FN Thomson Reuters Web of Science™ VR 1.0 PT J AU FREDERIKSE, PH DUBIN, RA HAYNES, JI PIATIGORSKY, J AF FREDERIKSE, PH DUBIN, RA HAYNES, JI PIATIGORSKY, J TI STRUCTURE AND ALTERNATE TISSUE-PREFERRED TRANSCRIPTION INITIATION OF THE MOUSE ALPHA-B-CRYSTALLIN SMALL HEAT-SHOCK PROTEIN GENE SO NUCLEIC ACIDS RESEARCH LA English DT Article ID LENS-SPECIFIC EXPRESSION; NON-LENTICULAR TISSUES; A-CRYSTALLIN; TRANSGENIC MICE; GAMMA-CRYSTALLIN; BETA-CRYSTALLIN; MESSENGER-RNAS; 2 PROMOTERS; TATA BOX; EVOLUTION AB We have determined the complete nucleotide sequence (-865 to +3515) of the murine alpha B-crystallin/small heat shock protein gene, a major soluble protein of the vertebrate eye lens. Its 3 exon/2 intron structure is identical to that of the rat, hamster and human gene, with the exons being much more conserved than the introns. Previous reports indicated that there are two sizes of alpha B-crystallin mRNA; a larger alpha B-crystallin mRNA predominates in the lung and brain and is also found in low levels in most other tissues (except in lens and liver), while a smaller alpha B-crystallin mRNA exists at a high level in the lens and in variable amounts elsewhere. Sequence analysis suggests that secondary structure in the 5' untranslated sequence of the longer mRNA has led to difficulty in mapping the transcription initiation site of the longer transcript. Here we provide evidence by primer extension, S1 nuclease protection, and PCR (polymerase chain reaction) experiments for a transcription initiation site in the murine lung and brain at position -474. We also detected the utilization of the -474 initiation site in lens and of the +1 site in lung and brain, indicating that the tissue preference for these sites is not absolute, In vitro transcription experiments revealed that cell-free HeLa nuclear extracts specifically initiate transcription at the -474 and + 1 sites. alpha B-crystallin was immunocytochemically localized to the bronchioles of the lung. Thus, regulation of alpha B-crystallin/small heat shock protein expression involves the utilization of tissue-preferred transcription initiation sites. C1 NEI,MOLEC & DEV BIOL LAB,BETHESDA,MD 20892. NR 63 TC 26 Z9 27 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 DEC 25 PY 1994 VL 22 IS 25 BP 5686 EP 5694 DI 10.1093/nar/22.25.5686 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QC753 UT WOS:A1994QC75300023 PM 7838723 ER PT J AU POWELL, BS COURT, DL NAKAMURA, Y RIVAS, MP TURNBOUGH, CL AF POWELL, BS COURT, DL NAKAMURA, Y RIVAS, MP TURNBOUGH, CL TI RAPID CONFIRMATION OF SINGLE-COPY LAMBDA-PROPHAGE INTEGRATION BY PCR SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ESCHERICHIA-COLI; GENE; DNA; FRAGMENTS; SEQUENCE; PROTEIN; VECTOR C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,CHROMOSOME BIOL LAB,FREDERICK,MD 21702. UNIV ALABAMA,DEPT MICROBIOL,BIRMINGHAM,AL 35294. UNIV TOKYO,INST MED SCI,DEPT TUMOR BIOL,TOKYO 108,JAPAN. FU NCI NIH HHS [N01-CO74101]; NIAID NIH HHS [AI1459-10]; NIGMS NIH HHS [GM29466] NR 14 TC 173 Z9 175 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 DEC 25 PY 1994 VL 22 IS 25 BP 5765 EP 5766 DI 10.1093/nar/22.25.5765 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QC753 UT WOS:A1994QC75300035 PM 7838735 ER PT J AU FAWCETT, TW SYLVESTER, SL SARGE, KD MORIMOTO, RI HOLBROOK, NJ AF FAWCETT, TW SYLVESTER, SL SARGE, KD MORIMOTO, RI HOLBROOK, NJ TI EFFECTS OF NEUROHORMONAL STRESS AND AGING ON THE ACTIVATION OF MAMMALIAN HEAT-SHOCK FACTOR-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AGE-DEPENDENT RESPONSE; TRANSCRIPTION FACTOR; MOLECULAR-CLONING; PROTEIN INDUCTION; BINDING-ACTIVITY; GENE-EXPRESSION; ADRENAL-CORTEX; FACTOR-II; CELLS; FIBROBLASTS AB The mammalian heat shock response has been investigated extensively using tissue culture cells with only a limited amount of information available on animals and intact tissues. The neurohormonal stress response mediated by the hypothalamic-pituitary-adrenal axis leads to the activation of heat shock factor (HSF) in rat adrenal tissue. Here we show through the use of antibodies specific to each member of the HSF family that restraint-induced stress in intact Wistar rats and adrenocorticotropic hormone treatment of hypophysectomized animals leads to the activation of HSF1 monomers to trimers with DNA-binding activity Because HSF1 is also the target factor for metabolic and environmental stress, these data reveal an intersection of pathways leading to HSF1 activation. Comparison of the biochemical properties and levels of HSF1 in the Wistar and Fischer 344 rat strains reveals that HSF1 is constitutively present in an activated DNA-binding state in the adrenals of Fischer 344 rats. During aging, the levels of HSF1 remain constant, yet the transcription factor from aged animals exhibits a decreased ability to bind DNA. C1 NIA,GENE EXPRESS & AGING SECT,BALTIMORE,MD. UNIV KENTUCKY,ALBERT B CHANDLER MED CTR,DEPT BIOCHEM,LEXINGTON,KY 40536. NORTHWESTERN UNIV,DEPT BIOCHEM MOLEC BIOL & CELL BIOL,EVANSTON,IL 60208. NR 35 TC 77 Z9 78 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 DEC 23 PY 1994 VL 269 IS 51 BP 32272 EP 32278 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PX304 UT WOS:A1994PX30400041 PM 7798227 ER PT J AU DIBRINO, M PARKER, KC MARGULIES, DH SHILOACH, J TURNER, RV BIDDISON, WE COLIGAN, JE AF DIBRINO, M PARKER, KC MARGULIES, DH SHILOACH, J TURNER, RV BIDDISON, WE COLIGAN, JE TI THE HLA-B14 PEPTIDE BINDING-SITE CAN ACCOMMODATE PEPTIDES WITH DIFFERENT COMBINATIONS OF ANCHOR RESIDUES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; LYMPHOCYTE-T RECOGNITION; INFLUENZA-VIRUS PROTEINS; ENDOGENOUS PEPTIDES; MATRIX PEPTIDE; VIRAL PEPTIDES; CELL EPITOPES; MHC; MOLECULES; ANTIGEN AB Most peptides that bind to a particular major histocompatibility complex class I molecule share amino acid residues important for binding at one or two positions. Sequence analyses of peptides bound to HLA-B14 revealed at least four candidates for these so-called anchor residues: Arg at P2, Tyr at P3, Arg at P5, and Leu at P9. Combinations of any three of these amino acids sufficed for binding to HLA-B14 in vitro. Using this information, we identified an antigenic peptide critical for cytotoxic T lymphocyte recognition of virus-infected cells. Molecular models of HLA-B14 peptide complexes were constructed to investigate how the potential anchor residues might function. By using binding data to calculate the contribution to binding of each amino acid at anchor positions and predicting the stability of all possible nonapeptide complexes that could be formed from antigenic proteins, we estimate that three known antigenic nonapeptides are in the highest affinity cohort of peptides, Thus, even when multiple combinations of anchor residues contribute to binding, antigenic peptides are routinely identifiable. C1 NIAID, MOLEC STRUCT LAB, BETHESDA, MD 20892 USA. NIAID, IMMUNOL LAB, MOLEC BIOL SECT, BETHESDA, MD 20892 USA. NIDDK, CELLULAR & DEV BIOL LAB, BETHESDA, MD 20892 USA. NINCDS, NEUROIMMUNOL BRANCH, MOLEC IMMUNOL SECT, BETHESDA, MD 20892 USA. RI Margulies, David/H-7089-2013; OI Margulies, David/0000-0001-8530-7375; Parker, Kenneth/0000-0002-6282-2478 NR 46 TC 42 Z9 42 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 23 PY 1994 VL 269 IS 51 BP 32426 EP 32434 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PX304 UT WOS:A1994PX30400062 PM 7528217 ER PT J AU ABRUZZO, LV REITMAN, M AF ABRUZZO, LV REITMAN, M TI ENHANCER ACTIVITY OF UPSTREAM HYPERSENSITIVE SITE-2 OF THE CHICKEN BETA-GLOBIN CLUSTER IS MEDIATED BY GATA SITES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LOCUS-CONTROL REGION; STAGE SELECTOR ELEMENT; HUMAN ERYTHROID-CELLS; TRANSCRIPTION FACTOR; DEVELOPMENTAL REGULATION; GENE-TRANSCRIPTION; TRANSGENIC MICE; ACTIVATION REGION; MAMMALIAN-CELLS; BINDING-PROTEIN AB Upstream of the chicken beta-globin gene cluster are four DNase I-hypersensitive sites (HS1-4), Hypersensitive sites located upstream of the mammalian beta-globin clusters have enhancer activity and mediate position-independent gene expression, In contrast, a region inside the chicken cluster has enhancer activity and mediates position-independent expression, Here we investigate the function of the chicken upstream sites, which are different from the mammalian ones in sequence, number, and distance from the genes, Each was tested for its effect on reporter gene expression in transfected primary erythroid cells, HS2 and HS3 (4.4 and 6.4 kilobases upstream of rho-globin) showed significant enhancer activity while HS1 and HS4 (1.6 and 11 kilobases upstream of rho-globin) did not, A 237-base pair region of HS2 contained the sequences necessary for enhancer activity. Proteins from erythroid extracts bound HS2 in seven different regions; six of these sites were characterized, GATA-1 bound to four of the sites, Each site contributed to the enhancer activity of HS2, Two Other sequences bound proteins that may be related to Spl and erythroid krup-pel-like factor. Surprisingly, mutations in these elements, which disrupted protein binding, did not affect enhancer activity, Thus, the observed enhancer activity of HS2 is due to the four GATA sites, The existence of multiple GATA sites in both chicken HS2 and the mammalian upstream sites may be due to evolution from a common element with preservation of only very short sequences or to convergent evolution. These observations highlight the crucial role for GATA proteins in globin regulation. C1 NIDDK,DIABET BRANCH,BETHESDA,MD 20892. RI Reitman, Marc/B-4448-2013 OI Reitman, Marc/0000-0002-0426-9475 NR 55 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 DEC 23 PY 1994 VL 269 IS 51 BP 32565 EP 32571 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PX304 UT WOS:A1994PX30400081 PM 7798259 ER PT J AU RAO, GN BAAS, AS GLASGOW, WC ELING, TE RUNGE, MS ALEXANDER, RW AF RAO, GN BAAS, AS GLASGOW, WC ELING, TE RUNGE, MS ALEXANDER, RW TI ACTIVATION OF MITOGEN-ACTIVATED PROTEIN-KINASES BY ARACHIDONIC-ACID AND ITS METABOLITES IN VASCULAR SMOOTH-MUSCLE CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GROWTH-FACTOR; MAP KINASE; ENDOTHELIAL-CELLS; SIGNAL-TRANSDUCTION; MESANGIAL CELLS; ANGIOTENSIN-II; MESSENGER-RNA; LINOLEIC-ACID; DNA-SYNTHESIS; 3T3 CELLS AB Previous studies from this laboratory and others suggest that arachidonic acid and its metabolites play important roles in a variety of biological processes such as signal transduction, contraction, chemotaxis, and cell growth and differentiation. Here we studied the effect of arachidonic acid on mitogen-activated protein (MAP) kinases in vascular smooth muscle cells (VSMC). Arachidonic acid activated MAP kinases in VSMC in a time-and dose-dependent manner. Nordihydroguaiaretic acid (NDGA), a potent inhibitor of the Lipoxygenase system, significantly blocked the arachidonic acid-induced activation of MAP kinases, whereas indomethacin, an inhibitor of cyclooxygenase, had no effect. In VSMC, arachidonic acid was converted to 15-hydroxyeicosatetraenoic acid (15-HETE); NDGA inhibited the formation of this HETE. Exogenous addition of 15-HETE to VSMC caused stimulation of MAP kinases. Depletion of protein kinase C attenuated both the arachidonic acid- and 15-HETE-induced activation of MAP kinases in VSMC. Together these results suggest that 1) arachidonic acid activates MAP kinases in VSMC; 2) 15-HETE, a 15-lipoxygenase product of arachidonic acid, at least in part, mediates the arachidonic acid effect on MAP kinases; and 3) protein kinase C appears to be important in arachidonic acid activation of MAP kinases, Therefore, MAP kinases may play an important role in arachidonic acid signaling of VSMC growth and function. C1 EMORY UNIV,SCH MED,DIV CARDIOL,ATLANTA,GA 30322. NIEHS,MOLEC BIOPHYS LAB,RES TRIANGLE PK,NC 27709. NR 62 TC 206 Z9 210 U1 1 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 DEC 23 PY 1994 VL 269 IS 51 BP 32586 EP 32591 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PX304 UT WOS:A1994PX30400084 PM 7798262 ER PT J AU CARRIER, F SMITH, ML BAE, I KILPATRICK, KE LANSING, TJ CHEN, CY ENGELSTEIN, M FRIEND, SH HENNER, WD GILMER, TM KASTAN, MB FORNACE, AJ AF CARRIER, F SMITH, ML BAE, I KILPATRICK, KE LANSING, TJ CHEN, CY ENGELSTEIN, M FRIEND, SH HENNER, WD GILMER, TM KASTAN, MB FORNACE, AJ TI CHARACTERIZATION OF HUMAN GADD45, A P53-REGULATED PROTEIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GENE-TRANSCRIPTION; KINASE-C; P53; ACTIVATION; CELLS; RNA; RADIATION; INDUCTION; ARREST AB GADD45 (growth arrest and DNA damage) is a DNA-damage-inducible gene regulated in part by the tumor suppressor p53. A role in negative growth control has recently been suggested based on significant (more than 75%) reduction of colony formation following over expression of Gadd45. To better understand the role of Gadd45, we have developed specific rabbit and murine antibodies raised against the human recombinant protein. Using these antibodies, we have found that in ML-1 cells Gadd45 is predominantly a nuclear protein. MyD118, a protein induced by terminal differentiation sharing 57% homology with Gadd45, does not cross-react with any of the antibodies produced. As expected, the induction of Gadd45 protein by ionizing radiation (IR) was also found to be dependent on a mild type p53 phenotype. Interestingly, WI-L2-NS, a human lymphoid cell line, showed very high basal levels of Gadd45 mRNA and protein in addition to a high constitutive level of a mutated p53 protein. In this cell Line, the high levels of GADD45 did not inhibit cellular growth in spite of the fact that no mutations were found in GADD45 sequence. These results indicate that some cell line(s) can tolerate high levels of Gadd45 and abrogate its growth suppression function. C1 GLAXO INC,RES INST,DEPT CELL PHYSIOL,RES TRIANGLE PK,NC 27709. GLAXO INC,RES INST,DEPT CELL BIOL,RES TRIANGLE PK,NC 27709. OREGON HLTH SCI UNIV,SCH MED,DIV HEMATOL & MED ONCOL,PORTLAND,OR 97201. MASSACHUSETTS GEN HOSP E,BOSTON,MA 02129. RP CARRIER, F (reprint author), NCI,DCT,DTP,MOLEC PHARMACOL LAB,BETHESDA,MD 20892, USA. RI Carrier, France/C-3063-2008 NR 23 TC 105 Z9 108 U1 1 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 23 PY 1994 VL 269 IS 51 BP 32672 EP 32677 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PX304 UT WOS:A1994PX30400097 PM 7798274 ER PT J AU GU, LY HUANG, SM SANDER, M AF GU, LY HUANG, SM SANDER, M TI SINGLE AMINO-ACID CHANGES ALTER THE REPAIR SPECIFICITY OF DROSOPHILA RRP1 - ISOLATION OF MUTANTS DEFICIENT IN REPAIR OF OXIDATIVE DNA-DAMAGE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID APURINIC APYRIMIDINIC ENDONUCLEASE; COLI EXONUCLEASE-III; ENZYME APEX NUCLEASE; ESCHERICHIA-COLI; 3'-5' EXONUCLEASE; POLYMERASE-I; CDNA; MUTAGENESIS; EXPRESSION; HOMOLOGY AB Drosophila Rrp1 has several tightly associated enzymatic activities, including double-strand DNA 3'-exo-nuclease, apurinic/apyrimidinic endonuclease, 3'-phosphatase, and 3'-phosphodiesterase. The carboxyl-terminal third of Rrp1, homologous to Escherichia coli exonuclease III, is sufficient to repair oxidative and alkylation-induced DNA damage in vivo. Using a screen for partial complementation of repair-deficient E., coli, we isolated three mutants of the nuclease domain of Rrp1: T462A, K463Q, and L484P, that protect against methyl methanesulfonate (MMS)-induced but not t-BuO(2)H-induced DNA damage, Thr-462 and Lys-463 are highly conserved residues found in a cluster of 5 conserved amino acids (LQETK), while Leu-484 is poorly conserved. Gln-460 Glu-461, Thr-462, and Lys-463 and Leu-484 were altered by site-directed mutagenesis using a plasmid including the entire Rrp1 gene and mutant proteins were purified, Mutants of the three residues Glu-461, Thr-462, and Lys-463 demonstrate 8-200-fold lower phosphodiesterase specific activity than wild-type Rrp1., E46lA has a 30-fold reduction in AP endonuclease and is MMS-sensitive, but all other mutants have near-normal AP endonuclease and are MMS-resistant, Glu-461 appears to be essential for the nuclease function of Rrp1. Lys-463 and, to a lesser extent, Thr-462 influence the substrate specificity of the Rrp1 nuclease. C1 NIEHS, MOLEC GENET LAB, RES TRIANGLE PK, NC 27709 USA. NR 34 TC 16 Z9 16 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 23 PY 1994 VL 269 IS 51 BP 32685 EP 32692 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PX304 UT WOS:A1994PX30400099 PM 7798276 ER PT J AU WANG, SM ZAHAREVITZ, DW SHARMA, R MARQUEZ, VE LEWIN, NE DU, L BLUMBERG, PM MILNE, GWA AF WANG, SM ZAHAREVITZ, DW SHARMA, R MARQUEZ, VE LEWIN, NE DU, L BLUMBERG, PM MILNE, GWA TI THE DISCOVERY OF NOVEL, STRUCTURALLY DIVERSE PROTEIN-KINASE-C AGONISTS THROUGH COMPUTER 3D-DATABASE PHARMACOPHORE SEARCH - MOLECULAR MODELING STUDIES SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID TUMOR PROMOTERS; SEMIEMPIRICAL METHODS; MAMMALIAN-TISSUES; DRUG DESIGN; ACTIVATION; PHORBOL; DIACYLGLYCEROL; OPTIMIZATION; PARAMETERS; PROENZYME AB A computer protein kinase C (PK-C) pharmacophore search on 206 876 nonproprietary structures in the NCI 3D-database led to the discovery of five compounds which were found to possess PK-C binding affinities in the low micromolar range and six others having detectable, but marginal, binding affinities. Molecular modeling studies showed that in addition to, the presence of the defined pharmacophore, hydrophobicity and conformational energy are the two other important factors determining the PK-C binding affinity of a compound. The modeling results were confirmed by synthetic modification of two inactive compounds, producing two active derivatives. These newly discovered, structurally diverse lead compounds are being used as the basis for further synthetic modifications aimed at more potent PK-C ligands that will compete with the phorbol esters. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MED CHEM LAB,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,FREDERICK,MD 21702. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,MOLEC MECHANISMS TUMOR PROMOT SECT,BETHESDA,MD 20892. RI Wang, Shaomeng/E-9686-2010 NR 27 TC 68 Z9 76 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD DEC 23 PY 1994 VL 37 IS 26 BP 4479 EP 4489 DI 10.1021/jm00052a007 PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA PY518 UT WOS:A1994PY51800007 PM 7799398 ER PT J AU DYDA, F HICKMAN, AB JENKINS, TM ENGELMAN, A CRAIGIE, R DAVIES, DR AF DYDA, F HICKMAN, AB JENKINS, TM ENGELMAN, A CRAIGIE, R DAVIES, DR TI CRYSTAL-STRUCTURE OF THE CATALYTIC DOMAIN OF HIV-1 INTEGRASE - SIMILARITY TO OTHER POLYNUCLEOTIDYL TRANSFERASES SO SCIENCE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; REVERSE-TRANSCRIPTASE; ESCHERICHIA-COLI; DNA INTEGRATION; ANGSTROM RESOLUTION; NUCLEOTIDE-SEQUENCE; PROTEIN INVITRO; RIBONUCLEASE-H; AIDS VIRUS; IDENTIFICATION AB HIV integrase is the enzyme responsible for inserting the viral DNA into the host chromosome; it is essential for HIV replication. The crystal structure of the catalytically active core domain (residues 50 to 212) of HIV-7 integrase was determined at 2.5 Angstrom resolution. The central feature of the structure is a five-stranded beta sheet flanked by helical regions. The overall topology reveals that this domain of integrase belongs to a superfamily of polynucleotidyl transferases that includes ribonuclease H and the Holliday junction resolvase RuvC. The active site region is identified by the position of two of the conserved carboxylate residues essential for catalysis, which are located at similar positions in ribonuclease H. In the crystal, two molecules form a dimer with an extensive solvent-inaccessible interface of 1300 Angstrom(2) per monomer. C1 NIDDK,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 81 TC 628 Z9 649 U1 5 U2 18 PU AMER ASSOC ADVAN SCIENCE PI WASHINGTON PA 1333 H ST NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD DEC 23 PY 1994 VL 266 IS 5193 BP 1981 EP 1986 DI 10.1126/science.7801124 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PZ267 UT WOS:A1994PZ26700027 PM 7801124 ER PT J AU METELEV, V LISZIEWICZ, J AGRAWAL, S AF METELEV, V LISZIEWICZ, J AGRAWAL, S TI STUDY OF ANTISENSE OLIGONUCLEOTIDE PHOSPHOROTHIOATES CONTAINING SEGMENTS OF OLIGODEOXYNUCLEOTIDES AND 2'-O-METHYLOLIGORIBONUCLEOTIDES SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID HUMAN IMMUNODEFICIENCY VIRUS; CHRONICALLY INFECTED-CELLS; INHIBITION; REPLICATION; EXPRESSION; ANALOGS; INVITRO; AGENTS AB Antisense oligonucleotide phosphorothioates have been designed, which contain segments of oligodeoxynucleotide and 2'-O-methyloligoribonucleotides and studied for their biophysical and biochemical properties. Oligonucleotide phosphorothioates containing segments of 2'-O-methyloligoribonucleotides at both 3'- and 5'-ends show increased nuclease resistance, bind more strongly to complementary RNA targets, activate RNase H and show increased inhibition of human immunodeficiency virus type 1 replication in infected cells. C1 HYBRIDON INC,WORCESTER,MA 01605. WORCESTER FDN EXPTL BIOL INC,SHREWSBURY,MA 01545. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. RI Metelev, Valeri/I-3238-2012 NR 26 TC 49 Z9 50 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD DEC 22 PY 1994 VL 4 IS 24 BP 2929 EP 2934 DI 10.1016/S0960-894X(01)80842-8 PG 6 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA QB545 UT WOS:A1994QB54500023 ER PT J AU SUZUKI, WA AMARAL, DG AF SUZUKI, WA AMARAL, DG TI PERIRHINAL AND PARAHIPPOCAMPAL CORTICES OF THE MACAQUE MONKEY - CORTICAL AFFERENTS SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Review DE HIPPOCAMPAL FORMATION; MEMORY; ENTORHINAL CORTEX; POLYSENSORY CORTEX; MEDIAL TEMPORAL LOBE ID INFERIOR TEMPORAL CORTEX; POSTERIOR CINGULATE CORTEX; ENTORHINAL AREA 28; SHORT-TERM-MEMORY; RHESUS-MONKEY; HIPPOCAMPAL-FORMATION; PREFRONTAL CORTEX; CORTICOCORTICAL CONNECTIONS; INFEROTEMPORAL CORTEX; VISUAL RECOGNITION AB Neuropsychological studies have recently demonstrated that the macaque monkey perirhinal (areas 35 and 36) and parahippocampal (areas TH and TF) cortices contribute importantly to normal memory function. Unfortunately, neuroanatomical information concerning the cytoarchitectonic organization and extrinsic connectivity of these cortical regions is meager. We investigated the organization of cortical inputs to the macaque monkey perirhinal and parahippocampal cortices by placing discrete injections of the retrograde tracers fast blue, diamidino yellow, and wheat germ agglutinin conjugated to horseradish peroxidase throughout these areas. We found that the macaque monkey perirhinal and parahippocampal cortices receive different complements of cortical inputs. The major cortical inputs to the perirhinal cortex arise from the unimodal visual areas TE and rostral TEO and from area TF of the parahippocampal cortex. The perirhinal cortex also receives projections from the dysgranular and granular subdivisions of the insular cortex and from area 13 of the orbitofrontal cortex. In contrast, area TF of the parahippocampal cortex receives its strongest input from more caudal visual areas V4, TEO, and caudal TE, as well as prominent inputs from polymodal association cortices, including the retrosplenial cortex and the dorsal bank of the superior temporal sulcus. Area TF also receives projections from areas 7a and LIP of the posterior parietal lobe, insular cortex, and areas 46, 13, 45, and 9 of the frontal lobe. As with area TF, area TH receives substantial projections from the retrosplenial cortex as well as moderate projections from the dorsal bank of the superior temporal sulcus; unlike area TF, area TH receives almost no innervation from areas TE and TEO. It does, however, receive relatively strong inputs from auditory association areas on the convexity of the superior temporal gyrus. (C) 1994 Wiley-Liley, Inc. C1 SUNY STONY BROOK,CTR BEHAV NEUROSCI,STONY BROOK,NY 11794. RP SUZUKI, WA (reprint author), NIMH,NEUROPSYCHOL LAB,BLDG 49,ROOM 1B80,49 CONVENT DR,MSC 4415,BETHESDA,MD 20892, USA. RI Frank, David/E-8213-2012 FU NCRR NIH HHS [RR 00169]; NIMH NIH HHS [MH10033]; NINDS NIH HHS [NS 16980] NR 108 TC 713 Z9 716 U1 2 U2 16 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 DEC 22 PY 1994 VL 350 IS 4 BP 497 EP 533 DI 10.1002/cne.903500402 PG 37 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA QF849 UT WOS:A1994QF84900001 PM 7890828 ER PT J AU CUMMINGS, SL YOUNG, WS KING, JS AF CUMMINGS, SL YOUNG, WS KING, JS TI EARLY DEVELOPMENT OF CEREBELLAR AFFERENT SYSTEMS THAT CONTAIN CORTICOTROPIN-RELEASING FACTOR SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE CLIMBING FIBERS; MOSSY FIBERS; CORTICOTROPIN-RELEASING FACTOR; ONTOGENY; NEUROPEPTIDES ID CHOLECYSTOKININ-LIKE IMMUNOREACTIVITY; INSITU HYBRIDIZATION HISTOCHEMISTRY; NORTH-AMERICAN OPOSSUM; PURKINJE-CELLS; PRECEREBELLAR NUCLEI; DIDELPHIS-VIRGINIANA; MOUSE CEREBELLUM; CLIMBING FIBERS; RAT CEREBELLUM; IMMUNOHISTOCHEMISTRY AB Corticotropin-releasing factor (CRF) and CRF binding sites have been described in the cerebellum of several species, including the North American opossum (Didelphis marsupialis virginiana), the species used in the present study. Iontophoretic application of this peptide in the adult cerebellum enhances the spontaneous and amino acid-induced firing rate of Purkinje cells and overcomes the GABA-induced suppression of Purkinje cell activity. The present account provides immunohistochemical evidence for the localization of CRF in the North American opossum within developing axons and their growth cones prior to the formation of the Purkinje cell and granule cell layers. CRF mRNA is present on postnatal day (PD) 1 within the internal migratory stream of the ventral lateral medulla, which contains migrating olivary neurons, and within the ventral medulla in the region, where inferior olivary neurons first aggregate to form the inferior olivary complex. The olivary complex can first be identified on PD2 and is well defined by PD3. CRF-immunoreactive axons are evident within the cerebellar primordium on PD4 and penetrate the nascent Purkinje cell layer between PD14 and PD26. By PD26, CRF-immunoreactive puncta are organized within the Purkinje cell layer as parasagittal bands. Thus, olivary neurons express CRF mRNA prior to the time that the first CRF-labeled axons are present in the cerebellar anlage (PD4), suggesting that olivary axons are among the first to reach the developing cerebellum. Coincident (PD1-3) with the early transcription of CRF mRNA in the inferior olive, cells in the medullary reticular formation (PD1) and locus coeruleus (PD2) also transcribe CRF mRNA. These brainstem sites also could provide CRF-immunoreactive axons to the developing cerebellum; however, based on the results of this study and correlative data reported in the literature, we propose that the primary source of early-arriving CRF fibers is the inferior olivary complex. The early arrival of CRF-containing axons in the cerebellum prior to synaptogenesis and migration of both granule cells and Purkinje cells suggests a role for this peptide in target recognition and synaptic organization. (C) 1994 Wiley-Liss, Inc. C1 OHIO STATE UNIV,DEPT CELL BIOL NEUROBIOL & ANAT,COLUMBUS,OH 43210. UNIV CALIF DAVIS,DEPT ANAT PHYSIOL & CELL BIOL,DAVIS,CA 95616. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. RI Young, W Scott/A-9333-2009 OI Young, W Scott/0000-0001-6614-5112 FU NINDS NIH HHS [NS-08798] NR 39 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 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD DEC 22 PY 1994 VL 350 IS 4 BP 534 EP 549 DI 10.1002/cne.903500403 PG 16 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA QF849 UT WOS:A1994QF84900002 PM 7890829 ER PT J AU SMITH, D LEWIS, CE PERKINS, L BURKE, G BILD, DE AF SMITH, D LEWIS, CE PERKINS, L BURKE, G BILD, DE TI CHANGES IN ADIPOSITY ASSOCIATED WITH PREGNANCY - REPLY SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID WEIGHT C1 DOW CORNING CORP,MIDLAND,MI. BOWMAN GRAY SCH MED,WINSTON SALEM,NC. NHLBI,BETHESDA,MD. RP SMITH, D (reprint author), UNIV ALABAMA,BIRMINGHAM,AL, USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 21 PY 1994 VL 272 IS 23 BP 1820 EP 1821 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA PW980 UT WOS:A1994PW98000020 ER PT J AU ALAVANJA, MCR BROWNSON, RC LUBIN, JH BERGER, E CHANG, J BOICE, JD AF ALAVANJA, MCR BROWNSON, RC LUBIN, JH BERGER, E CHANG, J BOICE, JD TI RESIDENTIAL RADON EXPOSURE AND LUNG-CANCER AMONG NONSMOKING WOMEN SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID INDOOR RADON; URANIUM MINERS; UNITED-STATES; RISK; RN AB Background: Radon at sufficiently high concentrations is known to cause lung cancer among underground miners and in experimental laboratory animals. Purpose: Our aim was to determine whether indoor levels of radon are associated with a detectable increase in lung cancer. Nonsmoking women were selected because they offer the best opportunity to detect radon-related risk while minimizing the potentially confounding influences of cigarette smoking and occupation. Methods: A population-based, case-control study of incident lung cancer was conducted in Missouri. A total of 538 nonsmoking white women diagnosed with lung cancer between 1986 and 1992 and 1183 age-matched control subjects were identified from the Missouri Cancer Registry and from driver's license and Medicare listings, respectively. Information on lung cancer risk factors was obtained by telephone interview. Year-long radon measurements were sought in every dwelling occupied for the previous 5-30 years. Results: Radon measurements covered 78% of the relevant residential period, and women reported being indoors for 84% of this time. The time-weighted average radon concentrations were exactly the same for case subjects and control subjects (1.82 pCi/L of air [pCi L(-1)]). Radon levels greater than 4 pCi L(-1) were experienced by 6.5% of the case subjects and 6.8% of the control subjects. For all data combined, there was little evidence for a trend of lung cancer with increasing radon concentrations (two-tailed trend test, P = .99 continuous data analysis; P = .19 categorical data analysis). A positive dose-response trend was suggested for the adenocarcinoma cell type and among directly interviewed women (two-tailed trend test; P = .31 continuous data analysis; P = .04 categorical data analysis), but not for other histologies or among those who had surrogate interviews. Conclusions: The possibility of detecting a risk from indoor radon in this study was maximized by (a) including a large number of nonsmoking women with high indoor occupancy, (b) conducting a large number of radon measurements near the time of the diagnosis of cancer, and (c) controlling for known causes of lung cancer. However, an association between lung cancer and the exposure to domestic levels of radon was not convincingly demonstrated. Implications: The magnitude of the lung cancer risk from radon levels commonly found in U.S. dwellings appears low. C1 NCI,DIV CANC PREVENT & CONTROL,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. MISSOURI DEPT HLTH,DIV CHRON DIS PREVENT & HLTH PROMOT,COLUMBIA,MO. INFORMAT MANAGEMENT SERV INC,ROCKVILLE,MD. FU NCI NIH HHS [N01CP05609, N01CP71096] NR 29 TC 120 Z9 125 U1 3 U2 10 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 DEC 21 PY 1994 VL 86 IS 24 BP 1829 EP 1837 DI 10.1093/jnci/86.24.1829 PG 9 WC Oncology SC Oncology GA PX380 UT WOS:A1994PX38000008 PM 7990157 ER PT J AU HOWLETT, AR PETERSEN, OW STEEG, PS BISSELL, MJ AF HOWLETT, AR PETERSEN, OW STEEG, PS BISSELL, MJ TI A NOVEL FUNCTION FOR THE NM23-H1 GENE - OVEREXPRESSION IN HUMAN BREAST-CARCINOMA CELLS LEADS TO THE FORMATION OF BASEMENT-MEMBRANE AND GROWTH ARREST SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID NUCLEOSIDE DIPHOSPHATE KINASE; PROTEIN EXPRESSION; GOOD PROGNOSIS; DIFFERENTIATION; CANCER; TRANSFECTION; ASSOCIATION; METASTASIS AB Background: We have developed a culture system using reconstituted basement membrane components in which normal human mammary epithelial cells exhibit several aspects of the development and differentiation process, including formation of acinar-like structures, production and basal deposition of basement membrane components, and production and apical secretion of sialomucins. Cell lines and cultures from human breast carcinomas failed to recapitulate this process. The data indicate the importance of cellular interactions with the basement membrane in the regulation of normal breast differentiation and, potentially, its loss in neoplasia. Purpose: Our purpose was to use this assay to investigate the role of the putative metastasis suppresser gene nm23-H1 in mammary development and differentiation. Methods: The metastatic human breast carcinoma cell line MDA-MB-435, clones transfected with a control pCMVBamneo vector, and clones transfected with pCMVBamneo vector containing nm23-H1 complementary DNA (the latter of which exhibited a substantial reduction in spontaneous metastatic potential in vivo) were cultured within a reconstituted basement membrane. Clones were examined for formation of acinus-like spheres, deposition of basement membrane components, production of sialomucin, polarization, and growth arrest. Results: In contrast to the parental cell line and control transfectants, MDA-MB-435 breast carcinoma cells overexpressing Nm23-H1 protein regained several aspects of the normal phenotype within reconstituted basement membrane. Nm23-H1 protein-positive cells formed organized acinus-like spheres, deposited the basement membrane components type IV collagen and, to some extent, laminin to the outside of the spheres, expressed sialomucin, and growth arrested. Growth arrest of Nm23-H1 protein-positive cells was preceded by and correlated with formation of a basement membrane, suggesting a causal relationship. Conclusion: The data indicate a previously unidentified cause-and-effect relationship between nm23-H1 gene expression and morphological-biosynthetic-growth aspects of breast differentiation in this model system. Implications: While the basement membrane microenvironment is capable of directing the differentiation of normal human breast cells, neoplastic transformation abrogates this relationship, suggesting that intrinsic cellular events are also critical to this process. The data identify nm23-H1 gene expression as one of these events, suggesting an important role in the modulation of cellular responsiveness to the microenvironment. The data also identify previously unknown growth inhibitory effects of nm23-H1 gene overexpression. C1 UNIV COPENHAGEN,PANUM INST,DEPT MED ANAT A,COPENHAGEN N,DENMARK. DANISH CANC SOC,DIV CANC BIOL,DEPT TUMOR ENDOCRINOL,COPENHAGEN O,DENMARK. NCI,DIV CANC BIOL DIAG & CTR,PATHOL LAB,WOMENS CANC SECT,BETHESDA,MD 20892. RP HOWLETT, AR (reprint author), UNIV CALIF BERKELEY,LAWRENCE BERKELEY LAB,DIV LIFE SCI,BERKELEY,CA 94720, USA. FU NCI NIH HHS [U54 CA126552, R01 CA057621, R01 CA057621-07, R01 CA064786, R01 CA064786-04A1, U01 CA143233, U01 CA143233-01, U54 CA112970, U54 CA112970-01, U54 CA126552-01, U54 CA143836, U54 CA143836-01] NR 19 TC 124 Z9 129 U1 0 U2 4 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 DEC 21 PY 1994 VL 86 IS 24 BP 1838 EP 1844 DI 10.1093/jnci/86.24.1838 PG 7 WC Oncology SC Oncology GA PX380 UT WOS:A1994PX38000009 PM 7990158 ER PT J AU CASCIARI, JJ HOLLINGSHEAD, MG ALLEY, MC MAYO, JG MALSPEIS, L MIYAUCHI, S GREVER, MR WEINSTEIN, JN AF CASCIARI, JJ HOLLINGSHEAD, MG ALLEY, MC MAYO, JG MALSPEIS, L MIYAUCHI, S GREVER, MR WEINSTEIN, JN TI GROWTH AND CHEMOTHERAPEUTIC RESPONSE OF CELLS IN A HOLLOW-FIBER IN-VITRO SOLID TUMOR-MODEL SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID MULTICELLULAR SPHEROIDS; INVITRO; DRUGS; LINES; CULTURE; OXYGEN; ASSAY; CYTOTOXICITY; DEPENDENCE; TRANSPORT AB Background: Cancer treatments that appear promising in tissue culture are often less effective in solid tumors, in part because of the proliferative and microenvironmental heterogeneity that develops in these tumors as they grow. Heterogeneous tumor models are thus needed for drug screening. Purpose: Our goal was to develop and test for drug evaluation a solid tumor model based on cell growth inside biocompatible hollow fibers. Methods: Building on the experience of Hollingshead and co-workers with a sparse-cell, hollow-fiber tumor model, we tested six human tumor cell lines for in vitro growth inside 450-mu m internal-diameter polyvinylidine fluoride fibers and examined them histologically. Human SW620 colon carcinoma cells grown in hollow fibers were also examined using electron microscopy, and their doxorubicin sensitivity was assessed. A colorimetric assay based on sulforhodamine B was adopted to replace the more cumbersome clonogenic cell survival assay. Results: Five of the human tumor cell lines tested grew to confluence, forming heterogeneous in vitro tumors with subpopulations of viable and necrotic cells. For SW620 hollow-fiber tumors, maximum viable cell populations in excess of 10(8) cells/ml were obtained after 8 days of growth. This viable cell density remained roughly constant for 3-4 days, permitting dose-response experiments over this time interval. Tumor cells in hollow fibers were much more resistant to a 4-hour doxorubicin exposure than were tumor cells in monolayers: LC(50) values (i.e., the drug concentrations at which the plating efficiency equals one-half the plating efficiency of untreated cells) of 3.5 mu M and 0.16 mu M were obtained for hollow-fiber tumors and monolayers, respectively. LC(50) values decreased when drug exposure time was increased. Results from the colorimetric assay were in agreement with those from the clonogenic assay. Conclusion: The successful growth of tumor cells to confluence in hollow fibers and the feasibility of performing in vitro drug dose-response experiments with a relatively easy colorimetric assay demonstrate the potential of the hollow-fiber solid tumor model as a tool for experimental therapeutic research. Implication: Hollow-fiber solid tumors may prove useful for experimental drug evaluation. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,FREDERICK,MD 21702. HOKKAIDO UNIV,FAC PHARMACEUT SCI,DEPT BIOPHYS CHEM,SAPPORO,HOKKAIDO 060,JAPAN. NR 29 TC 57 Z9 59 U1 0 U2 4 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 DEC 21 PY 1994 VL 86 IS 24 BP 1846 EP 1852 DI 10.1093/jnci/86.24.1846 PG 7 WC Oncology SC Oncology GA PX380 UT WOS:A1994PX38000010 PM 7990159 ER PT J AU VANOSDOL, WW MYERS, TG PAULL, KD KOHN, KW WEINSTEIN, JN AF VANOSDOL, WW MYERS, TG PAULL, KD KOHN, KW WEINSTEIN, JN TI USE OF THE KOHONEN SELF-ORGANIZING MAP TO STUDY THE MECHANISMS OF ACTION OF CHEMOTHERAPEUTIC-AGENTS SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID DIFFERENTIAL CYTOTOXICITY DATA; TUBULIN AB Background: Many natural and synthetic compounds might prove to be effective in cancer chemotherapy. To identify potentially useful agents, the National Cancer Institute screens over 10 000 compounds annually against a panel of 60 distinct human tumor cell lines in vitro. This screening program generates large amounts of data that are organized into relational databases. Important questions concern the information content of the data and ways to extract that information. Previously, statistical techniques have revealed that compounds with similar patterns of activity against the 60 cell lines are often similar in structure and mechanism of action, Feed-forward, backpropagation neural networks have been trained on this type of data to predict broadly defined mechanisms of action of chemotherapeutic agents. Purpose and Method: In this report, we examine the information that can be extracted from the screening data by means of another type of neural network paradigm, the Kohonen self-organizing map. This is a topology-preserving function, obtained by unsupervised learning, that nonlinearly projects the high-dimensional activity patterns into two dimensions. Our dataset is almost identical to that used in the earlier neural network study. Results: The self-organizing maps we constructed have several important characteristics. 1) They partition the two-dimensional array into distinct regions, each of which is principally occupied by agents having the same broadly defined mechanism of action. 2) These regions can be resolved into distinct subregions that conform to plausible submechanisms and chemically defined subgroups of submechanism. 3) These results (and exceptions to them) are consistent with those obtained with the use of such deterministic measures of similarity among activity patterns as the Euclidean distance or Pearson correlation coefficient. Conclusions: Our results indicate that the activity patterns obtained from the screen contain detailed information about mechanism of action and its basis in chemical structure. The self-organizing map can be used to suggest the mechanism of action of compounds identified by the screen as potentially useful chemotherapeutic agents and to probe the biology of the cell lines in the cancer screen. Kohonen self-organizing maps, unlike the previously applied neural networks, preserve and reveal the relationships among compounds acting by similar mechanisms and therefore have the potential to identify compounds that act by novel cytotoxic mechanisms. C1 NCI,DIV CANC TREATMENT,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,INFORMAT TECHNOL BRANCH,BETHESDA,MD 20892. NR 18 TC 66 Z9 66 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 DEC 21 PY 1994 VL 86 IS 24 BP 1853 EP 1859 DI 10.1093/jnci/86.24.1853 PG 7 WC Oncology SC Oncology GA PX380 UT WOS:A1994PX38000011 PM 7990160 ER PT J AU TSAO, DHH GRUSCHUS, JM WANG, LH NIRENBERG, M FERRETTI, JA AF TSAO, DHH GRUSCHUS, JM WANG, LH NIRENBERG, M FERRETTI, JA TI ELONGATION OF HELIX-III OF THE NK-2 HOMEODOMAIN UPON BINDING TO DNA - A SECONDARY STRUCTURE STUDY BY NMR SO BIOCHEMISTRY LA English DT Article ID ANTENNAPEDIA HOMEODOMAIN; SOLVENT SUPPRESSION; CRYSTAL-STRUCTURE; H-1-NMR SPECTRA; SPECTROSCOPY; PROTEINS; COMPLEX; DOMAIN; SPECIFICITY; RESOLUTION AB The secondary structure of the homeodomain encoded by the NK-2 gene from Drosophila melanogaster, in both the free and DNA-bound states, was determined in solution using two- and three-dimensional (2D and 3D) NMR Spectroscopy. Proton and N-15 studies were carried out on a 77 amino acid residue protein that contains the homeodomain, which was synthesized in Escherichia coli. On the basis of NOE connectivities, vicinal coupling constants, and proton-deuterium exchange behavior, three helical segments were found that consist of homeodomain amino acid residues 10-22, 28-38, and 42-52 for the protein in the absence of DNA. The major structural differences between free NK-2 and other homeodomains are the increased internal mobility of the second helix and the shorter length of the third helix, also termed the recognition helix. Despite this shorter helix, NK-2 exhibits high-affinity binding to DNA compared to other homeodomains (k(D) = 2.0 x 10(-10) M; L.-H. Wang and M. Nirenberg, unpublished results). The formation of the complex of NK-2 with the duplex DNA (TGTGTCAAGTGGCTGT) significantly increases the thermal stability of the protein. The T-m increases from 25 degrees C (free NK-2) to >47 degrees C (DNA-bound NK-2). Also, a dramatic increase in the length of helix m is observed. In the absence of DNA, the DNA recognition helix is 11 amino acid residues long (residues 42-52), whereas in the presence of DNA, the length of this helix extends to 19 amino acids (residues 42-60). The exchange rates of the amide protons in the proton-deuterium exchange experiments are slower in general for the DNA-bound protein than for the free NK-2 homeodomain, which is indicative of a stable conformation for NK-2. A preliminary model of the unbound NK-2 tertiary structure is presented. C1 NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. NHLBI,BIOCHEM GENET LAB,BETHESDA,MD 20892. NR 36 TC 65 Z9 65 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA PO BOX 57136, WASHINGTON, DC 20037-0136 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 20 PY 1994 VL 33 IS 50 BP 15053 EP 15060 DI 10.1021/bi00254a014 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PY287 UT WOS:A1994PY28700014 PM 7999763 ER PT J AU PASCUALLEONE, A HALLETT, M AF PASCUALLEONE, A HALLETT, M TI INDUCTION OF ERRORS IN A DELAYED-RESPONSE TASK BY REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION OF THE DORSOLATERAL PREFRONTAL CORTEX SO NEUROREPORT LA English DT Article DE REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION; DELAYED RESPONSE TASK; DORSOLATERAL PREFRONTAL CORTEX; MOTOR CORTEX; HUMANS ID MEMORY; ORGANIZATION AB WE used repetitive transcranial magnetic stimulation to study the function of the dorsolateral frontal cortex in a delayed response task in 10 normal volunteers. Unilateral stimulation of right or left prefrontal cortex during the delay period between instruction and execution cues led to a significantly greater number of response errors than stimulation of motor cortex or in unstimulated trials. Repetitive transcranial stimulation of appropriate intensity and frequency seems to disrupt the function of mnemonic cells in the prefrontal cortex and is useful for the study of the role of the prefrontal cortex in short-term motor memory. C1 NINCDS,HUMAN MOTOR CONTROL SECT,MED NEUROL BRANCH,BETHESDA,MD 20892. UNIV VALENCIA,DEPT FISIOL,NEUROBIOL UNIT,VALENCIA,SPAIN. NR 21 TC 92 Z9 93 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD DEC 20 PY 1994 VL 5 IS 18 BP 2517 EP 2520 DI 10.1097/00001756-199412000-00028 PG 4 WC Neurosciences SC Neurosciences & Neurology GA QB547 UT WOS:A1994QB54700028 PM 7696593 ER PT J AU DASSO, M DIMITROV, S WOLFFE, AP AF DASSO, M DIMITROV, S WOLFFE, AP TI NUCLEAR ASSEMBLY IS INDEPENDENT OF LINKER HISTONES SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE NUCLEUS; CHROMATIN; XENOPUS ID VIRUS-40 DNA-REPLICATION; CELL-FREE-EXTRACT; XENOPUS EGGS; MITOTIC CHROMOSOMES; FORMATION INVITRO; POLYMERASE-ALPHA; CHROMATIN; PROTEIN; H1; TRANSCRIPTION AB The role of linker histones in the assembly of functional nuclei was examined with the use of a cell-free extract of Xenopus eggs that transforms condensed sperm chromatin into DNA replication-competent pronuclei. When linker histones were removed from the extract, the resultant pronuclei were indistinguishable from those formed in the complete extract. The assembly of functional nuclear membrane, nuclear lamina, and prereplication centers allowed identical DNA replication efficiencies. Thus, linker histones are not required for the assembly of morphologically normal nuclei capable of DNA replication. C1 NICHHD,MOLEC EMBRYOL LAB,MOLEC BIOL SECT,BETHESDA,MD 20892. RP DASSO, M (reprint author), NICHHD,MOLEC EMBRYOL LAB,CELL CYCLE REGULAT UNIT,BLDG 6,ROOM B1A-13,BETHESDA,MD 20892, USA. RI dimitrov, stefan/M-7697-2013; OI Dasso, Mary/0000-0002-5410-1371 NR 43 TC 64 Z9 66 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 20 PY 1994 VL 91 IS 26 BP 12477 EP 12481 DI 10.1073/pnas.91.26.12477 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PY294 UT WOS:A1994PY29400026 PM 7809061 ER PT J AU DRAGO, J GERFEN, CR LACHOWICZ, JE STEINER, H HOLLON, TR LOVE, PE OOI, GT GRINBERG, A LEE, EJ HUANG, SP BARTLETT, PF JOSE, PA SIBLEY, DR WESTPHAL, H AF DRAGO, J GERFEN, CR LACHOWICZ, JE STEINER, H HOLLON, TR LOVE, PE OOI, GT GRINBERG, A LEE, EJ HUANG, SP BARTLETT, PF JOSE, PA SIBLEY, DR WESTPHAL, H TI ALTERED STRIATAL FUNCTION IN A MUTANT MOUSE LACKING D-1A DOPAMINE-RECEPTORS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID C-FOS; LOCOMOTOR-ACTIVITY; STRIATOPALLIDAL NEURONS; INSITU HYBRIDIZATION; MATRIX COMPARTMENTS; NUCLEUS ACCUMBENS; GENE-EXPRESSION; STEM-CELLS; RAT-BRAIN; D1 AB Of the five known dopamine receptors, D-1A and D-2 represent the major subtypes expressed in the striatum of the adult brain. Within the striatum, these two subtypes are differentially distributed in the two main neuronal populations that provide direct and indirect pathways between the striatum and the output nuclei of the basal ganglia. Movement disorders, including Parkinson disease and various dystonias, are thought to result from imbalanced activity in these pathways. Dopamine regulates movement through its differential effects on D-1A receptors expressed by direct output neurons and D-2 receptors expressed by indirect output neurons. To further examine the interaction of D-1A and D-2 neuronal pathways in the striatum, we used homologous recombination to generate mutant mice lacking functional D-1A receptors (D-1A-/-) D-1a-/- mutants are growth retarded and die shortly after weaning age unless their diet is supplemented with hydrated food. With such treatment the mice gain weight and survive to adulthood. Neurologically, D-1A-/- mice exhibit normal coordination and locomotion, although they display a significant decrease in rearing behavior. Examination of the striatum revealed changes associated with the altered phenotype of these mutants. D-1A receptor binding was absent in striatal sections from D-1A-/- mice. Striatal neurons normally expressing functional D-1A receptors are formed and persist in adult homozygous mutants. Moreover, substance P mRNA, which is colocalized specifically in striatal neurons with D-1A receptors, is expressed at a reduced level. In contrast, levels of enkephalin mRNA, which is expressed in striatal neurons with D-2 receptors, are unaffected. These findings show that D-1A-/- mice exhibit selective functional alterations in the striatal neurons giving rise to the direct striatal output pathway. C1 NIMH,CELL BIOL LAB,BETHESDA,MD 20892. NINCDS,EXPTL THERAPEUT BRANCH,BETHESDA,MD 20892. NIDDKD,BETHESDA,MD 20892. WALTER & ELIZA HALL INST MED RES,MELBOURNE,VIC 3050,AUSTRALIA. GEORGETOWN UNIV,MED CTR,WASHINGTON,DC 20007. RP DRAGO, J (reprint author), NICHHD,MAMMALIAN GENES & DEV LAB,BLDG 6B,ROOM 211,BETHESDA,MD 20892, USA. RI Bartlett, Perry/F-3813-2012 NR 43 TC 278 Z9 279 U1 1 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 20 PY 1994 VL 91 IS 26 BP 12564 EP 12568 DI 10.1073/pnas.91.26.12564 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PY294 UT WOS:A1994PY29400044 PM 7809078 ER PT J AU KANNO, T FRANZOSO, G SIEBENLIST, U AF KANNO, T FRANZOSO, G SIEBENLIST, U TI HUMAN T-CELL LEUKEMIA-VIRUS TYPE-I TAX-PROTEIN-MEDIATED ACTIVATION OF NF-KAPPA-B FROM P100 (NF-KAPPA-B2)-INHIBITED CYTOPLASMIC RESERVOIRS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DNA-BINDING; ONCOPROTEIN BCL-3; PRECURSOR P105; HTLV-I; LOCALIZATION; ASSOCIATION; EXPRESSION; INHIBITION; COMPONENT; PRODUCT AB The human T-cell leukemia virus type I Tax protein transforms T cells through induced expression of many cellular genes, including those encoding the growth-related proteins interleukin 2 and the alpha chain of its receptor. Induction of these genes is mediated, at least in part, through Tax-dependent posttranslational activation of NF-kappa B, typically heterodimers of p50 (NF-kappa B1) and p65 (RelA). The preexisting NF-kappa B proteins are retained in the cytoplasm of cells by association with inhibitory ankyrin-motif-containing I kappa B proteins, primarily I kappa B-alpha but also including the precursor proteins p105 (NF-kappa B1) and p100 (NF-kappa B2). Here we demonstrate the existence of a previously undescribed multimeric cytoplasmic complex in which NF-kappa B diners are associated with the p100 inhibitor in a manner dependent on the precursor protein's ankyrin domain. We also demonstrate an antagonistic effect of the Tax protein on the cytoplasmic sequestration function of p100; this in turn leads to nuclear translocation of NF-kappa B dimers liberated from multimeric complexes. Tax may exert these effects through the physical association with p100. Tax also relieves the p100-mediated inhibition of DNA binding by p50-p65 heterodimers in vitro. The results demonstrate a mechanism by which Tax may activate NF-kappa B in T cells. C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. UNIV PADUA,COMPLESSO CONVENZIONATO OSPED,MICROBIOL SERV,I-35100 PADUA,ITALY. NR 22 TC 60 Z9 60 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 20 PY 1994 VL 91 IS 26 BP 12634 EP 12638 DI 10.1073/pnas.91.26.12634 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PY294 UT WOS:A1994PY29400058 PM 7809091 ER PT J AU WANG, ZE ZHENG, SC CORRY, DB DALTON, DK SEDER, RA REINER, SL LOCKSLEY, RM AF WANG, ZE ZHENG, SC CORRY, DB DALTON, DK SEDER, RA REINER, SL LOCKSLEY, RM TI INTERFERON-GAMMA-INDEPENDENT EFFECTS OF INTERLEUKIN-12 ADMINISTERED DURING ACUTE OR ESTABLISHED INFECTION DUE TO LEISHMANIA-MAJOR SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CELL-MEDIATED IMMUNITY; INTERLEUKIN 4; LEISHMANIASIS; CYTOKINES ID CELL STIMULATORY FACTOR; CD4+ T-CELLS; MURINE LEISHMANIASIS; MONOCLONAL-ANTIBODY; MICE; PROLIFERATION; INHIBITION; INDUCTION; CYTOKINE; SUBSETS AB Interleukin 12 (IL-12) is a powerful stimulus for the growth of activated T and natural killer cells, their generation of interferon gamma (IFN-gamma), and the differentiation of T helper type 1 (T-h1) effector cells from naive precursors in vitro. These activities are consistent with the capacity of exogenons IL-12 to heal otherwise susceptible BALB/c mice infected with the intramacrophage parasite Leishmania major. Using this characterized model of CD4 cell subset differentiation, we examined the immunologic effects of IL-12 administered either at the time of infection, when naive T cells are primed, or after 14 days of infection, by which time CD4(+) subset differentiation has occurred. Given with the inoculation of parasites, IL-12 induced IFN-gamma and IL-10 and markedly suppressed IL-4. Effects on IL-10 and IL-4 were comparable in mice with homozygous disruption of the IFN-gamma gene (IFN-gamma(0/0)), and suppression of IL-4 was unchanged by administration of neutralizing anti-IL-10 antibody. Induction of IFN-gamma and IL-10 mRNA by IL-12 also occurred in infected SCID mice. Given after day 14 of infection, however, IL-12 not only induced IFN-gamma and IL-10 but also induced IL-4 in normal and IFN-gamma(0/0) mice. These data demonstrate direct effects of IL-12 independent of IFN-gamma, IL-10, and IL-4 and demonstrate that the ineffectiveness of IL-12 administered following infection with L. major correlates with resistance of differentiated T-h2 cells to the IL-4-suppressing activity of IL-12. C1 UNIV CALIF SAN FRANCISCO,DEPT IMMUNOL MICROBIOL,SAN FRANCISCO,CA 94143. SYSTEMIX INC,PALO ALTO,CA 94304. NIAID,CLIN INVEST LAB,BETHESDA,MD 20892. RP WANG, ZE (reprint author), UNIV CALIF SAN FRANCISCO,DEPT MED,SAN FRANCISCO,CA 94143, USA. RI Dalton, Dyana/D-2460-2009 FU NHLBI NIH HHS [HL07185]; NIAID NIH HHS [AI26918] NR 32 TC 145 Z9 145 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 20 PY 1994 VL 91 IS 26 BP 12932 EP 12936 DI 10.1073/pnas.91.26.12932 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PY294 UT WOS:A1994PY29400119 PM 7809149 ER PT J AU CHERNEY, BW BHATIA, K TOSATO, G AF CHERNEY, BW BHATIA, K TOSATO, G TI A ROLE FOR DEREGULATED C-MYC EXPRESSION IN APOPTOSIS OF EPSTEIN-BARR VIRUS-IMMORTALIZED B-CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GROWTH-FACTOR; BURKITT-LYMPHOMA; MACROMOLECULAR-SYNTHESIS; DEATH; LINES; PROTOONCOGENES; INTERLEUKIN-6; MECHANISMS; CONVERSION; ARREST AB When deprived of autocrine growth factors, Epstein-Barr virus (EBV)-immortalized B cells stop growing and die. In this study, we show that death of EBV-immortalized cells deprived of autocrine growth factors occurred by apoptosis. Cycloheximide, a protein synthesis inhibitor, inhibited apoptosis, suggesting that de novo protein synthesis is required. Because p53, Bcl-2, and c-Myc were previously implicated in the induction or prevention of apoptosis in other systems, we assessed their possible involvement here. Unlike normal cells that respond to growth factor deprivation by down-regulating c-Myc expression, EBV-immortalized tells continued to express c-Myc, p53, and Bcl-2 at levels comparable to those measured prior to starvation. Consistent with data demonstrating that c-Myc expression is sufficient to drive quiescent cells into the cell cycle, autocrine growth factor-deprived EBV-immortalized cells did not undergo growth arrest but rather continued to proliferate until death, which occurred randomly throughout the cell cycle. In contrast to EBV-immortalized B cells, normal peripheral blood B cells activated in vitro with anti-CD40 monoclonal antibody and interleukin 4 rapidly down-regulated c-Myc expression and underwent growth arrest in response to growth factors and serum deprivation. These findings demonstrated that c-Myc expression is deregulated in EBV-immortalized cells. Addition of antisense oligonucleotides to c-Myc specifically promoted the survival of starved EBV-immortalized cells and suppressed growth of nonstarved EBV-immortalized cells. Thus, deregulated expression of c-Myc in EBV-immortalized cells promotes proliferation and apoptosis following autocrine growth factor deprivation. C1 NCI,PEDIAT ONCOL BRANCH,BETHESDA,MD 20892. RP CHERNEY, BW (reprint author), US FDA,CTR BIOL EVALUAT & RES,IMMUNOL LAB,BETHESDA,MD 20892, USA. NR 30 TC 43 Z9 43 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 20 PY 1994 VL 91 IS 26 BP 12967 EP 12971 DI 10.1073/pnas.91.26.12967 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PY294 UT WOS:A1994PY29400126 PM 7809156 ER PT J AU JAFFREY, SR COHEN, NA ROUAULT, TA KLAUSNER, RD SNYDER, SH AF JAFFREY, SR COHEN, NA ROUAULT, TA KLAUSNER, RD SNYDER, SH TI THE IRON-RESPONSIVE ELEMENT-BINDING PROTEIN - A TARGET FOR SYNAPTIC ACTIONS OF NITRIC-OXIDE SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE GLUTAMATE; N-METHYL-D-ASPARTATE; GMP; ACONITASE; FERRITIN ID FERRITIN MESSENGER-RNA; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; ADP-RIBOSYLATION; L-ARGININE; TRANSLATIONAL REGULATION; UNTRANSLATED REGION; S-NITROSYLATION; SULFUR CLUSTER; TUMOR-CELLS; RAT-BRAIN AB Molecular targets for the actions of nitric oxide (NO) have only been partially clarified. The dynamic properties of the iron-sulfur (Fe-S) cluster of the iron responsive-element binding protein (IRE-BP) suggested that it might serve as a target for NO produced in response to glutamatergic stimulation in neurons. In the present study, we demonstrate that N-methyl-D-aspartate, acting through NO, stimulates the RNA-binding function of the IRE-BP in brain slices while diminishing its aconitase activity. In addition, we demonstrate a selective localization of the IRE-BP in discrete neuronal structures, suggesting a potential role for this protein in the response of neurons to NO. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PHARMACOL & MOLEC SCI,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,BALTIMORE,MD 21205. NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. OI Cohen, Noam/0000-0002-9462-3932 FU NIDA NIH HHS [DA-00266, DA-00074]; NIMH NIH HHS [MH-18501] NR 43 TC 58 Z9 58 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 20 PY 1994 VL 91 IS 26 BP 12994 EP 12998 DI 10.1073/pnas.91.26.12994 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PY294 UT WOS:A1994PY29400132 PM 7809162 ER PT J AU KOSUGI, S SHENKER, A MORI, T AF KOSUGI, S SHENKER, A MORI, T TI CONSTITUTIVE ACTIVATION OF CYCLIC-AMP BUT NOT PHOSPHATIDYLINOSITOL SIGNALING CAUSED BY 4 MUTATIONS IN THE 6TH TRANSMEMBRANE HELIX OF THE HUMAN THYROTROPIN RECEPTOR SO FEBS LETTERS LA English DT Article DE DUAL SIGNALING; G PROTEIN; RECEPTOR ACTIVATION MECHANISM; GLYCOPROTEIN HORMONE RECEPTOR ID LUTEINIZING-HORMONE RECEPTOR; 3RD CYTOPLASMIC LOOP; TSH-RECEPTOR; PRECOCIOUS PUBERTY; PHOSPHOINOSITIDE; SUBSTITUTIONS; DISEASE; REGION; SITES; GENE AB Four different somatic mutations (F631C, T632I, D633E, and D633Y) in the putative 6th transmembrane helix of the human thyrotropin receptor (TSHR) were recently described in hyperfunctioning thyroid adenomas [Porcellini et al. (1994) J. Clin. Endocrinol. Metab. 