR CLEVIDENCE, BA AF FERRETTI, A JUDD, JT BALLARDBARBASH, R NAIR, PP TAYLOR, PR CLEVIDENCE, BA TI EFFECT OF FISH OIL SUPPLEMENTATION ON THE EXCRETION OF THE MAJOR METABOLITE OF PROSTAGLANDIN-E IN HEALTHY MALE-SUBJECTS SO LIPIDS LA English DT Article ID DIETARY EICOSAPENTAENOIC ACID; OMEGA-3 FATTY-ACIDS; IMMUNE-RESPONSE; COLON CARCINOGENESIS; GREENLAND ESKIMOS; MASS-SPECTROMETRY; MAMMARY-TUMOR; HUMAN-URINE; EICOSANOIDS; INVIVO AB We investigated the effect of fish oil supplementation on the synthesis of prostaglandin E (PGE) in vivo by measuring the excretion of its catabolite, PGE-M, in 24-hr urine by gas chromatography/mass spectrometry. Forty healthy male volunteers (24-57 years of age) consumed a controlled basal diet providing 40% of energy from fat (P/S ratio about 0.8:1), 130 mg/1000 kcal cholesterol, and a minimum of 22 mg/day of alpha-tocopherol (alpha-T), for three experimental periods lasting a total of 28 weeks. During period 1 (10 weeks) the diet was supplemented with placebo (PO) capsules (15 X 1 g/day) consisting of a blend of fats approaching the fatty acid profile of the basal diet. This was followed by a second 10-week period during which the subjects received 15 X 1 g/day capsules of fish oil concentrate (FOC). During period 3 (8 weeks) they continued the 15 g/day intake of FOC but received an additional 200 mg/day of alpha-T. PO and FOC capsules contained 1 mg alpha-T/g fat as antioxidant. A 14% reduction of PGE-M excretion was observed after 10 weeks of FOC supplementation (period 2), compared to an identical period of placebo supplementation (period 1), P = 0.009. PGE-M excretion during the last week of period 3 was not significantly different from that at the end of period 2. The reduction in PGE synthesis in response to the relatively high marine oil supplementation was large in many subjects participating in this study. C1 NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. RP FERRETTI, A (reprint author), USDA ARS,BELTSVILLE AGR RES CTR,BELTSVILLE HUMAN NUTR RES CTR,LIPID NUTR LAB,BLDG 308,BELTSVILLE,MD 20705, USA. NR 41 TC 17 Z9 17 U1 0 U2 0 PU AMER OIL CHEMISTS SOC PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 SN 0024-4201 J9 LIPIDS JI Lipids PD JUL PY 1991 VL 26 IS 7 BP 500 EP 503 DI 10.1007/BF02536593 PG 4 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA FW217 UT WOS:A1991FW21700004 PM 1943493 ER PT J AU BRANCH, CA HELPERN, JA EWING, JR WELCH, KMA AF BRANCH, CA HELPERN, JA EWING, JR WELCH, KMA TI F-19 NMR IMAGING OF CEREBRAL BLOOD-FLOW SO MAGNETIC RESONANCE IN MEDICINE LA English DT Note ID NUCLEAR-MAGNETIC-RESONANCE; SPECTROSCOPY; INDICATOR; TOXICITY; CATS C1 OAKLAND UNIV,DEPT PHYS,ROCHESTER,MI 48063. RP BRANCH, CA (reprint author), HENRY FORD HOSP,DEPT NEUROL,NIH,CTR STROKE RES,DETROIT,MI 48202, USA. FU NINDS NIH HHS [NS23393IH] NR 14 TC 15 Z9 15 U1 0 U2 0 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 JUL PY 1991 VL 20 IS 1 BP 151 EP 157 DI 10.1002/mrm.1910200116 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA FU082 UT WOS:A1991FU08200015 PM 1943655 ER PT J AU KOPPSCHNEIDER, A PORTIER, CJ RIPPMANN, F AF KOPPSCHNEIDER, A PORTIER, CJ RIPPMANN, F TI THE APPLICATION OF A MULTISTAGE MODEL THAT INCORPORATES DNA DAMAGE AND REPAIR TO THE ANALYSIS OF INITIATION PROMOTION EXPERIMENTS SO MATHEMATICAL BIOSCIENCES LA English DT Article ID RISK ASSESSMENT; TUMOR-INCIDENCE; 2-STAGE MODEL; NMRI MICE; CARCINOGENESIS; CANCER; SKIN AB In a previous article, a multistage model of carcinogenesis was introduced that takes into account the role of DNA damage, DNA repair, and cell replication on the incidence of malignancies. For this model the number of detectable clones of initiated cells is derived and model parameters are estimated using data arising from a two-stage skin-painting experiments in mice. The data from this experiment are interpretable in terms of the cellular events involved in initiation and promotion. C1 NIEHS,DIV BIOMETRY & RISK ASSESSMENT,RES TRIANGLE PK,NC 27709. NATL INST MED RES,MATH BIOL LAB,LONDON NW7 1AA,ENGLAND. RP KOPPSCHNEIDER, A (reprint author), DEUTSCH KREBSFORSCHUNGSZENTRUM,INST EPIDEMIOL & BIOMETRIE,BIOSTAT ABT,W-6900 HEIDELBERG,GERMANY. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 37 TC 22 Z9 22 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0025-5564 J9 MATH BIOSCI JI Math. Biosci. PD JUL PY 1991 VL 105 IS 2 BP 139 EP 166 DI 10.1016/0025-5564(91)90079-X PG 28 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA FT121 UT WOS:A1991FT12100001 PM 1806098 ER PT J AU FERGUSON, JH AF FERGUSON, JH TI RESEARCH ON THE DELIVERY OF MEDICAL-CARE USING HOSPITAL FIRMS - FOREWORD SO MEDICAL CARE LA English DT Editorial Material RP FERGUSON, JH (reprint author), NIH,OFF MED APPL RES,BETHESDA,MD 20892, USA. NR 1 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0025-7079 J9 MED CARE JI Med. Care PD JUL PY 1991 VL 29 IS 7 SU S BP JS1 EP JS2 PG 2 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA FY116 UT WOS:A1991FY11600002 ER PT J AU SCHREIBER, G AVISSAR, S AF SCHREIBER, G AVISSAR, S TI LITHIUM SENSITIVE G-PROTEIN HYPERFUNCTION - A DYNAMIC-MODEL FOR THE PATHOGENESIS OF BIPOLAR AFFECTIVE-DISORDER SO MEDICAL HYPOTHESES LA English DT Article ID ADENYLATE-CYCLASE; KINASE-C; INOSITOL TRISPHOSPHATE; HUMAN-PLATELETS; PHORBOL ESTER; DEPRESSION; BINDING; MANIA; PHOSPHORYLATION; MECHANISMS AB Guanine nucleotide binding proteins (G proteins) play a pivotal role in information transduction from various membrane receptors to a variety of intracellular effector systems. By influencing the metabolism of adenylate cyclase and phosphatidylinositol, G proteins affect the activities of both cAMP-dependent protein kinase (kinase A) and protein kinase C. The hypothesis of this present study addresses the oscillatory behavior of symptoms observed in manic-depressive patients by suggesting that the cellular phosphorylation state in the central nervous system, which results from the relative activity of protein kinase A and protein kinase C, determines the affective state. From this hypothesis, we developed a kinetic model based on self- and inter-regulatory steps between these two protein kinase systems. The solutions of the differential equations governing this kinetic model can describe oscillatory pathological affective states. More specifically, we show that hyperfunction of G proteins leads to an unstable 'catastrophic' dynamic system characteristic of a manic or depressive state, and that lithium treatment attenuates G protein function and damps the oscillatory system to yield a stable state. C1 NIMH,CLIN SCI LAB,CLIN NEUROPHARMACOL SERV,BETHESDA,MD 20892. RP SCHREIBER, G (reprint author), BEN GURION UNIV NEGEV,BEER SHEVA MENTAL HLTH CTR,POB 4600,IL-84170 BEER SHEVA,ISRAEL. NR 46 TC 18 Z9 18 U1 1 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0306-9877 J9 MED HYPOTHESES JI Med. Hypotheses PD JUL PY 1991 VL 35 IS 3 BP 237 EP 243 DI 10.1016/0306-9877(91)90239-U PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA FW619 UT WOS:A1991FW61900012 PM 1943867 ER PT J AU MARX, SJ AF MARX, SJ TI FAMILIAL MULTIPLE ENDOCRINE ADENOMA PEPTIC-ULCER COMPLEX - A CLASSIC IN MEDICINE SO MEDICINE LA English DT Editorial Material ID ISLET CELL TUMORS; NEOPLASIA TYPE-I; MANAGEMENT; PROLACTIN; GENE RP MARX, SJ (reprint author), NIDDKD,METAB DIS BRANCH,BLDG 10,RM 9C-101,BETHESDA,MD 20892, USA. NR 18 TC 0 Z9 0 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0025-7974 J9 MEDICINE JI Medicine (Baltimore) PD JUL PY 1991 VL 70 IS 4 BP 283 EP 285 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA FX419 UT WOS:A1991FX41900007 ER PT J AU HOLCOMB, WF CLARK, RL AF HOLCOMB, WF CLARK, RL TI PHS COMMISSIONED OFFICERS AND EPA - A NATURAL COALITION FOR ENVIRONMENTAL-QUALITY AND PUBLIC-HEALTH SO MILITARY MEDICINE LA English DT Article RP HOLCOMB, WF (reprint author), NIH,RADIAT SAFETY BRANCH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ASSN MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0026-4075 J9 MIL MED JI Milit. Med. PD JUL PY 1991 VL 156 IS 7 BP 346 EP 350 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA FW957 UT WOS:A1991FW95700011 PM 1922845 ER PT J AU RAGHAVAN, N MCREYNOLDS, LA MAINA, CV FEINSTONE, SM JAYARAMAN, K OTTESEN, EA NUTMAN, TB AF RAGHAVAN, N MCREYNOLDS, LA MAINA, CV FEINSTONE, SM JAYARAMAN, K OTTESEN, EA NUTMAN, TB TI A RECOMBINANT CLONE OF WUCHERERIA-BANCROFTI WITH DNA SPECIFICITY FOR HUMAN LYMPHATIC FILARIAL PARASITES SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE LYMPHATIC FILARIASIS; WUCHERERIA-BANCROFTI; GENOMIC EXPRESSION LIBRARY; MYOSIN; POLYMERASE CHAIN REACTION ID MYOSIN HEAVY-CHAIN; BRUGIA-MALAYI; CAENORHABDITIS-ELEGANS; ONCHOCERCA-VOLVULUS; ESCHERICHIA-COLI; SHOCK PROTEIN; ANTIGEN; IDENTIFICATION; SEQUENCE; GENE AB In order to understand the immune response to Wuchereria bancrofti and to aid in the diagnosis of W. bancrofti infections, recombinant antigens were identified from a W. bancrofti genomic expression library made in lambda-gt11 using a pool of sera from infected Indian patients. One of the recombinant clones, lambda-WbN1, containing a 2.5-kb insert, reacted strongly to a pool of sera from patients with lymphatic filariasis but not to normal human sera. In addition, this clone showed restricted specificity at the genomic level to the major lymphatic filarial parasites W. bancrofti and Brugia malayi but not to the closely related filarial parasite Brugia pahangi or to other filarial and non-filarial species tested. Nucleotide sequence analysis indicated the cloned DNA to have homology to myosin-like myofibrillar proteins. Polymerase chain reaction amplification initiated by specific synthetic oligomers amplified DNA in a species-specific manner from as little as 16 pg of isolated DNA or from one microfilaria. C1 NEW ENGLAND BIOLABS INC,BEVERLY,MA. NIAID,INFECT DIS LAB,BETHESDA,MD 20892. ANNA UNIV,CTR BIOTECHNOL,MADRAS,INDIA. RP RAGHAVAN, N (reprint author), NIAID,PARASIT DIS LAB,BLDG 4,RM 126,BETHESDA,MD 20892, USA. NR 46 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD JUL PY 1991 VL 47 IS 1 BP 63 EP 71 DI 10.1016/0166-6851(91)90148-Y PG 9 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA FR985 UT WOS:A1991FR98500007 PM 1857386 ER PT J AU YANG, WM GAHL, W HAMER, D AF YANG, WM GAHL, W HAMER, D TI ROLE OF HEAT-SHOCK TRANSCRIPTION FACTOR IN YEAST METALLOTHIONEIN GENE-EXPRESSION SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DNA-BINDING PROTEIN; SACCHAROMYCES-CEREVISIAE; FACTOR CONTAINS; ACTIVATION; COPPER; SEQUENCES AB The induction of Saccharomyces cerevisiae metallothionein gene transcription by Cu and Ag is mediated by the ACE1 transcription factor. In an effort to detect additional stimuli and factors that regulate metallothionein gene transcription, we isolated a Cu-resistant suppressor mutant of an ACE1 deletion strain. Even in the absence of metals, the suppressor mutant exhibited high basal levels of metallothionein gene transcription that required upstream promoter sequences. The suppressor gene was cloned, and its predicted product was shown to correspond to yeast heat shock