FN Thomson Reuters Web of Science™ VR 1.0 PT J AU GAWRISCH, K RUSTON, D ZIMMERBERG, J PARSEGIAN, VA RAND, RP FULLER, N AF GAWRISCH, K RUSTON, D ZIMMERBERG, J PARSEGIAN, VA RAND, RP FULLER, N TI MEMBRANE DIPOLE POTENTIALS, HYDRATION FORCES, AND THE ORDERING OF WATER AT MEMBRANE SURFACES SO BIOPHYSICAL JOURNAL LA English DT Article ID MAGNETIC-RESONANCE SPECTROSCOPY; POLAR GROUP CONFORMATION; BILAYER-MEMBRANES; PHOSPHOLIPID-BILAYERS; HYDROPHOBIC IONS; LIPID BILAYER; ETHER; PHOSPHATIDYLCHOLINES; PHASE; 1,2-DIACYL AB We have compared hydration forces, electrical dipole potentials, and structural parameters of dispersions of dipalmitoylphosphatidylcholine (DPPC) and dihexadecylphosphatidylcholine (DHPC) to evaluate the influence of fatty acid carbonyl groups on phospholipid bilayers. NMR and x-ray investigations performed over a wide range of water concentrations in the samples show, that in the liquid crystalline lamellar phase, the presence of carbonyl groups is not essential for lipid structure and hydration. Within experimental error, the two lipids have identical repulsive hydration forces between their bilayers. The higher transport rate of the negatively charged tetraphenylboron over the positively charged tetraphenylarsonium indicates that the dipole potential is positive inside the membranes of both lipids. However, the lack of fatty acid carbonyl groups in the ether lipid DHPC decreased the Potential by (118 +/- 15) mV. By considering the sign of the potential and the orientation of carbonyl groups and headgroups, we conclude that the first layer of water molecules at the lipid water interface makes a major contribution to the dipole potential. C1 NIDDK,BETHESDA,MD 20892. NICHHD,BETHESDA,MD 20892. BROCK UNIV,ST CATHARINES L2S 3A1,ONTARIO,CANADA. RP GAWRISCH, K (reprint author), DCRT,BETHESDA,MD 20892, USA. NR 57 TC 338 Z9 345 U1 8 U2 45 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD MAY PY 1992 VL 61 IS 5 BP 1213 EP 1223 PG 11 WC Biophysics SC Biophysics GA HT993 UT WOS:A1992HT99300016 PM 1600081 ER PT J AU LONCHARICH, RJ BROOKS, BR PASTOR, RW AF LONCHARICH, RJ BROOKS, BR PASTOR, RW TI LANGEVIN DYNAMICS OF PEPTIDES - THE FRICTIONAL DEPENDENCE OF ISOMERIZATION RATES OF N-ACETYLALANYL-N'-METHYLAMIDE SO BIOPOLYMERS LA English DT Article ID STOCHASTIC MOLECULAR-DYNAMICS; CONFORMATIONAL TRANSITIONS; BROWNIAN DYNAMICS; CHAIN MOLECULES; SIMULATIONS; PROTEIN; CYCLOHEXANE; ALGORITHMS; KRAMERS; ENERGY AB The rate constant for the transition between the equatorial and axial conformations of N-acetylalanyl-N'-methylamide has been determined from Langevin dynamics (LD) simulations with no explicit solvent. The isomerization rate is maximum at collision frequency gamma = 2 ps-1, shows diffusive character for gamma greater-than-or-equal-to 10 ps-1, but does not approach zero even at gamma = 0.01 ps-1. This behavior differs from that found for a one-dimensional bistable potential and indicates that both collisional energy transfer with solvent and vibrational energy transfer between internal modes are important in the dynamics of barrier crossing for this system. It is suggested that conformational searches of peptides be carried out using LD with a collision frequency that maximizes the isomerization rate (i.e., gamma almost-equal-to 2 ps-1). This method is expected to be more efficient than either molecular dynamics in vacuo (which corresponds to LD with gamma = 0) or molecular dynamics in solvent (where dynamics is largely diffusive). C1 US FDA,CTR BIOL EVALUAT & RES,BIOPHYS LAB,BETHESDA,MD 20892. NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. NR 50 TC 297 Z9 299 U1 3 U2 27 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PD MAY PY 1992 VL 32 IS 5 BP 523 EP 535 DI 10.1002/bip.360320508 PG 13 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA HQ085 UT WOS:A1992HQ08500007 PM 1515543 ER PT J AU SUN, Y HEGAMYER, G COLBURN, NH AF SUN, Y HEGAMYER, G COLBURN, NH TI A SIMPLE METHOD USING PCR FOR DIRECT SEQUENCING OF GENOMIC DNA FROM FROZEN TUMOR-TISSUE EMBEDDED IN OPTIMAL CUTTING TEMPERATURE COMPOUND SO BIOTECHNIQUES LA English DT Note AB Described here is a three-day protocol that directly yields DNA sequence after isolating and PCR amplifying genomic DNA from a small sample of frozen nasopharyngeal carcinoma tissue embedded in optimal cutting temperature (OCT) compound. The method is consistently successful, reproducible and will facilitate the rapid analysis of DNA sequence from very small samples. C1 NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,CELL BIOL SECT,FREDERICK,MD 21702. NCI,DYNCORP,PROGRAM RESOURCES INC,BCDP,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74102] NR 5 TC 17 Z9 17 U1 1 U2 2 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD MAY PY 1992 VL 12 IS 5 BP 639 EP 640 PG 2 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HT696 UT WOS:A1992HT69600003 PM 1515127 ER PT J AU JAIN, VK MAGRATH, IT SHIMADA, T AF JAIN, VK MAGRATH, IT SHIMADA, T TI DUAL REPORTER VECTORS FOR DETERMINATION OF ACTIVITY OF BIDIRECTIONAL PROMOTERS SO BIOTECHNIQUES LA English DT Note ID MAMMALIAN-CELLS C1 NHLBI,CLIN HEMATOL BRANCH,BETHESDA,MD 20892. RP JAIN, VK (reprint author), NHLBI,PEDIAT BRANCH,BLDG 10,ROOM 13N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 7 TC 7 Z9 7 U1 0 U2 1 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD MAY PY 1992 VL 12 IS 5 BP 681 EP & PG 0 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HT696 UT WOS:A1992HT69600013 PM 1325163 ER PT J AU SHIMADA, Y MIGLIACCIO, G RUSCETTI, S ADAMSON, JW MIGLIACCIO, AR AF SHIMADA, Y MIGLIACCIO, G RUSCETTI, S ADAMSON, JW MIGLIACCIO, AR TI EXPRESSION OF THE INTERLEUKIN-3 AND GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR GENES IN FRIEND SPLEEN FOCUS-FORMING VIRUS-INDUCED ERYTHROLEUKEMIA SO BLOOD LA English DT Article ID MURINE LEUKEMIA-VIRUS; MULTI-CSF IL-3; CELL-LINES; HEMATOPOIETIC-CELLS; MESSENGER-RNA; TUMORIGENIC CELLS; GROWTH; INVITRO; ACTIVATION; DIFFERENTIATION C1 NEW YORK BLOOD CTR,LINDSLEY F KIMBALL RES INST,HEMATOPOIET GROWTH FACTORS LAB,310 E 67TH ST,NEW YORK,NY 10021. IST SUPER SANITA,BIOL CELLULAIRE LAB,I-00161 ROME,ITALY. FREDERICK CANC RES FACIL,DIV CANC ETIOL,FREDERICK,MD 21701. FU NIDDK NIH HHS [DK-41937] NR 51 TC 5 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD MAY 1 PY 1992 VL 79 IS 9 BP 2423 EP 2431 PG 9 WC Hematology SC Hematology GA HW884 UT WOS:A1992HW88400032 PM 1571554 ER PT J AU ROJAS, E ARISPE, N HAIGLER, HT BURNS, AL POLLARD, HB AF ROJAS, E ARISPE, N HAIGLER, HT BURNS, AL POLLARD, HB TI IDENTIFICATION OF ANNEXINS AS CALCIUM CHANNELS IN BIOLOGICAL-MEMBRANES SO BONE AND MINERAL LA English DT Article; Proceedings Paper CT 5TH INTERNATIONAL CONF ON CELL MEDIATED CALCIFICATION AND MATRIX VESICLES CY NOV 16-20, 1991 CL HILTON HEAD, SC SP NIH, NIAMSD, CIBA GEIGY, DEPUY, ELECTROBIOLOGY, GLAXO, INST RECH INT SERVIER, LILLY RES LABS, MILES, ABBOTT LABS DE ANNEXIN-VII; ANNEXIN-V; CALCIUM CHANNELS; BIOLOGICAL MEMBRANES; MEMBRANE FUSION; MATRIX VESICLES; SECRETORY VESICLES ID BILAYER-MEMBRANES; BINDING PROTEIN; ENDONEXIN-II C1 UNIV CALIF IRVINE,DEPT PHYSIOL & BIOPHYS,IRVINE,CA 92717. RP ROJAS, E (reprint author), NIDDKD,CELL BIOL & GENET LAB,BETHESDA,MD 20892, USA. RI Haigler, Harry/C-3788-2011 NR 10 TC 41 Z9 41 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-6009 J9 BONE MINER JI Bone Miner. PD MAY PY 1992 VL 17 IS 2 BP 214 EP 218 DI 10.1016/0169-6009(92)90739-Z PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HT304 UT WOS:A1992HT30400021 PM 1319252 ER PT J AU EANES, ED AF EANES, ED TI MIXED PHOSPHOLIPID LIPOSOME CALCIFICATION SO BONE AND MINERAL LA English DT Article; Proceedings Paper CT 5TH INTERNATIONAL CONF ON CELL MEDIATED CALCIFICATION AND MATRIX VESICLES CY NOV 16-20, 1991 CL HILTON HEAD, SC SP NIH, NIAMSD, CIBA GEIGY, DEPUY, ELECTROBIOLOGY, GLAXO, INST RECH INT SERVIER, LILLY RES LABS, MILES, ABBOTT LABS ID CALCIUM-PHOSPHATE FORMATION; CONTAINING ANIONIC LIPOSOMES; EPIPHYSEAL CARTILAGE; AQUEOUS SUSPENSIONS; MATRIX VESICLES AB Synthetic lipid vesicle (liposome) suspensions have been used to experimentally model many of the calcium phosphate precipitation steps observed in matrix vesicle (MV) calcification. In particular, precipitate development in liposomes can be made to preferentially follow the progression seen in MV, i.e. to occur initially in intraliposomal spaces and then to expand into the surrounding suspending medium. This paper reviews results from studies by us which show that certain phospholipid (PL) constituents of the liposomal membrane can modulate this progression. Of greatest relevance to MV calcification is the observation that phosphatidylserine and sphingomyelin, two lipids selectively enriched in MV, slow the expansion of the precipitation from inside to outside the liposome. RP EANES, ED (reprint author), NATL INST STAND & TECHNOL,NIDR,BONE RES BRANCH,RES ASSOCIATE PROGRAM,GAITHERSBURG,MD 20899, USA. NR 10 TC 15 Z9 15 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-6009 J9 BONE MINER JI Bone Miner. PD MAY PY 1992 VL 17 IS 2 BP 269 EP 272 DI 10.1016/0169-6009(92)90749-4 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HT304 UT WOS:A1992HT30400031 PM 1611319 ER PT J AU LEVY, A MATOVELLE, MC LIGHTMAN, SL YOUNG, WS AF LEVY, A MATOVELLE, MC LIGHTMAN, SL YOUNG, WS TI THE EFFECTS OF PITUITARY-STALK TRANSECTION, HYPOPHYSECTOMY AND THYROID-HORMONE STATUS ON INSULIN-LIKE GROWTH-FACTOR 2-LIKE, GROWTH-HORMONE RELEASING HORMONE-LIKE, AND SOMATOSTATIN MESSENGER-RNA PREVALENCE IN RAT-BRAIN SO BRAIN RESEARCH LA English DT Article DE INSULIN-LIKE GROWTH FACTOR-II; GENE EXPRESSION; PITUITARY; SOMATOSTATIN; GROWTH HORMONE RELEASING FACTOR; CHOROID PLEXUS; ARCUATE; GROWTH FACTOR ID FACTOR-II GENE; CENTRAL NERVOUS-SYSTEM; MESSENGER-RNA; CHOROID-PLEXUS; EXPRESSION; LOCALIZATION; HYPOTHALAMUS; PRECURSOR; PROTEIN-2; INVITRO AB We have used in situ hybridization histochemistry to determine the effects of pituitary stalk transection, hypophysectomy and drug-induced changes in thyroid status on mRNA levels encoding insulin-like growth factor 2. somatostatin. and growth hormone-releasing factor in the choroid plexus, hypothalamic periventricular nucleus, and arcuate nucleus, respectively. Pituitary stalk transection and hypophysectomy in Sprague-Dawley rats decreased insulin-like growth factor 2 and somatostatin mRNA and increased growth hormone-releasing factor mRNA. In each case, the effect of hypophysectomy exceeded that of pituitary stalk transection. Treatment with propylthiouracil for 10 days decreased somatostatin mRNA, markedly increased growth hormone-releasing factor mRNA but had no significant effect on insulin-like growth factor 2 mRNA. Treatment with triiodothyronine had no effect on the mRNAs measured. These findings corroborate the clinical observation of abnormal somatic growth in disturbances of thyroid and growth hormone status and provide further evidence of the effects of these metabolic disturbances and of pituitary disconnection and hypophysectomy on insulin-like growth factor 2 mRNA prevalence. C1 NIMH,CELL BIOL LAB,BLDG 36,ROOM 2D10,BETHESDA,MD 20892. RI Young, W Scott/A-9333-2009 OI Young, W Scott/0000-0001-6614-5112 NR 32 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAY 1 PY 1992 VL 579 IS 1 BP 1 EP 7 DI 10.1016/0006-8993(92)90735-R PG 7 WC Neurosciences SC Neurosciences & Neurology GA HU780 UT WOS:A1992HU78000001 PM 1352477 ER PT J AU MARLEY, RJ GOLDBERG, SR AF MARLEY, RJ GOLDBERG, SR TI PHARMACOGENETIC ASSESSMENT OF THE EFFECTS OF CARBAMAZEPINE ON COCAINE-KINDLED AND COCAINE-INDUCED SEIZURES SO BRAIN RESEARCH LA English DT Article DE CARBAMAZEPINE; COCAINE; GENETICS; INBRED MOUSE STRAIN; KINDLING; LETHALITY; SEIZURE ID LIDOCAINE AB The effects of chronic carbamazepine (CBZ) on the development and expression of cocaine-kindled seizures and seizures produced by an acute injection of cocaine were evaluated in BALB/cByJ, C57B1/6J and SJL/J mice. The repeated administration of a subconvulsant dose of cocaine initially resulted in the development of an increased sensitivity to the convulsant effects of cocaine in the three strains. Chronic, dietary carbamazepine attenuated this initial sensitization to cocaine-induced seizures. While the continued administration of cocaine resulted in a relatively permanent sensitization to cocaine-induced seizures among SJL mice, tolerance to cocaine-induced seizures ultimately developed among C57 mice and to a lesser degree among BALB mice. Genetic factors were found to mediate the effects of chronic CBZ on the development of sensitization and/or tolerance to the convulsant effects of cocaine. Among BALB mice, chronic CBZ appears to have eliminated the development of tolerance to cocaine-induced seizures and allowed an underlying sensitization to be manifest. Among SJL mice, however, the sensitization observed following repeated cocaine injections was reduced, but not eliminated. Genetic factors were also found to be associated with the effects of CBZ on seizures induced by the acute administration of cocaine. BALB and C57 mice, but not SJL mice, chronically treated with dietary CBZ were less susceptible to a consulvant dose of cocaine than their corresponding dietary controls for at least 72 h after stopping CBZ administration. In addition, there were genotype-specific lethal effects associated with the concurrent administration of CBZ and cocaine. RP MARLEY, RJ (reprint author), NIDA,ADDICT RES CTR,BOX 5180,BALTIMORE,MD 21224, USA. NR 25 TC 6 Z9 6 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAY 1 PY 1992 VL 579 IS 1 BP 43 EP 49 DI 10.1016/0006-8993(92)90739-V PG 7 WC Neurosciences SC Neurosciences & Neurology GA HU780 UT WOS:A1992HU78000005 PM 1623406 ER PT J AU YOUNG, NS DUNBAR, C AF YOUNG, NS DUNBAR, C TI ORAL MEGADOSE METHYLPREDNISOLONE FOR TREATMENT OF DIAMOND-BLACKFAN ANEMIA - REPLY SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Letter RP YOUNG, NS (reprint author), NHLBI,CLIN HEMATOL BRANCH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD MAY PY 1992 VL 81 IS 1 BP 136 EP 136 PG 1 WC Hematology SC Hematology GA HT212 UT WOS:A1992HT21200035 ER PT J AU HERRMANN, DJ CRAWFORD, M HOLDSWORTH, M AF HERRMANN, DJ CRAWFORD, M HOLDSWORTH, M TI GENDER-LINKED DIFFERENCES IN EVERYDAY MEMORY PERFORMANCE SO BRITISH JOURNAL OF PSYCHOLOGY LA English DT Article ID SKILL; SEX AB Recent research has demonstrated that people hold beliefs about how well others perform everyday memory tasks according to another's sex. For example, meta-memory ratings indicate that other men and other women are believed to differ in their success at performing certain memory tasks (Crawford, Herrmann, Holdsworth, Randall & Robbins, 1989). In the present study, two experiments investigated whether gender stereotypes concerning everyday memory have any validity. Experiment 1 presented female and male subjects with two tasks that the aforementioned meta-memory ratings had shown are implicitly gender marked: learning a shopping list (a stereotypically feminine task) and learning directions to go to a particular place (a stereotypically masculine task). The results were consistent with the gender stereotypes, i.e. women recalled more of the shopping list than men whereas men recalled more of the directions than women. The second experiment investigated whether memory performance would be influenced by mere changes in the label of materials in memory tasks to be biased toward male or female gender background: labelling a shopping list as pertaining to 'groceries' or to 'hardware store'; and a set of directions to 'make a shirt' or to 'make a workbench'. The results also indicated that memory performance varied in ways consistent with gender stereotypes. C1 HAMILTON COLL,DEPT PSYCHOL,CLINTON,NY 13323. NATL INST MENTAL HLTH,SOCIOENVIRONM STUDIES LAB,WASHINGTON,DC. W CHESTER UNIV,W CHESTER,PA 19380. NR 25 TC 18 Z9 18 U1 2 U2 2 PU BRITISH PSYCHOLOGICAL SOC PI LEICESTER PA ST ANDREWS HOUSE, 48 PRINCESS RD EAST, LEICESTER, LEICS, ENGLAND LE1 7DR SN 0007-1269 J9 BRIT J PSYCHOL JI Br. J. Psychol. PD MAY PY 1992 VL 83 BP 221 EP 231 PN 2 PG 11 WC Psychology, Multidisciplinary SC Psychology GA HY204 UT WOS:A1992HY20400004 PM 1611409 ER PT J AU REICHERT, T STORKEL, S BECKER, K FISHER, LW AF REICHERT, T STORKEL, S BECKER, K FISHER, LW TI THE ROLE OF OSTEONECTIN IN HUMAN TOOTH DEVELOPMENT - AN IMMUNOHISTOLOGICAL STUDY SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE OSTEONECTIN; MINERALIZATION; TOOTH DEVELOPMENT ID BASEMENT-MEMBRANE TUMOR; IMMUNOHISTOCHEMICAL LOCALIZATION; MESSENGER-RNA; PROTEIN BM-40; BONE-CELLS; CALF BONE; COLLAGEN; SPARC; DIFFERENTIATION; DENTIN AB We investigated immunohistologically 160 teeth and dental germs in various stages of tooth development taken from human individuals (13th week of pregnancy to the 24th year of life) to study the osteonectin expression in dental hard tissue. In the course of dentinogenesis, the predentin, the odontoblasts, and their cell processes show a positive osteonectin staining reaction. During cemetogenesis, osteonectin is synthesized by cement-producing fibroblasts, cementoblasts, and cementocytes. The expression of osteonectin during dentinogenesis and cementogenesis is closely related to the development of the respective calcified tissue. All cells of the inner and outer enamel epithelium, the cells of the stratum reticulare and stratum intermedium, the ameloblasts, and the enamel substance are osteonectin negative, just as dentin and cement are. The results of this study indicate one important physiological role of osteonectin as a protein associated with the formation of collagen containing mineralizing tissues like human bone, as well as human dentin and cement. C1 UNIV MAINZ,DEPT PAIDOPATHOL,W-6500 MAINZ,GERMANY. NIDR,BETHESDA,MD 20892. RP REICHERT, T (reprint author), UNIV MAINZ,DEPT PATHOL,LANGENBECKSTR 1,W-6500 MAINZ,GERMANY. NR 27 TC 59 Z9 60 U1 0 U2 1 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 MAY PY 1992 VL 50 IS 5 BP 468 EP 472 DI 10.1007/BF00296779 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HM773 UT WOS:A1992HM77300013 PM 1596782 ER PT J AU BOYE, O BROSSI, A YEH, HJC HAMEL, E WEGRZYNSKI, B TOOME, V AF BOYE, O BROSSI, A YEH, HJC HAMEL, E WEGRZYNSKI, B TOOME, V TI NATURAL-PRODUCTS - ANTITUBULIN EFFECT OF CONGENERS OF N-ACETYLCOLCHINYL METHYL-ETHER - SYNTHESIS OF OPTICALLY-ACTIVE 5-ACETAMIDODEAMINOCOLCHINYL METHYL-ETHER AND OF DEMETHOXY ANALOGS OF DEAMINOCOLCHINYL METHYL-ETHER SO CANADIAN JOURNAL OF CHEMISTRY-REVUE CANADIENNE DE CHIMIE LA English DT Article ID CONFIGURATION; COLCHICINE; TUBULIN AB Trimethoxy-substituted dihydrodibenzocycloheptenes 4-7, required for a structure-activity study measuring the inhibition of tubulin polymerization in vitro, were synthesized by four different routes: (1) Synthesis of 4 was achieved from 2,3-dimethoxybenzaldehyde via biphenyl aldehyde 17, chain lengthening to propionic acid 20, acid-catalyzed cyclization toward ketone 21, and removal of the carbonyl group. (2) Compound 5 was obtained by eliminating the sterically most hindered methoxy group in 25 or 26 by metal reduction in alcohol. (3) Compound 6 was prepared from biphenyl aldehyde 34 obtained by Grignard reaction on oxazoline 32. (4) Compound 7 was obtained by reductive deoxygenation of the tetrazolyl ether derivative of N-acetylcolchinol 41. The key role of the aromatic oxygen atoms in colchicine and allo congeners as points of interaction with the colchicine binding site on tubulin was demonstrated by the lack of inhibitory activity of compounds 4-7. Optically active 5-acetamide 8a,b isomers of N-acetylcolchinyl methyl ether 2 were obtained after chemical resolution of amine 47. The absolute configuration of the optical isomers 47a,b and 8a,b was determined by H-1 NMR and CD measurements. These compounds were found inactive as inhibitors of tubulin polymerization. C1 NIDDK,NAT PROD SECT,STRUCT BIOL LAB,BETHESDA,MD 20892. NIDDK,ANALYT CHEM LAB,BETHESDA,MD 20892. NCI,DCT,DTP,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. HOFFMANN LA ROCHE INC,DIV RES,NUTLEY,NJ 07110. NR 27 TC 29 Z9 30 U1 1 U2 1 PU NATL RESEARCH COUNCIL CANADA PI OTTAWA PA RESEARCH JOURNALS, MONTREAL RD, OTTAWA ON K1A 0R6, CANADA SN 0008-4042 J9 CAN J CHEM JI Can. J. Chem.-Rev. Can. Chim. PD MAY PY 1992 VL 70 IS 5 BP 1237 EP 1249 DI 10.1139/v92-160 PG 13 WC Chemistry, Multidisciplinary SC Chemistry GA JL870 UT WOS:A1992JL87000002 ER PT J AU MOHR, E MANN, UM MILETICH, RS SAMPSON, M GOLDBERG, TE GRIMES, JD CHASE, TN AF MOHR, E MANN, UM MILETICH, RS SAMPSON, M GOLDBERG, TE GRIMES, JD CHASE, TN TI NEUROPSYCHOLOGICAL AND GLUCOSE METABOLIC PROFILES IN ASYMMETRIC PARKINSONS-DISEASE SO CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; LATERALIZED PARKINSONISM; ALZHEIMERS-DISEASE; DEFICITS; MEMORY; HEMIPARKINSONISM; DOPAMINE; DEMENTIA AB Patients with predominantly unilateral parkinsonian signs may provide a unique opportunity to evaluate the cerebral representation of cognitive functions characteristically affected in idiopathic Parkinson's disease. Twenty hemiparkinsonian patients (ten left and ten right) and 10 healthy controls, matched for age and education were studied with neuropsychological tests and positron emission tomography. Both right and left hemiparkinsonians evidenced impairments in visuospatial and verbal episodic memory function, but had no deficits in executive abilities, compared to controls. None of the neuropsychological test scores distinguished right from left hemiparkinsonians. Glucose metabolic profiles were identical for the three groups in all cortical areas assessed; in the subcortex however, lenticular hypermetabolism contralateral to the predominant side of motor involvement was evident in the left hemiparkinsonian group. Correlational analysis revealed that higher glucose metabolic rates in the basal ganglia of these hemiparkinsonians were associated with lower visuospatial test scores. In frontal and parietal cortex. decreasing glucose metabolism was positively associated with neurobehavioral function: in temporal cortex, measures of attention and memory decreased with increasing glucose metabolic rates. C1 UNIV HAMBURG,KRANKENHAUS EPPENDORF,DEPT NEUROL,W-2000 HAMBURG 20,GERMANY. UNIV OTTAWA,LOEB INST MED RES,OTTAWA K1N 6N5,ONTARIO,CANADA. NINCDS,BETHESDA,MD 20892. ST ELIZABETH HOSP,NIMH,WASHINGTON,DC 20032. RP MOHR, E (reprint author), INST MENTAL HLTH RES,1145 CARLING AVE,OTTAWA K1Z 7K4,ONTARIO,CANADA. RI Sampson, Margaret/A-9128-2011; OI Sampson, Margaret/0000-0003-2550-9893 NR 51 TC 28 Z9 29 U1 2 U2 2 PU CANADIAN J NEUROL SCI INC PI CALGARY PA PO BOX 4220, STATION C EDITORIAL & SUBSCRIPTION SERV, CALGARY AB T2T 5N1, CANADA SN 0317-1671 J9 CAN J NEUROL SCI JI Can. J. Neurol. Sci. PD MAY PY 1992 VL 19 IS 2 BP 163 EP 169 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA HV210 UT WOS:A1992HV21000001 PM 1623440 ER PT J AU CAMPO, E BRUNIER, MN MERINO, MJ AF CAMPO, E BRUNIER, MN MERINO, MJ TI SMALL-CELL CARCINOMA OF THE ENDOMETRIUM WITH ASSOCIATED OCULAR PARANEOPLASTIC SYNDROME SO CANCER LA English DT Article ID NEOPLASTIC CEREBELLAR DEGENERATION; CANCER-ASSOCIATED RETINOPATHY; PHOTORECEPTOR DEGENERATION; IMMUNOHISTOCHEMICAL ANALYSIS; ENDOCRINE-CELLS; LUNG-CANCER; ANTIBODIES; TUMORS; LIGHT; CERVIX AB Small cell carcinomas are well-recognized tumors known to occur predominantly in the lung. These neoplasms occasionally are associated with a variety of symptoms caused by hormones and other products produced by the tumor cells (paraneoplastic syndromes). However, in the gynecologic tract such neoplasms are extremely rare. The authors report the case of an elderly woman who presented with visual disturbances caused by a primary small cell carcinoma of the uterus. The literature is reviewed. C1 NCI,PATHOL LAB,BLDG 10,ROOM 2N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NEI,BETHESDA,MD 20892. OI Campo, elias/0000-0001-9850-9793 NR 34 TC 48 Z9 51 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD MAY 1 PY 1992 VL 69 IS 9 BP 2283 EP 2288 DI 10.1002/1097-0142(19920501)69:9<2283::AID-CNCR2820690913>3.0.CO;2-V PG 6 WC Oncology SC Oncology GA HP194 UT WOS:A1992HP19400012 PM 1314128 ER PT J AU KONISHI, N ENOMOTO, T BUZARD, G OHSHIMA, M WARD, JM RICE, JM AF KONISHI, N ENOMOTO, T BUZARD, G OHSHIMA, M WARD, JM RICE, JM TI K-RAS ACTIVATION AND RAS P21 EXPRESSION IN LATENT PROSTATIC-CARCINOMA IN JAPANESE MEN SO CANCER LA English DT Article ID MOUSE SKIN CARCINOGENESIS; POLYMERASE CHAIN-REACTION; CELLULAR ONCOGENES; BLADDER-CARCINOMA; ADENOCARCINOMA; MUTATIONS; ANTIBODIES; TISSUE; TUMORIGENESIS; AMPLIFICATION AB Twenty-three clinically silent prostatic carcinomas discovered in Japanese men at autopsy were surveyed for ras proto-oncogene mutations by mutation-specific oligonucleotide probe hybridization after polymerase chain reaction (PCR) amplification from a section of formalin-fixed, paraffin-embedded tissue. Six of the 22 that were satisfactorily amplified contained activating point mutations in codon 12 of K-ras, a significantly higher frequency than has been reported in patients with clinically advanced disease in the United States. Of the six cases with activating point mutations in codon 12 of K-ras, one had a GGT --> GAT transition, four had GGT --> GTT transversions, and one had both GGT --> GAT and GGT --> GTT mutations. Sections from the same tissues were immunohistochemically stained with an anti-ras p21 antibody. Carcinoma cells stained for ras p21 to some degree in 13 cases. Immunohistochemically detectable expression of p21 was always focal and was not necessarily associated with K-ras mutation. K-ras oncogene activation in prostatic carcinoma appears to merit additional study as a significant event in the pathogenesis of this neoplasm. C1 NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21701. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC,DYNCORP,FREDERICK,MD 21701. NISSEI HOSP,DEPT PATHOL,NISHI KU,OSAKA,JAPAN. RP KONISHI, N (reprint author), NARA MED UNIV,DEPT PATHOL 2,KASHIHARA,NARA 634,JAPAN. FU NCI NIH HHS [N01-CO-74102] NR 38 TC 101 Z9 104 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD MAY 1 PY 1992 VL 69 IS 9 BP 2293 EP 2299 DI 10.1002/1097-0142(19920501)69:9<2293::AID-CNCR2820690915>3.0.CO;2-O PG 7 WC Oncology SC Oncology GA HP194 UT WOS:A1992HP19400014 PM 1562975 ER PT J AU TRAVIS, LB GONZALEZ, CL HANKEY, BF JAFFE, ES AF TRAVIS, LB GONZALEZ, CL HANKEY, BF JAFFE, ES TI HODGKINS-DISEASE FOLLOWING NON-HODGKINS-LYMPHOMA SO CANCER LA English DT Article ID REED-STERNBERG CELLS; MYCOSIS-FUNGOIDES; COMPOSITE LYMPHOMA; DIAGNOSIS AB The risk of Hodgkin's disease following non-Hodgkin's lymphoma (NHL) was estimated using information collected by the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Histopathologic material representing both diagnoses was reviewed for 11 patients in whom Hodgkin's disease was reported after NHL. Diagnoses of both diseases were confirmed in nine patients. Comparisons with population rates indicated that patients with NHL are at an almost threefold risk of subsequently having Hodgkin's disease. Survival in this series was poor; seven of the nine patients died within 16 months after the diagnosis of Hodgkin's disease. C1 NCI,DIV CANC BIOL & DIAG,PATHOL LAB,HEMATOPATHOL SECT,BETHESDA,MD 20892. NCI,DIV CANC PREVENT & CONTROL,SURVEILLANCE PROGRAM,CANC STAT BRANCH,BETHESDA,MD 20892. RP TRAVIS, LB (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,EXECUT PLAZA N,BETHESDA,MD 20892, USA. NR 27 TC 34 Z9 34 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD MAY 1 PY 1992 VL 69 IS 9 BP 2337 EP 2342 DI 10.1002/1097-0142(19920501)69:9<2337::AID-CNCR2820690923>3.0.CO;2-K PG 6 WC Oncology SC Oncology GA HP194 UT WOS:A1992HP19400022 PM 1562981 ER PT J AU HOWARD, J HANKEY, BF GREENBERG, RS AUSTIN, DF CORREA, P CHEN, VW DURAKO, S AF HOWARD, J HANKEY, BF GREENBERG, RS AUSTIN, DF CORREA, P CHEN, VW DURAKO, S TI A COLLABORATIVE STUDY OF DIFFERENCES IN THE SURVIVAL RATES OF BLACK PATIENTS AND WHITE PATIENTS WITH CANCER SO CANCER LA English DT Article ID COLLEGE-OF-SURGEONS; BREAST-CANCER; RACIAL-DIFFERENCES; UNITED-STATES; SOCIOECONOMIC-STATUS; PROSTATE-CANCER; NATIONAL SURVEY; ESTROGEN; WOMEN; DISEASE AB In 1983, the National Cancer Institute began a social-epidemiologic study of possible behavioral and biologic determinants of black/white racial disparities in cancer survival. The design, methodology, underlying hypotheses, and patient accrual of this study are discussed. Survival differences in four organ sites are investigated: cancers of the uterine corpus, breast, bladder, and colon. The first three sites were chosen because of significant observed black/white differentials in survival. Although racial disparities in survival from colon cancer are less prominent, this site was included because it is a leading cause of deaths attributable to cancer, because regional variations have been observed in black/white survival disparities, and because colon data permit cross-gender comparisons. Data collection centers for the study included the Georgia Center for Cancer Statistics, the Louisiana Tumor Registry, and the California Tumor Registry. Probability samples of patients newly diagnosed with these cancers were drawn from the areas served by these registries. Diagnostic years of eligibility were 1985 to 1986 for breast and colon cancer, and 1985 to 1987 for bladder and uterine corpus cancer. Data were collected by personal interview, medical records abstract, physician records, and pathology review. Analyses focus on seven main explanatory hypotheses. C1 NIAAA,DIV CLIN & PREVENT RES,ROCKVILLE,MD 20852. EMORY UNIV,SCH PUBL HLTH,ATLANTA,GA 30322. CALIF DEPT HLTH SERV,EMERYVILLE,CA. LOUISIANA STATE UNIV,MED CTR,NEW ORLEANS,LA 70112. WESTAT CORP,ROCKVILLE,MD. NR 88 TC 92 Z9 94 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD MAY 1 PY 1992 VL 69 IS 9 BP 2349 EP 2360 DI 10.1002/1097-0142(19920501)69:9<2349::AID-CNCR2820690925>3.0.CO;2-7 PG 12 WC Oncology SC Oncology GA HP194 UT WOS:A1992HP19400024 PM 1562983 ER PT J AU CHOW, WH SCHUMAN, LM MCLAUGHLIN, JK BJELKE, E GRIDLEY, G WACHOLDER, S CHIEN, HTC BLOT, WJ AF CHOW, WH SCHUMAN, LM MCLAUGHLIN, JK BJELKE, E GRIDLEY, G WACHOLDER, S CHIEN, HTC BLOT, WJ TI A COHORT STUDY OF TOBACCO USE, DIET, OCCUPATION, AND LUNG-CANCER MORTALITY SO CANCER CAUSES & CONTROL LA English DT Article DE COHORT STUDY; DIET; LUNG CANCER; LUTHERAN BROTHERHOOD STUDY; OCCUPATION; UNITED-STATES AB In 1966, a cohort of White males aged 35 or over, who were policy-holders with the Lutheran Brotherhood Insurance Society (United States), completed a mail questionnaire on tobacco use, diet, and demographic characteristics. During the 20 years of follow-up, 219 lung cancer deaths occurred. Besides the strong relationship with cigarette smoking, we observed an effect on lung cancer risk among current users of cigars or pipes who were nonsmokers of cigarettes (relative risk [RR] = 3.5,95 percent confidence interval [CI] = 1.0-12.6) or who were past/occasional users of cigarettes (RR = 2.7, CI = 1.4-5.3). In addition, elevated risks (from 1.5 to 2.6) of lung cancer were found among craftsmen and laborers, with the highest risks among subjects who worked in the mining or manufacturing industry. No association between current (as of 1966) use of beer or hard liquor and lung cancer was observed, although past users were at elevated risk. An inverse association between lung cancer and intake of fruits was observed, and risks of lung cancer were lower among persons in the highest dietary intake quintiles of vitamins A and C. Except for oranges, however, none of the inverse associations with fruits or dietary nutrients had statistically significant trends. The findings from this cohort study add to the evidence of an adverse effect of cigar/pipe smoking and possibly protective effect of dietary factors on lung cancer risk. RP CHOW, WH (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,6130 EXECUTIVE BLVD,BETHESDA,MD 20892, USA. NR 0 TC 69 Z9 69 U1 0 U2 3 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAY PY 1992 VL 3 IS 3 BP 247 EP 254 DI 10.1007/BF00124258 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA HU587 UT WOS:A1992HU58700008 PM 1610971 ER PT J AU LALIBERTE, J MARQUEZ, VE MOMPARLER, RL AF LALIBERTE, J MARQUEZ, VE MOMPARLER, RL TI POTENT INHIBITORS FOR THE DEAMINATION OF CYTOSINE-ARABINOSIDE AND 5-AZA-2'-DEOXYCYTIDINE BY HUMAN CYTIDINE DEAMINASE SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE DEAMINATION; CYTIDINE DEAMINASE; CYTOSINE ARABINOSIDE; 5-AZA-2'-DEOXYCYTIDINE ID LEUKEMIC-CELLS; ANTILEUKEMIC ACTIVITY; 1-BETA-D-ARABINOFURANOSYLCYTOSINE; NUCLEOSIDES; METABOLISM; TETRAHYDROURIDINE; MOUSE AB Deamination of the nucleoside analogues ARA-C and 5-AZA-CdR by CR deaminase results in a loss of antileukemic activity. To prevent the inactivation of these analogues, inhibitors of CR deaminase may prove to be useful agents. In the present study we investigated the effects of the deaminase inhibitors Zebularine, 5-F-Zebularine, and diazepinone riboside on the deamination of CR, ARA-C, and 5-AZA-CdR using highly purified human CR deaminase (EC 3.5.4.5). These inhibitors produced a competitive type of inhibition with each substrate, the potency of which followed the patterns diazepinone riboside > 5-F-Zebularine and THU > Zebularine. 5-AZA-CdR was more sensitive than ARA-C to the inhibition produced by these deaminase inhibitors. The inhibition constants for diazepinone riboside lay in the range of 5-15 nm, suggesting that this inhibitor could be an excellent candidate for use in combination chemotherapy with either ARA-C or 5-AZA-CdR in patients with leukemia. C1 UNIV MONTREAL,DEPT PHARMACOL,MONTREAL H3T 1C5,QUEBEC,CANADA. NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MED CHEM LAB,BETHESDA,MD 20892. HOP ST JUSTINE,CTR RECH PEDIAT,MONTREAL H3T 1C5,QUEBEC,CANADA. NR 29 TC 86 Z9 87 U1 0 U2 5 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD MAY PY 1992 VL 30 IS 1 BP 7 EP 11 DI 10.1007/BF00686478 PG 5 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA HQ037 UT WOS:A1992HQ03700002 PM 1375134 ER PT J AU GARRY, VF DANZL, TJ TARONE, R GRIFFITH, J CERVENKA, J KRUEGER, L WHORTON, EB NELSON, RL AF GARRY, VF DANZL, TJ TARONE, R GRIFFITH, J CERVENKA, J KRUEGER, L WHORTON, EB NELSON, RL TI CHROMOSOME REARRANGEMENTS IN FUMIGANT APPLIERS - POSSIBLE RELATIONSHIP TO NON-HODGKINS-LYMPHOMA RISK SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID NON-RANDOMNESS; ABNORMALITIES; TRANSLOCATIONS; BREAKPOINTS; PHOSPHINE; NEOPLASIA; CANCER; GENES AB Appliers of pesticides (n = 18) who are exposed to the fumigant phosphine or who have a mixed exposure to other pesticides and phosphine demonstrate a significant increase in chromosome rearrangements in G-banded chromosomes from peripheral blood compared to control subjects (n = 26). Appliers who had discontinued using phosphine for at least 8 months prior to specimen collection (n = 5) do not demonstrate significant increases in chromosome rearrangements compared to controls. Breakpoint analysis of 6138 metaphases from all subjects demonstrates 196 breaks per 3605 metaphases in exposed subjects and 102 breaks per 2533 metaphases in control subjects. Bands with significantly more breaks than expected based on band length in all study subjects were 1q32, 3p14, 7p15, and 14q11. Three of these four bands had significantly more breaks than expected in the exposed group, and all four bands had a significant excess of breaks in the control group. There are four bands with a significant excess of breaks in the exposed group and no breaks in the control group; each of these occurs in a known protooncogene region. These are 1p13 (NRAS), 2p23 (NMYC), 14q32 (ELK2), and 21q12 (ETS-2). Most breaks at bands 1p13, 14q32, and 21q22 are associated with chromosome rearrangements and occurred in appliers who have a mixed exposure to phosphine and other pesticides. Cytogenetic abnormalities, i.e., rearrangements and/or deletions involving bands 1p13, 2p23, and 14q32, are associated with non-Hodgkin's lymphoma. We speculate that these findings could relate to the risk of evolution of a neoplastic clone in these workers. Epidemiological studies of similarly exposed workers indicate an excess of non-Hodgkin's lymphoma. C1 NCI,BIOSTAT BRANCH,BETHESDA,MD 20892. US EPA,HLTH EFFECTS RES LAB,RES TRIANGLE PK,NC 27711. UNIV MINNESOTA,SCH DENT,MINNEAPOLIS,MN 55455. UNIV TEXAS,MED BRANCH,GALVESTON,TX 77550. RP GARRY, VF (reprint author), UNIV MINNESOTA,DEPT LAB MED & PATHOL,DIV ENVIRONM MED & PATHOL,STONE LAB 1,1ST FLOOR,MINNEAPOLIS,MN 55414, USA. NR 31 TC 38 Z9 38 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY-JUN PY 1992 VL 1 IS 4 BP 287 EP 291 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA JE467 UT WOS:A1992JE46700007 PM 1303128 ER PT J AU SINHA, R BLOCK, G TAYLOR, PR AF SINHA, R BLOCK, G TAYLOR, PR TI DETERMINANTS OF PLASMA ASCORBIC-ACID IN A HEALTHY MALE-POPULATION SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; VITAMIN-C STATUS; ELDERLY POPULATION; BETA-CAROTENE; CANCER; SERUM; DIETARY; WOMEN; RISK; ANTIOXIDANT AB The antioxidant properties of vitamin C may be involved in the prevention of cancer. The correlation between dietary vitamin C intake as estimated by a dietary questionnaire and plasma ascorbic acid (AA) was examined in 68 nonsmoking male volunteers aged 30-59 years. Determinants of plasma AA as well as interrelationships between various antioxidants in plasma were also explored. The determinants of plasma AA were examined by a multiple regression model containing dietary vitamin C, calories, body weight, and amount of beverages consumed. Higher vitamin C intake (P < 0.0002) increased plasma AA, while greater body weight (P < 0.005) decreased plasma AA. A significant correlation (r = 0.43; P < 0.0003) between vitamin C intake and plasma AA was observed. There was a negative correlation between plasma AA and plasma uric acid (r = -0.32; P < 0.007) and positive associations between plasma-beta-carotene and plasma alpha-tocopherol (r = 0.39; P < 0.001) and between plasma-beta-carotene and plasma glutathione peroxidase (r = 0.32; P < 0.008). Vitamin C supplement users had higher plasma AA compared to nonusers. The relationship between plasma AA and vitamin C intake appears to be curvilinear with the non-supplement users at the linear part of the curve and the supplement users at the plateau. Plasma AA is an appropriate biomarker, in our subjects, of dietary vitamin C except for people consuming large amounts of this vitamin either in their diet or in supplemental form. RP SINHA, R (reprint author), NCI,DIV CANC PREVENT & CONTROL,EXECUT PLAZA N,ROOM 313,BETHESDA,MD 20892, USA. RI Block, Gladys/E-3304-2010; Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 NR 54 TC 30 Z9 30 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY-JUN PY 1992 VL 1 IS 4 BP 297 EP 302 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA JE467 UT WOS:A1992JE46700009 PM 1303130 ER PT J AU TANGREA, JA ADRIANZA, ME HELSEL, WE AF TANGREA, JA ADRIANZA, ME HELSEL, WE TI PATIENTS PERCEPTIONS ON PARTICIPATION IN A CANCER CHEMOPREVENTION TRIAL SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CLINICAL-TRIALS; ATTITUDES AB The perceptions of patients regarding the benefits, disadvantages, and importance of their participation in a long-term cancer chemoprevention trial, the Isotretinoin-Basal Cell Carcinoma Prevention Trial, were assessed through a questionnaire mailed at the conclusion of the 3-year treatment period of the trial. Responses were evaluated overall, as well as within subgroups defined by sex, age, education level, treatment group, presence of side effects, and the number of skin biopsies performed during the 3-year intervention phase. Overall, "careful medical follow-up received" (43%) and "being part of a research effort" (24%) were the most frequently cited important benefits, while the "amount of time taken to attend clinic" (32%) and "side effects" (20%) were the most frequently cited unpleasant aspects of trial participation. Most surveyed patients viewed the study as "very or extremely important" to their general health (62%) and their skin cancer condition (88%) and, as a result of participation, felt "much or somewhat better" physically (52%). The majority indicated that they would "definitely or probably" be willing to take part in another research study (79%) and take the study medication, if it were shown to be effective in the trial (78%). Overall and subgroup data provide important insights into patient motivations and attitudes regarding cancer chemoprevention trial participation, adherence, and satisfaction. C1 INFORMAT MANAGEMENT SERV INC,SILVER SPRING,MD 20904. RP TANGREA, JA (reprint author), NCI,DIV CANC PREVENT & CONTROL,CANC PREVENT STUDIES BRANCH,BETHESDA,MD 20892, USA. NR 15 TC 25 Z9 25 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY-JUN PY 1992 VL 1 IS 4 BP 325 EP 330 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA JE467 UT WOS:A1992JE46700013 PM 11656233 ER PT J AU URBA, WJ EWEL, C KOPP, W SMITH, JW STEIS, RG ASHWELL, JD CREEKMORE, SP ROSSIO, J SZNOL, M SHARFMAN, W FENTON, R JANIK, J WATSON, T BEVERIDGE, J LONGO, DL AF URBA, WJ EWEL, C KOPP, W SMITH, JW STEIS, RG ASHWELL, JD CREEKMORE, SP ROSSIO, J SZNOL, M SHARFMAN, W FENTON, R JANIK, J WATSON, T BEVERIDGE, J LONGO, DL TI ANTI-CD3 MONOCLONAL-ANTIBODY TREATMENT OF PATIENTS WITH CD3-NEGATIVE TUMORS - A PHASE-IA/B STUDY SO CANCER RESEARCH LA English DT Article ID T-CELL FUNCTION; TRANSPLANT RECIPIENTS; CYTOLYTIC ACTIVITY; NECROSIS FACTOR; OKT3; ACTIVATION; INVIVO; MICE; INTERFERON; MECHANISM AB Anti-CD3 monoclonal antibodies induce the proliferation of human T-cells in vitro and activate specific and nonspecific cytolysis by human T-cell clones and human peripheral blood lymphocytes. In vivo administration of anti-CD3 prevents tumor growth of a UV-induced mouse fibrosarcoma. We conducted a phase I trial to determine the toxicity and immunomodulatory properties of low doses of anti-CD3 in 36 patients with cancer. In 23 patients, anti-CD3 was given i.v. over 3 h at 1, 10, 30, and 100 mcg/patient. Five other patients received anti-CD3 at 30 mcg by i.v. bolus. Patients were treated every 3 days for a total of four doses. An additional eight patients received anti-CD3 daily for 14 days at 3 mcg by i.v. bolus, 3-h infusion, or 24-h infusion. Dose-limiting toxicity was headache. Headache was often accompanied by signs and symptoms of meningeal irritation leading to performance of a lumbar puncture in nine patients. The opening pressure was usually elevated, and six patients had a cerebrospinal fluid lymphocytosis with an elevated protein. Increased levels of interleukin 6 were identified in the cerebrospinal fluid. The maximum tolerated dose by 3-h infusion was 30 mcg. There were no objective tumor responses. There was a dose-related increase in the number of peripheral blood lymphocytes expressing the T-cell activation antigen CD69 (Leu 23), but no changes were seen in CD25 (interleukin 2 receptor) expression, and no changes were observed in the serum levels of the soluble interleukin 2 receptor. Even at these low doses of anti-CD3, 8 of 16 patients tested developed human anti-mouse antibodies. C1 NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,INVEST DRUG BRANCH,BETHESDA,MD 20892. FREDERICK MEM HOSP,FREDERICK,MD 21701. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. RP URBA, WJ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DYN CORP,PROGRAM RESOURCES INC,CLIN SERV PROGRAM,POB B,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102] NR 28 TC 24 Z9 24 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 1992 VL 52 IS 9 BP 2394 EP 2401 PG 8 WC Oncology SC Oncology GA HR290 UT WOS:A1992HR29000004 PM 1533172 ER PT J AU CANTOR, KP BLAIR, A EVERETT, G GIBSON, R BURMEISTER, LF BROWN, LM SCHUMAN, L DICK, FR AF CANTOR, KP BLAIR, A EVERETT, G GIBSON, R BURMEISTER, LF BROWN, LM SCHUMAN, L DICK, FR TI PESTICIDES AND OTHER AGRICULTURAL RISK-FACTORS FOR NON-HODGKINS-LYMPHOMA AMONG MEN IN IOWA AND MINNESOTA SO CANCER RESEARCH LA English DT Article ID SOFT-TISSUE SARCOMA; FARM BUREAU MEMBERS; MALIGNANT-LYMPHOMA; NEW-ZEALAND; CANCER MORTALITY; MULTIPLE-MYELOMA; LUNG-CANCER; RETROSPECTIVE COHORT; NORTH-CAROLINA; HERBICIDE USE AB Data from an in-person interview study of 622 white men with newly diagnosed non-Hodgkin's lymphoma and 1245 population-based controls in Iowa and Minnesota were used to measure the risk associated with farming occupation and specific agricultural exposures. Men who ever farmed were at slightly elevated risk of non-Hodgkin's lymphoma (odds ratio = 1.2, 95% confidence interval = 1.0-1.5) that was not linked to specific crops or particular animals. Elevated risks were found, with odds ratio generally 1.5-fold or greater, for personal handling, mixing, or application of several pesticide groups and for individual insecticides, including carbaryl, chlordane, dichlorodiphenyltrichloroethane, diazinon, dichlorvos, lindane, malathion, nicotine, and toxaphene. Associations were generally stronger for first use prior to 1965 than more recently, and when protective clothing or equipment was not used. Small risks were associated with the use of the phenoxyacetic acid herbicide 2,4-dichlorophenoxyacetic acid, but the risks did not increase with latency or failure to use protective equipment. Exposure to numerous pesticides poses problems of interpreting risk associated with a particular chemical, and multiple comparisons increase the chances of false-positive findings. In contrast, nondifferential exposure misclassification due to inaccurate recall can bias risk estimates toward the null and mask positive associations. In the face of these methodological and statistical issues, the consistency of several findings, both within this study and with observations of others, suggests an important role for several insecticides in the etiology of non-Hodgkin's lymphoma among farmers. C1 UNIV IOWA,DEPT PATHOL,IOWA CITY,IA 52242. UNIV IOWA,DEPT PREVENT MED,IOWA CITY,IA 52242. UNIV MINNESOTA,DEPT EPIDEMIOL,MINNEAPOLIS,MN 55455. ORLANDO REG MED CTR INC,DEPT INTERNAL MED,ORLANDO,FL. RP CANTOR, KP (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,ENVIRONM EPIDEMIOL BRANCH,443 EXECUT PLAZA N,BETHESDA,MD 20892, USA. NR 64 TC 240 Z9 243 U1 3 U2 13 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 1992 VL 52 IS 9 BP 2447 EP 2455 PG 9 WC Oncology SC Oncology GA HR290 UT WOS:A1992HR29000012 PM 1568215 ER PT J AU DEDRICK, RL MORRISON, PF AF DEDRICK, RL MORRISON, PF TI CARCINOGENIC POTENCY OF ALKYLATING-AGENTS IN RODENTS AND HUMANS SO CANCER RESEARCH LA English DT Article ID ORAL MELPHALAN PHARMACOKINETICS; PHENYLACETIC ACID MUSTARD; I CLINICAL-TRIALS; ANTITUMOUR ACTIVITY; CHLORAMBUCIL; OXAZAPHOSPHORINES; PREDNIMUSTINE; CHEMICALS; TOXICITY; BRAIN AB Alkylating agents are known to produce second tumors in cancer patients treated for their primary cancer. Since therapeutic doses are high and the pharmacokinetics of the drugs are thoroughly studied, these agents provide a unique opportunity to compare intrinsic carcinogenic potency between experimental animals and humans. We have examined the carcinogenicity of melphalan, chlorambucil, and cyclophosphamide in causing leukemia in patients treated for cancer or polycythemia vera and lymphosarcoma in rats and mice. A good correlation among species is observed when the carcinogenic potency is based on the total lifetime exposure to active species derived from these drugs. RP DEDRICK, RL (reprint author), NIH,NATL CTR RES RESOURCES,BIOMED ENGN,BLDG 13,ROOM 3W13,BETHESDA,MD 20892, USA. NR 27 TC 35 Z9 36 U1 2 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 1992 VL 52 IS 9 BP 2464 EP 2467 PG 4 WC Oncology SC Oncology GA HR290 UT WOS:A1992HR29000015 PM 1568217 ER PT J AU YOKOZAKI, H TORTORA, G PEPE, S MARONDE, E GENIESER, HG JASTORFF, B CHOCHUNG, YS AF YOKOZAKI, H TORTORA, G PEPE, S MARONDE, E GENIESER, HG JASTORFF, B CHOCHUNG, YS TI UNHYDROLYZABLE ANALOGS OF ADENOSINE 3'/5'-MONOPHOSPHATE DEMONSTRATING GROWTH-INHIBITION AND DIFFERENTIATION IN HUMAN CANCER-CELLS SO CANCER RESEARCH LA English DT Article ID DEPENDENT PROTEIN-KINASES; CYCLIC-NUCLEOTIDE ANALOGS; SELECTIVE CAMP ANALOGS; AMINO-ACID SEQUENCE; BINDING-SITES; ISOZYME SPECIFICITY; RECEPTOR PROTEINS; AMP ANALOGS; ACTIVATION; DNA AB A set of adenosine 3':5'-monophosphate (cAMP) analogues that combine exocyclic sulfur substitutions in the equatorial (Rp) or the axial (Sp) position of the cyclophosphate ring with modifications in the adenine base of cAMP were tested for their effect on the growth of HL-60 human promyelocytic leukemia cells and LS-174T human colon carcinoma cells. Both diastereomers of the phosphorothioate derivatives were growth inhibitory, exhibiting a concentration inhibiting 50% of cell proliferation of 3-100-mu-M. Among the analogues tested, Rp-8-Cl-cAMPS and Sp-8-Br-cAMPS were the two most potent. Rp-8-Cl-cAMPS was 5- to 10-fold less potent than 8-Cl-cAMP while Sp-8-Br-cAMPS was approximately 6-fold more potent than 8-Br-cAMP. The growth inhibition was not due to a block in a specific phase of the cell cycle or due to cytotoxicity. Rp-8-Cl-cAMPS enhanced its growth-inhibitory effect when added together with 8-Cl-cAMP and increased differentiation in combination with N6-benzyl-cAMP. The binding kinetics data showed that these Sp and Rp modifications brought about a greater decrease in affinity for Site B than for Site A of RI (the regulatory subunit of type I cAMP-dependent protein kinase) and a substantial decrease of affinity for Site A of RII (the regulatory subunit of type II protein kinase) but only a small decrease in affinity for Site B of RII, indicating the importance of the Site B binding of RII in the growth-inhibitory effect. These results show that the phosphorothioate analogues of cAMP are useful tools to investigate the mechanism of action of cAMP in growth control and differentiation and may have practical implication in the suppression of malignancy. C1 NCI,TUMOR IMMUNOL & BIOL LAB,CELLULAR BIOCHEM SECT,BLDG 10,ROOM 5B38,BETHESDA,MD 20892. UNIV BREMEN,INST ORGAN CHEM,W-2800 BREMEN 33,GERMANY. BIOLOG LIFE SCI INST,BREMEN,GERMANY. OI Yokozaki, Hiroshi/0000-0001-5276-3331 NR 34 TC 43 Z9 43 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 1992 VL 52 IS 9 BP 2504 EP 2508 PG 5 WC Oncology SC Oncology GA HR290 UT WOS:A1992HR29000021 PM 1314695 ER PT J AU METCALF, RA WELSH, JA BENNETT, WP SEDDON, MB LEHMAN, TA PELIN, K LINNAINMAA, K TAMMILEHTO, L MATTSON, K GERWIN, BI HARRIS, CC AF METCALF, RA WELSH, JA BENNETT, WP SEDDON, MB LEHMAN, TA PELIN, K LINNAINMAA, K TAMMILEHTO, L MATTSON, K GERWIN, BI HARRIS, CC TI P53 AND KIRSTEN-RAS MUTATIONS IN HUMAN MESOTHELIOMA CELL-LINES SO CANCER RESEARCH LA English DT Note ID LUNG-CANCER; TUMOR-ANTIGEN; MALIGNANT MESOTHELIOMA; TRANSFORMED-CELLS; GENE; ASBESTOS; ONCOGENE; EXPRESSION; GROWTH; TUMORIGENICITY AB Twenty cell lines from 17 individuals with malignant mesothelioma have been examined for p53 alterations by direct sequencing of genomic DNA, by evaluation of mRNA expression levels, and by immunocytochemical analysis of p53 protein expression in comparison with normal human pleural mesothelial cells. The results of this study show p53 abnormalities in cell lines from 3 individuals. These include 2 point mutations and one null cell line. Interestingly, while both cell lines with point mutations exhibit high levels of p53 protein, normal mesothelial cells as well as 12 of the mesotheliomas evaluated express low but significant levels. In addition, sequencing of K-ras at codons 12, 13, and 61 reveals wild-type sequence in all 20 mesothelioma cell lines. The capacity to induce tumors in athymic nude mice did not correlate with the presence of a p53 mutation or elevated p53 protein levels. These data suggest that neither p53 alteration nor K-ras activation constitutes a critical step in the development of human mesothelioma. C1 NCI,HUMAN CARCINOGENESIS LAB,BLDG 37,ROOM 2C05,BETHESDA,MD 20892. UNIV HELSINKI,DEPT PULM MED,SF-00290 HELSINKI 29,FINLAND. INST OCCUPAT HLTH,SF-00250 HELSINKI,FINLAND. NR 70 TC 138 Z9 139 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 1992 VL 52 IS 9 BP 2610 EP 2615 PG 6 WC Oncology SC Oncology GA HR290 UT WOS:A1992HR29000037 PM 1568228 ER PT J AU FUTREAL, PA SODERKVIST, P MARKS, JR IGLEHART, JD COCHRAN, C BARRETT, JC WISEMAN, RW AF FUTREAL, PA SODERKVIST, P MARKS, JR IGLEHART, JD COCHRAN, C BARRETT, JC WISEMAN, RW TI DETECTION OF FREQUENT ALLELIC LOSS ON PROXIMAL CHROMOSOME-17Q IN SPORADIC BREAST-CARCINOMA USING MICROSATELLITE LENGTH POLYMORPHISMS SO CANCER RESEARCH LA English DT Note ID CANCER; REGION AB Analyses of losses of heterozygosity and linkage studies have implicated a gene(s) on chromosome 17q in the genesis of sporadic and early-onset familial breast carcinomas, respectively. To define the critical region of 17q, we examined DNAs from a series of 20 sporadic breast carcinomas and corresponding blood samples for allelic losses of chromosome 17q using microsatellite length polymorphisms. With these highly informative markers (average heterozygosity, 0.73), we observed frequent deletions of 17q at several loci. We found that D17S250 was deleted in 50% (7 of 14), THPA1 in 79% (11 of 14), D17S579 in 59% (11 of 19), NME1 in 29% (5 of 17), MPO in 36% (4 of 11), and GH in 25% (4 of 16) in the tumor set examined. A common region of deletion was found that was flanked by D17S250 to D15S579. These markers have recently been localized to a 6-cM interval of proximal chromosome 17q in bands 17q11.2-q21 and map within the region of the early-onset familial breast cancer locus, implying that the same gene or genes may be involved in both sporadic and familial breast tumors. Thyroid hormone receptor a and retinoic acid receptor-alpha are two potential candidate genes in this region. C1 DUKE UNIV, MED CTR, DEPT SURG, DURHAM, NC 27710 USA. UNIV N CAROLINA, DEPT PATHOL, CHAPEL HILL, NC 27599 USA. RP FUTREAL, PA (reprint author), NIEHS, MOLEC CARCINOGENESIS LAB, RES TRIANGLE PK, NC 27709 USA. NR 23 TC 208 Z9 217 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 1992 VL 52 IS 9 BP 2624 EP 2627 PG 4 WC Oncology SC Oncology GA HR290 UT WOS:A1992HR29000040 PM 1568230 ER PT J AU BIRRER, MJ BROWN, PH AF BIRRER, MJ BROWN, PH TI APPLICATION OF MOLECULAR-GENETICS TO THE EARLY DIAGNOSIS AND SCREENING OF LUNG-CANCER SO CANCER RESEARCH LA English DT Article; Proceedings Paper CT WORKSHOP ON INVESTIGATIONAL STRATEGIES FOR DETECTION AND INTERVENTION IN EARLY LUNG CANCER CY APR 21-24, 1991 CL ANNAPOLIS, MD SP NCI ID GROWTH-FACTOR RECEPTOR; HUMAN SMALL CELL; K-RAS ONCOGENE; POLYMERASE CHAIN-REACTION; HUMAN-BREAST CANCER; NEU ONCOGENE; L-MYC; CARCINOMA-CELLS; PROTO-ONCOGENE; P53 GENE AB Recent studies of the molecular biology of lung cancer have identified multiple abnormalities. Despite this vast cataloging of genetic lesions, the chronology of these events and those which occur early remains essentially unknown. This review summarizes the genetic abnormalities in lung cancer cells, including mutation, amplification, and overexpression of dominant protooncogenes as well as deletion and mutation of recessive oncogenes. In addition, possible candidate genes exist which may participate in the early activation events of lung cancer, and evidence for their role in the early development of cancer is discussed. These lesions may be helpful in developing strategies to screen for lung cancer. C1 NCI,DIV CANC PREVENT & CONTROL,BIOMARKER & PREVENT RES BRANCH,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,USN HOSP,BETHESDA,MD 20814. NR 112 TC 44 Z9 44 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 1992 VL 52 IS 9 SU S BP S2658 EP S2664 PG 7 WC Oncology SC Oncology GA HT047 UT WOS:A1992HT04700004 ER PT J AU GIACCONE, G BATTEY, J GAZDAR, AF OIE, H DRAOUI, M MOODY, TW AF GIACCONE, G BATTEY, J GAZDAR, AF OIE, H DRAOUI, M MOODY, TW TI NEUROMEDIN-B IS PRESENT IN LUNG-CANCER CELL-LINES SO CANCER RESEARCH LA English DT Article; Proceedings Paper CT WORKSHOP ON INVESTIGATIONAL STRATEGIES FOR DETECTION AND INTERVENTION IN EARLY LUNG CANCER CY APR 21-24, 1991 CL ANNAPOLIS, MD SP NCI ID GASTRIN-RELEASING PEPTIDE; BOMBESIN-LIKE PEPTIDES; MESSENGER-RNAS; RAT-BRAIN; BIOCHEMICAL-CHARACTERIZATION; GROWTH-FACTORS; SPINAL-CORD; CARCINOMA; GENE; LOCALIZATION AB Previously, high levels of gastrin-releasing peptide and its mRNA were detected in classic small cell lung cancer cell lines. Here the ability of lung cancer cell lines to synthesize neuromedin B (NMB), a structurally similar mammalian bombesin-like peptide, was investigated. By radioimmunoassay, NMB (0.1-0.7 pmol/mg of protein) was detected in 23 of 33 lung cancer cell lines. In contrast, gastrin-releasing peptide (0.1-12.9 pmol/mg of protein) was detected in 16 of 32 cell lines. Using gel filtration and high pressure liquid chromatography techniques, the main peak of immunoreactive NMB coeluted with synthetic NMB. By Northern analysis, a 0.8-kilobase mRNA species was present, using poly(A) mRNA derived from two of three lung cancer cell lines. Using a more sensitive S1 nuclease protection assay, NMB mRNA was present in most of the 15 lung cancer cell lines examined. These data suggest that NMB may be a regulatory peptide in lung cancer. C1 GEORGE WASHINGTON UNIV,MED CTR,DEPT BIOCHEM & MOLEC BIOL,2300 EYE ST NW,WASHINGTON,DC 20037. NCI,USN,MED ONCOL BRANCH,BETHESDA,MD 20889. NINCDS,NEUROCHEM LAB,BETHESDA,MD 20892. RI Giaccone, Giuseppe/E-8297-2017 OI Giaccone, Giuseppe/0000-0002-5023-7562 NR 34 TC 58 Z9 58 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 1992 VL 52 IS 9 SU S BP S2732 EP S2736 PG 5 WC Oncology SC Oncology GA HT047 UT WOS:A1992HT04700017 ER PT J AU IHDE, DC LIPPMAN, S AF IHDE, DC LIPPMAN, S TI INTERVENTION APPROACHES IN EARLY LUNG-CANCER AND PREMALIGNANT DISEASE - BREAKOUT GROUP-REPORT SO CANCER RESEARCH LA English DT Editorial Material C1 MD ANDERSON CANC CTR,HOUSTON,TX. RP IHDE, DC (reprint author), NCI,OFF DIRECTOR,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 1992 VL 52 IS 9 SU S BP S2767 EP S2768 PG 2 WC Oncology SC Oncology GA HT047 UT WOS:A1992HT04700025 ER PT J AU MULSHINE, JL SHUKE, N DAGHIGHIAN, F CARRASQUILLO, J GHOSH, B WALSH, T AVIS, I REYNOLDS, JC CUTTITTA, F LARSON, SM AF MULSHINE, JL SHUKE, N DAGHIGHIAN, F CARRASQUILLO, J GHOSH, B WALSH, T AVIS, I REYNOLDS, JC CUTTITTA, F LARSON, SM TI THE CORRECT DOSE - PHARMACOLOGICALLY GUIDED END-POINT FOR ANTI-GROWTH FACTOR THERAPY SO CANCER RESEARCH LA English DT Article; Proceedings Paper CT WORKSHOP ON INVESTIGATIONAL STRATEGIES FOR DETECTION AND INTERVENTION IN EARLY LUNG CANCER CY APR 21-24, 1991 CL ANNAPOLIS, MD SP NCI ID BOMBESIN-LIKE PEPTIDES; CELL LUNG-CARCINOMA; CANCER AB Strategies to block the effects of tumor growth factors, such as estrogen, and to recruit other regulatory elements, such as with retinoids, have focused interest on the possibility of successful tumor intervention approaches. Approaches that neutralize the effects of critical molecules that drive tumor promotion are attractive targets for evaluation as new intervention agents. Clinical intervention trials with early stage patients or with subjects from 'high risk" populations impose stricter types of constraints than conventional chemotherapy approaches in advanced stage patients. The potential for short-term toxicity has to be considered, as it may affect subject accrual or compliance. The longer expected survival of intervention subjects mandates closer attention to the possibilities of unexpected long-term toxicities with chronic administration of an intervention agent. As part of a Phase I clinical trial evaluating the utility of a monoclonal antibody directed against the autocrine growth factor, gastrin-releasing peptide to block the growth of small cell lung cancer, we developed a mathematical model to predict the requisite amount of antibody to neutralize growth factor effect. This model requires knowledge of the equilibrium concentration of the secreted growth factor, specific receptor, and bioavailability of the antibody in the tumor interstitium. A range of possible target doses of antibody can be developed to address the potential for heterogeneity frequently encountered in such systems, including a range of levels for peptide production and specific receptor expression. This approach could be applied to rationally derive treatment or intervention in which specific information regarding the relevant binding parameters is available. Through refinement of this modeling approach more context-specific dosing of agonist/antagonists could be determined which may decrease side effects associated with the drug administration. C1 NIH,DEPT NUCL MED,BETHESDA,MD 20892. NATL USN MED CTR,DEPT SURG,BETHESDA,MD. NATL USN MED CTR,DEPT MED,PULM SECT,BETHESDA,MD. MEM SLOAN KETTERING CANC CTR,DEPT RADIOL,NEW YORK,NY 10021. MEM SLOAN KETTERING CANC CTR,DEPT MED PHYS,NEW YORK,NY 10021. RP MULSHINE, JL (reprint author), NCI,DIV CANC PREVENT & CONTROL,BIOMARKERS & PREVENT RES BRANCH,KENSINGTON,MD 20895, USA. RI Carrasquillo, Jorge/E-7120-2010 NR 22 TC 13 Z9 13 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 1992 VL 52 IS 9 SU S BP S2743 EP S2746 PG 4 WC Oncology SC Oncology GA HT047 UT WOS:A1992HT04700019 ER PT J AU MULSHINE, JL AF MULSHINE, JL TI NCI WORKSHOP ON INVESTIGATIONAL STRATEGIES FOR DETECTION AND INTERVENTION IN EARLY LUNG-CANCER SO CANCER RESEARCH LA English DT Article; Proceedings Paper CT WORKSHOP ON INVESTIGATIONAL STRATEGIES FOR DETECTION AND INTERVENTION IN EARLY LUNG CANCER CY APR 21-24, 1991 CL ANNAPOLIS, MD SP NCI RP MULSHINE, JL (reprint author), NCI,DIV CANC PREVENT & CONTROL,BIOMARKERS & PREVENT RES BRANCH,ROCKVILLE,MD 20850, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 1992 VL 52 IS 9 SU S BP S2639 EP S2640 PG 2 WC Oncology SC Oncology GA HT047 UT WOS:A1992HT04700001 ER PT J AU MULSHINE, JL TOCKMAN, MS AF MULSHINE, JL TOCKMAN, MS TI DIAGNOSTIC RESEARCH - BREAKOUT GROUP-REPORT SO CANCER RESEARCH LA English DT Editorial Material C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,BALTIMORE,MD 21205. RP MULSHINE, JL (reprint author), NCI,DCPC,BIOMARKERS & PREVENT RES BRANCH,ROCKVILLE,MD 20850, USA. NR 0 TC 2 Z9 2 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 1992 VL 52 IS 9 SU S BP S2766 EP S2766 PG 1 WC Oncology SC Oncology GA HT047 UT WOS:A1992HT04700024 ER PT J AU TOCKMAN, MS GUPTA, PK PRESSMAN, NJ MULSHINE, JL AF TOCKMAN, MS GUPTA, PK PRESSMAN, NJ MULSHINE, JL TI CONSIDERATIONS IN BRINGING A CANCER BIOMARKER TO CLINICAL-APPLICATION SO CANCER RESEARCH LA English DT Article; Proceedings Paper CT WORKSHOP ON INVESTIGATIONAL STRATEGIES FOR DETECTION AND INTERVENTION IN EARLY LUNG CANCER CY APR 21-24, 1991 CL ANNAPOLIS, MD SP NCI ID HUMAN-LUNG CANCER; NON-SMALL-CELL; LACTO-N-FUCOPENTAOSE; IMAGE-ANALYSIS; MONOCLONAL-ANTIBODIES; DNA POLYMORPHISMS; SUGAR SEQUENCE; JOHNS-HOPKINS; CARCINOMA; MARKERS AB Specific challenges face our application of emerging biomarkers to early lung cancer detection. These challenges might be considered frontiers to be bridged between established biomedical disciplines, requiring expertise often beyond the range of individual investigators. Cross-disciplinary research already has led to new appreciation of the mechanisms which underlie the phenotypic expression of the transformed cell and places within our grasp the tools which might lead to successful early lung cancer detection. Prior to the successful application of newly described markers, further cross-disciplinary research must (a) refine the selection of biologically appropriate markers, (b) validate such markers against acknowledged disease end points, (c) establish quantitative criteria for marker presence/absence, and (d) confirm marker predictive value in prospective population trials. C1 UNIV PENN,DEPT PATHOL & LAB MED,PHILADELPHIA,PA 19104. CELL SYST INT INC,ROCKLAND,DE 19732. NCI,BIOMARKERS & PREVENT RES BRANCH,BETHESDA,MD 20814. RP TOCKMAN, MS (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT ENVIRONM HLTH SCI,BALTIMORE,MD 21205, USA. NR 72 TC 18 Z9 18 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 1992 VL 52 IS 9 SU S BP S2711 EP S2718 PG 8 WC Oncology SC Oncology GA HT047 UT WOS:A1992HT04700013 ER PT J AU WEINSTEIN, JN VANOSDOL, W AF WEINSTEIN, JN VANOSDOL, W TI EARLY INTERVENTION IN CANCER USING MONOCLONAL-ANTIBODIES AND OTHER BIOLOGICAL LIGANDS - MICROPHARMACOLOGY AND THE BINDING-SITE BARRIER SO CANCER RESEARCH LA English DT Article ID INTERSTITIAL PRESSURE; MODELING ANALYSIS; HUMAN-COLON; TUMOR; MACROMOLECULES; IMMUNOLYMPHOSCINTIGRAPHY; MELANOMA; F(AB')2; THERAPY; BIODISTRIBUTION AB Monoclonal antibodies and other biological ligands tend to distribute nonuniformly in bulky tumors after systemic administration. In part, that observation reflects intrinsic heterogeneity of the tumor; in part, it represents poor percolation through tumor substance. Theoretical considerations led us several years ago to formulate the "binding site barrier" hypothesis, the idea that macromolecular ligands could be prevented from penetrating tumors by the very fact of their successful binding to the target receptor. All else being equal, the higher the density of target moieties (e.g., antigens) and the higher the affinity, the greater the barrier. Experimental evidence for this hypothesis remained circumstantial until we recently obtained direct experimental verification in an animal tumor system. As shown by calculations in the present study, metabolism of ligand in free form or once it has bound to the target can also limit dramatically the extent of penetration. The PERC program package, developed to examine these issues in the case of monoclonal antibodies, has now been applied to other types of ligands as well. We speculate that the same microscopic factors have influenced the evolution of biological ligands, such as the autocrine-paracrine and chemotactic factors. Micropharmacological issues (binding sites, molecular size, and charge) should be taken into account as we design the next generation of biological ligands for systemic administration. The same issues are, perhaps, even more important with respect to molecular design of biological factors to be secreted by genetically modified cells in the treatment of cancer and in cancer vaccines. Since the PERC calculations and experiments relate to aggregates of tumor cells no more than a few hundred-mu-m across, the ideas appear relevant to the problems of early detection and intervention. However, barriers associated with organized epithelial cell layers and basement membrane in the case of early carcinomas and carcinomatous change remain to be understood. RP WEINSTEIN, JN (reprint author), NCI, DCBDC, THEORET IMMUNOL SECT, MATH BIOL LAB, BETHESDA, MD 20892 USA. NR 39 TC 94 Z9 94 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 1992 VL 52 IS 9 SU S BP S2747 EP S2751 PG 5 WC Oncology SC Oncology GA HT047 UT WOS:A1992HT04700020 PM 1563006 ER PT J AU BUTCH, ER LAU, HHS SHAW, KL SMOLAREK, TA SCHMEROLD, I ANDERSON, JN BAIRD, WM YAGI, H JERINA, DM AF BUTCH, ER LAU, HHS SHAW, KL SMOLAREK, TA SCHMEROLD, I ANDERSON, JN BAIRD, WM YAGI, H JERINA, DM TI HIGH SELECTIVITY OF POLYCLONAL ANTIBODIES AGAINST DNA MODIFIED BY DIASTEREOMERIC BENZO[C]PHENANTHRENE-3,4-DIOL-1,2-EPOXIDES SO CARCINOGENESIS LA English DT Note ID BENZOPYRENE DIOL EPOXIDE; EMBRYO CELL-CULTURES; MOUSE SKIN; MONOCLONAL-ANTIBODIES; ADDUCTS; BINDING; BENZO(C)PHENANTHRENE; QUANTITATION; 7,12-DIMETHYLBENZ(A)ANTHRACENE; CARCINOGENESIS AB Polyclonal antibodies were developed in New Zealand White rabbits against DNA modified with diastereomeric benzo[c]-phenanthrene-3,4-diol-1,2-epoxide (B[c]PhDE)-1 (4-hydroxyl and epoxide cis) and B[c]PhDE-2 (4-hydroxyl and epoxide trans). Antiserum developed against B[c]PhDE-2-DNA was stereoselective. In competitive ELISA assays using wells coated with 160 fmol B[c]PhDE-2-DNA adducts, B[c]PhDE-2-DNA gave 50% inhibition at 200 fmol adducts/well. B[c]PhDE-1-DNA required a 10-fold higher amount of adducts/well to give 50% inhibition. Benzo[a]pyrene-7,8-diol-9,10-epoxide-2-DNA and 7,12-dimethylbenz[a]-anthracene-3,4-diol-1,2-epoxide-1-DNA caused only a 30% inhibition even at the highest doses tested (> 4000 fmol adducts/well). For antiserum developed against B[c]PhDE-1-DNA, 50% inhibition required 570 fmol B[c]PhDE-1-DNA adducts in wells coated with 100 fmol B[c]PhDE-1-DNA adducts. 7,12-Dimethylbenz[a]anthracene-3,4-diol-1,2-epoxide-1-DNA and B[c]PhDE-2-DNA were also effective competitors: they caused 50% inhibition at 1900 and 1800 fmol adducts/well respectively. In contrast, benzo[a]-pyrene-7,8-diol-9,10-epoxide-2-DNA gave no inhibition at the highest dose of competitor tested (4050 fmol adducts/well). Antisera from three rabbits immunized, with B[c]PhDE-2-DNA demonstrated similar antigen specificities. The properties of these antisera differ from those reported previously for antibodies developed against benzo[a]-pyrene-DNA in that they show selectivity for DNA modified by specific hydrocarbon diolepoxides, in one case for B[c]PhDE-2-DNA and in the other for B[c]PhDE-DNA or 7,12-dimethylbenz[a]anthracene-3,4-diol-1,2-epoxide-1-DNA. The specificity of these antisera will facilitate analysis of the modification of DNA by different polycyclic aromatic hydrocarbon diolepoxides. C1 PURDUE UNIV,SCH PHARM & PHARMACAL SCI,DEPT MED CHEM,W LAFAYETTE,IN 47907. PURDUE UNIV,SCH SCI,DEPT BIOL SCI,W LAFAYETTE,IN 47907. NIDDK,BIOORGAN CHEM LAB,BETHESDA,MD 20892. FU NCI NIH HHS [1T32-CA09634, CA28825] NR 25 TC 6 Z9 6 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAY PY 1992 VL 13 IS 5 BP 895 EP 899 DI 10.1093/carcin/13.5.895 PG 5 WC Oncology SC Oncology GA HV458 UT WOS:A1992HV45800028 PM 1587005 ER PT J AU MUNGER, K PIETENPOL, JA PITTELKOW, MR HOLT, JT MOSES, HL AF MUNGER, K PIETENPOL, JA PITTELKOW, MR HOLT, JT MOSES, HL TI TRANSFORMING GROWTH-FACTOR BETA-1 REGULATION OF C-MYC EXPRESSION, PRB PHOSPHORYLATION, AND CELL-CYCLE PROGRESSION IN KERATINOCYTES SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID RETINOBLASTOMA SUSCEPTIBILITY GENE; ADENOVIRUS E1A PROTEINS; SERUM-FREE MEDIUM; SV40 LARGE-T; HUMAN PROKERATINOCYTES; PRODUCT; INHIBITION; DIFFERENTIATION; PROLIFERATION; TRANSCRIPTION AB Transforming growth factor-beta-1 (TGF-beta-1) is a potent inhibitor of cellular proliferation in a variety of cell types, including skin keratinocytes. TGF-beta-1 suppression of c-myc transcription has been implicated in the mechanism of TGF-beta-1 inhibition of keratinocytes, and evidence suggests that the protein product of the retinoblastoma gene (pRB) is a necessary component in this pathway. Following growth factor stimulation of quiescent keratinocytes, TGF-beta-1 can inhibit cell cycle progression into S phase at any point prior to the G1-S transition but does not inhibit progression through the S phase of the cell cycle. Since pRB is hypophosphorylated during G1 and hyperphosphorylated during S and G2, the G1-S-specific phosphorylation of pRB becomes an attractive target for the growth-inhibitory activities of TGF-beta-1. However, in TGF-beta-1-treated primary human keratinocytes and in a series of human papilloma virus and SV40 immortalized human keratinocyte cell lines, the phosphorylation status of pRB strictly correlated with cell growth. No evidence was found for a direct effect of TGF-beta-1 on the phosphorylation state of pRB in these cells. It was further demonstrated that synthesis of c-myc protein can be rapidly inhibited by TGF-beta-1 addition throughout G1 and S phases, indicating that the phosphorylation state of pRB, at least as it varies during the cell cycle, does not alter the ability of TGF-beta-1 to suppress c-myc expression. Use of antisense c-myc oligonucleotides that suppress myc protein synthesis inhibited progression through the cell cycle in a pattern very similar to that observed with TGF-beta-1. The oligonucleotides inhibited entry into S phase when added at any point in G1 but had no inhibitory effect when added during S phase. This indicates that in keratinocytes the c-myc protein may be important for the initiation of S phase but is not absolutely required for progression through S phase. C1 VANDERBILT UNIV,MED CTR,SCH MED,DEPT CELL BIOL,NASHVILLE,TN 37232. MAYO CLIN & MAYO FDN,DEPT DERMATOL,ROCHESTER,MN 55905. MAYO CLIN & MAYO GRAD SCH MED,ROCHESTER,MN 55901. RP MUNGER, K (reprint author), NCI,TUMOR VIRUS BIOL LAB,BLDG 41,BETHESDA,MD 20892, USA. OI Munger, Karl/0000-0003-3288-9935 FU NCI NIH HHS [CA 09592, CA 42572, CA 48799] NR 40 TC 90 Z9 90 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD MAY PY 1992 VL 3 IS 5 BP 291 EP 298 PG 8 WC Cell Biology SC Cell Biology GA HU319 UT WOS:A1992HU31900004 PM 1633111 ER PT J AU SETH, A ASCIONE, R FISHER, RJ MAVROTHALASSITIS, GJ BHAT, NK PAPAS, TS AF SETH, A ASCIONE, R FISHER, RJ MAVROTHALASSITIS, GJ BHAT, NK PAPAS, TS TI THE ETS GENE FAMILY SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID LONG TERMINAL REPEAT; DNA-BINDING; TRANSCRIPTIONAL ACTIVATION; MOLECULAR-ORGANIZATION; PROTEIN; ONCOGENE; ENHANCER; SEQUENCE; PHOSPHORYLATION; EXPRESSION C1 PROGRAM RESOURCES INC,FREDERICK,MD 21702. RP SETH, A (reprint author), NCI,MOLEC ONCOL LAB,BLDG 469,ROOM 211,FREDERICK,MD 21702, USA. RI Fisher, Robert/B-1431-2009 NR 49 TC 148 Z9 149 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD MAY PY 1992 VL 3 IS 5 BP 327 EP 334 PG 8 WC Cell Biology SC Cell Biology GA HU319 UT WOS:A1992HU31900008 PM 1633115 ER PT J AU HUGHES, MF SMITH, BJ ELING, TE AF HUGHES, MF SMITH, BJ ELING, TE TI THE OXIDATION OF 4-AMINOBIPHENYL BY HORSERADISH-PEROXIDASE SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID PROSTAGLANDIN-H SYNTHASE; CARCINOGENIC AROMATIC-AMINES; CATALYZED METABOLISM; CO-OXIDATION; BENZIDINE; ACTIVATION; REDUCTION; CYCLOOXYGENASE; IDENTIFICATION; GLUTATHIONE AB The oxidation of the carcinogen 4-aminobiphenyl (4-ABP) catalyzed by the model peroxidase enzyme horseradish peroxidase (HRP) was investigated. 4-ABP served as a reducing cosubstrate for HRP during the enzyme-catalyzed reduction of the synthetic hydroperoxide, 5-phenyl-4-penten-1-yl hydroperoxide, to its corresponding alcohol. Spectral analysis during the incubation of HRP, 4-ABP, and H2O2 showed an increase in absorbance at 230 and 325 nm and decrease at 270 run, suggesting metabolite formation. Oxygen consumption was not detected in incubations of HRP, 4-ABP, and H2O2. However, oxygen uptake was observed after the addition of glutathione, which indicated that a free radical metabolite of 4-ABP was formed by the peroxidase. The 4-ABP free radical reacted with glutathione forming a glutathionyl radical which, in turn, reacted with and consumed oxygen. HPLC analysis of organic extracts of incubations with HRP, [H-3]-4-ABP, and H2O2 showed the formation of one major peak identified by mass spectroscopy as 4,4'-azobis(biphenyl). The addition of glutathione to the incubations decreased the formation of 4-ABP metabolites, suggesting a reduction of the 4-ABP free radical and/or the formation of glutathione conjugates. Subsequent HPLC analysis of incubations including [S-35]glutathione indicated formation of several unidentified 4-ABP-glutathione conjugates as well as recovery of parent compound. These studies suggest that HRP metabolizes 4-ABP by a one-electron oxidation mechanism, resulting in formation of a free radical. This radical can either react with a second radical to form azobis(biphenyl), be reduced by glutathione back to parent, or react with glutathione to form glutathione conjugates. C1 NIEHS,MOLEC BIOPHYS LAB,POB 12233,RES TRIANGLE PK,NC 27709. NR 31 TC 14 Z9 14 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD MAY-JUN PY 1992 VL 5 IS 3 BP 340 EP 345 DI 10.1021/tx00027a004 PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA HV374 UT WOS:A1992HV37400004 PM 1504256 ER PT J AU BUTLER, LE THOMASSEN, D MARTIN, JL MARTIN, BM KENNA, JG POHL, LR AF BUTLER, LE THOMASSEN, D MARTIN, JL MARTIN, BM KENNA, JG POHL, LR TI THE CALCIUM-BINDING PROTEIN CALRETICULIN IS COVALENTLY MODIFIED IN RAT-LIVER BY A REACTIVE METABOLITE OF THE INHALATION ANESTHETIC HALOTHANE SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID ENDOPLASMIC-RETICULUM; HEPATOTOXICITY; PERTURBATION; ANTIBODIES; HEPATITIS; MECHANISM; SERA AB A general procedure is presented for the isolation of several liver microsomal target proteins of the reactive trifluoroacetyl halide metabolite of halothane. It was found that most of these proteins could be selectively extracted from microsomes with 0.1 % sodium deoxycholate and separated into partially purified fractions by DEAE-Sepharose anion-exchange chromatography. Using this method, we describe the isolation and identification of a 63-kDa target protein of halothane in rat liver. Amino acid sequences of the N-terminal and of several internal peptides of the protein, as well as the deduced amino acid sequence of a nearly full-length rat liver cDNA clone of the protein, showed 98% identity with a reported murine cDNA that encodes for calreticulin, a major calcium-binding protein of the lumen of endoplasmic reticulum. Although it remains to be determined what role calreticulin has in the development of halothane hepatitis, this study has shown that calreticulin can be a target of reactive metabolites of xenobiotics. C1 NHLBI,CHEM PHARMACOL LAB,BLDG 10,ROOM 8N115,BETHESDA,MD 20892. NIMH,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. JOHNS HOPKINS MED INST,DEPT ANESTHESIOL & CRIT CARE MED,BALTIMORE,MD 21205. NR 36 TC 54 Z9 54 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD MAY-JUN PY 1992 VL 5 IS 3 BP 406 EP 410 DI 10.1021/tx00027a014 PG 5 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA HV374 UT WOS:A1992HV37400014 PM 1504264 ER PT J AU SMITH, BJ DEBRUIN, L JOSEPHY, PD ELING, TE AF SMITH, BJ DEBRUIN, L JOSEPHY, PD ELING, TE TI MUTAGENIC ACTIVATION OF BENZIDINE REQUIRES PRIOR BACTERIAL ACETYLATION AND SUBSEQUENT CONVERSION BY PROSTAGLANDIN-H SYNTHASE TO 4-NITRO-4'-(ACETYLAMINO)BIPHENYL SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID HETEROCYCLIC AROMATIC-AMINES; TYPHIMURIUM STRAINS TA98; SALMONELLA-TYPHIMURIUM; ENDOPEROXIDE SYNTHETASE; DEPENDENT ACTIVATION; ACETYLTRANSFERASE LEVELS; PEROXIDATIVE ACTIVATION; HORSERADISH-PEROXIDASE; TESTER STRAINS; CO-OXIDATION AB We have used the Ames test in combination with prostaglandin H synthase (PHS) to study the bioactivation of benzidine as well as other aromatic amines. Previous investigations established that the formation of benzidine mutagens by PHS is dramatically enhanced in Salmonella typhimurium strains with high levels of acetyl CoA-dependent arylamine N-acetyltransferase/arylhydroxylamine O-acetyltransferase activity despite the fact that acetylation of aromatic amines decreases their susceptibility to oxidation by peroxidases. In this study, we used a new strain (YG1012) that has very high acetylation capability to investigate the metabolism and mutagenicity of. benzidine and N-acetylbenzidine catalyzed by PHS (from ram seminal vesicle microsomes) and horseradish peroxidase (HRP). YG1012 bacteria rapidly acetylated benzidine to N-acetylbenzidine and NN'-diacetylbenzidine. Preincubation of the bacteria with benzidine before addition of PHS increased the mutagenicity. Under conditions identical to those used to assess mutagenicity, PHS metabolized benzidine rapidly, but the substrate was not totally consumed, with about 40% of the original concentration remaining intact. These data suggest that conversion to N-acetylbenzidine may be the initial step in the bioactivation of benzidine in the PHS-mediated Ames assay. N-Acetylbenzidine is a cosubstrate for PHS peroxidase activity as measured by 5-phenyl-4-pentenyl hydroperoxide reduction, spectral changes, and formation of protein adducts. N-Acetylbenzidine was converted to mutagens by PHS but not HRP, with enhanced mutagenicity observed in bacteria with high acetylation activity. We used reverse-phase HPLC to characterize the metabolites of N-acetylbenzidine formed by PHS and HRP. On the basis of UV/vis spectral evidence we suggest that HRP converted N-acetylbenzidine to dimers or polymers while the major product of PHS oxidations was identified as 4-nitro-4'-(acetylamino)biphenyl by cochromatography with an authentic standard and by UV/vis spectrophotometry. 4-Nitro-4'-(acetylamino)biphenyl was a direct-acting mutagen in YG1012. The results indicate that benzidine must be converted by the bacteria to N-acetylbenzidine prior to metabolism by PHS. PHS peroxidase then converts N-acetylbenzidine to 4-nitro-4'-(acetylamino)biphenyl, a potent mutagen. The data suggest that extracellular generation of free radical metabolites of benzidine does not play a role in bacterial mutagenesis. C1 NIEHS,MOLEC BIOPHYS LAB,EICOSANOID BIOCHEM SECT,POB 12233,RES TRIANGLE PK,NC 27709. UNIV GUELPH,GUELPH WATERLOO CTR GRAD WORK CHEM,DEPT CHEM & BIOCHEM,GUELPH N1G 2W1,ONTARIO,CANADA. NR 37 TC 33 Z9 33 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD MAY-JUN PY 1992 VL 5 IS 3 BP 431 EP 439 DI 10.1021/tx00027a018 PG 9 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA HV374 UT WOS:A1992HV37400018 PM 1504268 ER PT J AU KLUES, HG MARON, BJ DOLLAR, AL ROBERTS, WC AF KLUES, HG MARON, BJ DOLLAR, AL ROBERTS, WC TI DIVERSITY OF STRUCTURAL MITRAL-VALVE ALTERATIONS IN HYPERTROPHIC CARDIOMYOPATHY SO CIRCULATION LA English DT Article DE HYPERTROPHY; CARDIOMYOPATHIES; VALVES; GENETICS; LEFT VENTRICLE ID SYSTOLIC ANTERIOR MOTION; TWO-DIMENSIONAL ECHOCARDIOGRAPHY; LEFT-VENTRICULAR HYPERTROPHY; OBSTRUCTIVE CARDIOMYOPATHY; CLINICAL MANIFESTATIONS; SUBAORTIC STENOSIS; PRESSURE-GRADIENT; PATHO-PHYSIOLOGY; MOLECULAR-BASIS; WIDE-ANGLE AB Background. Hypertrophic cardiomyopathy (HCM) is characterized by an asymmetrically hypertrophied left ventricle and is regarded as a disease of cardiac muscle. Methods and Results. To assess the possibility that the mitral valve itself may be involved in the disease process, we studied mitral valves from 94 patients with HCM and 45 normal control subjects. The area of the mitral leaflets was increased in patients with HCM compared with control subjects (12.9 +/- 3.7 versus 8.7 +/- 2.0 cm2; p < 0.001). For the overall group of patients, this increase was largely caused by an increase in anterior leaflet length (2.2 +/- 0.5 cm for HCM versus 1.8 +/- 0.3 cm for control subjects; p < 0.001), because circumference did not differ between the two groups. Mitral leaflet area was increased (greater-than-or-equal-to 12.0 cm2) in 55 (58%) of the 94 valves. In 12 of these 55 valves, both the anterior and posterior leaflets were enlarged; the other 43 valves had asymmetrical or segmental enlargement of either the anterior leaflet (36 patients) or a portion of posterior leaflet (seven patients). In addition, nine patients had a congenital malformation of the mitral apparatus in which one or both papillary muscles inserted directly into anterior mitral leaflet (mitral valve area was normal in seven of the nine). Conclusions. Sixty-two (66%) of 94 mitral valves had a constellation of structural malformations, including increased leaflet area and elongation of the leaflets or anomalous papillary muscle insertion directly into anterior mitral leaflet. These findings expand the morphological definition of HCM by demonstrating that the disease process is not confined to cardiac muscle but rather many patients also have structural abnormalities of the mitral valve that are unlikely to be acquired or secondary to mechanical factors. C1 NHLBI,CARDIOL BRANCH,BLDG 10,ROOM 7B-15,BETHESDA,MD 20892. NHLBI,PEDIAT BRANCH,BETHESDA,MD 20892. NR 50 TC 169 Z9 174 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY PY 1992 VL 85 IS 5 BP 1651 EP 1660 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA HR947 UT WOS:A1992HR94700001 PM 1572023 ER PT J AU EISENHOFER, G ESLER, MD MEREDITH, IT DART, A CANNON, RO QUYYUMI, AA LAMBERT, G CHIN, J JENNINGS, GL GOLDSTEIN, DS AF EISENHOFER, G ESLER, MD MEREDITH, IT DART, A CANNON, RO QUYYUMI, AA LAMBERT, G CHIN, J JENNINGS, GL GOLDSTEIN, DS TI SYMPATHETIC NERVOUS FUNCTION IN HUMAN HEART AS ASSESSED BY CARDIAC SPILLOVERS OF DIHYDROXYPHENYLGLYCOL AND NOREPINEPHRINE SO CIRCULATION LA English DT Article DE UPTAKE, NEURONAL; DESIPRAMINE; DIHYDROXYPHENYLALANINE ID PLASMA 3,4-DIHYDROXYPHENYLGLYCOL; NEURONAL UPTAKE; NORADRENALINE; RABBIT; METABOLISM; SYSTEM; CATECHOLAMINES; DISPOSITION; RESPONSES; KINETICS AB Background. Measurement of cardiac norepinephrine spillover may indicate the amount of transmitter at neuroeffector sites but does not distinguish neuronal release or reuptake in determining this amount or provide information about other aspects of sympathetic function. This report examines how cardiac spillover of the norepinephrine metabolite dihydroxyphenylglycol (DHPG) provides additional distinct information about cardiac sympathetic function. Methods and Results. Arterial and coronary venous blood samples were taken during cardiac catheterization and intravenous infusion of [H-3]norepinephrine in 57 subjects. Subjects were given intravenous yohimbine or underwent mental stress, handgrip exercise, and cycling exercise to activate sympathetic nerves or were given intravenous desipramine to block norepinephrine reuptake. Cardiac DHPG spillover (601 +/- 41 pmol/min) was eightfold greater than norepinephrine spillover (78 +/- 10 pmol/min) at rest and increased during sympathetic activation by 65% of the increase of norepinephrine. This and the desipramine-sensitive cardiac production of [H-3]-labeled DHPG from [H-3]norepinephrine indicated that 10.5 times more endogenous norepinephrine is recaptured than escapes into plasma; that more than 90% of recaptured norepinephrine is sequestered into storage vesicles; and that under resting conditions, most cardiac spillover of DHPG and turnover of norepinephrine are from metabolism of transmitter leaking from vesicles; the latter process is independent of exocytotic transmitter release with a rate at rest over 100-fold that of norepinephrine spillover and over 10-fold that of norepinephrine reuptake. Conclusions. Cardiac spillover of DHPG provides information about processes close to or within sympathetic nerve endings that cannot be provided by measurements of norepinephrine spillover alone. This includes quantitative information about the role of neuronal uptake in terminating the actions of norepinephrine at neuroeffector sites and the importance of vesicular-axoplasmic exchange of norepinephrine as a dynamic process contributing to norepinephrine turnover. C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. BAKER MED RES INST,PRAHRAN,VIC 3181,AUSTRALIA. RP EISENHOFER, G (reprint author), NINCDS,CLIN NEUROSCI BRANCH,BLDG 10,ROOM 5N-214,BETHESDA,MD 20892, USA. RI Jennings, Garry/B-3914-2009; Lambert, Gavin/E-7384-2010; Dart, Anthony/E-7461-2010 OI Lambert, Gavin/0000-0003-0315-645X; Dart, Anthony/0000-0003-1360-3778 NR 33 TC 99 Z9 99 U1 0 U2 1 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY PY 1992 VL 85 IS 5 BP 1775 EP 1785 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA HR947 UT WOS:A1992HR94700015 PM 1572033 ER PT J AU CARRIER, L BOHELER, KR CHASSAGNE, C DELABASTIE, D WISNEWSKY, C LAKATTA, EG SCHWARTZ, K AF CARRIER, L BOHELER, KR CHASSAGNE, C DELABASTIE, D WISNEWSKY, C LAKATTA, EG SCHWARTZ, K TI EXPRESSION OF THE SARCOMERIC ACTIN ISOGENES IN THE RAT-HEART WITH DEVELOPMENT AND SENESCENCE SO CIRCULATION RESEARCH LA English DT Article DE ALPHA-SKELETAL ACTIN; ALPHA-CARDIAC ACTIN; DEVELOPMENT; AGING; RAT ID CARDIAC ALPHA-ACTIN; SKELETAL-MUSCLE; GENE-EXPRESSION; MESSENGER-RNAS; PRESSURE-OVERLOAD; THYROID-HORMONE; HYPERTROPHY; MYOSIN; TRANSCRIPTION; INDUCTION AB Sarcomeric actin genes, alpha-cardiac and alpha-skeletal, are coexpressed in neonatal rodent hearts and are regulated in response to hormonal and hemodynamic stimuli; however, their precise developmental pattern of expression has not been determined, and it is unknown whether they are coexpressed during senescence. We have, therefore, investigated the accumulation of sarcomeric actin transcripts in rat heart during fetal and postnatal development and with senescence by two different techniques: primer extension analysis with an oligonucleotide common to both sarcomeric actins and RNA hybridization with specific cardiac alpha-actin cRNA probes. We found that at 17-19 days in utero both isogenes are coexpressed and alpha-skeletal actin mRNAs represent 28.0 +/- 0.8% of the sarcomeric actin mRNA total. Skeletal actin mRNAs increase to 40% of the total 1 week after birth (NS, p = 0.15), remain constant for 3 weeks, and decrease to less than 20% of the total in ventricles and atria of 1-month-old rats. The alpha-skeletal actin transcripts further decline to less than 5% of the total at 2 months of age and do not reaccumulate in senescent animals. There was no significant difference between male and female rat ventricles. By comparison with the known accumulations of alpha- and beta-myosin heavy chain mRNAs, our results demonstrate that whatever the developmental stage the kinetics of expression for the sarcomeric myosin and actin multigene families are independent. C1 NIA,BALTIMORE,MD 21224. RP CARRIER, L (reprint author), HOP LARIBOISIERE,INSERM,U127,41 BLVD CHAPELLE,F-75475 PARIS 10,FRANCE. NR 41 TC 67 Z9 67 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD MAY PY 1992 VL 70 IS 5 BP 999 EP 1005 PG 7 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA HQ041 UT WOS:A1992HQ04100014 PM 1568307 ER PT J AU PITT, B COHN, JN FRANCIS, GS KOSTIS, JB PACKER, M PFEFFER, MA SWEDBERG, K YUSUF, S AF PITT, B COHN, JN FRANCIS, GS KOSTIS, JB PACKER, M PFEFFER, MA SWEDBERG, K YUSUF, S TI THE EFFECT OF TREATMENT ON SURVIVAL IN CONGESTIVE-HEART-FAILURE SO CLINICAL CARDIOLOGY LA English DT Article DE CONGESTIVE HEART FAILURE; MORTALITY; PROGNOSIS; DRUG TREATMENT ID MYOCARDIAL-INFARCTION; VENTRICULAR ARRHYTHMIAS; PROGNOSTIC IMPORTANCE; MORTALITY; THERAPY; ENALAPRIL; RATS; PREDICTORS; MILRINONE; CAPTOPRIL AB Congestive heart failure (CHF is a disorder characterized by a variety of clinical, biochemical, electrophysiological, and hemodynamic abnormalities. During the past two decades, numerous drugs have been employed in the treatment of this complex syndrome, and many agents have been shown to improve symptoms and ventricular function in patients with CHF. Because CHF is associated with a high risk of death, treatment should be directed not only toward the relief of symptoms, but also toward a reduction in mortality. Many variables have been shown to be related to survival; taken individually, however, each is limited in its utility in predicting prognosis. In recent years, large-scale studies with large sample sizes have directly assessed the effects of treatment on mortality in CHF Results from these trials indicate that vasodilators and angiotensin-converting enzyme (ACE) inhibitors may improve mortality in patients with symptoms of heart failure. Additional trials are now in progress to evaluate the effect of treatment on patients with asymptomatic left ventricular dysfunction. C1 UNIV MINNESOTA,SCH MED,MINNEAPOLIS,MN 55455. UNIV MINNESOTA HOSP & CLIN,MINNEAPOLIS,MN 55455. UNIV MED & DENT NEW JERSEY,NEW BRUNSWICK,NJ. CUNY MT SINAI SCH MED,NEW YORK,NY 10029. HARVARD UNIV,SCH MED,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DIV CARDIOVASC,BOSTON,MA 02115. NHLBI,BETHESDA,MD 20892. OSTRA HOSP,S-41685 GOTHENBURG,SWEDEN. RP PITT, B (reprint author), UNIV MICHIGAN,MED CTR,3910 TAUBMAN,ANN ARBOR,MI 48109, USA. NR 38 TC 9 Z9 9 U1 0 U2 0 PU CLINICAL CARDIOLOGY PUBL CO PI MAHWAH PA PO BOX 832, MAHWAH, NJ 07430-0832 SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD MAY PY 1992 VL 15 IS 5 BP 323 EP 329 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA HU304 UT WOS:A1992HU30400003 PM 1623652 ER PT J AU KOVACS, JA MASUR, H AF KOVACS, JA MASUR, H TI PROPHYLAXIS FOR PNEUMOCYSTIS-CARINII PNEUMONIA IN PATIENTS INFECTED WITH HUMAN-IMMUNODEFICIENCY-VIRUS SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID CONTROLLED TRIAL; SULFAMETHOXAZOLE; CHEMOPROPHYLAXIS; EFFICACY; AIDS AB Following the initial observation by Dr. Margaret Fischl that trimethoprim-sulfamethoxazole can prevent Pneumocystis carinii infection in patients with Kaposi's sarcoma, initiating prophylaxis for pneumocystic infection in all patients with < 200 CD4+ cells/mm3 has become accepted practice. This prophylactic intervention has been found not only to reduce the development of pneumonia due to P. carinii but also to prolong life. Drs. Henry Masur and Joseph A. Kovacs first reviewed prophylaxis for P. carinii pneumonia in patients infected with the human immunodeficiency virus for the AIDS Commentary 3 years ago. They have updated that initial review for this AIDS Commentary, placing currently available information into concise clinical perspective and detailing a rational plan for the clinician to follow based on results of recent studies. C1 NIH,CTR CLIN,DEPT CRIT CARE MED,BLDG 10,ROOM 7D43,BETHESDA,MD 20892. NR 16 TC 30 Z9 30 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAY PY 1992 VL 14 IS 5 BP 1005 EP 1009 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA HQ569 UT WOS:A1992HQ56900002 PM 1350925 ER PT J AU WILLIAMSON, PR KWONCHUNG, KJ GALLIN, JI AF WILLIAMSON, PR KWONCHUNG, KJ GALLIN, JI TI SUCCESSFUL TREATMENT OF PAECILOMYCES-VARIOTII INFECTION IN A PATIENT WITH CHRONIC GRANULOMATOUS-DISEASE AND A REVIEW OF PAECILOMYCES SPECIES INFECTIONS SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID RENAL-TRANSPLANT PATIENT; N-SUBSTITUTED IMIDAZOLES; PROSTHETIC AORTIC-VALVE; MOLECULAR-BASIS; LILACINUS; ENDOPHTHALMITIS; ENDOCARDITIS; CELLULITIS; TRIAZOLES; THERAPY AB An 8-year-old boy who had chronic granulomatous disease developed a soft tissue infection of the right heel after riding on a motor scooter. Infection was insidious, and minor heel pain and fevers occurred only on the day interferon-gamma was injected. Soft tissue biopsy showed hyphal elements, and Paecilomyces variotii grew in culture. The infection was treated with amphotericin B for 7 weeks (total dose, 40 mg/kg) followed by 1 year of therapy with itraconazole (100 mg twice daily). Complete cure was achieved during the follow-up period of 10 months. C1 NIAID,CLIN INVEST LAB,BLDG 10,ROOM 11N104,BETHESDA,MD 20892. NIAID,HOST DEF LAB,BETHESDA,MD 20892. RI Lambrecht, Bart/M-4734-2015 NR 39 TC 63 Z9 65 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAY PY 1992 VL 14 IS 5 BP 1023 EP 1026 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA HQ569 UT WOS:A1992HQ56900005 PM 1318085 ER PT J AU BLUM, MS FOOTTIT, R FALES, HM AF BLUM, MS FOOTTIT, R FALES, HM TI DEFENSIVE CHEMISTRY AND FUNCTION OF THE ANAL EXUDATE OF THE THRIPS HAPLOTHRIPS-LEUCANTHEMI SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-PHARMACOLOGY TOXICOLOGY & ENDOCRINOLOGY LA English DT Article; Proceedings Paper CT 7TH SYMP ON INVERTEBRATE NEUROBIOLOGY CY JUN 23-28, 1991 CL HUNGARIAN ACAD SCI, BALATON LIMNOL RES INST, TIHANY, HUNGARY HO HUNGARIAN ACAD SCI, BALATON LIMNOL RES INST ID ORIENTAL FRUIT MOTHS; SECRETION; PHLAEOTHRIPIDAE; THYSANOPTERA; IDENTIFICATION; PHEROMONE AB 1. The red clover thrips Haplothrips leucanthemi discharges a copious anal exudate when tactually stimulated. 2. This secretion is dominated by the isocoumarin mellein which is the only volatile compound detectable. 3. The anal discharge of each thrips contains about 25 ng of mellein. 4. The defensive role of mellein was demonstrated by its effectiveness in repelling workers of the fire ant Solenopsis invicta. C1 AGR CANADA,RES BRANCH,BIOSYSTEMAT RES CTR,OTTAWA K1A 0C6,ONTARIO,CANADA. NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. RP BLUM, MS (reprint author), UNIV GEORGIA,DEPT ENTOMOL,ATHENS,GA 30602, USA. NR 14 TC 13 Z9 14 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0742-8413 J9 COMP BIOCHEM PHYS C JI Comp. Biochem. Physiol. C-Pharmacol. Toxicol. Endocrinol. PD MAY PY 1992 VL 102 IS 1 BP 209 EP 211 DI 10.1016/0742-8413(92)90066-G PG 3 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Toxicology; Zoology SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Toxicology; Zoology GA JC669 UT WOS:A1992JC66900034 ER PT J AU SNEIDERMAN, CA COOKSON, JP HOOD, AF AF SNEIDERMAN, CA COOKSON, JP HOOD, AF TI USE OF COMPUTER GRAPHIC IMAGES IN TEACHING DERMATOLOGY SO COMPUTERIZED MEDICAL IMAGING AND GRAPHICS LA English DT Article DE DERMATOLOGY EDUCATION; IMAGE PERCEPTION; COLOR GRAPHICS; CRT DISPLAY AB A microcomputer-based system for copying, storing, retrieving, and displaying color still images was assembled from commercially available components. The system was tested against 35-mm color photographic transparencies by measuring the performance of 91 medical students in a task of identifying the primary morphology of eight skin lesion images from the displayed images. There was no significant difference in the students' performance between the two display media. C1 NATL LIB MED,LISTER HILL CTR BIOMED COMMUN,COMMUN ENGN BRANCH,BETHESDA,MD 20894. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21218. RP SNEIDERMAN, CA (reprint author), NATL LIB MED,EDUC TECHNOL BRANCH,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. NR 4 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 0895-6111 J9 COMPUT MED IMAG GRAP JI Comput. Med. Imaging Graph. PD MAY-JUN PY 1992 VL 16 IS 3 BP 151 EP 152 DI 10.1016/0895-6111(92)90069-L PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA HY862 UT WOS:A1992HY86200003 PM 1623490 ER PT J AU GOLDSTEIN, LJ PASTAN, I GOTTESMAN, MM AF GOLDSTEIN, LJ PASTAN, I GOTTESMAN, MM TI MULTIDRUG RESISTANCE IN HUMAN CANCER SO CRITICAL REVIEWS IN ONCOLOGY/HEMATOLOGY LA English DT Review ID P-GLYCOPROTEIN EXPRESSION; BACTERIAL TRANSPORT PROTEINS; INTRINSIC DRUG-RESISTANCE; NON-HODGKINS LYMPHOMA; MDR1 GENE-EXPRESSION; HUMAN-BREAST CANCER; HUMAN-TISSUES; IMMUNOHISTOCHEMICAL LOCALIZATION; POTENTIAL CIRCUMVENTION; DOXORUBICIN RESISTANCE C1 FOX CHASE CANC INST,DEPT MED ONCOL,PHILADELPHIA,PA 19111. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. NCI,CELL BIOL LAB,BETHESDA,MD 20892. NR 75 TC 99 Z9 100 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1040-8428 J9 CRIT REV ONCOL HEMAT JI Crit. Rev. Oncol./Hematol. PD MAY PY 1992 VL 12 IS 3 BP 243 EP 253 DI 10.1016/1040-8428(92)90057-W PG 11 WC Oncology; Hematology SC Oncology; Hematology GA HW437 UT WOS:A1992HW43700004 PM 1353966 ER PT J AU RODRIGUES, MM RAJAGOPALAN, S LEE, L NAIR, CN ADVANI, SH DONOSO, L CHADER, GJ WIGGERT, B AF RODRIGUES, MM RAJAGOPALAN, S LEE, L NAIR, CN ADVANI, SH DONOSO, L CHADER, GJ WIGGERT, B TI RETINOBLASTOMA - MESSENGER-RNA FOR INTERPHOTORECEPTOR RETINOID BINDING-PROTEIN SO CURRENT EYE RESEARCH LA English DT Article ID S-ANTIGEN; IRBP; LOCALIZATION; CELLS; GENE; ROD; IMMUNOHISTOCHEMISTRY; DIFFERENTIATION; IDENTIFICATION; PHOTORECEPTORS AB Surgically excised retinoblastomas from 14 patients (age range nine months to two years) were assessed by immunocytochemistry for the expression of photoreceptor-specific proteins and neuronal and glial cell markers. Adjacent tissues were examined for messenger RNA expression of interphotoreceptor retinoid-binding protein (IRBP) using Northern blots. For immunocytochemical stains (ABC method), monoclonal and polyclonal antibodies included S-Ag, rhodopsin, neuron specific enolase (NSE), glial fibrillary acidic protein (GFAP), IRBP, neural adhesion molecule (N-CAM), and rod and cone specific transducin (T(R-alpha) and T(C-alpha). Histopathology revealed mostly poorly differentiated tumors with necrosis and lack of Flexner-Wintersteiner rosettes. Immunocytochemical staining and S-antigen in two cases. Immunoreactivity with rhodopsin was negative. N-CAM, a neural adhesive protein which appears to be involved in the regulation of adhesive interaction during neuronal differentiation, was positive except in two cases. All tumors showed immunoreactivity with NSE, whereas GFAP staining was limited to the perivascular glial tissue confirming the essential neuronal nature of retinoblastoma cells. T(C-alpha) was detected in all tumors and T(R-alpha) in one case. Messenger RNA for IRBP was detected in tumors in which IRBP immunoreactivity could not be detected. C1 NEI,RETINAL CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. TATA MEM HOSP,BOMBAY,INDIA. WILLS EYE HOSP & RES INST,PHILADELPHIA,PA 19107. RP RODRIGUES, MM (reprint author), UNIV MARYLAND,DEPT OPHTHALMOL,BALTIMORE,MD 21201, USA. NR 45 TC 7 Z9 7 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD MAY PY 1992 VL 11 IS 5 BP 425 EP 433 DI 10.3109/02713689209001796 PG 9 WC Ophthalmology SC Ophthalmology GA HV459 UT WOS:A1992HV45900005 PM 1606838 ER PT J AU DU, XY LINSER, P RUSSELL, P ZIGLER, JS AF DU, XY LINSER, P RUSSELL, P ZIGLER, JS TI CARBONIC ANHYDRASE-III IS EXPRESSED IN BOVINE LENS SO CURRENT EYE RESEARCH LA English DT Article ID PURIFICATION; MUSCLE; GENE AB A highly basic protein isolated from bovine lens has been shown to be carbonic anhydrase III by immunological and peptide sequencing techniques. This is the first demonstration of the presence of this isoenzyme, which is primarily found in skeletal muscle, in the lens or other ocular tissues. The physiological function of this enzyme in the lens is unknown. C1 NEI,MOLEC & DEV BIOL LAB,BETHESDA,MD 20892. RP DU, XY (reprint author), NEI,MECHANISMS OCULAR DIS LAB,BETHESDA,MD 20892, USA. FU NCI NIH HHS [IPA 9-8 CAN 326756] NR 14 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 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD MAY PY 1992 VL 11 IS 5 BP 475 EP 478 DI 10.3109/02713689209001802 PG 4 WC Ophthalmology SC Ophthalmology GA HV459 UT WOS:A1992HV45900011 PM 1606843 ER PT J AU WENDT, SL MCINNES, PM DICKINSON, GL AF WENDT, SL MCINNES, PM DICKINSON, GL TI THE EFFECT OF THERMOCYCLING IN MICROLEAKAGE ANALYSIS SO DENTAL MATERIALS LA English DT Article ID COMPOSITE RESTORATIONS; MARGINAL LEAKAGE; DENTIN; BOND AB The purpose of this study was to evaluate the effect of thermocycling on dye penetration during in vitro microleakage analysis of composites. Fifty non-carious human molars, stored in 75% ethanol, were divided into five groups (N = 10). Each tooth was prepared for a MOD slot preparation using a high speed handpiece and water, one proximal cervical margin in cementum, the other in enamel. The enamel margins were etched, rinsed, dried, and the composite inserted and cured in multiple increments. Group A was not thermocycled (TC) and was immersed in 0.5% basic fuchsin dye for 24 h at 37-degrees +/- 1-degrees-C. Group A' was not TC and was immersed in 0.5% basic fuchsin dye for 4 h at 37-degrees +/- 1-degrees-C. Group B was TC in a water bath and immersed in dye as with Group A, Group B' was TC and immersed in dye as in Group A'. Group C was TC, as in Group B, but in a basic fuchsin dye bath. Thermocycling consisted of 250 cycles, 15 s dwell time each in 5-degrees-C and 50-degrees-C bath. The teeth were mounted in acrylic, and multiple cross-sections of all surfaces were prepared. Dye penetration was read on a scale of 0 (no leakage) to 4 (leakage to the pulpal floor) and means calculated for each surface and tooth. There was no significant increase of microleakage in restorations when thermocycling was used to simulate temperature extremes, either in dye or water baths, as opposed to restorations which were not thermocycled. C1 NIAID,BETHESDA,MD 20892. W VIRGINIA UNIV,SCH DENT,DEPT OPERAT DENT,MORGANTOWN,WV 26506. RP WENDT, SL (reprint author), UNIV CONNECTICUT,CTR HLTH,SCH DENT MED,DEPT RESTORAT DENT & ENDODONTOL,MC-1715,FARMINGTON,CT 06032, USA. NR 27 TC 41 Z9 45 U1 0 U2 0 PU ACAD DENTAL MATERIALS PI DALLAS PA BAYLOR COLLEGE DENTISTRY, 3302 GASTON AVE, DALLAS, TX 75266-0677 SN 0109-5641 J9 DENT MATER JI Dent. Mater. PD MAY PY 1992 VL 8 IS 3 BP 181 EP 184 DI 10.1016/0109-5641(92)90079-R PG 4 WC Dentistry, Oral Surgery & Medicine; Materials Science, Biomaterials SC Dentistry, Oral Surgery & Medicine; Materials Science GA JD541 UT WOS:A1992JD54100009 PM 1521707 ER PT J AU MAHMOOD, R FLANDERS, KC MORRISSKAY, GM AF MAHMOOD, R FLANDERS, KC MORRISSKAY, GM TI INTERACTIONS BETWEEN RETINOIDS AND TGF BETA-S IN MOUSE MORPHOGENESIS SO DEVELOPMENT LA English DT Article DE TGF BETA; RETINOIC ACID; MOUSE EMBRYOGENESIS; IMMUNOCYTOCHEMISTRY ID TRANSFORMING GROWTH-FACTOR; CRANIAL NEURAL CREST; CELL-ADHESION RECEPTORS; DIFFERENTIAL EXPRESSION; INTERSTITIAL MATRIX; EMBRYONIC HEART; MESSENGER-RNA; ADULT TISSUES; RAT EMBRYO; FACTOR-BETA-1 AB Using immunocytochemical methods we describe the distribution of different TGF-beta-isoforms and the effects of excess retinoic acid on their expression during early mouse embryogenesis (8 1/2-1O 1/2 days of development). In normal embryos at 9 days, intracellular TGF-beta-1 is expressed most intensely in neuroepithelium and cardiac myocardium whereas extracellular TGF-beta-1 is expressed in mesenchymal cells and in the endocardium of the heart. At later stages, intracellular TGF-beta-1 becomes very restricted to the myocardium and to a limited number of head mesenchymal cells; extracellular TGF-beta-1 continues to be expressed widely in cells of mesenchymal origin, particularly in head and trunk mesenchyme, and also in endocardium. TGF-beta-2 is widely expressed at all stages investigated while TGF-beta-3 is not expressed strongly in any tissue at the stages examined. Exposure of early neural plate stage embryos to retinoic acid caused reduced expression of TGF-beta-1 and TGF-beta-2 proteins but had no effect on TGF-beta-3. Intracellular TGF-beta-1 expression was reduced in all tissues except in the myocardium, while extracellular TGF-beta-1 was specifically reduced in neuroepithelium and cranial neural crest cells at early stages. TGF-beta-2 was reduced in all embryonic tissues. The down-regulation of intracellular TGF-beta-1 was observed up to 48 hours after initial exposure to retinoic acid while some down-regulation of TGF-beta-2 was still seen up to 60 hours after initial exposure. TGF-beta-s are known to modulate the expression of various extracellular matrix molecules involved in cell growth, differentiation and morphogenesis. The interaction between retinoic acid and TGF-beta is discussed in relation to morphogenesis. C1 NIH,CHEMOPREVENT LAB,BETHESDA,MD 20892. RP MAHMOOD, R (reprint author), DEPT HUMAN ANAT,S PARKS RD,OXFORD OX1 3QX,ENGLAND. NR 65 TC 63 Z9 64 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 MAY PY 1992 VL 115 IS 1 BP 67 EP 74 PG 8 WC Developmental Biology SC Developmental Biology GA HX130 UT WOS:A1992HX13000007 PM 1638993 ER PT J AU BEEBE, SJ LEYTON, L BURKS, D ISHIKAWA, M FUERST, T DEAN, J SALING, P AF BEEBE, SJ LEYTON, L BURKS, D ISHIKAWA, M FUERST, T DEAN, J SALING, P TI RECOMBINANT MOUSE ZP3 INHIBITS SPERM BINDING AND INDUCES THE ACROSOME REACTION SO DEVELOPMENTAL BIOLOGY LA English DT Article ID ZONA PELLUCIDA GLYCOPROTEIN; O-LINKED OLIGOSACCHARIDES; RECEPTOR ACTIVITY; EXPRESSION VECTOR; PROTEINS; GENE; CHLORTETRACYCLINE; IDENTIFICATION; FERTILIZATION; BIOSYNTHESIS C1 EASTERN VIRGINIA MED SCH,JONES INST REPROD MED,DEPT OBSTET & GYNECOL,NORFOLK,VA 23410. MEDIMMUNE INC,GAITHERSBURG,MD 20878. NIDDK,CELLULAR & DEV BIOL LAB,BETHESDA,MD 20892. DUKE UNIV,MED CTR,DEPT OBSTET GYNECOL,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT CELL BIOL,DURHAM,NC 27710. EASTERN VIRGINIA MED SCH,CHILDRENS HOSP KINGS DAUGHTERS,DEPT PHYSIOL,PEDIAT RES CTR,NORFOLK,VA 23510. RP BEEBE, SJ (reprint author), EASTERN VIRGINIA MED SCH,CHILDRENS HOSP KINGS DAUGHTERS,DEPT PEDIAT,PEDIAT RES CTR,NORFOLK,VA 23510, USA. FU NICHD NIH HHS [HD18201] NR 31 TC 71 Z9 76 U1 0 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD MAY PY 1992 VL 151 IS 1 BP 48 EP 54 DI 10.1016/0012-1606(92)90212-Y PG 7 WC Developmental Biology SC Developmental Biology GA HT364 UT WOS:A1992HT36400006 PM 1577197 ER PT J AU PARIA, BC JONES, KL FLANDERS, KC DEY, SK AF PARIA, BC JONES, KL FLANDERS, KC DEY, SK TI LOCALIZATION AND BINDING OF TRANSFORMING GROWTH-FACTOR-BETA ISOFORMS IN MOUSE PREIMPLANTATION EMBRYOS AND IN DELAYED AND ACTIVATED BLASTOCYSTS SO DEVELOPMENTAL BIOLOGY LA English DT Article ID CELL-ADHESION RECEPTORS; TGF-BETA; MESSENGER-RNA; DEVELOPMENTAL EXPRESSION; MAMMALIAN DEVELOPMENT; BIOLOGICAL-ACTIVITIES; COMPLEMENTARY-DNA; GENE FAMILY; IDENTIFICATION; FACTOR-BETA-2 C1 UNIV KANSAS, MED CTR, RALPH L SMITH RES CTR, DEPT OBSTET GYNECOL, KANSAS CITY, KS 66103 USA. UNIV KANSAS, MED CTR, RALPH L SMITH RES CTR, DEPT PHYSIOL, KANSAS CITY, KS 66103 USA. NCI, CHEMOPREVENT LAB, BETHESDA, MD 20892 USA. FU NICHD NIH HHS [HD 12304] NR 74 TC 89 Z9 90 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD MAY PY 1992 VL 151 IS 1 BP 91 EP 104 DI 10.1016/0012-1606(92)90216-4 PG 14 WC Developmental Biology SC Developmental Biology GA HT364 UT WOS:A1992HT36400010 PM 1577201 ER PT J AU BUONO, RJ LINSER, PJ CUTHBERTSON, RA PIATIGORSKY, J AF BUONO, RJ LINSER, PJ CUTHBERTSON, RA PIATIGORSKY, J TI MOLECULAR ANALYSES OF CARBONIC ANHYDRASE-II EXPRESSION AND REGULATION IN THE DEVELOPING CHICKEN LENS SO DEVELOPMENTAL DYNAMICS LA English DT Article DE LENS; CHICK DEVELOPMENT; GENE REGULATION; PROMOTER ANALYSIS ID A-CRYSTALLIN GENE; DELTA-CRYSTALLIN; DELTA-1-CRYSTALLIN GENE; GLUTAMINE-SYNTHETASE; EXTRACELLULAR PH; FROG RETINA; PROMOTER; CELLS; MOUSE; CDNA AB The expression of carbonic anhydrase-II (CA-II) in the developing chicken lens was examined and compared with that in the retina of the chicken embryo. CA-II expression was measured by immunohistochemistry and radioimmunoassay during development, and CA-II mRNA was quantified by Northern blot and densitometric scanning and localized by in situ hybridization. A functional promoter of the chicken CA-II gene was identified by transfection of primary embryonic chicken lens epithelial cells and analyzed in deletion mutants. The results establish that CA-II makes up about 0.1% of the total soluble protein of the embryonic chicken lens, an amount insufficient to make it a candidate for an enzyme crystallin in this species. Lens fiber differentiation coincided with a loss of CA-II mRNA and protein; by contrast, CA-II persisted in the epithelial cells of the embryonic and mature lens. This and previous studies showed that CA-II amounts to as much as 3% of the protein of the embryonic chicken retina and follows a different developmental time course of expression; like the lens, CA-II decreases until day 10 in the embryonic retina, but, unlike the lens, it increases thereafter and plateaus at hatching. Progressive deletions of the 5' flanking regions (from position -1314 to +32) of the CA-II gene fused to the bacterial chloramphenicol acetyltransferase (CAT) reporter gene resulted in a gradual loss of promoter activity, consistent with an additive effect of putative cis-regulatory elements found in many crystallin genes. These experiments provide the foundation for a molecular analysis of the developmental and differential regulation of the CA-II gene in lens and retina. C1 NEI,MOLEC & DEV BIOL LAB,BLDG 6,ROOM 201,BETHESDA,MD 20892. UNIV FLORIDA,DEPT ANAT & CELL BIOL,WHITNEY LAB,ST AUGUSTINE,FL 32086. FU NCI NIH HHS [IPA9-8-CAN 326756] NR 44 TC 5 Z9 5 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD MAY PY 1992 VL 194 IS 1 BP 33 EP 42 PG 10 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA JN152 UT WOS:A1992JN15200004 PM 1421518 ER PT J AU DARRIBERE, T KOTELIANSKY, VE CHERNOUSOV, MA AKIYAMA, SK YAMADA, KM THIERY, JP BOUCAUT, JC AF DARRIBERE, T KOTELIANSKY, VE CHERNOUSOV, MA AKIYAMA, SK YAMADA, KM THIERY, JP BOUCAUT, JC TI DISTINCT REGIONS OF HUMAN FIBRONECTIN ARE ESSENTIAL FOR FIBRIL ASSEMBLY IN AN INVIVO DEVELOPING SYSTEM SO DEVELOPMENTAL DYNAMICS LA English DT Article DE FIBRONECTIN; ASSEMBLY; AMPHIBIAN ID CELL-BINDING DOMAIN; AMPHIBIAN EMBRYOS; MONOCLONAL-ANTIBODY; MATRIX; GASTRULATION AB In early vertebrate development, the proper assembly of fibronectin into fibrils is crucial for embryonic cells to adhere and to migrate on the extracellular matrix. The molecular mechanisms by which such a process occurs in vivo are poorly understood. In the amphibian embryo Pleurodeles waltl fibronectin fibrils appear first at the blastula stage. They form a fibrillar matrix on the basal surface of animal cells facing the blastocoel. Using competition and perturbation experiments with purified proteolytic fragments and domain-specific monoclonal antibodies, we demonstrate that at least three fibronectin sites are essential for assembly of fibronectin fibrils in the blastula of Pleurodeles waltl. Two sites, the RGDS sequence and the synergistic domain in the 10th type III repeat, are both involved in receptor recognition. A third site that spans the 9th type I and lst type III homology sequences is also likely to participate in fibronectin-fibronectin interactions. C1 CNRS,PHYSIOPATHOL DEV LAB,URA 1337,F-75230 PARIS 05,FRANCE. ACAD MED SCI,CARDIOL RES CTR,INST EXPTL CARDIOL,121552 MOSCOW,USSR. NIDR,DEV BIOL LAB,BETHESDA,MD 20892. RP DARRIBERE, T (reprint author), UNIV PARIS 06,BIOL EXPTL LAB,CNRS,URA 1135,9 QUAI ST BERNARD,F-75230 PARIS 05,FRANCE. OI Yamada, Kenneth/0000-0003-1512-6805 NR 23 TC 35 Z9 36 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD MAY PY 1992 VL 194 IS 1 BP 63 EP 70 PG 8 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA JN152 UT WOS:A1992JN15200007 PM 1421520 ER PT J AU KOCHANSKA, G AF KOCHANSKA, G TI CHILDRENS INTERPERSONAL INFLUENCE WITH MOTHERS AND PEERS SO DEVELOPMENTAL PSYCHOLOGY LA English DT Article ID COMPETENCE; BEHAVIOR; NONCOMPLIANCE; CHILDHOOD; PATTERNS AB Interpersonal influence attempts toward mothers and peers were examined in 75 five-year-olds. Consistent with a Piagetian view, children were less often immediately successful in their mother-directed attempts than in their peer-directed attempts. However, they were more often able to negotiate a compromise with mothers than with peers. This indicates that interaction with mothers may be more conducive to the development of social competence than interaction with peers. Linkages between both contexts were identified. Children who used abrasive strategies with mothers were aggressive and unsuccessful with peers. Mothers' influence strategies, assessed when children were toddlers and at age 5, predicted children's influence styles with peers: Children whose mothers often used negative control were aggressive and unsuccessful; those whose mothers used polite guidance were rarely inarticulate or coercive; and those whose mothers often issued unclear commands were less successful and less prosocial with their peers. C1 NIMH,BETHESDA,MD 20892. RP KOCHANSKA, G (reprint author), UNIV IOWA,DEPT PSYCHOL,IOWA CITY,IA 52242, USA. NR 37 TC 17 Z9 19 U1 1 U2 3 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0012-1649 J9 DEV PSYCHOL JI Dev. Psychol. PD MAY PY 1992 VL 28 IS 3 BP 491 EP 499 DI 10.1037//0012-1649.28.3.491 PG 9 WC Psychology, Developmental SC Psychology GA HT003 UT WOS:A1992HT00300015 ER PT J AU BROWN, ZA MILLS, JL METZGER, BE KNOPP, RH SIMPSON, JL JOVANOVICPETERSON, L SCHEER, K VANALLEN, MI AARONS, JH REED, GF AF BROWN, ZA MILLS, JL METZGER, BE KNOPP, RH SIMPSON, JL JOVANOVICPETERSON, L SCHEER, K VANALLEN, MI AARONS, JH REED, GF TI EARLY SONOGRAPHIC EVALUATION FOR FETAL GROWTH DELAY AND CONGENITAL-MALFORMATIONS IN PREGNANCIES COMPLICATED BY INSULIN-REQUIRING DIABETES SO DIABETES CARE LA English DT Article ID MATERNAL HEMOGLOBIN-A1C; SPONTANEOUS-ABORTION; EARLY ORGANOGENESIS; EARLY EMBRYOGENESIS; MOUSE EMBRYOS; RAT; INFANTS; MOTHERS; TERATOGENESIS; HYPERGLYCEMIA AB OBJECTIVE - It has been reported that early fetal growth retardation may be a useful marker for congenital malformations in diabetic pregnancies. To test this hypothesis, diabetic and nondiabetic women were sonographically evaluated during the first trimester. RESEARCH DESIGN AND METHODS - Fetal crown-rump lengths were measured sonographically at least once during the first 15 wk of pregnancy in 329 nondiabetic and 312 diabetic women. Of these, 289 nondiabetic and 269 diabetic women had sonograms before 10 wk of gestation and 283 nondiabetic and 269 diabetic women had sonograms between 10 and 15 wk of gestation. Early fetal growth delay was defined as a sonographic gestational age of greater-than-or-equal-to 6 days less than menstrual gestational age. RESULTS - The mean crown-rump lengths at 8 wk were 17.9 +/- 4.6 mm in the diabetic and 18.7 +/- 4.9 mm in the nondiabetic groups (P = 0.13). At 12 wk, the mean fetal crown-rump length was 58.5 +/- 8.8 mm for diabetic subjects and 60.6 +/- 8.7 mm for nondiabetic subjects (P = 0.04). Between 5 and 9 wk, 28 of 289 (9.7%) fetuses of nondiabetic subjects, 34 of 259 (13.1%) normal fetuses of diabetic subjects, and 2 of 10 (20%) malformed fetuses of diabetic subjects demonstrated growth delay (P = 0.31, normal vs. malformed diabetic). Between 10 and 15 wk of gestation, 28 of 283 (9.9%) fetuses of nondiabetic subjects, 32 of 256 (12.5%) normal fetuses of diabetic subjects, and 4 of 13 (30.8%) malformed fetuses of diabetic subjects demonstrated growth delay (P = 0.06, normal vs. malformed diabetic). Early fetal growth delay did not predict a reduced birth weight at term. CONCLUSIONS - Among insulin-dependent diabetic subjects who were moderately well controlled at conception, statistically significant but mild early fetal growth delay was present but did not appear to be useful clinically in predicting congenital malformations. Recommendations that growth delay demonstrated on early ultrasound be used as a predictor of congenital malformation require careful reexamination. C1 CORNELL UNIV,ITHACA,NY 14853. HARVARD UNIV,CAMBRIDGE,MA 02138. UNIV PITTSBURGH,PITTSBURGH,PA 15260. NORTHWESTERN UNIV,EVANSTON,IL 60201. NICHHD,EPIDEMIOL BRANCH,BETHESDA,MD 20892. RP BROWN, ZA (reprint author), UNIV WASHINGTON,RH-20,SEATTLE,WA 98195, USA. NR 30 TC 31 Z9 31 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAY PY 1992 VL 15 IS 5 BP 613 EP 619 DI 10.2337/diacare.15.5.613 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HR039 UT WOS:A1992HR03900002 PM 1516479 ER PT J AU TSIGOS, C WHITE, A YOUNG, RJ AF TSIGOS, C WHITE, A YOUNG, RJ TI DISCRIMINATION BETWEEN PAINFUL AND PAINLESS DIABETIC NEUROPATHY BASED ON TESTING OF LARGE SOMATIC NERVE AND SYMPATHETIC-NERVE FUNCTION SO DIABETIC MEDICINE LA English DT Article DE DIABETES; NEUROPATHY; PAIN; FOOT ULCERATION; SYMPATHETIC NERVOUS SYSTEM AB The syndromes of painful diabetic neuropathy and painless foot ulceration are distinct clinical entities. To investigate whether there is a pattern of nerve fibre involvement that could clearly discriminate between them, we have studied three groups of diabetic patients, 19 with painful neuropathy, 14 with painless foot ulceration, and 19 with no clinical neuropathy. Large somatic nerve fibre function was assessed by nerve conduction studies and vibration thresholds, small somatic nerve function by cooling and warming thresholds, the parasympathetic system by heart-rate dependent cardiac autonomic reflexes, and the sympathetic system by postural drop in blood pressure and plasma noradrenaline (supine and erect). Normal ranges were obtained from 25 age-matched healthy subjects. Painful neuropathy was characterized by uniform dysfunction of small somatic fibres and preserved sympathetic nerve activity (plasma noradrenaline) with a wide range of large somatic fibre and autonomic reflex abnormalities. By contrast, in painless foot ulceration there was universal severe dysfunction of all nerve fibre populations. Discriminant analysis identified peroneal motor conduction velocity as the best single variable for distinguishing between painful and painless neuropathy (81 % of cases). A combination of peroneal motor conduction velocity with vibration threshold and plasma noradrenaline discriminated completely between the two clinical syndromes. These findings suggest that the key differences between painful and painless diabetic neuropathy are in large somatic and sympathetic fibre function. RP TSIGOS, C (reprint author), NIH,DEV ENDOCRINOL BRANCH,BLDG 10,ROOM 10N262,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI White, Anne/C-3753-2011; OI White, Anne/0000-0002-7686-2884 NR 0 TC 21 Z9 22 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PD MAY PY 1992 VL 9 IS 4 BP 359 EP 365 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HT218 UT WOS:A1992HT21800009 PM 1600708 ER PT J AU STEIN, DS LIBERTIN, CR AF STEIN, DS LIBERTIN, CR TI GENETIC-HETEROGENEITY AMONG NUTRITIONALLY DEFICIENT STREPTOCOCCI SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article ID VARIANT STREPTOCOCCI; VIRIDANS STREPTOCOCCI; ENDOCARDITIS; HYBRIDIZATION; CHROMOPHORE; STRAINS; TESTS AB The nutritionally deficient (variant) streptococci (NDS) share the auxotrophic characteristic of requiring pyridoxal or thiol group supplementation for growth. The deoxyribonucleic acid relatedness of these organisms among themselves is unknown. Improved speciation of NDS would lead to a better knowledge of their pathogenesis and possible insight into improved clinical management. Therefore, DNA-DNA hybridization and biotyping of 23 nutritionally deficient streptococci were performed. Biochemical testing using the API Rapid Strept Identification method revealed that the organisms in this study were characterized among three broad biotype groups. Only one strain was nontypeable. DNA-DNA hybridization among the nutritionally deficient streptococci that we compared revealed genetic heterogeneity. Only four (17%) of 23 isolates were highly homologous; all were of biotypes 2 and 3. Reference viridans streptococcal strains had minimal homology to the NDS strains, The data indicate that the NDS are genetically heterogeneous. C1 LOYOLA UNIV,DEPT MED,2160 S 1ST AVE,MAYWOOD,IL 60153. NIAID,MED BRANCH,DIV AIDS,ROCKVILLE,MD. LOYOLA UNIV,DEPT PATHOL,MAYWOOD,IL 60153. NR 22 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0732-8893 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD MAY-JUN PY 1992 VL 15 IS 4 BP 281 EP 285 DI 10.1016/0732-8893(92)90011-H PG 5 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA HW925 UT WOS:A1992HW92500002 PM 1611842 ER PT J AU ARMBRUSTER, L CAVARD, C BRIAND, P BERTOLOTTI, R AF ARMBRUSTER, L CAVARD, C BRIAND, P BERTOLOTTI, R TI SELECTION OF VARIANT HEPATOMA-CELLS IN LIVER-SPECIFIC GROWTH MEDIA - REGULATION AT THE MESSENGER-RNA LEVEL SO DIFFERENTIATION LA English DT Article ID EPSTEIN-BARR VIRUS; MAMMALIAN-CELLS; RAT HEPATOMA; GLUCONEOGENIC ENZYMES; ARGININE SYNTHESIS; MOLECULAR-CLONING; ORNITHINE; EXPRESSION; PROTEINS; CDNA AB Three liver-specific growth media, respectively free of arginine (Arg-), tyrosine (Tyr-) and glucose (G-), have been used to characterize cells of the rat H4IIEC3, human HepG2 and mouse BW hepatoma lines. Cells of clone FaO, a derivative of tine H4IIEC3, freely grew in Tyr- and G- media, and gave rise to stable variants in Arg- conditions. Cells ot' tine HepG2 and clone BWTG3, a derivative of line BW, degenerated in all three media. Arg and tyr variants were however derived from HepG2 cells; their genesis appeared to be pathway specific, illustrating the complexity of the regulatory loops that are implicated in the control of the differentiated state. No variant was ever obtained with BWTG3 cells, demonstrating the stability of their deficiency in the post-natal hepatic functions that are involved in Arg-, Tyr- and G- selections. Variant clones of HepG2 and FaO cells that have been isolated in Arg-medium were characterized in details for liver-specific urea-cycle enzyme activities and mRNA. These variants were shown to be controlled at the mRNA level, most likely at transcription. Isolation of stable FaO and HepG2 variant clones as well as the converse demonstration of the stable deficiency of BWTG3 cells in postnatal hepatic functions were aimed at expression cloning. Our results are thus discussed in terms of transfection with full-length cDNA expression libraries and cloning of regulatory genes that could activate or extinguish liver specific genes. C1 NIMH,CELL BIOL LAB,BETHESDA,MD 20892. INST COCHIN GENET MOLEC GENET & PATHOL EXPTL,INSERM,F-75014 PARIS,FRANCE. NR 53 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0301-4681 J9 DIFFERENTIATION JI Differentiation PD MAY PY 1992 VL 50 IS 1 BP 25 EP 33 DI 10.1111/j.1432-0436.1992.tb00482.x PG 9 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA HZ648 UT WOS:A1992HZ64800003 PM 1322334 ER PT J AU PUGA, A NEBERT, DW CARRIER, F AF PUGA, A NEBERT, DW CARRIER, F TI DIOXIN INDUCES EXPRESSION OF C-FOS AND C-JUN PROTOONCOGENES AND A LARGE INCREASE IN TRANSCRIPTION FACTOR AP-1 SO DNA AND CELL BIOLOGY LA English DT Review ID HEPATIC PLASMA-MEMBRANE; SERUM-RESPONSE ELEMENT; HALOGENATED AROMATIC-HYDROCARBONS; EPIDERMAL GROWTH-FACTOR; CYTOCHROME P-450C GENE; AH RECEPTOR COMPLEX; HA-RAS GENE; KINASE-C; DNA INTERACTIONS; GUINEA-PIG AB Among environmental pollutants, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dioxin) is one of the most potent tumor promoters and teratogens known. The molecular mechanisms responsible for the biological activity of TCDD, however, remain largely unknown. In this report, we show that the first observable effects of TCDD in cultured murine hepatoma cells are a rapid, transient increase in Ca2+ influx and a minor but significant elevation of activated, membrane-bound protein kinase C. These changes are then followed by induction of the immediate early proto-oncogenes c-fos, jun-B, c-jun, and jun-D, and by large increases in AP-1 transcription factor activity. Induction of these changes by TCDD is delayed compared with that by phorbol esters, although the magnitude of the effects caused by both treatments is similar, and both induction processes can be blocked by staurosporine, a protein kinase C inhibitor. In cultured cells, proto-oncogene induction by TCDD appears to be independent of the presence of a functional aryl hydrocarbon (Ah) receptor or nuclear translocation protein. These results reveal early events that may lead to the elucidation of the molecular basis of TCDD-induced tumor promotion. C1 NICHHD,DEV PHARMACOL LAB,BETHESDA,MD 20892. RI Puga, Alvaro/B-7676-2008; Carrier, France/C-3063-2008 NR 111 TC 183 Z9 186 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD MAY PY 1992 VL 11 IS 4 BP 269 EP 281 DI 10.1089/dna.1992.11.269 PG 13 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA JG735 UT WOS:A1992JG73500001 PM 1605850 ER PT J AU KRAFT, HG DEMOSKY, SJ SCHUMACHER, K BREWER, HB HOEG, JM AF KRAFT, HG DEMOSKY, SJ SCHUMACHER, K BREWER, HB HOEG, JM TI REGULATION OF LDL RECEPTOR, APO-B, AND APOE PROTEIN AND MESSENGER-RNA IN HEP G2 CELLS SO DNA AND CELL BIOLOGY LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA; CULTURED HUMAN HEPATOCYTES; MESSENGER-RNA LEVELS; BILE-ACID SYNTHESIS; APOLIPOPROTEIN-B; CHOLESTEROL-METABOLISM; LIVER-TRANSPLANTATION; PLASMA-CHOLESTEROL; LINE HEP-G2 AB The regulation of low-density lipoprotein (LDL) receptor activity, protein synthesis, and cellular mRNA content was evaluated in the human hepatoma cell line Hep (.2. Incubation of the cells with LDL led to a complete downregulation of LDL receptor mRNA and LDL receptor protein synthesis. This LDL regulation of the LDL receptor and its mRNA was both time- and concentration-dependent. In contrast to protein synthesis and cellular mRNA concentrations of the LDL receptor, which were reduced to undetectable levels by prolonged incubation in the presence of LDL, LDL receptor activity was reduced to only 44% of preincubation levels. These findings support the presence of a second metabolic pathway for LDL uptake in human hepatocytic cells. The effect of LDL on cellular LDL receptor expression was specific for LDL because incubation in the presence of HDL did not affect any of these study end points. The potential coordinate regulation of the expression of the LDL receptor with its principal ligands, apolipoproteins (apo) B and E, was also investigated. In contrast to the LDL receptor mRNA downregulation with LDL incubation, cellular apoB and apoE mRNA concentrations were not affected by either LDL or HDL. Secretion of apoB, however, was significantly increased by incubating Hep G2 cells, with LDL. These findings indicate that, in contrast to LDL receptor which is regulated at the mRNA level, the ligands for the LDL receptor are regulated either co- or post-translationally. C1 NHLBI,MOLEC DIS BRANCH,BETHESDA,MD 20892. NR 55 TC 10 Z9 10 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD MAY PY 1992 VL 11 IS 4 BP 291 EP 300 DI 10.1089/dna.1992.11.291 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA JG735 UT WOS:A1992JG73500003 PM 1605852 ER PT J AU REILLY, JA HALLETT, M COHEN, LG TARKKA, IM DANG, NY AF REILLY, JA HALLETT, M COHEN, LG TARKKA, IM DANG, NY TI THE N30 COMPONENT OF SOMATOSENSORY EVOKED-POTENTIALS IN PATIENTS WITH DYSTONIA SO ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY LA English DT Article DE SOMATOSENSORY EVOKED POTENTIALS; DYSTONIA; BASAL GANGLIA; BRAIN MAPPING; MEDIAN NERVE; SUPPLEMENTARY MOTOR AREA ID RECIPROCAL INHIBITION; SYMPTOMATIC HEMIDYSTONIA; FINGER STIMULATION; NEURAL MECHANISMS; PARIETAL; AREAS; 2-DEOXYGLUCOSE; RESPONSES; LESIONS; REFLEX AB We recorded short-latency median nerve somatosensory evoked potentials (SEPs) in 10 patients with dystonia (6 with focal dystonia, 3 with generalized dystonia, and 1 with segmental dystonia) and compared them with those of 10 normal controls. The EEG was recorded from 29 sites on the scalp with linked earlobe electrodes for reference. Latencies and amplitudes of P15, postcentral N20 and P45, and frontal N30 were evaluated. The latencies of all potentials were the same in patients and controls. The amplitudes of P15, N20 and P45 were also the same in both groups. but the N30 amplitude of the patients was larger than that of the controls. The amplitude of N30 did not vary from the affected side to the unaffected side. Previous work has shown decreased N30 amplitude in patients with Parkinson's disease. Changes in N30 amplitude may be indicative of abnormal excitatory effects on cortex resulting from disorders of the basal ganglia. C1 NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,BLDG 10,ROOM 5N226,BETHESDA,MD 20892. NR 22 TC 101 Z9 102 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0013-4694 J9 ELECTROEN CLIN NEURO JI Electroencephalogr. Clin. Neurophysiol. PD MAY-JUN PY 1992 VL 84 IS 3 BP 243 EP 247 PG 5 WC Engineering, Biomedical; Clinical Neurology SC Engineering; Neurosciences & Neurology GA HY970 UT WOS:A1992HY97000005 PM 1375883 ER PT J AU TIETZ, D CHRAMBACH, A AF TIETZ, D CHRAMBACH, A TI CONCAVE FERGUSON PLOTS OF DNA FRAGMENTS AND CONVEX FERGUSON PLOTS OF BACTERIOPHAGES - EVALUATION OF MOLECULAR AND FIBER PROPERTIES, USING DESK-TOP COMPUTERS SO ELECTROPHORESIS LA English DT Article ID AGAROSE-GEL ELECTROPHORESIS; SUBCELLULAR PARTICLES; SIZE STANDARDS; FREE MOBILITY; POLYACRYLAMIDE; DEPENDENCE; FIELDS AB A desktop computer program evaluating physical properties of DNA and bacteriophages is presented. The analysis is based on data obtained from capillary and submarine-type agarose electrophoresis. Native molecular/particle properties and properties of the gel (or polymer) medium can be derived from electrophoresis at several gel concentrations. This is done conveniently by a computerized evaluation of the semi-logarithmic plot of mobility vs. gel concentration, designated the Ferguson plot. In application to most proteins, this plot is linear and computer programs exist to evaluate it. However, nonlinear Ferguson plots have assumed great importance in view of the fact that the plots are concave for DNA. Similarly, convex plots are important since they prevail in the electrophoresis of large particles in agarose. The computer program reported here is the first to (i) address concave Ferguson plots and (ii) allow for the evaluation of both cases using a desktop computer. Program ELPHOFIT version 2.0, a Macintosh application, is available upon request. RP TIETZ, D (reprint author), NICHHD,THEORET & PHYS BIOL LAB,MACROMOLEC ANAL SECT,BLDG 10,RM 6C-101,BETHESDA,MD 20892, USA. NR 44 TC 43 Z9 43 U1 1 U2 5 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD MAY PY 1992 VL 13 IS 5 BP 286 EP 294 DI 10.1002/elps.1150130160 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA JA251 UT WOS:A1992JA25100005 PM 1396523 ER PT J AU WIRTH, PJ LUO, LD FUJIMOTO, Y BISGAARD, HC AF WIRTH, PJ LUO, LD FUJIMOTO, Y BISGAARD, HC TI 2-DIMENSIONAL ELECTROPHORETIC ANALYSIS OF TRANSFORMATION-SENSITIVE POLYPEPTIDES DURING CHEMICALLY, SPONTANEOUSLY, AND ONCOGENE-INDUCED TRANSFORMATION OF RAT-LIVER EPITHELIAL-CELLS SO ELECTROPHORESIS LA English DT Article ID CULTURED-CELLS; OVAL CELLS; V-RAF; NEOPLASTIC TRANSFORMATION; SEQUENTIAL-ANALYSIS; TUMOR PROGRESSION; HUMAN-FIBROBLASTS; COMPUTER-ANALYSIS; TROPOMYOSIN; EXPRESSION AB Recently, we described the establishment of a computerized database of rat liver epithelial (RLE) cellular polypeptides (Wirth et al., Electrophoresis, 1991,12,931-954). This database has now been expanded to include the analysis of cellular polypeptide alterations during chemically (aflatoxin B1; AFB), spontaneously, and oncogene (v-Ha-ras, v-raf, and v-myc/v-raf)-induced transformation of RLE cells. Two-dimensional mapping of [S-35]methionine-labeled whole cell lysate, cell-free in vitro translation products and [P-32]orthophosphate-labeled polypeptides revealed subsets of polypeptides specific for each transformation modality. A search of the RLE protein database indicated the specific subcellular location for the majority of these transformation-sensitive proteins. Significant alterations in the expression of the extracellular matrix protein, fibronectin, as well as tropomyosin- and intermediate filament-related polypeptides (vimentin, beta-tubulin, the cytokeratins, and actin) were observed among the various transformant cell lines. Immunoprecipitation and Western immunoblot analysis of tropomyosin expression in four individual AFB-, as well as four spontaneously induced, and each of the oncogene-transformed cell lines indicated that five major tropomyosin (Tm 1-5) isoforms were variably expressed in the various cell lines, including one polypeptide tentatively identified as Tm6. Whereas alterations in tropomyosin expression appeared to be transformation-specific, alterations in the individual intermediate filament polypeptides were related more to the differentiation state of the individual cell lines rather than to the transformation phenotype. These studies extend our earlier efforts toward the establishment of a comprehensive computerized database of RLE cellular proteins and demonstrates how such a database may serve as a useful source for studies concerning the regulation of growth and differentiation as well as transformation of RLE cells. RP WIRTH, PJ (reprint author), NCI,EXPTL CARCINOGENESIS LAB,BLDG 37,ROOM 3C28,BETHESDA,MD 20892, USA. NR 67 TC 23 Z9 23 U1 0 U2 1 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD MAY PY 1992 VL 13 IS 5 BP 305 EP 320 DI 10.1002/elps.1150130163 PG 16 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA JA251 UT WOS:A1992JA25100008 PM 1396525 ER PT J AU STOJILKOVIC, SS CATT, KJ AF STOJILKOVIC, SS CATT, KJ TI CALCIUM OSCILLATIONS IN ANTERIOR-PITUITARY-CELLS SO ENDOCRINE REVIEWS LA English DT Review ID THYROTROPIN-RELEASING-HORMONE; PROTEIN-KINASE-C; CYTOSOLIC FREE CALCIUM; DEPENDENT POTASSIUM CURRENTS; FREE CA-2+ CONCENTRATIONS; RAT LACTOTROPH CELLS; SENSITIVE G-PROTEIN; INOSITOL TRISPHOSPHATE; GONADOTROPIN-SECRETION; INTRACELLULAR CALCIUM RP STOJILKOVIC, SS (reprint author), NICHHD,ENDOCRINOL & REPROD RES BRANCH,BLDG 10,ROOM B1-L 400,BETHESDA,MD 20892, USA. NR 187 TC 163 Z9 163 U1 1 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD MAY PY 1992 VL 13 IS 2 BP 256 EP 280 DI 10.1210/er.13.2.256 PG 25 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HV906 UT WOS:A1992HV90600009 PM 1319898 ER PT J AU SAAVEDRA, JM AF SAAVEDRA, JM TI BRAIN AND PITUITARY ANGIOTENSIN SO ENDOCRINE REVIEWS LA English DT Review ID II-BINDING-SITES; SPONTANEOUSLY HYPERTENSIVE RATS; ATRIAL-NATRIURETIC-PEPTIDE; ANTEROVENTRAL 3RD VENTRICLE; CENTRAL NERVOUS-SYSTEM; CORTICOTROPIN-RELEASING-FACTOR; CONVERTING ENZYME-ACTIVITY; NUCLEUS TRACTUS SOLITARIUS; PLASMA-RENIN ACTIVITY; QUANTITATIVE AUTORADIOGRAPHIC DETERMINATION RP SAAVEDRA, JM (reprint author), NIMH,CLIN SCI LAB,PHARMACOL SECT,9000 ROCKVILLE PIKE,BLDG 10,ROOM 2D-45,BETHESDA,MD 20892, USA. NR 761 TC 400 Z9 408 U1 0 U2 0 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD MAY PY 1992 VL 13 IS 2 BP 329 EP 380 DI 10.1210/er.13.2.329 PG 52 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HV906 UT WOS:A1992HV90600013 PM 1618166 ER PT J AU AGUI, T YAMADA, T LEGROS, G NAKAJIMA, T CLARK, M PESCHEL, C MATSUMOTO, K AF AGUI, T YAMADA, T LEGROS, G NAKAJIMA, T CLARK, M PESCHEL, C MATSUMOTO, K TI EXPRESSION OF RECEPTORS FOR ATRIAL-NATRIURETIC-PEPTIDE ON THE MURINE BONE MARROW-DERIVED STROMAL CELLS SO ENDOCRINOLOGY LA English DT Article ID COLONY-STIMULATING ACTIVITY; GUANYLATE-CYCLASE; BINDING-SITES; AUTORADIOGRAPHIC LOCALIZATION; ENDOTHELIAL-CELLS; ADENYLATE-CYCLASE; CULTURE; INVITRO; CDNA; GRANULOPOIESIS AB Atrial natriuretic peptide (ANP) receptors were identified on both murine bone marrow-derived stromal cell lines A-3 and ALC and primary cultured cells using [I-125]ANP binding assays and Northern blot analyses. The binding of [I-125] ANP to the stromal cells was rapid, saturable, and of high affinity. The dissociation constants between ANP and its receptors on these cells showed no difference among cell types, while maximal binding capacity values were different among cell types. Competitive inhibition of [I-125]ANP binding with C-atrial natriuretic factor, specific for ANP clearance receptor (ANPR-C), revealed that most of [I-125]ANP-binding sites corresponded to ANPR-C. Northern blotting data corroborated that bone marrow-derived stromal cells expressed ANPR-C. However, in ALC cells, ANP biological receptors (either ANPR-A or ANPR-B), the mol wt of which is approximately 130K, were detected, and cGMP was accumulated after stimulation with ANP. On the other hand, in another stromal cell clone, A-3 cells, the expression of biological receptor was not detected in the affinity cross-linking and competitive inhibition experiments using [I-125]ANP. However, A-3 cells accumulated cGMP by responding to ANPR-B-specific ligand, C-type natriuretic peptide. These results suggest that ALC cells equally express ANPR-A and ANPR-B, while A-3 cells express ANPR-B dominantly. Although the physiological roles of these receptors in the bone marrow is still not resolved, ANP is expected to play a role in the regulation of stromal cell functions in bone marrow. C1 UNIV HOSP MAINZ,DEPT HEMATOL,W-6500 MAINZ,GERMANY. NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. CIBA GEIGY AG,RES LABS,CH-4002 BASEL,SWITZERLAND. RP AGUI, T (reprint author), UNIV TOKUSHIMA,SCH MED,INST ANIM EXPERIMENTAT,KURAMOTO 3,TOKUSHIMA 770,JAPAN. NR 39 TC 9 Z9 9 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 MAY PY 1992 VL 130 IS 5 BP 2487 EP 2494 DI 10.1210/en.130.5.2487 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HR339 UT WOS:A1992HR33900008 PM 1315245 ER PT J AU INSEL, TR WINSLOW, JT WITT, DM AF INSEL, TR WINSLOW, JT WITT, DM TI HOMOLOGOUS REGULATION OF BRAIN OXYTOCIN RECEPTORS SO ENDOCRINOLOGY LA English DT Article ID INDUCED MOTOR DISTURBANCES; PARAVENTRICULAR NUCLEUS; FEMALE RATS; ESTROGEN-TREATMENT; MATERNAL-BEHAVIOR; SPINAL-CORD; HYPOTHALAMUS; VASOPRESSIN; BINDING; LESIONS AB Specific receptors for oxytocin have been identified in rat forebrain. Previous studies have demonstrated that in select regions, these receptors are dependent on heterologous induction by gonadal steroids. To investigate whether brain oxytocin receptors are homologously regulated by oxytocin, we measured oxytocin receptor binding after hypothalamic paraventricular nucleus lesions, repeated central injections of oxytocin, and continuous central infusion of oxytocin via osmotic minipump. Neither lesions of the paraventricular nucleus nor repeated oxytocin injections altered the binding of the selective oxytocin receptor ligand [I-125]OTA [I-125] d(CH2)5[Tyr(Me)2,Thr4,Tyr-NH29] ornithine vasotocin, as measured by in vitro receptor autoradiography. After 10 days of continuous oxytocin infusion by osmotic minipump, oxytocin receptor binding decreased in every target field by at least 50%. This decrease appeared to represent a down-regulation of receptors and not displacement by exogenous peptide, as it persisted for at least 24 h after pump removal, and binding remained reduced in the presence of a saturating concentration of [I-125] OTA. Reduction of oxytocin receptors in response to increased oxytocin release may represent an important physiological mechanism for the regulation of central oxytocin neurotransmission. RP INSEL, TR (reprint author), NIMH,NEUROPHYSIOL LAB,POB 289,POOLESVILLE,MD 20837, USA. NR 30 TC 45 Z9 45 U1 1 U2 3 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD MAY PY 1992 VL 130 IS 5 BP 2602 EP 2608 DI 10.1210/en.130.5.2602 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HR339 UT WOS:A1992HR33900023 PM 1315251 ER PT J AU MIGLIACCIO, S DAVIS, VL GIBSON, MK GRAY, TK KORACH, KS AF MIGLIACCIO, S DAVIS, VL GIBSON, MK GRAY, TK KORACH, KS TI ESTROGENS MODULATE THE RESPONSIVENESS OF OSTEOBLAST-LIKE CELLS (ROS 17/2.8) STABLY TRANSFECTED WITH ESTROGEN-RECEPTOR SO ENDOCRINOLOGY LA English DT Article ID MENOPAUSAL BONE LOSS; ESTRADIOL RECEPTORS; PARATHYROID-HORMONE; MOUSE UTERUS; BINDING; CYTOSOL; SARCOMA; 17-BETA-ESTRADIOL; EXPRESSION; PREVENTION AB Recent studies have demonstrated the presence of estrogen receptor (ER) in both normal human osteoblast-like and osteoblast-like osteosarcoma cells. The number of ER in cultured osteoblastic cells is very low (200-500 sites/cell). This has complicated characterization of the biological role of estrogens in bone cells. To study the responsiveness of bone cells to estrogens, we established osteoblast-like cell lines expressing higher ER levels. ROS 17/2.8, an osteoblastic cell line, was stably transfected with the cDNA encoding for the mouse ER. After a selection period, positive clones were isolated and evaluated for the presence of ER by both Northern blot analysis and ligand binding assays. Using these techniques, we detected a significant increase in the level of both ER transcript and binding compared to that in wild-type cells. The levels of expressed ER protein were similar to those reported in normal human osteoblast-like cells in primary culture (approximately 2000 sites/cell). To test whether the exogenously inserted ER was responsive, both wild-type and ER stably transfected cells were transiently transfected with a reporter construct containing an estrogen-responsive element linked to a truncated thymidine kinase promoter and a chloramphenicol acetyltransferase (CAT) reporter gene. Exposure of the cells to increased concentrations of estradiol induced a slight increase in CAT activity in wild-type cells (approximately 1.5-fold) at maximal stimulation; however, it provoked a clear concentration-dependent increase in CAT activity in the ER stably transfected cells, with a maximal stimulation of approximately 10-fold. This event was receptor mediated, since ICI 164,384, an ER antagonist, blocked the enhancement of estradiol-induced CAT activity, and it was specific, since other steroid hormones did not stimulate CAT activity. Finally, we evaluated the ability of ER to modulate an endogenous estrogen-responsive gene by measuring the activity of the enzyme alkaline phosphatase. In addition, diethylstilbestrol, a synthetic estrogen agonist, increased the activity of both the CAT reporter gene and the endogenous alkaline phosphatase enzyme. In summary, we have established osteoblast-like cells expressing high levels of an exogenously inserted ER, which has characteristics similar to those of the endogenous ER in terms of its K(d). Finally, the exogenous ER regulates both exogenously inserted construct (VITERECAT) and endogenous properties of the cells (enzymatic activity and proliferation). C1 NIEHS,REPROD & DEV TOXICOL LAB,RECEPTOR BIOL SECT,POB 12233,MD 13-03,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,SCH MED,DEPT MED,CHAPEL HILL,NC 27599. OI Migliaccio, Silvia/0000-0002-4563-6630; Korach, Kenneth/0000-0002-7765-418X NR 50 TC 67 Z9 67 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 MAY PY 1992 VL 130 IS 5 BP 2617 EP 2624 DI 10.1210/en.130.5.2617 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HR339 UT WOS:A1992HR33900025 PM 1572285 ER PT J AU MULRONEY, SE LUMPKIN, MD ROBERTS, CT LEROITH, D HARAMATI, A AF MULRONEY, SE LUMPKIN, MD ROBERTS, CT LEROITH, D HARAMATI, A TI EFFECT OF A GROWTH HORMONE-RELEASING FACTOR ANTAGONIST ON COMPENSATORY RENAL GROWTH, INSULIN-LIKE GROWTH FACTOR-I (IGF-I), AND IGF-I RECEPTOR GENE-EXPRESSION AFTER UNILATERAL NEPHRECTOMY IN IMMATURE RATS SO ENDOCRINOLOGY LA English DT Article ID GLOMERULAR-FILTRATION RATE; HYPOPHYSECTOMIZED RATS; RIBONUCLEIC-ACID; PLASMA-FLOW; HYPERTROPHY; KIDNEY; TESTOSTERONE; BIOLOGY AB We have recently reported that pulsatile GH secretion is elevated 24 h after unilateral nephrectomy (UNX) in adult rats. In addition, suppression of the increase in GH with an antagonist to GH-releasing factor (GRF-AN) significantly attenuated compensatory renal growth (CRG) in adult rats. The present study examined the role of GH in CRG in immature animals. Pulsatile GH release was determined 24 h post-UNX in immature (26-28 days of age) sham-operated and UNX male Wistar rats. In contrast to the adult UNX rats, no increase in GH secretion was seen in the immature UNX rats compared with that in the controls. When pulsatile GH release was suppressed with GRF-AN, there was preferential growth of the remnant kidney despite the attenuated gain in whole body weight. In addition, insulin-like growth factor-I (IGF-1) and IGF-I receptor mRNA levels were elevated 3-fold in the remnant kidneys of GRF-AN-treated rats, despite the suppression of pulsatile GH release. These findings suggest that the initial phase of CRG is GH independent in the immature rat and, further, that CRG is associated with an increase in IGF-I and IGF-I receptor gene expression that is independent of episodic GH secretion. C1 NIDDKD,DIABET BRANCH,MOLEC & CELLULAR PHYSIOL SECT,BETHESDA,MD 20892. RP MULRONEY, SE (reprint author), GEORGETOWN UNIV,SCH MED,DEPT PHYSIOL & BIOPHYS,ROOM 256B,BASIC SCI BLDG,3900 RESERVOIR RD NW,WASHINGTON,DC 20007, USA. OI Roberts, Charles/0000-0003-1756-5772 FU NIDDK NIH HHS [DK-36111]; NINDS NIH HHS [NS-23036] NR 37 TC 30 Z9 30 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 MAY PY 1992 VL 130 IS 5 BP 2697 EP 2702 DI 10.1210/en.130.5.2697 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HR339 UT WOS:A1992HR33900035 PM 1315253 ER PT J AU SCHAAD, NC KLEIN, DC AF SCHAAD, NC KLEIN, DC TI CHARACTERIZATION OF ALPHA-2-ADRENERGIC RECEPTORS ON RAT PINEALOCYTES SO ENDOCRINOLOGY LA English DT Article ID ADRENERGIC REGULATION; N-ACETYLTRANSFERASE; HUMAN-PLATELET; EXPRESSION; CLONING; ADENOSINE-3',5'-MONOPHOSPHATE; BINDING; IDENTIFICATION; ADRENOCEPTORS; STIMULATION AB alpha-2-Adrenergic receptors in rat pineal membranes were characterized using p-[I-125]iodoclonidine, a highly selective, high specific activity ligand. Binding was rapid (association constant rate = 0.0462 nM/min-1) and reversible after the addition of phentolamine (apparent dissociation rate constant = 0.04 min-1). Saturation experiments indicate the presence of a single class of noncooperative binding sites, with an equilibrium binding constant (K(d)) of 1.1 +/- 0.3 nM and a binding capacity (B(max)) of 69 +/- 9 fmol/mg protein. Analysis of the relative potency of selected adrenoreceptor agonists and antagonists in competition studies with p-[I-125]iodoclonidine indicates that the ligand is binding to a member of the family of alpha-2-adrenergic receptors that has a high affinity for oxymetazoline, phentolamine, and (-)norepinephrine and a low affinity for prazosin, similar to the recently described alpha-2-adrenergic receptor present in the bovine pineal gland, classified as belonging to the newly described alpha-2D-adrenergic receptor subtype. Rat pineal alpha-2-adrenergic receptors were unaltered after nerve endings degenerated. This observation and the recent finding that alpha-2-adrenergic agonists potentiate N6,2'-O-dibutyryl-cAMP or isobutylmethylxanthine stimulation of arylalkylamine N-acetyltransferase in the rat pineal gland establish that alpha-2D-like adrenergic receptors are located on pinealocytes. C1 NICHHD,DEV NEUROBIOL LAB,NEUROENDOCRINOL SECT,BLDG 36,ROOM 4A07,BETHESDA,MD 20892. NR 38 TC 17 Z9 17 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 MAY PY 1992 VL 130 IS 5 BP 2804 EP 2810 DI 10.1210/en.130.5.2804 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HR339 UT WOS:A1992HR33900049 PM 1315259 ER PT J AU PHILLIP, M PALESE, T HERNANDEZ, ER ROBERTS, CT LEROITH, D KOWARSKI, AA AF PHILLIP, M PALESE, T HERNANDEZ, ER ROBERTS, CT LEROITH, D KOWARSKI, AA TI EFFECT OF TESTOSTERONE ON INSULIN-LIKE GROWTH FACTOR-I (IGF-I) AND IGF-I RECEPTOR GENE-EXPRESSION IN THE HYPOPHYSECTOMIZED RAT SO ENDOCRINOLOGY LA English DT Article ID OSTEOBLAST-LIKE CELLS; PRECOCIOUS PUBERTY; HORMONE DEFICIENCY; RIBONUCLEIC-ACID; SOMATOMEDIN-C; SEX STEROIDS; CHILDREN; PROLIFERATION; SECRETION; BINDING AB Circulating levels of insulin-like growth factor-I (IGF-1) increase during puberty, concurrent with an increase in the levels of GH and the gonadal steroids. The relationship between the changes observed in IGF-I and testosterone (T) levels are not understood. This study was designed to determine whether T has a direct effect on IGF-I serum levels, liver IGF-I gene expression, and epiphyseal growth plate IGF-I and IGF-I receptor gene expression. Hypophysectomized castrated rats were divided into four groups of six animals. The T group was treated with sc T for 5 days. The GH group was treated with a single dose of GH. The GH plus T group was treated with T for 5 days and with GH on the last day of treatment. The control group was injected for 5 days with vehicle alone. Serum IGF-I levels in the T group were not significantly different from those in the control group, and the levels in the GH plus T group were not significantly different from those in the GH group. There was an 11-fold increase in liver IGF-I mRNA abundance in the GH group compared to the control group (P < 0.01). Liver IGF-I mRNA levels in the T group were not significantly different from those in the control group. When liver IGF-I mRNA levels in the GH plus T group were compared to those in the GH-treated group, no significant differences were found. In the epiphyseal growth plate region, there was a 12-fold increase in IGF-I mRNA levels in the GH group compared to those in the control group, but there was no statistical difference between the control and T groups. IGF-I mRNA levels in the GH plus T group were not significantly different from those in the GH-treated group. IGF-I receptor mRNA abundance was not significantly different in the T group compared to that in the control group. GH decreased IGF-I receptor mRNA by 2.3-fold, but T treatment before GH injection did not change this effect. We conclude that in castrated hypophysectomized rats, T does not stimulate IGF-I gene expression in the liver, nor does it increase IGF-I serum levels. T alone also does not have a stimulatory effect on IGF-I or IGF-I receptor gene expression in the epiphyseal growth plate region. When given with GH, T did not increase the stimulatory effect GH had on liver and epiphyseal growth plate region IGF-I gene expression or IGF-I serum levels. T also did not change the effect GH had on IGF-I receptor mRNA levels in the epiphyseal growth plate region. C1 NIH,DIABET BRANCH,MOLEC & CELLULAR PHYSIOL SECT,BETHESDA,MD 20892. RP PHILLIP, M (reprint author), UNIV MARYLAND,SCH MED,DIV PEDIAT ENDOCRINOL,BRB 10-047,655 W BALTIMORE ST,BALTIMORE,MD 21201, USA. OI Roberts, Charles/0000-0003-1756-5772 NR 24 TC 34 Z9 35 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 MAY PY 1992 VL 130 IS 5 BP 2865 EP 2870 DI 10.1210/en.130.5.2865 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HR339 UT WOS:A1992HR33900056 PM 1315260 ER PT J AU KONONEN, J HONKANIEMI, J ALHO, H KOISTINAHO, J IADAROLA, M PELTOHUIKKO, M AF KONONEN, J HONKANIEMI, J ALHO, H KOISTINAHO, J IADAROLA, M PELTOHUIKKO, M TI FOS-LIKE IMMUNOREACTIVITY IN THE RAT HYPOTHALAMIC-PITUITARY AXIS AFTER IMMOBILIZATION STRESS SO ENDOCRINOLOGY LA English DT Article ID CORTICOTROPIN-RELEASING-FACTOR; PROOPIOMELANOCORTIN GENE-TRANSCRIPTION; DIFFERENTIALLY REGULATES ANTERIOR; NUCLEAR PRECURSOR RNA; C-FOS; GLUCOCORTICOID RECEPTOR; INTERMEDIATE LOBE; BETA-ENDORPHIN; IMMUNOCYTOCHEMICAL LOCALIZATION; ADRENAL-CORTEX AB The effect of immobilization stress on the expression of the protooncogene c-fos in the rat pituitary and hypothalamus was investigated immunohistochemically using different polyclonal antibodies raised against the c-fos protein (Fos). After a 4 h immobilization, Fos-like immunoreactivity (Fos-LI) increased substantially in the parvocellular part of the paraventricular nucleus and in the intermediate and anterior lobe of the pituitary. The majority of the Fos-immunoreactive cells in the pituitary contained corticotropin, which was demonstrated by immunohistochemical double-staining. Since the paraventricular nucleus contains a large number of glucocorticoid receptor immunoreactive cells, the effect of a synthetic glucocorticoid, dexamethasone, on the induction of Fos-LI was studied. Dexamethasone treatment before immobilization considerably reduced the stress-induced expression of Fos-LI in the anterior and intermediate lobe of the pituitary but did not alter the induction of Fos-LI in the paraventricular nucleus. The present results demonstrate that immobilization stress induces Fos-LI both in the hypothalamus and in the pituitary, suggesting that Fos may be involved in regulating the synthesis of different mediators of stress response, such as CRF- and POMC-derived peptides. Apparently glucocorticoids do not directly repress c-fos expression, since dexamethasone did not affect the induction of Fos-LI in the paraventricular nucleus. The reduction of stress-induced Fos-LI in the pituitary by dexamethasone is possibly due to the diminished release of CRF factor from the paraventricular neurons. C1 NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD 20892. RP KONONEN, J (reprint author), UNIV TAMPERE,DEPT BIOMED SCI,POB 607,SF-33101 TAMPERE,FINLAND. NR 42 TC 91 Z9 92 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 MAY PY 1992 VL 130 IS 5 BP 3041 EP 3047 DI 10.1210/en.130.5.3041 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HR339 UT WOS:A1992HR33900081 PM 1315265 ER PT J AU DOSEMECI, M ALAVANJA, M VETTER, R EATON, B BLAIR, A AF DOSEMECI, M ALAVANJA, M VETTER, R EATON, B BLAIR, A TI MORTALITY AMONG LABORATORY WORKERS EMPLOYED AT THE UNITED-STATES DEPARTMENT-OF-AGRICULTURE SO EPIDEMIOLOGY LA English DT Note DE LABORATORY WORKERS; COLON CANCER; OCCUPATIONAL RISK; BREAST CANCER; LYMPHOMA; MORTALITY; NEOPLASMS; SUICIDE AB We evaluated the mortality of 835 white male and 36 female laboratory workers employed by the U.S. Department of Agriculture who died between January 1, 1970, and December 31, 1979. For males, the mortality odds ratio for all cancers was 1.0 (95% confidence interval = 0.8-1.2). Colon cancer, lymphosarcoma and reticulosarcoma, nonmalignant diseases of the blood and blood-forming organs, and suicide showed elevated mortality odds ratios. Only colon cancer showed an association with duration of employment as a laboratory worker. In an accompanying case-control study, the risk of colon cancer rose to 3.2 among those who had 20 or more years of employment as a laboratory worker. Among females, breast cancer was elevated (mortality odds ratio = 5.3; 95% confidence interval = 2.8-10.1). RP DOSEMECI, M (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,OCCUPAT STUD SECT,BLDG EPN,ROOM 418,BETHESDA,MD 20892, USA. NR 0 TC 20 Z9 20 U1 1 U2 4 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAY PY 1992 VL 3 IS 3 BP 258 EP 262 DI 10.1097/00001648-199205000-00012 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA HT912 UT WOS:A1992HT91200012 PM 1591326 ER PT J AU FOJO, SS BEG, O DICHEK, H BREWER, HB AF FOJO, SS BEG, O DICHEK, H BREWER, HB TI THE MOLECULAR DEFECTS IN LIPOPROTEIN-LIPASE DEFICIENT PATIENTS SO EUROPEAN JOURNAL OF EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT 56TH MEETING OF THE EUROPEAN ATHEROSCLEROSIS SOC CY OCT 10-13, 1992 CL CAGLIARI, ITALY SP EUROPEAN ATHEROSCLEROSIS SOC DE HYPERCHYLOMICRONEMIA; GENE DEFECTS AB The underlying molecular defects that lead to a deficiency of lipoprotein lipase in two patients from different kindreds presenting with the familial hyperchylomicronemia syndrome have been identified. Sequence analysis of amplified LPL cDNA of the patient from the Bethesda kindred revealed a single point mutation (G to A) at position 781 of the normal gene that resulted in the substitution of an alanine for a threonine at residue 176 and the loss of an SfaN1 site present in the normal LPL gene. Amplification of patient cDNA by the PCR followed by restriction enzyme digestion with SfaN1 established that the patient is a true homozygote for the defect. The proband from the second kindred was found to be a compound heterozygote for two separate allelic mutations, including a T to C transition at nucleotide 836 and a G to A mutation at base 983 that led to the substitution of Ile194 by Thr and Arg243 by His, respectively. Transient expression of the mutant LPL cDNAs from both kindreds in human embryonal kidney-293 cells resulted in the synthesis of enzymatically inactive proteins, establishing the functional significance of the mutations. RP FOJO, SS (reprint author), NHLBI,MOLEC DIS BRANCH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0393-2990 J9 EUR J EPIDEMIOL JI Eur. J. Epidemiol. PD MAY PY 1992 VL 8 SU 1 BP 59 EP 63 DI 10.1007/BF00145351 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA HX756 UT WOS:A1992HX75600011 PM 1505655 ER PT J AU WALSH, TJ PIZZO, PA AF WALSH, TJ PIZZO, PA TI EXPERIMENTAL GASTROINTESTINAL AND DISSEMINATED CANDIDIASIS IN IMMUNOCOMPROMISED ANIMALS SO EUROPEAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE CANDIDIASIS; EXPERIMENTAL INFECTIONS; IMMUNOCOMPROMISED HOST; ANTIFUNGAL THERAPY RP WALSH, TJ (reprint author), NATL CANC INST,INFECT DIS SECT,PEDIAT BRANCH,BETHESDA,MD 20892, USA. NR 0 TC 9 Z9 10 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0393-2990 J9 EUR J EPIDEMIOL JI Eur. J. Epidemiol. PD MAY PY 1992 VL 8 IS 3 BP 477 EP 483 DI 10.1007/BF00158585 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA JN157 UT WOS:A1992JN15700024 PM 1397212 ER PT J AU VANLINGEN, A HUIJGENS, PC VISSER, FC OSSENKOPPELE, GJ HOEKSTRA, OS MARTENS, HJM HUITINK, H HERSCHEID, KDM GREEN, MV TEULE, GJJ AF VANLINGEN, A HUIJGENS, PC VISSER, FC OSSENKOPPELE, GJ HOEKSTRA, OS MARTENS, HJM HUITINK, H HERSCHEID, KDM GREEN, MV TEULE, GJJ TI PERFORMANCE-CHARACTERISTICS OF A 511-KEV COLLIMATOR FOR IMAGING POSITRON EMITTERS WITH A STANDARD GAMMA-CAMERA SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE PLANAR 511-KEV IMAGING; COLLIMATOR PERFORMANCE; F-18 FLUORODEOXYGLUCOSE ID TUMOR; PET; GA-67-CITRATE; LYMPHOMA AB Line-source experiments were conducted to assess the performance of a gamma-camera equipped with a specially designed 511-keV collimator for the planar imaging of positron emitters. The results were compared with the camera performance with routinely used collimators and radionuclides (thallium-201, technetium-99m and gallium-67). With positron emitters, scatter contributed less to the widening of the line spread function than with radionuclides emitting lower photon energies. These observations can be explained by the relative deterioration in the discrimination power of the gamma-camera to reject scattered radiation at low energies. Planar 511-keV imaging may provide relevant clinical information, as we showed by fluorodeoxyglucose studies in a patient with a myocardial infarction and in a patient with a malignant lymphoma. It is concluded that positron emitters can be effectively applied for planar imaging with the generally available gamma-cameras. This study implies that radiotracers developed for positron emission tomography may find a place in the practice of conventional nuclear medicine. C1 FREE UNIV AMSTERDAM HOSP,DEPT HAEMATOL,1081 HV AMSTERDAM,NETHERLANDS. FREE UNIV AMSTERDAM HOSP,DEPT CARDIOL,1081 HV AMSTERDAM,NETHERLANDS. FREE UNIV AMSTERDAM HOSP,DEPT PHARMACOL,1081 HV AMSTERDAM,NETHERLANDS. FREE UNIV AMSTERDAM,CTR RADIONUCLIDE,1007 MC AMSTERDAM,NETHERLANDS. NIH,BETHESDA,MD 20892. RP VANLINGEN, A (reprint author), FREE UNIV AMSTERDAM HOSP,DEPT NUCL MED,DE BOELELAAN 1117,1081 HV AMSTERDAM,NETHERLANDS. RI Huitink, Johannes/K-2761-2016 OI Huitink, Johannes/0000-0002-9999-7933 NR 14 TC 75 Z9 77 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6997 J9 EUR J NUCL MED JI Eur. J. Nucl. Med. PD MAY PY 1992 VL 19 IS 5 BP 315 EP 321 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA JA027 UT WOS:A1992JA02700002 PM 1296592 ER PT J AU WAESPE, W SCHWARZ, U WOLFENSBERGER, M AF WAESPE, W SCHWARZ, U WOLFENSBERGER, M TI FIRING CHARACTERISTICS OF VESTIBULAR NUCLEI NEURONS IN THE ALERT MONKEY AFTER BILATERAL VESTIBULAR NEURECTOMY SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE VESTIBULAR NEURECTOMY; VELOCITY STORAGE; SINGLE CELL; INTEGRATOR; OPTOKINETIC; SMOOTH PURSUIT; LABYRINTHECTOMY; MONKEY ID OPTOKINETIC AFTER-NYSTAGMUS; TERM ADAPTIVE-CHANGES; EYE-MOVEMENTS; VESTIBULOOCULAR REFLEX; BRAIN-STEM; ANGULAR-ACCELERATION; OCULAR REFLEX; HEAD ROTATION; FLOCCULUS; STIMULATION AB After destruction of the peripheral vestibular system which is not activated by moving large-field visual stimulation, not only labyrinthine-ocular reflexes but also optokinetic-ocular responses related to the "velocity storage" mechanism are abolished. In the normal monkey optokinetic-ocular responses are reflected in sustained activity changes of central vestibular neurons within the vestibular nuclei. To account for the loss of optokinetic responses after labyrinthectomy, inactivation of central vestibular neurons consequent on the loss of primary vestibular activity is assumed to be of major importance. To test this hypothesis we recorded the neural activity within the vestibular nuclear complex in two chronically prepared Rhesus monkeys during a period from one up to 9 and 12 months after both vestibular nerves had been cut. The discharge characteristics of 829 cells were studied in relation to eye fixation, and to a moving small and large (optokinetic) visual stimulus producing smooth pursuit (SP) eye movements and optokinetic nystagmus (OKN). Units were grouped into different subclasses. After chronic bilateral vestibular neurectomy (BVN) we have found: (1) a rich variety of spontaneously active cells within the vestibular nuclear complex, which - as far as comparison before and after BVN is possible - belong to all subclasses of neurons functionally defined in normal monkey; and (2) no sustained activity changes which are related to the activation of the "velocity storage" mechanism; this is especially true for "pure-vestibular", "vestibular-pause" and "tonic-vestibular-pause" cells in normal monkey which show a "pure", "pause" and "tonic-pause" firing pattern after BVN. Neurons which are modulated by eye position are, however, modulated with the velocity of slow eye movements with comparable sensitivity during SP and OKN. Retinal slip is extremely rarely encoded. The results of the present study do not directly answer the question why the "velocity storage" mechanism is abolished after BVN but they suggest that only a small number of central vestibular cells may be inactivated by neurectomy. C1 NIH, BETHESDA, MD 20892 USA. UNIV MAINZ, DEPT OTOLARYNGOL, W-6500 MAINZ, GERMANY. RP WAESPE, W (reprint author), UNIV ZURICH, DEPT NEUROL, FRAUENKLINIKSTR 26, CH-8091 ZURICH, SWITZERLAND. NR 42 TC 25 Z9 25 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0014-4819 EI 1432-1106 J9 EXP BRAIN RES JI Exp. Brain Res. PD MAY PY 1992 VL 89 IS 2 BP 311 EP 322 PG 12 WC Neurosciences SC Neurosciences & Neurology GA HU991 UT WOS:A1992HU99100007 PM 1378026 ER PT J AU DEDIEGO, JG ROUILLER, DG GORDEN, P CARPENTIER, JL AF DEDIEGO, JG ROUILLER, DG GORDEN, P CARPENTIER, JL TI EPIDERMAL GROWTH-FACTOR RECEPTOR INTERNALIZATION AND BIOSYNTHESIS IN THE DIABETIC RAT SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID MEDIATED ENDOCYTOSIS; DECREASED EXPRESSION; FACTOR DEFICIENCY; PRIMARY CULTURES; DNA-SYNTHESIS; EGF RECEPTOR; OWN RECEPTOR; LIVER; HEPATOCYTES; INSULIN C1 NIDDKD,DIABET BRANCH,BETHESDA,MD. UNIV GENOA,MED CTR,LABS LOUIS JEANTET,I-16126 GENOA,ITALY. RP DEDIEGO, JG (reprint author), UNIV GENOA,MED CTR,INST HISTOL & EMBRYOL,I-16126 GENOA,ITALY. NR 41 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 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD MAY PY 1992 VL 200 IS 1 BP 77 EP 82 DI 10.1016/S0014-4827(05)80073-4 PG 6 WC Oncology; Cell Biology SC Oncology; Cell Biology GA HP230 UT WOS:A1992HP23000010 PM 1532938 ER PT J AU CHEN, P CARRINGTON, JL PARALKAR, VM PIERCE, GF REDDI, AH AF CHEN, P CARRINGTON, JL PARALKAR, VM PIERCE, GF REDDI, AH TI CHICK LIMB BUD MESODERMAL CELL CHONDROGENESIS - INHIBITION BY ISOFORMS OF PLATELET-DERIVED GROWTH-FACTOR AND REVERSAL BY RECOMBINANT BONE MORPHOGENETIC PROTEIN SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID FACTOR-BETA; CULTURE; CARTILAGE; EMBRYOS; MATRIX; PDGF; SIS C1 NIDR,BONE CELL BIOL SECT,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,F EDWARD HEBERT SCH MED,DEPT ANAT & CELL BIOL,BETHESDA,MD 20814. AMGEN INC,DEPT EXPTL PATHOL,THOUSAND OAKS,CA 91320. NR 31 TC 37 Z9 39 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD MAY PY 1992 VL 200 IS 1 BP 110 EP 117 DI 10.1016/S0014-4827(05)80078-3 PG 8 WC Oncology; Cell Biology SC Oncology; Cell Biology GA HP230 UT WOS:A1992HP23000015 PM 1314187 ER PT J AU PUTILINA, T SMITH, S GENTLEMAN, S CHADER, G AF PUTILINA, T SMITH, S GENTLEMAN, S CHADER, G TI RAPID PCR-BASED CONSTRUCTION OF SPECIFICALLY ENRICHED LIBRARIES FROM SMALL RETINA SAMPLES SO EXPERIMENTAL EYE RESEARCH LA English DT Letter ID CDNA; DEGENERATION; MOUSE RP PUTILINA, T (reprint author), NEI,RETINAL CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD MAY PY 1992 VL 54 IS 5 BP 825 EP 826 DI 10.1016/0014-4835(92)90041-P PG 2 WC Ophthalmology SC Ophthalmology GA HY289 UT WOS:A1992HY28900023 PM 1623970 ER PT J AU SHIMIZU, T NETTESHEIM, P EDDY, EM RANDELL, SH AF SHIMIZU, T NETTESHEIM, P EDDY, EM RANDELL, SH TI MONOCLONAL-ANTIBODY (MAB) MARKERS FOR SUBPOPULATIONS OF RAT TRACHEAL EPITHELIAL (RTE) CELLS SO EXPERIMENTAL LUNG RESEARCH LA English DT Article ID BASAL CELLS; BRONCHIAL EPITHELIUM; MECHANICAL INJURY; VITAMIN-A; DIFFERENTIATION; ANTIGENS; REGENERATION; SECRETIONS; INVITRO; RABBIT AB We sought monoclonal antibodies (Mabs) that would recognize distinct subsets of rat tracheal epithelial (RTE) cells. Mice were immunized with pronase-dissociated RTE cells and hybridomas whose supernatants immunocytochemically stained subpopulations of tracheal cells were selected. We report the immunohistochemical staining properties of the antibodies and give the results of preliminary biochemical characterization of the antigens. Four different types of antibodies were produced. Antibody RTE 1 stained most RTE cells. Three antibodies (RTE 2, 7, and 13) recognized a subpopulation of nonciliated cells, both columnar and basal cells. Antibody RTE 3 intensely labeled the surface of ciliated cells. Three antibodies reacted with granule components of secretory cells; antibodies RTE 9 and 11 reacted with mucous-type secretory cells and antibody RTE 12 stained all tracheal surface secretory cells. As described in detail, some antibodies were RTE cell specific while others also reacted with cells and secretions in other organs; the antibodies did not cross react with guinea pig or rabbit tissues. Periodate sensitivity of the antigens suggested that some antibodies recognized carbohydrate moieties while others detected peptide epitopes. In some cases, Western blotting revealed the molecular weights of the antigens, but some antigens were denatured by sodium dodecyl sulfate (SDS) and beat treatment. These antibody probes provide a useful means to immunochemically study changes in cell type distribution and/or epitope expression during development, injury, and regeneration. C1 NIEHS,PULM PATHOBIOL LAB,POB 12233,MD D2-01,RES TRIANGLE PK,NC 27709. NIEHS,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC 27709. NR 30 TC 24 Z9 24 U1 0 U2 0 PU HEMISPHERE PUBL CORP PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0190-2148 J9 EXP LUNG RES JI Exp. Lung Res. PD MAY-JUN PY 1992 VL 18 IS 3 BP 323 EP 342 DI 10.3109/01902149209031688 PG 20 WC Respiratory System SC Respiratory System GA HV573 UT WOS:A1992HV57300002 PM 1378386 ER PT J AU CLARK, CG CUNNICK, CC DIAMOND, LS AF CLARK, CG CUNNICK, CC DIAMOND, LS TI ENTAMOEBA-HISTOLYTICA - IS CONVERSION OF NONPATHOGENIC AMEBAE TO THE PATHOGENIC FORM A REAL PHENOMENON SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE AMEBAE; BACTERIAL FLORA; CYSTS; ENTAMOEBA-HISTOLYTICA; ISOENZYMES; PATHOGENICITY; RIBOPRINTING ID SURFACE-ANTIGEN; ISOENZYME PATTERNS; DNA PROBES; DIFFERENTIATION RP CLARK, CG (reprint author), NIAID,PARASIT DIS LAB,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. RI Clark, C Graham/H-3683-2011 OI Clark, C Graham/0000-0002-0521-0977 NR 24 TC 16 Z9 16 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 MAY PY 1992 VL 74 IS 3 BP 307 EP 314 DI 10.1016/0014-4894(92)90154-3 PG 8 WC Parasitology SC Parasitology GA HR047 UT WOS:A1992HR04700008 PM 1582483 ER PT J AU KAHN, RA DER, CJ BOKOCH, GM AF KAHN, RA DER, CJ BOKOCH, GM TI THE RAS SUPERFAMILY OF GTP-BINDING PROTEINS - GUIDELINES ON NOMENCLATURE SO FASEB JOURNAL LA English DT Article C1 LA JOLLA CANC RES FDN, LA JOLLA, CA 92037 USA. SCRIPPS RES INST, LA JOLLA, CA 92037 USA. RP KAHN, RA (reprint author), NCI, DIV CANC TREATMENT, BIOL CHEM LAB, DEV THERAPEUT PROGRAM, BETHESDA, MD 20892 USA. NR 4 TC 85 Z9 94 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 MAY PY 1992 VL 6 IS 8 BP 2512 EP 2513 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HU423 UT WOS:A1992HU42300002 PM 1592203 ER PT J AU KRIEG, AM GOURLEY, MF PERL, A AF KRIEG, AM GOURLEY, MF PERL, A TI ENDOGENOUS RETROVIRUSES - POTENTIAL ETIOLOGIC AGENTS IN AUTOIMMUNITY SO FASEB JOURNAL LA English DT Review DE RETROVIRUS; AUTOIMMUNITY; ANTISENSE; PATHOGENESIS; LUPUS ID MAMMARY-TUMOR VIRUS; MURINE LEUKEMIA-VIRUS; PROTEIN-KINASE-C; HUMAN DNA; SJOGRENS-SYNDROME; TRANSFER RNAPRO; HUMAN-CELLS; SEQUENCES; EXPRESSION; ELEMENTS AB The genomes of all organisms, from yeast to humans, contain thousands of endogenous retroviruses (ERV). In most species all or almost all ERV are noninfectious, but some ERV retain open reading frames capable of encoding proteins. RNA and proteins derived from ERV are expressed in humans and other species. Until recently, there was little evidence that this ERV expression resulted in any immunologic effects. Recent studies make it increasingly clear that some ERV have important immunologic effects. The immune effects of ERV expression raise the question of a possible pathogenic role in idiopathic autoimmune diseases. Interest in this question has been heightened by the observation that some infectious retroviruses cause manifestations of autoimmunity. Nonetheless, attempts to isolate infectious retroviruses from patients with idiopathic autoimmune diseases have generally failed. The possible role of ERV in idiopathic autoimmune diseases has not yet been fully explored. This review focuses on the known and the potential immune effects of ERV, especially as they may relate to autoimmune diseases. C1 NEW YORK STATE DEPT HLTH,ROSWELL PK MEM INST,DEPT MOLEC MED & IMMUNOL,BUFFALO,NY 14263. NIAMSD,CELLULAR IMMUNOL SECT,BETHESDA,MD 20892. RP KRIEG, AM (reprint author), UNIV IOWA,COLL MED,DEPT MED,DIV RHEUMATOL,540 EMRB,IOWA CITY,IA 52242, USA. OI Perl, Andras/0000-0002-5017-1348 NR 74 TC 124 Z9 124 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 MAY PY 1992 VL 6 IS 8 BP 2537 EP 2544 PG 8 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA HU423 UT WOS:A1992HU42300006 PM 1592206 ER PT J AU MILLER, CJ ALEXANDER, NJ GETTIE, A HENDRICKX, AG MARX, PA AF MILLER, CJ ALEXANDER, NJ GETTIE, A HENDRICKX, AG MARX, PA TI THE EFFECT OF CONTRACEPTIVES CONTAINING NONOXYNOL-9 ON THE GENITAL TRANSMISSION OF SIMIAN IMMUNODEFICIENCY VIRUS IN RHESUS MACAQUES SO FERTILITY AND STERILITY LA English DT Note DE SIMIAN IMMUNODEFICIENCY VIRUS; GENITAL TRANSMISSION; NONOXYNOL-9 ID INACTIVATION C1 NICHHD,CTR POPULAT RES,BETHESDA,MD 20892. RP MILLER, CJ (reprint author), UNIV CALIF DAVIS,CALIF PRIMATE RES CTR,DAVIS,CA 95616, USA. FU NCRR NIH HHS [RR00169] NR 7 TC 57 Z9 57 U1 0 U2 0 PU AMER SOC REPRODUCTIVE MEDICINE PI BIRMINGHAM PA 1209 MONTGOMERY HIGHWAY, BIRMINGHAM, AL 35216-2809 SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD MAY PY 1992 VL 57 IS 5 BP 1126 EP 1128 PG 3 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA HR343 UT WOS:A1992HR34300031 PM 1315297 ER PT J AU METCALFE, DD AF METCALFE, DD TI THE NATURE AND MECHANISMS OF FOOD ALLERGIES AND RELATED DISEASES SO FOOD TECHNOLOGY LA English DT Article; Proceedings Paper CT SYMP ON FOOD SAFETY EDUCATIONAL OUTREACH, AT THE 1991 ANNUAL MEETING OF THE INST OF FOOD TECHNOLOGISTS CY JUN 01-05, 1991 CL DALLAS, TX SP INST FOOD TECHNOLOGISTS ID ADVERSE REACTIONS; HYPERSENSITIVITY; CHILDREN RP METCALFE, DD (reprint author), NIAID,CLIN INVEST LAB,MAST CELL PHYSIOL SECT,BLDG 10,ROOM 11C210,BETHESDA,MD 20892, USA. NR 25 TC 8 Z9 8 U1 0 U2 0 PU INST FOOD TECHNOLOGISTS PI CHICAGO PA SUITE 300 221 N LASALLE ST, CHICAGO, IL 60601-1291 SN 0015-6639 J9 FOOD TECHNOL-CHICAGO JI Food Technol. PD MAY PY 1992 VL 46 IS 5 BP 136 EP 139 PG 4 WC Food Science & Technology SC Food Science & Technology GA HU753 UT WOS:A1992HU75300010 ER PT J AU CALLAHAN, R AF CALLAHAN, R TI CELLULAR AND MOLECULAR HETEROGENEITY OF BREAST-CANCER CELLS SO FRESENIUS JOURNAL OF ANALYTICAL CHEMISTRY LA English DT Article; Proceedings Paper CT 13TH INTERNATIONAL CONF ON BIOCHEMICAL ANALYSIS CY MAY 05-08, 1992 CL MUNICH, GERMANY RP CALLAHAN, R (reprint author), NCI,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0937-0633 J9 FRESEN J ANAL CHEM JI Fresenius J. Anal. Chem. PD MAY PY 1992 VL 343 IS 1 BP 19 EP 19 DI 10.1007/BF00331952 PG 1 WC Chemistry, Analytical SC Chemistry GA HT012 UT WOS:A1992HT01200021 ER PT J AU BOSSERT, NL REEL, JR LAWTON, AD GEORGE, JD LAMB, JC AF BOSSERT, NL REEL, JR LAWTON, AD GEORGE, JD LAMB, JC TI REPRODUCTIVE TOXICITY OF TRIETHYLENE GLYCOL AND ITS DIACETATE AND DIMETHYL ETHER DERIVATIVES IN A CONTINUOUS BREEDING PROTOCOL IN SWISS CD-1 MICE SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID DEVELOPMENTAL TOXICITY; MOUSE C1 RES TRIANGLE INST,CHEM & LIFE SCI GRP,RES TRIANGLE PK,NC 27709. RP BOSSERT, NL (reprint author), NIEHS,NATL TOXICOL PROGRAM,DEV & REPROD TOXICOL GRP,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 14 TC 6 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD MAY PY 1992 VL 18 IS 4 BP 602 EP 608 DI 10.1016/0272-0590(92)90120-7 PG 7 WC Toxicology SC Toxicology GA HU393 UT WOS:A1992HU39300015 PM 1526373 ER PT J AU REEL, JR TYL, RW LAWTON, AD LAMB, JC AF REEL, JR TYL, RW LAWTON, AD LAMB, JC TI REPRODUCTIVE TOXICITY OF SULFAMETHAZINE IN SWISS CD-1 MICE DURING CONTINUOUS BREEDING SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID B6C3F1 MICE; RESIDUES; PORK; CARCINOGENICITY; RATS C1 RES TRIANGLE INST,CHEM & LIFE SCI GRP,RES TRIANGLE PK,NC 27709. NIEHS,NATL TOXICOL PROGRAM,DEV & REPROD TOXICOL GRP,RES TRIANGLE PK,NC 27709. FU NIEHS NIH HHS [N01-ES-2-5014, N01-ES-9-6515] NR 45 TC 5 Z9 6 U1 1 U2 5 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD MAY PY 1992 VL 18 IS 4 BP 609 EP 615 DI 10.1016/0272-0590(92)90121-W PG 7 WC Toxicology SC Toxicology GA HU393 UT WOS:A1992HU39300016 PM 1526374 ER PT J AU MULLIN, GE LAZENBY, AJ HARRIS, ML BAYLESS, TM JAMES, SP AF MULLIN, GE LAZENBY, AJ HARRIS, ML BAYLESS, TM JAMES, SP TI INCREASED INTERLEUKIN-2 MESSENGER-RNA IN THE INTESTINAL MUCOSAL LESIONS OF CROHNS-DISEASE BUT NOT ULCERATIVE-COLITIS SO GASTROENTEROLOGY LA English DT Article ID INFLAMMATORY BOWEL-DISEASE; KILLER CELL-ACTIVITY; HELPER T-CELLS; MONONUCLEAR-CELLS; LYMPHOCYTE-SUBPOPULATIONS; NONHUMAN-PRIMATES; IMMUNE REACTIVITY; LAMINA PROPRIA; RECEPTOR; EXPRESSION C1 NIAID,CLIN INVEST LAB,MUCOSAL IMMUN SECT,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV GASTROENTEROL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PATHOL,DIV GASTROENTEROL,BALTIMORE,MD 21205. OI Mullin, Gerard/0000-0001-5317-6788 NR 40 TC 194 Z9 194 U1 2 U2 4 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 MAY PY 1992 VL 102 IS 5 BP 1620 EP 1627 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA HR049 UT WOS:A1992HR04900022 PM 1568572 ER PT J AU ADAMSON, M REINER, B OLSON, JL GOODMAN, Z PLOTNICK, L BERNARDINI, I GAHL, WA AF ADAMSON, M REINER, B OLSON, JL GOODMAN, Z PLOTNICK, L BERNARDINI, I GAHL, WA TI INDIAN CHILDHOOD CIRRHOSIS IN THE AMERICAN CHILD SO GASTROENTEROLOGY LA English DT Article ID COPPER STORAGE DISEASE; WILSONS DISEASE; LIVER; TOXICOSIS; EXCRETION; PROTEIN; RAT C1 NICHHD,HUMAN GENET BRANCH,HUMAN BIOCHEM GENET SECT,BLDG 10,ROOM 95242,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,DIV ENDOCRINOL,BALTIMORE,MD 21205. USAF,INST PATHOL,WASHINGTON,DC 20330. JOHNS HOPKINS UNIV,SCH MED,DEPT PATHOL,BALTIMORE,MD 21205. FU NCRR NIH HHS [RR-0052]; NIDDK NIH HHS [5-T32-DK-07116] NR 40 TC 43 Z9 43 U1 1 U2 2 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 MAY PY 1992 VL 102 IS 5 BP 1771 EP 1777 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA HR049 UT WOS:A1992HR04900042 PM 1568588 ER PT J AU LUCIER, GW THOMPSON, CL HOEL, DG AF LUCIER, GW THOMPSON, CL HOEL, DG TI OMEPRAZOLE, CYTOCHROME P450, AND CHEMICAL CARCINOGENESIS SO GASTROENTEROLOGY LA English DT Letter ID 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN; RATS RP LUCIER, GW (reprint author), NIEHS,RES TRIANGLE PK,NC 27709, USA. NR 16 TC 6 Z9 6 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 1992 VL 102 IS 5 BP 1823 EP 1824 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA HR049 UT WOS:A1992HR04900051 PM 1314754 ER PT J AU SUZUKI, T KOIKE, Y YANAURA, S GEORGE, FR MEISCH, RA AF SUZUKI, T KOIKE, Y YANAURA, S GEORGE, FR MEISCH, RA TI SEX-DIFFERENCES IN PHYSICAL-DEPENDENCE ON PENTOBARBITAL IN 4 INBRED STRAINS OF RATS SO GENERAL PHARMACOLOGY LA English DT Article ID ETHANOL; MICE; IMMUNOASSAY; TIME AB 1. In Lewis (LEW), Fischer 344 (F344), Spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats, pentobarbital (PB)-induced sleep time was much longer in female than in male rats. 2. At the time of awakening, brain levels of PB were significantly higher in the female F344 than in the male rats, but there was no sex differences in other strains. 3. Each strain of rats was treated with PB-admixed food for 47 days. There were significant sex differences in mean drug intake of the SHR and LEW strains, but not the WKY and F344 strains during the final concentration. 4- Only female rats exhibited moderate to severe motor impairment by PB. 5. After PB treatment ended, various signs of PB withdrawal occurred in female, but not male, rats. These marked sex differences were observed in all four inbred strains. 6. The sex differences in physical dependence on PB may be due mainly to differences in rates of drug metabolism for the LEW, SHR and WKY rats, and to differences in CNS sensitivity for the F344 rats. C1 UNIV MINNESOTA,SCH MED,DEPT PSYCHIAT & PHARMACOL,MINNEAPOLIS,MN 55455. NIDA,ADDICT RES CTR,PRECLIN PHARMACOL BRANCH,BEHAV GENET LAB,BALTIMORE,MD 21224. UNIV MARYLAND,SCH PHARM,DEPT PHARMACOL & TOXICOL,COLLEGE PK,MD 20742. RP SUZUKI, T (reprint author), HOSHI UNIV,SCH PHARM,DEPT PHARMACOL,SHINAGAWA KU,TOKYO 142,JAPAN. FU NIAAA NIH HHS [AA-06104, AA-06924]; NIDA NIH HHS [DA-00944] NR 14 TC 11 Z9 11 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-3623 J9 GEN PHARMACOL JI Gen. Pharmacol. PD MAY PY 1992 VL 23 IS 3 BP 487 EP 492 DI 10.1016/0306-3623(92)90116-2 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA HV109 UT WOS:A1992HV10900030 PM 1511856 ER PT J AU KITADA, K JOHNSTON, LH SUGINO, T SUGINO, A AF KITADA, K JOHNSTON, LH SUGINO, T SUGINO, A TI TEMPERATURE-SENSITIVE CDC7 MUTATIONS OF SACCHAROMYCES-CEREVISIAE ARE SUPPRESSED BY THE DBF4 GENE, WHICH IS REQUIRED FOR THE G1/S CELL-CYCLE TRANSITION SO GENETICS LA English DT Article ID PROTEIN-KINASE; DNA-SYNTHESIS; S-PHASE; YEAST; SEQUENCE; INITIATION; REPLICATION; HOMOLOGY; PRODUCT; ENCODES AB When present on a multicopy plasmid, a gene from a Saccharomyces cerevisiae genomic library suppresses the temperature-sensitive cdc7-1 mutation. The gene was identified as DBF4, which was previously isolated by complementation in dbf4-1 mutant cells and is required for the G1 --> S phase progression of the cell cycle. DBF4 has an open reading frame encoding 695 amino acid residues and the predicted molecular mass of the gene product is 80 kD. The suppression is allele-specific because a CDC7 deletion is not suppressed by DBF4. Suppression is mitosis-specific and the sporulation defect of cdc7 mutations is not suppressed by DBF4. Conversely, CDC7 on a multicopy plasmid suppresses the dbf4-1, -2, -3 and -4 mutations but not dbf4-5 and DBF4 deletion mutations. Furthermore, cdc7 mutations are incompatible with the temperature-sensitive dbf4 mutations. These results suggest that the CDC7 and DBF4 polypeptides interact directly or indirectly to permit initiation of yeast chromosome replication. C1 NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709. NATL INST MED RES,CELL PROPAGAT LAB,LONDON NW7 1AA,ENGLAND. NR 38 TC 82 Z9 83 U1 1 U2 2 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD MAY PY 1992 VL 131 IS 1 BP 21 EP 29 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA HR346 UT WOS:A1992HR34600005 PM 1592236 ER PT J AU DEAN, M WHITE, MB GERRARD, B MILUNSKY, A AMOS, J AF DEAN, M WHITE, MB GERRARD, B MILUNSKY, A AMOS, J TI A 22-BP DELETION IN THE CODING REGION OF THE CYSTIC-FIBROSIS GENE SO GENOMICS LA English DT Note ID MUTATIONS C1 NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. BOSTON UNIV,MED CTR,CTR HUMAN GENET,BOSTON,MA 02118. RP DEAN, M (reprint author), FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702, USA. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 FU NCI NIH HHS [N01-CO-74102] NR 8 TC 8 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD MAY PY 1992 VL 13 IS 1 BP 235 EP 236 DI 10.1016/0888-7543(92)90233-I PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA HM699 UT WOS:A1992HM69900041 PM 1374361 ER PT J AU GREWAL, RP MARTINEZ, M HOEHE, M BONNER, TI GERSHON, ES DETERAWADLEIGH, S AF GREWAL, RP MARTINEZ, M HOEHE, M BONNER, TI GERSHON, ES DETERAWADLEIGH, S TI GENETIC-LINKAGE MAPPING OF THE M4 HUMAN MUSCARINIC RECEPTOR (CHRM4) SO GENOMICS LA English DT Note ID PHYSICAL MAP; CHROMOSOME-11; REGION C1 NIMH,DIRP,CLIN NEUROGENET BRANCH,9000 ROCKVILLE PIKE,BLDG 10,RM 3N218,BETHESDA,MD 20892. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. NINCDS,DEV & METAB NEUROL BRANCH,BETHESDA,MD 20892. RI Martinez, Maria/B-3111-2013 OI Martinez, Maria/0000-0003-2180-4537 NR 12 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 0888-7543 J9 GENOMICS JI Genomics PD MAY PY 1992 VL 13 IS 1 BP 239 EP 240 DI 10.1016/0888-7543(92)90236-L PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA HM699 UT WOS:A1992HM69900044 PM 1577490 ER PT J AU STORM, HH CLEMMENSEN, IH MANDERS, T BRINTON, LA AF STORM, HH CLEMMENSEN, IH MANDERS, T BRINTON, LA TI SUPRAVAGINAL UTERINE AMPUTATION IN DENMARK 1978-1988 AND RISK OF CANCER SO GYNECOLOGIC ONCOLOGY LA English DT Article ID CERVICAL STUMP; HYSTERECTOMY; PROGRAM C1 NCI,ENVIRONM EPIDEMIOL BRANCH,ROCKVILLE,MD 20892. RP STORM, HH (reprint author), INST CANC EPIDEMIOL,DANISH CANC SOC,DANISH CANC REGISTRY,ROSENVAENGETS HOVEDVEJ 35,BOX 839,DK-2100 COPENHAGEN,DENMARK. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 FU NCI NIH HHS [N01-CP-85639-02] NR 24 TC 45 Z9 46 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAY PY 1992 VL 45 IS 2 BP 198 EP 201 DI 10.1016/0090-8258(92)90285-Q PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA HW355 UT WOS:A1992HW35500015 PM 1592287 ER PT J AU BREWERTON, TD MURPHY, DL LESEM, MD BRANDT, HA JIMERSON, DC AF BREWERTON, TD MURPHY, DL LESEM, MD BRANDT, HA JIMERSON, DC TI HEADACHE RESPONSES FOLLOWING META-CHLOROPHENYLPIPERAZINE IN BULIMICS AND CONTROLS SO HEADACHE LA English DT Article DE META-CHLOROPHENYLPIPERAZINE (META-CPP); SEROTONIN; BULIMIA; MIGRAINE ID BETA-ADRENERGIC RECEPTORS; SEROTONIN AGONIST; MIGRAINE HEADACHES; DEPRESSION; DISEASE AB We have previously reported that the serotonin (5-HT) agonist meta-chlorophenylpiperazine (m-CPP) induced late occurring migraine-like headaches in a group of patients with eating disorders and controls (n=52). 1 In this report, we extend our analyses of these data and describe results indicating that headache responses following m-CPP are greater in patients with bulimia nervosa than controls, regardless of the presence of anorexia nervosa or major depression. Although patients with severe migraine-like headaches had higher peak m-CPP levels than patients without severe headaches, these levels are not higher than other groups studied who did not get headaches. These findings suggest that post-synaptic 5-HT receptor sensitivity is altered in the vascular tissues of bulimic patients. Additional disturbances in 5-HT function, perhaps presynaptic ones, may be associated with anorexia nervosa and major depression. Similar alterations in other 5-HT pathways at or above the level of the hypothalamus may contribute to binge eating and other behavioral symptoms of bulimia nervosa. Further studies exploring the functional integrity of 5-HT receptors and their subtypes are warranted in bulimic patients, as well as in patients with nonbulimic anorexia nervosa, minor and major depression without an eating disorder, and migraine and other headache patients. C1 BETH ISRAEL HOSP,DEPT PSYCHIAT,BOSTON,MA 02215. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,BOSTON,MA 02215. UNIV MARYLAND,SCH MED,DEPT PSYCHIAT,BALTIMORE,MD 21201. UNIV TEXAS,HLTH SCI CTR,DEPT PSYCHIAT,HOUSTON,TX 77225. RP BREWERTON, TD (reprint author), MED UNIV S CAROLINA,INST PSYCHIAT,171 ASHLEY AVE,CHARLESTON,SC 29425, USA. NR 43 TC 20 Z9 20 U1 0 U2 0 PU AMER ASSOC STUDY HEADACHE PI WOODBURY PA 875 KINGS HIGHWAY, STE 200, WOODBURY, NJ 08096 SN 0017-8748 J9 HEADACHE JI Headache PD MAY PY 1992 VL 32 IS 5 BP 217 EP 222 DI 10.1111/j.1526-4610.1992.hed3205217.x PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA HW350 UT WOS:A1992HW35000001 PM 1628957 ER PT J AU SILBERSTEIN, SD FOZARD, JR MURPHY, DL AF SILBERSTEIN, SD FOZARD, JR MURPHY, DL TI MORE ON META-CPP AND MIGRAINE SO HEADACHE LA English DT Letter C1 TEMPLE UNIV,HLTH SCI CTR,SCH MED,PHILADELPHIA,PA 19140. SANDOZ LTD,PRECLIN RES,CH-4002 BASEL,SWITZERLAND. NIH,CTR CLIN,CLIN SCI LAB,BETHESDA,MD 20892. RP SILBERSTEIN, SD (reprint author), GERMANTOWN HOSP & MED CTR,CTR COMPREHENS HEADACHE,NEUROL SECT,PHILADELPHIA,PA 19144, USA. NR 7 TC 7 Z9 7 U1 0 U2 0 PU AMER ASSOC STUDY HEADACHE PI WOODBURY PA 875 KINGS HIGHWAY, STE 200, WOODBURY, NJ 08096 SN 0017-8748 J9 HEADACHE JI Headache PD MAY PY 1992 VL 32 IS 5 BP 242 EP 243 DI 10.1111/j.1526-4610.1992.hed3205242_1.x PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA HW350 UT WOS:A1992HW35000007 PM 1628963 ER PT J AU DECHESNE, CJ KIM, HN NOWAK, TS WENTHOLD, RJ AF DECHESNE, CJ KIM, HN NOWAK, TS WENTHOLD, RJ TI EXPRESSION OF HEAT-SHOCK PROTEIN, HSP72, IN THE GUINEA-PIG AND RAT COCHLEA AFTER HYPERTHERMIA - IMMUNOCHEMICAL AND INSITU HYBRIDIZATION ANALYSIS SO HEARING RESEARCH LA English DT Article DE HSP72; HYPERTHERMIA; COCHLEA; IMMUNOBLOTTING; IMMUNOCYTOCHEMISTRY; INSITU HYBRIDIZATION; GUINEA PIG; RAT ID MESSENGER-RNA; INNER-EAR; BRAIN; ISCHEMIA; INDUCTION; LOCALIZATION; TRAUMA; GENE; TISSUES; DAMAGE AB The induction of the heat shock protein, HSP72, was studied in the cochlea of guinea pigs and rats subjected to a hyperthermic stress. Analyses were done by immunoblotting and immunocytochemistry at 6 and 12 h after heat shock, using a commercially available monoclonal antibody (Amersham), and by in situ hybridization 1 h after heat shock using an oligonucleotide probe. In guinea pig immunoblots of the cochlea, HSP72 was present in both unstressed and heat stressed animals and immunocytochemistry did not reveal any difference of staining between them. As opposed to guinea pig, HSP72 was not found in unstressed rat cochlea. Heat shock induced HSP72 expression in most inner ear tissues of the rat examined by immunoblotting. Immunocytochemistry and in situ hybridization localized HSP72 synthesis in ganglion neurons, Schwann cells, spiral limbus, spiral ligament and stria vascularis. The strongest immunoreactivity and highest density of silver grains were seen in the stria vascularis. All blood vessels were strongly immunoreactive and were outlined with silver grains. These results show that HSP72 synthesis can be induced by hyperthermia in rat cochlea and suggest that this protein could be a useful marker for assessment of the effects of specific stresses in this organ. C1 NIDCD,NEUROCHEM LAB,BETHESDA,MD. NINCDS,STROKE BRANCH,BETHESDA,MD 20892. RP DECHESNE, CJ (reprint author), UNIV MONTPELLIER 2,INSERM,U254,NEUROPHYSIOL SENSORIELLE LAB,CP 089,PL BATAILLON,F-34095 MONTPELLIER 05,FRANCE. NR 37 TC 34 Z9 35 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD MAY PY 1992 VL 59 IS 2 BP 195 EP 204 DI 10.1016/0378-5955(92)90116-5 PG 10 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA HU756 UT WOS:A1992HU75600009 PM 1618710 ER PT J AU VITIELLO, B BEHAR, D AF VITIELLO, B BEHAR, D TI MENTAL-RETARDATION AND PSYCHIATRIC-ILLNESS SO HOSPITAL AND COMMUNITY PSYCHIATRY LA English DT Article ID FRAGILE-X-SYNDROME; RETARDED ADULTS; BEHAVIOR DISTURBANCE; DOWNS-SYNDROME; DEPRESSION; DISORDERS; HANDICAP; PEOPLE; MORBIDITY; CHILDREN AB Although traditional diagnostic criteria are accepted for use with mentally retarded persons, diagnosis of psychiatric disorders in this population is often complicated by clinicians' ignoring or underestimating such disorders and by patients' communication problems. The revision of DSM-III and changes in policies of third-party payers have sensitized clinicians to the presence of psychopathology among mentally retarded persons. The authors discuss the relationship between mental illness and mental retardation and review recent research on the diagnosis of specific psychiatric disorders in these patients. Some problems, such as behavioral disruptiveness, psychoses, and phobias, are more prevalent among mentally retarded persons than among other populations, whereas other problems, such as alcoholism and suicide, may be less common. C1 MED COLL PENN,EASTERN PENN PSYCHIAT INST,3200 HENRY AVE,PHILADELPHIA,PA 19129. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. FU PHS HHS [R01-H-43851] NR 68 TC 22 Z9 22 U1 2 U2 2 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0022-1597 J9 HOSP COMMUNITY PSYCH PD MAY PY 1992 VL 43 IS 5 BP 494 EP 499 PG 6 WC Public, Environmental & Occupational Health; Psychiatry SC Public, Environmental & Occupational Health; Psychiatry GA HQ847 UT WOS:A1992HQ84700013 PM 1587514 ER PT J AU SUDO, K MAEKAWA, M TOMONAGA, A TSUKADA, T NAKAYAMA, T KITAMURA, M LI, SSL KANNO, T TORIUMI, J AF SUDO, K MAEKAWA, M TOMONAGA, A TSUKADA, T NAKAYAMA, T KITAMURA, M LI, SSL KANNO, T TORIUMI, J TI MOLECULAR CHARACTERIZATION OF GENETIC MUTATIONS IN HUMAN LACTATE-DEHYDROGENASE (LDH)-B (H) VARIANT SO HUMAN GENETICS LA English DT Article ID AMINO-ACID-SEQUENCE; PROTEIN SEQUENCES; A ISOZYME; B HEART; SUBUNIT; MUSCLE; MOUSE; CDNA; DEFICIENCY; DNA AB We have previously detected a single base substitution of G by A at the Arg codon CGC in exon 4 of the mutant lactate dehydrogenase (LDH) gene, an unstable LDH-B variant (case 1). Here, we use the polymerase chain reaction (PCR) to amplify genomic DNA of two cases (the original case 1 and a new patient, case 2). We were able to confirm that case 1 is homozygous for the mutation, causing a replacement of the conserved Arg by His at residue 173. The resulting LDH-B variant subunit is unstable in vivo. Whereas the mutation in exon 4 was not observed in case 2, a different single base substitution of A by C was detected at the Ser codon AGT in exon 3. This mutation causes a replacement of the conserved Ser by Arg at residue 131. Genomic analysis of the family of case 2 by mismatched PCR showed that the missense mutation was consistent with their biochemical phenotypes. The replacement results in a conformational change of the residues near the Ser, probably because the side chain of Arg is much more bulky than that of Ser. The change may affect the arrangement of the cofactor binding site and result in the loss of enzyme activity. The experimental observations are consistent with computer graphics analyses. C1 HAMAMATSU UNIV SCH MED, DEPT LAB MED, HAMAMATSU, SHIZUOKA 431-31, JAPAN. KUREHA CHEM IND CO LTD, SHINJUKU KU, TOKYO 169, JAPAN. TORANOMON GEN HOSP, DEPT CLIN CHEM, MINATO KU, TOKYO 105, JAPAN. OGATA INST MED & CHEM RES, TIYODA KU, TOKYO 101, JAPAN. NIEHS, GENET LAB, RES TRIANGLE PK, NC 27709 USA. RP SUDO, K (reprint author), JIKEI UNIV, DAISAN HOSP, SCH MED, DEPT LAB MED, 4-11-1 IZUMI HONCHO, KOMAE 201, JAPAN. NR 32 TC 12 Z9 13 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD MAY PY 1992 VL 89 IS 2 BP 158 EP 162 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA HU979 UT WOS:A1992HU97900004 PM 1587525 ER PT J AU MULLER, B DECHANT, C MENG, G LIECHTIGALLATI, S DOHERTY, RA HEITMANCIK, JF BAKKER, E READ, AP JEANPIERRE, M FISCHBECK, KH ROMEO, G FRANCKE, U WILICHOWSKI, E GREENBERG, CR VAN BROECKHOVEN, C JUNIEN, C MULLER, CR GRIMM, T AF MULLER, B DECHANT, C MENG, G LIECHTIGALLATI, S DOHERTY, RA HEITMANCIK, JF BAKKER, E READ, AP JEANPIERRE, M FISCHBECK, KH ROMEO, G FRANCKE, U WILICHOWSKI, E GREENBERG, CR VAN BROECKHOVEN, C JUNIEN, C MULLER, CR GRIMM, T TI ESTIMATION OF THE MALE AND FEMALE MUTATION-RATES IN DUCHENNE MUSCULAR-DYSTROPHY (DMD) SO HUMAN GENETICS LA English DT Article ID SEGREGATION ANALYSIS; PRENATAL-DIAGNOSIS; GERMLINE MOSAICISM; FAMILIES; POWER AB We present the results of an international collaborative study aimed at estimating the ratio of male to female mutation rates in Duchenne muscular dystrophy based on the method of C. Muller and T. Grimm. With a sample size of 295, this ratio is found to be very close to 1, thus giving evidence for equal mutation rates in males and females in Duchenne muscular dystrophy. C1 UNIV WURZBURG, INST HUMAN GENET, W-8700 WURZBURG, GERMANY. INSELSPITAL BERN, MED GENET ABT, CH-3010 BERN, SWITZERLAND. FDN BLOOD RES, SCARBOROUGH, ME 04074 USA. NEI, BETHESDA, MD 20892 USA. LEIDEN UNIV, DEPT HUMAN GENET, 2300 RA LEIDEN, NETHERLANDS. UNIV MANCHESTER, DEPT MED GENET, MANCHESTER M13 9PL, LANCS, ENGLAND. HOP COCHIN, BIOCHIM GENET LAB, F-75674 PARIS 14, FRANCE. UNIV PENN, DEPT NEUROL, PHILADELPHIA, PA 19104 USA. IST GIANNINA GASLINI, I-16148 GENOA, ITALY. STANFORD UNIV, MED CTR, HOWARD HUGHES MED INST, STANFORD, CA 94305 USA. STANFORD UNIV, MED CTR, DEPT GENET, STANFORD, CA 94305 USA. UNIV GOTTINGEN, INST HUMAN GENET, NEUROPADIAT ABT, W-3400 GOTTINGEN, GERMANY. UNIV MANITOBA, FAC MED, WINNIPEG R3T 2N2, MANITOBA, CANADA. UNIV INSTELLING ANTWERP, DEPT BIOCHEM, B-2610 WILRIJK, BELGIUM. INSERM, U73, F-75005 PARIS, FRANCE. RP MULLER, B (reprint author), UNIV MUNICH, KINDER POLIKLIN, PADIATR GENET & PRANATALE DIAGNOST ABT, GOETHESTR 29, W-8000 MUNICH 2, GERMANY. RI Bakker, Egbert/D-3525-2009; Muller-Myhsok, Bertram/A-3289-2013 OI Bakker, Egbert/0000-0002-2843-7357; NR 15 TC 8 Z9 8 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 EI 1432-1203 J9 HUM GENET JI Hum. Genet. PD MAY PY 1992 VL 89 IS 2 BP 204 EP 206 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA HU979 UT WOS:A1992HU97900012 PM 1587532 ER PT J AU TRAVIS, WD FOX, CH DEVANEY, KO WEISS, LM OLEARY, TJ OGNIBENE, FP SUFFREDINI, AF ROSEN, MJ COHEN, MB SHELHAMER, J AF TRAVIS, WD FOX, CH DEVANEY, KO WEISS, LM OLEARY, TJ OGNIBENE, FP SUFFREDINI, AF ROSEN, MJ COHEN, MB SHELHAMER, J TI LYMPHOID PNEUMONITIS IN 50 ADULT PATIENTS INFECTED WITH THE HUMAN-IMMUNODEFICIENCY-VIRUS - LYMPHOCYTIC INTERSTITIAL PNEUMONITIS VERSUS NONSPECIFIC INTERSTITIAL PNEUMONITIS SO HUMAN PATHOLOGY LA English DT Article DE LUNG; LYMPHOCYTIC INTERSTITIAL PNEUMONITIS; NONSPECIFIC INTERSTITIAL PNEUMONITIS; HUMAN IMMUNODEFICIENCY VIRUS; ACQUIRED IMMUNODEFICIENCY SYNDROME; LYMPHOCYTIC ALVEOLITIS; EPSTEIN-BARR VIRUS; CYTOMEGALOVIRUS ID IMMUNE-DEFICIENCY-SYNDROME; BRONCHOALVEOLAR LAVAGE FLUID; PNEUMOCYSTIS-CARINII PNEUMONIA; AIDS-RELATED LYMPHADENOPATHY; FOLLICULAR DENDRITIC CELLS; SYNDROME-RELATED COMPLEX; PULMONARY INVOLVEMENT; HIV INFECTION; LYMPHOPROLIFERATIVE DISORDER; LUNG DISORDERS C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NIH,DEPT CRIT CARE MED,WARREN MAGNUSON CLIN CTR,BETHESDA,MD 20892. ARMED FORCES INST PATHOL,DEPT ORTHOPED PATHOL,WASHINGTON,DC 20306. ARMED FORCES INST PATHOL,DEPT CELLULAR PATHOL,WASHINGTON,DC 20306. CITY HOPE NATL MED CTR,DEPT PATHOL,DUARTE,CA 91010. BETH ISRAEL MED CTR,DEPT PULM MED,NEW YORK,NY 10003. UNIV IOWA,DEPT PATHOL,IOWA CITY,IA 52242. RP TRAVIS, WD (reprint author), NCI,PATHOL LAB,BLDG 10,ROOM 2N212,BETHESDA,MD 20892, USA. NR 69 TC 106 Z9 107 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 MAY PY 1992 VL 23 IS 5 BP 529 EP 541 DI 10.1016/0046-8177(92)90130-U PG 13 WC Pathology SC Pathology GA HU056 UT WOS:A1992HU05600010 PM 1314778 ER PT J AU HIJAZI, YM NIEMAN, LK MEDEIROS, LJ AF HIJAZI, YM NIEMAN, LK MEDEIROS, LJ TI MEDULLARY CARCINOMA OF THE THYROID AS A CAUSE OF CUSHINGS-SYNDROME - A CASE WITH ECTOPIC ADRENOCORTICOTROPIN SECRETION CHARACTERIZED BY DOUBLE ENZYME IMMUNOSTAINING SO HUMAN PATHOLOGY LA English DT Article DE MEDULLARY CARCINOMA OF THYROID; CUSHINGS SYNDROME; CALCITONIN; ACTH; DOUBLE IMMUNOSTAINING ID CORTICOTROPIN-RELEASING FACTOR; ACTH; CALCITONIN; CELLS; SOMATOSTATIN C1 NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. RP HIJAZI, YM (reprint author), NCI,PATHOL LAB,SURG PATHOL SECT,BLDG 10,ROOM 2A10,BETHESDA,MD 20892, USA. NR 17 TC 15 Z9 15 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 MAY PY 1992 VL 23 IS 5 BP 592 EP 596 DI 10.1016/0046-8177(92)90140-X PG 5 WC Pathology SC Pathology GA HU056 UT WOS:A1992HU05600020 PM 1568756 ER PT J AU COHEN, MH ANDREOU, AG AF COHEN, MH ANDREOU, AG TI CURRENT-MODE SUBTHRESHOLD MOS IMPLEMENTATION OF THE HERAULT-JUTTEN AUTOADAPTIVE NETWORK SO IEEE JOURNAL OF SOLID-STATE CIRCUITS LA English DT Article ID INTEGRATED-CIRCUITS; ANALOG; ARRAY AB In this paper we explore translinear circuits in subthreshold MOS technology and current-mode design techniques for the implementation of neuromorphic analog network processing. The architecture, also known as the Herault-Jutten (H-J) network, performs an independent component analysis and is essentially a continuous-time recursive linear adaptive filter. Analog I/O interface, weight coefficients, and adaptation blocks are all integrated on the chip. A small network with six neurons and 30 synapses was fabricated in a 2-mu-n-well double-polysilicon, double-metal CMOS process. Circuit designs at the transistor level yield area-efficient implementations for neurons, synapses, and the adaptation blocks. We discuss the design methodology and constraints as well as test results from the fabricated chips. C1 JOHNS HOPKINS UNIV, DEPT ELECT & COMP ENGN, BALTIMORE, MD 21218 USA. RP NEI, BETHESDA, MD 20892 USA. RI Andreou, Andreas G./A-3271-2010 OI Andreou, Andreas G./0000-0003-3826-600X NR 40 TC 26 Z9 26 U1 1 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9200 EI 1558-173X J9 IEEE J SOLID-ST CIRC JI IEEE J. Solid-State Circuit PD MAY PY 1992 VL 27 IS 5 BP 714 EP 727 DI 10.1109/4.133158 PG 14 WC Engineering, Electrical & Electronic SC Engineering GA HP270 UT WOS:A1992HP27000004 ER PT J AU LLOYD, AR OPPENHEIM, JJ AF LLOYD, AR OPPENHEIM, JJ TI POLYS LAMENT - THE NEGLECTED ROLE OF THE POLYMORPHONUCLEAR NEUTROPHIL IN THE AFFERENT LIMB OF THE IMMUNE-RESPONSE SO IMMUNOLOGY TODAY LA English DT Article ID COLONY-STIMULATING FACTOR; TUMOR-NECROSIS-FACTOR; PERIPHERAL-BLOOD NEUTROPHILS; MESSENGER-RNA; GROWTH-FACTOR; FACTOR-ALPHA; LEUKOCYTES; EXPRESSION; CELLS; INTERLEUKIN-6 AB The polymorphonuclear leucocyte (PMN) has traditionally been thought to participate in the inflammatory response only as an effector cell. However, recent data demonstrate that PMNs can synthesize and release cytokines, such as IL-1, TNF-alpha and IL-6, and hence modulate both T- and B-cell activities in the evolution of an immune response. RP LLOYD, AR (reprint author), NCI,MOLEC IMMUNOREGULAT LAB,FREDERICK,MD 21702, USA. NR 38 TC 385 Z9 388 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD MAY PY 1992 VL 13 IS 5 BP 169 EP 172 DI 10.1016/0167-5699(92)90121-M PG 4 WC Immunology SC Immunology GA HR184 UT WOS:A1992HR18400006 PM 1642755 ER PT J AU HEBERT, CD ENDO, S KORACH, KS BOYD, J BARRETT, JC MCLACHLAN, JA NEWBOLD, RR AF HEBERT, CD ENDO, S KORACH, KS BOYD, J BARRETT, JC MCLACHLAN, JA NEWBOLD, RR TI CHARACTERIZATION OF MURINE CELL-LINES FROM DIETHYLSTILBESTROL-INDUCED UTERINE ENDOMETRIAL ADENOCARCINOMAS SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Article DE UTERINE ADENOCARCINOMA; DIETHYLSTILBESTROL; HORMONAL CARCINOGENESIS ID NEOPLASTIC TRANSFORMATION; EMBRYO FIBROBLASTS; CARCINOMA; GENE; CARCINOGENESIS; ACTIVATION; ONCOGENE; CULTURE AB Neonatal treatment with estrogens is associated with development of uterine adenocarcinomas in CD-1 mice. Treatment with the synthetic estrogen diethylstilbestrol (DES) on Days 1 to 5 after birth results in 90% incidence of these hormone-dependent lesions in 18-mo.-old mice. Three cell lines were established from these DES-associated tumors. Each of these cell lines exhibited morphologic and ultrastructural characteristics of transformed epithelial cells, including an increased nuclear:cytoplasmic ratio, enlarged and irregular nuclei with multiple nucleoli and areas of chromatin condensation, positive staining for cytokeratin, desmosomes, and microvilli. After subcutaneous injection into nude mice, all three cell lines formed solid tumors within 4 wk. Although the primary uterine tumors and tumor transplants in nude mice had been shown to be estrogen-dependent and estrogen-receptor positive, neither the monolayer growth nor the tumorigenicity of any of the three cell lines in this study was enhanced by or dependent on estrogen. Estrogen receptor levels were low in early and intermediate passage cells. Allele-specific oligonucleotide hybridization analysis of PCR-amplified cell line DNA revealed no point mutations in the 12th, 13th, or 61st codons of the K-ras or H-ras protooncogenes. Southern analysis revealed no changes in genomic organization of the putative tumor suppressor gene DCC, but demonstrated a three- to four-fold amplification of the c-myc gene in one cell line. Expression of c-myc RNA was concomitantly increased in the same cell line. These three transformed cell lines represent thc end point in the process of hormone-associated tumorigenesis and as such should prove useful in investigating the molecular changes and the mechanisms involved in hormonal carcinogenesis. C1 NIEHS,DIV INTRAMURAL RES,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. RP HEBERT, CD (reprint author), NIEHS,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC 27709, USA. OI Korach, Kenneth/0000-0002-7765-418X NR 24 TC 3 Z9 3 U1 0 U2 0 PU SOC IN VITRO BIOLOGY PI COLUMBIA PA 8815 CENTRE PARK DR,STE 210, COLUMBIA, MD 21045 SN 1071-2690 J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD MAY PY 1992 VL 28A IS 5 BP 327 EP 336 PG 10 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA HW839 UT WOS:A1992HW83900007 ER PT J AU KWONCHUNG, KJ WICKES, BL STOCKMAN, L ROBERTS, GD ELLIS, D HOWARD, DH AF KWONCHUNG, KJ WICKES, BL STOCKMAN, L ROBERTS, GD ELLIS, D HOWARD, DH TI VIRULENCE, SEROTYPE, AND MOLECULAR CHARACTERISTICS OF ENVIRONMENTAL STRAINS OF CRYPTOCOCCUS-NEOFORMANS VAR GATTII SO INFECTION AND IMMUNITY LA English DT Article ID EPIDEMIOLOGIC DIFFERENCES; FILOBASIDIELLA AB Four strains of Cryptococcus neoformans var. gattii originating from Eucalyptus camaldulensis, three from Australia and one from San Francisco, were tested for their serotype, virulence for mice, and a number of genetic and molecular characteristics. All were found to be serotype B and showed significantly higher virulence for mice than did the type strains of C. neoformans var. gattii and Filobasidiella neoformans var. bacillispora, which were obtained from human cryptococcosis cases. Electrophoretic karyotypes of the strains from Australia were identical, although they were collected from sites at least 15 to 500 km apart. The electrophoretic karyotype of the strain from San Francisco was the same as that of the Australian isolates except for the mobility of one chromosome. On the contrary, no two isolates of serotype B (of a total of 11) from clinical sources were the same, regardless of their geographic origin. Furthermore, none of the clinical isolates showed a chromosomal banding pattern identical to that of Eucalyptus-originated strains. The Eucalyptus-originated strains failed to form dikaryons when crossed with the tester strains of the two varieties of F. neoformans. Hybridization analysis with a nucleic acid probe (AccuProbe C. neoformans Culture Confirmation Test; Gen-Probe Inc., San Diego, Calif.), however, showed signals of equal intensity for clinical strains and the Eucalyptus-originated strains. Various fungi phylogenetically related to C. neoformans, including a phenol oxidase-positive strain of Cryptococcus laurentii obtained from E. camaldulensis, were negative in the nucleic acid hybridization test. These observations confirm that, in spite of karyotypic differences and the lack of dikaryon formation with the tester strains of F. neoformans, Eucalyptus-originated C. neoformans var. gattii is the same organism as those isolated from cases of human infection. Furthermore, the C. neoformans culture confirmation test using a commercial nucleic acid probe is specific for C. neoformans. C1 MAYO CLIN & MAYO FDN,CLIN MICROBIOL SECT,ROCHESTER,MN 55905. ADELAIDE CHILDRENS HOSP INC,ADELAIDE,SA 5006,AUSTRALIA. UNIV CALIF LOS ANGELES,SCH MED,DEPT MICROBIOL & IMMUNOL,LOS ANGELES,CA 90024. RP KWONCHUNG, KJ (reprint author), NIAID,CLIN INVEST LAB,BETHESDA,MD 20892, USA. RI Ellis, David/B-3677-2011 NR 29 TC 77 Z9 85 U1 3 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 1992 VL 60 IS 5 BP 1869 EP 1874 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA HR065 UT WOS:A1992HR06500023 PM 1563776 ER PT J AU HOLLAND, SM HUDSON, AP BOBO, L WHITTUMHUDSON, JA VISCIDI, RP QUINN, TC TAYLOR, HR AF HOLLAND, SM HUDSON, AP BOBO, L WHITTUMHUDSON, JA VISCIDI, RP QUINN, TC TAYLOR, HR TI DEMONSTRATION OF CHLAMYDIAL RNA AND DNA DURING A CULTURE-NEGATIVE STATE SO INFECTION AND IMMUNITY LA English DT Article ID POLYMERASE CHAIN-REACTION; GAMMA-INTERFERON; DISEASE PATHOGENESIS; ANIMAL-MODEL; HOST DEFENSE; ROLE INVIVO; TRACHOMATIS; INFECTION; HYPERSENSITIVITY; PROTEIN AB Trachoma is a common blinding disease of humans caused by ocular infections with Chlamydia trachomatis. The cynomolgus monkey is a valuable primate model for the detection, pathobiology, and treatment of this infection. We have used this model system to compare the relative ability of tissue culture, direct fluorescence cytology, a modified polymerase chain reaction, and RNA blotting to detect C. trachomatis following primary infection and reinfection over 34 weeks. Six cynomolgus monkeys were given a primary ocular chlamydia infection, and 20 weeks later they were reinoculated with the same organism. All animals showed brisk inflammatory responses to the primary infection and milder inflammatory reactions to reinfection. All four diagnostic techniques detected chlamydia at 1 week after primary infection, but both nucleic acid detection methods suggested that organisms were present longer after primary infection than did either tissue culture or direct fluorescence cytology (16 weeks for RNA blotting versus 12 weeks for tissue culture). Following reinoculation at 20 weeks, the period of C. trachomatis detection by tissue culture or direct fluorescence cytology (4 weeks) was much shorter than after primary infection. In contrast, nucleic acid detection was positive for up to 5 weeks longer than tissue culture or direct fluorescence cytology. Both polymerase chain reaction and RNA blotting, which involved no amplification step, indicated the presence of organisms during the culture-negative period. These data suggest that live chlamydiae may remain at a site of infection and produce inflammation beyond the time at which standard microbiological techniques are able to detect them. C1 JOHNS HOPKINS UNIV HOSP,DIV PEDIAT INFECT DIS,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV HOSP,DANA CTR PREVENT OPHTHALMOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,WILMER INST,IMMUNOL LABS,BALTIMORE,MD 21205. NIMH,HOST DEF LAB,BETHESDA,MD 20892. NIMH,IMMUNOREGULAT LAB,BETHESDA,MD 20892. MED COLL PENN,DEPT MICROBIOL & IMMUNOL,PHILADELPHIA,PA 19129. RP HOLLAND, SM (reprint author), JOHNS HOPKINS UNIV HOSP,DIV INFECT DIS,BALTIMORE,MD 21205, USA. OI Taylor, Hugh/0000-0002-9437-784X NR 32 TC 69 Z9 69 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 1992 VL 60 IS 5 BP 2040 EP 2047 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA HR065 UT WOS:A1992HR06500049 PM 1373404 ER PT J AU RACKE, MK CANNELLA, B ALBERT, P SPORN, M RAINE, CS MCFARLIN, DE AF RACKE, MK CANNELLA, B ALBERT, P SPORN, M RAINE, CS MCFARLIN, DE TI EVIDENCE OF ENDOGENOUS REGULATORY FUNCTION OF TRANSFORMING GROWTH FACTOR-BETA-1 IN EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; TRANSFORMING GROWTH FACTOR-BETA ID MYELIN BASIC-PROTEIN; NECROSIS FACTOR-ALPHA; CENTRAL-NERVOUS-SYSTEM; FACTOR-BETA; ADOPTIVE TRANSFER; LYMPHOCYTES-T; CELLS; EXPRESSION; INVITRO; MICE AB Experimental allergic encephalomyelitis (EAE) is an autoimmune disease characterized by inflammation and demyelination in the central nervous system (CNS). Administration of transforming growth factor-beta (TGF-beta) has been shown to inhibit EAE. In this study, the possible role of endogenous TGF-beta in the regulation of relapsing EAE produced by the transfer of myelin basic protein-specific T cell lines was assessed. Although TGF-beta is not present in the normal CNS, this cytokine was detected by immunohistology in areas of central nervous system inflammation in both acute and chronic disease. The administration of anti-TGF-beta at the disease onset led to a worsening of the clinical course of EAE and more extensive pathological lesions. These findings provide direct evidence for a role of endogenous TGF-beta in the remissions seen in chronic relapsing EAE. C1 NINCDS,BIOMETRY & FIELD STUDIES BRANCH,BETHESDA,MD 20892. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. YESHIVA UNIV ALBERT EINSTEIN COLL MED,DIV NEUROPATHOL,BRONX,NY 10461. RP RACKE, MK (reprint author), NINCDS,NEUROIMMUNOL BRANCH,BETHESDA,MD 20892, USA. FU NINDS NIH HHS [NS 11920, NS 08952] NR 28 TC 111 Z9 112 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD MAY PY 1992 VL 4 IS 5 BP 615 EP 620 DI 10.1093/intimm/4.5.615 PG 6 WC Immunology SC Immunology GA HX034 UT WOS:A1992HX03400009 PM 1378298 ER PT J AU WUNDERLICH, JR MEZZANZANICA, D GARRIDO, MA NEBLOCK, DS DADDONA, PE ANDREW, SM ZURAWSKI, VR CANEVARI, S COLNAGHI, MI SEGAL, DM AF WUNDERLICH, JR MEZZANZANICA, D GARRIDO, MA NEBLOCK, DS DADDONA, PE ANDREW, SM ZURAWSKI, VR CANEVARI, S COLNAGHI, MI SEGAL, DM TI BISPECIFIC ANTIBODIES AND RETARGETED CELLULAR CYTOTOXICITY - NOVEL APPROACHES TO CANCER-THERAPY SO INTERNATIONAL JOURNAL OF CLINICAL & LABORATORY RESEARCH LA English DT Review DE BISPECIFIC ANTIBODY; OVARIAN CARCINOMA; ATHYMIC MICE ID HUMAN OVARIAN-CARCINOMA; LYMPHOCYTES-T; CELLS; MICE AB We have used a relatively new technology to increase the number of human lymphocytes that will react with human ovarian carcinoma cells. This technology, often called "retargeting of the immune system," can temporarily redirect the activity of immune cells that were originally committed to react with foreign substances other than cancer cells. In the example presented here, the antitumor effects of retargeted human T lymphocytes, collected from normal donors, were tested in immunodeficient mice with a human ovarian carcinoma line growing intraperitoneally. We retargeted T cells in vitro with a bispecific antibody that reacted with the T cell receptor complex and with a cell-surface antigen expressed by the ovarian carcinoma cells. Retargeted lymphocytes, injected intraperitoneally into mice 4 days after intraperitoneal injection of the tumor cells, impeded tumor growth and doubled the host survival time. These findings provide support for the concept that treatment of ovarian cancer patients with retargeted T cells could prove beneficial. C1 CENTOCOR INC,MALVERN,PA 19355. INST NAZL TUMORI,I-20133 MILAN,ITALY. HARVARD UNIV,SCH MED,DEPT OBSTET & GYNECOL,BOSTON,MA 02115. RP WUNDERLICH, JR (reprint author), NCI,EXPTL IMMUNOL BRANCH,BLDG 10,ROOM 4B-17,BETHESDA,MD 20892, USA. RI Mezzanzanica, Delia/C-2607-2017 OI Mezzanzanica, Delia/0000-0002-9664-6871 NR 19 TC 9 Z9 9 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0940-5437 J9 INT J CLIN LAB RES JI Int. J. Clin. Lab. Res. PD MAY PY 1992 VL 22 IS 1 BP 17 EP 20 DI 10.1007/BF02591388 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA HW201 UT WOS:A1992HW20100004 PM 1633315 ER PT J AU NEEL, NR GOLDENBERG, RL TAMURA, T CLIVER, SP AVENT, K HOFFMAN, HJ AF NEEL, NR GOLDENBERG, RL TAMURA, T CLIVER, SP AVENT, K HOFFMAN, HJ TI MATERNAL ALPHA-2-MACROGLOBULIN LEVELS AND FETAL GROWTH IN GUATEMALA SO INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS LA English DT Article DE ALPHA-2-MACROGLOBULIN; FETAL GROWTH; INTRAUTERINE GROWTH RETARDATION AB Maternal serum alpha-2-macroglobulin (alpha(2)M) levels were measured at the time of delivery in 244 women in the central highlands of Guatemala. Significantly higher alpha(2)M levels were found in thin women and in poor women. In multiple regression analysis controlling for gestational age, race, sex, maternal triceps skinfold thickness and socioeconomic status, high alpha(2)M levels were significantly associated with decreased birthweight. These findings agree with those in a predominantly black population in the United States and extend the relationship between alpha(2)M and decreased birthweight to a developing country. C1 NICHHD,PREVENT RES PROGRAM,BETHESDA,MD 20892. UNIV ALABAMA,DEPT MED,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT NUTR SCI,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT OBSTET & GYNECOL,PERINATAL EPIDEMIOL UNIT,BIRMINGHAM,AL 35294. RP NEEL, NR (reprint author), UNIV ALABAMA,SCH PUBL HLTH,DIV MATERNAL & CHILD HLTH,ROOM 235,TIDWELL HALL,BIRMINGHAM,AL 35294, USA. FU NICHD NIH HHS [N01-HD-4-2811] NR 20 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0020-7292 J9 INT J GYNECOL OBSTET JI Int. J. Gynecol. Obstet. PD MAY PY 1992 VL 38 IS 1 BP 25 EP 29 DI 10.1016/0020-7292(92)90725-X PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA HN780 UT WOS:A1992HN78000005 PM 1373694 ER PT J AU ROYCE, LS MARTIN, GR KLEINMAN, HK AF ROYCE, LS MARTIN, GR KLEINMAN, HK TI INDUCTION OF AN INVASIVE PHENOTYPE IN BENIGN-TUMOR CELLS WITH A LAMININ A-CHAIN SYNTHETIC PEPTIDE SO INVASION & METASTASIS LA English DT Article DE LAMININ; IKVAV-CONTAINING PEPTIDE; CLONE-10 CELL LINE; INVASIVE PHENOTYPE; MALIGNANCY; BASEMENT MEMBRANE ID IV COLLAGENASE ACTIVITY; AMINO-ACID-SEQUENCE; LUNG COLONIZATION; TISSUE INHIBITOR; MALIGNANT-CELLS; MELANOMA-CELLS; METASTASIS; MEMBRANE; METALLOPROTEINASES; IDENTIFICATION AB K-1735 clones 10 and M2 are cell lines cloned from a UV-induced murine melanoma. While both lines are highly tumorigenic, only the M2 cells are highly invasive in vitro and metastatic in vivo. Here we have exposed the clone 10 cells to the synthetic peptide PA22-2, which contains the IKVAV sequence from the A chain of laminin and which, like laminin, induces collagenase IV production and enhances metastasis formation by B16F10 cells. Zymogram analysis of conditioned media from clone 10 cells cultured on the peptide demonstrated a dose-dependent increase in collagenase IV activity. When clone 10 cells were cultured on a reconstituted basement membrane (Matrigel), this peptide caused an invasive phenotype comparable to the M2 cells. The invasive clone 10 cells were, however, unable to form lung colonies in vivo in the presence of this peptide. We conclude that this peptide represents an active site on laminin which is able to stimulate the invasiveness of this tumor cell line, but that this activity is not sufficient to confer metastatic potential. C1 NIDR,DEV BIOL LAB,BLDG 30,ROOM 407,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NIDR,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892. NIA,BALTIMORE,MD 21224. NR 33 TC 13 Z9 13 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0251-1789 J9 INVAS METAST JI Invasion Metastasis PD MAY-AUG PY 1992 VL 12 IS 3-4 BP 149 EP 155 PG 7 WC Oncology SC Oncology GA KP371 UT WOS:A1992KP37100001 PM 1294529 ER PT J AU MACKAY, AR BALLIN, M PELINA, MD FARINA, AR NASON, AM HARTZLER, JL THORGEIRSSON, UP AF MACKAY, AR BALLIN, M PELINA, MD FARINA, AR NASON, AM HARTZLER, JL THORGEIRSSON, UP TI EFFECT OF PHORBOL ESTER AND CYTOKINES ON MATRIX METALLOPROTEINASE AND TISSUE INHIBITOR OF METALLOPROTEINASE EXPRESSION IN TUMOR AND NORMAL-CELL LINES SO INVASION & METASTASIS LA English DT Article DE 12-O-TETRADECANOYLPHORBOL-13-ACETATE; INTERLEUKIN-1; TUMOR NECROSIS FACTOR-ALPHA; MATRIX METALLOPROTEINASES; METALLOPROTEINASE INHIBITORS; AP-1-BINDING PROTEIN ID PROTEIN-KINASE-C; HUMAN FIBROBLAST COLLAGENASE; HUMAN ALVEOLAR MACROPHAGES; NECROSIS FACTOR-ALPHA; IV COLLAGENASE; ENDOTHELIAL-CELLS; SYNOVIAL FIBROBLASTS; GENE-EXPRESSION; ONCOGENE; JUN AB The effect of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) and the cytokines interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) on matrix metalloproteinases (MMP) and metalloproteinase inhibitors was studied in a variety of human cell lines. Expression of the mammalian collagenase (MMP-1), 72-kD gelatinase/type IV collagenase (MMP-2), stromelysin (MMP-3), 92-kD getatinase/type IV collagenase (MMP-9), and tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) was assessed by zymography and Northern blot analysis. MMP-2 and TIMP-2 activities were refractory to TPA, IL-1 and TNF-alpha treatment in most of the cell lines. In contrast, MMP-3, MMP-9 and TIMP-1 activities were markedly stimulated by TPA in most of the tumor cell lines and human umbilical vein endothelial cells (HUVEC), whereas the fibroblast lines were minimally stimulated or unresponsive to TPA. The MMP-3, MMP-9 and TIMP-1 stimulation in response to IL-1 and TNF-alpha treatment was detected in some of the tumor cell lines and HUVEC. The increase in activity was less marked than in TPA. A breast carcinoma cell line, MDA-MB-231, which did not express MMP-2, had high expression of MMP-3 and MMP-9 which were unaffected bv TPA and cytokine treatment. Northern blot analysis of MMP and TIMP mRNA expression reflected the zymogram findings for most of the cell lines. TPA-mediated stimulation of MMP-1 was similar to that of MMP-3 and MMP-9. Exceptions were the fibroblast cell lines which showed either a much more marked mRNA response of MMP-9 to TPA than observed at protein level, or a high constitutive MMP-9 mRNA when MMP-9 activity was not detectable by zymography. TPA-mediated stimulation of MMP-9 and TIMP-1 activity was blocked by staurosporine, an inhibitor of protein kinase C (PKC). A non-PKC-activating phorbol ester, 4alpha-phorbol-12,13-didecanoate, did not stimulate MMP-9 and TIMP-1 activity. TPA treatment caused the increased expression of c-fos containing AP-1-specific binding activity in selected tumor cell lines. This activity was maximal at 6 h. An association was observed between AP-1 binding activity and increased expression of MMP-1, MMP-3 and MMP-9. which possess TPA-responsive elements (TRE). TPA-sensitive MMPs and TIMP-1 were variably stimulated by biologically relevant cytokines, such as IL-1 and TNF-alpha. TNF-alpha mediated an increase in MMP-9, but not TIMP-1 activity, in a lung carcinoma cell line (A-549). This suggests that cytokines may cause an imbalance in metalloproteinase and TIMP secretion by tumor cells in certain cases, which would favor extracellular matrix degradation. These data from a variety of normal and human tumor cell lines suggest that MMP-2 and TIMP-2 are regulated differently from MMP-1, MMP-3, MMP-9 and TIMP-1 by activators of PKC. C1 SPERIMENTALE COLLEMAGGIO,DIPARTIMENTO MED,LAQUILA,ITALY. RP MACKAY, AR (reprint author), NCI,DIV CANC ETIOL,OFF DIRECTOR,BETHESDA,MD 20892, USA. OI Mackay, Andrew Reay/0000-0001-7096-3759; FARINA, Antonietta Rosella/0000-0003-0962-6088 NR 62 TC 214 Z9 214 U1 3 U2 12 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0251-1789 J9 INVAS METAST JI Invasion Metastasis PD MAY-AUG PY 1992 VL 12 IS 3-4 BP 168 EP 184 PG 17 WC Oncology SC Oncology GA KP371 UT WOS:A1992KP37100003 PM 1284126 ER PT J AU HOOLEY, JM RICHTERS, JE AF HOOLEY, JM RICHTERS, JE TI ALLURE OF SELF-CONFIRMATION - A COMMENT SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Note AB Swann, Wenzlaff, Krull, and Pelham (1992) described the results of 4 studies designed to examine the relation of depression and negative feedback seeking. Unfortunately, problems of the characterization of subjects and of constructs, as well as the interpretation of data trends, combine to limit the conclusions that can be drawn from these studies. We provide a brief review of these problems. C1 NIMH,BETHESDA,MD 20892. RP HOOLEY, JM (reprint author), HARVARD UNIV,DEPT PSYCHOL,WILLIAM JAMES HALL,CAMBRIDGE,MA 02138, USA. RI Hooley, Jill/A-3945-2013 OI Hooley, Jill/0000-0002-1162-3540 NR 2 TC 10 Z9 10 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD MAY PY 1992 VL 101 IS 2 BP 307 EP 309 DI 10.1037/0021-843X.101.2.307 PG 3 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA HQ821 UT WOS:A1992HQ82100013 PM 1583223 ER PT J AU PHAIR, J JACOBSON, L DETELS, R RINALDO, C SAAH, A SCHRAGER, L MUNOZ, A AF PHAIR, J JACOBSON, L DETELS, R RINALDO, C SAAH, A SCHRAGER, L MUNOZ, A TI ACQUIRED-IMMUNE-DEFICIENCY-SYNDROME OCCURRING WITHIN 5 YEARS OF INFECTION WITH HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 - THE MULTICENTER AIDS COHORT STUDY SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE COFACTORS; HIV-1; MACS ID HOMOSEXUAL MEN; ASSOCIATION AB The objective of this study is to describe participants in the Multicenter AIDS Cohort Study (MACS) with incident infection due to the human immunodeficiency virus type-I (HIV-1) in whom AIDS developed by March 1990 and within 5 years of seroconversion (group A). Secondly, behavioral, clinical, and immunologic characteristics of these men are compared to those of matched seroconverters remaining AIDS free (group B). Between entry into the MACS (April 1984-March 1985) and July 1989, 345 seronegative homosexual/bisexual men had HIV-1 antibody; of these men, AIDS developed in 32 by March 1990. The Kaplan-Meier estimates of the proportion of men with incident HIV-1 infection with AIDS were 6 months. 0%; 12 months, 1%; 24 months, 3%; and 48 months, 10%. These 32 men engaged in receptive anal intercourse with more partners before (p < 0.005) and after seroconversion (p < 0.005) and reported more sexually transmitted disease preseroconversion (p = 0.05) than did group B. These findings suggest that sexually transmitted co-factors, preseroconversion and/or postseroconversion, play a role in the progression of HIV-1 infection. Alternatively, greater sexual activity could increase the hazard of exposure to a more virulent HIV-1 strain. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,BALTIMORE,MD 21218. UNIV CALIF LOS ANGELES,SCH PUBL HLTH,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,LOS ANGELES,CA 90024. UNIV PITTSBURGH,SCH PUBL HLTH,PITTSBURGH,PA 15260. NIAID,BETHESDA,MD 20892. RP PHAIR, J (reprint author), NORTHWESTERN UNIV,SCH MED,HOWARD BROWN MEM CLIN,CTR COMPREHENS AIDS,680 N LAKE SHORE DR,CHICAGO,IL 60611, USA. FU PHS HHS [N01-A1-32535, N01-A1-72634, N01-A1-72676] NR 13 TC 144 Z9 148 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD MAY PY 1992 VL 5 IS 5 BP 490 EP 496 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA HP068 UT WOS:A1992HP06800010 PM 1560346 ER PT J AU BARANIUK, JN SILVER, PB KALINER, MA BARNES, PJ AF BARANIUK, JN SILVER, PB KALINER, MA BARNES, PJ TI IBUPROFEN AUGMENTS BRADYKININ-INDUCED GLYCOCONJUGATE SECRETION BY HUMAN NASAL-MUCOSA INVIVO SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE BRADYKININ; IBUPROFEN; ALBUMIN; GLYCOCONJUGATE; MUCUS; LYSOZYME; MUCOSAL SECRETION; RHINITIS ID PLATELET-ACTIVATING-FACTOR; HUMAN AIRWAYS INVITRO; PATHO-PHYSIOLOGY; MONOHYDROXYEICOSATETRAENOIC ACID; RESPIRATORY GLYCOCONJUGATE; MUCUS HYPERSECRETION; TRACHEA INVIVO; GUINEA-PIG; RHINITIS; RELEASE AB Bradykinin (BK) stimulates vascular permeability and glycoconjugate secretion in human nasal mucosa. Since some of the effects of BK may be mediated by autocrine generation of arachidonic acid metabolites, the influence of ibuprofen, a cyclooxygenase inhibitor, on BK-induced nasal secretion was studied. Six normal male subjects had nasal provocations with 0, 10, 100, and 1000 nmol of BK before and after treatment with 400 mg of ibuprofen. Secretions were collected by nasal lavage. Total protein (marker of protein secretion), glycoconjugate (mucous cell marker), lysozyme (serous cell marker), and albumin (marker of vascular permeability) were measured. Basal glycoconjugate secretion was higher after ibuprofen (219 +/- 32-mu-g/ml) than before (81 +/- 56 -mu-g/ml; p < 0.05 by analysis of variance). BK stimulated significant, dose-dependent albumin, total protein, and glycoconjugate secretion. Lysozyme secretion was not stimulated. BK (1000 nmol) significantly increased total protein secretion, tenfold to twentyfold, and albumin secretion by 40-fold to 60-fold. Ibuprofen did not alter BK-induced total protein or albumin secretion. Glycoconjugate secretion after ibuprofen treatment was significantly higher than normal at 10 nmol (p < 0.05), 100 nmol (p < 0.02), and 1000 nmol of BK (519-mu-g/ml +/- 74 versus 213 +/- 15-mu-g/ml; p < 0.05). Therefore, BK induces vascular permeability and exocytosis from glycoconjugate-containing cells but does not stimulate serous cells. Ibuprofen increases baseline secretion of glycoconjugate and enhances BK-induced glycoconjugate secretion. Ibuprofen does not alter BK-induced vascular permeability. C1 NHLBI, DEPT THORAC MED, BETHESDA, MD 20892 USA. RP NIAID, CLIN INVEST LAB, ALLERG DIS SECT, BLDG 10, ROOM 11-C-205, BETHESDA, MD 20892 USA. NR 51 TC 11 Z9 11 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD MAY PY 1992 VL 89 IS 5 BP 1032 EP 1039 DI 10.1016/0091-6749(92)90226-R PG 8 WC Allergy; Immunology SC Allergy; Immunology GA HU542 UT WOS:A1992HU54200014 PM 1583245 ER PT J AU ENGEL, BT TALAN, MI CHEW, PH AF ENGEL, BT TALAN, MI CHEW, PH TI EFFECT OF NOCTURNAL ATRIAL DEMAND CARDIAC PACING ON DIURNAL HEMODYNAMIC PATTERNS SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE CIRCADIAN; PLASMA VOLUME; CARDIAC WORK ID OUTPUT; DOGS AB Heart rate (HR), stroke volume (SV), intra-arterial blood pressure, and central venous pressure were recorded on a beat-to-beat basis, 18 h/day (1800-1200 h the following day), for approximately 2 mo in four monkeys (Macaca mulatta). Cardiac output, left ventricular work, and total peripheral resistance were derived from these primary measurements. During the lst mo we measured these parameters under control conditions, and during the 2nd mo the animals were studied while HR was paced by atrial demand pacing sufficient to prevent the normal nocturnal fall in HR (approximately 10 beats/min above the fastest hourly average rate recorded during the control condition). The main hypothesis of this study was that when HR is prevented from falling, SV, which normally does not fall overnight, would fall; this hypothesis was confirmed. In addition, we observed that, during the period of pacing, relative to the control period, SV was approximately 14% greater during the early evening and 4% lower during the early morning; total peripheral resistance was similar during the early evening but was 13% higher by morning. Throughout the night, systolic pressure was approximately 4% greater, diastolic pressure was 17% higher, central venous pressure was 43% greater, and left ventricular work was 27% higher. These findings show that when HR is prevented from falling overnight by atrial demand pacing, even to a relatively modest degree, there can be very significant sustained changes in cardiovascular function. C1 NIA,GERONTOL RES CTR,BEHAV SCI LAB,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,DIV CARDIOL,FRANCIS SCOTT KEY MED CTR,BALTIMORE,MD 21224. NR 17 TC 6 Z9 6 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD MAY PY 1992 VL 72 IS 5 BP 1798 EP 1802 PG 5 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA HU331 UT WOS:A1992HU33100023 PM 1601788 ER PT J AU TALAN, MI ENGEL, BT CHEW, PH AF TALAN, MI ENGEL, BT CHEW, PH TI SYSTEMATIC NOCTURNAL ATRIAL DEMAND PACING RESULTS IN HIGH-OUTPUT HEART-FAILURE SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE CARDIOVASCULAR; CIRCADIAN; HEMODYNAMICS ID DOGS; TACHYCARDIA; PATTERNS AB Beat-to-beat parameters of heart rate (HR), intra-arterial blood pressure (BP), central venous pressure, and derived indexes of cardiac output and total peripheral resistance were recorded 18 h/day (from 1800 to 1200 h the following day) in four monkeys (Macaca mulatta) during 20 control days followed by 20 days of atrial demand pacing. The pacing rate was set at approximately 10 beats/min above the fastest hourly average HR recorded during the control period, i.e., sufficient to prevent the normal nocturnal fall in HR. Nocturnal pacing resulted in progressive weekly increases in central venous BP and arterial BP. Analyses of levels and diurnal trends in hemodynamic parameters and cardiac function curves across consecutive 5-day periods of nocturnal pacing revealed a hemodynamic pattern characteristic of high-output heart failure, which progressively increased (week by week) during the early morning hours (0500-0700). Sustained elevated left ventricular work resulting from the prevention of a nocturnal fall in HR may have been responsible for the reduction in cardiac function seen in this experimental model. C1 JOHNS HOPKINS UNIV,SCH MED,DIV CARDIOL,FRANCIS SCOTT KEY MED CTR,BALTIMORE,MD 21224. RP TALAN, MI (reprint author), NIA,GERONTOL RES CTR,BEHAV SCI LAB,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 17 TC 4 Z9 4 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD MAY PY 1992 VL 72 IS 5 BP 1803 EP 1809 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA HU331 UT WOS:A1992HU33100024 PM 1601789 ER PT J AU JENSEN, JC POGREBNIAK, HW PASS, HI BURESH, C MERINO, MJ KAUFFMAN, D VENZON, D LANGSTEIN, HN NORTON, JA AF JENSEN, JC POGREBNIAK, HW PASS, HI BURESH, C MERINO, MJ KAUFFMAN, D VENZON, D LANGSTEIN, HN NORTON, JA TI ROLE OF TUMOR-NECROSIS-FACTOR IN OXYGEN-TOXICITY SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE CYTOKINES; MANGANOUS SUPEROXIDE DISMUTASE; CACHECTIN; INTERLEUKIN-1 ID MANGANOUS SUPEROXIDE-DISMUTASE; PASSIVE-IMMUNIZATION; HUMAN NEUTROPHIL; FACTOR CACHECTIN; ENDOTOXIN; RATS; TNF; PROTECTION; INTERLEUKIN-6; EXPRESSION AB mRNA from lungs of mice exposed to high-dose oxygen (> 95%) for 3 days demonstrated increased expression of the genes for tumor necrosis factor (TNF), interleukin-1, and interleukin-6 compared with mRNA from lungs of mice exposed to room air. Daily treatment of mice exposed to high-dose oxygen with an antibody to TNF improved survival compared with mice receiving a similar dose of control immunoglobulin G. Pretreatment of mice with repetitive sublethal intraperitoneal doses of recombinant human TNF for 3 days or a single intravenous dose followed by exposure to high-dose oxygen afforded a significant survival advantage compared with high-dose oxygen-exposed mice pretreated with vehicle or interleukin-1. The repetitive intraperitoneal TNF pretreatment reduced the development of interstitial pneumonitis, pulmonary edema, and lung weight gain associated with oxygen toxicity and enhanced expression of the gene for the free radical protective enzyme manganous superoxide dismutase in lung tissue, a gene that is augmented as mice are exposed to high-dose oxygen. Furthermore a single intravenous dose of TNF 24 h after oxygen exposure was still protective. The results suggest that the toxicity of oxygen therapy can be partially ameliorated by either treatment with anti-TNF antibody or pretreatment and early treatment with TNF. These findings are consistent with the hypothesis that oxygen exposure induces TNF, which causes part of the toxicity of high-dose oxygen, and that pretreatment or early treatment with TNF induces the gene for an enzyme that recently has been shown to be very effective in protecting mice from the toxicity of oxygen. C1 NCI,SURG BRANCH,SURG METAB SECT,BLDG 10,RM 2B07,BETHESDA,MD 20892. NCI,SURG BRANCH,THORAC ONCOL SECT,BETHESDA,MD 20892. NCI,RADIAT ONCOL BRANCH,PATHOL LAB,BETHESDA,MD 20892. NCI,BIOSTAT & DATA MANAGEMENT BRANCH,BETHESDA,MD 20892. RI Venzon, David/B-3078-2008 NR 34 TC 72 Z9 74 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD MAY PY 1992 VL 72 IS 5 BP 1902 EP 1907 PG 6 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA HU331 UT WOS:A1992HU33100036 PM 1601798 ER PT J AU THOMPSON, J NGUYEN, NY ROBRISH, SA AF THOMPSON, J NGUYEN, NY ROBRISH, SA TI SUCROSE FERMENTATION BY FUSOBACTERIUM-MORTIFERUM ATCC-25557 - TRANSPORT, CATABOLISM, AND PRODUCTS SO JOURNAL OF BACTERIOLOGY LA English DT Article ID CHEMICALLY DEFINED MEDIUM; STREPTOCOCCUS-MUTANS; NISIN PRODUCTION; PHOSPHOTRANSFERASE SYSTEM; NUCLEOTIDE-SEQUENCE; FERMENTING ABILITY; SUCROSE-6-PHOSPHATE HYDROLASE; KLEBSIELLA-PNEUMONIAE; NUCLEATUM ATCC-10953; FRUCTOSE METABOLISM AB Studies of sucrose utilization by Fusobacterium mortiferum ATCC 25557 have provided the first definitive evidence for phosphoenolpyruvate-dependent sugar:phosphotransferase activity in the family Bacteroidaceae. The phosphoenolpyruvate-dependent sucrose:phosphotransferase system and the two enzymes required for the dissimilation of sucrose 6-phosphate are induced specifically by growth of F. mortiferum on the disaccharide. Monomeric sucrose 6-phosphate hydrolase (M(r), 52,000) and a dimeric ATP-dependent frucktokinase (subunit M(r), 32,000) have been purified to electrophoretic homogeneity. The physicochemical and catalytic properties of these enzymes have been examined, and the N-terminal amino acid sequences for both proteins are reported. The characteristics of sucrose 6-phosphate hydrolase and fructokinase from F. mortiferum are compared with the same enzymes from both gram-positive and gram-negative species. Butyric, acetic, and D-lactic acids are the end products of sucrose fermentation by F. mortiferum. A pathway is proposed for the translocation, phosphorylation, and metabolism of sucrose by this anaerobic pathogen. C1 US FDA,CTR BIOL EVALUAT & RES DIV CYTOKINE BIOL,BETHESDA,MD 20014. RP THOMPSON, J (reprint author), NIDR,MICROBIAL ECOL LAB,BETHESDA,MD 20892, USA. NR 59 TC 17 Z9 19 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 MAY PY 1992 VL 174 IS 10 BP 3227 EP 3235 PG 9 WC Microbiology SC Microbiology GA HU938 UT WOS:A1992HU93800018 PM 1533618 ER PT J AU PAVAN, A COVELLI, E PASCALE, MC LUCANIA, G BONATTI, S DASILVA, PP TORRISI, MR AF PAVAN, A COVELLI, E PASCALE, MC LUCANIA, G BONATTI, S DASILVA, PP TORRISI, MR TI DYNAMICS OF TRANSMEMBRANE PROTEINS DURING SINDBIS VIRUS BUDDING SO JOURNAL OF CELL SCIENCE LA English DT Article DE FRACTURE-FLIP; LABEL FRACTURE; SINDBIS VIRUS ID HUMAN-LYMPHOCYTES; LABEL-FRACTURE; PLASMA-MEMBRANE; CELL-SURFACES; HLA ANTIGENS; GLYCOPROTEINS; FLIP; MATURATION; CD4 AB Label-fracture and immunogold fracture-flip techniques are used to address at the ultrastructural level the dynamics of viral and cellular transmembrane proteins during the budding of Sindbis virus on the plasma membrane of infected cells. Immunolabeling with anti-Sindbis spike antibodies shows that the viral proteins are mostly in clusters, all associated with budding viruses. Ultrastructural observation of the unlabeled freeze-fractured plasma membranes shows that membrane particles aggregate over the budding viruses. These results indicate that the concentration of viral transmembrane proteins gives rise to a parallel concentration of membrane particles. Immunolabeling with anti-CD8 antibodies of cells expressing by transfection the CD8 transmembrane protein and infected with Sindbis virus shows absence of labeling on the particle aggregates over the forming virions. These findings indicate the exclusion of CD8 proteins from the portions of the membrane where budding occurs. C1 UNIV ROMA LA SAPIENZA ROMA,DIPARTIMENTO MED SPERIMENTALE,VIALE REGINA ELENA 324,I-00161 ROME,ITALY. NAPLES UNIV,FAC MED & CHIRURG 2,IST BIOCHIM CELLULARE & MOLEC,I-80138 NAPLES,ITALY. NCI,FREDERICK CANC RES FACIL,MATH BIOL LAB,MEMBRANE BIOL SECT,FREDERICK,MD 21701. RI Pascale, Maria/B-4273-2012 NR 25 TC 10 Z9 10 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD MAY PY 1992 VL 102 BP 149 EP 155 PN 1 PG 7 WC Cell Biology SC Cell Biology GA HW400 UT WOS:A1992HW40000017 PM 1500437 ER PT J AU FEDARKO, NS VETTER, UK WEINSTEIN, S ROBEY, PG AF FEDARKO, NS VETTER, UK WEINSTEIN, S ROBEY, PG TI AGE-RELATED-CHANGES IN HYALURONAN, PROTEOGLYCAN, COLLAGEN, AND OSTEONECTIN SYNTHESIS BY HUMAN BONE-CELLS SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID HUMAN ARTICULAR-CARTILAGE; SULFATE PROTEOGLYCAN; HEPARAN-SULFATE; TENDON COLLAGEN; CORE PROTEIN; EXPRESSION; GROWTH; DECORIN; HETEROGENEITY; LOCALIZATION AB Human bone cells grown in culture, representative of a preosteoblastic stage of maturation, produce an extracellular matrix composed of collagen, several noncollagenous glycoproteins, hyaluronan, and four distinct proteoglycans (PGs). The influence of donor age on the levels of expression of these molecules in vitro has not been well characterized. In this study, human bone cells derived from sources ranging from fetal to 60-year-old donors were grown in culture, radiolabeled for 24 h, and the amount of incorporation of [S-35]sulfate into PGs, [H-3]glucosamine into hyaluronan, [H-3]leucine/proline into osteonectin, and [H-3]proline into collagen was determined. Cell proliferation was most rapid in fetal-derived bone cells and decreased with increasing age. Total protein and PG synthesis also decreased with increasing age, falling to 1/3 and 1/4, respectively, of fetal levels after age 30. A large chondroitin sulfate PG (M(r) approximately 600,000 Da) was the major fetal PG and its levels were highly correlated with cellular proliferation. [H-3]Collagen and [S-35]decorin levels increased with the increasing age of the donor, reached a maximum in puberty-derived cells, and decreased to 1/3 maximal levels after age 20. The heparan sulfate PG (M(r) approximately 400,000 Da) exhibited steady-state levels regardless of donor age. [H-3]Osteonectin and [S-35]biglycan levels were high in fetal-derived cells and in cells derived from pubescent donors. The percentage of collagen and four proteoglycans associated with the cell layer pool changed with donor age. All fetal-derived PG core proteins possessed more N- and O-linked oligosaccharides than newborn or adult derived PGs. C1 UNIV IOWA,DEPT ORTHOPED SURG,IOWA CITY,IA 52242. RP FEDARKO, NS (reprint author), NIDR,BETHESDA,MD 20892, USA. RI Robey, Pamela/H-1429-2011; OI Robey, Pamela/0000-0002-5316-5576; Fedarko, Neal/0000-0001-6055-6279 NR 50 TC 73 Z9 76 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD MAY PY 1992 VL 151 IS 2 BP 215 EP 227 DI 10.1002/jcp.1041510202 PG 13 WC Cell Biology; Physiology SC Cell Biology; Physiology GA HR760 UT WOS:A1992HR76000001 PM 1572898 ER PT J AU HAY, DF ZAHNWAXLER, C CUMMINGS, EM IANNOTTI, RJ AF HAY, DF ZAHNWAXLER, C CUMMINGS, EM IANNOTTI, RJ TI YOUNG CHILDRENS VIEWS ABOUT CONFLICT WITH PEERS - A COMPARISON OF THE DAUGHTERS AND SONS OF DEPRESSED AND WELL WOMEN SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES LA English DT Article DE SOCIAL CONFLICT; MATERNAL DEPRESSION; SOCIAL UNDERSTANDING; GENDER DIFFERENCES ID EARLY-CHILDHOOD; AGGRESSION; ADJUSTMENT; PSYCHOPATHOLOGY; PATTERNS; MOTHERS AB Forty five-year-olds were interviewed about conflict with peers, based on a simulated dispute between two glove puppets. Recommendations about tactics to be used in resolving conflicts were affected by the child's gender and experience of being cared for by a depressed mother. In particular, the daughters of depressed women were less likely than other children to recommend aggressive solutions to peer conflict; in contrast, the sons of depressed women were more likely than others to advocate aggression. Girls in general recommended more socialized tactics than boys did. C1 NIMH,DEV PSYCHOL LAB,BETHESDA,MD 20892. W VIRGINIA UNIV,MORGANTOWN,WV 26506. GEORGETOWN UNIV,WASHINGTON,DC 20057. RP HAY, DF (reprint author), INST PSYCHIAT,MRC,CHILD PSYCHIAT UNIT,DE CRESPIGNY PK,DENMARK HILL,LONDON SE5 8AF,ENGLAND. RI Hay, Dale/A-1779-2010 NR 36 TC 35 Z9 35 U1 1 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0021-9630 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry Allied Discip. PD MAY PY 1992 VL 33 IS 4 BP 669 EP 683 DI 10.1111/j.1469-7610.1992.tb00904.x PG 15 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA HV094 UT WOS:A1992HV09400003 PM 1601942 ER PT J AU CHIK, CL ALMEIDA, OFX LIBRE, EA BOOTH, JD RENQUIST, D MERRIAM, GR AF CHIK, CL ALMEIDA, OFX LIBRE, EA BOOTH, JD RENQUIST, D MERRIAM, GR TI PHOTOPERIOD-DRIVEN CHANGES IN REPRODUCTIVE FUNCTION IN MALE RHESUS-MONKEYS SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID LUTEINIZING-HORMONE SECRETION; FOLLICLE-STIMULATING-HORMONE; PLASMA TESTOSTERONE LEVELS; MACACA-MULATTA; GONADOTROPIN-SECRETION; SEXUAL DEVELOPMENT; CIRCADIAN-RHYTHMS; POSITIVE FEEDBACK; HOUSED OUTDOORS; PROLACTIN AB Environmental lighting, which regulates seasonal breeding in many animal species, has not been examined as a regulator of reproduction or puberty in man or nonhuman primates. In this study we examined the effects of controlled alternating long and short daily photoperiods, independent of other environmental variables, on testicular size and function in rhesus monkeys. Sixteen animals, some pubertal, others prepubertal, were individually caged indoors in light-controlled rooms. They were subjected to a 32-week "year" with alternating 16-week cycles of long (16 h of light and 8 h of darkness) or short (8 h of light and 16 h of darkness) days. Animals were examined every 2 weeks over four 32-week "years." Body weight, testicular diameter, and testicular volume were measured, and blood was collected for testosterone and PRL determinations. We found that although short days did not trigger testicular development in prepubertal animals, testicular growth was markedly enhanced by short days in postpubertal animals, accompanied by increased plasma testosterone levels and reduced PRL levels. In long days, testes regressed, testosterone levels fell, and PRL levels rose. The periodicity of testicular size, as determined by spectral analysis, showed a strong signal at a cycle length of 31 +/- 1.3 weeks, but no signal at intervals close to the natural 52-week year, indicating that the observed periodicity is induced by the changes in lighting, rather than by circannual changes in other variables. These studies establish that changes in photoperiod alone can modulate reproductive function in a higher primate and suggest that the onset of puberty is not directly driven by seasonal fluctuations in day length. RP CHIK, CL (reprint author), NICHHD, DEV ENDOCRINOL BRANCH, BLDG 10, ROOM 10N262, BETHESDA, MD 20892 USA. RI Almeida, Osborne/E-8402-2010 OI Almeida, Osborne/0000-0001-7331-6928 NR 37 TC 27 Z9 27 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 1992 VL 74 IS 5 BP 1068 EP 1074 DI 10.1210/jc.74.5.1068 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HQ472 UT WOS:A1992HQ47200020 PM 1569154 ER PT J AU REICHMAN, ME JUDD, JT TAYLOR, PR NAIR, PP JONES, DY CAMPBELL, WS AF REICHMAN, ME JUDD, JT TAYLOR, PR NAIR, PP JONES, DY CAMPBELL, WS TI EFFECT OF DIETARY-FAT ON LENGTH OF THE FOLLICULAR PHASE OF THE MENSTRUAL-CYCLE IN A CONTROLLED DIET SETTING SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HUMAN BREAST-CANCER; PREMENOPAUSAL WOMEN; WEIGHT; IRREGULARITIES; HYPOTHESIS; VEGETARIAN; ETIOLOGY; DISEASE; AGE AB The length of the follicular phase of the menstrual cycle (defined as the time from the first day of menses until the day of urinary LH peak, inclusive) was examined in 30 healthy, premenopausal women. The women consumed defined, weight maintaining diets, with a ratio of polyunsaturated to saturated fatty acids (P/S ratio) of either 0.3 or 1.0. Both P/S groups consumed a high fat diet (40% energy from fat) for 4 menstrual cycles, followed by 4 menstrual cycles of a low fat diet (20% energy from fat). There was a significant increase (P < 0.006) in the length of the follicular phase of the menstrual cycle during consumption of the low fat diet. Two thirds of the women showed increases in follicular phase length with an average increase of 1.9 days. C1 USDA ARS, BELTSVILLE AGR RES CTR, BELTSVILLE HUMAN NUTR RES CTR, LIPID NUTR LAB, BELTSVILLE, MD 20705 USA. RP REICHMAN, ME (reprint author), NCI, DIV CANC PREVENT & CONTROL, CANC PREVENT STUDIES BRANCH, EPN 211, BETHESDA, MD 20892 USA. NR 34 TC 16 Z9 16 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 MAY PY 1992 VL 74 IS 5 BP 1171 EP 1175 DI 10.1210/jc.74.5.1171 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HQ472 UT WOS:A1992HQ47200036 PM 1569164 ER PT J AU DAVEY, RT DEYTON, LR METCALF, JA EASTER, M KOVACS, JA VASUDEVACHARI, M PSALLIDOPOULOS, M THOMPSON, LM FALLOON, J POLIS, MA MASUR, H LANE, HC AF DAVEY, RT DEYTON, LR METCALF, JA EASTER, M KOVACS, JA VASUDEVACHARI, M PSALLIDOPOULOS, M THOMPSON, LM FALLOON, J POLIS, MA MASUR, H LANE, HC TI INDETERMINATE WESTERN-BLOT PATTERNS IN A COHORT OF INDIVIDUALS AT HIGH-RISK FOR HUMAN-IMMUNODEFICIENCY-VIRUS (HIV-1) EXPOSURE SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE INDETERMINATE WESTERN BLOT; SEROLOGY; HUMAN IMMUNODEFICIENCY VIRUS (HIV-1); POLYMERASE CHAIN REACTION ID HOMOSEXUAL MEN; FOLLOW-UP; DONORS; INFECTION; ANTIBODY; TYPE-1; TESTS; REACTIVITY; ABSENCE AB Our objective was to map serial patterns of Western blot reactivity over time of a cohort of initially ELISA-negative, Western blot-indeterminate individuals from a high-risk group and to determine if these individuals were at increased risk of harboring occult HIV-1 infection. A 2-year prospective study used serial ELISA, two types of Western blot, immunologic profiles, HIV-1 culture, and analysis by polymerase chain reaction. Subjects were 20 ELISA-negative, Western blot indeterminate homosexual volunteers and 20 matched seronegative controls. Results showed that 19 of 20 study subjects completed a mean of 17.0 months of clinical and laboratory follow-up. Reactivities with p24 and/or with p55 were the two most commonly observed Western blot patterns, occurring in 70% of individuals. Specific Western blot reactivity was dependent upon the particular immunoblot preparation being used and varied considerably on a longitudinal basis. No individual pattern appeared predictive of an increased likelihood of subsequent seroconversion to HIV-1 relative to controls. By all other criteria including polymerase chain reaction analysis, samples from 17 of 19 individuals remained negative for HIV-1 at each time point. Two individuals evolved from an indeterminate to a positive Western blot and, simultaneously, from a negative to a positive polymerase chain reaction analysis, during follow-up. Our conclusions were as follows. ELISA-negative, Western blot-indeterminate individuals from a high-risk group show marked variability in immunoblot findings over time, and these patterns do not appear predictive of an increased likelihood of infection. Polymerase chain reaction analysis is clearly of value in providing confirmation of the low probability of infection in this group, although in patients who do become infected, detection by this test may not always precede diagnosis by serologic methods. C1 NIAID,IMMUNOREGULAT LAB,CLIN & MOLEC RETROVIROL SECT,BLDG 10,ROOM 11B13,BETHESDA,MD 20892. GEORGETOWN UNIV,DIV MOLEC VIROL & IMMUNOL,WASHINGTON,DC 20007. NIH,DEPT CRIT CARE MED,BETHESDA,MD 20892. OI Polis, Michael/0000-0002-9151-2268 NR 28 TC 6 Z9 6 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD MAY PY 1992 VL 12 IS 3 BP 185 EP 192 DI 10.1007/BF00918087 PG 8 WC Immunology SC Immunology GA HT462 UT WOS:A1992HT46200005 PM 1400898 ER PT J AU KING, CL KUMARASWAMI, V POINDEXTER, RW KUMARI, S JAYARAMAN, K ALLING, DW OTTESEN, EA NUTMAN, TB AF KING, CL KUMARASWAMI, V POINDEXTER, RW KUMARI, S JAYARAMAN, K ALLING, DW OTTESEN, EA NUTMAN, TB TI IMMUNOLOGICAL-TOLERANCE IN LYMPHATIC FILARIASIS - DIMINISHED PARASITE-SPECIFIC LYMPHOCYTE-T AND LYMPHOCYTE-B PRECURSOR FREQUENCY IN THE MICROFILAREMIC STATE SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE LIMITING DILUTION ANALYSIS; ELISPOT ASSAY; IGE ID LIMITING DILUTION ANALYSIS; BRUGIA-MALAYI; IMMUNE-RESPONSES; CELLULAR UNRESPONSIVENESS; SUPPRESSOR CELLS; HUMAN INFECTIONS; ANTIGEN; INVITRO; IGE; DIETHYLCARBAMAZINE AB To explore the mechanisms of antigen-specific immune unresponsiveness seen in microfilaremic patients with bancroftian filariasis, T and B cell precursor frequency analysis was performed using PBMC from individuals with either asymptomatic microfilaremia (MF, n = 7) or chronic lymphatic obstruction (CP, n = 20). Highly purified CD3+ cells were partially reconstituted with adherent cells and their proliferative response to parasite antigens determined in cultures of T cells by limiting dilution analysis. A filter immunoplaque assay also assessed the frequency of both total and parasite-specific Ig-producing B cells. While the lymphocyte proliferation to mitogens and to a nonparasite antigen (Streptolysin-O, [SLO]) were similar in all groups of patients, the frequency of parasite-specific CD3+ T cells was significantly lower (geometric mean [GM], 1/3,757) in MF patients when compared to that in CP patients (GM 1/1,513; P < 0.001). Similarly, the proportion of lymphocytes producing parasite-specific IgE or IgG was significantly lower in MF patients (IgE mean, 0.2%; IgG mean, 0.33%) compared with CP patients (IgE mean, 3.2%; IgG mean, 1.76%; P < 0.05 for both comparisons). These observations imply that low numbers of parasite-specific T and B lymphocytes may be partially responsible for the severely diminished capacity of lymphocytes from patients with MF to produce parasite-specific antibody and to proliferate to parasite antigen in vitro. Such differences in parasite-specific lymphocyte responses suggest that tolerance by clonal anergy may be a critical mechanism for maintaining the microfilaremic state. C1 NIH,PARASIT DIS LAB,BLDG 4,ROOM 126,BETHESDA,MD 20892. NIAID,BETHESDA,MD 20892. TB RES RES CTR,MADRAS,INDIA. ANNA UNIV,DEPT BIOTECHNOL,MADRAS,INDIA. NR 43 TC 79 Z9 79 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 1992 VL 89 IS 5 BP 1403 EP 1410 DI 10.1172/JCI115729 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA HT983 UT WOS:A1992HT98300006 PM 1569183 ER PT J AU NAKAMURA, H YOSHIMURA, K MCELVANEY, NG CRYSTAL, RG AF NAKAMURA, H YOSHIMURA, K MCELVANEY, NG CRYSTAL, RG TI NEUTROPHIL ELASTASE IN RESPIRATORY EPITHELIAL LINING FLUID OF INDIVIDUALS WITH CYSTIC-FIBROSIS INDUCES INTERLEUKIN-8 GENE-EXPRESSION IN A HUMAN BRONCHIAL EPITHELIAL-CELL LINE SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE CYTOKINE; ANTI-SERINE PROTEASE; BRONCHIAL EPITHELIUM; NEUTROPHIL CHEMOATTRACTANT; AIRWAY INFLAMMATION ID POLYMORPHONUCLEAR LEUKOCYTES; CHEMOTACTIC ACTIVITY; CATHEPSIN-G; PSEUDOMONAS; LUNG; IDENTIFICATION; ACTIVATION; RECEPTOR; INVITRO; RELEASE AB The respiratory manifestations of cystic fibrosis (CF) are characterized by neutrophil-dominated airway inflammation. Since a variety of inflammatory stimuli are capable of inducing bronchial epithelial cells to express the gene for IL-8, a cytokine that attracts and activates neutrophils, mediators in respiratory epithelial lining fluid (ELF) of CF individuals might induce IL-8 production by epithelial cells, thus recruiting neutrophils to the airways. BET-1A human bronchial epithelial cells at rest or incubated with normal ELF showed little IL-8 gene expression, but after incubation with CF ELF, a marked increase in IL-8 transcript levels was observed. CF ELF contained high levels of neutrophil elastase (NE) and various serine protease inhibitors prevented CF ELF from inducing IL-8 gene expression in BET-1A cells, suggesting that NE was the dominant inducer for IL-8 production in CF ELF. The addition of purified NE caused BET-1A cells to increase IL-8 gene transcription with accumulation of mRNA transcripts and to release IL-8-like neutrophil chemotactic activity. These observations suggest a self-perpetuating inflammatory process on the CF bronchial surface where NE released by neutrophils induced the bronchial epithelium to secrete IL-8, which in turn recruits additional neutrophils to the bronchial surface. C1 NHLBI,PULM BRANCH,BLDG 10,ROOM 6D03,BETHESDA,MD 20892. RI McElvaney, Noel/A-6809-2010 NR 66 TC 380 Z9 384 U1 1 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 1992 VL 89 IS 5 BP 1478 EP 1484 DI 10.1172/JCI115738 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA HT983 UT WOS:A1992HT98300015 PM 1569186 ER PT J AU ERICKSON, RW MALAWISTA, SE GARRETT, MC VANBLARICOM, G LETO, TL CURNUTTE, JT AF ERICKSON, RW MALAWISTA, SE GARRETT, MC VANBLARICOM, G LETO, TL CURNUTTE, JT TI IDENTIFICATION OF A THERMOLABILE COMPONENT OF THE HUMAN NEUTROPHIL NADPH OXIDASE - A MODEL FOR CHRONIC GRANULOMATOUS-DISEASE CAUSED BY DEFICIENCY OF THE P67-PHOX CYTOSOLIC COMPONENT SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID RESPIRATORY BURST OXIDASE; BLOOD POLYMORPHONUCLEAR LEUKOCYTES; FULLY SOLUBLE SYSTEM; CYTOCHROME-B; CYTOKINEPLASTS; ACTIVATION; CHAIN; DEFECT; FORMS; HEAT AB Mild heating of human neutrophils inactivates the respiratory burst oxidase, producing a defect in superoxide production and bacterial killing comparable to that seen in patients afflicted with chronic granulomatous disease (CGD). We have now investigated the mechanism and specificity of this inactivation by examining the effect of mild heating on the known oxidase components: the membrane-bound subunits of the cytochrome b558 (gp9l-phox and p22-phox) and the two cytosolic oxidase factors (p47-phox and p67-phox). Heating (46-degrees-C for 7.5 min) caused intact neutrophils to lose > 85% of their capacity to produce superoxide, a defect which was localized to the cytosolic, but not the membrane, fraction. Complementation studies with CGD cytosols deficient in either p47-phox or p67-phox suggested that the defective component of heat-inactivated cytosol was p67-phox. This was confirmed by experiments showing that recombinant p67-phox, but not p47-phox, exhibited lability at 46-degrees-C and completely reconstituted oxidase activity of heat-treated cytosol. These studies indicate that mild heating of either intact neutrophils or normal neutrophil cytosol results in a selective inactivation of p67-phox, providing a model oxidase system for the extremely rare p67-phox-deficient form of CGD. C1 SCRIPPS RES INST, DEPT MOLEC & EXPTL MED, SBR 12, LA JOLLA, CA 92037 USA. YALE UNIV, SCH MED, DEPT INTERNAL MED, NEW HAVEN, CT 06510 USA. NIAID, HOST DEF LAB, BETHESDA, MD 20892 USA. FU NCRR NIH HHS [RR-00833]; NIAID NIH HHS [AI-24838]; NIAMS NIH HHS [AR-10493] NR 46 TC 26 Z9 27 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 1992 VL 89 IS 5 BP 1587 EP 1595 DI 10.1172/JCI115753 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA HT983 UT WOS:A1992HT98300030 PM 1314852 ER PT J AU OHNO, I LEA, RG FLANDERS, KC CLARK, DA BANWATT, D DOLOVICH, J DENBURG, J HARLEY, CB GAULDIE, J JORDANA, M AF OHNO, I LEA, RG FLANDERS, KC CLARK, DA BANWATT, D DOLOVICH, J DENBURG, J HARLEY, CB GAULDIE, J JORDANA, M TI EOSINOPHILS IN CHRONICALLY INFLAMED HUMAN UPPER AIRWAY TISSUES EXPRESS TRANSFORMING GROWTH FACTOR-BETA-1 GENE (TGF-BETA-1) SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Note DE NASAL POLYPOSIS; INFLAMMATION; CYTOKINES; HISTOCHEMISTRY; INSITU HYBRIDIZATION ID FACTOR-BETA; MESSENGER-RNA; COLLAGEN-SYNTHESIS; HUMAN-FIBROBLASTS; NASAL POLYPS; FACTOR-ALPHA; FIBROSIS; STIMULATION; FIBRONECTIN; TRANSCRIPTS AB Transforming growth factor-beta (TGF-beta) is a multifunctional protein which has been suggested to play a central role in the pathogenesis of chronic inflammation and fibrosis. Nasal polyposis is a condition affecting the upper airways characterized by the presence of chronic inflammation and varying degrees of fibrosis. To examine the potential role of TGF-beta in the pathogenesis of this condition, we investigated gene expression and cytokine production in nasal polyp tissues as well as in the normal nasal mucosa. By Northern blot analysis using a porcine TGF-beta-1 cDNA probe, we detected TGF-beta-1-specific mRNA in nasal polyp tissues, as well as in the tissue from a patient with allergic rhinitis, but not in the normal nasal mucosa. By the combination of tissue section staining with chromotrope 2R with in situ hybridization using the same TGF-beta-1 probe, we found that approximately 50% of the eosinophils infiltrating the polyp tissue express the TGF-beta-1 gene. In addition, immunohistochemical localization of TGF-beta-1 was detected associated with extracellular matrix as well as in cells in the stroma. These results suggest that in nasal polyposis where eosinophils are the most prevalent inflammatory cell, TGF-beta-1 synthesized by these cells may contribute to the structural abnormalities such as stromal fibrosis and basement membrane thickening which characterize this disease. C1 MCMASTER UNIV,DEPT PATHOL,ROOM 4H-17A,1200 MAIN ST W,HAMILTON L8N 3Z5,ONTARIO,CANADA. MCMASTER UNIV,DEPT MED,HAMILTON L8N 3Z5,ONTARIO,CANADA. MCMASTER UNIV,DEPT PEDIAT,HAMILTON L8N 3Z5,ONTARIO,CANADA. MCMASTER UNIV,DEPT BIOCHEM,HAMILTON L8N 3Z5,ONTARIO,CANADA. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. NR 33 TC 208 Z9 213 U1 0 U2 6 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 1992 VL 89 IS 5 BP 1662 EP 1668 DI 10.1172/JCI115764 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA HT983 UT WOS:A1992HT98300041 PM 1569205 ER PT J AU BEHETS, F KASHAMUKA, M PAPPAIOANOU, M GREEN, TA RYDER, RW BATTER, V GEORGE, JR HANNON, WH QUINN, TC AF BEHETS, F KASHAMUKA, M PAPPAIOANOU, M GREEN, TA RYDER, RW BATTER, V GEORGE, JR HANNON, WH QUINN, TC TI STABILITY OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ANTIBODIES IN WHOLE-BLOOD DRIED ON FILTER-PAPER AND STORED UNDER VARIOUS TROPICAL CONDITIONS IN KINSHASA, ZAIRE SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID HIV-INFECTION; SEROPREVALENCE; NEWBORNS; PROGRAM AB The use of whole-blood spots on filter paper for the detection of antibody to human immunodeficiency virus type 1 (HIV-1) was evaluated during a 20-week period under a variety of storage environments simulating the harsh tropical field conditions in Kinshasa, Zaire. During the first 6 weeks of storage, all replicates of high- and low-titer HIV-1-positive reference samples remained positive by enzyme immunoassay and Western blotting (immunoblotting), and all replicates of HIV-1-negative samples remained negative under all storage conditions. However, hot and humid storage conditions for up to 20 weeks caused a progressive decline in enzyme immunoassay optical density ratio values, which was particularly noticeable in samples with a low HIV-1 antibody titer. Harsh tropical operational conditions did not cause any repeatedly false-positive results during the 20-week storage period. The use of gas-impermeable bags with desiccant for the storage of blood spots on filter paper improved the stability of HIV-1 antibody detection over time and is recommended for the storage of whole-blood spots on filter paper in harsh tropical field settings. C1 PROJECT SIDA,KINSHASA,ZAIRE. INST TROP MED PRINCE LEOPOLD,DEPT MICROBIOL,B-2000 ANTWERP,BELGIUM. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NR 14 TC 69 Z9 71 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAY PY 1992 VL 30 IS 5 BP 1179 EP 1182 PG 4 WC Microbiology SC Microbiology GA HP828 UT WOS:A1992HP82800025 PM 1583117 ER PT J AU ROTHENBERG, ML OZOLS, RF GLATSTEIN, E STEINBERG, SM REED, E YOUNG, RC AF ROTHENBERG, ML OZOLS, RF GLATSTEIN, E STEINBERG, SM REED, E YOUNG, RC TI DOSE-INTENSIVE INDUCTION THERAPY WITH CYCLOPHOSPHAMIDE, CISPLATIN, AND CONSOLIDATIVE ABDOMINAL RADIATION IN ADVANCED-STAGE EPITHELIAL OVARIAN-CANCER SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HYPERTONIC SALINE; IRRADIATION; CARCINOMA; DISEASE C1 NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,BIOSTAT & DATA MANAGEMENT SECT,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,BIOSTAT & DATA MANAGEMENT SECT,MED BRANCH,BETHESDA,MD 20892. RP ROTHENBERG, ML (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT MED,DIV ONCOL,7703 FLOYD CURL DR,SAN ANTONIO,TX 78284, USA. NR 24 TC 32 Z9 32 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 1992 VL 10 IS 5 BP 727 EP 734 PG 8 WC Oncology SC Oncology GA HR228 UT WOS:A1992HR22800007 PM 1569445 ER PT J AU GREINER, JW GUADAGNI, F GOLDSTEIN, D SMALLEY, RV BORDEN, EC SIMPSON, JF MOLINOLO, A SCHLOM, J AF GREINER, JW GUADAGNI, F GOLDSTEIN, D SMALLEY, RV BORDEN, EC SIMPSON, JF MOLINOLO, A SCHLOM, J TI INTRAPERITONEAL ADMINISTRATION OF INTERFERON-GAMMA TO CARCINOMA PATIENTS ENHANCES EXPRESSION OF TUMOR-ASSOCIATED GLYCOPROTEIN-72 AND CARCINOEMBRYONIC ANTIGEN ON MALIGNANT ASCITES-CELLS SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID MONOCLONAL-ANTIBODY B72.3; MELANOMA-ASSOCIATED ANTIGEN; OVARIAN-CARCINOMA; ALPHA-INTERFERON; IFN-GAMMA; INVIVO; ADENOCARCINOMA; MODULATION; TAG-72; POTENTIATION C1 UNIV WISCONSIN,CTR CLIN CANC,DEPT HUMAN ONCOL,MADISON,WI 53706. RP GREINER, JW (reprint author), NCI,TUMOR IMMUNOL & BIOL LAB,BLDG 10,RM 8B07,BETHESDA,MD 20892, USA. RI Guadagni, Fiorella/J-4432-2013 OI Guadagni, Fiorella/0000-0003-3652-0457 FU NCI NIH HHS [N01-CM-47669]; NCRR NIH HHS [RR03186] NR 44 TC 72 Z9 73 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 1992 VL 10 IS 5 BP 735 EP 746 PG 12 WC Oncology SC Oncology GA HR228 UT WOS:A1992HR22800008 PM 1569446 ER PT J AU SMITH, MA PARKINSON, DR CHESON, BD FRIEDMAN, MA AF SMITH, MA PARKINSON, DR CHESON, BD FRIEDMAN, MA TI RETINOIDS IN CANCER-THERAPY SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID ACUTE PROMYELOCYTIC LEUKEMIA; EMBRYONAL CARCINOMA-CELLS; ACID-BINDING-PROTEIN; PHASE-II TRIAL; COLONY-STIMULATING FACTOR; CHICK LIMB BUD; SYNERGISTICALLY INDUCE DIFFERENTIATION; CHRONIC MYELOGENOUS LEUKEMIA; REGENERATING AXOLOTL LIMBS; TERATOCARCINOMA STEM-CELLS C1 NCI,PEDIAT SECT,BETHESDA,MD 20892. NCI,MED SECT,INVEST DRUG BRANCH,BETHESDA,MD 20892. NCI,BIOL EVALUAT SECT,CLIN INVEST BRANCH,BETHESDA,MD 20892. RP SMITH, MA (reprint author), NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,CLIN INVEST BRANCH,EXECUT PLAZA N,BETHESDA,MD 20892, USA. NR 369 TC 531 Z9 538 U1 0 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 1992 VL 10 IS 5 BP 839 EP 864 PG 26 WC Oncology SC Oncology GA HR228 UT WOS:A1992HR22800022 PM 1569455 ER PT J AU CHESON, BD AF CHESON, BD TI THE PURINE ANALOGS - A THERAPEUTIC BEAUTY CONTEST SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID CHRONIC LYMPHOCYTIC-LEUKEMIA; HAIRY-CELL LEUKEMIA; PHASE-II TRIAL; FLUDARABINE PHOSPHATE; PENTOSTATIN; 2'-DEOXYCOFORMYCIN; CANCER; 2-CHLORODEOXYADENOSINE; DEOXYCOFORMYCIN; MONOPHOSPHATE RP CHESON, BD (reprint author), NCI,BETHESDA,MD 20892, USA. NR 39 TC 15 Z9 15 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 1992 VL 10 IS 5 BP 868 EP 871 PG 4 WC Oncology SC Oncology GA HR228 UT WOS:A1992HR22800030 PM 1349035 ER PT J AU BRAUNSTEIN, NS WEBER, DA WANG, XC LONG, EO KARP, D AF BRAUNSTEIN, NS WEBER, DA WANG, XC LONG, EO KARP, D TI SEQUENCES IN BOTH CLASS-II MAJOR HISTOCOMPATIBILITY COMPLEX ALPHA AND BETA CHAINS CONTRIBUTE TO THE BINDING OF THE SUPERANTIGEN TOXIC SHOCK SYNDROME TOXIN-1 SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID STAPHYLOCOCCAL ENTEROTOXIN-B; T-CELLS; HLA-DR; ALLELIC POLYMORPHISM; MHC MOLECULES; ANTIGEN; STIMULATION; REQUIREMENT; EXPRESSION; RESPONSES AB Class II major histocompatibility complex (MHC) molecules present peptides derived from processed antigen to antigen-specific CD4-positive T cells. In addition, class II molecules bind with high affinity another class of antigens, termed superantigens. T cell stimulation by superantigens depends almost exclusively on the V-beta segment expressed by the T cell receptor (TCR). Mapping of the superantigen binding site on class II molecules should provide valuable information on how MHC and TCR molecules interact. Recombinant mouse I-A class II molecules expressed on transfected L cells were analyzed for their ability to bind the toxic shock syndrome toxin 1. Polymorphic residues in the alpha-helices of both the alpha and beta-chains of I-A contributed to quantitative toxin binding, suggesting that the toxin binds to either a combinatorial or a conformational site on class II MHC molecules. C1 NIAID,IMMUNOGENET LAB,ROCKVILLE,MD 20852. RP BRAUNSTEIN, NS (reprint author), COLUMBIA UNIV COLL PHYS & SURG,DEPT MED,630 W 168TH ST,NEW YORK,NY 10032, USA. RI Long, Eric/G-5475-2011 OI Long, Eric/0000-0002-7793-3728 FU NIGMS NIH HHS [GM-39275] NR 26 TC 33 Z9 33 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAY 1 PY 1992 VL 175 IS 5 BP 1301 EP 1305 DI 10.1084/jem.175.5.1301 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA HQ184 UT WOS:A1992HQ18400016 PM 1569399 ER PT J AU WANG, B RIEGER, A KILGUS, O OCHIAI, K MAURER, D FODINGER, D KINET, JP STINGL, G AF WANG, B RIEGER, A KILGUS, O OCHIAI, K MAURER, D FODINGER, D KINET, JP STINGL, G TI EPIDERMAL LANGERHANS CELLS FROM NORMAL HUMAN SKIN BIND MONOMERIC IGE VIA FC-EPSILON-RI SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID HUMAN MAST-CELLS; ATOPIC-DERMATITIS; IMMUNOGLOBULIN-E; MOLECULAR-STRUCTURE; DENDRITIC CELLS; RECEPTOR; EXPRESSION; GENE; ANTIGEN; LYMPHOCYTES AB Human epidermal Langerhans cells (LC) bearing IgE are found in disease states associated with hyperimmunoglobulinemia E. When studying the mechanism(s) underlying this phenomenon, immunohistology revealed that a majority of epidermal LC from normal skin of healthy individuals can specifically bind monomeric IgE. IgE binding to LC could neither be prevented by preincubation of the tissue with monoclonal antibodies (mAb) against either Fc-epsilon-RII/CD23 or Fc-gamma-RII/CD32, nor by the addition of lactose. However, binding could be entirely abrogated by preincubation with the anti-Fc-epsilon-RI-alpha mAb 15-1, which interferes with IgE binding to Fc-epsilon-RI-alpha-gamma transfectants. These observations indicated that IgE binding to epidermal LC is mediated by Fc-epsilon-RI rather than by CD23, CD32, or the D-galactose-specific IgE-binding protein. This assumption gained support from our additional findings that: (a) the majority of LC exhibited distinct surface immunolabeling with the anti-Fc-epsilon-RI-alpha mAbs 15-1 and 19-1, but not with any of eight different anti-Fc-epsilon-RII/CD23 mAbs; and (b) transcripts for the alpha, beta, and gamma-chains of Fc-epsilon-RI could be amplified by polymerase chain reaction from RNA preparations of LC-enriched, but not of LC-depleted, epidermal cell suspensions. In view of the preeminent role of Fc-epsilon-RI crosslinking on mast cells and basophils in triggering the synthesis and release of mediators of allergic reactions, the demonstration of this receptor on epidermal LC may have important implications for our understanding of allergic reactions after epicutaneous contact with allergens. C1 UNIV VIENNA,SCH MED,DEPT DERMATOL 1,DIV CUTANEOUS IMMUNOL,ALSER STR 4,A-1090 VIENNA,AUSTRIA. NIAID,MOLEC ALLERGY & IMMUNOL SECT,ROCKVILLE,MD 20892. NR 40 TC 316 Z9 318 U1 0 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAY 1 PY 1992 VL 175 IS 5 BP 1353 EP 1365 DI 10.1084/jem.175.5.1353 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA HQ184 UT WOS:A1992HQ18400022 PM 1533243 ER PT J AU JIANG, H ROBEY, FA GEWURZ, H AF JIANG, H ROBEY, FA GEWURZ, H TI LOCALIZATION OF SITES THROUGH WHICH C-REACTIVE PROTEIN BINDS AND ACTIVATES COMPLEMENT TO RESIDUES 14-26 AND 76-92 OF THE HUMAN C1Q-A CHAIN SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID GUINEA-PIG COMPLEMENT; 1ST COMPONENT; SUBCOMPONENT C1Q; CLQ; COMPLEXES; SYSTEM; CONSUMPTION; LOCATION; CRP; IGG AB Studies were initiated to localize the C-reactive protein (CRP) binding site on the collagen-like region (CLR) of C1q. CRP bound preferentially to the A chain of reduced C1q, in contrast to aggregated immunoglobulin G (Agg-IgG), which reacted preferentially with the C chain. A group of C1q A chain peptides, including peptides identical to residues 81-97, 76-92, and 14-26, respectively, were synthesized from predicted binding regions. Peptide 76-92 contained two proximal lysine groups, and peptide 14-26 contained four proximal arginine groups. CRP-trimers and CRP-ligand complexes did not bind to immobilized peptide 81-97, but bound avidly to immobilized peptides 76-92 and 14-26. Agg-IgG did not bind to any of the peptides. Peptide 76-92 partially, and peptide 14-26 completely, inhibited binding of CRP to intact C1q. Peptide 14-26 also blocked C consumption initiated by CRP, but not by IgG. Replacement of the two prolines with alanines, or scrambling the order of the amino acids, resulted in loss of ability of peptide 14-26 to inhibit C1q binding and C activation by CRP, indicating a sequence specificity, and not a charge specificity alone, as the basis for the inhibitory activity of the peptide. Similar investigations with scrambled peptides showed a sequence specificity for the effects of peptide 76-92 as well. DNA and heparin inhibited binding of CRP trimers to intact C1q, as well as to each peptide 14-26 and 76-92, suggesting involvement of these regions in C1q-CLR binding reactions generally. Collectively, these data identify two cationic regions within residues 14-26 and 76-92 of the C1q A chain CLR as sites through which CRP binds and activates the classical C pathway, and suggest that these residues represent significant regions for C1q CLR binding reactions generally. To our knowledge, this represents the first delineation of sites on C1q through which binding and activation of the classical C pathway can occur. C1 RUSH MED COLL,DEPT IMMUNOL MICROBIOL,CHICAGO,IL 60612. NIDR,CELLULAR DEV & ONCOL LAB,BETHESDA,MD 20892. NR 38 TC 80 Z9 80 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAY 1 PY 1992 VL 175 IS 5 BP 1373 EP 1379 DI 10.1084/jem.175.5.1373 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA HQ184 UT WOS:A1992HQ18400024 PM 1569403 ER PT J AU VACCHIO, MS KANAGAWA, O TOMONARI, K HODES, RJ AF VACCHIO, MS KANAGAWA, O TOMONARI, K HODES, RJ TI INFLUENCE OF T-CELL RECEPTOR V-ALPHA EXPRESSION ON MLSA SUPERANTIGEN-SPECIFIC T-CELL RESPONSES SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Note ID CLONAL DELETION; VARIABLE REGION; BETA-CHAIN; MICE AB Recognition of conventional foreign antigen by T cells is determined by the expression of multiple variable regions of both alpha and beta-chains of the T cell receptor (TCR) alpha/beta-heterodimer. In contrast, there exists a class of antigens that appears to interact with the TCR alpha/beta-heterodimer through the variable region on the beta-chain (V-beta), independent of other TCR components, a property that has led to their designation as superantigens. The goal of the present study was to analyze V-alpha use in V-beta-6+ T cells responsive to the superantigen, Mla(a). Results indicate that while deletion of T cells expressing V-beta-6 in Mls(a)-expressing mice is essentially complete and therefore appears to occur regardless of V-alpha usage, in vitro Mls(a) stimulation of T cells from MlS(a)-negative mice results in significant skewing of V-alpha use among responding V-beta-6+ T cells. This indicates that V-alpha expression influences recognition of the superantigen, Mls(a) by mature peripheral T cells. C1 WASHINGTON UNIV,SCH MED,DEPT PATHOL,ST LOUIS,MO 63110. CLIN RES CTR,MRC,TRANSPLANTAT BIOL SECT,HARROW HA1 3UJ,MIDDX,ENGLAND. RP VACCHIO, MS (reprint author), NCI,EXPTL IMMUNOL BRANCH,BIOL RESPONSE MODIFIERS PROGRAM,BLDG 10,BETHESDA,MD 20892, USA. NR 19 TC 93 Z9 93 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAY 1 PY 1992 VL 175 IS 5 BP 1405 EP 1408 DI 10.1084/jem.175.5.1405 PG 4 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA HQ184 UT WOS:A1992HQ18400028 PM 1533244 ER PT J AU WICKES, BL HICKS, JB MERZ, WG KWONCHUNG, KJ AF WICKES, BL HICKS, JB MERZ, WG KWONCHUNG, KJ TI THE MOLECULAR ANALYSIS OF SYNONYMY AMONG MEDICALLY IMPORTANT YEASTS WITHIN THE GENUS CANDIDA SO JOURNAL OF GENERAL MICROBIOLOGY LA English DT Article ID STELLATOIDEA; ALBICANS; STRAINS AB Three sets of medically important yeasts, Candida albicans, C. tropicalis, and C krusei, were compared with their putative synonyms (C. langeronii and C. claussenii, C. paratropicalis, and Itssatchenkia orientalis, respectively) to determine if these synonyms are genetically distinguishable from each other. Pulsed-field electrophoresis and hybridization to species-specific probes were used to accomplish this goal. The species-specific probes for C. albicans and C tropicalis have been previously described (27A and CT13.8, respectively) whereas the probe for C. krusei (CK3) was cloned in this study. No distinguishing characteristics between synonyms were identified, thus supporting the current taxonomic treatment of these organisms. C1 NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. ICOS INC,BOTHELL,WA 98021. JOHNS HOPKINS MED INST,DEPT LAB MED,BALTIMORE,MD 21205. NR 24 TC 26 Z9 26 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA HARVEST HOUSE 62 LONDON ROAD, READING, BERKS, ENGLAND RG1 5AS SN 0022-1287 J9 J GEN MICROBIOL JI J. Gen. Microbiol. PD MAY PY 1992 VL 138 BP 901 EP 907 PN 5 PG 7 WC Microbiology SC Microbiology GA HU158 UT WOS:A1992HU15800006 PM 1353786 ER PT J AU CHRISTENSEN, ND KREIDER, JW SHAH, KV RANDO, RF AF CHRISTENSEN, ND KREIDER, JW SHAH, KV RANDO, RF TI DETECTION OF HUMAN SERUM ANTIBODIES THAT NEUTRALIZE INFECTIOUS HUMAN PAPILLOMAVIRUS TYPE-11 VIRIONS SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID OPEN READING FRAMES; MEDIATED NEUTRALIZATION; ESCHERICHIA-COLI; FUSION PROTEINS; LINEAR EPITOPES; UTERINE CERVIX; L1; IDENTIFICATION; ANTIGENS; INVIVO AB A selection of human sera were tested for the presence of antibodies that neutralized infectious human papillomavirus (HPV) type 11. Neutralizing antibodies were detected by prevention of HPV-11-induced condylomatous transformation of human foreskin chips transplanted subrenally into athymic mice. Test sera were obtained from 21 female patients with genital condylomas and eight patients with laryngeal papillomas. Control patients consisted of 57 adult random blood donors and five asymptomatic children. ELISAs demonstrated that all sera from patients with genital papillomas were strongly reactive to disrupted papillomavirus (PV) antigens of HPV-11, bovine PV type 1 and cottontail rabbit PV, but only two were weakly reactive to intact HPV-11. None of the eight sera from the laryngeal papilloma bearers reacted significantly to disrupted PV antigens, but four of the eight showed strong specific responses to intact HPV-11 only. The majority of the sera that were reactive to intact HPV-11 by ELISA neutralized HPV-11 infectivity in the athymic mouse xenograft system. The data indicated that ELISA reactivity to intact HPV-11 virions was a good predictor for the presence of HPV-11 neutralizing antibodies. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT IMMUNOL & INFECT DIS,BALTIMORE,MD 21205. NIDR,BETHESDA,MD 20892. MILTON S HERSHEY MED CTR,DEPT MICROBIOL & IMMUNOL,HERSHEY,PA 17033. RP CHRISTENSEN, ND (reprint author), MILTON S HERSHEY MED CTR,DEPT PATHOL,HERSHEY,PA 17033, USA. FU NCI NIH HHS [CA47622] NR 36 TC 64 Z9 67 U1 0 U2 2 PU SOC GENERAL MICROBIOLOGY PI READING PA HARVEST HOUSE 62 LONDON ROAD, READING, BERKS, ENGLAND RG1 5AS SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD MAY PY 1992 VL 73 BP 1261 EP 1267 DI 10.1099/0022-1317-73-5-1261 PN 5 PG 7 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA HT192 UT WOS:A1992HT19200027 PM 1316943 ER PT J AU BERGASA, NV ROTHMAN, RB VERGALLA, J XU, H SWAIN, MG JONES, EA AF BERGASA, NV ROTHMAN, RB VERGALLA, J XU, H SWAIN, MG JONES, EA TI CENTRAL MU-OPIOID RECEPTORS ARE DOWN-REGULATED IN A RAT MODEL OF CHOLESTASIS SO JOURNAL OF HEPATOLOGY LA English DT Note ID BINDING; PRURITUS AB Ameliorations of the pruritus of cholestasis by opioid antagonists are consistent with this form of pruritus being centrally mediated by the opioid system. To determine whether the central opioid system is altered in cholestasis, the specific binding of a selective mu-opioid receptor ligand, H-3-DAMGO, to mu-opioid receptors was studied in rats with acute cholestasis due to bile duct resection. Using whole brain membranes and subcellular mitochondrial-synaptosomal fractions the density of mu-receptor sites was 30% (p < 0.01) and 22% (p = 0.03) less in bile-duct-resected rats than in sham-resected rats. Using membranes from individual brain regions specific binding of H-3-DAMGO was reduced by 43-53% in the cerebral cortex, hippocampus and caudate nucleus of bile-duct-resected rats. Thus mu-opioid receptors in the brain are down-regulated in a classical model of cholestasis. This alteration of the central opioid system could be a consequence of increased exposure of opioid receptors to endogenous opioids in cholestasis and may reflect an important mechanism in the pathogenesis of the pruritus of cholestasis. C1 NIADDKD, MED CHEM LAB, BETHESDA, MD 20892 USA. NIDA, ADDICT RES CTR, CLIN PSYCHOPHARMACOL LAB, BALTIMORE, MD USA. RP BERGASA, NV (reprint author), NIADDKD, LIVER DIS SECT, BLDG 10, 4D-52, BETHESDA, MD 20892 USA. NR 10 TC 103 Z9 104 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 EI 1600-0641 J9 J HEPATOL JI J. Hepatol. PD MAY PY 1992 VL 15 IS 1-2 BP 220 EP 224 DI 10.1016/0168-8278(92)90040-V PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JB762 UT WOS:A1992JB76200039 PM 1324272 ER PT J AU HUSSAIN, R POINDEXTER, RW OTTESEN, EA AF HUSSAIN, R POINDEXTER, RW OTTESEN, EA TI CONTROL OF ALLERGIC REACTIVITY IN HUMAN FILARIASIS - PREDOMINANT LOCALIZATION OF BLOCKING ANTIBODY TO THE IGG4 SUBCLASS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMEDIATE HYPERSENSITIVITY RESPONSES; MONOCLONAL-ANTIBODIES; IGE RESPONSES; SERUM IGG; SENSITIZATION; IMMUNOTHERAPY; ANTIGENS AB Patients with chronic helminth infections, despite having abundant basophils and mast cells specifically sensitized with antiparasite IgE and often exposed repeatedly to parasite Ag, rarely manifest allergic symptoms. This control of clinical allergic reactivity likely results from Ag-specific IgG "blocking antibodies" shown previously to be abundant in the sera of such patients. In the present study we used two approaches to determine in which of the four IgG subclasses this blocking activity was localized. First, specific antifilarial antibodies of each of the four IgG subclasses were quantified in the sera of 28 patients with Bancroftian filariasis and correlated with the levels of blocking activity in these sera (determined by histamine release assays). A significant correlation with blocking activity was seen only for antibodies of the IgG4 subclass, and, indeed, the correlation was especially strong in the group of totally asymptomatic patients (but with microfilariae circulating in the blood) in whom blocking antibody levels were highest. Interestingly, however, if the analysis excluded these asymptomatic microfilaremic patients and focused instead on those with lymphatic inflammatory pathology (who had relatively low levels of both serum blocking activity and specific IgG4 antibodies), then the small amount of blocking activity found in these sera correlated only with the levels of IgG1 subclass antibodies. The second approach utilized selective depletion of IgG4 (by anti-IgG4 affinity columns) from the sera of three microfilaremic patients with high levels of blocking activity and demonstrated clearly that removal of IgG4 abolished the majority of the blocking activity in these sera (53, 78, and 81%). These two sets of findings demonstrate a predominant role for specific IgG4 antibodies in blocking IgE-mediated allergic responses to the parasite Ag in vitro, but they also indicate that in some situations IgG1 antibodies can block such reactions. Furthermore, the correlation demonstrated between patients'clinical presentations and the levels of both their specific IgG4 antibodies and serum blocking activity suggests that these antibodies play a similar role in vivo as well. C1 NIAID,PARASIT DIS & CLIN INVEST LAB,BETHESDA,MD 20892. AGA KHAN UNIV,KARACHI,PAKISTAN. RI Hussain, Rabia/E-9982-2015; Hussain, Rabia/M-6649-2015 OI Hussain, Rabia/0000-0001-9995-8742 NR 34 TC 174 Z9 183 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 1992 VL 148 IS 9 BP 2731 EP 2737 PG 7 WC Immunology SC Immunology GA HQ182 UT WOS:A1992HQ18200011 PM 1573266 ER PT J AU LIEBERMAN, J FABRY, JA KUO, MC EARL, P MOSS, B SKOLNIK, PR AF LIEBERMAN, J FABRY, JA KUO, MC EARL, P MOSS, B SKOLNIK, PR TI CYTOTOXIC LYMPHOCYTES-T FROM HIV-1 SEROPOSITIVE INDIVIDUALS RECOGNIZE IMMUNODOMINANT EPITOPES IN GP160 AND REVERSE-TRANSCRIPTASE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; RECOMBINANT VACCINIA VIRUS; CYTO-TOXIC RESPONSES; INFECTED INDIVIDUALS; SYNTHETIC PEPTIDES; HTLV-III; ENVELOPE GLYCOPROTEIN; FINE SPECIFICITY; NEF PROTEIN; AIDS VIRUS AB The CTL response to HIV-1 is more vigorous than for any known human pathogen and may be a significant factor in preventing the progression to symptomatic disease. T cell lines, generated by nonspecific stimulation with PHA and IL-2, may be reproducibly used to identify HIV-1 isolate-invariant epitopes recognized by the CTL of infected individuals. The CTL response in each of 12 infected individuals to envelope and reverse transcriptase (RT) is dominated by the recognition of one or two viral isolate-invariant epitopes. Seven subjects respond to a single gp160 epitope; three subjects recognize 2 gp160 epitopes. There is a significant increase in recognition of epitopes in the C terminal 104 amino acids of gp41 (p < 0.002); in fact 40% of the subjects that respond to gp160 recognize the C terminal 20-mer. The CTL-mediated lysis of gp160-expressing targets is MHC restricted, but not all individuals that share the same serologically defined class I-restricting element respond to the same epitope. Recognition of the terminal 20mer is restricted by both A30 and B8. The response to RT in six subjects is distributed over the RT protein. The six subjects recognize four separate regions defined by truncated RT-vaccinia recombinants, but none of the subjects' CTL demonstrate significant recognition of the RT epitope identified in H-2k mice and some humans. C1 NEW ENGLAND MED CTR HOSP,DEPT MED,DIV HEMATOL ONCOL,BOSTON,MA 02111. TUFTS UNIV,SCH MED,BOSTON,MA 02111. IMMULOG PHARMACEUT CORP,CAMBRIDGE,MA 02139. NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. NEW ENGLAND MED CTR HOSP,DEPT MED,DIV GEOG MED & INFECT DIS,BOSTON,MA 02111. RI Lieberman, Judy/A-2717-2015 FU NCI NIH HHS [KO8 CA01449-01A1]; NIAID NIH HHS [R01 AI30926-01A1] NR 47 TC 71 Z9 71 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 MAY 1 PY 1992 VL 148 IS 9 BP 2738 EP 2747 PG 10 WC Immunology SC Immunology GA HQ182 UT WOS:A1992HQ18200012 PM 1374097 ER PT J AU ANASTASSIOU, ED PALIOGIANNI, F BALOW, JP YAMADA, H BOUMPAS, DT AF ANASTASSIOU, ED PALIOGIANNI, F BALOW, JP YAMADA, H BOUMPAS, DT TI PROSTAGLANDIN-E2 AND OTHER CYCLIC AMP-ELEVATING AGENTS MODULATE IL-2 AND IL-2R-ALPHA GENE-EXPRESSION AT MULTIPLE LEVELS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CELL ANTIGEN RECEPTOR; LYMPHOCYTE-T ACTIVATION; PROTEIN KINASE-C; TYROSINE PHOSPHORYLATION; SIGNAL TRANSDUCTION; MESSENGER-RNA; INOSITOL PHOSPHATES; MEDIATED ACTIVATION; HUMAN INTERLEUKIN-2; CD2 PATHWAY AB cAMP is an intracellular second messenger that conveys inhibitory signals for T cell activation and clonal proliferation. cAMP also inhibits the production of IL-2 and IL-2R alpha-chain expression. To determine the mechanisms of this inhibition, human peripheral blood T lymphocytes were stimulated with anti-CD3 mAb, PHA, PMA, or ionomycin, alone or in combination. cAMP elevation by PGE2, cholera toxin, or the cell-permeable analogue 8-bromo-cAMP inhibited the tyrosine phosphorylation of a protein of 100 kDa. This inhibition was associated with decreased IL-2 production and IL-2R-alpha expression at both the protein product and the mRNA levels. Nuclear run-off assays showed that the inhibitory effect of cAMP on IL-2 and IL-2R-alpha-gene expression is mediated at the transcriptional level. H-8, an inhibitor of protein kinase A, reversed the inhibitory effect of cAMP on nuclear transcription of the IL-2 gene, suggesting that this is mediated through activation of protein kinase A. Post-transcriptionally, cAMP elevation decreased the t1/2 Of IL-2 mRNA by more than 50%. These data indicate that cAMP inhibits cell membrane, cytoplasmic, and nuclear events associated with T cell activation and highlight the complexities of its action of lymphocyte function. C1 NIDDKD,KIDNEY DIS SECT,BLDG 10,ROOM 3N114,BETHESDA,MD 20892. UNIV PATRAS,SCH MED,DEPT MICROBIOL,GR-26110 PATRAS,GREECE. USN,MED RES INST,IMMUN & CELL BIOL PROGRAM,BETHESDA,MD 20889. NR 52 TC 205 Z9 206 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 1992 VL 148 IS 9 BP 2845 EP 2852 PG 8 WC Immunology SC Immunology GA HQ182 UT WOS:A1992HQ18200026 PM 1374102 ER PT J AU MURPHY, WJ BENNETT, M KUMAR, V LONGO, DL AF MURPHY, WJ BENNETT, M KUMAR, V LONGO, DL TI DONOR-TYPE ACTIVATED NATURAL-KILLER-CELLS PROMOTE MARROW ENGRAFTMENT AND B-CELL DEVELOPMENT DURING ALLOGENEIC BONE-MARROW TRANSPLANTATION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELLS; INTERLEUKIN-2; REJECTION; ALLOGRAFTS; LEUKEMIA; MICE; INVITRO; MEDIATE; INVIVO AB Purified NK cells were obtained from mice with severe combined immune deficiency and were activated with human IL-2 (hrIL-2) in vitro to determine if, once activated, these cells could be transferred with compatible bone marrow cells (BMC) and promote marrow engraftment in irradiated allogeneic recipients. After culture with hrIL-2, these cells maintained a phenotypic and lytic spectrum consistent with a pure population of activated NK cells. These activated NK cells were then adoptively transferred with the donor BMC and rhIL-2 into lethally irradiated allogeneic hosts. The addition of NK cells with the BMC allowed for more rapid hematopoietic engraftment as determined through short term studies, and greater donor-derived chimerism with accelerated reconstitution of the B cell population as determined with long term analysis. No evidence of graft-vs-host disease was detected in the recipients receiving the activated NK cells with allogeneic T cell replete BMC and hrIL-2. The mechanism by which the transferred NK cells improved BMC engraftment was at least partly through the abrogation of the host effector cell's ability to mediate resistance to the marrow graft. Thus, the administration of donor-type activated NK cells with BMC and hrIL-2 may significantly augment hematopoietic engraftment and immune reconstitution in the clinical setting of allogeneic BMT without giving rise to graft-vs-host disease. C1 UNIV TEXAS,SW MED CTR,DEPT PATHOL,DALLAS,TX 75235. RP MURPHY, WJ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,BLDG 567,ROOM 141,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102] NR 20 TC 50 Z9 51 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 1992 VL 148 IS 9 BP 2953 EP 2960 PG 8 WC Immunology SC Immunology GA HQ182 UT WOS:A1992HQ18200041 PM 1573278 ER PT J AU RIMER, HC WASSERMAN, SS FLORES, J PICHICHERO, ME LOSONSKY, GA AF RIMER, HC WASSERMAN, SS FLORES, J PICHICHERO, ME LOSONSKY, GA TI ROTAVIRUS-SPECIFIC BREAST-MILK ANTIBODY IN 2 POPULATIONS AND POSSIBLE CORRELATES OF INTERFERENCE WITH RHESUS ROTAVIRUS VACCINE SEROCONVERSION SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID BOVINE ROTAVIRUS; MONOCLONAL-ANTIBODIES; VENEZUELAN INFANTS; SURFACE-PROTEINS; NEUTRALIZATION; GASTROENTERITIS; PROTECTION; COLOSTRUM; RESPONSES; VP3 AB Milk was collected from 56 New York and 70 Venezuelan mothers participating in Rhesus rotavirus (RRV) pediatric vaccine trials. Plaque reduction neutralization antibody (PRNA) to RRV (VP7:3, VP4:RRV) and human P rotavirus (VP7:3, VP4:P) and epitope-blocking antibody to one RRV VP4 and VP7 epitope were determined. Controlling for postpartum age, more Venezuelan milk samples had detectable RRV and P PRNA, RRV VP4 epitope-blocking antibody (P less-than-or-equal-to .001), and higher RRV and P PRNA geometric mean titers (P = .01) than New York samples. Using a logistic regression model, both milk and infants' serum preimmunization RRV PRNA titers had a negative effect on seroconversion (P = .008 and .02, respectively). Only 25% (2/8) infants fed milk containing greater-than-or-equal-to 1:160 RRV PRNA seroconverted compared with 83% (5/6) fed milk containing < 1:160 RRV PRNA (P = .1). Of milk samples containing greater-than-or-equal-to 1:160 RRV PRNA, seven (88%) of eight had greater than fourfold neutralizing activity against RRV versus P (P = .035), suggesting that VP4-specific milk antibodies may interfere with RRV seroconversion. C1 UNIV MARYLAND,SCH MED,DEPT PEDIAT,DIV INFECT DIS & TROP PEDIAT,CTR VACCINE DEV,BALTIMORE,MD 21201. UNIV MARYLAND,SCH MED,DEPT MED,DIV GEOG MED,CTR VACCINE DEV,BALTIMORE,MD 21201. NIAID,INFECT DIS LAB,BETHESDA,MD 20892. UNIV ROCHESTER,DEPT PEDIAT,ROCHESTER,NY 14627. UNIV ROCHESTER,ELWOOD PEDIAT GRP,ROCHESTER,NY 14627. NR 30 TC 17 Z9 17 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY PY 1992 VL 165 IS 5 BP 826 EP 830 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA HQ275 UT WOS:A1992HQ27500006 PM 1373753 ER PT J AU BOLLINGER, RC KLINE, RL FRANCIS, HL MOSS, MW BARTLETT, JG QUINN, TC AF BOLLINGER, RC KLINE, RL FRANCIS, HL MOSS, MW BARTLETT, JG QUINN, TC TI ACID DISSOCIATION INCREASES THE SENSITIVITY OF P24-ANTIGEN DETECTION FOR THE EVALUATION OF ANTIVIRAL THERAPY AND DISEASE PROGRESSION IN ASYMPTOMATIC HUMAN-IMMUNODEFICIENCY-VIRUS INFECTED PERSONS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Note ID AIDS-RELATED COMPLEX; HIV P24 ANTIGEN; IMMUNE-COMPLEXES; CONTROLLED TRIAL; ZIDOVUDINE AZT; SERUM; AZIDOTHYMIDINE; ANTIBODY; MARKERS AB Because the time from primary infection to symptoms in human immunodeficiency virus type 1 (HIV-1) infection is typically 8-10 years, the use of surrogate markers to monitor disease progression and therapeutic efficacy is of interest. An acid dissociation procedure that disrupts the p24 antigen-antibody complexes found in early HIV-1 infection has greatly increased the sensitivity of p24 detection assays. The utility of p24 antigen after acid treatment as a surrogate marker of disease progression and therapeutic effect in asymptomatic HIV-infected subjects receiving zidovudine (AZT) was determined. After acid treatment, the sensitivity of p24 antigen detection increased fivefold. The proportion of subjects who were antigenemic increased over the 48-week follow-up in the placebo group; approximately 50% of subjects who were p24 antigen-positive at entry and who received AZT showed clearance or a > 50% reduction in baseline p24 antigen levels at 16 and 32 weeks. Thus, acid treatment of plasma may allow the use of p24 antigen as a marker of disease progression and therapeutic response. C1 JOHNS HOPKINS UNIV,DEPT MED,DIV INFECT DIS,BALTIMORE,MD 21205. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. FU NIAID NIH HHS [AI-62538] NR 15 TC 55 Z9 55 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 MAY PY 1992 VL 165 IS 5 BP 913 EP 916 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA HQ275 UT WOS:A1992HQ27500020 PM 1569343 ER PT J AU WIKTOR, SZ CANNON, RO ATKINSON, WL LUTZ, B HOOK, EW BLATTNER, WA QUINN, TC AF WIKTOR, SZ CANNON, RO ATKINSON, WL LUTZ, B HOOK, EW BLATTNER, WA QUINN, TC TI INFECTION WITH HUMAN T-LYMPHOTROPIC VIRUS TYPE-I AND TYPE-II IN SEXUALLY-TRANSMITTED DISEASE CLINICS IN BALTIMORE AND NEW-ORLEANS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Note ID HTLV-I; HOMOSEXUAL MEN; DRUG-ABUSERS; SEROPREVALENCE; TRANSMISSION; TRINIDAD; USA; HIV AB Patients attending sexually transmitted disease (STD) clinics in Baltimore (n = 4880) and New Orleans (n = 1054) were surveyed in 1987 to estimate the prevalence of human T lymphotropic virus (HTLV)-I/II infection. In Baltimore, 0.4% (95% confidence interval [CI], 0.2-1.1) were HTLV-I/II-seropositive and 4.9% were human immunodeficiency virus (HIV-1)-positive. In New Orleans, 1.8% (CI, 1.2-2.9) of sera were HTLV-I/II-seropositive and 5.1% were HIV-1-seropositive. In both cities, HTLV-I/II prevalence increased significantly with age, and the New Orleans age- and sex-adjusted HTLV-I/II prevalence was significantly higher than that of Baltimore (P <.001). In Baltimore, almost all HTLV-I/II seropositivity was associated with a history of parenteral drug use or sexual contact with partners who were drug users or male homosexuals. In addition, individuals in both cities who were seropositive for HIV-1 or syphilis were significantly more likely to be HTLV-I/II-seropositive. C1 NCI,VIRAL EPIDEMIOL SECT,BETHESDA,MD 20892. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,DIV INFECT DIS,BALTIMORE,MD 21218. CITY HLTH DEPT,BALTIMORE,MD. CTR DIS CONTROL,DIV STD HIV PREVENT,ATLANTA,GA 30333. TULANE UNIV,SCH PUBL HLTH & TROP MED,LOUISIANA DEPT HLTH & HUMAN SERV,DEPT BIOSTAT & EPIDEMIOL,NEW ORLEANS,LA 70118. NEW ORLEANS DEPT HLTH,NEW ORLEANS,LA. NR 17 TC 38 Z9 38 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 MAY PY 1992 VL 165 IS 5 BP 920 EP 924 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA HQ275 UT WOS:A1992HQ27500022 PM 1569344 ER PT J AU BEVER, CT MCFARLIN, DE LEVY, HB AF BEVER, CT MCFARLIN, DE LEVY, HB TI A COMPARISON OF INTERFERON RESPONSES TO POLY ICLC IN MALES AND FEMALES SO JOURNAL OF INTERFERON RESEARCH LA English DT Article ID MULTIPLE-SCLEROSIS; INDUCER; VIRUS AB Interferon (IFN) responses to polyriboinosinic acid polyribocytidylic acid in poly-L-lysine and carboxymethylcellulose (poly ICLC) have been studied in detail in 6 men and 3 women as part of a preliminary trial in patients with multiple sclerosis (MS). Patients received intravenous (i.v.) doses of 100-mu-g/kg poly ICLC, and serum IFN levels were determined serially every 4 h for 16 h. Men and women produced substantial levels of IFN at 8, 12, and 16 h after infusion, but levels in men were consistently and significantly higher (p < 0.05). Interferon responses were examined also in 3 male and 3 female Rhesus monkeys. Serum samples were obtained 8 and 24 h after i.v. injections of 1 mg/kg of poly ICLC. Again, there were significantly higher levels of IFN in males. The observed differences may reflect sex-linked differences in either drug metabolism or specific sensitivity to IFN induction by poly ICLC. The most interesting possibility is that the difference is due to a more general difference in IFN response between males and females. Studies are currently in progress to evaluate these possibilities. C1 NIAID,VIRAL DIS LAB,FREDERICK,MD 21701. RP BEVER, CT (reprint author), NINCDS,NEUROIMMUNOL BRANCH,BETHESDA,MD 20892, USA. NR 20 TC 2 Z9 4 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0197-8357 J9 J INTERFERON RES JI J. Interferon Res. PD MAY PY 1992 SI SI BP 85 EP 90 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HY930 UT WOS:A1992HY93000013 ER PT J AU MICHEL, S BERNERD, F JETTEN, AM FLOYD, EE SHROOT, B REICHERT, U AF MICHEL, S BERNERD, F JETTEN, AM FLOYD, EE SHROOT, B REICHERT, U TI EXPRESSION OF KERATINOCYTE TRANSGLUTAMINASE MESSENGER-RNA AS REVEALED BY INSITU HYBRIDIZATION SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 CTR INT RECH DERMATOL GALDERMA,VALBONNE,FRANCE. NIEHS,PULM PATHOBIOL LAB,CELL BIOL SECT,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 1992 VL 98 IS 5 BP 828 EP 828 PG 1 WC Dermatology SC Dermatology GA HR030 UT WOS:A1992HR03000086 ER PT J AU STADLER, R THEWES, M KORGE, B MISCHKE, D AF STADLER, R THEWES, M KORGE, B MISCHKE, D TI NORMAL PSORIATIC EPIDERMIS EXPRESSED HYPERPROLIFERATION-ASSOCIATED KERATINS SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 MED CTR MINDEN,DEPT DERMATOL,MINDEN,GERMANY. FREE UNIV BERLIN,W-1000 BERLIN 33,GERMANY. NIAMSD,SKIN BIOL LAB,BETHESDA,MD. FREE UNIV BERLIN,KLINIKUM CHARLOTTENBURG,W-1000 BERLIN 19,GERMANY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 1992 VL 98 IS 5 BP 829 EP 829 PG 1 WC Dermatology SC Dermatology GA HR030 UT WOS:A1992HR03000092 ER PT J AU MICHEL, S BERNERD, F JETTEN, AM FLOYD, EE SHROOT, B REICHERT, U AF MICHEL, S BERNERD, F JETTEN, AM FLOYD, EE SHROOT, B REICHERT, U TI EXPRESSION OF KERATINOCYTE TRANSGLUTAMINASE (TGM) MESSENGER-RNA AS REVEALED BY INSITU HYBRIDIZATION SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 CTR INT RECH DERMATOL,F-06565 VALBONNE,FRANCE. NIEHS,CELL BIOL SECT,PULM PATHOBIOL LAB,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 1992 VL 98 IS 5 BP 839 EP 839 PG 1 WC Dermatology SC Dermatology GA HR030 UT WOS:A1992HR03000145 ER PT J AU GRALNICK, HR AF GRALNICK, HR TI VONWILLEBRAND-FACTOR, INTEGRINS, AND PLATELETS - THEIR ROLE IN CANCER SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Editorial Material ID ENDOTHELIAL-CELLS; SYNTHETIC PEPTIDE; GLYCOPROTEIN-IIB; ALPHA-SUBUNITS; VITRONECTIN; FIBRONECTIN; FIBRINOGEN; RECEPTOR; METASTASIS; MELANOMA RP GRALNICK, HR (reprint author), NIH,HEMATOL SERV,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 42 TC 12 Z9 12 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-2143 J9 J LAB CLIN MED JI J. Lab. Clin. Med. PD MAY PY 1992 VL 119 IS 5 BP 444 EP 447 PG 4 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA HU536 UT WOS:A1992HU53600001 PM 1583396 ER PT J AU RADER, DJ GREGG, RE MENG, MS SCHAEFER, JR ZECH, LA BENSON, MD BREWER, HB AF RADER, DJ GREGG, RE MENG, MS SCHAEFER, JR ZECH, LA BENSON, MD BREWER, HB TI INVIVO METABOLISM OF A MUTANT APOLIPOPROTEIN, APOA-IIOWA, ASSOCIATED WITH HYPOALPHALIPOPROTEINEMIA AND HEREDITARY SYSTEMIC AMYLOIDOSIS SO JOURNAL OF LIPID RESEARCH LA English DT Article DE HIGH DENSITY LIPOPROTEINS; KINETICS; APOA-I KINETICS ID HIGH-DENSITY LIPOPROTEIN; CORONARY-ARTERY DISEASE; AMINO-ACID SEQUENCE; A-I-VARIANTS; CHOLESTEROL ACYLTRANSFERASE; ATHEROSCLEROSIS; SUBSTITUTIONS; QUANTITATION; LECITHIN; PROTEINS AB Apolipoprotein (apo) A-I is the major protein constituent of plasma high density lipoproteins (HDL). A kindred has been identified in which a glycine to arginine mutation at residue 26 in apoA-I is associated with hypoalphalipoproteinemia and hereditary systemic amyloidosis. We isolated the mutant protein, termed apoA-I(Iowa), from the plasma of an affected subject and studied its in vivo metabolism compared to that of normal apoA-I in two heterozygous apoA-I(Iowa) subjects and two normal controls. Normal and mutant apoA-I were radioiodinated with I-131 and I-125, respectively, reassociated with autologous plasma lipoproteins, and simultaneously injected into all subjects. Kinetic analysis of the plasma radioactivity curves demonstrated that the mutant apoA-I(Iowa) was rapidly cleared from plasma (mean fractional catabolic rate [FCR] 0.559 day-1) compared with normal apoA-I (mean FCR 0.244 day-1) in all four subjects. The FCR of normal apoA-1 was also substantially faster in the heterozygous apoA-I(Iowa) subjects (mean FCR 0.281 days-1) than in the normal controls (mean FCR 0.203 days-1). Despite the rapid removal from plasma of apoA-I(Iowa), the cumulative urinary excretion of its associated radioactivity after 2 weeks (44%) of the injected dose) was substantially less than that associated with normal apoA-I (78% of injected dose), indicating extravascular sequestration of radiolabeled apoA-I(Iowa). Therefore, the single amino acid substitution in apoA-I(Iowa) results in both rapid clearance of apoA-I, explaining the low levels of plasma HDL and apoA-I, as well as extravascular sequestration of the mutant apolipoprotein, consistent with the formation of amyloid deposits containing aggregates of apoA-I(Iowa), in heterozygous carriers of this unique apoA-I variant. C1 INDIANA UNIV,SCH MED,DEPT MED,INDIANAPOLIS,IN 46202. INDIANA UNIV,SCH MED,DEPT MED GENET,INDIANAPOLIS,IN 46202. RP RADER, DJ (reprint author), NHLBI,MOLEC DIS BRANCH,BLDG 10,ROOM 7N117,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 40 TC 87 Z9 87 U1 0 U2 2 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD MAY PY 1992 VL 33 IS 5 BP 755 EP 763 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HW810 UT WOS:A1992HW81000014 PM 1619367 ER PT J AU ARCHER, SJ BALDISSERI, DM TORCHIA, DA AF ARCHER, SJ BALDISSERI, DM TORCHIA, DA TI OPTIMIZATION OF BASE-LINE AND FOLDING IN SPECTRA OBTAINED USING THE TPPI FORMAT SO JOURNAL OF MAGNETIC RESONANCE LA English DT Note RP ARCHER, SJ (reprint author), NIDR,BONE RES BRANCH,BETHESDA,MD 20892, USA. NR 5 TC 14 Z9 14 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0022-2364 J9 J MAGN RESON JI J. Magn. Reson. PD MAY PY 1992 VL 97 IS 3 BP 602 EP 606 DI 10.1016/0022-2364(92)90038-9 PG 5 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA HT482 UT WOS:A1992HT48200012 ER PT J AU LAKATTA, E SOLLOTT, S GAMBASSI, G SPURGEON, H AF LAKATTA, E SOLLOTT, S GAMBASSI, G SPURGEON, H TI REGULATION OF CONTRACTION AND RELAXATION IN SINGLE CARDIAC MYOCYTES SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Meeting Abstract C1 NIA, GERONTOL RES CTR, BALTIMORE, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD MAY PY 1992 VL 24 SU 2 BP S26 EP S26 DI 10.1016/0022-2828(92)90921-L PG 1 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA HY933 UT WOS:A1992HY93300058 ER PT J AU TISCHLER, M CARDELLINA, JH BOYD, MR CRAGG, GM AF TISCHLER, M CARDELLINA, JH BOYD, MR CRAGG, GM TI CYTOTOXIC QUASSINOIDS FROM CEDRONIA-GRANATENSIS SO JOURNAL OF NATURAL PRODUCTS LA English DT Article AB The NCI in vitro primary disease-oriented antitumor screen has been used to select and guide the fractionation of the organic and aqueous extracts of Cedronia granatensis. Two quassinoids, sergiolide [1] and isobrucein B [2], to which the screening panel cell lines exhibited up to a 1000-fold range of differential sensitivity, were isolated. At concentrations of 10(-5)-10(-8) M, the compounds typically produced LC50-level responses against a majority of the melanoma lines and several of the colon, lung, and other solid tumor lines. These and related quassinoids may, therefore, be of interest for in vivo evaluation in appropriate xenograft tumor models. C1 NCI,DRUG DISCOVERY RES & DEV LAB,BLDG 1052,FREDERICK,MD 21702. NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,NAT PROD BRANCH,FREDERICK,MD 21702. NR 14 TC 9 Z9 9 U1 0 U2 0 PU AMER SOC PHARMACOGNOSY PI CINCINNATI PA LLOYD LIBRARY & MUSEUM 917 PLUM ST, CINCINNATI, OH 45202 SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD MAY PY 1992 VL 55 IS 5 BP 667 EP 671 DI 10.1021/np50083a018 PG 5 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA HT828 UT WOS:A1992HT82800018 PM 1517739 ER PT J AU TUOMINEN, RK MCMILLIAN, MK YE, H STACHOWIAK, MK HUDSON, PM HONG, JS AF TUOMINEN, RK MCMILLIAN, MK YE, H STACHOWIAK, MK HUDSON, PM HONG, JS TI LONG-TERM ACTIVATION OF PROTEIN-KINASE-C BY NICOTINE IN BOVINE ADRENAL CHROMAFFIN CELLS SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE NICOTINE; BOVINE ADRENAL MEDULLARY CHROMAFFIN CELLS; PROTEIN KINASE-C; DIACYLGLYCEROL; PHORBOL 12-MYRISTATE 13-ACETATE ID PHORBOL ESTER TREATMENT; MEDULLARY CELLS; CATECHOLAMINE SECRETION; INOSITOL TRISPHOSPHATE; MUSCARINIC RECEPTORS; CALCIUM CHANNELS; CA-2+; MECHANISMS; MESSENGER; DIACYLGLYCEROL AB Previous results from our laboratory suggest that long-term treatment of primary cultured bovine adrenal medullary (BAM) chromaffin cells with nicotine or phorbol 12-myristate 13-acetate, either of which directly activates protein kinase C (PKC), increases the mRNA levels encoding catecholamine-synthesizing enzymes and proenkephalin. In the present study, we have examined the effects of nicotine on BAM cell PKC activity with special emphasis on long-term effects. Nicotine increased particulate PKC activity in a concentration-dependent manner when measured using in vitro enzyme assay with histone as the substrate. This effect is mediated through nicotinic cholinergic receptors, because 1,1-dimethylphenylpiperazinium, a nicotinic agonist, had a similar effect. In addition, chlorisondamine, a specific nicotine-receptor blocking drug, antagonized the effect of nicotine. Nicotine also increased specific [H-3]phorbol 12,13-dibutyrate ([H-3]PdBu) binding within 1 min, the effect of which was maximal between 3 and 12 min. This effect was reversed by chlorisondamine similarly after 12 min and after 18 h of nicotine treatment, indicating that continual nicotinic-receptor occupancy is required for persistent PKC activation. Compared to PKC activation, the onset of nicotine-stimulated diacylglycerol production was slow, and it was observed after 12 min of incubation with nicotine. The diacylglycerol levels, specific [H-3]PdBu binding, and PKC activity remained significantly elevated for at least 18 h with continuous nicotine incubation. Furthermore, nicotine increased the PKC immunoreactivity of a particulate protein with a molecular mass of 82 kDa in the western blot. These results suggest that nicotinic-receptor activation increases PKC activity and immunoreactivity in BAM cells. The long-term PKC activation may serve several functions, such as activation of mRNA production and a negative feedback regulation of either nicotinic receptors or voltage-dependent Ca2+ channels. RP NIEHS, NEUROPHARMACOL SECT, MOLEC & INTEGRAT NEUROSCI LAB, POB 12233, RES TRIANGLE PK, NC 27709 USA. FU PHS HHS [4066] NR 43 TC 40 Z9 40 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 1992 VL 58 IS 5 BP 1652 EP 1658 DI 10.1111/j.1471-4159.1992.tb10037.x PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA HN274 UT WOS:A1992HN27400008 PM 1560224 ER PT J AU MOLLER, JR RAMASWAMY, SG JACOBOWITZ, DM QUARLES, RH AF MOLLER, JR RAMASWAMY, SG JACOBOWITZ, DM QUARLES, RH TI A RABBIT AUTOANTIBODY SPECIFIC FOR THE 46-KDA FORM OF 2',3'-CYCLIC NUCLEOTIDE 3'-PHOSPHODIESTERASE SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE AUTOANTIBODY; 2',3'-CYCLIC NUCLEOTIDE 3'-PHOSPHODIESTERASE (CNP); ISOFORM; MYELIN; OLIGODENDROCYTE ID AMINO-ACID SEQUENCE; POLYACRYLAMIDE GELS; MOLECULAR-CLONING; WOLFGRAM PROTEIN; NERVOUS-SYSTEM; MESSENGER-RNA; CDNA CLONING; MYELIN; BRAIN; 3'-PHOSPHOHYDROLASE AB An autoantibody occurring in the serum of an apparently normal rabbit that immunocytochemically stains myelin sheaths and oligodendrocytes in rat brain was shown to react specifically with the 46-kDa isoform of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) (EC 3.1.4.37) in a number of species. Identification of the shorter isoform of the enzyme (CNP1) as the antigen was achieved by comparing the immunostaining of Western blots by the autoantibody with that of a well-characterized anti-CNP antiserum. The 46-kDa antigen reacting with the autoantibody exhibited the same M(r) and pI as the small isoform of CNP on two-dimensional gels and showed a similar enrichment in purified CNS myelin. The autoantibody has very high affinity for CNP1 and is capable of detecting the very low amounts of this enzyme in peripheral nerve, spleen, adrenal gland, pancreas, testis, and intestine. Testing the reactivity of the autoantibody with synthetic peptides by enzyme-linked immunosorbent assay revealed that it reacted with the N-acetylated decapeptide corresponding to the N-terminus of CNP1, but did not react if the peptide was not acetylated or if the acetyl group was replaced with a palmityl group. The lack of reactivity with CNP2, which differs from CNP1 by a 20-amino acid extension at the N-terminus of the protein as a result of alternative splicing, may be due to the absence of the N-acetyl moiety that is part of the epitope and/or blocking of antibody binding to the decapeptide by extension of the polypeptide chain. This highly specific antibody for the shorter isoform of CNP may be useful in studies to establish possible differences in the location or function of the two isoforms of this enzyme. C1 NIMH, CLIN SCI LAB, BETHESDA, MD 20892 USA. RP NINCDS, MYELIN & BRAIN DEV SECT, MOLEC & CELLULAR NEUROBIOL LAB, PK BLDG, BETHESDA, MD 20892 USA. NR 24 TC 6 Z9 6 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 1992 VL 58 IS 5 BP 1829 EP 1835 DI 10.1111/j.1471-4159.1992.tb10059.x PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA HN274 UT WOS:A1992HN27400030 PM 1373178 ER PT J AU WELLER, M AF WELLER, M TI HOW TO DEFINE THE OPERCULAR SYNDROME SO JOURNAL OF NEUROLOGY LA English DT Letter ID CHAVANY-MARIE SYNDROME RP WELLER, M (reprint author), NIH,CLIN NEUROSCI BRANCH,BLDG 10,ROOM 3N256,BETHESDA,MD 20892, USA. NR 5 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-5354 J9 J NEUROL JI J. Neurol. PD MAY PY 1992 VL 239 IS 5 BP 294 EP 295 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA HT306 UT WOS:A1992HT30600016 PM 1472191 ER PT J AU YAO, DL BRENNER, M KOMOLY, S BONDY, C JAKAB, G WEBSTER, H AF YAO, DL BRENNER, M KOMOLY, S BONDY, C JAKAB, G WEBSTER, H TI ASTROCYTIC IGF-I AND GFAP MESSENGER-RNA AND PEPTIDE EXPRESSION DURING CUPRIZONE-INDUCED DEMYELINATION AND REMYELINATION SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 NINCDS,BETHESDA,MD 20892. NICHHD,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1992 VL 51 IS 3 BP 338 EP 338 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA HT972 UT WOS:A1992HT97200102 ER PT J AU MESSING, A SU, Y KISSEBERTH, WC BESNARD, F BRENNER, M AF MESSING, A SU, Y KISSEBERTH, WC BESNARD, F BRENNER, M TI ASTROCYTE-SPECIFIC EXPRESSION IN TRANSGENIC MICE SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 UNIV WISCONSIN,MADISON,WI 53706. NIH,BETHESDA,MD 20892. NR 1 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1992 VL 51 IS 3 BP 349 EP 349 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA HT972 UT WOS:A1992HT97200145 ER PT J AU SHARER, LR WEIHE, E NOHR, D MURRAY, EA RAUSCH, DM LENDVAY, J EIDEN, LE AF SHARER, LR WEIHE, E NOHR, D MURRAY, EA RAUSCH, DM LENDVAY, J EIDEN, LE TI CORTICAL GLIOSIS IN SIV-INFECTED MACAQUES WITH DOCUMENTED COGNITIVE-MOTOR IMPAIRMENT SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 UNIV MED & DENT NEW JERSEY,NEW JERSEY MED SCH,NEWARK,NJ 07103. UNIV MAINZ,W-6500 MAINZ,GERMANY. NIMH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1992 VL 51 IS 3 BP 354 EP 354 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA HT972 UT WOS:A1992HT97200166 ER PT J AU GRESSENS, P LANGSTON, C MITCHELL, WJ MARTIN, JR AF GRESSENS, P LANGSTON, C MITCHELL, WJ MARTIN, JR TI USE OF THE POLYMERASE CHAIN-REACTION (PCR) IN NEUROPATHOLOGICAL STUDY OF HERPES-SIMPLEX VIRUS (HSV) ENCEPHALITIS IN NEONATES SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. TEXAS CHILDRENS HOSP,HOUSTON,TX 77030. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 1992 VL 51 IS 3 BP 372 EP 372 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA HT972 UT WOS:A1992HT97200234 ER PT J AU HYLDEN, JLK NOGUCHI, K RUDA, MA AF HYLDEN, JLK NOGUCHI, K RUDA, MA TI NEONATAL CAPSAICIN TREATMENT ATTENUATES SPINAL FOS ACTIVATION AND DYNORPHIN GENE-EXPRESSION FOLLOWING PERIPHERAL TISSUE INFLAMMATION AND HYPERALGESIA SO JOURNAL OF NEUROSCIENCE LA English DT Article ID IMMEDIATE-EARLY GENES; PRIMARY AFFERENT NEURONS; PRIMARY SENSORY NEURONS; CENTRAL NERVOUS-SYSTEM; DORSAL HORN NEURONS; C-FOS; NOXIOUS-STIMULATION; THERMAL NOCICEPTION; PROJECTION NEURONS; MESSENGER-RNAS AB An animal model of nociception involving unilateral hindpaw inflammation has been used to examine behavioral, molecular, and biochemical aspects of well-characterized spinal cord neural circuits involved in pain transmission. The neurotoxin capsaicin administered neonatally was used to modify this neuronal system by producing a selective destruction of most small, unmeylinated primary afferent axons. Capsaicin had minimal effects on the behavioral hyperalgesia and edema associated with the hindpaw inflammation and on the constitutive expression of preprodynorphin (PPD) mRNA and preproenkephalin mRNA in the spinal cord. However, the inflammation-induced increases in Fos-like immunoreactivity (Fos-LI) and in PPD mRNA were greatly attenuated by neonatal capsaicin treatment. The data indicate that input from small-diameter unmyelinated primary afferents is important for the stimulus-induced increase in Fos-LI and PPD mRNA. Our finding that neonatal capsaicin reduces the levels of Fos-LI and PPD mRNA in a related fashion in the spinal dorsal horn provides further evidence for a relationship between the protein product of the c-fos proto-oncogene and regulation of dynorphin gene transcription. C1 NIDR, NEUROBIOL & ANESTHESIOL BRANCH, 9000 ROCKVILLE PIKE, BLDG 30, BETHESDA, MD 20892 USA. NR 51 TC 68 Z9 68 U1 0 U2 0 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAY PY 1992 VL 12 IS 5 BP 1716 EP 1725 PG 10 WC Neurosciences SC Neurosciences & Neurology GA HT837 UT WOS:A1992HT83700015 PM 1374461 ER PT J AU BONOW, RO DILSIZIAN, V AF BONOW, RO DILSIZIAN, V TI TL-201 AND TECHNETIUM-99M-SESTAMIBI FOR ASSESSING VIABLE MYOCARDIUM SO JOURNAL OF NUCLEAR MEDICINE LA English DT Editorial Material ID VENTRICULAR DYSFUNCTION; HIBERNATING MYOCARDIUM; TL-201 REINJECTION; BYPASS SURGERY; WALL-MOTION; VIABILITY; REST; REDISTRIBUTION; REVASCULARIZATION; SCINTIGRAPHY C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. NR 44 TC 47 Z9 48 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAY PY 1992 VL 33 IS 5 BP 815 EP 818 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA HT117 UT WOS:A1992HT11700033 PM 1533248 ER PT J AU CREMER, SA KESSLER, LG AF CREMER, SA KESSLER, LG TI THE FAT AND FIBER CONTENT OF FOODS - WHAT AMERICANS KNOW SO JOURNAL OF NUTRITION EDUCATION LA English DT Article C1 NCI,DIV CANC PREVENT & CONTROL,BALTIMORE,MD 21211. NR 0 TC 16 Z9 16 U1 0 U2 1 PU DECKER PERIODICALS INC PI HAMILTON PA 4 HUGHSON STREET SOUTH PO BOX 620, LCD 1, HAMILTON ON L8N 3K7, CANADA SN 0022-3182 J9 J NUTR EDUC JI J. Nutr. Educ. PD MAY-JUN PY 1992 VL 24 IS 3 BP 149 EP 152 PG 4 WC Education, Scientific Disciplines; Nutrition & Dietetics SC Education & Educational Research; Nutrition & Dietetics GA JC526 UT WOS:A1992JC52600007 ER PT J AU DESIMONE, DP REDDI, AH AF DESIMONE, DP REDDI, AH TI VASCULARIZATION AND ENDOCHONDRAL BONE-DEVELOPMENT - CHANGES IN PLASMINOGEN-ACTIVATOR ACTIVITY SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE PLASMINOGEN; VASCULARIZATION; CALCIFICATION; CARTILAGE; ENDOTHELIUM; ENDOCHONDRAL BONE FORMATION ID CYCLIC NUCLEOTIDES; TRANSFORMATION; MODULATION; MORPHOLOGY; OVULATION; SECRETION; CARTILAGE; INVASION; ENZYMES; INVITRO AB Changes in plasminogen activator activity were studied during the sequential developmental stages of matrix-induced cartilage, bone, and bone marrow development. The morphological transitions were correlated with biochemical parameters. Morphologic evidence of vascularization of calcified hypertrophic cartilage was accompanied by a concomitant rise in plasminogen activator activity. Thereafter, a steady decline during mineralization and deposition of new bone was observed. Maximal plasminogen activator activity occurs at approximately the same time as peak activity of alkaline and acid phosphatase. These results imply a role for plasminogen activator during angiogenesis, vascular invasion, and attendant bone differentiation. C1 MT SINAI MED CTR,DEPT ORTHOPAED,NEW YORK,NY 10029. NIDR,BONE CELL BIOL SECT,BETHESDA,MD 20892. NR 23 TC 10 Z9 10 U1 0 U2 1 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 SN 0736-0266 J9 J ORTHOPAED RES JI J. Orthop. Res. PD MAY PY 1992 VL 10 IS 3 BP 320 EP 324 DI 10.1002/jor.1100100303 PG 5 WC Orthopedics SC Orthopedics GA HP829 UT WOS:A1992HP82900002 PM 1373768 ER PT J AU ANDERSSON, HC MARKELLO, T SCHNEIDER, JA GAHL, WA AF ANDERSSON, HC MARKELLO, T SCHNEIDER, JA GAHL, WA TI EFFECT OF GROWTH-HORMONE TREATMENT ON SERUM CREATININE CONCENTRATION IN PATIENTS WITH CYSTINOSIS AND CHRONIC RENAL-DISEASE SO JOURNAL OF PEDIATRICS LA English DT Article ID NEPHROPATHIC CYSTINOSIS; CHILDREN; PROGRESSION; CYSTEAMINE; FAILURE AB Three patients with nephropathic cystinosis and chronic renal disease, treated since early childhood with orally administered cysteamine, had an accelerated rate of rise of serum creatinine values after receiving recombinant human growth hormone. During 18 to 24 months of growth hormone treatment, each patient had a twofold to fourfold increase in growth velocity. The slope of the plot of reciprocal serum creatinine values versus age for each patient after growth hormone treatment was significantly steeper than the pretreatment slope. Growth hormone treatment had no effect on the rate of change of the uncorrected 24-hour renal creatinine clearance. We conclude that these patients gained body size but failed to compensate for their increased creatinine production with an increase in glomerular filtration rate. The result was an accelerated rate of rise of their serum creatinine values, hastening renal transplantation in one patient and the anticipated need for transplantation in another. C1 NICHHD, HUMAN GENET BRANCH,BLDG 10,ROOM 9S242, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. UNIV CALIF SAN DIEGO, DEPT PEDIAT, LA JOLLA, CA 92093 USA. NR 19 TC 19 Z9 19 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 MAY PY 1992 VL 120 IS 5 BP 716 EP 720 DI 10.1016/S0022-3476(05)80233-1 PG 5 WC Pediatrics SC Pediatrics GA HT981 UT WOS:A1992HT98100008 PM 1578305 ER PT J AU RELLING, MV EVANS, R DASS, C DESIDERIO, DM NEMEC, J AF RELLING, MV EVANS, R DASS, C DESIDERIO, DM NEMEC, J TI HUMAN CYTOCHROME-P450 METABOLISM OF TENIPOSIDE AND ETOPOSIDE SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID STRANDED PHI-X174 DNA; O-DEMETHYLATION; ORTHO-QUINONE; VP-16-213; INACTIVATION; OXIDATION; CHILDREN; CATECHOL; BINDING; LIVER AB Although teniposide (VM26) and etoposide (VP16) are eliminated mostly by nonrenal mechanisms, their cytochrome P450 metabolism in humans has not been reported. Our objective was to determine the affinity and capacity of P450 O-demethylation of VM26 and VP16 in a variety of human livers. Formation of catechols of VM26 and VP16 was detected in 24 and 26 of 26 liver microsomal preparations, respectively, with wide variability in maximum catechol formation rates from VM26 (41-fold) and VP16 (39-fold range), even among normal livers. Maximal activity measurements at 500-mu-M substrate were lower for VM26 catechol formation (mean = 1.5 nmol/mg/hr) than for VP16 catechol (mean = 3.2 nmol/mg/hr) in 26 livers (P < .001). Maximal activities for VP16 and VM26 O-demethylation, and ethoxycoumarin O-deethylation were significantly higher in normal than in diseased livers. No differences were found in activities related to age, sex or race of the liver donor. In all five livers tested over a range of substrate concentrations, K(m) (19.7, 23.2, 43.5, 30.1 and 22.0-mu-M) and V(max) values (1.0, 1.2, 4.4, 8.2 and 4.0 nmol/mg/hr) for VM26 were lower compared to values for VP16 (K(m) = 60.2, 115.1, 87.3, 42.1 and 81.9-mu-m; V(max) = 1.4, 3.3, 10.3, 27.5 and 10.1 nmol/mg/hr). Despite higher VP16 catechol formation, VM26 underwent greater overall reduced nicotinamide adenine dinucleotide phosphate-dependent metabolism than VP16, consistent with greater nonrenal clearance of VM26 in vivo. In addition to the role of O-demethylation as a route of catabolism for VM26 and VP16 in humans, the significant variability in formation of the reactive catechol metabolites may play a role in their clinical efficacy and toxicity. C1 UNIV TENNESSEE CTR HLTH SCI, CTR PEDIAT PHARMACOKINET & THERAPEUT, DEPT CLIN PHARM, MEMPHIS, TN 38163 USA. UNIV TENNESSEE CTR HLTH SCI, DEPT NEUROL, CHARLES B STOUT NEUROSCI MASS SPECT LAB, MEMPHIS, TN 38163 USA. UNIV TENNESSEE CTR HLTH SCI, DEPT BIOCHEM, CHARLES B STOUT NEUROSCI MASS SPECT LAB, MEMPHIS, TN 38163 USA. NCI, FREDERICK CANC RES & DEV CTR, PRI DYNCORP, CHEM SYNTH & ANAL LAB, FREDERICK, MD 21701 USA. RP RELLING, MV (reprint author), ST JUDE CHILDRENS RES HOSP, DIV PHARMACEUT, 332 N LAUDERDALE, MEMPHIS, TN 38105 USA. FU NCI NIH HHS [CA21765, R29 CA51001]; NIGMS NIH HHS [GM 266666] NR 23 TC 67 Z9 69 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD MAY PY 1992 VL 261 IS 2 BP 491 EP 496 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA HT700 UT WOS:A1992HT70000014 PM 1578365 ER PT J AU RICAURTE, GA MARTELLO, AL KATZ, JL MARTELLO, MB AF RICAURTE, GA MARTELLO, AL KATZ, JL MARTELLO, MB TI LASTING EFFECTS OF (+/-)-3,4-METHYLENEDIOXYMETHAMPHETAMINE (MDMA) ON CENTRAL SEROTONERGIC NEURONS IN NONHUMAN-PRIMATES - NEUROCHEMICAL OBSERVATIONS SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID RAT-BRAIN; RHESUS-MONKEYS; METHYLENEDIOXYMETHYLAMPHETAMINE MDMA; 3,4-METHYLENEDIOXYMETHAMPHETAMINE; NEUROTOXICITY; TERMINALS; DOPAMINE; METHYLENEDIOXYMETHAMPHETAMINE; LESIONS; AXONS AB The purpose of this study was to assess the duration of (+/-)-3,4-ethylenedioxymethamphetamine's (MDMA's) effects on serotonin containing neurons in nonhuman primates. Fifteen squirrel monkeys were used: three served as controls, 12 received MDMA s.c. at a dose of 5 mg/kg twice daily for 4 consecutive days. Two weeks, 10 weeks, 8 months and 18 months after drug treatment, groups (n = 3) of MDMA-treated monkeys, along with controls, were examined for regional brain content of serotonin and 5-hydroxyindoleacetic acid, and for the number of [H-3] paroxetine-labeled serotonin uptake sites. Two weeks after MDMA treatment, monkeys showed profound reductions in all three serotonergic presynaptic markers. By 10 weeks, there was evidence of partial recovery in some brain regions (e.g., hippocampus, caudate nucleus, frontal cortex). However, by 18 months, it was evident that recovery did not continue, as serotonergic deficits returned to the level of severity observed 2 weeks after MDMA treatment. This was the case in all brain regions examined except the thalamus and hypothalamus. In the thalamus, the level of serotonin increased to 63% of control, whereas that of 5-hydroxyindoleacetic acid recovered completely. In the hypothalamus, concentrations of serotonin and 5-hydroxyindoleacetic acid were 140 and 187% of control, respectively. These results suggest that MDMA produces lasting effects on serotonergic neurons in nonhuman primates, with most brain regions showing evidence of persistent denervation and some showing signs of reinnervation (thalamus) or possibly even hyperinnervation (hypothalamus). The morphological and functional correlates of these enduring neurochemical changes in the MDMA-treated primate remain to be delineated. C1 NIDA, ADDICT RES CTR, BALTIMORE, MD USA. RP RICAURTE, GA (reprint author), JOHNS HOPKINS UNIV, SCH MED, FRANCIS SCOTT KEY MED CTR, DEPT NEUROL, 4940 EASTERN AVE, BALTIMORE, MD 21224 USA. OI Katz, Jonathan/0000-0002-1068-1159 FU NIDA NIH HHS [DA 05707] NR 26 TC 192 Z9 192 U1 0 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD MAY PY 1992 VL 261 IS 2 BP 616 EP 622 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA HT700 UT WOS:A1992HT70000032 PM 1374470 ER PT J AU SKOPOULI, FN KOUSVELARI, EE MERTZ, P JAFFE, ES FOX, PC MOUTSOPOULOS, HM AF SKOPOULI, FN KOUSVELARI, EE MERTZ, P JAFFE, ES FOX, PC MOUTSOPOULOS, HM TI C-MYC MESSENGER-RNA EXPRESSION IN MINOR SALIVARY-GLANDS OF PATIENTS WITH SJOGRENS-SYNDROME SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE SJOGRENS SYNDROME; SALIVARY GLAND PROTOONCOGENES; EPITHELIAL CELLS ID EPSTEIN-BARR VIRUS; TRANSGENIC MICE; CELLS; AUTOIMMUNE; ONCOGENE; EXOCRINOPATHY; INVOLVEMENT; SICCA; BLOOD AB c-myc protooncogene is implicated in the pathogenesis of B cell lymphoid malignancies and high levels of c-myc mRNA expression are observed in activated blood mononuclear cells. Sjogren's syndrome (SS) is characterized by lymphocytic infiltrates of exocrine glands, remarkable B cell hyperreactivity and a strong predisposition to B cell neoplasia. In this study, c-myc protooncogene mRNA expression in 29 labial minor salivary gland biopsies from patients with primary SS and 15 controls was examined using in situ hybridization histochemistry. Two 40mer oligonucleotides from the 1st and the 2nd exon of the c-myc gene, labeled with S-35, were used as probes. To detect the origin of the cell hybridized with a c-myc probe, a combined immunochemistry in situ hybridization histochemistry technique was used. High c-myc mRNA expression was detected on acinar epithelial cells. c-myc did not correlate with c-fos and c-jun protein expression. Stronger c-myc mRNA expression was detected in labial salivary glands of patients with longer disease duration (p less-than-or-equal-to 0.002) and more intense T lymphocyte infiltrates (p < 0.05) although these patients revealed no hypergammaglobulinemia. No correlation was observed between c-myc mRNA and B lymphocyte monoclonicity or lymphoma. In conclusion, strong c-myc mRNA expression was observed on epithelial cells of labial salivary glands from patients with primary SS. Our findings may indicate the presence of a reactivated virus hosted in these cells. C1 NIDR,CLIN INVEST & CARE BRANCH,BETHESDA,MD 20892. NCI,PATHOL LAB,HEMATOPATHOL SECT,BETHESDA,MD 20892. RP SKOPOULI, FN (reprint author), UNIV IOANNINA,SCH MED,DEPT INTERNAL MED,DIV RHEUMATOL,GR-45110 IOANNINA,GREECE. NR 38 TC 27 Z9 27 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO ON M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD MAY PY 1992 VL 19 IS 5 BP 693 EP 699 PG 7 WC Rheumatology SC Rheumatology GA HW156 UT WOS:A1992HW15600007 PM 1613697 ER PT J AU UNSER, M STONE, M AF UNSER, M STONE, M TI AUTOMATED DETECTION OF THE TONGUE SURFACE IN SEQUENCES OF ULTRASOUND IMAGES SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID MODEL; SHAPE AB An image processing system has been developed for a Macintosh II personal computer. It is designed to process sequences of sagittal tongue sections that are digitized in real time and stored in standard tagged image file format (TIFF). The successive processing steps are: (a) a low-pass filter for noise reduction, (b) a resampling of the sector of interest in polar coordinates, (c) a matched filter (vertical differentiator) for the enhancement of the tissue/air interface in the surface region of the tongue, and (d) an extraction of border points by searching for an optimal radial path along the angular dimension. This latter task is achieved by dynamic programming, which has the following advantages. First, due to the use of a global criterion to guide the detection, it is very robust. Second, as a result of certain restrictions of the allowable transitions, the extracted contours are smooth. Finally, the method permits the specification of particular predefined contour points. This system was implemented in a program that can handle image sequences in a fully automatic mode. Results obtained using ultrasound data are presented. C1 NIH,DEPT REHABIL MED,BETHESDA,MD 20892. RP UNSER, M (reprint author), NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BLDG 13,BETHESDA,MD 20892, USA. RI Unser, Michael/A-1550-2008 NR 15 TC 13 Z9 13 U1 0 U2 1 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD MAY PY 1992 VL 91 IS 5 BP 3001 EP 3007 DI 10.1121/1.402934 PG 7 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA HT688 UT WOS:A1992HT68800053 PM 1629491 ER PT J AU KAMEYAMA, K MORITA, M SUGAYA, K NISHIYAMA, S HEARING, VJ AF KAMEYAMA, K MORITA, M SUGAYA, K NISHIYAMA, S HEARING, VJ TI TREATMENT OF RETICULATE ACROPIGMENTATION OF KITAMURA WITH AZELAIC ACID - AN IMMUNOHISTOCHEMICAL AND ELECTRON-MICROSCOPIC STUDY SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID S91 MELANOMA-CELLS; DICARBOXYLIC-ACIDS; MELANOCYTES; INHIBITION; CULTURES; INVITRO AB No successful therapy has been reported for reticulate acropigmentation of Kitamura, which is an autosomal dominant dermatosis. We treated a patient with 20% azelaic acid ointment. Within several weeks the pigmentation was remarkably decreased and no side effects were observed. Histologic examination revealed an increased number of dopa-positive melanocytes. These cells reacted strongly to staining with antityrosinase antibody or antityrosinase-related protein antibody. Electron microscopic findings showed many melanosomes within melanocytes, keratinocytes, and melanophages. These findings suggest that the hyperpigmentation of reticulate acropigmentation of Kitamura is the result of an excess amount of melanin production caused by activation of melanocytes in the basal layer. C1 NIH,CELL BIOL LAB,BETHESDA,MD 20892. RP KAMEYAMA, K (reprint author), KITASATO UNIV,SCH MED,DEPT DERMATOL,1-15-1 KITASATO,SAGAMIHARA,KANAGAWA 228,JAPAN. NR 25 TC 16 Z9 17 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 MAY PY 1992 VL 26 IS 5 BP 817 EP 820 DI 10.1016/0190-9622(92)70112-S PN 2 PG 4 WC Dermatology SC Dermatology GA HR214 UT WOS:A1992HR21400004 PM 1613143 ER PT J AU SALIVE, ME CORNONIHUNTLEY, J GURALNIK, JM PHILLIPS, CL WALLACE, RB OSTFELD, AM COHEN, HJ AF SALIVE, ME CORNONIHUNTLEY, J GURALNIK, JM PHILLIPS, CL WALLACE, RB OSTFELD, AM COHEN, HJ TI ANEMIA AND HEMOGLOBIN LEVELS IN OLDER PERSONS - RELATIONSHIP WITH AGE, GENDER, AND HEALTH-STATUS SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID URBAN SWEDISH POPULATION; LABORATORY VALUES; PEOPLE; SEX AB Objective: To determine the relationship of hemoglobin levels and anemia with age and health status in older adults. Design: Survey. Setting: Community. Participants and Methods: Hematologic tests were obtained from 3,946 adults aged greater-than-or-equal-to 71 years in three communities (East Boston, MA; lowa and Washington counties, IA; and New Haven, CT). Results: Hemoglobin level was inversely associated with age, although this was more pronounced in men than in women. The proportion anemic was equal for men and women aged 71-74 years (8.6%) and increased differentially with age, reaching 41% and 21% for men and women aged greater-than-or-equal-to 90 years, respectively. Hemoglobin and anemia were independently associated with age, race, body-mass index, smoking, cancer, hospitalization, renal insufficiency, and hypoalbuminemia. The adjusted relative odds of anemia for a 5-year increase in age was 1.5 (95% confidence interval [CI] 1.3-1.8) for men and 1.2 (95% CI 1.1-1.4) for women. Conclusions: Age is significantly associated with both hemoglobin levels and anemia, with a stronger effect in men compared with women, even after simultaneously adjusting for demographic characteristics and health status. The decline of hemoglobin and concomitant increased anemia with age is not necessarily a result of "normal aging" so the detection of anemia in an older person should prompt appropriate clinical attention. C1 UNIV IOWA,DEPT PREVENT MED & ENVIRONM HLTH,IOWA CITY,IA 52242. YALE UNIV,SCH MED,DEPT EPIDEMIOL,NEW HAVEN,CT 06510. DUKE UNIV,CTR STUDY AGING & HUMAN DEV,DURHAM,NC 27706. RP SALIVE, ME (reprint author), NIA,EPIDEMIOL DEMOG & BIOMETRY PROGRAM,7201 WISCONSIN AVE,BETHESDA,MD 20892, USA. FU NIA NIH HHS [N01-AG-02105, N01-AG-02106, N01-AG-02107] NR 32 TC 120 Z9 124 U1 3 U2 5 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAY PY 1992 VL 40 IS 5 BP 489 EP 496 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA HT856 UT WOS:A1992HT85600011 PM 1634703 ER PT J AU BUSBY, MJ BELLANTONI, MF TOBIN, JD MULLER, DC KAFONEK, SD BLACKMAN, MR ANDRES, R AF BUSBY, MJ BELLANTONI, MF TOBIN, JD MULLER, DC KAFONEK, SD BLACKMAN, MR ANDRES, R TI GLUCOSE-TOLERANCE IN WOMEN - THE EFFECTS OF AGE, BODY-COMPOSITION, AND SEX-HORMONES SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID DEPENDENT DIABETES-MELLITUS; DOSE ORAL-CONTRACEPTIVES; CARBOHYDRATE-METABOLISM; MENSTRUAL-CYCLE; FAT DISTRIBUTION; INSULIN; ESTROGEN; INTOLERANCE; DIAGNOSIS; ESTRADIOL AB Objective: To determine the separate and interactive effects of age, phase of the menstrual cycle, menopausal hormone status, body fat mass, and regional fat distribution on glucose tolerance in healthy women. Design: Retrospective study. Setting: The Baltimore Longitudinal Study of Aging. Patients: Two hundred sixty healthy women aged 22-89 years. Measurements: Plasma levels of estradiol and progesterone, body mass index (BMI), waist-to-hip ratio (WHR), and plasma glucose values in the fasting state (FPG) as well as 120 minutes after 40 gm/m2 of oral glucose (G120) were measured for each participant. Results: We found a progressive decline in oral glucose tolerance of 0.4 mm (6.7 mg/dL)/decade at G120) in women from early to late adult years, with no relationship to phase of the menstrual cycle and no abrupt change associated with the menopause. Multiple regression analysis revealed significant, independent effects of BMI and WHR on FPG and G120. The influence of age (P < 0.01) on G120 was stronger than that of the BMI or WHR (P < 0.05). There was no significant relationship between the levels of endogenous sex hormones and glucose tolerance after adjustments for age, BMI, and WHR. However, women taking oral contraceptives, but not those receiving postmenopausal replacement therapy, did exhibit mildly elevated G120 values. Conclusions: Age per se, and to a lesser extent BMI and WHR, but not levels of endogenous sex steroids, contribute to the physiological decline in glucose tolerance in older women. C1 NIA,GERONTOL RES CTR,CLIN PHYSIOL LAB,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. RP BUSBY, MJ (reprint author), FRANCIS SCOTT KEY MED CTR,GEN CLIN RES CTR,DEPT MED,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. OI Bellantoni, Michele/0000-0001-8525-2247 NR 57 TC 11 Z9 11 U1 7 U2 9 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAY PY 1992 VL 40 IS 5 BP 497 EP 502 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA HT856 UT WOS:A1992HT85600012 PM 1634704 ER PT J AU MOSELEY, MA JORGENSON, JW SHABANOWITZ, J HUNT, DF TOMER, KB AF MOSELEY, MA JORGENSON, JW SHABANOWITZ, J HUNT, DF TOMER, KB TI OPTIMIZATION OF CAPILLARY ZONE ELECTROPHORESIS ELECTROSPRAY IONIZATION PARAMETERS FOR THE MASS-SPECTROMETRY AND TANDEM MASS-SPECTROMETRY ANALYSIS OF PEPTIDES SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article ID FUSED-SILICA; PROTEINS; INTERFACE; BUFFERS; ADSORPTION; SEPARATION; PHASES; SALTS AB The solution chemistry conditions necessary for optimum analysis of peptides by capillary zone electrophoresis (CZE)/electrospray ionization mass spectrometry and CZE electrospray ionization tandem mass spectrometry have been studied. To maximize the signal-to-noise ratio of the spectra it was found necessary to use acidic CZE buffers of low ionic strength. This not only increases the total ion current, but it also serves to fully protonate the peptides, minimizing the distribution of ion current across the ensemble of possible charge states. The use of acidic buffers protonates the peptides, which is advantageous for mass spectrometry and tandem mass spectrometry analysis, but is problematic with CZE when bare fused silica CZE columns are used. These conditions produce positively charged peptides, and negatively charged silanol moieties on the column wall, inducing adsorption of the positively charged peptides, thus causing zone broadening and a loss in separation efficiency. This problem was circumvented by the preparation of chemically modified CZE columns, which, when used with acidic CZE buffers, will have a positively charged inner column wall. The electrostatic repulsion between the positively charged peptides and the positively charged CZE column wall minimizes adsorption problems and facilitates high efficiency separations. Full-scan mass spectra were acquired from injections of as little as 160 fmols of test peptides, with CZE separation efficiencies of up to 250,000 theoretical plates. C1 UNIV N CAROLINA,DEPT CHEM,CHAPEL HILL,NC 27514. UNIV VIRGINIA,DEPT CHEM,CHARLOTTESVILLE,VA 22903. NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. RI Tomer, Kenneth/E-8018-2013; Hunt, Donald/I-6936-2012 OI Hunt, Donald/0000-0003-2815-6368 NR 45 TC 120 Z9 121 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD MAY PY 1992 VL 3 IS 4 BP 289 EP 300 DI 10.1016/1044-0305(92)87056-5 PG 12 WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA HV637 UT WOS:A1992HV63700003 PM 24243039 ER PT J AU WALTHER, MM MALECH, H BERMAN, A CHOYKE, P VENZON, DJ LINEHAN, WM GALLIN, JI AF WALTHER, MM MALECH, H BERMAN, A CHOYKE, P VENZON, DJ LINEHAN, WM GALLIN, JI TI THE UROLOGICAL MANIFESTATIONS OF CHRONIC GRANULOMATOUS-DISEASE SO JOURNAL OF UROLOGY LA English DT Article DE GRANULOMATOUS DISEASE, CHRONIC; GRANULOMA; URETHRAL STRICTURE; URETERAL OBSTRUCTION; URINARY TRACT INFECTION ID CHILDHOOD; CYSTITIS; GLOMERULONEPHRITIS; CORTICOSTEROIDS; TRIMETHOPRIM; THERAPY; OXIDASE AB Chronic granulomatous disease is a rare disorder of phagocytic cell oxidative metabolism. Patients have recurrent infections with catalase positive organisms and granulomatous lesions throughout the body. The genitourinary tract can be an occult site of involvement. We reviewed the prevalence of urological abnormalities in 60 patients with chronic granulomatous disease. Chart review revealed that 23 of the 60 patients (38%) had urological manifestations. Seven patients had 10 ureteral strictures. Treatment of the granulomatous strictures with steroids caused at least a temporary decrease in size or a resolution of the granulomas and relief of the obstruction. Three patients had bladder granulomas and 1 had a urethral stricture. A total of 12 patients had urinary tract infections and 7 had altered renal function. Ten patients had other manifestations of genitourinary disease. Abnormalities in the urinary tract are relatively frequent. Risk factors include X-linked disease and low percentile weight. Genitourinary manifestations can cause significant morbidity in chronic granulomatous disease patients. A variety of therapies, including judicious use of steroids and gamma-interferon, are proving to be useful in the treatment of this disorder and in some cases they may offer a nonoperative alternative for relief of chronic granulomatous obstructive disease in these patients. C1 NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. NIAID,HOST DEF LAB,BETHESDA,MD 20892. CLIN CTR,DEPT DIAGNOST RADIOL,BETHESDA,MD. RP WALTHER, MM (reprint author), NCI,SURG BRANCH,UROL ONCOL SECT,BETHESDA,MD 20892, USA. RI Venzon, David/B-3078-2008 NR 30 TC 35 Z9 37 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAY PY 1992 VL 147 IS 5 BP 1314 EP 1318 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA HR463 UT WOS:A1992HR46300040 PM 1569675 ER PT J AU PALLANSCH, LA LACKMANSMITH, CS GONDA, MA AF PALLANSCH, LA LACKMANSMITH, CS GONDA, MA TI BOVINE IMMUNODEFICIENCY-LIKE VIRUS ENCODES FACTORS WHICH TRANSACTIVATE THE LONG TERMINAL REPEAT SO JOURNAL OF VIROLOGY LA English DT Article ID ACETYLTRANSFERASE GENE-EXPRESSION; ACTING TRANSCRIPTIONAL REGULATION; HTLV-III; GENOME ORGANIZATION; MOLECULAR-CLONING; INFECTED-CELLS; MESSENGER-RNA; RAPID ASSAY; VISNA VIRUS; AIDS VIRUS AB Lentiviruses are known to encode factors which trans activate expression from the viral long terminal repeat (LTR); the primary trans activator is the tat gene product. One of the putative accessory genes (tat) of the bovine immunodeficiency-like virus (BIV) bears sequence similarity to other lentivirus tat genes. This finding suggests that BIV may encode a trans-activating protein capable of stimulating LTR-directed gene expression. To test this hypothesis in vitro, BIV LTR-chloramphenicol acetyltransferase (CAT) reporter gene plasmids were constructed and transfected into three cell lines established from canine, bovine, or lapine tissues that are susceptible to BIV infection. The level of BIV LTR-directed CAT gene expression was significantly elevated in BIV-infected cells compared with uninfected cells. The relatively high basal-level expression of BIV LTR-CAT in uninfected canine and bovine cell lines suggests that cellular factors play a role in regulating BIV LTR-directed gene expression. Additionally, by using a clonal canine cell line in which the BIV LTR-CAT plasmid is stably expressed, BIV LTR-directed CAT expression is elevated 15- to 80-fold by cocultivation with BIV-infected cells, supporting the notion that BIV encodes a trans activator. The relative specificity of this viral activation was assessed by coculturing the clonal BIV LTR-CAT cell line with bovine leukemia virus- or bovine syncytial virus-infected cells; these bovine retroviruses increased expression from the BIV LTR only two- to threefold. Thus, BIV LTR regulatory elements in infected cells, like those of human immunodeficiency virus type 1 and other lentiviruses, are trans activated, presumably through the action of a Tat-like protein and cellular factors. C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,CELL & MOLEC STRUCT LAB,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74102] NR 51 TC 29 Z9 29 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 MAY PY 1992 VL 66 IS 5 BP 2647 EP 2652 PG 6 WC Virology SC Virology GA HP817 UT WOS:A1992HP81700007 PM 1313891 ER PT J AU MASUDA, M REMINGTON, MP HOFFMAN, PM RUSCETTI, SK AF MASUDA, M REMINGTON, MP HOFFMAN, PM RUSCETTI, SK TI MOLECULAR CHARACTERIZATION OF A NEUROPATHOGENIC AND NONERYTHROLEUKEMOGENIC VARIANT OF FRIEND MURINE LEUKEMIA-VIRUS PVC-211 SO JOURNAL OF VIROLOGY LA English DT Article ID LONG TERMINAL REPEAT; FOCUS-INDUCING VIRUSES; NONDEFECTIVE FRIEND; ENVELOPE GENE; 3' END; DISEASE SPECIFICITY; NUCLEOTIDE-SEQUENCE; ENHANCER REGION; POINT MUTATIONS; SARCOMA-VIRUS AB PVC-211 murine leukemia virus (MuLV) is a replication-competent, ecotropic type C retrovirus that was isolated after passage of the Friend virus complex through F344 rats. Unlike viruses in the Friend virus complex, it does not cause erythroleukemia but causes a rapidly progressive hind limb paralysis when injected into newborn rats and mice. We have isolated an infectious DNA clone (clone 3d) of this virus which causes neurological disease in animals as efficiently as parental PVC-211 MuLV. The restriction map of clone 3d is very similar to that of the nonneuropathogenic, erythroleukemogenic Friend murine leukemia virus (F-MuLV), suggesting that PVC-211 MuLV is a variant of F-MuLV and that no major structural alteration was involved in its derivation. Studies with chimeric viruses between PVC-211 MuLV clone 3d and wild-type F-MuLV clone 57 indicate that at least one determinant for neuropathogenicity resides in the 2.1-kb XbaI-ClaI fragment containing the gp70 coding region of PVC-211 MuLV. Compared with nonneuropathogenic ecotropic MuLVs, the env gene of PVC-211 MuLV encodes four unique amino acids in the gp70 protein. Nucleotide sequence analysis also revealed a deletion in the U3 region of the long terminal repeat (LTR) of PVC-211 MuLV clone 3d compared with F-MuLV clone 57. In contrast to the env gene of PVC-211 MuLV, particular sequences within the U3 region of the viral LTR do not appear to be required for neuropathogenicity. However, the changes in the LTR of PVC-211 MuLV may be responsible for the failure of this virus to cause erythroleukemia, because chimeric viruses containing the U3 region of F-MuLV clone 57 were erythroleukemogenic whereas those with the U3 of PVC-211 MuLV clone 3d were not. C1 NCI,MOLEC ONCOL LAB,FREDERICK,MD 21702. VET ADM MED CTR,RETROVIRUS RES CTR,BALTIMORE,MD 21218. NR 45 TC 62 Z9 63 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 MAY PY 1992 VL 66 IS 5 BP 2798 EP 2806 PG 9 WC Virology SC Virology GA HP817 UT WOS:A1992HP81700025 PM 1560524 ER PT J AU SODDU, S LEWIS, AM AF SODDU, S LEWIS, AM TI DRIVING ADENOVIRUS TYPE-12-TRANSFORMED BALB/C MOUSE CELLS TO EXPRESS HIGH-LEVELS OF CLASS-I MAJOR HISTOCOMPATIBILITY COMPLEX PROTEINS ENHANCES, RATHER THAN ABROGATES, THEIR TUMORIGENICITY SO JOURNAL OF VIROLOGY LA English DT Article ID NATURAL-KILLER CELLS; CYTOTOXIC LYMPHOCYTES-T; TRANSFORMED CELLS; SIMIAN VIRUS-40; TUMOR-CELLS; ANTIGEN; GENE; SENSITIVITY; E1A; TRANSPLANTATION AB The tumorigenicity of adenovirus type 12 (Ad12)-transformed cells has been attributed to the low levels of class I major histocompatibility complex (MHC) protein expression by these cells. These levels of class I proteins are thought to be below the threshold critical for cytotoxic T-lymphocyte recognition, a process that may be involved in tumor cell immunosurveillance. We have used gene transfer experiments to investigate the role played by class I protein expression in the tumorigenicity of Ad12-transformed BALB/c mouse cells in naive, syngeneic adult mice. Our Ad12-transformed mouse cells were tumorigenic in adult mice and were similar to other Ad12-transformed mammalian cells in that they expressed low levels of class I MHC mRNA and cell surface proteins. Despite these low levels of expression, the cells were highly immunogenic in syngeneic mice and were rejected as allografts by allogeneic mice. Transfection of genomic H-2D(d) or H-2L(d) fragments into these cells produced a variety of cell clones that expressed increased levels of cell surface class I proteins. These cells expressing high levels of class I protein were up to 16-fold more tumorigenic than the parental cells in syngeneic adult mice. Thus, by quantitative assays, the tumorigenicity of Ad12-transformed BALB/c mouse cells is not functionally related to the low levels of class I MHC proteins they express. The increased tumorigenicity expressed by H-2D(d)- and H-2L(d)-transfected cells was not detected in BALB/c nu/nu mice, suggesting that a thymus-dependent mechanism that is not mediated by evasion of cytotoxic T-lymphocyte recognition could contribute to the difference in tumorigenicity of Ad12-transformed BALB/c mouse cells that express low and high levels of class I MHC proteins. C1 NIAID,IMMUNOPATHOL LAB,BETHESDA,MD 20892. NR 60 TC 16 Z9 16 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 MAY PY 1992 VL 66 IS 5 BP 2875 EP 2884 PG 10 WC Virology SC Virology GA HP817 UT WOS:A1992HP81700035 PM 1313906 ER PT J AU ALEXANDER, WA MOSS, B FUERST, TR AF ALEXANDER, WA MOSS, B FUERST, TR TI REGULATED EXPRESSION OF FOREIGN GENES IN VACCINIA VIRUS UNDER THE CONTROL OF BACTERIOPHAGE-T7 RNA-POLYMERASE AND THE ESCHERICHIA-COLI LAC REPRESSOR SO JOURNAL OF VIROLOGY LA English DT Article ID MAMMARY-TUMOR VIRUS; MAMMALIAN-CELLS; NUCLEOTIDE-SEQUENCE; SYSTEM; SELECTION; PLASMIDS; ELEMENTS; VECTORS AB The gene encoding bacteriophage T7 RNA polymerase (T7gene1) was placed under the control of regulatory elements from the Escherichia coli lac operon to construct an inducible vaccinia virus expression system consisting entirely of prokaryotic transcriptional machinery. Regulated expression of T7 RNA polymerase was necessary to construct a stable recombinant vaccinia virus harboring a T7 promoter; otherwise, uncontrolled expression led to interference with endogenous virus replication. To this end, the gene encoding the repressor protein of the lac operon was fused to a viral early/late promoter so that it was expressed constitutively, and the lac operator was interposed between a viral major late promoter and T7gene1. Greater than 99% repression of T7 RNA polymerase, which was relieved approximately 80-fold in the presence of the inducer isopropyl-beta-D-thiogalactopyranoside (IPTG), was obtained. An expression cassette containing a T7 promoter-controlled beta-galactosidase reporter gene was recombined into a different region of the viral genome containing T7gene1. A stable, double recombinant virus was isolated and grown to a high titer. In the absence of inducer, beta-galactosidase expression was substantially repressed. Addition of increasing amounts of IPTG induced expression of beta-galactosidase to the point of suppression of viral replication. This hybrid vaccinia virus system (Vac/Op/T7) has potential applications for the efficient bioproduction of a wide variety of gene products. C1 MEDIMMUNE INC,DEPT MOLEC GENET,GAITHERSBURG,MD 20878. NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. FU NIGMS NIH HHS [1R43-GM43638] NR 31 TC 146 Z9 146 U1 2 U2 10 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 MAY PY 1992 VL 66 IS 5 BP 2934 EP 2942 PG 9 WC Virology SC Virology GA HP817 UT WOS:A1992HP81700041 PM 1560532 ER PT J AU AMEGADZIE, BY AHN, BY MOSS, B AF AMEGADZIE, BY AHN, BY MOSS, B TI CHARACTERIZATION OF A 7-KILODALTON SUBUNIT OF VACCINIA VIRUS DNA-DEPENDENT RNA-POLYMERASE WITH STRUCTURAL SIMILARITIES TO THE SMALLEST SUBUNIT OF EUKARYOTIC RNA POLYMERASE-II SO JOURNAL OF VIROLOGY LA English DT Article ID EARLY TRANSCRIPTION FACTOR; GEL-ELECTROPHORESIS; SEQUENCE-ANALYSIS; EARLY GENES; IDENTIFICATION; PURIFICATION; EXPRESSION; INITIATION; PROMOTERS; PROTEINS AB A previously unrecognized 7-kDa polypeptide copurified with the DNA-dependent RNA polymerase of vaccinia virus virions. Internal amino acid sequences of the small protein matched a viral genomic open reading frame of 63 codons. Antipeptide antiserum was used to confirm the specific and complete association of the 7-kDa protein with RNA polymerase. The amino acid sequence predicted from the viral gene, named rpo7, was 23% identical to that of the smallest subunit of Saccharomyces cerevisiae RNA polymerase II, and a metal-binding motif, Cys-X-X-Cys-Gly, was located at precisely the same location near the N terminus in the two proteins. RNA analyses demonstrated early transcriptional initiation and termination signals in the rpo7 gene sequence. The viral RNA polymerase subunit was synthesized during the early phase of infection and continued to accumulate during the late phase. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. NR 37 TC 42 Z9 43 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 MAY PY 1992 VL 66 IS 5 BP 3003 EP 3010 PG 8 WC Virology SC Virology GA HP817 UT WOS:A1992HP81700048 PM 1560534 ER PT J AU AURIGEMMA, RE BLAIR, DG RUSCETTI, SK AF AURIGEMMA, RE BLAIR, DG RUSCETTI, SK TI TRANSACTIVATION OF ERYTHROID TRANSCRIPTION FACTOR GATA-1 BY A MYB-ETS-CONTAINING RETROVIRUS SO JOURNAL OF VIROLOGY LA English DT Article ID ERYTHROLEUKEMIA CELL-DIFFERENTIATION; PUTATIVE ONCOGENE SPI-1; DNA-BINDING FACTOR; C-MYB; ERYTHROPOIETIN RECEPTOR; GENE-EXPRESSION; LEUKEMIA-VIRUS; MESSENGER-RNA; GLOBIN GENES; ACTIVATION AB ME26 virus is a recombinant mouse retrovirus construct homologous to the avian E26 virus. Both encode a 135-kDa gag-myb-ets fusion protein which is localized in the nucleus. We have recently shown that ME26 virus can induce erythropoietin (Epo) responsiveness in hematopoietic cells. Mice infected with ME26 virus develop a hyperplasia of Epo-dependent hematopoietic precursor cells from which permanent cell lines can be established. In vitro, ME26 virus specifically induces Epo responsiveness in the interleukin-3-dependent myeloid cell line FDC-P2 by enhancing expression of the Epo receptor (EpoR). In the present study we demonstrate that ME26 virus infection of FDC-P2 cells also results in enhanced expression of beta-globin and the erythroid-specific transcription factor GATA-1, a protein which can transactivate both the EpoR promoter and globin genes. In addition, these cells exhibit a down-regulation of c-myb expression similar to that seen in differentiating erythroid cells. To determine the molecular basis for activation of erythroid genes in ME26 virus-infected cells, we carried out transient expression assays with DNA constructs of either the EpoR promoter or the GATA-1 promoter linked to reporter genes. Our results indicate that while ME26 virus did not directly enhance expression from the EpoR promoter, both it and its avian parent, E26, transactivated the GATA-1 promoter. Furthermore, ME26 virus cooperates with the GATA-1 protein to enhance expression of the EpoR gene. We propose that the mechanism by which ME26 virus induces erythroleukemia involves transactivation of the GATA-1 gene, thus positively regulating the expression of the EpoR and leading to the proliferation of a unique population of Epo-responsive cells. By specifically inducing Epo responsiveness in hematopoietic cells via transactivation of a transcription factor, ME26 virus utilizes a novel mechanism for retrovirus pathogenesis. C1 NCI,MOLEC ONCOL LAB,FREDERICK,MD 21702. NR 47 TC 28 Z9 28 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 MAY PY 1992 VL 66 IS 5 BP 3056 EP 3061 PG 6 WC Virology SC Virology GA HP817 UT WOS:A1992HP81700055 PM 1560536 ER PT J AU CLEMENS, DL WOLFINBARGER, JB MORI, S BERRY, BD HAYES, SF BLOOM, ME AF CLEMENS, DL WOLFINBARGER, JB MORI, S BERRY, BD HAYES, SF BLOOM, ME TI EXPRESSION OF ALEUTIAN MINK DISEASE PARVOVIRUS CAPSID PROTEINS BY A RECOMBINANT VACCINIA VIRUS - SELF-ASSEMBLY OF CAPSID PROTEINS INTO PARTICLES SO JOURNAL OF VIROLOGY LA English DT Article ID MINUTE VIRUS; STRUCTURAL PROTEINS; AUTONOMOUS PARVOVIRUS; NUCLEOTIDE-SEQUENCE; NUCLEAR LOCATION; MESSENGER-RNAS; INFECTED MINK; MICE; STRAINS; CLONING AB A portion of a cDNA clone containing coding sequences for both structural proteins (VP1 and VP2) of Aleutian mink disease parvovirus (ADV) was inserted into recombinant vaccinia viruses, VV:ADSP. Immunohistochemical staining of VV:ADSP-infected cells revealed that the ADV antigen was readily detected and localized in the nuclei of infected cells. Analysis of VV:ADSP-infected cell lysates indicated that both VP1 and VP2 were produced and comigrated with authentic VP1 and VP2 from ADV-infected Crandell feline kidney cells. These results suggested, therefore, that both VP1 and VP2 were synthesized from a single cloned transcript. CsCl density gradient centrifugation of partially purified VV:ADSP-infected cell lysates indicated that the majority of the antigen was located in a fraction with a density near 1.33 g/ml, indicative of empty ADV particles. Subsequent electron microscopic examination revealed the presence of 27-nm icosahedral virion-like structures at the same density, suggesting that the proteins self-assembled into empty virions. Furthermore, sera from eight of eight mice inoculated with VV:ADSP contained ADV-specific antibodies and two of these eight serum samples had neutralizing activity, indicating that the particles produced in VV:ADSP-infected cells were immunogenic. Finally, when lysates from VV:ADSP-infected cells were compared with standard ADV antigens in counterimmunoelectrophoresis assays, a similar pattern of specific reactivity was observed for sera from normal and infected mink. C1 NIAID,ROCKY MT LABS,VECTORS & PATHOGENS LAB,HAMILTON,MT 59840. NR 45 TC 21 Z9 27 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1992 VL 66 IS 5 BP 3077 EP 3085 PG 9 WC Virology SC Virology GA HP817 UT WOS:A1992HP81700058 PM 1313919 ER PT J AU WYATT, LS FRENKEL, N AF WYATT, LS FRENKEL, N TI HUMAN HERPESVIRUS-7 IS A CONSTITUTIVE INHABITANT OF ADULT HUMAN SALIVA SO JOURNAL OF VIROLOGY LA English DT Note ID ACQUIRED IMMUNODEFICIENCY SYNDROME; AIDS-RELATED COMPLEX; HTLV-III; EXANTHEM SUBITUM; T-CELLS; INFECTION; ANTIBODY; VIRUS; DNA; IDENTIFICATION AB We report the frequent isolation of human herpesvirus 7 from the saliva of healthy adults. Virus isolates recovered from different individuals exhibited minimal restriction enzyme polymorphism, which was mostly confined to heterogenous (het) sequences in the genome. DNAs of isolates recovered from the same individual over a period of several months showed the same characteristic het fragments, indicating the stability of the het sequences upon virus replication and shedding in vivo. In contrast to the results of previous reports, human herpesvirus 6, the causative agent of roseola infantum, could not be isolated from the saliva specimens, raising questions regarding oral transmission of human herpesvirus 6 and human herpesvirus 7 to young children. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. NR 34 TC 144 Z9 147 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 MAY PY 1992 VL 66 IS 5 BP 3206 EP 3209 PG 4 WC Virology SC Virology GA HP817 UT WOS:A1992HP81700077 PM 1348548 ER PT J AU ERBE, JG GREEN, KA CRASSI, KM MORSE, HC GREEN, WR AF ERBE, JG GREEN, KA CRASSI, KM MORSE, HC GREEN, WR TI CYTOLYTIC LYMPHOCYTES-T SPECIFIC FOR TUMORS AND INFECTED-CELLS FROM MICE WITH A RETROVIRUS-INDUCED IMMUNODEFICIENCY SYNDROME SO JOURNAL OF VIROLOGY LA English DT Note ID MURINE LEUKEMIA-VIRUS; C57BL/6 MICE; MAIDS; DISEASE; AIDS; SUSCEPTIBILITY; INDIVIDUALS; EXPRESSION; INDUCTION; LYMPHOMAS AB LP-BM5 retrovirus complex-infected C57BL/6 mice develop immunodeficiency, somewhat analogous to AIDS, termed murine AIDS (MAIDS). After secondary stimulation with syngeneic B-cell lymphomas from LP-BM5-infected mice, C57BL/6 mice produced vigorous CD8+ cytotoxic T lymphocytes specific for MAIDS-associated tumors. An anti-LP-BM5 specificity was suggested because spleen and lymph node cells from LP-BM5-infected mice served as target cells in competition assays, and cells from LP-BM5, but not ecotropic, virus-infected mice functioned as secondary in vitro stimulators to generate cytotoxic T lymphocytes to MAIDS tumors. C1 DARTMOUTH COLL,HITCHCOCK MED CTR,DARTMOUTH MED SCH,DEPT MICROBIOL,HANOVER,NH 03756. DARTMOUTH COLL,HITCHCOCK MED CTR,DARTMOUTH MED SCH,NORRIS COTTON CANC CTR,HANOVER,NH 03756. NIAID,IMMUNOPATHOL LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA36860, CA50157]; NIAID NIH HHS [N01-AI-72622] NR 36 TC 11 Z9 13 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1992 VL 66 IS 5 BP 3251 EP 3256 PG 6 WC Virology SC Virology GA HP817 UT WOS:A1992HP81700086 PM 1560546 ER PT J AU HAZZARD, DG BRONSON, RT MCCLEARN, GE STRONG, R AF HAZZARD, DG BRONSON, RT MCCLEARN, GE STRONG, R TI SELECTION OF AN APPROPRIATE ANIMAL-MODEL TO STUDY AGING PROCESSES WITH SPECIAL EMPHASIS ON THE USE OF RAT STRAINS SO JOURNALS OF GERONTOLOGY LA English DT Editorial Material C1 TULANE UNIV,SCH VET MED,DEPT PATHOL,NEW ORLEANS,LA 70118. TULANE UNIV,SCH MED,NEW ORLEANS,LA 70112. PENN STATE UNIV,COLL HLTH & HUMAN DEV,UNIV PK,PA 16802. ST LOUIS UNIV,SCH MED,DEPT INTERNAL MED,ST LOUIS,MO 63104. RP HAZZARD, DG (reprint author), NIA,BIOL AGING PROGRAM,BETHESDA,MD 20892, USA. NR 4 TC 31 Z9 31 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 MAY PY 1992 VL 47 IS 3 BP B63 EP B64 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA HT691 UT WOS:A1992HT69100030 PM 1573179 ER PT J AU METTER, EJ WALEGA, D METTER, EL PEARSON, J BRANT, LJ HISCOCK, BS FOZARD, JL AF METTER, EJ WALEGA, D METTER, EL PEARSON, J BRANT, LJ HISCOCK, BS FOZARD, JL TI HOW COMPARABLE ARE HEALTHY 60-YEAR-OLD AND 80-YEAR-OLD MEN SO JOURNALS OF GERONTOLOGY LA English DT Article AB A critical issue in cross-sectional aging studies is the comparability of subjects of different ages, particularly regarding health status. For example, it is typically assumed that healthy 60-year-old men are equivalent to healthy 80-year-old men when both age groups are selected using the same criteria. The 60-year-old, however, may not survive or be healthy at age 80. To examine this issue, 212 healthy 60-year-old men in the Baltimore Longitudinal Study of Aging were identified. By life table analysis, 30% were expected to survive and remain healthy to age 80. In this study, 61 healthy 60-year-old men were followed to age 80. When compared with 125 healthy 80-year-old men, they had more heart disease, cancer, stroke, arterial, digestive, and peripheral nervous system diseases. Twenty-seven of the 61 men (44%) actually continued to be healthy at age 80. At age 60, systolic pressure and total serum cholesterol were predictive of who would be healthy at age 80. RP METTER, EJ (reprint author), NIA,LONGITUDINAL STUDIES BRANCH,GERONTOL RES CTR,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. RI Fozard, James Leonard/B-3660-2009 NR 11 TC 6 Z9 6 U1 0 U2 0 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 MAY PY 1992 VL 47 IS 3 BP M73 EP M78 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA HT691 UT WOS:A1992HT69100003 PM 1573187 ER PT J AU PAPPAS, BA SUNDERLAND, T WEINGARTNER, HM VITIELLO, B MARTINSON, H PUTNAM, K AF PAPPAS, BA SUNDERLAND, T WEINGARTNER, HM VITIELLO, B MARTINSON, H PUTNAM, K TI ALZHEIMERS-DISEASE AND FEELING-OF-KNOWING FOR KNOWLEDGE AND EPISODIC MEMORY SO JOURNALS OF GERONTOLOGY LA English DT Article ID FRONTAL-LOBE LESIONS; COGNITIVE ESTIMATION; AMNESIC PATIENTS; METAMEMORY; DEMENTIA; ACCURACY AB The metamemory (knowledge of the veracity of memories) of moderately impaired Alzheimer's patients was compared to that of aged controls. Despite their profoundly impaired recall of information from both long-term (knowledge) and recent (episodic) memory, Alzheimer's patients were as accurate as controls in assigning confidence ratings related to the probability that their recalls were correct. They were impaired, however, at predicting the likelihood that they would subsequently recognize correct answers (feeling-of-knowing) to knowledge memory questions which they had been unable to recall correctly. Nevertheless, their performance on this task did exceed chance. Thus, the moderately impaired Alzheimer's patient demonstrates intact awareness of the veracity of recall from knowledge and episodic memory but shows impaired feeling-of-knowing for knowledge memory. C1 NIMH,CLIN SCI LAB,BETHESDA,MD 20892. NIA,BETHESDA,MD 20892. RP PAPPAS, BA (reprint author), CARLETON UNIV,DEPT PSYCHOL,OTTAWA K1S 5B6,ONTARIO,CANADA. NR 22 TC 7 Z9 7 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 MAY PY 1992 VL 47 IS 3 BP P159 EP P164 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA HT691 UT WOS:A1992HT69100014 PM 1573198 ER PT J AU FERNANDEZ, PL MERINO, MJ NOGALES, FF CHARONIS, AS STETLERSTEVENSON, W LANCELIOTTA AF FERNANDEZ, PL MERINO, MJ NOGALES, FF CHARONIS, AS STETLERSTEVENSON, W LANCELIOTTA TI IMMUNOHISTOCHEMICAL PROFILE OF BASEMENT-MEMBRANE PROTEINS AND 72 KILODALTON TYPE-IV COLLAGENASE IN THE IMPLANTATION PLACENTAL SITE - AN INTEGRATED VIEW SO LABORATORY INVESTIGATION LA English DT Article ID EXTRACELLULAR-MATRIX PROTEINS; INTERMEDIATE TROPHOBLAST; INTERSTITIAL COLLAGENASE; LAMININ RECEPTOR; TUMOR-CELLS; INVITRO; TISSUE; ENZYME; LOCALIZATION; PURIFICATION AB An immunohistochemical study was performed to investigate the interactions between trophoblast and the extracellular matrix in the implantation site of early pregnancies. Two basement membrane-related proteins (type IV collagen and laminin), as well as the expression of the 72 kilodalton type IV collagenase, were studied with affinity-purified antibodies. human placental lactogen, human chorionic gonadotropins, and AE1/AE3 cytokeratins were used to identify the different cell populations involved in the implantation process. All types of trophoblastic cells, from villous cells to the different types of intermediate trophoblast, expressed the 72 kilodalton type IV collagenase. Decidual cells, Hofbauer's cells, villous fibroblasts, and amnion were also positive. Laminin and type IV collagen were expressed in all basement membranes, including large decidual and intermediate trophoblast cells, and the villous stroma. Nitabuch's layer, an acellular degradative zone at the site of initial attachment, showed positivity for type IV collagen. The extracellular matrix in the implantation site seems to be a meshwork of, among other components, laminin and type IV collagen, in which the invading trophoblastic cells are embedded. The invasive capacity of these cells in vivo may be, at least in part, mediated by their type IV collagenolytic activity along with that of the decidual cells, thus regulating the permeability of the extracellular matrix. C1 NCI,PATHOL LAB,BLDG 10,ROOM 2N212,BETHESDA,MD 20892. UNIV GRANADA,DEPT PATHOL,GRANADA,SPAIN. UNIV MINNESOTA,DEPT LAB MED & PATHOL,MINNEAPOLIS,MN 55455. RI Stetler-Stevenson, William/H-6956-2012; OI Stetler-Stevenson, William/0000-0002-5500-5808; Charonis, Aristidis/0000-0001-9956-732X NR 61 TC 61 Z9 61 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD MAY PY 1992 VL 66 IS 5 BP 572 EP 579 PG 8 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA HU762 UT WOS:A1992HU76200007 PM 1374139 ER PT J AU PARSEGIAN, VA RAND, RP AF PARSEGIAN, VA RAND, RP TI COMPARISONS OF SOLUBILITIES PREDICTED BY THE PROTRUSION MODEL WITH EXPERIMENTAL CRITICAL MICELLE CONCENTRATION ESTIMATES FROM THE EQUATIONS OF CEVC AND MARSH SO LANGMUIR LA English DT Note C1 BROCK UNIV,DEPT BIOL,ST CATHARINES L2S 3A1,ONTARIO,CANADA. RP PARSEGIAN, VA (reprint author), NIH,DIV COMP RES & TECHNOL,PHYS SCI LAB,BETHESDA,MD 20892, USA. NR 3 TC 9 Z9 9 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0743-7463 J9 LANGMUIR JI Langmuir PD MAY PY 1992 VL 8 IS 5 BP 1502 EP 1502 DI 10.1021/la00041a044 PG 1 WC Chemistry, Multidisciplinary; Chemistry, Physical; Materials Science, Multidisciplinary SC Chemistry; Materials Science GA HV782 UT WOS:A1992HV78200045 ER PT J AU ROST, K SMITH, GR BURNAM, MA BURNS, BJ AF ROST, K SMITH, GR BURNAM, MA BURNS, BJ TI MEASURING THE OUTCOMES OF CARE FOR MENTAL-HEALTH PROBLEMS - THE CASE OF DEPRESSIVE-DISORDERS SO MEDICAL CARE LA English DT Article; Proceedings Paper CT 3RD CONF ON ADVANCES IN HEALTH STATUS ASSESSMENT CY SEP 12-14, 1991 CL GEORGETOWN UNIV CONF CTR, WASHINGTON, DC SP NATL ACAD SCI, INST MED, AGCY HLTH CARE POLICY & RES, CTR DIS CONTROL, NIH, ELI LILLY, GLAXO, PFIZER HO GEORGETOWN UNIV CONF CTR ID DIAGNOSTIC INTERVIEW SCHEDULE; MAJOR DEPRESSION; MEDICAL PATIENTS; OUTPATIENTS; PREVALENCE; QUESTIONNAIRE; RECOGNITION; PHYSICIANS; PREDICTORS; RELAPSE AB To conduct effectiveness research in mental health, many nontrivial problems need to be addressed. A multidisciplinary expert panel designed an outcomes module for major depression and dysthymia to measure disease-specific outcomes, treatments routinely provided, and patient characteristics that influence treatment or its outcomes. The outcomes module was pilot-tested to evaluate its ability to identify a diagnostically homogeneous group of patients, to establish its reliability and validity, and to assess the feasibility of administering the module in a mental health setting. In a cohort of 40 patients, the module identified all 31 patients who had a research diagnosis of major depression or dysthymia (100% sensitivity), and 2 of 9 patients who did not have this diagnosis (77.8% specificity). The outcomes module measured key constructs accurately enough to discriminate between groups of depressed patients expected to differ, indicating positive construct validity. High rates of instrument completion supported the feasibility of using the module in specialty settings. Extensive efforts locating patients for follow-up will be needed to draw valid conclusions about treatment effectiveness. C1 UNIV ARKANSAS MED SCI HOSP,VET ADM HLTH SERV RES & DEV FIELD PROGRAM MENTAL HLTH,LITTLE ROCK,AR 72205. RAND CORP,SANTA MONICA,CA 90406. DUKE UNIV,DEPT PSYCHIAT,DURHAM,NC 27706. RP ROST, K (reprint author), UNIV ARKANSAS MED SCI HOSP,CTR RURAL MENTAL HEALTHCARE RES,NIMH,DEPT PSYCHIAT,SLOT 554,LITTLE ROCK,AR 72205, USA. NR 35 TC 30 Z9 30 U1 2 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0025-7079 J9 MED CARE JI Med. Care PD MAY PY 1992 VL 30 IS 5 SU S BP MS266 EP MS273 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA HU834 UT WOS:A1992HU83400026 ER PT J AU WITKOP, B AF WITKOP, B TI REMEMBERING WIELAND,HEINRICH (1877-1957) PORTRAIT OF AN ORGANIC CHEMIST AND FOUNDER OF MODERN BIOCHEMISTRY SO MEDICINAL RESEARCH REVIEWS LA English DT Review ID MORPHINE; COFACTOR; ENZYMES; CODEINE RP WITKOP, B (reprint author), NIDDKD, BETHESDA, MD 20892 USA. NR 180 TC 5 Z9 5 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0198-6325 EI 1098-1128 J9 MED RES REV JI Med. Res. Rev. PD MAY PY 1992 VL 12 IS 3 BP 195 EP 274 DI 10.1002/med.2610120303 PG 80 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA HQ699 UT WOS:A1992HQ69900001 PM 1578969 ER PT J AU WITKOP, B AF WITKOP, B TI PEPTIDES IN HEALTH AND DISEASE - RETROSPECTION AND OUTLOOK SO MEDICINAL RESEARCH REVIEWS LA English DT Review ID ALPHA-AMINOISOBUTYRIC-ACID; SERUM AMINE OXIDASE; CYSTEINE RESIDUES; LEUCINE ZIPPER; EUKARYOTIC ENZYMES; CRYSTAL-STRUCTURE; BINDING-PROTEINS; NUCLEAR LOCATION; BIPHENOMYCIN-A; REDOX COFACTOR RP WITKOP, B (reprint author), NIDDKD,BETHESDA,MD 20892, USA. NR 137 TC 3 Z9 3 U1 0 U2 2 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0198-6325 J9 MED RES REV JI Med. Res. Rev. PD MAY PY 1992 VL 12 IS 3 BP 275 EP 296 DI 10.1002/med.2610120304 PG 22 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA HQ699 UT WOS:A1992HQ69900002 PM 1578970 ER PT J AU BECKER, PB WU, C AF BECKER, PB WU, C TI CELL-FREE SYSTEM FOR ASSEMBLY OF TRANSCRIPTIONALLY REPRESSED CHROMATIN FROM DROSOPHILA EMBRYOS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SIMIAN VIRUS 40; SACCHAROMYCES-CEREVISIAE; ACTIVE CHROMATIN; REPLICATING DNA; XENOPUS EGGS; INVITRO; HISTONE-H1; PURIFICATION; EXTRACTS; PROTEINS AB We describe a cell-free system, derived from preblastoderm Drosophila embryos, for the efficient assembly of cloned DNA into chromatin. The chromatin assembly system utilizes endogenous core histones and assembly factors and yields long arrays of regularly spaced nucleosomes with a repeat length of 180 bp. The assembly system is also capable of complementary-strand DNA synthesis accompanied by rapid nucleosome formation when the starting template is single-stranded circular DNA. Chromatin assembled with the preblastoderm embryo extract is naturally deficient in histone H1, but exogenous H1 can be incorporated during nucleosome assembly in vitro. Regular spacing of nucleosomes with or without histone H1 is sufficient to maximally repress transcription from hsp70 and fushi tarazu gene promoters. The Drosophila assembly system should be particularly useful for in vitro studies of chromatin assembly during DNA synthesis and for elucidating the action of transcription factors in the context of native chromatin. C1 NCI,BIOCHEM LAB,BLDG 37,ROOM 4C-09,BETHESDA,MD 20892. NR 51 TC 169 Z9 172 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 MAY PY 1992 VL 12 IS 5 BP 2241 EP 2249 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA HQ338 UT WOS:A1992HQ33800037 PM 1569951 ER PT J AU KULKOSKY, J JONES, KS KATZ, RA MACK, JPG SKALKA, AM AF KULKOSKY, J JONES, KS KATZ, RA MACK, JPG SKALKA, AM TI RESIDUES CRITICAL FOR RETROVIRAL INTEGRATIVE RECOMBINATION IN A REGION THAT IS HIGHLY CONSERVED AMONG RETROVIRAL RETROTRANSPOSON INTEGRASES AND BACTERIAL INSERTION-SEQUENCE TRANSPOSASES SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ESCHERICHIA-COLI; DNA INTEGRATION; VIRAL-DNA; PROTEIN; INVITRO; VIRUS; IDENTIFICATION AB Our comparison of deduced amino acid sequences for retroviral/retrotransposon integrase (IN) proteins of several organisms, including Drosophila melanogaster and Schizosaccharomyces pombe, reveals strong conservation of a constellation of amino acids characterized by two invariant aspartate (D) residues and a glutamate (E) residue, which we refer to as the D,D(35)E region. The same constellation is found in the transposases of a number of bacterial insertion sequences. The conservation of this region suggests that the component residues are involved in DNA recognition, cutting, and joining, since these properties are shared among these proteins of divergent origin. We introduced amino acid substitutions in invariant residues and selected conserved and nonconserved residues throughout the D,D(35)E region of Rous sarcoma virus IN and in human immunodeficiency virus IN and assessed their effect upon the activities of the purified, mutant proteins in vitro. Changes of the invariant and conserved residues typically produce similar impairment of both viral long terminal repeat (LTR) oligonucleotide cleavage referred to as the processing reaction and the subsequent joining of the processed LTR-based oligonucleotides to DNA targets. The severity of the defects depended upon the site and the nature of the amino acid substitution(s). All substitutions of the invariant acidic D and E residues in both Rous sarcoma virus and human immunodeficiency virus IN dramatically reduced LTR oligonucleotide processing and joining to a few percent or less of wild type, suggesting that they are essential components of the active site for both reactions. On the basis of similarities with enzymes that catalyze analogous reactions, we propose that the invariant D and E residues may participate in coordination of the metal cofactor (Mn2+ or Mg2+) required for the catalytic activities of IN. We further speculate that a metal-DNA complex may be necessary to position both LTR and target DNA substrates for nucleophilic attack during the cleavage and joining reactions. C1 FOX CHASE CANC INST, INST CANC RES, PHILADELPHIA, PA 19111 USA. NCI, FREDERICK CANC RES & DEV CTR, CRYSTALLOG LAB, FREDERICK, MD 21702 USA. FU NCI NIH HHS [CA-06927, CA-47486, N01-CO-74101] NR 35 TC 499 Z9 505 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 1992 VL 12 IS 5 BP 2331 EP 2338 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA HQ338 UT WOS:A1992HQ33800046 PM 1314954 ER PT J AU SCHOENLEIN, PV SHEN, DW BARRETT, JT PASTAN, I GOTTESMAN, MM AF SCHOENLEIN, PV SHEN, DW BARRETT, JT PASTAN, I GOTTESMAN, MM TI DOUBLE MINUTE CHROMOSOMES CARRYING THE HUMAN MULTIDRUG RESISTANCE-1 AND RESISTANCE-2 GENES ARE GENERATED FROM THE DIMERIZATION OF SUBMICROSCOPIC CIRCULAR DNAS IN COLCHICINE-SELECTED KB CARCINOMA-CELLS SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID P-GLYCOPROTEIN GENE; EXTRACHROMOSOMAL ELEMENTS; MAMMALIAN-CELLS; MDR1 GENE; AMPLIFICATION; EXPRESSION; LINES; VINBLASTINE; MOLECULES; SEQUENCE AB This study characterizes amplified structures carrying the human multidrug resistance (MDR) genes in colchicine-selected multidrug resistant KB cell lines and strongly supports a model of gene amplification in which small circular extrachromosomal DNA elements generated from contiguous chromosomal DNA regions multimerize to form cytologically detectable double minute chromosomes (DMs). The human MDR1 gene encodes the 170-kDa P-glycoprotein, which is a plasma membrane pump for many structurally unrelated chemotherapeutic drugs. MDR1 and its homolog, MDR2, undergo amplification when KB cells are subjected to stepwise selection in increasing concentrations of colchicine. The structure of the amplification unit at each step of drug selection was characterized using both high-voltage gel electrophoresis and pulsed-field gel electrophoresis (PFGE) techniques. An 890-kb submicroscopic extrachromosomal circular DNA element carrying the MDR1 and MDR2 genes was detected in cell line KB-Ch(R)-8-5-11, the earliest step in drug selection in which conventional Southern/hybridization analyses detected MDR gene amplification. When KB-Ch(R)-8-5-11 was subjected to stepwise increases in colchicine, this circular DNA element dimerized as detected by PFGE with and without digestion with Not 1, which linearizes the 890-kb amplicon. This dimerization process, which also occurred at the next step of colchicine selection, resulted in the formation of cytologically detectable DMs revealed by analysis of Giemsa-stained metaphase spreads. C1 NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. RP SCHOENLEIN, PV (reprint author), NCI,CELL BIOL LAB,BETHESDA,MD 20892, USA. NR 56 TC 49 Z9 49 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD MAY PY 1992 VL 3 IS 5 BP 507 EP 520 PG 14 WC Cell Biology SC Cell Biology GA HY164 UT WOS:A1992HY16400004 PM 1611154 ER PT J AU MASIBAY, AS BOEGGEMAN, E QASBA, PK AF MASIBAY, AS BOEGGEMAN, E QASBA, PK TI DELETION ANALYSIS OF THE NH2-TERMINAL REGION OF BETA-1,4-GALACTOSYLTRANSFERASE SO MOLECULAR BIOLOGY REPORTS LA English DT Article DE GLYCOSYLTRANSFERASE; EXPRESSION; STRUCTURE FUNCTION ID INFLUENZA-VIRUS NEURAMINIDASE; EUKARYOTIC RIBOSOMES; SIGNAL ANCHOR; GLYCOSYLTRANSFERASES; SIALYLTRANSFERASE; LOCALIZATION; PROTEIN; DOMAIN; SITES; CELLS AB To determine the biological role, if any, of the NH2-terminal region of beta-1,4-galactosyltransferase (GT; EC 2.4.1.90), we constructed deletion mutants and expressed them in COS-7 cells. Each deletion construct was analyzed for enzymatic activity, protein production and mRNA transcription. All of the deletion mutants were transcribed to produce GT mRNA, but the GT protein was not detected in those constructs whose transmembrane (aa 14-42) domain was deleted. The results suggest that the transmembrane region is essential for the stability of the protein and perhaps contain sequences critical for the proper targeting of the molecule. The possible role of the NH2-terminal signal anchor domain in the in vivo regulation of GT is discussed. RP MASIBAY, AS (reprint author), NCI,DIV CANC BIOL DIAG & CTR,MATH BIOL LAB,BETHESDA,MD 20892, USA. NR 21 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 0301-4851 J9 MOL BIOL REP JI Mol. Biol. Rep. PD MAY PY 1992 VL 16 IS 2 BP 99 EP 104 DI 10.1007/BF00419755 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HV722 UT WOS:A1992HV72200006 PM 1608403 ER PT J AU SHIMADA, S KITAYAMA, S WALTHER, D UHL, G AF SHIMADA, S KITAYAMA, S WALTHER, D UHL, G TI DOPAMINE TRANSPORTER MESSENGER-RNA - DENSE EXPRESSION IN VENTRAL MIDBRAIN NEURONS SO MOLECULAR BRAIN RESEARCH LA English DT Note DE DOPAMINE TRANSPORTER MESSENGER RNA; SUBSTANTIA-NIGRA; VENTRAL TEGMENTAL AREA ID PARKINSONS-DISEASE; TEGMENTAL AREA; RECEPTORS; COCAINE; RAT AB Oligonucleotides and a full-length cDNA encoding a functional dopamine transporter (DAT1) hybridize to a 3.7 kb mRNA that is concentrated in mRNA prepared from midbrain and absent in specimens from cerebellum or cerebral cortex. In situ hybridization reveals substantial hybridization densities overlying neurons of the substantia nigra, pars compacta, and the parabrachialis pigmentosus region of the ventral tegmental area (VTA). Neurons in the linear and paranigral VTA regions display lower levels of expression. Preliminary studies in arcuate neurons suggest modest hybridization. Different dopaminergic cell groups display different levels of DAT1 dopamine transporter expression. C1 JOHNS HOPKINS UNIV,SCH MED,NATL INST DRUG ABUSE,ADDICT RES CTR,MOLEC NEUROBIOL LAB,POB 5180,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21224. NR 16 TC 113 Z9 113 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 MAY PY 1992 VL 13 IS 4 BP 359 EP 362 DI 10.1016/0169-328X(92)90220-6 PG 4 WC Neurosciences SC Neurosciences & Neurology GA HT160 UT WOS:A1992HT16000011 ER PT J AU VOLLBERG, TM NERVI, C GEORGE, MD FUJIMOTO, W KRUST, A JETTEN, AM AF VOLLBERG, TM NERVI, C GEORGE, MD FUJIMOTO, W KRUST, A JETTEN, AM TI RETINOIC ACID RECEPTORS AS REGULATORS OF HUMAN EPIDERMAL KERATINOCYTE DIFFERENTIATION SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID VITAMIN-A; TERMINAL DIFFERENTIATION; SQUAMOUS DIFFERENTIATION; RESPONSIVE ELEMENT; OSTEOCALCIN GENE; CARCINOMA-CELLS; BETA-GENE; EXPRESSION; GAMMA; CLONING AB To examine the role of nuclear retinoic acid (RA) receptors (RARs) in the regulation of squamous differentiation in normal human epidermal keratinocytes (NHEK), we analyzed binding activity, mRNA expression, and transcriptional activity of the endogenously expressed RARs. Specific RA-binding activity eluted from size-exclusion HPLC with an apparent mol wt of 50 kilodaltons and was predominantly (> 95%) associated with the NHEK nuclear cell fraction. This RAR-binding activity represented in part the expression of RAR-alpha and RAR-gamma genes, whose transcripts were expressed in similar abundance in undifferentiated NHEK. Differentiation resulted in lower mRNA expression of RAR-alpha relative to the mRNA expression of RAR-gamma. Treatment of NHEK cells with 10(-6) M RA did not induce expression of RAR-beta mRNA. Similarly, three squamous cell carcinoma cell lines derived from human skin and oral cavity expressed RAR-alpha and RAR-gamma transcripts, but not RAR-beta transcripts. Transfection of NHEK with chloramphenicol acetyltransferase (CAT) reporter plasmids indicated that the endogenously expressed RARs could activate transcription through the RAR-beta response element in a concentration-dependent manner with doses of 10(-9) M RA and higher. CAT expression was not activated through TRE, a palindromic thyroid hormone response element with purported RA responsiveness. The competitive binding of benzoic acid derivatives of RA to RAR correlated with the ability of each analog to suppress mRNA expression of the squamous cell markers, involucrin, type I transglutaminase, and SQ37, and to activate transcription of the RAR-beta response element-CAT reporter. These results demonstrate that the control of NHEK differentiation by RA is consistent with the interaction of the retinoid with RAR and the regulation of transcription by that ligand-receptor complex. C1 NIEHS,PULM PATHOBIOL LAB,CELL BIOL SECT,POB 12233,RES TRIANGLE PK,NC 27709. OKAYAMA UNIV,SCH MED,DEPT DERMATOL,OKAYAMA 700,JAPAN. CNRS,LGME,FAC MED,INST CHIM BIOL,F-63085 STRASBOURG,FRANCE. OI Jetten, Anton/0000-0003-0954-4445; NERVI, Clara/0000-0001-9341-0188 NR 58 TC 46 Z9 46 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 MAY PY 1992 VL 6 IS 5 BP 667 EP 676 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HV306 UT WOS:A1992HV30600001 PM 1318502 ER PT J AU LEI, KJ GLUZMAN, Y PAN, CJ CHOU, JY AF LEI, KJ GLUZMAN, Y PAN, CJ CHOU, JY TI IMMORTALIZATION OF VIRUS-FREE HUMAN PLACENTAL CELLS THAT EXPRESS TISSUE-SPECIFIC FUNCTIONS SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID PREGNANCY-SPECIFIC BETA-1-GLYCOPROTEIN; HUMAN CARCINOEMBRYONIC ANTIGEN; HUMAN CHORIONIC-GONADOTROPIN; GENE FAMILY; SODIUM-BUTYRATE; CHROMOSOMAL LOCALIZATION; DIFFERENTIAL EXPRESSION; GLYCOPROTEIN GENES; MULTIGENE FAMILY; RETINOIC ACID AB Human pregnancy-specific glycoproteins (PSGs) are a family of closely related placental proteins that, together with the carcinoembryonic antigen members, comprise a subfamily within the immunoglobulin superfamily. To facilitate study of the control of PSG expression, we immortalized human placental cell lines with adenovirus-origin-minus (ori-)-simian virus-40 (SV40) recombinant viruses containing either wild-type or temperature-sensitive (ts) A mutants of SV40. Cells transformed with the SV40 tsA chimera (HP-A1 and HP-A2), but not the SV40 wild-type chimera (HP-W1), were temperature sensitive for transformation. All three cell lines expressed trophoblast-specific genes, including PSG and the alpha- and beta-subunits of hCG. Human CG-alpha expression was greatly stimulated by (Bu)2cAMP in all three cell lines; shifting HP-A1 and HP-A2 cells to the nonpermissive temperature (39.5 C) further increased hCG-alpha expression. At both 33 C (permissive temperature) and 39.5 C, the transformed placental cells expressed PSG mRNAs of 2.2 and 1.7 kilobases; expression was greatly stimulated by sodium butyrate. In the absence of an inducer, the three placental lines synthesized a PSG of 64 kilodaltons (kDa). In the presence of butyrate, they synthesized PSGs of 72, 64, and 54 kDa, similar to the placental PSGs. However, in placenta the predominant species is the 72-kDa product. At 39.5 C, butyrate selectively increased synthesis of the 72-kDa PSG in HP-A1 and HP-A2 cells. To characterize PSG promoter activity, we constructed chloramphenicol acetyltransferase (CAT) fusion genes containing -809 to -44 basepairs up-stream of the translational start site of the PSG6 gene. Using transient expression assays, we demonstrated that the -809/-44 region of the PSG6 gene contained cis-acting sequences that can direct CAT expression in human placental cells. Sodium butyrate, which stimulates PSG expression, greatly increased CAT activity, indicating that butyrate-induced PSG expression is regulated primarily at the level of gene transcription. C1 NICHHD, HUMAN GENET BRANCH, BLDG 10, ROOM 95242, BETHESDA, MD 20892 USA. COLD SPRING HARBOR LAB, COLD SPRING HARBOR, NY 11724 USA. NR 64 TC 38 Z9 38 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD MAY PY 1992 VL 6 IS 5 BP 703 EP 712 DI 10.1210/me.6.5.703 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HV306 UT WOS:A1992HV30600004 PM 1318503 ER PT J AU IKUYAMA, S NILLER, HH SHIMURA, H AKAMIZU, T KOHN, LD AF IKUYAMA, S NILLER, HH SHIMURA, H AKAMIZU, T KOHN, LD TI CHARACTERIZATION OF THE 5'-FLANKING REGION OF THE RAT THYROTROPIN RECEPTOR GENE SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; GROWTH FACTOR-I; PROMOTER REGION; THYROID-CELLS; GRANULOSA-CELLS; SOMATOMEDIN-C; CHROMOSOMAL ASSIGNMENT; THYROGLOBULIN PROMOTER; NUCLEOTIDE-SEQUENCE; EPITHELIAL-CELLS AB Genomic clones containing 1.7 kilobases of the 5'-flanking region of the rat TSH receptor (TSHR) plus coding sequence from the ATG initiation codon [1 basepair (bp)] to the start of the first intron (170 bp) have been isolated and characterized. RNAase protection, primer extension, and cDNA sequences cloned by the anchored polymerase chain reaction identified multiple transcriptional start sites, the major ones clustered between -89 to -68 bp. This portion of the 5'-flanking region has neither a TATA nor a CCAAT box, is GC rich but has no GC box motif, and has features of promoters seen in "housekeeping" genes. Chimeras containing 1.7 kilobases (-1707 to -2 bp) of the 5'-flanking region, or deletions thereof, and the bacterial chloramphenicol acetyltransferase (CAT) gene expressed significant CAT activity when transfected into rat thyroid cell lines, FRTL-5 and FRT, but not BRL rat liver or HeLa cells. TSH decreased CAT activity in the FRTL-5 thyroid cells that had been stably transfected with the TSHR-CAT chimeric constructs. Negative regulation of promoter activity by TSH was duplicated by 10-mu-M forskolin in FRT thyroid cells, which express no TSHR mRNA. Deletion analyses indicated that a "minimal" region, exhibiting promoter activity, tissue specificity, and negative regulation by TSH, is located between -195 and -39 bp; this region is highly conserved in rat and human TSHR genes. Differential digestion of genomic DNA by MspI and HpaII revealed that the TSHR promoter is methylated in FRT, but not FRTL-5, cells; methylation of the promoter may be associated with loss of endogenous TSHR gene expression in FRT cells. C1 NIDDKD, BIOCHEM & METAB LAB, CELL REGULAT SECT, BETHESDA, MD 20892 USA. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 64 TC 84 Z9 85 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD MAY PY 1992 VL 6 IS 5 BP 793 EP 804 DI 10.1210/me.6.5.793 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HV306 UT WOS:A1992HV30600013 PM 1318504 ER PT J AU DAVIS, MA MARTIN, KA AUSTIN, SJ AF DAVIS, MA MARTIN, KA AUSTIN, SJ TI BIOCHEMICAL ACTIVITIES OF THE PARA PARTITION PROTEIN OF THE P1 PLASMID SO MOLECULAR MICROBIOLOGY LA English DT Article ID UNIT-COPY MINIPLASMIDS; CENTROMERE-LIKE SITE; ESCHERICHIA-COLI; DAUGHTER CELLS; SEQUENCE DETERMINATION; REPLICATOR REGION; HOST FACTOR; DNA; BINDING; PURIFICATION AB The unit-copy P1 plasmid depends for stability on a plasmid-encoded partition region called par, consisting of the parA and parB genes and the parS site. ParA is absolutely required for partition, but its partition-critical role is not known. Purified ParA protein is shown to possess an ATPase activity in vitro which is specifically stimulated by purified ParB protein and by DNA. ParA is responsible for regulation of expression of parA and parB, and purified ParA has an ATP-dependent, site-specific DNA binding activity which recognizes a sequence that overlaps the parA promoter. The role of the ATP-dependence of the binding activity, as well as other possible functions of the ATPase activity in partition, is discussed. C1 CENT CONNECTICUT STATE UNIV,DEPT BIOL SCI,NEW BRITAIN,CT 06050. RP DAVIS, MA (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74101] NR 36 TC 133 Z9 133 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD MAY PY 1992 VL 6 IS 9 BP 1141 EP 1147 DI 10.1111/j.1365-2958.1992.tb01552.x PG 7 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA HT324 UT WOS:A1992HT32400008 PM 1534133 ER PT J AU KNECHT, KT DEGRAY, JA MASON, RP AF KNECHT, KT DEGRAY, JA MASON, RP TI FREE-RADICAL METABOLISM OF HALOTHANE INVIVO - RADICAL ADDUCTS DETECTED IN BILE SO MOLECULAR PHARMACOLOGY LA English DT Article ID ELECTRON-SPIN RESONANCE; RAT-LIVER; HYPOXIA; HEPATOTOXICITY; BINDING AB Two radical adduct species have been detected in the bile of living rats treated with halothane and phenyl-N-t-butylnitrone (PBN). The treatment of rats with 12% oxygen was required for radical adduct detection. Analysis of the corresponding EPR spectra obtained when deuterated PBN and deuterated halothane or [2-C-13]halothane was used shows that these two species result from the spin trapping of two halothane-derived free radicals. Coupling constants were a(N) = 15.72 G, a(beta)H = 2.09 G, a(gamma)H 0.79 G, and a(F) = 0.63 G(3F) and a(N) = 1516 G, a(beta)H = 4.14 G, a(gamma)H = 0.48 G, and a(F) = 0.3 G(3F) for the two species. Two radical adducts with similar coupling constants were detected when halothane was reduced by zinc dust in the presence of PBN, suggesting that the formation of these two distinct species from halothane can be attributed to the one-electron reduction of halothane and the formation of diastereomeric radical adducts. The identification of both radical adducts as halothane-derived species indicates that there is no in vivo EPR evidence for lipid radical formation during halothane intoxication, as had previously been reported. C1 UNIV N CAROLINA,CURRICULUM TOXICOL,CHAPEL HILL,NC 27599. RP KNECHT, KT (reprint author), NIEHS,MOLEC BIOPHYS LAB,MD 4-01,POB 12233,RES TRIANGLE PK,NC 27709, USA. FU NIEHS NIH HHS [ES 07126] NR 23 TC 19 Z9 21 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 MAY PY 1992 VL 41 IS 5 BP 943 EP 949 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA HU620 UT WOS:A1992HU62000018 PM 1317002 ER PT J AU LANE, HC MAYER, L AF LANE, HC MAYER, L TI IMMUNOREGULATION, IMMUNE DEFECTS, AND CLINICAL STRATEGIES IN HIV-INFECTION SO MOUNT SINAI JOURNAL OF MEDICINE LA English DT Article RP LANE, HC (reprint author), NIAID,IMMUNOREGULAT LAB,BLDG 10,ROOM 11B-13,BETHESDA,MD 20892, USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU MOUNT SINAI HOSPITAL PI NEW YORK PA BOX 1094 ONE GUSTAVE L LEVY PLACE ATTN: CIRCULATION ASST, NEW YORK, NY 10029-6574 SN 0027-2507 J9 MT SINAI J MED JI Mt. Sinai J. Med. PD MAY PY 1992 VL 59 IS 3 BP 244 EP 252 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA JQ267 UT WOS:A1992JQ26700013 PM 1534869 ER PT J AU WILKIE, TM GILBERT, DJ OLSEN, AS CHEN, XN AMATRUDA, TT KORENBERG, JR TRASK, BJ DEJONG, P REED, RR SIMON, MI JENKINS, NA COPELAND, NG AF WILKIE, TM GILBERT, DJ OLSEN, AS CHEN, XN AMATRUDA, TT KORENBERG, JR TRASK, BJ DEJONG, P REED, RR SIMON, MI JENKINS, NA COPELAND, NG TI EVOLUTION OF THE MAMMALIAN G-PROTEIN ALPHA-SUBUNIT MULTIGENE FAMILY SO NATURE GENETICS LA English DT Article ID GTP-BINDING PROTEIN; GENETIC-LINKAGE MAP; SIGNAL-TRANSDUCTION; MOLECULAR CHARACTERIZATION; HEREDITARY OSTEODYSTROPHY; INTERSPECIFIC BACKCROSS; INSITU HYBRIDIZATION; ADENYLATE-CYCLASE; PERTUSSIS TOXIN; HIGH-RESOLUTION AB Heterotrimeric guanine nucleotide binding proteins (G proteins) transduce extracellular signals received by transmembrane receptors to effector proteins. The multigene family of G protein alpha-subunits, which interact with receptors and effectors, exhibit a high level of sequence diversity. In mammals, 15 G-alpha subunit genes can be grouped by sequence and functional similarities into four classes. We have determined the murine chromosomal locations of all 15 G-alpha subunit genes using an interspecific backcross derived from crosses of C57BL/6J and Mus spretus mice. These data, in combination with mapping studies in humans, have provided insight into the events responsible for generating the genetic diversity found in the mammalian alpha-subunit genes and a framework for elucidating the role of the G-alpha subunits in disease. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. CALTECH,DIV BIOL 14775,PASADENA,CA 91125. JOHNS HOPKINS UNIV,SCH MED,HOWARD HUGHES MED INST,DEPT MOLEC BIOL & GENET,BALTIMORE,MD 21205. LAWRENCE LIVERMORE NATL LAB,DIV BIOMED SCI L452,LIVERMORE,CA 94550. CEDARS SINAI MED CTR,DEPT PEDIAT,CTR BIRTH DEFECTS,LOS ANGELES,CA 90048. NR 76 TC 212 Z9 214 U1 1 U2 9 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAY PY 1992 VL 1 IS 2 BP 85 EP 91 DI 10.1038/ng0592-85 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA JC980 UT WOS:A1992JC98000005 PM 1302014 ER PT J AU WINSKY, L HARVEY, JA AF WINSKY, L HARVEY, JA TI 6-HYDROXYDOPAMINE INDUCED IMPAIRMENT OF PAVLOVIAN CONDITIONING IN THE RABBIT SO NEUROCHEMICAL RESEARCH LA English DT Article DE 6-HYDROXYDOPAMINE; MONOAMINES; RABBIT; PAVLOVIAN CONDITIONING; NICTITATING MEMBRANE ID NICTITATING-MEMBRANE RESPONSE; PARKINSONS-DISEASE; DOPAMINE; SYSTEMS; RATS; NOREPINEPHRINE; ALZHEIMERS; BEHAVIOR; ABDUCENS; NUCLEUS AB This study employed bilateral, intraventricular injections of 6-hydroxydopamine (6-HDA) to examine the effects of monoamine depletion on Pavlovian conditioning of the rabbit's nictitating membrane response. 6-HDA produced dose-dependent and highly correlated decreases in the rate of acquisition of conditioned responses and in the telencephalic content of 5-HT, DA, and NE. At the highest dose of 6-HDA (1340-mu-g), 5-HT, DA, and NE were reduced by 42, 48, and 89%, respectively, and the number of trials required to achieve criterion acquisition was increased by 123%. Control experiments established that the highest dose of 6-HDA: 1) had no effect on the unconditioned nictitating membrane reflex; 2) had no effect on the threshold of the conditioned stimulus for eliciting conditioned responses; and 3) produced only a small, less than 5%, decrease in nonassociative responding. It was concluded that decreases in 5-HT, DA, and NE can impair associative learning without altering sensory or motor function. C1 MED COLL PENN,EPPI,DEPT PHARMACOL,DIV BEHAV NEUROBIOL,3200 HENRY AVE,PHILADELPHIA,PA 19129. NIMH,CLIN SCI LAB,HISTOPHARMACOL SECT,BETHESDA,MD 20892. FU NIMH NIH HHS [MH-16841] NR 28 TC 7 Z9 7 U1 1 U2 1 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 MAY PY 1992 VL 17 IS 5 BP 415 EP 422 DI 10.1007/BF00969886 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA HQ704 UT WOS:A1992HQ70400004 PM 1528351 ER PT J AU LAITINEN, JT VAKKURI, O SAAVEDRA, JM AF LAITINEN, JT VAKKURI, O SAAVEDRA, JM TI PINEAL MUSCARINIC PHOSPHOINOSITIDE RESPONSES - AGE-ASSOCIATED SENSITIZATION, AGONIST-INDUCED DESENSITIZATION AND INCREASE IN MELATONIN RELEASE FROM CULTURED PINEAL GLANDS SO NEUROENDOCRINOLOGY LA English DT Article DE ACETYLCHOLINE; HOMOLOGOUS DESENSITIZATION; INDOLES; MUSCARINIC RECEPTORS; PROTEIN KINASES; 2ND MESSENGERS ID PROTEIN KINASE-C; SPONTANEOUSLY HYPERTENSIVE RATS; INOSITOL PHOSPHATES; RECEPTOR SUBTYPES; PHOSPHOLIPASE-C; BINDING-SITES; CYCLIC-AMP; HYDROLYSIS; CELLS; BRAIN AB Regulation of phosphoinositide (PI) signaling through the muscarinic cholinergic receptors (mAChRs) and their possible role were explored in the rat pineal gland. A sensitization of the PI signaling pathway was seen with advancing age. Binding of the mAChR ligand [N-methyl-H-3]scopolamine to pineal sections, as detected by autoradiography, significantly decreased with advancing age and thus negatively correlated with the gland's ability to respond to cholinergic stimulus. The cholinergic agonist carbachol induced a time-dependent desensitization of the muscarinic PI signaling after 2 h of pretreatment in vitro (43 and 61% dampening of the PI response after 2 and 11 h pretreatment, respectively). This homologous desensitization was not mimicked by forskolin or phorbol esters, suggesting that proteins kinases A and C were not involved. Carbachol stimulation of the pineal glands in vitro increased melatonin release 2-fold, an effect quantitatively similar to that seen after adenylyl cyclase activation. Carbachol failed, however, to affect pineal cAMP levels. These results suggest that the PI signaling through pineal mAChRs is desensitized in young rats, possibly due to higher exposure to endogenous acetylcholine. Thus acetylcholine might play a prominent role in the developing gland. Moreover, acetylcholine could modulate melatonin release from the adult pineal gland in vivo. C1 NIMH,CLIN SCI LAB,PHARMACOL SECT,BLDG 10,RM 2D-45,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. UNIV OULU,DEPT PHYSIOL,SF-90100 OULU 10,FINLAND. OI Laitinen, Jarmo T/0000-0002-9490-3686 NR 39 TC 13 Z9 13 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PD MAY PY 1992 VL 55 IS 5 BP 492 EP 499 DI 10.1159/000126162 PG 8 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA HQ328 UT WOS:A1992HQ32800002 PM 1316561 ER PT J AU EVANS, JJ ROBINSON, G CATT, KJ AF EVANS, JJ ROBINSON, G CATT, KJ TI LUTEINIZING-HORMONE RESPONSE TO OXYTOCIN IS STEROID-DEPENDENT SO NEUROENDOCRINOLOGY LA English DT Article DE ESTRADIOL; ESTROUS CYCLE; LUTEINIZING HORMONE; OXYTOCIN; PITUITARY; PROGESTERONE; TESTOSTERONE ID GONADOTROPIN-RELEASING-HORMONE; RAT PITUITARY-CELLS; PROLACTIN SECRETION; ESTROUS-CYCLE; PHORBOL ESTER; RESPONSIVENESS; RECEPTORS; LHRH; PROGESTERONE; MODULATION AB Oxytocin-induced LH release from dispersed rat anterior pituitary cells in vitro was shown to be dependent on the steroidal environment. Preincubation of anterior pituitary cells with estradiol for 48 h enhanced the subsequent LH response to oxytocin (p < 0.001). Maximal sensitization was observed with estradiol at 1 nM. Release of LH induced by oxytocin was inhibited in the presence of progesterone or to a greater extent in the presence of equimolar testosterone. Complete suppression of oxytocin-induced LH secretion occurred with 1 nM progesterone. Incubation of hemipituitaries with oxytocin revealed that the pituitary was sensitive in vitro to oxytocin at proestrus (p < 0.05) but not at other stages of the cycle. The results indicate that there is altered sensitivity to oxytocin of the pituitary at different stages of the estrous cycle. Therefore activity of the neuropeptide in vivo might be modulated by steroids. C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892. RP EVANS, JJ (reprint author), UNIV CHRISTCHURCH,CHRISTCHURCH WOMENS HOSP,DEPT OBSTET & GYNAECOL,CHRISTCHURCH,NEW ZEALAND. NR 36 TC 15 Z9 15 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PD MAY PY 1992 VL 55 IS 5 BP 538 EP 543 DI 10.1159/000126167 PG 6 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA HQ328 UT WOS:A1992HQ32800008 PM 1584337 ER PT J AU CALOGERO, AE STERNBERG, EM BAGDY, G SMITH, C BERNARDINI, R AKSENTIJEVICH, S WILDER, RL GOLD, PW CHROUSOS, GP AF CALOGERO, AE STERNBERG, EM BAGDY, G SMITH, C BERNARDINI, R AKSENTIJEVICH, S WILDER, RL GOLD, PW CHROUSOS, GP TI NEUROTRANSMITTER-INDUCED HYPOTHALAMIC-PITUITARY-ADRENAL AXIS RESPONSIVENESS IS DEFECTIVE IN INFLAMMATORY DISEASE-SUSCEPTIBLE LEWIS RATS - INVIVO AND INVITRO STUDIES SUGGESTING GLOBALLY DEFECTIVE HYPOTHALAMIC SECRETION OF CORTICOTROPIN-RELEASING HORMONE SO NEUROENDOCRINOLOGY LA English DT Article DE CORTICOTROPIN-RELEASING HORMONE; HYPOTHALAMIC-PITUITARY-ADRENAL AXIS; LEWIS RATS; FISCHER RATS; NOREPINEPHRINE; SEROTONIN; ACETYLCHOLINE ID CENTRAL NERVOUS-SYSTEM; ADRENOCORTICOTROPIN SECRETION; BIOCHEMICAL MANIFESTATIONS; RECEPTOR SUBTYPES; AGONISTS; ACTIVATION; STRESS; NEUROBIOLOGY; ANTAGONISTS; DEPRESSION AB The susceptibility of female Lewis (LEW/N) rats to the development of streptococcal cell wall (SCW)-induced arthritis and other autoimmune phenomena is associated with the inability of their hypothalamic-pituitary-adrenal (HPA) axis to adequately respond to inflammatory stimuli. In contrast, resistance to the development of SCW-induced arthritis and other inflammatory autoimmune manifestations in histocompatible female Fischer rats (F344/N) is related to their intact HPA axis response to inflammatory mediators. To evaluate the mechanism and the specificity of the HPA axis defect in LEW/N rats, we examined the ability of three major excitatory neurotransmitter systems to activate the HPA axis in both Lewis and Fisher rats. The responsiveness of plasma ACTH and corticosterone to the cholinergic muscarinic receptor agonist arecoline, the alpha-1-adrenergic receptor agonist methoxamine and the serotonin (5-HT) type 2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)2-aminopropane were significantly blunted and/or abolished in LEW/N compared to F344/N rats. To localize the HPA axis defect to the hypothalamic CRH neuron, we evaluated the ability of explanted hypothalami from the two strains to secrete immunoreactive CRH in vitro, in response to acetylcholine (ACh), norepinephrine (NE), 5-HT and the 5-HT agonist quipazine. LEW/N hypothalami released less immunoreactive CRH (iCRH) in response to ACh, NE, 5-HT and quipazine than F344/N hypothalami. The dose-response curves of these compounds in the former were shifted to the right and/or abolished. suggesting decreased sensitivity of LEW/N hypothalami to these neurotransmitters. The lack of difference in binding affinity and concentration of muscarinic, alpha-1/alpha-2-adrenergic or 5-HT2 receptors in LEW/N and F344/N hypothalami or cerebral cortex, suggested that the impaired hypothalamic iCRH responsiveness to these neurotransmitters may relate to a faulty intracellular transducing or regulatory mechanism, which, however, apparently pertains only to CRH producing neurons. We conclude that the HPA axis of LEW/N rats is hyporesponsive to a variety of neurotransmitter stimuli and that this impairment may relate to a defective hypothalamic CRH-secreting neuron. Hence, the defect in the activation of the HPA axis in these rats is not specific to inflammatory mediators, but rather represents a global defect in the regulation of hypothalamic CRH secretion. This is reflected also in a characteristic behavioral syndrome in the LEW/N rats, which is compatible with CRH hyposecretion. This defect is possibly related to an alteration(s) in transduction mechanisms common to the range of neurotransmitter and inflammatory mediator stimuli studied but limited to the CRH neuron, or specifically related with the regulatory region of the CRH gene in these animals. C1 NICHHD,DEV ENDOCRINOL BRANCH,BLDG 10,ROOM 10N262,BETHESDA,MD 20892. NIH,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. NIAMSD,ARTHRITIS & RHEUMATISM BRANCH,BETHESDA,MD. NIH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. NR 35 TC 107 Z9 108 U1 1 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PD MAY PY 1992 VL 55 IS 5 BP 600 EP 608 DI 10.1159/000126173 PG 9 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA HQ328 UT WOS:A1992HQ32800015 PM 1350069 ER PT J AU GERFEN, CR ENGBER, TM AF GERFEN, CR ENGBER, TM TI MOLECULAR NEUROANATOMICAL MECHANISMS OF PARKINSONS-DISEASE - A PROPOSED THERAPEUTIC APPROACH SO NEUROLOGIC CLINICS LA English DT Article ID NIGRA PARS RETICULATA; ANTI-SCHIZOPHRENIC DRUGS; D1 DOPAMINE RECEPTOR; SUBSTANTIA-NIGRA; OCULOMOTOR FUNCTIONS; GLOBUS PALLIDUS; BASAL GANGLIA; INTRACELLULAR INJECTION; IMMUNOREACTIVE NEURONS; HORSERADISH-PEROXIDASE C1 NINCDS,EXPTL THERAPEUT BRANCH,BETHESDA,MD 20892. RP GERFEN, CR (reprint author), NIMH,CELL BIOL LAB,BLDG 36,ROOM 3D-10,BETHESDA,MD 20892, USA. NR 49 TC 17 Z9 17 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0733-8619 J9 NEUROL CLIN JI Neurol. Clin. PD MAY PY 1992 VL 10 IS 2 BP 435 EP 449 PG 15 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA HT499 UT WOS:A1992HT49900011 PM 1350051 ER PT J AU HANBAUER, I WINK, D OSAWA, Y EDELMAN, GM GALLY, JA AF HANBAUER, I WINK, D OSAWA, Y EDELMAN, GM GALLY, JA TI ROLE OF NITRIC-OXIDE IN NMDA-EVOKED RELEASE OF [H-3] DOPAMINE FROM STRIATAL SLICES SO NEUROREPORT LA English DT Article DE NEUROTRANSMITTER RELEASE; TETRAHYDROBIOPTERIN; CATECHOLAMINE; STRIATUM; PRESYNAPTIC RECEPTORS; SPATIAL SIGNAL ID RAT STRIATUM; GMP AB EVIDENCE that excitatory amino acids act via N-methyl-D-aspartate (NMDA) receptors to evoke the release of catecholamines from axonal terminals and synaptosomes has been used to argue for the presence of pre-synaptic NMDA receptors. NMDA receptor agonists also generate nitric oxide (NO) which rapidly diffuses through neural tissue. We find that exogenously applied NO evokes [H-3]-dopamine release from cultured neurons. This release is not blocked by the NMDA antagonist MK-801 nor by tetrodotoxin. Both N(G)-nitroarginine which inhibits NO synthesis, and hemoglobin which binds extracellular NO, block NMDA-evoked [H-3]-dopamine release from striatal slices. A major role of endogenously-synthesized NO may be to evoke neurotransmitter release in local volumes of neural tissue. C1 NEUROSCI RES PROGRAM,INST NEUROSCI,NEW YORK,NY 10021. NHLBI,CHEM PHARMACOL LAB,BETHESDA,MD 20892. NCI,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21701. ROCKEFELLER UNIV,NEW YORK,NY 10021. FU NICHD NIH HHS [HD09635] NR 24 TC 245 Z9 247 U1 3 U2 3 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD MAY PY 1992 VL 3 IS 5 BP 409 EP 412 DI 10.1097/00001756-199205000-00008 PG 4 WC Neurosciences SC Neurosciences & Neurology GA HY928 UT WOS:A1992HY92800008 PM 1633278 ER PT J AU GULYAS, AI MIETTINEN, R JACOBOWITZ, DM FREUND, TF AF GULYAS, AI MIETTINEN, R JACOBOWITZ, DM FREUND, TF TI CALRETININ IS PRESENT IN NONPYRAMIDAL CELLS OF THE RAT HIPPOCAMPUS .1. A NEW TYPE OF NEURON SPECIFICALLY ASSOCIATED WITH THE MOSSY FIBER SYSTEM SO NEUROSCIENCE LA English DT Article ID CALCIUM-BINDING PROTEIN; GAMMA-AMINOBUTYRIC ACID; MONKEY CEREBRAL-CORTEX; GUINEA-PIG HIPPOCAMPUS; SOMATOSTATIN-LIKE IMMUNOREACTIVITY; LACUNOSUM-MOLECULARE INTERNEURONS; INTESTINAL POLYPEPTIDE-LIKE; GOLGI-ELECTRON MICROSCOPE; FIBERS FORM SYNAPSES; DENTATE GYRUS AB Calretinin-containing cells were visualized with immunocytochemistry in the rat dorsal hippocampal formation. Calretinin immunoreactivity was present exclusively in non-pyramidal cells in all layers of the dentate gyrus and the CA1-3 areas. Calretinin-positive neurons and processes were most abundant in the hilus of the dentate gyrus and in the stratum lucidum of the CA3 region. Several calretinin-immunoreactive cells were located within the hippocampal fissure. A distinct band of calretinin-immunoreactive fibres occupied the superficial part of the granule cell layer and the lowest part of the molecular layer. Closer examination of the calretinin-positive cells revealed that they formed two distinct cell groups. One group of cells, found exclusively in the stratum lucidum of the CA3 area and in the hilus of the dentate gyrus, was covered with numerous spines. Their somata and dendrites were restricted to stratum lucidum and to the hilus. Cells of the other group had smooth, often varicose, radially running dendrites, and were present in all areas and layers of the hippocampal formation. Two to three thick primary dendrites arose from the irregularly shaped cell body of spiny cells and emitted fine secondary branches only distally (70-100-mu-m) from the soma, where they formed a profuse network. The extensive dendritic tree of the cells spread horizontally within stratum lucidum and span a distance of 400-600-mu-m both in the septotemporal and in the transverse directions. The layer-specific location of these cells and their processes suggested that the majority of their input may derive from mossy fibres. This presumption has been confirmed by electron microscopic examination. A large number of asymmetrical synapses were found to cover the soma, the dendritic shafts and the spines (four to six synapses/spine) of the cells. A large proportion of the synapses were formed by boutons, which showed the distinctive features of mossy fibre terminals. Three to six primary dendrites arose from the multipolar, bipolar or pyramidal-shaped somata of spine-free cells, which were smaller than the somata of spiny cells. The smooth and frequently varicose dendrites branched proximally and ran primarily radially. Dendrites ascended or descended through several layers and received both asymmetrical and symmetrical synapses. In the CA1 subfield, the vertically running dendrites frequently contacted other calretinin-immunoreactive spine-free dendrites or cell bodies. Two or three calretinin-immunoreactive dendrites were often seen to be attached for over 100 or, occasionally, 200-mu-m and several puncta adherentia were observed between them using the electron microscope. The axons of the cells arborized in all layers, had small en passant varicosities, and were found to establish symmetrical synapses with dendritic shafts. In summary, spine-free calretinin-immunoreactive cells showed the characteristic features of GABAergic interneurons both at the light and the electron microscopic levels. Axon terminals of the dense calretinin-immunoreactive fibre network in the superficial part of the granule cell layer formed synapses with dendritic shafts and spines of putative granule cells. the characteristic location and features of the synapses, i.e. a very thick and dense postsynaptic specialization, suggest that these fibres derive from the supramammillary nucleus, rather than from calretinin-immunoreactive neurons in the hippocampus. C1 HUNGARIAN ACAD SCI,INST EXPTL MED,DEPT FUNCT NEUROANAT,POB 67,H-1450 BUDAPEST,HUNGARY. UNIV KUOPIO,DEPT NEUROL,SF-70211 KUOPIO,FINLAND. UNIV KUOPIO,DEPT PATHOL,SF-70211 KUOPIO,FINLAND. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. NR 84 TC 193 Z9 194 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD MAY PY 1992 VL 48 IS 1 BP 1 EP 27 DI 10.1016/0306-4522(92)90334-X PG 27 WC Neurosciences SC Neurosciences & Neurology GA HN141 UT WOS:A1992HN14100001 PM 1584417 ER PT J AU MIETTINEN, R GULYAS, AI BAIMBRIDGE, KG JACOBOWITZ, DM FREUND, TF AF MIETTINEN, R GULYAS, AI BAIMBRIDGE, KG JACOBOWITZ, DM FREUND, TF TI CALRETININ IS PRESENT IN NONPYRAMIDAL CELLS OF THE RAT HIPPOCAMPUS .2. COEXISTENCE WITH OTHER CALCIUM-BINDING PROTEINS AND GABA SO NEUROSCIENCE LA English DT Article ID GAMMA-AMINOBUTYRIC ACID; SOMATOSTATIN-LIKE IMMUNOREACTIVITY; LACUNOSUM-MOLECULARE INTERNEURONS; MONKEY CEREBRAL-CORTEX; GABAERGIC NEURONS; DENTATE GYRUS; PARVALBUMIN IMMUNOREACTIVITY; INHIBITORY INTERNEURONS; SYNAPTIC CONNECTIONS; NONPYRAMIDAL NEURONS AB The possible co-existence of calretinin with other calcium binding proteins, parvalbumin and calbindin D28k, and with GABA, was studied in non-pyramidal cells of the rat dorsal hippocampal formation, using the mirror technique. The majority of the calretinin-containing neurons (83%) were found to be immunoreactive for GABA (79% in the dentate gyrus, 84% in the CA2-3, and 88% in the CA1 subfield). Most of the GABA-negative calretinin-immunoreactive neurons were located in the hilus of the dentate gyrus and in stratum lucidum of the CA3 subfield. Detailed analysis of the calretinin-immunoreactive cells of these subfields revealed that the two morphologically distinct types of calretinin neurons, i.e. the spiny and the spine-free cells, differ in their immunoreactivity for GABA. The overwhelming majority (92%) of the spine-free neurons were GABA-positive, whereas the immunoreactivity of spiny cells was ambiguous. At the sensitivity threshold of the immunocytochemical techniques used in the present study, most of the spiny cells (89%) had to be considered as GABA-negative, although the staining intensity in their cell bodies was somewhat above background level. Colchicine treatment resulted in a degeneration of calretinin-immunoreactive neurons; therefore, its effect on the GABA content of spiny neurons could not be evaluated. Nevertheless, the observations suggest that calretinin-containing neurons are heterogeneous both morphologically and neurochemically. Examination of the co-existence of calcium binding proteins revealed that none of the hippocampal cells contained both calretinin and parvalbumin in any regions of the hippocampal formation. Some overlap was detected between the calretinin- and the calbindin D28k-containing cell populations, 5.1% of the former and 6.2% of the latter were immunoreactive for both calcium binding proteins. This may be due to a small degree of cross-reactivity of the calbindin D28k antiserum with calretinin. Thus, our results demonstrate that the majority of calretinin-immunoreactive neurons are GABAergic and represent a subpopulation of non-pyramidal cells with no or only a negligible overlap with the subpopulations containing the other calcium binding proteins, parvalbumin and calbindin. C1 HUNGARIAN ACAD SCI,INST EXPTL MED,DEPT FUNCT NEUROANAT,POB 67,H-1450 BUDAPEST,HUNGARY. UNIV KUOPIO,DEPT NEUROL,SF-70211 KUOPIO,FINLAND. UNIV KUOPIO,DEPT PATHOL,SF-70211 KUOPIO,FINLAND. UNIV BRITISH COLUMBIA,DEPT PHYSIOL,VANCOUVER V6T 1W5,BC,CANADA. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. NR 49 TC 182 Z9 182 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD MAY PY 1992 VL 48 IS 1 BP 29 EP 43 DI 10.1016/0306-4522(92)90335-Y PG 15 WC Neurosciences SC Neurosciences & Neurology GA HN141 UT WOS:A1992HN14100002 PM 1584423 ER PT J AU RAMIREZ, M SANCHEZ, B ARECHAGA, G GARCIA, S LARDELLI, P VENZON, D DEGANDARIAS, JM AF RAMIREZ, M SANCHEZ, B ARECHAGA, G GARCIA, S LARDELLI, P VENZON, D DEGANDARIAS, JM TI DIURNAL RHYTHM IN BRAIN LYSYL ARGINYL AMINOPEPTIDASE ACTIVITY - A BILATERAL STUDY SO NEUROSCIENCE RESEARCH COMMUNICATIONS LA English DT Article DE AMINOPEPTIDASES; DIURNAL RHYTHM; RAT BRAIN; ASYMMETRY ID SPINAL-CORD; LH-RH; HYPOTHALAMUS; ENKEPHALIN; MELATONIN; BINDING; SYSTEM AB Diurnal variations in the soluble activity of lysyl/arginyl aminopeptidase, assayed fluorometrically as arylamidase activity, in selected photoneuroendocrine structures were investigated in male rats maintained on a 12h light-12h dark schedule (7h to 19h light). A significant diurnal variation in the activity was observed in the left anterior hypothalamus, left retina, intermediate-posterior pituitary, superior cervical ganglia, pineal gland and posterior hypothalamus. In addition, a left or right predominance in the enzymatic activity depending of the time point studied, was disclosed in retina and anterior hypothalamus. These results may suggest a role of this activity in the circadian variation observed in the concentrations of its appropriate substrates. C1 NIMH,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. RP RAMIREZ, M (reprint author), UNIV BASQUE COUNTRY,FAC MED,DEPT PHYSIOL,POB 699,BILBAO,SPAIN. RI Venzon, David/B-3078-2008 NR 17 TC 7 Z9 7 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0893-6609 J9 NEUROSCI RES COMMUN JI Neurosci. Res. Commun. PD MAY-JUN PY 1992 VL 10 IS 3 BP 141 EP 147 PG 7 WC Neurosciences SC Neurosciences & Neurology GA HX136 UT WOS:A1992HX13600003 ER PT J AU OLSON, JJ SHELLEY, C ORR, K DELANEY, T OLDFIELD, EH AF OLSON, JJ SHELLEY, C ORR, K DELANEY, T OLDFIELD, EH TI THE CEREBRAL RADIOPROTECTIVE EFFECT OF ALTERNATIVE BARBITURATES TO PENTOBARBITAL SO NEUROSURGERY LA English DT Article DE BARBITURATES; BRAIN TUMOR; PENTOBARBITAL; RADIATION INJURY; RADIATION PROTECTION ID RADIATION INACTIVATION; BRAIN INJURY; IRRADIATION; COMPLEX; PROTECTION; THERAPY AB The potential for normal brain tissue injury is one of the limiting factors in the use of radiotherapy for brain tumors. As attempts to enhance brain tumor radiation sensitivity have been unsuccessful, the use of cerebral radioprotectants provides an attractive alternative. Pentobarbital has recently been shown to be a cerebral radioprotectant in the rodent and primate models of single fraction radiation injury. Because daily high doses of pentobarbital bring certain significant risks, the potential usefulness of alternative barbiturates was explored. Seven groups of rats received 70 Gy of whole-brain-only irradiation in the single fraction. Group 1 was treated while awake. Groups 2, 3, and 4 received pentobarbital, thiopental, and methohexital, respectively. Groups 5, 6, and 7 received increasing doses of phenobarbital. Mean group survival at 30 days after treatment was determined and compared with the survival of animals treated while awake. Thiopental enhanced survival, similar to pentobarbital. Methohexital and phenobarbital were of no radioprotective value. The differences in the hypnotic effects of these barbiturates is based on dissimilar effects on the kinetics of chloride ion channel patency. We propose that these differences also influence their radioprotective properties. Thiopental is a shorter acting alternative to pentobarbital for cerebral radioprotection. Use of it should permit safer and easier investigation of this radioprotective effect in human trials. C1 NINCDS,SURG NEUROL BRANCH,BETHESDA,MD 20892. NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. NR 33 TC 7 Z9 7 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD MAY PY 1992 VL 30 IS 5 BP 720 EP 723 PG 4 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA HP340 UT WOS:A1992HP34000012 PM 1584384 ER PT J AU HAYNES, SR AF HAYNES, SR TI THE RNP MOTIF PROTEIN FAMILY SO NEW BIOLOGIST LA English DT Review DE RNA BINDING; RNA PROCESSING; RNP MOTIF; PROTEIN STRUCTURE ID HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN; POLY(A) BINDING-PROTEIN; HELIX-DESTABILIZING PROTEIN; AMINO-ACID SEQUENCE; B-HNRNP PROTEIN; MESSENGER-RNA; CDNA CLONING; U1 RNA; POLY(A)-BINDING PROTEIN; XENOPUS-LAEVIS RP HAYNES, SR (reprint author), NICHHD,BETHESDA,MD 20892, USA. NR 109 TC 39 Z9 40 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 1043-4674 J9 NEW BIOL PD MAY PY 1992 VL 4 IS 5 BP 421 EP 429 PG 9 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA JR313 UT WOS:A1992JR31300003 PM 1381215 ER PT J AU GOLDENBERG, RL TAMURA, T CLIVER, SP CUTTER, GR HOFFMAN, HJ COPPER, RL AF GOLDENBERG, RL TAMURA, T CLIVER, SP CUTTER, GR HOFFMAN, HJ COPPER, RL TI SERUM FOLATE AND FETAL GROWTH-RETARDATION - A MATTER OF COMPLIANCE SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID FOLIC-ACID SUPPLEMENT; PREGNANCY; PREMATURITY AB Serum folate levels were measured at 30 weeks' gestational age in 289 pregnant women, each of whom had been provided with folate supplementation at enrollment in prenatal care. There was a significant association between low serum folate levels and fetal growth retardation. High folate levels were most likely explained by recent folic acid intake. Therefore, we were concerned that the, decreased fetal growth associated with low folate levels may have been related to a combination of psychological and behavioral characteristics for which low serum folate levels were only a surrogate measure. A profile of maternal psychosocial status was created, which included measures of depression, anxiety, self-esteem, mastery, stress, and social support. Poorer psychological scores were significantly related to lower serum folate levels. However, in women with both good and poor psychosocial scores, high folate levels were significantly associated with increased birth weight, a relationship that persisted even after adjusting for maternal race, body mass index, smoking, history of a low birth weight infant, and infant gender. Our findings suggest that women with good psychosocial scores are more likely to take folate, but that the use of folate itself is related to a lower risk of fetal growth retardation and increased birth weight. C1 UNIV ALABAMA,DEPT NUTR SCI,BIRMINGHAM,AL 35233. UNIV ALABAMA,SCH PUBL HLTH,BIRMINGHAM,AL 35233. NICHHD,PREVENT RES PROGRAM,BIOMETRY BRANCH,BALTIMORE,MD 21224. RP GOLDENBERG, RL (reprint author), UNIV ALABAMA,DEPT OBSTET & GYNECOL,PERINATAL EPIDEMIOL UNIT,UNIV STN,BIRMINGHAM,AL 35233, USA. FU CSAP SAMHSA HHS [SP01-CA-28103]; NICHD NIH HHS [N01-HD-4-2811] NR 18 TC 46 Z9 46 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD MAY PY 1992 VL 79 IS 5 BP 719 EP 722 PN 1 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA HQ290 UT WOS:A1992HQ29000017 PM 1565355 ER PT J AU LINK, DC GUTKIND, SJ ROBBINS, KC LEY, TJ AF LINK, DC GUTKIND, SJ ROBBINS, KC LEY, TJ TI CHARACTERIZATION OF THE 5' UNTRANSLATED REGION OF THE HUMAN C-FGR GENE AND IDENTIFICATION OF THE MAJOR MYELOMONOCYTIC C-FGR PROMOTER SO ONCOGENE LA English DT Article ID NF-KAPPA-B; PROTO-ONCOGENE; MESSENGER-RNA; CELL-LINES; EXPRESSION; PROTOONCOGENE; VIRUS; DIFFERENTIATION; TRANSCRIPTS; ACTIVATION AB In this study, we have characterized the 5' region of the human c-fgr proto-oncogene and identified the major myelomonocytic c-fgr promoter. Seven distinct 5' untranslated exons were identified and localized to a region extending 13 kb upstream from the first coding exon. Two major promoters were identified, one utilized exclusively in Epstein-Barr virus (EBV)-infected B-lymphocyte cell lines, and the other functional only in myelomonocytic cells. Differential promoter utilization and alternative splicing of the 5' untranslated exons give rise to at least six distinct c-fgr mRNA species that differ only in their 5' untranslated regions. Two major mRNAs were identified, c-fgr A and c-fgr 4; these two mRNAs were detected exclusively in EBV-infected B-lymphocyte cell lines and myelomonocytic cells respectively. We have previously demonstrated that c-fgr is transcriptionally activated in U937 cells treated with either 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or cycloheximide (CHX). We now show that a DNA fragment extending from -772 to +97 (with respect to the transcription initiation site upstream from exon M4) is responsive to TPA but not CHX treatment in U937 cells. These results suggest that TPA and CHX induce c-fgr mRNA accumulation by different mechanisms. C1 WASHINGTON UNIV,JEWISH HOSP ST LOUIS,MED CTR,DEPT MED,DIV HEMATOL ONCOL,ST LOUIS,MO 63110. WASHINGTON UNIV,JEWISH HOSP ST LOUIS,MED CTR,DEPT GENET,ST LOUIS,MO 63110. NIDR,CELLULAR DEV & ONCOL LAB,BETHESDA,MD 20892. RI Gutkind, J. Silvio/A-1053-2009 FU NCI NIH HHS [CA 49712]; NIDDK NIH HHS [DK 38682] NR 31 TC 13 Z9 13 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY PY 1992 VL 7 IS 5 BP 877 EP 884 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA HP642 UT WOS:A1992HP64200006 PM 1373875 ER PT J AU HOWARD, OMZ DEAN, M YOUNG, H RAMSBURG, M TURPIN, JA MICHIEL, DF KELVIN, DJ LEE, L FARRAR, WL AF HOWARD, OMZ DEAN, M YOUNG, H RAMSBURG, M TURPIN, JA MICHIEL, DF KELVIN, DJ LEE, L FARRAR, WL TI CHARACTERIZATION OF A CLASS-3 TYROSINE KINASE SO ONCOGENE LA English DT Article ID COLONY-STIMULATING FACTOR; SIGNAL TRANSDUCTION; CATALYTIC DOMAINS; CELL-LINES; EXPRESSION; GENE; IDENTIFICATION; ACTIVATION; SEQUENCE; P56LCK AB In an effort to identify unique tyrosine kinases found in human leukemia cell lines, we utilized polymerase chain reaction (PCR) technology and degenerate oligonucleotide primers to produce a cDNA library of kinase catalytic domains found in the human monocytic cell line AML-193. This search yielded a member of the class 3 tyrosine kinases closely related to the murine kinase FD-22. Previous work has identified this kinase as JAK1. This class of tyrosine kinases is characterized by being ubiquitously expressed, lacking both a ligand-binding domain and a SH2 domain, while containing a second domain similar to a degenerate kinase domain. Our studies focused on the further characterization of this class 3 tyrosine kinase using Northern blot analysis to demonstrate an increase in steady-state mRNA by interferon-gamma in human monocytes. A human-hamster somatic cell hybrid panel and linkage mapping was used to assign JAK1 (aml-116) to human chromosome 1. C1 NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21701. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21701. WALTER REED ARMY MED CTR,DEPT CELLULAR IMMUNOL,WASHINGTON,DC 20307. RP HOWARD, OMZ (reprint author), NCI,PROGRAM RESOURCES INC DYNCORP,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21701, USA. RI Dean, Michael/G-8172-2012; Howard, O M Zack/B-6117-2012 OI Dean, Michael/0000-0003-2234-0631; Howard, O M Zack/0000-0002-0505-7052 FU NCI NIH HHS [N01-CO-74102] NR 28 TC 14 Z9 14 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY PY 1992 VL 7 IS 5 BP 895 EP 900 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA HP642 UT WOS:A1992HP64200008 PM 1373877 ER PT J AU SRIVASTAVA, S TONG, YA DEVADAS, K ZOU, ZQ SYKES, VW CHEN, Y BLATTNER, WA PIROLLO, K CHANG, EH AF SRIVASTAVA, S TONG, YA DEVADAS, K ZOU, ZQ SYKES, VW CHEN, Y BLATTNER, WA PIROLLO, K CHANG, EH TI DETECTION OF BOTH MUTANT AND WILD-TYPE P53-PROTEIN IN NORMAL SKIN FIBROBLASTS AND DEMONSTRATION OF A SHARED 2ND HIT ON P53 IN DIVERSE TUMORS FROM A CANCER-PRONE FAMILY WITH LI-FRAUMENI SYNDROME SO ONCOGENE LA English DT Note ID ONCOGENE; GENE; SUPPRESSION; MUTATIONS; PROTEIN; GROWTH AB Germline transmission of mutant p53 gene in cancerprone families with Li-Fraumeni syndrome has revealed a new role for p53 in the genetic predisposition to cancer. The studies reported here focus on the analysis of the expression of normal and mutant p53 RNA and protein in germline configuration and demonstrate that normal skin fibroblasts derived from members of a family with Li-Fraumeni syndrome express mutant p53Gly --> Asp(245) protein and RNA at levels similar to the wild-type p53. Thus, these fibroblasts represent a unique biological system in which endogenous promoters are utilized for the expression of both mutant and normal p53. We have further extended the earlier observations on the analysis of mutant p53 with a limited number of tumors derived from individuals with Li-Fraumeni syndrome. Tumors arising from two different germ layers in four individuals in a single family clearly exhibited the loss of the wild-type allele and the retention of the mutant allele observed in the normal skin fibroblasts derived from the same individuals. These observations further support the notion that germline p53 mutation plays a key role in the tumorigenesis of individuals with Li-Fraumeni syndrome. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT PATHOL,BETHESDA,MD 20814. UNIFORMED SERV UNIV HLTH SCI,DEPT SURG,BETHESDA,MD 20814. NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892. NR 25 TC 62 Z9 62 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY PY 1992 VL 7 IS 5 BP 987 EP 991 PG 5 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA HP642 UT WOS:A1992HP64200019 PM 1373881 ER PT J AU PERRAUD, F YOSHIMURA, K LOUIS, B DALEMANS, W ALIHADJI, D SCHULTZ, H CLAUDEPIERRE, MC CHARTIER, C DANEL, C BELLOCQ, JP CRYSTAL, RG LECOCQ, JP PAVIRANI, A AF PERRAUD, F YOSHIMURA, K LOUIS, B DALEMANS, W ALIHADJI, D SCHULTZ, H CLAUDEPIERRE, MC CHARTIER, C DANEL, C BELLOCQ, JP CRYSTAL, RG LECOCQ, JP PAVIRANI, A TI THE PROMOTER OF THE HUMAN CYSTIC-FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR GENE DIRECTING SV40 T-ANTIGEN EXPRESSION INDUCES MALIGNANT PROLIFERATION OF EPENDYMAL CELLS IN TRANSGENIC MICE SO ONCOGENE LA English DT Note ID IDENTIFICATION; MUTATIONS; PROTEIN; TUMORS; LINES; DEFECT AB Transgenic mice bearing a human cystic fibrosis transmembrane conductance regulator (CFTR) promoter-SV40 T antigen fusion transgene were generated in order to localize in vivo the potential oncogenesis linked to the tissue-specific activity of the promoter for the CFTR gene. Surprisingly, the only site of tumors resulting from expression of the reporter onc gene was ependymal cells lining the brain ventricles. SV40 T antigen expression in these cells led to a consistent pathology in the first weeks of age: ependymoma and consequent hydrocephaly. Tumor-derived cell lines were established, characterized and shown to originate from SV40 T antigen-induced ependymoma. No pathological alterations were found in other organs, such as lungs and pancreas, in which cystic fibrosis is pathologically manifest in humans. Such transgenic mice and derived cell lines may represent valid models for analysing (1) the role of SV40 T antigen in ependymoma formation and (2) CFTR function in ependymal cells. C1 TRANSGENE SA,DEPT ANIM SYST,11 RUE MOLSHEIM,F-67082 STRASBOURG,FRANCE. NHLBI,PULM BRANCH,BETHESDA,MD 20892. HOP HAUTE PIERRE,SERV ANAT PATHOL GEN,F-67200 STRASBOURG,FRANCE. NR 46 TC 12 Z9 12 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAY PY 1992 VL 7 IS 5 BP 993 EP 997 PG 5 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA HP642 UT WOS:A1992HP64200020 PM 1373882 ER PT J AU LAROCCA, RV PARK, JG DANESI, R DELTACCA, M STEINBERG, SM GAZDAR, AF AF LAROCCA, RV PARK, JG DANESI, R DELTACCA, M STEINBERG, SM GAZDAR, AF TI PATTERN OF GROWTH-FACTOR, PROTOONCOGENE AND CARCINOEMBRYONIC ANTIGEN GENE-EXPRESSION IN HUMAN COLORECTAL-CARCINOMA CELL-LINES SO ONCOLOGY LA English DT Article DE COLON CANCER; CELL LINES; GENE EXPRESSION; CLINICOBIOLOGICAL CORRELATION ID FACTOR RECEPTOR; FACTOR-BETA; C-MYC; CANCER; HOMOLOGY; TUMORS; VIRUS; DNA AB The aim of the present study was to examine whether the expression of growth factor genes, proto-oncogenes and carcinoembryonic antigen (CEA) gene in human colorectal cancer cell lines was related to their clinicobiological behavior. A significant variability among cell lines was detected for both insulin-like growth factor II and transforming growth factor-beta-gene message. Detectable levels of c-myc, Her-2, c-myb, K-ras and EGF receptor mRNA were found in most cell lines, whereas only 1/11 and 2/11 cell lines were positive for N-myc and c-sis message, respectively. N-myc expression was limited to a cell line originated from a tumor with neuroendocrine features, while high levels of K-ras message were found only in a cell line derived from a radioresistant tumor. CEA mRNA levels correlated well with the concentration of antigen in each cell line. On the basis of these results, our findings demonstrated that human colorectal cancer cell lines show heterogeneous expression of growth factor and CEA genes and proto-oncogenes; however, with the exception of K-ras, N-myc and CEA, other correlations between gene expression and the clinicobiological characteristics of these cell lines could not be demonstrated. C1 UNIV PISA,INST MED PHARMACOL,VIA ROMA 55,I-56126 PISA,ITALY. UNIV LOUISVILLE,J GRAHAM BROWN CANC CTR,DEPT MED ONCOL,LOUISVILLE,KY 40292. SEOUL NATL UNIV,COLL MED,DEPT SURG,SEOUL 151,SOUTH KOREA. SEOUL NATL UNIV HOSP,SEOUL,SOUTH KOREA. UNIV PISA,INST MED PHARMACOL,I-56100 PISA,ITALY. NCI,BIOSTAT & DATA,MANAGEMENT SECT,BETHESDA,MD 20892. NCI,NAVY MED ONCOL BRANCH,BETHESDA,MD 20892. USN HOSP,BETHESDA,MD 20814. RI Park, Jae-Gahb/J-5494-2012 NR 22 TC 9 Z9 9 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-2414 J9 ONCOLOGY JI Oncology PD MAY-JUN PY 1992 VL 49 IS 3 BP 209 EP 214 PG 6 WC Oncology SC Oncology GA JG512 UT WOS:A1992JG51200007 PM 1495747 ER PT J AU GORDON, SL CORBIN, SB AF GORDON, SL CORBIN, SB TI SUMMARY OF WORKSHOP ON DRINKING-WATER FLUORIDE INFLUENCE ON HIP FRACTURE ON BONE HEALTH - (NATIONAL-INSTITUTES-OF-HEALTH, 10 APRIL, 1991) SO OSTEOPOROSIS INTERNATIONAL LA English DT Editorial Material ID MECHANICAL-PROPERTIES; SODIUM-FLUORIDE; OSTEOPOROSIS; WOMEN C1 CTR DIS CONTROL,NATL CTR PREVENT SERV,ATLANTA,GA 30333. RP GORDON, SL (reprint author), NIAMSD,MUSCULOSKELETAL DIS BRANCH,WESTWOOD BLDG,ROOM 407,5333 WESTBARD AVE,BETHESDA,MD 20892, USA. NR 26 TC 31 Z9 32 U1 0 U2 0 PU SPRINGER-VERLAG LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL ROAD, GODALMING, SURREY, ENGLAND GU7 3DJ SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD MAY PY 1992 VL 2 IS 3 BP 109 EP 117 DI 10.1007/BF01623816 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA HR558 UT WOS:A1992HR55800001 PM 1627897 ER PT J AU BEINFELD, MC HAUN, RS ALLARD, LR DIXON, JE AF BEINFELD, MC HAUN, RS ALLARD, LR DIXON, JE TI REGULATION OF CHOLECYSTOKININ SECRETION FROM A RAT MEDULLARY-THYROID CARCINOMA CELL-LINE - ROLE OF CALCIUM, CYCLIC-NUCLEOTIDES, GLUCOCORTICOIDS, NEUROTENSIN, AND CALCITONIN GENE-RELATED PEPTIDE SO PEPTIDES LA English DT Article DE CCK; CALCIUM; CAMP; PEPTIDE SECRETION; THYROID CELLS; CGRP; NEUROTENSIN ID C-FOS; EXPRESSION; ESTABLISHMENT; TUMOR; ANTAGONIST; RELEASE; CLONING; POTENT; GROWTH AB CCK-secreting WE rat medullary thyroid carcinoma cell line resembles other calcitonin-producing (C-cell) lines in that calcium, cAMP, or agents which raise cAMP, dexamethasone, and beta-adrenergic agents all stimulate peptide secretion. Unlike other C-cell lines, the WE cells respond similarly to IBMX (3-isobutyl-1-methyl-xanthine, a phospho-diesterase inhibitor) in the presence and absence of forskolin, implying that these cells secrete substances that raise cAMP levels, whose effect is accentuated by IBMX. Both CGRP and neurotensin, peptides that may be secreted by these cells, caused a small, but significant, increase in CCK secretion. It is possible that these or other secreted substances that activate adenylate cyclase are responsible for the cell's high rate of CCK secretion. Their high rate of CCK synthesis and their regulated secretion suggest that these cells will be a good model for studies of CCK expression, biosynthesis, and processing. C1 NHLBI,CELLULAR METAB LAB,BETHESDA,MD 20892. PURDUE UNIV,DEPT BIOCHEM,W LAFAYETTE,IN 47907. RP BEINFELD, MC (reprint author), ST LOUIS UNIV,SCH MED,DEPT PHARMACOL & PHYSIOL SCI,1402 S GRAND BLVD,ST LOUIS,MO 63104, USA. FU NIDDK NIH HHS [NIDDKD 18849]; NINDS NIH HHS [NS 18667] NR 27 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 0196-9781 J9 PEPTIDES JI Peptides PD MAY-JUN PY 1992 VL 13 IS 3 BP 545 EP 550 DI 10.1016/0196-9781(92)90087-J PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA JB248 UT WOS:A1992JB24800019 PM 1523166 ER PT J AU GLOWA, JR BARRETT, JE RUSSELL, J GOLD, PW AF GLOWA, JR BARRETT, JE RUSSELL, J GOLD, PW TI EFFECTS OF CORTICOTROPIN RELEASING HORMONE ON APPETITIVE BEHAVIORS SO PEPTIDES LA English DT Review DE CORTICOTROPIN RELEASING HORMONE(CRH); FOOD INTAKE; BEHAVIORAL EFFECTS; FOOD-ASSOCIATED BEHAVIORS ID CENTRALLY ADMINISTERED CRF; PITUITARY-ADRENAL AXIS; CENTRAL NERVOUS-SYSTEM; ANOREXIA-NERVOSA; CEREBROSPINAL-FLUID; EXPLORATORY-BEHAVIOR; RESPONSE SUPPRESSION; SQUIRREL-MONKEYS; RHESUS-MONKEYS; BETA-ENDORPHIN AB Corticotropin releasing hormone (CRH) is a 41 -residue hypothalamic neuropeptide that has been shown to have potent behavioral effects in animals and has been implicated in clinical disorders in man. This review focuses on those aspects of the behavioral effects of CRH related to food-associated behaviors. The effects of CRH on food intake are compared with its effects on performances maintained by food presentation, and contrasted with the effects of CRH on performances maintained by other events. The effects of CRH antagonists and drugs that interact with the behavioral effects of CRH are also reviewed, particularly with respect to their direct effects on food intake. Lastly, data assessing the effects of CRH administration on central neurotransmitter levels are presented and compared with levels seen in clinical populations. The effect of CRH on food intake seen in animals is consistent with a putative role for CRH in clinical syndromes where appetite suppression is apparent. Since some of the effects of CRH on food intake are subject to pharmacological intervention, strategies directed at peptidergic mechanisms of psychiatric disorders should be explored. C1 NIMH,CLIN NEUROENDOCRINOL BRANCH,BEHESDA,MD 20891. ELI LILLY & CO,LILLY CORP CTR,LILLY RES LABS,INDIANAPOLIS,IN 46285. NR 87 TC 69 Z9 69 U1 0 U2 4 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 MAY-JUN PY 1992 VL 13 IS 3 BP 609 EP 621 DI 10.1016/0196-9781(92)90097-M PG 13 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA JB248 UT WOS:A1992JB24800029 PM 1523173 ER PT J AU LI, SJ WONG, SC HONG, JS INGENITO, AJ AF LI, SJ WONG, SC HONG, JS INGENITO, AJ TI AGE-RELATED-CHANGES IN OPIOID PEPTIDE CONCENTRATIONS IN BRAIN AND PITUITARY OF SPONTANEOUSLY HYPERTENSIVE RATS - EFFECT OF ANTIHYPERTENSIVE DRUGS AND COMPARISON WITH DEOXYCORTICOSTERONE ACETATE AND SALT HYPERTENSION SO PHARMACOLOGY LA English DT Article DE ANTIHYPERTENSIVE DRUGS; DEOXYCORTICOSTERONE ACETATE PLUS SALT HYPERTENSION; DYNORPHINS; ENDORPHINS; ENKEPHALINS; HYPERTENSION; NEURAL CONTROL OF CIRCULATION; OPIOID PEPTIDES; SPONTANEOUSLY HYPERTENSIVE RAT ID WISTAR-KYOTO RATS; BETA-ENDORPHIN; PERIPHERAL-TISSUES; NORMOTENSIVE RATS; IMMUNOREACTIVITY; NUCLEI; NEUROPEPTIDES; ENKEPHALIN; CLONIDINE; GLAND AB The relationship of age-dependent changes in concentrations of various opioid peptides in the brain and pituitary to the development of hypertension was studied in the spontaneously hypertensive rat (SHR). Normotensive Wistar-Kyoto (WKY) and Sprague-Dawley rats served as controls. Opioids determined were dynorphin A (1-8) [DN-A(1-8)], beta-endorphin (BE) and Met-enkephalin (ME). Three approaches were used: (1) temporal correlations of opioid concentrations with the onset of hypertension in 4-, 8-, 12- and 16-week-old rats; (2) study of opioid changes when hypertension development was prevented with antihypertensive drugs and (3) determination of possible opioid peptide changes in another rat model of hypertension, the deoxycorticosterone acetate (DOCA) + salt model. Opioid peptide concentration differences (SHR/ WKY) found were as follows. There were much lower DN-A(1-8) levels in the SHR hippocampus and hypothalamus at all ages studied. At 12 and 16 weeks, coincidently with the onset of hypertension, lower levels of BE were found in the anterior lobe of the pituitary, but there were higher BE and ME levels found in the neurointermediate lobe (NIL). Prevention of hypertension in SHR by 8 weeks of oral therapy with guanethidine and hydralazine reversed the BE and ME changes in the NIL but not in the anterior lobe. There were no brain or pituitary changes in opioid peptide concentrations associated with DOCA-salt hypertension. The results are interpreted as supporting a role for altered concentrations of brain and pituitary opioids in the genesis of SHR hypertension. C1 E CAROLINA UNIV,SCH MED,DEPT PHARMACOL,GREENVILLE,NC 27858. NIEHS,MOLEC & INTEGRAT NEUROSCI LAB,NEUROPHARMACOL SECT,RES TRIANGLE PK,NC 27709. NR 28 TC 11 Z9 13 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0031-7012 J9 PHARMACOLOGY JI Pharmacology PD MAY PY 1992 VL 44 IS 5 BP 245 EP 256 DI 10.1159/000138926 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA HX662 UT WOS:A1992HX66200002 PM 1352404 ER PT J AU WONG, G SKOLNICK, P AF WONG, G SKOLNICK, P TI RO-15-4513 BINDING TO GABA-A RECEPTORS - SUBUNIT COMPOSITION DETERMINES LIGAND EFFICACY SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE BENZODIAZEPINE RECEPTORS; RO 15-4513; GABA; DIAZEPAM-SENSITIVE RECEPTORS; DIAZEPAM-INSENSITIVE RECEPTORS ID PARTIAL INVERSE AGONIST; BENZODIAZEPINE RECEPTORS; ALCOHOL SENSITIVITY; RO 15-4513; ANTAGONIST; DIAZEPAM; BETA-CARBOLINE-3-CARBOXYLATE; IMIDAZOBENZODIAZEPINE; ETHANOL; SYSTEM AB The bidirectional modulation of ligand binding to benzodiazepine receptors (BzR) by GABA (the "GABA shift") has been widely used to predict ligand efficacy. The present study examined the effects of GABA and muscimol on [H-3]Ro 15-4513 binding to "diazepam-insensitive' (DI) and "diazepam-sensitive" (DS) BzR. Neither GABA nor muscimol significantly altered [H-3]Ro 15-4513 binding to DI in cerebellum, while both compounds inhibit [H-3]Ro 15-4513 binding to cerebellar DS in a concentration-dependent fashion. The maximum reductions in [H-3]Ro 15-4513 binding to cerebral cortical and hippocampal membranes elicited by GABA were comparable to those obtained in cerebellar DS, but significantly less than obtained with the full inverse agonist [H-3]3-carbomethoxy-beta-carboline. The qualitatively different effect of GABAmimetics on [H-3]Ro 15-4513 binding to DS and DI is not species specific since identical effects were obtained in rat and mouse brain. Based on previously established criteria, Ro 15-4513 can be classified as a "GABA-neutral" (antagonist) ligand at DI and "GABA negative" (inverse agonist) at other BzR. These findings suggest that GABA(A) receptor subunit composition determines not only ligand affinity but also ligand efficacy. RP WONG, G (reprint author), NIDDKS,NEUROSCI LAB,BLDG 8,RM 111,BETHESDA,MD 20892, USA. NR 21 TC 26 Z9 26 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 MAY PY 1992 VL 42 IS 1 BP 107 EP 110 DI 10.1016/0091-3057(92)90454-N PG 4 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA HZ471 UT WOS:A1992HZ47100018 PM 1326771 ER PT J AU BARR, AE SIEGEL, KL DANOFF, JV MCGARVEY, CL TOMASKO, A SABLE, I STANHOPE, SJ AF BARR, AE SIEGEL, KL DANOFF, JV MCGARVEY, CL TOMASKO, A SABLE, I STANHOPE, SJ TI BIOMECHANICAL COMPARISON OF THE ENERGY-STORING CAPABILITIES OF SACH AND CARBON COPY II PROSTHETIC FEET DURING THE STANCE PHASE OF GAIT IN A PERSON WITH BELOW-KNEE AMPUTATION SO PHYSICAL THERAPY LA English DT Editorial Material DE AMPUTATIONS; PROSTHETICS; KINESIOLOGY BIOMECHANICS; GAIT ANALYSIS; PROSTHESIS ID WALKING; ANKLE; MOTION AB In this study, the energy-storing capabilities of solid-ankle cushion heel (SACH) and Carbon Copy II prosthetic feet during the stance phase of gait were compared. A person with a unilateral below-knee amputation served as a component of the instrumentation to test the feet under dynamic loads. Ten trials per foot of bilateral stride at "free" velocity were collected with a video-based, three-dimensional data-acquisition system and two force plates. There were no differences between the prosthetic conditions in step length, single-limb support time, and swing period (analysis of variance) or in double-limb support time, cadence, and velocity (Student's t test), Angular kinematics and moments of the hip and knee were unaffected bilaterally by the type of foot. The progression of the center of pressure under the Carbon Copy II was delayed from 15% to 80% of stance as compared with the SACH foot. The Carbon Copy II showed slower unloading in late stance and a later peak propulsive force than did the SACH foot. The Carbon Copy II performed greater work in both the energy-storage (Carbon Copy II = 2.33 J, SACH = 1.16 J) and energy-return (Carbon Copy II = 1.33 J, SACH = 0.34 J) phase of stance and returned energy with 57% efficiency. Although the energy returned by the Carbon Copy II was clinically insignificant during level walking, these results confirm that it performs as an energy-storing device. C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT REHABIL MED,BIOMECH SECT,BETHESDA,MD 20892. HOWARD UNIV,DEPT PHYS THERAPY,WASHINGTON,DC 20059. CAPITOL ORTHOPED,BETHESDA,MD 20814. NIH,WARREN G MAGNUSON CLIN CTR,DEPT REHABIL MED,BIOMECH LAB,BETHESDA,MD 20892. RI Siegel, Karen Lohmann/B-5898-2008; OI Siegel, Karen Lohmann/0000-0002-0788-6612 NR 23 TC 36 Z9 36 U1 2 U2 6 PU AMER PHYS THER ASSN PI ALEXANDRIA PA 1111 N FAIRFAX ST, ALEXANDRIA, VA 22314 SN 0031-9023 J9 PHYS THER JI Phys. Ther. PD MAY PY 1992 VL 72 IS 5 BP 344 EP 354 PG 11 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA HR349 UT WOS:A1992HR34900003 PM 1631203 ER PT J AU GOLBUS, MT AF GOLBUS, MT TI SPECIAL ISSUE - COLLABORATIVE STUDIES ON CHORION VILLUS SAMPLING IN NORTH-AMERICA - INVITED EDITORIAL SO PRENATAL DIAGNOSIS LA English DT Editorial Material C1 GEORGE WASHINGTON UNIV,WASHINGTON,DC 20052. UNIV TENNESSEE CTR HLTH SCI,MEMPHIS,TN 38163. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. NORTHWESTERN UNIV,CHICAGO,IL 60611. ILLINOIS MASONIC HOSP,CHICAGO,IL. YALE UNIV,NEW HAVEN,CT 06520. CUNY MT SINAI SCH MED,NEW YORK,NY 10029. GENET & INVITRO FERTILIZAT INST,FAIRFAX,VA. UNIV MIAMI,MIAMI,FL 33152. NICHHD,BETHESDA,MD. RP GOLBUS, MT (reprint author), BAYLOR COLL MED,INST MOLEC GENET,HOUSTON,TX 77030, USA. NR 9 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 0197-3851 J9 PRENATAL DIAG JI Prenat. Diagn. PD MAY PY 1992 VL 12 IS 5 BP 313 EP 315 DI 10.1002/pd.1970120502 PG 3 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA HW557 UT WOS:A1992HW55700001 PM 1523200 ER PT J AU LEDBETTER, DH ZACHARY, JM SIMPSON, JL GOLBUS, MS PERGAMENT, E JACKSON, L MAHONEY, MJ DESNICK, RJ SCHULMAN, J COPELAND, KL VERLINSKY, Y YANGFENG, T SCHONBERG, SA BABU, A THARAPEL, A DORFMANN, A LUBS, HA RHOADS, GG FOWLER, SE DELACRUZ, F AF LEDBETTER, DH ZACHARY, JM SIMPSON, JL GOLBUS, MS PERGAMENT, E JACKSON, L MAHONEY, MJ DESNICK, RJ SCHULMAN, J COPELAND, KL VERLINSKY, Y YANGFENG, T SCHONBERG, SA BABU, A THARAPEL, A DORFMANN, A LUBS, HA RHOADS, GG FOWLER, SE DELACRUZ, F TI CYTOGENETIC RESULTS FROM THE UNITED-STATES COLLABORATIVE STUDY ON CVS SO PRENATAL DIAGNOSIS LA English DT Article DE PRENATAL DIAGNOSIS; CHORIONIC VILLUS SAMPLING; CYTOGENETICS; MOSAICISM ID FALSE-NEGATIVE FINDINGS; FLUID CELL-CULTURES; CHORIONIC VILLUS; PRENATAL-DIAGNOSIS; AMNIOTIC-FLUID; CHROMOSOME MOSAICISM; PSEUDOMOSAICISM AB Cytogenetic data are presented for 11 473 chorionic villus sampling (CVS) procedures from nine centres in the U.S. NICHD collaborative study. A successful cytogenetic diagnosis was obtained in 99.7 per cent of cases, with data obtained from the direct method only (26 per cent), culture method only (42 per cent), or a combination of both (32 per cent). A total of 1.1 per cent of patients had a second CVS or amniocentesis procedure for reasons related to the cytogenetic diagnostic procedure, including laboratory failures (27 cases), maternal cell contamination (4 cases), or mosaic or ambiguous cytogenetic results (98 cases). There were no diagnostic errors involving trisomies for chromosomes 21, 18, and 13. For sex chromosome aneuploidies, one patient terminated her pregnancy on the basis of non-mosaic 47,XXX in the direct method prior to the availability of results from cultured cells. Subsequent analysis of the CVS cultures and fetal tissues showed only normal female cells. Other false-positive predictions involving non-mosaic aneuploidies (n = 13) were observed in the direct or culture method, but these cases involved rare aneuploidies: four cases of tetraploidy, two cases of trisomy 7, and one case each of trisomies 3, 8, 11, 15, 16, 20, and 22. This indicates that rare aneuploidies observed in the direct or culture method should be subjected to follow-up by amniocentesis. Two cases of unbalanced structural abnormalities detected in the direct method were not confirmed in cultured CVS or amniotic fluid. In addition, one structural rearrangement was misinterpreted as unbalanced from the direct method, leading to pregnancy termination prior to results from cultured cells showing a balanced, inherited translocation. False-negative results (n = 8) were observed only in the direct method, including one non-mosaic fetal abnormality (trisomy 18) detected by the culture method and seven cases of fetal mosaicism (all detected by the culture method). Mosaicism was observed in 0.8 per cent of all cases, while pseudomosaicism (including single trisomic cells) was observed in 1.6 per cent of cases. Mosaicism was observed with equal frequency in the direct and culture methods, but was confirmed as fetal mosaicism more often in cases from the culture method (24 per cent) than in cases from the direct method (10 per cent). The overall rate of maternal cell contamination was 1.8 per cent for the culture method, but there was only one case of incorrect sex prediction due to complete maternal cell contamination which resulted in the birth of a normal male. The rate of maternal cell contamination was significantly higher in samples obtained by the transcervical sampling method (2.16 per cent) than in samples obtained by the transabdominal method (0.79 per cent). From these data, it is clear that the culture method has a higher degree of diagnostic accuracy than the direct method, which should not be used as the sole diagnostic technique. The direct method can be a useful adjunct to the culture method, in which maternal cell contamination can lead to incorrect sex prediction and potentially to false-negative diagnostic results. C1 GEORGE WASHINGTON UNIV,WASHINGTON,DC 20052. UNIV TENNESSEE CTR HLTH SCI,MEMPHIS,TN 38163. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. NORTHWESTERN UNIV,CHICAGO,IL 60611. ILLINOIS MASONIC HOSP,CHICAGO,IL. YALE UNIV,NEW HAVEN,CT 06520. CUNY MT SINAI SCH MED,NEW YORK,NY 10029. GENET & INVITRO FERTILIZAT INST,FAIRFAX,VA. UNIV MIAMI,MIAMI,FL 33152. NICHHD,BETHESDA,MD. RP LEDBETTER, DH (reprint author), BAYLOR COLL MED,INST MOLEC GENET,HOUSTON,TX 77030, USA. NR 33 TC 246 Z9 248 U1 0 U2 3 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 MAY PY 1992 VL 12 IS 5 BP 317 EP 345 DI 10.1002/pd.1970120503 PG 29 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA HW557 UT WOS:A1992HW55700002 PM 1523201 ER PT J AU WAPNER, RJ SIMPSON, JL GOLBUS, MS ZACHARY, JM LEDBETTER, DH DESNICK, RJ FOWLER, SE JACKSON, LG LUBS, H MAHONY, RJ PERGAMENT, E RHOADS, GG SHULMAN, JD DELACRUZ, F AF WAPNER, RJ SIMPSON, JL GOLBUS, MS ZACHARY, JM LEDBETTER, DH DESNICK, RJ FOWLER, SE JACKSON, LG LUBS, H MAHONY, RJ PERGAMENT, E RHOADS, GG SHULMAN, JD DELACRUZ, F TI CHORIONIC MOSAICISM - ASSOCIATION WITH FETAL LOSS BUT NOT WITH ADVERSE PERINATAL OUTCOME SO PRENATAL DIAGNOSIS LA English DT Article DE MOSAICISM; CHORIONIC VILLUS SAMPLING; PRENATAL DIAGNOSIS; FETAL LOSS AB Cytogenetic data from the United States NICHD collaborative study of chorionic villus sampling (CVS) were used to evaluate the clinical significance of chorionic mosaicism. The 10 754 patients with normal cytogenetic results were compared with 108 patients(1.0 percent) with placental mosaicism and 181 patients (1.6 per cent) with pseudomosaicism. Of the pregnancies intended to continue, the pregnancy loss rate was significantly greater in patients with placental mosaicism than in thc cytogenetically normal cohort (8.6 vs. 3.4 per cent. p < 0.05). However, there was no difference in the frequencies of abruptio placenta, preterm labour or delivery, small-for-gestational-age newborns, pregnancy-induced hypertension, or neonates with Apgar scores less than 7. C1 UNIV TENNESSEE CTR HLTH SCI,MEMPHIS,TN 38163. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. GEORGE WASHINGTON UNIV,WASHINGTON,DC 20052. BAYLOR COLL MED,HOUSTON,TX 77030. CUNY MT SINAI SCH MED,NEW YORK,NY 10029. HENRY FORD HOSP,SOUTHFIELD,MI. UNIV MIAMI,MIAMI,FL 33152. YALE UNIV,NEW HAVEN,CT 06520. NORTHWESTERN UNIV,SCH MED,CHICAGO,IL 60611. ROBERT WOOD JOHNSON SCH MED,NEW BRUNSWICK,NJ. GENET & INVITRO FERTILIZAT INST,FAIRFAX,VA. NICHHD,BETHESDA,MD. RP WAPNER, RJ (reprint author), THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,1025 WALNUT ST,ROOM 310,PHILADELPHIA,PA 19107, USA. NR 8 TC 53 Z9 53 U1 0 U2 0 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 MAY PY 1992 VL 12 IS 5 BP 347 EP 355 DI 10.1002/pd.1970120504 PG 9 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA HW557 UT WOS:A1992HW55700003 PM 1523202 ER PT J AU DESNICK, RJ SCHUETTE, JL GOLBUS, MS JACKSON, L LUBS, HA LEDBETTER, DH MAHONEY, MJ PERGAMENT, E SIMPSON, JL ZACHARY, JM FOWLER, SE RHOADS, GG DELACRUZ, F AF DESNICK, RJ SCHUETTE, JL GOLBUS, MS JACKSON, L LUBS, HA LEDBETTER, DH MAHONEY, MJ PERGAMENT, E SIMPSON, JL ZACHARY, JM FOWLER, SE RHOADS, GG DELACRUZ, F TI 1ST-TRIMESTER BIOCHEMICAL AND MOLECULAR DIAGNOSES USING CHORIONIC VILLI - HIGH-ACCURACY IN THE UNITED-STATES COLLABORATIVE STUDY SO PRENATAL DIAGNOSIS LA English DT Article DE PRENATAL DIAGNOSIS; CHORIONIC VILLUS SAMPLING; INHERITED METABOLIC DISEASE; ENZYMES; MOLECULAR DIAGNOSTICS; LINKAGE ANALYSIS ID EARLY PRENATAL-DIAGNOSIS; 1ST TRIMESTER; DISEASE; ENZYME; CHROMOSOME; PREGNANCY; EXPERIENCE; BIOPSY; RISK; DNA AB The accuracy of biochemical and molecular prenatal diagnoses using chorionic villi as the fetal source was assessed by seven centres participating in the NICHD collaborative study on the safety and accuracy of chorionic villus sampling (CVS) and amniocentesis. Of 601 pregnancies studied, biochemical methods were used to determine the diagnosis in 283 fetuses at risk for 15 different metabolic disorders. Fifteen different lysosomal storage diseases accounted for 81 per cent of the biochemical prenatal diagnoses performed, with 57 per cent of these pregnancies at risk for Tay-Sachs disease. No errors were made in the biochemical diagnoses that predicted affected or unaffected fetuses. However, the diagnoses of certain disorders (e.g., mucopolysaccharidosis type IH, metachromatic leukodystrophy, and Krabbe disease) occasionally required confirmatory studies in cultured amniocytes because the enzyme results were inconclusive in direct and/or cultured villi or due to the presence of a pseudodeficiency allele. Of these, only the diagnosis of a fetus at risk for Krabbe disease remained inconclusive after special studies to discriminate between mutant and pseudodeficiency alleles. Recombinant DNA techniques were used to predict the diagnosis of 318 fetuses at risk for 16 different disorders in which the defective disease gene could be detected either directly or by linkage analysis to a nearby polymorphic marker. Of these, 32 per cent were for haemoglobinopathies, 25 per cent for cystic fibrosis, 24 per cent for Duchenne or Becker muscular dystrophy, and 7 per cent for haemophilias. Pregnancies at risk for known disorders with specific molecular lesions (e.g., sickle cell disease) were accurately diagnosed in direct and/or cultured villi. Diagnoses requiring analyses with closely linked polymorphic markers were occasionally uninformative or inconclusive. Maternal contamination was not reported in any biochemical or molecular-based diagnosis. These studies document the high accuracy and rapidity of both biochemical and mutation-specific prenatal diagnoses with direct and cultured chorionic villi. C1 UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. JEFFERSON SCH MED,PHILADELPHIA,PA. UNIV MIAMI,MIAMI,FL 33152. BAYLOR COLL MED,HOUSTON,TX 77030. YALE UNIV,SCH MED,NEW HAVEN,CT 06510. NORTHWESTERN UNIV,CHICAGO,IL 60611. ILLINOIS MASONIC HOSP,CHICAGO,IL. UNIV TENNESSEE CTR HLTH SCI,MEMPHIS,TN 38163. GEORGE WASHINGTON UNIV,WASHINGTON,DC 20052. NIH,BETHESDA,MD 20892. RP DESNICK, RJ (reprint author), CUNY MT SINAI SCH MED,5TH AVE & 100TH ST,NEW YORK,NY 10029, USA. FU NICHD NIH HHS [U03 HD19888] NR 33 TC 17 Z9 17 U1 0 U2 2 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 MAY PY 1992 VL 12 IS 5 BP 357 EP 372 DI 10.1002/pd.1970120505 PG 16 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA HW557 UT WOS:A1992HW55700004 PM 1523203 ER PT J AU GOLBUS, MS SIMPSON, JL FOWLER, SE DELACRUZ, F DESNICK, RJ WAPNER, R LEDBETTER, DH LUBS, H MAHONEY, MJ PERGAMENT, E RHOADS, GG SCHULMAN, JD ZACHARY, J AF GOLBUS, MS SIMPSON, JL FOWLER, SE DELACRUZ, F DESNICK, RJ WAPNER, R LEDBETTER, DH LUBS, H MAHONEY, MJ PERGAMENT, E RHOADS, GG SCHULMAN, JD ZACHARY, J TI RISK-FACTORS ASSOCIATED WITH TRANSCERVICAL CVS LOSSES SO PRENATAL DIAGNOSIS LA English DT Article DE PRENATAL DIAGNOSIS; CHORIONIC VILLUS SAMPLING; RISK FACTORS; SPONTANEOUS ABORTION AB Factors found to be associated with pregnancy loss after transcervical CVS were race (higher for non-white), history of spontaneous abortion, unplanned pregnancy, history of spotting or bleeding during the pregnancy prior to CVS, and placental position (higher for fundal or lateral locations). Whether the increase in loss risk is due to the factor, per se, or the factor plus the CVS cannot be determined due to the lack of appropriate control data. C1 UNIV TENNESSEE CTR HLTH SCI,MEMPHIS,TN 38163. GEORGE WASHINGTON UNIV,WASHINGTON,DC 20052. HENRY FORD HOSP,SOUTHFIELD,MI. NICHHD,BETHESDA,MD 20892. CUNY MT SINAI SCH MED,NEW YORK,NY 10029. JEFFERSON SCH MED,PHILADELPHIA,PA. BAYLOR COLL MED,HOUSTON,TX 77030. UNIV MIAMI,MIAMI,FL 33152. YALE UNIV,NEW HAVEN,CT 06520. NORTHWESTERN UNIV,SCH MED,CHICAGO,IL 60611. ROBERT WOOD JOHNSON SCH MED,NEW BRUNSWICK,NJ. GENET & INVITRO FERTILIZAT INST,FAIRFAX,VA. RP GOLBUS, MS (reprint author), UNIV CALIF SAN FRANCISCO,MED CTR,U-262,SAN FRANCISCO,CA 94143, USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0197-3851 J9 PRENATAL DIAG JI Prenat. Diagn. PD MAY PY 1992 VL 12 IS 5 BP 373 EP 376 DI 10.1002/pd.1970120506 PG 4 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA HW557 UT WOS:A1992HW55700005 PM 1523204 ER PT J AU FRUMAN, DA KLEE, CB BIERER, BE BURAKOFF, SJ AF FRUMAN, DA KLEE, CB BIERER, BE BURAKOFF, SJ TI CALCINEURIN PHOSPHATASE-ACTIVITY IN LYMPHOCYTES-T IS INHIBITED BY FK-506 AND CYCLOSPORINE-A SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE IMMUNOPHILINS; IMMUNOSUPPRESSION ID CELL ACTIVATION; PROTEIN PHOSPHATASES; LIMITED PROTEOLYSIS; MACROLIDES FK-506; RAPAMYCIN; FK506; IMMUNOPHILIN; SPECIFICITY; EXPRESSION; MECHANISMS AB The immunosuppressive agents cyclosporin A (CsA) and FK 506 bind to distinct families of intracellular proteins (immunophilins) termed cyclophilins and FK 506-binding proteins (FKBPs). Recently, it has been shown that, in vitro, the complexes of CsA-cyclophilin and FK 506-FKBP-12 bind to and inhibit the activity of calcineurin, a calcium-dependent serine/threonine phosphatase. We have investigated the effects of drug treatment on phosphatase activity in T lymphocytes. Calcineurin is expressed in T cells, and its activity can be measured in cell lysates. Both CsA and FK 506 specifically inhibit cellular calcineurin at drug concentrations that inhibit interleukin 2 production in activated T cells. Rapamycin, which binds to FKBPs but exhibits different biological activities than FK 506, has no effect on calcineurin activity. Furthermore, excess concentrations of rapamycin prevent the effects of FK 506, apparently by displacing FK 506 from FKBPs. These results show that calcineurin is a target of drug-immunophilin complexes in vivo and establish a physiological role for calcineurin in T-cell activation. C1 HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV PEDIAT ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DIV MED SCI,COMM IMMUNOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115. HARVARD UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. NCI,BIOCHEM LAB,BETHESDA,MD 20892. BRIGHAM & WOMENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. FU NCI NIH HHS [CA39542] NR 31 TC 679 Z9 687 U1 4 U2 10 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 1 PY 1992 VL 89 IS 9 BP 3686 EP 3690 DI 10.1073/pnas.89.9.3686 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HR853 UT WOS:A1992HR85300004 PM 1373887 ER PT J AU MEACCI, E TAIRA, M MOOS, M SMITH, CJ MOVSESIAN, MA DEGERMAN, E BELFRAGE, P MANGANIELLO, V AF MEACCI, E TAIRA, M MOOS, M SMITH, CJ MOVSESIAN, MA DEGERMAN, E BELFRAGE, P MANGANIELLO, V TI MOLECULAR-CLONING AND EXPRESSION OF HUMAN MYOCARDIAL CGMP-INHIBITED CAMP PHOSPHODIESTERASE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE; RECENT CLINICAL DEVELOPMENTS; POSITIVE INOTROPIC AGENTS; CONGESTIVE HEART-FAILURE; AMINO-ACID SEQUENCE; AMP PHOSPHODIESTERASE; CDNA; PHOSPHORYLATION; IDENTIFICATION; PURIFICATION AB We have cloned a cDNA for a myocardial cGMP-inhibited cAMP phosphodiesterase (cGI PDE) from a human heart cDNA library in lambda-Zap II. The open reading frame [3.5 kilobases (kb)] of cDNA clone n.13.2 (7.7 kb) encodes a protein of 125 kDa. In Northern blots of total human ventricle RNA, a single mRNA species (8.3 kb) hybridized with a 4-kb EcoRI restriction fragment of clone n.13.2 cDNA (containing the entire open reading frame). The carboxyl-terminal region of the deduced amino acid sequence of the cGI PDE contains the putative catalytic domain conserved among mammalian PDE families. A partial cDNA clone, n.2, encoding a truncated, 54-kDa cGI PDE containing the conserved domain was expressed as a catalytically active fusion protein in Escherichia coli. cAMP hydrolytic activity was inhibited by cGMP and OPC 3911 but not by rolipram. Thus, this report provides direct proof that the conserved domain contains the catalytic core of cGI PDEs. C1 NIH,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. UNIV UTAH,DIV CARDIOL,SALT LAKE CITY,UT 84132. UNIV LUND,DEPT PHYSIOL & MED CHEM,S-22101 LUND,SWEDEN. RP MEACCI, E (reprint author), NHLBI,CELLULAR METAB LAB,BLDG 10,ROOM 5N-307,BETHESDA,MD 20892, USA. RI Moos, Malcolm/F-3673-2011 OI Moos, Malcolm/0000-0002-9575-9938 NR 33 TC 131 Z9 134 U1 0 U2 2 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 1 PY 1992 VL 89 IS 9 BP 3721 EP 3725 DI 10.1073/pnas.89.9.3721 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HR853 UT WOS:A1992HR85300011 PM 1315035 ER PT J AU GORDENIN, DA MALKOVA, AL PETERZEN, A KULIKOV, VN PAVLOV, YI PERKINS, E RESNICK, MA AF GORDENIN, DA MALKOVA, AL PETERZEN, A KULIKOV, VN PAVLOV, YI PERKINS, E RESNICK, MA TI TRANSPOSON TN5 EXCISION IN YEAST - INFLUENCE OF DNA POLYMERASE-ALPHA, POLYMERASE-DELTA AND POLYMERASE-EPSILON AND REPAIR GENES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE RECOMBINATION; DNA REPAIR; RAD50, RAD52 ID CEREVISIAE CDC2 GENE; DOUBLE-STRAND BREAKS; SACCHAROMYCES-CEREVISIAE; INVERTED REPEATS; RECOMBINATION; MUTANTS; MUTATIONS; RAD52; DELETION; MEIOSIS AB Interaction between short repeats may be a source of genomic rearrangements and deletions. We investigated possible interactions between short (9 base pairs) direct repeats in yeast by using our previously described system for analyzing bacterial transposon Tn5 excision in yeast. Mutations of either POL3 or POL1, the proposed structural genes for polymerases-delta and alpha, respectively, yield high levels of excision at semipermissive temperatures. pol2 (corresponding to polymerase-epsilon) and pol2 pol3 double mutants do not exhibit enhanced excision. A majority of excision events involve direct repeats and are precise; the remaining imprecise excisions occur within or in the vicinity of the repeats. The three DNA repair pathways identified by rad1, rad6 and rad18, rad50 and rad52 mutations were examined for their possible role in Tn5 excision; no enhancement was observed in mutants. However, the pol3-stimulated Tn5 excision was reduced in rad52 and rad50 mutants. This suggests the potential for interaction between the systems for DNA double-strand break/recombinational repair and DNA synthesis. Based on the suggestion of Morrison et al. [Morrison, A., Araki, H., Clark, A. B., Hamatake, R. H. & Sugino, A. (1990) Cell 62, 1143-115 1] that polymerases-delta and alpha are responsible for lagging-strand synthesis and that polymerase-epsilon is responsible for leading-strand synthesis, we suggest that Tn5 excision is stimulated under conditions of altered lagging-strand synthesis, possibly due to extended opportunities for single-strand interactions between the inverted insertion sequence I550 repeats of Tn5. C1 NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709. RP GORDENIN, DA (reprint author), LENINGRAD UNIV,DEPT GENET,LENINGRAD 199034,USSR. OI Gordenin, Dmitry/0000-0002-8399-1836 NR 40 TC 77 Z9 77 U1 0 U2 0 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 1 PY 1992 VL 89 IS 9 BP 3785 EP 3789 DI 10.1073/pnas.89.9.3785 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HR853 UT WOS:A1992HR85300024 PM 1315039 ER PT J AU DANCIS, A ROMAN, DG ANDERSON, GJ HINNEBUSCH, AG KLAUSNER, RD AF DANCIS, A ROMAN, DG ANDERSON, GJ HINNEBUSCH, AG KLAUSNER, RD TI FERRIC REDUCTASE OF SACCHAROMYCES-CEREVISIAE - MOLECULAR CHARACTERIZATION, ROLE IN IRON UPTAKE, AND TRANSCRIPTIONAL CONTROL BY IRON SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LACZ FUSIONS; YEAST; DNA; PROTEIN; GENES; CLONING; SYSTEM; CELLS AB The principal iron uptake system of Saccharomyces cerevisiae utilizes a reductase activity that acts on ferric iron chelates external to the cell. The FRE1 gene product is required for this activity. The deduced amino acid sequence of the FRE1 protein exhibits hydrophobic regions compatible with transmembrane domains and has significant similarity to the sequence of the plasma membrane cytochrome b558 (the X-CGD protein), a critical component of a human phagocyte oxidoreductase, suggesting that FRE1 is a structural component of the yeast ferric reductase. FRE1 mRNA levels are repressed by iron. Fusion of 977 base pairs of FRE1 DNA upstream from the translation start site of an Escherichia coli lacZ reporter gene confers iron-dependent regulation on expression of beta-galactosidase in yeast. An 85-base-pair segment of FRE1 5' noncoding sequence contains a RAP1 binding site and a repeated sequence, TTTTTGCTCAYC; this segment is sufficient to confer iron-repressible transcriptional activity on heterologous downstream promoter elements. C1 NICHHD,MOLEC GENET LAB,MOLEC GENET LOWER EUKARYOTES SECT,BETHESDA,MD 20892. RP DANCIS, A (reprint author), NICHHD,MOLEC GENET LAB,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892, USA. RI Anderson, Gregory/G-4148-2013 OI Anderson, Gregory/0000-0002-8814-5866 NR 32 TC 287 Z9 294 U1 1 U2 4 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 1 PY 1992 VL 89 IS 9 BP 3869 EP 3873 DI 10.1073/pnas.89.9.3869 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HR853 UT WOS:A1992HR85300041 PM 1570306 ER PT J AU CUTHBERTSON, RA TOMAREV, SI PIATIGORSKY, J AF CUTHBERTSON, RA TOMAREV, SI PIATIGORSKY, J TI TAXON-SPECIFIC RECRUITMENT OF ENZYMES AS MAJOR SOLUBLE-PROTEINS IN THE CORNEAL EPITHELIUM OF 3 MAMMALS, CHICKEN, AND SQUID SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID AMINO-ACID SEQUENCE; ALDEHYDE DEHYDROGENASE; LENS CRYSTALLINS; PHYSICOCHEMICAL CHARACTERIZATION; RAT; EYE; NITROCELLULOSE; CYCLOPHILIN; EXPRESSION; EVOLUTION AB Studies of others have shown that class 3 aldehyde dehydrogenase is a major component of the epithelial cells of the mammalian cornea. Here we demonstrate by peptide sequencing that other major proteins of the corneal epithelium are also identical or related to enzymes in the human, mouse, kangaroo, chicken, and squid. Aldehyde dehydrogenase class 3 was found to be the major protein of human, mouse, and kangaroo corneal epithelial cells. Peptidyl prolyl cis-trans isomerase (cyclophilin) or a homologue thereof is strikingly abundant in the corneal epithelial cells of chicken, but not mammals, and appears to be absent from the cornea of squid. By contrast, enolase or its homologue is relatively abundant in both the mammalian and chicken corneal epithelial cells. In some instances, abundant enzymes are common to cornea and lens in the same species-for example, argininosuccinate lyase/delta-1-crystallin in the chicken and glutathione S-transferase-like protein in the squid; in other cases, the abundant proteins in the cornea have not been found as lens crystallins in any specie-for example, aldehyde dehydrogenase class 3 and cyclophilin. These data suggest that enzymes and certain enzyme-crystallins have been recruited as major corneal proteins in a taxon-specific manner and may serve structural rather than, or as well as, enzymatic roles in corneal epithelial cells. RP CUTHBERTSON, RA (reprint author), NEI, MOLEC & DEV BIOL LAB, BETHESDA, MD 20892 USA. NR 46 TC 68 Z9 69 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 1 PY 1992 VL 89 IS 9 BP 4004 EP 4008 DI 10.1073/pnas.89.9.4004 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HR853 UT WOS:A1992HR85300069 PM 1570326 ER PT J AU STOJILKOVIC, SS KUKULJAN, M IIDA, T ROJAS, E CATT, KJ AF STOJILKOVIC, SS KUKULJAN, M IIDA, T ROJAS, E CATT, KJ TI INTEGRATION OF CYTOPLASMIC CALCIUM AND MEMBRANE-POTENTIAL OSCILLATIONS MAINTAINS CALCIUM SIGNALING IN PITUITARY GONADOTROPHS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE GONADOTROPIN-RELEASING HORMONE; CALCIUM OSCILLATIONS; MEMBRANE POTENTIAL OSCILLATIONS ID GROWTH-HORMONE SECRETION; INOSITOL TRISPHOSPHATE; INTRACELLULAR CALCIUM; CHANNELS; CELLS; METABOLISM; RELEASE; CA-2+ AB Pituitary gonadotrophs exhibit spontaneous low-amplitude fluctuations in cytoplasmic calcium concentration ([Ca2+]i) due to intermittent firing of nifedipine-sensitive action potentials. The hypothalamic neuropeptide, gonadotropin-releasing hormone, terminates such spontaneous [Ca2+]i transients and plasma-membrane electrical activity and initiates high-amplitude [Ca2+]i oscillations and concomitant oscillations in membrane potential (V(m)). The onset of agonist-induced [Ca2+]i oscillations is not dependent on V(m) or extracellular Ca2+ but is associated with plasma-membrane hyperpolarization interrupted by regular waves of depolarization with firing of action potentials at the peak of each wave. The V(m) and Ca2+ oscillations are interdependent during continued gonadotropin-releasing hormone action (> 3-5 min), when sustained Ca2+ entry is necessary for the maintenance of [Ca2+]i spiking. The initial and sustained agonist-induced Ca2+ transients and V(m) oscillations are abolished by blockade of endoplasmic reticulum Ca2+-ATPase, consistent with the role of Ca2+ re-uptake by internal stores in the oscillatory response during both phases. Such a pattern of synchronization of electrical activity and Ca2+ spiking in cells regulated by Ca2+-mobilizing receptors shows that the operation of the cytoplasmic oscillator can be integrated with a plasma-membrane oscillator to provide a long-lasting-signal during sustained agonist stimulation. C1 NIDDKD,CELL BIOL & GENET,BETHESDA,MD 20892. RP STOJILKOVIC, SS (reprint author), NICHHD,ENDOCRINOL & RES BRANCH,BLDG 10,ROOM B1-L400,BETHESDA,MD 20892, USA. NR 33 TC 83 Z9 83 U1 0 U2 2 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 1 PY 1992 VL 89 IS 9 BP 4081 EP 4085 DI 10.1073/pnas.89.9.4081 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HR853 UT WOS:A1992HR85300085 PM 1373893 ER PT J AU WETSEL, WC VALENCA, MM MERCHENTHALER, I LIPOSITS, Z LOPEZ, FJ WEINER, RI MELLON, PL NEGROVILAR, A AF WETSEL, WC VALENCA, MM MERCHENTHALER, I LIPOSITS, Z LOPEZ, FJ WEINER, RI MELLON, PL NEGROVILAR, A TI INTRINSIC PULSATILE SECRETORY ACTIVITY OF IMMORTALIZED LUTEINIZING-HORMONE-RELEASING HORMONE-SECRETING NEURONS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE DYE-COUPLING; SYNAPSE-LIKE CONNECTIONS; IMMORTALIZED CELLS ID FOLLICLE-STIMULATING-HORMONE; MESSENGER RIBONUCLEIC-ACIDS; LH-SECRETION; OVARIECTOMIZED EWES; ESTROUS-CYCLE; MALE-MICE; RATS; GNRH; HYPOTHALAMUS; PROLACTIN AB Mammalian reproduction is dependent upon intermittent delivery of luteinizing hormone-releasing hormone (LHRH) to the anterior-pituitary. This mode of secretion is required to sensitize maximally the gonadotrophs to LHRH stimulation and to regulate gonadotropin gene expression. While LHRH secretion is pulsatile in nature, the origin of the pulse generator is unknown. In this report, we show that this oscillator could be located within the LHRH neuronal network. When immortalized LHRH neurons are placed into a perifusion system, LHRH is secreted into the medium in a pulsatile fashion under basal conditions. LHRH secretion and the number of LHRH pulses are reduced when calcium is removed from the medium. Perifusion also influences pro-LHRH processing, since the molar ratio of its processed products varies dramatically when the cells are transferred from a static system. Several different cellular mechanisms may underlie these changes in secretion and processing. Lucifer yellow experiments reveal that some cells are dye-coupled. Hence, these cells could be electrically coupled through gap junctions such that secretion from individual cells could be coordinated. Secretion could also be synchronized through the observed synapse-like contacts. These contacts could perform a negative-feedback role to regulate not only the amount of LHRH released but also the molecular forms secreted. The organization of LHRH neurons into interconnected clusters could serve to coordinate LHRH secretion from individual cells and, thereby, orchestrate functions in vivo as diverse as the onset of puberty, the timing of ovulation, and the duration of lactational infertility. C1 NIEHS,MOLEC & INTEGRAT NEUROSCI LAB,FUNCT MORPHOL SECT,RES TRIANGLE PK,NC 27709. UNIV CALIF SAN FRANCISCO,CTR REPROD ENDOCRINOL,SAN FRANCISCO,CA 94143. SALK INST BIOL STUDIES,LA JOLLA,CA 92037. RP WETSEL, WC (reprint author), NIEHS,MOLEC & INTEGRAT NEUROSCI LAB,REPROD NEUROENDOCRINOL SECT,RES TRIANGLE PK,NC 27709, USA. RI Valenca, Marcelo/A-4302-2013 OI Valenca, Marcelo/0000-0003-0678-3782 FU NIDDK NIH HHS [R01 DK044838] NR 36 TC 251 Z9 254 U1 1 U2 5 PU NATL ACAD PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 1 PY 1992 VL 89 IS 9 BP 4149 EP 4153 DI 10.1073/pnas.89.9.4149 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HR853 UT WOS:A1992HR85300099 PM 1570341 ER PT J AU SUMMERS, MF HENDERSON, LE CHANCE, MR BESS, JW SOUTH, TL BLAKE, PR SAGI, I PEREZALVARADO, G SOWDER, RC HARE, DR ARTHUR, LO AF SUMMERS, MF HENDERSON, LE CHANCE, MR BESS, JW SOUTH, TL BLAKE, PR SAGI, I PEREZALVARADO, G SOWDER, RC HARE, DR ARTHUR, LO TI NUCLEOCAPSID ZINC FINGERS DETECTED IN RETROVIRUSES - EXAFS STUDIES OF INTACT VIRUSES AND THE SOLUTION-STATE STRUCTURE OF THE NUCLEOCAPSID PROTEIN FROM HIV-1 SO PROTEIN SCIENCE LA English DT Article DE HIV-1; NMR STRUCTURE; NUCLEOCAPSID PROTEIN; ZINC FINGER ID MURINE LEUKEMIA-VIRUS; ACID BINDING-PROTEIN; CYS-HIS BOX; 3-DIMENSIONAL STRUCTURE; NUCLEIC-ACIDS; METAL-IONS; DOMAIN; RNA; SEQUENCE; RESOLUTION AB All retroviral nucleocapsid (NC) proteins contain one or two copies of an invariant 3Cys-1His array (CCHC = C-X2-C-X4-H-X4-C; C = Cys, H = His, X = variable amino acid) that are essential for RNA genome packaging and infectivity and have been proposed to function as zinc-binding domains. Although the arrays are capable of binding zinc in vitro, the physiological relevance of zinc coordination has not been firmly established. We have obtained zinc-edge extended X-ray absorption fine structure (EXAFS) spectra for intact retroviruses in order to determine if virus-bound zinc, which is present in quantities nearly stoichiometric with the CCHC arrays (Bess, J.W., Jr., Powell, P.J., Issaq, H.J., Schumack, L.J., Grimes, M.K., Henderson, L.E., & Arthur, L.O., 1992, J. Virol. 66, 840-847), exists in a unique coordination environment. The viral EXAFS spectra obtained are remarkably similar to the spectrum of a model CCHC zinc finger peptide with known 3Cys-1His zinc coordination structure. This finding, combined with other biochemical results, indicates that the majority of the viral zinc is coordinated to the NC CCHC arrays in mature retroviruses. Based on these findings, we have extended our NMR studies of the HIV-1 NC protein and have determined its three-dimensional solution-state structure. The CCHC arrays of HIV-1 NC exist as independently folded, noninteracting domains on a flexible polypeptide chain, with conservatively substituted aromatic residues forming hydrophobic patches on the zinc finger surfaces. These residues are essential for RNA genome recognition, and fluorescence measurements indicate that at least one residue (Trp37) participates directly in binding to nucleic acids in vitro. The NC is only the third HIV-1 protein to be structurally characterized, and the combined EXAFS, structural, and nucleic acid-binding results provide a basis for the rational design of new NC-targeted antiviral agents and vaccines for the control of AIDS. C1 NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC,DYNCORP,FREDERICK,MD 21701. HARE RES INC,WOODINVILLE,WA 98072. GEORGETOWN UNIV,DEPT CHEM,WASHINGTON,DC 20057. RP SUMMERS, MF (reprint author), UNIV MARYLAND,DEPT CHEM & BIOCHEM,CATONSVILLE,MD 21228, USA. RI Bess, Jr., Julian/B-5343-2012 FU NIAID NIH HHS [AI30917]; NIGMS NIH HHS [GM42561]; PHS HHS [N01-C0-74012] NR 60 TC 268 Z9 272 U1 0 U2 7 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD MAY PY 1992 VL 1 IS 5 BP 563 EP 574 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HW905 UT WOS:A1992HW90500001 PM 1304355 ER PT J AU DURONIO, RJ GORDON, JI BOGUSKI, MS AF DURONIO, RJ GORDON, JI BOGUSKI, MS TI COMPARATIVE-ANALYSIS OF THE BETA-TRANSDUCIN FAMILY WITH IDENTIFICATION OF SEVERAL NEW MEMBERS INCLUDING PWP1, A NONESSENTIAL GENE OF SACCHAROMYCES-CEREVISIAE THAT IS DIVERGENTLY TRANSCRIBED FROM NMT1 SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS LA English DT Article DE FUNGAL GENES; MOLECULAR CLONING; MOLECULAR SEQUENCE DATA; GENE EXPRESSION; DATABASE SEARCHING; SEQUENCE ALIGNMENT; REPETITIVE SEQUENCES; SIGNAL TRANSDUCTION; PROTEIN N-MYRISTOYLATION ID DNA-BINDING DOMAIN; MYB PROTOONCOGENE PRODUCT; ADP-RIBOSYLATION FACTOR; NUCLEAR ANTIGEN GENE; MAMMALIAN G-PROTEIN; N-MYRISTOYLTRANSFERASE; HYPOTHETICAL STRUCTURE; SIGNAL TRANSDUCTION; TRYPTOPHAN CLUSTER; MOLECULAR-CLONING AB While investigating the expression of the Saccharomyces cerevisiae myristoyl-CoA:protein N-myristoyltransferase gene (NMT: E.C. 2.3.1.97) by Northern blot analysis, we observed another RNA transcript whose expression resembled that of NMT1 during meiosis and was derived from a gene located < 1 kb immediately upstream of NMT1. This new gene, designated PWP1 (for periodic tryptophan protein), is divergently transcribed from NMT1 and encodes a 576-residue protein. Null mutants of PWP1 are viable, but their growth is severely retarded and steady-state levels of several cellular proteins (including at least two proteins that label with exogenous [H-3]myristic acid) are drastically reduced. New methods for database searching and assessing the statistical significance of sequence similarities identify PWP1 as a member of the beta-transducin protein superfamily. Two other previously unrecognized beta-transducin-like proteins (S. cerevisiae MAK11 and D. discoideum AAC3) were also identified, and an unexpectedly high degree of sequence homology was found between a Chlamydomonas beta-like polypeptide and the C12.3 gene of chickens. A systematic and quantitative comparative analysis resulted in classifying all beta-transducin-like sequences into 11 nonorthologous families. Based on specific sequence attributes, however, not all beta-transducin-like sequences are expected to be functionally similar, and quantitative criteria for inferring functional analogies are discussed. Possible roles of repetitive tryptophan residues in proteins are also considered. C1 NIH, NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BLDG 38A, ROOM 8S-810,8600 ROCKVILLE PIKE, BETHESDA, MD 20894 USA. WASHINGTON UNIV, SCH MED, DEPT MOLEC BIOL & PHARMACOL, ST LOUIS, MO 63110 USA. FU NIAID NIH HHS [AI27179] NR 67 TC 90 Z9 91 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0887-3585 EI 1097-0134 J9 PROTEINS JI Proteins PD MAY PY 1992 VL 13 IS 1 BP 41 EP 56 DI 10.1002/prot.340130105 PG 16 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA HP212 UT WOS:A1992HP21200004 PM 1594577 ER PT J AU CHIAPPELLI, F GORMLEY, GJ GWIRSTMAN, HE LOWY, MT NGUYEN, LD NGUYEN, L ESMAIL, I STROBER, M WEINER, H AF CHIAPPELLI, F GORMLEY, GJ GWIRSTMAN, HE LOWY, MT NGUYEN, LD NGUYEN, L ESMAIL, I STROBER, M WEINER, H TI EFFECTS OF INTRAVENOUS AND ORAL DEXAMETHASONE ON SELECTED LYMPHOCYTE SUBPOPULATIONS IN NORMAL SUBJECTS SO PSYCHONEUROENDOCRINOLOGY LA English DT Article ID KILLER-CELL-ACTIVITY; HUMAN PERIPHERAL-BLOOD; SUPPRESSION TEST; GLUCOCORTICOID RECEPTORS; ENDOGENOUS-DEPRESSION; INVIVO HYDROCORTISONE; CORTISOL SUPPRESSION; SUB-POPULATIONS; SENSITIVITY; ANTIBODIES AB Our studies describe the effects of 1 mg oral (PO) and intravenous (IV) administration of dexamethasone (DEX) on certain subpopulations of circulating lymphocytes in normal subjects. We compared the outcomes of PO and IV DEX administration because of individual differences in gastro-intestinal absorption of DEX and the issue of noncompliance in patients undergoing the dexamethasone suppression test (DST). Both routes of DEX administration were equally effective in suppressing plasma cortisol levels below 5 mug/dl, the customary criterion level. Both routes of DEX administration also significantly decreased the percent and absolute number of CD4+ cells, the CD4+/CD8+ ratio, and the percent and absolute number of virgin, but not of memory, CD4+ cells. C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT PSYCHIAT & BIOBEHAV SCI,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT PEDIAT,LOS ANGELES,CA 90024. UNIV CALIF LOS ANGELES,SCH MED,DEPT MICROBIOL & IMMUNOL,CTR INTERDISCIPLINARY RES IMMUNOL DIS,LOS ANGELES,CA 90024. NIMH,BETHESDA,MD 20892. CASE WESTERN RESERVE UNIV,DEPT PSYCHIAT,CLEVELAND,OH 44106. FU NIAID NIH HHS [AI 07126] NR 35 TC 19 Z9 19 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD MAY-JUL PY 1992 VL 17 IS 2-3 BP 145 EP 152 DI 10.1016/0306-4530(92)90053-A PG 8 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA JT033 UT WOS:A1992JT03300006 PM 1359598 ER PT J AU FREO, U HOLLOWAY, HW GREIG, NH SONCRANT, TT AF FREO, U HOLLOWAY, HW GREIG, NH SONCRANT, TT TI CHRONIC TREATMENT WITH META-CHLOROPHENYLPIPERAZINE (META-CPP) ALTERS BEHAVIORAL AND CEREBRAL METABOLIC RESPONSES TO THE SEROTONIN AGONISTS META-CPP AND QUIPAZINE BUT NOT 8-HYDROXY-2(DI-N-PROPYLAMINO)TETRALIN SO PSYCHOPHARMACOLOGY LA English DT Article DE DEOXYGLUCOSE; SEROTONIN; META-CHLOROPHENYLPIPERAZINE; QUIPAZINE; 8-HYDROXY-2(DI-N-PROPYLAMINO)TETRALIN ID RAT-BRAIN; LOCOMOTOR-ACTIVITY; STIMULUS PROPERTIES; GLUCOSE-UTILIZATION; BINDING-SITES; FOOD-INTAKE; RECEPTORS; ANTAGONISTS; TRAZODONE; 1-(M-TRIFLUOROMETHYLPHENYL)PIPERAZINE AB The effects of the serotonin (5-HT) agonists meta-chlorophenylpiperazine (m-CPP), quipazine and 8-hydroxy-2(di-n-propylamino)tetralin (DPAT) on behavior and on regional cerebral metabolic rates for glucose (rCMRglc) were measured in control rats or in rats pretreated for 2 weeks with continuous infusion of saline or m-CPP (2.5 mg/kg/day, subcutaneously). rCMRglc was measured in 71 brain regions, using the quantitative autoradiographic [C-14]2-deoxy-D-glucose technique, at 15 min after acute administration of m-CPP 2.5 mg/kg, 60 min after quipazine 20 mg/kg, or 10 min after DPAT 1 mg/kg. Behavioral effects were assessed for m-CPP with an activity monitor, for quipazine by counting head shakes and for DPAT by scoring the serotonin syndrome. Chronic m-CPP pretreatment produced tolerance to hypolocomotion induced by acute m-CPP and to head shakes caused by acute quipazine, but did not alter the serotonin syndrome produced by DPAT. m-CPP 2.5 mg/kg IP produced widespread rCMRglc reductions in control rats but failed to modify rCMRglc in any region after chronic m-CPP pretreatment. Quipazine increased rCMRglc in 4 regions in control rats, but reduced rCMRglc in 14 brain areas of chronically m-CPP-pretreated animals. DPAT altered rCMRglc to the same degree in control (25 regions affected) and in chronically m-CPP-pretreated rats (28 regions affected). Reduced behavioral and metabolic effects of acute m-CPP in chronically m-CPP-pretreated rats were not due to pharmacokinetic alterations. These results demonstrate that chronic administration of m-CPP produces behavioral and metabolic tolerance to acute administration of m-CPP, but not of DPAT. They suggest that hypolocomotion and the serotonin syndrome are mediated by different 5-HT receptor subtypes, and that chronic m-CPP administration produces functional down-regulation of 5-HT1B/1C but not of 5-HT1A-coupled mechanisms. C1 NIA,NEUROSCI LAB,BETHESDA,MD 20892. NR 52 TC 22 Z9 22 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD MAY PY 1992 VL 107 IS 1 BP 30 EP 38 DI 10.1007/BF02244962 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA HK561 UT WOS:A1992HK56100005 PM 1534179 ER PT J AU ANDERSON, DM DUFFY, K HALLETT, CD MARCUS, AC AF ANDERSON, DM DUFFY, K HALLETT, CD MARCUS, AC TI CANCER PREVENTION COUNSELING ON TELEPHONE HELPLINES SO PUBLIC HEALTH REPORTS LA English DT Article ID INFORMATION-SERVICE; QUIT SMOKING; CAMPAIGN AB Since 1983, the National Cancer Institute (NCI) has collected data by means of its Cancer Information Service (CIS), a toll-free telephone helpline for health care professionals and members of the public who have questions about cancer treatment, diagnosis, and prevention. These data reveal information about the characteristics of callers and their questions and about how inquires reflect mass media promotions and secular trends. A request for a publication is the most common type of inquiry, followed by information about specific cancer sites, smoking prevention and cessation, other types of prevention, cancer treatment, cancer symptoms, referrals to physicians, NCI clinical trials, hospital and clinic-based screening programs, and general counseling or coping. Breast cancer is the most common cancer of interest, followed by respiratory system cancers, colon and prostate cancers, leukemia, melanoma, nonHodgkin's lymphoma, cervical cancer, general or unspecified skin cancer, and ovarian cancer. Responding to these other caller inquiries, CIS counselors may proactively guide callers to a desirable goal, such as screening mammography. Protocols have been developed to assist counselors' proactive efforts, and preliminary results are beginning to support this approach. The findings gathered in this study underscore the health education potential of telephone helplines and point to the need for controlled evaluation research on the effectiveness of proactive counselor advice. C1 NCI,CANC INFORMAT SERV,BETHESDA,MD 20892. RP ANDERSON, DM (reprint author), NCI,DIV CANC PREVENT & CONTROL,318 EXECUT PLAZA N,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 19 TC 34 Z9 34 U1 0 U2 1 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD MAY-JUN PY 1992 VL 107 IS 3 BP 278 EP 283 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA HX556 UT WOS:A1992HX55600007 PM 1594737 ER PT J AU LESHNER, AI AF LESHNER, AI TI A NATIONAL AGENDA FOR HELPING HOMELESS MENTALLY-ILL PEOPLE SO PUBLIC HEALTH REPORTS LA English DT Article AB The Interagency Council on the Homeless is responsible for coordinating all Federal activities concerning the homeless population. Its Chairman is Jack Kemp, Secretary of Housing and Urban Development, and its Vice Chairman is Louis W. Sullivan, MD, Secretary of Health and Human Services and head of the Federal Department that includes the Public Health Service. In May 1990, the Council convened a 12-member Task Force on Homelessness and Severe Mental Illness, consisting of representatives from all major Federal Departments and Agencies whose policies and programs directly affect the homeless severely mentally ill population. Its charge was to develop a national plan of action to end homelessness among mentally ill persons. The members of the Task Force have been guided in their deliberations by a 16-member Advisory Committee appointed by Dr. Sullivan that includes experts in diverse fields ranging from mental health research to housing administration. Citizen advocates, mental health consumers, and family members are represented, as well as State and local officials concerned with severe mental illnesses and homelessness. In addition, the Task Force has made extensive efforts to reach out to relevant non-Federal organizations and groups to solicit information and guidance. In mid-June 1991, a letter of inquiry was sent to nearly 20,000 individuals and organizations throughout the nation, soliciting advice and recommendations. The responses to this letter were carefully read and analyzed. A series of workshops was convened with groups of experts on topics central to the Task Force charge-including housing, minority, consumer, rehabilitation, and legal issues. Finally, Task Force members participated in a public hearing on severe mental illness and homelessness held September 5, 1991, in Chicago. The hearing, jointly sponsored by the National Advisory Mental Health Council and the National Mental Health Leadership Forum, resulted in relevant testimony from numerous individuals and organizations around the country. In response to its charge from the Interagency Council on the Homeless, the Task Force, in its report, offers more than 50 action steps that Federal Departments will take to end homelessness among severely mentally ill people. These steps are intended to improve substantially this country's system of care and housing options for homeless mentally ill persons by making essential resources, both traditional and novel, more accessible to these disabled Americans. Following are excerpts from the Task Force report, including major findings, recommendations, and action steps to end homelessness among people with severe mental illnesses. RP LESHNER, AI (reprint author), NIMH,OFF PROGRAMS HOMELESS MENT ILL,ROOM 7C-08,PARKLAWN BLDG,ROCKVILLE,MD 20857, USA. NR 0 TC 1 Z9 1 U1 2 U2 3 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD MAY-JUN PY 1992 VL 107 IS 3 BP 352 EP 355 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA HX556 UT WOS:A1992HX55600018 PM 1594747 ER PT J AU SHIMIZU, Y KATO, H SCHULL, WJ HOEL, DG AF SHIMIZU, Y KATO, H SCHULL, WJ HOEL, DG TI STUDIES OF THE MORTALITY OF A-BOMB SURVIVORS .9. MORTALITY, 1950-1985 .3. NONCANCER MORTALITY BASED ON THE REVISED DOSES (DS86) SO RADIATION RESEARCH LA English DT Article ID ANKYLOSING-SPONDYLITIS; CANCER; RADIATION; RATES C1 NIEHS,RES TRIANGLE PK,NC 27709. RP SHIMIZU, Y (reprint author), RADIAT EFFECTS RES FDN,DEPT EPIDEMIOL,HIROSHIMA 730,JAPAN. NR 24 TC 57 Z9 65 U1 0 U2 1 PU RADIATION RESEARCH SOC PI OAK BROOK PA 820 JORIE BOULEVARD, OAK BROOK, IL 60523 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD MAY PY 1992 VL 130 IS 2 BP 249 EP 266 DI 10.2307/3578283 PG 18 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA HV321 UT WOS:A1992HV32100014 PM 1574582 ER PT J AU IKURA, M CLORE, GM GRONENBORN, AM ZHU, G KLEE, CB BAX, A AF IKURA, M CLORE, GM GRONENBORN, AM ZHU, G KLEE, CB BAX, A TI SOLUTION STRUCTURE OF A CALMODULIN-TARGET PEPTIDE COMPLEX BY MULTIDIMENSIONAL NMR SO SCIENCE LA English DT Article ID LIGHT CHAIN KINASE; NUCLEAR-MAGNETIC-RESONANCE; RESTRAINED MOLECULAR-DYNAMICS; MEMBRANE CA-2+ PUMP; BINDING DOMAIN; 3-DIMENSIONAL STRUCTURE; DISTANCE GEOMETRY; HETERONUCLEAR NMR; PROTEIN-KINASE; CENTRAL HELIX AB The three-dimensional solution structure of the complex between calcium-bound calmodulin (Ca2+-CaM) and a 26-residue synthetic peptide comprising the CaM binding domain (residues 577 to 602) of skeletal muscle myosin light chain kinase, has been determined using multidimensional heteronuclear filtered and separated nuclear magnetic resonance spectroscopy. The two domains of CaM (residues 6 to 73 and 83 to 146) remain essentially unchanged upon complexation. The long central helix (residues 65 to 93), however, which connects the two domains in the crystal structure of Ca2+-CaM, is disrupted into two helices connected by a long flexible loop (residues 74 to 82), thereby enabling the two domains to clamp residues 3 to 21 of the bound peptide, which adopt a helical conformation. The overall structure of the complex is globular, approximating an ellipsoid of dimensions 47 by 32 by 30 angstroms. The helical peptide is located in a hydrophobic channel that passes through the center of the ellipsoid at an angle of approximately 45-degrees with its long axis. The complex is mainly stabilized by hydrophobic interactions which, from the CaM side, involve an unusually large number of methionines. Key residues of the peptide are Trp4 and Phe17, which serve to anchor the amino- and carboxyl-terminal halves of the peptide to the carboxyl- and amino-terminal domains of CaM, respectively. Sequence comparisons indicate that a number of peptides that bind CaM with high affinity share this common feature containing either aromatic residues or long-chain hydrophobic ones separated by a stretch of 12 residues, suggesting that they interact with CaM in a similar manner. C1 NIDDKD,CHEM PHYS LAB,BLDG 2,BETHESDA,MD 20892. UNIV MARYLAND,CHEM PHYS PROGRAM,COLLEGE PK,MD 20740. NCI,BIOCHEM LAB,BETHESDA,MD 20892. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 89 TC 1109 Z9 1118 U1 8 U2 71 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD MAY 1 PY 1992 VL 256 IS 5057 BP 632 EP 638 DI 10.1126/science.1585175 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HR185 UT WOS:A1992HR18500024 PM 1585175 ER PT J AU COLOMBO, MF RAU, DC PARSEGIAN, VA AF COLOMBO, MF RAU, DC PARSEGIAN, VA TI PROTEIN SOLVATION IN ALLOSTERIC REGULATION - A WATER EFFECT ON HEMOGLOBIN SO SCIENCE LA English DT Article ID HYDRATION FORCES; VOLUME CHANGES; ENERGETICS; BINDING; CHANNEL; SOLVENT; LINKAGE AB The oxygen affinity of hemoglobin varies linearly with the chemical potential of water in the bathing medium, as seen from the osmotic effect of several neutral solutes, namely sucrose, stachyose, and two polyethyleneglycols (molecular weights of 150 and 400). The data, analyzed either by Wyman linkage equations or by Gibbs-Duhem relations, show that approximately 60 extra water molecules bind to hemoglobin during the transition from the fully deoxygenated tense (T) state to the fully oxygenated relaxed (R) state. This number, independent of the nature of the solute, agrees with the difference in water-accessible surface areas previously computed for the two conformations. The work of solvation in allosteric regulation can no longer go unrecognized. C1 NIDDKD,DIV COMP RES & TECHNOL,PHYS SCI LAB,BETHESDA,MD 20892. RP COLOMBO, MF (reprint author), NIDDKD,BIOCHEM & METAB LAB,BETHESDA,MD 20892, USA. RI Colombo, Marcio/K-5229-2013 OI Colombo, Marcio/0000-0003-3035-3926 NR 28 TC 302 Z9 304 U1 1 U2 25 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD MAY 1 PY 1992 VL 256 IS 5057 BP 655 EP 659 DI 10.1126/science.1585178 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HR185 UT WOS:A1992HR18500029 PM 1585178 ER PT J AU PAVLAKIS, GN AF PAVLAKIS, GN TI STRUCTURE AND FUNCTION OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SO SEMINARS IN LIVER DISEASE LA English DT Review ID GENE-EXPRESSION; AIDS; VACCINE RP PAVLAKIS, GN (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL,BASIC RES PROGRAM,HUMAN RETROVIRUS SECT,POB B,BLDG 539,FREDERICK,MD 21702, USA. NR 20 TC 1 Z9 1 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0272-8087 J9 SEMIN LIVER DIS JI Semin. Liver Dis. PD MAY PY 1992 VL 12 IS 2 BP 103 EP 107 DI 10.1055/s-2007-1007382 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA JE346 UT WOS:A1992JE34600002 PM 1636115 ER PT J AU CHOU, JY PLOUZEK, CA AF CHOU, JY PLOUZEK, CA TI PREGNANCY-SPECIFIC BETA-1-GLYCOPROTEIN SO SEMINARS IN REPRODUCTIVE ENDOCRINOLOGY LA English DT Review RP CHOU, JY (reprint author), NICHHD,HUMAN GENET BRANCH,BLDG 10,ROOM 9S242,BETHESDA,MD 20892, USA. NR 0 TC 23 Z9 23 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 381 PARK AVE SOUTH, NEW YORK, NY 10016 SN 0734-8630 J9 SEMIN REPROD ENDOCR JI Semin. Reprod. Endocrinol. PD MAY PY 1992 VL 10 IS 2 BP 116 EP 126 DI 10.1055/s-2007-1018867 PG 11 WC Endocrinology & Metabolism; Obstetrics & Gynecology; Reproductive Biology SC Endocrinology & Metabolism; Obstetrics & Gynecology; Reproductive Biology GA HV703 UT WOS:A1992HV70300008 ER PT J AU UNSER, M AF UNSER, M TI AN IMPROVED LEAST-SQUARES LAPLACIAN PYRAMID FOR IMAGE COMPRESSION SO SIGNAL PROCESSING LA English DT Article DE LAPLACIAN PYRAMID; MULTIRESOLUTION REPRESENTATION; IMAGE COMPRESSION; IMAGE CODING; GAUSSIAN PYRAMID; LEAST SQUARES APPROXIMATION; RECURSIVE FILTER; QUADRATURE MIRROR FILTERS; WAVELET TRANSFORM AB This paper describes two ways of improving Burt and Adelson's Laplacian pyramid, a technique developed for image compression. The Laplacian pyramid is a multi-resolution image representation that captures the loss of information occurring through repeated reduction of the spatial resolution. The generation of this data structure involves the use of two complementary functions: EXPAND, which increases the size of an image by a factor of 2, and REDUCE, which performs the reverse operation. The first modification is the adjunction of a pre-filter to the initial EXPAND function in order to guarantee an image extrapolation that is an exact interpolation of the coarser resolution level. The second refinement is a REDUCE operation modified to. minimize information loss. The corresponding least squares Laplacian pyramid (LSLP) is generated by adding a post-filter to the initial REDUCE function. These new functions have an efficient implementation using recursive algorithms. Preliminary experiments indicate improved performance: for a Gaussian-like kernel (a=3/8), the new EXPAND function exhibits a 2 to 2.5 dB attenuation of the first level of the Laplacian pyramid, while the complete scheme (LSLP) leads to a 4.7 to 8.5 dB improvement in the two images used to test the procedure. For comparable compression ratios, the subjective image quality for the LSLP appears to be significantly better. A theoretical relationship between the present approach and the family of quadrature mirror filter image pyramids is also derived. RP UNSER, M (reprint author), NIH,NATL CTR RES RESOURCES,BIOMED ENGN & INSTRUMENTAT PROGRAM,BLDG 13,BETHESDA,MD 20892, USA. RI Unser, Michael/A-1550-2008 NR 0 TC 28 Z9 29 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-1684 J9 SIGNAL PROCESS JI Signal Process. PD MAY PY 1992 VL 27 IS 2 BP 187 EP 203 DI 10.1016/0165-1684(92)90007-J PG 17 WC Engineering, Electrical & Electronic SC Engineering GA HY634 UT WOS:A1992HY63400007 ER PT J AU DRUMMOND, MF DAVIES, LM FERRIS, FL AF DRUMMOND, MF DAVIES, LM FERRIS, FL TI ASSESSING THE COSTS AND BENEFITS OF MEDICAL-RESEARCH - THE DIABETIC-RETINOPATHY STUDY SO SOCIAL SCIENCE & MEDICINE LA English DT Article; Proceedings Paper CT 2ND WORLD CONGRESS ON HEALTH ECONOMICS CY SEP, 1990 CL ZURICH, SWITZERLAND DE COST-EFFECTIVENESS ANALYSIS; CLINICAL TRIALS; MEDICAL RESEARCH; DIABETIC RETINOPATHY ID CLINICAL-TRIALS; PREVALENCE; DIAGNOSIS; RISK; AGE AB Significant amounts of scarce resources are devoted to medical research, but there have been few attempts to assess whether the benefits to society of these investments exceed the costs. A method for undertaking such an assessment has been developed and applied retrospectively to the Diabetic Retinopathy Study, a major clinical trial funded by the National Eye Institute from 1972-1981. It was estimated that the trial, which cost $10.5 million, generated a net saving of $2816 million to society ($231 million when the costs of lost production are excluded) (1982 prices) and a gain to patients of 279,000 vision years. This approach could be applied prospectively in considering priorities for medical research, in conjunction with traditional criteria such as the scientific merit of the proposal and the capabilities of the investigators. The key factors affecting the economic returns from medical research are the prevalence, incidence and economic burden of the disease in question, the costs and effectiveness of the medical intervention concerned, the likely impact of the clinical trial on clinical practice and the likely timespan of benefits from knowledge obtained during the trial. C1 NEI,BETHESDA,MD 20892. RP DRUMMOND, MF (reprint author), UNIV YORK,CTR HLTH ECON,YORK YO1 5DD,N YORKSHIRE,ENGLAND. OI Davies, Linda/0000-0001-8801-3559 NR 25 TC 29 Z9 30 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD MAY PY 1992 VL 34 IS 9 BP 973 EP 981 DI 10.1016/0277-9536(92)90128-D PG 9 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA HV170 UT WOS:A1992HV17000005 PM 1631610 ER PT J AU BRANT, LJ DUNCAN, DB DIXON, DO AF BRANT, LJ DUNCAN, DB DIXON, DO TI K-RATIO T-TESTS FOR MULTIPLE COMPARISONS INVOLVING SEVERAL TREATMENTS AND A CONTROL SO STATISTICS IN MEDICINE LA English DT Article AB We consider the problem of simultaneously comparing several treatment means with a control mean and also with one another. Following an elementary decision-theoretic Bayesian approach requiring the choice of a type-I to type-II error-seriousness ratio k, a posteriori t tests are derived for testing both treatment versus control (TvC) and treatment versus treatment (TvT) differences. These k-ratio t tests are strictly comparisonwise in nature. That is, the test applied to any TvC or TvT difference d, depends in no way at all on whether the other differences are being tested. The test for d, however, does depend on the sizes of the other differences through t(G), the standardized average of the observed TvC differences, and through F(T), the observed between-treatments F ratio. From these adaptive dependences on t(G) and F(T), the critical t values can be large or small, thus avoiding the intuitive objections of under- or over-conservatism in classical comparisonwise or experimentwise level testing rules. C1 JOHNS HOPKINS UNIV,PEBBLE BEACH,CA 93953. NIAID,DIV AIDS,ROCKVILLE,MD 20892. RP BRANT, LJ (reprint author), NIA,GERONTOL RES CTR,4940 EASTERN AVE,BETHESDA,MD 20892, USA. NR 20 TC 5 Z9 5 U1 1 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD MAY PY 1992 VL 11 IS 7 BP 863 EP 873 DI 10.1002/sim.4780110704 PG 11 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 HU183 UT WOS:A1992HU18300002 PM 1604066 ER PT J AU MUNOZ, A CAREY, V TAYLOR, JMG CHMIEL, JS KINGSLEY, L VANRADEN, M HOOVER, DR AF MUNOZ, A CAREY, V TAYLOR, JMG CHMIEL, JS KINGSLEY, L VANRADEN, M HOOVER, DR TI ESTIMATION OF TIME SINCE EXPOSURE FOR A PREVALENT COHORT SO STATISTICS IN MEDICINE LA English DT Article ID HUMAN IMMUNODEFICIENCY VIRUS; MULTICENTER AIDS COHORT; HIV; SEROCONVERSION; INFECTION; MODEL; MEN AB In natural history studies of human immunodeficiency virus type 1 (HIV-1) infection a substantial proportion of participants are seropositive at time of enrolment in the study. These participants form a prevalent subcohort. Estimation of the unknown times since exposure to HIV-1 in the prevalent subcohort is of primary importance for estimation of the incubation time of AIDS. The subset of the cohort that tested negative for antibody to HIV-1 at study entry and was observed to seroconvert forms the incident subcohort that provides longitudinal data on markers of maturity (that is, duration) of infection. We use parametric life table regression models incorporating truncation to describe the conditional distribution (imputing model) of the times since seroconversion given a vector of the markers of maturity. Using the fitted model and the values of the markers of maturity of infection provided by the seroprevalent subcohort at entry into the study, we can impute the unknown times since seroconversion for the prevalent subcohort. We implement multiple imputation based on a model-robust estimate of the covariance matrix of parameters of the imputing model to provide confidence intervals for the geometric mean of the time since seroconversion in the prevalent subcohort, and to compare maturity of infection of cohorts recruited in different cities. The accuracy of imputation is further validated by comparisons of imputation-based estimates of AIDS incubation distribution in the seroprevalent subcohort with more direct estimates obtained from the seroincident subcohort. C1 JOHNS HOPKINS UNIV,SCH PUBL HLTH,DEPT BIOSTAT,BALTIMORE,MD 21205. UNIV CALIF LOS ANGELES,SCH PUBL HLTH,DEPT BIOSTAT,LOS ANGELES,CA 90024. NORTHWESTERN UNIV,SCH MED,CTR CANC,BIOMETRY SECT,CHICAGO,IL 60611. UNIV PITTSBURGH,DEPT INFECT DIS & MICROBIOL,PITTSBURGH,PA 15213. NIAID,EPIDEMIOL & BIOMETRY BRANCH,BETHESDA,MD 20892. RP MUNOZ, A (reprint author), JOHNS HOPKINS UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,624 N BROADWAY,BALTIMORE,MD 21205, USA. NR 23 TC 39 Z9 39 U1 1 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0277-6715 J9 STAT MED JI Stat. Med. PD MAY PY 1992 VL 11 IS 7 BP 939 EP 952 DI 10.1002/sim.4780110711 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 HU183 UT WOS:A1992HU18300009 PM 1351308 ER PT J AU BEEBE, L FOX, SD RIGGS, CW PARK, SS GELBOIN, HV ISSAQ, HJ ANDERSON, LM AF BEEBE, L FOX, SD RIGGS, CW PARK, SS GELBOIN, HV ISSAQ, HJ ANDERSON, LM TI PERSISTENT EFFECTS OF A SINGLE DOSE OF AROCLOR-1254 ON CYTOCHROMES P450IA1 AND IIB1 IN MOUSE LUNG SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID POLYCHLORINATED-BIPHENYLS; MONOCLONAL-ANTIBODIES; BINDING-PROTEIN; METABOLITE 4,4'-BIS(METHYLSULFONYL)-2,2',5,5'-TETRACHLOROBIPHENYL; LIVER-TUMORS; RAT; INDUCTION; DEALKYLATION; 3-METHYLCHOLANTHRENE; ENZYMES C1 NCI,FREDERICK CANC RES & DEV CTR,DATA MANAGEMENT SERV INC,FREDERICK,MD 21702. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCE INC,FREDERICK,MD 21702. RP BEEBE, L (reprint author), NCI,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102] NR 43 TC 17 Z9 18 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD MAY PY 1992 VL 114 IS 1 BP 16 EP 24 DI 10.1016/0041-008X(92)90091-6 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA HU419 UT WOS:A1992HU41900003 PM 1585368 ER PT J AU KENNEDY, CH HATCH, GE SLADE, R MASON, RP AF KENNEDY, CH HATCH, GE SLADE, R MASON, RP TI APPLICATION OF THE EPR SPIN-TRAPPING TECHNIQUE TO THE DETECTION OF RADICALS PRODUCED INVIVO DURING INHALATION EXPOSURE OF RATS TO OZONE SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID 0.1 PPM OZONE; VITAMIN-E; PULMONARY ALTERATIONS; LIPID PEROXIDATION; LUNGS; MECHANISM; LIPOSOMES; AIRWAYS; DAMAGE; CELLS C1 NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. US EPA,HLTH EFFECTS RES LAB,RES TRIANGLE PK,NC 27711. FU NIEHS NIH HHS [5T32 ES-07126] NR 41 TC 36 Z9 36 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 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD MAY PY 1992 VL 114 IS 1 BP 41 EP 46 DI 10.1016/0041-008X(92)90094-9 PG 6 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA HU419 UT WOS:A1992HU41900006 PM 1316646 ER PT J AU SYKES, M ABRAHAM, VS AF SYKES, M ABRAHAM, VS TI THE MECHANISM OF IL-2-MEDIATED PROTECTION AGAINST GVHD IN MICE .2. PROTECTION OCCURS INDEPENDENTLY OF NK/LAK CELLS SO TRANSPLANTATION LA English DT Article ID VERSUS-HOST DISEASE; ACTIVATED KILLER-CELLS; MARROW GRAFT-REJECTION; MURINE BONE-MARROW; T-CELL; IFN-GAMMA; INTERLEUKIN-2; ANTIBODY; MOUSE; PHENOTYPE AB We have recently demonstrated that high-dose IL-2, when begun on the day of bone marrow transplantation, has a potent protective effect against graft-vs.-host disease mortality, especially when coadministered with T cell-depleted syngeneic bone marrow cells. Because several groups of investigators have demonstrated that lymphokine-activated killer cells can mediate GVHD protection, we hypothesized that the mechanism of protection by IL-2 administration might involve the in vivo activation of natural killer and/or LAK cells. In order to test this hypothesis, we evaluated the effect of IL-2 administration on the number of NK1+ cells and on NK-mediated cytotoxic activity in recipients of GVHD-producing inocula. Furthermore, we evaluated the effects on IL-2-induced GVHD protection of depleting NK cells and LAK precursor cells in vivo with mAb against NK1.1 or antiserum against asialo GM1. The results demonstrate that: (1) The number of NK1+ cells is not increased in spleens of IL-2-treated compared with control recipients of GVHD-producing inocula; (2) NK activity is not increased in IL-2-treated compared with control recipients of GVHD-producing inocula during or immediately following the period of IL-2 administration; (3) depletion of NK cells and LAK precursors from the donor and host influenced the time course of GVHD-related mortality in a complex fashion; and (4) IL-2-induced GVHD protection is largely independent of the activity of an NK or LAK cell population of donor or host origin. IL-2-induced GVHD protection therefore reflects primarily the activity of non-LAK protective cell populations, or it may be a direct inhibitory effect on responding donor cell populations as they encounter host antigen. C1 NCI,IMMUNOL BRANCH,BETHESDA,MD 20892. RP SYKES, M (reprint author), HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,TRANSPLANTAT BIOL RES CTR,SURG SERV,BLDG 149,13TH ST,BOSTON,MA 02129, USA. FU NIAID NIH HHS [AI 31158-01, R01AI31158] NR 36 TC 17 Z9 17 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAY PY 1992 VL 53 IS 5 BP 1063 EP 1070 DI 10.1097/00007890-199205000-00018 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA HU814 UT WOS:A1992HU81400018 PM 1533968 ER PT J AU AKSENTIJEVICH, I SACHS, DH SYKES, M AF AKSENTIJEVICH, I SACHS, DH SYKES, M TI HUMORAL TOLERANCE IN XENOGENEIC BMT RECIPIENTS CONDITIONED BY A NONMYELOABLATIVE REGIMEN SO TRANSPLANTATION LA English DT Article ID MONOCLONAL-ANTIBODIES; MICE; RESISTANCE; ANTIGENS; BARRIER; GRAFTS; CELLS; L3T4 AB We have recently demonstrated that mixed xenogeneic chimerism and donor-specific tolerance can be produced across a species barrier using a nonmyeloablative conditioning regimen (1). This regimen involves pretreatment of B10 mice with mAbs against CD4+, CD8+, Thy1+, and NK1+ cells, followed by a low dose (3 Gy) of whole-body irradiation and a higher dose (7 Gy) of local irradiation to the thymus and administration of T cell-depleted (TCD) F344 strain rat BMC. Although initial mixed chimerism and de novo maturation of donor rat T cells can be demonstrated in such animals, chimerism is gradually lost, and is no longer detectable by 6 months following BMT (1). When rat skin was grafted onto such animals 4 months following BMT, however, donor-specific skin graft survival was markedly prolonged, while non-donor type rat skin grafts were rapidly rejected (1). These results suggested that a state of donor-specific T cell tolerance existed, and that loss of chimerism was not due to a T cell-mediated immune mechanism. In order to evaluate the possibility that a humoral mechanism might mediate delayed loss of xenogeneic bone marrow grafts, we have now examined sera at various times for the presence of antibody against donor cells. Groups of animals not receiving the complete tolerizing mAb pretreatment regimen produced antidonor lymphocytotoxic antibody in response to BMT and skin grafting. Flow cytometric studies demonstrated high levels of IgM and of IgG of all subclasses against rat BMC and spleen cells in these control mice immunized by BMT. In contrast, such antibodies were not detectable in sera from animals receiving BMT following pretreatment with the tolerance-inducing mAb regimen. Furthermore, the tolerant animals did not develop cytotoxic antibodies or high levels of IgM or IgG against donor BMC after loss of hematopoietic chimerism. Donor-type skin grafts were eventually rejected, but rejection of these and repeat skin grafts did not lead to a cytotoxic antibody response. Low levels of rat BMC-binding IgM antibody were also detected in sera of tolerant mice, but the intensity of staining of rat BMC was lower than that of control animals receiving conditioning without BMT. These results suggest that a state of tolerance exists among cells responsible for T cell-dependent IgG antibody subclasses and natural IgM antibodies in animals receiving BMT following this nonmyeloablative conditioning regimen. C1 HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,TRANSPLANTAT BIOL RES CTR,SURG SERV,BLDG 149,BOSTON,MA 02129. NCI,IMMUNOL BRANCH,BETHESDA,MD 20892. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 20 TC 54 Z9 54 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAY PY 1992 VL 53 IS 5 BP 1108 EP 1114 DI 10.1097/00007890-199205000-00025 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA HU814 UT WOS:A1992HU81400025 PM 1585475 ER PT J AU SIMPSON, RM GLIATTO, JM CASEY, HW HENK, WG AF SIMPSON, RM GLIATTO, JM CASEY, HW HENK, WG TI THE HISTOLOGIC, ULTRASTRUCTURAL, AND IMMUNOHISTOCHEMICAL FEATURES OF A BLASTEMA-PREDOMINANT CANINE NEPHROBLASTOMA SO VETERINARY PATHOLOGY LA English DT Note DE DOGS; IMMUNOHISTOCHEMISTRY; KIDNEY; NEPHROBLASTOMA; POLYCYTHEMIA; ULTRASTRUCTURE ID WILMS TUMOR RP SIMPSON, RM (reprint author), NIAID,IMMUNOGENET LAB,12441 PARKLAWN DR,ROCKVILLE,MD 20852, USA. NR 9 TC 14 Z9 14 U1 0 U2 0 PU AMER COLL VET PATHOLOGIST PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 SN 0300-9858 J9 VET PATHOL JI Vet. Pathol. PD MAY PY 1992 VL 29 IS 3 BP 250 EP 253 PG 4 WC Pathology; Veterinary Sciences SC Pathology; Veterinary Sciences GA HV547 UT WOS:A1992HV54700010 PM 1320304 ER PT J AU GREEN, KY SARASINI, A QIAN, Y GERNA, G AF GREEN, KY SARASINI, A QIAN, Y GERNA, G TI GENETIC-VARIATION IN ROTAVIRUS SEROTYPE-4 SUBTYPES SO VIROLOGY LA English DT Note ID NEUTRALIZING MONOCLONAL-ANTIBODIES; IMMUNE ELECTRON-MICROSCOPY; NUCLEOTIDE-SEQUENCE; GLYCOPROTEIN VP7; STRUCTURAL PROTEINS; ANTIGENIC VARIANTS; RHESUS ROTAVIRUS; EPITOPES; STRAINS; IDENTIFICATION C1 UNIV PAVIA,INST INFECT DIS,VIRUS LAB,I-27100 PAVIA,ITALY. RP GREEN, KY (reprint author), NIAID,EPIDEMIOL SECT,INFECT DIS LAB,BETHESDA,MD 20892, USA. NR 45 TC 17 Z9 18 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD MAY PY 1992 VL 188 IS 1 BP 362 EP 368 DI 10.1016/0042-6822(92)90766-I PG 7 WC Virology SC Virology GA HN251 UT WOS:A1992HN25100038 PM 1314460 ER PT J AU KONIG, R HUANG, LY GERMAIN, RN AF KONIG, R HUANG, LY GERMAIN, RN TI MHC CLASS-II INTERACTION WITH CD4 MEDIATED BY A REGION ANALOGOUS TO THE MHC CLASS-I BINDING-SITE FOR CD8 SO NATURE LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; T-CELL HYBRIDOMA; DIRECTED MUTAGENESIS; SURFACE EXPRESSION; LYMPHOCYTES-T; MOLECULES; ANTIGENS; GENE; RECOGNITION; L3T4 AB INTERACTIONs between major histocompatibility complex (MHC) molecules and the CD4 or CD8 coreceptors have a major role in intrathymic T-cell selection 1. On mature T cells, each of these two glycoproteins is associated with a class-specific bias in MHC molecule recognition by the T-cell receptor. CD4+ T cells respond to antigen in association with MHC class II molecules and CD8+ T cells respond to antigen in association with MHC class I molecules. Physical interaction between the CD4/MHC class II molecules and CD8/MHC class I molecules has been demonstrated by cell adhesion assay 2-5, and a binding site for CD8 on class I has been identified 6,7. Here we demonstrate that a region of the MHC class II beta-chain beta-2-domain, structurally analogous to the CD8-binding loop in the MHC class I alpha-3 domain, is critical for function with both mouse and human CD4. RP KONIG, R (reprint author), NIAID,IMMUNOL LAB,LYMPHOCYTE BIOL SECT,BETHESDA,MD 20892, USA. RI Konig, Rolf/B-3128-2008 NR 37 TC 277 Z9 278 U1 0 U2 2 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD APR 30 PY 1992 VL 356 IS 6372 BP 796 EP 798 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HR186 UT WOS:A1992HR18600051 PM 1574118 ER PT J AU YUSEF, S PITT, B DAVIS, CE AF YUSEF, S PITT, B DAVIS, CE TI TREATMENT OF CHRONIC CONGESTIVE-HEART-FAILURE - REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter RP YUSEF, S (reprint author), NHLBI,BETHESDA,MD 20892, USA. NR 3 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 APR 30 PY 1992 VL 326 IS 18 BP 1220 EP 1221 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA HR008 UT WOS:A1992HR00800014 ER PT J AU WHITCUP, SM BUTLER, KM PIZZO, PA NUSSENBLATT, RB AF WHITCUP, SM BUTLER, KM PIZZO, PA NUSSENBLATT, RB TI RETINAL LESIONS IN CHILDREN TREATED WITH DIDEOXYINOSINE SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; AIDS-RELATED COMPLEX; PHASE-I TRIAL; 2',3'-DIDEOXYINOSINE DDI RP WHITCUP, SM (reprint author), NIH,BETHESDA,MD 20892, USA. NR 4 TC 17 Z9 17 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 APR 30 PY 1992 VL 326 IS 18 BP 1226 EP 1227 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA HR008 UT WOS:A1992HR00800030 PM 1557108 ER PT J AU ZHU, ZW GOODRICH, M ISAB, AA SHAW, CF AF ZHU, ZW GOODRICH, M ISAB, AA SHAW, CF TI BIPHASIC REACTIONS OF DTNB WITH LOBSTER CD6-METALLOTHIONEIN-2 AND CD5CU-METALLOTHIONEIN-2 WHICH HAVE 2 TYPE-B (M3S9) CLUSTERS SO INORGANIC CHEMISTRY LA English DT Article ID COPPER-METALLOTHIONEINS; HOMARUS-AMERICANUS; METAL-BINDING; LIVER METALLOTHIONEIN; CALLINECTES-SAPIDUS; CADMIUM-BINDING; BLUE-CRAB; PROTEINS; METABOLISM; DOMAIN AB Lobster metallothionein (MT), which has two three-metal clusters instead of the four-metal and three-metal clusters found in mammalian MTs, was used to determine the origin of the biphasic reactions of MT with DTNB. Cd-rich MTs (Cd5Cu-MT-2 and Cd6-MT-2) were isolated from lobster hepatopancreas after Cd treatment preceded by dexamethasone injection or an applied stress. Each lobster MT-2 preparation reacts biphasically with DTNB [5,5'-dithiobis(2-nitrobenzoic acid)], as do mammalian MTs, and the reaction proceeds about 1 order of magnitude faster than that of mammalian MTs. The slow step and fast step each have first- and second-order components, resulting in a four-term rate law: rate = k1s + k2s[DTNB] + k1f + k2f [DTNB]. At 25-degrees-C, in 5 mM Tris/HCl buffer with 100 mM KCl, at pH 7.4, the rate constants are k1s = 1.34 x 10(-3) s-1, k2s = 0.706 s-1 M-1, k1f = 3.23 x 10(-3) s-1, k2f = 2.92 s-1 M-1 for Cd5Cu-Mt-2; k1s = 1.23 x 10(-3) s-1, k2s = 0.663 s-1 M-1, k1f = 2.27 x 10(-3) s-1, k2f = 8.13 s-1 M-1 for Cd6-MT-2. The biphasic nature of these reactions establish that the MT amino acid sequences, and not the structures of the individual clusters, determine the reactivity toward DTNB. Comparison of the lobster MT sequence with those for mammalian MTs leads to the prediction that the clusters of crustacean MTs are also located in separate domains. Consistent with this prediction, the presence of a single copper reduces the rate of the fast step, but does not alter the slow step for lobster MT-2. C1 UNIV WISCONSIN,DEPT CHEM,POB 413,MILWAUKEE,WI 53201. UNIV WISCONSIN,NIEHS AQUAT & MARINE BIOMED CORE CTR,MILWAUKEE,WI 53201. NR 37 TC 12 Z9 12 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0020-1669 J9 INORG CHEM JI Inorg. Chem. PD APR 29 PY 1992 VL 31 IS 9 BP 1662 EP 1667 DI 10.1021/ic00035a027 PG 6 WC Chemistry, Inorganic & Nuclear SC Chemistry GA HR759 UT WOS:A1992HR75900027 ER PT J AU LIU, J ALBERS, MW WANDLESS, TJ LUAN, S ALBERG, DG BELSHAW, PJ COHEN, P MACKINTOSH, C KLEE, CB SCHREIBER, SL AF LIU, J ALBERS, MW WANDLESS, TJ LUAN, S ALBERG, DG BELSHAW, PJ COHEN, P MACKINTOSH, C KLEE, CB SCHREIBER, SL TI INHIBITION OF T-CELL SIGNALING BY IMMUNOPHILIN LIGAND COMPLEXES CORRELATES WITH LOSS OF CALCINEURIN PHOSPHATASE-ACTIVITY SO BIOCHEMISTRY LA English DT Article ID PURE 4-ALKYL-3-HYDROXY-2-AMINO ACIDS; CYTOSOLIC BINDING-PROTEIN; PEPTIDYL-PROLYL ISOMERASE; CYCLOSPORINE-A; N-(9-PHENYLFLUOREN-9-YL)-ALPHA-AMINO ALDEHYDES; IMMUNOSUPPRESSANT FK506; LIMITED PROTEOLYSIS; MACROLIDES FK-506; CHIRAL EDUCTS; MEBMT PRESENT AB Calcineurin, a Ca2+, calmodulin-dependent protein phosphatase, was recently found to bind with high affinity to two different immunosuppressant binding proteins (immunophilins) with absolute dependence on the presence of the immunosuppressants FK506 or cyclosporin A (CsA) [Liu et al. (1991) Cell 66, 807-815]. The binding affinities of the immunophilin-drug complexes toward calcineurin and the stoichiometry of the resultant multimeric complexes have now been determined, and structural elements of FK506, CsA, and calcineurin that are critical for mediating their interactions have been identified. Analogues of FK506 (FK520, FK523, 15-O-demethyl-FK520) and CsA (MeBm2t1-CsA and MeAla6-CsA) whose affinities for their cognate immunophilins do not correlate with their immunosuppressive activities have been prepared and evaluated in biochemical and cellular assays. We demonstrate a strong correlation between the ability of these analogues, when bound to their immunophilins, to inhibit the phosphatase activity of calcineurin and their ability to inhibit transcriptional activation by NF-AT, a T cell specific transcription factor that regulates IL-2 gene synthesis in human T cells. In addition, FKBP-FK506 and CyP-CsA do not inhibit members of the PP1, PP2A, and PP2C classes of serine/threonine phosphatases. These data suggest that calcineurin is the relevant cellular target of these immunosuppressive agents and is involved in Ca2+-dependent signal transduction pathways in, among others, T cells and mast cells. C1 HARVARD UNIV,DEPT MED,CAMBRIDGE,MA 02138. NCI,BIOCHEM LAB,BETHESDA,MD 20892. UNIV DUNDEE,DEPT BIOCHEM,MRC,PROT PHOSPHORYLAT UNIT,DUNDEE DD1 4HN,SCOTLAND. RI MacKintosh, Carol/B-8210-2011 OI MacKintosh, Carol/0000-0001-9166-589X FU NIGMS NIH HHS [GM-38627, GM-40660] NR 43 TC 506 Z9 512 U1 0 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 28 PY 1992 VL 31 IS 16 BP 3896 EP 3901 DI 10.1021/bi00131a002 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HR187 UT WOS:A1992HR18700002 PM 1373650 ER PT J AU OMICHINSKI, JG CLORE, GM ROBIEN, M SAKAGUCHI, K APPELLA, E GRONENBORN, AM AF OMICHINSKI, JG CLORE, GM ROBIEN, M SAKAGUCHI, K APPELLA, E GRONENBORN, AM TI HIGH-RESOLUTION SOLUTION STRUCTURE OF THE DOUBLE CYS2HIS2 ZINC FINGER FROM THE HUMAN ENHANCER BINDING-PROTEIN MBP-1 SO BIOCHEMISTRY LA English DT Article ID NUCLEAR MAGNETIC-RESONANCE; POTATO CARBOXYPEPTIDASE INHIBITOR; INTERPROTON DISTANCE RESTRAINTS; VIRUS TYPE-1 ENHANCER; 3-DIMENSIONAL STRUCTURES; MOLECULAR-DYNAMICS; YEAST ADR1; GEOMETRY; DNA; SPECTROSCOPY AB The high-resolution three-dimensional structure of a synthetic 57-residue peptide comprising the double zinc finger of the human enhancer binding protein MBP-1 has been determined in solution by nuclear magnetic resonance spectroscopy on the basis of 1280 experimental restraints. A total of 30 simulated annealing structures were calculated. The backbone atomic root-mean-square distributions about the mean coordinate positions are 0.32 and 0.33 angstrom for the N- and C-terminal fingers, respectively, and the corresponding values for all atoms, excluding disordered surface side chains, are 0.36 and 0.40 angstrom. Each finger comprises an irregular antiparallel sheet and a helix, with the zinc tetrahedrally coordinated to two cysteines and two histidines. The overall structure is nonglobular in nature, and the angle between the long axes of the helices is 47 +/- 5-degrees. The long axis of the antiparallel sheet in the N-terminal finger is approximately parallel to that of the helix in the C-terminal finger. Comparison of this structure with the X-ray structure of the Zif-268 triple finger complexed with DNA indicates that the relative orientation of the individual zinc fingers is clearly distinct in the two cases. This difference can be attributed to the presence of a long Lys side chain in the C-terminal finger of MBP-1 at position 40, instead of a short Ala or Ser side chain at the equivalent position in Zif-268. This finding suggests that different contacts may be involved in the binding of the zinc fingers of MBP-1 and Zif-268 to DNA, consistent with the findings from methylation interference experiments that the two fingers of MBP-1 contact 10 base pairs, while the three fingers of Zif-268 contact only 9 base pairs. C1 NIDDKD,CHEM PHYS LAB,BLDG 2,BETHESDA,MD 20892. NIH,CELL BIOL LAB,BETHESDA,MD 20892. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 57 TC 52 Z9 54 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 APR 28 PY 1992 VL 31 IS 16 BP 3907 EP 3917 DI 10.1021/bi00131a004 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HR187 UT WOS:A1992HR18700004 PM 1567844 ER PT J AU WOLFF, J HWANG, J SACKETT, DL KNIPLING, L AF WOLFF, J HWANG, J SACKETT, DL KNIPLING, L TI COLCHICINE PHOTOSENSITIZES COVALENT TUBULIN DIMERIZATION SO BIOCHEMISTRY LA English DT Article ID FLUORESCENCE STOPPED FLOW; BINDING; PODOPHYLLOTOXIN; KINETICS; DIMER AB Pure rat brain tubulin can be cross-linked by ultraviolet irradiation of tubulin-colchicine complexes at the high-wavelength maximum of colchicine to form covalent dimers > trimers > tetramers. With colchicine concentrations approximately 3 x 10(-4) M (mole ratio to tubulin 3-12) and irradiation for 5-10 min at 95-109 mW/cm2, the yield of dimers is 11-17% and of trimers is 4-6% of the total tubulin. The oligomers show polydispersity and anomalously high apparent molecular masses that converge toward expected values in low-density gels. Maximal dimer yields are obtained with MTC and the decreasing photosensitizing potency is MTC > colchicine > colchicide > isocolchicine > thiocolchicine. Single-ring troponoids also promote dimerization. Evidence is presented suggesting that the initial, low-affinity, binding step of colchicine and its analogues is sufficient to photosensitize tubulin dimerization. RP WOLFF, J (reprint author), NIDDKD,BIOCHEM PHARMACOL LAB,BETHESDA,MD 20892, USA. NR 30 TC 8 Z9 8 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 APR 28 PY 1992 VL 31 IS 16 BP 3935 EP 3940 DI 10.1021/bi00131a007 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HR187 UT WOS:A1992HR18700007 PM 1567846 ER PT J AU FISHER, MT AF FISHER, MT TI PROMOTION OF THE INVITRO RENATURATION OF DODECAMERIC GLUTAMINE-SYNTHETASE FROM ESCHERICHIA-COLI IN THE PRESENCE OF GROEL (CHAPERONIN-60) AND ATP SO BIOCHEMISTRY LA English DT Article ID HEAT-SHOCK; MOLECULAR CHAPERONE; PROTEINS; PURIFICATION; CARBOXYLASE; PRECURSOR; COMPLEXES; LAMBDA; MODEL AB The folding and assembly of dodecameric glutamine synthetase (GS) from Escherichia coli was examined in the absence and presence of the E. coli heat shock protein, GroEL (chaperonin-60). At nonphysiological temperatures (15-20-degrees-C), unfolded GS spontaneously renatured to 80-90% of its original activity in the absence of GroEL. At near-physiological temperatures (37-degrees-C), only 20-40% of the original activity returns. Under the latter solution conditions, GroEL and ATP enhance the extent of GS renaturation to 70-80% of the original activity at 37-degrees-C. In the absence of ATP, GroEL arrests the renaturation of unfolded GS by forming a stable binary complex. The addition of ATP to this complex resulted in the release of GS subunits and formation of active dodecameric GS. The order of addition of ATP or unfolded GS to GroEL results in differences in the t1/2 Values where half-maximal GS activity is attained. At a constant GS concentration, the formation of the GroEL.GS complex followed by ATP addition resulted in approximately a 2-fold increase in the observed t1/2 value compared to that observed when GroEL was preincubated with ATP before the GS renaturation reaction was initiated. These differences in renaturation rates may be related to binding affinity differences between the ATP-free and -bound GroEL conformer for unfolded or partially folded protein substrates [Badcoe, I. G., Smith, C. J., Wood, S., Halsall, D. J., Holbrook, J. J., Lund, P., & Clarke, A. R. (1991) Biochemistry 30, 9195-9200]. Although the smaller chaperonin protein, GroES (chaperonin-10), was not required for the in vitro renaturation of GS, the renaturation rates were accelerated when it was included in the reaction mixture. The addition of ATP analogues, adenosine 5'-O-thiomonophosphate (ATP-gamma-S) and 5'-adenylylimidodiphosphate (AMP-PNP), to the arrested complex also results in the release of GS from GroEL but with slower renaturation rates and/or lower extents of GS renaturation. This suggests that ATP hydrolysis by GroEL is not required to initiate GS renaturation. RP FISHER, MT (reprint author), NHLBI,BIOCHEM LAB,BLDG 3,ROOM 207,BETHESDA,MD 20892, USA. NR 40 TC 118 Z9 120 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 APR 28 PY 1992 VL 31 IS 16 BP 3955 EP 3963 DI 10.1021/bi00131a010 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HR187 UT WOS:A1992HR18700010 PM 1348957 ER PT J AU HIGUCHI, O MIZUNO, K VANDEWOUDE, GF NAKAMURA, T AF HIGUCHI, O MIZUNO, K VANDEWOUDE, GF NAKAMURA, T TI EXPRESSION OF C-MET PROTOONCOGENE IN COS CELLS INDUCES THE SIGNAL TRANSDUCING HIGH-AFFINITY RECEPTOR FOR HEPATOCYTE GROWTH-FACTOR SO FEBS LETTERS LA English DT Article DE HEPATOCYTE GROWTH FACTOR; HGF; HGF RECEPTOR; C-MET PROTOONCOGENE; MITOGENIC SIGNAL ID RAT PLATELETS; MESSENGER-RNA; PURIFICATION AB By transfection of the expression plasmid containing a human c-met cDNA into COS-7 cells, high-affinity binding sites specific for HGF with a K(d) value of 30 pM were newly detected. Furthermore, only in the c-met transfected COS-7 cells, but not in the control COS-7 cells, DNA synthesis was markedly induced in response to HGF. Thus, transient expression of exogenous c-met cDNA resulted in the appearance of high-affinity receptor for HGF and conversion of the normally non-responsive COS-7 cells into the HGF-responsive cells. These results provide evidence for identifying the c-met product as a signal transducing high-affinity receptor for HGF. C1 KYUSHU UNIV,FAC SCI,DEPT BIOL,FUKUOKA 812,JAPAN. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21701. RI Mizuno, Kensaku/G-8631-2015 NR 26 TC 79 Z9 79 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 APR 27 PY 1992 VL 301 IS 3 BP 282 EP 286 DI 10.1016/0014-5793(92)80257-H PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA HR636 UT WOS:A1992HR63600010 PM 1315694 ER PT J AU KAJANDER, KC WAKISAKA, S BENNETT, GJ AF KAJANDER, KC WAKISAKA, S BENNETT, GJ TI SPONTANEOUS DISCHARGE ORIGINATES IN THE DORSAL-ROOT GANGLION AT THE ONSET OF A PAINFUL PERIPHERAL NEUROPATHY IN THE RAT SO NEUROSCIENCE LETTERS LA English DT Article DE AXONAL PATHOLOGY; ECTOPIC DISCHARGE; PAINFUL PERIPHERAL NEUROPATHY; POTASSIUM CHANNEL ID CHANNEL BLOCKADE; NERVE; 4-AMINOPYRIDINE; AFFERENT; NEURONS; FIBERS; MONONEUROPATHY; STIMULATION; CURRENTS; AXOTOMY AB The activity of myelinated primary afferents was recorded from the dorsal roots 1-3 days after creation of a painful peripheral neuropathy in rats. The effects on spontaneous discharge of acute transections at various points along the injured sciatic nerve and the dorsal root were determined, as were the effects of K+ channel blockers applied topically to two putative sites of impulse origin: the injured region of the nerve and the dorsal root ganglion (DRG). Transections just proximal to the nerve injury and just distal to the DRG failed to halt the discharge, but spontaneous discharge disappeared when the transection was made just proximal to the DRG (i.e. between the DRG and recording electrode). K+ channel blockers (4-aminopyridine and gallamine triethiodide) applied to the DRG increased the frequency of spontaneous discharge or initiated activity from silent fibers. Applications of K+ channel blockers to the injured region of the nerve were without effect. Thus, the spontaneous discharge and the sensitivity to K+ channel blockade seen in A-beta and A-delta primary afferents at the time of the onset of the neuropathic pain syndrome appear to originate in the DRG. C1 NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BLDG 30,ROOM B20,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. NR 18 TC 306 Z9 315 U1 1 U2 8 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 APR 27 PY 1992 VL 138 IS 2 BP 225 EP 228 DI 10.1016/0304-3940(92)90920-3 PG 4 WC Neurosciences SC Neurosciences & Neurology GA HV125 UT WOS:A1992HV12500007 PM 1319012 ER PT J AU OTSU, K KINSELLA, JL KOH, E FROEHLICH, JP AF OTSU, K KINSELLA, JL KOH, E FROEHLICH, JP TI PROTON DEPENDENCE OF THE PARTIAL REACTIONS OF THE SODIUM-PROTON EXCHANGER IN RENAL BRUSH-BORDER MEMBRANES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NA+-H+ EXCHANGER; INTRACELLULAR PH REGULATION; PRESTEADY-STATE KINETICS; FROG SKIN; VESICLES; AMILORIDE; ANTIPORT; KIDNEY; MECHANISM; TRANSPORT AB The pre-steady state time dependence of Na+ accumulation by the Na+-H+ exchanger in renal brush border membrane vesicles was investigated at 0-degrees-C by a manual mixing technique using amiloride to quench the reaction. Dilution of acid-loaded (pH(i) 5.7) vesicles into an alkaline medium (pH(o) 7.7) containing 1 mM Na-22(+) produced a time course of amiloride-sensitive Na+ uptake that consisted of three distinct phases: 1) a lag, 2) a monoexponential "burst," and 3) a linear or steady state phase. Experiments testing for the presence of Na-22(+) backflux, residual Na+ binding to the membrane, and hysteresis were negative, lending support to the hypothesis that the burst phase corresponds to Na+ translocation during the initial turnover of Na+-H+ exchanger. Lowering the internal pH increased the amount of Na+ uptake in each of the phases without affecting the apparent burst rate, whereas lowering the external pH inhibited Na+ uptake while increasing the duration of the lag phase. The pattern of inhibition produced by external H+ was of the simple competitive type, indicating that Na+ and H+ share a common binding site. Steady state Na+ uptake showed a sigmoidal dependence on internal pH (Hill coefficient = 1.67), consistent with the presence of an internal allosteric H+ activation site. Alkaline loading conditions (pH(i) 7.7), which favor desaturation of the internal H+ binding sites, completely abolished Na+ uptake in the steady state. In contrast, Na+ accumulation during the burst phase was reduced to 25% of an acid-loaded (pH(i) 5.7) control. The persistence of the burst phase and the disappearance of steady state Na+ uptake under alkaline loading conditions suggest that recycling of the H+-loaded exchanger is a late event in the transport cycle that follows Na+ translocation (ping-pong mechanism) and controls the steady state rate of Na+ accumulation. Activation of the recycling step involves sequential binding of H+ to the allosteric and transport sites, thus accounting for the cooperative dependence of steady state Na+ uptake on the internal [H+]. C1 UNIV TORONTO,CHARLES H BEST INST,BANTING & BEST DEPT MED RES,TORONTO M5G 1L6,ONTARIO,CANADA. NIA,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. NR 35 TC 17 Z9 17 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 APR 25 PY 1992 VL 267 IS 12 BP 8089 EP 8096 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HQ185 UT WOS:A1992HQ18500022 PM 1373720 ER PT J AU CHEN, Q YU, KF HOLBROOK, NJ STEVENS, JL AF CHEN, Q YU, KF HOLBROOK, NJ STEVENS, JL TI ACTIVATION OF THE GROWTH ARREST AND DNA DAMAGE-INDUCIBLE GENE GADD-153 BY NEPHROTOXIC CYSTEINE CONJUGATES AND DITHIOTHREITOL SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEAT-SHOCK RESPONSE; BETA-LYASE; MECHANISM; BINDING; CELLS; METABOLISM; CALCIUM; EXPRESSION; ONCOGENES; TOXICITY AB The cellular and biochemical events which transduce chemical insults into signals for increased expression of the stress-responsive gene gadd 153 were investigated using nephrotoxic cysteine conjugates. In LLC-PK1 cells, cysteine conjugate toxicity is initiated by covalent binding, but depletion of cellular thiols, an increase in cytosolic free calcium, and lipid peroxidation couple the binding to cell death (Chen, Q., Jones, T. W., Brown, P. C., and Stevens, J. L. (1990) J. Biol. Chem. 265, 21603-2161 1; Chen, Q., Jones, T. W., and Stevens, J. L. (1991) Toxicologist 11, 101, 1991). Three different toxic cysteine conjugates induced gadd 153 mRNA. With S-(1,2-dichlorovinyl)-L-cysteine (DCVC), the induction was both concentration and time-dependent. Preventing the metabolism of DCVC and covalent binding of DCVC-derived reactive metabolites to cellular macromolecules with the beta-lyase inhibitor (aminooxy)acetic acid blocked the induction. However, buffering free calcium with a cell permeable calcium chelator or blocking lipid peroxidation with an antioxidant did not affect the induction of gadd 153 mRNA by DCVC even though these treatments inhibit toxicity. These data suggest that covalent binding of reactive metabolites to cellular macromolecules may serve as a primary signal for the induction of gadd 153 mRNA by nephrotoxic cysteine conjugates. Interestingly, the sulfhydryl agent dithiothreitol, which was nontoxic and prevented the toxicity of DCVC, also induced an increase in gadd 153 mRNA. When both dithiothreitol and DCVC were added to cells, there were no inhibitory or additive effects on expression. Therefore, cellular thiol-disulfide status may also play a role in gadd 153 induction. C1 W ALTON JONES CELL SCI CTR,LAKE PLACID,NY 12946. NIA,MOLEC GENET LAB,BALTIMORE,MD 21224. FU NIDDK NIH HHS [DK38925]; NIEHS NIH HHS [ES05670] NR 47 TC 75 Z9 76 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 25 PY 1992 VL 267 IS 12 BP 8207 EP 8212 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HQ185 UT WOS:A1992HQ18500039 PM 1569075 ER PT J AU DEGUCHI, Y THEVENIN, C KEHRL, JH AF DEGUCHI, Y THEVENIN, C KEHRL, JH TI STABLE EXPRESSION OF HB24, A DIVERGED HUMAN HOMEOBOX GENE, IN LYMPHOCYTES-T INDUCES GENES INVOLVED IN T-CELL ACTIVATION AND GROWTH SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ALPHA-CHAIN GENE; LEUKEMIA-VIRUS; TRANSCRIPTION FACTOR; HOMEOTIC GENES; PROTO-ONCOGENE; BETA-ACTIN; B-CELLS; PROTEINS; DROSOPHILA; SEQUENCE AB A diverged homeobox gene, HB24, which is known to be induced following lymphocyte activation, was introduced into Jurkat T cells under the control of a constitutive promoter. Stable transfectants of HB24 were established that expressed high levels of HB24 mRNA and possessed an altered phenotype suggestive of activated T cells. A number of genes known to be induced following T cell activation and associated with cell growth were increased in the transfectants, including c-fos, c-myc, c-myb, HLA-DR, lck, NF-kappa-B, interleukin-2 and interleukin-2 receptor-alpha (IL-2R-alpha). Analysis of IL-2R-alpha-expression by transient transfection of IL-2R-alpha-promoter constructs into the HB24 transfectants revealed constitutive expression (about 60% of phytohemagglutinin- and phorbol ester-activated Jurkat cells) that was dependent on the kappa-B site in the IL-2R-alpha-promoter. Furthermore, as a consequence of the increased HB24 mRNA levels, the Jurkat HB24 transfectants proliferated more rapidly than control cell lines. Thus, stable expression of HB24 confers an activation phenotype on a human T cell line, implicating this gene as an important transcriptional factor during T cell activation and growth. C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NR 53 TC 21 Z9 21 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 APR 25 PY 1992 VL 267 IS 12 BP 8222 EP 8229 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HQ185 UT WOS:A1992HQ18500041 PM 1349016 ER PT J AU GLENNON, MC BIRD, GS KWAN, CY PUTNEY, JW AF GLENNON, MC BIRD, GS KWAN, CY PUTNEY, JW TI ACTIONS OF VASOPRESSIN AND THE CA2+-ATPASE INHIBITOR, THAPSIGARGIN, ON CA2+ SIGNALING IN HEPATOCYTES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID 1,4,5-TRISPHOSPHATE-SENSITIVE CA-2+ POOL; HUMAN-NEUTROPHILS; PLASMA-MEMBRANE; CYTOSOLIC CA-2+; CALCIUM INFLUX; MN-2+ ENTRY; STIMULATE; CELLS; MANGANESE; CHANNELS AB When hepatocytes were loaded with fura-2 by incubation with the acetoxymethyl ester (fura-2/AM), addition of Mn2+ resulted in a rapid quench of a fraction of cellular fura-2 fluorescence. Addition of vasopressin caused a second, rapid quench of cellular fura-2, whereas the addition of thapsigargin had no effect. When hepatocytes were loaded by microinjection of fura-2 acid, addition of Mn2+ caused a slower, sustained rate of quench, and both vasopressin and thapsigargin increased this rate of quench. When Mn2+ was removed from the medium of fura-2/AM-loaded cells after preincubation with Mn2+, vasopressin still caused quench of cellular fura-2. In contrast, neither vasopressin nor thapsigargin increased fura-2 quench when Mn2+ was removed from fura-2-injected cells. When fura-2/AM-loaded cells were permeabilized with saponin, only a fraction of the cell-associated fura-2 was quenched by addition of Mn2+. A second fraction was then quenched by addition of inositol 1,4,5-trisphosphate. These results indicate that in hepatocytes loaded with the acetoxymethyl ester of fura-2, the increased quench of cellular fura-2 seen with phospholipase C-linked agonists is not due to effects of the agonist on Mn2+ entry across the plasma membrane, but rather is due to agonist activation of Mn2+ penetration into an intracellular organelle, presumably through inositol 1,4,5-trisphosphate-regulated channels. Thus, it appears that compartmentalization of fura-2 accounts for previously reported anomalies in Ca2+ signaling in hepatocytes, such as the apparent failure of Ca2+-ATPase inhibition to increase divalent cation entry, as well as the apparent ability of phospholipase C-linked agonists to stimulate efflux of Ca2+. RP GLENNON, MC (reprint author), NIEHS,CELLULAR & MOLEC PHARMACOL LAB,CALCIUM REGULAT SECT,RES TRIANGLE PK,NC 27709, USA. NR 23 TC 87 Z9 88 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 APR 25 PY 1992 VL 267 IS 12 BP 8230 EP 8233 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HQ185 UT WOS:A1992HQ18500042 PM 1533221 ER PT J AU CAMA, A QUON, MJ SIERRA, M TAYLOR, SI AF CAMA, A QUON, MJ SIERRA, M TAYLOR, SI TI SUBSTITUTION OF ISOLEUCINE FOR METHIONINE AT POSITION-1153 IN THE BETA-SUBUNIT OF THE HUMAN INSULIN-RECEPTOR - A MUTATION THAT IMPAIRS RECEPTOR TYROSINE KINASE-ACTIVITY, RECEPTOR ENDOCYTOSIS, AND INSULIN ACTION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GROWTH FACTOR-I; MONOCLONAL-ANTIBODIES; PHOSPHORYLATION SITES; ACANTHOSIS NIGRICANS; RESISTANT PATIENT; GLUCOSE-TRANSPORT; INTACT-CELLS; PROTEIN; ACTIVATION; GENE AB The intracellular domain of the insulin receptor possesses activity as a tyrosine-specific protein kinase. The receptor tyrosine kinase is stimulated by insulin binding to the extracellular domain of the receptor. Previously, we have identified a patient with a genetic form of insulin resistance who is heterozygous for a mutation substituting Ile for Met1153 in the tyrosine kinase domain of the receptor near the cluster of the three major autophosphorylation sites (Tyr1158, Tyr1162, and Tyr1163). In this investigation, the Ile1153 mutant receptor was expressed by transfection of mutant cDNA into NIH-3T3 cells. The mutation impairs receptor tyrosine kinase activity and also inhibits the ability of insulin to stimulate 2-deoxyglucose uptake and thymidine incorporation. These data support the hypothesis that the receptor tyrosine activity plays a necessary role in the ability of the receptor to mediate insulin action in vivo. Furthermore, expression of the Ile1153 mutant receptor exerted a dominant negative effect to inhibit the ability of endogenous murine receptors for insulin and insulin-like growth factor I to mediate their actions upon the cell. This observation is consistent with previous suggestions that mutant receptors dimerize with wild type receptors, thereby creating hybrid molecules which lack biological activity. The dominant negative effect of the mutant receptor may explain the dominant mode of inheritance of insulin resistance caused by the Ile1153 mutation. Finally, the mutation inhibits the ability of insulin to stimulate receptor endocytosis. This may explain the normal number of insulin receptors on the surface of the patient's cells in vivo. Despite the presence of markedly elevated levels of insulin in the patient's plasma, the receptors were resistant to down-regulation. C1 NIDDKD,DIABET BRANCH,BLDG 10,RM 8S-243,BETHESDA,MD 20892. RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915 NR 55 TC 56 Z9 56 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 APR 25 PY 1992 VL 267 IS 12 BP 8383 EP 8389 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HQ185 UT WOS:A1992HQ18500067 PM 1314826 ER PT J AU WU, YN YANG, YC WAGNER, PD AF WU, YN YANG, YC WAGNER, PD TI MODIFICATION OF CHROMAFFIN CELLS WITH PERTUSSIS TOXIN OR N-ETHYLMALEIMIDE LOWERS CYTOSKELETAL F-ACTIN AND ENHANCES CA2+-DEPENDENT SECRETION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; ADRENAL-MEDULLARY CELLS; CATECHOLAMINE SECRETION; HUMAN-NEUTROPHILS; PHORBOL ESTER; RELEASE; EXOCYTOSIS; CALCIUM; STAUROSPORINE; FILAMENTS AB In an attempt to identify proteins involved in the secretory response, bovine chromaffin cells were modified with N-ethylmaleimide (NEM). NEM concentrations less than 30-mu-M enhanced norepinephrine secretion evoked by nicotine or by K+ depolarization and increased Ca2+-dependent secretion from digitonin-permeabilized cells. Higher concentrations of NEM inhibited secretion. The protein modified by NEM which was responsible for the enhancement of secretory activity appeared to rapidly diffuse out of the digitonin-permeabilized cells. When proteins which diffuse from control digitonin-permeabilized cells were incubated with pertussis toxin and [P-32]NAD, several proteins were ADP-ribosylated. However, when proteins from cells preincubated with 30-mu-M NEM were incubated with pertussis toxin and [P-32]NAD, these GTP-binding proteins (G-proteins) were not ADP-ribosylated, which suggests that they were modified in the cell by NEM. Stimulation of norepinephrine secretion by NEM was not additive with that caused by pertussis toxin. Modification of chromaffin cells with pertussis toxin or with 30-mu-M NEM caused a 40-50% decrease in the amount of cytoskeletal F-actin. This decrease in cytoskeletal F-actin may account for the increase in secretory activity. C1 NCI,BIOCHEM LAB,BLDG 37,RM 4C24,BETHESDA,MD 20892. NR 46 TC 38 Z9 39 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 APR 25 PY 1992 VL 267 IS 12 BP 8396 EP 8403 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HQ185 UT WOS:A1992HQ18500069 PM 1569091 ER PT J AU TOMAREV, SI ZINOVIEVA, RD PIATIGORSKY, J AF TOMAREV, SI ZINOVIEVA, RD PIATIGORSKY, J TI CHARACTERIZATION OF SQUID CRYSTALLIN GENES - COMPARISON WITH MAMMALIAN GLUTATHIONE-S-TRANSFERASE GENES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CONTROLLING INDUCIBLE EXPRESSION; EYE LENS CRYSTALLINS; YA SUBUNIT GENE; PHYSICOCHEMICAL CHARACTERIZATION; EVOLUTIONARY STRATEGY; NUCLEOTIDE-SEQUENCE; P-GENE; PROTEINS; DNA; PROMOTER AB Previous experiments have indicated that the crystallins of the squid lens (S-crystallins) are evolutionarily related to glutathione S-transferases (GST) (EC 2.5.1.18). Here we confirm by peptide sequencing that the crystallins of the lens of the squid Ommastrephes sloani pacificus comprise a family of GST-like proteins. Squid lens extracts showed 400 times less GST activity than those of liver using 1-chloro-2,4-dinitrobenzene as a substrate, suggesting that the abundant GST-like crystallins lack enzymatic activity. Four different cDNAs (pSL20-1, pSL18, pSL11, and pSL4) showed 20-25% similarity in homologous regions with mammalian GST polypeptides. pSL20-1, pSL18, and pSL4 each encode an S-crystallin with a unique internal peptide that is unrelated to mammalian GSTs or any other sequence in GenBank. The S-crystallin family is encoded in a minimum of 9-10 genes, and the exon-intron structures of at least two of these (SL20-1 and SL11) are similar to those of the mammalian GST genes. The SL20-1 gene has six exons, with the its unique internal peptide encoded precisely in exon 4; the SL11 gene lacks a unique internal peptide and has five exons. Experiments using bacterial chloramphenicol acetyltransferase as a reporter gene showed that at least 84 and 111 base pairs of 5'-flanking sequence are needed for function of the SL20-1 and SL11 promoters, respectively, in a transfected rabbit lens epithelial cell line (N/N1003A). Within these regions each has a putative TATA box and an upstream AP-1 site overlapping with antioxidant responsive-like elements, which are regulatory elements in the rat GST Ya and quinone reductase genes responsive to oxidative stress. RP TOMAREV, SI (reprint author), NIA,MOLEC & DEV BIOL LAB,BETHESDA,MD 20892, USA. NR 62 TC 46 Z9 50 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 APR 25 PY 1992 VL 267 IS 12 BP 8604 EP 8612 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HQ185 UT WOS:A1992HQ18500097 PM 1373730 ER PT J AU SUGITANI, M INCHAUSPE, G SHINDO, M PRINCE, AM AF SUGITANI, M INCHAUSPE, G SHINDO, M PRINCE, AM TI SENSITIVITY OF SEROLOGICAL ASSAYS TO IDENTIFY BLOOD-DONORS WITH HEPATITIS-C VIREMIA SO LANCET LA English DT Note ID NON-B HEPATITIS; NON-A AB Blood donors at high risk of hepatitis C virus (HCV) infection were tested for viraemia by the polymerase chain reaction (PCR). PCR results were accepted as positive only if reactive in 3 of 4 tests and if confirmed in an independent laboratory. The sera were also tested by 6 different assays to determine the ability of current serological assays to detect viraemic blood donors. Of 19 PCR-positive sera, only 13 (68%) were detected by the most sensitive of the serological assays. If these results are confirmed, automated PCR assays may be required for blood-donor screening to prevent transmission of HCV. C1 NEW YORK BLOOD CTR,VIROL & PARASITOL LAB,310 E 67TH ST,NEW YORK,NY 10021. NIHON UNIV,SCH MED,DEPT PATHOL 1,TOKYO 173,JAPAN. NIH,LIVER DIS SECT,BETHESDA,MD 20892. NR 9 TC 145 Z9 145 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD APR 25 PY 1992 VL 339 IS 8800 BP 1018 EP 1019 DI 10.1016/0140-6736(92)90538-E PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA HQ435 UT WOS:A1992HQ43500006 PM 1349053 ER PT J AU KOONIN, EV AF KOONIN, EV TI DNAC PROTEIN CONTAINS A MODIFIED ATP-BINDING MOTIF AND BELONGS TO A NOVEL FAMILY OF ATPASES INCLUDING ALSO DNAA SO NUCLEIC ACIDS RESEARCH LA English DT Note ID SEQUENCE RP KOONIN, EV (reprint author), NIH,NATL CTR BIOTECHNOL INFORMAT,NATL LIB MED,BLDG 38A,8600 ROCKVILLE PIKE,BETHESDA,MD 20894, USA. NR 7 TC 41 Z9 41 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 APR 25 PY 1992 VL 20 IS 8 BP 1997 EP 1997 DI 10.1093/nar/20.8.1997 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HT335 UT WOS:A1992HT33500028 PM 1533715 ER PT J AU YAMADA, M KAKITA, A MIZUGUCHI, M RHEE, SG KIM, SU IKUTA, F AF YAMADA, M KAKITA, A MIZUGUCHI, M RHEE, SG KIM, SU IKUTA, F TI ULTRASTRUCTURAL-LOCALIZATION OF INOSITOL 1,4,5-TRISPHOSPHATE 3-KINASE IN RAT CEREBELLAR CORTEX SO BRAIN RESEARCH LA English DT Article DE INOSITOL 1,4,5-TRISPHOSPHATE; INOSITOL 1,3,4,5-TETRAKISPHOSPHATE; INOSITOL 1,4,5-TRISPHOSPHATE 3-KINASE; IMMUNOHISTOCHEMISTRY; RAT; CEREBELLUM; ULTRASTRUCTURE ID PROTEIN KINASE-C; DENDRITIC SPINES; PURKINJE-CELLS; RECEPTOR; CALCIUM; CA-2+; 1,3,4,5-TETRAKISPHOSPHATE; PHOSPHATES; CALMODULIN; TETRAKISPHOSPHATE AB Subcellular localization of inositol 1,4,5-trisphosphate 3-kinase in the rat cerebellar cortex was studied immunohistochemically using a monoclonal antibody. Electron microscopy revealed intense immunoreactivity in the dendritic spines of Purkinje cells forming synapses with the parallel fibers, climbing fibers and recurrent collaterals of Purkinje cell axons. The labelling was associated with the hypolemmal cisternae, surrounding matrix and plasmalemma including the postsynaptic densities. Weaker immunoreactivity was present in the dendritic spines of basket cells and in certain segments of Purkinje cell recurrent collaterals. The postsynaptic regions of the dendritic trunks of Purkinje and basket cells were negative. These results indicate that inositol 1,4,5-trisphosphate 3-kinase is distributed amongst the spines of various synaptic relations with different electrophysiological properties, and that axon terminals of certain cell types are another functional site for the enzyme. C1 NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. UNIV BRITISH COLUMBIA,DEPT MED,DIV NEUROL,VANCOUVER V6T 1W5,BC,CANADA. RP YAMADA, M (reprint author), NIIGATA UNIV,BRAIN RES INST,DEPT PATHOL,ASAHIMACHI 1,NIIGATA 951,JAPAN. NR 27 TC 16 Z9 16 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD APR 24 PY 1992 VL 578 IS 1-2 BP 41 EP 48 DI 10.1016/0006-8993(92)90227-Z PG 8 WC Neurosciences SC Neurosciences & Neurology GA HU298 UT WOS:A1992HU29800007 PM 1324766 ER PT J AU SMITH, MA BANERJEE, S GOLD, PW GLOWA, J AF SMITH, MA BANERJEE, S GOLD, PW GLOWA, J TI INDUCTION OF C-FOS MESSENGER-RNA IN RAT-BRAIN BY CONDITIONED AND UNCONDITIONED STRESSORS SO BRAIN RESEARCH LA English DT Article DE CONDITIONED STRESS; C-FOS; LOCUS CERULEUS; PARAVENTRICULAR NUCLEUS; INSITU HYBRIDIZATION ID IMMEDIATE-EARLY GENES; SINGLE-UNIT RESPONSE; FREELY MOVING CATS; GLUCOCORTICOID RECEPTOR; NORADRENERGIC NEURONS; PRESENTED STRESSFUL; LOCUS COERULEUS; SPINAL-CORD; EXPRESSION; JUN AB Intense depolarizing stimuli induce the expression of the proto-oncogene c-fos which may be useful as a marker of neuronal activity. To determine if mild physical and behavioral stressors may also induce c-fos expression, we subjected rats to an unconditioned stressor (footshock) or a conditioned stressor (a tone previously paired with footshock) and measured c-fos mRNA levels in various brain regions using in situ hybridization. Removing rats from their home cage and exposing them to a tone was sufficient to cause increases in c-fos mRNA in several forebrain areas while further increases in c-fos occurred in the septum, cingulate cortex, and endopiriform nucleus in response to acute footshock stress. Both unconditioned and conditioned stressors increased c-fos mRNA levels in the locus ceruleus which correlated with stress-induced plasma corticosterone concentrations. Unconditioned footshock stress also increased c-fos mRNA in the hypothalamic paraventricular nucleus (PVN). However, neither conditioned nor unconditioned stressors induced c-fos in the PVN in rats which had been previously exposed to footshock. C-fos appears to be a sensitive marker for stress-responsive brain areas and may be important in mediating long-term neurochemical changes that result from stress. RP SMITH, MA (reprint author), NIMH,CLIN NEUROENDOCRINOL BRANCH,BLDG 36,RM 2D-15,BETHESDA,MD 20892, USA. NR 37 TC 148 Z9 152 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 APR 24 PY 1992 VL 578 IS 1-2 BP 135 EP 141 DI 10.1016/0006-8993(92)90240-A PG 7 WC Neurosciences SC Neurosciences & Neurology GA HU298 UT WOS:A1992HU29800020 PM 1511271 ER PT J AU NAKATA, H AF NAKATA, H TI AFFINITY-CHROMATOGRAPHY IN PURIFICATION OF ADENOSINE-A1-RECEPTORS SO JOURNAL OF CHROMATOGRAPHY LA English DT Article; Proceedings Paper CT 9TH INTERNATIONAL SYMP ON AFFINITY CHROMATOGRAPHY AND BIOLOGICAL RECOGNITION CY SEP 24-28, 1991 CL YOKOHAMA, JAPAN ID A1 ADENOSINE RECEPTOR; RAT-BRAIN MEMBRANES; BINDING-PROTEINS; BOVINE BRAIN; SOLUBILIZATION; SITES AB Purification of A1 adenosine receptor of rat brain membranes was performed using a newly developed affinity gel employing xanthine amine congener (XAC) as an immobilized ligand. The A1 adenosine receptor was solubilized with digitonin-cholate from brain membranes and then purified by a sequential use of affinity chromatography on XAC-agarose, hydroxyapatite chromatograpby and reaffinity chromatography on XAC-agarose. The A1 adenosine receptor was purified ca. 45 000-fold with a yield of 5%. The final receptor preparation gave a single broad band on sodium dodecyl sulfate polyacrylamide gel electrophoresis with a M(r) almost-equal-to 34 000. This band was also shown to be specifically labelled with an affinity labelling reagent for A1 adenosine receptors. This purification method was also applicable for the complete purification of A1 adenosine receptors from rat testis and human brain membranes. C1 TOKYO METROPOLITAN INST NEUROSCI,DEPT MOLEC & CELLULAR NEUROBIOL,FUCHU,TOKYO 183,JAPAN. RP NAKATA, H (reprint author), NIMH,CLIN SCI LAB,BETHESDA,MD 20892, USA. NR 27 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR PD APR 24 PY 1992 VL 597 IS 1-2 BP 335 EP 343 DI 10.1016/0021-9673(92)80129-I PG 9 WC Chemistry, Analytical SC Chemistry GA HT264 UT WOS:A1992HT26400039 PM 1517337 ER PT J AU COHEN, DI TANI, Y TIAN, H BOONE, E SAMELSON, LE LANE, HC AF COHEN, DI TANI, Y TIAN, H BOONE, E SAMELSON, LE LANE, HC TI PARTICIPATION OF TYROSINE PHOSPHORYLATION IN THE CYTOPATHIC EFFECT OF HUMAN-IMMUNODEFICIENCY-VIRUS .1. SO SCIENCE LA English DT Article ID T-CELL RECEPTOR; PROTEIN-KINASE; HTLV-III/LAV; SYNCYTIUM FORMATION; ANTIGEN RECEPTOR; HERBIMYCIN-A; ACTIVATION; CD4; INHIBITION; RETROVIRUS AB Protein tyrosine phosphorylation is a common mechanism of signaling in pathways that regulate T cell receptor-mediated cell activation, cell proliferation, and the cell cycle. Because human immunodeficiency virus (HIV) is thought to affect normal cell signaling, tyrosine phosphorylation may be associated with HIV cytopathicity. In both HIV-infected cells and transfected cells that stably express HIV envelope glycoproteins undergoing HIVgp41-induced cell fusion, a 30-kilodalton protein was phosphorylated on tyrosine with kinetics similar to those of syncytium formation and cell death. When tyrosine phosphorylation was inhibited by the protein tyrosine kinase inhibitor herbimycin A, envelope-mediated syncytium formation was coordinately reduced. These studies show that specific intracellular signals, which apparently participate in cytopathicity, are generated by HIV and suggest strategies by which the fusion process might be interrupted. C1 NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. RP COHEN, DI (reprint author), NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892, USA. NR 41 TC 104 Z9 105 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 APR 24 PY 1992 VL 256 IS 5056 BP 542 EP 545 DI 10.1126/science.1570514 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HQ187 UT WOS:A1992HQ18700070 PM 1570514 ER PT J AU WARREN, HS DANNER, RL MUNFORD, RS AF WARREN, HS DANNER, RL MUNFORD, RS TI ANTIENDOTOXIN MONOCLONAL-ANTIBODIES SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID GRAM-NEGATIVE BACTEREMIA; SEPTIC SHOCK; ESCHERICHIA-COLI C1 NIH,BETHESDA,MD 20205. UNIV TEXAS,SW MED CTR,DALLAS,TX 75235. RP WARREN, HS (reprint author), MASSACHUSETTS GEN HOSP,BOSTON,MA 02114, USA. NR 27 TC 176 Z9 177 U1 0 U2 1 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 23 PY 1992 VL 326 IS 17 BP 1153 EP 1157 DI 10.1056/NEJM199204233261711 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA HP800 UT WOS:A1992HP80000011 PM 1552919 ER PT J AU SASTRY, SM PAUL, BK CHAMPION, H AF SASTRY, SM PAUL, BK CHAMPION, H TI EFFECTS OF RESTRICTIVE HANDGUN LAWS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 WASHINGTON HOSP CTR,WASHINGTON,DC 20010. RP SASTRY, SM (reprint author), NIH,BETHESDA,MD 20892, USA. NR 1 TC 1 Z9 1 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 APR 23 PY 1992 VL 326 IS 17 BP 1159 EP 1159 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA HP800 UT WOS:A1992HP80000016 PM 1552924 ER PT J AU RUTTIMAN, UE GETSON, PR POLLACK, MM AF RUTTIMAN, UE GETSON, PR POLLACK, MM TI THE OUTCOME OF PEDIATRIC INTENSIVE-CARE - REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 CHILDRENS NATL MED CTR,WASHINGTON,DC 20010. RP RUTTIMAN, UE (reprint author), NIH,BETHESDA,MD 20892, USA. NR 4 TC 0 Z9 0 U1 1 U2 1 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 23 PY 1992 VL 326 IS 17 BP 1162 EP 1162 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA HP800 UT WOS:A1992HP80000023 ER PT J AU VARGA, K KUNOS, G AF VARGA, K KUNOS, G TI INHIBITION OF BAROREFLEX BRADYCARDIA BY ETHANOL INVOLVES BOTH GABA(A) AND GABA(B) RECEPTORS IN THE BRAIN-STEM OF THE RAT SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE BAROREFLEX; ETHANOL; GABA (GAMMA-AMINOBUTYRIC ACID); DORSAL VAGAL COMPLEX ID GAMMA-AMINOBUTYRIC ACID; NUCLEUS-TRACTUS-SOLITARIUS; BARORECEPTOR REFLEX CONTROL; SPINAL-CORD NEURONS; HEART-RATE; BLOOD-PRESSURE; CHLORIDE CHANNELS; ENDOGENOUS GABA; B RECEPTORS; HYPERTENSION AB The effects of ethanol on baroreceptor reflex bradycardia and its interactions with cardiovascular effects mediated by GABA receptors in the dorsal vagal complex were studied in urethane-anaesthetised rats. Ethanol, 1 g kg-1 administered i.v. or 25-200 nmol microinjected bilaterally into the dorsal vagal complex, inhibited the reflex bradycardic response to bolus i.v. doses of phenylephrine both in spontaneously breathing and in paralysed, arteficially ventilated animals, and this effect could be prevented by pretreatment with the GABA-depleting agent, 3-mercaptopropionate in both groups of rats. Ethanol, 1 g kg-1 i.v., did not influence the bradycardic response to electrical stimulation of the cervical vagus. Microinjection of muscimol into the dorsal vagal complex caused a dose-dependent pressor response and inhibited baroreflex bradycardia. The pressor response was potentiated and a tachycardic response to muscimol emerged following microinjection of ethanol into the dorsal vagal complex. Similar administration of baclofen caused dose-dependent increases in blood pressure and heart rate and inhibited baroreflex bradycardia. Injection of ethanol into the dorsal vagal complex potentiated the pressor response to a low dose of baclofen but did not affect the tachycardic response. Bicuculline, 10 pmol/side into the dorsal vagal complex, blocked the effects of muscimol but not those of baclofen and reduced the baroreflex inhibitory action of ethanol. 2-Hydroxysaclofen, microinjected at 400 pmol to 1 nmol/side, blocked the effects of baclofen but not those of muscimol. 