79, 657-661]. We transiently expressed these mutant receptors in Cos-7 cells and measured [I-125]TSH binding, basal and TSH-stimulated cAMP production, and phosphatidylinositol hydrolysis. The concentration of receptors expressed at the cell surface was lower for the mutants than for the wild type (WT) TSHR. Compared to the WT, all four mutant receptors caused a marked increase in basal cAMP levels, but did not increase basal production of inositolphosphates. This suggests that autonomous thyroid function and adenoma formation may be related to constitutive activation of the cAMP pathway alone. A cluster of conserved residues at the base of the 6th transmembrane helix of the TSHR and other glycoprotein hormone receptors appears important for maintaining an inactive receptor conformation. C1 NIDDKD,METAB DIS BRANCH,BETHESDA,MD 20892. RP KOSUGI, S (reprint author), KYOTO UNIV,SCH MED,DEPT LAB MED,SAKYO KU,1ST CLIN RES BLDG,ROOM 223,54 KAWAHARA CHO,KYOTO 60601,JAPAN. NR 32 TC 40 Z9 40 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 DEC 19 PY 1994 VL 356 IS 2-3 BP 291 EP 294 DI 10.1016/0014-5793(94)01286-5 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA PY477 UT WOS:A1994PY47700032 PM 7805857 ER PT J AU HELLMICH, MR KENNISON, JA HAMPTON, LL BATTEY, JF AF HELLMICH, MR KENNISON, JA HAMPTON, LL BATTEY, JF TI CLONING AND CHARACTERIZATION OF THE DROSOPHILA-MELANOGASTER CDK5 HOMOLOG SO FEBS LETTERS LA English DT Article DE CDK5; CDNA; CYCLIN-DEPENDENT KINASE; DEVELOPMENT; DROSOPHILA ID CYCLIN-DEPENDENT KINASES; DIRECTED PROTEIN-KINASE; CELL-CYCLE; GENE; FAMILY; BRAIN; YEAST AB The D. melanogaster homolog of mammalian CDK5 has been cloned and its chromosomal location determined. The gene for Cdk5 consists of 4 exons separated by 3 short introns ranging in size from 61-160 bp. Northern blot analysis revealed a single mRNA of approximately 1.6 kb that is expressed at highest levels in the adult fly. The putative amino acid sequence for Drosophila Cdk5 predicts a protein with a mass of approximately 32 kDa that is 77% identical to its mammalian counter-parts. Drosophila Cdk5 gene is located in polytene chromosomal region 52BC of the right arm of chromosome 2. This study provides the framework for a molecular genetic analysis of CDK5 function. C1 NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892. RP HELLMICH, MR (reprint author), NCI,DIV CANC TREATMENT,BIOL CHEM LAB,DEV THERAPEUT PROGRAM,BLDG 37,ROOM 5D02,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 28 TC 16 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD DEC 19 PY 1994 VL 356 IS 2-3 BP 317 EP 321 DI 10.1016/0014-5793(94)01298-9 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA PY477 UT WOS:A1994PY47700039 PM 7805863 ER PT J AU DOSEMECI, A GOLLOP, N JAFFE, H AF DOSEMECI, A GOLLOP, N JAFFE, H TI IDENTIFICATION OF A MAJOR AUTOPHOSPHORYLATION SITE ON POSTSYNAPTIC DENSITY-ASSOCIATED CA2+/CALMODULIN-DEPENDENT PROTEIN-KINASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID LONG-TERM POTENTIATION; II MUTANT MICE; CA-2+ CALMODULIN; CA-2+-INDEPENDENT ACTIVITY; SEQUENCE-ANALYSIS; INHIBITION; PHOSPHORYLATION; EXPRESSION; FOREBRAIN; FRACTION AB One of the most abundant proteins in postsynaptic densities is identical or very similar to the ar subunit of the Ca2+/calmodulin-dependent protein kinase II. Autophosphorylation of this protein in isolated postsynaptic densities was studied under various conditions, following inhibition of endogenous phosphatase activity with microcystin-LR. Phosphorylation accompanied by a shift in the enzyme's electrophoretic mobility was observed upon incubation with Ca2+ and calmodulin at 37 degrees C. Brief incubation with Ca2+ and calmodulin at 0 degrees C resulted in a low level of phosphorylation and no change in mobility, Following this limited Ca2+-dependent phosphorylation, however, a high level of phosphorylation could be achieved in the absence of Ca2+, upon incubation at 37 degrees C. Comparison of reverse-phase HPLC phosphopeptide elution profiles obtained following phosphorylation at 37 degrees C, in the presence and absence of Ca2+, as described above, showed differences, suggesting that certain distinct sites may be phosphorylated under each condition, A major phosphopeptide peak, however, with the amino acid sequence Met-Leu-Thr(P)-Ile Asn-Pro Ser-Lys was identified under both conditions, This sequence is identical to the predicted sequence containing Thr-253 of the Ca2+/calmodulin-dependent protein kinase II, The results suggest that phosphorylation at Thr-253 requires an initial Ca2+-dependent phosphorylation, which may be at a different site, but does not depend on the continued presence of Ca2+ to proceed. The observed mode of regulation of autophosphorylation at Thr-253 appears to be unique to the postsynaptic density-associated enzyme. C1 NINCDS,NEUROCHEM LAB,PROTEIN & PEPTIDE SEQUENCING FACIL,BETHESDA,MD 20892. NHLBI,BIOCHEM GENET LAB,BETHESDA,MD 20892. RP DOSEMECI, A (reprint author), NINCDS,NEUROBIOL LAB,BLDG 36,RM 2A21,BETHESDA,MD 20892, USA. NR 32 TC 19 Z9 20 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 DEC 16 PY 1994 VL 269 IS 50 BP 31330 EP 31333 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PX303 UT WOS:A1994PX30300003 PM 7989295 ER PT J AU HUNYADY, L BOR, M BALLA, T CATT, KJ AF HUNYADY, L BOR, M BALLA, T CATT, KJ TI IDENTIFICATION OF A CYTOPLASMIC SER-THR-LEU MOTIF THAT DETERMINES AGONIST-INDUCED INTERNALIZATION OF THE AT(1) ANGIOTENSIN RECEPTOR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BETA-ADRENERGIC-RECEPTOR; II TYPE-1 RECEPTOR; MEDIATED ENDOCYTOSIS; POTENTIAL MECHANISM; PHEROMONE RECEPTOR; CARBOXYL-TERMINUS; MOLECULAR-CLONING; EXPRESSION; SEQUESTRATION; SUBTYPE AB The type 1 angiotensin II (AT(1)) receptor undergoes rapid endocytosis and down-regulation after agonist binding. In studies on the structural determinants of agonist-induced endocytosis, serial deletions in the cytoplasmic tail of the rat AT(1a) receptor showed that the carboxyl-terminal 22 amino acids are not necessary for its internalization. However, internalization was markedly impaired by the removal of one additional amino acid (Leu(337)) and was reduced by 95% after removal of Ser(335) and Thr(336). Single alanine replacements of amino acids in this region showed that individual substitutions of Thr(332), Ser(335), Thr(336), Leu(337), and Ser(338) caused moderate but significant impairment of the internalization rate, Replacement of both Ser(335) and Thr(336) with alanine residues further impaired the internalization rate, and triple alanine replacement of the Ser-Thr-Leu motif reduced internalization to almost the same extent as the corresponding tail deletion mutant. The Ser-Thr-Leu motif is highly conserved in mammalian AT(1) receptors but is mot present in the noninternalizing type 2 angiotensin II receptor. These data demonstrate that a serine/threonine-rich region including Leu(337) in the cytoplasmic tail of the AT(1) receptor is a major requirement for endocytosis of the hormone-receptor complex and support the concept that similar motifs in other G protein-coupled receptors are determinants of their agonist-induced internalization. C1 NICHHD,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892. SEMMELWEIS UNIV MED,SCH MED,DEPT PHYSIOL,H-1444 BUDAPEST,HUNGARY. OI Balla, Tamas/0000-0002-9077-3335 NR 39 TC 153 Z9 154 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 16 PY 1994 VL 269 IS 50 BP 31378 EP 31382 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PX303 UT WOS:A1994PX30300011 PM 7989302 ER PT J AU LENG, XH BLANCO, J TSAI, SY OZATO, K OMALLEY, BW TSAI, MJ AF LENG, XH BLANCO, J TSAI, SY OZATO, K OMALLEY, BW TSAI, MJ TI MECHANISMS FOR SYNERGISTIC ACTIVATION OF THYROID-HORMONE RECEPTOR AND RETINOID-X RECEPTOR ON DIFFERENT RESPONSE ELEMENTS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EMBRYONAL CARCINOMA-CELLS; CLASS-I GENES; ACID RECEPTOR; DNA-BINDING; TRANSCRIPTION FACTOR; NUCLEAR RECEPTORS; SIGNALING PATHWAYS; DIRECT REPEATS; VITAMIN-D; RXR AB The thyroid hormone receptors (TR) form heterodimers with the retinoid X receptors (RXR) and activate target genes through thyroid-responsive elements (TRE). Heterodimerization elevates the DNA binding efficiency and thus can result in functional synergism between TR and RXR. Here we demonstrate that DNA sequences dictate the cooperative activation between TR and RXR despite the high affinity binding of the heterodimer to those TREs. We provide evidence that the C-terminal activation domain of RXR can modulate the triiodothyronine (T-3) responsiveness of TR/RXR heterodimers on reporter genes without altering the DNA binding properties of the heterodimers. The modulation function of this relatively small region is under the control of specific TRE sequences and promoter context. These data indicate that this C-terminal region of RXR is likely involved in receptor-cellular factor(s) interactions. Finally, we propose that the synergistic activation by TR and RXR is achieved through elevated DNA binding and, dependent on the DNA sequence, the interaction of RXR with other transcription factors. C1 BAYLOR COLL MED,DEPT CELL BIOL,HOUSTON,TX 77030. NICHHD,MOLEC GROWTH REGULAT LAB,BETHESDA,MD 20892. NR 48 TC 49 Z9 49 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 16 PY 1994 VL 269 IS 50 BP 31436 EP 31442 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PX303 UT WOS:A1994PX30300020 PM 7989311 ER PT J AU SHIMURA, Y SHIMURA, H OHMORI, M IKUYAMA, S KOHN, LD AF SHIMURA, Y SHIMURA, H OHMORI, M IKUYAMA, S KOHN, LD TI IDENTIFICATION OF A NOVEL INSULIN-RESPONSIVE ELEMENT IN THE RAT THYROTROPIN RECEPTOR PROMOTER SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GROWTH FACTOR-I; NUCLEAR-PROTEIN; GENE-EXPRESSION; CELLS; DNA; AMPLIFICATION; TRANSCRIPTION; ENHANCER; BINDS AB By transfecting TSH receptor (TSHR)-chloramphenicol acetyltransferase (CAT) chimeras into FRTL-5 thyroid cells in the presence or absence of insulin, we identify an insulin-responsive element (IRE) between -220 and -190 bp of the TSHR 5'-flanking region. The region between -220 and -192 bp is footprinted by nuclear extracts from FRTL-5 cells and, coupled to a heterologous SV40-CAT chimera, an oligonucleotide containing the protected region induces insulin responsiveness in FRTL-5 cells. FRTL-5 cell nuclear extracts form two groups of protein-DNA complexes, A and B, in gel shift assays using an oligonucleotide having the protected sequence; mutation data indicate only the A complexes are increased by exposure of FRTL-5 cells to insulin; TSH can also increase A complex formation, but the TSH action is insulin-dependent. The nuclear factor(s) in FRTL-5 cells that interact with the TSHR IRE are distinct from thyroid transcription factor-2 (TTF-2), the insulin regulatory factor of the thyroglobulin promoter, as evidenced by the absence of competition in gel shift assays; there is no apparent sequence similarity of this region with other known IREs. The IRE is immediately upstream of a thyroid transcription factor-1 (TTF-1) binding site, -189 to -175 bp; mutation of the TTE-1 site causing a loss of TTE-1 activity also causes a loss of insulin responsiveness when the TSHR-CAT chimera at -220 bp is transfected into FRTL-5 cells and an altered IRE footprint by nuclear extracts, The TSHR appears, therefore, to contain a novel IRE whose activity depends at least in part on TTF-1, a thyroid-specific, homeodomain-containing transcription factor important both for thyroid-specific TSHR gene expression and TSH/cAMP autoregulation of the TSHR. RP SHIMURA, Y (reprint author), NIDDK,BIOCHEM & METAB LAB,CELL REGULAT SECT,BETHESDA,MD 20892, USA. NR 27 TC 32 Z9 32 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 DEC 16 PY 1994 VL 269 IS 50 BP 31908 EP 31914 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PX303 UT WOS:A1994PX30300088 PM 7989366 ER PT J AU RODRIGUEZ, IR MAZURUK, K SCHOEN, TJ CHADER, GJ AF RODRIGUEZ, IR MAZURUK, K SCHOEN, TJ CHADER, GJ TI STRUCTURAL-ANALYSIS OF THE HUMAN HYDROXYINDOLE-O-METHYLTRANSFERASE GENE - PRESENCE OF 2 DISTINCT PROMOTERS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CHICKEN PINEAL-GLAND; MELATONIN BIOSYNTHESIS; TRANSCRIPTION FACTORS; RETINA; BINDING; SITE; CREM; RAT; LOCALIZATION; ACTIVATION AB Hydroxyindole-O-methyltransferase (HIOMT) catalyzes the last step in the metabolic pathway that synthesizes sizes the hormone melatonin. We have found HIOMT mRNA present in small amounts in human retina and in relatively high abundance in the pineal gland, Two dis tinct 5' ends were found in human retina using a solid-phase 5'-rapid amplification of cDNA ends technique, The two 5' regions appear to originate from two distinct putative promoters, Although many similarities exist between the two promoters, they contain distinctive elements. Putative promoter A, for example, contains a recently discovered photoreceptor-conserved element (PCE-1, CAATTAAG) at -27 not found in promoter B, while promoter B contains an Apl site (ATGAGTCAA at -166 and an octamer site (ATGCAAT) at -59 not found in promoter A. The HIOMT messages are also alternatively spliced in between exons 6 and 8, generating three dis tinct messages, One of the alternatively spliced messages contains a line-1 repetitive element that is spliced into the mRNA precisely as exon 6. Importantly, the downstream open reading frame is not altered by any of these splicing combinations, The gene is approximately 35 kilobases long containing either 9 or 10 exons (including the line-1 element) depending on which promoter is active. Ah of the splice sites follow the GT/AG rule. The dual promoters and opportunities for alternative splicing suggest a variety of mechanisms for control of HIOMT expression and biological activity in different tissues not previously recognized. RP RODRIGUEZ, IR (reprint author), NEI,RETINAL CELL & MOLEC BIOL LAB,BLDG 6,RM 304,BETHESDA,MD 20892, USA. NR 34 TC 75 Z9 77 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 16 PY 1994 VL 269 IS 50 BP 31969 EP 31977 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PX303 UT WOS:A1994PX30300097 PM 7989373 ER PT J AU MELLENTINMICHELOTTI, J JOHN, S PENNIE, WD WILLIAMS, T HAGER, GL AF MELLENTINMICHELOTTI, J JOHN, S PENNIE, WD WILLIAMS, T HAGER, GL TI THE 5' ENHANCER OF THE MOUSE MAMMARY-TUMOR VIRUS LONG TERMINAL REPEAT CONTAINS A FUNCTIONAL AP-2 ELEMENT SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTION FACTOR AP-2; MULTIPLE REGULATORY ELEMENTS; NEGATIVE REGULATION; TRANSGENIC MICE; GENE-EXPRESSION; PROMOTER; BINDING; INVITRO; REGION; DNA AB The mouse mammary tumor virus (MMTV) retrovirus causes mammary adenocarcinomas in mice by proviral insertion near members of the wnt family of proto-oncogenes, leading to their deregulation and cellular transformation. The 5' end of the MMTV long terminal repeat (LTR) has been implicated in tissue-specific activation of these gems. In this study, we characterize an enhancer element (Ban2; -1075 to -978) at the 5' end of the MMTV LTR, We show that this enhancer is 8-fold more active in a murine mammary carcinoma cell fine (34i) than in a fibroblast cell line (NIH3T3), and is inactive in the liver carcinoma cell line HepG2. Mutagenesis of the enhancer reveals four cis-acting elements that are required for maximal activity, DNA-binding proteins that interact with each of the four elements have been identified, One of these factors, designated mp5, is either identical to, or closely related to, the transcription factor AP-2, The mp5/AP-2 DNA binding activity co-migrates with recombinant AP-2 and is supershifted by anti-AP-2 antibodies, We also show that the lack of enhancer activity in HepG2 cells results from the absence of AP-2 protein in these cells. Co-transfection of an AP-2 expression vector restores the activity of this enhancer in HepG2 cells, and requires an intact mp5-binding site. C1 NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 35 TC 20 Z9 20 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 DEC 16 PY 1994 VL 269 IS 50 BP 31983 EP 31990 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PX303 UT WOS:A1994PX30300099 PM 7989375 ER PT J AU BALLOU, WR DIGGS, CL LANDRY, S HALL, BF AF BALLOU, WR DIGGS, CL LANDRY, S HALL, BF TI MALARIA VACCINE RESEARCH SO SCIENCE LA English DT Letter C1 US AGCY INT DEV,MALARIA VACCINE DEV PROGRAM,WASHINGTON,DC 20523. NIAID,BETHESDA,MD 20892. RP BALLOU, WR (reprint author), WALTER REED ARMY INST RES,DEPT IMMUNOL,WASHINGTON,DC 20307, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD DEC 16 PY 1994 VL 266 IS 5192 BP 1792 EP 1792 DI 10.1126/science.7864993 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PX383 UT WOS:A1994PX38300006 PM 7864993 ER PT J AU WHELAN, EA SANDLER, DP ROOT, JL SMITH, KR WEINBERG, CR AF WHELAN, EA SANDLER, DP ROOT, JL SMITH, KR WEINBERG, CR TI MENSTRUAL-CYCLE PATTERNS AND RISK OF BREAST-CANCER SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE BREAST NEOPLASMS; MENSTRUAL CYCLE; PROSPECTIVE STUDIES; WOMEN ID RESTING HUMAN-BREAST; CELL TURNOVER; WOMEN; EPIDEMIOLOGY; PREVENTION; ESTROGENS; PROLACTIN; MENARCHE; DISEASE; AGE AB Menstrual cycle characteristics may reflect underlying endocrine patterns that influence the risk of breast cancer. Most previous studies of menstrual function and breast cancer risk have used retrospective reports of menstrual bleeding, which may be unreliable. To examine this association, the authors conducted a mail survey among 997 women who had recorded menstrual events prospectively over as many as 50 years, beginning in 1934. Compared with women with a median menstrual cycle length of 26-29 days, women who had cycles of extreme length at ages 25-29 years had a nearly twofold increased incidence of breast cancer (for a median cycle length of less than 26 days, adjusted relative risk (RR) = 1.9, 95% CI 0.9-4.1; for greater than or equal to 34 days, RR = 1.9, 95% CI 0.9-3.9). Statistical adjustment was made for age, family history of breast cancer, parity, age at menopause, age at first pregnancy, and Quetelet index (weight (kg)/height (m)(2)). Adjusting for age and other potential confounders and restricting the analysis to women who did not use hormones, women who experienced either a lesser (<150) or a greater (>350) cumulative number of cycles had an increased incidence of breast cancer (adjusted RR = 1.9, 95% CI 0.3-10.6, and RR = 1.8, 95% CI 0.5-6.0, respectively) compared with women who experienced 150-350 cycles. The findings are discussed in the context of current hormonal theories of breast cancer etiology. C1 NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC 27709. UNIV UTAH,COLL NURSING,TREMIN TRUST RES PROGRAM,SALT LAKE CITY,UT 84112. UNIV UTAH,DEPT FAMILY & CONSUMER STUDIES,SALT LAKE CITY,UT 84112. NIEHS,STAT & BIOMATH BRANCH,RES TRIANGLE PK,NC 27709. OI Sandler, Dale/0000-0002-6776-0018 FU NCI NIH HHS [R03 CA48908-01]; PHS HHS [MO1-R00064] NR 26 TC 60 Z9 61 U1 2 U2 5 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 15 PY 1994 VL 140 IS 12 BP 1081 EP 1090 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PY632 UT WOS:A1994PY63200002 PM 7998590 ER PT J AU DEHOVITZ, JA KELLY, P FELDMAN, J SIERRA, MF CLARKE, L BROMBERG, J WAN, JY VERMUND, SH LANDESMAN, S AF DEHOVITZ, JA KELLY, P FELDMAN, J SIERRA, MF CLARKE, L BROMBERG, J WAN, JY VERMUND, SH LANDESMAN, S TI SEXUALLY-TRANSMITTED DISEASES, SEXUAL-BEHAVIOR, AND COCAINE USE IN INNER-CITY WOMEN SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE COCAINE; HIV; SEX BEHAVIOR; SEXUALLY TRANSMITTED DISEASES; SUBSTANCE ABUSE; WOMEN ID UNITED-STATES; SYPHILIS; EPIDEMIOLOGY; INFECTIONS AB The prevalence of untreated sexually transmitted diseases (STDs) was assessed in a cohort of 372 sexually active inner-city women (92% black, 49% US-born) with no history of injection drug use who were recruited in Brooklyn, New York, in 1990 and 1991. The presence of STDs was assessed via culture, serologic analyses, and medical history. Sexual and drug-use histories were obtained, as was a urine sample for toxicologic analysis. Thirty-five percent of the women had at least one STD (27% Trichomonas vaginalis, 6.8% Chlamydia trachomatis, 5.2% syphilis, 2.4% human immunodeficiency virus (HIV), and 1.4% Neisseria gonorrhoeae). US-born women were more likely than foreign-born (96% Caribbean) women to have an STD (50% vs. 22%; p < 0.001). Among US-born women, 61% of crack and/or cocaine users had an STD as opposed to 34% of non-users (OR = 2.9, 95% CI 1.6-5.5). Recent crack cocaine use was the strongest predictor of syphilis infection (OR = 12.8, p = 0.019), and was reported by each of the seven HIV-positive women. This study, based on a large sample with laboratory confirmation of both STDs and drug use, documents that women who use crack cocaine are at substantially higher risk of contracting an STD than other women. STD/HIV prevention programs in inner cities should target US-born women, particularly crack cocaine users. C1 SUNY HLTH SCI CTR,DEPT MED,BROOKLYN,NY. SUNY HLTH SCI CTR,DEPT PATHOL,BROOKLYN,NY. UNIV MICHIGAN,SCH PUBL HLTH,DEPT BIOSTAT,ANN ARBOR,MI 48109. NIAID,DIV AIDS,BETHESDA,MD 20892. RP DEHOVITZ, JA (reprint author), SUNY HLTH SCI CTR,DEPT PREVENT MED & COMMUNITY HLTH,BOX 43,450 CLARKSON AVE,BROOKLYN,NY 11203, USA. OI Vermund, Sten/0000-0001-7289-8698 FU NIAID NIH HHS [N01-AI-95014, N01-AI-95015, R01-AI-31834-03] NR 24 TC 98 Z9 99 U1 1 U2 3 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 15 PY 1994 VL 140 IS 12 BP 1125 EP 1134 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PY632 UT WOS:A1994PY63200006 PM 7998594 ER PT J AU TAYLOR, JA WILCOX, AJ AF TAYLOR, JA WILCOX, AJ TI RISK OF MISCARRIAGE AND A COMMON VARIANT OF THE ESTROGEN-RECEPTOR GENE - REPLY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter RP TAYLOR, JA (reprint author), NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC 27709, USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER J EPIDEMIOLOGY PI BALTIMORE PA 624 N BROADWAY RM 225, BALTIMORE, MD 21205 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 15 PY 1994 VL 140 IS 12 BP 1145 EP 1145 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PY632 UT WOS:A1994PY63200011 ER PT J AU PARADIS, J CALIS, KA AF PARADIS, J CALIS, KA TI ZIDOVUDINE-ASSOCIATED MYOPATHY SO AMERICAN JOURNAL OF HOSPITAL PHARMACY LA English DT Letter ID MITOCHONDRIAL; THERAPY C1 NIH,WARREN G MAGNUSON CLIN CTR,DRUG INFORMAT SERV,BETHESDA,MD 20892. RP PARADIS, J (reprint author), WOODHAVEN INST PHARM,BALTIMORE,MD 21201, USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 SN 0002-9289 J9 AM J HOSP PHARM JI Am. J. Hosp. Pharm. PD DEC 15 PY 1994 VL 51 IS 24 BP 3026 EP 3028 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PX954 UT WOS:A1994PX95400005 PM 7856620 ER PT J AU BERG, K MULLICAN, C MAESTRI, N SHORE, D AF BERG, K MULLICAN, C MAESTRI, N SHORE, D TI PSYCHIATRIC GENETIC RESEARCH AT THE NATIONAL-INSTITUTE-OF-MENTAL-HEALTH SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE ASSOCIATION STUDIES; ETHICAL ISSUES; GENETIC EPIDEMIOLOGY; LINKAGE; PSYCHIATRIC GENETICS ID ALZHEIMERS-DISEASE; LINKAGE ANALYSIS; DISORDERS; LOCUS AB For some time it has been known through the results of family, twin, and adoption studies that heredity appears to play a significant causal role in many mental disorders, including schizophrenia, bipolar disorder, and other mood disorders, Alzheimer's Disease, panic disorder, obsessive compulsive disorder, autism, dyslexia, and Tourette's Syndrome, The precise patterns of inheritance of these complex disorders have not been determined, nor have the relevant genes been localized or cloned, Because the genetics are complex and because there is also clearly an environmental contribution to behavior, we expect the analysis of the genetics of mental illness to be arduous, and not quickly resolved, There are several compelling reasons to continue to focus our attention on uncovering the genetic factors for severe mental illness, Prominent among these are the implications for better treatment of mental disorders, The National Institute of Mental Health supports a wide range of studies on psychiatric genetic research. (C) 1994 Wiley-Liss, Inc. C1 NIMH,DIV CLIN TREATMENT RES,GENET RES PROGRAM,ROCKVILLE,MD 20857. NR 16 TC 4 Z9 4 U1 4 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD DEC 15 PY 1994 VL 54 IS 4 BP 295 EP 299 DI 10.1002/ajmg.1320540403 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA QF860 UT WOS:A1994QF86000002 PM 7726198 ER PT J AU GORDON, HW AF GORDON, HW TI HUMAN NEUROSCIENCE AT NATIONAL-INSTITUTE-ON-DRUG-ABUSE - IMPLICATIONS FOR GENETICS RESEARCH SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE SUBSTANCE ABUSE; VULNERABILITY; ADOPTION; TWIN; GENETICS ID DOPAMINE-D2 RECEPTOR GENE; SUBSTANCE-ABUSE; ALCOHOLISM; ASSOCIATION; ALLELES; LOCUS; TWINS AB It is becoming clear that there is a genetic component to drug abuse. Family studies, adoption studies, and critical twin studies have all pointed to some genetic vulnerability or risk, factors for an individual to abuse psychoactive drugs depending on certain psychopathologies in the biological parents and/or parents' own drug use. The question for the next generation of research at the National]institute on Drug Abuse (NIDA) is to apply the rapidly developing technology in molecular genetics in an effort to determine the candidate genes contributing to the risk. (C) 1994 Wiley-Liss, Inc. C1 NIDA,DIV EPIDEMIOL & PREVENT RES,ROCKVILLE,MD. NR 19 TC 7 Z9 7 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD DEC 15 PY 1994 VL 54 IS 4 BP 300 EP 303 DI 10.1002/ajmg.1320540404 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA QF860 UT WOS:A1994QF86000003 PM 7726199 ER PT J AU KARP, RW AF KARP, RW TI GENETIC-STUDIES IN ALCOHOL RESEARCH SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE ALCOHOLISM; LINKAGE; GENE MAPPING; ANIMAL BEHAVIOR; HUMAN GENETICS ID NONRESTRICTED ACCESS SITUATION; PRECURSOR PROTEIN GENE; II MUTANT MICE; RETINOIC ACID; LINKAGE ANALYSIS; DEVELOPMENTAL DEFECTS; TARGETED DISRUPTION; ALZHEIMERS-DISEASE; ETHANOL; HINDBRAIN AB The National Institute on Alcohol Abuse and Alcoholism (NIAAA) supports research to elucidate the specific genetic factors, now largely unknown, which underlie susceptibility to alcoholism and its medical complications (including fetal alcohol syndrome). Because of the genetic complexity and heterogeneity of alcoholism, identification of the multiple underlying factors will require the development of new study designs and methods of analysis of data from human families. While techniques of genetic analysis of animal behavioral traits (e.g., targeted gene disruption, quantitative trait locus (QTL) mapping) are more powerful than those applicable to humans (e.g., linkage and allelic association studies), the validation of animal behaviors as models of aspects of human alcoholism has been problematic, Newly developed methods for mapping and QTL influencing animal behavioral traits can not only permit analyses of human family data to be directly informed by the results of animal studies, but can also serve as a novel means of validating animal models of aspects of alcoholism. (C) 1994 Wiley-Liss, Inc. RP KARP, RW (reprint author), NIAAA,DIV BASIC RES,SUITE 402,6000 EXECUT BLVD,BETHESDA,MD 20892, USA. NR 55 TC 9 Z9 9 U1 2 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD DEC 15 PY 1994 VL 54 IS 4 BP 304 EP 308 DI 10.1002/ajmg.1320540405 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA QF860 UT WOS:A1994QF86000004 PM 7726200 ER PT J AU GERHARD, DS LABUDA, MC BLAND, SD ALLEN, C EGELAND, JA PAULS, DL AF GERHARD, DS LABUDA, MC BLAND, SD ALLEN, C EGELAND, JA PAULS, DL TI INITIAL REPORT OF A GENOME SEARCH FOR THE AFFECTIVE-DISORDER PREDISPOSITION GENE IN THE OLD-ORDER AMISH PEDIGREES - CHROMOSOME-1 AND CHROMOSOME-11 SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE MAJOR AFFECTIVE DISORDER; OLD ORDER AMISH; LINKAGE ANALYSIS; CHROMOSOME 1; CHROMOSOME 11 ID BIPOLAR AFFECTIVE-DISORDERS; LINKAGE MAP; PROTO-ONCOGENE; DNA MARKERS; SHORT ARM; LOCALIZATION; ILLNESS; REGION; TRANSLOCATION; CONSTRUCTION AB Family data have suggested that some forms of major affective disorder are genetic. Certain of the Old Order Amish pedigrees have a familial form of the disease. In this report we present the results of genetic analyses under autosomal dominant mode of transmission with reduced penetrance and three different disease hierarchies. The pedigrees were genotyped with 28 markers from chromosome 1 and 23 markers from chromesomes 11. None of the markers result in a significantly positive led score. (C) 1994 Wiley-Liss, Inc. C1 WASHINGTON UNIV,SCH MED,DEPT PSYCHIAT,ST LOUIS,MO 63110. NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. UNIV MIAMI,SCH MED,DEPT PSYCHIAT,MIAMI,FL 33152. YALE UNIV,SCH MED,CTR CHILD STUDY,NEW HAVEN,CT. YALE UNIV,SCH MED,DEPT GENET,NEW HAVEN,CT 06510. YALE UNIV,SCH MED,DEPT PSYCHOL,NEW HAVEN,CT. RP GERHARD, DS (reprint author), WASHINGTON UNIV,SCH MED,DEPT GENET,660 S EUCLID AVE,ST LOUIS,MO 63110, USA. FU NCI NIH HHS [CA26854]; NIMH NIH HHS [MH28287, MH00508] NR 49 TC 8 Z9 8 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD DEC 15 PY 1994 VL 54 IS 4 BP 398 EP 404 DI 10.1002/ajmg.1320540421 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA QF860 UT WOS:A1994QF86000020 PM 7726215 ER PT J AU YANNUZZI, LA SORENSON, JA SOBEL, RS DALY, JR DEROSA, JT SEDDON, JM GRAGOUDAS, ES PULIAFITO, CA GELLES, E GONET, R BURTON, TC CULVER, J METZGER, K KALBFLEISCH, N ZARLING, D FARBER, MD BLAIR, N STELMACK, T AXELROD, A WAITR, SE CROSS, A ROLNICK, C FLOM, T HALLER, J PUSIN, S CASSEL, G APPLEGATE, CA SEIGEL, D SPERDUTO, RD HILLER, R MOWERY, R CHEW, E TAMBOLI, A DUNN, M SHAMBAN, K LENTO, D AF YANNUZZI, LA SORENSON, JA SOBEL, RS DALY, JR DEROSA, JT SEDDON, JM GRAGOUDAS, ES PULIAFITO, CA GELLES, E GONET, R BURTON, TC CULVER, J METZGER, K KALBFLEISCH, N ZARLING, D FARBER, MD BLAIR, N STELMACK, T AXELROD, A WAITR, SE CROSS, A ROLNICK, C FLOM, T HALLER, J PUSIN, S CASSEL, G APPLEGATE, CA SEIGEL, D SPERDUTO, RD HILLER, R MOWERY, R CHEW, E TAMBOLI, A DUNN, M SHAMBAN, K LENTO, D TI RISK-FACTORS FOR IDIOPATHIC MACULAR HOLES SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID FELLOW EYES; BREAKS AB PURPOSE: A case-control study was conducted to identify possible risk factors for idiopathic macular holes. METHODS: One hundred ninety-eight patients with idiopathic macular holes and 1,023 control subjects were identified at five clinical centers, Data were obtained through interviews, clinical examinations, and laboratory analyses of blood specimens. RESULTS: One hundred forty-three (72%) affected patients were women. Very few of a broad array of possible risk factors were statistically significant. In a logistic regression model that included both genders, higher plasma fibrinogen levels (P = .0007) and a history of glaucoma (P = .04) were associated with an increased risk of idiopathic macular holes. When the same model was used for women, with estrogen use and parity added as variables, a higher fibrinogen level (P = .002) was positively associated, and estrogen use (P = .04) was negatively associated with risk of macular holes. CONCLUSIONS: Of the two factors that stood out as possible risk factors for idiopathic macular holes, the increased risk for women has long been recognized. The association with fibrinogen level was unexpected, and it is unclear whether this is a chance finding or whether higher levels of fibrinogen can increase susceptibility to the forces of vitreous traction, perhaps by compromising the macular blood supply or by some yet unexplained mechanism. C1 NEI,BIOMETRY & EPIDEMIOL PROGRAM,BETHESDA,MD 20892. MANHATTAN EYE EAR & THROAT HOSP,NEW YORK,NY 10021. HARVARD UNIV,MASSACHUSETTS EYE & EAR INFIRM,SCH MED,BOSTON,MA. MED COLL WISCONSIN,MILWAUKEE,WI 53226. UNIV ILLINOIS,CHICAGO,IL. JOHNS HOPKINS UNIV HOSP,WILMER OPHTHALMOL INST,BALTIMORE,MD 21205. ORKAND CORP,COORDINATING CTR,SILVER SPRING,MD. PHOTOG READING CTR,BOSTON,MA. NR 20 TC 45 Z9 46 U1 0 U2 0 PU OPHTHALMIC PUBL CO PI CHICAGO PA 77 WEST WACKER DR, STE 660, CHICAGO, IL 60601 SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD DEC 15 PY 1994 VL 118 IS 6 BP 754 EP 761 PG 8 WC Ophthalmology SC Ophthalmology GA PW189 UT WOS:A1994PW18900009 ER PT J AU CHAISSON, RE BENSON, CA DUBE, MP HEIFETS, LB KORVICK, JA ELKIN, S SMITH, T CRAFT, JC SATTLER, FR STOOL, EW MACGREGOR, RR BUEHNER, T WU, AW BARNES, GL BECKER, R URBANSKI, P RICHARDSON, W HAFNER, R DIXON, D FEIGAL, DW DELLERSON, M GUPTA, S HENRY, D SCHLAGER, S AF CHAISSON, RE BENSON, CA DUBE, MP HEIFETS, LB KORVICK, JA ELKIN, S SMITH, T CRAFT, JC SATTLER, FR STOOL, EW MACGREGOR, RR BUEHNER, T WU, AW BARNES, GL BECKER, R URBANSKI, P RICHARDSON, W HAFNER, R DIXON, D FEIGAL, DW DELLERSON, M GUPTA, S HENRY, D SCHLAGER, S TI CLARITHROMYCIN THERAPY FOR BACTEREMIC MYCOBACTERIUM-AVIUM COMPLEX DISEASE - A RANDOMIZED, DOUBLE-BLIND, DOSE-RANGING STUDY IN PATIENTS WITH AIDS SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE MYCOBACTERIUM AVIUM COMPLEX; MYCOBACTERIUM AVIUM INTRACELLULARE INFECTION; CLARITHROMYCIN; ACQUIRED IMMUNODEFICIENCY SYNDROME; DOSE RESPONSE RELATIONSHIP, DRUG ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; IMMUNE-DEFICIENCY-SYNDROME; INTRACELLULARE BACTEREMIA; NATURAL-HISTORY; INFECTION; CLOFAZIMINE; ETHAMBUTOL; VIRUS; CIPROFLOXACIN; AZITHROMYCIN AB Objective: To determine the antimicrobial activity and tolerability of clarithromycin for treating bacteremic Mycobacterium avium complex disease in patients with the acquired immunodeficiency syndrome (AIDS). Design: A randomized, double-blind, dose-ranging study. Setting: Outpatient clinics. Patients: 154 patients with human immunodeficiency virus (HIV) infection and blood cultures positive for M. avium complex who had symptomatic disease. Interventions: Random assignment to clarithromycin at dosages of 500 mg, 1000 mg, or 2000 mg twice daily for 12 weeks. Main Outcome Measure: Median number of colony-forming units of M. avium complex per milliliter of blood. Results: Clarithromycin decreased mycobacterial CFUs from 2.7 to 2.8 log 10/mL of blood at baseline to less than 0 log 10/mL during follow-up (P < 0.0001). After 2 weeks, patients receiving 500 mg twice daily were less likely to be culture negative than were patients receiving 1000 or 2000 mg twice daily (11% compared with 33% or 29%; P = 0.08). At 6 weeks, the median number of CFUs of M. avium complex/mL of blood was 0 or 1 for all three groups. Clarithromycin-resistant isolates of M. avium complex developed in 46% of patients at a median of 16 weeks. Median survival was longer in patients assigned to 500 mg twice daily (median, 249 days) than in patients assigned to 1000 mg or 2000 mg. Death in the first 12 weeks was lowest in the 500-mg group (P = 0.007). Conclusions: Clarithromycin therapy acutely decreased M. avium complex bacteremia in patients with HIV infection by more than 99%. Clarithromycin, 500 mg twice daily, was well tolerated and associated with better survival. Emergence of clarithromycin-resistant organisms was an important problem. C1 RUSH MED COLL,RUSH PRESBYTERIAN ST LUKES MED CTR,INFECT DIS SECT,CHICAGO,IL 60612. UNIV SO CALIF,LOS ANGELES CTY MED CTR,LOS ANGELES,CA 90033. NATL JEWISH CTR IMMUNOL & RESP MED,DENVER,CO 80206. ABBOTT LABS,ABBOTT PK,IL 60064. NIAID,BETHESDA,MD 20892. BIOPHARM INC,PHILADELPHIA,PA. AMI PK PLAZA HOSP,HOUSTON,TX. UNIV PENN,PHILADELPHIA,PA 19104. SAN DIEGO COMMUNITY RES GRP,SAN DIEGO,CA. UNIV CALIF SAN DIEGO,SAN DIEGO,CA 92103. RP CHAISSON, RE (reprint author), JOHNS HOPKINS UNIV,SCH MED,AIDS SERV,600 N WOLFE ST,CARNEGIE 292,BALTIMORE,MD 21287, USA. FU NCRR NIH HHS [5M01RR00722] NR 28 TC 225 Z9 228 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 DEC 15 PY 1994 VL 121 IS 12 BP 905 EP 911 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA PW083 UT WOS:A1994PW08300001 PM 7978715 ER PT J AU FUKUDA, K STRAUS, SE HICKIE, I SHARPE, MC DOBBINS, JG KOMAROFF, A SCHLUEDERBERG, A JONES, JF LLOYD, AR WESSELY, S GANTZ, NM HOLMES, GP BUCHWALD, D ABBEY, S REST, J LEVY, JA JOLSON, H PETERSON, DL VERCOULEN, JHMM TIRELLI, U EVENGARD, B NATELSON, BH STEELE, L REYES, M REEVES, WC AF FUKUDA, K STRAUS, SE HICKIE, I SHARPE, MC DOBBINS, JG KOMAROFF, A SCHLUEDERBERG, A JONES, JF LLOYD, AR WESSELY, S GANTZ, NM HOLMES, GP BUCHWALD, D ABBEY, S REST, J LEVY, JA JOLSON, H PETERSON, DL VERCOULEN, JHMM TIRELLI, U EVENGARD, B NATELSON, BH STEELE, L REYES, M REEVES, WC TI THE CHRONIC FATIGUE SYNDROME - A COMPREHENSIVE APPROACH TO ITS DEFINITION AND STUDY SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID DIAGNOSTIC INTERVIEW; MENTAL-HEALTH; FOLLOW-UP; EPIDEMIOLOGY; PREVALENCE; POPULATION; INSTRUMENT; DISORDERS; HISTORY; SCALE AB The complexities of the chronic fatigue syndrome and the methodologic problems associated with its study indicate the need for a comprehensive, systematic, and integrated approach to the evaluation, classification, and study of persons with this condition and other fatiguing illnesses. We propose a conceptual framework and a set of guidelines that provide such an approach. Our guidelines include recommendations for the clinical evaluation of fatigued persons, a revised case definition of the chronic fatigue syndrome, and a strategy for subgrouping fatigued persons in formal investigations. C1 NIH,CLIN INVEST LAB,BETHESDA,MD 20892. PRINCE HENRY HOSP,SYDNEY,NSW,AUSTRALIA. UNIV NEW S WALES,SYDNEY,NSW,AUSTRALIA. UNIV OXFORD,WARNEFORD HOSP,DEPT PSYCHIAT,OXFORD OX3 7JX,ENGLAND. BRIGHAM & WOMENS HOSP,DIV GEN MED,BOSTON,MA 02115. HARVARD UNIV,BOSTON,MA 02115. UNIV COLORADO,DENVER,CO 80202. UNIV LONDON KINGS COLL,SCH MED & DENT,LONDON WC2R 2LS,ENGLAND. POLYCLIN MED CTR,HARRISBURG,PA. PENN STATE COLL MED,HARRISBURG,PA. TEXAS A&M UNIV,HLTH SCI CTR,TEMPLE,TX 76508. SCOTT & WHITE MEM HOSP & CLIN,TEMPLE,TX 76508. UNIV WASHINGTON,MED CTR,SEATTLE,WA 98195. UNIV TORONTO,TORONTO,ON,CANADA. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. US FDA,ROCKVILLE,MD 20857. LAKE TAHOE MED CTR,INCLINE VILLAGE,NV. UNIV NIJMEGEN HOSP,6500 HB NIJMEGEN,NETHERLANDS. CTR REG RIFERMINENTO ONCOL,AVIANO,ITALY. HUDDINGE UNIV HOSP,KAROLINSKA INST,STOCKHOLM,SWEDEN. UNIV MED & DENT NEW JERSEY,NEW JERSEY MED SCH,NEWARK,NJ 07103. ALTA BATES COMMUNITY HOSP,BERKELEY,CA. RP FUKUDA, K (reprint author), CTR DIS CONTROL & PREVENT,NATL CTR INFECT DIS,DIV VIRAL & RICKETTSIAL DIS,MAILSTOP A15,ATLANTA,GA 30333, USA. RI Wessely, Simon/A-8713-2008; Vercoulen, J.H.M.M./L-4706-2015 NR 46 TC 2548 Z9 2639 U1 22 U2 121 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 DEC 15 PY 1994 VL 121 IS 12 BP 953 EP 959 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA PW083 UT WOS:A1994PW08300009 PM 7978722 ER PT J AU GOLDBERGER, M MASUR, H AF GOLDBERGER, M MASUR, H TI CLARITHROMYCIN THERAPY FOR MYCOBACTERIUM-AVIUM COMPLEX DISEASE IN PATIENTS WITH AIDS - POTENTIAL AND PROBLEMS SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; INFECTION; CIPROFLOXACIN; ETHAMBUTOL; RIFAMPIN; AMIKACIN; REGIMEN C1 NIH,DEPT CRIT CARE MED,BETHESDA,MD 20892. US FDA,DIV ANTIVIRAL DRUGS,ROCKVILLE,MD 20852. NR 20 TC 10 Z9 10 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 DEC 15 PY 1994 VL 121 IS 12 BP 974 EP 976 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA PW083 UT WOS:A1994PW08300012 PM 7978725 ER PT J AU ROBERTS, BJ SHOAF, SE JEONG, KS SONG, BJ AF ROBERTS, BJ SHOAF, SE JEONG, KS SONG, BJ TI INDUCTION OF CYP2E1 IN LIVER, KIDNEY, BRAIN AND INTESTINE DURING CHRONIC ETHANOL ADMINISTRATION AND WITHDRAWAL - EVIDENCE THAT CYP2E1 POSSESSES A RAPID PHASE HALFLIFE OF 6 HOURS OR LESS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID BLOOD-ALCOHOL CONCENTRATIONS; NITROSODIMETHYLAMINE DEMETHYLASE; INDUCIBLE CYTOCHROME-P-450; N-NITROSODIMETHYLAMINE; EXPOSURE OCCURS; FAT DIET; RAT; 2E1; STABILIZATION; DEGRADATION AB Controversy exists as to whether the induction of CYP2E1 by ethanol occurs via increased protein synthesis or protein stabilization. To address these issues in vivo, we chronically administered ethanol to rats and determined levels of immunoreactive CYP2E1 in liver, kidney, brain and upper gastro-intestinal tract (GI). Our data shows that chronic ethanol administration induces hepatic (5-6-foId over pair-fed controls) and extra-hepatic CYP2E1, an effect which is strikingly absent 12 hours after ethanol withdrawal. No changes in CYP2E1 mRNA were observed at any time, suggesting these changes are mainly post-translational at a blood ethanol concentration of 0.15% w/v. Our experimental data indicates that CYP2E1 possesses a half-life of 6 hours or less in the liver and is rapidly degraded following the removal of ethanol. This pattern of CYP2E1 turnover was also observed in other tissues, suggestive of a similar mode of regulation. (C) 1994 Academic Press, Inc. C1 NIAAA,NEUROGENET LAB,ROCKVILLE,MD 20892. RP ROBERTS, BJ (reprint author), NIAAA,CLIN STUDIES LAB,ROCKVILLE,MD 20892, USA. NR 21 TC 77 Z9 81 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 15 PY 1994 VL 205 IS 2 BP 1064 EP 1071 DI 10.1006/bbrc.1994.2774 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PY706 UT WOS:A1994PY70600013 PM 7802633 ER PT J AU KALEBIC, T MASIERO, L ONISTO, M GARBISA, S AF KALEBIC, T MASIERO, L ONISTO, M GARBISA, S TI HIV-1 MODULATES THE EXPRESSION OF GELATINASE-A AND GELATINASE-B IN MONOCYTIC CELLS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; IV COLLAGENASE; BASEMENT-MEMBRANE; N-ACETYLCYSTEINE; METALLOPROTEINASES; FIBROBLASTS; INVASION; MATRIX AB The levels of mRNA of both gelatinases A and B were dramatically decreased in HIV-infected cells, when compared to uninfected cells. The expression of gelatinase A in HIV-infected cells was selectively increased by tumor necrosis factor (TNF alpha) while the expression of gelatinase B was not affected. In contrast, in uninfected cells TNF alpha down regulated gelatinase B mRNA level, without affecting the gelatinase A. N-acethylcysteine (NAC) increased the levels of mRNA of both gelatinases. The conditioned media from HIV-infected and uninfected cells had comparable level of secreted gelatinase A protein. These data suggest that in monocytic cells different regulatory pathways control gelatinases A and B and that HIV could modulate in vivo the expression of these proteolytic enzymes, critically involved in regulation of invasion of basement membrane. (C) 1994 Academic Press, Inc. C1 UNIV PADUA,INST HISTOL & GEN EMBRYOL,PADUA,ITALY. RP KALEBIC, T (reprint author), NCI,PEDIAT BRANCH,ONCOL MOLEC SECT,BLDG 10,13N240,BETHESDA,MD 20892, USA. NR 22 TC 8 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 15 PY 1994 VL 205 IS 2 BP 1243 EP 1249 DI 10.1006/bbrc.1994.2798 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PY706 UT WOS:A1994PY70600037 PM 7802656 ER PT J AU SETH, P AF SETH, P TI MECHANISM OF ADENOVIRUS-MEDIATED ENDOSOME LYSIS - ROLE OF THE INTACT ADENOVIRUS CAPSID STRUCTURE SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID EPIDERMAL GROWTH-FACTOR; CELL-MEMBRANE PERMEABILITY; PENTON BASE; KB-CELLS; PH; TOXICITY; PROTEINS; INTERNALIZATION; ENHANCEMENT; PARTICLES AB Adenoviruses have been previously shown to enhance the delivery of many ligands including proteins and plasmid DNAs to the cells. The key biochemical step during this process is the ability of adenovirus to disrupt (lyse) the endosome membrane releasing the co-internalized virus and the other ligands into the cytosol (Seth et al, 1986, In: Adenovirus attachment and entry into cells, pp 191-195, American Society for Microbiology, Washington, D.C.). To understand the role of the adenovirus proteins involved in the endosome lysis, it is further shown here that empty capsids of adenovirus also possess this membrane vesicle lytic activity; though the activity is about 5 -times lower than the adenovirus. Incubation of adenovirus with low concentration of ionic detergent or brief exposure to 45 degrees C destroyed this lytic activity without affecting the adenovirus binding to cell surface receptor, suggesting the lytic activity of adenovirus to be of enzymatic nature. However, exposing adenovirus to conditions that can disrupt adenovirus capsid structure such as heating at 65 degrees C, treating with 0.5% SDS, treating with different proteases, dialyzing against no glycerol buffer, treating with 6 M urea or with 10% pyridine, and sonication destroyed the adenovirus-associated lytic activity. Results suggest the requirement of an intact capsid structure for adenovirus-mediated lysis of the endosome. (C) 1994 Academic Press, Inc. C1 NCI,DIV CANC BIOL & DIAG,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 28 TC 41 Z9 42 U1 1 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 15 PY 1994 VL 205 IS 2 BP 1318 EP 1324 DI 10.1006/bbrc.1994.2809 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PY706 UT WOS:A1994PY70600048 PM 7802664 ER PT J AU KNABLE, MB HYDE, TM HERMAN, MM CARTER, JM BIGELOW, L KLEINMAN, JE AF KNABLE, MB HYDE, TM HERMAN, MM CARTER, JM BIGELOW, L KLEINMAN, JE TI QUANTITATIVE AUTORADIOGRAPHY OF DOPAMINE-D1 RECEPTORS, D2 RECEPTORS, AND DOPAMINE UPTAKE SITES IN POSTMORTEM STRIATAL SPECIMENS FROM SCHIZOPHRENIC-PATIENTS SO BIOLOGICAL PSYCHIATRY LA English DT Article DE SCHIZOPHRENIA; D1 RECEPTORS; D2 RECEPTORS; DOPAMINE UPTAKE SITES; SCH-23390; RACLOPRIDE; CFT; AUTORADIOGRAPHY ID POSITRON EMISSION TOMOGRAPHY; POST-MORTEM BRAIN; BASAL GANGLIA; RAT STRIATUM; BINDING; D1; ORGANIZATION; GENE; COMPARTMENTS; D1-DOPAMINE AB A number of previously published homogenate receptor binding studies have postulated that dopaminergic dysfunction in schizophrenia may be related to abnormalities in dopamine receptors, In this study, postmortem striatal specimens from patients with schizophrenia, normal controls, and psychiatric controls that had received neuroleptics were studied with quantitative autoradiography for dopamine receptors, Autoradiography with single concentrations of [H-3] - SCH 23390 for D1 receptors, [H-3] - raclopride for D2 receptors, and [H-3] - CFT for dopamine uptake sites failed to define significant differences between the study groups, [H-3] - CFT bound in a patchy distribution in the striatum that is believed to correspond to striosomal and matrix striatal compartments. There were no differences between groups when [H-3] - CFT binding density was examined in the striosomal and matrix compartments. There were also no differences between groups in the percentage of striatal area occupied by striosomal or matrix compartments as defined by [H-3] - CFT binding, We conclude that abnormalities of these dopamine receptor subtypes are probably not primary features of the schizophrenic syndrome in the brain collection examined, Previous reports of elevated D2 receptor binding in schizophrenia may have been related to drug treatment effects, Alternatively, the relatively high affinity of ligands used in previous studies for D4 receptors may explain the discrepancy in our findings, Unchanged [H-3] - CFT binding in the schizophrenic group also suggests that the density of mesostriatal neurornal terminals is not altered in schizophrenia, C1 OFF CHIEF MED EXAMINER DIST COLUMBIA,WASHINGTON,DC. RP KNABLE, MB (reprint author), NIMH,INTRAMURAL RES PROGRAM,CLIN BRAIN DISORDERS BRANCH,2700 MARTIN LUTHER KING JR AVE SE,WASHINGTON,DC 20032, USA. NR 46 TC 52 Z9 52 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiat. PD DEC 15 PY 1994 VL 36 IS 12 BP 827 EP 835 DI 10.1016/0006-3223(94)90593-2 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA PY929 UT WOS:A1994PY92900004 PM 7893846 ER PT J AU ORLIC, D BODINE, DM AF ORLIC, D BODINE, DM TI WHAT DEFINES A PLURIPOTENT HEMATOPOIETIC STEM-CELL (PHSC) - WILL THE REAL PHSC PLEASE STAND UP SO BLOOD LA English DT Editorial Material ID COLONY-FORMING CELLS; BONE-MARROW TRANSPLANTATION; MEDIATED GENE-TRANSFER; CFU-S CELL; REPOPULATING ABILITY; MOUSE; SEPARATION; EXPRESSION; 5-FLUOROURACIL; SPLEEN RP ORLIC, D (reprint author), NIH,NATL CTR HUMAN GENOME RES,GENE TRANSFER LAB,HEMATOPOIESIS SECT,BLDG 49,ROOM 3W16,BETHESDA,MD 20892, USA. NR 58 TC 103 Z9 103 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 DEC 15 PY 1994 VL 84 IS 12 BP 3991 EP 3994 PG 4 WC Hematology SC Hematology GA PX146 UT WOS:A1994PX14600001 PM 7994018 ER PT J AU LIU, JM BUCHWALD, M WALSH, CE YOUNG, NS AF LIU, JM BUCHWALD, M WALSH, CE YOUNG, NS TI FANCONI-ANEMIA AND NOVEL STRATEGIES FOR THERAPY SO BLOOD LA English DT Review ID DNA-CROSS-LINKING; BONE-MARROW TRANSPLANTATION; COMPLEMENTATION GROUP-A; UMBILICAL-CORD BLOOD; CELL GROWTH-FACTOR; COLONY-STIMULATING FACTOR; RIBOSOMAL-RNA GENES; GROUP-C GENE; MITOMYCIN-C; SUPEROXIDE-DISMUTASE C1 HOSP SICK CHILDREN,DEPT GENET,TORONTO M5G 1X8,ON,CANADA. RP LIU, JM (reprint author), NHLBI,HEMATOL BRANCH,BLDG 10,ROOM 7C103,BETHESDA,MD 20892, USA. NR 149 TC 123 Z9 123 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 DEC 15 PY 1994 VL 84 IS 12 BP 3995 EP 4007 PG 13 WC Hematology SC Hematology GA PX146 UT WOS:A1994PX14600002 PM 7994019 ER PT J AU XIAO, WH BENNETT, GJ AF XIAO, WH BENNETT, GJ TI MAGNESIUM SUPPRESSES NEUROPATHIC PAIN RESPONSES IN RATS VIA A SPINAL SITE OF ACTION SO BRAIN RESEARCH LA English DT Article DE ALLODYNIA; HYPERALGESIA; MAGNESIUM THERAPY; NEUROPATHIC PAIN; PERIPHERAL NEUROPATHY ID PERIPHERAL MONONEUROPATHY; EPILEPTIFORM ACTIVITY; HIPPOCAMPAL SLICES; NERVE INJURY; NEURONS; CHANNELS; HYPERALGESIA; CONVULSIONS; DEPRESSION; DISCHARGES AB We tested the ability of Mg2+ therapy to block the heat-hyperalgesia, mechano-allodynia and mechano-hyperalgesia that are seen in rats with an experimental painful peripheral neuropathy (the CCI model of Bennett and Xie [4]). Systemic Mg2+ (magnesium sulfate, 600 mg/kg, s.c.) significantly reduced heat-hyperalgesia and mechano-allodynia for 2-24 h post-injection, but had no effect on mechano-hyperalgesia. Intrathecal (i.t.) injections of Mg2+ (185-750 mu g) at the level of the lumbar spinal cord significantly reduced heat-hyperalgesia, but perineural application (750 and 7,000 mu g) to the site of nerve injury had no effect. Neither s.c. nor i.t. Mg2+ had any effect on the responses from the control, sham-operated side. We conclude that Mg2+ has a spinal site of action. Mg2+ therapy may be of limited use in the treatment of human painful peripheral neuropathy. C1 NIDR,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD 20892. NR 29 TC 69 Z9 72 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 DEC 15 PY 1994 VL 666 IS 2 BP 168 EP 172 DI 10.1016/0006-8993(94)90768-4 PG 5 WC Neurosciences SC Neurosciences & Neurology GA PW803 UT WOS:A1994PW80300002 PM 7882026 ER PT J AU WHITE, RL SCHWARTZENTRUBER, DJ GULERIA, A MACFARLANE, MP WHITE, DE TUCKER, E ROSENBERG, SA AF WHITE, RL SCHWARTZENTRUBER, DJ GULERIA, A MACFARLANE, MP WHITE, DE TUCKER, E ROSENBERG, SA TI CARDIOPULMONARY TOXICITY OF TREATMENT WITH HIGH-DOSE INTERLEUKIN-2 IN 199 CONSECUTIVE PATIENTS WITH METASTATIC MELANOMA OR RENAL-CELL CARCINOMA SO CANCER LA English DT Article DE IMMUNOTHERAPY; CARDIOPULMONARY TOXICITY; RENAL CELL CARCINOMA; HYPOTENSION; INTERLEUKIN-2; MELANOMA; ARRHYTHMIA; INTUBATION ID TUMOR-NECROSIS-FACTOR; ACTIVATED KILLER-CELLS; PROSPECTIVE RANDOMIZED TRIAL; BLOOD MONONUCLEAR-CELLS; RECOMBINANT INTERLEUKIN-2; INFILTRATING LYMPHOCYTES; CANCER-PATIENTS; VASCULAR-PERMEABILITY; HEMODYNAMIC-CHANGES; INTERFERON-GAMMA AB Background. Administration of recombinant interleukin-2 (rIL-2) can mediate tumor regression in patients with metastatic melanoma and renal cell carcinoma. In response to recent FDA approval of high dose rIL-2 for use in renal cell carcinoma, the authors recent experience with the cardiopulmonary toxicity associated with high dose IL-2 therapy is reviewed. Methods. The treatment courses of all patients receiving high dose intravenous holus rIL-2 from January, 1988, until December, 1992, were evaluated for cardiopulmonary toxicity. Results. One hundred ninety-nine patients received 310 courses of treatment. There were no treatment-related deaths. Respiratory distress occurred in 3.2% of the courses, requiring intubation in one patient. Three obtunded patients were endotracheally intubated for airway control. Arrhythmias occurred in 6% of the courses (18 patients) with hypotension developing in two of the 199 patients as a result. Eleven of these patients were retreated and recurrent atrial fibrillation developed in two. One episode of significant ventricular tachycardia was noted. Hypotension occurred in 53% of courses; no patients developed hypotension unresponsive to vasopressors. There were no myocardial infarctions; however, 2.5% of patients experienced elevated creatine phosphokinase levels associated with elevated MB isoenzymes attributed to cardiac toxicity. Only one of these patients developed symptoms. Response rates of 19.6% and 15.7% were noted in patients with renal cell carcinoma and melanoma, respectively. Hypotension requiring vasopressors was associated with a significantly improved rate of response in patients with melanoma compared with patients not requiring vasopressors (23.2% vs. 6.5%, P-2 = 0.037). Conclusions. Although high dose intravenous rIL-2 therapy can be associated with cardiopulmonary toxicity, toxic side effects generally are not severe and are rapidly reversible. C1 NCI,DIV CANC TREATMENT,SURG BRANCH,BETHESDA,MD 20892. NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. NR 41 TC 61 Z9 61 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD DEC 15 PY 1994 VL 74 IS 12 BP 3212 EP 3222 DI 10.1002/1097-0142(19941215)74:12<3212::AID-CNCR2820741221>3.0.CO;2-I PG 11 WC Oncology SC Oncology GA PW268 UT WOS:A1994PW26800020 PM 7982185 ER PT J AU OHTA, T SUEOKA, E IIDA, N KOMORI, A SUGANUMA, M NISHIWAKI, R TATEMATSU, M KIM, SJ CARMICHAEL, WW FUJIKI, H AF OHTA, T SUEOKA, E IIDA, N KOMORI, A SUGANUMA, M NISHIWAKI, R TATEMATSU, M KIM, SJ CARMICHAEL, WW FUJIKI, H TI NODULARIN, A POTENT INHIBITOR OF PROTEIN PHOSPHATASE-1 AND PHOSPHATASE-2A, IS A NEW ENVIRONMENTAL CARCINOGEN IN MALE F344 RAT-LIVER SO CANCER RESEARCH LA English DT Article ID CLASS TUMOR PROMOTERS; OKADAIC ACID; BIOASSAY SYSTEM; MICROCYSTIN-LR; CELLS; HYPERPHOSPHORYLATION; KERATINOCYTES; CYTOKERATINS; EXPRESSION; INDUCTION AB Nodularin and microcystin-1R are cyanobacterial toxins and environmental hazards, Nodularin inhibits protein phosphatases 1 and 2A with the same potency as does microcystin-1R, which has recently been identified as a potent tumor promoter in rat liver, Our results suggested that nodularin is also a new tumor promoter in rat liver. A two-stage carcinogenesis experiment in rat liver initiated with diethylnitrosamine and without partial hepatectomy revealed that nodularin stimulated glutathione S-transferase placental form-positive foci in rat liver more effectively than did microcystin-1R, and that nodularin alone induced glutathione S-transferase placental form-positive foci as well as did diethylnitrosamine alone, Thus, nodularin itself is a new liver carcinogen, and microcystin-LR is a tumor promoter rather than a carcinogen. Nodularin induced hyperphosphorylation of cytokeratin peptides 8 and 18 in primary cultured rat hepatocytes 20% more effectively than did microcystin-LR, suggesting that nodularin penetrates more easily into the hepatocytes than does microcystin-LR. Nodularin up-regulated induction of c-jun, jun-B,jun-D, c-fos,fos-B, and fra-1 mRNA transcripts in rat liver after i.p. administration, and the accumulation of the mRNA transcripts was sustained for over 9 h after treatment, The environmental hazards of cyanobacterial toxins are discussed in relation to human primary liver cancer in Qidong county in the People's Republic of China. Our results support this hypothesis and indicate the need for prevention measures against cyanobacterial toxins, C1 SAITAMA CANC CTR,RES INST,INA,SAITAMA 362,JAPAN. AICHI CANC CTR,RES INST,NAGOYA,AICHI 464,JAPAN. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. WRIGHT STATE UNIV,DEPT BIOL SCI,DAYTON,OH 45435. NR 32 TC 199 Z9 208 U1 2 U2 13 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 DEC 15 PY 1994 VL 54 IS 24 BP 6402 EP 6406 PG 5 WC Oncology SC Oncology GA PX306 UT WOS:A1994PX30600024 PM 7527297 ER PT J AU DLUGOSZ, AA CHENG, C WILLIAMS, EK DHARIA, AG DENNING, MF YUSPA, SH AF DLUGOSZ, AA CHENG, C WILLIAMS, EK DHARIA, AG DENNING, MF YUSPA, SH TI ALTERATIONS IN MURINE KERATINOCYTE DIFFERENTIATION-INDUCED BY ACTIVATED RAS(HA) GENES ARE MEDIATED BY PROTEIN-KINASE C-ALPHA SO CANCER RESEARCH LA English DT Article ID CULTURED EPIDERMAL-CELLS; MOUSE SKIN TUMORS; V-RAS ONCOGENE; CHEMICAL CARCINOGENESIS; ULTRASTRUCTURAL-LOCALIZATION; PHOSPHOLIPID-METABOLISM; TRANSFORMED CELLS; HA-RAS; EXPRESSION; CALCIUM AB Primary mouse keratinocytes expressing the v-ras(Ha) oncogene (v-ras(Ha) keratinocytes) produce squamous papillomas when grafted onto nude mice and respond abnormally to signals for terminal differentiation both in vivo and in vitro. Since protein kinase C (PKC) activators and v-ras(Ha) induce similar phenotypic changes in cultured keratinocytes, and cellular diacylglycerol levels are constitutively elevated in ras-transformed keratinocytes, we tested whether PKC is a downstream target for oncogenic ras in this cell type, Ca2+-dependent PKC activity was increased in lysates from cultured v-ras(Ha) keratinocytes when compared to control cells; in contrast, Ca2+-independent activity decreased. Similar to PKC activators, v-ras(Ha) blocked Ca2+-mediated expression of the early epidermal differentiation markers keratins K1 and K10 while inducing aberrant expression of K8. Pretreatment of v-ras(Ha) keratinocytes with bryostatin to block PKC function restored Ca2+ mediated expression of K1 and K10 and blocked abnormal expression of K8, suggesting that these responses are mediated by the PKC pathway. Furthermore, expression of K1 is restored at bryostatin doses which specifically down-modulate PKC-alpha, the only Ca2+-dependent PKC isozyme detected in cultured keratinocytes. In contrast to the inhibition of K1 and K10, Ca2+-induced expression of the late epidermal differentiation markers loricrin, filaggrin, and keratinocyte transglutaminase was accelerated by v-ras(Ha), as previously reported in normal keratinocytes treated with PKC activators. Pretreatment of vras(Ha) keratinocytes with bryostatin blocked expression of late markers in these cells, and this response was correlated with down-regulation of PKC-alpha. The results of this study suggest that oncogenic ras alters keratinocyte differentiation by altering the function of the PKC signaling pathway, and that PKC-alpha is the specific isozyme involved in down-modulating expression of keratins K1 and K10 and up-regulating expression of loricrin, filaggrin, and keratinocyte transglutaminase. RP DLUGOSZ, AA (reprint author), NCI, DIV CANC ETIOL, CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB, BLDG 37, ROOM 3B08, BETHESDA, MD 20892 USA. NR 82 TC 87 Z9 88 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 DEC 15 PY 1994 VL 54 IS 24 BP 6413 EP 6420 PG 8 WC Oncology SC Oncology GA PX306 UT WOS:A1994PX30600026 PM 7987836 ER PT J AU WEINSTATSASLOW, DL ZABRENETZKY, VS VANHOUTTE, K FRAZIER, WA ROBERTS, DD STEEG, PS AF WEINSTATSASLOW, DL ZABRENETZKY, VS VANHOUTTE, K FRAZIER, WA ROBERTS, DD STEEG, PS TI TRANSFECTION OF THROMBOSPONDIN-1 COMPLEMENTARY-DNA INTO A HUMAN BREAST-CARCINOMA CELL-LINE REDUCES PRIMARY TUMOR-GROWTH, METASTATIC POTENTIAL, AND ANGIOGENESIS SO CANCER RESEARCH LA English DT Article ID EXTRACELLULAR-MATRIX; ENDOTHELIAL-CELLS; PLATELET THROMBOSPONDIN; ADHESIVE GLYCOPROTEIN; EPITHELIAL-CELLS; MELANOMA-CELLS; BINDING DOMAIN; EXPRESSION; ANTIBODIES; INHIBITOR AB Previous studies demonstrated that metastatic MDA-MB-435 breast carcinoma cells synthesized and secreted less of the extracellular matrix protein thrombospondin 1 (TSP1) than nonmetastatic breast carcinoma cell lines, a trend also observed for melanoma and lung carcinoma cell lines. To directly examine the effect of tumor cell TSP1 expression on tumor growth and metastasis, MDA-MB-435 cells were transfected with full length THBS-1 cDNA linked to a constitutive cytomegalovirus promoter, or with the cytomegalovirus vector alone, Injection of transfected clones that overexpressed TSP1 into the mammary fat pad of nude mice resulted in a dose-dependent inhibition of primary tumor size and an inhibition of spontaneous pulmonary metastases, which occurred in 21-30% of THBS-1 transfectants compared to 44-49% of controls (P = 0.007). An additional clone was identified that overexpressed a COOH-terminally truncated TSP1. This clone produced larger primary tumors and an increase in the occurrence of metastases relative to control transfectants, suggesting the participation of a previously understudied region of TSP1 in the regulation of tumor progression, The THBS-1 and control transfectants did not exhibit significant differences in growth, colonization, or motility in vitro. However, a relative reduction in capillary densities in primary tumors formed by the wild-type THBS-1 transfectants was observed, suggestive of an angiostatic effect, The data indicate that tumor cell production of TSP1 can exert a significant inhibitory effect on tumor progression in the MDA-MB-435 breast carcinoma cell line, which may be attributable in part to a reduction in angiogenesis. C1 NCI,PATHOL LAB,WOMENS CANC SECT,BETHESDA,MD 20892. NCI,PATHOL LAB,BIOCHEM PATHOL SECT,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. ST LOUIS UNIV,SCH MED,DEPT BIOL CHEM,ST LOUIS,MO 63110. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 NR 44 TC 302 Z9 309 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 1994 VL 54 IS 24 BP 6504 EP 6511 PG 8 WC Oncology SC Oncology GA PX306 UT WOS:A1994PX30600041 PM 7527299 ER PT J AU WARZYNSKI, MJ BARBOUR, SD WINKLERPICKETT, RT ORTALDO, JR AF WARZYNSKI, MJ BARBOUR, SD WINKLERPICKETT, RT ORTALDO, JR TI CD3(+), CD56(+) NON-MHC RESTRICTED CYTOTOXIC T-LYMPHOCYTES IN 2 FRATERNAL AIDS PATIENTS - A CASE-REPORT SO CYTOMETRY LA English DT Note DE HEMOPHILIA; CHILDREN; HIV; FLOW CYTOMETRY; CYTOTOXIC T CELLS; NATURAL KILLER ACTIVITY ID NATURAL-KILLER-CELLS; HUMAN IMMUNODEFICIENCY VIRUS; NK-CELLS; INFECTION; SUBSET; IL-2; EXPRESSION; ANTIBODIES; PHENOTYPE; ANTIGEN AB We describe two brothers with hemophilia and AIDS, with an unusually large percentage of CD3(+), CD56(+) lymphocytes, They experienced no major complications with opportunistic infections (01) and infrequent secondary infections, even though they had nearly 0% CD4 lymphocytes for 3 years, Both patients died in 1991 of progressive cardiomyopathy, The patients' lymphocytes were immunophenotyped by flow cytometry and analyzed for functional cytolytic activity against K562 and HIV infected HUT 78 cell lines, Single color CD4 counts were 2-9% for 4 years. Dual color CD4 counts at our laboratory demonstrated 0-1% CD4 for the last 6 months, When CD3(+) lymphocytes were examined, both patient 1 and patient 2 demonstrated a significantly higher proportion and absolute number of CD3(''bright''+), CD56(+) double-positive cells, 47% and 22%, respectively, compared to other HIV-positive children with hemophilia (less than or equal to 2%). Functional studies with the K562 target cell line demonstrated the highest natural killer (NK) lymphocyte activity in patient 1 that could not be augmented by in vitro addition of IL-2, whereas patient 2 had no NK activity unless IL-2 was added, Functional studies with HIV-infected HUT-78 cells demonstrated patient 2 had cytolytic activity against HIV-infected cells and patient I had high nonspecific cytolytic activity even against uninfected HUT-78 cells, whereas controls had minimal activity to HUT-78 cells or HIV-infected HUT-78 cells, The case report raises a speculative question requiring a larger database, whether the anti-HIV activity and/or unusual clinical course without typical O.I. of some AIDS patients may be related to the presence of CD3(''bright''+), CD56(+) lymphocytes of their immune system, (C) 1994 Wiley-Liss, Inc. C1 BUTTERWORTH HOSP,DEPT PEDIAT,DIV PEDIAT INFECT DIS,GRAND RAPIDS,MI. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. RP WARZYNSKI, MJ (reprint author), FERGUSON HOSP,W MICHIGAN FLOW CYTOMETRY SERV,72 SHELDON BLVD SE,GRAND RAPIDS,MI 49503, USA. NR 23 TC 4 Z9 4 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0196-4763 J9 CYTOMETRY JI Cytometry PD DEC 15 PY 1994 VL 18 IS 4 BP 231 EP 236 DI 10.1002/cyto.990180408 PG 6 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QF963 UT WOS:A1994QF96300007 PM 7534677 ER PT J AU KOBAYASHI, T URABE, K WINDER, A JIMENEZCERVANTES, C IMOKAWA, G BREWINGTON, T SOLANO, F GARCIABORRON, JC HEARING, VJ AF KOBAYASHI, T URABE, K WINDER, A JIMENEZCERVANTES, C IMOKAWA, G BREWINGTON, T SOLANO, F GARCIABORRON, JC HEARING, VJ TI TYROSINASE-RELATED PROTEIN-1 (TRP1) FUNCTIONS AS A DHICA OXIDASE IN MELANIN BIOSYNTHESIS SO EMBO JOURNAL LA English DT Article DE MELANIN; MELANOGENESIS; PIGMENTATION; TRP1; TYROSINASE ID EYED DILUTION LOCUS; DOPACHROME TAUTOMERASE; MAMMALIAN TYROSINASE; REGULATORY FACTORS; MOUSE TYROSINASE; COATED VESICLES; PRADER-WILLI; B-LOCUS; MELANOCYTE; EXPRESSION AB Several genes critical to the enzymatic regulation of melanin production in mammals have recently been cloned and mapped to the albino, brown and slaty loci in mice. All three genes encode proteins with similar structures and features, but with distinct catalytic capacities; the functions of two of those gene products have previously been identified. The albino locus encodes tyrosinase, an enzyme with three distinct melanogenic functions, while the slaty locus encodes tyrosinase-related protein 2 (TRP2), an enzyme with a single specific, but distinct, function as DOPAchrome tautomerase. Although the brown locus, encoding TRP1, was actually the first member of the tyrosinase gene family to be cloned, its catalytic function (which results in the production of black rather than brown melanin) has been in general dispute. In this study we have used two different techniques (expression of TRP1 in transfected fibroblasts and immunoaffinity purification of TRP1 from melanocytes) to examine the enzymatic function(s) of TRP1. The data demonstrate that the specific melanogenic function of TRP1 is the oxidation of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) to a carboxylated indole-quinone at a downstream point in the melanin biosynthetic pathway. This enzyme activity appears to be essential to the further metabolism of DHICA to a high molecular weight pigmented biopolymer. C1 NCI,CELL BIOL LAB,BETHESDA,MD 20892. UNIV OXFORD,SIR WILLIAM DUNN SCH PATHOL,OXFORD OX1 3RE,ENGLAND. UNIV MURCIA,FAC MED,DEPT BIOCHEM,MURCIA,SPAIN. KAO INST FUNDAMENTAL RES,HAGA,TOCHIGI 32134,JAPAN. RI Jimenez-Cervantes, Celia/H-1953-2015; Garcia-Borron, Jose Carlos/H-2247-2015; Solano, Francisco/G-5001-2013 OI Jimenez-Cervantes, Celia/0000-0002-5821-9510; Garcia-Borron, Jose Carlos/0000-0002-9192-588X; Solano, Francisco/0000-0001-9612-761X NR 56 TC 304 Z9 313 U1 3 U2 8 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD DEC 15 PY 1994 VL 13 IS 24 BP 5818 EP 5825 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QA637 UT WOS:A1994QA63700003 PM 7813420 ER PT J AU URFER, R TSOULFAS, P SOPPET, D ESCANDON, E PARADA, LF PRESTA, LG AF URFER, R TSOULFAS, P SOPPET, D ESCANDON, E PARADA, LF PRESTA, LG TI THE BINDING EPITOPES OF NEUROTROPHIN-3 TO ITS RECEPTORS TRKC AND GP75 AND THE DESIGN OF A MULTIFUNCTIONAL HUMAN NEUROTROPHIN SO EMBO JOURNAL LA English DT Article DE NEUROTROPHIN; NT-3; RECEPTOR BINDING; SPECIFICITY; TYROSINE KINASE ID NERVE GROWTH-FACTOR; RESOLUTION CRYSTAL-STRUCTURE; MOLECULAR-CLONING; FACTOR FAMILY; SCANNING MUTAGENESIS; KINASE RECEPTOR; BRAIN; NGF; PROTEIN; EXPRESSION AB Survival and maintenance of vertebrate neurons are influenced by neurotrophic factors which mediate their signal by binding to specific cell surface receptors. We determined the binding sites of human neurotrophin-3 (NT-3) to its receptors trkC and gp75 by mutational analysis and compared them to the analogous interactions of nerve growth factor (NGF) with trkA and gp75. The trkC binding site extends around the central P-strand bundle and in contrast to NGF does not make use of non-conserved loops and the six N-terminal residues. The gp75 epitope is dominated by loop residues and the C-terminus of NT-3. A novel rapid biological screening procedure allowed the identification of NT-3 mutants that are able to signal efficiently through the non-preferred receptors trkA and trkB, which are specific for NGF and BDNF respectively. Mutation of only seven residues in NT-3 resulted in a human neurotrophin variant which bound to all receptors of the trk family with high affinity and efficiently supported the survival of NGF-, BDNF- and NT-3-dependent neurons. Our results suggest that the specificity among neurotrophic factors is not solely encoded in sequence diversity, but rather in the way each neurotrophin interacts with its preferred receptor. C1 GENENTECH INC,DEPT NEUROSCI,S SAN FRANCISCO,CA 94080. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOLEC EMBRYOL SECT,FREDERICK,MD 21702. RP URFER, R (reprint author), GENENTECH INC,DEPT PROT ENGN,460 POINT SAN BRUNO BLVD,S SAN FRANCISCO,CA 94080, USA. RI Parada, luis/B-9400-2014; OI Tsoulfas, Pantelis/0000-0003-1974-6366 FU PHS HHS [N01-C0-74101] NR 60 TC 90 Z9 90 U1 1 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD DEC 15 PY 1994 VL 13 IS 24 BP 5896 EP 5909 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QA637 UT WOS:A1994QA63700013 PM 7529173 ER PT J AU TRAUTH, K MUTSCHLER, B JENKINS, NA GILBERT, DJ COPELAND, NG KLEMPNAUER, KH AF TRAUTH, K MUTSCHLER, B JENKINS, NA GILBERT, DJ COPELAND, NG KLEMPNAUER, KH TI MOUSE A-MYB ENCODES A TRANSACTIVATOR AND IS EXPRESSED IN MITOTICALLY ACTIVE-CELLS OF THE DEVELOPING CENTRAL-NERVOUS-SYSTEM, ADULT TESTIS AND B-LYMPHOCYTES SO EMBO JOURNAL LA English DT Article DE MOUSE A-MYB; MYB-RELATED GENE; NEURONAL DIFFERENTIATION; SPERMATOGENESIS; TRANSACTIVATION ID DNA-BINDING DOMAIN; GENETIC-LINKAGE MAP; ONCOGENE C-MYB; V-MYB; PROTO-ONCOGENE; REGULATED EXPRESSION; CILIARY BODY; CDNA CLONES; MIM-1 GENE; AVIAN EYE AB C-myb encodes a transcriptional activator that is essential for the development of the hematopoietic system but appears to lack major roles in non-hematopoietic cells. The identification of two conserved myb-related genes, designated A-myb and B-myb, has raised the possibility that these genes are functional equivalents of c-myb in non-hematopoietic cells. Here, we report the isolation and preliminary characterization of the mouse A-myb gene. Mouse A-myb maps to the proximal region of chromosome 1 and encodes a transcriptional activator with properties similar to those of the c-myb and v-myb proteins. During embryogenesis A-myb is predominantly expressed in several regions of the developing central nervous system (CNS) and the urogenital ridge. Expression in the CNS is confined to the neural tube, the hindbrain, the neural retina and the olfactory epithelium, and coincides with the presence of proliferating immature neuronal precursor cells. In the adult mouse, A-myb is expressed during the early stages of sperm cell differentiation and in B lymphocytes located in germinal centers of the spleen. Taken together, these results suggest a role for A-myb in the proliferation and/or differentiation of neurogenic, spermatogenic and B-lymphoid cells. C1 MAX PLANCK INST IMMUNBIOL,HANS SPEMANN LAB,D-79108 FREIBURG,GERMANY. NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101] NR 63 TC 93 Z9 96 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD DEC 15 PY 1994 VL 13 IS 24 BP 5994 EP 6005 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QA637 UT WOS:A1994QA63700023 PM 7813437 ER PT J AU STANIMIROVIC, DB NIKODIJEVIC, B NIKODIJEVICKEDEVA, D MCCARRON, RM SPATZ, M AF STANIMIROVIC, DB NIKODIJEVIC, B NIKODIJEVICKEDEVA, D MCCARRON, RM SPATZ, M TI SIGNAL-TRANSDUCTION AND CA2+ UPTAKE ACTIVATED BY ENDOTHELINS IN RAT-BRAIN ENDOTHELIAL-CELLS SO EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION LA English DT Article DE CEREBRAL ENDOTHELIUM; ENDOTHELIN; CA2+ UPTAKE; SIGNAL TRANSDUCTION ID INTRACELLULAR CALCIUM; IMMUNOREACTIVE ENDOTHELIN-1; SUBARACHNOID HEMORRHAGE; CYTOSOLIC CALCIUM; CAPILLARY; RESPONSES; CURRENTS; RECEPTOR; NIMODIPINE; SECRETION AB The activation of signal transduction pathways by endothelin-l or endothelin-3 were investigated in rat cerebromicrovascular endothelial cells. Endothelin-l induced a rapid increase in inositol triphosphate (IF,) formation in these cells, whereas endothelin-3 was only moderately effective at high concentrations. Both endothelins also increased uptake of Ca-45(2+) in, these cells. Endothelin-l-induced IP3 formation or Ca-45(2+) uptake were inhibited by endothelin ET, receptor antagonist BQ-123. Ryanodine, an inhibitor of intracellular Ca2+ mobilization, selectively attenuated endothelin-l-induced Ca-45(2+) uptake, whereas nickel or suramin inhibited endothelin-3-induced Ca-45(2+) uptake. The results indicate that endothelin-1 elevates Ca-45(2+) uptake in rat brain endothelial cells by mechanisms coupled to the mobilization of intracellular Ca2+ stores. Both endothelin-1- and endothelin-3-induced Ca-45(2+) uptake were inhibited by receptor operated Ca2+ channel blocker SK&F 96365, whereas they were insensitive to dihydropyridine derivatives nifedipine and nitrendipine. The release of arachidonic acid from rat brain endothelial cells observed in response to endothelin-l was inhibited by ryanodine or SK&F 96365, implicating participation of both intra- and extra- cellular components of Ca2+ signaling in activating endothelial secretion of vasoactive substances. C1 NINCDS,STROKE BRANCH,BETHESDA,MD 20892. NICHHD,GROWTH FACTORS SECT,BETHESDA,MD 20892. NR 37 TC 18 Z9 19 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 DEC 15 PY 1994 VL 288 IS 1 BP 1 EP 8 DI 10.1016/0922-4106(94)90003-5 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QA464 UT WOS:A1994QA46400001 PM 7705461 ER PT J AU BECKER, KG JEDLICKA, P TEMPLETON, NS LIOTTA, L OZATO, K AF BECKER, KG JEDLICKA, P TEMPLETON, NS LIOTTA, L OZATO, K TI CHARACTERIZATION OF HUCRBP (YY1, NF-E1, DELTA) - A TRANSCRIPTION FACTOR THAT BINDS THE REGULATORY REGIONS OF MANY VIRAL AND CELLULAR GENES SO GENE LA English DT Article DE ZINC FINGER; DNA BINDING; PHOSPHOPROTEIN; ACTIVATOR; REPRESSOR ID MURINE LEUKEMIA-VIRUS; RESTRICTED EXPRESSION; MAMMALIAN-CELLS; PROTEIN; MEMBER; FAMILY; HOMEOBOX; ELEMENT; IDENTIFICATION; DROSOPHILA AB The UCRBP (YY1, delta, NF-E1) protein has been isolated for its ability to bind to the UCR (upstream conserved region) site present in the conserved murine leukemia virus long terminal repeat. UCRBP carries a highly charged N-terminal domain and four C2-H2-type zinc fingers at its C-terminal end. The present study reveals the following results: (i) The UCR site is present in the upstream and/or regulatory regions of numerous mammalian cellular and viral genes to which both recombinant and cellular UCRBP bind. UCR sites are also found in the regulatory regions of repetitive sequences including human LINE-1 elements and mouse intracisternal-A particle sequences. (ii) By immuuological and UV cross-linking experiments, we found that two proteins, of approx. 68 kDa and an antigenically related protein of approx. 40 kDa, account for much of the UCR-binding activity in T-lymphocytes. (iii) There is evidence that UCRBP acts as it phosphoprotein. Eight consensus phosphorylation bites are found rn the deduced amino-acid sequence of human UCRB. The cellular UCR-binding activity was abolished by phosphatase treatment, and there is an incremental increase in apparent molecular mass between the cytoplasmic and nuclear forms of the protein, suggesting phosphorylation. (iv) Although UCRBP has been previously shown to act as a transcriptional repressor, we show here that UCRBP can also act as a positive transactivator of a reporter driven by UCR elements when used in co-transfection assays, This transactivation occurred in a dose-restricted manner and was absent at high concentrations of a UCRBP expression plasmid, indicating a complex mode of function. Taken together, these results indicate that a very large number of cellular and viral genes are controlled by UCRBP, whose function is manifested in both a positive and negative manner. C1 NICHHD,MOLEC GROWTH REGULAT LAB,BETHESDA,MD 20892. NCI,PATHOL LAB,BETHESDA,MD 20892. OI Becker, Kevin/0000-0002-6794-6656 NR 26 TC 55 Z9 56 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD DEC 15 PY 1994 VL 150 IS 2 BP 259 EP 266 DI 10.1016/0378-1119(94)90435-9 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA QC200 UT WOS:A1994QC20000007 PM 7821790 ER PT J AU ROSINARBESFELD, R MASHIAH, P WILLBOLD, D ROSCH, P TRONICK, SR YANIV, A GAZIT, A AF ROSINARBESFELD, R MASHIAH, P WILLBOLD, D ROSCH, P TRONICK, SR YANIV, A GAZIT, A TI BIOLOGICAL-ACTIVITY AND INTRACELLULAR LOCATION OF THE TAT PROTEIN OF EQUINE INFECTIOUS-ANEMIA VIRUS SO GENE LA English DT Note DE RECOMBINANT PROTEIN; EIAV; LENTIVIRUSES; TRANSACTIVATION; HIS TAG; PET PROKARYOTIC EXPRESSION VECTOR ID MUTATIONAL ANALYSIS; FUNCTIONAL-CHARACTERIZATION; TRANS-ACTIVATION; GENE-EXPRESSION; LENTIVIRUS TAT; BASIC DOMAIN; RNA; HIV-1; REV; TRANSACTIVATOR AB The Tat protein of equine infectious anemia virus (EIAV) was synthesized in Escherichia coli using the inducible expression plasmid, pET16b, which contains a His.Tag leader, thus allowing for rapid and efficient enrichment of the histidine-tagged protein by metal affinity chromatography. Yields of up to 20 mg of Tat were obtained from 10(11) bacterial cells. The recombinant Tat protein was shown to potently trans-activate the EIAV long terminal repeat (LTR) following its introduction into canine cells by 'scrape loading'. The EIAV Tat protein was found to localize predominantly within the cytoplasm, in contrast to HIV-1 Tat. The availability of large amounts of purified functional EIAV Tat protein should greatly facilitate detailed structure-function analyses. C1 TEL AVIV UNIV,SACKLER SCH MED,DEPT HUMAN MICROBIOL,IL-69978 TEL AVIV,ISRAEL. UNIV BAYREUTH,LEHRSTUHL STRUKTUR & CHEM BIOPOLYMERE,D-95440 BAYREUTH,GERMANY. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. RI Willbold, Dieter/A-6280-2013; Rosch, Paul/I-5445-2014 OI Willbold, Dieter/0000-0002-0065-7366; Rosch, Paul/0000-0003-3330-2446 NR 32 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD DEC 15 PY 1994 VL 150 IS 2 BP 307 EP 311 DI 10.1016/0378-1119(94)90443-X PG 5 WC Genetics & Heredity SC Genetics & Heredity GA QC200 UT WOS:A1994QC20000015 PM 7821797 ER PT J AU BERGSAGEL, PL TIMBLIN, CR KOZAK, CA KUEHL, WM AF BERGSAGEL, PL TIMBLIN, CR KOZAK, CA KUEHL, WM TI SEQUENCE AND EXPRESSION OF MURINE CDNAS ENCODING XLR3 A AND XLR3B, DEFINING A NEW X-LINKED LYMPHOCYTE-REGULATED XLR GENE SUBFAMILY SO GENE LA English DT Note DE X CHROMOSOME; PLASMA CELL; DIFFERENTIATION; MOUSE; TESTIS; SUBTRACTIVE HYBRIDIZATION ID FAMILY XLR; PLASMA-CELLS; CHROMOSOME; IDENTIFICATION; PLASMACYTOMAS; RECEPTOR; CHAIN; SET AB Using a subtractive cDNA approach we have identified two nearly identical genes, Xlr3a and Xlr3b (X-linked lymphocyte regulated), expressed at a consistently high level in 14 out of 14 murine plasmacytoma cell lines, at a high level in 1 out of 8 B-lymphoma cell lines, and at a very low level in 2 out of the 8 B-lymphoma cell lines. The messages are not detected in 10 pre-B-lymphoma cell lines. These genes express 2.0-kb mRNAs that encode 226-amino-acid proteins that are extremely basic, with an estimated pI of 8.1 and 9.0, respectively, By sequence comparison they are homologous to Xlr1, an acidic nuclear protein that is produced in lymphoid cell lines corresponding to the late stages of lymphocyte differentiation. Xlr2 is a highly homologous gene that is expressed in differentiating male germ cells. Xlr3a and Xlr3b are members of a new subfamily in the Xlr multigene family. Like Xlr1, they are up-regulated during B-cell terminal differentiation in normal and neoplastic B-cells, and cross-hybridize with a message in testis RNA. Also, like Xlr1, they do not cross-hybridize with human genomic DNA. C1 NCI,NAVY MED ONCOL BRANCH,BETHESDA,MD 20889. NIAID,MOLEC BIOL LAB,BETHESDA,MD 20892. RI Bergsagel, Peter/A-7842-2011 OI Bergsagel, Peter/0000-0003-1523-7388 NR 25 TC 15 Z9 18 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD DEC 15 PY 1994 VL 150 IS 2 BP 345 EP 350 DI 10.1016/0378-1119(94)90450-2 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA QC200 UT WOS:A1994QC20000022 PM 7821804 ER PT J AU HEINEMAN, EF ZAHM, SH MCLAUGHLIN, JK VAUGHT, JB AF HEINEMAN, EF ZAHM, SH MCLAUGHLIN, JK VAUGHT, JB TI INCREASED RISK OF COLORECTAL-CANCER AMONG SMOKERS - RESULTS OF A 26-YEAR FOLLOW-UP OF US VETERANS AND A REVIEW SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID LARGE-BOWEL-CANCER; CIGARETTE-SMOKING; RECTAL-CANCER; ALCOHOL-CONSUMPTION; ADENOMATOUS POLYPS; DIGESTIVE-TRACT; COLON CANCER; SOCIOECONOMIC-STATUS; PHYSICAL-ACTIVITY; BRITISH DOCTORS AB To clarify the relationship between tobacco use and risk of colorectal cancer, we evaluated a cohort of 248,046 American veterans followed prospectively for 26 years. In comparison with veterans who had never used tobacco, the risk of death was significantly increased for colon cancer and rectal cancer among current and former cigarette smokers and among pipe or cigar smokers, controlling for social class and occupational physical activity. Rectal-cancer risk was also significantly elevated among users of chewing tobacco or snuff. For both sites, risk increased significantly with pack-years, earlier age at first use, and number of cigarettes. These results reinforce 2 recent reports of the association of cigarette smoking and colorectal cancer in men and women. Inconsistencies in the findings of earlier epidemiologic studies appear to be due in large part to differences in length of follow-up or in choice of controls. Studies with at least 20 years of follow-up or population-based controls have tended to find elevated risk with tobacco smoking, while those with shorter follow-up or hospital controls have not. This, plus the strength and consistency of the association of smoking and colon polyps, suggest that smoking may primarily affect an early stage in the development of colon cancer. If this association is causal, tobacco use may be responsible for 16% of colon-cancer and 22% of rectal-cancer deaths among these veterans. (C) 1995 Wiley-Liss, Inc.* C1 WESTAT CORP,ROCKVILLE,MD 20850. RP HEINEMAN, EF (reprint author), NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,6130 EXECUT BLVD,ROOM 418,ROCKVILLE,MD 20852, USA. RI Zahm, Shelia/B-5025-2015 NR 72 TC 97 Z9 100 U1 2 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD DEC 15 PY 1994 VL 59 IS 6 BP 728 EP 738 DI 10.1002/ijc.2910590603 PG 11 WC Oncology SC Oncology GA QF916 UT WOS:A1994QF91600002 PM 7989109 ER PT J AU HUPPI, K SIWARSKI, D AF HUPPI, K SIWARSKI, D TI CHIMERIC TRANSCRIPTS WITH AN OPEN READING FRAME ARE GENERATED AS A RESULT OF TRANSLOCATION TO THE PVT-1 REGION IN MOUSE B-CELL TUMORS SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID MYC ONCOGENE; XIST GENE; MU-CHAINS; C-MYC; KB; PLASMACYTOMAS; LYMPHOMA; PRODUCT; NUCLEUS; RNA AB Some mouse plasmacytomas exhibit a t(6; 15) chromosomal translocation in which the breakpoint resides within the Pvt-l locus located 260 kilobases (kb) downstream of c-myc on mouse chromosome 15. In this report, we show that the Pvt-l locus does not exhibit allelic exclusion in that Pvt-l transcripts continue to be expressed from the non-translocated allele in t(6;15) plasmacytomas. From the translocated allele, we find chimeric transcripts containing a short 57-bp segment of Pvt-l (termed Pvt-la) spliced directly to the immunoglobulin constant region sequence (Ig-Ck). These short transcripts have replaced a Jk segment with a trytophan residue via RNA splicing and contain a continuous open reading frame (ORF) from Pvt-la through tk. Since this Pvt-la/Ck transcript is found in all 3 t(6;15) plasmacytomas examined, regardless of the location of the chromosomal breakpoint, we suggest that the Pvt-la/Ck chimera may have a functional role in the development of mouse plasmacytomas. (C) 1994 Wiley-Liss, Inc.* RP HUPPI, K (reprint author), NCI,GENET LAB,MOLEC GENET SECT,BLDG 37,RM 2B-21,BETHESDA,MD 20892, USA. NR 18 TC 8 Z9 9 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD DEC 15 PY 1994 VL 59 IS 6 BP 848 EP 851 DI 10.1002/ijc.2910590623 PG 4 WC Oncology SC Oncology GA QF916 UT WOS:A1994QF91600022 PM 7989128 ER PT J AU SCONOCCHIA, G TITUS, JA SEGAL, DM AF SCONOCCHIA, G TITUS, JA SEGAL, DM TI CD44 IS A CYTOTOXIC TRIGGERING MOLECULE IN HUMAN PERIPHERAL-BLOOD NK CELLS SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; METASTASIS-ASSOCIATED VARIANT; STIMULATORY FACTOR NKSF; PREVENT TUMOR-GROWTH; TOXIC LYMPHOCYTES-T; ANTI-TARGET CELL; MONOCLONAL-ANTIBODIES; CYTOLYTIC ACTIVITY; HOMING RECEPTOR; ENDOTHELIAL-CELLS AB Previous studies have shown that target cells that bind to CD44 adhesion molecules on cloned cytotoxic T cells are lysed by the CTL. To determine whether CD44 is also a cytotoxic trigger molecule in human PBL, we tested a bispecific Ab consisting of anti-CD44 Fab cross-linked to a Fab against a target cell Ag, in cytotoxicity assays using PBL as effecters. We found that PBL mediated lysis in the presence of the anti-CD44 bispecific Ab provided that the effector cells were stimulated with either IL-2 or IL-12. Cell fractionation experiments showed that CD44-directed cytolysis was mediated exclusively by CD56(+) low buoyant density cells, mainly by NK(CD16(+)) cells, but also to a lesser extent by CD56(+) T cells. CD44-directed cytolysis appeared in these subsets 24 to 48 h after addition of IL-2 and paralleled the acquisition of Ab-independent (LAK) activity; in contrast, these cells mediated Ab-dependent cellular cytotoxicity and CD3 redirected lysis before stimulation with IL-2. Unstimulated CD56(+) cells uniformly expressed high levels of CD44 that increased modestly after incubation with IL-2. No changes in isoform expression in the extracellular domain of CD44 could be detected upon activation with the use of isoform-specific mAbs. Thus, lymphokine stimulation caused CD44 to become a cytotoxic trigger in subsets of PBL that mediated other forms of cytotoxicity and expressed CD44 before activation, suggesting that activation of these cells was accompanied by a coupling of CD44 to their lytic machinery. C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. NR 63 TC 52 Z9 52 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 1994 VL 153 IS 12 BP 5473 EP 5481 PG 9 WC Immunology SC Immunology GA PW703 UT WOS:A1994PW70300013 PM 7527443 ER PT J AU SIDERAS, P MULLER, S SHIELS, H JIN, H KHAN, WN NILSSON, L PARKINSON, E THOMAS, JD BRANDEN, L LARSSON, I PAUL, WE ROSEN, FS ALT, FW VETRIE, D SMITH, CIE XANTHOPOULOS, KG AF SIDERAS, P MULLER, S SHIELS, H JIN, H KHAN, WN NILSSON, L PARKINSON, E THOMAS, JD BRANDEN, L LARSSON, I PAUL, WE ROSEN, FS ALT, FW VETRIE, D SMITH, CIE XANTHOPOULOS, KG TI GENOMIC ORGANIZATION OF MOUSE AND HUMAN BRUTONS AGAMMAGLOBULINEMIA TYROSINE KINASE (BTK) LOCI SO JOURNAL OF IMMUNOLOGY LA English DT Article ID X-LINKED AGAMMAGLOBULINEMIA; SIGNALING PROTEINS; HEMATOPOIETIC-CELLS; CLOSE LINKAGE; SRC FAMILY; PH DOMAIN; B-CELLS; GENE; IMMUNODEFICIENCY; TRANSCRIPTION AB Btk is a cytoplasmic protein tyrosine kinase (PTK) that has been directly implicated in the pathogenesis of X-linked agammaglobulinaemia (XLA) in humans and X-linked immunodeficiency (Xid) in mice. We have isolated phage and cosmid clones that allowed us to deduce the genomic structure of mouse and human Btk loci. The mouse and human genes are contained within genomic regions that span approximately 43.5 kb and 37.5 kb, respectively. Both loci contain 18 coding exons ranging between 55 and 560 bp in size with introns ranging in size from 164 bp to approximately 9 kb. The 5'-untranslated regions are encoded by single exons located approximately 9 kb upstream of the first coding exon. Exon 18 encodes for the last 23 carboxyl-terminal amino acids and the entire 3'-untranslated region. The location of intron/exon boundaries in the catalytic domains of the mouse and human Btk loci differs from that found in other described sub-families of intracellular PTKs, namely that of Src, Fes/Fer, Csk, and Abl/Arg. This observation is consistent with the classification of Btk together with the recently characterized kinases, Tec and Itk, into a separate sub-family of cytoplasmic PTKs. Putative transcription initiation sites in the mouse and human Btk loci have been determined by using the rapid amplification of cDNA ends assay. Similar to many other PTK specific genes, the putative Btk promoters lack obvious TATAA and CAAAT motifs. Putative initiator elements and potential binding sites for Ets (PEA-3), zeste, and PuF transcription factors are located within the 300 bp which are located upstream of the major transcription start site in both species. These sequences can mediate promoter activity when placed upstream of a promotorless chloramphenicol acetyl transferase reporter gene in an orientation-dependent manner. The present analysis will significantly facilitate the mutational analyses of patients with XLA and the further characterization of the function and regulation of the Btk molecule. C1 KAROLINSKA INST,NOVUM,CTR BIOTECHNOL,HUDDINGE,SWEDEN. CHILDRENS HOSP,HOWARD HUGHES MED INST,BOSTON,MA 02115. CTR BLOOD RES,BOSTON,MA 02115. UNITED MED & DENT SCH,DIV MED & MOLEC GENET,LONDON SE1 9RT,ENGLAND. NIAID,IMMUNOL LAB,BETHESDA,MD 20892. RP SIDERAS, P (reprint author), UMEA UNIV,APPL CELL & MOLEC BIOL UNIT,S-90187 UMEA,SWEDEN. NR 53 TC 72 Z9 75 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 DEC 15 PY 1994 VL 153 IS 12 BP 5607 EP 5617 PG 11 WC Immunology SC Immunology GA PW703 UT WOS:A1994PW70300026 PM 7989760 ER PT J AU TAIRA, M OTANI, H SAINTJEANNET, JP DAWID, IB AF TAIRA, M OTANI, H SAINTJEANNET, JP DAWID, IB TI ROLE OF THE LIM CLASS HOMEODOMAIN PROTEIN XLIM-1 IN NEURAL AND MUSCLE INDUCTION BY THE SPEMANN ORGANIZER IN XENOPUS SO NATURE LA English DT Article ID MESSENGER-RNAS; DNA-BINDING; GENE; EXPRESSION; MESODERM; DOMAIN; LAEVIS; EMBRYOS; NOGGIN; PLATE AB LIKE all known LIM class homeobox genes, Xlim-1 encodes a protein with two tandemly repeated cysteine-rich LIM domains upstream of the homeodomain(1). In Xenopus laevis, Xlim-1 is specifically expressed in the Spemann organizer, whose major functions include neural induction and dorsalization of ventral mesoderm(2-4). From RNA injection experiments we conclude here that: (1) the LIM domains behave as negative regulatory domains; (2) LIM domain mutants of Xlim-1 elicited neural differentiation in animal explants; (3) mutant, and to a lesser extent wild-type, Xlim-1 enhanced muscle formation after coinjection with Xbra; (4) both of these activities are mediated by extracellular signals as seen in combined explant experiments;. (5) Xlim-1 mutants activated goosecoid (gsc) expression in animal explants, but not expression of noggin or follistatin; (6) mutant Xlim-1 elicited formation of partial secondary axes, and cooperated with gsc in notochord formation. Thus Xlim-1 has latent activities, implicating it in organizer functions. C1 UNIV TOULOUSE 3,CNRS,UNITE MIXTE RECH 9925,CTR DEV BIOL,F-31062 TOULOUSE,FRANCE. RP TAIRA, M (reprint author), NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892, USA. NR 28 TC 175 Z9 176 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 DEC 15 PY 1994 VL 372 IS 6507 BP 677 EP 679 DI 10.1038/372677a0 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PX307 UT WOS:A1994PX30700086 PM 7990959 ER PT J AU AMOR, JC HARRISON, DH KAHN, RA RINGE, D AF AMOR, JC HARRISON, DH KAHN, RA RINGE, D TI STRUCTURE OF THE HUMAN ADP-RIBOSYLATION FACTOR-1 COMPLEXED WITH GDP SO NATURE LA English DT Article ID PHOSPHOLIPASE-D; PROTEIN; BINDING; RESOLUTION; COFACTOR; ARF AB ADP-ribosylation factors (ARFs) are essential and ubiquitous in eukaryotes, being involved in vesicular transport and functioning as an activator of phospholipase D (refs 1, 2) and cholera toxin(3,4). The functions of ARF proteins in membrane traffic and organelle integrity(5,6) are intimately tied to its reversible association with membranes and specific interactions with membrane phospholipids. One common feature of these functions is their regulation by the binding and hydrolysis of GTP. Here we report the three-dimensional structure of full-length human ARF1 (M(r) 21,000) in its GDP-bound non-myristoylated form. The presence of a unique amino-terminal alpha-helix and loop, together with differences in Mg2+ ligation and the existence of a non-crystallographic dimer, set this structure apart from other GTP-binding proteins. These features provide a structural basis for the GTP-dependent modulation of membrane affinity, the lack of intrinsic GTPase activity, and the nature of effector binding surfaces. C1 BRANDEIS UNIV,ROSENSTIEL BASIC MED SCI RES CTR,WALTHAM,MA 02254. BRANDEIS UNIV,DEPT BIOCHEM,PROGRAM BIOORGAN CHEM,WALTHAM,MA 02254. BRANDEIS UNIV,DEPT CHEM & BIOCHEM,WALTHAM,MA 02254. NCI,DEV THERAPEUT PROGRAM,BIOL CHEM LAB,BETHESDA,MD 20892. NR 29 TC 229 Z9 233 U1 5 U2 12 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD DEC 15 PY 1994 VL 372 IS 6507 BP 704 EP 708 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PX307 UT WOS:A1994PX30700094 PM 7990966 ER PT J AU SHAKIL, AO DIBISCEGLIE, AM AF SHAKIL, AO DIBISCEGLIE, AM TI VASCULITIS AND CRYOGLOBULINEMIA RELATED TO HEPATITIS-C SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Note RP SHAKIL, AO (reprint author), NIH,BETHESDA,MD 20892, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 15 PY 1994 VL 331 IS 24 BP 1624 EP 1624 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA PW446 UT WOS:A1994PW44600005 PM 7969343 ER PT J AU GORDIS, E AF GORDIS, E TI UNRAVELING THE BRAIN CHEMISTRY BEHIND ALCOHOL-ABUSE SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material RP GORDIS, E (reprint author), NIAAA,BETHESDA,MD, USA. NR 3 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 DEC 14 PY 1994 VL 272 IS 22 BP 1733 EP 1733 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA PV815 UT WOS:A1994PV81500020 PM 7966919 ER PT J AU SWEDO, SE AF SWEDO, SE TI SYDENHAMS CHOREA - A MODEL FOR CHILDHOOD AUTOIMMUNE NEUROPSYCHIATRIC DISORDERS SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; RHEUMATIC-FEVER; VITUS-DANCE; SYMPTOMS; CHILDREN RP SWEDO, SE (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BEHAV PEDIAT SECT,BLDG 10,ROOM 6N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 41 TC 200 Z9 208 U1 0 U2 3 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 DEC 14 PY 1994 VL 272 IS 22 BP 1788 EP 1791 DI 10.1001/jama.272.22.1788 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA PV815 UT WOS:A1994PV81500030 PM 7661914 ER PT J AU OLKEN, NM OSAWA, Y MARLETTA, MA AF OLKEN, NM OSAWA, Y MARLETTA, MA TI CHARACTERIZATION OF THE INACTIVATION OF NITRIC-OXIDE SYNTHASE BY N-G-METHYL-L-ARGININE - EVIDENCE FOR HEME LOSS SO BIOCHEMISTRY LA English DT Article ID HYDROXY-L-ARGININE; MACROPHAGE OXIDATION; BRAIN; PURIFICATION; INTERMEDIATE; SUBSTRATE; TETRAHYDROBIOPTERIN; BIOSYNTHESIS; FLAVOPROTEIN; REDUCTASE AB The nitric oxide synthases (NOS) are a unique family of P450-type hemoproteins that catalyze the formation of .NO and citrulline from L-arginine, oxygen, and NADPH. NG-Methyl-L-arginine (L-NMA) has been shown to function as a slow, partially uncoupled alternate substrate and mechanism-based inhibitor of the inducible NOS [Olken, N. M., and Marletta, M. A. (1993) Biochemistry 32, 9677-9685]. In this report, the inactivation of NOS by L-NMA has been investigated in detail. Inactivation fails to occur under an argon atmosphere, establishing turnover dependence. The partition ratio, defined as the number of molecules of citrulline formed per NOS monomer inactivated, is 108 +/- 3. By utilizing N-G-methyl-L-[2,3-H-3(2)]arginine and N-G-[C-14]methyl-L-arginine, the stoichiometry of radiolabeling is 0.11 +/- 0.01 equiv of tritium and 0.41 +/- 0.10 equiv of carbon-14 per inactivated NOS monomer. Dialysis under native conditions does not change this stoichiometry. However, dialysis of NOS following denaturation decreases the stoichiometry of radiolabeling to 0.08 +/- 0.04 equiv of tritium and 0.12 +/- 0.04 equiv of carbon-14 per inactivated NOS monomer. Absolute and CO-reduced difference spectroscopy indicates that inactivation of L-NMA is accompanied by a substantial loss of the heme chromophore, which is not prevented by catalase. HPLC analysis of NOS heme following inactivation with L-NMA indicates substantial loss of heme. These findings suggest that multiple mechanisms may contribute to the loss of NOS activity by L-NMA, including heme loss and possibly protein and cofactor modification. C1 UNIV MICHIGAN,COLL PHARM,INTDEPT PROGRAM MED CHEM,ANN ARBOR,MI 48109. UNIV MICHIGAN,SCH MED,DEPT BIOL CHEM,ANN ARBOR,MI 48109. NHLBI,CHEM PHARMACOL LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA 50414]; NIGMS NIH HHS [T32 GM 07767] NR 33 TC 64 Z9 66 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 DEC 13 PY 1994 VL 33 IS 49 BP 14784 EP 14791 DI 10.1021/bi00253a017 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PW706 UT WOS:A1994PW70600017 PM 7527657 ER PT J AU LEE, YL SCHULKIN, J DAVIS, M AF LEE, YL SCHULKIN, J DAVIS, M TI EFFECT OF CORTICOSTERONE ON THE ENHANCEMENT OF THE ACOUSTIC STARTLE REFLEX BY CORTICOTROPIN-RELEASING FACTOR (CRF) SO BRAIN RESEARCH LA English DT Article DE ADRENALECTOMY; AMYGDALA; STEROID ID EXPLORATORY-BEHAVIOR; PARAVENTRICULAR NUCLEUS; DEFENSIVE-WITHDRAWAL; CONDITIONED FEAR; AMYGDALA; BRAIN; RATS; SECRETION; LESIONS; SYSTEMS AB The present study evaluated the effects of adrenalectomy and chronic administration of corticosterone on the ability of CRF given intraventricularly to increase the amplitude of the acoustic startle reflex in rats. Experiment 1 showed that CRF-enhanced startle was not affected by adrenalectomy, indicating a central effect independent of the integrity of the hypothalamic-pituitary-adrenal axis. In Experiment 2, chronic injection of corticosterone augmented CRF-enhanced startle using a dose of CRF (0.25 mu g) that normally is ineffective in increasing startle amplitude. Chronic injection of corticosterone by itself did not increase startle amplitude (Experiment 3). We suggest that the potentiation of CRF-enhanced startle by corticosterone may result from an activation of CRF in the central nucleus of the amygdala. C1 NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. RP LEE, YL (reprint author), YALE UNIV,SCH MED,CONNECTICUT MENTAL HLTH CTR,ABRAHAM RIBICOFF RES FACIL,34 PK ST,NEW HAVEN,CT 06508, USA. FU NIMH NIH HHS [MH-25642, MH-47840, MH-18397] NR 33 TC 75 Z9 77 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 DEC 12 PY 1994 VL 666 IS 1 BP 93 EP 98 DI 10.1016/0006-8993(94)90286-0 PG 6 WC Neurosciences SC Neurosciences & Neurology GA PV595 UT WOS:A1994PV59500011 PM 7889373 ER PT J AU SELL, SM REESE, D OSSOWSKI, VM AF SELL, SM REESE, D OSSOWSKI, VM TI INSULIN-INDUCIBLE CHANGES IN INSULIN-RECEPTOR MESSENGER-RNA SPLICE VARIANTS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID DEPENDENT DIABETES-MELLITUS; MESSENGER-RNA; ALTERED EXPRESSION; PREMESSENGER RNA; SKELETAL-MUSCLE; HEPATOMA-CELLS; 2 ISOFORMS; GENE; DEXAMETHASONE; TISSUES AB Alternative splicing of insulin receptor pre-mRNA has been shown to be regulated in a tissue specific and developmental manner. We investigated whether the receptor ligand might regulate the relative distribution of alternatively spliced mRNA in insulin-sensitive cells and found that changes in the relative expression of the two alternatively spliced insulin receptor RNA isotypes expressed in hepatocytes are regulated by insulin. In addition, we observed significant differences (p less than or equal to 0.001) in insulin receptor isotype expression in subjects who were hyperinsulinemic and insulin-resistant versus subjects who were insulin sensitive. These results support a role for insulin in the regulation of the relative expression of alternatively spliced mRNA expressed in insulin-responsive cells and tissues. RP NIDDKD, CLIN DIABET & NUTR SECT, 4212 N 16TH ST, PHOENIX, AZ 85016 USA. FU DRS NIH HHS [ISRSA0005-01 ISR73] NR 35 TC 38 Z9 39 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 9 PY 1994 VL 269 IS 49 BP 30769 EP 30772 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PV510 UT WOS:A1994PV51000008 PM 7983004 ER PT J AU DEGTYAREV, MY SPIEGEL, AM JONES, TLZ AF DEGTYAREV, MY SPIEGEL, AM JONES, TLZ TI PALMITOYLATION OF A G-PROTEIN ALPHA(I) SUBUNIT REQUIRES MEMBRANE LOCALIZATION NOT MYRISTOYLATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEOTIDE-BINDING PROTEINS; BETA-GAMMA-SUBUNITS; PHOSPHOLIPID-VESICLES; LIPID MODIFICATIONS; AMINO TERMINUS; COS CELLS; BRAIN; ATTACHMENT; ANTIBODIES; RECEPTOR AB Palmitoylation is a dynamic, post-translational modification of the amino terminus of heterotrimeric G protein alpha subunits. Since myristoylation, beta gamma interactions, and membrane attachment also involve the amino terminus of the G protein alpha(i1) subunit, we studied the relationships between palmitoylation and these events. Using COS cell transfection, the turnover of palmitate was slower on alpha(i1) subunits co-expressed with beta and gamma subunits than on the alpha(i1) subunit expressed alone. Mutation of cysteine 3 of alpha(i1) prevented [H-3]palmitate but not [H-3]myristate incorporation and decreased the membrane localization of this protein. This nonpalmitoylated mutant could form a heterotrimer with co-expressed beta gamma subunits which restored its membrane localization. A nonmyristoylated alpha(i1) mutant (glycine 2 to alanine) could incorporate [H-3]palmitate when co-expressed with beta gamma subunits and localized to the membrane. The [H-3]palmitate turnover of this nonmyristoylated mutant was more rapid than seen with the wild-type alpha(i1) subunit. While myristoylation is not required for palmitoylation, both myristoylation and beta gamma association can slow the turnover of palmitate on alpha(i1). These results suggest that palmitoylation maintains the membrane attachment of the free alpha subunit and changes in beta gamma association could modulate palmitoylation during signaling. C1 NIDDK,METAB DIS BRANCH,BETHESDA,MD 20892. NR 42 TC 84 Z9 84 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 DEC 9 PY 1994 VL 269 IS 49 BP 30898 EP 30903 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PV510 UT WOS:A1994PV51000028 PM 7983022 ER PT J AU SAMANIEGO, F CHIN, J IWAI, K ROUAULT, TA KLAUSNER, RD AF SAMANIEGO, F CHIN, J IWAI, K ROUAULT, TA KLAUSNER, RD TI MOLECULAR CHARACTERIZATION OF A 2ND IRON-RESPONSIVE ELEMENT-BINDING PROTEIN, IRON REGULATORY PROTEIN-2 - STRUCTURE, FUNCTION, AND POSTTRANSLATIONAL REGULATION SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FERRITIN MESSENGER-RNA; TRANSFERRIN RECEPTOR; SULFUR CLUSTER; AFFINITY PURIFICATION; UNTRANSLATED REGION; ACONITASE ACTIVITY; REPRESSOR PROTEIN; IDENTIFICATION; EXPRESSION; CLONING AB Several genes critical to the uptake, sequestration, and utilization of iron are regulated at the post-transcriptional level. The mRNAs encoded by these genes contain highly conserved stem-loop structures called iron-responsive elements (IREs). IREs function as the nucleic acid-binding sites for a cytosolic RNA-binding protein called the IRE-binding protein or IRE-BP. Binding of the IRE-BP to IREs is reversibly regulated by the iron status of the cell. The IRE-BP is highly conserved among human, rat, mouse, and rabbit, and it is identical to the cytosolic form of aconitase. In this study, we demonstrate that a distinct human gene encoding a protein which is 57% identical to the initially described IRE-BP, now referred to as iron regulatory protein 1 or IRP1, is also capable of binding to IREs with the same in vitro affinity and specificity as the originally identified protein. This second gene product, which we call IRP2, is expressed in many tissues, but its mRNA abundance and tissue distribution are different from IRP1. In most cell lines tested, levels of IRP2 are inversely regulated by iron levels due to iron-dependent regulation of the half-life of the protein. In addition to changes in total amounts of IRP2, we demonstrate that the IRE binding activity of IRP2 can also vary up to 4-fold in the absence of any change in IRP2 protein levels. The possible reasons for the existence of a second IRP are discussed. C1 NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. NR 44 TC 188 Z9 190 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 9 PY 1994 VL 269 IS 49 BP 30904 EP 30910 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PV510 UT WOS:A1994PV51000029 PM 7983023 ER PT J AU AMIN, N PETERKOFSKY, A AF AMIN, N PETERKOFSKY, A TI IMPORTANCE OF THE REGION AROUND LYSINE-196 FOR CATALYTIC ACTIVITY OF ADENYLYL-CYCLASE FROM ESCHERICHIA-COLI SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEOTIDE-SEQUENCE; BACILLUS-ANTHRACIS; ATP BINDING; EXPRESSION; CLONING; GENE; PURIFICATION; STIMULATION; COMPLEX AB Escherichia coli adenylyl cyclase contains no sequence that corresponds to the previously defined ATP/GTP binding consensus (A,G)XXXXGK(S,T). Using a search for lysine residues located adjacent to glycine residues, three regions that were possible candidates for part of the ATP binding site were identified. These were the residues located at positions 59, 90, and 196. A plasmid vector capable of overexpressing the cya gene under the control of the lambda P-L promoter was mutated at these three loci to convert those lysine residues to methionine. Assays for catalytic activity of the mutated hyper-expressed proteins revealed that only the mutation at position 196 led to loss of activity. Photoaffinity labeling experiments using 8-azido-ATP provided evidence that the loss of activity was associated with a loss of the capability of the enzyme to bind ATP. A further series of replacement mutations in the hyperexpression vector was created at position 196. Assays of the adenylyl cyclase activity of the mutated proteins showed that replacement of lysine 196 by arginine led to minimal change in the activity. Replacements by histidine, glutamine, or glutamic acid resulted in approximately 10-20-fold reductions in the activity; replacements by methionine, isoleucine, or aspartic acid resulted in total loss of activity. When the mutated forms of the cya gene were expressed under the control of the cya promoter, the activity of the wild-type protein was higher than that of all the mutants, including the arginine replacement mutant. All of the mutants that retained activity also retained the capability of adenylyl cyclase to be stimulated by either inorganic orthophosphate or GTP. A helical wheel analysis of the region of adenylyl cyclase around lysine 196 revealed a structure compatible with an amphipathic helix with one face enriched with basic amino acid residues. Assays for adenylyl cyclase activity of a series of replacement mutations of residues on the hydrophilic face of the helix (R188I, R192I, G195I) as well as on the hydrophobic face (R197I) indicated that the R188I, G195I, and K196I replacement mutants were inactive, and R192I was approximately 30% as active as the wild-type, while the R197I mutant was equivalent to the mild-type control. A model is suggested for a unique binding motif in E. coli adenylyl cyclase in which there is a repetition of 3 basic residues on one face of a helix where there is an interaction with the three phosphate groups of ATP. C1 NHLBI,BIOCHEM GENET LAB,BETHESDA,MD 20892. NR 27 TC 2 Z9 2 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 DEC 9 PY 1994 VL 269 IS 49 BP 31074 EP 31079 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PV510 UT WOS:A1994PV51000054 PM 7983047 ER PT J AU LEVYTOLEDANO, R TAOUIS, M BLAETTLER, DH GORDEN, P TAYLOR, SI AF LEVYTOLEDANO, R TAOUIS, M BLAETTLER, DH GORDEN, P TAYLOR, SI TI INSULIN-INDUCED ACTIVATION OF PHOSPHATIDYL-INOSITOL 3-KINASE - DEMONSTRATION THAT THE P85 SUBUNIT BINDS DIRECTLY TO THE COOH TERMINUS OF THE INSULIN-RECEPTOR IN INTACT-CELLS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TYROSINE KINASE-ACTIVITY; SIGNAL TRANSDUCTION; PROTEIN IRS-1; ASSOCIATION; PHOSPHORYLATION; SUBSTRATE; 3'-KINASE; ENDOCYTOSIS; TRUNCATION; AUTOPHOSPHORYLATION AB Insulin activates the insulin receptor tyrosine kinase to phosphorylate signaling molecules such as insulin receptor substrate-1 (IRS-1). Phosphorylated IRS-1 binds to SH2 domains in the p85 regulatory subunit of phosphatidyl inositol (PI) 3-kinase, thereby stimulating the catalytic activity of PI 3-kinase. For most growth factor receptor tyrosine kinases (including receptors for epidermal growth factor and platelet-derived growth factor), the p85 regulatory subunit of PI 3-kinase binds directly to phosphorylated YXXM motifs contained in the cytoplasmic domain of the receptor itself. Previous studies in cell-free systems have shown that the phosphorylated YHTM sequence (amino acid residues 1322-1325) in the COOP terminus of the insulin receptor has the ability to bind to the p85 subunit of PI 3-kinase, thereby activating the enzyme. In this investigation, we demonstrate the occurrence of the same direct binding interaction in intact cells. Subsequent to insulin-stimulated phosphorylation of the insulin receptor, a complex is formed that contains the insulin receptor and PI 3-kinase. This complex can be immunoprecipitated by antibodies directed against either the insulin receptor or the p85 subunit of PI 3-kinase. The Delta 43 mutant insulin receptor that lacks 43 amino acids at the COOH terminus does not bind p85. In addition, the Delta 43 truncation impairs the ability of the receptor to mediate the activation of PI 3-kinase. Thus, by binding directly to p85, the phosphorylated YHTM motif in the COOH terminus of the insulin receptor contributes partially to mediating the effect of insulin to activate PI 3-kinase. C1 NIDDKD,DIABET BRANCH,BETHESDA,MD 20892. NR 33 TC 74 Z9 74 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 9 PY 1994 VL 269 IS 49 BP 31178 EP 31182 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PV510 UT WOS:A1994PV51000068 PM 7983060 ER PT J AU MOL, PC PARK, HM MULLINS, JT CABIB, E AF MOL, PC PARK, HM MULLINS, JT CABIB, E TI A GTP-BINDING PROTEIN REGULATES THE ACTIVITY OF (1-]3)-BETA-GLUCAN SYNTHASE, AN ENZYME DIRECTLY INVOLVED IN YEAST-CELL WALL MORPHOGENESIS SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BETA-(1->3)GLUCAN SYNTHETASE; SACCHAROMYCES-CEREVISIAE; 1,3-BETA-GLUCAN SYNTHASE; PRODUCT ENTRAPMENT; NEUROSPORA-CRASSA; MUTANTS; RAS; BIOSYNTHESIS; PURIFICATION; GROWTH AB Synthesis of (1-->3)-beta-D-glucan, the major structural component of the yeast cell wall, is synchronized with the budding cycle. Membrane-bound, GTP-stimulated (1-->3)-beta-glucan synthase was dissociated by stepwise treatment with salt and detergents into two soluble fractions, A and B, both required for activity. Fraction A was purified about 800-fold by chromatography on Mono and and Sephacryl S-300 columns. During purification, GTP binding to protein correlated with synthase complementing activity. A 20-kDa GTP-binding protein was identified by photolabeling in the purified preparation. This preparation no longer required GTP for activity, but incubation with another fraction from the Mono Q column (A1) led to hydrolysis of bound GTP to GDP with a concomitant return of the GTP requirement. Thus, fraction A1 appears to contain a GTPase-activating protein. These results show that the GTP-binding protein not only regulates glucan synthase activity but can be regulated in turn, constituting a potential link between cell cycle controls and wall morphogenesis. C1 NIDDKD,BIOCHEM & METAB LAB,BETHESDA,MD 20892. NR 25 TC 60 Z9 60 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 DEC 9 PY 1994 VL 269 IS 49 BP 31267 EP 31274 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PV510 UT WOS:A1994PV51000080 PM 7983071 ER PT J AU DU, QH LI, MJ CHENG, Q ZHANG, TY ITO, Y AF DU, QH LI, MJ CHENG, Q ZHANG, TY ITO, Y TI PURIFICATION OF (-)-EPIGALLOCATECHIN FROM ENZYMATIC HYDROLYSATE OF ITS GALLATE USING HIGH-SPEED COUNTERCURRENT CHROMATOGRAPHY SO JOURNAL OF CHROMATOGRAPHY A LA English DT Note AB Epigallocatechin gallate (EGCG) was hydrolyzed at various concentrations of tannase under pH 6.0 at 35 degrees C, and the reaction mixtures were separated by high-speed counter-current chromatography with a two-phase solvent system composed of hexane-ethyl acetate-water (1:13:20). The best results were obtained when 2 mg/ml of the enzyme buffer solution was added to 0.3 M EGCG buffers at a rate of 0.1 ml/min. Using 10 mg of the enzyme, 342 mg of epigallocatechin were obtained at a purity of 99.1%. C1 NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. BEIJING INST NEW TECHNOL APPLICAT,BEIJING 100035,PEOPLES R CHINA. CHINESE ACAD AGR SCI,TEA RES INST,HANGZHOU 310008,PEOPLES R CHINA. NR 8 TC 15 Z9 15 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD DEC 9 PY 1994 VL 687 IS 1 BP 174 EP 177 DI 10.1016/0021-9673(94)00917-1 PG 4 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA QB867 UT WOS:A1994QB86700017 PM 7849987 ER PT J AU FULLER, RW CARDELLINA, JH JUREK, J SCHEUER, PJ ALVARADOLINDNER, B MCGUIRE, M GRAY, GN STEINER, JR CLARDY, J MENEZ, E SHOEMAKER, RH NEWMAN, DJ SNADER, KM BOYD, MR AF FULLER, RW CARDELLINA, JH JUREK, J SCHEUER, PJ ALVARADOLINDNER, B MCGUIRE, M GRAY, GN STEINER, JR CLARDY, J MENEZ, E SHOEMAKER, RH NEWMAN, DJ SNADER, KM BOYD, MR TI ISOLATION AND STRUCTURE-ACTIVITY FEATURES OF HALOMON-RELATED ANTITUMOR MONOTERPENES FROM THE RED ALGA PORTIERIA-HORNEMANNII SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID TUMOR-CELL-LINES; DIVERSE PANEL AB Ten halogenated monoterpenes (2-6 and 8-12) related to the novel antitumor compound halomon (1) or to the carbocyclic analog 7 have been isolated from different geographic collections of the red alga, Portieria hornemannii. Structures were assigned on the basis of spectral analyses (primarily NMR and MS). The absolute configuration of isohalomon (2) was further established by X-ray crystallography. The compounds were comparatively evaluated alongside 1 and 7 in the U.S. National Cancer Institute's in vitro human tumor cell line screening panel. The results provide some interesting initial insights into the structure/activity relationships in this series. C1 UNIV HAWAII,DEPT CHEM,HONOLULU,HI 96822. NCI,FREDERICK CANC RES & DEV CTR,DYNCORP,PROGRAM RESOURCES INC,FREDERICK,MD 21702. CORNELL UNIV,BAKER LAB,DEPT CHEM,ITHACA,NY 14853. SMITHSONIAN INST,WASHINGTON,DC 20560. NCI,FAIRVIEW CTR,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,NAT PROD BRANCH,FREDERICK,MD 21701. FU NCI NIH HHS [CA 24487] NR 14 TC 64 Z9 66 U1 0 U2 7 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 DEC 9 PY 1994 VL 37 IS 25 BP 4407 EP 4411 DI 10.1021/jm00051a019 PG 5 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA PW566 UT WOS:A1994PW56600019 PM 7996553 ER PT J AU EPSTEIN, AH LEBOVICS, RS GOFFMAN, T TEAGUE, D FUETSCH, ES GLATSTEIN, E OKUNIEFF, P COOK, JA AF EPSTEIN, AH LEBOVICS, RS GOFFMAN, T TEAGUE, D FUETSCH, ES GLATSTEIN, E OKUNIEFF, P COOK, JA TI TREATMENT OF LOCALLY ADVANCED CANCER OF THE HEAD AND NECK WITH 5'-IODODEOXYURIDINE AND HYPERFRACTIONATED RADIATION-THERAPY - MEASUREMENT OF CELL LABELING AND THYMIDINE REPLACEMENT SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CONTINUOUS INTRAVENOUS INFUSIONS; GLIOBLASTOMA-MULTIFORME; HALOGENATED PYRIMIDINES; OROPHARYNGEAL CARCINOMA; RANDOMIZED TRIAL; PHASE-II; RADIOTHERAPY; RADIOSENSITIZATION; BROMODEOXYURIDINE; IODODEOXYURIDINE AB Background: The halogenated pyrimidines 5'-iododeoxyuridine (IdUrd) and 5'-bromodeoxyuridine (BrdUrd) are under active study as radiation sensitizers for a variety of malignancies. Head and neck neoplasms may also be suitable for halogenated pyrimidine-mediated sensitization; previous regimens using intra-arterial BrdUrd delivery, however, were poorly tolerated. Purpose: A pilot study was undertaken with the use of intravenous IdUrd with hyperfractionated radiotherapy to assess tolerance. In addition, serial tumor biopsy specimens were obtained to determine the kinetics of IdUrd labeling and incorporation. Methods: Twelve patients with squamous cell carcinomas of the head and neck (one patient had stage II cancer, one had stage III, and 10 had stage IV) were treated with hyperfractionated radiation therapy at a dose of 1.2 or 1.5 Gy twice a day, to a total dose in the range of 70-76 Gy. IdUrd (1000 mg/m(2) per day) was infused for a maximum of 14 days at the beginning and then again during the middle of the radiotherapy. A tumor biopsy specimen was obtained from 11 patients following initiation of treatment with IdUrd. Eight patients consented to serial biopsy to allow the study of IdUrd-labeling indices and thymidine replacement over time. Incorporation of IdUrd into tumor DNA was determined by highperformance liquid chromatography, and cell labeling was determined with the use of an anti-BrdUrd/IdUrd monoclonal antibody in conjunction with flow cytometry. Patients continue to be followed to assess local control. Results: A plot of corrected IdUrd replacement as a function of infusion time suggests the possibility of a plateau after 5-7 days of infusion at 7.5%-8%. The average rate of replacement from days 1 to 5 was 1.3% per day and was determined by linear regression analysis. Acute toxic effects, especially mucositis, were severe enough to require delays in the radiation therapy. Eleven of 12 patients treated had complete clinical remissions. Seven of these patients remain clinically free of local disease at the time of death or most recent follow-up. Conclusions: The level of IdUrd incorporation and cell labeling should be adequate to produce sensitization. However, the treatment as prescribed in this study (two 14-day infusions of IdUrd during radical radiotherapy with only one planned split) was not completed in a single patient because of either dose-limiting hematologic toxicity or severe mucositis necessitating treatment break. Since this particular regimen is not tolerable, future protocols will have shorter exposures to IdUrd. Implications: Previous regimens using halogenated pyrimidine radiosensitizers have generally used protracted drug delivery schedules. In this study, a high level of IdUrd labeling was measured after 5-7 days of drug infusion. The halogenated pyrimidines deserve further study with the use of repetitive short courses to reduce toxicity and possibly improve efficacy. C1 NCI,DIV CANC TREATMENT,RADIAT BIOL BRANCH,BETHESDA,MD 20892. NIDOCD,DIV INTRAMURAL RES,BETHESDA,MD. UNIV TEXAS,SW MED CTR,SIMMONS CANC CTR,DALLAS,TX. RP EPSTEIN, AH (reprint author), NCI,DIV CANC TREATMENT,RADIAT ONCOL BRANCH,BLDG 10,RM B3B69,BETHESDA,MD 20892, USA. NR 31 TC 18 Z9 19 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 7 PY 1994 VL 86 IS 23 BP 1775 EP 1780 DI 10.1093/jnci/86.23.1775 PG 6 WC Oncology SC Oncology GA PU633 UT WOS:A1994PU63300013 PM 7966416 ER PT J AU CLERICI, M SARIN, A COFFMAN, RL WYNN, TA BLATT, SP HENDRIX, CW WOLF, SF SHEARER, GM HENKART, PA AF CLERICI, M SARIN, A COFFMAN, RL WYNN, TA BLATT, SP HENDRIX, CW WOLF, SF SHEARER, GM HENKART, PA TI TYPE-1 TYPE-2 CYTOKINE MODULATION OF T-CELL PROGRAMMED CELL-DEATH AS A MODEL FOR HUMAN-IMMUNODEFICIENCY-VIRUS PATHOGENESIS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GLUCOCORTICOID-INDUCED APOPTOSIS; HUMAN MEDULLARY THYMOCYTES; MARROW TRANSPLANTATION; ACTIVATION; INTERLEUKIN-2; LYMPHOCYTES; INFECTION; INDIVIDUALS; DYSFUNCTION; ANTIBODIES AB In vitro T-cell receptor-induced programed cell death in both activated T cells from human immunodeficiency virus-seronegative (HIV-) donors and resting T cells from HIV+ donors was substantially influenced by cytokines. Addition of exogenous recombinant ''type 1'' lymphokines interferon gamma and interleukin 2 (IL-2), as well as the macrophage-produced IL-12, which favor cell-mediated T-cell responses, blocks both systems of T-lymphocyte programed cell death. In contrast, the ''type 2'' lymphokines IL-4 and IL-10, which favor antibody responses, either had no effect or enhanced these systems of in vitro T-cell programed cell death. A role for endogenously produced cytokines was suggested by the inhibition of T-cell receptor-mediated death by antibodies against IL-4 and IL-10 and its enhancement by anti-IL-12 in cultures containing monocytes. These results demonstrate that the functional properties of type 1 and type 2 cytokine classes may be further extended to include their effects on T-cell programed cell death and their possible role in the pathogenesis of HIV infection. C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. DNAX RES INST MOLEC & CELLULAR BIOL INC,PALO ALTO,CA 94304. WILFORD HALL USAF MED CTR,HIV UNIT,LACKLAND AFB,TX 78236. GENET INST INC,CAMBRIDGE,MA 02140. RI Wynn, Thomas/C-2797-2011; Hendrix, Craig/G-4182-2014 OI Hendrix, Craig/0000-0002-5696-8665 NR 30 TC 211 Z9 213 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 6 PY 1994 VL 91 IS 25 BP 11811 EP 11815 DI 10.1073/pnas.91.25.11811 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PW708 UT WOS:A1994PW70800010 PM 7991540 ER PT J AU TESSAROLLO, L VOGEL, KS PALKO, ME REID, SW PARADA, LF AF TESSAROLLO, L VOGEL, KS PALKO, ME REID, SW PARADA, LF TI TARGETED MUTATION IN THE NEUROTROPHIN-3 GENE RESULTS IN LOSS OF MUSCLE SENSORY NEURONS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NERVE GROWTH-FACTOR; TYROSINE PROTEIN-KINASE; RAT TRKC; RECEPTOR; SURVIVAL; PROTOONCOGENE; DEPENDENCE; DISRUPTION; FAMILY; SYSTEM AB Neurotrophin 3 (NT-3) is one of four related polypeptide growth factors that share structural and functional homology to nerve growth factor (NGF). NT-3 and its receptor, called neurotrophic tyrosine kinase receptor type 3 (Ntrk3; also called TrkC), are expressed early and throughout embryogenesis. We have inactivated the NT-3 gene in embryonic stem (ES) cells by homologous recombination. The mutated allele has been transmitted through the mouse germ line, and heterozygote intercrosses have yielded homozygous mutant newborn pups. The NT3-deficient mutants fail to thrive and exhibit severe neurological dysfunction, Analysis of mutant embryos uncovers loss of Ntrk3/TrkC-expressing sensory neurons and abnormalities at early stages of sensory neuronal development. NT3-deficient mice will permit further study of the role of this neurotrophin in neural development. C1 NCI,FREDERICK CANC RES & DEV CTR,ADV BIOSCI LABS,BASIC RES PROGRAM,MOLEC EMBRYOL SECT,FREDERICK,MD 21702. RI Parada, luis/B-9400-2014 FU NCI NIH HHS [N01-CO-74101] NR 44 TC 182 Z9 183 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 6 PY 1994 VL 91 IS 25 BP 11844 EP 11848 DI 10.1073/pnas.91.25.11844 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PW708 UT WOS:A1994PW70800017 PM 7991545 ER PT J AU SZPIRER, C MOLNE, M ANTONACCI, R JENKINS, NA FINELLI, P SZPIRER, J RIVIERE, M ROCCHI, M GILBERT, DJ COPELAND, NG GALLO, V AF SZPIRER, C MOLNE, M ANTONACCI, R JENKINS, NA FINELLI, P SZPIRER, J RIVIERE, M ROCCHI, M GILBERT, DJ COPELAND, NG GALLO, V TI THE GENES ENCODING THE GLUTAMATE-RECEPTOR SUBUNITS KA1 AND KA2 (GRIK4 AND GRIK5) ARE LOCATED ON SEPARATE CHROMOSOMES IN HUMAN, MOUSE, AND RAT SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE LIGAND-GATED ION CHANNELS; HUMAN CHROMOSOMES 19Q13.2 AND 11Q22-23; MOUSE CHROMOSOMES 7 AND 9; RAT CHROMOSOMES 8 AND 1 ID AMINO-ACID RECEPTORS; HIGH-AFFINITY; LINKAGE MAP; LOCALIZATION; ORGANIZATION; EPILEPSY; KAINATE; IDENTIFICATION; NORVEGICUS; CHANNELS AB The chromosomal localization of the human and rat genes encoding the kainate-preferring glutamate receptor subunits KA1 and KA2 (GRIK4 and GRIK5, respectively) was determined by Southern analysis of rat x mouse and human x mouse somatic cell hybrid panels and by fluorescence in situ hybridization. The localization of the mouse genes (Grik4 and Grik5) was established by interspecific backcross mapping. GRIK4 and GRIK5 are located on separate chromosomes (Chrs) in all species. GRIK4 mapped to human Chr 11q22.3, mouse Chr 9, and rat Chr 8. GRIK5 mapped to human Chr 19q13.2, mouse Chr 7, and rat Chr 1. The genes encoding the (R,S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-preferring subunit GluR4, or GluRD (GRIA4), the neural cell adhesion molecule (NCAM), the D2 dopamine receptor (DRD2), and the Thy-1 cell surface antigen (THY1) have all been previously mapped to the human Chr 11q22 region. The mapping of the human GRIK4 and GRIK5 genes confirms and extends the relationship between human Chr 11 and mouse Chr 9 and also human Chr 19 and mouse Chr 7. GRIK4 is the fifth gene shared by human Chr 11 and rat Chr 8, whereas GRIK5 is 1 out of the 12 genes that are located on both human Chr 19 and rat Chr 1. Our data extend the conserved synteny established between certain human, mouse, and rat Chrs. C1 NICHHD, CELLULAR & MOLEC NEUROPHYSIOL LAB, BETHESDA, MD 20892 USA. UNIV BRUSSELS, DEPT BIOL MOLEC, B-1640 RHODE ST GENESE, BELGIUM. UNIV BARI, IST GENET, I-70126 BARI, ITALY. NCI, FREDERICK CANC RES & DEV CTR,ADV BIOSCI LABS, BASIC RES PROGRAM,MAMMALIAN GENET LAB, FREDERICK, MD 21702 USA. RI Antonacci, Rachele/C-5635-2013; Finelli, Palma/A-3578-2016 OI Antonacci, Rachele/0000-0002-5601-1118; Finelli, Palma/0000-0001-8464-6906 FU NCI NIH HHS [N01-CO-74101] NR 41 TC 15 Z9 15 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 6 PY 1994 VL 91 IS 25 BP 11849 EP 11853 DI 10.1073/pnas.91.25.11849 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PW708 UT WOS:A1994PW70800018 PM 7527545 ER PT J AU RHIM, JS WEBBER, MM BELLO, D LEE, MS ARNSTEIN, P CHEN, LS JAY, G AF RHIM, JS WEBBER, MM BELLO, D LEE, MS ARNSTEIN, P CHEN, LS JAY, G TI STEPWISE IMMORTALIZATION AND TRANSFORMATION OF ADULT HUMAN PROSTATE EPITHELIAL-CELLS BY A COMBINATION OF HPV-18 AND V-KI-RAS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE PROSTATE CARCINOGENESIS; MALIGNANT TRANSFORMATION ID HUMAN PAPILLOMAVIRUS; HUMAN KERATINOCYTES; NEOPLASTIC TRANSFORMATION; HIGH PREVALENCE; CANCER; DNA; EXPRESSION; ONCOGENE; P21; ACTIVATION AB Recent investigations have shown the presence of ras gene mutations and human papillomavirus (HPV) DNA in prostate carcinomas. In the present study, secondary