transcription factor with a single-amino-acid substitution in the DNA-binding domain. The mutant heat shock factor bound strongly to metallothionein gene upstream promoter sequences, whereas wild-type heat shock factor interacted weakly with the same region. Heat treatment led to a slight but reproducible induction of metallothionein gene expression in both wild-type and suppressor strains, and Cd induced transcription in the mutant strain. These studies provide evidence for multiple pathways of metallothionein gene transcriptional regulation in S. cerevisiae. C1 NCI,BIOCHEM LAB,BETHESDA,MD 20892. NICHHD,HUMAN GENET BRANCH,BETHESDA,MD 20892. NR 28 TC 33 Z9 33 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 JUL PY 1991 VL 11 IS 7 BP 3676 EP 3681 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA FT582 UT WOS:A1991FT58200029 PM 1904545 ER PT J AU YU, JC HEIDARAN, MA PIERCE, JH GUTKIND, JS LOMBARDI, D RUGGIERO, M AARONSON, SA AF YU, JC HEIDARAN, MA PIERCE, JH GUTKIND, JS LOMBARDI, D RUGGIERO, M AARONSON, SA TI TYROSINE MUTATIONS WITHIN THE ALPHA-PLATELET-DERIVED GROWTH-FACTOR RECEPTOR KINASE INSERT DOMAIN ABROGATE RECEPTOR-ASSOCIATED PHOSPHATIDYLINOSITOL-3 KINASE-ACTIVITY WITHOUT AFFECTING MITOGENIC OR CHEMOTACTIC SIGNAL TRANSDUCTION SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PHOSPHOLIPASE-C-GAMMA; FACTOR-I RECEPTOR; GTPASE ACTIVATING PROTEIN; MIDDLE T-ANTIGEN; PDGF RECEPTOR; PHOSPHORYLATION; 3-KINASE; CELLS; DIACYLGLYCEROL; INDUCTION AB A phosphatidylinositol-3 (PI-3) kinase activity of unknown biological function associates with tyrosine kinase-containing proteins, including a number of growth factor receptors after ligand stimulation. In the beta platelet-derived growth factor (betaPDGF) receptor, phosphorylation of a specific tyrosine residue within the kinase insert domain was required for its interaction with this enzyme. We show that substitutions of phenylalanine for tyrosine residue 731 or 742 within the kinase insert domain of the alphaPDGF receptor do not impair PDGF-induced tyrosine phosphorylation of the receptor or of an in vivo substrate, phospholipase C-gamma. Moreover, phosphatidylinositol turnover in response to ligand stimulation is unaffected. However, both lesions markedly impair receptor association with PI-3 kinase. Antiphosphotyrosine antibody-recoverable PI-3 kinase was also dramatically reduced in PDGF-stimulated cells expressing either mutant receptor. Since neither mutation abolished PDGF-induced mitogenesis or chemotaxis, we conclude that alphaPDGF receptor-associated PI-3 kinase activity is not required for either of these major PDGF signalling functions. C1 NCI,CELLULAR & MOLEC BIOL LAB,37-1E24,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. IST RIC SIGMA TAU,I-20019 SETTIMO,ITALY. NIDR,BETHESDA,MD 20892. RI Gutkind, J. Silvio/A-1053-2009 NR 38 TC 92 Z9 96 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 JUL PY 1991 VL 11 IS 7 BP 3780 EP 3785 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA FT582 UT WOS:A1991FT58200041 PM 1646396 ER PT J AU LAFYATIS, R LECHLEIDER, R ROBERTS, AB SPORN, MB AF LAFYATIS, R LECHLEIDER, R ROBERTS, AB SPORN, MB TI SECRETION AND TRANSCRIPTIONAL REGULATION OF TRANSFORMING GROWTH FACTOR-BETA-3 DURING MYOGENESIS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID BETA-GENE FAMILY; COMPLEMENTARY-DNA; MESSENGER-RNA; DIFFERENTIAL EXPRESSION; ADULT TISSUES; MEMBER; MYOD; IDENTIFICATION; ACTIVATION; SEQUENCE AB Transforming growth factor-beta-3 (TGF-beta-3)mRNA is differentially expressed in developing and mature mouse tissues, including high-level expression in developing and adult cardiac tissue. We show now that TGF-beta-3 mRNA is also expressed highly in skeletal muscle as well as in the mouse skeletal myoblast cell line C2C12. We also show that C2C12 cells secrete TGF-beta-3, and that this TGF-beta is able to inhibit C2C12 myoblast fusion after activation. In order to begin to understand how the TGF-beta-3 promoter is regulated in specific tissues during development, we therefore studied the regulation of TGF-beta-3 during myoblast fusion. After fusion of C2C12 cells into myotubes, TGF-beta-3 mRNA levels increased eightfold as a result of increased TGF-beta-3 transcription. TGF-beta-3 transcriptional regulation was studied in myoblasts and myotubes by transfection of chimeric TGF-beta-3/CAT promoter plasmids. Chloramphenicol acetyltransferase (CAT) activity was stimulated in myoblasts by several upstream regions between -301 and -47 of the TGF-beta-3 promoter and by the TGF-beta-3 5' untranslated region. CAT activity directed by the TGF-beta-3 promoter in myotubes was stimulated by a distinct upstream region located between -499 and -221. Therefore, the high level of TGF-beta-3 mRNA expression in muscle cells appears to be dependent on multiple regulatory events during different stages of myogenesis. RP LAFYATIS, R (reprint author), NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892, USA. NR 41 TC 62 Z9 62 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 JUL PY 1991 VL 11 IS 7 BP 3795 EP 3803 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA FT582 UT WOS:A1991FT58200043 PM 1710772 ER PT J AU SCHULTZBERG, M AUSTIN, MC CRAWLEY, JN PAUL, SM AF SCHULTZBERG, M AUSTIN, MC CRAWLEY, JN PAUL, SM TI REPEATED ADMINISTRATION OF DESMETHYLIMIPRAMINE BLOCKS THE RESERPINE-INDUCED INCREASE IN TYROSINE-HYDROXYLASE MESSENGER-RNA IN LOCUS-CERULEUS NEURONS OF THE RAT SO MOLECULAR BRAIN RESEARCH LA English DT Article DE COEXISTENCE; NORADRENALINE; GALANIN; GENE REGULATION; TRICYCLIC ANTIDEPRESSANT ID BETA-ADRENERGIC RECEPTORS; CENTRAL NERVOUS-SYSTEM; ADRENAL-MEDULLA; CEREBRAL-CORTEX; BRAIN; EXPRESSION; BINDING; ANTIDEPRESSANTS; RESPONSIVENESS; MODULATION AB The levels of tyrosine hydroxylase and galanin mRNA were measured by in situ hybridization histochemistry in the rat locus coeruleus after repeated (21 days) administration of desmethylimipramine (10 mg/kg/day), of reserpine (0.25 mg/kg/day), of coadministered desmethylimipramine and reserpine, or of vehicle. Reserpine administration resulted in increased levels of both tyrosine hydroxylase and galanin mRNAs in locus coeruleus neurons as compared to vehicle-treated controls. Administration of desmethylimipramine alone failed to alter either the tyrosine hydroxylase or galanin mRNA. However, coadministration of desmethylimipramine with reserpine blocked the elevation in tyrosine hydroxylase mRNA induced by reserpine alone. C1 NIMH,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. RI Schultzberg, Marianne/E-7076-2014 OI Schultzberg, Marianne/0000-0002-8314-0927 NR 33 TC 12 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD JUL PY 1991 VL 10 IS 4 BP 307 EP 314 DI 10.1016/0169-328X(91)90089-G PG 8 WC Neurosciences SC Neurosciences & Neurology GA FY050 UT WOS:A1991FY05000004 ER PT J AU IIDA, T STOJILKOVIC, SS IZUMI, S CATT, KJ AF IIDA, T STOJILKOVIC, SS IZUMI, S CATT, KJ TI SPONTANEOUS AND AGONIST-INDUCED CALCIUM OSCILLATIONS IN PITUITARY GONADOTROPHS SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID CYTOSOLIC FREE CALCIUM; PAROTID ACINAR-CELLS; PROTEIN KINASE-C; PHORBOL-ESTER; INTRACELLULAR CALCIUM; SECRETORY RESPONSES; CA-2+ OSCILLATIONS; HORMONE; ACTIVATION; MEMBRANE AB Basal and receptor-regulated changes in cytoplasmic calcium concentration ([Ca2+]i) were monitored by fluorescence analysis in individual rat pituitary gonadotrophs loaded with the calcium-sensitive dye indo-1. Most gonadotrophs exhibited low amplitude spontaneous oscillations in basal [Ca2+]i that were interspersed by quiescent periods and abolished by removal of extracellular Ca2+ or addition of calcium channel blockers. Such random fluctuations in [Ca2+]i, which reflect the operation of a plasma membrane oscillator, were not coupled to basal gonadotropin secretion. The physiological agonist GnRH induced high amplitude [Ca2+]i oscillations; when a threshold [Ca2+]i level was reached, a cytoplasmic oscillator began to generate extremely regular Ca2+ transients. The time required to reach the threshold [Ca2+]i level was inversely correlated with agonist dose; the frequency, but not the amplitude, of agonist-induced Ca2+ spiking increased with agonist concentration. The duration of the latent period decreased and the frequency of Ca2+ spiking increased with the increase in ambient temperature. At high GnRH concentrations, the calcium transients merged into biphasic responses similar to those observed in cell suspensions at all GnRH concentrations. The presence of spontaneous fluctuations in basal [Ca2+]i did not significantly change the patterns of agonist-induced [Ca2+]i responses. Also, removal of extracellular Ca2+ did not interfere with the frequency or amplitude of Ca2+ spikes, but caused the loss of the plateau phase. Blockade of intracellular Ca2+-ATPase pumps by thapsigargin was usually accompanied by a subthreshold increase in [Ca2+]i. In such cells the agonist-induced oscillatory pattern was transformed into the biphasic response. In about 10% of the cells, however, high thapsigargin concentrations induced coarse [Ca2+]i oscillations; subsequent stimulation of such cells with GnRH was ineffective. The cytoplasmic oscillatory and biphasic responses may represent a mechanism for differential activation of Ca2+-dependent enzymes and their dependent cellular processes, including hormone secretion. The membrane oscillator is probably responsible for refilling of agonist-sensitive pools during and after agonist stimulation. C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892. NR 27 TC 80 Z9 80 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JUL PY 1991 VL 5 IS 7 BP 949 EP 958 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA FX715 UT WOS:A1991FX71500009 PM 1944300 ER PT J AU CURTIS, SW KORACH, KS AF CURTIS, SW KORACH, KS TI UTERINE ESTROGEN RECEPTOR-DNA COMPLEXES - EFFECTS OF DIFFERENT ERE SEQUENCES, LIGANDS, AND RECEPTOR FORMS SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID CELL-FREE TRANSCRIPTION; RESPONSIVE ELEMENT; PS2 GENE; IDENTIFICATION; BINDING; PROTEIN; REGION; ACTIVATION; ESTRADIOL; UPSTREAM AB Previous studies used the gel retardation assay to examine the binding of the mouse estrogen receptor (ER) to the estrogen-responsive element (ERE) from the vitellogenin A2 gene (VitA2ERE). Multiple specific complexes were formed when the ER was bound to various estrogen agonists or antagonists, or in the absence of bound hormone. The ERE from the human PS2 gene, which varies from the consensus ERE by one base change in the right arm, was used in this study to determine the effect of DNA sequence on ER-ERE interaction with various ligand-receptor complexes. Partially purified ligand-free soluble ER showed a 3-fold lower affinity for the PS2ERE than for the VitA2ERE, suggesting a possible influence of the imperfect DNA sequence on certain binding interactions. However, multiple complexes of similar affinity were formed with the PS2 sequence by nuclear ER regardless of the agonist or antagonist bound. In gel retardation experiments, antagonist (LY117018) nuclear