2-Hydroxysaclofen or phaclofen, 2 mg kg-1 s.c., prevented the baroreflex inhibitory action of ethanol and also prevented ethanol potentiation of the pressor and, less effectively, the tachycardic effects of muscimol. It is concluded that ethanol inhibits baroreflex bradycardia through potentiation of the actions of endogenous GABA in the dorsal vagal complex. Both GABA(A) and GABA(B) receptors appear to be involved in this action of ethanol. RP VARGA, K (reprint author), NIAAA,PHYSIOL & PHARMACOL STUDIES LAB,12501 WASHINGTON AVE,ROCKVILLE,MD 20852, USA. NR 41 TC 24 Z9 24 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD APR 22 PY 1992 VL 214 IS 2-3 BP 223 EP 232 DI 10.1016/0014-2999(92)90122-K PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA HT715 UT WOS:A1992HT71500016 PM 1325357 ER PT J AU RIVA, P ARISTA, A STURIALE, C MOSCATELLI, G TISON, V MARIANI, M SECCAMANI, E LAZZARI, S FAGIOLI, L FRANCESCHI, G SARTI, G RIVA, N NATALI, PG ZARDI, L SCASSELLATI, GA AF RIVA, P ARISTA, A STURIALE, C MOSCATELLI, G TISON, V MARIANI, M SECCAMANI, E LAZZARI, S FAGIOLI, L FRANCESCHI, G SARTI, G RIVA, N NATALI, PG ZARDI, L SCASSELLATI, GA TI TREATMENT OF INTRACRANIAL HUMAN GLIOBLASTOMA BY DIRECT INTRATUMORAL ADMINISTRATION OF I-131-LABELED ANTI-TENASCIN MONOCLONAL-ANTIBODY BC-2 SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID COLORECTAL-CARCINOMA; LOCALIZATION; GLIOMAS; IMMUNOSCINTIGRAPHY; CHEMOTHERAPY; THERAPY; TUMOR AB Ten patients with bulky brain glioblastoma, recurring after surgery, radiotherapy or chemotherapy, underwent direct intralesional radioimmunotherapy (RIT) using a monoclonal antibody (MAb), BC-2, raised against tenascin and labelled with I-131. Tenascin, the BC-2-recognized glycoprotein, is an antigen expressed by the stroma of malignant gliomas but not by normal cerebral tissue. Preliminary studies in animals have demonstrated the ability of anti-tenascin radiolabelled MAbs to detect and reduce tumours. A mean MAb dose of 1.93 mg (corresponding to 55 1.3 MBq of I-131) Was injected directly into the tumour by means of a stereotaxic technique. Both systemic and local toxicity were negligible. After 24 hr, average tumour BC-2 uptake was 4.9% per gram and its effective half-life in neoplastic tissue was 66.5 hr: a mean radiation dose to target tissue of 36.48 cGy per MBq of injected I-131 was delivered. Normal brain tissue and the major organs were spared. Most patients underwent multiple injections, reaching a cumulative tumour radiation ranging from 7,000 to 41,000 cGy. RIT failed to achieve any result in 4 of the 10 patients; in 3, the disease was stabilized; in the remaining 3, CT scan or NMR revealed 2 partial remission ( > 50% reduction in tumour volume; PR) and I complete remission (CR). One patient with PR relapsed after II months; the other 2 patients were still maintaining their responses at the time of writing, 17 (CR) and 12 (PR) months after injection. C1 OSPED GEN PROVINCIALE M BUFALINI,DEPT NUCL MED,I-47023 CESENA,ITALY. OSPED GEN PROVINCIALE M BUFALINI,DEPT NEUROSURG,I-47023 CESENA,ITALY. OSPED GEN PROVINCIALE M BUFALINI,DEPT PATHOL,I-47023 CESENA,ITALY. SORIN,SALUGGIA,ITALY. OSPED GEN PROVINCIALE M BUFALINI,DEPT HLTH PHYS,I-47023 CESENA,ITALY. OSPED GEN PROVINCIALE M BUFALINI,DEPT NEURORADIOL,I-47023 CESENA,ITALY. REGINA ELENA INST CANC RES,DEPT IMMUNOL,ROME,ITALY. NATL CANC INST,GENOA,ITALY. RP RIVA, P (reprint author), OSPED GEN PROVINCIALE M BUFALINI,ROMAGNOLO ONCOL INST,VIA GHIROTTI 286,I-47023 CESENA,ITALY. NR 33 TC 59 Z9 59 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 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD APR 22 PY 1992 VL 51 IS 1 BP 7 EP 13 DI 10.1002/ijc.2910510103 PG 7 WC Oncology SC Oncology GA HQ417 UT WOS:A1992HQ41700002 PM 1373410 ER PT J AU LEVINE, PH EBBESEN, P ABLASHI, DV SAXINGER, WC NORDENTOFT, A CONNELLY, RR AF LEVINE, PH EBBESEN, P ABLASHI, DV SAXINGER, WC NORDENTOFT, A CONNELLY, RR TI ANTIBODIES TO HUMAN HERPES VIRUS-6 AND CLINICAL COURSE IN PATIENTS WITH HODGKINS-DISEASE SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID EPSTEIN-BARR VIRUS; REED-STERNBERG CELLS; HUMAN HERPESVIRUS-6; NASOPHARYNGEAL CARCINOMA; VIRAL GENOMES; LYMPHOMA; ANTIGENS; LEUKEMIA; EBV; DIAGNOSIS AB Serial serum samples from 37 patients with Hodgkin's disease (HD) and 39 healthy controls were studied for antibodies to human herpes virus-6 (HHV-6) using ELISA and indirect immunofluorescent antibody (IFA) tests and to the Epstein-Barr virus (EBV) using a radio-complement fixation assay. Antibodies to HHV-6 in the pre-treatment sera from the HD patients were not significantly different from those of controls, but significant changes in titers related to clinical course were noted among the HD patients. HHV-6 IFA titers increased significantly in the course of follow-up in patients who relapsed and decreased significantly over time in patients who did not. These serologic studies support tissue-based investigations indicating that EBV plays a greater etiologic role in HD than HHV-6, although HHV-6 serology may be of prognostic value or may assist in identifying individuals with immunologic abnormalities. The identification of diverse HHV-6 antibody patterns using different assays may reflect the presence of a number of antibodies with varying implications, similar to those identified for EBV. C1 CANC RES INST,AARHUS,DENMARK. RP LEVINE, PH (reprint author), NIH,BETHESDA,MD 20892, USA. NR 49 TC 25 Z9 25 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD APR 22 PY 1992 VL 51 IS 1 BP 53 EP 57 DI 10.1002/ijc.2910510111 PG 5 WC Oncology SC Oncology GA HQ417 UT WOS:A1992HQ41700010 PM 1314231 ER PT J AU GRACIA, F CASTILLO, L ARMIEN, B GIUSTI, RM LEVINE, PH BLATTNER, WA AF GRACIA, F CASTILLO, L ARMIEN, B GIUSTI, RM LEVINE, PH BLATTNER, WA TI HUMAN T-LYMPHOTROPIC VIRUS TYPE-II AMONG GUAYMI INDIANS - PANAMA (REPRINTED FROM MMWR, VOL 41, PG 209-211, 1992) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 CTR DIS CONTROL,NATL CTR INFECT DIS,DIV VIRAL & RICKETTSIAL DIS,ATLANTA,GA 30333. RP GRACIA, F (reprint author), NCI,BETHESDA,MD 20892, USA. NR 10 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 APR 22 PY 1992 VL 267 IS 16 BP 2163 EP 2164 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA HN841 UT WOS:A1992HN84100006 ER PT J AU CARTER, HB PEARSON, JD METTER, J BRANT, LJ CHAN, DW ANDRES, R FOZARD, JL WALSH, PC AF CARTER, HB PEARSON, JD METTER, J BRANT, LJ CHAN, DW ANDRES, R FOZARD, JL WALSH, PC TI LONGITUDINAL EVALUATION OF PROSTATE-SPECIFIC ANTIGEN LEVELS IN MEN WITH AND WITHOUT PROSTATE DISEASE SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID RADICAL PROSTATECTOMY; TREATED PATIENTS; ADENOCARCINOMA; HYPERPLASIA; CANCER; DIAGNOSIS AB Objective. - To evaluate longitudinal changes in prostate-specific antigen (PSA) levels in men with and without prostate disease. Design. - Case-control study of men with and without prostate disease who were participants in a prospective aging study. Setting. - Gerontology Research Center of the National institute on Aging; the Baltimore (Md) Longitudinal Study of Aging. Patients. - Sixteen men with no prostate disease (control group), 20 men with a histologic diagnosis of benign prostatic hyperplasia (BPH), and 18 men with a histologic diagnosis of prostate cancer. Outcome Measures. - Multiple PSA and androgen determinations on serum samples obtained from 7 to 25 years prior to histologic diagnosis or exclusion of prostate disease. Results. - Changes in androgen levels with age did not differ between groups. Control subjects did not show a significant change in PSA levels with age. There was a significant difference in the age-adjusted rate of change in PSA levels between groups (prostate cancer > BPH > control; P < .01). At 5 years before diagnosis when PSA levels did not differ between subjects with BPH and prostate cancer, rate of change in PSA levels (0.75-mu-g/L per year) was significantly greater in subjects with prostate cancer compared with control subjects and subjects with BPH. Also, rate of change in PSA levels distinguished subjects with prostate cancer from subjects with BPH and control subjects with a specificity of 90% and 100%, respectively. Conclusions. - The most significant factor affecting serum PSA levels with age is the development of prostate disease. Rate of change in PSA levels may be a sensitive and specific early clinical marker for the development of prostate cancer. C1 JOHNS HOPKINS UNIV HOSP,SCH MED,JAMES BUCHANAN BRADY UROL INST,DEPT LAB MED,BALTIMORE,MD 21205. NIA,GERONTOL RES CTR,CLIN PHYSIOL LAB,BETHESDA,MD 20892. NIA,GERONTOL RES CTR,LONGITUDINAL STUDIES BRANCH,BETHESDA,MD 20892. RP CARTER, HB (reprint author), JOHNS HOPKINS UNIV HOSP,SCH MED,JAMES BUCHANAN BRADY UROL INST,DEPT UROL,403 MARBURG,BALTIMORE,MD 21205, USA. RI Fozard, James Leonard/B-3660-2009 FU NCI NIH HHS [P50 CA058236] NR 19 TC 800 Z9 829 U1 1 U2 17 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 APR 22 PY 1992 VL 267 IS 16 BP 2215 EP 2220 DI 10.1001/jama.267.16.2215 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA HN841 UT WOS:A1992HN84100032 PM 1372942 ER PT J AU SPANDE, TF GARRAFFO, HM EDWARDS, MW YEH, HJC PANNELL, L DALY, JW AF SPANDE, TF GARRAFFO, HM EDWARDS, MW YEH, HJC PANNELL, L DALY, JW TI EPIBATIDINE - A NOVEL (CHLOROPYRIDYL)AZABICYCLOHEPTANE WITH POTENT ANALGESIC ACTIVITY FROM AN ECUADORIAN POISON FROG SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID SKIN ALKALOIDS; CLASSIFICATION; DENDROBATIDAE AB A potent non-opioid analgesic, epibatidine, has been isolated from skins of the Ecuadoran poison frog, Epipedobates tricolor, and its structure determined by MS, IR, and H-1 NMR analyses as exo-2-(6-chloro-3-pyridyl)-7-azabicyclo[2.2.1]heptane. It represents a unique new class of alkaloids. C1 NIDDKD,ANALYT CHEM LAB,BETHESDA,MD 20892. NIDDKD,BIOORGAN CHEM LAB,BETHESDA,MD 20892. NR 11 TC 504 Z9 510 U1 2 U2 20 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 APR 22 PY 1992 VL 114 IS 9 BP 3475 EP 3478 DI 10.1021/ja00035a048 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA HQ814 UT WOS:A1992HQ81400048 ER PT J AU PASCUALLEONE, A VALLSSOLE, J BRASILNETO, JP COHEN, LG HALLETT, M AF PASCUALLEONE, A VALLSSOLE, J BRASILNETO, JP COHEN, LG HALLETT, M TI SEIZURE INDUCTION AND TRANSCRANIAL MAGNETIC STIMULATION SO LANCET LA English DT Letter ID SAFETY RP PASCUALLEONE, A (reprint author), NINCDS,MED NEUROL BRANCH,BETHESDA,MD 20892, USA. RI Pascual-Leone, Alvaro/G-6566-2011 NR 11 TC 43 Z9 45 U1 0 U2 2 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD APR 18 PY 1992 VL 339 IS 8799 BP 997 EP 997 DI 10.1016/0140-6736(92)91582-S PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA HP036 UT WOS:A1992HP03600047 PM 1348836 ER PT J AU BRADY, DR CAREY, RG MUFSON, EJ AF BRADY, DR CAREY, RG MUFSON, EJ TI REDUCED NICOTINAMIDE ADENINE-DINUCLEOTIDE PHOSPHATE-DIAPHORASE (NADPH-D) PROFILES IN THE AMYGDALA OF HUMAN AND NEW-WORLD MONKEY (SAIMIRI-SCIUREUS) SO BRAIN RESEARCH LA English DT Article DE AMYGDALA; HUMAN; PRIMATE; HISTOCHEMISTRY ID NEUROPEPTIDE-Y; ALZHEIMERS-DISEASE; REACTIVE NEURONS; SENILE DEMENTIA; IMMUNOREACTIVE NEURONS; HIPPOCAMPAL-FORMATION; NEURITIC PLAQUES; CEREBRAL-CORTEX; RAT STRIATUM; SOMATOSTATIN AB The topographic distribution of nicotinamide adenine dinucleotide-diaphorase (NADPH-d) stained profiles in the amygdala of the human and new world monkey (Saimiri sciureus) were studied histochemically. Fiber and terminal staining were heterogeneously distributed within the amygdala. The most intense staining occurred in the basolateral subdivision, consisting of the lateral, basolateral and accessory basal nuclei. Moderate staining intensity was observed throughout the cortical and medial nuclei and cortical transition area, constituents of the corticomedial subdivision. The central amygdaloid area was characterized by minimal NADPH-d histochemical reactivity. NADPH-d positive neurons were pleomorphic and divisible into two classes based on their staining characteristics: intensely or lightly stained neurons. Their distribution was generally complementary, with the majority of intensely stained neurons occupying the basolateral subdivision. There were no appreciable species differences in the patterns of neuronal, fiber and terminal staining between monkey or human amygdala. These results may be relevant to our understanding of the selective vulnerability of neural systems within the human amygdala in neurodegenerative diseases. C1 SCI INSTRUMENTS,TEMPE,AZ 85282. RUSH MED COLL,DEPT NEUROL SCI,CHICAGO,IL 60612. RP BRADY, DR (reprint author), NIA,NEUROSCI LAB,BLDG 10,RM 6C103,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. FU NINDS NIH HHS [NS 26146] NR 61 TC 19 Z9 19 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD APR 17 PY 1992 VL 577 IS 2 BP 236 EP 248 DI 10.1016/0006-8993(92)90279-I PG 13 WC Neurosciences SC Neurosciences & Neurology GA HQ550 UT WOS:A1992HQ55000008 PM 1606498 ER PT J AU ZHANG, WQ PENNYPACKER, KR YE, H MERCHENTHALER, IJ GRIMES, L IADAROLA, MJ HONG, JS AF ZHANG, WQ PENNYPACKER, KR YE, H MERCHENTHALER, IJ GRIMES, L IADAROLA, MJ HONG, JS TI A 35 KDA FOS-RELATED ANTIGEN IS CO-LOCALIZED WITH SUBSTANCE-P AND DYNORPHIN IN STRIATAL NEURONS SO BRAIN RESEARCH LA English DT Note DE ENKEPHALIN; APOMORPHINE; 6-HYDROXYDOPAMINE; STRIATUM; SUBSTANCE-P; DYNORPHIN ID STRIATONIGRAL PATHWAY; MATRIX COMPARTMENTS; DOPAMINERGIC SYSTEM; RAT; EXPRESSION; GENE; ENKEPHALIN; NIGRA; METABOLISM; SEIZURE AB The rat striatum after dopamine denervation followed by repeated apomorphine treatment was examined for the co-expression of c-fos and Fos-related antigens with dynorphin, substance P and [Met5]enkephalin using Western blot and immunohistochemical techniques. Administration of apomorphine, a dopamine agonist, elevated the level of 35 kDa Fos-related antigen which co-localized with dynorphin and substance P, but not enkephalin, in striatal neurons. C1 NIEHS,MOLEC & INTEGRAT NEUROSCI LAB,RES TRIANGLE PK,NC 27709. NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD 20492. RI Pennypacker, Keith/I-5092-2012 NR 27 TC 26 Z9 26 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 APR 17 PY 1992 VL 577 IS 2 BP 312 EP 317 DI 10.1016/0006-8993(92)90289-L PG 6 WC Neurosciences SC Neurosciences & Neurology GA HQ550 UT WOS:A1992HQ55000018 PM 1376635 ER PT J AU DECLUE, JE PAPAGEORGE, AG FLETCHER, JA DIEHL, SR RATNER, N VASS, WC LOWY, DR AF DECLUE, JE PAPAGEORGE, AG FLETCHER, JA DIEHL, SR RATNER, N VASS, WC LOWY, DR TI ABNORMAL REGULATION OF MAMMALIAN P21(RAS) CONTRIBUTES TO MALIGNANT-TUMOR GROWTH IN VONRECKLINGHAUSEN (TYPE-1) NEUROFIBROMATOSIS SO CELL LA English DT Article ID GTPASE-ACTIVATING PROTEIN; RAS P21; SACCHAROMYCES-CEREVISIAE; GUANINE-NUCLEOTIDE; SCHWANN-CELLS; GENE-PRODUCT; GAP; DOMAIN; MUTATIONS; BINDING AB Tumor cell lines derived from malignant schwannomas removed from patients with neurofibromatosis type 1 (NF1) have been examined for the level of expression of NF1 protein. All three NF1 lines examined expressed lower levels of NF1 protein than control cells, and the level in one line was barely detectable. The tumor lines expressed normal levels of p120GAP and p21ras. Although the p21ras proteins isolated from the tumor cells had normal (nonmutant) biochemical properties in vitro, they displayed elevated levels of bound GTP in vivo. The level of total cellular GAP-like activity was reduced in extracts from the tumor line that expresses very little NF1 protein. Introduction of the catalytic region of GAP into this line resulted in morphological reversion and lower in vivo GTP binding by endogenous p21ras. These data implicate NF1 protein as a tumor suppressor gene product that negatively regulates p21ras and define a "positive" growth role for ras activity in NF1 malignancies. C1 BRIGHAM & WOMENS HOSP, DEPT PATHOL, BOSTON, MA 02115 USA. VIRGINIA COMMONWEALTH UNIV, MED COLL VIRGINIA, DEPT PSYCHIAT, RICHMOND, VA 23298 USA. VIRGINIA COMMONWEALTH UNIV, MED COLL VIRGINIA, DEPT HUMAN GENET, RICHMOND, VA 23298 USA. UNIV CINCINNATI, COLL MED, DEPT ANAT & CELL BIOL, CINCINNATI, OH 45267 USA. RP NCI, CELLULAR ONCOL LAB, BETHESDA, MD 20892 USA. FU NCI NIH HHS [CA 16059] NR 58 TC 474 Z9 475 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD APR 17 PY 1992 VL 69 IS 2 BP 265 EP 273 DI 10.1016/0092-8674(92)90407-4 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA HQ183 UT WOS:A1992HQ18300006 PM 1568246 ER PT J AU THURKAUF, A MATTSON, MV RICHARDSON, S MIRSADEGHI, S ORNSTEIN, PL HARRISON, EA RICE, KC JACOBSON, AE MONN, JA AF THURKAUF, A MATTSON, MV RICHARDSON, S MIRSADEGHI, S ORNSTEIN, PL HARRISON, EA RICE, KC JACOBSON, AE MONN, JA TI ANALOGS OF THE DIOXOLANES DEXOXADROL AND ETOXADROL AS POTENTIAL PHENCYCLIDINE-LIKE AGENTS - SYNTHESIS AND STRUCTURE-ACTIVITY-RELATIONSHIPS SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID BRAIN MEMBRANES; CONFIGURATION; BINDING AB A series of dioxolane analogues based on dexoxadrol ((4S,6S)-2,2-diphenyl-4-(2-piperidyl)-1,3-dioxolane) and etoxadrol ((2S,4S,6S)-2-ethyl-2-phenyl-4-(2-piperidyl)-1,3-dioxolane) were prepared and tested for their ability to displace [H-3]TCP (1-[1-(2-thienyl)cyclohexyl]piperidine) from PCP (1-(1-phenylcyclohexyl)piperidine) binding sites in rat brain tissue homogenates. Qualitative structure-activity relationships within this series were explored through modifications of the three major structural units of dexoxadrol, the piperidine, 1,3-dioxolane, and aromatic rings of the molecule. N-Alkyl derivatives of dexoxadrol were found to be inactive, as were those analogues where the dioxolane ring was modified. Phenyl-substituted etoxadrol analogues were compared to similarly substituted PCP analogues and distinct differences were found in their structure-activity relationships suggesting that the aromatic rings in these two drug classes interact differently with the PCP binding sites. The replacement of the phenyl ring in etoxadrol by either a 2- or 3-thienyl ring led to compounds with affinity comparable to etoxadrol, and the replacement of the ethyl moiety on etoxadrol's dioxolane ring with propyl (7) or isopropyl (8) led to compounds which were more potent than etoxadrol or PCP. The most potent compound was (2S,4S,6S)-2-ethyl-2-(1-chlorophenyl)-4-(2-piperidyl)-1,3-dioxolane (11), where a chlorine moiety was placed in the ortho position in the aromatic ring of etoxadrol. Its potency was comparable with TCP in vitro. C1 NIDDKD,MED CHEM LAB,BETHESDA,MD 20892. ELI LILLY & CO,INDIANAPOLIS,IN 46285. PENN STATE UNIV,YORK,PA 17403. RI Ornstein, Paul/E-4212-2016 OI Ornstein, Paul/0000-0002-4335-1877 FU NIDA NIH HHS [5F32 DAO5287-02] NR 27 TC 30 Z9 30 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD APR 17 PY 1992 VL 35 IS 8 BP 1323 EP 1329 DI 10.1021/jm00086a001 PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA HQ011 UT WOS:A1992HQ01100001 PM 1349351 ER PT J AU BARRY, CE HAYES, SF HACKSTADT, T AF BARRY, CE HAYES, SF HACKSTADT, T TI NUCLEOID CONDENSATION IN ESCHERICHIA-COLI THAT EXPRESS A CHLAMYDIAL HISTONE HOMOLOG SO SCIENCE LA English DT Article ID GENE-EXPRESSION; PSEUDOMONAS-AERUGINOSA; DNA; PROTEIN; TRACHOMATIS; VIRULENCE; BACTERIA; CYCLE; H1 AB Chlamydial cell types are adapted for either extracellular survival or intracellular growth. In the transcriptionally inert elementary bodies, the chromosome is densely compacted; in metabolically active reticulate bodies, the chromatin is loosely organized. Condensation of the chlamydial nucleoid occurs concomitant with expression of proteins homologous to eukaryotic histone H1. When the Chlamydia trachomatis 18-kilodalton histone homolog Hcl is expressed in Escherichia coli, a condensed nucleoid structure similar to that of chlamydiae is observed with both light and electron microscopy. These results support a role for Hc1 in condensation of the chlamydial nucleoid. C1 NIAID,ROCKY MT LABS,INTRACELLULAR PARASITES LAB,HAMILTON,MT 59840. NIAID,ROCKY MT LABS,VECTORS & PATHOGENS LAB,STRUCT PATHOBIOL SECT,HAMILTON,MT 59840. RI Barry, III, Clifton/H-3839-2012 NR 35 TC 87 Z9 87 U1 0 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD APR 17 PY 1992 VL 256 IS 5055 BP 377 EP 379 DI 10.1126/science.256.5055.377 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HP032 UT WOS:A1992HP03200036 PM 1566085 ER PT J AU CHESEBRO, B AF CHESEBRO, B TI SPONGIFORM ENCEPHALOPATHIES - PRP AND THE SCRAPIE AGENT SO NATURE LA English DT Editorial Material ID TRANSGENIC MICE; PRION PROTEIN RP CHESEBRO, B (reprint author), NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840, USA. NR 13 TC 28 Z9 28 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD APR 16 PY 1992 VL 356 IS 6370 BP 560 EP 560 DI 10.1038/356560a0 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HP031 UT WOS:A1992HP03100023 PM 1348569 ER PT J AU SHER, A AF SHER, A TI SCHISTOSOMIASIS - PARASITIZING THE CYTOKINE SYSTEM SO NATURE LA English DT Editorial Material RP SHER, A (reprint author), NIAID,PARASIT DIS LAB,BETHESDA,MD 20892, USA. NR 14 TC 12 Z9 14 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD APR 16 PY 1992 VL 356 IS 6370 BP 565 EP 566 DI 10.1038/356565a0 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HP031 UT WOS:A1992HP03100031 PM 1560840 ER PT J AU GRAHAM, NMH ZEGER, SL PARK, LP VERMUND, SH DETELS, R RINALDO, CR PHAIR, JP AF GRAHAM, NMH ZEGER, SL PARK, LP VERMUND, SH DETELS, R RINALDO, CR PHAIR, JP TI THE EFFECTS ON SURVIVAL OF EARLY TREATMENT OF HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PNEUMOCYSTIS-CARINII PNEUMONIA; PLACEBO-CONTROLLED TRIAL; MULTICENTER AIDS COHORT; HIV INFECTION; DOUBLE-BLIND; ZIDOVUDINE; EFFICACY; SAFETY; AZT AB Background. Zidovudine has been shown to prolong survival in patients with the acquired immunodeficiency syndrome (AIDS) and, in persons with human immunodeficiency virus (HIV) infection but not AIDS, to delay the progression to AIDS. However, it is still uncertain whether treatment before the development of AIDS prolongs survival. Methods. We analyzed data from a cohort of 2162 high-risk men who were already seropositive for HIV type 1 (HIV-1) and 406 men who seroconverted from October 1986 through April 1991. There were 306 deaths. The probabilities of death were compared among men at similar stages of disease who began zidovudine therapy before the diagnosis of AIDS and among those who did not. Relative risks of death were calculated for each of five initial disease states on the basis of CD4+ cell counts and clinical symptoms and signs appearing over follow-up periods of 6, 12, 18, and 24 months. Adjustments were also made for the use of prophylaxis against Pneumocystis carinii pneumonia (PCP). Results. After we controlled for CD4+ cell count and symptoms, the use of zidovudine with or without PCP prophylaxis before the development of AIDS significantly reduced mortality in all follow-up periods. The relative risks of death were 0.43 (95 percent confidence interval, 0.23 to 0.78) at 6 months, 0.54 (95 percent confidence interval, 0.38 to 0.78) at 12 months, 0.59 (95 percent confidence interval, 0.44 to 0.79) at 18 months, and 0.67 (95 percent confidence interval, 0.52 to 0.86) at 24 months. After we adjusted for the effects of PCP prophylaxis, zidovudine alone significantly reduced mortality at 6, 12, and 18 months (relative risks, 0.45, 0.59, and 0.70, respectively), but not at 24 months (relative risk, 0.81). Among zidovudine users, those who also used PCP prophylaxis before the development of AIDS had significantly lower mortality at 18 and 24 months than those who did not (relative risks, 0.62 and 0.60, respectively). Conclusions. The results of this study support the hypothesis that in HIV-1 infection, early treatment with zidovudine and PCP prophylaxis improves survival in addition to slowing the progression to AIDS. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT BIOSTAT,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. NIAID,DIV AIDS,BETHESDA,MD 20892. UNIV CALIF LOS ANGELES,SCH PUBL HLTH,DEPT EPIDEMIOL,LOS ANGELES,CA 90024. UNIV PITTSBURGH,SCH PUBL HLTH,DEPT INFECT DIS & MICROBIOL,PITTSBURGH,PA 15260. NORTHWESTERN UNIV,HOWARD BROWN MEM CLIN,CHICAGO,IL 60611. NORTHWESTERN UNIV,DEPT MED,CHICAGO,IL 60611. RP GRAHAM, NMH (reprint author), JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,624 N BROADWAY,BALTIMORE,MD 21205, USA. OI Vermund, Sten/0000-0001-7289-8698 FU PHS HHS [N01-A1-32535, N01-A1-72634, N01-A1-72676] NR 18 TC 220 Z9 221 U1 0 U2 2 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 16 PY 1992 VL 326 IS 16 BP 1037 EP 1042 DI 10.1056/NEJM199204163261601 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA HN738 UT WOS:A1992HN73800001 PM 1347907 ER PT J AU GONZALEZ, CL MEDEIROS, LJ JAFFE, ES AF GONZALEZ, CL MEDEIROS, LJ JAFFE, ES TI DELTA-POSITIVE T-CELL LYMPHOMA THAT PRODUCES INTERFERON-GAMMA SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID CYTOPHAGIC HISTIOCYTIC PANNICULITIS; MALIGNANT HISTIOCYTOSIS C1 NCI,BETHESDA,MD 20892. RP GONZALEZ, CL (reprint author), PORTER MEM HOSP,DENVER,CO 80210, USA. NR 8 TC 4 Z9 4 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 16 PY 1992 VL 326 IS 16 BP 1088 EP 1089 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA HN738 UT WOS:A1992HN73800026 PM 1549167 ER PT J AU EAKER, ED PINSKY, J CASTELLI, WP AF EAKER, ED PINSKY, J CASTELLI, WP TI MYOCARDIAL-INFARCTION AND CORONARY DEATH AMONG WOMEN - PSYCHOSOCIAL PREDICTORS FROM A 20-YEAR FOLLOW-UP OF WOMEN IN THE FRAMINGHAM-STUDY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE BEHAVIOR; CORONARY DISEASE; PSYCHOLOGY; SOCIOLOGY; WOMEN ID HEART-DISEASE; POPULATION; MORTALITY AB This study investigates the relation of psychosocial variables to the 20-year incidence of myocardial infarction or coronary death among women in the Framingham Study. In 1965-1967, a psychosocial interview was given along with the collection of other coronary risk factor data. This study includes 749 women aged 45-64 years who were free of coronary disease at this baseline examination. Demographic variables, psychosocial scales (such as tension and reactions of anger), and individual interview items (such as attitudes toward children, money, and religion) were measured. When age, systolic blood pressure, the ratio of serum total cholesterol to high-density lipoprotein cholesterol, diabetes, cigarette smoking, and body mass index were controlled for in multivariate proportional hazards models, the predictors of the 20-year incidence of myocardial infarction or coronary death were as follows: among employed women, perceived financial status only; among homemakers, symptoms of tension and anxiety, being lonely during the day, difficulty falling asleep, infrequent vacations, housework affecting health, and believing one is prone to heart disease (p < 0.05 for all variables); and among both groups of women combined, low educational level, tension, and lack of vacations. These results are discussed in relation to previous findings from the Framingham Study. C1 NHLBI,BETHESDA,MD 20892. RP EAKER, ED (reprint author), CTR DIS CONTROL,DIV SURVEILLANCE & EPIDEMIOL,EPIDEMIOL PROGRAM OFF,1600 CLIFTON RD,ATLANTA,GA 30333, USA. NR 19 TC 228 Z9 230 U1 0 U2 4 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD APR 15 PY 1992 VL 135 IS 8 BP 854 EP 864 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA HY448 UT WOS:A1992HY44800003 PM 1585898 ER PT J AU CLEMENS, JD VANLOON, FFPL RAO, M SACK, DA AHMED, F CHAKRABORTY, J KHAN, MR YUNUS, M HARRIS, JR SVENNERHOLM, AM HOLMGREN, J AF CLEMENS, JD VANLOON, FFPL RAO, M SACK, DA AHMED, F CHAKRABORTY, J KHAN, MR YUNUS, M HARRIS, JR SVENNERHOLM, AM HOLMGREN, J TI NONPARTICIPATION AS A DETERMINANT OF ADVERSE HEALTH OUTCOMES IN A FIELD TRIAL OF ORAL CHOLERA VACCINES SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE CHOLERA; CLINICAL TRIALS; COOPERATIVE BEHAVIOR; VACCINES ID BANGLADESH; EFFICACY AB The authors estimated the incidence rates of cholera and death between 1985 and 1988 for 32,642 age- and sex-eligible persons who did not participate in a randomized, placebo-controlled field trial of killed oral cholera vaccines in rural Bangladesh. As compared with 20,744 placebo recipients, the relative risk of cholera for all nonparticipants, adjusted for potentially confounding demographic variables, was 1.20 (95% confidence interval (CI) 1.03-1.41); this adjusted relative risk reflected elevated adjusted relative risks in nonparticipants who were medically ineligible (RR = 1.65; 95% CI 1.22-2.22) or refused to participate (RR = 1.19; 95% CI 1.01-1.41), but not in persons absent at the time of vaccination (RR = 1.00; 95% CI 0.78-1.28). The adjusted relative risk of death was also elevated in nonparticipants as compared with placebo recipients (RR = 1.28; 95% CI 1.10-1.48), with the same pattern of adjusted relative risks for different categories of nonparticipants: for ineligible subjects, 2.64 (95% CI 2.12-3.29); for refusers, 1.20 (95% CI 1.02-1.41); and for absentees, 0.95 (95% CI 0.75-1.22). The authors concluded that nonparticipation was associated with clinically cogent adverse health outcomes, but that the magnitude of these associations varied according to the reason for nonparticipation. These findings underscore the caution required in assessing vaccine efficacy with controls who are not vaccinated because of choices made by patients or vaccinators. C1 NICHHD,DIV EPIDEMIOL STAT & PREVENT RES,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH PUBL HLTH,DEPT INT HLTH,BALTIMORE,MD 21218. CTR DIS CONTROL,ENTER DIS BRANCH,ATLANTA,GA 30333. GOTHENBURG UNIV,DEPT MED MICROBIOL,S-41124 GOTHENBURG,SWEDEN. INT CTR DIARRHOEL DIS RES,DHAKA,BANGLADESH. OI Harris, Jeffrey/0000-0001-8728-7195 NR 25 TC 20 Z9 20 U1 2 U2 2 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD APR 15 PY 1992 VL 135 IS 8 BP 865 EP 874 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA HY448 UT WOS:A1992HY44800004 PM 1585899 ER PT J AU MANOLIO, TA FURBERG, CD WAHL, PW TRACY, RP BORHANI, NO GARDIN, JM FRIED, LP OLEARY, DH KULLER, LH AF MANOLIO, TA FURBERG, CD WAHL, PW TRACY, RP BORHANI, NO GARDIN, JM FRIED, LP OLEARY, DH KULLER, LH TI ELIGIBILITY FOR CHOLESTEROL REFERRAL IN COMMUNITY-DWELLING OLDER ADULTS - THE CARDIOVASCULAR-HEALTH-STUDY SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE LIPOPROTEINS; CORONARY DISEASE; HYPERCHOLESTEROLEMIA; ANTILIPEMIC AGENTS; GERIATRICS; HEALTH SERVICES FOR THE AGED ID CORONARY HEART-DISEASE; DENSITY-LIPOPROTEIN CHOLESTEROL; RISK-FACTORS; SERUM-CHOLESTEROL; EDUCATION-PROGRAM; SOCIAL-CLASS; PREVALENCE; LEVEL AB Objectives: To assess the proportion of community-dwelling adults aged 65 years or older who are eligible for referral for lipoprotein analysis and intervention according to the National Cholesterol Education Program (NCEP) guidelines. Design: Cross-sectional study based on examinations and questionnaires collected in 1989 and 1990. Setting: Four communities in the U.S. in the Cardiovascular Health Study (CHS), a study of risk factors for heart disease and stroke in older adults. Participants: A sample of 4810 men and women ages 65 to 100 randomly selected and recruited from Health Care Financing Administration Medicare eligibility lists for the four communities; not institutionalized, not wheelchair-bound, not currently receiving therapy for cancer, not currently taking lipid-lowering medications, and not having eaten in the preceding 9 hours. Measurements: Total cholesterol and lipoprotein analysis measured in all participants. Results: Total cholesterol levels were less than 5.17 mmol/L (200 mg/dL) in 37% of participants, 5.17 to 6.19 mmol/L (200 to 239 mg/dL) in 39%, and 6.20 mmol/L (240 mg/dL) or greater in 24%. Compared with their counterparts, older participants, especially those over 80 years of age, were more likely to have levels below 5.17 mmol/L, as were men, nonwhites, and those with coronary heart disease or two or more coronary heart disease risk factors (P < 0.008 for all values). Based on this screening measurement, 2174 participants were eligible for lipoprotein analysis, 80% were eligible for dietary or drug therapy using NCEP guidelines. Overall, 46% of CHS participants were eligible for lipoprotein analysis and 36% for intervention by NCEP guidelines, based on a single cholesterol measurement. Conclusion: A substantial proportion of older adults in this community sample were eligible for lipoprotein analysis and intervention. Prospective studies of elderly persons are needed to determine the risk for incident coronary heart disease according to NCEP classifications and the benefits of lipid-lowering treatments in persons in this age group so that intervention strategies may best be targeted to an appropriately high-risk group. C1 NHLBI,BETHESDA,MD 20892. WAKE FOREST UNIV,BOWMAN GRAY SCH MED,WINSTON SALEM,NC 27103. UNIV VERMONT,BURLINGTON,VT 05405. UNIV CALIF IRVINE,IRVINE,CA 92717. JOHNS HOPKINS UNIV,BALTIMORE,MD 21218. GEISINGER MED CTR,DANVILLE,PA 17822. UNIV PITTSBURGH,PITTSBURGH,PA 15260. RP MANOLIO, TA (reprint author), UNIV WASHINGTON,CTR CARDIOVASC HLTH STUD COORDINAT,JD-30,1107 NE 45TH ST,SUITE 530,SEATTLE,WA 98195, USA. FU NHLBI NIH HHS [N01-HC-85079, N01-HC-85081, N01-HC-85080] NR 38 TC 20 Z9 20 U1 2 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD APR 15 PY 1992 VL 116 IS 8 BP 641 EP 649 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA HN844 UT WOS:A1992HN84400006 PM 1546864 ER PT J AU AUSTIN, HA ANTONOVYCH, TT MACKAY, K BOUMPAS, DT BALOW, JE AF AUSTIN, HA ANTONOVYCH, TT MACKAY, K BOUMPAS, DT BALOW, JE TI MEMBRANOUS NEPHROPATHY SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE GLOMERULONEPHRITIS, MEMBRANOUS; NEPHROTIC SYNDROME; KIDNEY FAILURE, CHRONIC; HYPERLIPIDEMIA; IMMUNOSUPPRESSIVE AGENTS ID PASSIVE HEYMANN NEPHRITIS; SYSTEMIC LUPUS-ERYTHEMATOSUS; GLOMERULAR EPITHELIAL-CELLS; CORONARY HEART-DISEASE; NEPHROTIC SYNDROME; CONTROLLED TRIAL; URINARY-EXCRETION; ATTACK COMPLEX; RENAL-FUNCTION; B-CELLS AB Membranous nephropathy is a worldwide problem that accounts for about 20% of the cases of the adult-onset nephrotic syndrome. This disease places many patients at risk for both end-stage renal failure and the complications of hyperlipidemia. Immune-mediated injury to the glomerular capillary wall in patients with membranous nephropathy is characterized by subepithelial immune complex formation and generation of the membrane attack complex of complement. Glomerular capillary hypertension, hyperlipidemia, and possibly cytokines could contribute to the glomerular sclerosis seen in the advanced stages of the disorder. In some cases, production of pathogenic antibody can be suppressed by treating the underlying condition. The mechanisms of action of immunosuppressive agents are being investigated and treatments are being tested in clinical trials to optimize the balance of efficacy and toxicity. Alternate-day treatment with corticosteroids is often recommended for nephrotic patients with idiopathic membranous nephropathy, but this approach has not been proved beneficial. Ongoing studies are evaluating whether cytotoxic drugs or cyclosporin A combined with prednisone is more effective than treatment with corticosteroids alone. Lipid-lowering drug therapy is warranted in cases of the persistent nephrotic syndrome to avert the cardiovascular sequelae of hyperlipidemia. RP AUSTIN, HA (reprint author), NIH,BLDG 10,ROOM 3N112,BETHESDA,MD 20892, USA. NR 102 TC 30 Z9 32 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 APR 15 PY 1992 VL 116 IS 8 BP 672 EP 682 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA HN844 UT WOS:A1992HN84400011 PM 1546869 ER PT J AU CARR, DJJ RADULESCU, RT DECOSTA, BR RICE, KC BLALOCK, JE AF CARR, DJJ RADULESCU, RT DECOSTA, BR RICE, KC BLALOCK, JE TI OPIOID MODULATION OF IMMUNOGLOBULIN PRODUCTION BY LYMPHOCYTES ISOLATED FROM PEYER PATCHES AND SPLEEN SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID IMMUNE-SYSTEM; DELTA-CLASS; RECEPTORS; ENDORPHIN; CELLS C1 UNIV MUNSTER, SCH MED, W-4400 MUNSTER, GERMANY. NIDDK, MED CHEM LAB, BETHESDA, MD 20892 USA. RP UNIV ALABAMA, DEPT PHYSIOL & BIOPHYS, UAB STN, BIRMINGHAM, AL 35294 USA. NR 12 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 APR 15 PY 1992 VL 650 BP 125 EP 127 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM218 UT WOS:A1992JM21800024 ER PT J AU FRIDE, E MENG, R SKOLNICK, P ARORA, PK AF FRIDE, E MENG, R SKOLNICK, P ARORA, PK TI IMMUNOENHANCING EFFECTS OF ALPRAZOLAM, A BENZODIAZEPINE RECEPTOR AGONIST SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article ID PLASMA CORTICOSTEROIDS; IMMUNE-RESPONSE; STRESS; DIAZEPAM; SUPPRESSION; ANXIETY; RATS; CHLORDIAZEPOXIDE; MODULATION; BRAIN C1 NIDDK, NEUROSCI LAB, ROOM 111, BLDG 8, BETHESDA, MD 20892 USA. NR 39 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 APR 15 PY 1992 VL 650 BP 132 EP 139 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM218 UT WOS:A1992JM21800026 ER PT J AU COE, CL ERSHLER, WB CHAMPOUX, M OLSON, J AF COE, CL ERSHLER, WB CHAMPOUX, M OLSON, J TI PSYCHOSOCIAL FACTORS AND IMMUNE SENESCENCE IN THE AGED PRIMATE SO ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article C1 UNIV WISCONSIN, DEPT MED, MADISON, WI 53706 USA. NICHHD, COMPARAT ETHOL LAB, BETHESDA, MD 20892 USA. RP COE, CL (reprint author), UNIV WISCONSIN, DEPT PSYCHOL, 1202 W JOHNSON ST, MADISON, WI 53706 USA. NR 11 TC 1 Z9 1 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PD APR 15 PY 1992 VL 650 BP 276 EP 282 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA JM218 UT WOS:A1992JM21800052 ER PT J AU HATFIELD, D CHOI, IS MISCHKE, S OWENS, LD AF HATFIELD, D CHOI, IS MISCHKE, S OWENS, LD TI SELENOCYSTEYL-TRANSFER RNAS RECOGNIZE UGA IN BETA-VULGARIS, A HIGHER-PLANT, AND IN GLIOCLADIUM-VIRENS, A FILAMENTOUS FUNGUS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID TRYPTOPHAN CODON; PROTEIN; READ; GENE C1 USDA ARS,BELTSVILLE AGR RES CTR,BIOCONTROL PLANT DIS LAB,BELTSVILLE,MD 20705. USDA ARS,BELTSVILLE AGR RES CTR,PLANT MOLEC BIOL LAB,BELTSVILLE,MD 20705. RP HATFIELD, D (reprint author), NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892, USA. NR 26 TC 50 Z9 51 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 15 PY 1992 VL 184 IS 1 BP 254 EP 259 DI 10.1016/0006-291X(92)91186-T PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA HP168 UT WOS:A1992HP16800038 PM 1567433 ER PT J AU LANKIEWICZ, L BOWERS, CY REYNOLDS, GA LABROO, V COHEN, LA VONHOF, S SIREN, AL SPATOLA, AF AF LANKIEWICZ, L BOWERS, CY REYNOLDS, GA LABROO, V COHEN, LA VONHOF, S SIREN, AL SPATOLA, AF TI BIOLOGICAL-ACTIVITIES OF THIONATED THYROTROPIN-RELEASING-HORMONE ANALOGS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID HISTIDINE ANALOGS; RECEPTOR-BINDING; THIOAMIDES; PSEUDOPEPTIDES; PEPTIDE; BOND; RAT C1 UNIV LOUISVILLE,DEPT CHEM,LOUISVILLE,KY 40292. TULANE UNIV,SCH MED,NEW ORLEANS,LA 70112. NIH,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,DEPT NEUROL,BETHESDA,MD 20814. OI Siren, Anna-Leena/0000-0002-2217-0081 NR 26 TC 15 Z9 15 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 15 PY 1992 VL 184 IS 1 BP 359 EP 366 DI 10.1016/0006-291X(92)91201-Z PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA HP168 UT WOS:A1992HP16800053 PM 1314591 ER PT J AU YEDGAR, S EIDELMAN, O MALDEN, E ROBERTS, D ETCHEBERRIGARAY, R GOPING, G FOX, C POLLARD, HB AF YEDGAR, S EIDELMAN, O MALDEN, E ROBERTS, D ETCHEBERRIGARAY, R GOPING, G FOX, C POLLARD, HB TI CYCLIC AMP-INDEPENDENT SECRETION OF MUCIN BY SW1116-HUMAN COLON-CARCINOMA CELLS - DIFFERENTIAL CONTROL BY CA2+ IONOPHORE-A23187 AND ARACHIDONIC-ACID SO BIOCHEMICAL JOURNAL LA English DT Article ID MONOCLONAL-ANTIBODY 19-9; CYSTIC-FIBROSIS PATIENTS; PROTEIN KINASE-C; CHLORIDE CHANNELS; HUMAN AIRWAYS; RELEASE; LINE; CULTURE; SERUM; MUCUS AB The regulation of mucin secretion by SW1116 human colon carcinoma cells has been studied using monoclonal antibody 19-9, which has previously been used to detect mucin in the serum of cancer and cystic fibrosis patients. We found that SW1116 cells constitutively secrete considerable amounts of mucin as the predominant glycoprotein. The secretion of mucin by these cells is independent of cyclic AMP levels. but can be further stimulated by the Ca2+ ionophore A23187. However, arachidonic acid and its metabolites inhibit mucin secretion. Electron microscope studies reveal that the mucin is located near the plasma membrane as well as in vesicular and lysosome-like structures. However, the secretion pathway of mucin is different than that of the lysosomal contents, since arachidonic acid, while inhibiting mucin secretion, actually activates the secretion of the lysosomal enzyme beta-glucuronidase. We suggest that the mechanism of mucin secretion by SW1116 cells occurs by a pathway different from common exocytosis, and possibly by more than one pathway. The response of mucin secretion by SW1116 cells to common secretagogues resembles that of epithelial cells obtained from cystic fibrosis patients. Thus SW1116 cells are an especially interesting system for studying processes related to pathological states associated with excessive constitutive secretion of mucin. C1 HEBREW UNIV JERUSALEM,DEPT BIOL CHEM,IL-91010 JERUSALEM,ISRAEL. NIDDK,CELL BIOL & GENET LAB,BETHESDA,MD 20892. NIDR,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. NINCDS,NEURAL SYST SECT,BETHESDA,MD 20892. RP YEDGAR, S (reprint author), HEBREW UNIV JERUSALEM,HADASSAH MED SCH,DEPT BIOCHEM,IL-91010 JERUSALEM,ISRAEL. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 NR 24 TC 11 Z9 11 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 APR 15 PY 1992 VL 283 BP 421 EP 426 PN 2 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HQ878 UT WOS:A1992HQ87800018 PM 1374231 ER PT J AU RAUSCH, DM LIFSON, JD PADGETT, MP CHANDRASEKHAR, B LENDVAY, J HWANG, KM EIDEN, LE AF RAUSCH, DM LIFSON, JD PADGETT, MP CHANDRASEKHAR, B LENDVAY, J HWANG, KM EIDEN, LE TI CD4(81-92)-BASED PEPTIDE DERIVATIVES - STRUCTURAL REQUIREMENTS FOR BLOCKADE OF HIV-INFECTION, BLOCKADE OF HIV-INDUCED SYNCYTIUM FORMATION, AND VIROSTATIC ACTIVITY INVITRO SO BIOCHEMICAL PHARMACOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN CD4; T4 MOLECULE; HTLV-III; MONOCLONAL-ANTIBODIES; BINDING; RETROVIRUS; AIDS; IDENTIFICATION; RECEPTOR AB CD4(81-92) peptides block human immunodeficiency virus (HIV) infection, virus-induced cell fusion, and antigen production by HIV-1-infected cells when derivatized on specific amino acid residues. An extensive series of structural variants of 1.4,5-tribenzyl-10-acetyl-CD4(81-92) were tested as anti-viral agents in an attempt to define the sequence and derivatization requirements for antiviral activity, and to maximize potency and stability for use as potential therapeutic agents. Alteration of the primary amino acid sequence of the stem compound 1,4,5-tribenzyl-CD4(81-92) diminished or abolished in parallel all three indices of anti-viral activity in a series of altered sequence compounds. Replacement of d- for l-amino acid residues at positions 1, 2, 3, 4, 5, or 6 but not position 10 decreased anti-viral potency, again with parallel effects on infection, synctium formation, and virostatic activity. Omission of the glutamine residue at position 9 did not affect anti-viral potency, while removal of the glutamic acids at positions 11 and 12 resulted in virtually complete loss of biological activity. Changes in the derivatization pattern of the CD4(81-92) peptide backbone also affected anti-viral potency and efficacy. Optimal activity was obtained with benzyl residues at positions 1, 4, and 5, whereas the 1,4,7-tribenzyl-CD4 (81-92) compound was without activity in all assays tested. Replacement of one of the benzyl groups with an acetamidomethyl moiety resulted in complete loss of biological activity. The previously reported (Nara et al., Proc Natl Acad Sci USA 86: 7139-7143, 1989) virostatic activity of 1,4,5-tribenzyl-10-acetyl-CD4(81-92) (peptide #18) is apparently due to acetylation, since the desacetyl stem compound shows much less virostatic activity while still possessing full anti-infective and anti-syncytial activity, and acetylation of the N-terminus rather than the lysine of 1,4,5-tribenzyl-CD4 (81-92) yields a virostatic compound equipotent to peptide #18. Cyclization of the tribenzyl peptide to further conformationally restrict the molecule resulted in a compound with anti-infection, anti-syncytial, and virostatic activity at submicromolar concentrations, C1 GENELABS INC, DIV HIV & EXPLORATORY RES, REDWOOD CITY, CA 94063 USA. GENELABS INC, DIV BIOMED CHEM, REDWOOD CITY, CA 94063 USA. RP RAUSCH, DM (reprint author), NIMH, CELL BIOL LAB, MOLEC & CELLULAR BIOL UNIT, BETHESDA, MD 20892 USA. OI Eiden, Lee/0000-0001-7524-944X NR 44 TC 10 Z9 10 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD APR 15 PY 1992 VL 43 IS 8 BP 1785 EP 1796 DI 10.1016/0006-2952(92)90711-Q PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA HR716 UT WOS:A1992HR71600018 PM 1575773 ER PT J AU KORPI, ER UUSIOUKARI, M WEGELIUS, K CASANOVA, MF ZITO, M KLEINMAN, JE AF KORPI, ER UUSIOUKARI, M WEGELIUS, K CASANOVA, MF ZITO, M KLEINMAN, JE TI CEREBELLAR AND FRONTAL CORTICAL BENZODIAZEPINE RECEPTORS IN HUMAN ALCOHOLICS AND CHRONICALLY ALCOHOL-DRINKING RATS SO BIOLOGICAL PSYCHIATRY LA English DT Article ID GAMMA-AMINOBUTYRIC ACID; OPERATED CHLORIDE CHANNELS; INVERSE AGONIST ACTIONS; RO 15-4513; POSTMORTEM CHANGES; RO 15-4513; ETHANOL; BINDING; GABA; BRAIN AB Postmortem cerebellar and frontal cortical membrane homogenates from human alcoholics, control subjects without neurological or psychiatric illnesses, and rats that chronically drank alcohol were studied to determine the binding characteristics of an imidazobenzodiazepine, [H-3]Ro 154513. This ligand binds to classical gamma-aminobutyric acid(A) (GABA(A))/benzodiazepine receptors, as well as to a "diazempam-insensitive" site associated with the GABA(A) receptor complex in the cerebellar granule cell layer. There were no differences in the density of the binding sites between alcoholics and their controls, between alcohol-drinking AA rats that had a choice between 10% alcohol or water for about 10 weeks and their controls, or between Wistar rats that had been given 20% alcohol as their only fluid for 4 months and their controls, which were pair-fed isocalorically with sucrose. The affinity for the cerebellar binding of [H-3]Ro 15-4513 was higher in the alcoholics than the controls. No differences were observed in the frontocortical binding. No affinity differences were observed in the rat models. There were no differences between the groups in the characteristics of [H-3]Ro 154513 binding to human cerebellum in the presence of micromolar diazepam, thus revealing the diazepam-insensitive binding. When this component was subtracted from the total cerebellar binding, to reveal the diazepam sensitive binding, both the K(D) and B(max) were lower in the alcoholic than the control group. The binding of [H-3]muscimol, a GABA(A) agonist, tended to be higher in the frontal cortices of alcoholics; a similar trend for greater effects was observed in the alcoholics for the GABA inhibition of [H-3]Ro 154513 binding. These results suggest that no drastic changes occur through chronic alcohol abuse in the numbers of cerebellar and frontocortical benzodiazepine receptors in humans and rodent models; however, the data indicate that the alcoholics have either acquired or innate differences in classical benzodiazepine recognition sites of the cerebellum and in the coupling of these sites to GABA(A) sites in the frontal cortex, without any differences in cerebellar granule cell-specific diazepam-insensitive [H-3]Ro 154513 binding sites. C1 ST ELIZABETH HOSP, NIMH, CTR NEUROSCI, CLIN BRAIN DISORDERS BRANCH, WASHINGTON, DC 20032 USA. RP KORPI, ER (reprint author), ALKO LTD, RES LABS, POB 350, SF-00101 HELSINKI, FINLAND. OI Uusi-Oukari, Mikko/0000-0003-1756-4577 NR 48 TC 19 Z9 19 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 1992 VL 31 IS 8 BP 774 EP 786 DI 10.1016/0006-3223(92)90309-N PG 13 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA JA822 UT WOS:A1992JA82200003 PM 1322720 ER PT J AU HOURDILLE, P GRALNICK, HR HEILMANN, E DERLON, A FERRER, AM VEZON, G NURDEN, AT AF HOURDILLE, P GRALNICK, HR HEILMANN, E DERLON, A FERRER, AM VEZON, G NURDEN, AT TI VONWILLEBRAND-FACTOR BOUND TO GLYCOPROTEIN-IB IS CLEARED FROM THE PLATELET SURFACE AFTER PLATELET ACTIVATION BY THROMBIN SO BLOOD LA English DT Article ID IIB-IIIA COMPLEX; RECEPTOR LIGAND COMPLEXES; STIMULATED PLATELETS; BLOOD-PLATELETS; FACTOR-BINDING; GLANZMANNS THROMBASTHENIA; MONOCLONAL-ANTIBODIES; CANALICULAR SYSTEM; IIB/IIIA COMPLEX; MEMBRANE C1 NIH,CTR CLIN,DEPT CLIN PATHOL,HEMATOL SERV,BETHESDA,MD 20892. HOP COTE NARCE,HEMATOL LAB,CAEN,FRANCE. CTR REG TRANSFUS SANGUINE,BORDEAUX,FRANCE. RP HOURDILLE, P (reprint author), UNIV BORDEAUX 02,HOP CARDIOL,HEMOBIOL LAB,CNRS,URA 1464,AVE MAGELLAN,F-33604 PESSAC,FRANCE. NR 54 TC 46 Z9 47 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 APR 15 PY 1992 VL 79 IS 8 BP 2011 EP 2021 PG 11 WC Hematology SC Hematology GA HW416 UT WOS:A1992HW41600016 PM 1562727 ER PT J AU SLOAND, EM KLEIN, HG PASTAKIA, KB PIERCE, P PRODOUZ, KN AF SLOAND, EM KLEIN, HG PASTAKIA, KB PIERCE, P PRODOUZ, KN TI EFFECT OF ALBUMIN ON THE INHIBITION OF PLATELET-AGGREGATION BY BETA-LACTAM ANTIBIOTICS SO BLOOD LA English DT Article ID PARTICULARLY TISSUE PENETRATION; PROTEIN-BINDING; BLOOD-COAGULATION; ARACHIDONIC-ACID; FACTOR-VIII; INVITRO; MOXALACTAM; PENICILLIN; LATAMOXEF; INVIVO C1 WARREN G MAGNUSON CLIN CTR,BETHESDA,MD. NHLBI,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20014. GEORGETOWN UNIV,MED CTR,WASHINGTON,DC 20007. RP SLOAND, EM (reprint author), NIH,DEPT TRANSFUS MED,NIH BLDG 31,ROOM 5A21,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 31 TC 6 Z9 6 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD APR 15 PY 1992 VL 79 IS 8 BP 2022 EP 2027 PG 6 WC Hematology SC Hematology GA HW416 UT WOS:A1992HW41600017 PM 1562728 ER PT J AU BYRNE, J KESSLER, LG DEVESA, SS AF BYRNE, J KESSLER, LG DEVESA, SS TI THE PREVALENCE OF CANCER AMONG ADULTS IN THE UNITED-STATES - 1987 SO CANCER LA English DT Article ID SURVIVORS; CHILDHOOD AB No national data exist on the prevalence of cancer in the United States population. The authors report the first estimates of prevalence rates of cancer from a population-based sample of the adult population of the United States. Estimates are based on responses collected from the Cancer Control Supplements of the National Health Interview Survey, a population-based sample survey of all people older than 17 years of age in the United States in 1987. Of 44,123 adults questioned, 1593 said they had a nonskin cancer. In 1987, after adjustments, the overall prevalence rate of all types of cancer, excluding nonmelanoma skin cancer, was 3230 per 100,000 adults; the rates for men and women were 1930 and 4412, respectively. The authors estimate that, in 1987, 5.7 million adults in the United States were survivors of nonskin cancer, 3.3% of the adult population. Approximately 89,000 adults had cancer during childhood, or 1.6% of the total. Approximately 3.6 million people were at least 5-year survivors and 900,000 adults had their disease diagnosed during the year before interview. Despite the potential for underreporting and misclassification, these national estimates are in general accord with figures estimated from other sources. Increasing survival after cancer, especially childhood and adolescent cancer, indicates the importance of continued monitoring to provide information needed to plan for adequate services. C1 NCI,DIV CANC ETIOL,EPIDEMIOL BRANCH,BETHESDA,MD 20892. NCI,DIV CANC ETIOL,BIOSTAT BRANCH,BETHESDA,MD 20892. NCI,DIV CANC PREVENT & CONTROL,APPL RES BRANCH,BETHESDA,MD 20892. NR 16 TC 31 Z9 31 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 APR 15 PY 1992 VL 69 IS 8 BP 2154 EP 2159 DI 10.1002/1097-0142(19920415)69:8<2154::AID-CNCR2820690823>3.0.CO;2-R PG 6 WC Oncology SC Oncology GA HL102 UT WOS:A1992HL10200022 PM 1544121 ER PT J AU LIJINSKY, W KOVATCH, RM SAAVEDRA, JE AF LIJINSKY, W KOVATCH, RM SAAVEDRA, JE TI CARCINOGENESIS AND MUTAGENESIS BY N-NITROSO COMPOUNDS HAVING A BASIC CENTER SO CANCER LETTERS LA English DT Article DE NITROSAMINE; NITROSOUREA; RAT; NASAL TUMORS; ESOPHAGUS; HAMSTER ID ASSAY; RAT AB Two N-nitroso compounds that are derivatives of N,N-dimethylethylenediamine and are therefore strongly basic, were tested for carcinogenic activity. They were methylnitrosamino-N,N-dimethylethylamine (MNDMEA) and N,N-dimethylaminoethylnitrosoethylurea (DMENEU). Each was administered orally to male and female F344 rats by gavage. MNDMEA was also given by gavage to Syrian hamsters and to rats as a solution in drinking water. The response of rats treated with MNDMEA was almost the same by the two modes of treatment and all developed tumors of the esophagus and died in less than 40 weeks; many also had tumors of the nasal mucosa. Hamsters were less susceptible to the nitrosamine than rats, since they survived longer following a larger dose and the tumor incidence was small; several hamsters had tumors of the nasal mucosa, some males also had tumors of the liver and lung and one male and two females had a tumor of the colon. Although it is a strong directly acting mutagen, dimethylaminoethylnitrosoethylurea was weakly carcinogenic in rats, giving rise to tumors of the uterus and mammary gland in females, but having no particular target organ in male rats. The presence of a basic center in these N-nitroso compounds does not prevent their absorption nor their entry into cells, which they can transform to tumors. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. FU PHS HHS [N01-C0-74101] NR 14 TC 5 Z9 5 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 APR 15 PY 1992 VL 63 IS 2 BP 101 EP 107 DI 10.1016/0304-3835(92)90059-5 PG 7 WC Oncology SC Oncology GA HQ036 UT WOS:A1992HQ03600003 PM 1562986 ER PT J AU DABHOLKAR, M REED, E AF DABHOLKAR, M REED, E TI HOST-CELL REACTIVATION OF CISPLATIN-DAMAGED PLASMID DNA IN HUMAN NON-T-LEUKOCYTE CELL-LINES SO CANCER LETTERS LA English DT Article DE CISPLATIN; LEUKOCYTES; PRSVCAT; ELECTROPORATION; DNA REPAIR ID OVARIAN-CANCER PATIENTS; ACETYLTRANSFERASE GENE-EXPRESSION; ADDUCT LEVELS; RAPID ASSAY; CIS-DIAMMINEDICHLOROPLATINUM(II); CHEMOTHERAPY; SECRETION; IGM AB Host-cell reactivation of cisplatin-damaged pRSVcat was assessed in three B cell lines (SKW 6.4, WIL2-NS, RPMI 1788), the monocytic cell line THP-1, and promyelocytic HL-60 cells. IC50 values following a 3-day exposure of the five leukocyte cell lines to cisplatin ranged from 0.45 to 1.92-mu-M. Transfer of pRSVcat into all cell lines was effected by electroporation and the resultant CAT activity was measured 24 h later by a rapid single vial CAT assay. CAT activity corresponding to an average of 0.06 units of purified CAT enzyme was expressed by WIL2-NS cells. Very low to no expression of the CAT vector was observed in all other cell lines studied, despite the presence of intracellular levels of H-3-labelled pRSVcat comparable to WIL2-NS. Epstein-Barr virus transformed B cells (SKW 6.4 and RPMI 1788) did not successfully perform host cell reactivation. In WIL2-NS cells, platination of pRSVcat to defined levels of 5-40 platinum molecules per plasmid led to a graded reduction in CAT activity expressed following transfection. Platination levels of 20 and 40 platinum molecules per plasmid did not alter the efficiency of transfer of pRSVcat into these cells by electroporation. Data obtained in this study suggests that EBV transformation may possibly be a negative influence on host cell-reactivation assays for cisplatin-DNA damaged plasmid in non-T human leukocytes. C1 NCI,MED BRANCH,9000 ROCKVILLE PIKE,BLDG 10,ROOM 12N226,BETHESDA,MD 20892. NR 24 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 0304-3835 J9 CANCER LETT JI Cancer Lett. PD APR 15 PY 1992 VL 63 IS 2 BP 143 EP 150 DI 10.1016/0304-3835(92)90064-3 PG 8 WC Oncology SC Oncology GA HQ036 UT WOS:A1992HQ03600008 PM 1314131 ER PT J AU TAKADA, Y VISTICA, DT GREIG, NH PURDON, D RAPOPORT, SI SMITH, QR AF TAKADA, Y VISTICA, DT GREIG, NH PURDON, D RAPOPORT, SI SMITH, QR TI RAPID HIGH-AFFINITY TRANSPORT OF A CHEMOTHERAPEUTIC AMINO-ACID ACROSS THE BLOOD-BRAIN-BARRIER SO CANCER RESEARCH LA English DT Article ID PERFUSION TECHNIQUE; CEREBROVASCULAR TRANSPORT; CYTO-TOXICITY; MELPHALAN; RAT; PHARMACOKINETICS; CARRIER; BINDING; CHLORAMBUCIL; MUSTARD AB The therapeutic efficacy of many anticancer drugs against intracerebral tumors is limited by poor uptake into the central nervous system. One way to enhance brain delivery is to design agents that are transported into the brain by the saturable nutrient carriers of the blood-brain barrier. In this paper, we describe a nitrogen mustard amino acid, DL-2-amino-7-bis[(2-chloroethyl)amino]-1,2,3,4-tetrahydro-2-naphthoic acid, that is taken up into brain with high affinity by the large neutral amino acid carrier of the blood-brain barrier. Brain transport of DL-2-amino-7-bis[(2-chloroethyl)amino]-1,2,3,4-tetrahydro-2-naphthoic acid in the rat was found to be rapid (cerebrovascular permeability-surface area product approximately 2 x 10(-2) ml/s/g), saturable and inhibitable by large neutral amino acids. Maximal influx rate (V(max)) and half-saturation (K(m)) constants equaled 0.26 nmol/min/g and 0.19-mu-M, respectively, in the parietal cortex. Regional brain uptake of DL-2-amino-7-bis[(2-chloroethyl)amino]-1,2,3,4-tetrahydro-2-naphthoic acid exceeded that of the clinical analogue, melphalan, by > 20-fold. The results demonstrate that drug modification to produce high-affinity ligands for the cerebrovascular nutrient carriers is a viable means to enhance drug delivery to brain for the treatment of brain tumors and other central nervous system disorders. C1 NIA,NEUROSCI LAB,BLDG 10,ROOM 6C-103,BETHESDA,MD 20892. NCI,FREDERICK CANC RES CTR,DRUG DISCOVERY RES & DEV LAB,FREDERICK,MD 21702. NR 39 TC 41 Z9 42 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 APR 15 PY 1992 VL 52 IS 8 BP 2191 EP 2196 PG 6 WC Oncology SC Oncology GA HN842 UT WOS:A1992HN84200011 PM 1559223 ER PT J AU JIANG, MS PASSANITI, A PENNO, MB HART, GW AF JIANG, MS PASSANITI, A PENNO, MB HART, GW TI ADRENAL CARCINOMA TUMOR PROGRESSION AND PENULTIMATE CELL-SURFACE OLIGOSACCHARIDES SO CANCER RESEARCH LA English DT Article ID GALACTOSIDE ALPHA-2->3 SIALYTRANSFERASE; SIALIC-ACID; LINKED OLIGOSACCHARIDES; SIALYLATION; METASTASIS; SIALYLTRANSFERASE; GLYCOPROTEIN; LOCALIZATION; PURIFICATION; HOMOGENEITY AB Many previous studies have implicated cell surface saccharides, and sialylglycoconjugates in particular, as important mediators of tumor cell metastasis. In this report, we have used three different specific sialidases and a highly sensitive high-performance liquid chromatographic sialic acid assay to probe the cell surfaces of several murine adrenal carcinoma variants. In contrast to several earlier studies on other metastatic variants, we find no significant differences in the overall levels of cell surface or total cellular sialic acid among three Y1 murine adrenal carcinoma variants with widely different metastatic phenotypes. However, using highly purified, linkage-specific sialyltransferases, in conjunction with V. cholerae sialidase, to probe the cell surface saccharide topography of specific penultimate oligosaccharides, we do find striking differences in oligosaccharide structures underlying the sialic acid moieties. Two tumorigenic and metastatic variants (F2 and F4) contain about 6-fold more penultimate Gal-beta-1 --> 4GlcNAc sialylation sites than a related tumorigenic but nonmetastatic variant (HSR) when CMP-[H-3]-N-acetylneuraminic acid and the Gal-beta-1 --> 4GlcNAc alpha-2,6 sialyltransferase are used to probe the adrenal carcinoma cell surfaces. The metastatic variants also are found to contain 4- to 4.5-fold more Gal-beta-1 --> 3GalNAc sialylation sites than the nonmetastatic variant when the Gal-beta-1 --> 3GalNAc alpha-2,3 sialyltransferase is used as a cell surface probe. Earlier work, which used the same sialyltransferase probes on sialidase-treated murine melanoma variants (A. Passaniti and G. W. Hart, J. Biol. Chem., 263:7591-7603, 1988), also showed similar quantitative differences in penultimate structures between metastatic variants. However, in contrast to the adrenal carcinoma cells, the highly metastatic melanoma cells have severalfold lower levels of sialylatable penultimate Gal-beta-1 --> 4GlcNAc and Gal-beta-1 --> 3GalNAc saccharides compared to their nonmetastatic counterparts. Thus, while the precise structural alterations or surface accessibilities of penultimate saccharides appear to be cell type dependent, these results suggest that pronounced changes in penultimate cell surface sialo-oligosaccharide moieties occur during progression to a malignant phenotype in two widely different tumor systems. These types of alterations in the underlying penultimate oligosaccharide structures of cell surface sialoglycoconjugates may be a common feature of highly metastatic cells arising from very different tumor cell types. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT BIOL CHEM,725 N WOLFE ST,BALTIMORE,MD 21205. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21205. FU NCI NIH HHS [CA42486] NR 23 TC 5 Z9 5 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 APR 15 PY 1992 VL 52 IS 8 BP 2222 EP 2227 PG 6 WC Oncology SC Oncology GA HN842 UT WOS:A1992HN84200016 PM 1559226 ER PT J AU FELIX, CA KAPPEL, CC MITSUDOMI, T NAU, MM TSOKOS, M CROUCH, GD NISEN, PD WINICK, NJ HELMAN, LJ AF FELIX, CA KAPPEL, CC MITSUDOMI, T NAU, MM TSOKOS, M CROUCH, GD NISEN, PD WINICK, NJ HELMAN, LJ TI FREQUENCY AND DIVERSITY OF P53 MUTATIONS IN CHILDHOOD RHABDOMYOSARCOMA SO CANCER RESEARCH LA English DT Article ID GENE; SARCOMAS; CANCER; LINE; LOCALIZATION AB The p53 gene was examined in primary or metastatic tumors from six patients with rhabdomyosarcoma (RMS) and in rive RMS cell lines by screening methods including single-strand conformation polymorphism analysis, the RNase protection assay, sequencing of complementary DNA subclones, and Southern blotting. Six original tumors were of embryonal histology, four alveolar, and one mixed. p53 mutations were identified in four of the six tumors or cell lines derived from tumors with embryonal histology and in one of the four with alveolar histology. Consistent with p53 allele loss, each mutation was found in the homo- or hemizygous state. One tumor showed a G to C transversion at p53 codon 213 (arginine to proline), and another showed deletion of the entire gene. The p53 mutations in cell line included a codon 248 C to T transition (arginine to tryptophan) in RD and a codon 280 A to T transversion (arginine to serine) in RH30. The cell line CTR contained a 4-base pair deletion at codons 219/220 in exon 6 with resultant frame shift and premature termination in exon 7. These data support the role of diverse types of p53 mutations in the pathogenesis and/or progression of a significant proportion of cases of childhood RMS. C1 NCI,DEPT PATHOL,BALTIMORE,MD 21201. UNIV TEXAS,SW MED CTR,DEPT PEDIAT,DALLAS,TX 75235. NCI,PEDIAT BRANCH,BALTIMORE,MD 21201. NCI,NAVY MED ONCOL BRANCH,BALTIMORE,MD 21201. NR 24 TC 154 Z9 157 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 APR 15 PY 1992 VL 52 IS 8 BP 2243 EP 2247 PG 5 WC Oncology SC Oncology GA HN842 UT WOS:A1992HN84200019 PM 1559227 ER PT J AU TAKAHASHI, T CARBONE, D TAKAHASHI, T NAU, MM HIDA, T LINNOILA, I UEDA, R MINNA, JD AF TAKAHASHI, T CARBONE, D TAKAHASHI, T NAU, MM HIDA, T LINNOILA, I UEDA, R MINNA, JD TI WILD-TYPE BUT NOT MUTANT P53 SUPPRESSES THE GROWTH OF HUMAN LUNG-CANCER CELLS BEARING MULTIPLE GENETIC LESIONS SO CANCER RESEARCH LA English DT Note ID ABNORMALITIES; EXPRESSION; MUTATIONS; FREQUENT; LINE AB Accumulating evidence indicates that lung cancer arises due to multiple genetic changes in both dominant oncogenes, such as ras, and tumor suppressor genes, such as p53. In this report we examined whether the wild-type p53 gene is able to suppress in vitro and/or in vivo cellular growth of lung cancer cell lines which carry multiple genetic abnormalities. Introduction of a wild-type p53 complementary DNA expression vector into lung cancer cell lines carrying either a homozygous deletion (NCI-H358) or a missense mutation (NCI-H23) in the p53 gene greatly suppressed tumor cell growth. In contrast, p53 expression vectors bearing lung cancer derived mutations affecting single amino acids had lost this growth suppressing ability. C1 AICHI CANC CTR,IMMUNOL LABS,CHIKUSA KU,NAGOYA,AICHI 464,JAPAN. NCI,NAVY MED ONCOL BRANCH,BETHESDA,MD 20814. AICHI CANC CTR HOSP,DEPT INTERNAL MED,CHIKUSA KU,NAGOYA 464,JAPAN. UNIV TEXAS,SW MED CTR,HAROLD SIMMONS COMPREHENS CANC CTR,DALLAS,TX 75235. RP TAKAHASHI, T (reprint author), AICHI CANC CTR,CHEMOTHERAPY LABS,CHIKUSA KU,NAGOYA,AICHI 464,JAPAN. RI Takahashi, Takashi/I-7262-2014 NR 20 TC 203 Z9 205 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 15 PY 1992 VL 52 IS 8 BP 2340 EP 2343 PG 4 WC Oncology SC Oncology GA HN842 UT WOS:A1992HN84200034 PM 1559236 ER PT J AU MELCHIORI, A ALBINI, A RAY, JM STETLERSTEVENSON, WG AF MELCHIORI, A ALBINI, A RAY, JM STETLERSTEVENSON, WG TI INHIBITION OF TUMOR-CELL INVASION BY A HIGHLY CONSERVED PEPTIDE SEQUENCE FROM THE MATRIX METALLOPROTEINASE ENZYME PROSEGMENT SO CANCER RESEARCH LA English DT Note ID TISSUE INHIBITOR; IV COLLAGENASE; ACTIVATION; MEMBRANE AB The metastasis associated 72-kDa type IV collagenase is secreted as a latent proenzyme which is converted to an active 62-kDa form by autoproteolytic removal of an amino terminal profragment. The region immediately upstream from the cleavage site contains a highly conserved peptide sequence, MRKPRCGNPDV, which is present in all known members of the matrix metalloproteinase family. Evidence implicates the cysteine residue of this sequence as critical for maintenance of the latent form through coordination with the catalytic zinc atom of the active site. A synthetic peptide, TMRKPRCGNPDVAN (peptide 74), encompassing this conserved sequence, has been shown to inhibit the activated form of the 72-kDa type IV collagenase in vitro. In the present study we examine the ability of this peptide inhibitor to modulate tumor cell invasiveness. Peptide 74 and the control peptide 78, which contains a single substitution of serine for the "critical" cysteine residue, were added at 30-mu-M concentrations to the upper compartment of the Boyden chamber in the chemoinvasion assay using HT1080 and A2058 human tumor cells. In this assay a layer of reconstituted basement membrane, Matrigel, is coated onto chemotaxis filters and acts as a barrier to the migration of cells in the Boyden chambers. Only cells with invasive capacity can cross the Matrigel barrier. Peptide 74 containing the cysteine residue inhibited the invasion of both the HT1080 and A2058 cells through the Matrigel barrier, control peptide 78 was not inhibitory. Both peptides were shown to be without cytotoxic action and did not inhibit chemotaxis or affect cell number. This study demonstrates that addition of an excess peptide containing the matrix metalloproteinase prosegment inhibitory sequence can inhibit invasive activity at the cellular level and suggests that this may be a useful strategy to modulate tumor cell invasiveness in vivo. C1 NCI,DIV CANC BIOL DIAG & CTR,PATHOL LAB,BLDG 10,ROOM 2A33,BETHESDA,MD 20892. IST NAZL RIC CANC,GENOA,ITALY. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 15 TC 84 Z9 85 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 APR 15 PY 1992 VL 52 IS 8 BP 2353 EP 2356 PG 4 WC Oncology SC Oncology GA HN842 UT WOS:A1992HN84200038 PM 1313744 ER PT J AU JICHA, DL SCHWARZ, S MULE, JJ ROSENBERG, SA AF JICHA, DL SCHWARZ, S MULE, JJ ROSENBERG, SA TI INTERLEUKIN-7 MEDIATES THE GENERATION AND EXPANSION OF MURINE ALLOSENSITIZED AND ANTITUMOR CTL SO CELLULAR IMMUNOLOGY LA English DT Article ID LYMPHOCYTE-T GENERATION; CELL STIMULATORY FACTOR; ACTIVATED KILLER-CELLS; GROWTH-FACTOR; INVITRO SENSITIZATION; IL-7; PROLIFERATION; THYMOCYTES; TUMOR; DIFFERENTIATION C1 NCI,SURG BRANCH,BLDG 10,ROOM 2B46,BETHESDA,MD 20892. NR 25 TC 18 Z9 18 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD APR 15 PY 1992 VL 141 IS 1 BP 71 EP 83 DI 10.1016/0008-8749(92)90128-C PG 13 WC Cell Biology; Immunology SC Cell Biology; Immunology GA HM039 UT WOS:A1992HM03900007 PM 1555257 ER PT J AU HIBBS, JR FRICKHOFEN, N ROSENFELD, SJ FEINSTONE, SM KOJIMA, S BACIGALUPO, A LOCASCIULLI, A TZAKIS, AG ALTER, HJ YOUNG, NS AF HIBBS, JR FRICKHOFEN, N ROSENFELD, SJ FEINSTONE, SM KOJIMA, S BACIGALUPO, A LOCASCIULLI, A TZAKIS, AG ALTER, HJ YOUNG, NS TI APLASTIC-ANEMIA AND VIRAL-HEPATITIS - NON-A, NON-B, NON-C SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID VIRUS; HEMOPHILIACS; SERUM AB Objective. - To test the hypothesis that the rare, often fatal, syndrome of hepatitis-associated aplasia is associated with hepatitis C virus infection. Design. - Case series. Setting. - Tertiary referral centers in the United States, Japan, Italy, and Germany. Patients. - Twenty-eight patients with onset of aplastic anemia within 90 days after seeking medical attention for jaundice, or having serum transaminase levels 150% or more of normal (hepatitis-associated aplasia patients) and three patients who developed aplastic anemia following liver transplantation for non-A, non-B hepatitis. Outcome Measures. - Presence of hepatitis C in serum, bone marrow, and liver samples, detected by the polymerase chain reaction; antibody testing; and percentage of activated peripheral cytotoxic T lymphocytes determined by immunophenotyping. Results. - Hepatitis ribonucleic acid was present in the serum samples of 10 (36%) patients with hepatitis-associated aplasia. However, hepatitis C virus viremia was associated with transfusions received after the onset of aplasia: seven (58%) of 12 patients with hepatitis-associated aplasia who had received 21 or more units of blood products at the time of serum sampling were viremic, compared with only three (19%) of 16 patients with hepatitis-associated aplasia who had received 20 or less units of blood products (P < .05). Hepatitis C virus was not found in blood and bone marrow samples of three National Institutes of Health case patients tested at the time of diagnosis. None of three livers from non-A, non-B hepatitis patients who developed aplastic anemia after liver transplantation contained hepatitis C virus ribonucleic acid. Activated CD8+ T lymphocytes were elevated three- to 20-fold early in the course of hepatitis-associated aplasia. Conclusions. - Our results implicate a novel, non-A, non-B, and non-C agent in both hepatitis-associated aplasia and fulminant hepatitis. C1 US FDA,CTR BIOL EVALUAT & RES,DIV VIROL,KENSINGTON,MD. NIH,DEPT TRANSFUS MED,BETHESDA,MD 20892. NAGOYA HOSP 1ST,JAPANESE RED CROSS,CHILDRENS MED CTR,DIV HEMATOL ONCOL,NAGOYA,JAPAN. SAN MARTINO HOSP,DIV HEMATOL 2,CTR BONE MARROW TRANSPLANT,GENOA,ITALY. UNIV ULM,DEPT MED 3,W-7900 ULM,GERMANY. HOSP SAN GERARDO,DIV PEDIAT HEMATOL,MILAN,ITALY. UNIV PITTSBURGH,SCH MED,DEPT SURG,PITTSBURGH,PA 15261. RP HIBBS, JR (reprint author), NHLBI,CLIN HEMATOL BRANCH,10-7C103,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Kojima, Seiji/I-1601-2012 FU NHLBI NIH HHS [HL08279-02] NR 31 TC 70 Z9 71 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 APR 15 PY 1992 VL 267 IS 15 BP 2051 EP 2054 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA HM650 UT WOS:A1992HM65000030 PM 1313118 ER PT J AU BENHAMOU, M STEPHAN, V ROBBINS, KC SIRAGANIAN, RP AF BENHAMOU, M STEPHAN, V ROBBINS, KC SIRAGANIAN, RP TI HIGH-AFFINITY IGE RECEPTOR-MEDIATED STIMULATION OF RAT BASOPHILIC LEUKEMIA (RBL-2H3) CELLS INDUCES EARLY AND LATE PROTEIN-TYROSINE PHOSPHORYLATIONS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HISTAMINE-RELEASE; MAST-CELLS; KINASE-C; SECRETION; ACTIVATION; EXOCYTOSIS; MEMBRANE; P60C-SRC; SIGNALS AB We reported previously that stimulation of RBL-2H3 cells through the high-affinity IgE receptor resulted in tyrosine phosphorylation of a 72-kDa protein (pp72) that was coupled to signal transduction. In the present study, although pp72 tyrosine phosphorylation was induced only by antigen triggering, stimulation of RBL-2H3 cells by either antigen or the calcium-ionophore A23187 led to increased tyrosine phosphorylation of a 110-kDa protein (pp110). This tyrosine phosphorylated protein was also observed when RBL-2H3 cells were transfected with the G protein-coupled m3 muscarinic receptor and then stimulated to secrete with carbachol. In contrast to tyrosine phosphorylation of pp72, antigen-induced pp110 tyrosine phosphorylation required extracellular calcium, was absent in cells depleted of protein kinase C, and was detected between 1 and 5 min after stimulation. The protein-tyrosine kinase inhibitor genistein blocked both histamine release and tyrosine phosphorylation induced by A23187. Altogether, the data suggest a role for pp110 in secretion. However, protein kinase C activation induced pp110 tyrosine phosphorylation but not histamine release demonstrating that pp110 tyrosine phosphorylation alone is not sufficient for degranulation. We conclude that tyrosine phosphorylation of pp72 is associated with the early steps of IgE receptor-generated signaling, whereas pp110 tyrosine phosphorylation occurs secondary to calcium influx and protein kinase C activation. C1 NIDR,CELLULAR DEV & ONCOL LAB,BETHESDA,MD 20892. RP BENHAMOU, M (reprint author), NIDR,IMMUNOL LAB,BLDG 10,RM IA31,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 20 TC 100 Z9 100 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 APR 15 PY 1992 VL 267 IS 11 BP 7310 EP 7314 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HN485 UT WOS:A1992HN48500020 PM 1373133 ER PT J AU ESTIVARIZ, FE FRIEDMAN, TC CHIKUMA, T LOH, YP AF ESTIVARIZ, FE FRIEDMAN, TC CHIKUMA, T LOH, YP TI PROCESSING OF ADRENOCORTICOTROPIN BY 2 PROTEASES IN BOVINE INTERMEDIATE LOBE SECRETORY VESICLE MEMBRANES - A DISTINCT ACIDIC, TETRABASIC RESIDUE-SPECIFIC CALCIUM-ACTIVATED SERINE PROTEASE AND A PC2-LIKE ENZYME SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID OPIOMELANOCORTIN-CONVERTING ENZYME; MELANOCYTE STIMULATING HORMONE; PRO-OPIOMELANOCORTIN; GENE-PRODUCT; PITUITARY; KEX2; RAT; CARBOXYPEPTIDASE; PURIFICATION; PROTEOLYSIS AB Adrenocorticotropin (ACTH) is cleaved at the tetrabasic residue site, in pituitary intermediate lobe secretory vesicles, to yield ACTH1-17 and corticotropin-like intermediate lobe peptide (CLIP). ACTH1-17 is then converted to alpha-melanocyte-stimulating hormone (N-AcACTH1-13NH2) by first removing the Lys15-Lys16-Arg17 residues, followed by amidation of the COOH terminus and acetylation of the NH2 terminus. Bovine intermediate lobe secretory vesicle membranes were screened for proteolytic enzyme activity that will cleave the tetrabasic residues of ACTH. Two activities with pH optima of 5.0-6.0 and 7.5-8.0 were detected. The acidic, ACTH-converting enzyme cleaved ACTH1-39 at the tetrabasic residues between the Arg17-Arg18 bond to yield ACTH1-17 and CLIP, but did not cleave paired basic residues of pro-opiomelanocortin. This enzyme activity was characterized as a Ca2+-activated serine protease with unique specificity for the tetrabasic residues of ACTH1-39. The neutral activity preferentially generated ACTH1-17 and to a small extent ACTH1-16 from ACTH1-39 and ACTH1-24. This enzyme activity was Ca2+-dependent but was not inhibited by serine or aspartic protease inhibitors. The neutral activity was significantly immunodepleted by anti-serum raised against bovine PC2/PC3, and together with specificity studies, suggests that the enzyme is a PC2-like serine protease. The pH optimum, distinct specificity for tetrabasic residues, and subcellular localization of the acidic ACTH-converting enzyme indicate a function of this enzyme in the in vivo conversion of ACTH1-39 to alpha-melanocyte-stimulating hormone in intermediate lobe secretory vesicles which have an acidic internal pH. C1 NICHHD,CELLULAR NEUROBIOL SECT,DEV NEUROBIOL LAB,BLDG 36,RM 2A21,BETHESDA,MD 20892. NR 44 TC 37 Z9 37 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 15 PY 1992 VL 267 IS 11 BP 7456 EP 7463 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HN485 UT WOS:A1992HN48500039 PM 1313803 ER PT J AU YANG, XJ MILES, EW AF YANG, XJ MILES, EW TI THREONINE-183 AND ADJACENT FLEXIBLE LOOP RESIDUES IN THE TRYPTOPHAN SYNTHASE-ALPHA SUBUNIT HAVE CRITICAL ROLES IN MODULATING THE ENZYMATIC-ACTIVITIES OF THE BETA-SUBUNIT IN THE ALPHA-2-BETA-2 COMPLEX SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ULTRAVIOLET VISIBLE SPECTROSCOPY; SITE-SPECIFIC MUTAGENESIS; ESCHERICHIA-COLI; SALMONELLA-TYPHIMURIUM; L-SERINE; TRIOSEPHOSPHATE ISOMERASE; GUANIDINE-HYDROCHLORIDE; 3-DIMENSIONAL STRUCTURE; MULTIENZYME COMPLEX; MECHANISM AB This study investigates the catalytic and allosteric roles of a flexible loop in the tryptophan synthase alpha-2-beta-2-complex. This loop connects helix 6 and strand 6 in the alpha-subunit, an 8-fold alpha/beta-barrel polypeptide. We have engineered three mutations in this disordered loop: a deletion of residues 185-187 and the replacement of threonine 183 by serine (T183S) or by alanine (T183A). Position 183 is a site of an inactivating mutation identified by Yanofsky's group (Yanofsky, C., Drapeau, G. R., Guest, J. R., and Carlton, B. C. (1967) Proc. Natl. Acad. Sci. U.S.A. 57,296-298). The three engineered alpha-subunits form stable, stoichiometric alpha-2-beta-2-complexes with the beta-subunit which bind alpha and beta-subunit ligands. Although changing threonine 183 to serine has little effect on the enzymatic properties, changing threonine 183 to alanine or deleting residues 185-187 results in a 50-fold reduction in the intrinsic activity of the alpha-subunit alone and in the alpha-site activity of the alpha-2-beta-2-complex. The latter two mutations profoundly alter the way in which the alpha-subunit modulates the spectral properties and the activities of the wild-type beta-subunit. These mutations also eliminate the effects of alpha-subunit ligands on the beta-subunit. Although the beta-subunit ligand, L-serine, greatly stabilizes the wild-type alpha-2-beta-2 complex to dissociation and to proteolysis, L-serine stabilizes the T183A alpha-2-beta-2-complex weakly or not at all. Our findings suggest that the hydroxyl residue at position 183 and the adjacent residues in the alpha-subunit loop play critical roles in the reciprocal communication between the alpha and beta-subunits in the alpha-2-beta-2-complex. The results also help to explain how the wild-type alpha-subunit or ammonium ion modulates the activities of the beta-subunit. C1 NIDDKD, BIOCHEM PHARMACOL LAB, BLDG 8, RM 2A09, BETHESDA, MD 20892 USA. NR 72 TC 38 Z9 38 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 APR 15 PY 1992 VL 267 IS 11 BP 7520 EP 7528 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HN485 UT WOS:A1992HN48500048 PM 1559990 ER PT J AU MURPHY, PM OZCELIK, T KENNEY, RT TIFFANY, HL MCDERMOTT, D FRANCKE, U AF MURPHY, PM OZCELIK, T KENNEY, RT TIFFANY, HL MCDERMOTT, D FRANCKE, U TI A STRUCTURAL HOMOLOG OF THE N-FORMYL PEPTIDE RECEPTOR - CHARACTERIZATION AND CHROMOSOME MAPPING OF A PEPTIDE CHEMOATTRACTANT RECEPTOR FAMILY SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; XENOPUS OOCYTES; WASP VENOM; CDNA; CLONING; EXPRESSION; MASTOPARAN; SEQUENCE; BINDING; GENES AB Phagocytic cells of many higher species express calcium mobilizing G protein-coupled receptors for bacterial N-formyl peptides which mediate chemotaxis, degranulation, and the respiratory burst. cDNA encoding an N-formyl peptide receptor (FPR) has been reported. We now report the isolation of a closely related cDNA, 2.6 kilobase pairs in length, which we have designated as the FPRL1 receptor cDNA (FPRL1 = formyl peptide receptor like-1). FPR and the FPRL1 receptor derive from small, single-copy genes, both of which are located on human chromosome 19. The gene loci are designated FPR1 and FPRL1, respectively. Both FPR and FPRL1 cDNA cross-hybridize under high stringency conditions with a third gene, designated as FPRL2, which does not appear to be expressed in neutrophils. In contrast, transcripts for both the FPRL1 receptor and FPR are detected only in differentiated myeloid cells; the distribution of N-formyl peptide binding sites is also restricted to mature myeloid cells. FPRL1 cDNA encodes a 351-amino acid polypeptide whose sequence is 69% identical to that of FPR. G protein-coupled receptors that exhibit this degree of structural similarity typically possess a conserved ligand specificity. However, the FPRL1 receptor does not bind prototype N-formyl peptide ligands when expressed in heterologous cell types. These results suggest that FPR1 may be the only gene that is expressed by neutrophils that encodes a receptor capable of binding prototype N-formyl peptides. Moreover, discovery of the FPRL1 receptor indicates the existence of another as yet unidentified peptide that may recruit neutrophils to sites of inflammation. C1 HOWARD HUGHES MED INST, STANFORD, CA 94305 USA. STANFORD UNIV, MED CTR, DEPT GENET, STANFORD, CA 94305 USA. STANFORD UNIV, MED CTR, DEPT PEDIAT, STANFORD, CA 94305 USA. RP MURPHY, PM (reprint author), NIAID, HOST DEF LAB, BLDG 10, RM 11N113, BETHESDA, MD 20892 USA. OI McDermott, David/0000-0001-6978-0867 FU NHGRI NIH HHS [HG00298] NR 47 TC 184 Z9 185 U1 1 U2 4 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 APR 15 PY 1992 VL 267 IS 11 BP 7637 EP 7643 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HN485 UT WOS:A1992HN48500063 PM 1373134 ER PT J AU KIM, IG MCBRIDE, OW WANG, M KIM, SY IDLER, WW STEINERT, PM AF KIM, IG MCBRIDE, OW WANG, M KIM, SY IDLER, WW STEINERT, PM TI STRUCTURE AND ORGANIZATION OF THE HUMAN TRANSGLUTAMINASE-1 GENE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AMINO-ACID-SEQUENCE; BLOOD-COAGULATION FACTOR; HUMAN FACTOR-XIII; KERATINOCYTE TRANSGLUTAMINASE; GUINEA-PIG; ERYTHROCYTE-MEMBRANE; INSITU HYBRIDIZATION; SECONDARY STRUCTURE; GLOBULAR-PROTEINS; EPIDERMAL-CELLS AB Membrane-associated transglutaminases (TGase1) have recently been found to be common in mammalian cells, but it is not clear whether these derive from the same or different genes. In order to determine the complexity of this system, we have isolated and characterized the human gene (TGM1). The gene of 14,133 base pairs was found to contain 15 exons spliced by 14 introns. Interestingly, the positions of these introns have been conserved in comparison with the genes of two other transglutaminase-like activities described in the literature, but the TGM1 gene is by far the smallest characterized to date because its introns are relatively smaller. On the other hand, the TGase1 enzyme is the largest known transglutaminase (about 90 kDa), apparently because its gene acquired tracts that encode additional sequences on its amino and carboxyl termini that confer its unique properties. Southern blot analyses of total human genomic DNA cut with several restriction enzymes reveal only one band. Use of human-rodent cell hybrid panels and chromosomal in situ hybridization with biotin-labeled probes revealed that the human TGM1 gene maps to chromosome position 14q11.2-13. Such data suggest there is a single gene copy per haploid human genome. Comparisons of sequence identities and homologies indicate that the transglutaminase family of genes arose by duplications and subsequent divergent evolution from a common ancestor but later became scattered in the human genome. Although our present Southern blot and chromosomal localization studies revealed no restriction fragment length polymorphisms, comparisons of published sequences and our genomic clone indicate there are two sequence variants for TGase1 within the human population. The rare smaller variant contains a two-nucleotide deletion near the 5'-end, uses an alternate initiation codon, and differs from the common larger variant only in the first 15 amino acids. Furthermore, the DNA sequences of intron 14 possess several tracts of dinucleotide repeats that by polymerase chain reaction analysis show wide size polymorphism within the human population. Accordingly, this gene system constitutes a useful polymorphic marker for genetic linkage analyses. C1 NIAMSD,SKIN BIOL LAB,BLDG 10,RM 9N228,BETHESDA,MD 20892. NCI,BIOCHEM LAB,BETHESDA,MD 20892. NR 47 TC 93 Z9 96 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 APR 15 PY 1992 VL 267 IS 11 BP 7710 EP 7717 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HN485 UT WOS:A1992HN48500073 PM 1348508 ER PT J AU MACGREGOR, TM COPELAND, NG JENKINS, NA GIGUERE, V AF MACGREGOR, TM COPELAND, NG JENKINS, NA GIGUERE, V TI THE MURINE GENE FOR CELLULAR RETINOIC ACID-BINDING PROTEIN TYPE-II - GENOMIC ORGANIZATION, CHROMOSOMAL LOCALIZATION, AND POSTTRANSCRIPTIONAL REGULATION BY RETINOIC ACID SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MESSENGER-RNA DEGRADATION; EMBRYONAL CARCINOMA-CELLS; MOLECULAR-CLONING; GROWTH-FACTOR; GM-CSF; RECEPTOR; IDENTIFICATION; EXPRESSION; DIFFERENTIATION; STABILITY AB The cellular retinoic acid-binding protein type II (CRABP-II) is a member of the serum and cytoplasmic retinoid-binding protein family. It is expressed during embryonic development and in adult skin and is up-regulated by retinoic acid (RA) in F9 teratocarcinoma cells. We have determined the genomic organization of the murine CRABP-II gene and performed a detailed analysis of its transcriptional unit. The CRABP-II gene, located on mouse chromosome 2, is approximately 4.6 kilobases long and divided into four exons in a structure common to other members of the family of serum and cellular retinoid-binding proteins. Primer extension analysis and S1 nuclease protection assay were used to identify the transcription initiation site which is located 27 base pairs downstream of a typical TATAA box. Sequence analysis of the promoter also revealed a GC-rich region with overlapping putative SP1-binding sites at nucleotides -61 and AP-1 and AP-2-binding sites at nucleotides -518 and -544, respectively. The 3'-untranslated region contains two copies of the pentanucleotide AUUUA shown to be involved in messenger RNA destabilization. Consensus sequence for retinoic acid response elements were not detected in the promoter region of the CRABP-II gene. Results of nuclear run on experiments show that the CRABP-II gene is not transcriptionally activated by RA in F9 teratocarcinoma cells. These results suggest that the up-regulation of CRABP-II mRNA levels by RA is mainly controlled by a post-transcriptional mechanism. C1 HOSP SICK CHILDREN,RES INST,DIV ENDOCRINOL,555 UNIV AVE,TORONTO M5G 1X8,ONTARIO,CANADA. UNIV TORONTO,DEPT MOLEC & MED GENET,TORONTO M5S 1A8,ONTARIO,CANADA. NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. OI Giguere, Vincent/0000-0001-9567-3694 FU NCI NIH HHS [N01-CO-74101] NR 76 TC 48 Z9 49 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 15 PY 1992 VL 267 IS 11 BP 7777 EP 7783 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HN485 UT WOS:A1992HN48500082 PM 1313808 ER PT J AU PETRALIA, RS WENTHOLD, RJ AF PETRALIA, RS WENTHOLD, RJ TI LIGHT AND ELECTRON IMMUNOCYTOCHEMICAL LOCALIZATION OF AMPA-SELECTIVE GLUTAMATE RECEPTORS IN THE RAT-BRAIN SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE ULTRASTRUCTURE; HIPPOCAMPUS; CEREBELLUM; CEREBRAL CORTEX; OLFACTORY BULB ID AMINO-ACID RECEPTORS; CENTRAL-NERVOUS-SYSTEM; PUTATIVE KAINATE RECEPTOR; BETA-ADRENERGIC-RECEPTOR; METHYL-D-ASPARTATE; BINDING-SITES; CEREBELLAR CORTEX; DENTATE GYRUS; QUANTITATIVE AUTORADIOGRAPHY; DIFFERENTIAL DISTRIBUTION AB Since four AMPA-type excitatory amino acid receptor subunits have been cloned recently, it is now possible to localize these important molecules in the nervous system. A comprehensive study of AMPA receptor immunocytochemistry was carried out on vibratome sections of rat brain, which were immunolabeled with antibodies made against peptides corresponding to the C-terminal portions of AMPA-receptor subunits: GluR1, GluR2/3, and GluR4. Labeling was most prominent in forebrain structures such as the olfactory bulb and tubercle, septal nuclei, amygdaloid complex, hippocampus, induseum griseum, habenula, and interpeduncular nucleus, and in the cerebellum. Different patterns of immunolabeling were evident with the antibodies to the four subunits, with marked contrast between densely and lightly stained structures with antibody to GluR1, widespread dense staining with antibody to GluR2/3, and moderate staining with antibody to GluR4. In the parietal cortex, some non-pyramidal neurons were more densely stained than pyramidal cells with antibodies to GluR1. Neurons of the main olfactory bulb, other than granule cells, were most densely stained with antibody to GluR1. In the cerebellum, Bergmann glia were densely stained with antibodies to GluR1 and 4, while neurons, other than granule cells, were most densely stained with antibody to GluR2/3. Immunolabeling patterns of all antibodies were consistent with that of previous in situ hybridization histochemistry studies and with the overall pattern of H-3-AMPA binding. Electron microscopy of thin sections taken from immunolabeled vibratome sections of hippocampus and cerebral cortex showed staining which was restricted mainly to postsynaptic densities and adjacent dendritoplasm, and to neuron cell body cytoplasm. We saw no convincing examples of stained presynaptic terminals, and only limited evidence of glial staining, excepting Bergmann glia. RP PETRALIA, RS (reprint author), NATL INST DEAFNESS & OTHER COMMUN DISORDERS,NEUROCHEM LAB,BLDG 36,RM 5008,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 86 TC 881 Z9 885 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD APR 15 PY 1992 VL 318 IS 3 BP 329 EP 354 DI 10.1002/cne.903180309 PG 26 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA HL085 UT WOS:A1992HL08500008 PM 1374769 ER PT J AU CASPI, RR GRUBBS, BG CHAN, CC CHADER, GJ WIGGERT, B AF CASPI, RR GRUBBS, BG CHAN, CC CHADER, GJ WIGGERT, B TI GENETIC-CONTROL OF SUSCEPTIBILITY TO EXPERIMENTAL AUTOIMMUNE UVEORETINITIS IN THE MOUSE MODEL - CONCOMITANT REGULATION BY MHC AND NON-MHC GENES SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RETINOID-BINDING-PROTEIN; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; COLLAGEN-INDUCED ARTHRITIS; MYELIN BASIC-PROTEIN; II COLLAGEN; IMMUNE-RESPONSE; CELL; MICE; IRBP; IMMUNODOMINANT AB Experimental autoimmune uveoretinitis (EAU) in animals is a T cell-mediated autoimmune response directed against cells of the neural retina, in particular the photoreceptors. EAU can be induced in susceptible strains of mice by immunization with purified retinal Ag, and serves as a model for human uveitis. Because strong HLA associations have been noted in a number of human uveitic diseases, we investigated the role of MHC vs non-MHC genes in the control of susceptibility to ocular autoimmunity using the mouse EAU model. Selected strains representing most of the known independent H-2 haplotypes, as well as several H-2-recombinant and congenic strains, were immunized with interphotoreceptor retinoid-binding protein. Ocular pathology was induced in strains of the H-2k haplotype and their I-A-matched congenics, as well as in strains of the H-2r, H-2b, and H-2d haplotypes. In a series of experiments utilizing intra-H-2 recombinant strains, MHC control of susceptibility was tentatively mapped to the I-A subregion of the H-2k. Expression of the I-E(k) gene product was not required for susceptibility to EAU, and in fact appeared to have an ameliorating effect on disease. Incidence and severity of disease obtained in strains sharing the same H-2 on a different background, or sharing the same background in the context of a different H-2, indicated that non-MHC genes contribute significantly to the regulation of EAU. Disease expression of susceptible H-2 haplotypes was highest in strains with B10 background (permissive) and ranged from intermediate to absent in strains with other (nonpermissive) backgrounds. The data suggest that although the ability to develop ocular pathology is dependent on the I-A subregion of the H-2, the final expression of disease in susceptible haplotypes is largely determined by background, non-MHC genes. C1 NEI,RETINAL CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. RP CASPI, RR (reprint author), NEI,IMMUNOL LAB,BLDG 10,ROOM 10N222,BETHESDA,MD 20892, USA. NR 46 TC 68 Z9 68 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 APR 15 PY 1992 VL 148 IS 8 BP 2384 EP 2389 PG 6 WC Immunology SC Immunology GA HN740 UT WOS:A1992HN74000010 PM 1560198 ER PT J AU SCHWIETERMAN, WD WOOD, GM SCOTT, DE STEINBERG, AD AF SCHWIETERMAN, WD WOOD, GM SCOTT, DE STEINBERG, AD TI STUDIES OF BONE-MARROW PROGENITOR CELLS IN LUPUS-PRONE MICE .1. NZB MARROW-CELLS DEMONSTRATE INCREASED GROWTH IN WHITLOCK-WITTE CULTURE AND INCREASED SPLENIC COLONY-FORMING UNIT-ACTIVITY IN THE THY-1-, LINEAGE-POPULATION SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ZEALAND BLACK MICE; HEMATOPOIETIC STEM-CELLS; LONG-TERM CULTURE; AUTOIMMUNE-DISEASE; B-CELL; LYMPHOCYTES-B; CFU-S; INVITRO; RECIPIENTS; SEPARATION AB Previous studies have demonstrated that NZB marrow can transfer features of autoimmunity. Therefore, we undertook a study of NZB marrow to determine whether it demonstrated any phenotypic abnormalities. In Whitlock-Witte cultures, NZB marrow cells generated nonadherent cells at low seeding densities, densities at which marrow from other strains did not generate nonadherent cells. In contrast, NZB marrow grew less well than controls in Dexter cultures. Inasmuch as the latter favor growth of granulocyte-macrophage precursors and the former B cells, these results suggest a possible skewing of NZB marrow cells toward lymphocyte production. Unfractionated marrow cells from NZB mice were found to produce 10-fold more splenic colonies in lethally irradiated recipients than marrow cells from control mice. This result was independent of the genotype of the recipient. When the progenitor Thy-1lo, Lin- marrow subpopulation was studied, NZB mice did not differ substantially from controls regarding splenic CFU. Therefore, Thy-1-, Lin- marrow cells were studied as a possible source of the excess splenic CFU in NZB mice. Indeed, the NZB Thy-1-, Lin- population contained 30-fold more splenic CFU than did the Thy-1-, Lin- population from control mice. These results suggest that NZB mice have unusual marrow progenitor cells; such cells may play a role in their autoimmune disease. C1 NIAMSD,ARTHRIT & RHEUMATISM BRANCH,CELLULAR IMMUNOL SECT,BLDG 10,ROOM 9N-218,BETHESDA,MD 20892. NR 37 TC 7 Z9 7 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 APR 15 PY 1992 VL 148 IS 8 BP 2405 EP 2410 PG 6 WC Immunology SC Immunology GA HN740 UT WOS:A1992HN74000013 PM 1348517 ER PT J AU OSHEA, JJ MCVICAR, DW KUHNS, DB ORTALDO, JR AF OSHEA, JJ MCVICAR, DW KUHNS, DB ORTALDO, JR TI A ROLE FOR PROTEIN TYROSINE KINASE-ACTIVITY IN NATURAL CYTOTOXICITY AS WELL AS ANTIBODY-DEPENDENT CELLULAR CYTOTOXICITY - EFFECTS OF HERBIMYCIN-A SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LARGE GRANULAR LYMPHOCYTES; KILLER-CELLS; SIGNAL TRANSDUCTION; ANTIGEN RECEPTOR; C ACTIVATION; PHOSPHORYLATION; STIMULATION; CD16; INTERLEUKIN-2; MOBILIZATION AB NK cells, CD3- large granular lymphocytes, have diverse means by which they lyse targets, including antibody-dependent cellular cytotoxicity. The low affinity receptor for the Fc portion of Ig (Fc-gamma-RIIIA), like the TCR, is a multimeric receptor complex coupled to a protein tyrosine kinase. In the present study, we observed that inhibition of tyrosine kinase activity by herbimycin A interferes with receptor-mediated phosphorylation of a variety of substrates and mobilization of intracellular calcium. Fc-gamma-RIIIA induced IL-2R alpha-chain expression was also extremely sensitive to herbimycin A as was anti-body-dependent cellular cytotoxicity, in fact more so than receptor-mediated phosphorylation and calcium mobilization. In contrast to Fc-gamma-RIIIA, the surface molecules and biochemical mechanisms involved in NK cytotoxicity and lymphokine-activated killing are not well characterized. Interestingly, however, herbimycin A also blocks these modes of cytolysis, implicating a role for tyrosine kinase function in these processes. Whether FcR-mediated signaling and receptor-mediated signaling involved in NK activity share specific biochemical intermediates is not known, but the involvement of tyrosine kinase function in the latter means of cytotoxicity may provide novel avenues for understanding the biochemical basis of this perplexing cellular function. C1 NCI,DYNCORP,PROGRAM RESOURCES INC,FREDERICK CANC RES & DEV CTR,CLIN IMMUNOL SERV,FREDERICK,MD 21702. RP OSHEA, JJ (reprint author), NCI,DYNCORP,PROGRAM RESOURCES INC,FREDERICK CANC RES & DEV CTR,LEUKOCYTE CELL BIOL SECT,FREDERICK,MD 21702, USA. RI McVicar, Daniel/G-1970-2015 FU NCI NIH HHS [N01-CO-74102] NR 45 TC 73 Z9 73 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 APR 15 PY 1992 VL 148 IS 8 BP 2497 EP 2502 PG 6 WC Immunology SC Immunology GA HN740 UT WOS:A1992HN74000027 PM 1532816 ER PT J AU JENSEN, JP HOU, D RAMSBURG, M TAYLOR, A DEAN, M WEISSMAN, AM AF JENSEN, JP HOU, D RAMSBURG, M TAYLOR, A DEAN, M WEISSMAN, AM TI ORGANIZATION OF THE HUMAN T-CELL RECEPTOR ZETA-ETA GENE AND ITS GENETIC-LINKAGE TO THE FC-GAMMA-RII-FC-GAMMA-RIII GENE-CLUSTER SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; ANTIGEN RECEPTOR; MOLECULAR-CLONING; TYROSINE PHOSPHORYLATION; HUMAN CHROMOSOME-11; IMMUNOGLOBULIN-E; ALPHA-SUBUNIT; HIGH-AFFINITY; COMPLEX; CHAIN AB The zeta-subunit is the most recently characterized stoichiometric human TCR component. In this study we describe the molecular organization of the human zeta-gene. The zeta-transcript is generated as the spliced product of eight exons that are separated by distances of 0.7 kb to more than 8 kb. Ribonuclease protection studies revealed multiple transcription initiation sites distributed over a range of approximately 115 bases. A variable number tandem repeat restriction fragment polymorphism contained within the structural gene has allowed for the localization of zeta within the human genome. Additionally, a restriction fragment polymorphism within the Fc-gamma-RII-Fc-gamma-RIII gene cluster has allowed for its localization on the map of human chromosome 1q and for the establishment of its linkage to the zeta-gene locus. A region that is highly homologous on a nucleotide level with the eta-exon of the murine zeta-gene is localized to the 3' region of the human zeta-gene. Surprisingly, translation of this region into protein results in a structure that is markedly divergent from its murine counterpart. This finding has important implications regarding the potential role of eta in T cell function. C1 NCI,DCBDC,EXPTL IMMUNOL BRANCH,BLDG 10,RM 4B17,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21701. DYNCORP,PROGRAM RESOURCES INC,FREDERICK CANC RES & DEV CTR,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 FU NCI NIH HHS [N01-CO-74102] NR 60 TC 46 Z9 47 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 APR 15 PY 1992 VL 148 IS 8 BP 2563 EP 2571 PG 9 WC Immunology SC Immunology GA HN740 UT WOS:A1992HN74000036 PM 1532817 ER PT J AU MULE, JJ CUSTER, MC TRAVIS, WD ROSENBERG, SA AF MULE, JJ CUSTER, MC TRAVIS, WD ROSENBERG, SA TI CELLULAR MECHANISMS OF THE ANTITUMOR-ACTIVITY OF RECOMBINANT IL-6 IN MICE SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ESTABLISHED PULMONARY METASTASES; ACTIVATED KILLER-CELLS; TUMOR NECROSIS FACTOR; DISSEMINATED MURINE LEUKEMIA; HIGH-DOSE INTERLEUKIN-2; GROWTH-FACTOR; BEARING MICE; INVIVO; EFFICACY; IMMUNOTHERAPY AB The systemic administration of human rIL-6 to mice resulted in the regression of established, 3-day pulmonary micrometastases from two weakly immunogenic tumors, but not from a nonimmunogenic tumor, in the absence of observable toxicity. Although IL-6 alone failed to have a significant therapeutic impact on advanced, 10-day pulmonary macrometastases from weakly immunogenic tumors, substantial cure rates of mice could be achieved when this cytokine was combined with cyclophosphamide. Histologic analysis of the lungs of mice receiving IL-6 revealed infiltration with lymphoid cells during the regression of pulmonary nodules from a weakly immunogenic tumor. IL-6-mediated tumor regression could be abrogated after selective in vivo depletion of either CD4 or CD8 T cell subsets by the systemic administration of specific mAb. In vivo generation of tumor-specific CTL, but not of lymphokine-activated killer cells, was detected in the lungs of IL-6-treated mice during regression of pulmonary metastases. Collectively, these findings demonstrate a role for IL-6 in the treatment of established solid tumors that have the capacity to elicit T cell responses in the host. Differences in host cellular mechanisms involved in tumor regression mediated by immunotherapy using IL-6 vs IL-2 are discussed. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. RP MULE, JJ (reprint author), NCI,DIV CANC TREATMENT,SURG BRANCH,BLDG 10,ROOM 2B56,BETHESDA,MD 20892, USA. NR 44 TC 108 Z9 110 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 APR 15 PY 1992 VL 148 IS 8 BP 2622 EP 2629 PG 8 WC Immunology SC Immunology GA HN740 UT WOS:A1992HN74000044 PM 1348521 ER PT J AU GOTAY, CC KORN, EL MCCABE, MS MOORE, TD CHESON, BD AF GOTAY, CC KORN, EL MCCABE, MS MOORE, TD CHESON, BD TI QUALITY-OF-LIFE ASSESSMENT IN CANCER-TREATMENT PROTOCOLS - RESEARCH ISSUES IN PROTOCOL DEVELOPMENT SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID FUNCTIONAL LIVING INDEX; CELL LUNG-CANCER; SUPPORTIVE CARE; CHEMOTHERAPY; IMPACT AB Background: Interest in incorporating quality of life as an end point in clinical studies of cancer treatment has intensified in recent years. Purpose: We provide practical suggestions that will assist investigators considering including quality-of-life assessment in phase III therapeutic trials. Methods: We discuss issues important in study planning, including quality-of-life definition, priority studies for quality-of-life assessment, eligibility requirements, and design. Conclusions: Many of the problems that quality-of-life studies have encountered, from protocol approval to data analysis, could be addressed and alleviated during protocol development. This discussion is intended to assist and stimulate investigators conducting research in this area. C1 NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,BETHESDA,MD 20892. RP GOTAY, CC (reprint author), EMMES CORP,11325 7 LOCKS RD,SUITE 214,POTOMAC,MD 20854, USA. NR 36 TC 144 Z9 148 U1 1 U2 3 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 APR 15 PY 1992 VL 84 IS 8 BP 575 EP 579 DI 10.1093/jnci/84.8.575 PG 5 WC Oncology SC Oncology GA HN516 UT WOS:A1992HN51600010 PM 1556768 ER PT J AU NAM, JM MCLAUGHLIN, JK BLOT, WJ AF NAM, JM MCLAUGHLIN, JK BLOT, WJ TI CIGARETTE-SMOKING, ALCOHOL, AND NASOPHARYNGEAL CARCINOMA - A CASE-CONTROL STUDY AMONG UNITED-STATES WHITES SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID RISK-FACTORS; SALTED FISH; CHINESE; CANCER; MORTALITY; FORMALDEHYDE AB Background: Nasopharyngeal carcinoma (NPC) is a relatively uncommon cancer in the United States. Its etiology among White Americans is not well known, but cigarette smoking has been implicated in some epidemiologic studies. Purpose: The purpose of this study was to investigate the roles of cigarette use and alcohol consumption as risk factors for NPC in the United States. Methods: We conducted a case-control study using data from the National Mortality Followback Survey based on information from death certificates. In this study, we compared use of cigarettes and alcohol by 204 White American men and women who died of NPC with that by 408 who died of causes unrelated to cigarette smoking and alcohol use. Results: Risk of NPC increased in proportion to the amount and duration of smoking (with a more than threefold increase among persons smoking heavily) and declined following cessation of smoking. After controlling for smoking, we found an 80% excess risk of NPC among persons whose intake of alcohol was heavy. Conclusion: Use of cigarettes and consumption of alcohol were found to be statistically significant risk factors for NPC. The findings are among the strongest to date indicating that use of cigarettes and perhaps alcohol may contribute to the etiology of these relatively rare cancers among Whites in the United States. RP NAM, JM (reprint author), NIH,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,EXECUT PLAZA N,RM 407,BETHESDA,MD 20892, USA. NR 37 TC 73 Z9 73 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD APR 15 PY 1992 VL 84 IS 8 BP 619 EP 622 DI 10.1093/jnci/84.8.619 PG 4 WC Oncology SC Oncology GA HN516 UT WOS:A1992HN51600015 PM 1556772 ER PT J AU CHING, WM WYCHOWSKI, C BEACH, MJ WANG, H DAVIES, CL CARL, M BRADLEY, DW ALTER, HJ FEINSTONE, SM SHIH, JWK AF CHING, WM WYCHOWSKI, C BEACH, MJ WANG, H DAVIES, CL CARL, M BRADLEY, DW ALTER, HJ FEINSTONE, SM SHIH, JWK TI INTERACTION OF IMMUNE SERA WITH SYNTHETIC PEPTIDES CORRESPONDING TO THE STRUCTURAL PROTEIN REGION OF HEPATITIS-C VIRUS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE EPITOPE SCAN; IMMUNE RESPONSE ID NON-B-HEPATITIS; NON-A; ANTIGENIC DETERMINANTS; ANTIBODY-RESPONSE; AMINO-ACID; CHIMPANZEES; SEQUENCE; GENOME; ASSAY AB Comparison of the deduced amino acid sequence from the structural region of the Hutchinson strain of hepatitis C virus (HCV-H) with four other HCV isolates clearly divides the five isolates into two groups based on sequence homology. The first group includes HCV-H, HCV-1, and HC-J1, while the second includes HCV-J1 and HC-J4. Among the five isolates the first 190 residues (putative nucleocapsid) are highly conserved whereas residues 196-513 exhibit significant diversity and include a hypervariable region encompassing residues 386-404. A series of overlapping decapeptides were synthesized by solid-phase pin technology according to sequence from HCV-H (amino acids 1-513), HC-J4 (amino acids 181-513), and regions from the three other isolates which exhibited sequence variation. A modified ELISA was used to measure immunoreactivity of sera from clinical posttransfusion cases and experimentally infected chimpanzees. Comparison of pre- and postinfection samples revealed 16 clusters of immunoreactive peptides within the structural region, none of which was found in the hypervariable region. Only one cluster (amino acids 73-89) was recognized by all human and chimpanzee sera. Clear variation in the immune response was observed between individuals, although no obvious difference in reactivity between acute and chronic cases was observed. Within individual profiles, the reactivity to each peptide cluster and the total number of reactive clusters increased over time. C1 NIH,DEPT TRANSFUS MED,BLDG 10,ROOM 1C711,BETHESDA,MD 20892. USN,MED RES INST,BETHESDA,MD 20889. US FDA,ROCKVILLE,MD 20760. CTR DIS CONTROL,ATLANTA,GA 30333. NR 21 TC 48 Z9 49 U1 0 U2 0 PU NATL ACAD PRESS 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 APR 15 PY 1992 VL 89 IS 8 BP 3190 EP 3194 DI 10.1073/pnas.89.8.3190 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HP043 UT WOS:A1992HP04300006 PM 1373489 ER PT J AU HARA, Y ROVESCALLI, AC KIM, Y NIRENBERG, M AF HARA, Y ROVESCALLI, AC KIM, Y NIRENBERG, M TI STRUCTURE AND EVOLUTION OF 4 POU DOMAIN GENES EXPRESSED IN MOUSE-BRAIN SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE POU BRAIN-1; POU BRAIN-2; POU BRAIN-4; POU SCIP; HOMEOBOX ID CAENORHABDITIS-ELEGANS; DNA-BINDING; SEQUENCE; PIT-1; OCT-1; SCIP AB Four mouse POU domain genomic DNA clones-Brain-1, Brain-2, Brain-4, and Scip-and Brain-2 CDNA, which are expressed in adult brain, were cloned and the coding and noncoding regions of the genes were sequenced. The amino acid sequences of the four POU domains are highly conserved; sequences in other regions of the proteins also are conserved but to a lesser extent. The absence Of introns from the coding regions of the four POU domain genes and the similarity of amino acid sequences of the corresponding proteins suggest that the coding region of the ancestral class III POU domain gene lacked introns and therefore may have originated by reverse transcription of a molecule of POU domain mRNA followed by insertion of the cDNA into germ cell genomic DNA. Additional duplications of the ancestral class III POU domain gene (or mRNA) would create the Brain-1, Brain-2, Brain-4, and Scip genes. RP NHLBI, BIOCHEM GENET LAB, BLDG 36, ROOM 1C06, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 21 TC 134 Z9 138 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 15 PY 1992 VL 89 IS 8 BP 3280 EP 3284 DI 10.1073/pnas.89.8.3280 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HP043 UT WOS:A1992HP04300025 PM 1565620 ER PT J AU LEMOINE, C YOUNG, WS AF LEMOINE, C YOUNG, WS TI RHS2, A POU DOMAIN-CONTAINING GENE, AND ITS EXPRESSION IN DEVELOPING AND ADULT-RAT SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE DNA BINDING PROTEIN STRIATUM; PARAVENTRICULAR NUCLEUS; SUPRAOPTIC NUCLEUS; INSITU HYBRIDIZATION ID TRANSCRIPTION FACTOR; NERVOUS-SYSTEM; MESSENGER-RNAS; NEURONS; BRAIN; NEUROPEPTIDE; SEQUENCE; PROTEIN; SCIP AB Gene expression within the central nervous system is regulated by complex interactions of DNA-binding proteins, among which are the POU domain-containing proteins, which are distantly related to homeobox proteins. These POU domain-containing proteins have been implicated in control of transcription and replication within the central nervous system. We used degenerate primers with the PCR to isolate another POU domain-containing cDNA, RHS2, from hypothalamic RNA. Isolation of a putative full-length cDNA was accomplished by using serial dilutions of a hypothalamic cDNA library grown on solid medium. This member of the class III POU family is expressed in rats from embryonic day 11.5 into adulthood, being especially prominent in the brain. We performed double-labeling hybridization histochemistry and determined that RHS2 is coexpressed with a variety of neuropeptides in medium-sized neurons in the caudate putamen and with dynorphin in the paraventricular and supraoptic nuclei of the hypothalamus. Expression of RHS2 in the caudate putamen was increased by elimination of its nigrostriatal dopaminergic innervation. RP LEMOINE, C (reprint author), NIMH,CELL BIOL LAB,BETHESDA,MD 20892, USA. RI Young, W Scott/A-9333-2009; LE MOINE, Catherine/E-2671-2014; LE MOINE, Catherine/E-1918-2014 OI Young, W Scott/0000-0001-6614-5112; NR 28 TC 93 Z9 97 U1 0 U2 0 PU NATL ACAD PRESS 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 APR 15 PY 1992 VL 89 IS 8 BP 3285 EP 3289 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HP043 UT WOS:A1992HP04300026 PM 1348858 ER PT J AU BUSHMAN, FD CRAIGIE, R AF BUSHMAN, FD CRAIGIE, R TI INTEGRATION OF HUMAN-IMMUNODEFICIENCY-VIRUS DNA - ADDUCT INTERFERENCE ANALYSIS OF REQUIRED DNA SITES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE RETROVIRUS; LONG TERMINAL REPEAT; INTEGRATION PROTEIN; ACQUIRED IMMUNODEFICIENCY SYNDROME; RECOMBINATION ID MURINE LEUKEMIA-VIRUS; ECO RI ENDONUCLEASE; RETROVIRAL DNA; VIRAL-DNA; POL GENE; PROTEIN; SEQUENCE; INVITRO; RECOMBINATION; TYPE-1 AB The integration (IN) protein encoded by human immunodeficiency virus directs the integration of viral DNA into host DNA. We have probed the DNA sites required for the function of IN protein by attaching adducts to model DNA substrates and assaying their effects on integration in vitro. These experiments reveal that modifications in a short region on both DNA strands at the ends of the viral DNA block IN protein function. Modification of the target DNA near the point of DNA strand transfer also blocks IN protein function. Further experiments suggest that distinct subsets of the identified interactions are important for separate steps in the integration process. RP BUSHMAN, FD (reprint author), NIDDKD,BETHESDA,MD 20892, USA. NR 41 TC 52 Z9 52 U1 0 U2 0 PU NATL ACAD PRESS 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 APR 15 PY 1992 VL 89 IS 8 BP 3458 EP 3462 DI 10.1073/pnas.89.8.3458 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HP043 UT WOS:A1992HP04300062 PM 1533044 ER PT J AU AHN, BY MOSS, B AF AHN, BY MOSS, B TI RNA POLYMERASE-ASSOCIATED TRANSCRIPTION SPECIFICITY FACTOR ENCODED BY VACCINIA VIRUS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE RNA POLYMERASE SUBUNIT; SIGMA-FACTOR; RAP30 RNA POLYMERASE-BINDING PROTEIN; GENE EXPRESSION ID 5' POLY(A) LEADER; DNA-REPLICATION; LATE GENES; SEQUENCE; SUBUNITS; EXPRESSION; IDENTIFICATION; PURIFICATION; PROTEINS; GENOME AB Vaccinia virus encodes a multisubunit DNA-dependent RNA polymerase (EC 2.7.7.6) that is packaged in the infectious virus particle. This polymerase was found to contain a submolar polypeptide of approximately 85 kDa in addition to the core subunits, which consist of two larger and several smaller polypeptides. The polymerase containing the 85-kDa polypeptide was separated from the core polymerase by column chromatography. Although the core polymerase actively transcribed heterologous single-stranded DNA, only the form with the associated 85-kDa polypeptide could act in conjunction with an early stage-specific factor to transcribe double-stranded DNA containing a vaccinia virus early promoter. Peptide sequencing established that the RNA polymerase-associated 85-kDa protein was derived from the vaccinia virus H4L open reading frame, which encodes a 94-kDa polypeptide that we named RAP94. RAP94 is not closely related to prokaryotic sigma-70 or eukaryotic RAP30 RNA polymerase-binding proteins, although there are short regions of sequence similarity. The specific association of RAP94 with viral RNA polymerase was corroborated with antibody raised to a recombinant fusion protein. Unlike the previously defined subunits of vaccinia virus RNA polymerase, RAP94 is synthesized exclusively late in infection, and synthesis could be prevented by a DNA replication inhibitor. The role of RAP94 in mediating specific transcription was demonstrated by using an extract from cells in which the H4L open reading frame had been transiently expressed. RP AHN, BY (reprint author), NIAID,VIRAL DIS LAB,BETHESDA,MD 20892, USA. NR 34 TC 78 Z9 79 U1 0 U2 0 PU NATL ACAD PRESS 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 APR 15 PY 1992 VL 89 IS 8 BP 3536 EP 3540 DI 10.1073/pnas.89.8.3536 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HP043 UT WOS:A1992HP04300078 PM 1565650 ER PT J AU BANG, YJ KIM, SJ DANIELPOUR, D OREILLY, MA KIM, KY MYERS, CE TREPEL, JB AF BANG, YJ KIM, SJ DANIELPOUR, D OREILLY, MA KIM, KY MYERS, CE TREPEL, JB TI CYCLIC-AMP INDUCES TRANSFORMING GROWTH-FACTOR-BETA-2 GENE-EXPRESSION AND GROWTH ARREST IN THE HUMAN ANDROGEN-INDEPENDENT PROSTATE CARCINOMA CELL-LINE PC-3 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE NEGATIVE GROWTH FACTOR; HORMONE-REFRACTORY; CYCLIC AMP RESPONSE ELEMENT ID EMBRYO FIBROBLASTS; CANCER-CELLS; C-MYC; CAMP; RECEPTOR; DIFFERENTIATION; TRANSCRIPTION; FACTOR-BETA-1; PURIFICATION; INHIBITOR AB The standard therapy for advanced prostate cancer is androgen ablation. Despite transitory responses, hormonally treated patients ultimately relapse with androgen-independent disease that is resistant to further hormonal manipulation and cytotoxic chemotherapy. To develop an additional approach to the treatment of advanced prostate cancer, we have been studying the signal transductions controlling the growth of human androgen-independent prostate carcinoma cell lines. We report here that elevation of intracellular cAMP markedly inhibits the growth of the hormone-refractory cell line PC-3. To examine the mechanism of cAMP action in PC-3 cells, we tested the effect of the cAMP analog dibutyryl cAMP (Bt2-cAMP) on the regulation of the potent negative growth factor transforming growth factor-beta (TGF-beta). Bt2-cAMP selectively induced the secretion of TGF-beta-2 and not TGF-beta-1 by PC-3 cells. This TGF-beta-2 was shown to be bioactive by using the CCL-64 mink lung cell assay. TGF-beta-1 was not activated despite being present at 3-fold higher concentrations than TGF-beta-2. Northern analysis showed that Bt2-cAMP induced an increase in the five characteristic TGF-beta-2 transcripts and had no effect on the level of TGF-beta-1 or TGF-beta-3 transcripts. TGF-beta-2 induction was only weakly enhanced by cycloheximide and was completely inhibited by actinomycin D. These data show that Bt2-cAMP induces the expression of active TGF-beta-2 by PC-3 prostate carcinoma cells, suggesting a new approach to the treatment of prostate cancer and a new molecular mechanism of cAMP action. C1 NCI,CLIN ONCOL PROGRAM,CLIN PHARMACOL BRANCH,BLDG 10,ROOM 12N230,BETHESDA,MD 20892. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. RI Bang, Yung Jue/J-2759-2012 NR 33 TC 67 Z9 69 U1 0 U2 2 PU NATL ACAD PRESS 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 APR 15 PY 1992 VL 89 IS 8 BP 3556 EP 3560 DI 10.1073/pnas.89.8.3556 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HP043 UT WOS:A1992HP04300082 PM 1373503 ER PT J AU LOZIER, RH XIE, A HOFRICHTER, J CLORE, GM AF LOZIER, RH XIE, A HOFRICHTER, J CLORE, GM TI REVERSIBLE STEPS IN THE BACTERIORHODOPSIN PHOTOCYCLE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ABSORPTION SPECTROSCOPY; KINETICS; GLOBAL MODELING ID TESTING KINETIC-MODELS; RESONANCE RAMAN-SPECTROSCOPY; PURPLE MEMBRANE; CHROMOPHORE STRUCTURE; SCHIFF-BASE; LIGHT; INTERMEDIATE; PROTEIN; PUMP AB The absorbance changes that accompany the light-driven proton-pumping cycle of bacteriorhodopsin measured over a broad range of times, wavelengths, temperatures, and pH values have been globally fitted to the kinetic model K half arrow right over half arrow left L half arrow right over half arrow left X half arrow right over half arrow left M half arrow right over half arrow left N half arrow right over half arrow left O --> bR. A remarkably good fit to the data was obtained by optimizing the rate constants at 20-degrees-C and the corresponding activation energies at each pH value, together with the extinction coefficients for each intermediate, which were assumed to be independent of both pH and temperature. Back-reactions are included for all but the last step of the cycle and are found to be essential for fitting the data. The rates of these reactions are large, and the analogous irreversible model produced significantly worse fits to the data. Small systematic differences between the fit and the experimental data associated with the X, M, and O intermediates, together with the inability of the model to produce spectra for the X and M intermediates consistent with their assignment as molecular species, indicate that this model must be an incomplete description of the photocycle. We suggest that these problems arise from the presence of additional occupied states that are difficult to distinguish on the basis of their visible absorption spectra alone. C1 UNIV ILLINOIS,DEPT PHYS,URBANA,IL 61801. RP LOZIER, RH (reprint author), NIDDKD,CHEM PHYS LAB,BETHESDA,MD 20892, USA. NR 31 TC 72 Z9 72 U1 0 U2 7 PU NATL ACAD PRESS 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 APR 15 PY 1992 VL 89 IS 8 BP 3610 EP 3614 DI 10.1073/pnas.89.8.3610 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HP043 UT WOS:A1992HP04300093 PM 1565656 ER PT J AU LIAO, F SHIN, HS RHEE, SG AF LIAO, F SHIN, HS RHEE, SG TI TYROSINE PHOSPHORYLATION OF PHOSPHOLIPASE C-GAMMA-1 INDUCED BY CROSS-LINKING OF THE HIGH-AFFINITY OR LOW-AFFINITY FC RECEPTOR FOR IGG IN U937 CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID INOSITOL PHOSPHATES; GAMMA-RI; C-GAMMA; EXPRESSION; ACTIVATION; HYDROLYSIS; INVITRO; CA-2+ AB The human monocytic cell line U937 possesses two classes of the IgG Fc receptor (Fc-gamma-R), a high-affinity 72-kDa Fc-gamma-R (Fc-gamma-RI) and a low-affinity 40-kDa Fc-gamma-R (Fc-gamma-RII). Cross-linking of either class of Fc-gamma-R in U937 cells elicits an increase in the concentration of free intracellular Ca2+. A rapid rise in the concentration of inositol 1,4,5-trisphosphate (Ins-1,4,5-P3) and of several other inositol phosphates derived from Ins-1,4,5-P3 was observed after cross-linking of Fc-gamma-Rs in U937 cells. This result suggests that Ins-1,4,5-P3, generated by the action of phospholipase C (PLC), acts as a second messenger by which Fc-gamma-Rs mobilize intracellular Ca2+ in U937 cells. The mechanism by which the cross-linking of Fc-gamma-Rs triggers activation of PLC was studied. Cross-linking of Fc-gamma-RI or Fc-gamma-RII resulted in a rapid and transient phosphorylation of PLC-gamma-1 on tyrosine residues. It has previously been shown that phosphorylation of PLC-gamma-1 on tyrosine residues activates its enzymatic activity in cells. prior incubation of U937 cells with a protein tyrosine kinase inhibitor, herbimycin A, prevented the tyrosine phosphorylation of PLC-gamma-1 and the hydrolysis of phosphatidylinositol 4,5-bisphosphate induced by the cross-linking of Fc-gamma-Rs. Thus, Fc-gamma-RI and Fc-gamma-RII appear to be functionally coupled to a nonreceptor tyrosine kinase that phosphorylates PLC-gamma-1 after receptor cross-linking, thereby causing activation of PLC-gamma-1. C1 NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT MOLEC BIOL & GENET,BALTIMORE,MD 21205. NR 35 TC 139 Z9 139 U1 0 U2 2 PU NATL ACAD PRESS 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 APR 15 PY 1992 VL 89 IS 8 BP 3659 EP 3663 DI 10.1073/pnas.89.8.3659 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HP043 UT WOS:A1992HP04300103 PM 1373507 ER PT J AU PRIOR, TI FITZGERALD, DJ PASTAN, I AF PRIOR, TI FITZGERALD, DJ PASTAN, I TI TRANSLOCATION MEDIATED BY DOMAIN-II OF PSEUDOMONAS EXOTOXIN-A - TRANSPORT OF BARNASE INTO THE CYTOSOL SO BIOCHEMISTRY LA English DT Article ID TOXIN; AERUGINOSA; BARSTAR; RIBONUCLEASE; EXPRESSION; PROTEINS; GROWTH; CELLS AB Pseudomonas exotoxin A (PE) is a protein toxin composed of three structural domains. Functional analysis of PE has revealed that domain I is the cell-binding domain and that domain III functions in ADP ribosylation. Domain II was originally designated as the translocation domain, mediating the transfer of domain III to the cytosol, because mutations in this domain result in toxin molecules with normal cell-binding and ADP-ribosylation activities but which are not cytotoxic. However, the results do not rule out the possibility that regions of PE outside of domain II also participate in the translocation process. To investigate this problem, we have now constructed a toxin in which domain III of PE is replaced with barnase, the extracellular ribonuclease of Bacillus amyloliquefaciens. This chimeric toxin, termed PE1-412-Bar, is cytotoxic to a murine fibroblast cell line and to a murine hybridoma resistant to the ADP-ribosylation activity of PE. A mutant form of PE1-412-Bar with an inactivating mutation in domain II at position 276 was significantly less toxic. Because the cytotoxic effect of PE1-412-Bar was due to the ribonuclease activity of barnase molecules which had been translocated to the cytosol, we conclude that domain II of PE is not only essential but also probably sufficient to carry out the translocation process. C1 NCI,DIAGNOSIS & CTR,DIV CANC BIOL,MOLEC BIOL LAB,BLDG 37,ROOM 4E16,BETHESDA,MD 20892. NR 26 TC 37 Z9 41 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 APR 14 PY 1992 VL 31 IS 14 BP 3555 EP 3559 DI 10.1021/bi00129a001 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HN843 UT WOS:A1992HN84300001 PM 1567815 ER PT J AU KUKULJAN, M STOJILKOVIC, SS ROJAS, E CATT, KJ AF KUKULJAN, M STOJILKOVIC, SS ROJAS, E CATT, KJ TI APAMIN-SENSITIVE POTASSIUM CHANNELS MEDIATE AGONIST-INDUCED OSCILLATIONS OF MEMBRANE-POTENTIAL IN PITUITARY GONADOTROPHS SO FEBS LETTERS LA English DT Article DE PITUITARY; INTRACELLULAR CA2+; CA2+ CHANNEL; CA2+-SENSITIVE K+ CHANNEL ID PANCREATIC BETA-CELL; INOSITOL TRISPHOSPHATE; CALCIUM CHANNELS; K+ CHANNELS; ACTIVATION; RECEPTOR; MUSCLE AB In cultured rat pituitary gonadotrophs, gonadotropin-releasing hormone (GnRH) induces rapid hyperpolarization of the cell membrane and causes cessation of the spontaneous electrical activity present in non-stimulated cells. This initial response to GnRH is followed by slow oscillations of membrane potential (V(m)) which often exhibit brief bursts of action potentials (AP) fired from the peak of the oscillations. The hyperpolarization waves are synchronous with GnRH-induced elevations of cytoplasmic Ca2+ concentration ([Ca2+]i), such that V(m) maxima alternate with the peak values of [Ca2+]i. The V(m) oscillations result from repetitive activation of apamin-sensitive K+ channels by cytoplasmic Ca2+. Thus, GnRH activation of Ca2+ mobilization can generate a bursting pattern of membrane potential through the activation of K+ channels against a background of spontaneous electrical activity. C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892. RP KUKULJAN, M (reprint author), NIDDKD,CELL BIOL & GENET LAB,BETHESDA,MD 20892, USA. NR 21 TC 66 Z9 66 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD APR 13 PY 1992 VL 301 IS 1 BP 19 EP 22 DI 10.1016/0014-5793(92)80201-Q PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA HQ681 UT WOS:A1992HQ68100005 PM 1333410 ER PT J AU BAKER, ME BLASCO, R AF BAKER, ME BLASCO, R TI EXPANSION OF THE MAMMALIAN 3-BETA-HYDROXYSTEROID DEHYDROGENASE PLANT DIHYDROFLAVONOL REDUCTASE SUPERFAMILY TO INCLUDE A BACTERIAL CHOLESTEROL DEHYDROGENASE, A BACTERIAL UDP-GALACTOSE-4-EPIMERASE, AND OPEN READING FRAMES IN VACCINIA VIRUS AND FISH LYMPHOCYSTIS DISEASE VIRUS SO FEBS LETTERS LA English DT Article DE STEROID DEHYDROGENASE; VACCINIA VIRUS; EVOLUTION ID MOLECULAR-CLONING; ANTIGENIC SPECIFICITY; BREAST-CANCER; ZEA-MAYS; SEQUENCE; ESTROGENS; GENE; PROTEIN; GENOME; PHYTOESTROGENS AB Mammalian 3-beta-hydroxysteroid dehydrogenase and plant dihydroflavonol reductases are descended from a common ancestor. Here we present evidence that Nocardia cholesterol dehydrogenase, E coli UDP-galactose-4 epimerase, and open reading frames in vaccinia virus and fish lymphocystis disease virus are homologous to 3-beta-hydroxysteroid dehydrogenase and dihydroflavonol reductase. Analysis of a multiple alignment of these sequences indicates that viral ORFs are most closely related to the mammalian 3-beta-hydroxysteroid dehvdrogenases. The ancestral protein of this superfamily is likely to be one that metabolized sugar nucleotides. The sequence similarity between 3-beta-hydroxysteroid dehydrogenase and the viral ORFs is sufficient to suggest that these ORFs have an activity that is similar to 3-beta-hydroxysteroid dehydrogenase or cholesterol dehydrogenase. although the putative substrates are not vet known. C1 NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. RP BAKER, ME (reprint author), UNIV CALIF SAN DIEGO,DEPT MED,0623B,9500 GILMAN DR,LA JOLLA,CA 92093, USA. RI Blasco, Rafael/B-5829-2016 NR 41 TC 105 Z9 110 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 APR 13 PY 1992 VL 301 IS 1 BP 89 EP 93 DI 10.1016/0014-5793(92)80216-4 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA HQ681 UT WOS:A1992HQ68100020 PM 1451793 ER PT J AU FLEISCHHAUER, K PARK, JH DISANTO, JP MARKS, M OZATO, K YANG, SY AF FLEISCHHAUER, K PARK, JH DISANTO, JP MARKS, M OZATO, K YANG, SY TI ISOLATION OF A FULL-LENGTH CDNA CLONE ENCODING A N-TERMINALLY VARIANT FORM OF THE HUMAN RETINOID-X RECEPTOR BETA SO NUCLEIC ACIDS RESEARCH LA English DT Note ID SUPERFAMILY; MEMBER C1 MEM SLOAN KETTERING CANC CTR,HUMAN IMMUNOGENET LAB,NEW YORK,NY 10021. NIH,DEV & MOLEC IMMUN LAB,BETHESDA,MD 20892. RP FLEISCHHAUER, K (reprint author), MEM SLOAN KETTERING CANC CTR,BIOCHEM IMMUNOGENET LAB,NEW YORK,NY 10021, USA. RI Fleischhauer, Katharina/B-6980-2009 NR 9 TC 41 Z9 43 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 APR 11 PY 1992 VL 20 IS 7 BP 1801 EP 1801 DI 10.1093/nar/20.7.1801 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HQ054 UT WOS:A1992HQ05400053 PM 1315958 ER PT J AU OGINO, Y COSTA, T AF OGINO, Y COSTA, T TI THROMBIN IS THE MAJOR SERUM FACTOR STIMULATING PHOSPHOINOSITIDE TURNOVER, BUT NOT DNA-SYNTHESIS IN HUMAN NEUROBLASTOMA SH-EP CELLS SO EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION LA English DT Article DE PHOSPHOINOSITIDE TURNOVER; DNA SYNTHESIS; ALPHA-THROMBIN; NEUROBLASTOMA ID NEURO-BLASTOMA CELLS; GENERATION; SEROTONIN AB Fetal calf serum stimulates both phosphoinositide turnover and DNA synthesis in SH-EP cells. The phosphoinositide turnover-stimulating activity of serum is largely (70%) reduced in the presence of hirudin, a blocker of thrombin activity. Yet, hirudin does not alter the ability of serum to stimulate DNA synthesis. Purified a-thrombin is a potent (EC50, 35 pM) stimulator of phosphoinositide turnover in SH-EP cells, but induces DNA synthesis only at much higher concentrations (10 nM-1-mu-M). Thus, serum thrombin accounts for most of the ability of serum to stimulate phosphoinositide hydrolysis, but not for the effect of serum on cell division, since the concentration of thrombin in serum is not sufficient to induce DNA synthesis. These data suggest that hydrolysis of inositol lipids may not be the main signalling event mediating the mitogenic effects of alpha-thrombin. C1 NICHHD,THEORET & PHYS BIOL LAB,DCRT,ABS,BLD 12A,ROOM 2007,BETHESDA,MD 20892. OI costa, tommaso/0000-0002-8729-3357 NR 16 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0922-4106 J9 EUR J PHARM-MOLEC PH JI Eur. J. Pharmacol.-Molec. Pharmacol. Sect. PD APR 10 PY 1992 VL 225 IS 4 BP 299 EP 303 DI 10.1016/0922-4106(92)90103-3 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA HQ598 UT WOS:A1992HQ59800004 PM 1323475 ER PT J AU GUSOVSKY, F AF GUSOVSKY, F TI ENDOTHELIN-ELICITED STIMULATION OF PHOSPHOLIPASE-C IS MEDIATED BY GUANINE-NUCLEOTIDE BINDING PROTEIN(S) SO EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION LA English DT Article DE ENDOTHELIN RECEPTORS; PHOSPHOLIPASE-C; GUANINE NUCLEOTIDE BINDING PROTEINS ID VASCULAR SMOOTH-MUSCLE; PHOSPHOINOSITIDE HYDROLYSIS; PEPTIDE ENDOTHELIN; CELLS; RECEPTORS; PHOSPHATIDYLINOSITOL; DESENSITIZATION; MITOGENESIS; FIBROBLASTS; EXPRESSION AB In permeabilized C6 glioma cells and NIH 3T3 cells, the peptide endothelin 1 (ET-1) in combination with GTP-gamma-S stimulates the formation of inositol phosphates. In the presence of 10-mu-M GTP-gamma-S, ET-1 induces the formation of inositol phosphates with an EC50 value of 2.5 nM for C6 glioma cells and 1.6 nM for NIH 3T3 cells. The analogous peptide endothelin 3 (ET-3) is less potent than ET-1 in such action. In NIH 3T3 cells, ET-1 + GTP-gamma-S-induced formation of inositol phosphates could be detected after 1 min of stimulation, and it increased for up to 30 min. ET-1-induced effects were partially reduced by pretreatment of the cells with pertussis toxin (1-mu-g/ml) in C6 glioma cells, but were unaffected in NIH 3T3 cells. In binding studies in whole C6 cells and NIH 3T3 cells, specific binding for [I-125]ET-1 was detected. Cross-linking of [I-125]ET-1 in whole C6 cells revealed the presence of two binding proteins for ET-1 of 74 kDa and 55 kDa. ET-1 at 100 nM inhibited the labeling of both proteins by [I-125]ET-1. However, ET-3 inhibited the labeling of the 55 kDa protein only. The results provide direct evidence for endothelin receptor coupling to phospholipase C through guanine nucleotide binding (G) proteins. In addition, in C6 cells, endothelin-mediated phospholipase C activation is partially inhibited by pertussis toxin pretreatment. The endothelin receptor involved in phospholipase C stimulation in C6 cells seems to correspond to a 74 kDa protein which binds ET-1 but not ET-3. RP GUSOVSKY, F (reprint author), NIDDK,BIOORGAN CHEM LAB,BLDG 8,ROOM 1A-15,BETHESDA,MD 20892, USA. NR 24 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0922-4106 J9 EUR J PHARM-MOLEC PH JI Eur. J. Pharmacol.-Molec. Pharmacol. Sect. PD APR 10 PY 1992 VL 225 IS 4 BP 339 EP 345 DI 10.1016/0922-4106(92)90108-8 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA HQ598 UT WOS:A1992HQ59800009 PM 1323477 ER PT J AU KOVAC, P EDGAR, KJ AF KOVAC, P EDGAR, KJ TI SYNTHESIS OF LIGANDS RELATED TO THE O-SPECIFIC ANTIGEN OF TYPE-1 SHIGELLA-DYSENTERIAE .3. GLYCOSYLATION OF 4,6-O-SUBSTITUTED DERIVATIVES OF METHYL 2-ACETAMIDO-2-DEOXY-ALPHA-D-GLUCOPYRANOSIDE WITH GLYCOSYL DONORS DERIVED FROM MONOSACCHARIDES AND OLIGOSACCHARIDES SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID BETA-GLYCOSIDES; MONOCLONAL-ANTIBODY; CHEMICAL SYNTHESIS; BLOCKWISE APPROACH; POLYSACCHARIDE; TRISACCHARIDE; CLEAVAGE; STEPWISE; ACETALS AB Methyl O-(2,3,4-tri-O-benzoyl-alpha-L-rhamnopyranosyl)-(1 --> 3)-2,4-di-O-benzoyl-alpha-L-rhamnopyranoside, obtained by silver trifluoromethanesulfonate-mediated condensation of methyl 2,4-di-O-benzoyl-alpha-L-rhamnopyranoside and 2,3,4-tri-O-benzoyl-alpha-L-rhamnopyranosyl bromide (3), was cleaved with dichloromethyl methyl ether (DCMME) to give O-(2,3,4-tri-O-benzoyl-alpha-L-rhamnopyranosyl)-(1 --> 3)-2,4-di-O-benzoyl-alpha-L-rhamnopyranosyl chloride (9). Condensations of 1,3,4,6-tetra-O-acetyl-alpha-D-galactopyranose with 3 and 9, followed by treatment of the products with DCMME yielded, respectively, glycosyl chlorides 12 and 17. Each of these, as well as 2,3,4,6-tetra-O-benzyl-alpha-D-galactopyranosyl chloride was condensed with 4,6-O-substituted (benzylidene, tetraisopropyl-disiloxane-1,3-diyl, or benzyl) derivatives of methyl 2-acetamido-2-deoxy-alpha-D-glucopyranoside, using CH2Cl2, ether, or a mixture thereof as the solvent. The formation of the desired alpha-D-galactopyranosyl linkage was favored when ether was the solvent. Under these conditions, however, the combined yield of the condensation products decreased, especially when less reactive synthons were used. The alpha-linked products obtained were deprotected to give the methyl alpha-glycosides of the tetra, tri-, and the disaccharide related to the chemical repeating unit of the O-specific side chain of the lipopolysaccharide of Shigella dysenteriae type 1. Synthesis of methyl alpha-glycosides of three other constituents of the same polymeric antigen [alpha-L-Rha-(1 --> 3)-alpha-L-Rha, alpha-L-Rha-(1 --> 2)-alpha-D-Gal, and alpha-L-Rha-(1 --> 3)-alpha-L-Rha-(1 --> 2)-alpha-D-Gal] are also described. C1 EASTMAN KODAK CO,EASTMAN CHEM CO RES LABS,KINGSPORT,TN 37662. RP KOVAC, P (reprint author), NIDDK,BETHESDA,MD 20892, USA. NR 55 TC 50 Z9 50 U1 1 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD APR 10 PY 1992 VL 57 IS 8 BP 2455 EP 2467 DI 10.1021/jo00034a047 PG 13 WC Chemistry, Organic SC Chemistry GA HN858 UT WOS:A1992HN85800047 ER PT J AU HARDY, JA HIGGINS, GA AF HARDY, JA HIGGINS, GA TI ALZHEIMERS-DISEASE - THE AMYLOID CASCADE HYPOTHESIS SO SCIENCE LA English DT Editorial Material ID HEREDITARY CEREBRAL-HEMORRHAGE; DOWNS-SYNDROME; MESSENGER-RNA; NEUROFIBRILLARY TANGLES; PROTEIN-PRECURSOR; BRAIN; LOCALIZATION; CDNA; GENE; TAU C1 UNIV S FLORIDA, DEPT PSYCHIAT, TAMPA, FL 33612 USA. NIA, BIOL CHEM LAB, BALTIMORE, MD 21224 USA. RP HARDY, JA (reprint author), ST MARYS HOSP, SCH MED, DEPT BIOCHEM, LONDON W2 1PG, ENGLAND. RI Hardy, John/C-2451-2009 NR 64 TC 2449 Z9 2565 U1 57 U2 390 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD APR 10 PY 1992 VL 256 IS 5054 BP 184 EP 185 DI 10.1126/science.1566067 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HM896 UT WOS:A1992HM89600019 PM 1566067 ER PT J AU MOREL, A OCARROLL, AM BROWNSTEIN, MJ LOLAIT, SJ AF MOREL, A OCARROLL, AM BROWNSTEIN, MJ LOLAIT, SJ TI MOLECULAR-CLONING AND EXPRESSION OF A RAT VIA ARGININE VASOPRESSIN RECEPTOR SO NATURE LA English DT Article ID EUKARYOTIC MESSENGER-RNAS; TRANSLATIONAL START SITE; MUSCLE CELL-LINE; SEQUENCES UPSTREAM; ADENYLATE-CYCLASE; MAMMALIAN-CELLS; BINDING-SITES; CDNA; HEPATOCYTES; COMPILATION AB THE neurohypophyseal hormone arginine vasopressin has diverse actions 1-7, including the inhibition of diuresis, contraction of smooth muscle, stimulation of liver glycogenolysis and modulation of adrenocorticotropic hormone release from the pituitary. Arginine vasopressin receptors are G protein-coupled and have been divided into at least three types 8; the V1a (vascular/hepatic) 1-9-11 and V1b (anterior pituitary) 12 receptors which act through phosphatidylinositol hydrolysis to mobilize intracellular Ca2+, and the V2 (kidney) receptor 1,13,14 which is coupled to adenylate cyclase. We report here the cloning of a complementary DNA encoding the hepatic V1a arginine vasopressin receptor. The liver cDNA encodes a protein with seven putative transmembrane domains, which binds arginine vasopressin and related compounds with affinities similar to the native rat V1a receptor. The messenger RNA corresponding to the cDNA is distributed in rat tissues known to contain V1a receptors. C1 NIMH,CELL BIOL LAB,BLDG 36,ROOM 3A-17,BETHESDA,MD 20892. RI Brownstein, Michael/B-8609-2009 NR 31 TC 440 Z9 443 U1 0 U2 4 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD APR 9 PY 1992 VL 356 IS 6369 BP 523 EP 526 DI 10.1038/356523a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HN231 UT WOS:A1992HN23100059 PM 1560825 ER PT J AU KIMURA, T TANIZAWA, O MORI, K BROWNSTEIN, MJ OKAYAMA, H AF KIMURA, T TANIZAWA, O MORI, K BROWNSTEIN, MJ OKAYAMA, H TI STRUCTURE AND EXPRESSION OF A HUMAN OXYTOCIN RECEPTOR SO NATURE LA English DT Article ID MOLECULAR CHARACTERIZATION; FUNCTIONAL EXPRESSION; BOVINE ENDOMETRIUM; CDNA; OOCYTES; CLONING; PARTURITION; PREGNANCY; PROTEIN; GENE AB JUST before the onset of labour, uterine myometrium becomes extremely sensitive to oxytocin 1, for which it is a primary target tissue, because of a dramatic increase in the number of oxytocin receptors 2,3. We report here the structure and expression of the human oxytocin receptor complementary DNA isolated by expression cloning. The encoded receptor is a 388-amino-acid polypeptide with 7 transmembrane domains typical of G protein-coupled receptors. The oxytocin receptor, expressed in Xenopus oocytes, specifically responds to oxytocin and induces an inward membrane current. Messenger RNAs for the receptor are of two sizes, 3.6 kilobases in breast, and 4.4 kilobases in ovary, uterine endometrium and myometrium. The mRNA level in the myometrium is very high at term. We conclude that the increase in receptor number in the myometrium at labour is, at least in part, due to the increase in mRNA. C1 OSAKA BIOSCI INST,DEPT NEUROSCI,SUITA,OSAKA 565,JAPAN. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. OSAKA UNIV,MICROBIAL DIS RES INST,DEPT MOLEC GENET,SUITA,OSAKA 565,JAPAN. RP KIMURA, T (reprint author), OSAKA UNIV,SCH MED,DEPT OBSTET & GYNECOL,1-1-50 FUKUSHIMA,FUKUSHIMA KU,OSAKA 553,JAPAN. RI Brownstein, Michael/B-8609-2009 NR 27 TC 507 Z9 514 U1 2 U2 34 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD APR 9 PY 1992 VL 356 IS 6369 BP 526 EP 529 DI 10.1038/356526a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA HN231 UT WOS:A1992HN23100060 PM 1313946 ER PT J AU BRODER, S AF BRODER, S TI THE BETHESDA SYSTEM FOR REPORTING CERVICAL VAGINAL CYTOLOGIC DIAGNOSES - REPORT OF THE 1991 BETHESDA WORKSHOP SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP BRODER, S (reprint author), NCI,BETHESDA,MD 20892, USA. NR 3 TC 109 Z9 110 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 8 PY 1992 VL 267 IS 14 BP 1892 EP 1892 DI 10.1001/jama.267.14.1892 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA HL677 UT WOS:A1992HL67700004 PM 1548812 ER PT J AU ALEXANDER, RB BOLTON, ES KOENIG, S JONES, GM TOPALIAN, SL JUNE, CH ROSENBERG, SA AF ALEXANDER, RB BOLTON, ES KOENIG, S JONES, GM TOPALIAN, SL JUNE, CH ROSENBERG, SA TI DETECTION OF ANTIGEN SPECIFIC LYMPHOCYTES-T BY DETERMINATION OF INTRACELLULAR CALCIUM-CONCENTRATION USING FLOW-CYTOMETRY SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE CALCIUM; LYMPHOCYTE-T; ACTIVATION; FLOW CYTOMETRY; (HUMAN) ID CELLS; ACTIVATION; RECOGNITION; INCREASE; TARGETS; CYTOLYSIS; KILLER; CA2+ AB We present a method for the detection of lymphocytes with specific reactivity to antigens on stimulator cells using flow cytometry. Cultured human T lymphocytes were loaded with the intracellular fluorochrome indo-1 and were mixed with stimulator cells. Using flow cytometry we could detect a specific increase in intracellular calcium in the T lymphocytes as well as conjugation between the T cells and the stimulator cells. Examination of antigen-specific CD4+ and CD8+ T cell clones demonstrated that the vast majority of T cells which were conjugated to antigen-bearing stimulator cells manifested a rapid increase in intracellular calcium. In contrast T cells conjugated to stimulator cells which did not bear specific antigen demonstrated no such increase in calcium. A similar finding was observed when examining polyclonal tumor infiltrating lymphocytes obtained from patients with melanoma. Tumor infiltrating lymphocytes with specific antitumor reactivity demonstrated an increase in intracellular calcium when conjugated to autologous tumor but not to allogeneic melanoma. In contrast to the T cell clones, only a small subpopulation of tumor infiltrating lymphocytes manifested this specific signal upon conjugation with autologous tumor. This suggests that tumor infiltrating lymphocyte cultures contain T cells with varying reactivities to tumor or may also imply heterogeneity in the stimulating tumor cell lines. The method allows for the detection of specific T cells on an individual cell basis in real time. The procedure is not lethal to the cell and sorting and subculturing of reactive T cell populations can be readily performed. The method could also be used to sort stimulator cells based on their ability to elicit an increase in intracellular calcium in selected T cells. C1 USN,MED RES INST,BETHESDA,MD 20814. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. RP ALEXANDER, RB (reprint author), NCI,SURG BRANCH,BLDG 10,ROOM 2B56,BETHESDA,MD 20892, USA. NR 28 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD APR 8 PY 1992 VL 148 IS 1-2 BP 131 EP 141 DI 10.1016/0022-1759(92)90166-Q PG 11 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA HP092 UT WOS:A1992HP09200016 PM 1564323 ER PT J AU ZUCKER, S LYSIK, RM GURFINKEL, M ZARRABI, MH STETLERSTEVENSON, W LIOTTA, LA BIRKEDALHANSEN, H MANN, W AF ZUCKER, S LYSIK, RM GURFINKEL, M ZARRABI, MH STETLERSTEVENSON, W LIOTTA, LA BIRKEDALHANSEN, H MANN, W TI IMMUNOASSAY OF TYPE-IV COLLAGENASE GELATINASE (MMP-2) IN HUMAN PLASMA SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE TYPE-IV COLLAGENASE; GELATINASE; ELISA; PLASMA; PREGNANCY ID METASTATIC TUMOR-CELLS; TISSUE INHIBITOR; MONOCLONAL-ANTIBODIES; ENZYME; METALLOPROTEINASES; PURIFICATION; PROCOLLAGENASE; STROMELYSIN; TIMP-2 AB We have developed a sensitive and specific sandwich type enzyme-linked immunosorbent assay (ELISA) to detect type IV collagenase (MMP-2) in human plasma which employs the combination of affinity purified rabbit polyclonal antibodies and mouse monoclonal antibodies to human MMP-2. The MMP-2 ELISA detects latent and activated MMP-2, MMP-2 complexed with TIMP and MMP-2 complexed with alpha(2) macroglobulin (65% efficiency). To determine whether physiologic conditions associated with increased connective tissue turnover are accompanied by increased MMP-2 levels in plasma, we compared enzyme levels in pregnant and nonpregnant women. Plasma MMP-2 (mean +/- standard deviation) was significantly increased (p < 0.05) in the second half of pregnancy (650 +/- 312) as compared to early pregnancy (356 +/- 139) or the nonpregnant state (387 +/- 193). As a result of the linkage between type IV collagenase production by cancer cells and the metastatic phenotype, the assay of MMP-2 in plasma is of potential clinical value in cancer. C1 NCI,PATHOL LAB,TUMOR INVAS & METASTASIS SECT,BETHESDA,MD 20892. UNIV ALABAMA,ORAL BIOL RES CTR,DEPT ORAL BIOL,BIRMINGHAM,AL 35294. SUNY STONY BROOK,DEPT MED,STONY BROOK,NY 11794. SUNY STONY BROOK,DEPT OBSTET GYNECOL,STONY BROOK,NY 11794. RP ZUCKER, S (reprint author), DEPT VET AFFAIRS MED CTR,DEPT RES,MAIL CODE 151,NORTHPORT,NY 11768, USA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 29 TC 49 Z9 49 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 APR 8 PY 1992 VL 148 IS 1-2 BP 189 EP 198 DI 10.1016/0022-1759(92)90172-P PG 10 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA HP092 UT WOS:A1992HP09200022 PM 1373424 ER PT J AU HANIOKA, N GONZALEZ, FJ LINDBERG, NA LIU, G GELBOIN, HV KORZEKWA, KR AF HANIOKA, N GONZALEZ, FJ LINDBERG, NA LIU, G GELBOIN, HV KORZEKWA, KR TI SITE-DIRECTED MUTAGENESIS OF CYTOCHROME-P450S CYP2A1 AND CYP2A2 - INFLUENCE OF THE DISTAL HELIX ON THE KINETICS OF TESTOSTERONE HYDROXYLATION SO BIOCHEMISTRY LA English DT Article ID LIVER CYTOCHROME-P-450; SEQUENCE REQUIREMENTS; CATALYTIC ACTIVITY; RAT-LIVER; SUBSTRATE; REGIOSELECTIVITY; EXPRESSION AB Cytochrome P450s CYP2A1 and CYP2A2 exhibit 88% sequence similarity, yet CYP2A1 metabolizes testosterone almost exclusively (90%) at the 7-alpha-position, whereas CYP2A2 forms several metabolites, with 15-alpha-hydroxytestosterone as a major metabolite. One of the regions with relatively low sequence homology corresponds by sequence alignment to the I and J helices of P450cam. Since this region is known to be part of the active site for P450cam, 26 single point and two double point mutants were prepared where the amino acid for one form was substituted with that of the other. Mutant and wild-type enzymes were expressed in Hep G2 cells using the vaccinia virus vector. Analysis of testosterone regioselectivity revealed that 25 of the mutants show the same regioselectivity as the parent wild-type enzymes and three are inactive, suggesting that no single amino acid in this region is totally responsible for the different selectivities of CYP2A1 and CYP2A2. Kinetic analysis of the CYP2A1 mutants showed that four of the mutants with changes near the conserved oxygen-binding region had K(m) values with much higher and V(max) values much lower than those of the wild-type enzyme and one mutant had a V(max) value twice as high as that of the wild-type enzyme. Deuterium isotope effects on 7-alpha-hydroxylation were used to determine changes in the rate of reduction and estimate the relative amount of excess water formation. Changes in reduction rates and the amount of water produced are not sufficient to account for the differences in V(max) values, suggesting that the amount of hydrogen peroxide released is a primary determinant for changes in V(max). C1 NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. NR 31 TC 35 Z9 35 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 7 PY 1992 VL 31 IS 13 BP 3364 EP 3370 DI 10.1021/bi00128a009 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HM442 UT WOS:A1992HM44200009 PM 1554718 ER PT J AU RITTER, JK CHEN, F SHEEN, YY LUBET, RA OWENS, IS AF RITTER, JK CHEN, F SHEEN, YY LUBET, RA OWENS, IS TI 2 HUMAN LIVER CDNAS ENCODE UDP-GLUCURONOSYLTRANSFERASES WITH 2 LOG DIFFERENCES IN ACTIVITY TOWARD PARALLEL SUBSTRATES INCLUDING HYODEOXYCHOLIC ACID AND CERTAIN ESTROGEN DERIVATIVES SO BIOCHEMISTRY LA English DT Article ID BILE-ACIDS; CELL-CULTURE; GLUCURONIDATION; EXPRESSION; MICROSOMES; CLONING; SEQUENCE; ESTRIOL AB Two human liver UDP-glucuronosyltransferase cDNA clones, HLUG25 [Jackson, M. R., et al. (1987) Biochem. J. 242, 581-588] and UDPGT(h)-2 [Ritter, J. K., et al. (1990) J. Biol. Chem. 266, 7900-7906] have previously been shown to encode isozymes active in the glucuronidation of hyodeoxycholic acid (HDCA) and certain estrogen derivatives (estriols and 3,4-catechol estrogens), respectively. Here we report that the UDPGT(h)-2-encoded isoform (udpgt(h)-2) and the HLUG25-encoded isoform (udpgt(h)-1) have parallel aglycon specificities. Following expression in COS-1 cells, each isoform metabolized three types of dihydroxy- or trihydroxy-substituted ring structures, including the 3,4-catechol estrogen (4-hydroxyestrone), estriol and 17-epiestriol, and HDCA, but the udpgt(h)-2 isozyme is 100-fold more efficient than udpgt(h)-1. udPgt(h)-1 and udpgt(h)-2 are 86% identical overall (76 differences out of 528 amino acids), including 55 differences in the first 300 amino acids of the amino terminus, a domain which confers isoform substrate specificity. The data indicate that a high level of conservation in the amino terminus is not required for the preservation of substrate selectivity. Analysis of glucuronidation activity encoded by UDPGT(h)-1/UDPGT(h)-2 chimeric cDNAs constructed at their common restriction sites, SacI (codon 297), NcoI (codon 385), and HhaI (codon 469), showed that nine amino acids between residues 385 and 469 are important for catalytic efficiency, suggesting that this region represents a domain which is critical for catalysis but distinct from that responsible for aglycon selection. In parallel with the existence of liver and kidney microsomal HDCA glucuronosyl transferase activity, mRNA coding for udpgt(h)-2 is expressed in liver and kidney, whereas that for udpgt(h)-1 is expressed only in the liver. These data indicate that udpgt(h)-2 is a primary isoform responsible for the detoxification of the bile salt intermediate as well as the active estrogen in termediates. C1 NICHHD,HUMAN GENET BRANCH,BLDG 10,ROOM 9S-242,BETHESDA,MD 20892. NCI,COMPARAT CARCINOGENESIS LAB,BETHESDA,MD 20892. NR 21 TC 95 Z9 96 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 APR 7 PY 1992 VL 31 IS 13 BP 3409 EP 3414 DI 10.1021/bi00128a015 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HM442 UT WOS:A1992HM44200015 PM 1554722 ER PT J AU FORMANKAY, JD CLORE, GM GRONENBORN, AM AF FORMANKAY, JD CLORE, GM GRONENBORN, AM TI RELATIONSHIP BETWEEN ELECTROSTATICS AND REDOX FUNCTION IN HUMAN THIOREDOXIN - CHARACTERIZATION OF PH TITRATION SHIFTS USING 2-DIMENSIONAL HOMONUCLEAR AND HETERONUCLEAR NMR SO BIOCHEMISTRY LA English DT Article ID MAGNETIC-RESONANCE SPECTROSCOPY; ESCHERICHIA-COLI; REDUCED FORM; PROTEINS; RESOLUTION; COSY AB The electrostatic behavior of potentially titrating groups in reduced human thioredoxin was investigated using two-dimensional (2D) H-1 and N-15 nuclear magnetic resonance (NMR) spectroscopy. A total of 241 chemical shift titration curves were measured over the pH range of 2.1-10.6 from homonuclear H-1-H-1 Hartmann-Hahn (HOHAHA) and heteronuclear H-1-N-15 Overbodenhausen correlation spectra. Nonlinear least-squares fits of the data to simple relationships derived from the Henderson-Hasselbalch equation led to the determination of pK(a)s for certain isolated ionizable groups, including the single histidine residue at position 43 (pK(a) = 5.5 +/- 0.1) and a number of aspartic and glutamic acid carboxylate groups. Many of the titration curves demonstrate complex behavior due to the effects of interacting titrating groups, the long range of electrostatic interactions through the protein interior, and, perhaps, pH-induced conformational changes on the chemical shifts. Unambiguous assignment of the pK(a)s for most of the 38 potentially ionizing groups of human thioredoxin could therefore not be made. In addition, there was no clear evidence that Asp-26 titrates in a manner corresponding to that observed in the Escherichia coli protein [Dyson, H. J., Tennant, L. L., & Holmgren, A. (I 99 1) Biochemistry 30, 4262-4268]. The pK(a)s of the active site cysteines were measured, however, with Cys-32 having an anomalously low value of 6.3 +/- 0.1 and that of Cys-35 between 7.5 and 8.6. These pK(a)s are in agreement with proposed mechanisms for redox catalysis of thioredoxin and previously measured pK(a)s within the active site of E. coli thioredoxin [Kallis, G. B., & Holmgren, A. (1980) J. Biol. Chem. 255, 10261-10265]. The stabilization of a thiolate anion at physiological pH can be explained by the interaction of the S(gamma) of Cys-32 with the amide of Cys-35 observed in the previously determined high-resolution solution structure of reduced human thioredoxin [Forman-Kay, J. D., Clore, G. M., Wingfield, P. T., & Gronenborn, A. M. (1991) Biochemistry 30, 2685-2698]. C1 NIDDKD,CHEM PHYS LAB,BLDG 2,BETHESDA,MD 20892. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 34 TC 98 Z9 98 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 APR 7 PY 1992 VL 31 IS 13 BP 3442 EP 3452 DI 10.1021/bi00128a019 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HM442 UT WOS:A1992HM44200019 PM 1554726 ER PT J AU ROBIEN, MA CLORE, GM OMICHINSKI, JG PERHAM, RN APPELLA, E SAKAGUCHI, K GRONENBORN, AM AF ROBIEN, MA CLORE, GM OMICHINSKI, JG PERHAM, RN APPELLA, E SAKAGUCHI, K GRONENBORN, AM TI 3-DIMENSIONAL SOLUTION STRUCTURE OF THE E3-BINDING DOMAIN OF THE DIHYDROLIPOAMIDE SUCCINYL TRANSFERASE CORE FROM THE 2-OXOGLUTARATE DEHYDROGENASE MULTIENZYME COMPLEX OF ESCHERICHIA-COLI SO BIOCHEMISTRY LA English DT Article ID NUCLEAR MAGNETIC-RESONANCE; POTATO CARBOXYPEPTIDASE INHIBITOR; INTERPROTON DISTANCE RESTRAINTS; PYRUVATE-DEHYDROGENASE; NUCLEOTIDE-SEQUENCE; ACETYLTRANSFERASE COMPONENT; MOLECULAR-DYNAMICS; BACILLUS-STEAROTHERMOPHILUS; ACYLTRANSFERASE COMPONENTS; SACCHAROMYCES-CEREVISIAE AB The three-dimensional solution structure of a 51-residue synthetic peptide comprising the dihydrolipoamide dehydrogenase (E3)-binding domain of the dihydrolipoamide succinyltransferase (E2) core Of the 2-oxoglutarate dehydrogenase multienzyme complex of Escherichia coli has been determined by nuclear magnetic resonance spectroscopy and hybrid distance geometry-dynamical simulated annealing calculations. The structure is based on 630 approximate interproton distance and 101 torsion angle (phi, psi, chi-1) restraints. A total of 56 simulated annealing structures were calculated, and the atomic rms distribution about the mean coordinate positions for residues 12-48 of the synthetic peptide is 1.24 angstrom for the backbone atoms, 1.68 angstrom for all atoms, and 1.33 angstrom for all atoms excluding the six side chains which are disordered at chi-1 and the seven which are disordered at chi-2; when the irregular partially disordered loop from residues 31 to 39 is excluded, the rms distribution drops to 0.77 angstrom for the backbone atoms, 1.55 angstrom for all atoms, and 0.89 angstrom for ordered side chains. Although proton resonance assignments for the N-terminal 11 residues and the C-terminal 3 residues were obtained, these two segments of the polypeptide are disordered in solution as evidenced by the absence of nonsequential nuclear Overhauser effects. The solution structure of the E3-binding domain consists of two parallel helices (residues 14-23 and 40-48), a short extended strand (24-26), a five-residue helical-like turn, and an irregular (and more disordered) loop (residues 31-39). This report presents the first structure of an E3-binding domain from a 2-oxo acid dehydrogenase complex. Related domains from the E2 chains of other 2-oxo acid dehydrogenase complexes are likely to be structurally analogous, given their marked sequence similarity and the presence of a number of conserved residues at pivotal positions. This is particularly true for the E. coli pyruvate dehydrogenase complex since the E3 component which is bound by its dihydrolipoamide acetyltransferase core is identical to that bound by the dihydrolipoamide succinyltransferase core of the 2-oxoglutarate dehydrogenase complex. C1 NIDDKD,CHEM PHYS LAB,BLDG 2,BETHESDA,MD 20892. NCI,CELL BIOL LAB,BETHESDA,MD 20892. UNIV CAMBRIDGE,DEPT BIOCHEM,CAMBRIDGE CB2 1QW,ENGLAND. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 75 TC 88 Z9 90 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 APR 7 PY 1992 VL 31 IS 13 BP 3463 EP 3471 DI 10.1021/bi00128a021 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HM442 UT WOS:A1992HM44200021 PM 1554728 ER PT J AU POSSANI, LD MOCHCAMORALES, J AMEZCUA, J MARTIN, BM PRESTIPINO, G NOBILE, M AF POSSANI, LD MOCHCAMORALES, J AMEZCUA, J MARTIN, BM PRESTIPINO, G NOBILE, M TI ANIONIC CURRENTS OF CHICK SENSORY NEURONS ARE AFFECTED BY A PHOSPHOLIPASE-A2 PURIFIED FROM THE VENOM OF THE TAIPAN SNAKE SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Article DE DORSAL ROOT GANGLION; ANIONIC CHANNEL; WHOLE-CELL CLAMP; PHOSPHOLIPASE-A2; SNAKE VENOM; (OXYURANUS-SCUTELLATUS-SCUTELLATUS) ID OXYURANUS-S-SCUTELLATUS; AMINO-ACID-SEQUENCE; BUNGARUS-MULTICINCTUS VENOM; PRE-SYNAPTIC NEUROTOXIN; MOTOR-NERVE TERMINALS; BETA-BUNGAROTOXIN; ENZYMATIC-ACTIVITY; ISOLATED TOXIN; CONDUCTANCE; TAIPOXIN AB A neurotoxic phospholipase A2 was purified from the venom of the taipan snake Oxyuranus scutellatus scutellatus by three consecutive chromatographic steps on ion exchange resins, followed by an affinity column prepared with a phosphatidylcholine derivative attached to Sepharose. The phospholipase was shown to be of type A2 (specific activity of 85 units/mg protein), and an apparent molecular weight of 16000. Amino acid analysis shows the presence of approx. 150 residues with the N-terminal amino acid sequence: NLAQFGFMIRCANGGSRSALDYADYGC, different from all the phospholipases described until now. This enzyme is lethal to experimental mice (LD50 = 10-mu-g/20 g mouse weight) and affects ionic currents in chick (Gallus domesticus) dorsal root ganglion cells, measured by the whole-cell clamp technique. In symmetrical external/internal ionic solutions, after suppression of Na+, K+ and Ca2+ currents, external application of phospholipase at a low concentration (30 nM) was shown to increase the baseline current in a reversible manner. The augmented response was voltage-dependent and the effect was much greater for negative currents. In the presence of a salt gradient across the membrane (out 40 mM NaCl/in 140 mM CsCl), the current reversal potential revealed a shift in the positive direction typically due to Cl- ion flux through the membrane. External application of a 50-mu-M concentration of picrotoxin caused a reversible reduction of the phospholipase-induced chloride current. Moreover, no appreciable current block was detected after addition of 50-mu-M DIDS. C1 NIMH, CLIN NEUROSCI BRANCH, BETHESDA, MD 20892 USA. CNR, IST CIBERNET & BIOFIS, GENOA, ITALY. RP POSSANI, LD (reprint author), UNIV NACL AUTONOMA MEXICO, INST BIOTECNOL, DEPT BIOQUIM, APARTADO POSTAL 510-3, CUERNAVACA 62271, MORELOS, MEXICO. RI Possani, Lourival/J-2397-2013 NR 49 TC 3 Z9 4 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 APR 7 PY 1992 VL 1134 IS 3 BP 210 EP 216 DI 10.1016/0167-4889(92)90178-E PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA HQ546 UT WOS:A1992HQ54600005 PM 1373076 ER PT J AU ZIDOVETZKI, R LESTER, DS AF ZIDOVETZKI, R LESTER, DS TI THE MECHANISM OF ACTIVATION OF PROTEIN-KINASE-C - A BIOPHYSICAL PERSPECTIVE SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Review DE PROTEIN KINASE-C; ACTIVATION ID PHORBOL ESTER RECEPTOR; PHOSPHOLIPID-BILAYER MEMBRANES; HEXAGONAL PHASE-TRANSITION; RAT-BRAIN; PHOSPHATIDYLCHOLINE BILAYERS; KINETIC-ANALYSIS; HUMAN-PLATELETS; GROWTH-FACTOR; DIACYLGLYCEROL; CALCIUM C1 NIH,NEURAL SYST SECT,12420 PARKLAWN DR,RM 435,ROCKVILLE,MD 20852. UNIV CALIF RIVERSIDE,DEPT BIOL,RIVERSIDE,CA 92521. NR 111 TC 105 Z9 105 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 APR 7 PY 1992 VL 1134 IS 3 BP 261 EP 272 DI 10.1016/0167-4889(92)90185-E PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA HQ546 UT WOS:A1992HQ54600012 PM 1558850 ER PT J AU YANG, YC VU, ND WAGNER, PD AF YANG, YC VU, ND WAGNER, PD TI GUANINE-NUCLEOTIDE STIMULATION OF NOREPINEPHRINE SECRETION FROM PERMEABILIZED PC12 CELLS - EFFECTS OF MG2+, OTHER NUCLEOTIDE TRIPHOSPHATES AND N-ETHYLMALEIMIDE SO BIOCHIMICA ET BIOPHYSICA ACTA LA English DT Article DE GTP-BINDING PROTEIN; SECRETION; PC12 CELL; CELL PERMEABILIZATION; (RAT) ID ADRENAL CHROMAFFIN CELLS; GTP-BINDING PROTEINS; CATECHOLAMINE SECRETION; MAST-CELLS; KINASE-C; EXOCYTOSIS; SECRETAGOGUES; STAUROSPORINE; NEUTROPHILS; ACTIVATION AB The addition of either Ca2+ or guanosine 5'-O-3-(thiotriphosphate), GTP-gamma-S, to digitonin-permeabilized rat pheochromocytoma PC12 cells stimulates norepinephrine release. Unlike Ca2+-stimulated release, there is a delay between the time of addition of GTP-gamma-S to digitonin-permeabilized PC12 cells and stimulation of norepinephrine release. Preincubation of the permeabilized cells in the absence of Mg2+ eliminates this lag and increases the initial rate of GTP-gamma-S-stimulated norepinephrine secretion. This suggests that the rate of GDP dissociation from the GTP-binding protein responsible for this stimulation is faster in the absence of Mg2+ than in its presence. While an equimolar concentration of GTP gives 50% inhibition of GTP-gamma-S-stimulated release, 100-fold excesses of ITP, ATP, UTP and CTP gave no inhibition of GTP-gamma-S-stimulated release. Both the inability of ITP to inhibit GTP-gamma-S-stimulated secretion and the increase in GTP-gamma-S-stimulated secretion caused by preincubation in the absence of Mg2+ indicate that some of the properties of the GTP-binding protein responsible for this stimulation are more like those of the low molecular weight GTP-binding proteins rap1 and ras than those of a heterotrimeric G-protein. Low concentrations of N-ethylmaleimide gave more inhibition of GTP-gamma-S-stimulated release than Ca2+-stimulated release which suggests that the mechanisms by which Ca2+ and GTP-gamma-S stimulate norepinephrine release are at least in part distinct. C1 NCI,BIOCHEM LAB,BLDG 37,RM 4C24,BETHESDA,MD 20892. NR 41 TC 6 Z9 6 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 APR 7 PY 1992 VL 1134 IS 3 BP 285 EP 291 DI 10.1016/0167-4889(92)90188-H PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA HQ546 UT WOS:A1992HQ54600015 PM 1558851 ER PT J AU LIU, DT AF LIU, DT TI OPPORTUNITIES FOR SCIENTISTS OF ASIAN ORIGIN IN THE UNITED-STATES-PUBLIC-HEALTH-SERVICE SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH,CBER,DIV BIOCHEM & BIOPHYS,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 5 PY 1992 VL 203 BP 4 EP PROF PN 3 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA HK163 UT WOS:A1992HK16300896 ER PT J AU EASTIN, WC WALTERS, DB AF EASTIN, WC WALTERS, DB TI OVERVIEW OF THE NATIONAL TOXICOLOGY PROGRAMS TOXICOLOGY AND CARCINOGENESIS STUDIES SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIEHS,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 5 PY 1992 VL 203 BP 10 EP CHAS PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA HK161 UT WOS:A1992HK16102650 ER PT J AU BREWSTER, ME PITHA, J HUANG, M POP, E BODOR, N AF BREWSTER, ME PITHA, J HUANG, M POP, E BODOR, N TI SELECTIVE BASE-CONTROLLED HYDROXYPROPYLATION - AN AM1 STUDY OF GLUCOSE SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 PHARMATEC INC,ALACHUA,FL 32615. UNIV FLORIDA,CTR DRUG DISCOVERY,GAINESVILLE,FL 32610. NIA,MACROMOLEC CHEM SECT,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 5 PY 1992 VL 203 BP 11 EP CARB PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA HK161 UT WOS:A1992HK16100800 ER PT J AU BUENGER, GS MARQUEZ, VE AF BUENGER, GS MARQUEZ, VE TI SYNTHESIS AND BIOLOGICAL EVALUATION OF CYCLOPENTENYL 1,2-DIHYDROPYRIMIDIN-2-ONE (CPE-Z) SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,DCT,DTP,MED CHEM LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 5 PY 1992 VL 203 BP 12 EP CARB PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA HK161 UT WOS:A1992HK16100801 ER PT J AU HARDY, BJ AF HARDY, BJ TI CALCULATION OF ENSEMBLE AVERAGED MOLECULAR-PROPERTIES OF OLIGOSACCHARIDES FOR COMPARISON WITH EXPERIMENT SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH,CBER,DBB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 5 PY 1992 VL 203 BP 23 EP CELL PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA HK161 UT WOS:A1992HK16100913 ER PT J AU MARQUEZ, VE LIM, B BARCHI, JJ DRISCOLL, JS AF MARQUEZ, VE LIM, B BARCHI, JJ DRISCOLL, JS TI CONFORMATIONAL STUDIES AND ANTI-HIV ACTIVITY OF DIFLUORODIDEOXY NUCLEOSIDES SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,MED CHEM LAB,BETHESDA,MD 20892. RI Barchi Jr., Joseph/N-3784-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 5 PY 1992 VL 203 BP 25 EP CARB PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA HK161 UT WOS:A1992HK16100814 ER PT J AU PICHLER, EE AF PICHLER, EE TI RNNN - A PROGRAM FOR MODELING OF REACTION NETWORKS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NATL CTR BIOTECHNOL INFORMAT,NLM,BETHESDA,MD 20894. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 5 PY 1992 VL 203 BP 40 EP COMP PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA HK161 UT WOS:A1992HK16101925 ER PT J AU PERLMAN, ME AF PERLMAN, ME TI SYNTHESIS OF 2'-DEUTERIATED TUBERCIDIN AND ADENOSINE SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 5 PY 1992 VL 203 BP 41 EP CARB PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA HK161 UT WOS:A1992HK16100830 ER PT J AU KROEGERKOEPKE, MB MICHEJDA, CJ SMITH, RH AF KROEGERKOEPKE, MB MICHEJDA, CJ SMITH, RH TI DNA ALKYLATION BY NOVEL CHEMOTHERAPEUTIC 1,3-DIALKYL-3-ACYLTRIAZENES SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,ABL,BRP,FREDERICK,MD 21702. WESTERN MARYLAND COLL,WESTMINSTER,MD 21157. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 5 PY 1992 VL 203 BP 46 EP MEDI PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA HK162 UT WOS:A1992HK16200247 ER PT J AU LUNN, G SANSONE, EB AF LUNN, G SANSONE, EB TI DEGRADATION OF HYDRAZINES AND OTHER TOXIC COMPOUNDS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 DYNCORP,PROGRAM RESOURCES INC,NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 5 PY 1992 VL 203 BP 49 EP CHAS PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA HK161 UT WOS:A1992HK16101407 ER PT J AU WALTERS, DB HIXSON, EJ JOHNSON, MT KEITH, LH AF WALTERS, DB HIXSON, EJ JOHNSON, MT KEITH, LH TI HAZ-LABEL - AN EXPERT SYSTEM FOR LABELING NTP CHEMICALS FOR EMERGENCY RESPONSE SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIEHS,NATL TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709. RADIAN CORP,AUSTIN,TX 78720. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 5 PY 1992 VL 203 BP 51 EP CHAS PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA HK161 UT WOS:A1992HK16101409 ER PT J AU WONG, G GU, ZQ FRYER, RI RICE, KC SKOLNICK, P AF WONG, G GU, ZQ FRYER, RI RICE, KC SKOLNICK, P TI SYNTHESIS AND EVALUATION OF POTENTIAL LIGANDS FOR THE DIAZEPAM-INSENSITIVE (DI) ISOFORM OF BENZODIAZEPINE RECEPTOR SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDKD,NEUROSCI LAB,BETHESDA,MD 20892. NIDDKD,MED CHEM LAB,BETHESDA,MD 20892. RUTGERS STATE UNIV,DEPT CHEM,NEWARK,NJ 07102. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 5 PY 1992 VL 203 BP 82 EP MEDI PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA HK162 UT WOS:A1992HK16200283 ER PT J AU DOMINGUEZ, C RICE, KC DECOSTA, BR GEORGE, C AKUNNE, HC ROTHMAN, RB AF DOMINGUEZ, C RICE, KC DECOSTA, BR GEORGE, C AKUNNE, HC ROTHMAN, RB TI SYNTHESIS OF ISOTHIOCYANATE SUBSTITUTED N-[1-(2-BENZO[B]THIENYL]PIPERIDINES AS POTENTIAL AFFINITY LIGANDS FOR FURTHER CHARACTERIZATION OF THE COCAINE RECEPTOR SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDKD,MED CHEM LAB,BETHESDA,MD 20892. USN,RES LAB,WASHINGTON,DC 20375. NIDA,ADDICT RES CTR,CLIN PHARMACOL LAB,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 5 PY 1992 VL 203 BP 97 EP MEDI PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA HK162 UT WOS:A1992HK16200298 ER PT J AU CRAGG, GM BOYD, MR CARDELLINA, JH GREVER, MR SCHEPARTZ, SA SNADER, KM SUFFNESS, M AF CRAGG, GM BOYD, MR CARDELLINA, JH GREVER, MR SCHEPARTZ, SA SNADER, KM SUFFNESS, M TI THE ROLE OF PLANTS IN THE NATIONAL-CANCER-INSTITUTE DRUG DISCOVERY AND DEVELOPMENT PROGRAM SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 5 PY 1992 VL 203 BP 108 EP AGFD PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA HK161 UT WOS:A1992HK16100107 ER PT J AU SIEGALL, CB GAWLAK, SL PASTAN, I AF SIEGALL, CB GAWLAK, SL PASTAN, I TI TARGETED TOXINS AS CYTOTOXIC AGENTS AGAINST HUMAN CANCER SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 BRISTOL MYERS SQUIBB,PHARMACEUT RES INST,WALLINGFORD,CT 06492. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 5 PY 1992 VL 203 BP 111 EP NUCL PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA HK162 UT WOS:A1992HK16201334 ER PT J AU CARDELLINA, JH MCMAHON, JB SHOEMAKER, RH CRAGG, GM BOYD, MR AF CARDELLINA, JH MCMAHON, JB SHOEMAKER, RH CRAGG, GM BOYD, MR TI AIDS-ANTIVIRAL AND CYTOTOXIC AGENTS FROM TROPICAL PLANTS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,DEV THERAPEUT PROGRAM,DRUG DISCOVERY RES & DEV LAB,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 5 PY 1992 VL 203 BP 121 EP AGFD PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA HK161 UT WOS:A1992HK16100119 ER PT J AU BADEN, DG AF BADEN, DG TI METHODS FOR DETECTING BREVETOXINS IN SEAWATER, IN BIOLOGICAL MATRIX, AND ON EXCITABLE-MEMBRANES SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 UNIV MIAMI,NIEHS,CTR MARINE & FRESHWATER BIOMED SCI,MIAMI,FL 33149. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 5 PY 1992 VL 203 BP 128 EP AGFD PN 1 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA HK161 UT WOS:A1992HK16100126 ER PT J AU ABDELGHANY, Y DONKOR, I KADOR, P MIZOGUCHI, T MALIK, A MILLER, D AF ABDELGHANY, Y DONKOR, I KADOR, P MIZOGUCHI, T MALIK, A MILLER, D TI NOVEL ALRESTATIN ANALOGS WITH POTENT REVERSIBLE AND IRREVERSIBLE INHIBITORY ACTIVITY FOR THE ENZYME ALDOSE REDUCTASE SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 XAVIER UNIV LOUISIANA,NEW ORLEANS,LA 70125. OHIO STATE UNIV,COLL PHARM,COLUMBUS,OH 43210. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 5 PY 1992 VL 203 BP 135 EP MEDI PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA HK162 UT WOS:A1992HK16200335 ER PT J AU GANSOW, OA BRECHBIEL, MW PIPPIN, CG MCMURRY, TJ WALDMANN, TA CARRASQUILLO, J STRAND, M SQUIRE, RA HUNEKE, RB AF GANSOW, OA BRECHBIEL, MW PIPPIN, CG MCMURRY, TJ WALDMANN, TA CARRASQUILLO, J STRAND, M SQUIRE, RA HUNEKE, RB TI EFFECTIVE CHELATORS FOR Y-90 AND BI-212 RADIOIMMUNOTHERAPY OF CANCER SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,BALTIMORE,MD 21218. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 5 PY 1992 VL 203 BP 144 EP NUCL PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA HK162 UT WOS:A1992HK16201367 ER PT J AU TADIC, D ROTHMAN, RB XU, H JACOBSON, AE RICE, KC AF TADIC, D ROTHMAN, RB XU, H JACOBSON, AE RICE, KC TI EPIMERIC OXIDE BRIDGED 5-(3-HYDROXYPHENYL)2-METHYLMORPHANS AS OPIOID RECEPTOR PROBES SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDK,MED CHEM LAB,BETHESDA,MD 20892. NIDA,ADDICT RES CTR,CLIN PSYCHOPHARMACOL LAB,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 5 PY 1992 VL 203 BP 205 EP MEDI PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA HK162 UT WOS:A1992HK16200404 ER PT J AU CHRISTODOULOU, D WINK, DA KEEFER, LK GEORGE, C AF CHRISTODOULOU, D WINK, DA KEEFER, LK GEORGE, C TI NITRIC OXIDE-NUCLEOPHILE COMPLEXES AS LIGANDS - A NEW CLASS OF MIXED-LIGAND COPPER(II) COMPLEXES SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,FREDRICK CANC RES DEV CTR,COMPARAT CARCINOGENESIS LAB,CHEM SECT,FREDERICK,MD 21702. USN,RES LAB,STRUCT MATTER LAB,WASHINGTON,DC 20375. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 5 PY 1992 VL 203 BP 217 EP INOR PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA HK162 UT WOS:A1992HK16200627 ER PT J AU MCMURRY, TJ BRECHBIEL, MW WU, C PIPPIN, CG GANSOW, OA AF MCMURRY, TJ BRECHBIEL, MW WU, C PIPPIN, CG GANSOW, OA TI SOLUTION EQUILIBRIUM STUDIES OF BIFUNCTIONAL DTPA LIGANDS WITH FE(III) AND Y(III) SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 5 PY 1992 VL 203 BP 218 EP INOR PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA HK162 UT WOS:A1992HK16200628 ER PT J AU LEVY, HB SALAZAR, A REED, W MORALES, J AF LEVY, HB SALAZAR, A REED, W MORALES, J TI STUDIES OF POLYICLC IN AIDS PATIENTS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 ASHFORD HOSP,SAN JUAN,PR. NIAID,BETHESDA,MD 20892. WALTER REED ARMY MED CTR,WASHINGTON,DC 20307. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 5 PY 1992 VL 203 BP 248 EP PMSE PN 3 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA HK163 UT WOS:A1992HK16300870 ER PT J AU SMITH, RH PRUSKI, B PFALTZGRAFF, T MICHEJDA, CJ AF SMITH, RH PRUSKI, B PFALTZGRAFF, T MICHEJDA, CJ TI FORMATION OF ALIPHATIC AZIMINES IN AN UNEXPECTED REACTION SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 WESTERN MARYLAND COLL,DEPT CHEM,WESTMINSTER,MD 21157. NCI,FREDERICK CANC RES & DEV CTR,ABL,BRP,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 5 PY 1992 VL 203 BP 423 EP ORGN PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA HK162 UT WOS:A1992HK16201807 ER PT J AU EICHHORN, GL BUTZOW, J BEAL, R CHUKNYISKY, P GARLAND, C TARIEN, E STANKIS, R JANZEN, C AF EICHHORN, GL BUTZOW, J BEAL, R CHUKNYISKY, P GARLAND, C TARIEN, E STANKIS, R JANZEN, C TI A METAL-ION SWITCH FOR SECURING FIDELITY IN RNA-SYNTHESIS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,EYE LAB,BALTIMORE,MD 21224. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 5 PY 1992 VL 203 BP 662 EP INOR PN 2 PG 0 WC Chemistry, Multidisciplinary SC Chemistry GA HK162 UT WOS:A1992HK16201070 ER PT J AU SHIBATA, S MIDURA, RJ HASCALL, VC AF SHIBATA, S MIDURA, RJ HASCALL, VC TI STRUCTURAL-ANALYSIS OF THE LINKAGE REGION OLIGOSACCHARIDES AND UNSATURATED DISACCHARIDES FROM CHONDROITIN SULFATE USING CARBOPAC PA1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SWARM RAT CHONDROSARCOMA; PERFORMANCE LIQUID-CHROMATOGRAPHY; ANION-EXCHANGE CHROMATOGRAPHY; PULSED AMPEROMETRIC DETECTION; PROTEOGLYCAN BIOSYNTHESIS; CARTILAGE PROTEOGLYCAN; EMBRYONIC CHICKEN; DERMATAN SULFATE; CORNEAL EXPLANTS; HYALURONIC-ACID AB Swarm rat chondrosarcoma cell cultures were metabolically labeled with [S-35]sulfate, [H-3]glucose, or [H-3]glucosamine. Chondroitin sulfate chains were isolated from purified aggrecan using alkaline borohydride treatment and Superose 6 chromatography. Various linkage region oligosaccharide alditols were derived from these chains using sequential chondroitinase digestions (ABC lyase followed by ACII lyase). They were then further processed by mercuric acetate treatment, which removed the 4,5-unsaturated uronosyl residue from the nonreducing end of the linkage, and then beta-galactosidase digestion which liberated the 2 galactose residues from the xylitol reducing terminus. Alkaline phosphatase digestions were performed to verify the presence of phosphate esters. All linkage region structures were isolated and identified using a combination of Progel-TSK G2500 and CarboPac PA1 chromatography steps in conjunction with monosaccharide analyses. This study revealed that chondroitin sulfate chains from aggrecan synthesized by rat chondrosarcoma cells in vitro have the following properties: 1) three out of every four of their linkage regions carry a phosphate ester on xylose, 2) nearly three out of every five chains begin the repeating disaccharide region with an unsulfated first disaccharide unit, 3) nearly twice as many nonphosphorylated chains have a sulfated first disaccharide than their phosphorylated counterparts, and 4) the vast majority of these chains do not contain sulfated galactose in their linkage regions. This report also describes a borohydride reduction procedure to confer alkali stability to the 3-substituted, unsaturated disaccharides derived from chondroitinase digests of chondroitin sulfate. Furthermore, a CarboPac PA1 method is demonstrated that separates these reduced disaccharides with exceptional resolution. C1 NIDR,BONE RES BRANCH,PROTEOGLYCAN CHEM SECT,BLDG 30,RM 106,BETHESDA,MD 20892. NR 39 TC 63 Z9 66 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 APR 5 PY 1992 VL 267 IS 10 BP 6548 EP 6555 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HM053 UT WOS:A1992HM05300018 PM 1551866 ER PT J AU BATINIC, D ROBEY, FA AF BATINIC, D ROBEY, FA TI THE V3 REGION OF THE ENVELOPE GLYCOPROTEIN OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 BINDS SULFATED POLYSACCHARIDES AND CD4-DERIVED SYNTHETIC PEPTIDES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NEUTRALIZING MONOCLONAL-ANTIBODY; DEXTRAN SULFATE; HIV-1 GP120; SYNCYTIUM FORMATION; VIRION BINDING; CD4 MOLECULE; PROTEIN; CELLS; SITE; SEQUENCE AB Gp120 is the envelope glycoprotein found on the surface of human immunodeficiency virus type 1 (HIV-1), and it binds to human cell surface CD4 receptors to initiate the HIV-1 infection process. It is now well-established that synthetic peptides from the V3 region on gp120 elicit antibodies that block HIV-1 infection and HIV-1-mediated cell fusion. Here we show that synthetic peptides derived from similar V3 regions of several isolates of HIV-1 bind [H-3]heparin, and we also demonstrate that [H-3]heparin binds to recombinant gp120 IIIB. The binding could be blocked by unlabeled heparin, dextran sulfate, and by a highly anionic benzylated synthetic peptide derived from human CD4 (amino acids 81-92). The nonbenzylated peptides from the same region were considerably less active. Unlabeled heparin, dextran sulfate, and the CD4-derived peptides were able to compete with the binding of soluble gp120 to immobilized antibodies against fragments of the V3 from isolate IIIB, but they had no effect on the binding of gp120 to anti-peptide antibodies targeted against another unrelated region of gp120. Biotin conjugated to the benzylated CD4-peptide bound to gp120 and was blocked from this binding by anti-V3 antibodies. These results indicate that the three materials that have been demonstrated by others to block HIV-1 infection in vitro, sulfated polysaccharides, certain CD4-derived synthetic peptides, and anti-V3 antibodies, may be acting through a common mechanism that includes binding to the V3 region of gp120 on HIV-1. RP BATINIC, D (reprint author), NIDR,CELLULAR DEV & ONCOL LAB,BETHESDA,MD 20892, USA. NR 46 TC 132 Z9 133 U1 2 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 5 PY 1992 VL 267 IS 10 BP 6664 EP 6671 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HM053 UT WOS:A1992HM05300034 PM 1551875 ER PT J AU NIKLINSKA, BB YAMADA, H OSHEA, JJ JUNE, CH ASHWELL, JD AF NIKLINSKA, BB YAMADA, H OSHEA, JJ JUNE, CH ASHWELL, JD TI TYROSINE KINASE-REGULATED AND INOSITOL PHOSPHATE-INDEPENDENT CA2+ ELEVATION AND MOBILIZATION IN T-CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ANTIGEN RECEPTOR; SIGNAL TRANSDUCTION; PROTEIN-PHOSPHORYLATION; PHOSPHOLIPID BREAKDOWN; MONOCLONAL-ANTIBODY; ACTIVATION; CALCIUM; EXPRESSION; COMPLEX; CA-2+ AB Perturbation of the T cell antigen-specific receptor leads to a series of signaling events that includes a rapid increase in phosphoinositide hydrolysis, intracellular Ca2+, and tyrosine phosphorylation. We have examined the function of tyrosine phosphorylation in isolation by introducing the v-src tyrosine kinase into a T cell hybridoma. T cell receptor-mediated increases in phosphoinositide hydrolysis and, in particular the generation of inositol 1,4,5-trisphosphate, were comparable between v-src+ and v-src- cells. Unexpectedly, the v-src+ cells exhibited spontaneously elevated intracellular Ca2+ and exaggerated Ca2+ increases when stimulated via the T cell receptor. The enhanced Ca2+ response was not due to tyrosine phosphorylation of the T cell receptor itself, since the phenotype was evident in T cell receptor zeta-chain-/v-src+ cells as well. These results demonstrate that an active protein tyrosine kinase can markedly affect intracellular Ca2+ handling by a process independent of inositol 1,4,5-trisphosphate production and T cell receptor tyrosine phosphorylation and raise the possibility that tyrosine kinases may directly regulate T cell receptor-mediated changes in intracellular Ca2+. C1 USN,IMMUNE CELL BIOL PROGRAM,MED RES INST,BETHESDA,MD 20889. NCI,FREDERICK CANC RES & DEV CTR,EXPTL IMMUNOL LAB,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. RP NIKLINSKA, BB (reprint author), NIH,IMMUNE CELL BIOL SECT,BIOL RESPONSE MODIFIERS PROGRAM,BETHESDA,MD 20892, USA. NR 41 TC 43 Z9 43 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 APR 5 PY 1992 VL 267 IS 10 BP 7154 EP 7159 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HM053 UT WOS:A1992HM05300107 PM 1551921 ER PT J AU ROSENBERG, GA KORNFELD, M ESTRADA, E KELLEY, RO LIOTTA, LA STETLERSTEVENSON, WG AF ROSENBERG, GA KORNFELD, M ESTRADA, E KELLEY, RO LIOTTA, LA STETLERSTEVENSON, WG TI TIMP-2 REDUCES PROTEOLYTIC OPENING OF BLOOD-BRAIN-BARRIER BY TYPE-IV COLLAGENASE SO BRAIN RESEARCH LA English DT Article DE BASAL LAMINA; BLOOD-BRAIN BARRIER; INTRACEREBRAL HEMORRHAGE; METALLOPROTEINASE; RAT; STROKE; TIMP-2; TYPE-IV COLLAGENASE ID INTRACEREBRAL HEMORRHAGE; METALLOPROTEINASES; EXPRESSION; INHIBITORS; TUMORS; CELLS AB Intracerebral hemorrhage occurs in tumors, stroke and head trauma. Proteolysis of the extracellular matrix around cerebral capillaries by naturally occurring mammalian 72-kDa type IV collagenase may initiate this pathologic event. To investigate this hypothesis adult rats underwent intracerebral injection of type IV collagenase purified from human melanoma cells. Histologically, at 4 h there was perivascular cellular infiltration with hemorrhage, and by 24 h there was infarction with necrosis, edema and hemorrhage. Ultrastructurally, the basal lamina of endothelial cells was disrupted at 2 h. Brain uptake of [C-14]dextran and [H-3]sucrose increased after intracerebral injection of type IV collagenase compared to controls (P < 0.0001). Tissue inhibitor of metalloproteinase-2 (TIMP-2) reduced the tracer uptake (P < 0.02). Metalloproteinase inhibitors reduce extracellular matrix proteolysis and protect the blood-brain barrier. C1 UNIV NEW MEXICO,SCH MED,DEPT ANAT,ALBUQUERQUE,NM 87131. VET AFFAIRS MED CTR,NEUROL SERV,ALBUQUERQUE,NM. VET AFFAIRS MED CTR,RES SERV,ALBUQUERQUE,NM. UNIV NEW MEXICO,SCH MED,DEPT PATHOL NEUROPATHOL,ALBUQUERQUE,NM 87131. NCI,PATHOL LAB,BETHESDA,MD 20892. RP ROSENBERG, GA (reprint author), UNIV NEW MEXICO,SCH MED,DEPT NEUROL,ALBUQUERQUE,NM 87131, USA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 FU NINDS NIH HHS [R01-NS21169] NR 22 TC 220 Z9 224 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD APR 3 PY 1992 VL 576 IS 2 BP 203 EP 207 DI 10.1016/0006-8993(92)90681-X PG 5 WC Neurosciences SC Neurosciences & Neurology GA HP178 UT WOS:A1992HP17800003 PM 1381261 ER PT J AU YAMAGAMI, K JOSEPH, JA ROTH, GS AF YAMAGAMI, K JOSEPH, JA ROTH, GS TI DECREMENT OF MUSCARINIC RECEPTOR-STIMULATED LOW-KMGTPASE IN STRIATUM AND HIPPOCAMPUS FROM THE AGED RAT SO BRAIN RESEARCH LA English DT Note DE GTPASE; AGING; STRIATUM; HIPPOCAMPUS; MUSCARINIC RECEPTOR; SIGNAL TRANSDUCTION ID ALZHEIMERS-DISEASE; GTPASE ACTIVITY; G-PROTEINS; BRAIN; BINDING; SENESCENCE; DOPAMINE AB Previous studies have shown that there is an age-related loss of responsiveness in several different receptor systems (e.g. beta-adrenergic, dopaminergic and muscarinic). Our research, using perifused striatal slices and examining muscarinic agonist enhancement of K+-evoked dopamine release, has determined that at least part of the loss of sensitivty in muscarinic receptors (mAChR) may occur early in the post-receptor signal transduction process. The present study was carried out to further characterize and localize this deficit by examining carbachol- and oxotremorine-stimulated low-K(M) guanosine triphosphatase (GTPase) activity in striatal as well as hippocampal tissue obtained from adult (6 months) and old (24 months) Wistar rats. Receptor stimulated low-K(M) GTPase catalyzes the conversion of GTP to GDP to end the signal transduction cycle and is an indicator of receptor-G-protein coupling/uncoupling. The results showed that stimulated GTPase activity was significantly reduced in hippocampal and striatal tissue from the old animals. These findings suggest that there may be an age-related coupling/uncoupling deficit between muscarinic receptor and G-proteins, and that this deficit may contribute to the reduced mAChR responsiveness in senescence. C1 NIA, FRANCIS SCOTT KEY MED CTR, GERONTOL RES CTR, BETHESDA, MD 20892 USA. RI Yamagami, Keiji/E-9500-2012 NR 26 TC 48 Z9 48 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD APR 3 PY 1992 VL 576 IS 2 BP 327 EP 331 DI 10.1016/0006-8993(92)90698-9 PG 5 WC Neurosciences SC Neurosciences & Neurology GA HP178 UT WOS:A1992HP17800020 PM 1515926 ER PT J AU ROTH, DB NAKAJIMA, PB MENETSKI, JP BOSMA, MJ GELLERT, M AF ROTH, DB NAKAJIMA, PB MENETSKI, JP BOSMA, MJ GELLERT, M TI V(D)J RECOMBINATION IN MOUSE THYMOCYTES - DOUBLE-STRAND BREAKS NEAR T-CELL RECEPTOR DELTA REARRANGEMENT SIGNALS SO CELL LA English DT Article ID GAMMA-DELTA; SACCHAROMYCES-CEREVISIAE; IMMUNOGLOBULIN GENES; HOMOLOGOUS RECOMBINATION; SEQUENCE HOMOLOGIES; CODING SEGMENTS; MAMMALIAN-CELLS; DNA; GENERATION; MECHANISM AB In the murine T cell receptor delta-locus, V(D)J recombination events frequently involve the D2 and J1 elements. Here we report the presence of double-strand breaks at recombination signals flanking D2 in approximately 2% of thymus DNA. An excised linear species containing the sequences between D2 and J1 and a circular product of the joining of D2 and J1 recombination signals were also found. Although broken molecules with signal ends were detected, no species with coding ends could be identified. Observation of these broken molecules in thymus, but not in liver or spleen, provides the first direct evidence for an association between specific cleavage of chromosomal DNA and recombination in mammalian cells, and supports a breakage-reunion model of V(D)J recombination. C1 FOX CHASE CANC INST,INST CANC RES,PHILADELPHIA,PA 19111. RP ROTH, DB (reprint author), NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. FU NCI NIH HHS [CA-04946]; NCRR NIH HHS [RR-05539]; NIAID NIH HHS [AI-13323] NR 64 TC 172 Z9 172 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD APR 3 PY 1992 VL 69 IS 1 BP 41 EP 53 DI 10.1016/0092-8674(92)90117-U PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA HM445 UT WOS:A1992HM44500005 PM 1313336 ER PT J AU GAILANI, MR BALE, SJ LEFFELL, DJ DIGIOVANNA, JJ PECK, GL POLIAK, S DRUM, MA PASTAKIA, B MCBRIDE, OW KASE, R GREENE, M MULVIHILL, JJ BALE, AE AF GAILANI, MR BALE, SJ LEFFELL, DJ DIGIOVANNA, JJ PECK, GL POLIAK, S DRUM, MA PASTAKIA, B MCBRIDE, OW KASE, R GREENE, M MULVIHILL, JJ BALE, AE TI DEVELOPMENTAL DEFECTS IN GORLIN SYNDROME RELATED TO A PUTATIVE TUMOR SUPPRESSOR GENE ON CHROMOSOME-9 SO CELL LA English DT Article ID BASAL-CELL-CARCINOMA; NEVUS SYNDROME; CANCER; RETINOBLASTOMA; FIBROBLASTS; RADIATION; TISSUE AB Gorlin syndrome is an autosomal dominant disorder that predisposes to basal cell carcinomas of the skin, ovarian fibromas, and medulloblastomas. Unlike other hereditary disorders associated with cancer, it features widespread developmental defects. To investigate the possibility that the syndrome is caused by mutation in a tumor suppressor gene, we searched for loss of heterozygosity in 16 sporadic basal cell carcinomas, 2 hereditary basal cell carcinomas, and 1 hereditary ovarian fibroma and performed genetic linkage studies in five Gorlin syndrome kindreds. Eleven sporadic basal cell carcinomas and all 3 hereditary tumors had allelic loss of chromosome 9q31, and all informative kindreds showed tight linkage between the Gorlin syndrome gene and a genetic marker in this region. Loss of heterozygosity at this chromosomal location, particularly in hereditary tumors, implies that the gene is homozygously inactivated and normally functions as a tumor suppressor. In contrast, hemizygous germline mutations lead to multiple congenital anomalies. C1 NIH,CTR CLIN,DEPT RADIOL,BETHESDA,MD 20892. WESTAT CORP,ROCKVILLE,MD 20852. YALE UNIV,SCH MED,DEPT DERMATOL,NEW HAVEN,CT 06510. NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892. NIDR,CLIN INVEST & PATIENT CARE BRANCH,BETHESDA,MD 20892. NCI,DERMATOL BRANCH,BETHESDA,MD 20892. NCI,BIOCHEM LAB,BETHESDA,MD 20892. NCI,CLIN EPIDEMIOL BRANCH,BETHESDA,MD 20892. RP GAILANI, MR (reprint author), YALE UNIV,SCH MED,DEPT GENET,NEW HAVEN,CT 06510, USA. NR 46 TC 316 Z9 318 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD APR 3 PY 1992 VL 69 IS 1 BP 111 EP 117 DI 10.1016/0092-8674(92)90122-S PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA HM445 UT WOS:A1992HM44500010 PM 1348213 ER PT J AU SHIBUSAWA, Y ITO, Y IKEWAKI, K RADER, DJ BREWER, HB AF SHIBUSAWA, Y ITO, Y IKEWAKI, K RADER, DJ BREWER, HB TI COUNTERCURRENT CHROMATOGRAPHY OF LIPOPROTEINS WITH A POLYMER PHASE SYSTEM USING THE CROSS-AXIS SYNCHRONOUS COIL PLANET CENTRIFUGE SO JOURNAL OF CHROMATOGRAPHY LA English DT Note ID GEL-PERMEATION CHROMATOGRAPHY; PERFORMANCE LIQUID-CHROMATOGRAPHY; HIGH-DENSITY LIPOPROTEIN; SERUM-LIPOPROTEINS; SELECTIVE DETECTION; ENZYMATIC-REACTION; ROTARY SEALS; CHOLESTEROL; SEPARATION AB Lipoproteins were separated by counter-current chromatography using the type-XLL coil planet centrifuge. The separation was performed with a polymer phase system composed of 16% (w/w) polyethylene glycol 1000 and 12.5% (w/w) dibasic potassium phosphate by eluting the lower phase at a flow-rate of 0.5 ml min. About 5 ml of the sample solution containing approximately 150 mg of a lipoprotein mixture were loaded. High- and low-density lipoproteins were resolved within 12 h. Each component was detected by gel electrophoresis with oil red staining. C1 NHLBI,BIOPHYS CHEM LAB,BLDG 10,ROOM 7N322,BETHESDA,MD 20892. NHLBI,MOLEC DIS BRANCH,BETHESDA,MD 20892. NR 19 TC 14 Z9 15 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR PD APR 3 PY 1992 VL 596 IS 1 BP 118 EP 122 DI 10.1016/0021-9673(92)80212-D PG 5 WC Chemistry, Analytical SC Chemistry GA HP088 UT WOS:A1992HP08800016 PM 1522174 ER PT J AU RAMPINO, NJ CHRAMBACH, A AF RAMPINO, NJ CHRAMBACH, A TI DNA ELECTROPHORESIS IN UNCROSS-LINKED POLYACRYLAMIDE SOLUTION, STUDIED BY EPIFLUORESCENCE MICROSCOPY SO JOURNAL OF CHROMATOGRAPHY LA English DT Note ID GEL-ELECTROPHORESIS; SEPARATION; FRAGMENTS; MOLECULES AB Electrophoresis of human DNA fragments (approximately 1 . 10(5) to 1 . 10- bases in size) was conducted in a solution of uncross-linked polyacrylamide contained in a horizontally mounted 1 mm diameter glass tube and monitored by epifluorescence microscopy. In presence of the polymer, molecular conformations described as a "trailing network" of DNA and a globular "head" were observed. The migration velocity varies between species differing in the size of the "head", and in the ratio between the size of the "head" and that of the trailing "network". By contrast, in pure buffer, lambda-phage DNA migrates in a globular form at a mobility consistent with known macroscopic data. When electrophoresis in the polymer solution of an agarose plug preparation of Schizosaccharomyces pombe DNA was carried out after melting at 70-degrees-C, a migrating DNA-agarose complex was observed. The complex was not fully dissociated by an agarose-hydrolyzing enzyme (Gelase). RP RAMPINO, NJ (reprint author), NICHHD,THEORET & PHYS BIOL LAB,MACROMOLEC ANAL SECT,BETHESDA,MD 20892, USA. NR 22 TC 19 Z9 19 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR PD APR 3 PY 1992 VL 596 IS 1 BP 141 EP 149 DI 10.1016/0021-9673(92)80217-I PG 9 WC Chemistry, Analytical SC Chemistry GA HP088 UT WOS:A1992HP08800021 PM 1522176 ER PT J AU LAZARUS, LH SALVADORI, S BALBONI, G TOMATIS, R WILSON, WE AF LAZARUS, LH SALVADORI, S BALBONI, G TOMATIS, R WILSON, WE TI STEREOSPECIFICITY OF AMINO-ACID SIDE-CHAINS IN DELTORPHIN DEFINES BINDING TO OPIOID RECEPTORS SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID SOLID-PHASE SYNTHESIS; CONFORMATIONAL PROPERTIES; ENKEPHALIN ANALOGS; PEPTIDE-SYNTHESIS; OPIATE RECEPTORS; SUBSTANCE-P; MELANOTROPIN; SPECIFICITY; ANTAGONIST; DERMORPHIN AB A series of individual D-amino acid replacement analogues of deltorphin A, several of which were in combination with a His4 deletion, were used to probe alterations of side-chain orientation on peptide binding parameters with rat brain opioid receptors. Peptides with D-amino acids in residues 1, 3, and 5 exhibited diminished affinities primarily for delta-receptors (88-1200-fold) with selectivity decreasing by factors of 13-64-fold relative to deltorphin A (K(i)delta = 0.45 nM; K(i)mu/K(i)delta = 764): the aromatic side chains Tyr1 and Phe3, which lie in the N-terminal "message" domain and the aryl side chain of Leu5 in the C-terminal "address" domain, appear to play essential roles in conferring high delta-affinity and selectivity. Although D-His4 only decreased delta-affinity by 6-fold and selectivity by a factor of 4, His appears to be involved as an integral component of both domains: [des-His4]deltorphin A and [des-His4] analogues containing consecutive D-amino acid replacements in the remaining residues exhibited weak binding to delta-receptors and poor delta-selectivity. Substitution of D-Met2 in deltorphin A by D-Ala or D-Nle decreased delta-selectivities 3-6-fold through an elevation in mu-affinities; however, the converse replacement, D-Met for D-Ala2 in deltorphin B, diminished beta-selectivity by an order of magnitude only through the loss in delta-affinity. The data show that the high delta-affinity and selectivity of deltorphins correlate with and require a strict stereospecificity of the amino acid residue side chains. C1 UNIV FERRARA,DEPT PHARMACEUT SCI,I-44100 FERRARA,ITALY. RP LAZARUS, LH (reprint author), NIEHS,MOLEC & INTEGRAT NEUROSCI LAB,RES TRIANGLE PK,NC 27709, USA. OI SALVADORI, Severo/0000-0002-8224-2358 NR 41 TC 40 Z9 40 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD APR 3 PY 1992 VL 35 IS 7 BP 1222 EP 1227 DI 10.1021/jm00085a009 PG 6 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA HM691 UT WOS:A1992HM69100009 PM 1313878 ER PT J AU LOCKSHIN, MD SAMMARITANO, LR AF LOCKSHIN, MD SAMMARITANO, LR TI ANTIPHOSPHOLIPID ANTIBODIES AND FETAL LOSS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 HOSP SPECIAL SURG,NEW YORK,NY 10021. RP LOCKSHIN, MD (reprint author), NIH,BETHESDA,MD 20892, USA. NR 5 TC 4 Z9 4 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 2 PY 1992 VL 326 IS 14 BP 951 EP 952 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA HL261 UT WOS:A1992HL26100011 PM 1542347 ER PT J AU KORF, HW KORF, B SCHACHENMAYR, W CHADER, GJ WIGGERT, B AF KORF, HW KORF, B SCHACHENMAYR, W CHADER, GJ WIGGERT, B TI IMMUNOCYTOCHEMICAL DEMONSTRATION OF INTERPHOTORECEPTOR RETINOID-BINDING PROTEIN IN CEREBELLAR MEDULLOBLASTOMA SO ACTA NEUROPATHOLOGICA LA English DT Article DE INTERPHOTORECEPTOR RETINOID-BINDING PROTEIN (IRBP); MEDULLOBLASTOMA; RETINOBLASTOMA; PINEOCYTOMA (PINEALOBLASTOMA) ID S-ANTIGEN IMMUNOREACTIVITY; HUMAN RETINOBLASTOMA CELLS; PINEAL PARENCHYMAL TUMORS; PHOTORECEPTOR MARKERS; MONOCLONAL-ANTIBODY; LOCALIZATION; GENE; DIFFERENTIATION; ASSIGNMENT; TRANSPORT AB Previously, immunoreactive rod-opsin and S-antigen (arrestin). two highly characteristic markers of retinal photoreceptors and pinealocytes. were shown to be present in certain medulloblastoma cells. It, thus, has been suggested that such cells differentiate along the photoreceptor lineage. This is corroborated in the present immunocytochemical investigation using antibodies against another photoreceptor-cell marker, the interphotoreceptor retinoid-binding protein (IRBP). As shown in preparations of human retina and pineal organ, IRBP can be successfully demonstrated in formalin-fixed and paraffin-embedded tissue: the IRBP immunoreaction is located to the outer and inner segments of retinal photoreceptor cells and to perikarya of certain pinealocytes. Examination of formalin-fixed. paraffin-embedded biopsy specimens of 66 cerebellar medulloblastomas revealed varying numbers of IRBP-immunoreactive tumor cells in 19 cases that were formerly shown to contain rod-opsin and S-antigen immunoreaction. IRBP-immunoreactive tumor cells were also found in a retinoblastoma and a pineocytoma, but not in neuroblastoma, ganglioneuroblastoma, glioblastoma, oligodendroglioma and astrocytoma. The results indicate: (1) cerebellar medulloblastomas are heterogeneous in their differentiation potential, (2) one type of medulloblastoma displays photoreceptor characteristics; (3) this type appears to be closely related to retinoblastoma and pineal cell tumors; and (4) all three types of tumors may display additional common features to be explored in future studies. C1 NEI,RETINAL CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. UNIV GIESSEN,INST NEUROPATHOL,W-6300 GIESSEN,GERMANY. RP KORF, HW (reprint author), UNIV FRANKFURT,ZENTRUM MORPHOL,NEUROBIOL ABT,THEODOR STERN KAI 7,W-6000 FRANKFURT 1,GERMANY. NR 44 TC 20 Z9 20 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD APR PY 1992 VL 83 IS 5 BP 482 EP 487 PG 6 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA HQ511 UT WOS:A1992HQ51100005 PM 1377856 ER PT J AU PANCRAZIO, JJ OIE, HK KIM, YI AF PANCRAZIO, JJ OIE, HK KIM, YI TI VOLTAGE-SENSITIVE CALCIUM CHANNELS IN A HUMAN SMALL-CELL LUNG-CANCER CELL-LINE SO ACTA PHYSIOLOGICA SCANDINAVICA LA English DT Article DE CA2+ CHANNELS; LAMBERT-EATON SYNDROME; PATCH-CLAMP; SMALL-CELL LUNG CANCER ID EATON MYASTHENIC SYNDROME; BOMBESIN-LIKE PEPTIDES; VERTEBRATE CELLS; OMEGA-CONOTOXIN; CARCINOMA; MODULATION; SECRETION; CURRENTS AB Utilizing the whole-cell patch-clamp method we assessed the Ca2+ current (I(Ca)) in well-established cell lines from human small-cell carcinoma (SCC) of the lung, NCI-H209 and NCI-H187. The Ca2+ current was readily observed in H209 tumour cells (90% of the cells tested), whereas H187 tumour cells only occasionally expressed Ca2+ channels (26% of the cells tested). H209 Ca2+ current was evoked by potentials greater than -30 mV and exhibited partial inactivation over the duration of a 40 ms command potential. This inward current was unchanged by alteration of the holding potential from -80 to -40 mV and the activation phase of the Ca2+ current was best fitted by Hodgkin Huxley m(t)2 kinetics. H209 Ca2+ current was reduced over 80% by verapamil (100-mu-M), whereas w-conotoxin (5-mu-M) appeared to be without effect. In contrast, H209 Ca" current was rapidly abolished by nifedipine (10-mu-M), strongly suggesting the presence of L-type Ca2+ channels. Voltage-gated Ca2+ channels may be important to the secretion of ectopic hormones and the etiology and pathogenesis of Lambert-Eaton syndrome, an autoimmune disorder of the motor nerve terminal in which autoantibodies directed against voltage-gated Ca2+ channels are produced. C1 UNIV VIRGINIA,HLTH SCI CTR,DEPT BIOMED ENGN,BOX 377,CHARLOTTESVILLE,VA 22908. UNIV VIRGINIA,HLTH SCI CTR,DEPT NEUROL,CHARLOTTESVILLE,VA 22908. USN HOSP,NCI,MED ONCOL BRANCH,BETHESDA,MD 20814. RI Pancrazio, Joseph/M-3206-2015 OI Pancrazio, Joseph/0000-0001-8276-3690 FU NINDS NIH HHS [NS18607] NR 27 TC 15 Z9 16 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0001-6772 J9 ACTA PHYSIOL SCAND JI Acta Physiol. Scand. PD APR PY 1992 VL 144 IS 4 BP 463 EP 468 DI 10.1111/j.1748-1716.1992.tb09321.x PG 6 WC Physiology SC Physiology GA HP006 UT WOS:A1992HP00600009 PM 1318636 ER PT J AU TALAN, MI ENGEL, BT KAWATE, R AF TALAN, MI ENGEL, BT KAWATE, R TI OVERNIGHT INCREASES IN HEMATOCRIT - ADDITIONAL EVIDENCE FOR A NOCTURNAL FALL IN PLASMA-VOLUME SO ACTA PHYSIOLOGICA SCANDINAVICA LA English DT Article DE BLOOD VOLUME; CARDIOVASCULAR FUNCTION; DIURNAL PATTERNS ID SUDDEN CARDIAC DEATH; CORONARY-ARTERY DISEASE; CIRCADIAN VARIATION; PLATELET AGGREGABILITY; MYOCARDIAL-INFARCTION; MORNING INCREASE; HEMATOCRIT; AGGREGATION; FREQUENCY; PATTERNS AB Our previously published studies with monkeys describe a characteristic nocturnal haemodynamic pattern consisting of a monotonic decline in cardiac output and central venous pressure, and a concomitant rise in total peripheral resistance. These findings led us to hypothesize that there is a reduction in total plasma volume during the night. Since a fall in plasma volume should cause an increase in haemoglobin and plasma protein concentration, we designed this experiment to test the hypothesis that haematocrit levels would be significantly greater in the morning than in the evening. In a study of five monkeys, the levels of hacmatocrit were measured at 1700 h and at 0900 h the next morning for 14 days. The average morning haematocrit levels were 6.5% higher than the average evening values. Lower plasma volume and possibly greater blood viscosity could contribute to the pathophysiology of the morning increase in the incidence of 'silent' ischaemia and catastrophic vascular events such as sudden cardiac death, myocardial infarctions and strokes in man. RP TALAN, MI (reprint author), NIA,GERONTOL RES CTR,BEHAV SCI LAB,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 26 TC 17 Z9 17 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0001-6772 J9 ACTA PHYSIOL SCAND JI Acta Physiol. Scand. PD APR PY 1992 VL 144 IS 4 BP 473 EP 476 DI 10.1111/j.1748-1716.1992.tb09323.x PG 4 WC Physiology SC Physiology GA HP006 UT WOS:A1992HP00600011 PM 1605049 ER PT J AU SWANN, AC STOKES, PE CASPER, R SECUNDA, SK BOWDEN, CL BERMAN, N KATZ, MM ROBINS, E AF SWANN, AC STOKES, PE CASPER, R SECUNDA, SK BOWDEN, CL BERMAN, N KATZ, MM ROBINS, E TI HYPOTHALAMIC-PITUITARY-ADRENOCORTICAL FUNCTION IN MIXED AND PURE MANIA SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article DE MANIA; CORTISOL; DEXAMETHASONE SUPPRESSION TEST; AFFECTIVE DISORDER ID DEXAMETHASONE SUPPRESSION TEST; RAT-BRAIN; DEPRESSIVE-ILLNESS; BIPOLAR PATIENTS; DISORDERS; CORTEX AB There is little information about hypothalamic-pituitary-adrenocortical (HPA) axis function in mania, particularly in mixed states. We therefore investigated HPA function and its relationship to clinical state in 19 hospitalized manic patients meeting Schedule for Affective Disorders and Schizophrenia - Research Diagnostic Criteria for acute manic episodes, compared patients with and without a mixed presentation, and examined correlations between HPA activity and behavior. Data were available from 13-16 patients. Behavioral and biochemical analyses were conducted during a 15-d placebo period. Patients with mania had elevated cerebrospinal fluid (CSF) and urinary free cortisol excretion compared with healthy subjects, and did not differ from depressed patients in any cortisol measures. Mixed manics had significantly higher morning plasma cortisol, postdexamethasone plasma cortisol and CSF cortisol than pure manics. Five of 7 mixed manics and 3 of 9 pure manics were dexamethasone suppression test (DST) nonsuppressors. Afternoon plasma cortisol and CSF cortisol correlated significantly with depressed mood; urinary free cortisol correlated with anxiety. None of the cortisol measures correlated with mania or agitation scores. These data suggest that increased cortisol secretion is a characteristic of the depressed state in mixed manics, although pure manics may also have increased DST nonsuppression. C1 CORNELL UNIV,SCH MED,PAYNE WHITNEY CLIN,NEW YORK,NY 10021. MICHAEL REESE HOSP & MED CTR,CHICAGO,IL 60616. NIMH,SPRINGFIELD,PA. UNIV TEXAS,HLTH SCI CTR,DEPT PSYCHIAT,SAN ANTONIO,TX 78284. UNIV CALIF LOS ANGELES,LOS ANGELES CTY HARBOR MED CTR,INST RES & EDUC,TORRANCE,CA 90509. ALBERT EINSTEIN MED SCH,DEPT PSYCHIAT,BRONX,NY. WASHINGTON UNIV,SCH MED,DEPT PSYCHIAT,ST LOUIS,MO 63110. RP SWANN, AC (reprint author), UNIV TEXAS,SCH MED,DEPT PSYCHIAT,POB 20708,HOUSTON,TX 77225, USA. FU NIMH NIH HHS [MH26975, MH26977, UO1 MH38084] NR 32 TC 68 Z9 69 U1 1 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD APR PY 1992 VL 85 IS 4 BP 270 EP 274 DI 10.1111/j.1600-0447.1992.tb01468.x PG 5 WC Psychiatry SC Psychiatry GA HN637 UT WOS:A1992HN63700004 PM 1595360 ER PT J AU BLAY, R HERNANDEZ, D BETTS, M CLERICI, M LUCEY, DR HENDRIX, C HOFFMAN, T GOLDING, B AF BLAY, R HERNANDEZ, D BETTS, M CLERICI, M LUCEY, DR HENDRIX, C HOFFMAN, T GOLDING, B TI BRUCELLA-ABORTUS STIMULATES HUMAN T-CELLS FROM UNINFECTED AND HIV-INFECTED INDIVIDUALS TO SECRETE IFN-GAMMA - IMPLICATIONS FOR USE OF BRUCELLA-ABORTUS AS A CARRIER IN DEVELOPMENT OF HUMAN VACCINES SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID ACQUIRED IMMUNODEFICIENCY SYNDROME; INTERFERON-GAMMA; BACTERIAL LIPOPOLYSACCHARIDE; ANTIBODY-RESPONSES; B-CELLS; INVITRO; HELPER; HETEROGENEITY; LYMPHOKINES; ANTIGENS AB Brucella abortus has been characterized as a T-independent type 1 antigen/carrier in human and murine antibody responses. In this report it is shown that BA can activate human CD3+ T cells to secrete interferon-gamma (IFN-gamma). Unlike mitogens, such as phytohemagglutinin, this stimulation was associated with minimal T-cell proliferation or upregulation of interleukin-2 (IL-2) receptor. Monocytes inhibited BA-mediated IFN-gamma secretion since their removal resulted in increased responses, whereas adding monocytes back to cultures caused inhibition. BA elicited IFN-gamma from CD4+ and CD8+ T cells, although CD4+ T cells secrete significantly more (p < 0.05) IFN-gamma than CD8+ T cells. The ability of BA to elicit IFN-gamma from human T cells was inhibited in the presence of anti-Tac, suggesting that BA also induces IL-2 secretion and that IL-2 is involved in BA-mediated IFN-gamma secretion. Detectable IL-2 secretion was induced by BA in the presence of anti-Tac. Exogenous IL-2 acted synergistically with BA to enhance IFN-gamma secretion, suggesting that the amount of IL-2 released by BA alone was insufficient for optimal IFN-gamma release. Furthermore, addition of IL-2 to T cells from individuals with poor or absent responses to BA, including individuals infected with HIV-1, restored their ability to secrete IFN-gamma in response to BA. These data indicate that BA is capable not only of activating human B cells but can also induce T cells, probably of the TH1 phenotype, to secrete IFN-gamma. Production of IFN-gamma in response to BA has implications in the proposed development of BA as a carrier for human vaccines, since IFN-gamma has multiple effects including macrophage activation, B-cell differentiation, and antiviral activity. C1 US FDA,DIV HEMATOL,CELL BIOL LAB,BLDG 29,RM 231,8800 ROCKVILLE PIKE,BETHESDA,MD 20892. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. SCHMMI,HUMAN IMMUNODEFICIENCY VIRUS UNIT,LACKLAND AFB,TX 78236. RI Hendrix, Craig/G-4182-2014 OI Hendrix, Craig/0000-0002-5696-8665 NR 33 TC 17 Z9 17 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 APR PY 1992 VL 8 IS 4 BP 479 EP 486 DI 10.1089/aid.1992.8.479 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA HR877 UT WOS:A1992HR87700009 PM 1350916 ER PT J AU HARFORD, TC PARKER, DA GRANT, BF DAWSON, DA AF HARFORD, TC PARKER, DA GRANT, BF DAWSON, DA TI ALCOHOL-USE AND DEPENDENCE AMONG EMPLOYED MEN AND WOMEN IN THE UNITED-STATES IN 1988 SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article ID ALIENATION; COMMUNITY; WORK AB This paper provides estimates of alcohol consumption and alcohol dependence among employed men and women in the United States. Data from the 1988 National Health Interview Survey indicate that the percentages of drinkers in white-collar occupations are higher than the percentages of drinkers in blue-collar occupations among both men and women; however, the men and women in blue-collar occupations who drink have a higher average daily consumption than drinkers in white-collar occupations. DSM-III-R criteria were used to classify respondents as alcohol-dependent. Consistent with an earlier survey of employed adults in Detroit, the prevalence of alcohol dependence is highest in certain blue-collar occupations (craftsmen, laborers, and service workers among men; machine operators, laborers, and service workers among women). Directions for further research on the occupational and drinking experiences of employed men and women are discussed. C1 CALIF STATE UNIV LONG BEACH,DEPT SOCIOL,LONG BEACH,CA 90840. RP HARFORD, TC (reprint author), NIAAA,DIV BIOMETRY & EPIDEMIOL,RM 14C26,PARKLAWN BLDG,5600 FISHERS LA,ROCKVILLE,MD 20857, USA. NR 19 TC 26 Z9 27 U1 0 U2 5 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD APR PY 1992 VL 16 IS 2 BP 146 EP 148 DI 10.1111/j.1530-0277.1992.tb01357.x PG 3 WC Substance Abuse SC Substance Abuse GA HP802 UT WOS:A1992HP80200002 PM 1590533 ER PT J AU PARKER, DA HARFORD, TC AF PARKER, DA HARFORD, TC TI GENDER-ROLE ATTITUDES, JOB COMPETITION AND ALCOHOL-CONSUMPTION AMONG WOMEN AND MEN SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE ALCOHOL; ATTITUDES; GENDER ROLES; COMPETITION ID SEX-ROLE ATTITUDES; EMPLOYED MEN; DRINKING AB Attempting to account for greater alcohol consumption among women, social scientists have argued that traditional gender roles and gender-role attitudes concerning the division of labor in the family have provided women with a moral or cultural protection against heavier drinking but that the "breakdown" of this protection has allowed for greater alcohol use. This paper assesses the breakdown argument using data from two representative samples: a sample of 12,069 young adults in the United States and a sample of 1,367 employed men and women in metropolitan Detroit. Our analysis indicates that among young women the nontraditional role of employment and nontraditional gender-role attitudes concerning responsibilities for household labor and child care are associated with greater alcohol consumption. However, among the employed, our analysis indicates that it is not nontraditional women and traditional men but rather traditional women and nontraditional men who have greater alcohol use-it is the women and men who believe that they have substantial obligations at home and who have intense competition at the workplace that consume a greater quantity of alcohol. C1 ALCOHOL EPIDEMIOL DATA SYST,WASHINGTON,DC. NIAAA,ROCKVILLE,MD 20852. RP PARKER, DA (reprint author), CALIF STATE UNIV LONG BEACH,DEPT SOCIOL,1250 BELLFLOWER BLVD,LONG BEACH,CA 90840, USA. NR 22 TC 27 Z9 27 U1 1 U2 4 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD APR PY 1992 VL 16 IS 2 BP 159 EP 165 DI 10.1111/j.1530-0277.1992.tb01359.x PG 7 WC Substance Abuse SC Substance Abuse GA HP802 UT WOS:A1992HP80200004 PM 1590535 ER PT J AU GRANT, BF HARFORD, TC HASIN, DS CHOU, P PICKERING, R AF GRANT, BF HARFORD, TC HASIN, DS CHOU, P PICKERING, R TI DSM-III-R AND THE PROPOSED DSM-IV ALCOHOL-USE DISORDERS, UNITED-STATES 1988 - A NOSOLOGICAL COMPARISON SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE ALCOHOL ABUSE; ALCOHOL DEPENDENCE; DSM-III-R, DSM-IV; NOSOLOGICAL COMPARISON AB The purpose of the present study was to compare DSM-III-R and the proposed DSM-IV diagnostic criteria for alcohol abuse and dependence in a representative sample of the United States general population. Alcohol abuse and dependence diagnostic categories were contrasted in terms of prevalence and overlap. The prevalence of DSM-III-R diagnoses of alcohol abuse and dependence combined (8.63%) was greater than the corresponding DSM-IV diagnoses (6.00%). Disaggregation of abuse and dependence diagnoses showed that the major discrepancy between the classification systems resided between the abuse categories. Reasons for the discrepancies are discussed in terms of differences in the content of the DSM-III-R and DSM-IV abuse categories, in the relationship that each abuse category shares with its respective dependence category, and the impact of the DSM-III-R duration criterion. C1 COLUMBIA UNIV,NEW YORK,NY 10027. NEW YORK STATE PSYCHIAT INST & HOSP,DEPT RES ASSESSMENT & TRAINING,NEW YORK,NY 10032. RP GRANT, BF (reprint author), NIAAA,DIV BIOMETRY & EPIDEMIOL,ROOM 14C-26,5600 FISHERS LA,ROCKVILLE,MD 20857, USA. NR 5 TC 49 Z9 49 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD APR PY 1992 VL 16 IS 2 BP 215 EP 221 DI 10.1111/j.1530-0277.1992.tb01366.x PG 7 WC Substance Abuse SC Substance Abuse GA HP802 UT WOS:A1992HP80200011 PM 1590542 ER PT J AU HECHT, GM PANZA, JA MARON, BJ AF HECHT, GM PANZA, JA MARON, BJ TI CLINICAL COURSE OF MIDDLE-AGED ASYMPTOMATIC PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID LEFT-VENTRICULAR HYPERTROPHY; MUSCULAR SUBAORTIC STENOSIS; SUDDEN-DEATH; OBSTRUCTIVE CARDIOMYOPATHY; PATHO-PHYSIOLOGY; M-MODE; PROGNOSIS; EXTENT; ECHOCARDIOGRAPHY; INTERRELATIONS AB Patients with hypertrophic cardiomyopathy (HC) may present a wide spectrum of clinical and morphologic manifestations. Although many aspects of the natural history of HC are understood, the initial presentation and subsequent clinical course of certain subgroups are not yet well defined. To further our understanding in this regard, 241 middle-aged patients with HC (aged 35 to 55 years) were analyzed. The vast majority of patients (210) had already experienced symptoms, whereas the remaining 31 initially presented with no or minimal symptoms and are the focus of this investigation; 29 of these were followed for greater-than-or-equal-to 2 years (range to 11.5 years, mean 8). A separate group of 30 moderately symptomatic age- and gender-matched patients with HC were selected as control subjects for morphologic comparisons. Of the 29 study patients with follow-up, 22 (76%) are presently free of important cardiac symptoms, but 3 showed progression of symptoms, and 4 have died suddenly. Annual mortality rate was 1.7%. Eighteen of the middle-aged asymptomatic patients with HC (58%) had localized left ventricular hypertrophy, usually involving only the anterior ventricular septum; in contrast, only 9 of the 30 symptomatic control subjects (30%) had such localized hypertrophy (p = 0.02). In conclusion, of those patients with HC who achieved middle-age without developing important cardiac symptoms, approximately 75% remained asymptomatic during the ensuing average 8-year follow-up. However, such patients are not protected in absolute terms from unfavorable clinical events (despite relatively mild left ventricular hypertrophy and in most cases absence of outflow obstruction). This is evidenced by the fact that approximately 25% eventually experienced symptomatic deterioration or sudden cardiac death. C1 NHLBI,ECHOCARDIOG LAB,BLDG 10,ROOM 7B15,BETHESDA,MD 20892. NR 43 TC 18 Z9 19 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 APR 1 PY 1992 VL 69 IS 9 BP 935 EP 940 DI 10.1016/0002-9149(92)90796-2 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA HL061 UT WOS:A1992HL06100016 PM 1550024 ER PT J AU CONNOLLY, SJ YUSUF, S AF CONNOLLY, SJ YUSUF, S TI EVALUATION OF THE IMPLANTABLE CARDIOVERTER DEFIBRILLATOR IN SURVIVORS OF CARDIAC-ARREST - THE NEED FOR RANDOMIZED TRIALS SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Editorial Material ID MALIGNANT VENTRICULAR ARRHYTHMIAS; MYOCARDIAL-INFARCTION; EFFICACY; TACHYARRHYTHMIAS; DETERMINANTS; FIBRILLATION; DISEASE; THERAPY; DEATH C1 NHLBI,CLIN TRIALS BRANCH,FED BLDG 5C08,BETHESDA,MD 20892. MCMASTER UNIV,FAC HLTH SCI,HAMILTON L8S 4L8,ONTARIO,CANADA. NR 29 TC 61 Z9 62 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 APR 1 PY 1992 VL 69 IS 9 BP 959 EP 962 DI 10.1016/0002-9149(92)90801-5 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA HL061 UT WOS:A1992HL06100021 PM 1550027 ER PT J AU BROWN, LM GIBSON, R BLAIR, A BURMEISTER, LF SCHUMAN, LM CANTOR, KP FRAUMENI, JF AF BROWN, LM GIBSON, R BLAIR, A BURMEISTER, LF SCHUMAN, LM CANTOR, KP FRAUMENI, JF TI SMOKING AND RISK OF LEUKEMIA SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE CASE-CONTROL STUDIES; LEUKEMIA; SMOKING; TOBACCO ID ACUTE NONLYMPHOCYTIC LEUKEMIA; CIGARETTE-SMOKING; CANCER; ASSOCIATION; EXPOSURES; SUBSETS; HABITS AB The relation between tobacco use and leukemia was evaluated in a population-based case-control study of 578 white men with leukemia and 820 controls conducted in Iowa and Minnesota during 1981-1984. Risks were significantly elevated for all leukemia (odds ratio (OR) = 1.4) and chronic lymphocytic leukemia (OR = 1.6) for both tobacco users and cigarette smokers. There were significantly elevated risks for cigarette smokers of longest duration for all leukemia (OR = 1.6), chronic myelogenous leukemia (OR = 3.3), and chronic lymphocytic leukemia (OR = 1.6). Thus, the findings of this study provide additional support for an association between smoking and the risk of several types of leukemia. C1 UNIV MINNESOTA,DEPT EPIDEMIOL,MINNEAPOLIS,MN 55455. UNIV IOWA,DEPT PREVENT MED,IOWA CITY,IA 52242. RP BROWN, LM (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,EXECUT PLAZA N,SUITE 415,BETHESDA,MD 20892, USA. NR 38 TC 43 Z9 44 U1 0 U2 3 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD APR 1 PY 1992 VL 135 IS 7 BP 763 EP 768 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA HW647 UT WOS:A1992HW64700005 PM 1595675 ER PT J AU BI, WF HAYES, RB FENG, PW QI, YY YOU, XJ ZHEN, JG ZHANG, MQ QU, BQ FU, ZY CHEN, M CHIEN, HTC BLOT, WJ AF BI, WF HAYES, RB FENG, PW QI, YY YOU, XJ ZHEN, JG ZHANG, MQ QU, BQ FU, ZY CHEN, M CHIEN, HTC BLOT, WJ TI MORTALITY AND INCIDENCE OF BLADDER-CANCER IN BENZIDINE-EXPOSED WORKERS IN CHINA SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE BLADDER CANCER; BENZIDINE; AROMATIC AMINES; SULFIDE DYES; ETHNIC DIFFERENCES; SCRUBBING EFFECT AB We examined bladder cancer mortality and incidence to 1981 in 1,972 workers employed in benzidine-exposed jobs in Tianjin, Shanghai, and Jilin, China, between 1972 and 1977, and in 1,974 unexposed workers employed during the same time period. In comparison to general population rates, in the benzidine-exposed group the ratio of observed to expected deaths (SMR) was 17.5 (95% C.I.: 7.5-34.5) and the ratio of observed to expected incident cases (SIR) was 25.0 (95% C.I.: 16.9-35.7). No excess was noted in the unexposed group. The 25-fold increase in bladder cancer incidence in the exposed group was related to level of exposure, with the SIR rising from 4.8 for low exposure to 36.2 for medium exposure, and 158.4 for high exposure. Risks were elevated both for producers of benzidine (SIR = 45.7; 95% C.I.: 20.9-86.8) and for users (SIR = 20.9; 95% C.I.: 12.9-32.0) of benzidine dyes. Benzidine-exposed workers who smoked tobacco had a 31-fold risk (95% C.I.: 20.4-46.4), while non-smoking workers had an 11-fold risk (95% C.I.: 3.6-25.8), suggestive of a multiplicative relationship between these two carcinogens. C1 NCI,EPIDEMIOL PROGRAM,418 EXECUT PLAZA N,BETHESDA,MD 20892. CHINESE ACAD PREVENT MED,INST OCCUPAT MED,BEIJING,PEOPLES R CHINA. TIANJIN BUR CHEM IND,INST LABOUR HYG,TIANJIN,PEOPLES R CHINA. INST PREVENT & TREATMENT OCCUPAT DIS,TIANJIN,PEOPLES R CHINA. SHANGHAI INST OCCUPAT MED,SHANGHAI,PEOPLES R CHINA. JILIN CHEM IND CO,INST PREVENT & TREATMENT OCCUPAT DIS,JILIN,PEOPLES R CHINA. WESTAT CORP,ROCKVILLE,MD. NR 19 TC 68 Z9 69 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD APR PY 1992 VL 21 IS 4 BP 481 EP 489 DI 10.1002/ajim.4700210404 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA HL056 UT WOS:A1992HL05600003 PM 1580253 ER PT J AU PLATT, LD KOCH, R AZEN, C HANLEY, WB LEVY, HL MATALON, R ROUSE, B DELACRUZ, F WALLA, CA AF PLATT, LD KOCH, R AZEN, C HANLEY, WB LEVY, HL MATALON, R ROUSE, B DELACRUZ, F WALLA, CA TI MATERNAL PHENYLKETONURIA COLLABORATIVE STUDY, OBSTETRIC ASPECTS AND OUTCOME - THE 1ST 6 YEARS SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 10TH ANNUAL MEETING OF THE AMERICAN GYNECOLOGICAL AND OBSTETRICAL SOC CY SEP 05-07, 1991 CL CARLSBAD, CA SP AMER GYNECOL & OBSTET SOC DE MATERNAL PHENYLKETONURIA; FETUS; MENTAL RETARDATION; CONGENITAL DEFECTS; DIETARY THERAPY ID HUMAN BIOCHEMICAL GENETICS; WOMEN; HYPERPHENYLALANINEMIA; PREGNANCY; EPITOME; PKU AB OBJECTIVE: The purpose of this study was to evaluate the efficacy of a phenylalanine-restricted diet in reducing fetal morbidity associated with maternal hyperphenylalaninemia in women of childbearing age with blood phenylalanine levels > 240-mu-mol/L (> 4 mg/dl) on an unrestricted diet. STUDY DESIGN: Two hundred thirteen pregnant women with hyperphenylalaninemia that resulted in 134 live births have been enrolled in the study. Outcome measures were subject to the chi(2) test, Fisher exact test, analysis of variance, t test, or Wilcoxon nonparametric test for analysis. RESULTS: Optimal fetal outcome appeared to occur when blood phenylalanine levels < 600-mu-mol/L (< 10 mg/dl) were achieved by 8 to 10 weeks' gestation and maintained throughout pregnancy (trimester averages of less-than-or-equal-to 360-mu-mol/L (less-than-or-equal-to 6 mg/dl)). Initiation of dietary therapy during the third trimester of pregnancy appears to have little beneficial effect on the fetus. CONCLUSIONS: Preconceptual counseling and early entrance into a prenatal care program is essential in achieving optimal fetal outcome in women with hyperphenylalaninemia. C1 CHILDRENS HOSP LOS ANGELES,LOS ANGELES,CA. NICHHD,BETHESDA,MD 20892. UNIV SO CALIF,SCH MED,LOS ANGELES,CA 90033. UNIV TEXAS,MED BRANCH,GALVESTON,TX 77550. UNIV SO CALIF,WOMENS HOSP,LOS ANGELES,CA 90089. CHILDRENS HOSP MED CTR,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. UNIV ILLINOIS HOSP,CHICAGO,IL 60612. HOSP SICK CHILDREN,TORONTO M5G 1X8,ONTARIO,CANADA. FU NICHD NIH HHS [N01-HD-4-3807, N01-HD-4-2809, N01-HD-4-3810] NR 23 TC 52 Z9 52 U1 1 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 APR PY 1992 VL 166 IS 4 BP 1150 EP 1162 PG 13 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA HP869 UT WOS:A1992HP86900013 PM 1566767 ER PT J AU GERBER, LH AF GERBER, LH TI THE FUTURE OF REHABILITATION RESEARCH SO AMERICAN JOURNAL OF OCCUPATIONAL THERAPY LA English DT Article ID HEALTH-STATUS; IMPACT RP GERBER, LH (reprint author), NIH,DEPT REHABIL MED,9000 ROCKVILLE PIKE,BLDG 10,ROOM 65235,BETHESDA,MD 20892, USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU AMER OCCUPATIONAL THERAPY ASSOC PI ROCKVILLE PA 1383 PICCARD DRIVE PO BOX ROCKVILLE, MD 20850-4375 SN 0272-9490 J9 AM J OCCUP THER JI Am. J. Occup. Ther. PD APR PY 1992 VL 46 IS 4 BP 379 EP 381 PG 3 WC Rehabilitation SC Rehabilitation GA HJ434 UT WOS:A1992HJ43400011 PM 1566805 ER PT J AU FREUDENRICH, CC MURPHY, E LEVY, LA LONDON, RE LIEBERMAN, M AF FREUDENRICH, CC MURPHY, E LEVY, LA LONDON, RE LIEBERMAN, M TI INTRACELLULAR PH MODULATES CYTOSOLIC FREE MAGNESIUM IN CULTURED CHICKEN HEART-CELLS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE HYDROGEN ION; IONIZED MAGNESIUM; CALCIUM; FLUORESCENT DYES ID NA+-H+ EXCHANGE; FLUORESCENT INDICATOR; ACIDOSIS; CA-2+; TRANSPORT; MUSCLE; INHIBITION; CALMODULIN; MYOCYTES; CHANNEL AB To assess the role of pH in cellular Mg homeostasis, cytosolic pH (pH(i)) ws manipulated by the NH4Cl prepulse technique; pH(i), cytosolic Mg2+ (Mg(i)), and cytosolic Ca2+ (Ca(i)) were measured fluorometrically in single cultured embryonic chicken heart cells loaded with 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF), FURAPTRA, and fura-2, respectively. The basal values obtained were as follows: pH(i) = 7.21 +/- 0.10 (n = 7), [Mg]i = 0.51 +/- 0.08 mM (n = 9), [Ca]i = 126 +/- 15 nM (n = 7). When cells were perfused with 10 mM NH4Cl solution for 5 min, a transient alkalinization (0.53 U) of the cytosol was accompanied by a transient decrease (0.12 mM) in [Mg]i and a transient increase (59 nM) in [Ca]i; these changes approached control levels within 5 min. Upon removal of NH4Cl, a transient acidification (0.89 U) of the cytosol was accompanied by a transient increase (0.10 mM) in [Mg]i and a transient increase (125 nM) in [Ca]i; again, these changes returned toward control levels within 5 min. No significant changes in total cell Mg or Ca were observed during these manipulations. NH4Cl-evoked changes in [Mg]i were not altered significantly by either Mg-free or Ca-free conditions. Changes in [Mg]i were inversely correlated with changes in pH(i) and were not secondary to changes in [Ca]i. The results suggest that pH(i) modulates Mg(i), probably by affecting cytosolic Mg binding and/or the transport of Mg across subcellular organelles. C1 DUKE UNIV,MED CTR,DEPT CELL BIOL,DIV PHYSIOL,BOX 3709,DURHAM,NC 27710. NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. NR 30 TC 42 Z9 42 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD APR PY 1992 VL 262 IS 4 BP C1024 EP C1030 PN 1 PG 7 WC Physiology SC Physiology GA HQ053 UT WOS:A1992HQ05300028 ER PT J AU ABASSI, ZA POWELL, JR GOLOMB, E KEISER, HR AF ABASSI, ZA POWELL, JR GOLOMB, E KEISER, HR TI RENAL AND SYSTEMIC EFFECTS OF URODILATIN IN RATS WITH HIGH-OUTPUT HEART-FAILURE SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE KIDNEY FUNCTION; AORTOCAVAL FISTULA; ATRIAL NATRIURETIC PEPTIDE; SODIUM EXCRETION; NEUTRAL ENDOPEPTIDASE; GUANOSINE 3',5'-CYCLIC MONOPHOSPHATE ID ATRIAL NATRIURETIC PEPTIDE; PLASMA-LEVELS; KIDNEY; BINDING; SODIUM; ENDOPEPTIDASE; POTENTIATION; METABOLISM; MECHANISMS; RESPONSES AB Urodilatin is a recently discovered natriuretic peptide [ANP-(95-126)] of renal origin, with a primary structure similar to ANP-(99-126). However, urodilatin is not biologically inactivated by renal endopeptidase, and it is a more potent natriuretic agent than ANP-(99-126). The present study was carried out to investigate the renal and systemic effects of urodilatin in rats before and after the induction of congestive heart failure (CHF) by creation of an aortocaval fistula (ACF). Administration of urodilatin in incremental doses (0.75-12-mu-g.kg-1.h-1) to Inactin-anesthetized sham-operated control rats resulted in dose-dependent increases in urine flow, glomerular filtration rate (GFR), excretion of guanosine 3',5'-cyclic monophosphate (cGMP), sodium, and potassium, and a significant decrease in mean arterial blood pressure. In rats with ACF the baseline values for GFR and sodium excretion were significantly lower than in control rats. Urodilatin infusion in rats with ACF led to significant increases in urine flow and sodium excretion, but the absolute levels of diuresis and natriuresis were significantly lower in rats with CHF than in normal rats. When urodilatin was infused into rats with ACF pretreated with neutral endopeptidase inhibitor (NEP-I; SQ-28,063 at a dose of 40 mg/kg iv), the absolute urine flow and sodium excretion were not different from that obtained in control rats. Thus the attenuated natriuretic and diuretic response to ANP-(99-126) in heart failure was not observed with urodilatin. Furthermore, the potentiation of the natriuretic and diuretic effects of urodilatin in rats with CHF by NEP-I, despite its resistance to biological inactivation, indicates that mechanisms other than the inhibition of urodilatin degradation were involved in that augmentation. These results suggest that urodilatin may be useful in treatment of patients with CHF. Restoration of the absolute renal response to urodilatin by NEP-I in rats with CHF suggests that a combination of these agents might be better therapy for CHF than either agent alone. C1 SQUIBB INST MED RES,DEPT PHARMACOL,PRINCETON,NJ 08543. RP ABASSI, ZA (reprint author), NHLBI,HYPERTENS ENDOCRINE BRANCH,BLDG 10,ROOM 8C103,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 44 TC 30 Z9 31 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 APR PY 1992 VL 262 IS 4 BP F615 EP F621 PN 2 PG 7 WC Physiology SC Physiology GA HQ056 UT WOS:A1992HQ05600099 PM 1533100 ER PT J AU YAMADA, H SACKTOR, B KINSELLA, J AF YAMADA, H SACKTOR, B KINSELLA, J TI AGE-ASSOCIATED CHANGES IN AMMONIAGENESIS IN ISOLATED RAT RENAL TUBULE SEGMENTS SO AMERICAN JOURNAL OF PHYSIOLOGY LA English DT Article DE AGING; ISOLATED RENAL TUBULE; METABOLIC ACIDOSIS; RENAL FAILURE; ACID-BASE METABOLISM ID METABOLIC-ACIDOSIS; TRANSPORT; EXCRETION; NEPHRON AB We investigated renal ammoniagenesis in isolated nephron segments from control and acidotic senescent and young adult rats. When young (6 mo) and senescent (24 mo) control groups were compared, there was no significant difference in glutamine-dependent ammonia production in any nephron tubule segments. However, ammonia production rates in glomeruli from old rats were significantly greater than the rate from young rats and were correlated with the serum creatinine and blood urea nitrogen (BUN) levels. After giving young and old rats an equivalent acid load (by gavage) of ammonia chloride solutions (6 mo, blood pH 7.34; 24 mo, blood pH 7.07), we measured a significant increase in ammoniagenesis on the S1 and S2 segments of proximal tubules and the distal convoluted tubules from old rats, and no increase in any segment from young rats. When we increased the acid load in young rats to an equivalent severity of acidosis (blood pH 7.07), we found significant increases in ammonia production in the S1, S2, S3, and distal convoluted tubule. With comparable blood pH values, ammoniagenesis in S1, S2, and S3 segments from young rats was about double the values measured in segments from senescent rats. The severity of the acidosis in the 24-mo-old rats was related to serum creatinine and BUN. Our findings show that ammoniagenesis in isolated segments from sensecent rats is qualitatively similar to their younger counterparts but that this maximum capacity to generate ammonia is reduced. The change in nephron capacity to synthesize ammonia may be the result of age-associated physiological changes and/or the chronic renal failure exhibited in old rats. C1 NIA, GERONTOL RES CTR, BIOL CHEM LAB, BALTIMORE, MD 21224 USA. NR 25 TC 8 Z9 8 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9513 J9 AM J PHYSIOL JI Am. J. Physiol. PD APR PY 1992 VL 262 IS 4 BP F600 EP F605 PN 2 PG 6 WC Physiology SC Physiology GA HQ056 UT WOS:A1992HQ05600097 PM 1566873 ER PT J AU LARSON, DB SHERRILL, KA LYONS, JS CRAIGIE, FC THIELMAN, SB GREENWOLD, MA LARSON, SS AF LARSON, DB SHERRILL, KA LYONS, JS CRAIGIE, FC THIELMAN, SB GREENWOLD, MA LARSON, SS TI ASSOCIATIONS BETWEEN DIMENSIONS OF RELIGIOUS COMMITMENT AND MENTAL-HEALTH REPORTED IN THE AMERICAN-JOURNAL-OF-PSYCHIATRY-AND-ARCHIVES-OF-GENERAL-PSYCHIATRY - 1978-1989 SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID SYSTEMATIC ANALYSIS; FAMILY-PRACTICE; VARIABLES AB The authors assessed all measures of religious commitment (N = 139) reported in research studies published in the American Journal of Psychiatry and Archives of General Psychiatry in 1978 through 1989 (N < 35). For nearly two-thirds of the measures, the studies