adult human prostatic epithelial cells, upon transfection with a plasmid containing the entire HPV-18 genome, acquired an indefinite life-span in culture but did not undergo malignant conversion. Subsequent infection of these immortalized cells with the Kirsten murine sarcoma virus, which contains an activated Ki-ras oncogene, induced morphological transformation that led to the acquisition of neoplastic properties. These findings demonstrate the malignant transformation of adult human prostate epithelial cells in culture by a combination of viral oncogenes and the successive roles of HPV infection and Ki-ras activation in a multistep process responsible for prostate carcinogenesis. C1 MICHIGAN STATE UNIV,DEPT MED,E LANSING,MI 48824. MICHIGAN STATE UNIV,DEPT ZOOL,E LANSING,MI 48824. AMER RED CROSS,JEROME H HOLLAND LAB,DEPT VIROL,ROCKVILLE,MD 20855. RP RHIM, JS (reprint author), NCI,CELLULAR & MOLEC BIOL LAB,BLDG 37,BETHESDA,MD 20892, USA. RI Jay, Gregory/C-6346-2013 NR 25 TC 85 Z9 86 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 6 PY 1994 VL 91 IS 25 BP 11874 EP 11878 DI 10.1073/pnas.91.25.11874 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PW708 UT WOS:A1994PW70800023 PM 7991549 ER PT J AU BENHAR, I PADLAN, EA JUNG, SH LEE, B PASTAN, I AF BENHAR, I PADLAN, EA JUNG, SH LEE, B PASTAN, I TI RAPID HUMANIZATION OF THE FV OF MONOCLONAL-ANTIBODY B3 BY USING FRAMEWORK EXCHANGE OF THE RECOMBINANT IMMUNOTOXIN B3(FV)-PE38 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RESHAPING HUMAN-ANTIBODIES; GENES; REPERTOIRE; CARCINOMA; SEGMENTS; DOMAINS; REGIONS; MOUSE; MICE AB B3(Fv)-PE38 is a recombinant single-chain immunotoxin in which the Fv region of carcinoma-specific antibody B3 is fused to a truncated form of Pseudomonas exotoxin (PE). The efficacy of monoclonal antibody B3 and B3 immunotoxins in cancer therapy and diagnosis may be limited by the human anti-mouse response. Here we describe the humanization of the Fv of B3(Fv)-PE38 by ''framework exchange.'' The variable domains of the heavy (V-H) and light (V-L) chains were aligned with their best human homologs to identify framework residues that differ. Initially, 11 framework residues in V-H and six in V-L were changed by site-specific mutagenesis to human residues and introduced simultaneously into a preassembled single-chain Fv expression cassette. Six V-H and five V-L residues that differ were not changed because they were buried, in the interdomain interface, or previously found to result in decreased affinity when mutated. This basic design resulted in some 20-fold loss of activity. Changing V-L residues at the interdomain interfacial position 100 and at the buried position 104 to the human sequence increased the activity 8-fold. Changing V-H residue at position 82b from the human sequence back to that of the mouse restored the activity 2- to 3-fold to the full binding and cytotoxic activity of the mouse sequence, Humanized B3(Fv)-PE38 lost immunogenic epitopes recognized by sera from monkeys that had been immunized with B3(Fv)-PE38. C1 NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,BETHESDA,MD 20892. NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 36 TC 23 Z9 26 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 6 PY 1994 VL 91 IS 25 BP 12051 EP 12055 DI 10.1073/pnas.91.25.12051 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PW708 UT WOS:A1994PW70800059 PM 7991583 ER PT J AU MULLER, JR POTTER, M JANZ, S AF MULLER, JR POTTER, M JANZ, S TI DIFFERENCES IN THE MOLECULAR-STRUCTURE OF C-MYC-ACTIVATING RECOMBINATIONS IN MURINE PLASMACYTOMAS AND PRECURSOR CELLS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CHAIN SWITCH; IMMUNOGLOBULIN; TRANSLOCATION; NEUTROPHILS; SEQUENCES; MECHANISM; ONCOGENE; DELETION; DEATH; BCL-2 AB The translocation of c-myc on chromosome (chr.) 15 to an immunoglobulin heavy-chain switch region on chr. 12 is the critical oncogenic step in pristane induced plasmacytoma (PCT) development in BALB/cAnPt mice. Applying a recently developed PCR method, we have been able to detect the most commonly occurring illegitimate recombinations between alpha-chain switch region (S alpha) and c-myc in preneo-plastic B cells residing in mesenteric oil granuloma (OG) tissues 7-30 days postpristane. In this study, we compare the nucleotide sequences at the S-alpha/c-myc breaksites on both the c-myc-activating chr. 12(+) and the reciprocal chr. 15(-) from eight transplanted PCTs, seven primary PCTs, and five OGs that contained six B cell clones. These junction sequences revealed a remarkable diversity of S-alpha/c-myc recombinations. In nine cases-four PCTs and five B-cell clones-nearly precise reciprocal exchanges with a loss of only 3-35 bp in c-myc were found. Large deletions in c-myc that removed 369-878 bp were observed in seven PCTs but not in early B cells. Duplications of c-myc ranging from 103 to 229 bp were also restricted to PCTs and noticed in four cases. Clonally related but different reciprocal recombinations, 38 bp apart on chr. 12(+) and 15 bp apart on chr. 15(-), were isolated from two different specimens of the same OG tissue from a BALB/c mouse 30 days postpristane. A second OG from another 30-day mouse yielded four recombinational fragments-two clonally related chr. 12(+)-specific fragments and two chr. 15(-)-specific fragments-one of which carried a 143-bp insertion of a microsatellite at the breaksite. We suggest thatthe initial recombinational breakpoint regions between S-alpha and c-myc in plasmacytoma precursor cells at the time of immunoglobulin heavy-chain switching are intrinsically labile and characterized by a persisting instability of c-myc, which can result in large secondary deletions of c-myc. RP MULLER, JR (reprint author), NCI,DIV CANC BIOL DIAG & CTR,GENET LAB,BETHESDA,MD 20892, USA. NR 23 TC 33 Z9 33 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 6 PY 1994 VL 91 IS 25 BP 12066 EP 12070 DI 10.1073/pnas.91.25.12066 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PW708 UT WOS:A1994PW70800062 PM 7991585 ER PT J AU TATUSOV, RL ALTSCHUL, SF KOONIN, EV AF TATUSOV, RL ALTSCHUL, SF KOONIN, EV TI DETECTION OF CONSERVED SEGMENTS IN PROTEINS - ITERATIVE SCANNING OF SEQUENCE DATABASES WITH ALIGNMENT BLOCKS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ACID SUBSTITUTION MATRICES; BINDING-SITES; MULTIPLE ALIGNMENT; ESCHERICHIA-COLI; PATTERNS; IDENTIFICATION; PURIFICATION; GENERATION; SEARCH; MOTIFS AB We describe an approach to analyzing protein sequence databases that, starting from a single uncharacterized sequence or group of related sequences, generates blocks of conserved segments. The procedure involves iterative database scans with an evolving position-dependent weight matrix constructed from a coevolving set of aligned conserved segments. For each iteration, the expected distribution of matrix scores under a random model is used to set a cutoff score for the inclusion of a segment in the next iteration. This cutoff may be calculated to allow the chance inclusion of either a fixed number or a fixed proportion of false positive segments. With sufficiently high cutoff scores, the procedure converged for all alignment blocks studied, with varying numbers of iterations required. Different methods for calculating weight matrices from alignment blocks were compared. The most effective of those tested was a logarithm-of-odds, Bayesian-based approach that used prior residue probabilities calculated from a mixture of Dirichlet distributions. The procedure described was used to detect novel conserved moths of potential biological importance. C1 NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. NR 47 TC 246 Z9 246 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 6 PY 1994 VL 91 IS 25 BP 12091 EP 12095 DI 10.1073/pnas.91.25.12091 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PW708 UT WOS:A1994PW70800067 PM 7991589 ER PT J AU YANG, SW NASH, HA AF YANG, SW NASH, HA TI SPECIFIC PHOTO-CROSS-LINKING OF DNA-PROTEIN COMPLEXES - IDENTIFICATION OF CONTACTS BETWEEN INTEGRATION HOST FACTOR AND ITS TARGET DNA SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ARYL AZIDE; PEPTIDE SEQUENCE; DNA BEND ID ESCHERICHIA-COLI; BACTERIOPHAGE-LAMBDA; CRYSTAL-STRUCTURE; CROSS-LINKING; BINDING-SITES; FACTOR IHF; POLYMERASE; REAGENT; MUTANTS; RNA AB Azide moieties have been specifically placed in the backbone of DNA by chemical coupling between azidophenacyl bromide and uniquely positioned phosphorothioate residues. The derivatized DNA forms specific complexes with a DNA-binding protein and, following irradiation with 302-nm light, makes specific crosslinks to the protein. Isolation of this covalent complex, followed by tryptic digestion and Edman degradation of the resulting crosslinked peptide, identifies the portion of the protein that is near the derivatized segment of the target DNA. We use this method to probe the interaction between a specific DNA sequence and integration host factor (IHF) protein. A single IHF heterodimer is known to contact >25 bp of DNA and thereby introduce a sharp bend. Two segments of a typical IHF site were derivatized with aryl, azide. Although the segments were separated by only 5 bp, they crosslinked to different subunits of IHF. The locations of the crosslinks support our current view for the way IHF protein binds to and bends its specific targets. RP YANG, SW (reprint author), NIH,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 28 TC 59 Z9 59 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 6 PY 1994 VL 91 IS 25 BP 12183 EP 12187 DI 10.1073/pnas.91.25.12183 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PW708 UT WOS:A1994PW70800086 PM 7991603 ER PT J AU LEEHUANG, S KUNG, HF HUANG, PL BOURINBAIAR, AS MORELL, JL BROWN, JH HUANG, PL TSAI, WP CHEN, AY HUANG, HI CHEN, HC AF LEEHUANG, S KUNG, HF HUANG, PL BOURINBAIAR, AS MORELL, JL BROWN, JH HUANG, PL TSAI, WP CHEN, AY HUANG, HI CHEN, HC TI HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 (HIV-1) INHIBITION, DNA-BINDING, RNA-BINDING, AND RIBOSOME INACTIVATION ACTIVITIES IN THE N-TERMINAL SEGMENTS OF THE PLANT ANTI-HIV PROTEIN GAP31 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID EUKARYOTIC RIBOSOMES; MECHANISM; RICIN AB GAP31 (gelonium anti-HIV protein of 31 kDa) is an anti-HIV protein which we have identified and purified from a medicinal plant, Gelonium multiflorum. It is capable of inhibiting HIV-1 infection and replication. GAP31 also exhibits DNA topoisomerase inhibitor activity and RNA N-glycosidase activity. The ability of GAP31 to interrupt both DNA and RNA functions may be related to its multiple antiviral actions. To define the roles of these activities in the anti-HIV action of GAP31, a series of peptides corresponding to the N-terminal segment of GAP31 were synthesized and assayed for the aforementioned activities of the parent molecule. A 33-aa segment (KGATYITYVNFLNELRVKTKPEGNSHGIPSLRK) designated as K10-K42 is the shortest peptide necessary and sufficient for HIV-1 inhibition, DNA and RNA binding, and ribosome inactivation. The peptides were 2-5 orders of magnitude less active than GAP31. Truncation of 19 aa from the C terminus of K10-K42 resulted in the loss of all of these activities. On the other hand, deletion of N-terminal residues to give E23-K42 did not alter ribosome-inactivation activity but eliminated the other activities. These findings permit identification of a 7-aa sequence, KGATYIT, at the N terminus of K10-K42 that is critical for DNA binding and RNA binding, whereas a 9-aa sequence, SHGIPSLRK, at the C terminus is important to ribosome inactivation. Both regions contribute to anti-HIV activity. Histidine at position 35 is critical for all of these activities. The disparity of sequence requirements for inhibition of HIV infection and replication and for ribosome-inactivation activity suggests that the anti-HIV activity of most ribosome-inactivating proteins may not be the result of N-glycosidase activity alone. Mapping the minimal domain of GAP31 offers insights into the rational design of molecular mimetics of anti-HIV drugs. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC RES,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21701. NICHHD,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892. AMER BIOSCI,NEW YORK,NY 10021. RP LEEHUANG, S (reprint author), NYU,SCH MED,DEPT BIOCHEM,NEW YORK,NY 10016, USA. FU NIAID NIH HHS [R01 AI31334] NR 14 TC 50 Z9 54 U1 1 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 6 PY 1994 VL 91 IS 25 BP 12208 EP 12212 DI 10.1073/pnas.91.25.12208 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PW708 UT WOS:A1994PW70800091 PM 7527556 ER PT J AU WICKNER, S GOTTESMAN, S SKOWYRA, D HOSKINS, J MCKENNEY, K MAURIZI, MR AF WICKNER, S GOTTESMAN, S SKOWYRA, D HOSKINS, J MCKENNEY, K MAURIZI, MR TI A MOLECULAR CHAPERONE, CLPA, FUNCTIONS LIKE DNAK AND DNAJ SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE HEAT SHOCK PROTEINS; PLASMID P1; ATP-DEPENDENT PROTEOLYSIS; CLPP ID HEAT-SHOCK PROTEINS; ATP-DEPENDENT PROTEASE; ESCHERICHIA-COLI; NUCLEOPROTEIN STRUCTURES; BACTERIOPHAGE-LAMBDA; REPA MONOMERIZATION; ACTIVATED ATPASE; RNA-POLYMERASE; REPLICATION; GRPE AB The two major molecular chaperone families that mediate ATP-dependent protein folding and refolding are the heat shock proteins Hsp60s (GroEL) and Hsp70s (DnaK). Clp proteins, like chaperones, are highly conserved, present in all organisms, and contain ATP and polypeptide binding sites. We discovered that ClpA, the ATPase component of the ATP-dependent ClpAP protease, is a molecular chaperone. ClpA performs the ATP-dependent chaperone function of DnaK and DnaJ in the in vitro activation of the plasmid P1 RepA replication initiator protein. RepA is activated by the conversion of dimers to monomers. We show that ClpA targets RepA for degradation by ClpP, demonstrating a direct link between the protein unfolding function of chaperones and proteolysis. In another chaperone assay, ClpA protects luciferase from irreversible heat inactivation but is unable to reactivate luciferase. C1 NCI,CELL BIOL LAB,BETHESDA,MD 20892. CTR ADV RES BIOTECHNOL,ROCKVILLE,MD 20850. NATL INST STAND & TECHNOL,GAITHERSBURG,MD 20899. RP WICKNER, S (reprint author), NCI,MOLEC BIOL LAB,BLDG 37,ROOM 2D19,BETHESDA,MD 20892, USA. NR 27 TC 304 Z9 307 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 6 PY 1994 VL 91 IS 25 BP 12218 EP 12222 DI 10.1073/pnas.91.25.12218 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PW708 UT WOS:A1994PW70800093 PM 7991609 ER PT J AU HU, HM OROURKE, K BOGUSKI, MS DIXIT, VM AF HU, HM OROURKE, K BOGUSKI, MS DIXIT, VM TI NOVEL RING FINGER PROTEIN INTERACTS WITH THE CYTOPLASMIC DOMAIN OF CD40 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID ZINC-FINGER; DEFECTIVE EXPRESSION; ACTIVATION MOLECULE; HYPER-IGM; LIGAND; SYSTEM; IDENTIFICATION; MOTIFS AB CD40 is a member of the tumor necrosis factor receptor family and, like other members, it appears to possess no intrinsic signaling capacity (e.g. kinase activity), suggesting that signal transduction is likely mediated by associating molecules. To identify such molecules, we have utilized the yeast two-hybrid system to clone cDNAs encoding proteins that bind the CD40 cytoplasmic domain. One such interacting protein, designated CD40-binding protein, has a N-terminal RING finger motif that is found in a number of DNA-binding proteins, including the V(D)J recombination activating gene RAG1. In addition, it contains a prominent central coiled-coil segment that may allow homo- or hetero-oligomerization. The C terminus possesses substantial homology to the tumor necrosis factor receptor-associated factor (TRAF) domain that is found in two proteins (TRAF1 and TRAFS) that associate with the cytoplasmic domain of the related 75 kDa tumor necrosis factor receptor. This is the first identification of a molecule that interacts with CD40 and whose sequence suggests a potential role in signaling. C1 UNIV MICHIGAN,SCH MED,DEPT PATHOL,ANN ARBOR,MI 48109. NIH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894. RI dixit, vishva/A-4496-2012 OI dixit, vishva/0000-0001-6983-0326 FU NCI NIH HHS [CA61348] NR 28 TC 328 Z9 332 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 DEC 2 PY 1994 VL 269 IS 48 BP 30069 EP 30072 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PU525 UT WOS:A1994PU52500002 PM 7527023 ER PT J AU LI, CCH DAI, RM CHEN, E LONGO, DL AF LI, CCH DAI, RM CHEN, E LONGO, DL TI PHOSPHORYLATION OF NF-KAPPA-B1-P50 IS INVOLVED IN NF-KAPPA-B ACTIVATION AND STABLE DNA-BINDING SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID TUMOR-NECROSIS-FACTOR; PROTEIN-KINASE-C; TRANSCRIPTIONAL ACTIVATION; REL; DORSAL; CELLS; PRECURSOR; SUBUNITS; INVITRO; COMPLEX AB We have previously shown that NF-kappa B/Rel family members are physically associated phosphoproteins, and p105 and p50 are hyperphosphorylated after NF-kappa B activation. In this report, we further studied the phosphorylation involved in NF-kappa B activation in Jurkat T cells responding to phorbol 12-myristate 13-acetate and phytohemagglutinin. Immediately following stimulation, p50 is hyperphosphorylated, and a phosphorylated form of p50 (pp50) is translocated from the cytoplasm to the nucleus. The kinetics of this nuclear translocation paralleled that of the appearance of an active kappa B DNA-binding complex. An at least 30-fold higher level of kappa B DNA binding was detected in pp50 than p50. The enhanced binding could be attributed to a much greater stability detected in the complex consisting of kappa B DNA and pp50, but not p50. These results suggest that phosphorylation of p50, and perhaps other family members as well, may be involved in the activation of NF-kappa B/Rel family transcription factors. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. RP LI, CCH (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702, USA. NR 24 TC 63 Z9 63 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 DEC 2 PY 1994 VL 269 IS 48 BP 30089 EP 30092 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PU525 UT WOS:A1994PU52500007 PM 7982908 ER PT J AU LIN, B HOLLINGSHEAD, SK COLIGAN, JE EGAN, ML BAKER, JR PRITCHARD, DG AF LIN, B HOLLINGSHEAD, SK COLIGAN, JE EGAN, ML BAKER, JR PRITCHARD, DG TI CLONING AND EXPRESSION OF THE GENE FOR GROUP-B STREPTOCOCCAL HYALURONATE LYASE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Note ID NEURAMINIDASE; DISEASE AB Group B streptococci (GBS) are a major cause of serious human perinatal infections. Most clinical isolates of GBS secrete hyaluronate lyase, and production of high levels of the enzyme has been associated with strain virulence. Degenerate oligonucleotide primers, designed on the basis of the amino acid sequences of tryptic peptides prepared from the purified enzyme, permitted the polymerase chain reaction amplification from GBS chromosomal DNA of a 363-base pair internal DNA fragment of the GES hyaluronate lyase gene (hylB). This DNA fragment was used as a probe to screen a lambda phage library of GBS chromosomal DNA fragments. Sequence analysis of positive clones identified an open reading frame capable of coding for a 111-kDa protein. Since no single clone was found to contain the entire gene it was necessary to reconstruct the gene from two plasmids containing inserts with suitable overlapping sequences. When this reconstructed gene was transformed into Escherichia coli, high level expression of hyaluronate lyase activity was obtained. C1 UNIV ALABAMA,SCH MED,JOINT DEPT,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT MICROBIOL,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT MOLEC GENET & BIOCHEM,BIRMINGHAM,AL 35294. DEPT VET AFFAIRS MED CTR,BIRMINGHAM,AL 35233. NIAID,CELLULAR & MOLEC IMMUNOL LAB,BETHESDA,MD 20892. FU NIA NIH HHS [AG-10070]; NIAID NIH HHS [AI-30634]; NICHD NIH HHS [HD-17812] NR 16 TC 45 Z9 49 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 DEC 2 PY 1994 VL 269 IS 48 BP 30113 EP 30116 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PU525 UT WOS:A1994PU52500013 PM 7982914 ER PT J AU NOMIZU, M OTAKA, A UTANI, A ROLLER, PP YAMADA, Y AF NOMIZU, M OTAKA, A UTANI, A ROLLER, PP YAMADA, Y TI ASSEMBLY OF SYNTHETIC LAMININ PEPTIDES INTO A TRIPLE-STRANDED COILED-COIL STRUCTURE SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BASEMENT-MEMBRANES; CIRCULAR-DICHROISM; B2 CHAIN; LONG ARM; PROTEINS; GLYCOPROTEIN; MECHANISM; DOMAIN; TRIMERIZATION; HETERODIMER AB Laminin, a large multidomain glycoprotein specific to basement membranes, is a heterotrimer with alpha, beta, and gamma chains held together in an cu-helical coiled-coil structure. Synthetic peptides comprising two 51-mers (B1 and B2) from the beta 1 and gamma 1 subunits and a 55-mer (M) from alpha 2 were used to study the molecular mechanisms in laminin chain assembly. Using the synthetic peptides in various mixing experiments, the heterotrimer (B1-B2-M) was preferentially produced. The thermal stability of the heterotrimer increased dramatically (by approximately 20 degrees C) over that of the B1-B2 heterodimer as measured by circular dichroism (CD) spectroscopy. The B1-B1 homodimer (T-m = 60 degrees C) showed higher thermal stability when compared to B1-B2 and B2-B2 dimers. However, the B1+B2 mixture produced principally the B1-B2 heterodimer. These results suggested that the preferential formations of heterodimer was regulated by kinetic interactions between each chain. The B2 and M peptides have many hydrophobic isoleucine residues which were replaced by leucines. These substitutions were predicted to favor an alpha-helical conformation and a higher propensity for zipper formation. B2L and ML, in which all isoleucine residues were replaced by leucine, showed significantly increased alpha-helicities. While B2L was able to form heterodimers and heterotrimers similar to B2, ML was not able to participate in heterotrimer formation as efficiently as the M peptide, The thermal stability of B1-B2L was comparable to that of B1-B2, but B2L and/or ML containing trimers showed lower thermal stability than B1-B2-M. These results suggest that the isoleucine residues in the alpha 2 and gamma 1 chains are critical for stabilizing the heteromeric triple-stranded coiled coil structure. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,MED CHEM LAB,BETHESDA,MD 20892. RP NOMIZU, M (reprint author), NIDR,DEV BIOL LAB,BLDG 30,RM 427,BETHESDA,MD 20892, USA. NR 48 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 DEC 2 PY 1994 VL 269 IS 48 BP 30386 EP 30392 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PU525 UT WOS:A1994PU52500055 PM 7982952 ER PT J AU WEBB, DJ ATKINS, TL CROOKSTON, KP BURMESTER, JK QIAN, SW GONIAS, SL AF WEBB, DJ ATKINS, TL CROOKSTON, KP BURMESTER, JK QIAN, SW GONIAS, SL TI TRANSFORMING GROWTH-FACTOR-BETA ISOFORM 2-SPECIFIC HIGH-AFFINITY BINDING TO NATIVE ALPHA(2)-MACROGLOBULIN - CHIMERAS IDENTIFY A SEQUENCE THAT DETERMINES AFFINITY FOR NATIVE BUT NOT ACTIVATED ALPHA(2)-MACROGLOBULIN SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ALPHA-2-MACROGLOBULIN RECEPTOR; ALPHA-MACROGLOBULIN; ENDOTHELIAL-CELLS; CRYSTAL-STRUCTURE; PRIMARY AMINES; FAST FORMS; FACTOR-BETA-1; METHYLAMINE; COMPLEX; GROWTH-FACTOR-BETA-2 AB Transforming growth factor beta 2 (TGF-beta 2) is less potent than TGF-beta 1 in some endothelial cell proliferation as says due to the greater tendency of TGF-beta 2 to bind alpha(2)-macroglobulin (alpha(2)M). Substitution of TGF-beta 1 residues 40-47 into the TGF-beta 2 sequence yields a chimeric molecule that, like TGF-beta 1, expresses activity that is not substantially affected by serum alpha(2)M (Burmester, J. K., Qian, S. W., Roberts, A. B., Huang, A., Amatayakul-Chantler, S., Suardet, L., Odartchenko, N., Madri, J. A., and Sporn, M. B. (1993) Proc. Natl. Acad. Sci. U. S. A. 90, 8628-8632). In this investigation, we studied the binding of TGF-beta chimeras, which contain TGF-beta 1 residues 40-47, to both major conformations of human alpha(2)M under apparent equilibrium conditions. Native alpha(2)M, the primary form of this protein in serum, bound TGF-beta(2)/beta(1)(40-82) and TGF-beta(2)/beta(1)(40-47) with low affinity. The apparent K-D values for the two chimeras and native alpha(2)M were 310 and 330 nM, respectively. These values were much higher than the K-D determined for TGF-beta 2 and native alpha(2)M (11 nM) and equivalent to the K-D determined for TGF-beta 1 and native alpha(2)M. By contrast, both TGF-beta chimeras bound alpha(2)M-methylamine, an altered conformation of alpha(2)M, with high affinity (16 and 19 nM), which is characteristic of TGF-beta 2 and not TGF-beta 1. Fetal bovine heart endothelial cell DNA synthesis was inhibited to a similar degree by TGF-beta 1, TGF-beta 2, TGF-beta(2)/beta(1)(40-82), and TGF-beta(2)/beta(1)(40-47) in the presence of dilute (0.2%) fetal bovine serum. When 0.07 mu M alpha 2M-methylamine was added, the activities of TGF-beta 2, TGF-beta(2)/beta(1)(40-82), and TGF-beta(2)/beta(1)(40-47) were significantly counteracted while the activity of TGF-beta 1 was unchanged, as would be predicted by the equilibrium binding analyses. These studies indicate that the TGF-beta structural elements, which mediate binding to native alpha(2)M and conformationally transformed alpha(2)M, are not equivalent. Residues 40-47 are critical in determining affinity for native alpha(2)M but are less important in determining affinity for alpha(2)MM methylamine. C1 UNIV VIRGINIA,HLTH SCI CTR,DEPT BIOCHEM,CHARLOTTESVILLE,VA 22908. UNIV VIRGINIA,HLTH SCI CTR,DEPT PATHOL,CHARLOTTESVILLE,VA 22908. MARSHFIELD CLIN FDN MED RES & EDUC,MARSHFIELD,WI 54449. NIH,CHEMOPREVENT LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA-53462]; NHLBI NIH HHS [HL-02272]; NIGMS NIH HHS [GM 07267] NR 34 TC 25 Z9 25 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 DEC 2 PY 1994 VL 269 IS 48 BP 30402 EP 30406 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PU525 UT WOS:A1994PU52500057 PM 7527030 ER PT J AU MURATA, J LEE, HY CLAIR, T KRUTZSCH, HC ARESTAD, AA SOBEL, ME LIOTTA, LA STRACKE, ML AF MURATA, J LEE, HY CLAIR, T KRUTZSCH, HC ARESTAD, AA SOBEL, ME LIOTTA, LA STRACKE, ML TI CDNA CLONING OF THE HUMAN TUMOR MOTILITY-STIMULATING PROTEIN, AUTOTAXIN, REVEALS A HOMOLOGY WITH PHOSPHODIESTERASES SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL MEMBRANE GLYCOPROTEIN; FIBROBLAST GROWTH-FACTOR; AMINO-ACID-SEQUENCE; IV COLLAGENASE; 5'-NUCLEOTIDE PHOSPHODIESTERASE; NUCLEOTIDE PYROPHOSPHATASE; INTERSTITIAL COLLAGENASE; IDENTIFICATION; PC-1; EXPRESSION AB A human cDNA clone encoding autotaxin, a tumor cell motility-stimulating protein, reveals that this protein is an ecto/exo-enzyme with significant homology to the plasma cell membrane differentiation antigen PC-1. ATX is a 125-kDa glycoprotein, previously isolated from a human melanoma cell line (A2058), which elicits chemotactic and chemokinetic responses at picomolar to nanomolar concentrations. Affinity-purified antipeptide antibodies to the ATX peptide, ATX-102, were employed to screen an A2058 cDNA expression library made in lambda gt11. The partial cDNA sequence which was obtained was then extended by utilizing reverse transcriptase on total cellular RNA followed by polymerase chain reaction amplification. The isolated cDNA clone contained 3251 base pairs, and the mRNA message size was approximately 3.3 kilobases. The deduced amino acid sequence of autotaxin matched 30 previously sequenced peptides and comprised a protein of 915 amino acids. Data base analysis of the ATX sequence revealed a 45% amino acid identity (including 30 out of 33 cysteines) with PC-1, a pyrophosphatase/type I phosphodiesterase expressed on the surface of activated B cells and plasma cells. ATX, like PC-1, was found to hydrolyze the type I phosphodiesterase substrate p-nitrophenyl thymidine-5'-monophosphate. Autotaxin now defines a novel motility-regulating function for this class of ecto/exo-enzymes. C1 NCI, PATHOL LAB, BETHESDA, MD 20892 USA. NR 34 TC 168 Z9 172 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 2 PY 1994 VL 269 IS 48 BP 30479 EP 30484 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PU525 UT WOS:A1994PU52500068 PM 7982964 ER PT J AU CHENG, RH CASTON, JR WANG, GJ GU, F SMITH, TJ BAKER, TS BOZARTH, RF TRUS, BL CHENG, NQ WICKNER, RB STEVEN, AC AF CHENG, RH CASTON, JR WANG, GJ GU, F SMITH, TJ BAKER, TS BOZARTH, RF TRUS, BL CHENG, NQ WICKNER, RB STEVEN, AC TI FUNGAL VIRUS CAPSIDS, CYTOPLASMIC COMPARTMENTS FOR THE REPLICATION OF DOUBLE-STRANDED-RNA, FORMED AS ICOSAHEDRAL SHELLS OF ASYMMETRIC GAG DIMERS SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Note DE CRYOELECTRON MICROSCOPY; VIRUS CAPSID PROTEIN; 3-DIMENSIONAL IMAGE RECONSTRUCTION; QUASI-EQUIVALENCE; DOUBLE-STRANDED RNA ID CRYO-ELECTRON-MICROSCOPY; SACCHAROMYCES-CEREVISIAE; USTILAGO-MAYDIS; RECONSTRUCTION; PARTICLES AB The primary functions of most virus capsids are to protect the viral genome in the extra-cellular milieu and deliver it to the host. In contrast, the capsids of fungal viruses, like the cores of all other known double stranded RNA viruses, are not involved in host recognition but do shield their genomes, and they also carry out transcription and replication. Nascent (+) strands are extruded from transcribing virions. The capsids of the yeast virus L-A are composed of Gag (capsid protein; 76 kDa), with a few molecules of Gag-Pol (170 kDa). Analysis of these 420 Angstrom diameter shells and those of the fungal P4 virus by cryo-electron microscopy and image reconstruction shows that they share the same novel icosahedral structure. Both capsids consist of 60 equivalent Gag dimers, whose two subunits occupy non-equivalent bonding environments. Stoichiometry data on other double-stranded RNA viruses indicate that the 120-subunit structure is widespread, implying that this molecular architecture has features that are particularly favorable to the design of a capsid that is also a biosynthetic compartment. C1 PURDUE UNIV,DEPT BIOL SCI,W LAFAYETTE,IN 47907. NIAMSD,STRUCT BIOL LAB,BETHESDA,MD 20892. NIDDKD,DIV COMP RES & TECHNOL,COMP BIOSCI & ENGN LAB,BETHESDA,MD 20892. NIDDKD,BIOCHEM PHARMACOL LAB,BETHESDA,MD 20892. INDIANA STATE UNIV,DEPT BIOL,TERRE HAUTE,IN 47809. RI Cheng, Holland/A-8973-2008; Smith, Thomas/K-9086-2013; Caston, Jose/L-5896-2014 OI Smith, Thomas/0000-0003-3528-6793; Caston, Jose/0000-0003-2350-9048 FU NIGMS NIH HHS [R37 GM033050] NR 23 TC 80 Z9 82 U1 0 U2 4 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD DEC 2 PY 1994 VL 244 IS 3 BP 255 EP 258 DI 10.1006/jmbi.1994.1726 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PV293 UT WOS:A1994PV29300001 PM 7966336 ER PT J AU BOUFFARD, GG RUDD, KE ADHYA, SL AF BOUFFARD, GG RUDD, KE ADHYA, SL TI DEPENDENCE OF LACTOSE METABOLISM UPON MUTAROTASE ENCODED IN THE GAL OPERON IN ESCHERICHIA-COLI SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE GLUCOSE; GALACTOSE; BETA-D-GALACTOSIDE; ALDOSE-1-EPIMERASE; GALM ID ACINETOBACTER-CALCOACETICUS MUTAROTASE; HIGH-LEVEL EXPRESSION; GENES; SEQUENCE; K-12; LIPOPOLYSACCHARIDE; TRANSCRIPTION; MUTATIONS; GALACTOSE; PROTEINS AB A new gene (galM) has been identified as the fourth cistron of the gal operon, encoding enzymes for the metabolism of galactose and lactose in Escherichia coli. Induction of the gal operon either from the gal promoters or from a neighboring prophage lambda promoter expresses the galM gene as well. The new structure of the gal operon from the promoter end is galE-galT-galK-galM in counter-clockwise orientation on the chromosome. Genetic and biochemical analyses hare revealed that the galM gene product has mutarotase activity, which converts alpha-aldose to the beta-anomer. Unlike mutarotase from other bacteria in which the enzyme is primarily processed for export and secretion, the mutarotase from E. coli does not appear to be processed and yet is still found in periplasm (and culture media when overexpressed) in significant amounts. Although the interconversion of the sugar anomers occurs spontaneously in pure water in vitro, the in vivo formation of alpha-D-galactopyranose (the substrate for phosphorylation) from beta-D-galactopyranose (generated by beta-galactosidase hydrolysis of lactose) is largely dependent upon the presence of the mutarotase. This shows that efficient lactose metabolism requires mutarotase. These results give credence to the idea that the activity of intracellular water is not high enough to permit a simple extrapolation of observed in vitro reactions to in vivo situations in every case. C1 NCI, MOLEC BIOL LAB, BETHESDA, MD 20892 USA. GEORGE WASHINGTON UNIV, DEPT MICROBIOL & IMMUNOL, WASHINGTON, DC 20037 USA. NATL LIB MED, NATL CTR BIOTECHNOL INFORMAT, BETHESDA, MD 20894 USA. NR 45 TC 57 Z9 60 U1 1 U2 8 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 EI 1089-8638 J9 J MOL BIOL JI J. Mol. Biol. PD DEC 2 PY 1994 VL 244 IS 3 BP 269 EP 278 DI 10.1006/jmbi.1994.1728 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PV293 UT WOS:A1994PV29300003 PM 7966338 ER PT J AU KORACH, KS AF KORACH, KS TI INSIGHTS FROM THE STUDY OF ANIMALS LACKING FUNCTIONAL ESTROGEN-RECEPTOR SO SCIENCE LA English DT Article ID HORMONE; GENE; ADENOCARCINOMA; ACTIVATION; RESISTANCE; BINDING; CELLS AB Estrogen hormones produce physiological actions within a variety of target sites in the body and during development by activating a specific receptor protein. Hormone responsiveness for the estrogen receptor protein was investigated at different stages of development with the use of gene knockout techniques because no natural genetic mutants have been described. A mutant mouse line without a functional estrogen receptor was created and is being used to assess estrogen responsiveness. Both sexes of these mutant animals are infertile and show a variety of phenotypic changes, some of which are associated with the gonads, mammary glands, reproductive tracts, and skeletal tissues. RP KORACH, KS (reprint author), NIEHS,REPROD & DEV TOXICOL LAB,RECEPTOR BIOL SECT,RES TRIANGLE PK,NC 27709, USA. OI Korach, Kenneth/0000-0002-7765-418X NR 32 TC 456 Z9 463 U1 0 U2 6 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 DEC 2 PY 1994 VL 266 IS 5190 BP 1524 EP 1527 DI 10.1126/science.7985022 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA PV015 UT WOS:A1994PV01500034 PM 7985022 ER PT J AU CORN, M AF CORN, M TI FUNDING FOR COMPUTER-ASSISTED-INSTRUCTION PROJECTS SO ACADEMIC MEDICINE LA English DT Article RP CORN, M (reprint author), NATL LIB MED,DIV EXTRAMURAL PROGRAM,BETHESDA,MD, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 1040-2446 J9 ACAD MED JI Acad. Med. PD DEC PY 1994 VL 69 IS 12 BP 958 EP 960 DI 10.1097/00001888-199412000-00005 PG 3 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA PX393 UT WOS:A1994PX39300007 PM 7999183 ER PT J AU KOCH, R LEVY, HL MATALON, R ROUSE, B HANLEY, WB TREFZ, F AZEN, C FRIEDMAN, EG DELACRUZ, F GUTTLER, F ACOSTA, PB AF KOCH, R LEVY, HL MATALON, R ROUSE, B HANLEY, WB TREFZ, F AZEN, C FRIEDMAN, EG DELACRUZ, F GUTTLER, F ACOSTA, PB TI THE INTERNATIONAL COLLABORATIVE STUDY OF MATERNAL PHENYLKETONURIA - STATUS-REPORT 1994 SO ACTA PAEDIATRICA LA English DT Article; Proceedings Paper CT Symposium on Phenylketonuria - Past, Present, Future CY MAY 23-25, 1994 CL HELSINGOR, DENMARK DE CONGENITAL HEART DISEASE; FETAL ABNORMALITIES; MICROCEPHALY; PHENYLKETONURIA; PREGNANCY ID UNITED-STATES; HYPERPHENYLALANINEMIA; DIET; PKU AB Neonatal screening for phenylketonuria (PKU) has created a problem as females with PKU are reaching child-bearing age. Surveys have revealed that maternal phenylalanine blood concentrations greater than 1200 mu mol/l are associated with fetal microcephaly, congenital heart defects and intrauterine growth retardation. It is estimated that as many as 3000 hyperphenylalaninemic females may be at risk of producing these fetal abnormalities. To examine this problem, the international maternal PKU collaborative study was developed to evaluate the efficacy of a phenylalanine-restricted diet in reducing fetal morbidity. Preliminary findings have indicated that phenylalanine restriction should begin before conception for females with PKU planning a pregnancy. Dietary control should maintain maternal blood phenylalanine levels between 120 and 360 mu mol/l and should provide adequate energy, protein, vitamin and mineral intake. Pregnant hyperphenylalaninemic females who achieved metabolic control after conception or by the 10th week of pregnancy had a better offspring outcome than anticipated. The results of 402 pregnancies are reviewed. C1 UNIV SO CALIF,LOS ANGELES,CA. BOSTON CHILDRENS HOSP,BOSTON,MA. MIAMI CHILDRENS HOSP,RES INST,MIAMI,FL. UNIV TEXAS,MED BRANCH,GALVESTON,TX. HOSP SICK CHILDREN,TORONTO,ON,CANADA. UNIV TUBINGEN,REUTLINGEN,GERMANY. NICHHD,BETHESDA,MD. UNIV COPENHAGEN,JOHN F KENNEDY INST,GLOSTRUP,DENMARK. ABBOTT LABS,ROSS PROD DIV,COLUMBUS,OH. RP KOCH, R (reprint author), CHILDRENS HOSP LOS ANGELES,DIV MED GENET,PKU 73,46 SUNSET BLVD,LOS ANGELES,CA 90027, USA. NR 19 TC 2 Z9 2 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0803-5253 J9 ACTA PAEDIATR JI Acta Paediatr. PD DEC PY 1994 VL 83 SU 407 BP 111 EP 119 DI 10.1111/j.1651-2227.1994.tb13468.x PG 9 WC Pediatrics SC Pediatrics GA QK833 UT WOS:A1994QK83300030 ER PT J AU GURALNIK, JM SEEMAN, TE TINETTI, ME NEVITT, MC BERKMAN, LF AF GURALNIK, JM SEEMAN, TE TINETTI, ME NEVITT, MC BERKMAN, LF TI VALIDATION AND USE OF PERFORMANCE-MEASURES OF FUNCTIONING IN A NONDISABLED OLDER POPULATION - MACARTHUR STUDIES OF SUCCESSFUL AGING SO AGING-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE AGING; DISABILITY EVALUATION; ELDERLY; VALIDITY AB Assessment of physical functioning in older persons has generally focused on identifying and characterizing subjects at the disabled end of the functional spectrum. This paper examines the validity of objective, standardized performance measures of physical functioning in characterizing the hierarchy of functioning in non-disabled, higher functioning older persons. Data are from 1192 participants aged 70-79 years in The MacArthur Research Network on Successful Aging Field Study. Participants were drawn from three communitybased populations and represented the upper tertile of functioning, based on cognitive and physical screening assessments. The cohort showed a great deal of heterogeneity on most of the performance measures of functioning that were used. Several analyses provided evidence that this variability was not random and that the performance measures were valid measures of functioning in this cohort: 1) individual performance measures showed a moderate degree of correlation with each other; 2) a summary measure of performance showed an association with chronic diseases and other factors known to be associated with health status; and 3) a larger group than expected by chance alone was found to be functioning at the very highest level. RP GURALNIK, JM (reprint author), NIA,7201 WISCONSIN AVE,ROOM 3C-309,BETHESDA,MD 20892, USA. FU NIA NIH HHS [N01-AG-0-2105, N01-AG-0-2107, N01-AG-1-2102] NR 0 TC 100 Z9 100 U1 0 U2 5 PU EDITRICE KURTIS S R L PI MILANO PA VIA LUIGI ZOJA, 30-20153 MILANO, ITALY SN 0394-9532 J9 AGING-CLIN EXP RES JI Aging-Clin. Exp. Res. PD DEC PY 1994 VL 6 IS 6 BP 410 EP 419 PG 10 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA QB687 UT WOS:A1994QB68700003 PM 7748914 ER PT J AU HARIHARAN, K NARA, PL SHABAZZ, LA MCCUTCHAN, JA KANG, CY AF HARIHARAN, K NARA, PL SHABAZZ, LA MCCUTCHAN, JA KANG, CY TI ANALYSIS OF B-CELL REPERTOIRE SPECIFIC TO THE NEUTRALIZING EPITOPES OF GLYCOPROTEIN-120 IN HIV-INFECTED INDIVIDUALS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODY; ENVELOPE GLYCOPROTEIN; ANTI-GP120 ANTIBODIES; GP120; BINDING; CD4; IDENTIFICATION; CHIMPANZEES; ATTACHMENT AB This study describes the clonotypic analysis of neutralizing anti-gp120 antibodies elicited in HIV-infected individuals by a panel of anti-idiotype monoclonal antibodies (anti-Id MAbs). Sera from 80 HIV-infected individuals at various clinical stages of HIV-infection were tested for reactivity to 19 anti-Id MAbs in ELISA. Anti-idiotype MAbs reacted with between 0 and 26% of sera. Among the 13 idiotypes specific for anti-CD4 site antibodies, 4 were expressed in 15 to 20% of individuals, whereas 2 of 4 idiotypes specific for anti-V3 antibodies were expressed in 15 to 26% of the cases. These data suggest that each HIV-infected individuals has a diverse B cell repertoire to a given neutralizing epitope cluster and that certain clonotypes are more prevalent than others. To correlate the binding activity in ELISA with anti-gp120 specificity, the idiotype-positive antibodies (Id(+) Abs) from representative serum samples were isolated by anti-Id MAb-Sepharose affinity columns. In most cases, the epitope specificity and the neutralizing properties of the isolated Id(+) Abs correlated with that of anti-gp120 antibodies used for the generation of anti-Id MAbs. We propose that these anti-Id MAbs may be used to identify and measure neutralizing anti-gp120 antibodies of defined specificity in the sera of HIV-infected individuals, HIV-vaccinated individuals, and in HIV-infected mother-infant pairs. C1 NCI,FREDERICK CANC RES & DEV CTR,DCE,BCP,LTCP,VIRUS BIOL UNIT,FREDERICK,MD 21701. UNIV CALIF SAN DIEGO,SAN DIEGO,CA 92103. RP HARIHARAN, K (reprint author), IDEC PHARMACEUT CORP,11011 TORREYANA RD,SAN DIEGO,CA 92121, USA. FU NIAID NIH HHS [AI31310] NR 37 TC 5 Z9 5 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD DEC PY 1994 VL 10 IS 12 BP 1629 EP 1637 DI 10.1089/aid.1994.10.1629 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PZ088 UT WOS:A1994PZ08800008 PM 7888222 ER PT J AU KEEFER, MC GRAHAM, BS BELSHE, RB SCHWARTZ, D COREY, L BOLOGNESI, DP STABLEIN, DM MONTEFIORI, DC MCELRATH, MJ CLEMENTS, ML GORSE, GJ WRIGHT, PF MATTHEWS, TJ SMITH, GE LAWRENCE, D DOLIN, R AF KEEFER, MC GRAHAM, BS BELSHE, RB SCHWARTZ, D COREY, L BOLOGNESI, DP STABLEIN, DM MONTEFIORI, DC MCELRATH, MJ CLEMENTS, ML GORSE, GJ WRIGHT, PF MATTHEWS, TJ SMITH, GE LAWRENCE, D DOLIN, R TI STUDIES OF HIGH-DOSES OF A HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 RECOMBINANT GLYCOPROTEIN-160 CANDIDATE VACCINE IN HIV TYPE-1-SERONEGATIVE HUMANS SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID LYMPHOCYTE PROLIFERATIVE RESPONSES; NEUTRALIZING ANTIBODIES; GP160; ENVELOPE; INFECTION; IMMUNOGENICITY; INDUCTION; SAFETY; CD4+; IMMUNIZATION AB We examined the safety and immunogenicity of a baculovirus-derived recombinant HIV-1 envelope glycoprotein vaccine candidate, rgp160 (VaxSyn; MicroGeneSys, Meriden, CT), administered at doses of 160 or 640 mu g to 56 healthy, HIV-1-seronegative adults, in a randomized; double-blind, placebo-controlled study. Immunizations were given intramuscularly at 0, 1, 6, and 12 months. Both doses were generally well tolerated, although self-limited local reactions were frequent. No other clinical or laboratory toxicities were noted, and no effects on CD4 or CD8 lymphocyte counts or percentages were noted. Serum antibody responses to HIV proteins were detected by Western blot (WE) in 19 of 20 and in 19 of 19 recipients of four doses of 160 and 640 mu g, respectively. Western blot responses developed more rapidly in the 640-mu g group, High rates of EIA antibody responses to HIV-1 lysate were also present in both groups, and developed more rapidly in the 640-mu g group. Enzyme immunoassay antibody responses to the immunogen (rgp160) were also frequent, but were infrequent to V3 to gp41 peptides. Neutralizing antibodies against the homologous HIV-1 LAI isolate were seen in 3 of 20 subjects (GMT = 11) who received four doses of 160 mu g, and in 10 of 19 subjects who received four doses of 640 mu g (GMT = 32). Fusion inhibiting antibody was not detected, CD4 blocking activity was seen in 3 of 19 subjects who received four doses of 640 mu g. Complement-mediated antibody-dependent enhancement was found in sera from 11 of 19 volunteers in the 640-mu g group. Lymphocyte proliferative responses to the immunogen were detected in 4 of 4 subjects tested, but no cytotoxic T cell activity was noted in 11 subjects. Administration of the 640-mu g dose of this rgp160 vaccine candidate relative to the lower doses was associated with increased immunogenicity, including higher rates of homologous neutralizing antibody responses, although at low titer. C1 VANDERBILT UNIV,SCH MED,NASHVILLE,TN 37232. ST LOUIS UNIV,SCH MED,ST LOUIS,MO 63110. JOHNS HOPKINS UNIV,BALTIMORE,MD 21205. UNIV WASHINGTON,SEATTLE,WA 98144. DUKE UNIV,SCH MED,DURHAM,NC 27710. EMMES CORP,POTOMAC,MD 20854. MICROGENESYS INC,MERIDEN,CT 06450. NIAID,VACCINE RES & DEV BRANCH,DIV AIDS,ROCKVILLE,MD 20892. RP KEEFER, MC (reprint author), UNIV ROCHESTER,MED CTR,SCH MED & DENT,DEPT MED,INFECT DIS UNIT,BOX 689,601 ELMWOOD AVE,ROCHESTER,NY 14642, USA. FU NIAID NIH HHS [N01-AI-05063, N01-AI-05062, N01-AI-05064] NR 28 TC 47 Z9 47 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 DEC PY 1994 VL 10 IS 12 BP 1713 EP 1723 DI 10.1089/aid.1994.10.1713 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PZ088 UT WOS:A1994PZ08800017 PM 7888231 ER PT J AU LAL, RB OWEN, SM MINGLE, J LEVINE, PH MANNS, A AF LAL, RB OWEN, SM MINGLE, J LEVINE, PH MANNS, A TI PRESENCE OF HUMAN T-LYMPHOTROPIC VIRUS TYPE-I AND TYPE-II IN GHANA, WEST-AFRICA SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HTLV-II; INFECTION; INDIANS; ANTIBODIES; LYMPHOMA AB Until recently, HTLV-I was considered to be an Old World virus and HTLV-II was thought to be endemic in the Americas. However, the presence of HTLV-II among Pygmies and other populations of Africa has raised doubts as to whether HTLV-II is primarily a New World virus. The large serosurveys conducted in the urban and rural areas of southern Ghana have identified a 1-2% prevalence for HTLV-I/II. To define the HTLV type, we have used a Western blot assay (HTLV-2.3 blot) that allows simultaneous confirmation and differentiation between HTLVs. Samples (n = 139) were chosen on the basis of previous reactivity with either an enzyme immune assay or r21e-spiked WE results. The WE 2.3 analysis of these specimens identified 55 (40%) to be HTLV positive, 70 (50%) to be HTLV indeterminant, and 14 (10%) to be HTLV negative for HTLV. HTLV seroindeterminant patterns ranged from both gag and env (14 were r21(+), p24(+), and/or p19(+) [all were RIPA negative]) to gag only (21 were p24(+)/p19(+), 16 were p19(+), and 7 were p24(+)), and env only (8 were r21(+) and 4 were rgp46(+)) reactivities. Of the 55 HTLV-positive specimens, 41 were typed as HTLV-I, 9 were HTLV-II, and 5 could not be typed (HTLV-I/II). Of the nine HTLV-II-positive specimens, three were from patients with Burkitt's lymphoma and six were from healthy individuals (two pregnant women) with no obvious risk factors for HTLV-II. Interestingly, two of the infected individuals were children under 13 years of age. Although sexual transmission is unlikely, they may have been infected through breast-feeding. Thus, Ghana can be added to the list of African countries, including Zaire, Gabon, Ethiopia, Somalia, Ivory Coast, and Guinea, where HTLV-II has previously been reported. C1 NATL CTR INFECT DIS,CDC,DIV VIRAL & RICKETTSIAL DIS,RETROVIRUS DIS BRANCH,ATLANTA,GA 30333. BURKITT TUMOR PROJECT,ACCRA,GHANA. NCI,VIRAL EPIDEMIOL SECT,BETHESDA,MD 20852. NR 21 TC 4 Z9 4 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 DEC PY 1994 VL 10 IS 12 BP 1747 EP 1750 DI 10.1089/aid.1994.10.1747 PG 4 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA PZ088 UT WOS:A1994PZ08800021 PM 7888235 ER PT J AU HAWLEY, RJ NEMEROFF, CB BISSETTE, G GUIDOTTI, A RAWLINGS, R LINNOILA, M AF HAWLEY, RJ NEMEROFF, CB BISSETTE, G GUIDOTTI, A RAWLINGS, R LINNOILA, M TI NEUROCHEMICAL CORRELATES OF SYMPATHETIC ACTIVATION DURING SEVERE ALCOHOL-WITHDRAWAL SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE STRESS; ALCOHOL; WITHDRAWAL; NOREPINEPHRINE; 3-METHOXY-4-HYDROXYPHENYLGLYCOL; HOMOVANILLIC ACID ID CORTICOTROPIN-RELEASING-FACTOR; FACTOR-LIKE IMMUNOREACTIVITY; CEREBROSPINAL-FLUID; ETHANOL WITHDRAWAL; RAT-BRAIN; ELECTROCHEMICAL DETECTION; DOPAMINE RELEASE; CHRONIC STRESS; CSF; ANTAGONIST AB Cerebrospinal fluid (CSF) was obtained from 17 patients during acute alcohol withdrawal. Eight of these 17 patients had a second lumbar puncture a mean of 11.9 +/- 8.1 (SD) days later, when the clinical signs of alcohol withdrawal had subsided. CSF 3-methoxy-4-hydroxyphenylglycol concentrations declined significantly (p < 0.05) during the course of alcohol withdrawal from 52.0 +/- 22.1 (SD) to 39.6 +/- 12.6 pM/ml. In early withdrawal, there was a significant positive correlation between CSF norepinephrine (NE) and corticotropin releasing hormone (CRH) concentrations (r = 0.95, p < 0.0001). Both NE and CRH concentrations correlated positively with diastolic blood pressure (r = 0.88, p < 0.001 and r = 0.62, p < 0.05, respectively). In all samples, CSF 5-hydroxyindole acetic acid concentrations correlated positively with CSF-homovanillic acid concentrations (r = 0.83, p < 0.001). These findings indicate significant perturbations of the noradrenergic neuronal system and a change in CRH-NE interactions during acute alcohol withdrawal. C1 GEORGETOWN UNIV,SCH MED,DEPT NEUROL,VET ADM MED CTR,WASHINGTON,DC. GEORGETOWN UNIV,SCH MED,FIDIA RES FDN,WASHINGTON,DC. EMORY UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,ATLANTA,GA. DUKE UNIV,MED CTR,DEPT PSYCHIAT,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT PHARMACOL,DURHAM,NC 27710. NIAAA,DICBR,CLIN STUDIES LAB,BETHESDA,MD 20892. FU PHS HHS [42088] NR 37 TC 45 Z9 46 U1 2 U2 3 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 DEC PY 1994 VL 18 IS 6 BP 1312 EP 1316 DI 10.1111/j.1530-0277.1994.tb01429.x PG 5 WC Substance Abuse SC Substance Abuse GA PY265 UT WOS:A1994PY26500005 PM 7695023 ER PT J AU HASIN, D GRANT, B AF HASIN, D GRANT, B TI 1994 DRAFT DSM-IV CRITERIA FOR ALCOHOL-USE DISORDERS - COMPARISON TO DSM-III-R AND IMPLICATIONS SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE ALCOHOL ABUSE; ALCOHOL DEPENDENCE; DSM-III-R; DSM-IV; NOSOLOGICAL COMPARISON ID UNITED-STATES 1988; PSYCHIATRIC-DIAGNOSIS; DEPENDENCE; ABUSE AB In 1994, DSM-IV will be published, with new criteria for alcohol abuse and dependence. Implications of the changes in criteria for alcohol use disorders were investigated by comparing the diagnoses made by the DSM-IV criteria and DSM-III-R criteria. The study was conducted in a sample of 424 patients in an inpatient alcohol rehabilitation unit in the New York metropolitan area. DSM-III-R and DSM-IV criteria showed similar results and high agreement for any alcohol use disorder (abuse and dependence combined). Alcohol dependence was also consistently diagnosed with DSM-III-R and DSM-IV criteria. Agreement between DSM-III-R and DSM-IV abuse diagnoses was very low. Compared with DSM-III-R, DSM-IV classified over three times as many patients as alcohol abusers, although those with alcohol dependence still overwhelmingly dominated the sample. With some fluctuations, the results were stable over Black, Hispanic, and White subgroups of patients. The direction of the findings was consistent with results from a national general population survey in that the prevalence of alcohol abuse increased in both studies. However, the clinical results alone would not have suggested the marked changes in relative prevalence of abuse and dependence that occurred in the general population when DSM-IV criteria were used in place of DSM-III-R. Research on diagnostic criteria limited to patient samples omits important information on the implications of changing aspects of the diagnostic criteria. The need for a coherent theory of alcohol abuse is highlighted. C1 NIAAA,DIV BIOMETRY & EPIDEMIOL,ROCKVILLE,MD. RP HASIN, D (reprint author), NEW YORK STATE PSYCHIAT INST & HOSP,BOX 123,722 W 168TH ST,NEW YORK,NY 10032, USA. FU NIAAA NIH HHS [AA-08159, AA-08910]; NIMH NIH HHS [MH-30906] NR 15 TC 17 Z9 17 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 DEC PY 1994 VL 18 IS 6 BP 1348 EP 1353 DI 10.1111/j.1530-0277.1994.tb01435.x PG 6 WC Substance Abuse SC Substance Abuse GA PY265 UT WOS:A1994PY26500011 PM 7695029 ER PT J AU STEWART, PA DOSEMECI, M AF STEWART, PA DOSEMECI, M TI A BIBLIOGRAPHY FOR OCCUPATIONAL EXPOSURE ASSESSMENT FOR EPIDEMIOLOGIC STUDIES SO AMERICAN INDUSTRIAL HYGIENE ASSOCIATION JOURNAL LA English DT Review ID COPPER SMELTER WORKERS; CASE-CONTROL INTERVIEW; LUNG-CANCER; RETROSPECTIVE COHORT; SOLVENT EXPOSURE; CHEMICAL-AGENTS; RISK-FACTORS; STRUCTURED QUESTIONNAIRE; SURROGATE RESPONDENTS; CUMULATIVE EXPOSURES RP STEWART, PA (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,ROCKVILLE,MD 20892, USA. NR 181 TC 5 Z9 5 U1 1 U2 2 PU AMER INDUSTRIAL HYGIENE ASSOC PI FAIRFAX PA 2700 PROSPERITY AVE #250, FAIRFAX, VA 22031-4307 SN 0002-8894 J9 AM IND HYG ASSOC J JI Am. Ind. Hyg. Assoc. J. PD DEC PY 1994 VL 55 IS 12 BP 1178 EP 1187 DI 10.1202/0002-8894(1994)055<1178:ABFOEA>2.0.CO;2 PG 10 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA PV615 UT WOS:A1994PV61500009 PM 7825518 ER PT J AU HETHERINGTON, MM ALTEMUS, M NELSON, ML BERNAT, AS GOLD, PW AF HETHERINGTON, MM ALTEMUS, M NELSON, ML BERNAT, AS GOLD, PW TI EATING BEHAVIOR IN BULIMIA-NERVOSA - MULTIPLE MEAL ANALYSES SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE EATING BEHAVIOR; MOOD; BULIMIA NERVOSA; EATING DISORDERS; APPETITE ID ANOREXIA-NERVOSA; BINGE; DISORDERS; EPISODES; WOMEN; PRELOADS; HUNGER AB Ten bulimic individuals were admitted to an inpatient unit and for 7 consecutive days eating behavior was observed and recorded. Age, sex, and weight-matched control subjects (n = 10) were admitted to the same unit for 4 d. Ail food and fluid intake, frequency of binge eating and purging, and ratings of appetite and mood before and after eating were recorded every 24 h. Bulimic patients demonstrated chaotic eating patterns that varied within; as well as between individuals. Total daily energy intake was significantly higher for bulimic patients (41982 +/- 113 kJ; 10 034 +/- 2701 kcal) than for control subjects (8050 +/- 0427 kJ; 1924 +/- 102 kcal). On average, patients binged 1.6 times, purged three times, and ate one snack or meal without purging daily. Macronutrient analyses of intake revealed significantly less energy from protein and more energy from fat in bulimic patients compared with control subjects. Some improvement of mood was noted after binges, the magnitude of which was greatest after purging. C1 NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. RP HETHERINGTON, MM (reprint author), UNIV DUNDEE,DEPT PSYCHOL,DUNDEE DD1 4HN,SCOTLAND. RI Hetherington, Marion/A-4397-2013 NR 36 TC 31 Z9 32 U1 2 U2 6 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-2310, BETHESDA, MD 20814-3998 SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD DEC PY 1994 VL 60 IS 6 BP 864 EP 873 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA PV833 UT WOS:A1994PV83300007 PM 7985626 ER PT J AU HOAK, JC AF HOAK, JC TI STEARIC-ACID, CLOTTING, AND THROMBOSIS SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE STEARIC ACID; COAGULATION; PLATELETS; THROMBOSIS ID FATTY-ACIDS; PLATELET AGGREGATION; FACTOR-XII AB Stearic acid causes hypercoagulability of the blood by activation of factor XII and by aggregation of blood platelets. Injection of unbound stearic acid (sodium salt) into the systemic circulation of dogs was followed by massive generalized thrombosis and sudden death. Similar infusions into birds, which are deficient in factor XII, did not cause hypercoagulability or thrombosis. The effects of the long-chain saturated fatty acids could be prevented by using albumin to bind the stearic acid at a molar ratio of free fatty acid (FFA) to albumin of < 2. The major issue is whether eating foods rich in stearic acid can cause a thrombogenic effect. We have no experimental evidence to support this concept. If a thrombogenic effect of long-chain saturated fatty acids exists in humans, it is most likely to occur as an aberration of fatty acid transport in which the FFA-albumin molar ratio exceeds 2 either as a result of Very high plasma FFA concentrations from lipid mobilization or a low concentration of albumin in the blood as found in disease states such as the nephrotic syndrome. C1 NHLBI, DIV BLOOD DIS & RESOURCES, BETHESDA, MD 20892 USA. NR 16 TC 17 Z9 17 U1 0 U2 0 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD DEC PY 1994 VL 60 IS 6 SU S BP 1050S EP 1053S PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA PW203 UT WOS:A1994PW20300015 ER PT J AU KUCHNIO, M SAUSVILLE, EA JAFFE, ES GREINER, T FOSS, FM MCCLANAHAN, J FUKUSHIMA, P STETLERSTEVENSON, MA AF KUCHNIO, M SAUSVILLE, EA JAFFE, ES GREINER, T FOSS, FM MCCLANAHAN, J FUKUSHIMA, P STETLERSTEVENSON, MA TI FLOW CYTOMETRIC DETECTION OF NEOPLASTIC T-CELLS IN PATIENTS WITH MYCOSIS-FUNGOIDES BASED ON LEVELS OF T-CELL RECEPTOR EXPRESSION SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE MALIGNANT LYMPHOMA; CUTANEOUS NEOPLASMS; LYMPHOCYTE SUBSETS; FLOW CYTOMETRY ID MINIMAL RESIDUAL DISEASE; ACUTE-LEUKEMIA; LYMPHOMA AB The authors report the flow cytometric detection of neoplastic T cells in the peripheral blood of four out of five (80%) patients with peripheral blood involvement with mycosis fungoides (Sezary syndrome) based on the levels of T-cell receptor expression as measured by CD3 and TCR-alpha beta staining. Antigen receptor expression was abnormal in terms of increased density of surface CD3 or TCR-alpha beta per cell. Other immunophenotypic abnormalities were present in three of these patients. However, in one patient abnormal T-cell receptor expression was the only immunophenotypic evidence of neoplasia, although morphologically abnormal lymphocytes were present and a T-cell clone was detected by polymerase chain reaction (PCR). In another patient, the authors were able to detect development of a new, more aggressive neoplastic T-cell population based on levels of T-cell receptor expression. Levels of T-cell receptor expression may be of diagnostic utility in the evaluation of peripheral blood for the presence of neoplastic T-cell populations. C1 NCI,PATHOL LAB,BETHESDA,MD 20892. NCI,DEV THERAPEUT PROGRAM,BIOL CHEM LAB,BETHESDA,MD 20892. NCI,USN,MED ONCOL BRANCH,BETHESDA,MD 20892. NR 16 TC 32 Z9 33 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQUARE, PHILADELPHIA, PA 19106 SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD DEC PY 1994 VL 102 IS 6 BP 856 EP 860 PG 5 WC Pathology SC Pathology GA PX407 UT WOS:A1994PX40700028 PM 7801904 ER PT J AU BRINTON, LA MALONE, KE LIFF, J SCHOENBERG, JB AF BRINTON, LA MALONE, KE LIFF, J SCHOENBERG, JB TI SHOULD WE CONSIDER A SUBJECTS KNOWLEDGE OF THE ETIOLOGIC HYPOTHESIS IN THE ANALYSIS OF CASE-CONTROL STUDIES SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter C1 FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. EMORY UNIV,SCH PUBL HLTH,DEPT BIOSTAT & EPIDEMIOL,ATLANTA,GA 30329. NEW JERSEY STATE DEPT HLTH,SPECIAL EPIDEMIOL PROGRAM,TRENTON,NJ 08625. RP BRINTON, LA (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892, USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 2 TC 7 Z9 7 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 1 PY 1994 VL 140 IS 11 BP 1054 EP 1056 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PV077 UT WOS:A1994PV07700014 PM 7985655 ER PT J AU LYNESS, JM PEARSON, JL LEBOWITZ, BD KUPFER, DJ AF LYNESS, JM PEARSON, JL LEBOWITZ, BD KUPFER, DJ TI AGE AT ONSET OF LATE-LIFE DEPRESSION - A RESEARCH AGENDA REPORT OF A MACARTHUR FOUNDATION-NIMH WORKSHOP SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article AB A workshop titled ''Age of Onset in Late-Life Depression'' was cosponsored by the MacArthur Foundation Research Network on the Psychobiology of Depression and NIMH in November 1992. The purpose was to better define the relevant methodological and conceptual issues regarding age-at-onset research and to address the ways in which age at onset might more fruitfully inform progress in understanding and treating late-life depression. This paper summarizes the workshop and includes consensus recommendations for future investigation. C1 NIMH,CLIN RES CTR STUDY PSYCHOPATHOL ELDERLY,ROCHESTER,NY. NIMH,MENTAL DISORDERS AGING RES BRANCH,ROCKVILLE,MD 20857. UNIV PITTSBURGH,SCH MED,PITTSBURGH,PA 15261. RP LYNESS, JM (reprint author), UNIV ROCHESTER,MED CTR,DEPT PSYCHIAT,300 CRITTENDEN BLVD,ROCHESTER,NY 14642, USA. NR 9 TC 16 Z9 16 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD WIN PY 1994 VL 2 IS 1 BP 4 EP 8 PG 5 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA MY119 UT WOS:A1994MY11900002 PM 21629002 ER PT J AU RUSSELL, LJ DIGIOVANNA, JJ HASHEM, N COMPTON, JG BALE, SJ AF RUSSELL, LJ DIGIOVANNA, JJ HASHEM, N COMPTON, JG BALE, SJ TI LINKAGE OF AUTOSOMAL RECESSIVE LAMELLAR ICHTHYOSIS TO CHROMOSOME 14Q SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID GENOMIC ORGANIZATION; CELL-ENVELOPE; GENE; FILAMENTS; PROTEINS; CLUSTER; DNA AB We have mapped the locus for lamellar ichthyosis (LI), an autosomal recessive skin disease characterized by abnormal cornification of the epidermis. Analysis using both inbred and outbred families manifesting severe LI showed complete linkage to several markers within a 9.3-cM region on chromosome 14qll. Affected individuals in inbred families were also found to have striking homozygosity for markers in this region. Linkage-based genetic counseling and prenatal diagnosis is now available for informative at-risk families. Several transcribed genes have been mapped to the chromosome 14 region containing the LI gene. The transglutaminase 1 gene (TGM1), which encodes one of the enzymes responsible for crosslinking epidermal proteins during formation of the stratum corneum, maps to this interval. The TGM1 locus was completely linked to LI((Z) over cap=9.11), suggesting that TGM1 is a good candidate for further investigation of this disorder. The genes for four serine proteases also map to this region but are expressed only in hematopoietic or mast cells, making them less likely candidates. C1 NIAMSD,GENET STUDIES SECT,SKIN BIOL LAB,BETHESDA,MD 20892. AIN SHAMS UNIV,CTR MED GENET,CAIRO,EGYPT. NCI,DERMATOL BRANCH,BETHESDA,MD. NR 25 TC 70 Z9 73 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD DEC PY 1994 VL 55 IS 6 BP 1146 EP 1152 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA QB684 UT WOS:A1994QB68400010 PM 7977373 ER PT J AU STRIKER, GE AF STRIKER, GE TI STUDENTS, CLINICIAN, AND SENIOR INVESTIGATORS BENEFIT FROM DKUHD TRAINING AWARDS SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Note RP STRIKER, GE (reprint author), NIDDKD,DIV KIDNEY UROL & HEMATOL,BETHESDA,MD, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD DEC PY 1994 VL 24 IS 6 BP 1033 EP 1034 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA PW001 UT WOS:A1994PW00100024 ER PT J AU ROMERO, R BAUMANN, P GONZALEZ, R GOMEZ, R RITTENHOUSE, L BEHNKE, E MITCHELL, MD AF ROMERO, R BAUMANN, P GONZALEZ, R GOMEZ, R RITTENHOUSE, L BEHNKE, E MITCHELL, MD TI AMNIOTIC-FLUID PROSTANOID CONCENTRATIONS INCREASE EARLY DURING THE COURSE OF SPONTANEOUS LABOR AT TERM SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE PROSTANOIDS; PROSTAGLANDINS; EICOSANOIDS; PARTURITION; TERM LABOR ID HUMAN PARTURITION; PRETERM LABOR; PROSTAGLANDINS; PREGNANCY; PLASMA; SHEEP AB OBJECTIVE: The purpose of this study was to determine whether amniotic fluid concentrations of prostanoids increase during spontaneous labor at term. STUDY DESIGN: Amniotic fluid was retrieved transabdominally from 168 patients in spontaneous labor and from 82 patients not in labor. Prostaglandin E(2), prostaglandin F-2 alpha, 13, 14-dihydro-15-keto-prostaglandin F-2 alpha, thromboxane B-2, and 6-keto-prostaglandin F-1 alpha concentrations were measured with sensitive and specific radioimmunoassays previously validated for amniotic fluid. Statistical analysis was conducted with Kruskal-Wallis analysis of variance, followed by Dunn's test for multiple comparisons. RESULTS: (1) Amniotic fluid concentrations of all prostanoids were significantly higher in patients in early labor (cervical dilatation of less than or equal to 3 cm) than in patients not in labor. (2) The magnitude of the increase in amniotic fluid prostanoid concentrations during early labor was significantly greater for prostaglandin F-2 alpha and 13, 14 dihydro-15-keto-prostaglandin F-2 alpha than for prostaglandin E(2), thromboxane B-2, and 6-keto-prostaglandin F-1 alpha. (3) Patients in the active phase of labor with cervical dilatations between 4 and 7 cm did not have higher prostanoid concentrations than those in early labor (cervical dilatation of less than or equal to 3 cm). (4) A significant increase in amniotic fluid concentrations of prostaglandin F2 alpha and 13,14-dihydro-15-keto-prostaglandin F-2 alpha, was found in patients with advanced cervical dilatation (8 to 10 cm) in comparison with those in early labor (<3 cm). CONCLUSION: Amniotic fluid prostanoid concentrations increase early during the course of spontaneous labor at term. C1 NICHHD,PERINATOL BRANCH,BETHESDA,MD. UNIV UTAH,SALT LAKE CITY,UT. HOSP SOTERO DEL RIO,SANTIAGO,CHILE. RP ROMERO, R (reprint author), WAYNE STATE UNIV,HUTZEL HOSP,SCH MED,DEPT OBSTET & GYNECOL,4707 ST ANTOINE BLVD,DETROIT,MI 48201, USA. RI Mitchell, Murray/A-8639-2010 OI Mitchell, Murray/0000-0002-6167-7176 NR 24 TC 54 Z9 54 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 1994 VL 171 IS 6 BP 1613 EP 1620 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA PY268 UT WOS:A1994PY26800029 PM 7802078 ER PT J AU EMMERTBUCK, MR ROTH, MJ ZHUANG, ZP CAMPO, E ROZHIN, JR SLOANE, BF LIOTTA, LA STETLERSTEVENSON, WG AF EMMERTBUCK, MR ROTH, MJ ZHUANG, ZP CAMPO, E ROZHIN, JR SLOANE, BF LIOTTA, LA STETLERSTEVENSON, WG TI INCREASED GELATINASE A (MMP-2) AND CATHEPSIN-B ACTIVITY IN INVASIVE TUMOR REGIONS OF HUMAN COLON-CANCER SAMPLES SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Note ID HUMAN COLORECTAL-CARCINOMA; IV COLLAGENASE; BREAST-CANCER; PLASMA-MEMBRANE; MATRIX; RNA AB Gelatinase A (MMP-2) and cathepsin B are proteinases which have been proposed to participate in human tumor invasion and metastasis. Precise quantitation of the activity of these enzymes ill invading tumors has not been previously described. We utilized a novel tissue microdissection technique to determine levels of enzyme activity in specific microscopic areas of invasive human colon cancer. Tissue specimens smaller than one high power field call be extracted from the samples and analyzed. Increased levels of pro-enzyme and active enzyme forms of gelatinase A (MMP-2) and increased cathepsin B activity were localized in regions of tumor invasion as compared with a matched number of normal epithelial cells from the same patient. Levels of progelatinase B (MMP-9) were also increased ill the tumors; however, we did not observe activation of this enzyme. To investigate the mechanism of gelatinase A activation, we amplified DNA of specific microdissected tumor cell populations using polymerase chain reaction We did not detect a mutation ill the activation locus of the enzyme in any of the tumors studied which suggests that activation may be due to up-regulation of a tumor-associated gelatinase A activating species. Microdissection of frozen tissue sections may prove valuable in the study of proteinases in human tumor invasion as well as in the detection of genetic alterations in human cancers. C1 HOSP CLIN BARCELONA,DEPT PATHOL,BARCELONA,SPAIN. WAYNE STATE UNIV,DEPT PHARMACOL,DETROIT,MI 48201. RP EMMERTBUCK, MR (reprint author), NCI,PATHOL LAB,BLDG 10,RM 2N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Sloane, Bonnie/A-1050-2009; Stetler-Stevenson, William/H-6956-2012; OI Stetler-Stevenson, William/0000-0002-5500-5808; Campo, elias/0000-0001-9850-9793 FU NCI NIH HHS [CA 36481] NR 26 TC 210 Z9 211 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD DEC PY 1994 VL 145 IS 6 BP 1285 EP 1290 PG 6 WC Pathology SC Pathology GA PW173 UT WOS:A1994PW17300007 PM 7992833 ER PT J AU CHEN, M WANG, H WOODWORTH, CD LUSSO, P BERNEMAN, Z KINGMA, D DELGADO, G DIPAOLO, JA AF CHEN, M WANG, H WOODWORTH, CD LUSSO, P BERNEMAN, Z KINGMA, D DELGADO, G DIPAOLO, JA TI DETECTION OF HUMAN HERPESVIRUS-6 AND HUMAN PAPILLOMAVIRUS-16 IN CERVICAL-CARCINOMA SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID VIRUS HUMAN HERPESVIRUS-6; POLYMERASE CHAIN-REACTION; SEQUENCES; HBLV; IDENTIFICATION; EXPRESSION; HHV-6; DNA; INTEGRATION; NEOPLASIA AB A subset of human papillomaviruses (HPVs) is associated with the majority of cervical cancers; however, cofactors appear to be required for carcinogenic progression of HPV-induced neoplasia. As human herpesvirus-6 (HHV-6) was recently shown to infect cervical epithelial cells in vitro and activate transcription of HPV-transforming genes, human cervical dysplasia and cancers were analyzed for the presence of HHV-6 by multiple methods, including polymerase chain reaction, slot blot, Southern blot, and in situ hybridization, HHV-6 DNA sequences were detected in 6 of 72 cases of squamous cervical carcinoma and cervical intraepithelial neoplasia. HPV-16 was found in found of the HHV-6-positive cases (two squamous cervical carcinomas and two cervical intraepithelial neoplasias). None of the 30 normal cervices and biopsies of patients with cervicitis was positive for HHV-6 DNA. These results are the first suggestion of an in vivo association between HHV-6 and some cervical neoplasia. C1 NCI,BIOL LAB,BETHESDA,MD 20892. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. UNIV ANTWERP,EXPTL HEMATOL LAB,B-2020 ANTWERP,BELGIUM. LOYOLA UNIV,MED CTR,STRITCH SCH MED,NATL CANC INST,PATHOL LAB,MAYWOOD,IL 60153. LOYOLA UNIV,MED CTR,STRITCH SCH MED,DEPT OBSTET & GYNECOL,MAYWOOD,IL 60153. NR 39 TC 30 Z9 32 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD DEC PY 1994 VL 145 IS 6 BP 1509 EP 1516 PG 8 WC Pathology SC Pathology GA PW173 UT WOS:A1994PW17300029 PM 7992853 ER PT J AU BROOKES, N TURNER, RJ AF BROOKES, N TURNER, RJ TI K+-INDUCED ALKALINIZATION IN MOUSE CEREBRAL ASTROCYTES MEDIATED BY REVERSAL OF ELECTROGENIC NA+-HCO3- COTRANSPORT SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE INTRACELLULAR PH; 2',7'-BIS(CARBOXYETHYL)-5(6)-CARBOXYFLUORESCEIN; 4,4'-DIISOTHIOCYANOSTILBENE-2,2'-DISULFONIC ACID; SODIUM PROTON EXCHANGE; ETHYLISOPROPYLAMILORIDE; CARBON DIOXIDE; POTASSIUM ION; BICARBONATE ION ID INTRACELLULAR PH REGULATION; CENTRAL-NERVOUS-SYSTEM; CULTURED ASTROCYTES; GLIAL-CELLS; POTASSIUM; STOICHIOMETRY; DEPENDENCE; GLUTAMINE AB Raising extracellular K+ concentration ([K+](o)) induces an alkaline shift of intracellular pH (pH(i)) in astrocytes. The mechanism of this effect was examined using the fluorescent pH(i) indicator 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein in primary cultures of mouse cerebral astrocytes. Raising [K+](o) from 3 to 12 mM increased pH(i) by 0.28 pH units in 26 mM HCO3--buffered solution. In nominally HCO3--free solution (containing similar to 95 mu M HCO3-), the alkalinization fell to 0.21 pH units and further to 0.08 pH units on removal of atmospheric CO2, suggesting a process with high affinity for HCO3-. This effect was Na+ dependent, Cl- independent, and inhibited by 0.5 mM 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, indicating the involvement of Na+-HCO3- cotransport. The relationship between pH(i) and log[K+](o) was found to be linear and to predict a stoichiometry of at least two HCO3- transported with each Na+. After removal of exogenous CO2/HCO3-, the direction of changes in pH(i) elicited by adding 1 mM HCO3- showed that net flux of HCO3- via the Na+-HCO3- cotransporter was outward at rest and was reversed by depolarization. C1 NIDR, CLIN INVEST & PATIENT CARE BRANCH, BETHESDA, MD 20892 USA. RP BROOKES, N (reprint author), UNIV MARYLAND, SCH MED, DEPT PHARMACOL & EXPTL THERAPEUT, 655 W BALTIMORE ST, BALTIMORE, MD 21201 USA. NR 32 TC 60 Z9 60 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD DEC PY 1994 VL 267 IS 6 BP C1633 EP C1640 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA PY119 UT WOS:A1994PY11900014 ER PT J AU ADACHI, K TAKAHASHI, S MELZER, P CAMPOS, KL NELSON, T KENNEDY, C SOKOLOFF, L AF ADACHI, K TAKAHASHI, S MELZER, P CAMPOS, KL NELSON, T KENNEDY, C SOKOLOFF, L TI INCREASES IN LOCAL CEREBRAL BLOOD-FLOW ASSOCIATED WITH SOMATOSENSORY ACTIVATION ARE NOT MEDIATED BY NO SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE N-G-NITRO-L-ARGININE METHYL ESTER; WHISKER BARRELS; NITRIC OXIDE; NITRIC OXIDE SYNTHASE; FUNCTIONAL ACTIVATION; BRAIN; IODO[C-14]ANTIPYRINE ID NITRIC-OXIDE SYNTHASE; VASCULAR SMOOTH-MUSCLE; GLUCOSE-UTILIZATION; NEURAL ACTIVITY; RAT; INHIBITION; STIMULATION; HALOTHANE; PHYSIOLOGY; PATHWAYS AB Effects of inhibition of nitric oxide (NO) synthase by N-G-nitro-L-arginine methyl ester (L-NAME) on the increases in local cerebral blood flow (LCBF) produced in the whisker-to-barrel sensory pathway by vibrissal stimulation were studied in conscious rats with the autoradiographic iodo [C-14]antipyrine method. Unilateral whisker stroking increased LCBF in the ipsilateral trigeminal spinal and principal sensory nuclei, contralateral ventral posteromedial thalamic nucleus, and contralateral somatosensory barrel cortex. Intravenous L-NAME (30 mg/kg) lowered baseline LCBF without altering the percent increases due to stimulation. Intracisternal infusions of L-NAME in doses about 10 times the molar content of free arginine in brain inhibited brain NO synthase activity by 88%, but the percent augmentations of LCBF by stimulation remained unchanged. Chronic treatment with L-NAME (50 mg/kg ip twice daily for 4 days) inhibited NO synthase activity in brain by 84% but also failed to reduce the percent increases in LCBF due to stimulation. These results indicate that NO does not mediate the increases in LCBF associated with functional activation. C1 NIMH, CEREBRAL METAB LAB, BETHESDA, MD 20892 USA. NIMH, NEUROCHEM LAB, BETHESDA, MD 20892 USA. RI Takahashi, Shinichi/L-3454-2013 NR 42 TC 56 Z9 56 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD DEC PY 1994 VL 267 IS 6 BP H2155 EP H2162 PG 8 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA PX959 UT WOS:A1994PX95900009 ER PT J AU HOLLENBERG, SM TONG, W SHELHAMER, JH LAWRENCE, M CUNNION, RE AF HOLLENBERG, SM TONG, W SHELHAMER, JH LAWRENCE, M CUNNION, RE TI EICOSANOID PRODUCTION BY HUMAN AORTIC ENDOTHELIAL-CELLS IN RESPONSE TO ENDOTHELIN SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE PROSTAGLANDINS; LEUKOTRIENES; HYDROXYEICOSATETRAENOIC ACID; 5-LIPOXYGENASE ID SMOOTH-MUSCLE CELLS; RELAXING FACTOR; CORONARY-ARTERY; NITRIC-OXIDE; RABBIT AORTA; RELEASE; PROSTACYCLIN; MECHANISMS; RELAXATION; ACTIVATION AB Endothelial cells actively regulate their environment by secreting humoral substances, including endothelin-1 and a variety of eicosanoids, that have local actions. To elucidate interactions among these local mediators, we measured release of cyclooxygenase and lipoxygenase pathway products of arachidonate metabolism by human aortic endothelial cells after incubation with endothelin-1. Supernatants were collected, extracted, and fractionated using high-performance liquid chromatography. Radioimmunoassays for eicosanoids were performed on the appropriate fractions. After endothelin stimulation, production of the prostacyclin metabolite 6-ketoprostaglandin F-1 alpha (6-keto-PGF(1 alpha)), the thromboxane (Tx) metabolite TxB(2), and prostaglandin E(2) (PGE(2)) were increased (307 +/- 48, 320 +/- 91, and 315 +/- 74% of control, P < 0.05). Leukotriene B-4 (LTB(4)) release was modestly increased (195 +/- 19% of control, P < 0.05). The release of 5-hydroxyeicosatetraenoic acid (5-HETE) was increased (300 +/- 57% of control, P < 0.05); production of 12-HETE and 15-HETE was unchanged. Production of eicosanoids peaked between 30 and 120 min. Preincubation with pertussis toxin prevented increased production of PGE(2), LTB(4), and 5-HETE after endothelin-1 stimulation; pretreatment with sphingosine had no effect. Interactions between endothelin and eicosanoids may be important components of the complex network that regulates vascular tone, coagulation, and inflammation at the local level. C1 NIH, DEPT CRIT CARE MED, BETHESDA, MD 20814 USA. RP HOLLENBERG, SM (reprint author), RUSH PRESBYTERIAN ST LUKES MED CTR, CARDIOL SECT, 1653 W CONGRESS PKWY, CHICAGO, IL 60612 USA. NR 40 TC 25 Z9 25 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD DEC PY 1994 VL 267 IS 6 BP H2290 EP H2296 PG 7 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA PX959 UT WOS:A1994PX95900025 ER PT J AU ECELBARGER, CA MAEDA, Y GIBSON, CC KNEPPER, MA AF ECELBARGER, CA MAEDA, Y GIBSON, CC KNEPPER, MA TI EXTRACELLULAR ATP INCREASES INTRACELLULAR CALCIUM IN RAT TERMINAL COLLECTING DUCT VIA A NUCLEOTIDE RECEPTOR SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL FLUID AND ELECTROLYTE PHYSIOLOGY LA English DT Article DE URIDINE 5'-TRIPHOSPHATE; ADENOSINE; FURA 2 ID WATER PERMEABILITY; SIGNAL-TRANSDUCTION; ADENOSINE RECEPTOR; CA2+ MOBILIZATION; ENDOTHELIAL-CELLS; EPITHELIAL-CELLS; PHOSPHOLIPASE-C; SUBTYPES; UTP; VASOPRESSIN AB Recent studies in a variety of cell types have revealed several receptor subtypes that bind ATP and trigger increases in intracellular Ca2+ concentration ([Ca2+](i)) The present studies were aimed at determining whether similar receptors are present in the rat terminal inner medullary collecting duct (IMCD). [Ca2+](i) was measured using fura 2 in tubules dissected from collagenase-treated rat kidneys. ATP (1-100 mu M) caused a rapid increase in [Ca2+](i) with a prolonged late phase after an initial peak. A similar rise was observed in tubules exposed to UTP or to the poorly hydrolyzable analogue, adenosine 5'-0-(3-thiotriphosphate) (ATP gamma S). In contrast, agonists that bind P-2x, P-2y, P-2z, and P-2t purinergic receptors did not affect [Ca2+](i). Removal of extracellular Ca2+ inhibited the response to ATP by similar to 50% with obliteration of the late phase. Furthermore, indomethacin attenuated the rise in [Ca2+](i) produced by ATP. Adenosine analogues also increased [Ca2+](i) apparently by binding to distinct adenosine receptors rather than to the ATP receptor. We conclude that there is a nucleotide receptor in the rat terminal IMCD, which, when occupied, mobilizes intracellular Ca2+. C1 NHLBI, KIDNEY & ELECTROLYTE METAB LAB, BETHESDA, MD 20892 USA. FU NIDDK NIH HHS [1-F32-DK-08832] NR 33 TC 66 Z9 66 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6127 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Fluid Electrol. Physiol. PD DEC PY 1994 VL 267 IS 6 BP F998 EP F1006 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA PX951 UT WOS:A1994PX95100013 PM 7810708 ER PT J AU CASTELLANOS, FX GIEDD, JN ECKBURG, P MARSH, WL VAITUZIS, AC KAYSEN, D HAMBURGER, SD RAPOPORT, JL AF CASTELLANOS, FX GIEDD, JN ECKBURG, P MARSH, WL VAITUZIS, AC KAYSEN, D HAMBURGER, SD RAPOPORT, JL TI QUANTITATIVE MORPHOLOGY OF THE CAUDATE-NUCLEUS IN ATTENTION-DEFICIT HYPERACTIVITY DISORDER SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; BRAIN MORPHOLOGY; BASAL GANGLIA; DEVELOPMENTAL DYSLEXIA; CORPUS-CALLOSUM; RHESUS-MONKEY; CHILDREN; CORTEX; METABOLISM; MRI AB Objective: Because the caudate nuclei receive inputs from cortical regions implicated in executive functioning and attentional tasks, caudate and total brain volumes were examined in boys with attention deficit hyperactivity disorder (ADHD) and normal comparison subjects. To gain developmental perspective, a wade age range was sampled for both groups. Method: The brains of so male ADHD patients (aged 6-19) and 48 matched comparison subjects were scanned by magnetic resonance imaging (MRI). Volumetric measures of the head and body of the caudate nucleus were obtained from T-1-weighted coronal images. Interrater reliabilities (intraclass correlations) were 0.89 or greater. Results: The normal pattern of slight but significantly greater right caudate volume across all ages was not seen in ADHD. Mean right caudate volume was slightly but significantly smaller in the ADHD patients than in the comparison subjects, white there was no significant difference for the left. Together these facts accounted for the highly significant lack of normal asymmetry in caudate volume in the ADHD boys. Total brain volume was 5% smaller in the ADHD boys, and this was not accounted for by age, height, weight, or IQ. Smaller brain volume in ADHD did not account for the caudate volume or symmetry differences. For the normal boys, caudate volume decreased substantially (13%) and significantly with age, while in ADHD there was no age-related change. Conclusions: Along with previous MRI findings of low volumes in corpus callosum regions, these results support developmental abnormalities of frontal-striatal circuits in ADHD. RP CASTELLANOS, FX (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,RM 6N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015; OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978; Castellanos, Francisco/0000-0001-9192-9437 NR 49 TC 289 Z9 293 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 DEC PY 1994 VL 151 IS 12 BP 1791 EP 1796 PG 6 WC Psychiatry SC Psychiatry GA PU966 UT WOS:A1994PU96600013 PM 7977887 ER PT J AU OSMOND, DH PAGE, K WILEY, J GARRETT, K SHEPPARD, HW MOSS, AR SCHRAGER, L WINKELSTEIN, W AF OSMOND, DH PAGE, K WILEY, J GARRETT, K SHEPPARD, HW MOSS, AR SCHRAGER, L WINKELSTEIN, W TI HIV-INFECTION IN HOMOSEXUAL AND BISEXUAL MEN 18 TO 29 YEARS OF AGE - THE SAN-FRANCISCO YOUNG MENS HEALTH STUDY SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; RISK-FACTORS; SEROCONVERSION; PREVALENCE; COHORT AB Objectives. Recent studies suggest very high human immunodeficiency virus (HIV) infection rates in some populations of younger homosexual men, but these studies may represent only particularly high-risk populations. The current study obtained population-based data on the HIV epidemic in young homosexual/ bisexual men. Methods. A household survey of unmarried men 18 through 29 years of age involved a multistage probability sample of addresses in San Francisco. A follow-up interview and HIV test for men who were HIV negative at baseline were completed; the median follow-up was 8.9 months. Results. Sixty-eight of 380 homosexual/bisexual men (17.9%) tested HIV seropositive. Sixty-three percent of men reported one or more receptive anal intercourse partners in the previous 12 months, and 41% of those men did not use condoms consistently. The HIV seroincidence rate among those seronegative at first study was 2.6% per year. Conclusions. HIV infection rates in young homosexual men in San Francisco are lower than those in the early 1980s; however, the rate of infection in these men, most of whom became sexually active after awareness of AIDS had become widespread, threatens to continue the epidemic in the younger generation at a level not far below that of a decade ago. C1 UNIV CALIF BERKELEY, SCH PUBL HLTH, DIV EPIDEMIOL & POPULAT BIOL, BERKELEY, CA 94720 USA. UNIV CALIF BERKELEY, SURVEY RES CTR, BERKELEY, CA 94720 USA. CALIF DEPT HLTH SERV, BERKELEY, CA 94704 USA. NIAID, BETHESDA, MD 20892 USA. RP OSMOND, DH (reprint author), UNIV CALIF SAN FRANCISCO, MED CTR, SAN FRANCISCO GEN HOSP, DIV EPIDEMIOL & MED, SAN FRANCISCO, CA 94143 USA. OI Page, Kimberly/0000-0002-7120-1673 FU NIMH NIH HHS [MH42459]; PHS HHS [N01-A1-82515] NR 20 TC 149 Z9 152 U1 1 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 1994 VL 84 IS 12 BP 1933 EP 1937 DI 10.2105/AJPH.84.12.1933 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PY309 UT WOS:A1994PY30900014 PM 7998633 ER PT J AU MONTOYA, ID HESS, JM COVI, L FUDALA, PJ JOHNSON, RE AF MONTOYA, ID HESS, JM COVI, L FUDALA, PJ JOHNSON, RE TI A COMPARATIVE-STUDY OF PSYCHOPATHOLOGY AND COGNITIVE FUNCTIONS BETWEEN COCAINE-DEPENDENT AND OPIATE-DEPENDENT PATIENTS SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article; Proceedings Paper CT International Narcotics Research Conference CY JUN 23-27, 1992 CL KEYSTONE, CO ID OPIOID ADDICTS; ABUSERS; DISORDERS; IMPAIRMENT; DIAGNOSIS; ALCOHOL; MMPI AB The authors examined cognitive and psychological differences between cocaine- and opiate-dependent individuals, using the Symptom Check List-90-Revised (SCL-90-R) and the Shipley Institute of Living Scale (SILS). They studied a sample of 135 cocaine-dependent and 162 opiate-dependent patients entering drug abuse treatment studies at the National Institute on Drug Abuse-Addiction Research Center (NIDA-ARC) outpatient clinic. Cocaine-dependent patients had significantly higher estimated Wechsler Adult Intelligence Scale (WAIS-R) IQ, vocabulary, abstraction, and total T scores, as measured by the SILS. On the SCL-90-R, cocaine-dependent patients had significantly higher scores for interpersonal sensitivity, anxiety, phobic anxiety, paranoid ideation, and psychoticism; opiate-dependent patients had higher scores for somatization, The results suggest that cocaine-dependent patients have better cognitive function and more psychopathology than opiate-dependent patients entering drug abuse outpatient treatment studies. C1 DEPT VET AFFAIRS MED CTR,PHILADELPHIA,PA. UNIV PENN,DEPT PSYCHIAT,PHILADELPHIA,PA 19104. JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,BALTIMORE,MD 21205. RP MONTOYA, ID (reprint author), NIDA,ARC,TREATMENT BRANCH,POB 5180,BALTIMORE,MD 21224, USA. NR 31 TC 3 Z9 3 U1 1 U2 6 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD WIN PY 1994 VL 3 IS 1 BP 36 EP 42 PG 7 WC Substance Abuse SC Substance Abuse GA MY146 UT WOS:A1994MY14600004 ER PT J AU NEEDLE, RH BROWN, BS COYLE, SL WEISSMAN, G AF NEEDLE, RH BROWN, BS COYLE, SL WEISSMAN, G TI NIDAS HIV PREVENTION PROGRAMS SO AMERICAN PSYCHOLOGIST LA English DT Note ID INTRAVENOUS-DRUG-USERS; AIDS C1 UNIV N CAROLINA,DEPT PSYCHOL,WILMINGTON,NC 28401. HLTH RESOURCES & SERV ADM,ROCKVILLE,MD. RP NEEDLE, RH (reprint author), NIDA,ROCKVILLE,MD, USA. NR 10 TC 5 Z9 5 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0003-066X J9 AM PSYCHOL JI Am. Psychol. PD DEC PY 1994 VL 49 IS 12 BP 1089 EP 1090 PG 2 WC Psychology, Multidisciplinary SC Psychology GA PW536 UT WOS:A1994PW53600016 PM 7818223 ER PT J AU KLIPPEL, JH AF KLIPPEL, JH TI CURING LUPUS - VIEWS FROM THE FOOTHILLS SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID PULSE CYCLOPHOSPHAMIDE; ERYTHEMATOSUS; TRIAL; NEPHRITIS; MESNA; RISK RP KLIPPEL, JH (reprint author), NIAMSD,BETHESDA,MD, USA. NR 20 TC 7 Z9 7 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD DEC PY 1994 VL 53 IS 12 BP 785 EP 786 DI 10.1136/ard.53.12.785 PG 2 WC Rheumatology SC Rheumatology GA PW415 UT WOS:A1994PW41500001 PM 7864683 ER PT J AU ROILIDES, E ROBINSON, T SEIN, T PIZZO, PA WALSH, TJ AF ROILIDES, E ROBINSON, T SEIN, T PIZZO, PA WALSH, TJ TI IN-VITRO AND EX-VIVO EFFECTS OF CYCLOSPORINE-A ON PHAGOCYTIC HOST DEFENSES AGAINST ASPERGILLUS-FUMIGATUS SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID COLONY-STIMULATING FACTOR; LIVER-TRANSPLANT RECIPIENTS; CANDIDA-ALBICANS; GAMMA-INTERFERON; PULMONARY MACROPHAGE; HUMAN NEUTROPHIL; RHIZOPUS-ORYZAE; HYPHAL FORMS; INVITRO; DAMAGE AB Because cyclosporin A (CsA) is extensively used as an immunosuppressive agent, its effects on phagocytic defenses against Aspergillus fumigatus were studied in vitro and ex vivo. After incubation with 10 to 250 ng of CsA per ml at 37 degrees C for 60 min, polymorphonuclear leukocytes (PMNs) exhibited unaltered superoxide anion (O-2(-)) production in response to phorbol myristate acetate and N-formylmethionyl leucyl phenylalanine, whereas greater than or equal to 500 ng/ml significantly suppressed it (P < 0.01). Moreover, at < 250 ng of CsA per ml, PMNs exhibited no change in their capacity to damage unopsonized hyphae of A. fumigatus compared with controls, whereas at greater than or equal to 250 ng/ml, CsA suppressed the function (P < 0.01). Although neither CsA (250 ng/ml) nor hydrocortisone (10 mu g/ml) suppressed PMN O-2(-) production in response to phorbol myristate acetate and N-formylmethionyl leucyl phenylalanine, combination of the two agents reduced the function compared with that at the baseline (P < 0.05). Incubation of monocytes with 100 ng of CsA per ml for 1 or 2 days suppressed their antihyphal activity. No essential change in phagocytic activity of monocyte-derived macrophages (MDMs) against A. fumigatus conidia, tested as the percentage of phagocytosing MDMs and average number of MDM-associated conidia, was detected after 2 or 4 days of incubation with 10 to 1,000 ng of CsA per mi. Furthermore, in rabbits treated with CsA (up to 20 mg/kg of body weight per day intravenously for 7 days), neither O-2(-) production and hyphal damage caused by PMNs or monocytes against hyphae nor phagocytosis of conidia by pulmonary alveolar macrophages was significantly suppressed. Thus, these results demonstrated that CsA within therapeutically relevant concentrations does not suppress antifungal activity of phagocytes except that of circulating monocytes. However, it may induce significant immunosuppression of phagocytes' antifungal function at relatively high concentrations in vitro, especially when combined,vith corticosteroids. C1 NCI,PEDIAT BRANCH,INFECT DIS SECT,BETHESDA,MD 20892. UNIV THESSALONIKI,DEPT PEDIAT 3,THESSALONIKI,GREECE. NR 32 TC 25 Z9 25 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 DEC PY 1994 VL 38 IS 12 BP 2883 EP 2888 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA PU603 UT WOS:A1994PU60300033 PM 7695277 ER PT J AU ANDERSON, BD SHIRASAKA, T KOJIMA, E YARCHOAN, R MITSUYA, H AF ANDERSON, BD SHIRASAKA, T KOJIMA, E YARCHOAN, R MITSUYA, H TI IDENTIFICATION OF DRUG-RELATED GENOTYPIC CHANGES IN HIV-1 FROM SERUM USING THE SELECTIVE POLYMERASE CHAIN-REACTION SO ANTIVIRAL RESEARCH LA English DT Article DE HIV-1; SELECTIVE PCR; PROVIRAL DNA; VIRAL RNA ID HUMAN-IMMUNODEFICIENCY-VIRUS; REVERSE-TRANSCRIPTASE; ZIDOVUDINE RESISTANCE; SENSITIVITY; THERAPY; TYPE-1; AZT; AZIDOTHYMIDINE; MUTATIONS; CHILDREN AB We attempted to detect drug-related HIV-1 pol gene mutations by selective polymerase chain reaction (PCR) using both proviral DNA and viral RNA isolated from patients (pts) with AIDS or ARC receiving antiretroviral therapy. Peripheral blood mononuclear cell (PBM)-associated proviral DNA and serum-derived viral RNA were obtained from eight patients before and after receiving an alternating regimen of AZT and ddC for 15-41 months or ddI monotherapy for 12-26 months. These specimens were examined for the presence of mutations at positions 70, 74, 215 and 219. We noted that selective PCR results can be ambiguous depending on the quantity of DNA template employed. We, therefore, used the minimal quantity of DNA templates that yielded evaluable PCR products in this study. For all the eight pairs of pre- and post-therapy proviral DNA samples, selective PCR results agreed with independently determined nucleotide sequences. Results of reverse transcription of serum-derived viral RNA followed by selective PCR differed in some cases from those using the proviral DNA. In particular, the use of serum viral RNA appeared to allow earlier detection of changes in drug-related mutations than the use of PBM-associated proviral DNA. We conclude that (i) selective PCR using the minimum and sufficient number of PBM-associated proviral DNA and serum viral RNA copies successfully detects the presence of known pol gene mutations; (ii) drug-related mutations may be distinguished earlier in virions in serum (or plasma) than in proviral DNA in PBM; and (iii) quantification of HIV-1 prior to selective PCR may be an important component in monitoring the therapy of HIV-1 infection. C1 NCI,DIV CANC TREATMENT,MED BRANCH,EXPTL RETROVIROL SECT,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,MED BRANCH,RETROVIRUS DIS SECT,BETHESDA,MD 20892. NR 23 TC 3 Z9 3 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD DEC PY 1994 VL 25 IS 3-4 BP 245 EP 258 DI 10.1016/0166-3542(94)90007-8 PG 14 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA PY351 UT WOS:A1994PY35100007 PM 7710271 ER PT J AU CORWIN, RL ROWE, P CRAWLEY, JN AF CORWIN, RL ROWE, P CRAWLEY, JN TI GALANIN RECEPTOR ANTAGONIST M40 DOES NOT REDUCE INTAKE STIMULATED BY LIMITED ACCESS TO FAT IN THE EARLY DARK CYCLE SO APPETITE LA English DT Meeting Abstract C1 NIMH,EXPTL THERAPEUT BRANCH,BEHAV NEUROPHARMACOL SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS (LONDON) LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0195-6663 J9 APPETITE JI Appetite PD DEC PY 1994 VL 23 IS 3 BP 297 EP 298 PG 2 WC Behavioral Sciences; Nutrition & Dietetics SC Behavioral Sciences; Nutrition & Dietetics GA QB647 UT WOS:A1994QB64700025 ER PT J AU LANG, LX ECKELMAN, WC AF LANG, LX ECKELMAN, WC TI ONE-STEP SYNTHESIS OF F-18 LABELED [F-18] N-SUCCINIMIDYL 4-(FLUOROMETHYL)BENZOATE FOR PROTEIN LABELING SO APPLIED RADIATION AND ISOTOPES LA English DT Article ID MONOCLONAL-ANTIBODIES AB [F-18]-N-succinimidyl 4-(fluoromethyl)benzoate (1) has been prepared from N-succinimidyl-4-[(4-nitrobenzensulfonyl)oxymethyl]benzoate (2) in one step using Kryptofix 2.2.2/[F-18(-)]. The effect of solvents, potassium salts and temperatures were studied to determine optimum labeling condition. The best results were obtained using carbonate as the counter ion and acetone as the solvent at room temperature. Overall radiochemical yields of similar to 18% (EOS) for the synthesis of 1 were obtained in 30-35 min, including HPLC purification. Proteins were labeled with 1 with labeling yields of 50-70% in 15 min. RP LANG, LX (reprint author), NIH,DEPT POSITRON EMISS TOMOG,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 13 TC 73 Z9 78 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0969-8043 J9 APPL RADIAT ISOTOPES JI Appl. Radiat. Isot. PD DEC PY 1994 VL 45 IS 12 BP 1155 EP 1163 DI 10.1016/0969-8043(94)90031-0 PG 9 WC Chemistry, Inorganic & Nuclear; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Chemistry; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA QE683 UT WOS:A1994QE68300006 PM 7894395 ER PT J AU OHAMA, T YANG, DCH HATFIELD, DL AF OHAMA, T YANG, DCH HATFIELD, DL TI SELENOCYSTEINE TRANSFER-RNA AND SERINE TRANSFER-RNA ARE AMINOACYLATED BY THE SAME SYNTHETASE, BUT MAY MANIFEST DIFFERENT IDENTITIES WITH RESPECT TO THE LONG EXTRA ARM SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE SELENOCYSTEINE; SERINE; AMINOACYLATION; DISCRIMINATOR BASE; MUTANT TRANSFER-RNAS; RNA BASE MUTATIONS ID TRANSFER-RNA-SYNTHETASE; TRANSFER RNA(SER); ESCHERICHIA-COLI; TRANSFER RNASEC; GENETIC-CODE; RECOGNITION; ANTICODON; NUCLEOSIDE; ELEMENTS; CELLS AB Selenocysteine (Sec) tRNA([Ser]Sec) donates Sec to protein, but interestingly, this amino acid is synthesized on tRNA which is first aminoacylated with serine. Thus, the identity elements in tRNA([Ser]See) for aminoacylation correspond to elements for seryl-tRNA synthetase recognition. As tRNA([Ser]Sec) has low homology to the tRNA(Ser) isoacceptors, it would seem then that the identity elements in tRNA([Ser]Sec) involve (1) very specific sequences, (2) conformational features, and/or (3) different points or domains for tRNA([Ser]Sec):synthetase and tRNA(Ser):synthetase recognition. Initially, we confirmed that the same synthetase aminoacylates both tRNAs by showing that a mutant tRNA([Ser]Sec) which has a blocked 3'-terminus is a competitive inhibitor of tRNA(Ser) aminoacylation with a partially purified and a highly purified seryl-tRNA synthetase preparation. The discriminator base (base G73) is essential for aminoacylation of tRNA([Ser]Sec) and tRNA(Ser), while the long extra arm plays an important role which seems to be orientation- and length-specific in tRNA(Ser) and, in addition, may manifest sequence specificity in tRNA([Ser]Sec). This difference in the tRNA recognition specificity is discussed. The acceptor stem, DHU stem, and T psi C stem contribute to the recogntion process, but to a lesser extent than the discriminator base and the long extra arm. (C) 1994 Academic Press, Inc. C1 NCI, EXPTL CARCINOGENESIS LAB, BETHESDA, MD 20892 USA. GEORGETOWN UNIV, DEPT CHEM, WASHINGTON, DC 20057 USA. RI Yang, David/A-7294-2009 FU NIGMS NIH HHS [GM-25848] NR 40 TC 27 Z9 27 U1 0 U2 0 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 DEC PY 1994 VL 315 IS 2 BP 293 EP 301 DI 10.1006/abbi.1994.1503 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PV829 UT WOS:A1994PV82900012 PM 7986071 ER PT J AU CHUNG, KN PAIK, TH ROBERTS, S KIM, CH KIRASSOVA, M WEINSTEIN, JN TREPEL, JB ELWOOD, PC AF CHUNG, KN PAIK, TH ROBERTS, S KIM, CH KIRASSOVA, M WEINSTEIN, JN TREPEL, JB ELWOOD, PC TI SITE-DIRECTED MUTAGENESIS OF TRYPTOPHAN RESIDUES TO CONSERVED HYDROPHOBIC RESIDUES INHIBITS THE PROCESSING OF HUMAN KB CELL FOLATE RECEPTOR SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID HUMAN-LEUKEMIA CELLS; AMINO-ACID-SEQUENCE; BINDING-PROTEIN; METHOTREXATE TRANSPORT; RIBOFLAVIN-BINDING; COMPLEMENTARY-DNA; XENOPUS OOCYTES; MULTIPLE FORMS; HUMAN-PLACENTA; CLONED GENES AB We are interested in identifying the ligand binding site of the human folate receptor (hFR). Previous reports have suggested a role of tryptophan(W) residues in ligand binding. We used site-directed mutagenesis to change the conserved W residues in positions 86, 116, 142, 143, 156, 160, and 193 of the hFR to either leucine(L) or phenylalanine(F) to examine the role of these W residues in hFR function. Although all W to L changes except W86L produced unstable proteins, W to F changes were tolerated. Based on total folate binding and transport studies, Chinese hamster ovary (CHO) cells transfected with W86L, W116F, and W143F expressed high levels of functional hFR, equivalent to cells transfected with wt hFR. CHO cells transfected with W142F, W156F, W160F, and W193F expressed low or undetectable levels of functional hFR although mRNA was present. Of these four mutants, only W142F expressed easily detectable immunoprecipitable protein but it was not fully glycosylated. Since glycosylation may affect the ability of hFR to bind folate, we expressed W142F in Xenopus oocytes which glycosylate the mutant and wild type proteins to the same apparent extent. In oocytes, the stoichiometry of folate binding was identical between the fully processed mutant protein and the wild type hFR. These results indicate that in CHO cells three of the seven W mutations (W86L, W116F, and W143F) function normally, whereas four of the seven W mutations (W142F, W156F, W160F, and W193F) produce unstable or abnormally processed protein. Expression of wt and W142F hFR in Xenopus oocytes appears to circumvent the difference in glycosylation observed in CHO cells and more importantly demonstrates that the W142F mutation does not abolish folate binding. Thus, point mutations of individual mi residues do not abrogate folate binding. (C) 1994 Academic press, Inc. C1 NCI,MED BRANCH,ROCKVILLE,MD 20892. NR 58 TC 11 Z9 11 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 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD DEC PY 1994 VL 315 IS 2 BP 407 EP 414 DI 10.1006/abbi.1994.1518 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PV829 UT WOS:A1994PV82900027 PM 7986085 ER PT J AU TIPPER, JP CITRON, BA RIBEIRO, P KAUFMAN, S AF TIPPER, JP CITRON, BA RIBEIRO, P KAUFMAN, S TI CLONING AND EXPRESSION OF RABBIT AND HUMAN BRAIN TRYPTOPHAN-HYDROXYLASE CDNA IN ESCHERICHIA-COLI SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE TRYPTOPHAN HYDROXYLASE; RABBIT BRAIN; HUMAN BRAIN; MOLECULAR CLONING; EXPRESSION ID AMINO-ACID HYDROXYLASES; POLYMERASE CHAIN-REACTION; TYROSINE-HYDROXYLASE; PHOSPHORYLATION; RAT; SEQUENCE AB Rabbit and human brain tryptophan hydroxylase were cloned and expressed in Escherichia coli. Each of the respective cDNAs, including the complete coding sequence of tryptophan hydroxylase, was obtained by reverse transcription of rabbit or human brain mRNA and subcloned into the expression vector pET-3C. The expressed rabbit brain tryptophan hydroxylase activity, measured in the presence of tetrahydrobiopterin, represents approximately a 50-fold enhancement in yield (units/g tissue (wet wt) over that of a rabbit brain extract. Likewise, the level of expressed human brain tryptophan hydroxylase is approximately 57 times the average yield previously reported for a human brain homogenate and approximately 10-times the activity of homogenates of hyman raphe nucleus. The rabbit brain and pineal-derived tryptophan hydroxylase sequences varied by disparities in six amino acid residues (99% identity). The human carcinoid and brain peptide sequences varied by disparities in 18 amino acid residues (96% identity). Several properties of both expressed enzymes were studied and compared with those of native tryptophan hydroxylases. (C) 1994 Academic Press, Inc. C1 NIMH, NEUROCHEM LAB, BETHESDA, MD 20892 USA. NR 36 TC 23 Z9 25 U1 1 U2 6 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 DEC PY 1994 VL 315 IS 2 BP 445 EP 453 DI 10.1006/abbi.1994.1523 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PV829 UT WOS:A1994PV82900032 PM 7986090 ER PT J AU PICUR, B LISOWSKI, M TANIUCHI, H POERIO, E AF PICUR, B LISOWSKI, M TANIUCHI, H POERIO, E TI COMPARISON OF THERMODYNAMIC AND KINETIC EFFECTS BETWEEN THE LEU32-]NORVALINE AND LEU35-]NORVALINE SUBSTITUTIONS OF THE 3-FRAGMENT COMPLEX OF CYTOCHROME-C SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE CYTOCHROME C; PROTEIN FOLDING AND STABILIZATION; FRAGMENT COMPLEX ID FERRICYTOCHROME-C; FERROCYTOCHROME-C; HEME CREVICE; CONFORMATION CHANGE; ORDERED COMPLEXES; RESOLUTION; PROTEIN; HORSE; FORMS; EQUILIBRIUM AB The three fragment complex (1-25)H.(28-38).(39-104) of horse cytochrome c (e.g., (1-25)H, the heme fragment containing residues 1 to 25) closely resembles the native protein except for residues 39 to 55, which are flexible. We have investigated how the Leu35-->Nva (norvaline) substitution differs from the Leu32-->Nva in the perturbation of the stability of this complex. The side chains of Leu32 and Leu35 are adjacent in the well-packed hydrophobic core of tuna cytochrome c (T. Takano and R. E. Dickerson (1981) J. Mol. Biol. 153, 95-115). We measured the effects of the substitutions on (i) the binding of (28-38) with ferri- and ferrocomplexes on the right side of the heme (Dickerson's orientation); (ii) the heat stability of the 695-nm band which monitors the Fe-S bond on the left side of the heme (cf. Takano and Dickerson, 1981); and (iii) the rate constant for the direct dissociation of (39-104) of the ferrous complex as a function of temperature. The results suggest that the Leu32-->Nva is unique in that the stabilizing energy associated with the ground state is markedly more perturbed in the Leu32-->Nva than in the Leu35-->Nva. This is true despite the fact that both substitutions introduce no stereochemical conflict and remove only the gamma-methyl groups of the Leu side chains which are presumably positioned adjacently with respect to each other in the core. Furthermore, the effect of the perturbation of the structure imposed by the removal of the Leu32 gamma-methyl group propagates itself perhaps through the core and affects the stability of the Fe-S bond and the binding strength of (39-104). These properties resemble the core domain-domain interaction (A. Fisher and H. Taniuchi (1992) Arch. Biochem. Biophys. 296, 1-16). (C) 1994 Academic Press, Inc. C1 NIDDK,BIOL CHEM LAB,BETHESDA,MD 20892. NR 51 TC 4 Z9 4 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD DEC PY 1994 VL 315 IS 2 BP 533 EP 547 DI 10.1006/abbi.1994.1534 PG 15 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA PV829 UT WOS:A1994PV82900043 PM 7986101 ER PT J AU ENK, CD KATZ, SI AF ENK, CD KATZ, SI TI EXTRACTION AND QUANTITATION OF CYTOKINE MESSENGER-RNA FROM HUMAN EPIDERMAL BLISTER ROOFS SO ARCHIVES OF DERMATOLOGICAL RESEARCH LA English DT Article DE HUMAN EPIDERMIS; POLYMERASE CHAIN REACTION; CYTOKINES ID POLYMERASE CHAIN-REACTION; MESSENGER-RNA; GENE-EXPRESSION; AMPLIFICATION; ALPHA; CELLS; INTERLEUKIN-1; KERATINOCYTES; INVITRO AB The demonstration of cytokine mRNA expression in epidermal cells by the polymerase chain reaction technique preceded by reverse transcription (RT-PCR) requires linear test conditions (i.e. that the product obtained after amplification reflects the relative amounts of starting material) and high reproducibility, specificity, and sensitivity. By combining well-defined techniques for mRNA extraction and concentration measurement with a sensitive and well-calibrated RT-PCR technique, we demonstrated the presence of IL-1 alpha, IL-1 beta, IL-6, and TNF alpha in epidermal cells obtained from suction blister roofs from normal volunteers. Messenger RNA was extracted with superparamagnetic oligo(dT)(25) Dynabeads, and the amount of mRNA was measured by spectrophotometry using a Beckman 5-mu l Ultra-Microcell prior to RT-PCR. Linear PCR conditions were obtained by carefully titrating the amounts of mRNA and the number of cycles. Reproducibility was estimated at different steps of the procedure, and the specificity of the enhanced cDNA products was verified by liquid hybridization with end-labelled probes. We suggest that this combination of techniques might prove useful for the simultaneous assessment of the expression of various cytokines from small samples of fresh human epidermal cells. C1 NCI,DERMATOL BRANCH,BETHESDA,MD 20892. NR 27 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-3696 J9 ARCH DERMATOL RES JI Arch. Dermatol. Res. PD DEC PY 1994 VL 287 IS 1 BP 72 EP 77 DI 10.1007/BF00370722 PG 6 WC Dermatology SC Dermatology GA QC577 UT WOS:A1994QC57700014 PM 7726640 ER PT J AU TURNER, MLC MOSHELL, AN CORBETT, DW STERN, JB ROTH, MJ DIGIOVANNA, J HORN, TD KRAEMER, KH AF TURNER, MLC MOSHELL, AN CORBETT, DW STERN, JB ROTH, MJ DIGIOVANNA, J HORN, TD KRAEMER, KH TI CLEARING OF MELANOMA IN-SITU WITH INTRALESIONAL INTERFERON-ALFA IN A PATIENT WITH XERODERMA-PIGMENTOSUM SO ARCHIVES OF DERMATOLOGY LA English DT Note ID DNA-REPAIR; ALPHA C1 NIAMS,BETHESDA,MD. USN,MED CTR,BETHESDA,MD 20814. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD. RP TURNER, MLC (reprint author), NCI,BETHESDA,MD 20892, USA. FU Intramural NIH HHS [Z01 BC004517-31] NR 11 TC 14 Z9 14 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD DEC PY 1994 VL 130 IS 12 BP 1491 EP 1494 PG 4 WC Dermatology SC Dermatology GA PW468 UT WOS:A1994PW46800002 PM 7986121 ER PT J AU MARTIN, DF PARKS, DJ MELLOW, SD FERRIS, FL WALTON, RC REMALEY, NA CHEW, EY ASHTON, P DAVIS, MD NUSSENBLATT, RB AF MARTIN, DF PARKS, DJ MELLOW, SD FERRIS, FL WALTON, RC REMALEY, NA CHEW, EY ASHTON, P DAVIS, MD NUSSENBLATT, RB TI TREATMENT OF CYTOMEGALOVIRUS RETINITIS WITH AN INTRAOCULAR SUSTAINED-RELEASE GANCICLOVIR IMPLANT - A RANDOMIZED CONTROLLED CLINICAL-TRIAL SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; IMMUNE-DEFICIENCY-SYNDROME; RHEGMATOGENOUS RETINAL-DETACHMENT; DIHYDROXY PROPOXYMETHYL GUANINE; VIRUS RETINITIS; INTRAVITREAL GANCICLOVIR; AIDS; FOSCARNET; THERAPY; TERM AB Background and Methods: We performed a randomized controlled clinical trial to assess the safety and efficacy of a 1 mu g/h ganciclovir implant for the treatment of newly diagnosed cytomegalovirus (CMV) retinitis in patients with the acquired immunodeficiency syndrome (AIDS). Patients with previously untreated peripheral CMV retinitis were randomly assigned either to immediate treatment with the ganciclovir implant or to deferred treatment. Standardized fundus photographs were taken at 2-week intervals and analyzed in a masked fashion. The study end point was progression of retinitis based on the photographic assessment. Results: Twenty-six patients (30 eyes) were enrolled. The median time to progression of retinitis was 15 days in the deferred treatment group (n=16) vs 226 days in the immediate treatment group (n=14) (P<.00001, log-rank test). During the study, 39 primary implants and 12 exchange implants were placed in immediate-treatment eyes, deferred-treatment eyes that progressed, or contralateral eyes that developed CMV retinitis. Postoperative complications in the total series included seven late retinal detachments and one retinal tear without detachment. Final visual acuity was 20/25 or better in 34 of 39 eyes. The estimated risk of developing CMV retinitis in the fellow eye was 50% at 6 months. Biopsy-proven visceral CMV disease developed in eight (31%) of 26 patients. The median survival was 295 days. Conclusion: The ganciclovir implant is effective for the treatment of CMV retinitis. Patients with unilateral CMV retinitis treated with the implant are likely to develop CMV retinitis in the fellow eye, and some patients will develop visceral CMV disease. C1 NEI,BETHESDA,MD 20892. NEW ENGLAND EYE CTR,BOSTON,MA. UNIV WISCONSIN,DEPT OPHTHALMOL,MADISON,WI. RP MARTIN, DF (reprint author), EMORY UNIV,SCH MED,DEPT OPHTHALMOL,1327 CLIFTON RD NE,ATLANTA,GA 30322, USA. FU Intramural NIH HHS [Z99 EY999999] NR 40 TC 288 Z9 291 U1 1 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD DEC PY 1994 VL 112 IS 12 BP 1531 EP 1539 PG 9 WC Ophthalmology SC Ophthalmology GA PW469 UT WOS:A1994PW46900013 PM 7993207 ER PT J AU WHITCUP, SM DASTGHEIB, K NUSSENBLATT, RB WALTON, RC PIZZO, PA CHAN, CC AF WHITCUP, SM DASTGHEIB, K NUSSENBLATT, RB WALTON, RC PIZZO, PA CHAN, CC TI A CLINICOPATHOLOGICAL REPORT OF THE RETINAL LESIONS ASSOCIATED WITH DIDANOSINE SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID AIDS-RELATED COMPLEX; IMMUNODEFICIENCY-VIRUS INFECTION; DIDEOXYINOSINE; 2',3'-DIDEOXYINOSINE; CHILDREN; TOXICITY; DIDEOXYCYTIDINE; NEUROPATHY AB Didanosine, a purine analogue with antiretroviral activity, is used in the treatment of human immunodeficiency virus disease. Associated toxic effects of didanosine include pancreatitis,peripheral neuropathy, and retinopathy. The retinal lesions associated with didanosine therapy were studied in a 6-year-old girl with acquired immunodeficiency syndrome. Gross examination disclosed multiple well-circumscribed depigmented lesions in the midperipheral retina. Microscopic examination of these lesions showed multiple areas of retinal pigment epithelial (RPE) loss, some surrounded by areas of hypertrophy or hypopigmentation of the RPE. Partial loss of the choriocapillaris and neurosensory retina were also noted in areas of diseased RPE. Transmission electron microscopy showed numerous membranous lamellar inclusions and cytoplasmic bodies in the RPE cells. These data show that didanosine primarily affects the RPE and that the choriocapillaris and overlying neurosensory retina are also dystrophic in areas of RPE loss. C1 NIH,NEI,BETHESDA,MD. NIH,NCI,PEDIAT BRANCH,BETHESDA,MD. NR 13 TC 17 Z9 17 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD DEC PY 1994 VL 112 IS 12 BP 1594 EP 1598 PG 5 WC Ophthalmology SC Ophthalmology GA PW469 UT WOS:A1994PW46900023 PM 7993216 ER PT J AU EMMERTBUCK, MR STAY, EJ TSOKOS, M TRAVIS, WD AF EMMERTBUCK, MR STAY, EJ TSOKOS, M TRAVIS, WD TI PLEOMORPHIC RHABDOMYOSARCOMA ARISING IN ASSOCIATION WITH THE RIGHT PULMONARY-ARTERY SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID SARCOMA; TRUNK AB Pulmonary artery rhabdomyosarcomas are rare lesions, with a small number of cases reported in the literature. We report a case of pulmonary artery rhabdomyosarcoma that arose in the right pulmonary artery. The patient presented with cough, chest pain, and hemoptysis and was found to have a sarcoma arising in the right pulmonary artery and extending distally within the pulmonary vasculature into the right lung. The gross pathologic features, microscopic. appearance, immunohistochemical profile, and computed tomographic and electron microscopic findings are presented. The site of origin and differential diagnosis of these lesions are discussed. C1 ARLINGTON HOSP,DEPT SURG PATHOL,ARLINGTON,VA. RP EMMERTBUCK, MR (reprint author), NCI,DEPT SURG PATHOL,PATHOL LAB,BLDG 10,ROOM 2N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 17 TC 4 Z9 4 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD DEC PY 1994 VL 118 IS 12 BP 1220 EP 1222 PG 3 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA PV544 UT WOS:A1994PV54400017 PM 7979918 ER PT J AU LAMB, ME AF LAMB, ME TI HEREDITY, ENVIRONMENT, AND THE QUESTION WHY SO BEHAVIORAL AND BRAIN SCIENCES LA English DT Discussion RP LAMB, ME (reprint author), NICHHD,SOCIAL & EMOT DEV SECT,9190 ROCKVILLE PIKE,ROOM 331,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0140-525X J9 BEHAV BRAIN SCI JI Behav. Brain Sci. PD DEC PY 1994 VL 17 IS 4 BP 751 EP 751 PG 1 WC Psychology, Biological; Behavioral Sciences; Neurosciences SC Psychology; Behavioral Sciences; Neurosciences & Neurology GA PZ839 UT WOS:A1994PZ83900086 ER PT J AU GASKELL, J STEWART, P KERSTEN, PJ COVERT, SF REISER, J CULLEN, D AF GASKELL, J STEWART, P KERSTEN, PJ COVERT, SF REISER, J CULLEN, D TI ESTABLISHMENT OF GENETIC-LINKAGE BY ALLELE-SPECIFIC POLYMERASE CHAIN-REACTION - APPLICATION TO THE LIGNIN PEROXIDASE GENE FAMILY OF PHANEROCHAETE-CHRYSOSPORIUM SO BIO-TECHNOLOGY LA English DT Article ID WHITE-ROT BASIDIOMYCETE; DEGRADING BASIDIOMYCETE; GENOMIC ORGANIZATION; NITROGEN LIMITATION; ENCODING GENE; CLONING; EXPRESSION; SEQUENCE; TRANSCRIPTION; FUNGUS AB Determining linkage is problematic for genes lacking easily identifiable phenotypes and for organisms without well-defined genetic recombination systems. Phanerochaete chrysosporium with its lignin peroxidase (LiP) gene family typifies these difficulties. We describe an experimental approach whereby the segregation of specific alleles is directly monitored during sexual fruiting, The method establishes linkage relationships among genes for which there are no mutations, and it is applicable to a wide range of genes, gene families and organisms, Using this approach, five P. chrysosporium linkage groups were identified. Ten LiP genes were distributed among three of these groups. One co-segregating group contained eight closely linked LiP genes. Another LiP gene was linked to a cellobiohydrolase gene cluster These genetic linkages were consistent with physical mapping by pulsed field gel electrophoresis. Based on the identification of allelic relationships, a uniform nomenclature for LiP genes is also described. C1 US FOREST SERV,FOREST PROD LAB,MADISON,WI 53705. UNIV WISCONSIN,DEPT BACTERIOL,MADISON,WI 53706. UNIV GEORGIA,WARNELL SCH FOREST RESOURCES,ATHENS,GA 30602. NIH,BETHESDA,MD 20892. NR 45 TC 33 Z9 36 U1 0 U2 5 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 0733-222X J9 BIO-TECHNOL JI Bio-Technology PD DEC PY 1994 VL 12 IS 13 BP 1372 EP 1375 DI 10.1038/nbt1294-1372 PG 4 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA PV452 UT WOS:A1994PV45200023 PM 7765568 ER PT J AU ALI, H MAEYAMA, K SAGIEISENBERG, R BEAVEN, MA AF ALI, H MAEYAMA, K SAGIEISENBERG, R BEAVEN, MA TI ANTIGEN AND THAPSIGARGIN PROMOTE INFLUX OF CA2+ IN RAT BASOPHILIC RBL-2H3 CELLS BY OSTENSIBLY SIMILAR MECHANISMS THAT ALLOW FILLING OF INOSITOL 1,4,5-TRISPHOSPHATE-SENSITIVE AND MITOCHONDRIAL CA2+ STORES SO BIOCHEMICAL JOURNAL LA English DT Article ID TUMOR MAST-CELLS; CAPACITATIVE CALCIUM-ENTRY; PROTEIN-KINASE-C; INTRACELLULAR CALCIUM; HISTAMINE-RELEASE; LEUKEMIA-CELLS; IMMUNOGLOBULIN-E; CROSS-LINKING; SYNERGISTIC SIGNALS; ADENOSINE RECEPTOR AB In single, Fura 2-loaded RBL-2H3 cells, antigen and thapsigargin depleted the same intracellular pool of Ca2+ in the absence of external Ca2+, provision of external Ca2+ induced immediate increases in levels of free Ca2+ ([Ca2+](i)). These increases were dependent on the presence of external Ca2+ and, presumably, on influx of Ca2+ across the cell membrane. Both stimulants enhanced intracellular accumulation of Ca-45(2+) through ostensibly similar mechanisms because accumulation was blocked to similar extents by various multivalent cations or by depolarization with K+. Because thapsigargin blocked reuptake of Ca2+ into inositol 1,4,5-trisphosphate sensitive stores, uptake occurred independently of the refilling of these stores. Uptake was dependent instead on sequestration of Ca-45(2+) in a pool of high capacity that was insensitive to thapsigargin, caffeine, GTP and inositol 1,4,5-trisphosphate but sensitive to ionomycin and mitochondrial inhibitors. The existence of an inositol 1,4,5-trisphosphate-insensitive pool was also apparent in permeabilized cells; at 0.1 mu M [Ca2+](i), uptake of Ca-45(2+) was largely confined (> 80 %) to the inositol 1,4,5-trisphosphate-sensitive pool, but at 2 mu M [Ca2+](i) uptake was largely (> 60 %) into the inositol 1,4,5-trisphosphate-insensitive pool. Provision of mitochondrial inhibitors along with thapsigargin to block uptake into both pools, did not impair the thapsigargin-induced increase in [Ca2+](i) or influx of Ca2+, as indicated by changes in Fura 2 fluorescence, but did block the intracellular accumulation of Ca-45(2+). The studies illustrate the utility of simultaneous measurements of [Ca2+](i) and Ca-45(2+) uptake for a full accounting of Ca2+ homoeostasis as exemplified by the ability to distinguish between influx and mitochondrial uptake of Ca2+. C1 NHLBI,CHEM PHARMACOL LAB,BETHESDA,MD 20892. NR 56 TC 56 Z9 57 U1 0 U2 3 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD DEC 1 PY 1994 VL 304 BP 431 EP 440 PN 2 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PW115 UT WOS:A1994PW11500017 PM 7998977 ER PT J AU DALLINGA, JW PACHEN, DMFA KLEINJANS, JCS KOVAC, P AF DALLINGA, JW PACHEN, DMFA KLEINJANS, JCS KOVAC, P TI NEGATIVE-ION FAST ATOM BOMBARDMENT AND COLLISION-INDUCED DISSOCIATION MASS-SPECTROMETRY OF THE 2-DEOXY, 3-DEOXY, 4-DEOXY AND 6-DEOXY DERIVATIVES FROM METHYL BETA-D-GALACTOPYRANOSIDE AND RELATED-COMPOUNDS SO BIOLOGICAL MASS SPECTROMETRY LA English DT Article ID COMBINED LIQUID-CHROMATOGRAPHY; ELECTRON-IMPACT; PERMETHYLATED DISACCHARIDES; ACTIVATION SPECTRA; SMALL OLIGOSACCHARIDES; CYCLIC GLYCOLS; REDUCING END; REAGENT GAS; MONOSACCHARIDES; FRAGMENTATION AB The fast atom bombardment collision-induced dissociation mass spectra of the [M - H]- ions of the 2-, 3-, 4- and 6-deoxy derivatives from methyl beta-D-galactopyranoside and some related compounds have been recorded, The fragmentation reactions of these quasimolecular ions and of OD-labelled analogues have been examined and related to the molecular structure, In some cases distinct and common mechanisms can be derived, but it is also clear from these experiments that not only the site of deprotonation of the molecules, but also the anticipated charge localization in the fragment ions strongly direct the fragmentation reactions, C1 NIDDK,BETHESDA,MD 20892. RP DALLINGA, JW (reprint author), UNIV LIMBURG,FAC HLTH SCI,DEPT HLTH RISK ANAL & TOXICOL,POB 616,6200 MD MAASTRICHT,NETHERLANDS. RI Kleinjans, Jos/E-7241-2015 NR 46 TC 0 Z9 0 U1 1 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 1052-9306 J9 BIOL MASS SPECTROM JI Biol. Mass Spectrom. PD DEC PY 1994 VL 23 IS 12 BP 764 EP 770 DI 10.1002/bms.1200231208 PG 7 WC Biophysics; Spectroscopy SC Biophysics; Spectroscopy GA PX594 UT WOS:A1994PX59400007 PM 7841210 ER PT J AU DELDIN, PJ DUNCAN, CC MILLER, GA AF DELDIN, PJ DUNCAN, CC MILLER, GA TI SEASON, GENDER, AND P300 SO BIOLOGICAL PSYCHOLOGY LA English DT Article DE EVENT-RELATED BRAIN POTENTIALS; P300; SEASON; GENDER; SEASONAL AFFECTIVE DISORDER ID EVENT-RELATED POTENTIALS; AFFECTIVE-DISORDER; SCHIZOPHRENIA; THERAPY AB Light therapy in patients with seasonal affective disorder has been reported to enhance visual P300 amplitude. This finding raises the possibility that variations in P300 occur naturally in nonpatients as a function of seasonal variation in sunlight. In the present investigation, P300 was studied in a sample of psychiatrically screened normal subjects who were tested at different times of the year. P300 was larger in women than men and varied in relation to season. This pattern is relevant to studies in which subjects are tested under varying sunlight conditions, such as different seasons. In addition, variations in P300 in normal subjects may be relevant to an understanding of the effectiveness of light therapy for patients with seasonal affective disorder. C1 NIMH,PSYCHOL & PSYCHOPATHOL LAB,BETHESDA,MD 20892. UNIV ILLINOIS,DEPT PSYCHOL,CHAMPAIGN,IL 61820. FU NIMH NIH HHS [MH39628] NR 25 TC 22 Z9 22 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0511 J9 BIOL PSYCHOL JI Biol. Psychol. PD DEC PY 1994 VL 39 IS 1 BP 15 EP 28 DI 10.1016/0301-0511(94)90054-X PG 14 WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology, Experimental SC Psychology; Behavioral Sciences GA PU583 UT WOS:A1994PU58300002 PM 7880945 ER PT J AU TSAI, WY GOEDERT, JJ ORAZEM, J LANDESMAN, SH RUBINSTEIN, A WILLOUGHBY, A GAIL, MH AF TSAI, WY GOEDERT, JJ ORAZEM, J LANDESMAN, SH RUBINSTEIN, A WILLOUGHBY, A GAIL, MH TI A NONPARAMETRIC ANALYSIS OF THE TRANSMISSION RATE OF HUMAN-IMMUNODEFICIENCY-VIRUS FROM MOTHER-TO-INFANT SO BIOMETRICS LA English DT Article DE AIDS; HIV; MIXTURE MODEL; NONPARAMETRIC ANALYSIS; PERINATAL HIV TRANSMISSION AB Infants born to mothers who are infected with the human immunodeficiency virus (HIV) may or may not become infected by perinatal transmission. Unfortunately, passively transferred maternal antibodies make it hard to determine the infant's infection status from HIV antibody testing, because shortly after birth it is not possible to distinguish passively transferred maternal antibodies from antibodies produced by an infected infant. Usually, the infection status is unobservable for each infant, unless the infant reaches the age of 15 months or develops an HIV-related disease such as the acquired immunodeficiency syndrome (AIDS). Traditionally, statistical analyses of the perinatal transmission rate of HIV are based on infants who had been born at least 15 months before the date of analysis. Such analyses can be both inefficient and biased. In this note, we define a mixture model underlying the onset time of AIDS and then obtain the nonparametric maximum likelihood estimators of the HIV transmission rate and of the distribution function of AIDS onset time for infected infants. Nonparametric tests are also derived for detecting differences in HIV transmission rates among different groups of infants. Finally, the methods are applied to the Mothers and Infants Cohort Study in New York City. The transmission rate of HIV from infected mothers to their infants was estimated to be 30.0% with 95% confidence interval (22.3%, 39.1%). C1 NCI,EPIDEMIOL & BIOSTAT PROGRAM,ROCKVILLE,MD 20852. MEM SLOAN KETTERING CANC CTR,DEPT EPIDEMIOL & BIOSTAT,NEW YORK,NY 10021. SUNY HLTH SCI CTR,BROOKLYN,NY 11203. ALBERT EINSTEIN COLL MED,BRONX,NY 10461. NICHHD,ROCKVILLE,MD 20852. RP TSAI, WY (reprint author), COLUMBIA UNIV,DIV BIOSTAT,NEW YORK,NY 10032, USA. FU NIAID NIH HHS [5-R29-AI29004-02]; NICHD NIH HHS [N01-HD-82913]; NIMH NIH HHS [5-P50-MH43520] NR 11 TC 11 Z9 11 U1 0 U2 0 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD DEC PY 1994 VL 50 IS 4 BP 1015 EP 1028 DI 10.2307/2533440 PG 14 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA QP050 UT WOS:A1994QP05000010 PM 7786984 ER PT J AU AMFOH, KK SHAW, RF BONNEY, GE AF AMFOH, KK SHAW, RF BONNEY, GE TI THE USE OF LOGISTIC-MODELS FOR THE ANALYSIS OF CODON FREQUENCIES OF DNA-SEQUENCES IN TERMS OF EXPLANATORY VARIABLES SO BIOMETRICS LA English DT Article DE CODONS; LOGISTIC REGRESSION; MAXIMUM LIKELIHOOD ESTIMATION; POLYTOMOUS DATA; REGRESSIVE LOGISTIC MODEL; STRUCTURAL ZEROS ID MARKOV-CHAIN ANALYSIS; HEXANUCLEOTIDE COMPOSITION; EVOLUTION; MONONUCLEOTIDE; TRAITS AB The development of the regressive logistic model applicable to the analysis of codon frequencies of DNA sequences in terms of explanatory variables is presented. A codon is a triplet of nucleotides that code for an amino acid, and may be considered as a trivariate response (B-1, B-2, B-3,), where B-i (i = 1, 2, 3) is a categorical random variable with values A, C, G, T. The linear order of bases in the DNA and possible statistical dependence of the bases in a given codon make the regressive logistic model a suitable tool for the analysis of codon frequencies. A problem of structural zeros arises from the fact that the stopping codons (terminators) do not code for amino acids; this is solved by normalizing the likelihood function. Codon frequencies may also depend on the function of the gene and they are known to differ between genes of the same genome. Differences also occur between