ER complexes bound to either PS2 or VitA2ERE migrated more slowly than agonist complexes, indicating that the slower migrating form of the complex was not due to the DNA sequence. Interestingly, soluble ER bound by LY 117018 did not produce this decreased mobility complex, suggesting that it was specific to the nuclear form of the ER antagonist complex. Receptor activation has been linked with exposure to increased temperature, resulting in an ER form that has an increased affinity for DNA. The binding of molybdate-stabilized nonactivated 8S ER to VitA2ERE was studied to determine the effect of temperature on ER binding. Heat pretreatment of the stabilized soluble 8S ER did not cause an increase in ER-ERE binding during a 45-min reaction. Heat pretreatment slightly increased the final level of complex formed when followed for 24 h, but this temperature activation of the ER is also simply a reflection of an increased reaction rate of the complex formation between the ER and the ERE. Molybdate-stabilized soluble ER formed two specific ERE complexes. Partial purification of the stabilized soluble ER resulted in formation of only one specific ERE complex. This differential multiplicity of ER-ERE complexes formed with native ER extracts may be due to the presence of additional factors which contribute to the formation of the complexes. Studies are presently underway to identify these factors from uterine tissue. This study, using various uterine ER forms and different ERE sequences, suggests that the effect of estrogen on gene expression is not mediated only at the level of ER-ERE interaction, but may occur through regulation of ER interaction with additional nuclear structures or proteins involved in transcription. C1 NIEHS,REPROD & DEV TOXICOL LAB,RECEPTOR BIOL SECT,POB 12233,RES TRIANGLE PK,NC 27709. OI Korach, Kenneth/0000-0002-7765-418X NR 27 TC 47 Z9 47 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JUL PY 1991 VL 5 IS 7 BP 959 EP 966 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA FX715 UT WOS:A1991FX71500010 PM 1944301 ER PT J AU ITAYA, M CROUCH, RJ AF ITAYA, M CROUCH, RJ TI A COMBINATION OF RNASE H (RNH) AND RECBCD OR SBCB MUTATIONS IN ESCHERICHIA-COLI K12 ADVERSELY AFFECTS GROWTH SO MOLECULAR & GENERAL GENETICS LA English DT Article DE RNASE H; RECBCD; SBCB; R-LOOPS; RECOMBINATION ID STABLE DNA-REPLICATION; RIBONUCLEASE-H; STRUCTURAL GENE; BACTERIOPHAGE-LAMBDA; SELECTIVE-INHIBITION; EXONUCLEASE-V; PHAGE-LAMBDA; RECA PROTEIN; MUTANTS; INITIATION AB Colony forming ability of Escherichia coli strains carrying the rnh-339::cat mutant allele is strongly dependent on the recBCD and sbcB genes. A mutation inactivating either the RecBCD nuclease or exonuclease I (sbcB) is sufficient to restrict severly the efficiency of plating of strains carrying the rnh-339::cat mutation. Combining a non-lethal temperature-sensitive mutation in the RecBCD nuclease, recB270 (Ts) or recC271 (Ts), with rnh-339::cat renders strains temperature sensitive for growth, even though rnh+ strains with the recB270 (Ts) or recC271 (Ts) alleles are viable at 42-degrees-C. The recombinational functions of the RecBCD nuclease can be excluded as the source of lethality on the basis of the following observations. Introduction of a recombination proficient, exonuclease defective recD1009 allele or production of the phage lambda GamS protein (an inhibitor of the RecBCD exonuclease activity) in an rnh-339::cat strain dramatically delays or impairs the ability of such strains to form colonies. Restoration of recombination proficiency by inclusion of an sbcB15 mutation with recB21 recC22 mutations does not restore the ability of the rnh-339::cat mutant strains to plate normally. A recBCD+ strain bearing the rnh-339::cat and sbcB15 mutations forms very few visible colonies after 24 h but forms colonies at normal frequencies after 48 h of incubation. Finally, plating efficiencies of strains are unaffected when the RecBCD recombination pathway is inactivated by introduction of recA56 into an rnh-339::cat strain. These results imply that the defective growth of rnh-339::cat recBCD strains is due to a defect in repair and not recombination mediated by either the RecBCD or the RecF pathway. C1 NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892. NR 45 TC 52 Z9 52 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0026-8925 J9 MOL GEN GENET JI Mol. Gen. Genet. PD JUL PY 1991 VL 227 IS 3 BP 424 EP 432 DI 10.1007/BF00273933 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA FY647 UT WOS:A1991FY64700013 PM 1650908 ER PT J AU ITAYA, M CROUCH, RJ AF ITAYA, M CROUCH, RJ TI CORRELATION OF ACTIVITY WITH PHENOTYPES OF ESCHERICHIA-COLI PARTIAL FUNCTION MUTANTS OF RNH, THE GENE ENCODING RNASE-H SO MOLECULAR & GENERAL GENETICS LA English DT Article DE RNASE-H; RECBCD; DNAA ID STABLE DNA-REPLICATION; RIBONUCLEASE-H; FINE-STRUCTURE; RECA PROTEIN; INITIATION; K-12; MUTAGENESIS; MUTATIONS; DEFICIENT; ABSENCE AB The rnh gene of Escherichia coli encodes RNase H. rnh mutants display at least two phenotypes: (1) they require functional RecBCD enzyme for growth; thus rnh-339::cat recB270 (Ts) and rnh-339::cat recC271 (Ts) strains are temperature sensitive for growth; (2) rnh mutants permit replication that is independent of the chromosomal origin, presumably by failing to remove RNA-DNA hybrids from which extra-original replication can be primed. We report here that manifestation of these two phenotypes occurs at different levels of RNase H function; we have examined partially functional rnh mutants for their in vitro RNase H activity, their ability to rescue viability in recB or recC cells and their ability to permit growth of mutants incapable of using oriC [dnaA (Ts)]. C1 NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892. NR 32 TC 15 Z9 15 U1 1 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0026-8925 J9 MOL GEN GENET JI Mol. Gen. Genet. PD JUL PY 1991 VL 227 IS 3 BP 433 EP 437 DI 10.1007/BF00273934 PG 5 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA FY647 UT WOS:A1991FY64700014 PM 1650909 ER PT J AU ITAYA, M MCKELVIN, D CHATTERJIE, SK CROUCH, RJ AF ITAYA, M MCKELVIN, D CHATTERJIE, SK CROUCH, RJ TI SELECTIVE CLONING OF GENES ENCODING RNASE-H FROM SALMONELLA-TYPHIMURIUM, SACCHAROMYCES-CEREVISIAE AND ESCHERICHIA-COLI RNH MUTANT SO MOLECULAR & GENERAL GENETICS LA English DT Article DE RNASE-H; SALMONELLA-TYPHIMURIUM; SACCHAROMYCES-CEREVISIAE ID MURINE LEUKEMIA-VIRUS; NUCLEOTIDE-SEQUENCE; RIBONUCLEASE-H; REVERSE-TRANSCRIPTASE; DNA-POLYMERASE; RECB-MUTANTS; YEAST; REPLICATION; IDENTIFICATION; ORGANIZATION AB We have cloned genes encoding RNase H from Escherichia coli rnh mutants, Salmonella typhimurium and Saccharomyces cerevisiae. Selection was accomplished by suppression of the temperature-sensitive growth phenotype of Escherichia coli strains containing the rnh-339::cat and either recB270 (Ts) or recC271 (Ts) mutations. RNases H from E. coli and S. typhimurium contained 155 amino acid residues and differed at only 11 positions. The S. cerevisiae and E. coli RNases H were about 30% homologous. A comparison of the amino acid sequences of several RNases H from cellular and retroviral sources revealed some strongly conserved regions as well as variable regions; the carboxyl-terminus was particularly variable. The overlapping, divergent promoter gene organization found in E. coli was observed to be present in S. typhimurium. C1 NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892. NR 43 TC 62 Z9 64 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0026-8925 J9 MOL GEN GENET JI Mol. Gen. Genet. PD JUL PY 1991 VL 227 IS 3 BP 438 EP 445 DI 10.1007/BF00273935 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA FY647 UT WOS:A1991FY64700015 PM 1650910 ER PT J AU SNIDER, DP UPPENKAMP, IK TITUS, JA SEGAL, DM AF SNIDER, DP UPPENKAMP, IK TITUS, JA SEGAL, DM TI PROCESSING FATE OF PROTEIN ANTIGEN ATTACHED TO IGD OR MHC MOLECULES ON NORMAL LYMPHOCYTES-B USING HETEROCROSSLINKED BISPECIFIC ANTIBODIES SO MOLECULAR IMMUNOLOGY LA English DT Article ID T-CELL HYBRIDOMAS; FLOW CYTOFLUOROMETRIC ANALYSIS; MONOCLONAL-ANTIBODIES; CLASS-I; ENDOCYTOSIS; MACROPHAGES; REQUIREMENTS; ACTIVATION; ACIDIFICATION; PROTEOLYSIS AB We have studied the internalization, processing and presentation of hen egg lysozyme (HEL) attached to surface IgD (sIgD) or MHC molecules on normal murine B cells. using heterocrosslinked bispecific antibodies (HBA). Nearly all HEL attached to sIgD was internalized within one hour, with at least a portion rapidly entering a chloroquine-sensitive, acidic environment. Degradation and presentation of HEL to hybridoma T cells began several hours after internalization. Degraded HEL was found in the medium after about 6 hr incubation, but at no time were significant amounts of HEL peptides found within the cells. When HEL was attached to class I or class II MHC molecules, its rate of internalization was low. The fraction of antigen bound to MHC molecules that was inside the cell was always low, even at later stages of culture, but the internalized antigen was located in an acidic environment. Degradation and presentation of HEL internalized via MHC molecules followed internalization. No difference was observed in the processing fate of HEL attached to class I or class II MHC molecules. These results suggest that the rate limiting step in antigen processing and presentation is antigen degradation, when the antigen is bound to sIgD, and internalization when bound to MHC molecules. The slow and steady processing of bound or internalized antigen could provide a sustained presence of antigen on the B cell surface and enhance the potential for its presentation to T cells. C1 NCI,EXPT IMMUNOL BRANCH,BLDG 10,ROOM 4B17,BETHESDA,MD 20892. NR 49 TC 5 Z9 5 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD JUL PY 1991 VL 28 IS 7 BP 779 EP 788 DI 10.1016/0161-5890(91)90121-Y PG 10 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA FY725 UT WOS:A1991FY72500012 PM 1906983 ER PT J AU GOTTESMAN, S STOUT, V AF GOTTESMAN, S STOUT, V TI REGULATION OF CAPSULAR POLYSACCHARIDE SYNTHESIS IN ESCHERICHIA-COLI K12 SO MOLECULAR MICROBIOLOGY LA English DT Review ID ERWINIA-AMYLOVORA; TRANSCRIPTIONAL REGULATION; NUCLEOTIDE-SEQUENCE; MOLECULAR-CLONING; RCSA GENE; K-12; EXPRESSION; PROTEIN; BIOSYNTHESIS; DEGRADATION AB Synthesis of the capsular polysaccharide colanic acid in Escherichia coli K12 is regulated by a complex network of regulatory proteins. This regulation is expressed at the level of transcription of the cps (capsular polysaccharide synthesis) genes. Two positive regulators, RcsA and RcsB, are necessary for maximal capsule expression. The availability of RcsA is normally limited because the RcsA protein is rapidly degraded by the Lon ATP-dependent protease. Therefore Lon acts, indirectly, as a negative regulator of capsule synthesis. The sequence predicted for RcsB suggests that it is the effector component of a two-component system; a protein with homology to sensors, RcsC, also plays a role in capsule regulation. We propose a model for capsule