either made no hypotheses or reported no results concerning the relationship of religious commitment to mental health status. For the great majority of the measures assessed, the studies reported a positive relationship between religious commitment and mental health. C1 US DEPT HHS,WASHINGTON,DC 20201. NIMH,ROCKVILLE,MD 20857. NR 11 TC 123 Z9 124 U1 2 U2 6 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 APR PY 1992 VL 149 IS 4 BP 557 EP 559 PG 3 WC Psychiatry SC Psychiatry GA HL732 UT WOS:A1992HL73200023 PM 1532477 ER PT J AU ROMERO, R MAZOR, M BRANDT, F SEPULVEDA, W AVILA, C COTTON, DB DINARELLO, CA AF ROMERO, R MAZOR, M BRANDT, F SEPULVEDA, W AVILA, C COTTON, DB DINARELLO, CA TI INTERLEUKIN-1 ALPHA AND INTERLEUKIN-1 BETA IN PRETERM AND TERM HUMAN PARTURITION SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Article DE INTERLEUKIN-1; AMNIOTIC FLUID; PARTURITION; PRETERM LABOR; PREMATURE RUPTURE OF MEMBRANES; PREMATURITY; INTRAAMNIOTIC INFECTION ID TUMOR-NECROSIS-FACTOR; AMNIOTIC-FLUID INTERLEUKIN-6; RECEPTOR ANTAGONIST; PROSTAGLANDIN BIOSYNTHESIS; PREMATURE RUPTURE; SEPTIC SHOCK; CYTOKINES; INFECTION; LABOR; ENDOTOXIN AB Interleukin-1 (IL-1) has been implicated in the mechanism of human parturition in the setting of infection. The purpose of this study was to determine the effect of labor (term and preterm) and microbial invasion of the amniotic cavity on amniotic fluid (AF) concentrations IL-1-alpha and IL-1-beta. AF was retrieved by transabdominal amniocentesis from the following groups of women: midtrimester genetic amniocentesis (16 to 18 wk) (N = 15), preterm labor with intact membranes (21 to 36 wk) with or without infection (N = 72), preterm premature rupture of membranes (PROM) (N = 88), and term not in labor or in active labor with or without infection (N = 58). AF was cultured for aerobic and anaerobic bacteria as well as Mycoplasmas. IL-1 was measured with a commercially available immunoassay validated for AF (sensitivity: IL-1-alpha, 157 pg/ml; IL-1-beta, 50 pg/ml). All women at midtrimester had undetectable AF IL-1-alpha and IL-1-beta. Among women in preterm labor with positive AF cultures, IL-1-alpha and IL-1-beta were detectable in the AF in 86.6% (13/15) and 100% (15/15), respectively. In contrast, all women with negative AF cultures without labor (N = 36) had undetectable AF IL-1-alpha concentrations and 52.7% (19/36) had undetectable AF IL-1-beta concentrations. Histopathological chorioamnionitis was present in 92.8% (13/14) of patients who had positive AF cultures and detectable IL-1 in the AF. IL-1 was significantly higher in patients with preterm PROM, labor, and positive AF cultures than in the other subgroups of patients with preterm PROM. Among women at term who were not in labor, 26.3% (5/19) had detectable IL-1-alpha and 19.8% (3/19) had detectable IL-1-beta in the AF. Among those in active labor with positive AF cultures, 44.4% (4/9) had detectable IL-1-alpha and 88.8% (8/9) had detectable IL-1-beta in the AF. IL-1-beta was detected more frequently in patients at term with positive AF cultures than in those with negative AF cultures (88.8% [8/9] vs. 38.7% [19/49]; P = 0.0088). We conclude that AF IL-1 concentrations are elevated in women with preterm labor an microbial invasion of the amniotic cavity and in women with spontaneous parturition at term. C1 YALE UNIV,SCH MED,DEPT OBSTET & GYNECOL,NEW HAVEN,CT 06510. TUFTS UNIV,SCH MED,DEPT MED,BOSTON,MA 02111. NIH,INTRAUMURAL RES BRANCH PERINATOL,BETHESDA,MD 20892. RP ROMERO, R (reprint author), WAYNE STATE UNIV,SCH MED,DEPT OBSTET & GYNECOL,4707 ST ANTOINE,DETROIT,MI 48201, USA. FU NIAID NIH HHS [AI 15614] NR 31 TC 271 Z9 271 U1 0 U2 10 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 8755-8920 J9 AM J REPROD IMMUNOL JI Am. J. Reprod. Immunol. PD APR-MAY PY 1992 VL 27 IS 3-4 BP 117 EP 123 PG 7 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA JK800 UT WOS:A1992JK80000006 PM 1418402 ER PT J AU GERWIN, BI AF GERWIN, BI TI OVEREXPRESSION OF THE P185(ERB-2)TYROSINE KINASE GROWTH-FACTOR RECEPTOR - CONTROL OR CHAOS SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Editorial Material ID HUMAN-BREAST CANCER; EGF RECEPTOR; SIGNAL TRANSDUCTION; C-ERBB-2 ONCOPROTEIN; ONCOGENE; EXPRESSION; AMPLIFICATION; SURVIVAL; CELLS; GENE RP GERWIN, BI (reprint author), NCI,HUMAN CARCINOGENESIS LAB,BLDG 37,ROOM 2C09,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 26 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD APR PY 1992 VL 6 IS 4 BP 357 EP 358 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA HL724 UT WOS:A1992HL72400001 PM 1347998 ER PT J AU KERN, JA ROBINSON, RA GAZDAR, A TORNEY, L WEINER, DB AF KERN, JA ROBINSON, RA GAZDAR, A TORNEY, L WEINER, DB TI MECHANISMS OF P185(HER2) EXPRESSION IN HUMAN NON-SMALL-CELL LUNG-CANCER CELL-LINES SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR; RIBONUCLEIC-ACID; PROTEIN P185NEU; NEU ONCOGENE; HUMAN-BREAST; GENE; AMPLIFICATION; FRAGMENTS; CARCINOMA; LIGAND AB To identify mechanisms that allow p185HER2 expression in lung cancer, we performed Western, Southern, and Northern blot analyses of 14 cell lines derived from human non-small cell lung carcinomas and one cell line derived from a human mesothelioma. Human bronchiole epithelial cells and rat type II pneumocytes were found to express p185HER2 at low to undetectable levels by Western blot technique. In contrast, 13 lung cancer cell lines expressed p185HER2, and eight of these 13 expressed p185HER2 at levels at least 2-fold higher than that found in normal bronchiole epithelial cells or type II pneumocytes. Genomic Southern analysis showed that amplification of the HER2 gene was present in only one of the eight cell lines that expressed p185HER2 at these higher levels. Increased levels of steady-state HER2 mRNA occurred in the remaining seven cell lines. We conclude that in human non-small cell lung carcinoma cell lines the most common mechanism resulting in increased p185HER2 expression is due to mechanisms that increase HER2 mRNA levels, with HER2 gene amplification occurring less commonly. C1 UNIV IOWA,COLL MED,DEPT PATHOL,IOWA CITY,IA 52242. UNIV PENN,SCH MED,DEPT MED,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT PATHOL & LAB MED,PHILADELPHIA,PA 19104. NCI,BETHESDA,MD 20892. USN HOSP,BETHESDA,MD 20814. RP KERN, JA (reprint author), UNIV IOWA,COLL MED,DEPT INTERNAL MED,ROOM C-33A,GH,IOWA CITY,IA 52242, USA. RI Weiner, David/H-8579-2014 FU NHLBI NIH HHS [HL-01575] NR 23 TC 40 Z9 41 U1 0 U2 2 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD APR PY 1992 VL 6 IS 4 BP 359 EP 363 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA HL724 UT WOS:A1992HL72400002 PM 1312850 ER PT J AU FOX, CH DREYFUSS, R AF FOX, CH DREYFUSS, R TI PHOTOGRAPHY AND MOLECULAR-BIOLOGY - INSITU HYBRIDIZATION AUTORADIOGRAPHY AND IMMUNOGOLD SO AMERICAN LABORATORY LA English DT Article AB The photomicrographic techniques for recording the images from the use of radioactive molecular probe hybridization and immunogold-silver for the intensification of protein antigens in cells and tissues are discussed. C1 NIH,CTR CLIN,MED ARTS & PHOTOG BRANCH,BETHESDA,MD 20892. RP FOX, CH (reprint author), YALE UNIV,SCH MED,NEUROPATHOL SECT,NEW HAVEN,CT 06510, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU INT SCIENTIFIC COMMUN INC PI SHELTON PA PO BOX 870, 30 CONTROLS DRIVE, SHELTON, CT 06484-0870 SN 0044-7749 J9 AM LAB JI Am. Lab. PD APR PY 1992 VL 24 IS 6 BP 45 EP & PG 0 WC Chemistry, Analytical; Instruments & Instrumentation SC Chemistry; Instruments & Instrumentation GA HQ509 UT WOS:A1992HQ50900008 ER PT J AU KLION, AD EISENSTEIN, EM SMIRNIOTOPOULOS, TT NEUMANN, MP NUTMAN, TB AF KLION, AD EISENSTEIN, EM SMIRNIOTOPOULOS, TT NEUMANN, MP NUTMAN, TB TI PULMONARY INVOLVEMENT IN LOIASIS SO AMERICAN REVIEW OF RESPIRATORY DISEASE LA English DT Article ID LOA-LOA MICROFILARIAE; PLEURAL EFFUSIONS; INFECTION; FLUID AB A 40-yr-old West African man presented acutely with pleural effusion. Cytologic evaluation of the pleural fluid revealed Loa loa microfilariae. No additional etiology for the pleural effusion could be identified, and antifilarial treatment with diethylcarbamazine led to a rapid resolution of the patient's symptoms and pulmonary abnormalities. Loa loa must be considered as a treatable cause of eosinophilic pleural effusions in persons from endemic areas of West and Central Africa. C1 NIAID,CLIN INVEST LAB,PARASIT DIS LAB,BLDG 4,RM 126,BETHESDA,MD 20892. US DEPT STATE,OFF MED SERV,PULM DIS SECT,ALEXANDRIA,VA. ALEXANDRIA HOSP,ALEXANDRIA,VA. OI Klion, Amy/0000-0002-4986-5326 NR 21 TC 10 Z9 10 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 0003-0805 J9 AM REV RESPIR DIS JI Am. Rev. Respir. Dis. PD APR PY 1992 VL 145 IS 4 BP 961 EP 963 PG 3 WC Respiratory System SC Respiratory System GA HM120 UT WOS:A1992HM12000041 PM 1554227 ER PT J AU MARTIN, JL DUBBINK, DA PLEVAK, DJ PERONNE, A TASWELL, HF HAY, EJ PUMFORD, NR POHL, LR AF MARTIN, JL DUBBINK, DA PLEVAK, DJ PERONNE, A TASWELL, HF HAY, EJ PUMFORD, NR POHL, LR TI HALOTHANE HEPATITIS 28 YEARS AFTER PRIMARY EXPOSURE SO ANESTHESIA AND ANALGESIA LA English DT Article ID LIVER; ANTIBODIES; SERA; NEOANTIGENS; ANESTHESIA; ANTIGENS; RATS C1 MAYO CLIN & MAYO FDN,DEPT TRANSFUS MED,ROCHESTER,MN 55905. MAYO CLIN & MAYO FDN,DEPT GASTROENTEROL,ROCHESTER,MN 55905. JOHNS HOPKINS MED INST,DEPT ANESTHESIOL & CRIT CARE MED,BALTIMORE,MD 21205. MAYO CLIN & MAYO FDN,DEPT ANESTHESIOL & CRIT CARE MED,ROCHESTER,MN 55905. RP MARTIN, JL (reprint author), NHLBI,CHEM PHARMACOL LAB,BETHESDA,MD 20892, USA. NR 19 TC 20 Z9 21 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD APR PY 1992 VL 74 IS 4 BP 605 EP 608 PG 4 WC Anesthesiology SC Anesthesiology GA HK713 UT WOS:A1992HK71300024 PM 1554130 ER PT J AU LAGAKOS, SW HOTH, DF AF LAGAKOS, SW HOTH, DF TI SURROGATE MARKERS IN AIDS - WHERE ARE WE - WHERE ARE WE GOING SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material DE ACQUIRED IMMUNODEFICIENCY SYNDROME; ANTIGENS, CD4; BIOLOGICAL MARKERS; OUTCOME AND PROCESS ASSESSMENT (HEALTH CARE); ZIDOVUDINE AB The CD4 cell count and other surrogate markers of human immunodeficiency virus (HIV) infection possess enormous potential value for drug trials and for patient management. This usefulness, however, depends on our ability to reliably use surrogate markers to predict clinical outcomes. Current knowledge indicates that in persons with the acquired immunodeficiency syndrome (AIDS) or asymptomatic HIV infection, the beneficial effects of zidovudine-related clinical progression can be only partially explained by the drug's effect on CD4 cell count. Consequently, a drug's clinical efficacy cannot be confidently predicted solely by its effect on CD4 count. These results show the need for additional correlative studies to better understand whether and how markers can be used to predict clinical outcomes in comparative therapeutic trials, in the early approval of new anti-HIV drugs, and for the management of persons infected with HIV. C1 NIH,BETHESDA,MD 20892. RP LAGAKOS, SW (reprint author), HARVARD UNIV,SCH PUBL HLTH,677 HUNTINGTON AVE,BOSTON,MA 02115, USA. NR 4 TC 65 Z9 66 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 APR 1 PY 1992 VL 116 IS 7 BP 599 EP 601 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA HL258 UT WOS:A1992HL25800014 PM 1347443 ER PT J AU POLIS, MA NUSSENBLATT, RB LANE, HC AF POLIS, MA NUSSENBLATT, RB LANE, HC TI WHY WAS TREATMENT OF CYTOMEGALOVIRUS RETINITIS RANDOMIZED - REPLY SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 NEI,BETHESDA,MD 20892. NIAID,BETHESDA,MD 20892. RP POLIS, MA (reprint author), WARREN GRANT MAGNUSON CLIN CTR,BETHESDA,MD 20892, USA. NR 2 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 APR 1 PY 1992 VL 116 IS 7 BP 604 EP 605 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA HL258 UT WOS:A1992HL25800019 ER PT J AU CSAKO, G CORSO, DM KESTNER, J BOKSER, AD KENNEDY, PE PUCINO, F AF CSAKO, G CORSO, DM KESTNER, J BOKSER, AD KENNEDY, PE PUCINO, F TI EVALUATION OF 2 OVER-THE-COUNTER NATURAL THYROID-HORMONE PREPARATIONS IN HUMAN VOLUNTEERS SO ANNALS OF PHARMACOTHERAPY LA English DT Note AB OBJECTIVE: To determine the pharmacologic activity of over-the-counter (OTC) thyroid preparations. DESIGN: In vitro analysis and a prospective, crossover study in vivo. SETTING: Tertiary care center. PARTICIPANTS: Two healthy adult volunteers. INTERVENTION: Three OTC preparations (Thytrophin PMG [bovine thyroid PMG extract], Thyro Forte [thyroid lyphogland concentrate with synergistic complex], and Thyro Complex [thyroid lyophilized gland concentrate with synergistic complex]) were analyzed in vitro. Volunteers were administered two times the manufacturer's maximum recommended daily dose of either Thytrophin PMG or Thyro Forte for one week, washed out for four to five weeks, and crossed over to receive the opposite tablet preparation for an additional week. MAIN OUTCOME MEASURES: The triiodothyronine (T3) and thyroxine (T4) contents of OTC preparations were measured by HPLC. Vital signs, serum total and free T4, total T3, thyroid stimulating hormone, thyroxine binding globulin, thyroglobulin, and general chemistry tests (including glucose and cholesterol) were monitored before, during, and between administration of the products. RESULTS: HPLC analysis of the three OTC preparations showed no T4 but did show possible T3 in two of these products. We found no definite clinical or laboratory evidence of thyroid hormone excess with either product. CONCLUSIONS: Healthcare professionals should advise against the use of these scientifically unsound and relatively expensive OTC thyroid preparations, of which the therapeutic efficacy is unknown. C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT PHARM,ANALYT LAB,BETHESDA,MD 20892. NIH,WARREN G MAGNUSON CLIN CTR,DEPT CLIN PATHOL,BETHESDA,MD 20892. US BIOSCI,PHARMACEUT TECHNOL,W CONSHOHOCKEN,PA. NR 10 TC 0 Z9 0 U1 0 U2 1 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD APR PY 1992 VL 26 IS 4 BP 492 EP 494 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA HN282 UT WOS:A1992HN28200008 PM 1576386 ER PT J AU BOSKEN, C LENFANT, C AF BOSKEN, C LENFANT, C TI EXTRACORPOREAL MEMBRANE-OXYGENATION REVISITED ... AGAIN SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material ID RESPIRATORY-DISTRESS SYNDROME; FAILURE C1 NHLBI,BETHESDA,MD 20892. NR 10 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD APR PY 1992 VL 53 IS 4 BP 551 EP 552 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA HL854 UT WOS:A1992HL85400001 PM 1554260 ER PT J AU PETTIT, GR SENGUPTA, D BLUMBERG, PM LEWIN, NE SCHMIDT, JM KRAFT, AS AF PETTIT, GR SENGUPTA, D BLUMBERG, PM LEWIN, NE SCHMIDT, JM KRAFT, AS TI STRUCTURAL MODIFICATIONS OF BRYOSTATIN-2 SO ANTI-CANCER DRUG DESIGN LA English DT Article DE BRYOSTATIN-2; STRUCTURE MODIFICATIONS ID PROTEIN KINASE-C; ANTINEOPLASTIC AGENTS; CELLS; DIFFERENTIATION AB Continuation of a structure/activity relationship study of the bryostatins was focused on bryostatin 2. Stepwise catalytic hydrogenation of bryostatin 2 gave the following results. Reduction of the side-chain diene system to saturated ester 2a (P388 cell line ED50 8.5 x 10(-3)-mu-g/ml) did not significantly affect the murine P388 cell line inhibition by bryostatin 2. Further hydrogenation to hexahydro derivative 2b gave a reduced P388 ED50 Of 5.1 X 10(-2) mu-g/ml. Conversion to the octahydrobryostatin 2c caused a fur-ther reduction of P388 cell line activity to ED50 2.9 x 10(-1) mu-g/ml. Other structural modifications of bryostatin 2 in respect to esterification at the C-7 position significantly affected the P388 lymphocytic leukemia cell line response. Each of the bryostatin 2 derivatives was also evaluated with respect to protein kinase C binding. C1 ARIZONA STATE UNIV,DEPT CHEM,TEMPE,AZ 85287. NCI,BETHESDA,MD 20892. UNIV ALABAMA,DEPT MED,BIRMINGHAM,AL 35294. RP PETTIT, GR (reprint author), ARIZONA STATE UNIV,CANC RES INST,TEMPE,AZ 85287, USA. FU NCI NIH HHS [CA-44344-01AI-02, CA-16049-05-12]; NIAID NIH HHS [AI 25696-02-03] NR 19 TC 15 Z9 15 U1 1 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0266-9536 J9 ANTI-CANCER DRUG DES JI Anti-Cancer Drug Des. PD APR PY 1992 VL 7 IS 2 BP 101 EP 113 PG 13 WC Biochemistry & Molecular Biology; Oncology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Oncology; Pharmacology & Pharmacy GA HU261 UT WOS:A1992HU26100001 PM 1575884 ER PT J AU RENAUDIN, H TULLY, JG BEBEAR, C AF RENAUDIN, H TULLY, JG BEBEAR, C TI INVITRO SUSCEPTIBILITIES OF MYCOPLASMA-GENITALIUM TO ANTIBIOTICS SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Note ID DISCOVERED MYCOPLASMA; TRACT; PNEUMONIAE AB The susceptibilities of seven clinical isolates of Mycoplasma genitalium and three strains of Mycoplasma pneumoniae to a variety of antibiotics were examined by an agar dilution method. Macrolides, pristinamycin, and tetracyclines were very active against both species. Sparfloxacin was the most active quinolone tested. None of the 21 antibiotics tested had differential activity toward the two organisms. C1 HOP PELLEGRIN,BACTERIOL LAB,PL AMELIE RABA LEON,F-33076 BORDEAUX,FRANCE. NIAID,MYCOPLASMA SECT,FREDERICK,MD 21701. NR 21 TC 33 Z9 33 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD APR PY 1992 VL 36 IS 4 BP 870 EP 872 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA HM687 UT WOS:A1992HM68700030 PM 1503451 ER PT J AU PERNO, CF YARCHOAN, R BALZARINI, J BERGAMINI, A MILANESE, G PAUWELS, R DECLERCQ, E ROCCHI, G CALIO, R AF PERNO, CF YARCHOAN, R BALZARINI, J BERGAMINI, A MILANESE, G PAUWELS, R DECLERCQ, E ROCCHI, G CALIO, R TI DIFFERENT PATTERN OF ACTIVITY OF INHIBITORS OF THE HUMAN-IMMUNODEFICIENCY-VIRUS IN LYMPHOCYTES AND MONOCYTE MACROPHAGES SO ANTIVIRAL RESEARCH LA English DT Article; Proceedings Paper CT 4TH INTERNATIONAL CONF ON ANTIVIRAL RESEARCH CY APR 21-26, 1991 CL NEW ORLEANS, LA DE HIV; MACROPHAGE; LYMPHOCYTE; ANTI-HIV DRUG; CYTOKINE ID LYMPHADENOPATHY-ASSOCIATED VIRUS; AIDS-RELATED COMPLEX; HTLV-III/LAV INFECTION; MONONUCLEAR PHAGOCYTES; CLINICAL-PHARMACOLOGY; VIRAL RESERVOIRS; BRAIN-TISSUE; SINGLE AGENT; GM-CSF; REPLICATION AB Monocyte/macrophages (M/M) are important targets for HIV in the body, and represent the majority of cells infected by the virus in some body compartments such as the central nervous system (CNS). M/M can be different from T-lymphocytes in terms of surface antigens, cell replication and drug metabolism. Thus, we evaluated, in M/M and in T-lymphocytes, the pattern of viral inhibition induced by various anti-HIV drugs, and assessed some of the mechanisms of action related to such antiviral activity. Inhibitors of HIV binding on CD4 receptors have similar activity in M/M and T-lymphocytes, while AZT and other dideoxynucleosides (ddN) are in general more active against HIV in M/M than in T-lymphocytes. This phenomenon can be related to the increased ratio in M/M of ddN-triphosphate/deoxynucleoside-triphosphate, and can at least in part explain the ability of zidovudine and didanosine in improving neurological dysfunctions in AIDS patients. Moreover, the antiviral activity of AZT (but not of other ddN- or HIV-binding inhibitors) is potently enhanced by cytokines like granulocyte-macrophage colony stimulating factor (GM-CSF) in M/M, while anti-HIV activity of TIBO compounds in M/M is not down-modulated by GM-CSF and other cytokines. Finally, non-toxic concentrations of adriamycin, an anticancer drug reported to be active against DNA viruses, can inhibit HIV replication in M/M (but not in T-lymphocytes). Taken together, these results suggest that M/M are selective targets for HIV with peculiarities different from those of T-lymphocytes. Thus, promising anti-HIV compounds should be evaluated both in T-cells and in M/M before reaching clinical trials. This may help in selecting drugs with good chances of being effective in patients with HIV-related disease. C1 NCI,CLIN ONCOL PROGRAM,BETHESDA,MD 20892. UNIV ROME TOR VERGATA,DEPT EXPTL MED & BIOCHEM SCI,CHAIR VIROL,ROME,ITALY. UNIV ROME TOR VERGATA,DEPT PUBL HLTH,CHAIR INFECT DIS,ROME,ITALY. CATHOLIC UNIV LEUVEN,REGA INST MED RES,B-3000 LOUVAIN,BELGIUM. RI perno, carlo federico/O-1544-2016 NR 55 TC 32 Z9 32 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD APR PY 1992 VL 17 IS 4 BP 289 EP 304 DI 10.1016/0166-3542(92)90024-Y PG 16 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA HM673 UT WOS:A1992HM67300004 PM 1322645 ER PT J AU TREADO, PJ LEVIN, IW LEWIS, EN AF TREADO, PJ LEVIN, IW LEWIS, EN TI NEAR-INFRARED ACOUSTOOPTIC FILTERED SPECTROSCOPIC MICROSCOPY - A SOLID-STATE APPROACH TO CHEMICAL IMAGING SO APPLIED SPECTROSCOPY LA English DT Article DE INSTRUMENTATION, IMAGING; SPECTROSCOPIC TECHNIQUES; NEAR-INFRARED SPECTROSCOPY; VISIBLE SPECTROSCOPY; ACOUSTOOPTICS; CHARGE-COUPLED DEVICES; HISTOLOGY; PHOSPHOLIPIDS ID TRANSFORM RAMAN MICROSCOPY AB A new instrumental approach for performing spectroscopic imaging microscopy is described. The instrument integrates an acousto-optic tunable filter (AOTF) and charge-coupled-device (CCD) detector with an infinity-corrected microscope for operation in the visible and near-infrared (NIR) spectral regions. Images at moderate spectral resolution (2 nm) and high spatial resolution (1-mu-m) can be collected rapidly. Data are presented containing 128 x 128 pixels, although images with significantly larger formats can be collected in approximately the same time. In operation, the CCD is used as a true imaging detector, while wavelength selectivity is provided by using the AOTF and quartz tungsten halogen lamp to create a tunable source. The instrument is entirely solid state, containing no moving parts, and can be readily configured for both absorption and reflectance spectroscopies. We present visible absorption spectral images of human epithelial cells, as well as NIR vibrational absorption images of a hydrated phospholipid suspension, to demonstrate the potential of the technique in the study of biological materials. Extensions and future applications of this work are discussed. C1 NIDDKD,CHEM PHYS LAB,BLDG 2,ROOM 114,BETHESDA,MD 20892. NR 18 TC 68 Z9 68 U1 0 U2 4 PU SOC APPLIED SPECTROSCOPY PI FREDERICK PA 201B BROADWAY ST, FREDERICK, MD 21701 SN 0003-7028 J9 APPL SPECTROSC JI Appl. Spectrosc. PD APR PY 1992 VL 46 IS 4 BP 553 EP 559 DI 10.1366/0003702924125032 PG 7 WC Instruments & Instrumentation; Spectroscopy SC Instruments & Instrumentation; Spectroscopy GA HP473 UT WOS:A1992HP47300003 ER PT J AU KRISHNA, CM LIEBMANN, JE KAUFMAN, D DEGRAFF, W HAHN, SM MCMURRY, T MITCHELL, JB RUSSO, A AF KRISHNA, CM LIEBMANN, JE KAUFMAN, D DEGRAFF, W HAHN, SM MCMURRY, T MITCHELL, JB RUSSO, A TI THE CATECHOLIC METAL SEQUESTERING AGENT 1,2-DIHYDROXYBENZENE-3,5-DISULFONATE CONFERS PROTECTION AGAINST OXIDATIVE CELL-DAMAGE SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID HYDROGEN-PEROXIDE; CHELATING-AGENTS; SUPEROXIDE GENERATION; CHEMI-LUMINESCENCE; CYTO-TOXICITY; FREE-RADICALS; PHYTIC ACID; VITAMIN-E; ANTIOXIDANT; VANADATE C1 NCI, RADIAT ONCOL BRANCH, BLDG 10, ROOM B3-B69, BETHESDA, MD 20872 USA. NR 49 TC 83 Z9 83 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 EI 1096-0384 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD APR PY 1992 VL 294 IS 1 BP 98 EP 106 DI 10.1016/0003-9861(92)90142-J PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA HJ446 UT WOS:A1992HJ44600015 PM 1312813 ER PT J AU LUBET, RA NIMS, RW BEEBE, LE FOX, SD ISSAQ, HJ MCBEE, K AF LUBET, RA NIMS, RW BEEBE, LE FOX, SD ISSAQ, HJ MCBEE, K TI INDUCTION OF HEPATIC CYP1A ACTIVITY AS A BIOMARKER FOR ENVIRONMENTAL EXPOSURE TO AROCLOR-1254 IN FERAL RODENTS SO ARCHIVES OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY LA English DT Article ID POLYCHLORINATED-BIPHENYLS; IMMUNOCHEMICAL QUANTITATION; LIVER-MICROSOMES; AH RECEPTOR; 8 ISOZYMES; CYTOCHROME-P-450; RATS; CONGENERS; INDUCERS; ASSAY AB Specimens of the feral mouse species Reithrodontomys fulvescens trapped from a polychlorinated biphenyl (PCB)-contaminated field location had hepatic ethoxyresorufin (ETR) O-dealkylase activities and immunoreactive CYP1A protein contents which were two- to threefold higher than those measured in animals of the same species and sex collected from non PCB-contaminated reference sites. Specimens with hepatic ETR O-dealkylase activities differing by as little as 50% could readily be assigned as originating from the PCB or reference sites by the use of a specific chemical inhibitor of cytochrome P450IA (CYP1A). The relative levels of ETR O-dealkylase activity in R. fulvescens significantly correlated with hepatic PCB burdens (r = 0.819, P < 0.01). When the magnitudes of the induced ETR O-dealkylase activities corresponding to given hepatic PCB burdens were compared between the feral animals, F344/NCr rats (Rattus norvegicus) or B6C3F1 mice (Mus musculus) exposed in the laboratory to dietary Aroclor(R) 1254, the order of sensitivity to the inducing effects of PCBs were F344/NCr rat > B6C3F1 mouse > R. fulvescens. C1 FREDERICK CANC RES & DEV CTR,PRI DYN CORP,CHEM SYNTH & ANAL LAB,FREDERICK,MD 21702. OKLAHOMA STATE UNIV,DEPT ZOOL,STILLWATER,OK 74078. RP LUBET, RA (reprint author), NCI,FREDERICK CANC RES & DEV CTR,COMPARATIVE CARCINOGENESIS LAB,BLDG 538,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CO-74102] NR 33 TC 26 Z9 26 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0090-4341 J9 ARCH ENVIRON CON TOX JI Arch. Environ. Contam. Toxicol. PD APR PY 1992 VL 22 IS 3 BP 339 EP 344 PG 6 WC Environmental Sciences; Toxicology SC Environmental Sciences & Ecology; Toxicology GA HJ284 UT WOS:A1992HJ28400015 PM 1616319 ER PT J AU STEIN, MB TANCER, ME UHDE, TW AF STEIN, MB TANCER, ME UHDE, TW TI HEART-RATE AND PLASMA NOREPINEPHRINE RESPONSIVITY TO ORTHOSTATIC CHALLENGE IN ANXIETY DISORDERS - COMPARISON OF PATIENTS WITH PANIC DISORDER AND SOCIAL PHOBIA AND NORMAL CONTROL SUBJECTS SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID ALPHA-2-ADRENERGIC RECEPTOR-BINDING; MITRAL-VALVE PROLAPSE; BLOOD-PRESSURE; NORADRENERGIC FUNCTION; CARDIOVASCULAR CONTROL; MAJOR DEPRESSION; HEALTHY-SUBJECTS; ANXIOUS PATIENTS; POSTURAL CHANGE; NERVOUS-SYSTEM AB Heart rate and plasma norepinephrine responsivity to a physiologic challenge, ie, orthostasis, were measured in 20 patients with panic disorder (PD) and 20 age- and sex-matched normal control subjects. While the two groups exhibited similar supine heart rates, patients with PD had a significantly greater heart rate response to orthostatic challenge. Plasma norepinephrine responses did not differ between patients with PD and normal control subjects. In a matched subgroup of 14 patients with PD, 14 normal control subjects, and 14 patients with social phobia, the patients with social phobia exhibited supine and upright plasma norepinephrine levels that were significantly higher than those of the other two diagnostic groups. Taken together, and in the context of findings from other studies, these preliminary observations suggest that the anxiety disorders may demonstrate differing patterns of autonomic dysfunction. C1 NIMH,BIOL PSYCHIAT BRANCH,ANXIETY & AFFECT DISORDERS SECT,BLDG 10,BETHESDA,MD 20892. NR 76 TC 99 Z9 101 U1 2 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD APR PY 1992 VL 49 IS 4 BP 311 EP 317 PG 7 WC Psychiatry SC Psychiatry GA HM914 UT WOS:A1992HM91400007 PM 1558465 ER PT J AU HYDE, TM ZIEGLER, JC WEINBERGER, DR AF HYDE, TM ZIEGLER, JC WEINBERGER, DR TI PSYCHIATRIC DISTURBANCES IN METACHROMATIC LEUKODYSTROPHY - INSIGHTS INTO THE NEUROBIOLOGY OF PSYCHOSIS SO ARCHIVES OF NEUROLOGY LA English DT Article ID TEMPORAL-LOBE EPILEPSY; HUNTINGTONS-DISEASE; PARAHIPPOCAMPAL GYRUS; PREFRONTAL CORTEX; CLINICAL COURSE; SCHIZOPHRENIA; ADULT; BRAIN; ONSET; LEUCODYSTROPHY AB Metachromatic leukodystrophy is a rare inherited disorder of the nervous system. Symptoms initially can present during childhood, adolescence, or adulthood. Psychiatric symptoms, including complex auditory hallucinations and bizarre delusions, are a prominent feature of metachromatic leukodystrophy presenting when the patient is between 12 and 30 years. One hundred twenty-nine published case reports were reviewed, focusing on the presence of psychosis. Psychosis was present in 53% of the published case reports of adolescent and early adult-onset metachromatic leukodystrophy, a much higher prevalence than that seen with other primary neurological disorders. The pathological lesion of metachromatic leukodystrophy is demyelination of the central and peripheral nervous systems, particularly the subfrontal white matter, suggesting that psychosis may result from the disruption of corticocortical and corticosubcortical connections, especially involving the frontal lobes. While similar lesions appear in the infantile, juvenile, and late adult forms of metachromatic leukodystrophy, psychotic symptoms were reported only in those cases presenting in adolescence and young adulthood, suggesting that age is another important neurobiological factor in the development of psychosis. RP HYDE, TM (reprint author), ST ELIZABETH HOSP,NIMH,INTRAMURAL RES PROGRAM,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032, USA. NR 91 TC 189 Z9 191 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD APR PY 1992 VL 49 IS 4 BP 401 EP 406 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA HM463 UT WOS:A1992HM46300021 PM 1532712 ER PT J AU ZALZAL, GH LUYTEN, F AF ZALZAL, GH LUYTEN, F TI AN INVITRO MODEL FOR STUDYING GROWTH AND EFFECT OF TRAUMA AND EXTERNAL AGENTS ON THE CRICOID AT THE CELLULAR-LEVEL SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID MAMMALIAN CHONDROCYTES INVITRO; BOVINE ARTICULAR-CARTILAGE; PROTEOGLYCANS; CULTURE; RECONSTRUCTION; METABOLISM; EXPLANTS; GRAFTS; MATRIX; ASSAY AB Over the past several years it has become evident that expansion laryngotracheal surgery is effective in the treatment of laryngotracheal stenosis. Several clinical and animal studies have been performed to study the process of laryngotracheal stenosis and its treatment. However, there are still many questions that cannot be addressed by currently used clinical and animal research. Further indepth study of the behavior of the subglottis at the cellular level is necessary. We present an in vitro model for studying chondrocyte metabolism of the bovine cricoid. Cartilage was successfully grown in an explant culture system, and it was shown that the chondrocytes were metabolically active and responded to external agents. This model will serve to study the mechanism of growth and effects of trauma and external agents on the cricoid at the cellular level. C1 NIDR,BONE CELL BIOL SECT,CELLULAR DEV & ONCOL LAB,BETHESDA,MD 20892. RP ZALZAL, GH (reprint author), GEORGE WASHINGTON UNIV,CHILDRENS NATL MED CTR,DEPT PEDIAT OTOLARYNGOL,111 MICHIGAN AVE NW,WASHINGTON,DC 20010, USA. NR 18 TC 5 Z9 5 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD APR PY 1992 VL 118 IS 4 BP 407 EP 411 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA HN299 UT WOS:A1992HN29900012 PM 1554471 ER PT J AU PATTERSON, AP TENNYSON, GE HOEG, JM SVIRIDOV, DD BREWER, HB AF PATTERSON, AP TENNYSON, GE HOEG, JM SVIRIDOV, DD BREWER, HB TI ONTOGENIC REGULATION OF APOLIPOPROTEIN-B MESSENGER-RNA EDITING DURING HUMAN AND RAT DEVELOPMENT INVIVO SO ARTERIOSCLEROSIS AND THROMBOSIS LA English DT Article DE ARTERIOSCLEROSIS; LIPID METABOLISM; HUMAN DEVELOPMENT; MESSENGER RNA PROCESSING; CHOLESTEROL ID TRANSLATIONAL STOP CODON; HUMAN INTESTINE; FATTY-ACID; GENE; HYPOBETALIPOPROTEINEMIA; LIVER; FORMS; IDENTIFICATION; TRIGLYCERIDE; LIPOPROTEINS AB The solubilization and delivery of lipids in plasma rely on both forms of apolipoprotein B (apo B): apo B-100 and apo B-48. Apo B-48 is the translational product of apo B-100 mRNA that undergoes peritranscriptional conversion of C --> U, replacing codon CAA (glutamine 2,153) with the in-frame stop codon (UAA). We examined mRNA editing activity in the human and the rat by reverse transcription-polymerase chain reaction primer-extension analysis of intestine and liver total RNA. In rat intestine the percentage of apo B transcripts that undergo editing increases dramatically the day before birth (from approximately 1% to 80%), whereas the rat liver acquires an adult level of editing activity during the third postnatal week (rising from approximately 8% to 30%), when weaning is completed, bile acid composition matures, and plasma thyroid hormone levels peak. In contrast to the rat, the human intestine acquires adult levels of apo B mRNA editing relatively early in fetal development, rising from 10% at 10 weeks to approximately 80% by the end of the second trimester. Our results establish that apo B mRNA editing is 1) developmentally regulated in a tissue- and species-specific manner; 2) fully developed prenatally in both human and rat intestine, suggesting a crucial role of apo B-48 in mammalian fetal adaptation to extrauterine life; and 3) acquired early in human fetal intestine, implying a potential role for apo B-48 in prenatal lipid metabolism. C1 ACAD SCI USSR,CARDIOL RES CTR,INST EXPTL CARDIOL,MOSCOW V-71,USSR. RP PATTERSON, AP (reprint author), NHLBI,MOLEC DIS BRANCH,BLDG 10,ROOM 7N108,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Sviridov, Dmitri/E-7943-2010 NR 41 TC 23 Z9 23 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 APR PY 1992 VL 12 IS 4 BP 468 EP 473 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA HQ049 UT WOS:A1992HQ04900008 PM 1558838 ER PT J AU NEUER, G BUSTIN, M MICHELS, H TRUCKENBRODT, H BAUTZ, FA AF NEUER, G BUSTIN, M MICHELS, H TRUCKENBRODT, H BAUTZ, FA TI AUTOANTIBODIES TO THE CHROMOSOMAL PROTEIN HMG-17 IN JUVENILE RHEUMATOID-ARTHRITIS SO ARTHRITIS AND RHEUMATISM LA English DT Article ID ANTIBODIES; SERA AB Objective. To determine the antibody profiles in sera from patients with juvenile rheumatoid arthritis (JRA). Methods. Immunoblotting using nuclear extracts and recombinant high-mobility groups (HMG) nonhistone chromosomal proteins. Results. Antibodies directed against HMG-17 were found in 47% of antinuclear antibody (ANA)-positive patients with pauciarticular-onset JRA and in 16% of ANA-positive patients with polyarticular-onset JRA. HMG-17 values of 6% and 8%, respectively, were detected in ANA-negative patients with JRA and in those with nonrheumatic diseases. Conclusion. There is evidence for a high prevalence of anti-HMG-17 antibodies in sera of patients with pauciarticular-onset JRA. C1 UNIV HEIDELBERG,INST MOLEC GENET,NEUENHEIMER FELD 230,W-6900 HEIDELBERG,GERMANY. NCI,BETHESDA,MD 20892. RHEUMAT CHILDRENS HOSP,GARMISCH PARTENKIR,GERMANY. RI Bustin, Michael/G-6155-2015 NR 10 TC 25 Z9 25 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 APR PY 1992 VL 35 IS 4 BP 472 EP 475 DI 10.1002/art.1780350418 PG 4 WC Rheumatology SC Rheumatology GA HN287 UT WOS:A1992HN28700017 PM 1567496 ER PT J AU HIBBS, JR YOUNG, NS AF HIBBS, JR YOUNG, NS TI VIRUSES AND THE BLOOD SO BAILLIERES CLINICAL HAEMATOLOGY LA English DT Article ID EPSTEIN-BARR-VIRUS; HUMAN PARVOVIRUS B19; RED-CELL APLASIA; DENGUE HEMORRHAGIC-FEVER; NON-B HEPATITIS; COMPLICATING INFECTIOUS-MONONUCLEOSIS; LINKED LYMPHOPROLIFERATIVE SYNDROME; BONE-MARROW FAILURE; NON-A; ERYTHEMA-INFECTIOSUM RP HIBBS, JR (reprint author), NHLBI,CLIN HAEMATOL BRANCH,CLIN SERV,BLDG 10,ROOM 7C103,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 278 TC 3 Z9 3 U1 0 U2 0 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0950-3536 J9 BAILLIERE CLIN HAEM JI Baillieres Clin. Haematol. PD APR PY 1992 VL 5 IS 2 BP 245 EP 271 DI 10.1016/S0950-3536(11)80020-X PG 27 WC Hematology SC Hematology GA JJ874 UT WOS:A1992JJ87400001 PM 1511177 ER PT J AU CLINE, EJ TERRY, P CARROLL, FI KUHAR, MJ KATZ, JL AF CLINE, EJ TERRY, P CARROLL, FI KUHAR, MJ KATZ, JL TI STIMULUS-GENERALIZATION FROM COCAINE TO ANALOGS WITH HIGH INVITRO AFFINITY FOR DOPAMINE UPTAKE SITES SO BEHAVIOURAL PHARMACOLOGY LA English DT Article DE COCAINE; ANALOGS; RAT; DRUG DISCRIMINATION; DOPAMINE UPTAKE ID SQUIRREL-MONKEYS AB Previous research has shown that phenyltropane derivatives of cocaine are very potent ligands for dopamine transporters in in vitro binding and uptake, and in in vivo binding assays. In the present study, these analogs were tested for their ability to substitute for cocaine in rats trained to discriminate cocaine from saline. Results indicate that these compounds are from 6-13 times more potent than cocaine in producing cocaine-appropriate responding. This provides further evidence in support of the importance of dopamine uptake inhibition for the behavioral effects of cocaine, and suggests utility of these compounds in understanding cocaine abuse. C1 NIDA,ADDICT RES CTR,PRECLIN PHARMACOL BRANCH,PSYCHOBIOL LAB,POB 5180,BALTIMORE,MD 21224. NIDA,ADDICT RES CTR,NEUROSCI LAB,MOLEC PHARMACOL LAB,BALTIMORE,MD 21224. OI Katz, Jonathan/0000-0002-1068-1159 NR 15 TC 25 Z9 25 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD APR PY 1992 VL 3 IS 2 BP 113 EP 116 PG 4 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA HW249 UT WOS:A1992HW24900002 ER PT J AU SAVARESE, TM FRASER, CM AF SAVARESE, TM FRASER, CM TI INVITRO MUTAGENESIS AND THE SEARCH FOR STRUCTURE-FUNCTION-RELATIONSHIPS AMONG G-PROTEIN-COUPLED RECEPTORS SO BIOCHEMICAL JOURNAL LA English DT Review ID BETA-ADRENERGIC-RECEPTOR; MUSCARINIC ACETYLCHOLINE-RECEPTOR; SITE-DIRECTED MUTAGENESIS; HUMAN BETA-2-ADRENERGIC RECEPTOR; LIGHT-DEPENDENT PHOSPHORYLATION; SUBSTANCE-K RECEPTOR; HUMAN ALPHA-2-ADRENERGIC RECEPTOR; NUCLEOTIDE REGULATORY PROTEINS; MEMBRANE-SPANNING DOMAINS; AFFINITY AGONIST BINDING C1 NIAAAA,DRUG ABUSE & MENTAL HLTH ADM,MOLEC NEUROBIOL SECT,PHYSIOL & PHARMACOL STUDIES LAB,ROCKVILLE,MD 20852. OI Fraser, Claire/0000-0003-1462-2428 FU NCI NIH HHS [CA 01241] NR 181 TC 474 Z9 476 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 APR 1 PY 1992 VL 283 BP 1 EP 19 PN 1 PG 19 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA HN034 UT WOS:A1992HN03400001 PM 1314560 ER PT J AU YEE, LK ALLEGRA, CJ TREPEL, JB GREM, JL AF YEE, LK ALLEGRA, CJ TREPEL, JB GREM, JL TI METABOLISM AND RNA INCORPORATION OF CYCLOPENTENYL CYTOSINE IN HUMAN COLORECTAL-CANCER CELLS SO BIOCHEMICAL PHARMACOLOGY LA English DT Article ID COLON CARCINOMA-CELLS; 1-BETA-D-ARABINOFURANOSYLCYTOSINE 5'-TRIPHOSPHATE; NUCLEAR-RNA; 5-FLUOROURACIL; TRIPHOSPHATE; CYTIDINE; TOXICITY; DNA; DIPYRIDAMOLE; INHIBITION AB We studied the cytotoxicity and metabolism of the investigational cytidine analogue cyclopentenyl cytosine (CPE-C) in three human colorectal cancer cell lines: HCT 116, SNU-C4, and NCI-H630. CPE-C potently inhibited cell growth and decreased clonogenic capacity at concentrations achieved in murine and primate pharmacologic studies. CPE-C produced a concentration-dependent depletion of CTP, accompanied by changes in the dCTP pools. CPE-C exposure was associated with an accumulation of cells in the S phase at 48 hr. [H-3]CPE-C was metabolized predominantly to the triphosphate (CPE-CTP) form. Saturation of phosphorylation to the monophosphate form occurred above 5-10-mu-M. Plateau CPE-CTP pools were of a magnitude similar to that of the physiologic ribonucleotide triphosphate pools. The intracellular half-life of CPE-CTP was 24 hr. After a 24-hr exposure to 0.5-mu-M CPE-C, CPE-CTP was detected for up to 96 hr post-drug removal, accompanied by persistent depletion of the CTP pools. Cesium sulfate density centrifugation of purified nucleic acids indicated that [H-3]CPE-C incorporated into RNA, but was not detected in DNA. Agarose-gel electrophoresis of RNA from [H-3]CPE-C-treated cells indicated that it localized predominantly in low molecular weight (4-8 S) RNA species. When CPE-C was administered concurrently with [H-3]adenosine (Ado), the proportion of [H-3]Ado migrating with low molecular weight RNA species increased. Concurrent exposure to 10-mu-M cytidine (Cyd), sufficient to replete CTP pools, provided essentially complete protection against lethality resulting from a 24-hr exposure to less-than-or-equal-to 0.5-mu-M CPE-C. While 10-mu-M Cyd substantially decreased CPE-CTP formation and CPE-C-RNA incorporation during the initial 3 hr of exposure compared to CPE-C alone, after 24 hr the levels were not significantly different. Cyd rescue did not affect the accumulation of [H-3]CPE-C or [H-3]Ado into low molecular weight RNA species after a 24-hr exposure to CPE-C. Our results indicate that depletion of CTP and dCTP pools is an important component of CPE-C cytotoxicity. While CPE-C incorporation into RNA may not be the critical cytotoxic event during a 24-hr exposure to CPE-G, it may play a role during prolonged exposure to CPE-C. CPE-C is a highly potent new agent and merits clinical evaluation in the treatment of colorectal cancer. C1 NCI,MED BRANCH,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,BLDG 10,RM 12N226,BETHESDA,MD 20892. NCI,CLIN PHARMACOL BRANCH,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,BETHESDA,MD 20892. NR 29 TC 21 Z9 21 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 APR 1 PY 1992 VL 43 IS 7 BP 1587 EP 1599 DI 10.1016/0006-2952(92)90218-8 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA HN493 UT WOS:A1992HN49300027 PM 1567480 ER PT J AU STADTMAN, TC AF STADTMAN, TC TI INTERNATIONAL-CONGRESS ON VITAMINS AND BIOFACTORS IN LIFE-SCIENCE SO BIOFACTORS LA English DT Editorial Material RP STADTMAN, TC (reprint author), NHLBI,BIOCHEM LAB,BLDG 3,ROOM 108,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0951-6433 J9 BIOFACTORS JI Biofactors PD APR PY 1992 VL 3 IS 4 BP 269 EP 270 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA HQ143 UT WOS:A1992HQ14300009 PM 1351388 ER PT J AU VANVLEET, JF FERRANS, VJ AF VANVLEET, JF FERRANS, VJ TI ETIOLOGIC FACTORS AND PATHOLOGICAL ALTERATIONS IN SELENIUM-VITAMIN-E DEFICIENCY AND EXCESS IN ANIMALS AND HUMANS SO BIOLOGICAL TRACE ELEMENT RESEARCH LA English DT Article; Proceedings Paper CT INTERNATIONAL SYMP ON SELENIUM CY MAY 12-15, 1991 CL BELGRADE, YUGOSLAVIA SP SERBIAN ACAD SCI & ARTS ID HOME PARENTERAL-NUTRITION; MULBERRY HEART-DISEASE; ULTRASTRUCTURAL CHANGES; CYSTIC-FIBROSIS; KESHAN DISEASE; INTRAVENTRICULAR HEMORRHAGE; ENDEMIC CARDIOMYOPATHY; FATAL CARDIOMYOPATHY; MUSCULAR-DYSTROPHY; SWINE AB The etiology of selenium-vitamin E(Se-E) deficiency diseases may be complex. Many of the syndromes involve combined deficiency of selenium and vitamin E. Selenium moves into the animal and human food chain from soil and plants, which may contain inadequate amounts of the nutrient in many areas of the world. Vitamin E may be in low concentration in many animal feeds unless supplements are added. Some syndromes, such as steatitis in cats, result from an increased requirement of vitamin E in diets that contain large amounts of polyunsaturated fatty acids, and these diseases will only respond to vitamin E administration. Deficiency syndromes in animals owing to pure Se deficiency are infrequent and have been produced mainly by laboratory studies utilizing extreme deficiency conditions. Other factors that may affect the occurrence of these deficiency diseases are concurrent dietary deficiency of S-containing amino acids, bioavailability of different forms of dietary Se, intake of compounds that antagonize Se (e.g., silver salts), and exposure to various prooxidant substances (e.g., iron compounds, oxygen, ozone, and various drugs). C1 NHLBI,PATHOL BRANCH,BETHESDA,MD 20892. RP VANVLEET, JF (reprint author), PURDUE UNIV,SCH VET MED,DEPT PATHOBIOL,W LAFAYETTE,IN 47907, USA. NR 121 TC 44 Z9 45 U1 0 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 SN 0163-4984 J9 BIOL TRACE ELEM RES JI Biol. Trace Elem. Res. PD APR-JUN PY 1992 VL 33 BP 1 EP 21 PG 21 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA HZ945 UT WOS:A1992HZ94500002 PM 1379446 ER PT J AU VODYANOY, I BEZRUKOV, SM AF VODYANOY, I BEZRUKOV, SM TI SIZING OF AN ION PORE BY ACCESS RESISTANCE MEASUREMENTS SO BIOPHYSICAL JOURNAL LA English DT Article; Proceedings Paper CT CONF ON BIOPHYSICS AND RECOMBINANT DNA : PROBLEMS, STRATEGIES, AND NEW QUESTIONS CY JAN 19-22, 1992 CL AIRLIE, VA SP NIH, NATL SCI FDN, USN, OFF NAVAL RES C1 UNIV MARYLAND,COLLEGE PK,MD 20742. UNIV CALIF IRVINE,DEPT PHYSIOL & BIOPHYS,IRVINE,CA 92717. NIDDK BIOCHEM & METAB LAB,BETHESDA,MD 20892. RP VODYANOY, I (reprint author), OFF NAVAL RES,ARLINGTON,VA 22217, USA. NR 4 TC 38 Z9 40 U1 0 U2 16 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD APR PY 1992 VL 62 IS 1 BP 10 EP 11 DI 10.1016/S0006-3495(92)81762-9 PG 2 WC Biophysics SC Biophysics GA HT995 UT WOS:A1992HT99500005 PM 1376161 ER PT J AU POLLARD, HB GUY, HR ARISPE, N DELAFUENTE, M LEE, G ROJAS, EM POLLARD, JR SRIVASTAVA, M KECK, ZYZ MEREZHINSKAYA, N CAOHUY, H BURNS, AL ROJAS, E AF POLLARD, HB GUY, HR ARISPE, N DELAFUENTE, M LEE, G ROJAS, EM POLLARD, JR SRIVASTAVA, M KECK, ZYZ MEREZHINSKAYA, N CAOHUY, H BURNS, AL ROJAS, E TI CALCIUM-CHANNEL AND MEMBRANE-FUSION ACTIVITY OF SYNEXIN AND OTHER MEMBERS OF THE ANNEXIN GENE FAMILY SO BIOPHYSICAL JOURNAL LA English DT Article; Proceedings Paper CT CONF ON BIOPHYSICS AND RECOMBINANT DNA : PROBLEMS, STRATEGIES, AND NEW QUESTIONS CY JAN 19-22, 1992 CL AIRLIE, VA SP NIH, NATL SCI FDN, USN, OFF NAVAL RES ID BILAYER-MEMBRANES; PROTEIN C1 NCI,MATH BIOL LAB,BETHESDA,MD 20892. RP POLLARD, HB (reprint author), NIDDKD,CELL BIOL & GENET LAB,BETHESDA,MD 20892, USA. NR 10 TC 68 Z9 70 U1 0 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD APR PY 1992 VL 62 IS 1 BP 15 EP 18 DI 10.1016/S0006-3495(92)81764-2 PG 4 WC Biophysics SC Biophysics GA HT995 UT WOS:A1992HT99500007 PM 1318099 ER PT J AU GUY, HR DURELL, SR SCHOCH, C BLUMENTHAL, R AF GUY, HR DURELL, SR SCHOCH, C BLUMENTHAL, R TI ANALYZING THE FUSION PROCESS OF INFLUENZA HEMAGGLUTININ BY MUTAGENESIS AND MOLECULAR MODELING SO BIOPHYSICAL JOURNAL LA English DT Article; Proceedings Paper CT CONF ON BIOPHYSICS AND RECOMBINANT DNA : PROBLEMS, STRATEGIES, AND NEW QUESTIONS CY JAN 19-22, 1992 CL AIRLIE, VA SP NIH, NATL SCI FDN, USN, OFF NAVAL RES ID VIRUS; EVENTS RP GUY, HR (reprint author), NCI,DCBDC,MATH BIOL LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 12 TC 29 Z9 29 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD APR PY 1992 VL 62 IS 1 BP 95 EP 97 DI 10.1016/S0006-3495(92)81790-3 PG 3 WC Biophysics SC Biophysics GA HT995 UT WOS:A1992HT99500033 PM 1600107 ER PT J AU DURELL, SR GUY, HR AF DURELL, SR GUY, HR TI ATOMIC SCALE STRUCTURE AND FUNCTIONAL MODELS OF VOLTAGE-GATED POTASSIUM CHANNELS SO BIOPHYSICAL JOURNAL LA English DT Article; Proceedings Paper CT CONF ON BIOPHYSICS AND RECOMBINANT DNA : PROBLEMS, STRATEGIES, AND NEW QUESTIONS CY JAN 19-22, 1992 CL AIRLIE, VA SP NIH, NATL SCI FDN, USN, OFF NAVAL RES ID SODIUM-CHANNEL; PROTEINS; INACTIVATION; DROSOPHILA; ENERGIES; RESIDUES AB Recent mutagenesis experiments have confirmed our hypothesis that a segment between S5 and S6 forms the ion selective portion of voltage-gated ion channels. Based on these and other new data, we have revised previous models of the general folding pattern of voltage-gated channel proteins and have developed atomic scale models of the entire transmembrane region of the Shaker A K+ channel. In these models, the ion selective region is a beta-barrel that spans the outer half of the membrane. The inner half of the pore is larger, The voltage-dependent conformational changes of activation gating are modeled to occur by the "helical screw" mechanism, in which the four S4 segments move along and rotate about their axes. These changes are followed by a voltage-independent conformational change, in which the segments linking S4 to S5 move from blocking the intracellular entrance of the pore to forming part of the lining of the large inner portion of the pore. The NH2-terminal of the protein was modeled as an alpha-helix that plugs the intracellular half of the pore to inactivate the channel. C1 NCI,MATH BIOL LAB,BETHESDA,MD 20892. NR 40 TC 228 Z9 229 U1 1 U2 4 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD APR PY 1992 VL 62 IS 1 BP 238 EP 250 DI 10.1016/S0006-3495(92)81809-X PG 13 WC Biophysics SC Biophysics GA HT995 UT WOS:A1992HT99500052 PM 1600096 ER PT J AU PARSEGIAN, VA AF PARSEGIAN, VA TI BIOPHYSICAL DISCUSSIONS - BIOPHYSICS AND RECOMBINANT-DNA PROBLEMS, STRATEGIES, AND NEW QUESTIONS - EDITORS FOREWORD SO BIOPHYSICAL JOURNAL LA English DT Editorial Material C1 NIH,DCRT,PHYS SCI LAB,BETHESDA,MD 20892. RP PARSEGIAN, VA (reprint author), NIDDK,BIOCHEM & METAB LAB,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD APR PY 1992 VL 62 IS 1 BP U1 EP U1 PG 1 WC Biophysics SC Biophysics GA HT995 UT WOS:A1992HT99500001 ER PT J AU KREITMAN, RJ SIEGALL, CB FITZGERALD, DJP EPSTEIN, J BARLOGIE, B PASTAN, I AF KREITMAN, RJ SIEGALL, CB FITZGERALD, DJP EPSTEIN, J BARLOGIE, B PASTAN, I TI INTERLEUKIN-6 FUSED TO A MUTANT FORM OF PSEUDOMONAS EXOTOXIN KILLS MALIGNANT-CELLS FROM PATIENTS WITH MULTIPLE-MYELOMA SO BLOOD LA English DT Article ID MONOCLONAL-ANTIBODY; ESCHERICHIA-COLI; TUMOR-CELLS; PROTEIN; TOXIN; AERUGINOSA; GENERATION; RESISTANT; TOXICITY; IL6-PE40 C1 NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,9000 ROCKVILLE PIKE,BETHESDA,MD 20892. UNIV ARKANSAS MED SCI HOSP,DIV HEMATOL ONCOL,LITTLE ROCK,AR 72205. FU NCI NIH HHS [CA37161, CA28771] NR 19 TC 43 Z9 44 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 APR 1 PY 1992 VL 79 IS 7 BP 1775 EP 1780 PG 6 WC Hematology SC Hematology GA HL673 UT WOS:A1992HL67300020 PM 1558971 ER PT J AU WEISS, LM JAFFE, ES LIU, XF CHEN, YY SHIBATA, D MEDEIROS, LJ AF WEISS, LM JAFFE, ES LIU, XF CHEN, YY SHIBATA, D MEDEIROS, LJ TI DETECTION AND LOCALIZATION OF EPSTEIN-BARR VIRAL GENOMES IN ANGIOIMMUNOBLASTIC LYMPHADENOPATHY AND ANGIOIMMUNOBLASTIC LYMPHADENOPATHY-LIKE LYMPHOMA SO BLOOD LA English DT Article ID ANGIO-IMMUNOBLASTIC LYMPHADENOPATHY; NON-HODGKINS LYMPHOMA; MALIGNANT-LYMPHOMA; VIRUS-DNA; EVOLUTION; DIAGNOSIS; DISEASE; DYSPROTEINEMIA; LYMPHOCYTES; FEATURES C1 NCI,DEPT PATHOL,BETHESDA,MD 20892. UNIV SO CALIF,DEPT PATHOL,LOS ANGELES,CA 90089. RP WEISS, LM (reprint author), CITY HOPE NATL MED CTR,DIV PATHOL,1500 E DUARTE RD,DUARTE,CA 91010, USA. FU NCI NIH HHS [CA 50341, CA 50850] NR 33 TC 231 Z9 238 U1 0 U2 3 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 APR 1 PY 1992 VL 79 IS 7 BP 1789 EP 1795 PG 7 WC Hematology SC Hematology GA HL673 UT WOS:A1992HL67300022 PM 1373088 ER PT J AU COBBS, CS MALECH, HL LETO, TL FREEMAN, SM BLAESE, RM GALLIN, JI LOMAX, KJ AF COBBS, CS MALECH, HL LETO, TL FREEMAN, SM BLAESE, RM GALLIN, JI LOMAX, KJ TI RETROVIRAL EXPRESSION OF RECOMBINANT P47(PHOX) PROTEIN BY EPSTEIN-BARR VIRUS-TRANSFORMED LYMPHOCYTES-B FROM A PATIENT WITH AUTOSOMAL CHRONIC GRANULOMATOUS-DISEASE SO BLOOD LA English DT Article ID 2 CYTOSOLIC COMPONENTS; RESPIRATORY BURST; CELL-LINES; OXIDASE; GENE; ACTIVATION; GENERATION; INDUCTION; VECTORS; UPDATE C1 NIAID,HOST DEF LAB,BETHESDA,MD 20892. NCI,METAB BRANCH,BETHESDA,MD 20892. NR 25 TC 23 Z9 23 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD APR 1 PY 1992 VL 79 IS 7 BP 1829 EP 1835 PG 7 WC Hematology SC Hematology GA HL673 UT WOS:A1992HL67300028 PM 1313715 ER PT J AU DU, DL VOLPE, DA GRIESHABER, CK MURPHY, MJ AF DU, DL VOLPE, DA GRIESHABER, CK MURPHY, MJ TI INVITRO TOXICITY OF 3'-AZIDO-3'-DEOXYTHYMIDINE, CARBOVIR AND 2',3'-DIDEHYDRO-2',3'-DIDEOXYTHYMIDINE TO HUMAN AND MURINE HEMATOPOIETIC PROGENITOR CELLS SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; AIDS-RELATED COMPLEX; REVERSE-TRANSCRIPTASE; CELLULAR PHARMACOLOGY; CONDITIONED MEDIUM; COLONY FORMATION; ZIDOVUDINE AZT; MARROW-CELLS; CFU-E; AZIDOTHYMIDINE AB The myelotoxicities of three antiretroviral agents, 3'-azido-3'-deoxythymidine (AZT), carbovir (CBV) and 2',3'-didehydro-2',3'-dideoxythymidine (d4T), were evaluated in vitro with normal human and murine haematopoietic progenitor cells. These studies demonstrated that continuous AZT exposure was more inhibitory to human and murine colony formation than 1 h exposure, with murine and human progenitors similarly inhibited by continuous AZT exposure. These in vitro results on AZT's myelotoxicity correlate with both human and murine in vivo studies. CBV was only moderately toxic to human and murine cells following either 1 h or continuous exposure, with human and murine progenitors similarly suppressed by continuous CBV exposure. 1 h d4T exposure was less toxic to both human and murine marrow cells than continuous exposure and both species were equivalently inhibited when continuously exposed to d4T. In general, CBV was the least toxic agent to human and murine haematopoietic cells and AZT the most toxic. The study establishes CBV and d4T as less myelotoxic agents to human and murine haematopoietic progenitor cells in vitro than AZT which therefore could be considered as alternatives to AZT for the treatment of HIV infection. C1 HIPPLE CANC RES CTR,4100 S KETTERING BLVD,DAYTON,OH 45439. NCI,BETHESDA,MD 20892. FU NCI NIH HHS [N44-CM-77831] NR 39 TC 25 Z9 25 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD APR PY 1992 VL 80 IS 4 BP 437 EP 445 DI 10.1111/j.1365-2141.1992.tb04555.x PG 9 WC Hematology SC Hematology GA HM876 UT WOS:A1992HM87600004 PM 1316140 ER PT J AU HIBBS, ED ZAHN, TP HAMBURGER, SD KRUESI, MMPJ RAPOPORT, JL AF HIBBS, ED ZAHN, TP HAMBURGER, SD KRUESI, MMPJ RAPOPORT, JL TI PARENTAL EXPRESSED EMOTION AND PSYCHOPHYSIOLOGICAL REACTIVITY IN DISTURBED AND NORMAL-CHILDREN SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; SCHIZOPHRENIC-PATIENTS; DISRUPTIVE BEHAVIOR; FAMILY; ADOLESCENTS; RELATIVES; INTERVIEW; AGREEMENT; RELAPSE AB Increased spontaneous fluctuations in skin conductance (SC) in adult schizophrenics have been associated with high expressed emotion (EE) in their relatives. This is the first study in children where parental EE, parental psychopathology, and autonomic activity, indexed by SC levels and reactivity, have been assessed. The subjects were children and adolescents with disruptive behaviour disorders (DBD, n = 35), a psychiatric contrast group with obsessive-compulsive disorders (OCD, n = 42) and normal controls (NC, n = 45). Children living in homes with two high-EE parents had higher SC activity during rest period and slower adaptation to relaxation. Fathers' EE and maternal psychiatric diagnosis were related to higher SC activity, especially for the OCD group. C1 NIMH,DIRP,PSYCHOL & PSYCHOPATHOL LAB,BETHESDA,MD 20892. RP HIBBS, ED (reprint author), NIMH,CHILD PSYCHIAT BRANCH,DIRP,BLDG 10,ROOM 6N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 35 TC 18 Z9 18 U1 0 U2 1 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON, ENGLAND SW1X 8PG SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD APR PY 1992 VL 160 BP 504 EP 510 DI 10.1192/bjp.160.4.504 PG 7 WC Psychiatry SC Psychiatry GA HM347 UT WOS:A1992HM34700010 PM 1571750 ER PT J AU SAKAGUCHI, K COSTA, T SAKAMOTO, H SHIMOHIGASHI, Y AF SAKAGUCHI, K COSTA, T SAKAMOTO, H SHIMOHIGASHI, Y TI RECEPTOR INTERACTIONS OF SYNTHETIC MORPHICEPTIN ANALOGS CONTAINING PHENYLALANINE HOMOLOGS IN POSITION-4 SO BULLETIN OF THE CHEMICAL SOCIETY OF JAPAN LA English DT Article ID DELTA-OPIATE RECEPTOR; MU; HYDROGENATION AB A series of phenylalanine homologs with elongated phenylalkyl side chains (R = -(CH2)n-C6H5, n = 1-4) have been incorporated into opioid peptide morphiceptin at position 4 in order to elucidate a role of the amino acid residue in the molecular mechanism of receptor activation. The receptor specificity and selectivity of peptides synthesized were examined in the radio-ligand receptor binding assays using tritiated DAGO- and DADLE-enkephalins. [Phe4]Morphiceptin was most potent for the mu-receptors and showed the most pronounced mu/delta-receptor selectivity with a specific ratio of 410. Its mu-affinity was about three times stronger than morphiceptin. All analogs showed very similar CD spectra, suggesting that these peptides have a similar backbone conformation. The results strongly suggest that, besides the backbone conformation, the side-chain aromatic rings at positions 1 (Tyr), 3 (Phe), and 4 (Phe) array in a specific stereoorientation and this array is important to activate mu-receptors. Analogs with longer phenylalkyl side chains appeared not to retain such an arrangement due to the steric hindrance caused by the presence of more than two methylene groups. C1 KYUSHU UNIV, FAC SCI, DEPT CHEM, BIOCHEM LAB, FUKUOKA 812, JAPAN. NICHHD, BETHESDA, MD 20892 USA. RI Sakamoto, Hiroshi/A-3181-2011; OI costa, tommaso/0000-0002-8729-3357 NR 9 TC 2 Z9 2 U1 1 U2 2 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 APR PY 1992 VL 65 IS 4 BP 1052 EP 1056 DI 10.1246/bcsj.65.1052 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA HR906 UT WOS:A1992HR90600020 ER PT J AU SHERRY, RM PASS, HI ROSENBERG, SA YANG, JC AF SHERRY, RM PASS, HI ROSENBERG, SA YANG, JC TI SURGICAL RESECTION OF METASTATIC RENAL-CELL CARCINOMA AND MELANOMA AFTER RESPONSE TO INTERLEUKIN-2-BASED IMMUNOTHERAPY SO CANCER LA English DT Article ID HIGH-DOSE INTERLEUKIN-2; ACTIVATED KILLER CELLS; RECOMBINANT INTERLEUKIN-2; ADVANCED CANCER; LUNG; MANAGEMENT; SURGERY; EXPERIENCE; DIAGNOSIS; EXCISION AB Thirty-one patients with disseminated melanoma or renal cell cancer (RCC) who had a limited relapse or persistent disease after a partial or complete response to interleukin-2 (IL-2)-based immunotherapy underwent resection of progressing tumors or residual sites of disease. There were no surgery-related deaths. The median time to disease progression after resection for patients with RCC (n = 16) and melanoma (n = 15) was 11 and 5 months, respectively. All patients with melanoma had tumor progression within 10 months of surgery. Seven of 16 patients with RCC were free of tumor progression 4 to 44 months after surgery. Three of 12 patients with RCC rendered disease-free by surgery remain disease-free after 2 years. These data suggest that surgical resection is a reasonable option in selected patients who have a relapse after responding to IL-2-based immunotherapy. Although this retrospective study could not determine the relative survival benefits of surgery and immunotherapy, it showed that resection of metastatic disease after a response to immunotherapy can result in significant disease-free survival in patients with RCC but not melanoma. RP SHERRY, RM (reprint author), NCI,SURG BRANCH,BLDG 10,ROOM 2B42,BETHESDA,MD 20892, USA. NR 24 TC 39 Z9 39 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 APR 1 PY 1992 VL 69 IS 7 BP 1850 EP 1855 DI 10.1002/1097-0142(19920401)69:7<1850::AID-CNCR2820690729>3.0.CO;2-I PG 6 WC Oncology SC Oncology GA HK770 UT WOS:A1992HK77000028 PM 1551067 ER PT J AU KESSLER, LG AF KESSLER, LG TI THE RELATIONSHIP BETWEEN AGE AND INCIDENCE OF BREAST-CANCER - POPULATION AND SCREENING-PROGRAM DATA SO CANCER LA English DT Article; Proceedings Paper CT WORKSHOP ON GUIDELINES AND SCREENING FOR BREAST CANCER CY OCT 11-13, 1991 CL PASADENA, CA SP AMER CANC SOC ID RISING INCIDENCE; MAMMOGRAPHY; MORTALITY; TRENDS; WOMEN; STAGE; RISK AB Despite extensive study of breast cancer incidence, including specific studies of the relationship between age and breast cancer incidence, the picture remains confusing. This article examines not only the relationship between age and breast cancer, but also trends over time related to this relationship to discern the underlying true age-incidence pattern. The age-incidence curve changes around the menopausal period, most likely due to hormonal changes 10 to 15 years earlier, flattens out in the 40 to 50 year old age range, and then increases as age increases. Recent data showing decreased risk of breast cancer incidence at older ages, e.g., older than 75 years of age, relative to younger ages, are likely an artifact of recent increases in breast cancer screening in the United States. This picture is consistent with increases in screening and with notions of lead time created by increased screening. The increase in screening that has changed the age-incidence relationship may eventually deliver benefits to United States women in terms of mortality deficits, but this is not guaranteed unless screening becomes routine practice and high-quality therapeutic intervention and follow-up occurs as well. C1 NCI,APPL RES BRANCH,BETHESDA,MD 20892. NR 33 TC 30 Z9 30 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD APR 1 PY 1992 VL 69 IS 7 SU S BP 1896 EP 1903 DI 10.1002/1097-0142(19920401)69:7+<1896::AID-CNCR2820691704>3.0.CO;2-1 PG 8 WC Oncology SC Oncology GA HL795 UT WOS:A1992HL79500003 PM 1544088 ER PT J AU MUSHLIN, AI FINTOR, L AF MUSHLIN, AI FINTOR, L TI IS SCREENING FOR BREAST-CANCER COST-EFFECTIVE SO CANCER LA English DT Article; Proceedings Paper CT WORKSHOP ON GUIDELINES AND SCREENING FOR BREAST CANCER CY OCT 11-13, 1991 CL PASADENA, CA SP AMER CANC SOC AB As the toll taken by breast cancer continues unabated, screening programs are widely perceived to play a critical role to improve diagnosis and successful treatment. Breast cancer screening programs are increasingly promoted to women; however, the economic implications of mass screening is a subject of much health policy debate. Cost-effectiveness analysis is an economic methodology widely used to inform such decisions, yet there is a dearth of information available on the economic consequences of mass breast cancer screening. The authors evaluated nine breast cancer screening cost-effectiveness studies that are based on computer simulations, observational trial data, or a combination of both. The results of these studies, conducted in the United States and other countries, indicate that the cost-effectiveness of screening for breast cancer generally compares favorably with other expenditures in the health-care field, although screening younger women does not appear to be as favorable. However, there is considerable variability in the methodology used and a need for more comprehensive research in this area. C1 UNIV ROCHESTER,SCH MED,DEPT COMMUNITY & PREVENT MED,ROCHESTER,NY 14627. UNIV ROCHESTER,SCH MED,DEPT MED,ROCHESTER,NY 14627. NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892. NR 12 TC 65 Z9 67 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD APR 1 PY 1992 VL 69 IS 7 SU S BP 1957 EP 1962 DI 10.1002/1097-0142(19920401)69:7+<1957::AID-CNCR2820691716>3.0.CO;2-T PG 6 WC Oncology SC Oncology GA HL795 UT WOS:A1992HL79500015 PM 1544100 ER PT J AU BROWN, ML AF BROWN, ML TI SENSITIVITY ANALYSIS IN THE COST-EFFECTIVENESS OF BREAST-CANCER SCREENING SO CANCER LA English DT Article; Proceedings Paper CT WORKSHOP ON GUIDELINES AND SCREENING FOR BREAST CANCER CY OCT 11-13, 1991 CL PASADENA, CA SP AMER CANC SOC ID MAMMOGRAPHY RP BROWN, ML (reprint author), NCI,DIV CANC PREVENT & CONTROL,APPL RES BRANCH,SURVEILLANCE PROGRAM,BETHESDA,MD 20892, USA. NR 12 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 0008-543X J9 CANCER JI Cancer PD APR 1 PY 1992 VL 69 IS 7 SU S BP 1963 EP 1967 DI 10.1002/1097-0142(19920401)69:7+<1963::AID-CNCR2820691717>3.0.CO;2-0 PG 5 WC Oncology SC Oncology GA HL795 UT WOS:A1992HL79500016 PM 1544101 ER PT J AU SMITH, RA HAYNES, S AF SMITH, RA HAYNES, S TI BARRIERS TO SCREENING FOR BREAST-CANCER SO CANCER LA English DT Article; Proceedings Paper CT WORKSHOP ON GUIDELINES AND SCREENING FOR BREAST CANCER CY OCT 11-13, 1991 CL PASADENA, CA SP AMER CANC SOC ID MAMMOGRAPHY; PHYSICIANS; REMINDERS; WOMEN; GUIDELINES; PROJECT; TRIAL; CARE AB Despite strong epidemiologic evidence that screening for breast cancer with mammography and clinical breast examination results in mortality reductions, and the considerable effort to communicate this message to women and health-care providers, most US women are not screened according to recommended guidelines, Recent investigations have focused on trends in use, and factors associated with physicians' and women's knowledge, attitudes, and practices associated with mammography. Even as use of mammography has increased, the literature suggests that a number of significant impediments to participation in routine screening will need to be addressed to achieve high rates of screening among US women according to recommended guidelines. C1 NCI,BETHESDA,MD 20892. RP SMITH, RA (reprint author), CTR DIS CONTROL,CANC BRANCH MS-K52,1600 CLIFTON RD,ATLANTA,GA 30333, USA. NR 64 TC 80 Z9 80 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD APR 1 PY 1992 VL 69 IS 7 SU S BP 1968 EP 1978 DI 10.1002/1097-0142(19920401)69:7+<1968::AID-CNCR2820691718>3.0.CO;2-J PG 11 WC Oncology SC Oncology GA HL795 UT WOS:A1992HL79500017 PM 1544102 ER PT J AU BOONE, CW KELLOFF, GJ STEELE, VE AF BOONE, CW KELLOFF, GJ STEELE, VE TI NATURAL-HISTORY OF INTRAEPITHELIAL NEOPLASIA IN HUMANS WITH IMPLICATIONS FOR CANCER CHEMOPREVENTION STRATEGY SO CANCER RESEARCH LA English DT Article ID INTERMEDIATE END-POINTS; COLORECTAL ADENOMAS; ANALOGS RETINOIDS; TUMOR-DEVELOPMENT; FLOW-CYTOMETRY; DNA-ANALYSIS; VITAMIN-A; ANEUPLOIDY; PREVENTION; DYSPLASIA AB Intraepithelial neoplasia is of critical importance to the cancer chemoprevention field because it is a target condition for which drugs must be sought that will prevent its development or stop its progression. The term "dysplasia" refers to the morphological alterations that characterize intraepithelial neoplasia and according to many authors consists of seven basic morphological changes that occur in the majority of human epithelia, as well as in the epithelium of mouse skin papillomas induced by 7,12-dimethylbenz(a)anthracene and 12-O-tetradecanoylphorbol-13-acetate: increased nuclear size; altered nuclear shape; increased nuclear stain uptake; nuclear pleomorphism (increased variation in nuclear size, shape, and stain uptake); increased mitoses; abnormal mitoses; and disordered or absent maturation. Clonal evolution appears to begin early in the neoplastic process during intraepithelial neoplasia. Aneuploidy has been found during intraepithelial neoplasia in many human epithelia, and, in association with other forms of genetic instability, may provide the increase in genetically variant cells required for clonal evolution to occur. It is postulated that two major factors affecting the rate of progression of intraepithelial neoplasia are the cellular mutation rate, which is enhanced by environmental carcinogens, and the cellular proliferation rate, which is enhanced by agents that include sex hormones, inducers of chronic inflammation, and irritant chemicals which stimulate reactive hyperproliferation. A preferred chemoprevention strategy should consist of the development of drugs and drug combinations which will block mutagenic carcinogens or prevent epithelial hyperproliferation or its causes. Two examples of the induction of regression of intraepithelial neoplasia by chemopreventive drugs are the regression of oral leukoplakia produced by beta-carotene and the regression of colorectal polyps in patients with familial polyposis produced by sulindac. It is evident that there is a strong need for more research on the induction of regression of intraepithelial neoplasia with chemopreventive agents. There is also a critical need to identify and develop biomarkers that correlate with the appearance and regression of intraepithelial neoplasia. RP BOONE, CW (reprint author), NCI,DIV CANC PREVENT & CONTROL,CANC PREVENT RES PROGRAM,BETHESDA,MD 20892, USA. NR 86 TC 150 Z9 150 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 APR 1 PY 1992 VL 52 IS 7 BP 1651 EP 1659 PG 9 WC Oncology SC Oncology GA HL505 UT WOS:A1992HL50500001 PM 1551096 ER PT J AU GIACCONE, G GAZDAR, AF BECK, H ZUNINO, F CAPRANICO, G AF GIACCONE, G GAZDAR, AF BECK, H ZUNINO, F CAPRANICO, G TI MULTIDRUG SENSITIVITY PHENOTYPE OF HUMAN LUNG-CANCER CELLS ASSOCIATED WITH TOPOISOMERASE-II EXPRESSION SO CANCER RESEARCH LA English DT Article ID DNA CLEAVAGE ACTIVITY; RESISTANT HUMAN-CELLS; LEUKEMIA-CELLS; ANTITUMOR DRUGS; LINES; INHIBITORS; ETOPOSIDE; GENE; CARCINOMA; CHEMOTHERAPY AB Patterns of drug sensitivities in relation to topoisomerase II gene expression and activity were studied in eight human lung cancer cell lines not selected in vitro for drug resistance. The cytotoxicities of doxorubicin, etoposide, teniposide, cisplatin, camptothecin, and 5-fluorouracil were measured and, remarkably, these unselected cell lines were shown to have a common pattern of multidrug sensitivity, ie., a multidrug sensitivity phenotype. In fact, drug sensitivities were significantly correlated with each other in the studied cell lines, the correlation being best for the topoisomerase II-targeted agents and cisplatin, less strong with camptothecin, and weak with 5-fluorouracil. Almost 1-log range difference of topoisomerase II gene expression was found in these cell lines, and this was not explained by the cell-doubling time or cell cycle distribution. The level of topoisomerase II gene expression was positively and highly correlated with the cell sensitivity to epipodophyllotoxins, doxorubicin, and cisplatin in seven cell lines. Although weaker, an association was also observed between topoisomerase II gene expression and camptothecin cytotoxicity, while no association was observed with 5-fluorouracil. However, a non-small cell lung cancer cell line with neuroendocrine properties had very low levels of expression of the topoisomerase II gene, despite being highly sensitive to all drugs tested. The levels of topoisomerase I gene expression were not found to be correlated with the cytotoxicity of any drug tested. A specific enzymatic activity assay and a teniposide-stimulated DNA cleavage assay showed that the extent of active topoisomerase II present in nuclear extracts paralleled the level of topoisomerase II gene expression. Furthermore, in addition to the normal transcript, an abnormally sized topoisomerase II message and a rearrangement of the topoisomerase II gene were detected in a poorly sensitive small cell lung cancer cell line. Therefore, low levels of topoisomerase II gene expression, and possibly mutations, may predict a reduced sensitivity of unselected human lung cancer cell lines to several drugs, including agents with a cellular target other than topoisomerase II. It is hypothesized that topoisomerase II might be involved in a common pathway of cell death induced by drugs in tumor cell lines which present a multidrug sensitivity phenotype. C1 NCI,USN,MED ONCOL BRANCH,BETHESDA,MD 20892. IST NAZL STUDIO & CURA TUMORI,DIV EXPTL ONCOL B,I-20133 MILAN,ITALY. RI Capranico, Giovanni/K-1678-2014; Giaccone, Giuseppe/E-8297-2017 OI Capranico, Giovanni/0000-0002-8708-6454; Giaccone, Giuseppe/0000-0002-5023-7562 NR 43 TC 146 Z9 146 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 APR 1 PY 1992 VL 52 IS 7 BP 1666 EP 1674 PG 9 WC Oncology SC Oncology GA HL505 UT WOS:A1992HL50500003 PM 1312895 ER PT J AU WHITESELL, L SHIFRIN, SD SCHWAB, G NECKERS, LM AF WHITESELL, L SHIFRIN, SD SCHWAB, G NECKERS, LM TI BENZOQUINONOID ANSAMYCINS POSSESS SELECTIVE TUMORICIDAL ACTIVITY UNRELATED TO SRC KINASE INHIBITION SO CANCER RESEARCH LA English DT Article ID ROUS-SARCOMA VIRUS; TUMOR CELL-LINES; HERBIMYCIN-A; DIFFERENTIATION; APOPTOSIS; PROTEIN; PHOSPHORYLATION; INDUCTION; REDUCTION AB The benzoquinonoid ansamycin antibiotics herbimycin A and geldanamycin have been shown to reverse the oncogenic phenotype of pp60v-src transformed cells as well as induce differentiation in a number of in vitro model systems, reportedly due to their inhibition of src family protein tyrosine kinases. We now report that these agents are potent cytotoxins in vitro against a panel of highly malignant human tumor cell lines possessing primitive neural features. Proliferation and/or survival of fibroblasts, primary neuronal cultures, and several leukemia cell lines are unaffected at concentrations resulting in > 99% cell loss in sensitive lines. The tumorigenicity in nude mice of sensitive cell lines can also be markedly reduced by either systemic or topical administration of these agents without apparent toxicity to the whole animal. The cytocidal action of these ansamycins is initiated very rapidly, is irreversible, and is clearly distinct from the delayed inhibition of src family kinases that has been reported previously. Due to their potency, relative selectivity, and novel mechanism(s) of action, these drugs could prove clinically useful in the therapy of a number of human cancers of neural derivation. C1 NCI,CLIN PHARMACOL BRANCH,TUMOR CELL BIOL SECT,BETHESDA,MD 20892. NR 30 TC 157 Z9 162 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 1 PY 1992 VL 52 IS 7 BP 1721 EP 1728 PG 8 WC Oncology SC Oncology GA HL505 UT WOS:A1992HL50500012 PM 1551101 ER PT J AU HAHN, SM TOCHNER, Z KRISHNA, CM GLASS, J WILSON, L SAMUNI, A SPRAGUE, M VENZON, D GLATSTEIN, E MITCHELL, JB RUSSO, A AF HAHN, SM TOCHNER, Z KRISHNA, CM GLASS, J WILSON, L SAMUNI, A SPRAGUE, M VENZON, D GLATSTEIN, E MITCHELL, JB RUSSO, A TI TEMPOL, A STABLE FREE-RADICAL, IS A NOVEL MURINE RADIATION PROTECTOR SO CANCER RESEARCH LA English DT Article ID POLYFUNCTIONAL RADIOSENSITIZERS; SUPEROXIDE; RADIOPROTECTION; NITROXIDES; CELLS; MICE AB Nitroxide compounds are stable free radicals which were previously investigated as hypoxic cell radiosensitizers. The stable nitroxide 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (Tempol) has recently been shown to protect aerated cells in culture against superoxide generated from hypoxanthine/xanthine oxidase, hydrogen peroxide, and radiation-induced cytotoxicity and to modestly sensitize hypoxic cultured cells. To extend these observations from the cellular level to the whole animal, the toxicity, pharmacology, and in vivo radioprotective effects of Tempol were studied in C3H mice. The maximum tolerated dose of Tempol administered i.p. was found to be 275 mg/kg, which resulted in maximal Tempol levels in whole blood 5-10 min after injection. Mice were exposed to whole-body radiation in the absence or presence of injected Tempol (275 mg/kg) 5-10 min after administration. Tempol treatment provided significant radioprotection (P < 0.0001); the dose of radiation at which 50% of Tempol-treated mice die at 30 days was 9.97 Gy, versus 7.84 Gy for control mice. Tempol represents a new class of in vivo, non-sulfur-containing radiation protectors. Given the potential for hypoxic radiosensitization and aerobic cell radioprotection, Tempol or other analogues may have potential therapeutic application. C1 NCI,RADIAT ONCOL BRANCH,BLDG 10,ROOM B3-B69,BETHESDA,MD 20892. NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. HEBREW UNIV JERUSALEM,SCH MED,IL-91010 JERUSALEM,ISRAEL. RI Venzon, David/B-3078-2008 NR 27 TC 175 Z9 179 U1 2 U2 9 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 APR 1 PY 1992 VL 52 IS 7 BP 1750 EP 1753 PG 4 WC Oncology SC Oncology GA HL505 UT WOS:A1992HL50500016 PM 1551104 ER PT J AU SMITH, TJ GUO, Z GONZALEZ, FJ GUENGERICH, FP STONER, GD YANG, CS AF SMITH, TJ GUO, Z GONZALEZ, FJ GUENGERICH, FP STONER, GD YANG, CS TI METABOLISM OF 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE IN HUMAN LUNG AND LIVER-MICROSOMES AND CYTOCHROMES-P-450 EXPRESSED IN HEPATOMA-CELLS SO CANCER RESEARCH LA English DT Article ID TOBACCO-SPECIFIC NITROSAMINES; OXIDATIVE DRUG-METABOLISM; CULTURED HUMAN-TISSUES; CHEMICAL CARCINOGENESIS; A/J MICE; CYTOCHROME-P-450 ENZYMES; DEUTERIUM SUBSTITUTION; GENETIC-POLYMORPHISM; N-NITROSAMINES; RAT LUNG AB 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a potent tobacco-specific carcinogen in animals, has been linked to tobacco-related cancers in humans. The cytochrome(s) P450 (P-450) responsible for the metabolic activation of NNK in humans has not been identified. The present work investigated the ability of human lung and liver microsomes and 12 forms of human P-450, expressed in Hep G2 (hepatoma) cells, to metabolize NNK. Of the 12 P450 forms, P450 1A2 had the highest activity in catalyzing the conversion of NNK to the keto alcohol, 4-hydroxy-1-(3-pyridyl)-1-butanone. P-450s 2A6, 2B7, 2E1, 2F1, and 3A5 also had measurable activities in the formation of keto alcohol. The apparent K(m) and V(max) for the formation of keto alcohol in the P-450 1A2-expressed Hep G2 cell lysate were 309-mu-M and 55 pmol/min/mg protein, respectively. 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol, a reductive product, was the major metabolite formed, whereas the formation of keto alcohol and its aldehyde and acid derivatives (all alpha-hydroxylation products) constituted approximately 1% of the initial amount of NNK in P450-expressed Hep G2 cell lysate. A similar metabolite pattern was observed with human lung or liver microsomes. In human lung microsomes, the apparent K(m)s for the formation of 4-hydroxy-4-(3-pyridyl)butyric acid, 4-oxo-1-(3-pyridyl)-1-butanone, NNK-N-oxide, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol were 526, 653, 531, and 573-mu-M, respectively; the formation of keto alcohol was not observed. For human lung microsomes, there was no sex-related difference in NNK metabolism. Carbon monoxide (90% atmosphere) significantly inhibited the metabolism of NNK in human lung and liver microsomes. 7,8-Benzoflavone, an inhibitor of P-450s 1A1 and 1A2, had no effect on NNK metabolism in human lung microsomes but decreased the formation of keto alcohol by 47% in human liver microsomes. Similarly, antibodies against human P-450s 1A2 and 2E1 decreased keto alcohol formation by 42% and 53%, respectively, in human liver microsomes but did not affect NNK metabolism in lung microsomes. Inhibitory antibodies against P-450s 2A1, 2C8, 2D1, or 3A4 had little or no effect on the metabolism of NNK in human liver or lung microsomes. These results demonstrate that human liver and lung microsomes have the capacity to metabolize NNK and that different P-450 forms are responsible for the formation of different metabolites and suggest that other enzymes may be important in the activation of this carcinogen in the human lung. C1 RUTGERS STATE UNIV,COLL PHARM,CANC RES LAB,PISCATAWAY,NJ 08855. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. VANDERBILT UNIV,MED CTR,SCH MED,DEPT BIOCHEM,NASHVILLE,TN 37232. VANDERBILT UNIV,MED CTR,SCH MED,CTR MOLEC TOXICOL,NASHVILLE,TN 37232. MED COLL OHIO,DEPT PATHOL,TOLEDO,OH 43699. FU NCI NIH HHS [CA37037, CA44353, CA46535] NR 38 TC 125 Z9 126 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 1 PY 1992 VL 52 IS 7 BP 1757 EP 1763 PG 7 WC Oncology SC Oncology GA HL505 UT WOS:A1992HL50500018 PM 1312898 ER PT J AU NALDONI, C COSTANTINI, M DOGLIOTTI, L BRUZZI, P BUCCHI, L BUZZI, G TORTA, M ANGELI, A AF NALDONI, C COSTANTINI, M DOGLIOTTI, L BRUZZI, P BUCCHI, L BUZZI, G TORTA, M ANGELI, A TI ASSOCIATION OF CYST TYPE WITH RISK-FACTORS FOR BREAST-CANCER AND RELAPSE RATE IN WOMEN WITH GROSS CYSTIC-DISEASE OF THE BREAST SO CANCER RESEARCH LA English DT Article ID EPIDERMAL GROWTH-FACTOR; NATURAL-HISTORY; FLUID; SUBSEQUENT; SUBPOPULATIONS; EPIDEMIOLOGY AB The concentration of potassium (K+) and sodium (Na+) was measured in breast cyst fluid (BCF) from 611 cysts > 3 ml aspirated in 520 women with gross cystic disease of the breast. These women were enrolled, from 1983 on, in a cohort study aimed at assessing the relationship between cyst type, as defined by the K+/Na+ ratio in BCF, and the risk of breast cancer. The inverse relationship between K+ and Na+ and the bimodal distribution of the K+/Na+ ratio in BCF were confirmed. Type I cysts were defined as cysts with a K+/Na+ > 1.5 in BCF. Among women with type I cysts, a higher proportion of women with one or no births, of women with a history of apocrine cysts, of current smokers, and of women who do not drink coffee was found, as compared to women with other types of cysts. The risk of cyst relapse was significantly higher among women with type I cysts than among women with other types of cysts and among women with multiple cysts at presentation. These findings indicate that type I BCF is a marker of "active" gross cystic disease of the breast and suggest that it may be associated with increased breast cancer risk. C1 NATL CANC INST,CLIN EPIDEMIOL & TRIALS UNIT,VIALE BENEDETTO XV 10,I-16132 GENOA,ITALY. ST MARIA DELLE CROCI HOSP,CTR CANC PREVENT,I-48100 RAVENNA,ITALY. UNIV TURIN,ST LUIGI HOSP,DEPT CLIN & BIOL SCI,I-10043 ORBASSANO,ITALY. RI costantini, massimo/G-1443-2012 NR 42 TC 38 Z9 38 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 1 PY 1992 VL 52 IS 7 BP 1791 EP 1795 PG 5 WC Oncology SC Oncology GA HL505 UT WOS:A1992HL50500024 PM 1551110 ER PT J AU NOUSO, K THORGEIRSSON, SS BATTULA, N AF NOUSO, K THORGEIRSSON, SS BATTULA, N TI STABLE EXPRESSION OF HUMAN CYTOCHROME-P450IIE1 IN MAMMALIAN-CELLS - METABOLIC-ACTIVATION OF NITROSODIMETHYLAMINE AND FORMATION OF ADDUCTS WITH CELLULAR DNA SO CANCER RESEARCH LA English DT Article ID HEPATIC-MICROSOMAL CYTOCHROME-P-450; N-NITROSO COMPOUNDS; RAT-LIVER; ETHANOL; INDUCTION; ENZYME; CARCINOGENESIS; CDNA; RETROVIRUSES; DEMETHYLASE AB To introduce cytochrome P450IIE1 DNA stably into the chromosomal DNA of mammalian cells, we constructed recombinant retroviruses containing the full-length complementary DNA for human cytochrome P450IIE1 and a selectable neo gene. Rat and mouse cells were infected with these viruses, and clones expressing the neo marker gene product were selected in G418-containing medium. Analysis of the DNA of the clones by Southern blotting showed that the viral DNA was integrated into the cellular DNA. Enzymatic analysis of the clones showed that the transduced DNA directed the expression of enzymatically active cytochrome P450IIE1. Treatment of the cells with the carcinogen [C-14]-nitrosodimethylamine and analysis of the cellular DNA by CsCl equilibrium density gradients showed incorporation of the label into DNA, indicating the formation of covalent adducts with the cell DNA. Construction of recombinant cell lines constitutively expressing cytochrome P450IIE1 provides a permanent source for this enzyme and can aid in the analysis of its catalytic properties, such as the metabolic activation of chemical mutagens/carcinogens, and the consequent cytotoxic and genotoxic effects of these compounds. RP NOUSO, K (reprint author), NCI,EXPTL CARCINOGENESIS LAB,BLDG 37,ROOM 3C28,BETHESDA,MD 20892, USA. NR 33 TC 38 Z9 40 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 1 PY 1992 VL 52 IS 7 BP 1796 EP 1800 PG 5 WC Oncology SC Oncology GA HL505 UT WOS:A1992HL50500025 PM 1551111 ER PT J AU MINNITI, CP MAGGI, M HELMAN, LJ AF MINNITI, CP MAGGI, M HELMAN, LJ TI SURAMIN INHIBITS THE GROWTH OF HUMAN RHABDOMYOSARCOMA BY INTERRUPTING THE INSULIN-LIKE GROWTH FACTOR-II AUTOCRINE GROWTH LOOP SO CANCER RESEARCH LA English DT Article ID FACTOR RECEPTOR; CELLS; TRANSFORMATION; PROLIFERATION; SOMATOMEDINS; FIBROBLASTS; MECHANISM; SEQUENCE; BINDING; TUMORS AB Suramin is a polysulfonated naphthylurea with antineoplastic activity that binds various peptide growth factors. Since we previously demonstrated that insulin-like growth factor II (IGF-II) is an autocrine growth factor in human rhabdomyosarcoma (RMS), we studied the effect of suramin on the growth of human RMS cells. Suramin caused a dose-dependent decrease of RMS cell number grown either in 10% fetal bovine serum or in serum-free medium (half-maximal effective dose in mitogenic assays, 1.6 x 10(-4) and 9 x 10(5) M, respectively). IGF-II and IGF-I added to RMS cells in the presence of suramin reversed the suramin-induced inhibition of cell growth. Since IGF-II exerts its mitogenic effects on RMS cells by binding to the type I receptor, we performed radioreceptor assays using I-125-IGF-I and found that suramin displaced I-125-IGF-I from the type I IGF receptor. There was an excellent correlation between the doses of suramin effective in inhibiting the growth of RMS cells and those that displaced the binding of IGF-I. Our data indicate that suramin exerts its effect on RMS cell growth by interfering with the binding of IGF-II to the type I IGF receptor, thereby interrupting the IGF-II autocrine growth in these cells. Disrupting autonomous growth of RMS may be a promising novel therapeutic approach. C1 NCI,PEDIAT BRANCH,MOLEC GENET SECT,BLDG 10,ROOM 13N240,BETHESDA,MD 20892. NR 32 TC 66 Z9 66 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 APR 1 PY 1992 VL 52 IS 7 BP 1830 EP 1835 PG 6 WC Oncology SC Oncology GA HL505 UT WOS:A1992HL50500031 PM 1312901 ER PT J AU TANIZAWA, A POMMIER, Y AF TANIZAWA, A POMMIER, Y TI TOPOISOMERASE-I ALTERATION IN A CAMPTOTHECIN-RESISTANT CELL-LINE DERIVED FROM CHINESE-HAMSTER DC3F CELLS IN CULTURE SO CANCER RESEARCH LA English DT Article ID DNA STRAND BREAKS; PROTEIN KINASE-C; PHOSPHORYLATION INVITRO; CYTO-TOXICITY; CALF THYMUS; REPLICATION; INHIBITORS; ACTIVATION; EXPRESSION; MECHANISM AB Camptothecin-resistant DC3F Chinese hamster lung fibroblast cell lines were obtained after mutagenic treatment with ethylmethanesulfonate and subsequent exposure to 1-mu-M camptothecin (CPT). The most resistant cell line, which was obtained after exposure to CPT for 10 days, was designated DC3F/C-10. Comparison of 50% inhibitory concentration values after 8-h CPT treatments showed that DC3F/C-10 cells were 134-fold resistant to CPT. Resistance was associated with marked reduction of CPT-induced DNA single-strand breaks and DNA-protein cross-links. This reduction was not due to reduced amounts of immunoreactive DNA topoisomerase I protein, although nuclear extracts from DC3F/C-10 cells had less enzyme catalytic activity than those from DC3F cells. Also, fast protein liquid chromatography-purified DNA topoisomerase I from DC3F/C-10 had lower specific catalytic activity than that from DC3F cells. DNA topoisomerase I from DC3F/C-10 was resistant to inhibition of catalytic activity and induction of DNA cleavage by CPT. These results suggest that CPT resistance in DC3F/C-10 cells is due to qualitative alteration of DNA topoisomerase I. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MOLEC PHARMACOL LAB,BLDG 37,ROOM 5C27,BETHESDA,MD 20892. NR 37 TC 85 Z9 85 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 APR 1 PY 1992 VL 52 IS 7 BP 1848 EP 1854 PG 7 WC Oncology SC Oncology GA HL505 UT WOS:A1992HL50500034 PM 1312902 ER PT J AU SUN, Y POMMIER, Y COLBURN, NH AF SUN, Y POMMIER, Y COLBURN, NH TI ACQUISITION OF A GROWTH-INHIBITORY RESPONSE TO PHORBOL ESTER INVOLVES DNA DAMAGE SO CANCER RESEARCH LA English DT Article ID PROTEIN-KINASE-C; MOUSE EPIDERMAL-CELLS; TUMOR NECROSIS FACTOR; TPA-INDUCED-DIFFERENTIATION; TERMINAL DIFFERENTIATION; SUPEROXIDE-DISMUTASE; PROMOTER 12-O-TETRADECANOYLPHORBOL-13-ACETATE; ENDONUCLEASE ACTIVATION; THYMOCYTE APOPTOSIS; HUMAN KERATINOCYTES AB TPA (12-O-tetradecanoylphorbol-13-acetate), a potent tumor promoter, has been shown to stimulate or inhibit cell growth depending on the cell type investigated. We recently found that RT101 cells, a transformed mouse JB6 epidermal cell line, acquired a greater growth inhibition response to TPA during conventional subcultivation. The growth of low-passage RT101 cells was slightly inhibited by TPA in monolayer culture but stimulated in soft agar. In contrast, the growth of high-passage cells was greatly inhibited by TPA in both monolayer culture and in soft agar. Inhibition was dose dependent, directly correlated with protein kinase C-activating activities of tumor promoters, and was found to be reversible. TPA-treated high-passage cells were greatly reduced in volume, showed extensive abnormal mitoses, and were more susceptible to detachment. High-passage cells were also found to be less tumorigenic as indicated by in vivo tumorigenicity assay in nude mice. TPA treatment rendered cells still less tumorigenic in the case of both cell lines. The mechanism for acquisition of increased sensitivity to TPA of RT101 cells during subculture was investigated; it involved nonrandom DNA damage and detachment of nonviable cells. The results suggest the possibility that early-passage RT101 cells contained two subpopulations, one TPA-sensitive and one TPA-resistant population. Conventional subcultivation may have selected for the former subpopulation. The sensitive subpopulation may have been irreversibly inhibited as a result of TPA-induced cell killing, possibly apoptosis. C1 NCI, FREDERICK CANC RES & DEV CTR, VIRAL CARCINOGENESIS LAB, FREDERICK, MD 21701 USA. NCI, DIV CANC TREATMENT, DEV THERAPEUT PROGRAM, BETHESDA, MD 20892 USA. NCI, FREDERICK CANC RES & DEV CTR, DYNCORP, FREDERICK, MD 21701 USA. FU NCI NIH HHS [N01-CO-74102] NR 62 TC 55 Z9 55 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 1 PY 1992 VL 52 IS 7 BP 1907 EP 1915 PG 9 WC Oncology SC Oncology GA HL505 UT WOS:A1992HL50500044 PM 1372531 ER PT J AU SAMID, D SHACK, S SHERMAN, LT AF SAMID, D SHACK, S SHERMAN, LT TI PHENYLACETATE - A NOVEL NONTOXIC INDUCER OF TUMOR-CELL DIFFERENTIATION SO CANCER RESEARCH LA English DT Note ID LEUKEMIA CELLS; ACID; GLUTAMINE; PROTEIN; HL-60; IDENTIFICATION; ACIVICIN; THERAPY; CULTURE; GROWTH AB Sodium phenylacetate was found to affect the growth and differentiation of tumor cells in vitro at concentrations that have been achieved in humans with no significant adverse effects. Treatment of promyelocytic leukemia HL-60 cells resulted in the rapid decline of myc oncogene expression followed by growth arrest and granulocyte differentiation. Phenylacetate also induced highly efficient adipocyte conversion in immortalized mesenchymal C3H 10T1/2 cultures; yet, unlike the differentiating chemotherapeutic drug 5-aza-2'-deoxycytidine, phenylacetate did not cause neoplastic transformation in these susceptible cells. The results indicate that phenylacetate is both effective in inducing tumor cell maturation and free of cytotoxic and carcinogenic effects, a combination that warrants attention to its potential use in cancer intervention. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT PATHOL,BETHESDA,MD 20814. RP SAMID, D (reprint author), NCI,DIV CANC TREATMENT,CLIN PHARMACOL BRANCH,BLDG 10,ROOM 12N226,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 24 TC 158 Z9 163 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 APR 1 PY 1992 VL 52 IS 7 BP 1988 EP 1992 PG 5 WC Oncology SC Oncology GA HL505 UT WOS:A1992HL50500056 PM 1372534 ER PT J AU DAMICO, D CARBONE, DP JOHNSON, BE MELTZER, SJ MINNA, JD AF DAMICO, D CARBONE, DP JOHNSON, BE MELTZER, SJ MINNA, JD TI POLYMORPHIC SITES WITHIN THE MCC AND APC LOCI REVEAL VERY FREQUENT LOSS OF HETEROZYGOSITY IN HUMAN SMALL-CELL LUNG-CANCER SO CANCER RESEARCH LA English DT Note ID ABNORMALITIES; GENE; LINES AB Using single-strand conformation polymorphism we have found two polymorphic sites, AAC to AAT at codon 511 (exon 12) and GCT to GCG at codon 708 (exon 15), in the MCC gene. These sites and an RsaI polymorphic site in APC allowed us to study 23 human small cell lung cancer (SCLC) and 7 non-small cell lung cancer samples for allele loss. Of the 23 SCLC samples, 21 (91%) were informative for one or more of these markers, and we found allele loss in more than 80% (17 of 21). In non-small cell lung cancer samples, 5 of 7 (71%) were informative, and reduction or loss of one allele was found in 2 of 5 (40%). Seven cases were informative for both genes, loss of heterozygosity occurred for both genes in five, one retained heterozygosity for both, and one SCLC had loss of heterozygosity for APC but not for MCC. We conclude that loss of heterozygosity occurs frequently for MCC and APC in lung cancer of all histological types and is very frequent in SCLC. This suggests the presence of tumor suppressor gene(s) in the MCC/APC region of 5q21 involved in human lung cancer. C1 NCI,USN,MED ONCOL BRANCH,BETHESDA,MD 20889. UNIV MARYLAND,DEPT MED,DIV GASTROINTESTINAL,BALTIMORE,MD 21201. LOCH RAVEN VET AFFAIRS HOSP,BALTIMORE,MD 21201. RP DAMICO, D (reprint author), UNIV TEXAS,SW MED CTR,SIMMONS CANC CTR,5323 HARRY HINES BLVD,DALLAS,TX 75235, USA. NR 26 TC 114 Z9 114 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 APR 1 PY 1992 VL 52 IS 7 BP 1996 EP 1999 PG 4 WC Oncology SC Oncology GA HL505 UT WOS:A1992HL50500058 PM 1348017 ER PT J AU BLOT, WJ AF BLOT, WJ TI ALCOHOL AND CANCER SO CANCER RESEARCH LA English DT Article; Proceedings Paper CT CONF ON NUTRITION AND CANCER CY APR 17-19, 1991 CL ATLANTA, GA SP AMER CANC SOC, CTR DIS CONTROL, EMORY UNIV, NCI ID CHRONIC ETHANOL-CONSUMPTION; ESOPHAGEAL CANCER; PHARYNGEAL CANCER; BREAST-CANCER; SMOKING; METABOLISM; DRINKING; LIVER; RISK; RATS AB Although ethanol has generally not been found to induce cancer in experimental animals, the consumption of alcoholic beverages has been linked to increased risks of several cancers in humans. Risks of oral, pharyngeal, laryngeal, esophageal, and liver cancer are elevated among drinkers, typically in proportion to the amount consumed. Evidence associating colorectal and breast cancer with alcohol drinking is suggestive but awaits confirmation. All types of alcoholic beverages seem to be implicated, pointing to an etiological role for ethanol or its metabolites. The mechanisms, however, by which alcohol induces cancer in humans are not clear. This review summarizes epidemiological studies of alcohol and cancer, focusing primarily on characteristics of the association that may provide clues to causal pathways. RP BLOT, WJ (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892, USA. NR 52 TC 232 Z9 235 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 1 PY 1992 VL 52 IS 7 SU S BP S2119 EP S2123 PG 5 WC Oncology SC Oncology GA HL808 UT WOS:A1992HL80800020 PM 1544150 ER PT J AU CONNEY, AH ADAMSON, RH HART, RW SCHEUPLEIN, RJ SOMOGYI, A SUGIMURA, T AF CONNEY, AH ADAMSON, RH HART, RW SCHEUPLEIN, RJ SOMOGYI, A SUGIMURA, T TI PANEL DISCUSSION - NUTRITION AND CANCER CONFERENCE SO CANCER RESEARCH LA English DT Discussion C1 NATL CANC CTR,TOKYO 104,JAPAN. NCI,BETHESDA,MD 20892. NATL CTR TOXICOL RES,JEFFERSON,AR 72079. US FDA,WASHINGTON,DC 20204. MAX VON PETTENKOFFER INST,BERLIN,GERMANY. RP CONNEY, AH (reprint author), RUTGERS STATE UNIV,PISCATAWAY,NJ 08855, USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 1 PY 1992 VL 52 IS 7 SU S BP S2124 EP S2125 PG 2 WC Oncology SC Oncology GA HL808 UT WOS:A1992HL80800021 ER PT J AU SNYDERWINE, EG SCHUT, HAJ ADAMSON, RH THORGEIRSSON, UP THORGEIRSSON, SS AF SNYDERWINE, EG SCHUT, HAJ ADAMSON, RH THORGEIRSSON, UP THORGEIRSSON, SS TI METABOLIC-ACTIVATION AND GENOTOXICITY OF HETEROCYCLIC ARYLAMINES SO CANCER RESEARCH LA English DT Article; Proceedings Paper CT CONF ON NUTRITION AND CANCER CY APR 17-19, 1991 CL ATLANTA, GA SP AMER CANC SOC, CTR DIS CONTROL, EMORY UNIV, NCI ID AMINES; CARCINOGENICITY; BINDING; FOODS AB Because of the potential for human exposure to mutagenic and carcinogenic heterocyclic arylamines in the diet, the carcinogenicity of three HAAs, 2-amino-3-methylimidazo[4,5-f]quinoline, 2-amino-3,8-dimethyl-imidazo[4,5-f]quinoxaline, and 2-amino-1-methyl-6-phenylimidazo]4,5-b]pryidine, is being evaluated in nonhuman primates, especially cynomolgus monkeys. Concomitant with the carcinogenicity studies, the metabolic processing, disposition, and DNA-adduct formation of these compounds are being examined in these monkeys. This report highlights the results from studies in monkeys and from in vitro models examining metabolic activation and genotoxicity of HAAs. The extent of in vivo activation of HAAs in monkeys was assessed by measuring DNA adducts in various tissues. Both 2-amino-3-methylimidazo[4,5-b]quinoline and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine form high levels of DNA adducts in a number of organs, particularly the liver, kidney, and heart. The implications of metabolic activation and DNA-adduct formation to the carcinogenicity of HAAs are discussed. C1 NCI,DIV CANC ETIOL,OFF DIRECTOR,BETHESDA,MD 20892. MED COLL OHIO,DEPT PATHOL,TOLEDO,OH 43614. RP SNYDERWINE, EG (reprint author), NCI,DIV CANC ETIOL,EXPTL CARCINOGENESIS LAB,BLDG 37,ROOM 3C28,BETHESDA,MD 20892, USA. NR 13 TC 49 Z9 51 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 APR 1 PY 1992 VL 52 IS 7 SU S BP S2099 EP S2102 PG 4 WC Oncology SC Oncology GA HL808 UT WOS:A1992HL80800016 ER PT J AU ZIEGLER, RG SUBAR, AF CRAFT, NE URSIN, G PATTERSON, BH GRAUBARD, BI AF ZIEGLER, RG SUBAR, AF CRAFT, NE URSIN, G PATTERSON, BH GRAUBARD, BI TI DOES BETA-CAROTENE EXPLAIN WHY REDUCED CANCER RISK IS ASSOCIATED WITH VEGETABLE AND FRUIT INTAKE SO CANCER RESEARCH LA English DT Article; Proceedings Paper CT CONF ON NUTRITION AND CANCER CY APR 17-19, 1991 CL ATLANTA, GA SP AMER CANC SOC, CTR DIS CONTROL, EMORY UNIV, NCI ID DIETARY VITAMIN-A; LUNG-CANCER; SUBSEQUENT RISK; SEROLOGIC PRECURSORS; FOLLOW-UP; SERUM RETINOL; COLON CANCER; NEW-JERSEY; WHITE MEN; GREEN AB Increased intake of vegetables, fruits, and carotenoids and elevated blood levels of beta-carotene are consistently associated with reduced risk of lung cancer in epidemiologic studies. Epidemiologic research also suggests that carotenoids may reduce the risk of other cancers, although the evidence is less extensive and consistent. The simplest explanation is that beta-carotene is protective. However, the possible roles of other carotenoids, other constituents of vegetables and fruits, and associated dietary patterns have not been adequately explored. To evaluate these alternative hypotheses, we are undertaking three lines of research. (a) With dietary data from the 1987 National Health Interview Survey and the 1982-1984 Epidemiologic Follow-up of the first National Health and Nutrition Examination Study, we have determined which food groups and nutrients are highly correlated with vegetable and fruit intake. (b) We have developed and characterized a liquid chromatography method for optimal recovery and resolution of the common carotenoids in blood, specifically lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene, and beta-carotene. (c) In a population-based case-control study of lung cancer in white men in New Jersey, we are assessing whether estimates of the intake of the individual carotenoids might produce stronger inverse associations than estimates of provitamin A carotenoids based on current food composition tables. C1 NCI,DIV CANC PREVENT & CONTROL,SURVEILLANCE PROGRAM,APPL RES BRANCH,BETHESDA,MD 20892. NATL INST STAND & TECHNOL,CHEM SCI & TECHNOL LAB,ORGAN ANALYT RES DIV,GAITHERSBURG,MD 20899. UNIV CALIF LOS ANGELES,SCH PUBL HLTH,DEPT EPIDEMIOL,LOS ANGELES,CA 90024. NCI,DIV CANC PREVENT & CONTROL,BIOMETRY BRANCH,BETHESDA,MD 20892. RP ZIEGLER, RG (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892, USA. NR 51 TC 88 Z9 88 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 APR 1 PY 1992 VL 52 IS 7 SU S BP S2060 EP S2066 PG 7 WC Oncology SC Oncology GA HL808 UT WOS:A1992HL80800009 ER PT J AU FOUREMAN, GL KNECHT, KT ELING, TE AF FOUREMAN, GL KNECHT, KT ELING, TE TI PEROXIDASE-MEDIATED GLUTATHIONE CONJUGATION OF BENZO[A]PYRENE-7,8-DIHYDRODIOL IS ENHANCED BY BENZO[A]PYRENE PHENOLS INVITRO SO CARCINOGENESIS LA English DT Article ID PROSTAGLANDIN-H SYNTHASE; CATALYZED METABOLISM; THIYL RADICALS; OXIDATION; SUBSTRATE; MICROSOMES; MECHANISM; REDUCTION; ELECTRON; ADDUCTS AB We reported previously that glutathione (GSH) is oxidized by peroxidases to a thiyl radical that can react with a number of chemicals, including the penultimate carcinogenic metabolite benzo[a]pyrene-7,8-dihydrodiol (7,8-B[a]PD), to give GSH conjugates. Here, we report that phenolic metabolites of benzo[a]pyrene (B[a]P) enhance the peroxidase-mediated formation of glutathione conjugates of 7,8-B[a]PD. The GSH conjugation of 7,8-B[a]PD in a horseradish peroxidase/peroxide system was increased over control values as follows: 9-OH-B[a]P by 4-fold, 7-OH-B[a]P by 3-fold, 1-OH-B[a]P by 2-fold. In contrast 3-OH-B[a]P was ineffective. A phenolic derivative of another polycyclic aromatic hydrocarbon (PAH), benz[a]anthracene, also enhanced GSH conjugation of 7,8-B[a]PD. The enhancement was dependent upon the presence of the phenol, horseradish peroxidase and peroxide. The phenolic compounds, including 3-OH-B[a]P, were also efficient reducing cofactors for the peroxidase. With the exception of 3-OH-B[a]P, the phenolic metabolites of PAH enhanced peroxidase-mediated formation of thiyl radical as detected by electron spin resonance spectrometry. Since both phenols and dihydrodiols are metabolites of B[a]P catalyzed by the cytochromes P450 system, enhancement of peroxidase-dependent 7,8-B[a]PD-GSH conjugation by phenols suggests a possible interaction between peroxidases and cytochromes P450 systems. This interaction may contribute to the detoxication of the penultimate carcinogenic PAH-dihydrodiols and other chemicals. C1 NIEHS,MOLEC BIOPHYS LAB,POB 12233,RES TRIANGLE PK,NC 27709. NR 26 TC 7 Z9 7 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 APR PY 1992 VL 13 IS 4 BP 515 EP 518 DI 10.1093/carcin/13.4.515 PG 4 WC Oncology SC Oncology GA HT223 UT WOS:A1992HT22300001 PM 1576701 ER PT J AU ZHENG, ZS POLAKOWSKA, R JOHNSON, A GOLDSMITH, LA AF ZHENG, ZS POLAKOWSKA, R JOHNSON, A GOLDSMITH, LA TI TRANSCRIPTIONAL CONTROL OF EPIDERMAL GROWTH-FACTOR RECEPTOR BY RETINOIC ACID SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID EGF-RECEPTOR; CELL-DIFFERENTIATION; GENE-EXPRESSION; MESSENGER-RNA; GAMMA; PROMOTER; MOUSE; ALPHA; INTERNALIZATION; IDENTIFICATION AB Retinoic acid (RA) and epidermal growth factor (EGF) regulate growth and differentiation of epithelial cells. RA has both direct and indirect effects on gene expression. Direct effects result from modulation of the transcriptional activity of genes, which contain RA response elements (RARE) recognized by trans-acting nuclear RA receptors (RARs). A second indirect mechanism for the modulatory effects of RA is by the induction or repression of growth factors and growth factor receptors. There is evidence for functional interactions between RA and the EGF receptor (EGFR). RA enhances the proliferative response of cultured keratinocytes to EGF, increases the number of EGFRs on the surface of some cells, and induces EGFR promoter activity in most cells. In contrast, immunoprecipitation, Northern blot, and nuclear run-on analysis described in this paper show that RA suppresses EGFR synthesis at the transcriptional level in human epidermoid carcinoma ME 180 cells. Deletion analysis of EGFR gene promoter mutants linked to the chloramphenicol acetyltransferase gene revealed the existence of a region of the promoter, -771 to -384, which is responsive to RA. Gel retardation data indicated that a cell-type nuclear protein which binds to this novel element is suppressed by RA in a dose-dependent manner. This decrease coincides with a decreased steady-state level of RAR-gamma mRNA. These data strongly suggest that the EGFR promoter is regulated by RAR-gamma, which itself is under the control of RA. Other cell-specific trans-acting factors may be involved in this regulation. C1 UNIV ROCHESTER,SCH MED & DENT,DEPT DERMATOL,601 ELMWOOD AVE,ROCHESTER,NY 14642. COLUMBIA UNIV COLL PHYS & SURG,DEPT DERMATOL,NEW YORK,NY 10032. NCI,BETHESDA,MD 20892. NR 37 TC 63 Z9 63 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 APR PY 1992 VL 3 IS 4 BP 225 EP 232 PG 8 WC Cell Biology SC Cell Biology GA HM770 UT WOS:A1992HM77000004 PM 1515368 ER PT J AU COLE, PM BARRETT, KC ZAHNWAXLER, C AF COLE, PM BARRETT, KC ZAHNWAXLER, C TI EMOTION DISPLAYS IN 2-YEAR-OLDS DURING MISHAPS SO CHILD DEVELOPMENT LA English DT Article ID CHILDREN; DISTRESS AB Although it has been shown that toddlers express distress when personal or physical events violate their expectations, there has been little detailed examination of their emotional reactions to such events. In this study, 45 2-year-olds were observed during 2 mishaps: a doll breaking and juice spilling. Their emotional reactions and their attempts to fix the mishap were coded. 2 components to their reactions to mishaps were found: one of tension and frustration, and another of concerned reparation. Mishaps elicited more negative emotions in toddlers than free play, and most toddlers attempted to correct the mishap. Children's styles of emotional response to mishaps may be related to maternal mental health. Symptoms of depression and anxiety in mothers were related to a suppression of tension and frustration in their offspring. Maternal acting out symptoms were not related to toddlers' reactions to mishaps. The findings are discussed in terms of the role of emotion in the formation of individual differences in sociomoral functioning and factors contributing to early differences. C1 COLORADO STATE UNIV,FT COLLINS,CO 80523. RP COLE, PM (reprint author), NIMH,BLDG 15K,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 36 TC 67 Z9 68 U1 1 U2 8 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0009-3920 J9 CHILD DEV JI Child Dev. PD APR PY 1992 VL 63 IS 2 BP 314 EP 324 DI 10.1111/j.1467-8624.1992.tb01629.x PG 11 WC Psychology, Educational; Psychology, Developmental SC Psychology GA HP156 UT WOS:A1992HP15600006 PM 1611936 ER PT J AU KOCHANSKA, G RADKEYARROW, M AF KOCHANSKA, G RADKEYARROW, M TI INHIBITION IN TODDLERHOOD AND THE DYNAMICS OF THE CHILDS INTERACTION WITH AN UNFAMILIAR PEER AT AGE 5 SO CHILD DEVELOPMENT LA English DT Article ID BEHAVIORAL-INHIBITION; COMPETENCE; PSYCHOPATHOLOGY; PREDICTORS; ADJUSTMENT; STABILITY; PARENTS AB Measures of inhibition to social and nonsocial unfamiliar events, obtained in toddlerhood, were studied as predictors of social behaviors during an interaction with an unfamiliar peer in 100 5-year-old children. Social inhibition predicted a highly shy and inhibited behavioral pattern with peer and less frequent expression of affect during fantasy play; nonsocial inhibition predicted decreased involvement in group play. Analysis of the changing dynamics of the ongoing peer interaction revealed that the role of child inhibition as a predictor of social behavior may be mostly evident during the initial encounter with the peer. Children who as toddlers were particularly socially inhibited, during the initial phase of peer interaction showed a significantly stronger pattern of shy and inhibited behavior and proximity to mother. In contrast to existing evidence that maternal depression may be a risk factor for the child's long-term peer relationships, no differences in social behavior were found between children of normal and affectively ill mothers during a brief encounter with unfamiliar peers. C1 NIMH,DEV PSYCHOL LAB,BETHESDA,MD 20892. NR 41 TC 52 Z9 52 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0009-3920 J9 CHILD DEV JI Child Dev. PD APR PY 1992 VL 63 IS 2 BP 325 EP 335 DI 10.1111/j.1467-8624.1992.tb01630.x PG 11 WC Psychology, Educational; Psychology, Developmental SC Psychology GA HP156 UT WOS:A1992HP15600007 PM 1611937 ER PT J AU PANZA, JA MARIS, TJ MARON, BJ AF PANZA, JA MARIS, TJ MARON, BJ TI DEVELOPMENT AND DETERMINANTS OF DYNAMIC OBSTRUCTION TO LEFT-VENTRICULAR OUTFLOW IN YOUNG-PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY SO CIRCULATION LA English DT Article DE HYPERTROPHIC CARDIOMYOPATHY; MITRAL VALVE; ECHOCARDIOGRAPHY ID ASYMMETRIC SEPTAL HYPERTROPHY; SYSTOLIC ANTERIOR MOTION; M-MODE ECHOCARDIOGRAPHY; CLINICAL MANIFESTATIONS; SUBAORTIC STENOSIS; PRESSURE-GRADIENT; PATHO-PHYSIOLOGY; INTERRELATIONS; ABNORMALITIES; CHILDHOOD AB Background. To study the development of dynamic subaortic obstruction in young patients with hypertrophic cardiomyopathy (HCM), serial echocardiograms were retrospectively analyzed in a group of 26 consecutive children with this disease who showed no evidence of dynamic outflow obstruction at their initial evaluation (age, 11 +/- 3 years). Methods and Results. After a follow-up of 3-12 years (mean, 7 +/- 3 years), seven of the 26 patients (27%) developed echocardiographic evidence of subaortic obstruction, i.e., marked systolic anterior motion (SAM) of the mitral valve with mitral-septal apposition and increased left ventricular outflow tract systolic velocities (3.8 +/- 0.3 m/sec; range, 3.1-4.5). Patients who developed SAM had smaller transverse dimension of the left ventricular outflow tract and more anteriorly displaced mitral valve when initially evaluated than did patients without development of SAM (outflow tract dimension, 19.1 +/- 4 versus 24.6 +/- 4 mm; mitral valve position index, 1.07 +/- 0.2 versus 0.73 +/- 0.3; each p < 0.02). In patients with development of SAM, the already reduced outflow tract dimension decreased further during follow-up, and the mitral valve became even more anteriorly displaced within the left ventricular cavity. These developmental alterations in outflow tract size were associated with increases in left ventricular wall thickness, particularly of the basal anterior septum (11.0 +/- 8 mm; 72 +/- 33%) compared with control patients with HCM who did not develop SAM (3.0 +/- 3 mm; 17 +/- 10%; p < 0.05). Conclusions. Development of subaortic obstruction in young patients with HCM results from a process of dynamic remodeling of left ventricular geometry over several years and is characterized by progressive narrowing of the outflow tract with anterior displacement of the mitral valve and disproportionate thickening of the basal anterior ventricular septum. RP PANZA, JA (reprint author), NHLBI,CARDIOL BRANCH,ECHOCARDIOG LAB,BLDG 10,ROOM 7B-15,BETHESDA,MD 20892, USA. NR 30 TC 33 Z9 33 U1 0 U2 0 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD APR PY 1992 VL 85 IS 4 BP 1398 EP 1405 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA HN049 UT WOS:A1992HN04900020 PM 1555282 ER PT J AU ZIEGELSTEIN, RC ZWEIER, JL MELLITS, ED YOUNES, A LAKATTA, EG STERN, MD SILVERMAN, HS AF ZIEGELSTEIN, RC ZWEIER, JL MELLITS, ED YOUNES, A LAKATTA, EG STERN, MD SILVERMAN, HS TI DIMETHYLTHIOUREA, AN OXYGEN RADICAL SCAVENGER, PROTECTS ISOLATED CARDIAC MYOCYTES FROM HYPOXIC INJURY BY INHIBITION OF NA+-CA2+ EXCHANGE AND NOT BY ITS ANTIOXIDANT EFFECTS SO CIRCULATION RESEARCH LA English DT Article DE CALCIUM; NA+-CA2+ EXCHANGE; MYOCYTE; OXYGEN FREE RADICAL; DIMETHYLTHIOUREA; SUPEROXIDE DISMUTASE; HYPOXIA ID MYOCARDIAL REPERFUSION INJURY; HUMAN SUPEROXIDE-DISMUTASE; RAT VENTRICULAR MYOCYTES; RE-OXYGENATION; HEART MYOCYTES; GENERATION; REDUCTION; REOXYGENATION; ALLOPURINOL; RECOVERY AB Myocardial reoxygenation injury may be attenuated by oxygen free radical scavengers, arguing for a role of oxygen radicals in this process. To determine whether free radical scavengers affect reoxygenation injury in isolated cardiac myocytes, resting rat ventricular myocytes were exposed to hypoxic (PO2 < 0.02 mm Hg) glucose-free buffer alone (n = 50) or with the addition of the oxygen radical scavengers 1,3-dimethyl-2-thiourea (DMTU, 25 mM, n = 46), human recombinant superoxide dismutase (SOD, 1,000 units/ml, n = 40), or the combination of these agents (n = 41). All cells responded by undergoing contracture to a rigor form. Hypoxia was then continued for a second period (T2), the duration of which correlates inversely with survival. After reoxygenation, cells either retained their rectangular shape (survival) or hypercontracted to a rounded form (death). For the group of cells with a T2 period > 30 minutes, no cell exposed to buffer alone (n = 20) or to SOD (n = 16) survived, in contrast to 15 of 24 (63%) cells exposed to DMTU. The addition of SOD to DMTU offered no advantage to DMTU alone. The protective effect of DMTU was not observed when it was added at reoxygenation, suggesting that this agent has an important effect during the hypoxic period when intracellular Ca2+ is known to rise, most likely because of the reversal of Na+-Ca2+ exchange. Therefore, the effects of DMTU on Ca2+ regulation (indexed by indo-1 fluorescence) during hypoxia were studied. DMTU significantly blunted the [Ca2+] rise during the hypoxic period. When normoxic, electrically stimulated cells were exposed to this agent, they displayed a progressive rise in diastolic [Ca2+], an increase in the amplitude of the Ca2+ transient, and a parallel increase in contractility. These findings could be explained by inhibition of Na+-Ca2+ exchange. To test the hypothesis that DMTU inhibits Na+-Ca2+ exchange, myocyte Ca2+ loading via the exchanger was induced by exposing cells to normoxic buffer with Na+ fully replaced by choline. Cells exposed in this fashion displayed an intracellular [Ca2+] rise that was nearly abolished by DMTU, consistent with pharmacological inhibition of the exchanger. We conclude that Na+-Ca2+ exchange inhibition is responsible for an important part of the effect of DMTU on prevention of hypoxic injury of isolated cardiac myocytes. Although free radical scavenging may play a more important role in the intact heart than in isolated myocytes, the establishment of the role of DMTU as an inhibitor of the Na+-Ca2+ exchanger suggests that previous reports of improved postischemic myocardial function with DMTU attributed to free radical scavenging should be interpreted cautiously. C1 NIA,CARDIOVASC SCI LAB,BALTIMORE,MD 21224. NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. JOHNS HOPKINS MED INST,DEPT MED,DIV CARDIOL,BALTIMORE,MD 21205. FU NHLBI NIH HHS [R01 HL-42050, K08 HL-02539, P50 HL-17655] NR 37 TC 59 Z9 59 U1 0 U2 2 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7330 J9 CIRC RES JI Circ.Res. PD APR PY 1992 VL 70 IS 4 BP 804 EP 811 PG 8 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA HL576 UT WOS:A1992HL57600019 PM 1551203 ER EF