synonymous codons for the same amino acid. Thus, the use of covariates that differ between synonymous codons as well as covariates that are constant within codons of the same amino acid may be useful in explaining the frequencies. As an illustration, the method is applied to the human mitochondrial genome using the following as explanatory variables: (1) TSCORE, a measure of the number of single base mutations required for a given codon to become a terminator; (2) AARISK, an indicator of a codon's ability of changing by a single base substitution to triplets coding for amino acids with very different characteristics; (3) AVDIST, a measure of the typicality of the amino acid coded for by the triplets. The results indicate that models that incorporate dependency structure and covariates are to be preferred to either the models comprising covariates alone or dependency structure alone. C1 NIH,DIV COMP RES & TECHNOL,BETHESDA,MD 20892. UNIV CINCINNATI,COLL BUSINESS,CINCINNATI,OH 45219. RP AMFOH, KK (reprint author), FOX CHASE CANC CTR,DIV BIOSTAT,7701 BURNHOLME AVE,PHILADELPHIA,PA 19111, USA. FU NIGMS NIH HHS [GM39573] NR 20 TC 2 Z9 2 U1 0 U2 0 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD DEC PY 1994 VL 50 IS 4 BP 1054 EP 1063 DI 10.2307/2533443 PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA QP050 UT WOS:A1994QP05000013 PM 7786987 ER PT J AU PODGOR, MJ GASTWIRTH, JL AF PODGOR, MJ GASTWIRTH, JL TI A CAUTIONARY NOTE ON APPLYING SCORES IN STRATIFIED DATA SO BIOMETRICS LA English DT Article DE COMBINING INDEPENDENT TESTS; LINEAR RANK TESTS; POWER; SCORES; STRATIFIED DATA ID RANK TESTS AB When rank tests are used to analyze stratified data, three methods for assigning scores to the observations have been proposed: (S) independently within each stratum (see Lehmann, 1975, Nonparametrics: Statistical Methods Based on Ranks; San Francisco: Holden-Day); (A) after aligning the observations within each stratum and then pooling the aligned observations (Hedges and Lehmann, 1962, Annals of Mathematical Statistics 33, 482-497); and (P) after pooling the observations across ail strata (that is, without alignment) (Mantel, 1963, Journal of the American Statistical Association 58, 690-700; Mantel and Ciminera, 1979, Cancer Research 39, 4308-4315). Test statistics are formed for each method by combining the stratum-specific linear rank tests using the assigned scores. We show that method P is sensitive to the score function used in the case of two moderately sized strata. In general, we recommend methods S and A for use with moderate to large-sized strata. C1 GEORGE WASHINGTON UNIV,DEPT STAT,WASHINGTON,DC 20052. RP PODGOR, MJ (reprint author), NEI,DIV BIOMETRY & EPIDEMIOL,BLDG 31,ROOM 6A52,BETHESDA,MD 20892, USA. NR 15 TC 1 Z9 1 U1 0 U2 1 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 SN 0006-341X J9 BIOMETRICS JI Biometrics PD DEC PY 1994 VL 50 IS 4 BP 1215 EP 1218 DI 10.2307/2533460 PG 4 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA QP050 UT WOS:A1994QP05000030 PM 7787004 ER PT J AU EISENBERG, H AF EISENBERG, H TI PROTEIN AND NUCLEIC-ACID HYDRATION AND COSOLVENT INTERACTIONS - ESTABLISHMENT OF RELIABLE BASE-LINE VALUES AT HIGH COSOLVENT CONCENTRATIONS SO BIOPHYSICAL CHEMISTRY LA English DT Article DE PROTEIN HYDRATION; NUCLEIC ACID HYDRATION; COSOLVENT INTERACTION; GUANIDINIUM CHLORIDE DENATURATION; HALOPHILIC MALATE DEHYDROGENASE ID HALOPHILIC MALATE-DEHYDROGENASE; NUCLEOSOME CORE PARTICLE; BOVINE SERUM-ALBUMIN; SMALL-ANGLE NEUTRON; X-RAY-SCATTERING; ESCHERICHIA-COLI; SOLVENT; DNA; STABILIZATION; BINDING AB Hydration and cosolvent interactions of biological macromolecules can be derived, subject to excluded volume corrections, from studies of density increments at constant chemical potentials of diffusible solutes through a semipermeable membrane. In addition to precision density determinations of solutions dialyzed to equilibrium, the analytical ultracentrifuge, static and dynamic light and small angle X-ray and neutron scattering, and combined pairwise use of, for instance, ultracentrifugation and neutron scattering, considerably strengthen the experimental analysis and its interpretation. We have examined hydration of bovine serum albumin (BSA) in the native and denatured states, and binding of the denaturant guanidinium chloride (GdmCl) to the latter form; hydration of DNA and interaction with NaCl and CsCl; revised values of the halophilic malate dehydrogenase (hMDH) tetramer hydration and 'binding' of salts; probing of nucleosome core particle hydration as distinct from and additionally to the evaluation of volume exclusion (holes), by use of variously sized sugar related probes. Conclusions presented are compared to results from precision calorimetry and from X-ray crystallography structures, whenever applicable, and comparisons made with alternative interpretations and experimental approaches. C1 WEIZMANN INST SCI,DEPT BIOL STRUCT,IL-76100 REHOVOT,ISRAEL. RP EISENBERG, H (reprint author), NIDDK,MOLEC BIOL LAB,BLDG 5,ROOM 214,BETHESDA,MD 20892, USA. NR 63 TC 53 Z9 53 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-4622 J9 BIOPHYS CHEM JI Biophys. Chem. PD DEC PY 1994 VL 53 IS 1-2 BP 57 EP 68 DI 10.1016/0301-4622(94)00076-X PG 12 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA QA837 UT WOS:A1994QA83700007 PM 7841332 ER PT J AU KRUEGER, S ANDREWS, AP NOSSAL, R AF KRUEGER, S ANDREWS, AP NOSSAL, R TI SMALL-ANGLE NEUTRON-SCATTERING STUDIES OF STRUCTURAL CHARACTERISTICS OF AGAROSE GELS SO BIOPHYSICAL CHEMISTRY LA English DT Article DE NEUTRON SCATTERING; GELS; AGAROSE ID DIMETHYL-SULFOXIDE; ELECTRIC-FIELDS; ELECTROPHORESIS; ORIENTATION; PERCOLATION; MOLECULES; FRACTALS; SOLVENT; MATRIX; WATER AB The 30 m small angle neutron scattering facility at the National Institutes of Standards and Technology has been used to examine neutron scattering from agarose gels formed in D2O. Differential scattering cross sections have been acquired over a continuous range of Q between 0.005 and 0.3 Angstrom(-1). Subtle changes in gel structure are observed when pre-gelation agarose concentration is varied. Similarly, except when the gelling solution is rapidly cooled to a low temperature, the rate at which the gels are formed does not seem to have much effect. Clearer evidence of structural rearrangement is observed when the solvent quality is changed by the addition of dimethyl sulfoxide, or when the temperature of the gel is elevated above 70 degrees C. These data are consistent with a description of a randomly structured polymer network containing discrete self-similar, hydrogen-bonded, junctions normally of minimal thickness approximate to 35-40 Angstrom. C1 NIH,DIV COMP SCI & TECHNOL,BETHESDA,MD 20892. NATL INST STAND & TECHNOL,DIV REACTOR RADIAT,GAITHERSBURG,MD 20899. COLL WOOSTER,DEPT PHYS,WOOSTER,OH 44691. NR 34 TC 10 Z9 10 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-4622 J9 BIOPHYS CHEM JI Biophys. Chem. PD DEC PY 1994 VL 53 IS 1-2 BP 85 EP 94 DI 10.1016/0301-4622(94)00079-4 PG 10 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA QA837 UT WOS:A1994QA83700010 PM 7841333 ER PT J AU DURELL, SR GUY, HR ARISPE, N ROJAS, E POLLARD, HB AF DURELL, SR GUY, HR ARISPE, N ROJAS, E POLLARD, HB TI THEORETICAL-MODELS OF THE ION-CHANNEL STRUCTURE OF AMYLOID BETA-PROTEIN SO BIOPHYSICAL JOURNAL LA English DT Article ID ALZHEIMERS-DISEASE; BILAYER-MEMBRANES; CORTICAL-NEURONS; PEPTIDES; AGGREGATION; PRECURSOR; CALCIUM; CONFORMATION; DEPOSITION; FRAGMENTS AB Theoretical methods are used to develop models for the ion channel structure of the membrane-bound amyloid beta-protein. This follows recent observations that the beta-protein forms cation-selective channels in lipid bilayers in vitro. Amyloid beta-protein is the main component of the extracellular plaques in the brain that are characteristic of Alzheimer's disease. Based on the amino acid sequence and the unique environment of the membrane, the secondary structure of the 40-residue beta-protein is predicted to form a beta-hairpin followed by a helix-turn-helix motif. The channel structures were designed as aggregates of peptide subunits in identical conformations. Three types of models were developed that are distinguished by whether the pore is formed by the beta-hairpins, the middle helices, or by the more hydrophobic C-terminal helices. The latter two types can be converted back and forth by a simple conformational change, which would explain the variable conduction states observed for a single channel. It is also demonstrated how lipid headgroups could be incorporated into the pore lining, and thus affect the ion selectivity. The atomic-scale detail of the models make them useful for designing experiments to determine the real structure of the channel, and thus further the understanding of peptide channels in general. In addition, if beta-protein-induced channel activity is found to be the cause of cell death in Alzheimer's disease, then the models may be helpful in designing counteracting drugs. C1 NIDDKD,CELL BIOL & GENET LAB,BETHESDA,MD 20892. RP DURELL, SR (reprint author), NCI,MATH BIOL LAB,BETHESDA,MD 20892, USA. NR 41 TC 125 Z9 129 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 DEC PY 1994 VL 67 IS 6 BP 2137 EP 2145 PG 9 WC Biophysics SC Biophysics GA PV061 UT WOS:A1994PV06100005 PM 7535109 ER PT J AU GRIGORJEV, PA BEZRUKOV, SM AF GRIGORJEV, PA BEZRUKOV, SM TI HOFMEISTER EFFECT IN ION-TRANSPORT - REVERSIBLE BINDING OF HALIDE ANIONS TO THE ROFLAMYCOIN CHANNEL SO BIOPHYSICAL JOURNAL LA English DT Article ID DYNAMICS; CLUSTERS; NOISE; WATER AB We have studied the anion-dependent gating of roflamycoin ion channels using spectral analysis of noise in currents through multichannel planar lipid bilayers. We have found that in addition to tow frequency current fluctuations that may be attributed to channel switching between open and closed conformations, roflamycoin channels exhibit a pronounced higher frequency noise indicating that the open channel conductance has substates with short lifetimes. This noise is well described by a Lorentzian spectrum component with a characteristic cutoff frequency that depends on the type of halide anions according to their position in the Hofmeister series. It is suggested that transitions between the substates correspond to a reversible ionization of the channel by a penetrating anion that binds to the channel structure, more chaotropic anions being bound for longer times. Within a framework of a two-substate model, the duration of the substate with reduced electrostatic barrier for cation current varies exponentially with anion electron polarizability. This explains two features of the roflamycoin channel reported earlier: the increase in apparent single-channel conductance along the series F-3.0.CO;2-P PG 8 WC Oncology SC Oncology GA PT806 UT WOS:A1994PT80600023 PM 7954268 ER PT J AU ELING, TE GLASGOW, WC AF ELING, TE GLASGOW, WC TI CELLULAR PROLIFERATION AND LIPID-METABOLISM - IMPORTANCE OF LIPOXYGENASES IN MODULATING EPIDERMAL GROWTH FACTOR-DEPENDENT MITOGENESIS SO CANCER AND METASTASIS REVIEWS LA English DT Review DE EPIDERMAL GROWTH FACTOR; PROSTAGLANDINS; LINOLEIC ACID; MITOGENESIS; SIGNALING PATHWAYS; LIPOXYGENASE ID HAMSTER EMBRYO CELLS; SWISS 3T3 CELLS; ARACHIDONIC-ACID METABOLISM; HUMAN-BREAST-CANCER; PROTEIN-TYROSINE PHOSPHATASES; V-HA-RAS; LINOLEIC-ACID; MESSENGER-RNA; DNA-SYNTHESIS; A-431 CELLS AB In this article we have reviewed and discussed the results of our investigation of lipid metabolites as modulators of epidermal growth factor (EGF) signaling pathways. We have studied epidermal growth factor-dependent mitogenesis in BALB/c 3T3 and Syrian hamster embryo (SHE) cells in culture. We observed that EGF stimulates the formation of prostaglandins in BALB/c 3T3 cells and their formation appears to be necessary for EGF dependent mitogenesis. EGF did not stimulate PGE, formation in SHE cells and in fact, exogenously added PGE, inhibited mitogenesis. fn both cell lines, EGF stimulated the formation of lipoxygenase-derived 13(S)-hydroxyoctadecadienoic acid (13-HODE) and inhibition of 13-HODE formation attenuated mitogenesis. The addition of 13-(S)-HODE enhanced EGF-dependent mitogenesis but when added alone, the compound was not mitogenic. Other metabolites, including lipoxygenase metabolites of arachidonic acid, were either weak simulators of EGF-dependent mitogenesis or essentially inactive. The 13(S)-HODE appears to be formed by an apparently unique lipoxygenase that is regulated by the tyrosine kinase activity of the EGF receptor. The mechanisms by which lipids, particularly the lipoxygenase-derived linoleic acid metabolites, modulate the EGF signaling pathways leading to cell proliferation is discussed. The possible significance of lipoxygenase and prostaglandin H synthase-dependent metabolism of unsaturated fatty acids in breast and colon cancer is also discussed. RP ELING, TE (reprint author), NIEHS,MOLEC BIOPHYS LAB,EICOSANOID BIOCHEM SECT,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 57 TC 48 Z9 49 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-7659 J9 CANCER METAST REV JI Cancer Metastasis Rev. PD DEC PY 1994 VL 13 IS 3-4 BP 397 EP 410 DI 10.1007/BF00666106 PG 14 WC Oncology SC Oncology GA PZ311 UT WOS:A1994PZ31100013 PM 7712598 ER PT J AU HERMAN, EH ZHANG, J FERRANS, VJ AF HERMAN, EH ZHANG, J FERRANS, VJ TI COMPARISON OF THE PROTECTIVE EFFECTS OF DESFERRIOXAMINE AND ICRF-187 AGAINST DOXORUBICIN-INDUCED TOXICITY IN SPONTANEOUSLY HYPERTENSIVE RATS SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE DFO; ICRF-187; DOXORUBICIN-INDUCED TOXICITY; IRON CHELATION ID ADRIAMYCIN-INDUCED CARDIOTOXICITY; RESPIRATORY-CHAIN ACTIVITY; HYDROLYSIS PRODUCT; HYDROXYL RADICALS; CHELATING-AGENTS; BREAST-CANCER; IRON COMPLEX; HEART; DEFEROXAMINE; SUPEROXIDE AB Since the iron-mediated formation of free radicals is considered to be a critical factor in the pathogenesis of the toxicity of doxorubicin (DXR), comparisons were made of the protective effects of two iron chelators, ICRF 187 and desferrioxamine (DFO), against the chronic cardiac and renal toxicity induced by DXR in spontaneously hypertensive rats (SHR). Two preparations of DFO were studied: DFO mesylate (DFO-M) and a polymeric form (DFO-P) in which DFO is conjugated to hydroxyethyl starch. Groups of 5 SHR each were given 12 weekly i.v. injections of 1 mg/kg DXR either alone or 30 min after the i.p. injection of 25 mg/kg ICRF-187, 50 mg/kg DFO-M, 50 mg/kg DFO-P, or 100 mg/kg DFO-P. A semiquantitative assessment was made of the cardiomyopathy (Billingham scale) and nephropathy. Renal protection was minimal with DFO-M and moderate with ICRF-187 and both doses of DFO-P. There was no cardiac protection with DFO-M. Both doses of DFO-P provided similar but modest degrees of cardiac protection. DXR-induced mortality was not prevented by either preparation of DFO. ICRF-187 provided a higher degree of protection against the cardiotoxicity and the mortality induced by DXR. Since both DFO and ICRF-187 are highly efficient chelators of iron in vitro, the differences in their in vivo protective effects are thought to be related to their cellular uptake and intracellular distribution and to the relative availability of different intracellular iron pools to these agents. C1 NIH,NHLBI,PATHOL BRANCH,ULTRASTRUCT SECT,BETHESDA,MD 20892. RP HERMAN, EH (reprint author), US FDA,DIV RES & TESTING,8301 MUIRKIRK RD,LAUREL,MD 20708, USA. NR 47 TC 43 Z9 44 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD DEC PY 1994 VL 35 IS 2 BP 93 EP 100 DI 10.1007/BF00686629 PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA PU862 UT WOS:A1994PU86200001 PM 7987999 ER PT J AU DOLAN, ME PEGG, AE MOSCHEL, RC VISHNUVAJJALA, BR FLORA, KP GREVER, MR FRIEDMAN, HS AF DOLAN, ME PEGG, AE MOSCHEL, RC VISHNUVAJJALA, BR FLORA, KP GREVER, MR FRIEDMAN, HS TI BIODISTRIBUTION OF O-6-BENZYLGUANINE AND ITS EFFECTIVENESS AGAINST HUMAN BRAIN-TUMOR XENOGRAFTS WHEN GIVEN IN POLYETHYLENE-GLYCOL OR CREMOPHOR-EL SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE O-6-BENZYLGUANINE; HUMAN BRAIN-TUMOR XENOGRAFTS; POLYETHYLENE GLYCOL; CREMOPHOR EL ID MAMMALIAN O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; 1,3-BIS(2-CHLOROETHYL)-1-NITROSOUREA BCNU; HYPERSENSITIVITY REACTIONS; ALKYLATING-AGENTS; O6-BENZYLGUANINE; SENSITIVITY; CANCER; MEDULLOBLASTOMA; TAXOL; MODEL AB O-6-Benzylguanine effectively inactivates the DNA-repair protein O-6-alkylguanine-DNA alkyltransferase in tumor cells and has been shown to increase the cytotoxicity of chloroethylnitrosoureas. This study was undertaken to ascertain the optimal vehicle for further toxicological evaluation and eventual clinical trials of O-6- benzylguanine. The solubility, metabolism, bioavailability and effectiveness of O-6-benzylguanine as an adjuvant therapy with BCNU were compared using two vehicles, cremophor-EL and PEG 400. Nude mice bearing s.c. D456 MG glioblastoma xenografts were injected i.p. with 10-30 mg/kg O-6-benzylguanine dissolved in either 40% PEG 400/saline or 10% cremophor-EL/saline. The number of tumor regressions noted after treatment with 10 mg/kg O-6-benzylguanine followed by 12.7 mg/kg BCNU were 8/9 for the drug dissolved in PEG and 1/10 for the drug given in cremophor-EL. Using the same treatment regimen but increasing the dose of O-6-benzylguanine to 30 mg/kg led to a growth delay of 45.2 and 11.5 days for the drug dissolved in PEG 400 and cremophor-EL, respectively, although the number of regressions observed were the same for both treatments. 8-[H-3]-O-6-Benzylguanine was more rapidly distributed to the tumor when it was delivered in PEG vehicle than when it was given in cremophor-EL. In contrast, there was a 3-fold greater amount of O-6-benzylguanine in the small intestine of mice at 1 h after i.p. injection of the drug in cremophor-EL as compared with PEG 400. The rate and extent of metabolism in the liver was the same, whether the parent drug was given in PEG 400 or in cremophor-EL. These studies demonstrate that O-6-benzylguanine is a more effective enhancer of the antitumor activity of BCNU when it is given in PEG 400 than when it is delivered in cremophor-EL, which may be due to a more rapid distribution of the drug to the tumor. C1 PENN STATE UNIV,MILTON S HERSHEY MED CTR,COLL MED,DEPT CELLULAR & MOLEC PHYSIOL,HERSHEY,PA 17033. PENN STATE UNIV,MILTON S HERSHEY MED CTR,COLL MED,DEPT PHARMACOL,HERSHEY,PA 17033. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NIH,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,BETHESDA,MD 20892. DUKE UNIV,MED CTR,DEPT PEDIAT,DURHAM,NC 27710. DUKE UNIV,MED CTR,DEPT PATHOL,DURHAM,NC 27710. DUKE UNIV,MED CTR,PREUSS LAB BRAIN TUMOR RES,DURHAM,NC 27710. RP DOLAN, ME (reprint author), UNIV CHICAGO,MED CTR,DIV HEMATOL ONCOL,5841 S MARYLAND AVE,BOX MC2115,CHICAGO,IL 60637, USA. FU NCI NIH HHS [CA18137, CA47228, CA57725] NR 31 TC 24 Z9 24 U1 2 U2 2 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 DEC PY 1994 VL 35 IS 2 BP 121 EP 126 DI 10.1007/BF00686633 PG 6 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA PU862 UT WOS:A1994PU86200005 PM 7987987 ER PT J AU VOLPE, DA DU, DL GRIESHABER, CK MURPHY, MJ AF VOLPE, DA DU, DL GRIESHABER, CK MURPHY, MJ TI IN-VITRO CHARACTERIZATION OF THE MYELOTOXICITY OF CYCLOPENTENYL CYTOSINE (VOL 34, PG 103, 1994) SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Correction, Addition C1 NCI,BETHESDA,MD 20892. RP VOLPE, DA (reprint author), HIPPLE CANC RES CTR,DAYTON,OH, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD DEC PY 1994 VL 35 IS 2 BP 182 EP 182 PG 1 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA PU862 UT WOS:A1994PU86200017 ER PT J AU LI, FP FRAUMENI, JF AF LI, FP FRAUMENI, JF TI COLLABORATIVE INTERDISCIPLINARY STUDIES OF P53 AND OTHER PREDISPOSING GENES IN LI-FRAUMENI SYNDROME SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID CANCER FAMILY; MUTATIONS C1 HARVARD UNIV,SCH PUBL HLTH,BOSTON,MA 02115. NCI,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20893. RP LI, FP (reprint author), DANA FARBER CANC INST,44 BINNEY ST,BOSTON,MA 02115, USA. NR 10 TC 12 Z9 12 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 DEC PY 1994 VL 3 IS 8 BP 715 EP 717 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA PW570 UT WOS:A1994PW57000012 PM 7881346 ER PT J AU JENKINS, J WHEELER, V ALBRIGHT, L AF JENKINS, J WHEELER, V ALBRIGHT, L TI GENE-THERAPY FOR CANCER SO CANCER NURSING LA English DT Article DE GENE THERAPY; RETROVIRUS; NURSES ROLE ID LYMPHOCYTES; ISSUES AB Advances in molecular biology and technology now being made will open the way to using gene transfer as a therapeutic option for patients with cancer. Since there are > 5,000 known genetic diseases, the potential impact of these techniques is enormous. Possibilities for the application of gene therapy are emerging and along with them complex safety, ethical, and financial issues that will require resolution. Many of these concerns will become relevant to the oncology nurse, who will need to understand the science, ethics, safety considerations, and impact of this experimental therapy on the patient. Since gene therapy is a rapidly evolving method of treatment, it will be a challenge to remain up to date and knowledgeable. C1 CANC NURSING & BIOTHERAPY,SAN DIEGO,CA. RP JENKINS, J (reprint author), NIH,CANC & HUMAN GENOME NURSING SERV,BLDG 10,ROOM 7D37,BETHESDA,MD 20892, USA. NR 40 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0162-220X J9 CANCER NURS JI Cancer Nurs. PD DEC PY 1994 VL 17 IS 6 BP 447 EP 456 PG 10 WC Oncology; Nursing SC Oncology; Nursing GA PT817 UT WOS:A1994PT81700001 PM 7820822 ER PT J AU ALLIONE, A CONSALVO, M NANNI, P LOLLINI, PL CAVALLO, F GIOVARELLI, M FORNI, M GULINO, A COLOMBO, MP DELLABONA, P HOCK, H BLANKENSTEIN, T ROSENTHAL, FM GANSBACHER, B BOSCO, MC MUSSO, T GUSELLA, L FORNI, G AF ALLIONE, A CONSALVO, M NANNI, P LOLLINI, PL CAVALLO, F GIOVARELLI, M FORNI, M GULINO, A COLOMBO, MP DELLABONA, P HOCK, H BLANKENSTEIN, T ROSENTHAL, FM GANSBACHER, B BOSCO, MC MUSSO, T GUSELLA, L FORNI, G TI IMMUNIZING AND CURATIVE POTENTIAL OF REPLICATING AND NONREPLICATING MURINE MAMMARY ADENOCARCINOMA CELLS ENGINEERED WITH INTERLEUKIN (IL)-2, IL-4, IL-6, IL-7, IL-10, TUMOR-NECROSIS-FACTOR-ALPHA, GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR, AND GAMMA-INTERFERON GENE OR ADMIXED WITH CONVENTIONAL ADJUVANTS SO CANCER RESEARCH LA English DT Note ID VACCINATION; GROWTH AB To evaluate the efficacy of vaccinations with cytokine-gene-transduced tumor cells, BALB/c mice were challenged with 1 x 10(5) parental cells of a syngeneic adenocarcinoma cell line (TSA-pc). No protection was observed in mice immunized 30 days earlier with 1 x 10(5) nonreplicating mitomycin-C-treated TSA-pc alone, or with Corynebacterium parvum or Complete Freund Adjuvant (CFA). Ten to 30% of mice immunized with nonreplicating cells engineered to produce interleukin (IL)-2, IL-4, IL-6, IL-7, IL-10, tumor necrosis factor alpha, granulocyte-macrophage colony-stimulating factor, and gamma-interferon gene were protected. Fifty % of mice immunized with replicating TSA-pc admixed with C. parvum and 80-100% of mice immunized with replicating tumor cells transduced with IL-2, IL-4, IL-7, IL-10, or gamma-interferon gene were protected. No cure was afforded by TSA cells admired with C. parvum or CFA, nor by TSA cells engineered with IL-6, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor a gene injected starting I day after TSA-pc challenge. Complete tumor regression, however, was obtained in 10-20% of mice treated with TSA cells transduced with IL-2, IL-4, IL-7, or IL-10 and in 30% of those treated with TSA cells transduced with gamma-interferon gene. C1 UNIV TURIN,CNR,CIOS,DEPT CLIN & BIOL SCI,I-10126 TURIN,ITALY. UNIV TURIN,CNR,CTR IMMUNOGENET & EXPTL ONCOL,TURIN,ITALY. REGINA MARGHERITA CHILDRENS HOSP,DEPT PATHOL,TURIN,ITALY. UNIV BOLOGNA,INST ONCOL,BOLOGNA,ITALY. UNIV LAQUILA,DEPT EXPTL MED,I-67100 LAQUILA,ITALY. IST NAZL TUMORI,DIV EXPTL ONCOL D,I-20133 MILAN,ITALY. HS RAFFAELE,DEPT BIOTECHNOL,MILAN,ITALY. FREE UNIV BERLIN,INST IMMUNOL,W-1000 BERLIN,GERMANY. MAX DELBRUCK CTR MOLEC MED,BERLIN,GERMANY. MEM SLOAN KETTERING CANC CTR,NEW YORK,NY 10021. NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL SECT,FREDERICK,MD 21702. RI Lollini, Pier Luigi/A-7644-2008; Cavallo, Federica/C-5666-2011; Bosco, Maria Carla/J-7928-2016; OI Lollini, Pier Luigi/0000-0003-1702-4108; Cavallo, Federica/0000-0003-4571-1060; Bosco, Maria Carla/0000-0003-1857-7193; Allione, Alessandra/0000-0001-9599-309X NR 20 TC 187 Z9 187 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 1994 VL 54 IS 23 BP 6022 EP 6026 PG 5 WC Oncology SC Oncology GA PU942 UT WOS:A1994PU94200002 PM 7954438 ER PT J AU PARK, K BAE, H HEYDEMANN, A ROBERTS, AB DOTTO, GP SPORN, MB KIM, SJ AF PARK, K BAE, H HEYDEMANN, A ROBERTS, AB DOTTO, GP SPORN, MB KIM, SJ TI THE E1A ONCOGENE INDUCES RESISTANCE TO THE EFFECTS OF 1,25-DIHYDROXYVITAMIN D-3 ON INHIBITION OF GROWTH OF MOUSE KERATINOCYTES SO CANCER RESEARCH LA English DT Note ID RECEPTOR MESSENGER-RNA; VITAMIN-D; DEPENDENT REGULATION; CANCER-CELLS; BINDING; DIFFERENTIATION; EXPRESSION; INDUCTION; HORMONE; PROTEIN AB 1,25-Dihydroxyvitamin D-3 [1,25-(OH)(2)D-3] inhibited DNA synthesis in transformed mouse keratinocytes (Pam212) in a time- and dose-dependent manner as measured by [H-3]thymidine incorporation. To investigate the mechanism through which 1,25-(OH)(2)D-3 acts, we examined its effects on Pam212 cells further transformed with the E1A oncogene. Here, we show that transformation of the cells with the E1A oncogene induced resistance to the effects of 1,25-(OH)(2)D-3 on inhibition of growth of Pam212 cells. While 1,25-(OH)2(D3) treatment increased the level of expression of vitamin D receptor mRNA 20-fold in parental cells, the E1A-transformed cells failed to express vitamin D receptor mRNA even after treatment with 1,25-(OH)(2)D-3. Transfection of the E1A-transformed cell line with an expression construct encoding the vitamin D receptor restored receptor expression as well as the inhibition of growth by 1,25-(OH)(2)D-3 These results suggest that one of the mechanisms for acquisition of 1,25-(OH)(2)D-3 resistance induced by E1A may involve loss of vitamin D receptor inducibility by 1,25-(OH)(2)D-3. C1 NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. MASSACHUSETTS GEN HOSP E,CTR CUTANEOUS CANC,BOSTON,MA 02129. NR 33 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 DEC 1 PY 1994 VL 54 IS 23 BP 6087 EP 6089 PG 3 WC Oncology SC Oncology GA PU942 UT WOS:A1994PU94200017 PM 7954451 ER PT J AU SASAKI, M HONDA, T YAMADA, H WAKE, N BARRETT, JC OSHIMURA, M AF SASAKI, M HONDA, T YAMADA, H WAKE, N BARRETT, JC OSHIMURA, M TI EVIDENCE FOR MULTIPLE PATHWAYS TO CELLULAR SENESCENCE SO CANCER RESEARCH LA English DT Note ID HAMSTER EMBRYO CELLS; NEOPLASTIC TRANSFORMATION; POSSIBLE INVOLVEMENT; INDEFINITE DIVISION; IMMORTALIZATION; PROGRESSION; CHROMOSOME; INVITRO; LINE; FIBROBLASTS AB Normal cells in culture generally senesce whereas tumor-derived cells are often, but not without exception, immortal and grow indefinitely. For cells to escape the senescence program, normal genes must be lost or inactivated as shown by somatic cell genetic studies. For example, the introduction of specific chromosomes by microcell-mediated chromosome transfer has been shown to induce senescence of human and rodent tumor cell lines, and the mapping of over ten senescence genes has been achieved by this method. In this study, we observed that two different normal chromosomes induce senescence in the same human endometrial carcinoma cell line, which suggests that multiple pathways to senescence are inactivated in this cell line. This hypothesis has implications for the mechanisms of cellular senescence and its role in carcinogenesis. Furthermore, this hypothesis can explain why not all tumor-derived cells are immortal. C1 NIEHS,MOLEC CARCINOGENESIS LAB,ENVIRONM CARCINOGENESIS PROGRAM,RES TRIANGLE PK,NC 27709. TOTTORI UNIV,FAC MED,SCH LIFE SCI,DEPT MOLEC & CELL GENET,YONAGO,TOTTORI 683,JAPAN. KYUSHU UNIV,MED INST BIOREGULAT,DEPT REPROD PHYSIOL & ENDOCRINOL,BEPPU,OITA 874,JAPAN. HOKKAIDO UNIV,SCH MED,DEPT OBSTET & GYNECOL,SAPPORO,HOKKAIDO 060,JAPAN. NR 33 TC 76 Z9 76 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 DEC 1 PY 1994 VL 54 IS 23 BP 6090 EP 6093 PG 4 WC Oncology SC Oncology GA PU942 UT WOS:A1994PU94200018 PM 7954452 ER PT J AU SINHA, R ROTHMAN, N BROWN, ED MARK, SD HOOVER, RN CAPORASO, NE LEVANDER, OA KNIZE, MG LANG, NP KADLUBAR, FF AF SINHA, R ROTHMAN, N BROWN, ED MARK, SD HOOVER, RN CAPORASO, NE LEVANDER, OA KNIZE, MG LANG, NP KADLUBAR, FF TI PAN-FRIED MEAT CONTAINING HIGH-LEVELS OF HETEROCYCLIC AROMATIC-AMINES BUT LOW-LEVELS OF POLYCYCLIC AROMATIC-HYDROCARBONS INDUCES CYTOCHROME P4501A2 ACTIVITY IN HUMANS SO CANCER RESEARCH LA English DT Article ID HUMAN HEPATIC MICROSOMES; CHARCOAL-BROILED BEEF; COOKED FOOD; METABOLIC POLYMORPHISMS; CARCINOGENIC ARYLAMINES; COLORECTAL-CANCER; HUMAN-LIVER; RAT-LIVER; ACTIVATION; INDUCTION AB Heterocyclic aromatic amines (HAAs) are formed when meat juices are pyrolyzed. In humans HAAs are activated in vivo by cytochrome P4501A2 (CYP1A2) and N-acetyltransferase (NAT2) to mutagens or carcinogens. While activity of NAT2 is noninducible, exposure to cigarettes, polycyclic aromatic hydrocarbons, and cruciferous vegetables has been shown to induce CYP1A2 activity in humans. To date, it is unknown if pan-fried meat, which is consumed at high levels in the United States, is capable of inducing CYP1A2. In order to address this issue, we measured CYP1A2 and NAT2 activities in 66 healthy nonsmokers (33 males and 33 females) in a controlled metabolic feeding study. The study was designed to minimize the influence of known inducers of CYP1A2. Subjects consumed meat pan-fried at a low temperature (100 degrees C) for 7 days followed by 7 days of meat pan-fried at a high temperature (250 degrees C) The low temperature-cooked meat had undetectable levels of HAAs while the high temperature-cooked meat contained high amounts of HAAs [9.0 ng/g of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2.1 ng/g of 2-amino-3,7,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx), and 32.8 ng/g of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)]. In contrast, total polycyclic aromatic hydrocarbon content was similar in both meat samples (10.7 ng/g in low temperature-cooked meat and 10.1 ng/g in high temperature-cooked meat). At the end of each period, subjects were tested for CYP1A2 and NAT2 enzyme activity by caffeine metabolism phenotyping. NAT2 activity remained unchanged throughout the study while CYP1A2 activity increased in 47 of 65 (72%) of the subjects after consuming high temperature-cooked meat (P < 0.0002), suggesting induction by some compound(s) formed during high temperature cooking. If HAAs are shown to be human carcinogens in epidemiological studies, then meat cooked at high temperatures may pose an increased cancer risk because it contains both inducers of CYP1A2 and procarcinogens MeIQx, DiMeIQx, and PhIP known to be activated by this enzyme. C1 USDA ARS, BELTSVILLE AGR RES CTR, NUTR REQUIREMENTS & FUNCT LAB, BELTSVILLE, MD 20705 USA. LAWRENCE LIVERMORE NATL LAB, DIV BIOMED SCI, LIVERMORE, CA 94550 USA. UNIV ARKANSAS MED SCI HOSP, ARKANSAS CANC RES CTR, LITTLE ROCK, AR 72205 USA. NATL CTR TOXICOL RES, JEFFERSON, AR 72079 USA. RP SINHA, R (reprint author), NCI, ENVIRONM EPIDEMIOL BRANCH, EPIDEMIOL & BIOSTAT PROGRAM, EXECUTIVE PLAZA N, ROOM 443, ROCKVILLE, MD 20892 USA. RI Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 FU NCI NIH HHS [Y01-CP2-0521, Y01-CP2-0523-01, Y01-CP3-0553] NR 49 TC 160 Z9 161 U1 0 U2 7 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 DEC 1 PY 1994 VL 54 IS 23 BP 6154 EP 6159 PG 6 WC Oncology SC Oncology GA PU942 UT WOS:A1994PU94200030 PM 7954461 ER PT J AU OLIVERO, OA BELAND, FA FULLERTON, NF POIRIER, MC AF OLIVERO, OA BELAND, FA FULLERTON, NF POIRIER, MC TI VAGINAL EPITHELIAL DNA-DAMAGE AND EXPRESSION OF PRENEOPLASTIC MARKERS IN MICE DURING CHRONIC DOSING WITH TUMORIGENIC LEVELS OF 3'-AZIDO-2',3'-DIDEOXYTHYMIDINE SO CANCER RESEARCH LA English DT Article ID VIRUS REVERSE-TRANSCRIPTASE; AIDS-RELATED COMPLEX; CELLULAR DNA; 3'-AZIDO-3'-DEOXYTHYMIDINE; POLYMERASES; CELLS; 5'-TRIPHOSPHATE; TRIPHOSPHATE; PHARMACOLOGY; PROGRESSION AB 3'-Azido-2',3'-dideoxythymidine (AZT, Retrovir, zidovudine), a nucleoside analogue currently used in the therapy of acquired immunodeficiency syndrome, induces papillomas and carcinomas in vaginal epithelium of mice as a result of lifetime drug administration. In this study, female CD-1 mice were administered AZT at doses of 180, 360, and 720 mu g/ml of drinking water for 28 days to determine whether AZT became incorporated into vaginal DNA and whether this was associated with preneoplastic changes within the target tissue. In addition, bone marrow, a target for AZT-induced cytotoxicity in mice and humans, was examined for chromosomal aberrations. A positive correlation was observed between dose level of AZT, proliferation of cells in the basal layer of vaginal epithelium, and incorporation of AZT into vaginal DNA. Incorporation of AZT into vaginal DNA was originally detected by radioimmunoassay and confirmed by immunohistochemistry. An aberrant pattern for alpha 6 integrin distribution, similar to the pattern described in skin papillomas with high risk for malignant conversion, also increased with dose in mice given AZT. Chromosomal aberrations in bone marrow increased more than 4-fold in AZT-exposed animals. The genotoxicity demonstrated by incorporation of AZT into vaginal DNA and proliferation of vaginal epithelium may play an essential part in the ability of AZT to induce abnormal differentiation in vaginal epithelium and vaginal tumorigenesis in mice. C1 NATL CTR TOXICOL RES,DIV BIOCHEM TOXICOL,JEFFERSON,AR 72079. RP OLIVERO, OA (reprint author), NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BLDG 37,ROOM 3B 12,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 23 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 DEC 1 PY 1994 VL 54 IS 23 BP 6235 EP 6242 PG 8 WC Oncology SC Oncology GA PU942 UT WOS:A1994PU94200041 PM 7954472 ER PT J AU RINKERSCHAEFFER, CW HAWKINS, AL RU, N DONG, J STOICA, G GRIFFIN, CA ICHIKAWA, T BARRETT, JC ISAACS, JT AF RINKERSCHAEFFER, CW HAWKINS, AL RU, N DONG, J STOICA, G GRIFFIN, CA ICHIKAWA, T BARRETT, JC ISAACS, JT TI DIFFERENTIAL SUPPRESSION OF MAMMARY-CANCER AND PROSTATE-CANCER METASTASIS BY HUMAN CHROMOSOME-17 AND CHROMOSOME-11 SO CANCER RESEARCH LA English DT Article ID TUMORIGENICITY; LOCALIZATION; ALLELES AB Metastasis suppressor activities have previously been mapped to human chromosomes 17 and 11. Decreased expression of the metastasis suppressor gene NM23, which is located on chromosome 17, has been correlated with increased metastatic potential in mammary cancers. A region on human chromosome 11, from 11p11.2p13, has been shown to suppress metastasis in rat prostatic carcinoma cells. in both cases the metastasis suppressor activity had no effect on tumorigenicity or tumor growth rate, demonstrating that the encoded activities are distinct from effects of tumor suppression. To determine whether these human chromosomes encode general or tissue-specific metastasis suppressor activities, a truncated human chromosome 17 (ie., pter-q23) and a full-length human chromosome 11 were separately transferred into highly metastatic rat mammary and prostate cancer cell lines and tested for their ability to suppress spontaneous metastasis in vivo. These studies demonstrated that when the pter-q23 region of human chromosome 17 is retained by the microcell hybrids, the metastatic ability of both mammary and prostatic cancer cells is suppressed. In contrast, when the pter-q14 region of human chromosome 11 is retained, only the metastatic ability of prostatic cancer cells is suppressed. Additional studies demonstrated that the metastasis suppressor activity encoded by the chromosome 17 pter-q23 region is p53-independent and not due to enhanced expression of NM23 protein. C1 JOHNS HOPKINS UNIV,SCH MED,JOHNS HOPKINS ONCOL CTR,BALTIMORE,MD 21231. CHIBA UNIV,SCH MED,DEPT UROL,CHIBA 260,JAPAN. NIEHS,COLLEGE STN,TX 77843. TEXAS A&M UNIV,COLL VET MED,DEPT VET PATHOL,COLLEGE STN,TX 77843. FU NCI NIH HHS [CA 58236] NR 18 TC 80 Z9 80 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 DEC 1 PY 1994 VL 54 IS 23 BP 6249 EP 6256 PG 8 WC Oncology SC Oncology GA PU942 UT WOS:A1994PU94200043 PM 7954474 ER PT J AU HEGI, ME DEVEREUX, TR DIETRICH, WF COCHRAN, CJ LANDER, ES FOLEY, JF MARONPOT, RR ANDERSON, MW WISEMAN, RW AF HEGI, ME DEVEREUX, TR DIETRICH, WF COCHRAN, CJ LANDER, ES FOLEY, JF MARONPOT, RR ANDERSON, MW WISEMAN, RW TI ALLELOTYPE ANALYSIS OF MOUSE LUNG CARCINOMAS REVEALS FREQUENT ALLELIC LOSSES ON CHROMOSOME-4 AND AN ASSOCIATION BETWEEN ALLELIC IMBALANCES ON CHROMOSOME-6 AND K-RAS ACTIVATION SO CANCER RESEARCH LA English DT Article ID CHLORIDE-INDUCED LUNG; METHYLENE-CHLORIDE; B6C3F1 MICE; INTERFERON GENES; HUMAN NEOPLASIA; INBRED MICE; SKIN TUMORS; SHORT ARM; DELETIONS; LOCUS AB We generated allelotypes of 38 methylene chloride-induced lung carcinomas from female C57BL/6J x C3H/HeJ F-1 (hereafter called B6C3F(1)) mice. Two or more polymorphic markers per autosome, most of them microsatellites, were examined for loss of heterozygosity. Allelic losses throughout the genome were generally infrequent except for markers on chromosome 4, which were lost in approximately one-half of the carcinomas. Analysis of lung adenomas indicated that chromosome 4 toss was associated with malignant conversion. In addition, chromosome 4 loss was specific for Lung carcinomas based on comparison to methylene chloride-induced liver tumors and additional studies of lung tumors from a variety of treatment protocols and different mouse strains. preferential loss of the maternal chromosome 4 was observed in B6C3F(1) carcinomas. Analyses of additional tumors induced in mice from two reciprocal crosses, A/J x C3H/HeJ F-1 (hereafter called AC3F(1)) and C3H/HeJ x A/J F-1 (hereafter called C3AF(1)), provided evidence for the inactivation of one allele of the putative chromosome 4 tumor suppressor gene by parental imprinting. Most B6C3F(1) tumors lost all chromosome 4 markers examined, suggesting nondisjunction events. In contrast, several C3AF(1) and AC3F(1) tumors appeared to have interstitial deletions that defined the smallest region of overlap as a 9 cM interval between Ifa-2 and D4Nds2. The homologous region on human chromosome 9p21-22 is frequently lost in a variety of tumors including lung cancers. A candidate tumor suppresser gene, MTS1, is located in this region, which is homozygously deleted or mutated in cell Lines derived from a variety of human tumors. Finally, an association between K-ras gene activation and allelic imbalances on chromosome 6 was observed for B6C3F(1) lung tumors. C1 NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. NIEHS,MOLEC TOXICOL LAB,RES TRIANGLE PK,NC 27709. NIEHS,CHEM PATHOL LAB,RES TRIANGLE PK,NC 27709. MIT,WHITEHEAD INST BIOMED RES,CTR GENOME RES,CAMBRIDGE,MA 02139. MIT,WHITEHEAD INST BIOMED RES,DEPT BIOL,CAMBRIDGE,MA 02139. RI Hegi, Monika/O-4796-2015 OI Hegi, Monika/0000-0003-0855-6495 NR 48 TC 92 Z9 92 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 DEC 1 PY 1994 VL 54 IS 23 BP 6257 EP 6264 PG 8 WC Oncology SC Oncology GA PU942 UT WOS:A1994PU94200044 PM 7954475 ER PT J AU YEUDALL, WA CRAWFORD, RY ENSLEY, JF ROBBINS, KC AF YEUDALL, WA CRAWFORD, RY ENSLEY, JF ROBBINS, KC TI MTS1/CDK4I IS ALTERED IN CELL-LINES DERIVED FROM PRIMARY AND METASTATIC ORAL SQUAMOUS-CELL CARCINOMA SO CARCINOGENESIS LA English DT Article ID NECK-CANCER; MUTATIONS; HEAD AB The MTS1/CDK4I gene encodes a 16 kDa cyclin kinase inhibitor and maps to chromosome 9p21, Previous studies have suggested the presence of a major tumour suppressor gene at this locus which may be inactivated in head and neck squamous cell carcinoma (HNSCC). To determine the status of this gene in human primary and metastatic HNSCC, we examined the locus and its transcript for abnormalities by polymerase chain reaction (PCR), Out of 14 cell lines studied, four had lost only exon 1, one had lost only exon 2, three had lost both exons 1 and 2, and none of the remaining six lines expressed a normal p16 mRNA, These latter six cell lines expressed p16 transcripts that had suffered deletions ranging in size from 2 16 base pairs, In each case, deletions led to a change of reading frame. Furthermore, in two cases abnormalities in the MTS1/CDK4I gene were identical in cells derived from metastatic tumours as compared to cells derived independently from the corresponding primary tumour, The identical nature of mutations observed in primary tumours and metastases derived from the same patient provides strong evidence that inactivation of p16 function was an in vivo event. C1 WAYNE STATE UNIV,DIV HEMATOL & ONCOL,DETROIT,MI. RP YEUDALL, WA (reprint author), NIDR,CELLULAR DEV & ONCOL LAB,BETHESDA,MD 20892, USA. NR 16 TC 75 Z9 79 U1 1 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD DEC PY 1994 VL 15 IS 12 BP 2683 EP 2686 DI 10.1093/carcin/15.12.2683 PG 4 WC Oncology SC Oncology GA PZ539 UT WOS:A1994PZ53900001 PM 8001221 ER PT J AU SNYDERWINE, EG SCHUT, HAJ SUGIMURA, T NAGAO, M ADAMSON, RH AF SNYDERWINE, EG SCHUT, HAJ SUGIMURA, T NAGAO, M ADAMSON, RH TI DNA ADDUCT LEVELS OF 2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE (PHIP) IN TISSUES OF CYNOMOLGUS MONKEYS AFTER SINGLE OR MULTIPLE DOSING SO CARCINOGENESIS LA English DT Article ID METHYL-ALPHA-CARBOLINE; P-32-POSTLABELING METHOD; HETEROCYCLIC AMINES; SALIVARY-GLANDS; COOKED BEEF; RATS; CARCINOGEN; MEIQX; FOOD; IQ AB DNA adducts of 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine (PhIP), a heterocyclic amine derived from cooked meat, were measured by the P-32-postlabeling method in tissues of cynomolgus monkeys given PhIP, Monkeys received either a single dose of PhIP (20 mg/kg orally) or nine daily doses of PhIP (20 mg/kg orally, days 1-5 and 8-11) and tissue samples were obtained 24 h after the last dose, Over 28 different tissues were examined for PhIP-DNA adducts, Adducts were detected in all tissues examined except the fat and bone marrow, After a single dose, adduct levels (mean value/10(7) nucleotides, n = 2 monkeys) were highest in the liver (2.1), followed by the lung (1.7), gall bladder (1.7) and pancreas (0.9), Low adduct levels were detected in the brain and aorta (0.06 and 0.02 respectively), Following multiple doses of PhIP, adduct levels (mean value/10(7) nucleotides +/- SE, n = 3 monkeys) were highest in the heart (5.7 +/- 2.0) followed by the liver (3.8 +/- 0.8), submandibular gland (2.7 +/- 1.8) and pancreas (2.2 +/- 0.5), Comparison of the adduct levels after a single dose with those found after multiple doses indicates that accumulation of PhIP-DNA adducts occurred in certain tissues, Adduct levels in liver, pancreas, kidney, small intestine and colon increased about 1.5- to 2.4-fold, PhIP-DNA adduct levels in submandibular gland and brain increased 4- to 5-fold, Adduct levels in heart increased 10-fold and levels in the aorta increased 31-fold, Adducts in white blood cell DNA increased with daily dosing for 9 days. No apparent changes in adduct levels were seen in the lung, stomach, bladder, muscle and spleen, The wide distribution of PhIP-DNA adducts and their presence in ,white blood cells suggests that there is transport of reactive metabolites from the liver to extrahepatic tissues, The relatively high adduct levels in the gall bladder in comparison with the liver suggests biliary excretion and possible reabsorption of reactive metabolites, The presence of DNA adducts in tissues implicates PhIP as a potential carcinogen in non-human primates, The possibility that PhIP-DNA adducts in tissues such as the heart and aorta may have toxicological consequences is discussed. C1 NCI,DIV CANC ETIOL,OFF DIRECTOR,BETHESDA,MD 20892. MED COLL OHIO,DEPT PATHOL,TOLEDO,OH 43614. NATL CANC CTR,RES INST,TOKYO,JAPAN. RP SNYDERWINE, EG (reprint author), NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892, USA. NR 37 TC 33 Z9 33 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 DEC PY 1994 VL 15 IS 12 BP 2757 EP 2761 DI 10.1093/carcin/15.12.2757 PG 5 WC Oncology SC Oncology GA PZ539 UT WOS:A1994PZ53900012 PM 8001231 ER PT J AU MOSCOW, JA SCHMIDT, L INGRAM, DT GNARRA, J JOHNSON, B COWEN, KH AF MOSCOW, JA SCHMIDT, L INGRAM, DT GNARRA, J JOHNSON, B COWEN, KH TI LOSS OF HETEROZYGOSITY OF THE HUMAN CYTOSOLIC GLUTATHIONE-PEROXIDASE-I GENE IN LUNG-CANCER SO CARCINOGENESIS LA English DT Article ID SISTER CHROMATID EXCHANGES; SMALL-CELL CARCINOMA; DIETARY SELENIUM; SERUM SELENIUM; MESSENGER-RNA; HUMAN GENOME; LINKAGE MAP; RAT-LIVER; VITAMIN-A; SHORT ARM AB The consistent deletion of 3p21 in lung cancer has led to intensive efforts to identify a lung tumor suppressor gene at this locus. We recently mapped the gene for the selenium-dependent drug-detoxifying enzyme glutathione peroxidase 1 (GPX1) to this location by in situ hybridization, We developed a polymerase chain reaction-based assay which demonstrated the existence of three GPX1 alleles characterized by the number of alanines in a polyalanine coding sequence in exon 1, These three alleles produced a heterozygote frequency of 70% in two separate populations: normal tissue DNA taken from Centre d'Etude du Polmorphisme Humain (CEPH) parents and normal tissue taken from cancer patients, In contrast, 10 heterozygote tumors were detected out of 64 lung cancer specimens, Linkage analysis of GPX1 to Genethon 3p markers in CEPH pedigrees demonstrated that GPX1 was located between the two microsatellite markers believed to flank the lung cancer deletion site, Nucleotide sequence analysis of GPX1 alleles did not reveal any mutations of this gene in lung tumors, However, sequence analysis did reveal that the three GPX1 alleles were characterized by three nucleotide substitutions in addition to the polyalanine polymorphism, including a substitution at codon 198 which results in either a proline or leucine at that position, Therefore, the different GPX1 alleles encode structurally different hGPx1 subunits. In addition, analysis of allele frequency suggests that the GPX1*ALA7 allele may occur less frequently in tumors with 3p21 deletions. C1 NCI,SURG BRANCH,BETHESDA,MD 20892. NCI,NAVY BRANCH,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. RP MOSCOW, JA (reprint author), NCI,MED BRANCH,BETHESDA,MD 20892, USA. NR 46 TC 85 Z9 87 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 DEC PY 1994 VL 15 IS 12 BP 2769 EP 2773 DI 10.1093/carcin/15.12.2769 PG 5 WC Oncology SC Oncology GA PZ539 UT WOS:A1994PZ53900014 PM 8001233 ER PT J AU LUBET, RA STEELE, VE CASEBOLT, TL ETO, I KELLOFF, GJ GRUBBS, CJ AF LUBET, RA STEELE, VE CASEBOLT, TL ETO, I KELLOFF, GJ GRUBBS, CJ TI CHEMOPREVENTIVE EFFECTS OF THE AROMATASE INHIBITORS VOROZOLE (R-83842) AND 4-HYDROXYANDROSTENEDIONE IN THE METHYLNITROSOUREA (MNU)-INDUCED MAMMARY-TUMOR MODEL IN SPRAGUE-DAWLEY RATS SO CARCINOGENESIS LA English DT Article ID ADVANCED BREAST-CANCER; POSTMENOPAUSAL PATIENTS; TAMOXIFEN; AMINOGLUTETHIMIDE; INDUCTION; THERAPY AB The chemopreventive activity of the aromatase inhibitors vorozole and 4-hydroxyandrostenedione were determined in the methylnitrosourea (MNU)-induced model of rat mammary tumorigenesis. Vorozole (5 and 2.5 mg/kg body wt) and 4-hydroxyandrostenedione (15 and 6 mg/rat) were administered daily (by gavage) to virgin female Sprague-Dawley rats starting at an age of 43 days, Seven days later animals were given a single dose of MNU, Following treatment with MNU, animals continued to be treated with vorozole and 4-hydroxyandrostenedione daily until the end of the experiment (100 days post MNU treatment), Vorozole at either dose proved to be a profound inhibitor of MNU-induced mammary tumors, Vorozole decreased tumor incidence from 100% to 10%, while simultaneously decreasing tumor multiplicity from 5 tumors per animal to 0.1 tumors per animal. This chemopreventive effect was accompanied by significant increases in body weight gain in the animals treated with vorozole when compared with control rats, In contrast, neither dose of 4-hydroxyandrostenedione had any effect on tumor incidence and only the higher dose slightly decreased tumor multiplicity. C1 UNIV ALABAMA,DEPT NUTR SCI,BIRMINGHAM,AL. RP LUBET, RA (reprint author), NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892, USA. FU NCI NIH HHS [N0-CN-95156-03, CA 28103] NR 36 TC 51 Z9 51 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 DEC PY 1994 VL 15 IS 12 BP 2775 EP 2780 DI 10.1093/carcin/15.12.2775 PG 6 WC Oncology SC Oncology GA PZ539 UT WOS:A1994PZ53900015 PM 8001234 ER PT J AU CHALOUPKA, K SANTOSTEFANO, M GOLDFARB, IS LIU, G MYERS, MJ TSYROLV, IB GELBOIN, HV KRISHNAN, V SAFE, S AF CHALOUPKA, K SANTOSTEFANO, M GOLDFARB, IS LIU, G MYERS, MJ TSYROLV, IB GELBOIN, HV KRISHNAN, V SAFE, S TI ARYL-HYDROCARBON (AH) RECEPTOR-INDEPENDENT INDUCTION OF CYP1A2 GENE-EXPRESSION BY ACENAPHTHYLENE AND RELATED-COMPOUNDS IN B6C3F1 MICE SO CARCINOGENESIS LA English DT Article ID POLYNUCLEAR AROMATIC-HYDROCARBONS; XENOBIOTIC RESPONSIVE ELEMENTS; METHYLENEDIOXYPHENYL COMPOUNDS; MONOCLONAL-ANTIBODIES; RAT-LIVER; TRANSCRIPTIONAL ACTIVATION; CYTOCHROME-P-450 ISOZYMES; DIETARY INDOLE-3-CARBINOL; ESTRADIOL METABOLISM; DIOXIN RECEPTOR AB Treatment of B6C3F1 mice with acenaphthylene, acenaphthene, fluorene, phenanthrene, anthracene and dibenzofuran resulted in induction of hepatic microsomal methoxy-resorufin O-deethylase (MROD) activity, Acenaphthylene was the most potent inducer of MROD, a Cyp1a2-dependent activity, and was utilized as a prototypical inducer for this group of tricyclic hydrocarbons, Acenaphthylene (300 mg/kg) caused a >80-fold induction of hepatic microsomal MROD activity; no induction was observed in kidney or lung, Analysis of induced hepatic microsomes with antibodies to Cyp1a1 and Cyp1a2 showed that acenaphthylene induced immunoreactive Cyp1a2 but not Cyp1a1 proteins and subsequent mRNA analysis confirmed with a cDNA probe for Cyp1a1 and Cyp1a2 that acenaphthylene induced Cyp1a2 but not Cyp1a1 mRNA, Results from nuclear sun-on experiments using hepatic nuclei showed that acenaphthylene caused an similar to 4-fold increase in the rate of Cyp1a2 gene transcription in B6C3F1 mice, Results of competitive binding studies indicated that the tricyclic hydrocarbons did not competitively displace [H-3]2,3,7,8-tetrachlorodibenzo-p-dioxin or [H-3]benzo[a]pyrene from the mouse hepatic cytosolic aryl hydrocarbon (Ah) receptor or 4S carcinogen binding protein respectively, The data indicate that acenaphthylene and related tricyclic hydrocarbons induce Cyp1a2 gene expression in B6C3F1 mice via an Ah receptor-independent pathway. Thus, tricyclic hydrocarbons induce Cyp1a2 without the co-induction of Cyp1a1 and therefore these relatively non-toxic compounds can be used to further probe the role of Cyp1a2 in the metabolism and metabolic activation of diverse chemical carcinogens. C1 TEXAS A&M UNIV,COLLEGE STN,TX 77843. NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. FU NIEHS NIH HHS [ES04917] NR 47 TC 43 Z9 43 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 DEC PY 1994 VL 15 IS 12 BP 2835 EP 2840 DI 10.1093/carcin/15.12.2835 PG 6 WC Oncology SC Oncology GA PZ539 UT WOS:A1994PZ53900024 PM 8001243 ER PT J AU TIANO, HF WANG, RL HOSOKAWA, M CRESPI, C TINDALL, KR LANGENBACH, R AF TIANO, HF WANG, RL HOSOKAWA, M CRESPI, C TINDALL, KR LANGENBACH, R TI HUMAN CYP2A6 ACTIVATION OF 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE (NNK) - MUTATIONAL SPECIFICITY IN THE GPT GENE OF AS52 CELLS SO CARCINOGENESIS LA English DT Article ID TOBACCO-SPECIFIC NITROSAMINE; NITROSOUREA-INDUCED MUTATIONS; PYRIDYLOXOBUTYL DNA ADDUCTS; HUMAN LIVER-MICROSOMES; ESCHERICHIA-COLI; CHEMICAL CARCINOGENESIS; N-NITROSAMINES; LUNG-TUMORS; F344 RATS; ENVIRONMENTAL CARCINOGENS AB The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potential human carcinogen that is known to be metabolized to DNA-reactive intermediates by the cytochromes P450. We have examined the nature of NNK's DNA damaging effects in a mammalian cell system expressing a specific human cytochrome P450 (2A6) and containing a target gene for mutagenesis. Human CYP2A6, which is known to activate NNK to a mutagen, was lipofected via a retroviral vector into the Chinese hamster ovary AS52 cell line, which contains the bacterial gpt gene and can be mutated to 6-thioguanine resistance. AS52 cells expressed negligible CYP2A6-specific coumarin 7-hydroxylase activity (0.7 pmol/mg protein/min), while a CYP2A6 transfected clone (AS52-E8) expressed 30 pmol/mg protein/min. Both cell lines were equally sensitive to the cytotoxic and mutagenic effects of the direct-acting mutagen ethylmethanesulfonate; however, only the AS52-E8 cells exhibited a dose-dependent increase in cytotoxicity and mutant frequency upon treatment with NNK. At the highest NNK dose (1200 mu g/ml), the mutant frequency in AS52-E8 cells was 14-fold (339x10(-6)) greater than the spontaneous frequency of 24x10(-6). Ninety-eight mutant clones were isolated following NNK treatment. Based on PCR analysis, 21 clones contained deletions/rearrangements and 77 were putative point mutants. Sequencing potential point mutants showed that 81% contained G:C to A:T transitions. Four of six G:C to A:T hotspots were at the second G of the GGT motif, which is the motif and major mutation found in codon 12 of Ki-ras from NNK-induced lung tumors in strain A mice. Since NNK may be metabolized via different pathways to pyridyloxobutylate or methylate DNA, the data suggest that methylation damage causes the major mutagenic events in AS52-E8 cells when NNK is activated by human CYP2A6. C1 NIEHS, ENVIRONM CARCINOGENESIS & MUTAGENESIS LAB, RES TRIANGLE PK, NC 27709 USA. GENTEST CORP, WOBURN, MA 01801 USA. NR 58 TC 42 Z9 43 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD DEC PY 1994 VL 15 IS 12 BP 2859 EP 2866 DI 10.1093/carcin/15.12.2859 PG 8 WC Oncology SC Oncology GA PZ539 UT WOS:A1994PZ53900028 PM 8001247 ER PT J AU THRAVES, PJ VARGHESE, S JUNG, M GRDINA, DJ RHIM, JS DRITSCHILO, A AF THRAVES, PJ VARGHESE, S JUNG, M GRDINA, DJ RHIM, JS DRITSCHILO, A TI TRANSFORMATION OF HUMAN EPIDERMAL-KERATINOCYTES WITH FISSION NEUTRONS SO CARCINOGENESIS LA English DT Article ID RAT EMBRYO CELLS; LOW-DOSE RATE; NEOPLASTIC TRANSFORMATION; SPECTRUM NEUTRONS; K-RAS; P53 MUTATIONS; ONCOGENIC TRANSFORMATION; MALIGNANT TRANSFORMATION; IONIZING-RADIATION; GAMMA-RADIATION AB The biological effects of exposures to high LET radiations have particular relevance to radiation protection and risk assessment. Since most cancers are of epithelial origin, it is important to obtain a better understanding of radiation-induced oncogenic transformation in this cell type. Accordingly we have initiated studies to determine whether immortalized human epidermal keratinocytes (RHEK) can be transformed with high LET radiations. Exponentially growing RHEK cells were treated with single doses (1, 10, 25, 50 and 100 cGy) of 0.85 MeV fission neutrons from the Janus reactor. Neutron exposure led to the development of morphologically altered cells and foci formation after 6 weeks at confluence. These transformed cultures grew with an increased saturation density, exhibited anchorage-independent growth and formed tumors in athymic mice. Single-strand conformational polymorphism analysis and DNA sequencing demonstrated the absence of point mutations in codons 12/13 and 61 in the Ha-ras, Ki-ras, or N-ras genes and exons 4-9 of the p53 tumor suppressor gene. These studies demonstrate that high LET radiations (fission neutrons) can transform immortalized human epithelial cells to a malignant phenotype that does not appear to involve mutations in either the cellular p53 or ras genes. C1 ARGONNE NATL LAB,DIV BIOL & MED RES,ARGONNE,IL 60438. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. RP THRAVES, PJ (reprint author), GEORGETOWN UNIV,MED CTR,VINCENT T LOMBARDI CANC RES CTR,DEPT RADIAT MED,WASHINGTON,DC 20007, USA. FU NCI NIH HHS [CA5295, CA 52945] NR 56 TC 5 Z9 5 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 DEC PY 1994 VL 15 IS 12 BP 2867 EP 2873 DI 10.1093/carcin/15.12.2867 PG 7 WC Oncology SC Oncology GA PZ539 UT WOS:A1994PZ53900029 PM 8001248 ER PT J AU DLUGOSZ, AA CHENG, C DENNING, MF DEMPSEY, PJ COFFEY, RJ YUSPA, SH AF DLUGOSZ, AA CHENG, C DENNING, MF DEMPSEY, PJ COFFEY, RJ YUSPA, SH TI KERATINOCYTE GROWTH-FACTOR RECEPTOR LIGANDS INDUCE TRANSFORMING GROWTH-FACTOR-ALPHA EXPRESSION AND ACTIVATE THE EPIDERMAL GROWTH-FACTOR RECEPTOR SIGNALING PATHWAY IN CULTURED EPIDERMAL-KERATINOCYTES SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID TRANSGENIC MICE; TGF-ALPHA; EPITHELIAL-CELLS; MESSENGER-RNA; FACTOR-BETA; MOUSE; DIFFERENTIATION; BINDING; GENE; FGF AB Epidermal growth factor receptor (EGFR) ligands are fundamental regulators of epithelial growth, differentiation, and neoplastic transformation. In addition to being potent mitogens for murine epidermal keratinocytes in vitro, transforming growth factor alpha (TGF alpha) and EGF elicit distinctive changes in keratin expression: Ca2+-mediated induction of the differentiation-specific keratins K1 and K10 is blocked, while simple epithelial keratins K8 and K18 are expressed aberrantly (C. Cheng et al., Cell Growth. & Differ., 4: 317-327, 1993). We have evaluated several additional growth factors to determine the specificity of this response for EGFR ligands. TGF alpha, keratinocyte growth factor (KGF), and acidic fibroblast growth factor (aFGF), but not basic fibroblast growth factor (bFGF) or insulin-like growth factor type I, block Ca2+-mediated expression of K1 while inducing K8. Since KGF and aFGF (but not bFGF) are ligands for the KCF receptor (KGFR), we explored the possibility that the TGF alpha/EGFR pathway is an intermediary in signaling through the KGFR. TGF alpha mRNA was increased in cells treated with KGF, aFGF, or TGF alpha but not bFGF or insulin-like growth factor type I. Similar changes were detected at the protein level; TGF alpha in conditioned medium (CM) from control, KGF-, TGF alpha-, and aFGF-treated cultures was 54 (+/-8, SEM), 365 (+/-50), 146 (+/-20), and 120 (+/-50) pg/ml, respectively. KGF and TGF alpha also increased expression of cell-associated TGF alpha measured in keratinocyte lysates. KGF increased TGF alpha secretion and mRNA levels in human as well as mouse keratinocytes. CM From KGF-treated cultures stimulated cell growth when added to cultures of normal keratinocytes. Preincubation with neutralizing antibodies to both TGF alpha and KGF, but not KGF antibody alone, blocked cell growth in cultures treated with KGF CM, suggesting that the predominant keratinocyte mitogen in KGF CM is TGF alpha. In support of this hypothesis, treatment of keratinocytes for 5 min with either KGF CM or purified TGF alpha resulted in EGFR autophosphorylation. Furthermore, after similar to 24 h, KGF as well as TGF alpha induced EGFR down-regulation based on Western blot analysis and I-125-EGF binding. Induction of TGF alpha in KGF-treated keratinocytes, coupled to activation and down-modulation of the EGFR, suggests that TGF alpha may be a proximal effector of KGF action for at least certain aspects of epidermal growth and differentiation. C1 NCI,DIV CANC ETIOL,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. VANDERBILT UNIV,SCH MED,DEPT MED,NASHVILLE,TN 37232. VANDERBILT UNIV,SCH MED,DEPT CELL BIOL,NASHVILLE,TN 37232. NR 56 TC 63 Z9 64 U1 0 U2 5 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 DEC PY 1994 VL 5 IS 12 BP 1283 EP 1292 PG 10 WC Cell Biology SC Cell Biology GA PW217 UT WOS:A1994PW21700003 PM 7535082 ER PT J AU FYNAN, TM MORGAN, D YUSPA, SH LONGLEY, BJ ZHOU, ZL REISS, M AF FYNAN, TM MORGAN, D YUSPA, SH LONGLEY, BJ ZHOU, ZL REISS, M TI RESTORATION OF DIFFERENTIATION AND SUPPRESSION OF TUMORIGENICITY IN SOMATIC-CELL HYBRIDS OF HUMAN SQUAMOUS CARCINOMA-CELLS AND KERATINOCYTES SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID TRANSFORMING GROWTH-FACTOR; PAPILLOMAVIRUS TYPE-16 DNA; RAS ONCOGENE MUTATIONS; HUMAN EPIDERMAL-CELLS; TERMINAL DIFFERENTIATION; EPITHELIAL-CELLS; TUMOR-SUPPRESSOR; RETINOIC ACID; HUMAN SKIN; I TRANSGLUTAMINASE AB Somatic cell hybrid cell lines derived from the fusion of human squamous carcinoma cells (FaDu-Hyg) with human keratinocytes were used to examine the relationships between cell differentiation and tumorigenicity. Treatment of the parental keratinocytes or the two hybrid cell lines with the combination of calcium and fetal bovine serum increased the expression of the envelope precursor, involucrin, 4- to 8-fold, whereas it remained unchanged in FaDu-Hyg cells. Similarly, calcium- and serum-treated keratinocytes and the two hybrid cell lines displayed a 7- to 13-fold increase of the activity of membrane-associated type I transglutaminase, whereas transglutaminase activity in FaDu-Hyg cells did not change appreciably. FaDu-Hyg cells were tumorigenic in vivo, but tumorigenicity was suppressed in both hybrid cell lines. Analysis of additional tumor cell lines indicated that the expression of transglutaminase I and involucrin are under separate genetic control and that loss of transglutaminase activity can result either from a tack of protein or from a defect in the activation step. Thus, keratinization of squamous epithelial cells appears to be controlled by several different recessive genes, which cosegregate with but are probably only partly identical with the genes that suppress tumor formation in vivo. C1 YALE UNIV,SCH MED,DEPT INTERNAL MED,MED ONCOL SECT,NEW HAVEN,CT 06520. YALE UNIV,SCH MED,DEPT DERMATOL,NEW HAVEN,CT 06520. YALE UNIV,SCH MED,YALE CANC CTR,NEW HAVEN,CT 06520. YALE UNIV,SCH MED,YALE SKIN DIS RES CTR,NEW HAVEN,CT 06520. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA-08341, CA-41556] NR 63 TC 6 Z9 6 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 DEC PY 1994 VL 5 IS 12 BP 1293 EP 1300 PG 8 WC Cell Biology SC Cell Biology GA PW217 UT WOS:A1994PW21700004 PM 7696177 ER PT J AU LANGTONWEBSTER, BC XUAN, JA BRINK, JR SALOMON, DS AF LANGTONWEBSTER, BC XUAN, JA BRINK, JR SALOMON, DS TI DEVELOPMENT OF RESISTANCE TO CISPLATIN IS ASSOCIATED WITH DECREASED EXPRESSION OF THE GP185(C-ERBB-2) PROTEIN AND ALTERATIONS IN GROWTH-PROPERTIES AND RESPONSES TO THERAPY IN AN OVARIAN TUMOR-CELL LINE SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID MONOCLONAL-ANTIBODY; BREAST-CANCER; CARCINOMA CELLS; ERBB-2; HER-2/NEU; ONCOGENE; OVEREXPRESSION; AMPLIFICATION; SENSITIVITY; SURVIVAL AB Overexpression of the c-erbB-2 protein (gp185(c-erbB-2)) is correlated with a tumorigenic phenotype and may contribute to disease progression. We have reported previously on an anti-gp185(c-erbB-2) antibody, TAb 250, that inhibits in vitro and in vivo growth of breast and ovarian cell lines that overexpress the protein and enhances the inhibitory activity of cisplatin (CDDP). To assess whether CDDP resistance is related to gp185(c-erbB-2) expression levels, alterations in tumor cell growth characteristics, or efficacy of antibody plus drug combination treatments, an SKOV-3 ovarian tumor cell line was made resistant to escalating doses of CDDP. Parental cells were 12-fold more sensitive to CDDP with 7 times more gp185(c-erbB-2) sites than the most resistant variant (SKOV-3/C12). Additionally, the resistant cells demonstrated a longer lag phase for in vivo growth than the parental cells. While TAb 250 enhanced the in vivo inhibitory effect of CDDP against parental SKOV-3 cells, the antibody did not significantly alter the CDDP responsiveness of the resistant population. Growth inhibition by TAb 250 alone of both the parental and the SKOV-3-resistant variants was similar; however, TAb 250 was able to prolong the lag-phase of tumor growth of the resistant variant by up to 25 days. These results indicate that the development of CDDP resistance is associated with lowered levels of gp185(c-erbB-2) expression, slower tumor cell growth, and enhanced efficacy of antibody treatment of the resistant cells. C1 NCI,TUMOR IMMUNOL & BIOL LAB,TUMOR GROWTH FACTOR SECT,BETHESDA,MD 20892. RP LANGTONWEBSTER, BC (reprint author), BERLEX BIOSCI,DEPT ONCOL,15049 SAN PABLO AVE,RICHMOND,CA, USA. NR 26 TC 17 Z9 17 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 DEC PY 1994 VL 5 IS 12 BP 1367 EP 1372 PG 6 WC Cell Biology SC Cell Biology GA PW217 UT WOS:A1994PW21700012 PM 7696185 ER PT J AU STROBEL, MC AF STROBEL, MC TI THE 85TH ANNUAL-MEETING OF THE AMERICAN-ASSOCIATION-FOR-CANCER-RESEARCH SO CELL GROWTH & DIFFERENTIATION LA English DT Editorial Material RP STROBEL, MC (reprint author), NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD DEC PY 1994 VL 5 IS 12 BP 1409 EP 1412 PG 4 WC Cell Biology SC Cell Biology GA PW217 UT WOS:A1994PW21700018 PM 7696191 ER PT J AU MISHRA, BB FERNANDES, AM BLAESE, RM MUCHMORE, AV AF MISHRA, BB FERNANDES, AM BLAESE, RM MUCHMORE, AV TI CHARACTERIZATION OF T-CELL LIGANDS FOR UROMODULIN - A POSSIBLE ROLE IN COSTIMULATION SO CELLULAR IMMUNOLOGY LA English DT Article ID TAMM-HORSFALL GLYCOPROTEIN; HIGH MANNOSE GLYCOPEPTIDES; TUMOR-NECROSIS-FACTOR; HUMAN-PREGNANCY URINE; PROTEIN; RECEPTOR; LECTIN; INTERLEUKIN-2; LYMPHOCYTES; SPECIFICITY AB In this study, we demonstrate that uromodulin (UMN) is a costimulator of T cells and characterize the T cell ligand which might mediate its costimulatory effect. UMN is an 85-kDa human urinary glycoprotein which is better known for its ability to suppress antigen-induced proliferation of peripheral blood mononuclear cells. It also has a mitogenic effect on peripheral blood cells, which has not been investigated. In this study, costimulation of T cells by UMN is observed only in the absence of B cells and antigen-specific antiserum. Using ligand binding assays we also demonstrate a specific receptor for UMN on peripheral blood T cells and T cell lines (K-d Of 10(-8)). We describe two uromodulin binding proteins of approximate M(r) 35 and 55 kDa, isolated from detergent extract of T cells, either of which may represent a receptor for UMN or an associated signal transduction molecule involved in the stimulatory effect of UMN on T cells. Finally, we demonstrate a similar protein in a renal cell line, which may clarify the renal role of UMN. (C) 1994 Academic Press, Inc. C1 NCI,METAB BRANCH,BETHESDA,MD 20892. NIH,NATL CTR HUMAN GENOME RES,CLIN GENE THERAPY BRANCH,BETHESDA,MD 20892. RP MISHRA, BB (reprint author), TEMPLE UNIV HOSP & MED SCH,DEPT NEUROL,PHILADELPHIA,PA 19140, USA. NR 26 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD DEC PY 1994 VL 159 IS 2 BP 113 EP 123 DI 10.1006/cimm.1994.1301 PG 11 WC Cell Biology; Immunology SC Cell Biology; Immunology GA PX262 UT WOS:A1994PX26200001 PM 7994748 ER PT J AU KATZ, J NAGLER, R BARAK, S LIVNEH, A BAUM, B ATKINSON, J SHEMER, J AF KATZ, J NAGLER, R BARAK, S LIVNEH, A BAUM, B ATKINSON, J SHEMER, J TI CYTOKINES MODULATE INTERLEUKIN-6 PRODUCTION BY HUMAN SALIVARY-GLAND CELL-LINE SO CELLULAR IMMUNOLOGY LA English DT Article ID NECROSIS-FACTOR-ALPHA; PROLIFERATION; EXPRESSION; INTERFERON; GROWTH; GAMMA; IL-6 AB The ability of HrTNF-alpha, HrIL-1 beta, and HrIFN-gamma to modulate IL-6 production by cultured human salivary cell line (HSG) was examined. IL-6 activity was measured by the hybridoma growth factor biologic activity. HrTNF-alpha had a significant dose-dependent effect, whereas HrIL-1 beta and HrIFN-gamma had moderate and minor effects, respectively. Maximal effect (920 units) was noted when cytokines were applied in combination (1000 units HrIFN-gamma and 20 units HrTNF-alpha) and incubated with human salivary gland cells for 72 hr. The same combination of cytokines had also a marked inhibitory effect (70% of control) on human salivary gland cell growth. This is the first report of these concomitant pheonomena in a human cell line originating from salivary tissue. (C) 1994 Academic Press, Inc. C1 NIDR,CIPB,BETHESDA,MD. RP KATZ, J (reprint author), SHEBA MED CTR,HELLER INST,TEL AVIV,ISRAEL. NR 14 TC 18 Z9 18 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD DEC PY 1994 VL 159 IS 2 BP 211 EP 219 DI 10.1006/cimm.1994.1308 PG 9 WC Cell Biology; Immunology SC Cell Biology; Immunology GA PX262 UT WOS:A1994PX26200008 PM 7994755 ER PT J AU KAWANO, YI SASAMOTO, Y VACCHIO, MS HODES, RJ GERY, I AF KAWANO, YI SASAMOTO, Y VACCHIO, MS HODES, RJ GERY, I TI IMMUNE-RESPONSES AGAINST SELF-TCR PEPTIDES SO CELLULAR IMMUNOLOGY LA English DT Article ID T-CELL RECEPTOR; EXPERIMENTAL AUTOIMMUNE UVEORETINITIS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MYELIN BASIC-PROTEIN; MAJOR HISTOCOMPATIBILITY COMPLEX; RETINOID-BINDING PROTEIN; BETA-CHAIN USAGE; RAT; LYMPHOCYTES; VACCINATION AB Vaccination of rats against the TCR peptide V beta 8.2 (39-59) was reported to inhibit the immunopathogenic process of EAE. Analysis of the immune response to this peptide and several related TCR peptides yielded the following findings: (i) Lewis rats immunized in vivo and challenged in vitro responded with vigorous lymphocyte proliferative responses to peptide V beta 8.2 (39-59) and to three other rat TCR peptides, V beta 8.3 (15-32), V beta 8.3 (39-59), and V beta 14 (39-59). On the other hand, two other rat peptides, V beta 8.2 (18-38) and V beta 8.3 (62-76), were poorly immunogenic. (ii) Rat peptide V beta 8.2 (39-59) was found more immunogenic than its mouse homolog, in both Lewis rats and B10.A mice. A moderate level of cross-reactivity was observed between these two peptide homologs. (iii) Rats of different genetic makeups varied in their response to peptide V beta 8.2 (39-59), A similar pattern of response of the different rats was found with another TCR peptide, V beta 14 (39-59), Hybrids between high and low responder rat strains resembled the high responders in their response to the TCR peptides. (iv) Sensitized lymph node cells as well as lymphocytes of a cen line specific for peptide V beta 8.2 (39-59) failed to respond to T cells that express the V beta 8.2 gene product. This observation is interpreted to indicate that peptide V beta 8.2 (39-59) is a cryptic determinant of the V beta 8.2 protein. Moreover, the data suggest that lymphocytes proliferating against peptide V beta 8.2 (39-59) may not be responsible for the reported inhibition of EAE in rats vaccinated with this peptide. (C) 1994 Academic Press, Inc. C1 NEI,IMMUNOL LAB,BETHESDA,MD 20892. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. NR 38 TC 4 Z9 4 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD DEC PY 1994 VL 159 IS 2 BP 235 EP 245 DI 10.1006/cimm.1994.1310 PG 11 WC Cell Biology; Immunology SC Cell Biology; Immunology GA PX262 UT WOS:A1994PX26200010 PM 7527731 ER PT J AU MILLER, MJ PARMELEE, DC BENJAMIN, T SECHI, S DOOLEY, KL KADLUBAR, FF AF MILLER, MJ PARMELEE, DC BENJAMIN, T SECHI, S DOOLEY, KL KADLUBAR, FF TI PLASMA-PROTEINS AS EARLY BIOMARKERS OF EXPOSURE TO CARCINOGENIC AROMATIC-AMINES SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Article DE 4-AMINOBIPHENYL; ARYLAMINES; HAPTOGLOBIN; ALBUMIN; 2-DIMENSIONAL GEL ELECTROPHORESIS ID 2-DIMENSIONAL ELECTROPHORESIS; HEMOGLOBIN ADDUCT; BLADDER-CANCER; 4-AMINOBIPHENYL; SMOKING; IDENTIFICATION; RESOLUTION; PATTERNS; RATS; DOGS AB Two-dimensional gel electrophoresis (2DG) has been used to study the changes induced in dog plasma polypeptides by the known urinary bladder carcinogens, 4-aminobiphenyl (4-ABP) and 2-naphthylamine (2-NA). Treatment with 3-aminobiphenyl (3-ABP) and 1-naphthylamine (1-NA), both considered to be non-carcinogenic, were used as controls. The purpose of this study was: (1) to determine whether or not changes that occurred in the plasma protein patterns were specific to 4-ABP and/or other related carcinogenic arylamines; (2) to measure the time course in the changes of the major polypeptides during dosing and their resynthesis during a recovery period; and (3) to determine, by microsequencing, the biochemical identity of the affected proteins. The results indicate that only the most potent carcinogen, CABP, had the effect of suppressing the expression of some proteins, while the other aromatic amines caused no discernible change in the 2DG patterns during a 12-week dosing period. The 4-ABP caused dramatic suppression of two sets of proteins. One set of three spots had an apparent molecular weight of 32.5 kDa, and a pi of 5.8-6.0. The major component in this group was identified as the beta-chain of haptoglobin. Expression of this protein decreased markedly during the first 2 weeks of treatment and recovered slowly after dosing stopped. Since haptoglobin functions to bind with free hemoglobin and facilitates its elimination from the blood stream, these results can be rationalized as a consequence of 4-ABP binding to hemoglobin in the erythrocyte, resulting in cell death and hemolysis. The 4-ABP modified hemoglobin then binds to haptoglobin and this tertiary complex is purged from the blood stream, resulting in the disappearance of free haptoglobin. A second set of spots (mel. wt., 65 kDa; pI, 6.5-6.6) disappeared much faster than the haptoglobin, and recovered more quickly. The major protein is about one-fifth the intensity of haptoglobin and appeared to be N-terminally blocked. Internal microsequencing of four fragments obtained from tryptic cleavage of the major spot of this group showed significant similarity to the serum albumin sequence of several species. This spot group is not the major serum albumin spot, however, since the latter is readily identified as the most abundant spot on the plasma map. During the course of this study, several other polypeptides in the 2DG map of dog plasma were identified and are presented here. C1 NATL CTR TOXICOL RES, JEFFERSON, AR 72079 USA. RP NCI, DIV CANC ETIOL, EXPTL CARCINOGENESIS LAB, BLDG 37, ROOM 3C-28, BETHESDA, MD 20892 USA. NR 21 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0009-2797 EI 1872-7786 J9 CHEM-BIOL INTERACT JI Chem.-Biol. Interact. PD DEC PY 1994 VL 93 IS 3 BP 221 EP 234 DI 10.1016/0009-2797(94)90021-3 PG 14 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA PL519 UT WOS:A1994PL51900004 PM 7923441 ER PT J AU LEIDY, NK AF LEIDY, NK TI USING FUNCTIONAL STATUS TO ASSESS TREATMENT OUTCOMES SO CHEST LA English DT Editorial Material RP LEIDY, NK (reprint author), NATL INST NURSING RES,STUDY HUMAN RESPONSES HLTH & ILLNESS LAB,BETHESDA,MD, USA. NR 7 TC 33 Z9 33 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD DEC PY 1994 VL 106 IS 6 BP 1645 EP 1646 DI 10.1378/chest.106.6.1645 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA PX259 UT WOS:A1994PX25900004 PM 7988177 ER PT J AU FELD, R RUBINSTEIN, L THOMAS, PA AF FELD, R RUBINSTEIN, L THOMAS, PA TI ADJUVANT CHEMOTHERAPY WITH CYCLOPHOSPHAMIDE, DOXORUBICIN, AND CISPLATIN IN PATIENTS WITH COMPLETELY RESECTED STAGE-I NONSMALL CELL LUNG-CANCER - AN LCSG TRIAL SO CHEST LA English DT Article AB Objective: Two recent studies in resectable non-small cell lung cancer by the Lung Cancer Study Group (LCSG) suggested an advantage to adjuvant therapy with cyclophosphamide, doxorubicin (Adriamycin), and cisplatin (CAP). Neither study had a no-treatment control arm. The purpose of this study was to compare the CAP regimen with no treatment in patients with resectable early-stage non-small cell lung cancer. Methods: After complete resection, eligible patients with T1N1 or T2N0 non-small cell lung cancer were randomly assigned to receive or not to receive four courses of CAP at 3-week intervals beginning on day 30 after surgery after stratification for histology, preoperative white blood cell count, and Karnofsky performance status before surgery. The CAP regimen consisted of 400 mg/m(2) of cyclophosphamide, 40 mg/m(2) of doxorubicin, and 60 mg/m(2) of cisplatin. Of the 269 eligible patients entered in the study, 101 had recurrence and 127 had died at the time of analysis. The mean time since randomization is 6.4 years; mean follow-up is 3.8 years. There were no differences in time to recurrence or overall survival between the two groups even when analyses were adjusted for prognostic variables. Only 53% of the eligible patients received all four courses of CAP, and only 57% of such patients received all four cycles an time. Among the patients who had recurrences, 74% had their initial recurrence at a distant site. Conclusion: No survival benefit for CAP vs no-treatment control was found in this study. Therefore, adjuvant therapy with CAP should not be recommended for patients with resected early-stage non-small cell lung cancer. Further trials to test adjuvant therapy are indicated, but investigators should use better antiemetics to improve patient compliance as well as more active cisplatin-based chemotherapy regimens. C1 NCI,BETHESDA,MD. ILLINOIS CANC COUNCIL,CHICAGO,IL. RP FELD, R (reprint author), PRINCESS MARGARET HOSP,TORONTO,ON,CANADA. NR 11 TC 6 Z9 6 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD DEC PY 1994 VL 106 IS 6 SU S BP S307 EP S309 DI 10.1378/chest.106.6.307S PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA PY204 UT WOS:A1994PY20400008 PM 7988250 ER PT J AU GAIL, MH AF GAIL, MH TI A PLACEBO-CONTROLLED RANDOMIZED DOUBLE-BLIND-STUDY OF ADJUVANT INTRAPLEURAL BCG IN PATIENTS WITH RESECTED T1N0, T1N1, OR T2N0 SQUAMOUS-CELL CARCINOMA, ADENOCARCINOMA, OR LARGE-CELL CARCINOMA OF THE LUNG - LCSG PROTOCOL-771 SO CHEST LA English DT Article ID CANCER STUDY-GROUP; STAGE-I; IMMUNOTHERAPY; RECURRENCE AB This article reviews the design and findings of LCSG Protocol 771, a randomized double-blind comparison of postoperative adjuvant intrapleural bacillus Calmette-Guerin (BCG) against saline solution placebo control in 473 patients with resected T1N0, T1N1, or T2N0 nonsmall cell lung cancer. Patients were randomized from August 30, 1977, through October 20, 1980, and follow-up ended on January 1, 1990. There was no evidence of improved survival or time to recurrence among patients given BCG in contrast to earlier promising findings. A calculation suggests that false-positive results due to chance are not uncommon in small preliminary studies, indicating the need for larger confirmatory trials such as LCSG Protocol 771. Other contributions from this Protocol are also reviewed, including data on BCG toxicity, immunologic effects, patterns of recurrence, and identification of prognostic risk groups. C1 NCI,BIOSTAT BRANCH,BETHESDA,MD 20892. NR 19 TC 13 Z9 13 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD DEC PY 1994 VL 106 IS 6 SU S BP S287 EP S292 DI 10.1378/chest.106.6.287S PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA PY204 UT WOS:A1994PY20400004 PM 7988246 ER PT J AU LINNOILA, RI PIANTADOSI, S RUCKDESCHEL, JC AF LINNOILA, RI PIANTADOSI, S RUCKDESCHEL, JC TI IMPACT OF NEUROENDOCRINE DIFFERENTIATION IN NONSMALL CELL LUNG-CANCER - THE LCSG EXPERIENCE SO CHEST LA English DT Article ID NEURO-ENDOCRINE DIFFERENTIATION; L-DOPA DECARBOXYLASE; TUMORS; MARKERS; CHROMOGRANIN AB Non-small cell lung cancers with neuroendocrine differentiation (NSCLC-NE) may demonstrate biologic behavior intermediate between non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) with impact on prognosis. We studied the expression of four well-defined neuroendocrine (NE) markers: neuron-specific enolase (NSE), chromogranin A, Leu-7, gastrin-releasing peptide, and a panel of three non-NE markers, including vimentin, and the epithelial markers carcino-embryonic antigen (CEA) by immunohistochemistry, and mucin by histochemistry in 237 resected NSCLCs from patients on six LCSG protocols. Twenty-nine (12%) tumors were positive for 2 or more NE markers. An NE differentiation score was calculated but failed to correlate with recurrence as did other combinations of markers. However, the presence of tissue staining for CEA was strongly associated with improved survival (p=0.011), whereas the presence of mucin was associated with a worse outcome (p<0.001). Individually, CEA and mucin remained prognostic even when corrected for stage, histologic features, and performance status. We conclude that NE differentiation is not predictive of recurrence in patients with resected NSCLC but data on patterns of CEA and mucin expression may improve prognostication and permit rational design of new therapeutic approaches. C1 JOHNS HOPKINS UNIV HOSP,CTR ONCOL,BALTIMORE,MD 21205. UNIV S FLORIDA,COLL MED,H LEE MOFFITT CANC CTR & RES INST,TAMPA,FL. RP LINNOILA, RI (reprint author), NCI,BIOMARKERS & PREVENT RES BRANCH,9610 MED CTR DR,300,ROCKVILLE,MD 21710, USA. NR 15 TC 56 Z9 57 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD DEC PY 1994 VL 106 IS 6 SU S BP S367 EP S371 DI 10.1378/chest.106.6.367S PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA PY204 UT WOS:A1994PY20400024 PM 7988266 ER PT J AU TOCKMAN, MS EROZAN, YS GUPTA, P PIANTADOSI, S MULSHINE, JL RUCKDESCHEL, JC BUKOWSKI, RM LAD, T ETTINGER, DS DESLAURIERS, J GINSBERG, R KELLY, K HOLMES, EC MUGGIA, F ROTH, JA JOHNSTON, M MCKNEALLY, MF AF TOCKMAN, MS EROZAN, YS GUPTA, P PIANTADOSI, S MULSHINE, JL RUCKDESCHEL, JC BUKOWSKI, RM LAD, T ETTINGER, DS DESLAURIERS, J GINSBERG, R KELLY, K HOLMES, EC MUGGIA, F ROTH, JA JOHNSTON, M MCKNEALLY, MF TI THE EARLY DETECTION OF 2ND PRIMARY LUNG CANCERS BY SPUTUM IMMUNOSTAINING SO CHEST LA English DT Article ID NON-SMALL-CELL; MONOCLONAL-ANTIBODIES; JOHNS-HOPKINS; PREVALENCE; RECURRENCE; CARCINOMA; SURVIVAL AB Study objective: To determine whether monoclonal antibody (Mab) detection of tumor-associated antigen expressed on sputum epithelial cells precedes clinical presentation of second primary lung cancer. Design Setting/Participants: Eleven oncology centers collaborate in the accrual of 1,000 patients with stage I non-small cell lung cancer (NSCLC) who had undergone resection. The Mabs examined in this study (624H12, 703D4) detect two promising oncofetal/differentiation markers (ie, a difucosylated Lewis X and a 31-Kd glycoprotein antigen). Interventions: Induced sputum specimens are evaluated for quality, then are Papanicolaou and immunostained by independent central laboratories at enrollment and annually thereafter. The predictive value of Mab markers is compared with routine morphologic study for detection of second primary lung cancer during an anticipated 3 years of accrual and 1 year of follow-up. Measurements and results: Five hundred eighty of an anticipated 1,000 patients have been accrued on schedule. Patients are primarily white (88.6%), former smokers (75.9%), men (55.6%), with a median age of 66.7, and joined the study at an average of 3.7 years following resection of a stage 1 NSCLC (34.4% squamous, 43.6% adenocarcinoma). Central laboratories found less dysplasia and more unsatisfactory specimens (27.3%) than do the accrual institution laboratories. Immunostaining identifies more suspicious cells than does morphologic study. However, only two second primary lung cancers (eight total deaths) have occurred to date. Conclusions: Halfway through the accrual, we describe the study design and preliminary observations. This study illustrates rational selection of carcinogenesis markers by linkage of marker expression on preneoplastic specimens with subsequent expression on tumor tissue. C1 JOHNS HOPKINS MED INST,DEPT ENVIRONM HLTH SCI,BALTIMORE,MD. JOHNS HOPKINS MED INST,DEPT ONCOL,BALTIMORE,MD. JOHNS HOPKINS MED INST,DEPT PATHOL,BALTIMORE,MD. HOSP UNIV PENN,DEPT PATHOL,PHILADELPHIA,PA. NCI,DIV CANC PREVENT & CONTROL,EDCOP,BIOMARKERS & EARLY DETECT BRANCH,BETHESDA,MD 20892. UNIV S FLORIDA,H LEE MOFFIT CANC CTR & RES INST,TAMPA,FL. FU NCI NIH HHS [1P50 CA58184-01] NR 29 TC 41 Z9 42 U1 0 U2 3 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 SN 0012-3692 J9 CHEST JI Chest PD DEC PY 1994 VL 106 IS 6 SU S BP S385 EP S390 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA PY204 UT WOS:A1994PY20400028 PM 7988270 ER PT J AU LAMB, ME AF LAMB, ME TI THE INVESTIGATION OF CHILD SEXUAL ABUSE - AN INTERDISCIPLINARY CONSENSUS STATEMENT SO CHILD ABUSE & NEGLECT LA English DT Editorial Material RP LAMB, ME (reprint author), NICHHD,SOCIAL & EMOT DEV SECT,9190 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 44 Z9 45 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0145-2134 J9 CHILD ABUSE NEGLECT JI Child Abuse Negl. PD DEC PY 1994 VL 18 IS 12 BP 1021 EP 1028 DI 10.1016/0145-2134(94)90127-9 PG 8 WC Family Studies; Psychology, Social; Social Work SC Family Studies; Psychology; Social Work GA PT902 UT WOS:A1994PT90200004 PM 7850610 ER PT J AU LENFANT, C AF LENFANT, C TI TASK-FORCE ON RESEARCH IN EPIDEMIOLOGY AND PREVENTION OF CARDIOVASCULAR-DISEASES SO CIRCULATION LA English DT Editorial Material RP LENFANT, C (reprint author), NHLBI,BETHESDA,MD, USA. NR 0 TC 17 Z9 20 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 DEC PY 1994 VL 90 IS 6 BP 2609 EP 2617 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PX374 UT WOS:A1994PX37400002 PM 7994799 ER PT J AU TOWBIN, JA LI, H TAGGART, RT LEHMANN, MH SCHWARTZ, PJ SATLER, CA AYYAGARI, R ROBINSON, JL MOSS, A HEJTMANCIK, JF AF TOWBIN, JA LI, H TAGGART, RT LEHMANN, MH SCHWARTZ, PJ SATLER, CA AYYAGARI, R ROBINSON, JL MOSS, A HEJTMANCIK, JF TI EVIDENCE OF GENETIC-HETEROGENEITY IN ROMANO-WARD LONG-QT-SYNDROME - ANALYSIS OF 23 FAMILIES SO CIRCULATION LA English DT Article DE LONG QT SYNDROME; GENETICS ID LINKAGE ANALYSIS; LOCUS; CHROMOSOME-11; FRAGMENTS AB Background The Romano-Ward long-QT Syndrome (LQTS) is an autosomal dominant inherited trait characterized by prolonged QT interval on ECG, life-threatening arrhythmias, syncope, and sudden death in affected individuals. A gene responsible for this disorder has been shown to be linked to the Harvey ras-1 locus (H-ras-1) DNA marker on the short arm of chromosome 11 (11p) in 7 families. The purpose of this study was to determine, by analyzing 23 families with LQTS for linkage to chromosome 11p, whether evidence exists for more than one gene causing LQTS (ie, locus heterogeneity). Methods and Results Twenty-three families (262 family members) were clinically evaluated using medical histories, ECGs, and Holter recordings. Each corrected QT interval (QT(c)) was determined using Bazett's formula. Blood for DNA extraction and cell line immortalization was obtained after informed consent. Southern blotting and polymerase chain reaction were performed, and linkage analysis carried out using the LINKAGE computer program (v 5.03). Genetic heterogeneity was determined using the HOMOG 2 (v 2.51) computer program. Twenty-three families were studied for evidence of linkage to chromosome 11p using the H-ras-1 locus probe pTBB-2 and multiple flanking markers, including tyrosine hydroxylase (TH). Two-point linkage analysis using pTBB-2 and TH markers was consistent with linkage in 15 of 23 families, with the maximum single-family LOD score of +3.038 occurring at Theta=0. However, 8 of 23 families had negative LOD scores, with the values in 4 families being less than -2 at Theta=0, consistent with exclusion of linkage. Analysis with the HOMOG program was consistent with genetic heterogeneity (P<.0001). Multipoint linkage data using pTBB-2 and TH were also examined for evidence of heterogeneity. HOMOG analysis of multipoint LOD scores from 100 cM surrounding the H-ras-1 locus also supported heterogeneity (P<.001). Conclusions In the 23 families with LQTS analyzed for linkage to the H-ras-1 locus on chromosome 11p15.5, 15 of 23 families had LOD scores consistent with linkage. The remaining 8 of 23 families had negative LOD scores, 4 of which were definitively excluded from linkage. Thus, genetic heterogeneity is definitively (P<.001) demonstrated for this disorder. C1 CAROLINAS MED CTR,DEPT MOLEC BIOL,CHARLOTTE,NC. WAYNE STATE UNIV,DEPT MED,DETROIT,MI. UNIV PAVIA,DEPT MED,PAVIA,ITALY. HARVARD UNIV,BOSTON CHILDRENS HOSP,SCH MED,DEPT CARDIOL,BOSTON,MA. NEI,MECHANISMS OPHTHALMOL DIS LAB,BETHESDA,MD. UNIV ROCHESTER,DEPT COMMUNITY & PREVENT MED,ROCHESTER,NY. UNIV ROCHESTER,DEPT MED,ROCHESTER,NY. RP TOWBIN, JA (reprint author), BAYLOR COLL MED,INST MOLEC GENET,DEPT PEDIAT,CARDIOL SECT,1 BAYLOR PLAZA,RM 333E,HOUSTON,TX 77030, USA. RI Schwartz, Peter/J-4267-2016 OI Schwartz, Peter/0000-0003-0367-1048 NR 46 TC 68 Z9 68 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 DEC PY 1994 VL 90 IS 6 BP 2635 EP 2644 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PX374 UT WOS:A1994PX37400006 PM 7994803 ER PT J AU FANANAPAZIR, L EPSTEIN, ND CURIEL, RV PANZA, JA TRIPODI, D MCAREAVEY, D AF FANANAPAZIR, L EPSTEIN, ND CURIEL, RV PANZA, JA TRIPODI, D MCAREAVEY, D TI LONG-TERM RESULTS OF DUAL-CHAMBER (DDD) PACING IN OBSTRUCTIVE HYPERTROPHIC CARDIOMYOPATHY - EVIDENCE FOR PROGRESSIVE SYMPTOMATIC AND HEMODYNAMIC IMPROVEMENT AND REDUCTION OF LEFT-VENTRICULAR HYPERTROPHY SO CIRCULATION LA English DT Article DE PACING; CARDIOMYOPATHY ID FIBER STRAIN; ABNORMALITIES; ACTIVATION; PRESSURE AB Background We previously reported that 6 to 12 weeks of dual-chamber (DDD) pacing results in clinical and hemodynamic improvement in obstructive hypertrophic cardiomyopathy (HCM). This study examines the long-term results of DDD pacing in obstructive HCM. Methods and Results DDD devices were implanted in 84 patients (mean age, 49+/-16 years) with obstructive HCM and severe drug-refractory symptoms. At a mean follow-up of 2.3+/-0.8 years (maximum, 3.5 years), the New York Heart Association (NYHA) functional class had improved significantly (1.6+/-0.6 versus 3.2+/-0.5, P<.00001). Symptoms were eliminated in 28 patients (33%), improved in 47 patients (56%), but remained unchanged in 7 patients (8%). Two patients died suddenly (97% cumulative 3-year survival rate). In 74 patients with significant left ventricular outflow tract (LVOT) obstruction at rest, the LVOT gradients were significantly reduced at follow-up (27+/-31 versus 96+/-41 mm Hg, P<.00001). Symptoms and provokable LVOT gradients were also reduced in all 10 patients without significant resting but with provokable LVOT obstruction. Persistence of the LVOT obstruction and symptoms was attributed to inability to preexcite the interventricular septum (n=8) and onset of atrial fibrillation (n=7). Fifty patients had two cardiac catheterization evaluations, 3+/-1 and 16+/-4 months after implantation of a pacemaker. In this subgroup, the NYHA functional class improved from 3.2+/-0.5 at baseline to 1.8+/-0.7 at the initial evaluation (P<.00001), but with a further significant improvement at the second evaluation: 1.4+/-0.6, P<.001. This symptomatic improvement was associated with progressive reduction of LVOT gradient at the two evaluations: baseline, 100+/-47 mm Hg; first evaluation, 41+/-36 mm Hg (P<.0001); and second evaluation, 29+/-34 mm Hg (P<.01). Despite the presence of left bundle branch block, DDD pacing reduced LVOT obstruction significantly in 15 patients (LVOT gradient, baseline 89+/-36 mm Hg versus 18+/-26 mm Hg at follow-up, P<.0001). There was a weak but significant correlation between the reduction in LVOT gradients accomplished by AV pacing before implantation of DDD device and the eventual reduction in LVOT gradients recorded at the follow-up evaluation (r=.38, P=.0017). Echocardiography demonstrated significant thinning of the anterior septum and distal anterior LV wall in the absence of deterioration of LV systolic function. Conclusions (1) Although most of the improvement of symptoms and hemodynamic indexes occurs during the first few months of DDD pacing, further changes are often observed a year later; (2) DDD pacing is associated with an excellent prognosis in a subgroup of severely disabled patients, many of whom present with syncope or presyncope; (3) baseline pacing studies are not essential to identify patients who may benefit from pacing; (4) preexisting left bundle branch block is compatible with severe LVOT obstruction, and DDD pacing is also beneficial in this subgroup; (5) DDD pacing reduces both resting and provokable LVOT obstruction; (6) additional therapy, for example, radiofrequency ablation of the AV node, may be necessary in some patients either to preexcite the interventricular septum or to control atrial fibrillation; and (7) although LV hypertrophy has been considered a primary feature of HCM, pacing appears to reverse LV wall thickness in a significant subset of adult HCM patients. RP FANANAPAZIR, L (reprint author), NHLBI,INHERITED CARDIAC DIS SECT,CLIN ELECTROPHYSIOL LAB,CARDIOL BRANCH,BLDG 10,ROOM 7B-15,BETHESDA,MD 20892, USA. NR 27 TC 230 Z9 241 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 DEC PY 1994 VL 90 IS 6 BP 2731 EP 2742 PG 12 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PX374 UT WOS:A1994PX37400018 PM 7994815 ER PT J AU GILLIGAN, DM PANZA, JA KILCOYNE, CM WACLAWIW, MA CASINO, PR QUYYUMI, AA AF GILLIGAN, DM PANZA, JA KILCOYNE, CM WACLAWIW, MA CASINO, PR QUYYUMI, AA TI CONTRIBUTION OF ENDOTHELIUM-DERIVED NITRIC-OXIDE TO EXERCISE-INDUCED VASODILATION SO CIRCULATION LA English DT Article DE ENDOTHELIUM-DERIVED; RELAXING FACTOR; L-ARGININE; EXERCISE; VASCULAR TONE ID DEPENDENT VASCULAR RELAXATION; CONGESTIVE-HEART-FAILURE; MUSCLE BLOOD-FLOW; L-ARGININE; ESSENTIAL-HYPERTENSION; CORONARY-ARTERIES; HYPERCHOLESTEROLEMIC HUMANS; FOREARM EXERCISE; RELAXING FACTOR; RELEASE AB Background Endothelium-derived nitric oxide is an important modulator of resting vascular tone in animals and humans. However, the contribution of nitric oxide to exercise-induced vasodilation is unknown. Methods and Results The effect of NG-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide synthesis, on exercise-induced vasodilation was studied in 18 healthy subjects (mean+/-SD, 40+/-10 years; 10 women). Acetylcholine was used to test the efficacy of L-NMMA in inhibiting stimulation of nitric oxide synthesis and sodium nitroprusside to test the specificity of L-NMMA in inhibiting endothelium-dependent vasodilation. Intermittent handgrip exercise and infusions of acetylcholine and sodium nitroprusside were performed during intra-arterial infusion of 5% dextrose (control) and L-NMMA (4 to 16 mu mol/min). Forearm blood flow was determined by strain-gauge plethysmography. Forearm oxygen extraction was measured from arterial and venous oxygen saturations. In a separate study, 10 subjects performed exercise during infusions of 5% dextrose, L-arginine (the substrate for nitric oxide production), and D-arginine (the stereoisomer that is not a substrate for nitric oxide production). L-NMMA reduced exercise blood flow by 7+/-13% (P=.04), increased exercise resistance by 18+/-20% (P=.02), and increased exercise oxygen extraction by 16+/-17% (P<.001). The degree of inhibition of acetylcholine-induced vasodilation with L-NMMA correlated positively with the degree of reduction in exercise blood flow (r=.55, P=.02). The highest dose of L-NMMA (16 mu mol/min) produced the greatest effect; exercise blood flow was reduced by 11+/-14% (P=.03), and vascular resistance increased by 26+/-23% (P=.005). L-NMMA did not affect the forearm vasodilation produced by sodium nitroprusside. Exercise blood flow, resistance, and oxygen extraction were not significantly modified by infusions of either L- or D-arginine. Conclusions Inhibition of nitric oxide synthesis reduces exercise-induced vasodilation in the human forearm, indicating that nitric oxide plays a role in exercise-induced vasodilation. Increased availability of nitric oxide substrate does not enhance exercise-induced vasodilation in healthy subjects. These findings have important implications for disease states in which endothelium-derived nitric oxide production is impaired. C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. NHLBI,DEPT BIOSTAT,BETHESDA,MD 20892. NR 36 TC 233 Z9 234 U1 0 U2 4 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC PY 1994 VL 90 IS 6 BP 2853 EP 2858 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PX374 UT WOS:A1994PX37400033 PM 7994830 ER PT J AU TELL, GS POLAK, JF WARD, BJ KITTNER, SJ SAVAGE, PJ ROBBINS, J AF TELL, GS POLAK, JF WARD, BJ KITTNER, SJ SAVAGE, PJ ROBBINS, J TI RELATION OF SMOKING WITH CAROTID-ARTERY WALL THICKNESS AND STENOSIS IN OLDER ADULTS - THE CARDIOVASCULAR HEALTH STUDY SO CIRCULATION LA English DT Article DE ATHEROSCLEROSIS; STENOSIS; SMOKING; CAROTID ARTERIES ID B-MODE ULTRASOUND; CIGARETTE-SMOKING; RISK-FACTORS; ATHEROSCLEROSIS; MEN; ARTERIOSCLEROSIS; DISEASE AB Background Cigarette smoking has been associated with increased risk of atherosclerotic diseases in hospital-based studies and in studies of middle-aged populations but not in population-based studies of older adults with and without clinical cardiovascular disease. Methods and Results We investigated the relation of smoking to carotid artery atherosclerotic disease, expressed as intimal-medial wall thickness and arterial lumen narrowing (stenosis) measured by ultrasound. Subjects were 5116 older adults participating in the baseline examination of the Cardiovascular Health Study, a community-based study of cardiovascular diseases in older age. With increased smoking there was significantly greater internal and common carotid wall thickening and internal carotid stenosis: current smokers>former smokers>never-smokers; for instance, the unadjusted percent stenosis was 24%, 20%, and 16%, respectively (P<.0001). A significant dose-response relation was seen with pack-years of smoking. These findings persisted after adjusting for other cardiovascular risk factors and were also confirmed when analyses were restricted to those without prevalent cardiovascular disease. The difference in internal carotid wall thickness between current smokers and nonsmokers was greater than the difference associated with 10 years of age among never-smoking participants (0.39 mm versus 0.31 mm). Among all participants, the prevalence of clinically significant (greater than or equal to 50%) internal carotid stenosis increased from 4.4% in never-smokers to 7.3% in former smokers to 9.5% in current smokers (P<.0001). Conclusions These findings extend previous reports of a positive relation between smoking and carotid artery disease to a population-based sample of older adults using several different indicators of atherosclerotic disease. C1 WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT PUBL HLTH SCI,EPIDEMIOL SECT,WINSTON SALEM,NC 27103. BRIGHAM & WOMENS HOSP,DEPT RADIOL,BOSTON,MA 02115. UNIV MARYLAND,DEPT NEUROL,BALTIMORE,MD 21201. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. UNIV CALIFORNIA DAVIS,DEPT MED,SACRAMENTO,CA. RI Tell, Grethe/G-5639-2015 OI Tell, Grethe/0000-0003-1386-1638 FU NHLBI NIH HHS [N01-HC-85080, N01-HC-85079, N01-HC-85081] NR 22 TC 102 Z9 103 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 DEC PY 1994 VL 90 IS 6 BP 2905 EP 2908 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PX374 UT WOS:A1994PX37400040 PM 7994837 ER PT J AU PAUNIO, M HEINONEN, OP VIRTAMO, J KLAG, MJ MANNINEN, V ALBANES, D COMSTOCK, GW AF PAUNIO, M HEINONEN, OP VIRTAMO, J KLAG, MJ MANNINEN, V ALBANES, D COMSTOCK, GW TI HDL CHOLESTEROL AND MORTALITY IN FINNISH MEN WITH SPECIAL REFERENCE TO ALCOHOL INTAKE SO CIRCULATION LA English DT Article DE CHOLESTEROL; RISK FACTORS; MORTALITY; ALCOHOL ID HIGH-DENSITY-LIPOPROTEIN; CORONARY HEART-DISEASE; PRIMARY-PREVENTION TRIAL; CARDIOVASCULAR-DISEASE; SERUM-CHOLESTEROL; BLOOD-PRESSURE; ARTERY DISEASE; LIPID VALUES; RISK-FACTORS; CONSUMPTION AB Background There is substantial evidence that a low serum level of HDL cholesterol (HDLC) is a risk factor for coronary deaths. However, data on older people are scarce, and previous studies have not examined this association in relation to alcohol intake. Methods and Results Coronary mortality, all-cause mortality, and mortality due to alcohol and violence were related to HDLC levels among 7052 male smokers 50 to 69 years old in south and west Finland enrolled from 1984 to 1988 in the ATBC (AT, alpha-tocopherol; BC, beta-carotene) Study placebo group. During the average follow-up period of 4.7 years, 620 men died; 222 of these deaths were from coronary heart disease and 82 from causes related to alcohol and violence. HDLC levels were inversely associated with coronary mortality, irrespective of age, whereas high total cholesterol was positively associated with coronary mortality among the younger men, 50 to 59 years of age, but not among the older men, 60 to 69 years old. Correction for temporal variation in HDLC measurement indicated a 43% stronger inverse association between HDLC and coronary mortality compared with that based only on a single value. The inverse association of HDLC and coronary mortality was less marked at higher levels of alcohol intake. All-cause and alcohol- and violence-related mortality were positively associated with HDLC among the younger men. All-cause mortality showed a U-shaped dose response among men greater than or equal to 60 years old. Conclusions Previous studies may have underestimated the beneficial effect of high HDLC because of regression-dilution bias and the confounding effect of heavy alcohol intake. This study supports the view that, particularly among older men, lipoprotein fractions may be more appropriate for screening than total cholesterol. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD 21218. NATL PUBL HLTH FINLAND,OULU,FINLAND. JOHNS HOPKINS HLTH INST,WELCH CTR PREVENT EPIDEMIOL & CLIN RES,BALTIMORE,MD. UNIV HELSINKI,DEPT MED 1,HELSINKI,FINLAND. NCI,DIV CANC PREVENT & CONTROL,CANC PREVENT STUDIES BRANCH,BETHESDA,MD 20892. RP PAUNIO, M (reprint author), UNIV HELSINKI,DEPT PUBL HLTH,HAARTMANINKATU 3,SF-00014 HELSINKI,FINLAND. RI Albanes, Demetrius/B-9749-2015 FU NCI NIH HHS [N01-CN-45165]; NHLBI NIH HHS [HL-21620] NR 68 TC 51 Z9 52 U1 0 U2 3 PU AMER HEART ASSOC PI DALLAS PA 7272 GREENVILLE AVENUE, DALLAS, TX 75231-4596 SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC PY 1994 VL 90 IS 6 BP 2909 EP 2918 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA PX374 UT WOS:A1994PX37400041 PM 7994838 ER PT J AU ZWEIG, MH GLICKMAN, J CSAKO, G AF ZWEIG, MH GLICKMAN, J CSAKO, G TI ANALYTICAL INTERFERENCE CAUSED BY INCOMPLETELY CLOTTED SERUM SPECIMENS SO CLINICAL CHEMISTRY LA English DT Letter C1 NIH,WG MAGNUSON CLIN CTR,DEPT CLIN PATHOL,BETHESDA,MD 20892. RP ZWEIG, MH (reprint author), NIH,WG MAGNUSON CLIN CTR,CLIN CHEM SERV,ROOM 2C407,BETHESDA,MD 20892, USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD DEC PY 1994 VL 40 IS 12 BP 2325 EP 2326 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA PX754 UT WOS:A1994PX75400030 PM 7988026 ER PT J AU CHEN, ZP WANG, RYH ALTER, HJ SHIH, JWK AF CHEN, ZP WANG, RYH ALTER, HJ SHIH, JWK TI GENETIC IMMUNIZATION OF MICE WITH PLASMIDS CONTAINING HEPATITIS-C VIRUS CORE PROTEIN-ENCODING DNA SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BETHESDA,MD. ARMED FORCES INST PATHOL,AMER REGISTRY PATHOL,WASHINGTON,DC. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD DEC PY 1994 VL 40 IS 12 BP 2340 EP 2340 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA PX754 UT WOS:A1994PX75400065 ER PT J AU HARDEN, RN DUC, TA WILLIAMS, TR COLEY, D CATE, JC GRACELY, RH AF HARDEN, RN DUC, TA WILLIAMS, TR COLEY, D CATE, JC GRACELY, RH TI NOREPINEPHRINE AND EPINEPHRINE LEVELS IN AFFECTED VERSUS UNAFFECTED LIMBS IN SYMPATHETICALLY MAINTAINED PAIN SO CLINICAL JOURNAL OF PAIN LA English DT Article DE NOREPINEPHRINE; EPINEPHRINE; SYMPATHETICALLY MAINTAINED PAIN; REFLEX SYMPATHETIC DYSTROPHY; CAUSALGIA ID PLASMA NORADRENALINE; PERIPHERAL-NERVE; ONGOING ACTIVITY; DYSTROPHY; CAUSALGIA; INNERVATION; MECHANISMS; HYPOTHESIS; BLOCKADE; RAT AB Objective: To test the hypothesis that there is relative sympathetic hyperactivity in the affected limb in patients with sympathetically maintained pain syndromes by measuring serum norepinephrine and epinephrine in the affected versus the unaffected sides. Design: Venous pool samples were drawn just proximal to the affected area and from an identical site on the unaffected side. Serum norepinephrine and epinephrine were measured by high-pressure liquid chromatography with electrochemical detection. Subjects: Sixteen women and seven men with a mean age of 44.4 years diagnosed as having sympathetically maintained pain on the basis of a positive response to paravertebral block and a criteria-based diagnostic scheme. Results: The serum norephinephrine level was significantly lower in the affected limbs than the unaffected limbs (p = 0.024). The serum epinephrine level was not significantly different. Conclusions: These results are not consistent with the hypothesis of segmental sympathetic hyperactivity in the affected limb in sympathetically maintained pain and support a hypothesis of peripheral receptor upregulation with pathologic response to circulating catecholamines. Other possible explanations are discussed. C1 NINR,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD. MED UNIV S CAROLINA,DEPT LAB MED,CHARLESTON,SC 29425. MED UNIV S CAROLINA,DEPT ANESTHESIOL,PAIN MANAGEMENT SERV,CHARLESTON,SC 29425. RP HARDEN, RN (reprint author), NORTHWESTERN UNIV,REHABIL INST CHICAGO,CTR PAIN STUDIES,345 E SUPER,CHICAGO,IL 60611, USA. NR 45 TC 70 Z9 71 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0749-8047 J9 CLIN J PAIN JI Clin. J. Pain PD DEC PY 1994 VL 10 IS 4 BP 324 EP 330 DI 10.1097/00002508-199412000-00014 PG 7 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA PV142 UT WOS:A1994PV14200014 PM 7858364 ER PT J AU FANTIE, BD KOSMIDIS, MH AF FANTIE, BD KOSMIDIS, MH TI AVOIDANCE RESPONDING AND CLOSED-HEAD INJURY - REPLICATION AND REEVALUATION OF THE ANTICIPATORY BEHAVIOR DEFICIT SO CLINICAL NEUROPSYCHOLOGIST LA English DT Article AB Previous research suggests that survivors of closed-head injury (CHI), tested while inpatients, took more trials to learn to avoid a noxious noise in a conditioning task than did controls. In contrast, patients with CHI learned to escape at latencies equal to those of controls. The authors attributed these results to defective anticipation of the consequences of either the warning stimulus and/or the subject's own behaviour. They called this pattern of intact escape with putatively impaired avoidance an Anticipatory Behaviour Deficit (ABD). We tried to detect an ABD in nonhospitalized CHI survivors who had sustained an injury significant enough to produce a dectable deficit on a standard neuropsychological battery. The CHI group (n=24) and controls (n=13) had comparable avoidance latencies, escape latencies, and trials to criterion. Both groups escaped more quickly than they avoided. We conclude that ABD may not be unbiquitous in CHI survivors or that it may be a temporary condition, limited to a few months posttrauma. Since uninjured controls also escaped faster than they avoided, we suggest a reevaluation of the operational definition of an ABD. C1 AMERICAN UNIV,DEPT PSYCHOL,HUMAN NEUROPSYCHOL LAB,WASHINGTON,DC 20016. NIMH,PSYCHOL & PSYCHOPATHOL LAB,BETHESDA,MD 20892. NR 23 TC 2 Z9 2 U1 1 U2 1 PU SWETS ZEITLINGER BV PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 0920-1637 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PD DEC PY 1994 VL 8 IS 4 BP 379 EP 387 DI 10.1080/13854049408402040 PG 9 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA PX792 UT WOS:A1994PX79200001 ER PT J AU GOLDBERG, SR YASAR, S BERGMAN, J YOUDIM, MBH AF GOLDBERG, SR YASAR, S BERGMAN, J YOUDIM, MBH TI INTRODUCTION - EXAMINATION OF CLINICAL AND PRECLINICAL PHARMACOLOGICAL DATA RELATING TO ABUSE LIABILITY OF L-DEPRENYL (SELEGILINE) SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material ID MONOAMINE-OXIDASE; PARKINSONS-DISEASE; AMPHETAMINE; INHIBITORS; MADOPAR C1 UNIV MARYLAND, SCH MED, DEPT PHARMACOL & EXPTL THERAPEUT, BALTIMORE, MD 21201 USA. JOHNS HOPKINS UNIV, SCH MED, DEPT ANESTHESIOL & CRIT CARE MED, BALTIMORE, MD 21218 USA. HARVARD UNIV, NEW ENGLAND REG PRIMATE RES CTR, SCH MED, BOSTON, MA USA. TECHNION ISRAEL INST TECHNOL, BRUCE RAPPAPORT FAC MED, DEPT PHARMACOL, IL-32000 HAIFA, ISRAEL. GEORGETOWN UNIV, MED CTR, DEPT PHARMACOL, WASHINGTON, DC 20057 USA. RP GOLDBERG, SR (reprint author), NIDA, PRECLIN PHARMACOL BRANCH,INTRAMURAL RES PROGRAM, POB 5180,4940 EASTERN AVE, BLDG C, BALTIMORE, MD 21224 USA. NR 29 TC 4 Z9 4 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 EI 1532-6535 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD DEC PY 1994 VL 56 IS 6 SU S BP 721 EP 724 PN 2 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QA023 UT WOS:A1994QA02300001 PM 7995013 ER PT J AU YASAR, S BERGMAN, J AF YASAR, S BERGMAN, J TI AMPHETAMINE-LIKE EFFECT OF L-DEPRENYL (SELEGILINE) IN DRUG DISCRIMINATION STUDIES SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article; Proceedings Paper CT Special Symposium on Abuse Liability of 1-Deprenyl - Examination of the Clinical and Preclinical Pharmacological Data, at the 9th General Meeting of the European-Society-for-Neurochemistry CY AUG 19, 1992 CL TRINITY COLL, DUBLIN, IRELAND SP NIDA, NIH HO TRINITY COLL ID MONOAMINE-OXIDASE; RHESUS-MONKEYS; DOPAMINE; PHENYLETHYLAMINE; INHIBITORS; METABOLISM; BRAIN; RATS AB l-Deprenyl has dose-dependent amphetamine- and methamphetamine-like discriminative stimulus properties in rats and monkeys. However, these actions occur only at doses that are well above the clinically relevant dose range for l-deprenyl and are likely to reflect its metabolic conversion to amphetamine products. In view of its weak potency for producing amphetamine-like effects and their slow onset, it may not be surprising that l-deprenyl does not appear to have amphetamine-like abuse potential and has been used therapeutically in the treatment of Parkinson syndrome for more than 20 years with no reported instances of abuse. C1 HARVARD UNIV,NEW ENGLAND REG PRIMATE RES CTR,SCH MED,SOUTHBOROUGH,MA 01772. JOHNS HOPKINS UNIV,SCH MED,DEPT ANESTHESIOL & CRIT CARE MED,BALTIMORE,MD. NIDA,PRECLIN PHARMACOL BRANCH,INTRAMURAL RES PROGRAM,BALTIMORE,MD. FU NIDA NIH HHS [DA03774, DA00499]; NIMH NIH HHS [MH07658] NR 31 TC 20 Z9 20 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD DEC PY 1994 VL 56 IS 6 SU S BP 768 EP 773 PN 2 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QA023 UT WOS:A1994QA02300007 PM 7995019 ER PT J AU WINGER, GD YASAR, S NEGUS, SS GOLDBERG, SR AF WINGER, GD YASAR, S NEGUS, SS GOLDBERG, SR TI INTRAVENOUS SELF-ADMINISTRATION STUDIES WITH L-DEPRENYL (SELEGILINE) IN MONKEYS SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article; Proceedings Paper CT Special Symposium on Abuse Liability of 1-Deprenyl - Examination of the Clinical and Preclinical Pharmacological Data, at the 9th General Meeting of the European-Society-for-Neurochemistry CY AUG 19, 1992 CL TRINITY COLL, DUBLIN, IRELAND SP NIDA, NIH HO TRINITY COLL ID PARKINSONS-DISEASE; MONOAMINE-OXIDASE; RHESUS-MONKEYS; AMPHETAMINE; DOPAMINE; BRAIN; BEHAVIOR; ISOMERS; RATS AB l-Deprenyl and its stereoisomer d-deprenyl did not maintain intravenous self-administration behavior in rhesus monkeys. In contrast, l-methamphetamine, the major metabolite of l-deprenyl, as well as the baseline drug, cocaine, maintained high rates of intravenous self-administration behavior. Treatment with l-deprenyl doses up to 1.0 mg/kg before self-administration sessions failed to alter self-administration of either cocaine or l-methamphetamine. Thus l-deprenyl did not appear to have cocaine- or methamphetamine-like reinforcing properties in monkeys and was ineffective in altering established patterns of psychomotor-stimulant self-administration behavior. These results support clinical findings that despite long-term use of l-deprenyl for the treatment of Parkinson's disease by large numbers of patients, no instances of abuse have been documented. l-Deprenyl has recently been suggested as a potential medication for the treatment of various types of drug abuse, including cocaine abuse, but its failure to produce selective effects in decreasing cocaine or methamphetamine self-administration behavior in the present experiments makes such an application seem unlikely. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT ANESTHESIOL & CRIT CARE MED,BALTIMORE,MD. UNIV MARYLAND,SCH MED,DEPT PHARMACOL & EXPTL THERAPEUT,BALTIMORE,MD. GEORGETOWN UNIV,SCH MED,DEPT PHARMACOL,WASHINGTON,DC. NIDA,PRECLIN PHARMACOL BRANCH,INTRAMURAL RES PROGRAM,BALTIMORE,MD. RP WINGER, GD (reprint author), UNIV MICHIGAN,SCH MED,DEPT PHARMACOL,1301 MSRB III,1150 W MED CTR DR,ANN ARBOR,MI 48109, USA. FU NIDA NIH HHS [DA 05951, DA 04403] NR 39 TC 23 Z9 23 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD DEC PY 1994 VL 56 IS 6 SU S BP 774 EP 780 PN 2 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QA023 UT WOS:A1994QA02300008 PM 7995020 ER PT J AU RICK, ME AF RICK, ME TI LABORATORY DIAGNOSIS OF VON-WILLEBRAND DISEASE SO CLINICS IN LABORATORY MEDICINE LA English DT Article AB The diagnosis of von Willebrand's disease is becoming complex as more is understood about the disease. Clinical information and laboratory data are necessary for the diagnosis because of the overlap of normal and abnormal laboratory values. A complete evaluation including von Willebrand factor multimers, ristocetin-induced platelet aggregation, factor VIII activity level, and a template bleeding time is necessary to correctly classify the patient so that optimal treatment may be given. RP RICK, ME (reprint author), NIH,WARREN GRANT MAGNUSON CLIN CTR,HEMATOL SERV,BLDG 10,ROOM 2C390,BETHESDA,MD 20892, USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0272-2712 J9 CLIN LAB MED JI Clin. Lab. Med. PD DEC PY 1994 VL 14 IS 4 BP 781 EP 794 PG 14 WC Medical Laboratory Technology SC Medical Laboratory Technology GA PY439 UT WOS:A1994PY43900008 PM 7874871 ER PT J AU SMITH, SW OVERBEEK, R WOESE, CR GILBERT, W GILLEVET, PM AF SMITH, SW OVERBEEK, R WOESE, CR GILBERT, W GILLEVET, PM TI THE GENETIC DATA ENVIRONMENT AN EXPANDABLE GUI FOR MULTIPLE SEQUENCE-ANALYSIS SO COMPUTER APPLICATIONS IN THE BIOSCIENCES LA English DT Article ID PROGRAMS AB An X-Windows-based graphic user interface is presented which allows the seamless integration of numerous existing biomolecular programs into a single analysis environment. This environment is based on a core multiple sequence editor that is linked to external programs by a user-expandable menu system and is supported on Sun and DEC workstations. There is no limitation to the number of external functions that can be linked to the interface. The length and number of sequences that can be handled are limited only by the size of virtual memory present on the workstation, The sequence data itself is used as the reference point from which analysis is done, and scalable graphic views are supported. It is suggested that future software development utilizing this expandable, user-defined menu system and the I/O linkage of external programs will allow biologists to easily integrate expertise from disparate fields into a single environment. C1 NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. MILLIPORE BIOIMAGE,ANN ARBOR,MI. ARGONNE NATL LAB,DIV MATH & COMP SCI,ARGONNE,IL 60439. UNIV ILLINOIS,DEPT MICROBIOL,URBANA,IL 61801. HARVARD UNIV,HARVARD GENOME LAB,CAMBRIDGE,MA 02138. FU NHGRI NIH HHS [R01 HG00124] NR 20 TC 427 Z9 431 U1 0 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0266-7061 J9 COMPUT APPL BIOSCI JI Comput. Appl. Biosci. PD DEC PY 1994 VL 10 IS 6 BP 671 EP 675 PG 5 WC Computer Science, Interdisciplinary Applications SC Computer Science GA PY746 UT WOS:A1994PY74600011 PM 7704666 ER PT J AU OBRIEN, SJ AF OBRIEN, SJ TI THE CHEETAHS CONSERVATION CONTROVERSY SO CONSERVATION BIOLOGY LA English DT Note RP OBRIEN, SJ (reprint author), NCI,VIRAL CARCINOGENESIS LAB,FREDERICK CANC RES & DEV PROGRAM,FREDERICK,MD 21702, USA. NR 0 TC 34 Z9 34 U1 1 U2 17 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0888-8892 J9 CONSERV BIOL JI Conserv. Biol. PD DEC PY 1994 VL 8 IS 4 BP 1153 EP 1155 DI 10.1046/j.1523-1739.1994.08041153.x PG 3 WC Biodiversity Conservation; Ecology; Environmental Sciences SC Biodiversity & Conservation; Environmental Sciences & Ecology GA PZ557 UT WOS:A1994PZ55700034 ER PT J AU BROOKS, MM GORKIN, L SCHRON, EB WIKLUND, I CAMPION, J LEDINGHAM, RB AF BROOKS, MM GORKIN, L SCHRON, EB WIKLUND, I CAMPION, J LEDINGHAM, RB TI MORICIZINE AND QUALITY-OF-LIFE IN THE CARDIAC-ARRHYTHMIA SUPPRESSION TRIAL-II (CAST-II) SO CONTROLLED CLINICAL TRIALS LA English DT Article DE QUALITY OF LIFE; POSTMYOCARDIAL INFARCTION; CLINICAL TRIALS ID MYOCARDIAL-INFARCTION; OF-LIFE; ANTIHYPERTENSIVE THERAPY; FUNCTIONAL STATUS; MORTALITY; REHABILITATION AB The Cardiac Arrhythmia Suppression Trial II (CAST II) was a double-masked placebo-controlled randomized trial that compared the survival effects of moricizine to placebo in postmyocardial infarction arrhythmia patients. The quality-of-life outcome measures were designed prospectively for CAST and were previously shown to have high reliability and clinical discriminative validity. The CAST quality-of-life instrument detected significant differences between moricizine and placebo. In particular, moricizine was most strongly associated with inferior social activity and satisfaction scores (p =.014) and lower scores for overall contentment with life (p =.007). Moreover, the quality-of-life measures improved significantly for both the moricizine and placebo treatment groups after entry into the clinical trial. These results indicate that the CAST quality-of-life instrument is sensitive for assessing pharmacological therapies in the treatment of heart disease. C1 DEGGE GRP LTD, ARLINGTON, VA USA. UNIV WASHINGTON, DEPT BIOSTAT, SEATTLE, WA 98195 USA. NHLBI, CLIN TRIALS BRANCH, BETHESDA, MD 20892 USA. GOTHENBURG UNIV, DEPT MED, GOTHENBURG, SWEDEN. PRESBYTERIAN HOSP, DIV CARDIOL, NEW YORK, NY USA. RP BROOKS, MM (reprint author), CAST COORDINATING CTR, 1107 NE 45TH ST, ROOM 505, SEATTLE, WA 98105 USA. OI Brooks, Maria/0000-0002-2030-7873 NR 21 TC 7 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-2456 EI 1879-050X J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD DEC PY 1994 VL 15 IS 6 BP 437 EP 449 DI 10.1016/0197-2456(94)90002-7 PG 13 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA PU492 UT WOS:A1994PU49200002 PM 7851106 ER PT J AU THALL, PF SIMON, R AF THALL, PF SIMON, R TI A BAYESIAN-APPROACH TO ESTABLISHING SAMPLE-SIZE AND MONITORING CRITERIA FOR PHASE-II CLINICAL-TRIALS SO CONTROLLED CLINICAL TRIALS LA English DT Article DE CLINICAL TRIAL DESIGN; BAYESIAN INFERENCE; CONTINUOUS MONITORING; CANCER CHEMOTHERAPY ID PREDICTIVE PROBABILITY AB Thall and Simon [1] propose a Bayesian approach to phase II clinical trials with binary outcomes and continuous monitoring. The efficacy theta(E) of an experimental treatment E is evaluated relative to that of a standard treatment S based on data from an uncontrolled trial of E, an informative Frier for theta(S), and a noninformative prior for theta(E). The trial continues until E is shown with high posterior probability to be either promising or not promising, or until a predetermined maximum sample size is reached. Operating characteristics are evaluated under fixed values of the success probability of E. In this paper, we propose two extensions of this decision structure, describe sample size and monitoring criteria, and provide numerical guidelines for implementation. The first extension gives criteria from early termination of trials unlikely to yield conclusive results, based on the marginal (predictive) distribution of the observed success rate. The second extension allows early termination only if E is found to be not promising compared to S. Operating characteristics of each of these designs are evaluated numerically over a range of design parameterizations. We also examine the effects of intermittent monitoring on the design's properties. An application of this approach to a leukemia biochemotherapy trial is described. C1 NCI,DIV CANC TREATMENT,BIOMETR RES BRANCH,ROCKVILLE,MD. RP THALL, PF (reprint author), UNIV TEXAS,MD ANDERSON CANC CTR,DEPT BIOMATH,BOX 237,1515 HOLCOMBE BLVD,HOUSTON,TX 77030, USA. NR 12 TC 37 Z9 37 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD DEC PY 1994 VL 15 IS 6 BP 463 EP 481 DI 10.1016/0197-2456(94)90004-3 PG 19 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA PU492 UT WOS:A1994PU49200004 PM 7851108 ER PT J AU GEORGE, MS WASSERMANN, EM AF GEORGE, MS WASSERMANN, EM TI RAPID-RATE TRANSCRANIAL MAGNETIC STIMULATION AND ECT SO CONVULSIVE THERAPY LA English DT Editorial Material RP GEORGE, MS (reprint author), NIMH,BETHESDA,MD 20892, USA. NR 0 TC 69 Z9 71 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0749-8055 J9 CONVULSIVE THER JI Convulsive Therapy PD DEC PY 1994 VL 10 IS 4 BP 251 EP 254 PG 4 WC Psychiatry SC Psychiatry GA PX795 UT WOS:A1994PX79500001 PM 7850394 ER PT J AU PARKER, MM OGNIBENE, FP PARRILLO, JE AF PARKER, MM OGNIBENE, FP PARRILLO, JE TI PEAK SYSTOLIC PRESSURE END-SYSTOLIC VOLUME RATIO, A LOAD-INDEPENDENT MEASURE OF VENTRICULAR-FUNCTION, IS REVERSIBLY DECREASED IN HUMAN SEPTIC SHOCK SO CRITICAL CARE MEDICINE LA English DT Article DE SEPTIC SHOCK; VENTRICULAR FUNCTION; MYOCARDIAL DEPRESSION; SEPSIS; EJECTION FRACTION; SYSTOLE; BLOOD PRESSURE; CRITICAL ILLNESS; CARDIOPULMONARY EMERGENCIES; HEART ID MYOCARDIAL DEPRESSANT SUBSTANCE; PERFORMANCE; NONSURVIVORS; DYSFUNCTION; SURVIVORS; DISEASE; INVITRO AB Objective: To evaluate left ventricular performance in patients with septic shock, using a load-independent measure of left ventricular systolic function, the peak systolic pressure/ end-systolic volume index ratio. Setting: National Institutes of Health research facility. Design: Prospective study with retrospective analysis of data. Patients: Twenty-seven patients with septic shock, 13 critically ill, nonseptic control patients, and nine normal volunteers. Measurements: Hemodynamic measurements from indwelling arterial and pulmonary artery catheters and radionuclide-determined ejection fraction measurements. These data were used to calculate the peak systolic pressure/end-systolic volume index ratio in each patient group. The survivors and nonsurvivors of septic shock were evaluated on admission to the intensive care unit and at recovery in the survivors or within 24 hrs of death in the nonsurvivors. The ratio in each group was compared with the ratio in the critically ill, nonseptic patients and the normal volunteers. Main Results: Both survivors and nonsurvivors of septic shock had a decreased peak systolic pressure/end-systolic volume index ratio (1.2 +/- 0.1 and 1.7 +/- 0.2 mm Hg/mL/m(2), respectively) compared with critically ill, nonseptic patients (3.5 +/- 0.7 mm Hg/mL/m(2); both p < .05) and normal volunteers (4.3 +/- 0.4 mm Hg/mL/m(2); both p < .05). The differences between the groups were highly significant (p < .001) by analysis of variance. The survivors had a lower initial peak systolic pressure/end-systolic volume index ratio than the nonsurvivors (p < .05). In the survivors, the peak systolic pressure/end-systolic volume index ratio increased significantly (p < .05) with recovery to 2.4 +/- 0.3 mm Hg/mL/m(2). Serial determinations of peak systolic pressure/endsystolic volume index ratio in the nonsurvivors did not show any significant change. Conclusions: This study confirms that survivors and nonsurvivors of septic shock have significant depression of myocardial performance as measured by a load-independent technique. Survivors have greater depression of myocardial performance than nonsurvivors, and, with recovery, the ventricular performance in survivors increases toward normal values. C1 NIH,WARREN G MAGNUSON CLIN CTR,BETHESDA,MD 20892. NR 18 TC 26 Z9 27 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 1994 VL 22 IS 12 BP 1955 EP 1959 PG 5 WC Critical Care Medicine SC General & Internal Medicine GA PW272 UT WOS:A1994PW27200011 PM 7988132 ER PT J AU MCCRAE, RR COSTA, PT AF MCCRAE, RR COSTA, PT TI THE STABILITY OF PERSONALITY - OBSERVATIONS AND EVALUATIONS SO CURRENT DIRECTIONS IN PSYCHOLOGICAL SCIENCE LA English DT Article RP MCCRAE, RR (reprint author), NIA,GERONTOL RES CTR,PERSONAL STRESS & COPING SECT,PERSONAL & COGNIT LAB,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 16 TC 188 Z9 193 U1 4 U2 48 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0963-7214 J9 CURR DIR PSYCHOL SCI JI Curr. Dir. Psychol. PD DEC