synthesis in which RcsA interacts with RcsB to stimulate transcription of the cps genes. The mechanism of regulation of colanic acid synthesis in E. coli may apply to other capsules in a variety of Gram-negative bacteria. RP GOTTESMAN, S (reprint author), NCI,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 28 TC 163 Z9 166 U1 1 U2 10 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD JUL PY 1991 VL 5 IS 7 BP 1599 EP 1606 DI 10.1111/j.1365-2958.1991.tb01906.x PG 8 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA FX519 UT WOS:A1991FX51900004 PM 1943696 ER PT J AU MAHAN, LC MCVITTIE, LD SMYKRANDALL, EM NAKATA, H MONSMA, FJ GERFEN, CR SIBLEY, DR AF MAHAN, LC MCVITTIE, LD SMYKRANDALL, EM NAKATA, H MONSMA, FJ GERFEN, CR SIBLEY, DR TI CLONING AND EXPRESSION OF AN A1 ADENOSINE RECEPTOR FROM RAT-BRAIN SO MOLECULAR PHARMACOLOGY LA English DT Article ID PROTEIN COUPLED RECEPTOR; LIGAND-BINDING SYSTEMS; A1-ADENOSINE RECEPTORS; CYCLASE ACTIVITY; PURIFICATION; MEMBRANES; AGONIST; HIPPOCAMPUS; TISSUES; NEURONS AB We have used the polymerase chain reaction technique to selectively amplify guanine nucleotide-binding regulatory protein (G protein)-coupled receptor cDNA sequences from rat striatal mRNA, using sets of highly degenerate primers derived from transmembrane sequences of previously cloned G protein-coupled receptors. A novel cDNA fragment was identified, which exhibits considerable homology to various members of the G protein-coupled receptor family. This fragment was used to isolate a full-length cDNA from a rat striatal library. A 2.2-kilobase clone was obtained that encodes a protein of 326 amino acids with seven transmembrane domains, as predicted by hydropathy analysis. Stably transfected mouse A9-L cells and Chinese hamster ovary cells that expressed mRNA for this clone were screened with putative receptor ligands. Saturable and specific binding sites for the A1 adenosine antagonist [H-3]-1,3-dipropyl-8-cyclopentylxanthine were identified on membranes from transfected cells. The rank order of potency and affinities of various adenosine agonist and antagonist ligands confirmed the identity of this cDNA clone as an A1 adenosine receptor. The high affinity binding of Al adenosine agonists was shown to be sensitive to the nonhydrolyzable GTP analog guanylyl-5'-imidodiphosphate. in adenylyl cyclase assays, adenosine agonists inhibited forskolin-stimulated cAMP production by > 50%, in a pharmacologically specific fashion. Northern blot and in situ hybridization analyses of receptor mRNA in brain tissues revealed two transcripts of 5.6 and 3.1 kilobases, both of which were abundant in cortex, cerebellum, hippocampus, and thalamus, with lower levels in olfactory bulb, striatum, mesencephalon, and retina. These regional distribution data are in good agreement with previous receptor autoradiographic studies involving the Al adenosine receptor. We conclude that we have cloned a cDNA encoding an A1 adenosine receptor linked to the inhibition of adenylyl cyclase activity. C1 NINCDS,EXPTL THERAPEUT BRANCH,BETHESDA,MD 20892. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. RP MAHAN, LC (reprint author), NIMH,CELL BIOL LAB,BLDG 36,ROOM 2D20,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 34 TC 240 Z9 241 U1 0 U2 4 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JUL PY 1991 VL 40 IS 1 BP 1 EP 7 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA FX352 UT WOS:A1991FX35200001 PM 1857334 ER PT J AU TYNDALE, RF SUNAHARA, R INABA, T KALOW, W GONZALEZ, FJ NIZNIK, HB AF TYNDALE, RF SUNAHARA, R INABA, T KALOW, W GONZALEZ, FJ NIZNIK, HB TI NEURONAL CYTOCHROME-P450IID1 (DEBRISOQUINE SPARTEINE-TYPE) - POTENT INHIBITION OF ACTIVITY BY (-)-COCAINE AND NUCLEOTIDE-SEQUENCE IDENTITY TO HUMAN HEPATIC P450-GENE CYP2D6 SO MOLECULAR PHARMACOLOGY LA English DT Article ID RAT-BRAIN; DRUG-METABOLISM; HUMAN-LIVER; POLYMORPHISM; OXIDATION; 4-HYDROXYLASE; IDENTIFICATION; HYDROXYLATION; AMPHETAMINE; BUFURALOL AB Catalytic, pharmacological, and molecular criteria have been used to identify cytochrome P450IID1 in mammalian brain (enzyme, P450IID; gene, CYP2D). Sparteine metabolism in canine striatal membranes was shown to be inhibited in a concentration-dependent and stereoselective manner by quinidine K(i), approximately 51 nM), quinine (K(i) approximately 5.9-mu-m), and various other known substrates and inhibitors of hepatic P450IID1 activity. In addition, canine striatal P450IID1 was inhibited with high affinity by dopamine uptake blockers, such as (-)-cocaine (K(i) approximately 74 nM), d-amphetamine (K(i), approximately 4.5-mu-m), and methylphenidate (K(i) approximately 15-mu-m). Inhibitory constants (K(i)) of numerous compounds for inhibition of sparteine metabolism in canine striatal membranes correlated well with (a) K(i) values observed in human liver microsomes (r = 0.95), (b) [H-3]GBR-12935 binding to P450IID1 in canine striatal membranes (r = 0.85), and (c) the inhibition (IC50) of sparteine metabolism in HepG2 cells expressing human CYP2D6 cDNA (r = 0.93). Moreover, antibodies raised against rat hepatic enzyme inhibited, in a concentration-dependent manner, sparteine metabolism in canine striatal membranes. Enzymatic activity was unevenly distributed throughout the canine brain and ranged from 0.5 to 21 pmol/mg of protein/hr in cerebellum and supraorbital cortex, respectively, with the striatum displaying moderate levels of activity (8 pmol/mg of protein/hr). The polymerase chain reaction was used to amplify cDNA from a human caudate lambda-gt11 library encoding exons 6-9 of the human CYP2D6 gene, which revealed, upon sequencing, 100% nucleic acid sequence identity. These data indicate that P450IID1 is expressed centrally and is similar, at the functional and molecular levels, to the human hepatic P450IID1 enzyme. Because the debrisoquine/sparteine monooxygenase is a polymorphic enzyme, in which 5-10% of caucasians are deficient in metabolism of various drugs, a genetic difference in human brain metabolism of P450IID1 substrates may possibly lead to differences in drug response and toxicity. C1 UNIV TORONTO,DEPT PSYCHIAT,TORONTO M5S 1A8,ONTARIO,CANADA. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. CLARKE INST PSYCHIAT,MOLEC NEUROBIOL LAB,TORONTO M5T 1R8,ONTARIO,CANADA. RP TYNDALE, RF (reprint author), UNIV TORONTO,DEPT PHARMACOL,MED SCI BLDG,TORONTO M5S 1A8,ONTARIO,CANADA. NR 37 TC 144 Z9 145 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 JUL PY 1991 VL 40 IS 1 BP 63 EP 68 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA FX352 UT WOS:A1991FX35200010 PM 1857341 ER PT J AU HARTMAN, NR AHLUWALIA, GS COONEY, DA MITSUYA, H KAGEYAMA, S FRIDLAND, A BRODER, S JOHNS, DG AF HARTMAN, NR AHLUWALIA, GS COONEY, DA MITSUYA, H KAGEYAMA, S FRIDLAND, A BRODER, S JOHNS, DG TI INHIBITORS OF IMP DEHYDROGENASE STIMULATE THE PHOSPHORYLATION OF THE ANTI-HUMAN-IMMUNODEFICIENCY-VIRUS NUCLEOSIDES 2',3'-DIDEOXYADENOSINE AND 2',3'-DIDEOXYINOSINE SO MOLECULAR PHARMACOLOGY LA English DT Article ID HUMAN LYMPHOID-CELLS; AIDS-RELATED COMPLEX; ANTIRETROVIRAL AGENT 2',3'-DIDEOXYADENOSINE; PHASE-I TRIAL; CELLULAR PHARMACOLOGY; PYRIMIDINE 2',3'-DIDEOXYNUCLEOSIDES; RIBAVIRIN ANTAGONIZES; INVITRO; INFECTIVITY; 2',3'-DIDEOXYGUANOSINE AB 2',3'-Dideoxyadenosine (ddAdo) and its deamination product 2',3'-dideoxyinosine (ddIno) (didanosine) inhibit the replication and infectivity of the human immunodeficiency virus (HIV) in a number of in vitro assay systems. Early clinical studies (phase 1) have indicated a role for ddIno in the treatment of patients with severe HIV infection. In the present in vitro study, the formation in human T cells (MOLT-4, ATH8, and CCRF-CEM) of the pharmacologically active metabolite of ddIno and ddAdo, 2',3'-dideoxyadenosine-5'-triphosphate (ddATP), was found to be stimulated 2-4-fold by appropriate concentrations of inosinate dehydrogenase (IMPD) inhibitors such as ribavirin, tiazofurin, and mycophenolic acid. Concomitant with this increase in ddATP formation from ddIno was an increase in anti-HIV activity of this agent when it was combined with ribavirin in the ATH8 cell assay system and with tiazofurin in the MOLT-4 assay system. No change was noted in the intracellular concentration of the corresponding physiological deoxynucleoside-5'-triphosphate, dATP; positive correlation was observed, however, between the increase in ddATP formation from ddIno and the increase in intracellular IMP occurring as a consequence of IMPD inhibition. The results support the hypothesis that the stimulation of ddATP formation seen when ddIno is combined with ribavirin or other IMPD inhibitors is a consequence of an increased concentration of IMP, the major phosphate donor for the initial phosphorylation step in the anabolism of ddIno to ddATP, i.e., ddIno --> ddIMP. C1 NCI, MED CHEM LAB,DEV THERAPEUT PROGRAM,BLDG 37, ROOM 5B22, BETHESDA, MD 20892 USA. NCI, DIV CANC TREATMENT, CLIN ONCOL PROGRAM, BETHESDA, MD 20892 USA. ST JUDE CHILDRENS RES HOSP, DIV BIOCHEM & CLIN PHARMACOL, MEMPHIS, TN 38101 USA. NR 27 TC 62 Z9 63 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JUL PY 1991 VL 40 IS 1 BP 118 EP 124 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA FX352 UT WOS:A1991FX35200018 PM 1677450 ER PT J AU TOSHIMORI, K TANII, I OURA, C EDDY, EM AF TOSHIMORI, K TANII, I OURA, C EDDY, EM TI A MONOCLONAL-ANTIBODY, MN13, THAT RECOGNIZES SPECIFICALLY A NOVEL SUBSTANCE BETWEEN THE POSTACROSOMAL SHEATH AND THE OVERLYING PLASMA-MEMBRANE IN THE MAMMALIAN SPERM HEAD SO MOLECULAR REPRODUCTION AND DEVELOPMENT LA English DT Article DE POSTACROSOMAL REGION; CYTOSKELETON; ULTRASTRUCTURE; IMMUNOCYTOCHEMISTRY ID MATURATION ANTIGEN; MOUSE; SPERMATOZOA; SURFACE AB Monoclonal antibody MN13 raised against mouse spermatozoa specifically recognizes the postacrosomal region of the sperm head in several mammalian species. Colloidal gold-immunoelectron microscopy of demembranated mouse spermatozoa indicated that the antigen is associated with the outer layer of the periodic substructure apparently linking the postacrosomal sheath to the overlying plasma membrane. The antigen recognized by MN13 may contribute to the intimate association of the postacrosomal sheath with the overlying plasma membrane. C1 NIEHS,NATL TOXICOL PROGRAM,REPROD & DEV TOXICOL LAB,GAMETE BIOL SECT,RES TRIANGLE PK,NC 27709. RP TOSHIMORI, K (reprint author), MIYAZAKI MED COLL,DEPT ANAT,MIYAZAKI 88916,JAPAN. NR 9 TC 18 Z9 18 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 1040-452X J9 MOL REPROD DEV JI Mol. Reprod. Dev. PD JUL PY 1991 VL 29 IS 3 BP 289 EP 293 DI 10.1002/mrd.1080290312 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology SC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology GA FT151 UT WOS:A1991FT15100011 PM 1931046 ER PT J AU FOLEY, CK PEDERSEN, LG DARDEN, TA GLICKMAN, BW ANDERSON, MW AF FOLEY, CK PEDERSEN, LG DARDEN, TA GLICKMAN, BW ANDERSON, MW TI THEORETICAL AND EXPERIMENTAL MEASURES OF DNA HELIX STABILITY AND THEIR RELATION TO SEQUENCE SPECIFIC REPAIR OF O6-ETHYLGUANINE LESIONS SO MUTATION RESEARCH LA English DT Article DE DNA BINDING ENERGY; O6-ETHYLGUANINE; MOLECULAR MECHANICS; DNA HELIX STABILITY; HELIX TO COIL TRANSITIONS, THERMODYNAMICS ID ESCHERICHIA-COLI; NUCLEIC-ACIDS; FORCE-FIELD; PROTEINS AB Recent work (Breslauer et al. (1986) Proc. Natl. Acad. Sci. (U.S.A.), 83, 3746) has provided a method for calculating empirical thermodynamic quantities for helix to coil transitions from the base sequence of any oligomer. It is shown in this work that the DNA helix binding energy, calculated with the AMBER force field, for 9-mers of the type 5'-GGGXGeYGGG-3', where X and Y are any base and the central Ge is O6-ethylguanine, correlates well with the empirical AG for helix to strand transitions. The mutation spectrum of ethane methylsulfonate (EMS) in the lacI gene of Escherichia coli can be modeled using the calculated local binding energy but the empirical free energies, enthalpies and melting temperatures predict these levels of repair less well. The relation of the binding energy to the mutation spectrum can be somewhat improved by including entropic effects in a theoretical free energy of binding as given by DELTA-G(theoretical) = DELTA-E(binding) - T-DELTA-S. C1 UNIV N CAROLINA,DEPT CHEM,CHAPEL HILL,NC 27514. YORK UNIV,DEPT BIOL,N YORK M3J 1P3,ONTARIO,CANADA. RP FOLEY, CK (reprint author), NIEHS,MOLEC TOXICOL LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. RI Pedersen, Lee/E-3405-2013; OI Pedersen, Lee/0000-0003-1262-9861; Foley, Charles/0000-0001-6578-9629 NR 11 TC 5 Z9 5 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 JUL PY 1991 VL 255 IS 1 BP 89 EP 93 DI 10.1016/0921-8777(91)90021-G PG 5 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA FW092 UT WOS:A1991FW09200010 PM 2067552 ER PT J AU JONG, SC DAVIS, EE MCMANUS, C KRICHEVSKY, MI AF JONG, SC DAVIS, EE MCMANUS, C KRICHEVSKY, MI TI COMPUTER CODING OF STRAIN FEATURES OF THE SAPROLEGNIAN FUNGI SO MYCOTAXON LA English DT Article AB Saprolegnian fungi are the best known and most widely distributed of the water molds and are important in systematic, ecological, physiological, and biochemical research and teaching. A coding system that was developed for computer storage and analysis of microbial strain data has been expanded to include strain features specifically applicable to the identification of saprolegnian fungi. C1 NIDR,MICROBIAL SYSTEMAT SECT,BETHESDA,MD 20892. RP JONG, SC (reprint author), AMER TYPE CULTURE COLLECT,12301 PARKLAWN DR,ROCKVILLE,MD 20852, USA. NR 16 TC 7 Z9 7 U1 0 U2 0 PU MYCOTAXON LTD PI ITHACA PA PO BOX 264, ITHACA, NY 14851-0264 SN 0093-4666 J9 MYCOTAXON JI Mycotaxon PD JUL-SEP PY 1991 VL 41 IS 2 BP 407 EP 418 PG 12 WC Mycology SC Mycology GA GF741 UT WOS:A1991GF74100007 ER PT J AU DAVIS, MD KAUFMAN, S AF DAVIS, MD KAUFMAN, S TI STUDIES ON THE PARTIALLY UNCOUPLED OXIDATION OF TETRAHYDROPTERINS BY PHENYLALANINE-HYDROXYLASE SO NEUROCHEMICAL RESEARCH LA English DT Article DE TETRAHYDROBIOPTERIN; TETRAHYDROPTERIN; PHENYLALANINE; PHENYLALANINE HYDROXYLASE ID RAT-LIVER; TYROSINE-HYDROXYLASE; PURIFICATION; PROTEIN; 4A-CARBINOLAMINE; STIMULATOR; MECHANISM AB The uncoupled portion of the partially uncoupled oxidation of tetrahydropterins by phenylalanine hydroxylase can be described by the same model as we have recently derived for the fully uncoupled reaction (Davis, M.D. and Kaufman, S. (1989) J. Biol. Chem. 264, 8585-8596). Although essentially no hydrogen peroxide is formed during the fully coupled oxidation of tetrahydrobiopterin or 6-methyltetrahydropterin by phenylalanine hydroxylase when phenylalanine is the amino acid substrate, significant amounts of hydrogen peroxide are formed during the partially uncoupled oxidation of 6-methyltetrahydropterin when para-fluorophenylalanine or para-chlorophenylalanine are used in place of phenylalanine. Similarly, during the partially uncoupled oxidation of the unsubstituted pterin, tetrahydropterin, even in the presence of phenylalanine, hydrogen peroxide formation is detected. The 4a-carbinolamine tetrahydropterin intermediate has been observed during the fully uncoupled tyrosine-dependent oxidations of tetrahydropterin and 6-methyltetrahydropterin by lysolecithin-activated phenylalanine hydroxylase, suggesting that this species is also a common intermediate for uncoupled oxidations by this enzyme. C1 NIMH,NEUROCHEM LAB,BLDG 36,ROOM 3D30,BETHESDA,MD 20892. NR 29 TC 13 Z9 13 U1 3 U2 3 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 JUL PY 1991 VL 16 IS 7 BP 813 EP 819 DI 10.1007/BF00965691 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA GF625 UT WOS:A1991GF62500012 PM 1944771 ER PT J AU BALISH, M SATO, S CONNAUGHTON, P KUFTA, C AF BALISH, M SATO, S CONNAUGHTON, P KUFTA, C TI LOCALIZATION OF IMPLANTED DIPOLES BY MAGNETOENCEPHALOGRAPHY SO NEUROLOGY LA English DT Article; Proceedings Paper CT 42ND ANNUAL MEETING OF THE AMERICAN ACADEMY OF NEUROLOGY CY APR, 1990 CL MIAMI BEACH, FL SP AMER ACAD NEUROL ID MAGNETIC LOCALIZATION; MODEL; FIELD; EEG; SIMULATION; EPILEPSY; SPHERE; HEAD AB We attempted to validate the location of sources predicted by magnetoencephalography (MEG) by studying 19 specially designed dipole electrodes implanted in six patients with intractable partial seizures who were undergoing subdural electrode recording. We used a seven-channel magnetometer to measure the magnetic fields produced by passing through the dipoles a 40-mu-A, 5-msec square-wave pulse followed 40 msec later by a pulse of opposite polarity; 200 pulses were averaged for each magnetometer position. The actual dipole locations were measured from skull radiographs, and we based MEG localization on a spherical head model with the inclusion of volume currents. MEG estimates of the sources were within several centimeters (mean, 1.69 cm) of the measured locations. We conclude that MEG localization was promising. RP BALISH, M (reprint author), NINCDS,MED NEUROL BRANCH,NEUROPHYSIOL UNIT,BLDG 10,ROOM 5C408,BETHESDA,MD 20892, USA. NR 20 TC 37 Z9 38 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 JUL PY 1991 VL 41 IS 7 BP 1072 EP 1076 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA FX123 UT WOS:A1991FX12300021 PM 1906146 ER PT J AU BEVER, CT PANITCH, HS LEVY, HB MCFARLIN, DE JOHNSON, KP AF BEVER, CT PANITCH, HS LEVY, HB MCFARLIN, DE JOHNSON, KP TI GAMMA-INTERFERON INDUCTION IN PATIENTS WITH CHRONIC PROGRESSIVE MS SO NEUROLOGY LA English DT Article ID MULTIPLE-SCLEROSIS; IMMUNE INTERFERON; PLASMA-EXCHANGE; POLY ICLC; IA; EXACERBATIONS; MACROPHAGES; ACTIVATION; INVITRO; IMMUNOSUPPRESSION AB Although gamma interferon (gamma-IFN) may be involved in the pathogenesis of exacerbations of multiple sclerosis (MS), whether it plays a role in chronic progressive MS is not known. To investigate this, we retrospectively analyzed serum samples from nine chronic progressive MS patients who were treated with monthly intravenous infusions of the interferon inducer polyinosinic acid polycytidylic acid polylysine in carboxymethylcellulose (poly ICLC). Using a bioassay we found that the mean peak total interferon level was 177 U/ml 12 hours after infusion, and using a radioimmunoassay we found that the mean peak-gamma-IFN level was 15.9 U/ml 12 hours after infusion, so that gamma-IFN made up approximately 10% of the total. Greater gamma-IFN induction did not correlate with clinical worsening; induced gamma-IFN levels were not higher in two patients who worsened on treatment, and the highest levels were found in a patient who remained stable. Either chronic progressive MS is not sensitive to gamma-IFN or the effects of gamma-IFN are masked by other mediators induced by poly ICLC. C1 UNIV MARYLAND,SCH MED,DEPT NEUROL,BALTIMORE,MD 21201. NIAID,VIRAL DIS LAB,FREDERICK,MD 21701. NINCDS,NEUROIMMUNOL BRANCH,BETHESDA,MD 20892. DEPT VET AFFAIRS MED CTR,RES SERV,BALTIMORE,MD. NR 34 TC 17 Z9 17 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 JUL PY 1991 VL 41 IS 7 BP 1124 EP 1127 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA FX123 UT WOS:A1991FX12300031 PM 1829795 ER PT J AU ZHOU, GZ KATKI, AG SCHWARZ, S MUNSON, PJ RODBARD, D AF ZHOU, GZ KATKI, AG SCHWARZ, S MUNSON, PJ RODBARD, D TI QUANTITATIVE CHARACTERIZATION OF MULTIPLE BINDING-SITES FOR PHENCYCLIDINE AND N-ALLYLNORMETAZOCINE IN MEMBRANES FROM RAT AND GUINEA-PIG BRAIN SO NEUROPHARMACOLOGY LA English DT Article DE PHENCYCLIDINE RECEPTORS; SIGMA-RECEPTORS; NMDA RECEPTORS; RADIOLIGAND RECEPTOR ASSAYS; MATHEMATICAL MODELING; BRAIN NEUROTRANSMITTER RECEPTORS ID KAPPA-OPIOID RECEPTORS; CENTRAL NERVOUS-SYSTEM; SIGMA-OPIATE; COMPUTERIZED OPTIMIZATION; ANTIPSYCHOTIC-DRUGS; EXPERIMENTAL-DESIGN; ESTIMATING KD; LIGANDS; VISUALIZATION; SKF-10,047 AB Quantitative ligand binding studies have been used to characterize binding sites for N-allylnormetazocine ((+)SKF10,047) (SKF), 1-(1-phenylcyclohexyl) piperidine (PCP), N-[1-(2-thienyl) cyclohexyl] piperidine (TCP) and haloperidol in membranes from the brain of rat and guinea pig under conditions which permitted simultaneous analysis of the binding of both PCP and SKF. Using four labelled ligands (SKF, TCP, PCP and haloperidol), each displaced by the corresponding four unlabelled ligands, four classes of binding sites were observed in membranes from the brain of the rat, corresponding to sigma (sigma), two classes of PCP sites (PCP1, PCP2) and dopamine (D2) sites. The sigma-site was suppressed by 50 nM haloperidol, while the PCP1 and PCP2 sites were not. These results were confirmed by studies employing a self- and cross-displacement design and dose-response surfaces for SKF and TCP, with and without blockade by haloperidol of the sigma site. Using mathematical modelling, employing the program LIGAND , it was possible to reject simpler models involving a common "PCP/sigma" site or a model involving only two classes of sites (sigma and PCP). Similar methods were used to identify two classes of sigma-binding sites and two classes of PCP binding sites, in membranes prepared from the brain of the guinea pig. The relative potencies of 18 ligands for displacement of (+)[H-3]SKF10,047 and [H-3]TCP were compared: there were significant qualitative and quantitative differences in the "sigma" binding sites in the brain of rat and guinea pig, while the PCP binding sites were very similar in the two species. C1 NICHHD,THEORET & PHYS BIOL LAB,BETHESDA,MD 20892. NR 43 TC 8 Z9 8 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD JUL PY 1991 VL 30 IS 7 BP 775 EP 786 DI 10.1016/0028-3908(91)90186-F PG 12 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA FY817 UT WOS:A1991FY81700012 PM 1656309 ER PT J AU MARRIOTT, SJ LINDHOLM, PF REID, RL BRADY, JN AF MARRIOTT, SJ LINDHOLM, PF REID, RL BRADY, JN TI SOLUBLE HTLV-I TAX1 PROTEIN STIMULATES PROLIFERATION OF HUMAN PERIPHERAL-BLOOD LYMPHOCYTES SO NEW BIOLOGIST LA English DT Article DE TSP-HAM; ATL; HTLV-I; PROLIFERATION; TAX ID T-CELL LEUKEMIA; VIRUS TYPE-I; TROPICAL SPASTIC PARAPARESIS; HUMAN IMMUNODEFICIENCY VIRUS; GROWTH-FACTOR; INTERLEUKIN-2 RECEPTOR; NUCLEOTIDE-SEQUENCE; TRANSGENIC MICE; TAT GENE; KAPOSIS-SARCOMA C1 NCI,MOLEC VIROL LAB,BETHESDA,MD 20892. NR 50 TC 68 Z9 68 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1043-4674 J9 NEW BIOL PD JUL PY 1991 VL 3 IS 7 BP 678 EP 686 PG 9 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA GK722 UT WOS:A1991GK72200008 PM 1751450 ER PT J AU WANG, MY GEORGIADIS, JG AF WANG, MY GEORGIADIS, JG TI PARALLEL COMPUTATION OF FORCED-CONVECTION USING DOMAIN DECOMPOSITION SO NUMERICAL HEAT TRANSFER PART B-FUNDAMENTALS LA English DT Article ID COORDINATE SYSTEMS AB Boundary-fitted coordinate transformation broadens the applicability of finite difference methods. However, for a large class of geometries, coordinate transformation introduces singularities and increases grid skewness, which results in large numerical error and slow convergence rate. In this paper, we present the results of combining a finite difference scheme with domain decomposition to obtain a parallel scheme. This scheme is used to simulate steady-state forced convection in irregular axisymmetric and two-dimensional domains. The irregular domain is first dissected into subdomains that have smooth curves as their boundaries. Curvilinear coordinate systems are then generated for each subdomain. Each subdomain is mapped onto a processor in the BBN Butterfly computer. After the tasks of inner domain computation are completed in parallel, the inner boundary values are updated (also in parallel). This sets up an iterative (block Gauss-Seidel) procedure that terminates when convergence is achieved. The structure of our scheme allows a straightforward treatment of the load balance problem and alleviates memory contention. C1 DUKE UNIV,DEPT MECH ENGN & MAT SCI,DURHAM,NC 27706. RP WANG, MY (reprint author), DUKE UNIV,NIH NSF ENGN RES CTR EMERGING CARDIOVASC TECHNOL,DURHAM,NC 27706, USA. NR 8 TC 5 Z9 5 U1 0 U2 0 PU HEMISPHERE PUBL CORP PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 1040-7790 J9 NUMER HEAT TR B-FUND JI Numer Heat Tranf. B-Fundam. PD JUL-SEP PY 1991 VL 20 IS 1 BP 41 EP 59 PG 19 WC Thermodynamics; Mechanics SC Thermodynamics; Mechanics GA FX943 UT WOS:A1991FX94300003 ER PT J AU ENGLER, MM KARANIAN, JW SALEM, N AF ENGLER, MM KARANIAN, JW SALEM, N TI INFLUENCE OF DIETARY POLYUNSATURATED FATTY-ACIDS ON AORTIC AND PLATELET FATTY-ACID COMPOSITION IN THE RAT SO NUTRITION RESEARCH LA English DT Article DE RAT; GAMMA-LINOLENIC ACID; ALPHA-LINOLENIC ACID; AORTA; PLATELET; FATTY ACIDS ID CORONARY HEART-DISEASE; ADIPOSE-TISSUE; BIOSYNTHESIS; PROSTACYCLIN; FLUIDITY; PROSTAGLANDINS; THROMBOXANES; CHOLESTEROL; MEMBRANES; LIPIDS AB The effects of 18-carbon chain w-9, w-6 and w-3 fatty acid enriched diets on aortic and platelet fatty acid composition were studied in male Sprague-Dawley rats. Purified diets containing 11 wt % of either sesame oil (SES) rich in 18:1w9, borage oil (BOR) rich in 18:3w6 or a blend of linseed and saf- flower oils (LSO/SFO) rich in 18:3w3 were administered for 7 weeks. All diets provided comparable amounts of the essential fatty acid 18:2w6. Total lipids from aortic tissue and plate- lets were extracted, methylated and analyzed by gas chromatography. In general, the tissue fatty acid composition reflected the type of dietary fat. The SES diet resulted in increased levels of 18:1w9 whereas the BOR diet increased 18:3w6 and the LSO/SFO diet increased 18:3w3 in aortic and platelet lipids. However, the BOR diet also resulted in an increase in the longer chain metabolites 20:3w6 and 20:4w6. The LSO/SFO-based diet elevated the levels of 20:5w3 and 22:6w3. These results suggest that the profile of 20-carbon chain polyunsaturated fatty acids can be modified in vascular tissue and platelets by diets enriched with 18-carbon w-6 and w-3 fatty acids. C1 NIAAA, DIV INTRAMURAL CLIN & BIOL RES, CLIN STUDIES LAB, ANALYT CHEM SECT, BETHESDA, MD 20892 USA. NR 34 TC 11 Z9 13 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0271-5317 J9 NUTR RES JI Nutr. Res. PD JUL PY 1991 VL 11 IS 7 BP 753 EP 763 DI 10.1016/S0271-5317(05)80629-3 PG 11 WC Nutrition & Dietetics SC Nutrition & Dietetics GA FY238 UT WOS:A1991FY23800007 ER PT J AU BLAIR, A ZAHM, SH AF BLAIR, A ZAHM, SH TI CANCER AMONG FARMERS SO OCCUPATIONAL MEDICINE-STATE OF THE ART REVIEWS LA English DT Article RP BLAIR, A (reprint author), NCI,OCCUPAT STUDIES SECT,EXECUT PLAZA N,ROOM 418,ROCKVILLE,MD 20892, USA. RI Zahm, Shelia/B-5025-2015 NR 0 TC 177 Z9 178 U1 0 U2 3 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 0885-114X J9 OCCUP MED JI Occup. Med.-State Art Rev. PD JUL-SEP PY 1991 VL 6 IS 3 BP 335 EP 354 PG 20 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA GF147 UT WOS:A1991GF14700003 PM 1835166 ER PT J AU FUTREAL, PA BARRETT, JC AF FUTREAL, PA BARRETT, JC TI FAILURE OF SENESCENT CELLS TO PHOSPHORYLATE THE RB PROTEIN SO ONCOGENE LA English DT Article ID RETINOBLASTOMA SUSCEPTIBILITY GENE; HUMAN-DIPLOID FIBROBLASTS; SYRIAN-HAMSTER TUMORS; CELLULAR SENESCENCE; PRODUCT; EXPRESSION; CYCLE; IDENTIFICATION; SUPPRESSION; CARCINOMA AB The product of the RB susceptibility gene has been shown to be differentially phosphorylated during the cell cycle, suggesting a role in the regulation of cell cycle progression. We examined the expression and phosphorylation status of the RB protein in senescent Syrian hamster embryo cells. Both phosphorylated and unphosphorylated forms of the RB protein were observed in cells at early passages; however, only unphosphorylated RB protein was found in senescent cells. When nonsenescent cells at low population doubling levels were made quiescent by reducing the serum concentration of the media, the RB protein in these cells was mostly in the unphosphorylated protein in these cells was mostly in the unphosphorylated form. When stimulated with serum, phosphorylation of the RB protein occurred between 10-20 h after stimulation, which corresponded with the induction of DNA synthesis. Senescent cells, in contrast, did not show any phosphorylation of the RB protein in response to serum. In addition, cell lines that had escaped cellular senescence at various stages of neoplastic progression were examined; all 25 cell lines examined expressed RB protein, which was phosphorylated normally. These results suggest that the RB protein plays a role in cellular senescence with phosphorylation status determining this role. Factors controlling this phosphorylation are potential key factors in controlling cellular life span in culture. C1 UNIV N CAROLINA,DEPT PATHOL,CHAPEL HILL,NC 27514. RP FUTREAL, PA (reprint author), NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709, USA. NR 45 TC 72 Z9 73 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL PY 1991 VL 6 IS 7 BP 1109 EP 1113 PG 5 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA GV260 UT WOS:A1991GV26000003 PM 1861860 ER PT J AU PRIBYL, LJ WATSON, DK SCHULZ, RA PAPAS, TS AF PRIBYL, LJ WATSON, DK SCHULZ, RA PAPAS, TS TI D-ELG, A MEMBER OF THE DROSOPHILA-ETS GENE FAMILY - SEQUENCE, EXPRESSION AND EVOLUTIONARY COMPARISON SO ONCOGENE LA English DT Article ID PROTO-ONCOGENE; C-ETS; DEVELOPING EYE; DNA-BINDING; V-ETS; MELANOGASTER; INITIATION; PROTEINS; IDENTIFICATION; HYBRIDIZATION AB We have cloned a cDNA from the Drosophila elg gene, a new member of the ets family of genes. The D-elg gene is located at 97D on chromosome 3R and is expressed as a 2.0 kb RNA in the embryos, pupae and adults, with no detectable expression in third instar larvae. D-elg expression is observed in all cells of early stage embryos, prior to transcriptional activation of the zygotic genome, and is maintained throughout embryogenesis with no regional localization. The cDNA encodes a predicted protein of 15.4 kD that has an 86 amino acid sequence with 72% similarity to the carboxy terminal region of the Drosophila ets-2 gene. Comparison with all known ets genes allows us to define a minimal region required for assignment to the ets gene family. C1 UNIV TEXAS,MD ANDERSON CANC CTR,DEPT BIOCHEM & MOLEC BIOL,HOUSTON,TX 77030. RP PRIBYL, LJ (reprint author), NCI,MOLEC ONCOL LAB,FREDERICK,MD 21702, USA. NR 44 TC 37 Z9 38 U1 0 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL PY 1991 VL 6 IS 7 BP 1175 EP 1183 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA GV260 UT WOS:A1991GV26000012 PM 1713660 ER PT J AU PIERCE, JH ARNSTEIN, P DIMARCO, E ARTRIP, J KRAUS, MH LONARDO, F DIFIORE, PP AARONSON, SA AF PIERCE, JH ARNSTEIN, P DIMARCO, E ARTRIP, J KRAUS, MH LONARDO, F DIFIORE, PP AARONSON, SA TI ONCOGENIC POTENTIAL OF ERBB-2 IN HUMAN MAMMARY EPITHELIAL-CELLS SO ONCOGENE LA English DT Article ID NEU ONCOGENE; EGF RECEPTOR; AMPLIFICATION; LINES; GENE; TRANSFORMATION; OVEREXPRESSION; ADENOCARCINOMA; PROTOONCOGENE; CARCINOMAS AB Introduction of the normal erbB-2 gene into immortalized human mammary epithelial cells (184B5) by transfection conferred a growth advantage to these cells both in vitro and in vivo. The 184B5 cells overexpressing erbB-2 formed colonies in semi-solid medium, frequently induced transient nodules in athymic mice and produced progressive tumors in vivo at a low frequency. Those tumors which did arise from erbB-2-transfected cells displayed substantially higher levels of normal gp185erb-2 protein when compared to the original transfectants, consistent with their selection for increased erbB-2 expression. Introduction of genes encoding genetically altered erbB-2 molecules into 184B5 cells increased their colony-forming efficiency and converted the cells to a tumorigenic phenotype at a high frequency. When the biological and biochemical properties of human mammary carcinoma cell lines known to overexpress erbB-2 were compared to the transfected 184B5 lines, they behaved most like those overexpressing the normal erbB-2 protein. Results indicate that overexpression of normal erbB-2 may directly contribute to the transformation of human mammary epithelium if sufficient levels of erbB-2 protein are expressed or if the erbB-2 gene is genetically altered. C1 CALIF DEPT HLTH SERV,BERKELEY,CA 94704. IST NAZL RIC,I-16132 GENOA,ITALY. UNIV ROCHESTER,SCH MED,DEPT PATHOL,ROCHESTER,NY 14627. RP PIERCE, JH (reprint author), NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892, USA. RI Di Fiore, Pier Paolo/K-2130-2012 OI Di Fiore, Pier Paolo/0000-0002-2252-0950 NR 23 TC 143 Z9 145 U1 1 U2 4 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL PY 1991 VL 6 IS 7 BP 1189 EP 1194 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA GV260 UT WOS:A1991GV26000014 PM 1713661 ER PT J AU EISEMANN, A AHN, JA GRAZIANI, G TRONICK, SR RON, D AF EISEMANN, A AHN, JA GRAZIANI, G TRONICK, SR RON, D TI ALTERNATIVE SPLICING GENERATES AT LEAST 5 DIFFERENT ISOFORMS OF THE HUMAN BASIC-FGF RECEPTOR SO ONCOGENE LA English DT Article ID FIBROBLAST GROWTH-FACTOR; PROTEIN-TYROSINE KINASE; MESSENGER-RNA; ENZYMATIC AMPLIFICATION; MOUSE-BRAIN; GENE; DNA; EXPRESSION; CDNA; CELLS AB Fibroblast growth factors (FGFs) are polypeptide mitogens that induce the proliferation of a wide variety of cell types. Of the seven family members, the best characterized are basic and acidic FGF. In addition to their mitogenic effects, they participate in angiogenesis, differentiation and maintenance of survival of neurons, cell migration and embryonal development. Of all family members, keratinocyte growth factor (KGF) is unique in that it is a specific mitogen for epithelial cells and does not interact with the FGF receptor of fibroblasts. To study the interactions between KGF and its receptor, we isolated KGF and FGF receptors from keratinocytes and fibroblasts, respectively. In the course of this study, we isolated five different variants of the FGF receptor from human fibroblasts and showed that all were derived from a single genetic locus. Four of these variants encode transmembrane receptors and can be divided into two subgroups that differ from one another with respect to the number (two or three) of immunoglobulin (Ig)-like domains. Within each subgroup, one receptor differed from the other by the presence of a two-codon insertion. Thus, all the variations among the four isoforms are localized to their ligand binding domains. The fifth isoform encodes a molecule truncated just 3' to the first Ig-like domain and thus could be secreted from the cell. The transcripts encoding the long and short isoforms were found to be expressed in many cell types, but their reltive levels of expression varied greatly depending on the cell type. These findings indicate that alternative splicing generates diverse FGF receptor isoforms in human cells. C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. TECHNION ISRAEL INST TECHNOL,DEPT BIOL,IL-32000 HAIFA,ISRAEL. GEORGETOWN UNIV HOSP,DIV MED ONCOL,WASHINGTON,DC 20007. RP RON, D (reprint author), NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892, USA. RI Graziani, Grazia/G-5747-2012; OI GRAZIANI, GRAZIA/0000-0002-0221-768X NR 45 TC 114 Z9 117 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL PY 1991 VL 6 IS 7 BP 1195 EP 1202 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA GV260 UT WOS:A1991GV26000015 PM 1650441 ER PT J AU LU, D THOMPSON, JD GORSKI, GK RICE, NR MAYER, MG YUNIS, JJ AF LU, D THOMPSON, JD GORSKI, GK RICE, NR MAYER, MG YUNIS, JJ TI ALTERATIONS AT THE REL LOCUS IN HUMAN LYMPHOMA SO ONCOGENE LA English DT Article ID NF-KAPPA-B; DNA-BINDING SUBUNIT; C-REL; V-REL; RETICULOENDOTHELIOSIS VIRUS; PROTO-ONCOGENE; MESSENGER-RNA; NUCLEOTIDE-SEQUENCE; GENE-EXPRESSION; CELL-LINE AB The rel proto-oncogene has been mapped to chromosome region 2p11.2-14, a site associated with nonrandom rearrangements in non-Hodgkin's lymphoma. We have characterized an abnormal rel mRNA from a cell line derived from a diffuse large cell lymphoma, in which the evolutionarily conserved N-terminal half of the rel coding region was fused with the C-terminal coding region of an unrelated gene. In addition, rearrangement or amplification of the rel locus was found in the lymphomatous tissue of two follicular and one diffuse large cell lymphoma. The findings suggest involvement of rel in the pathogenesis of large cell lymphoma. C1 HAHNEMANN UNIV,SCH MED,DEPT NEOPLAST DIS,DIV HUMAN GENET & MOLEC BIOL,PHILADELPHIA,PA 19102. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. RP YUNIS, JJ (reprint author), HAHNEMANN UNIV,SCH MED,DEPT NEOPLAST DIS,DIV HUMAN GENET & MOLEC BIOL,PHILADELPHIA,PA 19102, USA. FU NCI NIH HHS [CA3314, N01-CO-74101] NR 52 TC 104 Z9 104 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL PY 1991 VL 6 IS 7 BP 1235 EP 1241 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA GV260 UT WOS:A1991GV26000020 PM 1650444 ER PT J AU RON, E KLEINERMAN, RA LIVOLSI, VA FRAUMENI, JF AF RON, E KLEINERMAN, RA LIVOLSI, VA FRAUMENI, JF TI FAMILIAL NONMEDULLARY THYROID-CANCER SO ONCOLOGY LA English DT Article DE NONMEDULLARY THYROID CANCER; FAMILIAL ID PAPILLARY CARCINOMA AB A 5-fold excess risk of nonmedullary thyroid cancer among close relatives of affected patients was detected in a population-based case-control study of thyroid cancer in Connecticut. The 2 familial cases with early onset and multiple foci suggest genetic susceptibility, whereas the 2 cases with late onset may be related to a common environmental exposure. C1 HOSP UNIV PENN,DEPT PATHOL & LAB MED,PHILADELPHIA,PA 19104. RP RON, E (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,RADIAT EPIDEMIOL BRANCH,EPN 408,BETHESDA,MD 20892, USA. OI Kleinerman, Ruth/0000-0001-7415-2478 NR 20 TC 42 Z9 43 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-2414 J9 ONCOLOGY JI Oncology PD JUL-AUG PY 1991 VL 48 IS 4 BP 309 EP 311 PG 3 WC Oncology SC Oncology GA GE184 UT WOS:A1991GE18400009 PM 1891173 ER PT J AU BENNETT, GJ MAX, MB AF BENNETT, GJ MAX, MB TI TISSUE DONORS - PAINFUL NERVE LESIONS AND REFLEX SYMPATHETIC DYSTROPHY SO PAIN LA English DT Letter RP BENNETT, GJ (reprint author), NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD 20892, 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 0304-3959 J9 PAIN JI Pain PD JUL PY 1991 VL 46 IS 1 BP 118 EP 118 DI 10.1016/0304-3959(91)90044-X PG 1 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA FW258 UT WOS:A1991FW25800021 ER PT J AU WARBURG, A MILLER, LH AF WARBURG, A MILLER, LH TI CRITICAL STAGES IN THE DEVELOPMENT OF PLASMODIUM IN MOSQUITOS SO PARASITOLOGY TODAY LA English DT Article ID ANOPHELES-STEPHENSI LISTON; MALARIA PARASITES; SALIVARY-GLANDS; GAMBIAE; MIDGUT; GALLINACEUM; SPOROZOITES; FALCIPARUM; CULICIDAE; DIPTERA AB One tool for the control of malaria that may become available to future generations of public health workers is the introduction of genes into the Anopheline vector populations that will render the mosquitoes refractory to Plasmodium. Insights from basic research that could transform this idea into a technical reality are presently lacking. In this review, Alon Warburg and Louis Miller focus on one crucial area of research: the identification of potentially vulnerable points in the developmental cycle of Plasmodium in mosquitoes. RP WARBURG, A (reprint author), NIAID,BETHESDA,MD 20892, USA. NR 34 TC 39 Z9 39 U1 1 U2 4 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 JUL PY 1991 VL 7 IS 7 BP 179 EP 181 DI 10.1016/0169-4758(91)90127-A PG 3 WC Parasitology SC Parasitology GA FV472 UT WOS:A1991FV47200011 PM 15463488 ER PT J AU EPPS, RP MANLEY, MW AF EPPS, RP MANLEY, MW TI A PHYSICIANS GUIDE TO PREVENTING TOBACCO USE DURING CHILDHOOD AND ADOLESCENCE SO PEDIATRICS LA English DT Article DE TOBACCO; SMOKING PREVENTION; CHILD; ADOLESCENT; PHYSICIAN TECHNIQUES ID SMOKELESS TOBACCO; SMOKING; CHILDREN AB Physicians who care for children can and should help patients avoid the use of tobacco. Physicians are well aware of the health hazards associated with tobacco use, inasmuch as smoking is the chief, single cause of premature mortality in this country. Each day, more than 3000 children in the United States begin to use tobacco. Physicians who care for children have patients at vastly different stages of intellectual and social maturity. Both the theory and practical details of tobacco-related interventions differ among infants, children, and adolescents. The physician is in a unique position to intervene in the early stages. Anticipatory guidance-the practice of providing counsel regarding potential problems-is a key part of health care for the young. If physicians provide messages about tobacco use that are appropriate to the patient's age and developmental stage, the potential for broad public health impact is great. Based on a series of clinical trials, the National Cancer Institute developed a manual to assist physicians in helping their patients stop smoking. The recommendations in this manual include four physician activities that begin with the letter A (four A's): Ask, Advise, Assist, and Arrange follow-up. For physicians who treat children, a fifth A, Anticipatory guidance, is added. C1 NCI,DIV CANC PREVENT & CONTROL,CANC CONTROL SCI PROGRAM,BETHESDA,MD 20892. NR 26 TC 48 Z9 48 U1 1 U2 2 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUL PY 1991 VL 88 IS 1 BP 140 EP 144 PG 5 WC Pediatrics SC Pediatrics GA FV062 UT WOS:A1991FV06200020 PM 2057249 ER PT J AU MILLAN, MA KISS, A AGUILERA, G AF MILLAN, MA KISS, A AGUILERA, G TI DEVELOPMENTAL-CHANGES IN BRAIN ANGIOTENSIN-II RECEPTORS IN THE RAT SO PEPTIDES LA English DT Article DE ANGIOTENSIN-II; BRAIN RECEPTORS; DEVELOPMENT ID CENTRAL NERVOUS-SYSTEM; SMOOTH-MUSCLE CELLS; BINDING-SITES; POSTNATAL-DEVELOPMENT; INVITRO AUTORADIOGRAPHY; CONVERTING ENZYME; IMMUNOCYTOCHEMICAL LOCALIZATION; OPIATE RECEPTORS; FETAL BRAIN; EXPRESSION AB All binding and distribution were measured in rat brain during development by autoradiographic techniques using radioiodinated [Sar1, Ile8]AII. At all ages, from 2 days to 7 weeks, binding was present in the circumventricular organs, and areas related to pituitary hormone secretion and modulation of sympathetic activity. At early stages of development, AII binding was transiently expressed in a number of motor- and sensory-related areas. These findings support a role for AII in the control of water intake and autonomic activity at all stages of development, and suggest that the peptide may be involved in the maturation of neuronal function during development. C1 NICHHD,DEV ENDOCRINOL BRANCH,ENDOCRINE PHYSIOL SECT,10 RM 10N262,BETHESDA,MD 20892. NR 51 TC 29 Z9 29 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0196-9781 J9 PEPTIDES JI Peptides PD JUL-AUG PY 1991 VL 12 IS 4 BP 723 EP 737 DI 10.1016/0196-9781(91)90125-9 PG 15 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA GG175 UT WOS:A1991GG17500007 PM 1788135 ER PT J AU JANEZIC, D BROOKS, BR AF JANEZIC, D BROOKS, BR TI HARMONIC-ANALYSIS OF LARGE SYSTEMS - APPLICATION TO BOVINE PANCREATIC TRYPSIN-INHIBITOR SO PERIODICUM BIOLOGORUM LA English DT Article; Proceedings Paper CT 20TH YUGOSLAV SYMP ON BIOPHYSICS CY NOV 06-09, 1990 CL ROGASKA SLATINA, YUGOSLAVIA SP YUGOSLAV BIOPHYS SOC ID DYNAMICS; FLUCTUATIONS C1 NCI,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. RP JANEZIC, D (reprint author), BORIS KIDRIC INST CHEM,POB 30,YU-61115 LJUBLJANA,YUGOSLAVIA. NR 6 TC 0 Z9 0 U1 0 U2 1 PU PERIODICUM BIOLOGORUM PI ZAGREB PA HRVATSKO PRIRODOSLOVNO DRUSTVO ILICA 16/111, 41000 ZAGREB, CROATIA SN 0031-5362 J9 PERIOD BIOL PD JUL PY 1991 VL 93 IS 2 BP 271 EP 274 PG 4 WC Biology SC Life Sciences & Biomedicine - Other Topics GA FY770 UT WOS:A1991FY77000033 ER PT J AU JURETIC, D AF JURETIC, D TI DAMPED OSCILLATORY CONTROL OF MITOCHONDRIAL ENERGY LINKED PROCESSES OBSERVED IN THE PRESENCE OF MAGAININS SO PERIODICUM BIOLOGORUM LA English DT Article; Proceedings Paper CT 20TH YUGOSLAV SYMP ON BIOPHYSICS CY NOV 06-09, 1990 CL ROGASKA SLATINA, YUGOSLAVIA SP YUGOSLAV BIOPHYS SOC ID RAT-LIVER MITOCHONDRIA; MEMBRANE C1 NHLBI,CELL BIOL LAB,BETHESDA,MD 20892. NR 8 TC 0 Z9 0 U1 0 U2 0 PU PERIODICUM BIOLOGORUM PI ZAGREB PA HRVATSKO PRIRODOSLOVNO DRUSTVO ILICA 16/111, 41000 ZAGREB, CROATIA SN 0031-5362 J9 PERIOD BIOL PD JUL PY 1991 VL 93 IS 2 BP 277 EP 278 PG 2 WC Biology SC Life Sciences & Biomedicine - Other Topics GA FY770 UT WOS:A1991FY77000035 ER PT J AU YEH, SY HAERTZEN, CA AF YEH, SY HAERTZEN, CA TI COCAINE-INDUCED LOCOMOTOR-ACTIVITY IN RATS SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE COCAINE; LOCOMOTOR ACTIVITY ID REVERSE TOLERANCE; STIMULATION; DISPOSITION; MICE; DOPAMINE; BEHAVIOR AB Rats were injected SC or IP with a dose of cocaine at 20 mg/kg twice daily or saline (2 ml/kg) for 15 consecutive doses. Horizontal (including ambulatory and repetitive activity) and ambulatory locomotor activities were assessed following the first (acute) and the 15th (chronic) injections. Total locomotor activity (area under curve, AUC) following the acute and the chronic administration of cocaine were comparable, regardless of the route of drug administration. However, the temporal patterns of activity were significantly different; the peak of locomotor activity occurred earlier (chronic vs. acute, 20 vs. 40 min after IP; 130 vs. 180 min after SC) following chronic cocaine administration. Furthermore, the peak activity was significantly higher (3-fold after IP and 50% after SC) in chronically than in acutely treated rats, providing evidence for sensitization. In contrast, activity in the late session (240-280 min after SC) was significantly lower following the chronic SC cocaine administration, providing evidence for desensitization. The absolute slope values of the ascending phase and the descending phase were significantly larger following chronic administration of cocaine than that following the acute dosing. The possibility of changes in locomotor activity with alteration of pharmacokinetics on chronic cocaine treatment is discussed. RP YEH, SY (reprint author), NIDA,ADDICT RES CTR,POB 5180,BALTIMORE,MD 21224, USA. NR 18 TC 33 Z9 33 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD JUL PY 1991 VL 39 IS 3 BP 723 EP 727 DI 10.1016/0091-3057(91)90154-T PG 5 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA GD543 UT WOS:A1991GD54300028 PM 1784601 ER PT J AU SUDDATH, RL STRAW, GM FREED, WJ BIGELOW, LB KIRCH, DG WYATT, RJ AF SUDDATH, RL STRAW, GM FREED, WJ BIGELOW, LB KIRCH, DG WYATT, RJ TI A CLINICAL-TRIAL OF NIFEDIPINE IN SCHIZOPHRENIA AND TARDIVE-DYSKINESIA SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE CALCIUM CHANNEL INHIBITORS; DIHYDROPYRIDINES; NIFEDIPINE; TARDIVE DYSKINESIA; SCHIZOPHRENIA ID INDUCED BEHAVIORAL STIMULATION; CALCIUM-CHANNEL ANTAGONISTS; TOURETTES-SYNDROME; VERAPAMIL; MICE; DILTIAZEM; BLOCKERS; BRAIN AB Effects of the dihydropyridine calcium channel inhibitor nifedipine on chronic schizophrenia and tardive dyskinesia were studied in an 8-week double-blind crossover trial. Four of the ten patients had tardive dyskinesia, and three of these were not receiving neuroleptics. No effects on symptoms of chronic schizophrenia were found using Psychiatric Symptom Assessment Scale ratings. In the four patients with tardive dyskinesia, an average improvement in total Abnormal Involuntary Movement Scale scores of 57% was observed. These data suggest that dihydropyridine calcium channel inhibitors may be effective in the treatment of tardive dyskinesia in schizophrenic patients. C1 NIMH,NEUROSCI CTR ST ELIZABETHS,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032. NR 28 TC 15 Z9 15 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD JUL PY 1991 VL 39 IS 3 BP 743 EP 745 DI 10.1016/0091-3057(91)90157-W PG 3 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA GD543 UT WOS:A1991GD54300031 PM 1686106 ER PT J AU NOWAK, G SKOLNICK, P PAUL, IA AF NOWAK, G SKOLNICK, P PAUL, IA TI DOWN-REGULATION OF DOPAMINE1 (D1) RECEPTORS BY CHRONIC IMIPRAMINE IS SPECIES-SPECIFIC SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Note DE D1 RECEPTORS; DOPAMINE; IMIPRAMINE; ANTIDEPRESSANTS; MICE; RATS; SPECIES-SPECIFICITY; LIMBIC SYSTEM; CORPUS STRIATUM ID FORCED SWIMMING TEST; LIMBIC SYSTEM; D-1 RECEPTORS; BINDING; ANTIDEPRESSANTS; RATS AB Chronic treatment with imipramine (15 mg/kg, twice daily for 14 days) induces a down-regulation of limbic D1 receptors in rats but not in mice. In this mouse strain, both chronic and acute imipramine treatment have been shown to produce clear behavioral effects in the forced swim test. While the data presented here are consistent with previously reported findings in rats, they demonstrate that the down-regulation of D1 receptors by chronic antidepressant treatment is species-specific. This phenomenon indicates that D1 receptor down-regulation is not critical to the therapeutic mechanism of action of antidepressants. RP NOWAK, G (reprint author), NIDDKD,NEUROSCI LAB,BLDG 8,ROOM 111,BETHESDA,MD 20892, USA. NR 8 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 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD JUL PY 1991 VL 39 IS 3 BP 769 EP 771 DI 10.1016/0091-3057(91)90162-U PG 3 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA GD543 UT WOS:A1991GD54300036 PM 1838413 ER PT J AU YEH, SY HSU, FL AF YEH, SY HSU, FL TI THE NEUROCHEMICAL AND STIMULATORY EFFECTS OF PUTATIVE METABOLITES OF 3,4-METHYLENEDIOXYAMPHETAMINE AND 3,4-METHYLENEDIOXYMETHAMPHETAMINE IN RATS SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Note DE NEUROTOXICITY; LOCOMOTOR ACTIVITY; MDA; MDMA; 5-HT; 5-HIAA; ALPHA-METHYLDOPAMINE; ALPHA-METHYLNOREPINEPHRINE; ALPHA-METHYLEPINEPHRINE; 4-HYDROXY-3-METHOXYAMPHETAMINE ID METHYLENEDIOXYAMPHETAMINE MDA; METHYLENEDIOXYMETHAMPHETAMINE; BRAIN; MDMA; AMPHETAMINE; SEROTONIN; TERMINALS; IDENTIFICATION; NEUROTOXICITY; INVIVO AB Rats were injected SC with a dose of 10 mg/kg (as base) of 3,4-methylenedioxyamphetamine (MDA), or 3,4-methylenedioxymethamphetamine (MDMA), 4-hydroxy-3-methoxyamphetamine, alpha-methyldopamine and alpha-methylnorepinephrine, metabolites of MDA, and alpha-methlepinephrine, a putative metabolite of MDMA, twice daily for either 5 or 7 consecutive doses. The rats were killed 24 h after the last injection and monoamines in discrete brain regions were assayed. MDA, MDMA, 4-hydroxy-3-methoxyamphetamine and alpha-methyldopamine, but not alpha-methylepinephrine, decreased the concentration of serotonin (5-HT) in the frontal cortex. MDA and MDMA, but not 4-hydroxy-3-methoxyamphetamine, alpha-methyldopamine and alpha-methylepinephrine, also decreased the concentration of 5-hydroxyindoleacetic acid (5-HIAA) in the frontal cortexes. In stimulatory studies, MDA and MDMA, but not their metabolites except alpha-methylepinephrine, which increased activity at 15 and 30 min, increased locomotor activity from 15 to 180 min following the drug administration. C1 USA,CTR CHEM RES DEV & ENGN,ABERDEEN PROVING GROUND,MD 21010. RP YEH, SY (reprint author), NIDA,ADDICT RES CTR,POB 5180,BALTIMORE,MD 21224, USA. NR 25 TC 18 Z9 18 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD JUL PY 1991 VL 39 IS 3 BP 787 EP 790 DI 10.1016/0091-3057(91)90165-X PG 4 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA GD543 UT WOS:A1991GD54300039 PM 1723801 ER PT J AU DORNAN, WA KATZ, JL RICAURTE, GA AF DORNAN, WA KATZ, JL RICAURTE, GA TI THE EFFECTS OF REPEATED ADMINISTRATION OF MDMA ON THE EXPRESSION OF SEXUAL-BEHAVIOR IN THE MALE-RAT SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Note DE 3,4-METHYLENEDIOXYMETHAMPHETAMINE; MDMA; ECSTASY; 5-HT; MALE RAT SEXUAL BEHAVIOR; NEUROTOXICITY ID BRAIN; SEROTONIN; 3,4-METHYLENEDIOXYMETHAMPHETAMINE AB 3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy") is a potent neurotoxin which preferentially produces 5-HT nerve terminal degeneration in the CNS in both rodents and primates. Timely research on the behavioral effects of acute and long term treatment of MDMA is critical due to the neuropathological effects of MDMA and its abuse liability. Presently, there are no published reports that have systematically examined the effects of acute or chronic treatment of MDMA on animal sexual behavior. Accordingly, the effects of repeated systemic administration of MDMA on a variety of parameters of male sexual behavior in sexually vigorous male rats were studied. Treatment consisted of subcutaneous injections of MDMA (40 mg/kg) or saline (1 mg/kg) every 12 hours for 4 consecutive days. In addition, neurochemical assessments of brain 5-HT and 5-HIAA depletion following repeated MDMA treatment were also conducted using reverse phase liquid chromatography. The results of this study revealed that repeated systemic administration of MDMA to sexually vigorous male rats produced a transient disruption of the expression of male copulatory behavior. In addition, in MDMA-treated males that did display copulatory behavior, both the ejaculation latency and postejaculatory interval were dramatically lengthened when compared to saline injected controls. Suprisingly, one week after the first behavioral test, copulatory behavior in MDMA treated rats appeared unaffected despite a marked depletion of 5-HT and 5-HIAA content in the striatum, and hippocampus. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21224. NIDA,ADDICT RES CTR,PSYCHOBIOL LAB,BETHESDA,MD 21224. RP DORNAN, WA (reprint author), ILLINOIS WESLEYAN UNIV,DEPT PSYCHOL,BLOOMINGTON,IL 61702, USA. OI Katz, Jonathan/0000-0002-1068-1159 NR 17 TC 27 Z9 27 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD JUL PY 1991 VL 39 IS 3 BP 813 EP 816 DI 10.1016/0091-3057(91)90171-W PG 4 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA GD543 UT WOS:A1991GD54300045 PM 1723802 ER PT J AU DABESTANI, R RESZKA, KJ DAVIS, DG SIK, RH CHIGNELL, CF AF DABESTANI, R RESZKA, KJ DAVIS, DG SIK, RH CHIGNELL, CF TI SPECTROSCOPIC STUDIES OF CUTANEOUS PHOTOSENSITIZING AGENTS .16. DISPERSE BLUE-35 SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID SINGLET OXYGEN; SUPEROXIDE; DYES; NMR AB The photochemistry (Type I and II) of the phototoxic textile dye Disperse Blue 35 (DB-35) and its purified components has been studied using electron spin resonance in conjunction with spin trapping technique and the direct detection of singlet oxygen (1O2) luminescence. The main components of DB-35 (which is synthesized by the successive nitration, reduction and methylation of 1,8-dihydroxy-anthraquinone) were separated by HPLC and identified by mass spectrometry and 2-D NMR as 4,5-diamino-1,8-dihydroxyanthraquinone (4,5-DDHAQ; 62% of total dye) and 2,7-diamino-1,8-dihydroxyanthraquinone (2,7-DDHAQ; 31% of total dye). Minor components included 2,5-diamino-1,8-dihydroxyanthraquinone (2,5-DDHAQ) and a monomethylated derivative of either 4,5-DDHAQ or 2,7-DDHAQ. Irradiation (624 nm) of 4,5-DDHAQ and 2,7-DDHAQ in dimethylsulfoxide resulted in the generation of superoxide which was trapped by 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). Visible light irradiation of the components in ethanol generated 1O2 with the yields decreasing in the following order: 4,5-DDHAQ > 2,5-DDHAQ > 2,7-DDHAQ. These findings indicate that upon irradiation by visible light DB-35 can generate active oxygen species which may be responsible for the photocontact dermatitis caused by this dye. RP DABESTANI, R (reprint author), NIEHS,MOLEC BIOPHYS LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 19 TC 3 Z9 3 U1 1 U2 2 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD JUL PY 1991 VL 54 IS 1 BP 37 EP 42 DI 10.1111/j.1751-1097.1991.tb01982.x PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA GB386 UT WOS:A1991GB38600006 PM 1658824 ER EF