PY 1994 VL 3 IS 6 BP 173 EP 175 DI 10.1111/1467-8721.ep10770693 PG 3 WC Psychology, Multidisciplinary SC Psychology GA PX253 UT WOS:A1994PX25300002 ER PT J AU MURALI, S HARDTEN, DR DEMARTELAERE, S OLEVSKY, OM MINDRUP, EA HECHT, ML KARLSTAD, R CHAN, CC HOLLAND, EJ AF MURALI, S HARDTEN, DR DEMARTELAERE, S OLEVSKY, OM MINDRUP, EA HECHT, ML KARLSTAD, R CHAN, CC HOLLAND, EJ TI EFFECT OF TOPICALLY ADMINISTERED PLATELET-DERIVED GROWTH-FACTOR ON CORNEAL WOUND STRENGTH SO CURRENT EYE RESEARCH LA English DT Article DE CORNEAL WOUND HEALING; PLATELET-DERIVED GROWTH FACTOR (PDGF); PENETRATING KERATOPLASTY; WOUND STRENGTH; RABBIT ID FACTOR-BETA; MESSENGER-RNA; TISSUE-REPAIR; FIBROBLASTS; CELLS; EXPRESSION; STIMULATION; CHEMOTAXIS; PROTEINS; INVITRO AB Since the cornea is an avascular tissue, the wound healing process is lengthy, with a need for sutures to stabilize the wound for a long time. Platelet-derived growth factor (PDGF) has been shown to accelerate wound healing in rat dermal models. Accelerated healing, if unaccompanied by side effects may reduce suture related complications such as astigmatism and infectious keratitis. This study evaluated the effect of PDGF on wound strength in corneal laceration and penetrating keratoplasty models using New Zealand white albino rabbits. Twenty-two rabbits were used in the corneal laceration model and sixteen rabbits in the penetrating keratoplasty model. The treated rabbits received 385 picomoles/drop of PDGF-BB dissolved in balanced salt solution six times on day 1 and three times a day for the remainder of the study. The control rabbits received balanced salt solution in the same dosing schedule. The pressure required to rupture the wound was measured using a pressure transducer. In the laceration model the PDGF treated group had mean (+/- standard deviation) average pressures on day 7 of 360 +/- 102 mm Hg for wound rupture compared to 210 +/- 102 mm Hg in the control group. (p = 0.005). The average pressures in the penetrating keratoplasty model on day 17 were 707 +/- 201 mm Hg for the controls and 1042 +/- 292 mm Hg for the PDGF treated group (p = 0.026). Histopathological evaluation of eyes not subjected to bursting showed increased fibroblasts at the wound junction with an increase in types III and type IV collagen production. In this model of rabbit corneal laceration and penetrating keratoplasty, PDGF significant improved wound strength without any serious side effects. C1 UNIV MINNESOTA,DEPT OPHTHALMOL,CORNEA SERV,MINNEAPOLIS,MN. NEI,BETHESDA,MD. NR 29 TC 17 Z9 18 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 DEC PY 1994 VL 13 IS 12 BP 857 EP 862 DI 10.3109/02713689409015086 PG 6 WC Ophthalmology SC Ophthalmology GA PZ423 UT WOS:A1994PZ42300002 PM 7720391 ER PT J AU GERY, I STREILEIN, JW AF GERY, I STREILEIN, JW TI AUTOIMMUNITY IN THE EYE AND ITS REGULATION SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID RETINOID-BINDING-PROTEIN; IMMUNE DEVIATION ACAID; GROWTH-FACTOR-BETA; T-CELL RECEPTOR; CANCER-ASSOCIATED RETINOPATHY; ANTERIOR UVEITIS EAAU; S-ANTIGEN; EPITHELIAL-CELLS; ORAL TOLERANCE; AQUEOUS-HUMOR AB Recent studies have provided new information concerning the development of autoimmune-mediated intraocular inflammation (uveitis) and the mechanisms that suppress this sight-robbing process. Newly collected data have led to several interesting advances: the discovery of additional uveitogenic antigens and novel uveitogenic reactions; dissection or the early steps of the pathogenic process; identification of the subsets of lymphocytes that selectively accumulate in the inflamed eye; analysis of the development of tolerance against sequestered antigens in the eye; elucidation of the cellular and molecular events of the anterior chamber-associated immune deviation, the major immunoregulatory mechanism in the eye; the capacity of this mechanism to inhibit and even treat uveitis; and examination of the mechanisms whereby oral tolerance inhibits ocular inflammation. C1 SCHEPENS EYE RES INST,BOSTON,MA 02114. RP GERY, I (reprint author), NEI,10 CTR DR,BLDG 10,ROOM 10N208,BETHESDA,MD 20892, USA. NR 71 TC 51 Z9 52 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD DEC PY 1994 VL 6 IS 6 BP 938 EP 945 DI 10.1016/0952-7915(94)90017-5 PG 8 WC Immunology SC Immunology GA PZ426 UT WOS:A1994PZ42600017 PM 7710718 ER PT J AU TRICKETT, PK MCBRIDECHANG, C PUTNAM, FW AF TRICKETT, PK MCBRIDECHANG, C PUTNAM, FW TI THE CLASSROOM PERFORMANCE AND BEHAVIOR OF SEXUALLY ABUSED FEMALES SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Article ID IMPACT AB This study examines the relationship of child sexual abuse to classroom academic performance and behavior in a sample of 6-16-year-old girls. Half of the sample was sexually abused by a family member. The other half is a demographically similar nonabused comparison group. Measures of academic performance include school records, teacher's ratings of classroom behavior and performance, and parental reports of school performance. Possible mediators of the impact of sexual abuse on classroom performance and behavior - cognitive capability, perceived competence, and behavior problems-are also measured. Results can be summarized as follows. (a) A history of sexual abuse does predict academic performance: Abuse is directly negatively related to ratings of classroom social competence, competent learner, and overall academic performance and positively related to school avoidant behavior, but is not related to grades. (b) Sexual abuse is negatively related to cognitive ability and positively related to measures of behavior problems indicating depression, destructiveness, and dissociation. (c) Cognitive ability and perceived competence predict the more ''academic'' aspects of academic performance - grades, ratings as a competent learner, and overall academic performance. Behavior problems predict ratings as a competent learner, classroom social competence, school avoidant behavior, and overall academic performance. C1 NIMH,BETHESDA,MD 20892. RP TRICKETT, PK (reprint author), UNIV SO CALIF,DEPT PSYCHOL,LOS ANGELES,CA 90089, USA. NR 28 TC 40 Z9 40 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0954-5794 J9 DEV PSYCHOPATHOL JI Dev. Psychopathol. PD WIN PY 1994 VL 6 IS 1 BP 183 EP 194 PG 12 WC Psychology, Developmental SC Psychology GA NA569 UT WOS:A1994NA56900011 ER PT J AU EGWUAGU, CE SZTEIN, J CHAN, CC MAHDI, R NUSSENBLATT, RB CHEPELINSKY, AB AF EGWUAGU, CE SZTEIN, J CHAN, CC MAHDI, R NUSSENBLATT, RB CHEPELINSKY, AB TI GAMMA-INTERFERON EXPRESSION DISRUPTS LENS AND RETINAL DIFFERENTIATION IN TRANSGENIC MICE SO DEVELOPMENTAL BIOLOGY LA English DT Article ID FIBROBLAST GROWTH-FACTOR; A-CRYSTALLIN GENE; ALPHA-CRYSTALLIN; CELL-DIFFERENTIATION; MOUSE LENS; CDNA CLONING; HYBRID GENE; RAT LENS; PROTEIN; RECEPTOR AB We previously generated an animal model for the study of autoimmune diseases of the eye by targeting gamma interferon (gamma IFN) expression to the lens of transgenic mice. Here, we have studied the effect of constitutive lens expression of gamma IFN on eye development of these transgenic mice. By Day 18 of embryonic development, lens and retinal differentiation programs are completely disrupted; normal lens epithelia and fibers are replaced by balloon-like cells and retinal differentiation into inner and outer neuroblastic layers is already affected. The mRNA levels of gamma E- and/or gamma F-crystallin and MIP, markers of lens cell differentiation, are drastically reduced, while expression of ICSBP, a gamma IFN-inducible transcriptional factor, is induced in the alpha ACry-gamma IFN transgenic mouse eyes. Taken together, our results suggest that constitutive expression of gamma IFN and its induction and activation of gamma IFN-inducible transcriptional factors in the eye altered the developmental fate of cells destined to become lens fiber cells by altering the pattern of lens gene expression. (C) 1994 Academic Press, Inc. C1 NEI,MOLEC & DEV BIOL LAB,BETHESDA,MD 20892. NEI,IMMUNOL LAB,BETHESDA,MD 20892. NEI,VET RES & RESOURCES SECT,BETHESDA,MD 20892. RI Sztein, Jorge/B-7165-2012 NR 68 TC 30 Z9 30 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD DEC PY 1994 VL 166 IS 2 BP 557 EP 568 DI 10.1006/dbio.1994.1337 PG 12 WC Developmental Biology SC Developmental Biology GA QA707 UT WOS:A1994QA70700016 PM 7813776 ER PT J AU SAINTJEANNET, JP DAWID, IB AF SAINTJEANNET, JP DAWID, IB TI A FATE MAP FOR THE 32-CELL STAGE OF RANA-PIPIENS SO DEVELOPMENTAL BIOLOGY LA English DT Article ID CENTRAL NERVOUS-SYSTEM; XENOPUS-LAEVIS; INDIVIDUAL BLASTOMERES; CLONAL ORGANIZATION; AMBYSTOMA-MEXICANUM; PROSPECTIVE AREAS; FROG; GASTRULA; EMBRYO; SPECIFICATION AB A fate map of the progeny derived from all blastomeres of the 32-cell stage embryo of the leopard frog Rana pipiens has been generated. Embryos presenting regular cleavages were injected into two pairs of blastomeres with fluorescein- and Texas red-lysine dextran. By stage 21, embryos were sectioned and the tissue distribution of labeled clones was determined. The results of 93 clones were pooled to give a fate map which represents the derivation of each tissue from the different blastomeres of the 32-cell embryo. The results show that all blastomeres give rise to multiple tissues and all tissues are derived from at least two, and usually more, pairs of blastomeres. Although there is a general tendency for ectoderm to derive from the animal hemisphere, endoderm from the vegetal hemisphere, and mesoderm from the equatorial region, the boundaries between germ layers are not sharply defined at the 32-cell stage but rather appear as a series of overlapping zones. The fate map of R. pipiens is quite similar to that of Xenopus laevis but differs in some details that are discussed. As in all vertebrates, the R. pipiens fate map is not fully deterministic but nevertheless has predictive value in that tissues are populated by the progeny of the same blastomeres in different embryos. C1 NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892. UNIV TOULOUSE 3,CTR DEV BIOL,CNRS,UMR 9925,F-31062 TOULOUSE,FRANCE. NR 31 TC 8 Z9 8 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD DEC PY 1994 VL 166 IS 2 BP 755 EP 762 DI 10.1006/dbio.1994.1353 PG 8 WC Developmental Biology SC Developmental Biology GA QA707 UT WOS:A1994QA70700032 PM 7813792 ER PT J AU SIMPSON, LH BATTEGAY, M HOOFNAGLE, JH WAGGONER, JG DIBISCEGLIE, AM AF SIMPSON, LH BATTEGAY, M HOOFNAGLE, JH WAGGONER, JG DIBISCEGLIE, AM TI HEPATITIS-DELTA VIRUS-RNA IN SERUM OF PATIENTS WITH CHRONIC DELTA-HEPATITIS SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE HEPATITIS DELTA VIRUS; HOT START TECHNIQUE; POLYMERASE CHAIN REACTION; CHRONIC HEPATITIS; VIREMIA ID POLYMERASE CHAIN-REACTION; HUMAN-IMMUNODEFICIENCY-VIRUS; C VIRAL-RNA; SENSITIVE METHOD; HBV INFECTION; HDV-RNA; DIAGNOSIS; REPLICATION; CLONING; ANTIGEN AB We studied 28 patients with chronic delta hepatitis for the presence of hepatitis delta virus (HDV) RNA in serum. The hot start polymerase chain reaction (PCR) method, in which the reaction begins at 60-80 degrees C, showed a higher sensitivity than conventional PCR reaction. Additionally, the presence of hepatitis B (HBV) and C virus (HCV) infections were determined by PCR. HDV RNA was detected in 26 patients (93%), HBV DNA in 22 (79%), and HCV RNA in only one. Detection of HDV RNA correlated very well with detection of hepatitis delta antigen by immunostaining in the liver. In six patients HDV RNA was detectable despite the absence of HBV DNA in serum, suggesting that high levels of HBV are not required for HDV replication. Of 29 control patients with chronic hepatitis B without antibody to HDV, none had detectable HDV RNA, while all had HBV DNA in serum. Detection of HDV RNA with PCR proved highly sensitive and specific, demonstrating that virtually all patients with chronic HDV infection had ongoing viral replication. C1 NIDDK,LIVER DIS SECT,BETHESDA,MD 20892. NR 30 TC 4 Z9 4 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD DEC PY 1994 VL 39 IS 12 BP 2650 EP 2655 DI 10.1007/BF02087704 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PX540 UT WOS:A1994PX54000022 PM 7995191 ER PT J AU MIELE, L PERI, A CORDELLAMIELE, E MUKHERJEE, AB AF MIELE, L PERI, A CORDELLAMIELE, E MUKHERJEE, AB TI NONRADIOMETRIC ELISA-BASED QUANTITATION AND VALIDATION OF POLYMERASE CHAIN REACTION-AMPLIFIED DNA, INCLUDING DETECTION OF POINT MUTATIONS, WITHOUT ALLELE-SPECIFIC AMPLIFICATION, OR LIGATION SO DNA AND CELL BIOLOGY LA English DT Article ID DEOXYRIBONUCLEIC-ACID SEQUENCES; OLIGONUCLEOTIDE PROBES; REACTION PRODUCTS; DUPLEX STABILITY; GENETIC-ANALYSIS; HYBRIDIZATION; DIAGNOSIS; PROTEIN; LIGASE AB We describe two simple novel procedures, one direct and the other involving hybridization, for the enzyme-linked immunosorbent assay (ELISA)-based detection, quantitation, and validation of polymerase chain reaction (PCR)-amplified DNA, Both procedures are applicable to any PCR reaction, and do not require specially synthesized or enzyme-tagged oligonucleotides, We obtained accurate quantitation of PCR-amplified human cc10kDa cDNA with a sensitivity of about 0.6 fmoles, This cDNA was also used to detect single-base insertions, deletions, and substitutions specifically, Additionally, we could readily distinguish zinc-finger Y chromosome-specific genomic sequences in mixtures of male and female cells and normal and mutant cystic fibrosis transmembrane conductance regulator (CFTR) gene sequences in crude fibroblast lysates, To our knowledge, this is the first report of point mutation detection in solution by ELISA without allele-specific amplification or ligation, These novel procedures have vast potential for basic and clinical applications, including gene expression studies, rapid screening of genetic diseases, detection of oncogene and anti-oncogene mutations, and identification of pathogens (e,g,, HIV-1) in clinical specimens, C1 NICHHD,HUMAN GENET BRANCH,DEV GENET SECT,BETHESDA,MD 20892. NR 32 TC 3 Z9 3 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD DEC PY 1994 VL 13 IS 12 BP 1233 EP 1242 DI 10.1089/dna.1994.13.1233 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA QA522 UT WOS:A1994QA52200009 PM 7529025 ER PT J AU SCHIFF, SJ ALDROUBI, A UNSER, M SATO, S AF SCHIFF, SJ ALDROUBI, A UNSER, M SATO, S TI FAST WAVELET TRANSFORMATION OF EEG SO ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY LA English DT Article DE SIGNAL PROCESSING; SPIKE DETECTION; SEIZURE DETECTION; FOURIER TRANSFORM; WAVELET TRANSFORM ID ORTHONORMAL BASES; SURROGATE DATA; TIME-SERIES; MULTIRESOLUTION; REPRESENTATION; FAMILY; SYSTEM AB Wavelet transforms offer certain advantages over Fourier transform techniques for the analysis of EEG. Recent work has demonstrated the applicability of wavelets for both spike and seizure detection, but the computational demands have been excessive. We compare the quality of feature extraction of continuous wavelet transforms using standard numerical techniques, with more rapid algorithms utilizing both polynomial splines and multiresolution frameworks. We further contrast the difference between filtering with and without the use of surrogate data to model background noise, demonstrate the preservation of feature extraction with critical versus redundant sampling, and perform the analyses with wavelets of different shape. Comparison is made with windowed Fourier transforms, similarly filtered, at different data window lengths. We here report a dramatic reduction in computational time required to perform this analysis, without compromising the accuracy of feature extraction. It now appears technically feasible to filter and decompose EEG using wavelet transforms in real time with ordinary microprocessors. C1 NIH,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. NIH,DEPT CLIN EEG,BETHESDA,MD 20892. RP SCHIFF, SJ (reprint author), CHILDRENS NATL MED CTR,DEPT NEUROSURG,111 MICHIGAN AVE NW,WASHINGTON,DC 20010, USA. RI Unser, Michael/A-1550-2008; Aldroubi, Akram/J-7186-2012 FU NIMH NIH HHS [1 R29 MH50006] NR 39 TC 125 Z9 130 U1 0 U2 9 PU ELSEVIER SCI PUBL 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 DEC PY 1994 VL 91 IS 6 BP 442 EP 455 DI 10.1016/0013-4694(94)90165-1 PG 14 WC Engineering, Biomedical; Clinical Neurology SC Engineering; Neurosciences & Neurology GA QG320 UT WOS:A1994QG32000004 PM 7529683 ER PT J AU BENKIRANE, M JEANG, KT DEVAUX, C AF BENKIRANE, M JEANG, KT DEVAUX, C TI THE CYTOPLASMIC DOMAIN OF CD4 PLAYS A CRITICAL ROLE DURING THE EARLY STAGES OF HIV-INFECTION IN T-CELLS SO EMBO JOURNAL LA English DT Article DE CD4; HIV INFECTION; SIGNALING ID HUMAN-IMMUNODEFICIENCY-VIRUS; PROTEIN-TYROSINE KINASE; LONG TERMINAL REPEAT; NF-KAPPA-B; BLOOD MONONUCLEAR-CELLS; HUMAN LYMPHOCYTES-T; ENVELOPE GLYCOPROTEIN; PHOSPHOLIPASE C-GAMMA-1; SIGNAL TRANSDUCTION; SYNCYTIA FORMATION AB The role played by the cytoplasmic domain of the CD4 molecule in the process of HIV infection was investigated, using A2.01 cells which express different forms of the CD4 gene. A delay in HIV production was consistently observed in cells expressing a truncated CD4 which lacks the cytoplasmic domain (CD4.401) compared with cells expressing the wild type CD4. The delay was much less in cells expressing a hybrid CD4-CD8 molecule (amino acids 1-177 of CD4 fused to the hinge, transmembrane and cytoplasmic domains of CD8). Yet the extent of viral entry and reverse transcription, monitored by semi-quantitative PCR, was similar in each cell type studied, For further study of the mechanism responsible for delayed HIV replication in the A2.01/CD4.401 cell line, cells were treated with phytohaemagglutinin (PHA), 24 h after HIV infection. Under such experimental conditions HIV production was detected at the same time in the culture supernatants of A2.01/CD4 and A2.01/CD4.401 cells. Moreover, we found that CD4 oligomerization by HIV-1 induced NF-kappa B translocation in A2.01/CD4 and A2.01/CD4-CD8 but not in A2.01/CD4.401 cells. This was consistent with CAT assay experiments which provided evidence for Tat-independent NF-kappa B mediated activation of HTV-1 LTR promoter after HIV binding to CD4 in A2.01/CD4 and A2.01/CD4-CD8 but not in A2.01/CD4.401 cells. In contrast to results published recently by Tremblay et al, (1994, EMBO J., 13, 774-783), we propose that a positive cellular signal initiated following oligomerization of the CD4 by the virus itself is involved in NF-kappa B-dependent early HIV transcription in A2.01/CD4 cells. C1 LAB IMMUNOL INFECT RETROVIRALES, CNRS, UPR 9008, F-34060 MONTPELLIER, FRANCE. INST BIOL, INSERM, U249, F-34060 MONTPELLIER, FRANCE. NIAID, MOLEC MICROBIOL LAB, BETHESDA, MD 20892 USA. RI Jeang, Kuan-Teh/A-2424-2008 NR 62 TC 65 Z9 65 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD DEC 1 PY 1994 VL 13 IS 23 BP 5559 EP 5569 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PW345 UT WOS:A1994PW34500007 PM 7988553 ER PT J AU DASSO, M SEKI, T AZUMA, Y OHBA, T NISHIMOTO, T AF DASSO, M SEKI, T AZUMA, Y OHBA, T NISHIMOTO, T TI A MUTANT FORM OF THE RAN/TC4 PROTEIN DISRUPTS NUCLEAR FUNCTION IN XENOPUS-LAEVIS EGG EXTRACTS BY INHIBITING THE RCC1 PROTEIN, A REGULATOR OF CHROMOSOME CONDENSATION SO EMBO JOURNAL LA English DT Article DE GUANINE NUCLEOTIDE EXCHANGE FACTOR; NUCLEAR ASSEMBLY; RAN; RCC1; XENOPUS EGG EXTRACTS ID GTP-BINDING PROTEINS; DNA-REPLICATION; SACCHAROMYCES-CEREVISIAE; ESCHERICHIA-COLI; INITIATION; MITOSIS; INVITRO; GENE; MUTATION; PRP20 AB The Ran protein is a small GTPase that has been implicated in a large number of nuclear processes including transport, RNA processing and cell cycle checkpoint control, A similar spectrum of nuclear activities has been shown to require RCC1, the guanine nucleotide exchange factor (GEF) for Ran, We have used the Xenopus laevis egg extract system and in vitro assays of purified proteins to examine how Ran or RCC1 could be involved in these numerous processes, In these studies, we employed mutant Ran proteins to perturb nuclear assembly and function, The addition of a bacterially expressed mutant form of Ran (T24N-Ran), which was predicted to be primarily in the GDP-bound state, profoundly disrupted nuclear assembly and DNA replication in extracts, We further examined the molecular mechanism by which T24N-Ran disrupts normal nuclear activity and found that T24N-Ran binds tightly to the RCC1 protein within the extract, resulting in its inactivation as a GEF. The capacity of T24N-Ran-blocked interphase extracts to assemble nuclei from de-membranated sperm chromatin and to replicate their DNA could be restored by supplementing the extract with excess RCC1 and thereby providing excess GEF activity, Conversely, nuclear assembly and DNA replication were both rescued in extracts lacking RCC1 by the addition of high levels of wild-type GTP-bound Ran protein, indicating that RCC1 does not have an essential function beyond its role as a GEF in interphase Xenopus extracts. C1 KYUSHU UNIV,GRAD SCH MED SCI,DEPT MOLEC BIOL,FUKUOKA 812,JAPAN. RP DASSO, M (reprint author), NICHHD,DEPT MOLEC EMBRYOL,BLDG 18,ROOM 101,BETHESDA,MD 20892, USA. NR 45 TC 116 Z9 118 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD DEC 1 PY 1994 VL 13 IS 23 BP 5732 EP 5744 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PW345 UT WOS:A1994PW34500025 PM 7988569 ER PT J AU RAPOPORT, JL AF RAPOPORT, JL TI OBSESSIVE-COMPULSIVE SPECTRUM DISORDER - A USEFUL CONCEPT SO ENCEPHALE-REVUE DE PSYCHIATRIE CLINIQUE BIOLOGIQUE ET THERAPEUTIQUE LA French DT Article ID CEREBRAL GLUCOSE-METABOLISM; AUTORADIOGRAPHIC LOCALIZATION; SEROTONIN RECEPTORS; RECOGNITION SITES; HUMAN-BRAIN; CLOMIPRAMINE; DESIPRAMINE; TRICHOTILLOMANIA; ADOLESCENTS; CHILDREN AB There is a second wave of research following the interest in Obsessive Compulsive Disorder (OCD) that explores a vast number of other conditions with some superficial similarity to OCD. These have in common an inability to delay or inhibit repetitive behaviors. While some interesting pharmacological treatment trials have emerged, few of the studies have truly explored the idea of a spectrum from the neurobiological point of view. Only for Tourette's Disorder, Trichotillomania and possibly Sydenham's Chorea have there been convincing biological evidence for continuity with OCD. C1 NIMH,BETHESDA,MD 20892. NR 27 TC 5 Z9 5 U1 0 U2 1 PU DOIN EDITEURS PI PARIS PA 47 RUE SAINT-ANDRE-DES-ARTS, F-75006 PARIS, FRANCE SN 0013-7006 J9 ENCEPHALE JI Enceph.-Rev. Psychiatr. Clin. Biol. Ther. PD DEC PY 1994 VL 20 SI SI BP 677 EP 680 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA QF395 UT WOS:A1994QF39500009 PM 7895635 ER PT J AU IMAI, Y IBARAKI, K ODAJIMA, R SHISHIBA, Y AF IMAI, Y IBARAKI, K ODAJIMA, R SHISHIBA, Y TI EFFECTS OF DIBUTYRYL-CYCLIC-AMP ON HYALURONAN AND PROTEOGLYCAN SYNTHESIS BY RETROOCULAR TISSUE FIBROBLASTS IN CULTURE SO ENDOCRINE JOURNAL LA English DT Article DE CAMP; HYALURONAN; PROTEOGLYCAN; GLYCOSAMINOGLYCAN; RETROOCULAR FIBROBLAST; GRAVES DISEASE ID GRAVES-DISEASE; CELLS-INVITRO; OPHTHALMOPATHY; PATHOGENESIS; ANTIBODIES; RECEPTOR; VERSICAN; PROTEINS; SERA; ACID AB Deposition of glycosaminoglycan is one of the histological features of Graves' ophthalmopathy. Although retroocular tissue fibroblasts are considered to be responsible for glycosaminoglycan accumulation, it is not known what is stimulating the fibroblasts. There are studies which are in support of and against the role of anti-TSH receptor antibodies in the pathogenesis of Graves' ophthalmopathy. TSH-receptor antibodies increase cAMP as a second messenger in thyroid cells. We studied the effects of dibutyryl cyclic AMP (Bt(2)cAMP) on glycosaminoglycan synthesis by retroocular tissue fibroblasts in order to know whether cAMP can modulate glycosaminoglycan synthesis. Retroocular tissue fibroblasts mainly synthesize hyaluronan, the large chondroitin sulfate proteoglycan and the small chondroitin sulfate proteoglycan as glycosaminoglycan in cell culture. The amount of hyaluronan synthesis was measured as [H-3]glucosamine incorporation into macromolecule susceptible to hyaluronidase digestion (from Streptomyces hyaluronlyticus). The amount of proteoglycan synthesis was measured as [S-35]sulfate incorporation into macromolecules in medium and cell layer fraction. Proteoglycans in medium were further separated into the large proteoglycan and the small proteoglycan on a Superose 6 column. Bt(2)cAMP increased both hyaluronan and proteoglycan synthesis by retroocular tissue fibroblasts, especially stimulating the secretion of the large proteoglycan. Effects of Bt(2)cAMP on glycosaminoglycan synthesis were then compared with those in adult skin fibroblasts. Although the magnitude of response between the two was indistinct, the stimulation of the large proteoglycan synthesis by Bt(2)cAMP was more prominent in retroocular tissue fibroblasts. The results suggest that the regulation of glycosaminoglycan synthesis by retroocular tissue fibroblasts is different from that by adult skin fibroblasts. Although further studies are required to determine its actual role, cAMP stimulates glycosaminoglycan synthesis by retroocular tissue fibroblasts and underlies the mechanism in Graves' ophthalmopathy. C1 TORANOMON GEN HOSP,DEPT MED,DIV ENDOCRINOL,MINATO KU,TOKYO 105,JAPAN. NIDR,BONE RES BRANCH,BETHESDA,MD 20892. NR 24 TC 11 Z9 11 U1 0 U2 0 PU JAPAN ENDOCRINE SOCIETY PI TOKYO PA C/O DEPT VETERINARY PHYSIOL, VET MED SCI, UNIV TOKYO, 1-1-1 YAYOI, BUNKYO-KU, TOKYO 113, JAPAN SN 0918-8959 J9 ENDOCR J JI Endocr. J. PD DEC PY 1994 VL 41 IS 6 BP 645 EP 654 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PZ158 UT WOS:A1994PZ15800007 PM 7704088 ER PT J AU ULISSE, S FARINA, AR PIERSANTI, D TIBERIO, A CAPPABIANCA, L DORAZI, G JANNINI, EA MALYKH, O STETLERSTEVENSON, WG DARMIENTO, M GULINO, A MACKAY, AR AF ULISSE, S FARINA, AR PIERSANTI, D TIBERIO, A CAPPABIANCA, L DORAZI, G JANNINI, EA MALYKH, O STETLERSTEVENSON, WG DARMIENTO, M GULINO, A MACKAY, AR TI FOLLICLE-STIMULATING-HORMONE INCREASES THE EXPRESSION OF TISSUE INHIBITORS OF METALLOPROTEINASES TIMP-1 AND TIMP-2 AND INDUCES TIMP-1 AP-1 SITE BINDING COMPLEX(ES) IN PREPUBERTAL RAT SERTOLI CELLS SO ENDOCRINOLOGY LA English DT Article ID APE LEUKEMIA-VIRUS; PHORBOL ESTER; RESPONSIVE ELEMENT; MATRIX METALLOPROTEINASE; GENE-TRANSCRIPTION; FOS TRANSCRIPTION; GRANULOSA-CELLS; PROTEIN-KINASE; MESSENGER-RNA; JUN AB Primary cultures of prepubertal rat Sertoli cells secrete two major tissue inhibitors of metalloproteinases: TIMP-1 (M(r) 28 K) and TIMP-2 (M(r) 21 K). FSH stimulated Sertoli cell TIMP-1 and TIMP-2 activity in a time- and dose-dependent manner and also stimulated TIMP-1 and TIMP-2 protein and messenger RNA levels. These effects were mimicked by the cAMP analog, 8-bromo-cAMP, and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. The protein kinase C activating phorbol ester phorbol myristrate acetate (TPA) stimulated TIMP-1 but not TIMP-2 activity and messenger RNA levels. Cycloheximide and actinomycin-D inhibited basal TIMP-1 and TIMP-2 activity and inhibited the ability of FSH, 8-bromo-cAMP, and TPA to stimulate TIMP activity. The protein kinase A (PKA) inhibitor AMP Rp isomer did not affect basal TIMP-1 and TIMP-2 activity or TPA-stimulated TIMP-1 activity. However, the PKA inhibitor markedly reduced FSH and 3-isobutyl-1-methylxanthine stimulation of TIMP-1 and TIMP-2 activity. FSH, 8-bromo-cAMP, and TPA stimuli induced DNA binding complexes capable of binding to a TIMP-1 AP-1 site consensus sequence oligonucleotide. The AP-1 site binding complex(es) induced by all three treatments reacted with antibodies directed broadly against fos and jun protooncogene families and against the specific family members c-fos, junB, and junD but not c-jun proteins. Constitutive cAMP response element binding activity capable of binding an artificial cAMP response element binding site oligonucleotide was demonstrated in Sertoli cell nuclear extracts. This activity was minimally modulated by FSH, 8-bromo-cAMP, or TPA treatment. In summary, Sertoli cells secrete TIMP-1 and TIMP-2 that can be coordinately up-regulated by FSH through a cAMP, PKA-dependent pathway. A convergence-of TPA, FSH, and cAMP mediated signals in prepubertal Sertoli cells may occur with the induction of specific AP-1 site binding complex(es) containing jun and fos proteins. Our data suggest that FSH stimulation of TIMP-2 expression may be regulated independently to that of TIMP-1. We propose that the ability of FSH to stimulate Sertoli cell TIMP activity suggests a central role for this hormone in the control of extracellular matrix turnover during testicular development at the level of metalloproteinase inhibition. C1 UNIV LAQUILA, DEPT EXPTL MED, I-67100 LAQUILA, ITALY. UNIV LAQUILA, MOLEC PATHOL LAB, I-67100 LAQUILA, ITALY. UNIV LAQUILA, ENDOCRINOL SECT, I-67100 LAQUILA, ITALY. UNIV CHIETI, DEPT GEN PATHOL, I-66100 CHIETI, ITALY. NCI, PATHOL LAB, BETHESDA, MD 20892 USA. RI Stetler-Stevenson, William/H-6956-2012; OI Stetler-Stevenson, William/0000-0002-5500-5808; cappabianca, lucia/0000-0002-9112-1750; Mackay, Andrew Reay/0000-0001-7096-3759; Jannini, Emmanuele A./0000-0002-5874-039X; FARINA, Antonietta Rosella/0000-0003-0962-6088; Ulisse, Salvatore/0000-0002-7573-0759 NR 56 TC 54 Z9 54 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 1994 VL 135 IS 6 BP 2479 EP 2487 DI 10.1210/en.135.6.2479 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PW235 UT WOS:A1994PW23500028 PM 7988435 ER PT J AU ABOUSAMRA, AB GOLDSMITH, PK XIE, LY JUPPNER, H SPIEGEL, AM SEGRE, GV AF ABOUSAMRA, AB GOLDSMITH, PK XIE, LY JUPPNER, H SPIEGEL, AM SEGRE, GV TI DOWN-REGULATION OF PARATHYROID (PTH) PTH-RELATED PEPTIDE RECEPTOR IMMUNOREACTIVITY AND PTH BINDING IN OPOSSUM KIDNEY-CELLS BY PTH AND DEXAMETHASONE SO ENDOCRINOLOGY LA English DT Article ID HORMONE-RELATED PEPTIDE; TUMOR-NECROSIS-FACTOR; OSTEOBLAST-LIKE CELLS; CULTURED BONE-CELLS; ADENYLATE-CYCLASE; OSTEOSARCOMA CELLS; DESENSITIZATION; MEMBRANES; RESPONSES; UMR-106 AB Recent data have shown that PTH down-regulation of its receptor on opossum kidney (OK) cells is not associated with any change in the steady state level of the PTH/PTH-related peptide (PTHrP) receptor messenger RNA. For analysis of down-regulation of the PTH/PTHrP receptor in OK cells, the present work uses a specific receptor antiserum, SR-2, that is useful for detection and quantification of PTH/PTHrP receptor immunoreactivity on intact cells bearing the opossum PTH/PTHrP receptor. SR-2 specifically binds to COS-7 cells transiently expressing the opossum PTH/PTHrP receptor complementary DNA (OK-O), to LLCPK1 cells stably expressing the recombinant opossum PTH/PTHrP receptor (AOK cells), and to OK cells expressing endogenous PTH/PTHrP receptors, but not to mock-transfected COS-7 cells or untransfected LLCPK1 cells. SR-2 binding was also linearly correlated with PTH binding in COS-7 cells transfected with different amounts of OK-O plasmid DNA. Treatment with PTH (100 nM) for 4 and 6 h did not significantly down-regulate the PTH/PTHrP receptor immunoreactivity, although PTH binding was decreased to 51% and 49% of control, respectively, and PTH-stimulated cAMP accumulation was decreased to 27% and 28% of control, respectively. Treatment with PTH (100 nM) for 24 and 48 h significantly decreased PTH binding to 51% and 60% of control and decreased PTH/PTHrP receptor immunoreactivity to 68% and 58% of control, respectively. Incubation of OK cells with 0.1 nM to 1 mu M PTH for 4 h did not downregulate the PTH/PTHrP receptor immunoreactivity, although PTH binding was decreased dramatically. Scatchard blot analysis revealed that the binding affinity was decreased by 7-fold in OK cells treated with PTH for 4 h without change in receptor number. Conversely, treatment of OK cells with PTH for 24 h resulted in a parallel decrease in both receptor number and receptor immunoreactivity without any change in receptor binding affinity. Treatment of OK cells with dexamethasone (0.1 nM to 1 mu M) had no effect on PTH binding or PTH/PTHrP receptor immunoreactivity. Incubation of OK cells with both dexamethasone (1 mu M) and PTH (0.1 nM to 1 mu M), however, caused a significantly greater down-regulation of both PTH binding and PTH/PTHrP receptor immunoreactivity than in cells treated with PTH alone. These data indicate that during the first 4 h of exposure of OK cells to PTH, PTH/PTHrP receptors remain on the cell surface but have lowered affinity to bind the ligand and that dexamethasone potentiates the effect of PTH on PTH/PTHrP receptor down-regulation in OK cells. C1 MASSACHUSETTS GEN HOSP, DEPT PEDIAT, BOSTON, MA 02114 USA. NIDDKD, METAB DIS BRANCH, BETHESDA, MD 20892 USA. RP ABOUSAMRA, AB (reprint author), HARVARD UNIV, MASSACHUSETTS GEN HOSP, SCH MED, ENDOCRINE UNIT, BLDG 327, BOSTON, MA 02114 USA. OI Abou-Samra, Abdul/0000-0001-8735-1142 FU NIDDK NIH HHS [DK-11794-26] NR 27 TC 27 Z9 27 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 1994 VL 135 IS 6 BP 2588 EP 2594 DI 10.1210/en.135.6.2588 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PW235 UT WOS:A1994PW23500042 PM 7988447 ER PT J AU YAMIN, M GORN, AH FLANNERY, MR JENKINS, NA GILBERT, DJ COPELAND, NG TAPP, DR KRANE, SM GOLDRING, SR AF YAMIN, M GORN, AH FLANNERY, MR JENKINS, NA GILBERT, DJ COPELAND, NG TAPP, DR KRANE, SM GOLDRING, SR TI CLONING AND CHARACTERIZATION OF A MOUSE-BRAIN CALCITONIN RECEPTOR COMPLEMENTARY DEOXYRIBONUCLEIC-ACID AND MAPPING OF THE CALCITONIN RECEPTOR GENE SO ENDOCRINOLOGY LA English DT Article ID MOLECULAR-CLONING; BINDING-SITES; EXPRESSION CLONING; XENOPUS EMBRYOS; RAT-BRAIN; PEPTIDE; PITUITARY; HORMONE; CYCLASE; POLYPEPTIDE AB We have identified and characterized a mouse brain calcitonin receptor (CTR) complementary DNA (cDNA). This cDNA encodes a receptor protein that, after expression, has high affinity binding for salmon calcitonin (K-d similar to, 12.5 nM) and is coupled to adenylate cyclase. The binding affinity of this expressed receptor for salmon calcitonin is lower than that described for the previously cloned porcine renal and human ovarian CTRs, but is similar to that of the recently described rat brain CTR, designated the C1b form of the receptor. Analysis of the deduced structure of the mouse brain CTR reveals that it is highly related to the other CTR cDNAs that belong to a distinct family of G-protein-coupled receptors with seven transmembrane-spanning domains. The major structural feature that distinguishes the mouse cDNA clone from the other CTRs is the presence of a consecutive 111-basepair nucleotide sequence that encodes a 37-amino acid sequence which is predicted to localize to the first extracellular loop between the second and third transmembrane-spanning domains. We have mapped the CTR gene in the mouse to the proximal region of chromosome 6, which is homologous to the 7q region of human chromosome 7; only a single CTR gene was identified. Preliminary analysis of the mouse CTR gene reveals that it is complex, consisting of multiple exons separated by lengthy introns that would allow for splice variants consistent with the existence of multiple CTR isoforms predicted from the CTR cDNA clones. The differential cellular and tissue distribution of these functionally distinct CTR isoforms provides the molecular basis for the previously reported widespread distribution and functional heterogeneity of the CTR. C1 HARVARD UNIV, MASSACHUSETTS GEN HOSP,SCH MED,DEPT MED,MED SERV, ARTHRIT UNIT, BOSTON, MA 02114 USA. NEW ENGLAND DEACONESS HOSP, DEPT MED, BOSTON, MA 02115 USA. NCI, FREDERICK CANC RES & DEV CTR, MAMMALIAN GENET LAB, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USA. FU NCI NIH HHS [N01-CO-74101]; NIAMS NIH HHS [AR-03564, K11-AR01895] NR 46 TC 58 Z9 59 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 1994 VL 135 IS 6 BP 2635 EP 2643 DI 10.1210/en.135.6.2635 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PW235 UT WOS:A1994PW23500048 PM 7988453 ER PT J AU VALOVE, FM FINCH, C ANASTI, JN FROEHLICH, J FLACK, MR AF VALOVE, FM FINCH, C ANASTI, JN FROEHLICH, J FLACK, MR TI RECEPTOR-BINDING AND SIGNAL-TRANSDUCTION ARE DISSOCIABLE FUNCTIONS REQUIRING DIFFERENT SITES ON FOLLICLE-STIMULATING-HORMONE SO ENDOCRINOLOGY LA English DT Article ID GLYCOPROTEIN HORMONES; LINKED OLIGOSACCHARIDES; CHORIONIC-GONADOTROPIN; TESTICULAR RECEPTOR; HUMAN FOLLITROPIN; LIGAND-BINDING; FSH RECEPTOR; EXPRESSION; ACTIVATION; LUTROPIN AB Separate sites for glycoprotein hormone receptor binding and signal transduction have yet to be elucidated. In general, certain peptide regions are thought to be critical for receptor binding, whereas the oligosaccharides are thought to be important for signal transduction. Using site-directed mutagenesis of FSH, we made selective amino acid substitutions and oligosaccharide alterations to try and identify specific sites mediating receptor binding distinct from signal transduction and vice versa. We substituted Lys or Asp for beta Arg(35) in the purported receptor binding loop between cysteine-32 and -51, and we substituted Gln for alpha Asn(52), alpha Asn(78), beta Asn(7), or beta Asn(24), the attachment sites for each of the oligosaccharide side-chains. We determined the binding and signal-transducing activity of wild-type and mutant human FSH at the human FSH receptor, as recent data suggest that glycoprotein hormone-receptor interactions are species specific. The binding activities of FSH with Lys or Asp substituted for beta Arg(35) were reduced 71% and 98%, respectively, but their signal transduction, at equivalent levels of binding activity, was unaffected. The binding activity of FSH lacking the oligosaccharide at alpha Asn(52) was enhanced 2- to 3-fold, but its signal-transducing activity, at equivalent levels of receptor binding, was decreased 72%. In contrast, the binding and signal-transducing activities of FSH lacking the alpha Asn(78), beta Asn(7), or beta Asn(24) oligosaccharide were unaffected. Thus, a specific amino acid (beta Arg(35)) is important for high affinity binding, but is not involved in signal transduction, whereas a specific oligosaccharide (alpha Asn(52)) is important for signal transduction, but is not required for high affinity binding. Therefore, receptor binding and signal transduction are dissociable functions involving different sites on the FSH glycoprotein. C1 NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. NR 26 TC 35 Z9 35 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 1994 VL 135 IS 6 BP 2657 EP 2661 DI 10.1210/en.135.6.2657 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PW235 UT WOS:A1994PW23500051 PM 7988456 ER PT J AU USDIN, TB BONNER, TI MEZEY, E AF USDIN, TB BONNER, TI MEZEY, E TI 2 RECEPTORS FOR VASOACTIVE INTESTINAL POLYPEPTIDE WITH SIMILAR SPECIFICITY AND COMPLEMENTARY DISTRIBUTIONS SO ENDOCRINOLOGY LA English DT Article ID CYCLASE-ACTIVATING POLYPEPTIDE; HORMONE-RELEASING HORMONE; MOLECULAR-CLONING; FUNCTIONAL EXPRESSION; CATECHOLAMINE SECRETION; TISSUE DISTRIBUTION; PEPTIDE RECEPTOR; BINDING-SITES; RAT-BRAIN; MAMMALIAN-CELLS AB Vasoactive intestinal polypeptide (VIP) has a variety of physiological effects. Pharmacological evidence suggesting that VIP acts via multiple receptors has been confirmed by the cloning of two VIP receptors (VIP1 and VIP2) with very different amino acid sequences. At both the VIP1 and the VIP2 receptor VIP, PHI, PACAP38, and PACAP27 have similar potency to each other. Only the VIP1 receptor is activated by secretin. The messenger RNAs (mRNAs) for the two receptors have completely different distributions as mapped by in situ. hybridization histochemistry. VIP1 receptor mRNA is predominantly found in the lung, small intestine, thymus, and within the brain in the cerebral cortex and hippocampus. VIP2 receptor mRNA is present in a number of areas where VIP acts but VIP1 receptor mRNA is not present, including the stomach and testes. In the CNS VIP2 receptor mRNA is exclusively present in areas associated with neuroendocrine function, including several hypothalamic nuclei. In the periphery, it is also present in the pituitary and in pancreatic islets. C1 NINCDS,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. RP USDIN, TB (reprint author), NIMH,CELL BIOL LAB,BLDG 36,ROOM 3A17,BETHESDA,MD 20892, USA. NR 65 TC 394 Z9 399 U1 1 U2 2 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 1994 VL 135 IS 6 BP 2662 EP 2680 DI 10.1210/en.135.6.2662 PG 19 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PW235 UT WOS:A1994PW23500052 PM 7988457 ER PT J AU BARON, J KLEIN, KO YANOVSKI, JA NOVOSAD, JA BACHER, JD BOLANDER, ME CUTLER, GB AF BARON, J KLEIN, KO YANOVSKI, JA NOVOSAD, JA BACHER, JD BOLANDER, ME CUTLER, GB TI INDUCTION OF GROWTH-PLATE CARTILAGE OSSIFICATION BY BASIC FIBROBLAST GROWTH-FACTOR SO ENDOCRINOLOGY LA English DT Article ID TERMINAL DIFFERENTIATION; CHONDROCYTES; DNA AB In mammals, longitudinal bone growth results from the precise coupling of chondrogenesis and osteogenesis within the epiphyseal growth plate, a process termed endochondral ossification. The mechanisms coupling chondrogenesis and osteogenesis are unknown. Previous studies have shown that both basic fibroblast growth factor (bFGF) and acidic FGF are expressed by growth plate chondrocytes. Here we show that bFGF, infused directly into the rabbit proximal tibial growth plate, accelerates vascular invasion and ossification of growth plate cartilage. Our results suggest the possibility that bFGF (or a related member of the FGF family) couples osteogenesis to chondrogenesis by attracting vascular and bone cell invasion from the adjacent metaphyseal bone. C1 NICHHD, DEV ENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. MAYO CLIN & MAYO FDN, DEPT ORTHOPED, ROCHESTER, MN 55905 USA. RP BARON, J (reprint author), NIH, NATL CTR RES RESOURCES,VET RESOURCES PROGRAM, SURG RADIOL & PHARM SECT,BLDG 10, ROOM 10N262, BETHESDA, MD 20892 USA. NR 17 TC 66 Z9 67 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD DEC PY 1994 VL 135 IS 6 BP 2790 EP 2793 DI 10.1210/en.135.6.2790 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PW235 UT WOS:A1994PW23500067 PM 7988472 ER PT J AU ANDERSON, S SADINSKI, W SHUGART, L BRUSSARD, P DEPLEDGE, M FORD, T HOSE, J STEGEMAN, J SUK, W WIRGIN, I WOGAN, G AF ANDERSON, S SADINSKI, W SHUGART, L BRUSSARD, P DEPLEDGE, M FORD, T HOSE, J STEGEMAN, J SUK, W WIRGIN, I WOGAN, G TI GENETIC AND MOLECULAR ECOTOXICOLOGY - A RESEARCH FRAMEWORK SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE GENETIC; MOLECULAR; ECOTOXICOLOGY; BIOMARKERS; GENOTYPES; GENOTOXIC; GLOBAL POLLUTION; POPULATIONS; ECOSYSTEMS; BIODIVERSITY; HAZARDOUS SUBSTANCES AB Participants at the Napa Conference on Genetic and Molecular Ecotoxicology assessed the status of this field in light of heightened concerns about the genetic effects of exposure to hazardous substances and recent advancements in our capabilities to measure those effects. We present here a synthesis of the ideas discussed throughout the conference, including definitions of import:ant concepts in the field and critical research needs and opportunities. While there were many opinions expressed on these topics. there was general agreement that there are substantive new opportunities to improve the impact of genetic and molecular ecotoxicology on prediction of sublethal effects of exposure to hazardous substances. Future studies should emphasize integration of genetic ecotoxicology, ecological genetics, and molecular biology and should be directed toward improving our understanding of the ecological implications of genotoxic responses. Ecological implications may be assessed at either the population or ecosystem level; however, a population-level focus may be most pragmatic. Recent technical advancements in measuring genetic and molecular responses to toxicant exposure will spur rapid progress. These new techniques have considerable promise for increasing our understanding of both mechanisms of toxicity on genes or gene products and the relevance of detrimental effects to individual fitness. C1 OAK RIDGE NATL LAB,OAK RIDGE,TN. UNIV NEVADA,RENO,NV 89557. UNIV PLYMOUTH,PLYMOUTH PL4 8AA,DEVON,ENGLAND. HARVARD UNIV,CAMBRIDGE,MA 02138. OCCIDENTAL COLL,LOS ANGELES,CA 90041. WOODS HOLE OCEANOG INST,WOODS HOLE,MA 02543. NIEHS,RES TRIANGLE PK,NC 27709. NYU,MED CTR,TUXEDO PK,NY. MIT,CAMBRIDGE,MA 02139. RP ANDERSON, S (reprint author), UNIV CALIF BERKELEY,LAWRENCE BERKELEY LAB,BLDG 70-193A,1 CYCLOTRON RD,BERKELEY,CA 94708, USA. NR 33 TC 97 Z9 105 U1 0 U2 8 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 1994 VL 102 SU 12 BP 3 EP 8 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA QE659 UT WOS:A1994QE65900001 PM 7713030 ER PT J AU MASON, RP HANNA, PM BURKITT, MJ KADIISKA, MB AF MASON, RP HANNA, PM BURKITT, MJ KADIISKA, MB TI DETECTION OF OXYGEN-DERIVED RADICALS IN BIOLOGICAL-SYSTEMS USING ELECTRON-SPIN-RESONANCE SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Oxygen Radicals and Lung Injury Conference CY AUG 30-SEP 02, 1993 CL MORGANTOWN, WV SP US EPA, NCI, NIEHS, NIOSH, PENN STATE GENER MINERAL TECHNOL CTR RESPIRABLE DUST, W VIRGINIA UNIV, GENER MINERAL TECHNOL CTR RESPIRABLE DUST, W VIRGINIA UNIV, DEPT PATHOL, W VIRGINIA UNIV, SECT PULMONARY & CRIT CARE MED, W VIRGINIA UNIV, SCH MED, ABBOTT LABS, CIBA GIEGY CORP, PROCTOR & GAMBLE CO, SMITH KLINE BEECHAM, UPJOHN CO DE SUPEROXIDE; HYDROXYL RADICAL; SPIN TRAPPING; ELECTRON SPIN RESONANCE; IRON; COPPER ID HYDROXYL RADICALS; SUPEROXIDE FORMATION; HYDROGEN-PEROXIDE; ADDUCTS; PARAQUAT; GENERATION; INVIVO; INHIBITION; OXIDATION; REDUCTION AB Oxygen-centered radicals, particularly the hydroxyl and superoxide radicals, have been postulated in many biochemical reactions and have been implicated in many adverse reactions in vivo. This article begins with a review of spin-trapping detection of oxygen-centered radicals in vitro and concludes with a presentation of our approach to the detection of the hydroxyl radicals in models of acute iron and copper poisoning. C1 ROWETT RES INST,ABERDEEN,SCOTLAND. RP MASON, RP (reprint author), NIEHS,MOLEC BIOPHYS LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 21 TC 54 Z9 56 U1 0 U2 1 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 1994 VL 102 SU 10 BP 33 EP 36 DI 10.2307/3432210 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA QA021 UT WOS:A1994QA02100007 PM 7705301 ER PT J AU SHIELDS, PG AF SHIELDS, PG TI PHARMACOGENETICS - DETECTING SENSITIVE POPULATIONS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Workshop on Pharmacokinetics - Defining the Dose for Risk Assessment CY MAR 04-05, 1992 CL WASHINGTON, DC SP NATL RES COUNCIL, BOARD ENVIRONM STUDIES & TOXICOL, COMM TOXICOL DE CYTOCHROME P450; CANCER; GENETIC POLYMORPHISMS; RISK ASSESSMENT ID DIOL-EPOXIDE-DNA; FRAGMENT-LENGTH-POLYMORPHISM; COKE-OVEN WORKERS; WHITE BLOOD-CELLS; HYDROCARBON HYDROXYLASE-ACTIVITY; SISTER CHROMATID EXCHANGE; SITE-SPECIFIC MUTAGENESIS; LUNG-CANCER PATIENTS; INTERINDIVIDUAL VARIATION; CYTOCHROME-P450IA1 GENE AB Risk assessment models strive to predict risks to humans from toxic agents. Safety factors and assumptions are incorporated into these models to allow a margin of error. In the case of cancer, substantial evidence shows that the carcinogenic process is a multistage process driven by the interaction of exogenous carcinogenic exposures, genetic trails, and other endogenous factors. Current risk assessment models fail to consider genetic predispositions that make people more sensitive or resistant to exogenous exposures and endogenous processes. Several cytochrome P450 enzymes, responsible for metabolically activating carcinogens and medications, express wide interindividual variation whose genetic coding has now been identified as polymorphic and linked to cancer risk. For example, a restriction fragment-length polymorphism for cytochrome P4501A1, which metabolizes polycyclic aromatic hydrocarbons, and cytochrome P4502E1, which metabolizes N-nitrosamines and benzene, is linked to lung cancer risk. Cytochrome P4502D6, responsible for metabolizing many clinically important medications, also is linked to lung cancer risk. The frequency for each of these genetic polymorphisms vary among different ethnic and racial groups. In addition to inherited factors for the detection of sensitive populations, determining the biologically effective doses for carcinogenic exposures also should quantitatively and qualitatively enhance the risk assessment process. Levels of carcinogen-DNA adducts reflect the net effect of exposure, absorption, metabolic activation, detoxification, and DNA repair. These effects are genetically predetermined, inducibility notwithstanding The combination of adduct and genotyping assays provide an assessment of risk that reflects recent exogenous exposure as well as one's lifetime ability to activate and detoxify carcinogens. RP SHIELDS, PG (reprint author), NCI,DIV CANC ETIOL,HUMAN CARCINOGENESIS LAB,BETHESDA,MD 20892, USA. NR 88 TC 31 Z9 31 U1 0 U2 1 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 1994 VL 102 SU 11 BP 81 EP 87 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA QH893 UT WOS:A1994QH89300012 PM 7737047 ER PT J AU ROGAN, WJ RAGAN, NB AF ROGAN, WJ RAGAN, NB TI CHEMICAL CONTAMINANTS, PHARMACOKINETICS, AND THE LACTATING MOTHER SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Workshop on Pharmacokinetics - Defining the Dose for Risk Assessment CY MAR 04-05, 1992 CL WASHINGTON, DC SP NATL RES COUNCIL, BOARD ENVIRONM STUDIES & TOXICOL, COMM TOXICOL DE BREAST FEEDING; LACTATION; PHARMACOKINETICS; RISK ASSESSMENT; POLYCHLOROBIPHENYL COMPOUNDS; DDE; DIOXINS; FURANS; OXYCHLORDANE; HEPTACHLOR; DIELDRIN ID DICHLORODIPHENYL DICHLOROETHENE DDE; POLYCHLORINATED-BIPHENYLS PCBS; HUMAN-MILK; BREAST-MILK; N-NITROSODIMETHYLAMINE; LIVER-TUMORS; EXPOSURE; BEHAVIOR; RESIDUES; FORMULA AB We review the commonly occurring persistent pesticides and industrial chemicals in breast milk. These chemicals are dichlorodiphenyl trichloroethane as dichlorodiphenyl dichloroethene dieldrin, chlordane as oxychlordane. heptachlor. polychlorinated biphenyls, polychlorinated dibenzofurans, and polychlorinated dibenzodioxins. We present a worked example of the kinds of pharmacokinetic assumptions and calculations necessary for setting regulatory limits of contaminants in the food supply, calculating dose of chemical contaminants to the nursed infant, converting risks from lifetime exposure in laboratory animals to risks for short-term exposure in humans, and estimating the excess cancer risk to the nursed infant. RP ROGAN, WJ (reprint author), NIEHS,OFF CLIN RES,RES TRIANGLE PK,NC 27709, USA. RI Rogan, Walter/I-6034-2012 OI Rogan, Walter/0000-0002-9302-0160 NR 56 TC 22 Z9 23 U1 0 U2 0 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 1994 VL 102 SU 11 BP 89 EP 95 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA QH893 UT WOS:A1994QH89300013 PM 7737048 ER PT J AU SHI, XL MAO, Y DANIEL, LN SAFFIOTTI, U DALAL, NS VALLYATHAN, V AF SHI, XL MAO, Y DANIEL, LN SAFFIOTTI, U DALAL, NS VALLYATHAN, V TI SILICA RADICAL-INDUCED DNA-DAMAGE AND LIPID-PEROXIDATION SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Oxygen Radicals and Lung Injury Conference CY AUG 30-SEP 02, 1993 CL MORGANTOWN, WV SP US EPA, NCI, NIEHS, NIOSH, PENN STATE GENER MINERAL TECHNOL CTR RESPIRABLE DUST, W VIRGINIA UNIV, GENER MINERAL TECHNOL CTR RESPIRABLE DUST, W VIRGINIA UNIV, DEPT PATHOL, W VIRGINIA UNIV, SECT PULMONARY & CRIT CARE MED, W VIRGINIA UNIV, SCH MED, ABBOTT LABS, CIBA GIEGY CORP, PROCTOR & GAMBLE CO, SMITH KLINE BEECHAM, UPJOHN CO DE SILICA-BASED RADICALS; HYDROXYL RADICAL; SINGLET OXYGEN; SUPEROXIDE RADICAL; DNA DAMAGE; LIPID PEROXIDATION; ELECTRON SPIN RESONANCE; SPIN TRAPPING; CRYSTALLINE SILICA; SILICOSIS; CARCINOGENESIS ID SINGLET OXYGEN; HYDROGEN-PEROXIDE; HYDROXYL RADICALS; ESR; MECHANISM; QUARTZ; CYTOTOXICITY; SUPEROXIDE; SURFACES AB In recent years, more attention has been given to the mechanism of disease induction caused by the surface properties of minerals. In this respect, specific research needs to be focused on the biologic interactions of oxygen radicals generated by mineral particles resulting in cell injury and DNA damage leading to fibrogenesis and carcinogenesis. In this investigation, we used electron spin resonance (ESR) and spin trapping to study oxygen radical generation from aqueous suspensions of freshly fractured crystalline silica. Hydroxyl radical ((OH)-O-.), superoxide radical (O-2(.-)) and singlet oxygen (O-1(2)) were all detected. Superoxide dismutase (SOD) partially inhibited (OH)-O-. yield, whereas catalase abolished (OH)-O-. generation. H2O2 enhanced (OH)-O-. generation while deferoxamine inhibited it, indicating that (OH)-O-. is generated via a Haber-Weiss type reaction. These spin trapping measurements provide the first evidence that aqueous suspensions of silica particles generate O-2(.-) and O-1(2). Oxygen consumption measurements indicate that freshly fractured silica uses molecular oxygen to generate O-2(.-) and O-1(2). Electrophoretic assays of in vitro DNA strand breakages showed that freshly fractured silica induced DNA strand breakage, which was inhibited by catalase and enhanced by H2O2. In an argon atmosphere, DNA damage was suppressed, showing that molecular oxygen is required for the silica-induced DNA damage. incubation of freshly fractured silica with linoleic acid generated linoleic acid-derived free radicals and caused dose-dependent lipid peroxidation as measured by ESR spin trapping and malondialdehyde formation. SOD, catalase, and sodium benzoate inhibited lipid peroxidation by 49, 52, and 75%, respectively, again showing the role of oxygen radicals in silica-induced lipid peroxidation. These results show that in addition to (OH)-O-., O-2(.-) and O-1(2) may play an important role in the mechanism of silica-induced cellular injury. C1 W VIRGINIA UNIV,DEPT CHEM,MORGANTOWN,WV. NIOSH,DIV RESP DIS STUDIES,MORGANTOWN,WV. RP SHI, XL (reprint author), NCI,EXPTL PATHOL LAB,BLDG 41,ROOM C301,BETHESDA,MD 20892, USA. RI Shi, Xianglin/B-8588-2012 NR 34 TC 66 Z9 72 U1 0 U2 5 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 1994 VL 102 SU 10 BP 149 EP 154 DI 10.2307/3432231 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA QA021 UT WOS:A1994QA02100028 PM 7705289 ER PT J AU SAFFIOTTI, U DANIEL, LN MAO, Y SHI, XG WILLIAMS, AO KAIGHN, ME AF SAFFIOTTI, U DANIEL, LN MAO, Y SHI, XG WILLIAMS, AO KAIGHN, ME TI MECHANISMS OF CARCINOGENESIS BY CRYSTALLINE SILICA IN RELATION TO OXYGEN RADICALS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Oxygen Radicals and Lung Injury Conference CY AUG 30-SEP 02, 1993 CL MORGANTOWN, WV SP US EPA, NCI, NIEHS, NIOSH, PENN STATE GENER MINERAL TECHNOL CTR RESPIRABLE DUST, W VIRGINIA UNIV, GENER MINERAL TECHNOL CTR RESPIRABLE DUST, W VIRGINIA UNIV, DEPT PATHOL, W VIRGINIA UNIV, SECT PULMONARY & CRIT CARE MED, W VIRGINIA UNIV, SCH MED, ABBOTT LABS, CIBA GIEGY CORP, PROCTOR & GAMBLE CO, SMITH KLINE BEECHAM, UPJOHN CO DE CRYSTALLINE SILICA; QUARTZ; CRISTOBALITE; TRIDYMITE; SILICOSIS; LUNG CARCINOGENESIS; DNA BINDING; DNA DAMAGE; JANUS GREEN B; NEOPLASTIC TRANSFORMATION; LUNG; ALVEOLAR TYPE II CELLS; CYTOKINES; TGF-BETA-1 ID MAMMALIAN-CELLS; LUNG; INDUCTION; QUARTZ; FIBER; RATS; DUST AB The carcinogenic effects of crystalline silica in rat lungs were extensively demonstrated by many experimental long-term studies, showing a marked predominance for adenocarcinomas originating from alveolar type II cells and associated with areas of pulmonary fibrosis (silicosis). In contrast with its effects in rats, silica did not induce alveolar type II hyperplasia and lung tumors in mice and hamsters, pointing to a critical role for host factors. Using these animal models, we are investigating the role of cytokines and other cellular mediators on the proliferation of alveolar type II cells. immunohistochemical localization of TGF-beta 1 precursor in alveolar type II cells adjacent to silicotic granulomas was shown to occur in rats, but not in mice, and hamsters, suggesting a pathogenetic role for this regulatory growth factor. Recent investigations in our laboratory on the biologic mechanisms of crystalline silica included determination of anionic sites on crystalline silica surfaces by binding of the cationic dye janus Green B; binding of crystalline silica to DNA, demonstrated by infrared spectrometry; production of oxygen radicals by crystalline silica in aqueous media; induction of DNA strand breakage and base oxidation in vitro and its potentiation by superoxide dismutase and by hydrogen peroxide; and induction by crystalline silica of neoplastic transformation and chromosomal damage in cells in culture. On the basis of these in vitro studies, we propose that DNA binding to crystalline silica surfaces may be important in silica carcinogenesis by anchoring DNA close to sites of oxygen radical production on the silica surface, so that the oxygen radicals are produced within a few Angstrom from their target DNA nucleotides. RP SAFFIOTTI, U (reprint author), NCI, EXPTL PATHOL LAB, DIV CANC ETIOL, BLDG 41, RM C-105, BETHESDA, MD 20892 USA. RI Shi, Xianglin/B-8588-2012 NR 24 TC 32 Z9 33 U1 0 U2 0 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 1994 VL 102 SU 10 BP 159 EP 163 DI 10.2307/3432233 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA QA021 UT WOS:A1994QA02100030 PM 7705291 ER PT J AU MAO, Y DANIEL, LN WHITTAKER, N SAFFIOTTI, U AF MAO, Y DANIEL, LN WHITTAKER, N SAFFIOTTI, U TI DNA-BINDING TO CRYSTALLINE SILICA CHARACTERIZED BY FOURIER-TRANSFORM INFRARED-SPECTROSCOPY SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Oxygen Radicals and Lung Injury Conference CY AUG 30-SEP 02, 1993 CL MORGANTOWN, WV SP US EPA, NCI, NIEHS, NIOSH, PENN STATE GENER MINERAL TECHNOL CTR RESPIRABLE DUST, W VIRGINIA UNIV, GENER MINERAL TECHNOL CTR RESPIRABLE DUST, W VIRGINIA UNIV, DEPT PATHOL, W VIRGINIA UNIV, SECT PULMONARY & CRIT CARE MED, W VIRGINIA UNIV, SCH MED, ABBOTT LABS, CIBA GIEGY CORP, PROCTOR & GAMBLE CO, SMITH KLINE BEECHAM, UPJOHN CO DE SILICA; DNA ADDUCTS; FOURIER-TRANSFORM INFRARED SPECTROSCOPY; SILICOSIS; CARCINOGENESIS ID INDUCED PULMONARY INFLAMMATION; POLYVINYLPYRIDINE-N-OXIDE; MAMMALIAN-CELLS; ALVEOLAR MACROPHAGES; PARTICLE SURFACE; QUARTZ; DUST; HEMOLYSIS; EXPOSURE; RADICALS AB The interaction of DNA with crystalline silica in buffered aqueous solutions at physiologic pH has been investigated by Fourier-transform infrared spectroscopy (FT-IR). In aqueous buffer, significant changes occur in the spectra of DNA and silica upon coincubation, suggesting that a DNA-silica complex forms as silica interacts with DNA. As compared to the spectrum of silica alone, the changes in the FT-IR spectrum of silica in the DNA-silica complex are consistent with an Si-O bond perturbation on the surface of the silica crystal. DNA remains in a B-form conformation in the DNA-silica complex. The most prominent changes in the DNA spectrum occur in the 1225 to 1000 cm(-1) region. Upon binding, the PO2- asymmetric stretch at 1225 cm(-1) is increased in intensity and slightly shifted to lower frequencies; the PO2- symmetric stretch at 1086 cm(-1) is markedly increased in intensity; and the band at 1053 cm(-1), representing either the phosphodiester or the C-O stretch of DNA backbone, is significantly reduced in intensity. In D2O buffer, the DNA spectrum reveals a marked increase in intensity of the peak at 1086 cm(-1) and a progressive decrease in intensity of the peak at 1053 cm(-1) when DNA is exposed to increasing concentrations of silica. The carbonyl band at 1688 cm(-1) diminishes and shifts to slightly lower frequencies with increasing concentrations of silica. The present study demonstrates that crystalline silica binds to the phosphate-sugar backbone of DNA. The close proximity of the silica surface to the DNA molecule, brought about by this binding, may contribute to DNA strand breakage produced by silica-derived free radicals. The ability of silica to form stable complexes with DNA may play an important role in the mechanisms of silica-induced toxicity and carcinogenesis. C1 NCI, DIV CANC ETIOL, EXPTL PATHOL LAB, BETHESDA, MD 20892 USA. NIDDKD, ANALYT CHEM LAB, BETHESDA, MD USA. NR 54 TC 56 Z9 56 U1 2 U2 13 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD DEC PY 1994 VL 102 SU 10 BP 165 EP 171 DI 10.2307/3432234 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA QA021 UT WOS:A1994QA02100031 PM 7705292 ER PT J AU IMAI, Y IBARAKI, K ODAJIMA, R SHISHIBA, Y AF IMAI, Y IBARAKI, K ODAJIMA, R SHISHIBA, Y TI ANALYSIS OF PROTEOGLYCAN SYNTHESIS BY RETRO-OCULAR TISSUE FIBROBLASTS UNDER THE INFLUENCE OF INTERLEUKIN-1-BETA AND TRANSFORMING GROWTH-FACTOR-BETA SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID GRAVES-DISEASE; SULFATE; EXPRESSION; PATHOLOGY; CARTILAGE; SEQUENCE; PROTEIN AB Retro-ocular tissue fibroblasts are supposed to be responsible for the deposition of glycosaminoglycan in Graves' ophthalmopathy. We have reported in a preliminary fashion that interleukin Ip (IL-1 beta) and transforming growth factor-beta (TGF-beta) increased the rate of [S-35]sulfate incorporation into proteoglycans two to five times the control in culture of retro-ocular tissue fibroblasts. The increase in the rate of [S-35]sulfate incorporation into proteoglycan will occur as a result of: (a) net increase of proteoglycan synthesis; (b) elongation of glycosaminoglycan chains: (c) increased number of glycosaminoglycan chains; (d) oversulfation of glycosaminoglycan chains; (e) increase in cell number; (f) decreased rate of degradation. We have analyzed which mechanism is important for the increase of [S-35]sulfate into proteoglycans observed In human retro-ocular tissue fibroblasts under the influence of cytokines. The last two possibilities (e, f) were ruled out because during the observation period there was do consistent proliferation of the cells and no decrease in the rate of degradation of proteoglycan examined by pulse-chase experiment. Cytokines did not change the size of glycosaminoglycan chains released from proteoglycan as measured by alkaline borohydride treatment, ruling out (b). Disaccharide analysis by HPLC after chondroitin sulfate ABC digestion revealed that glycosaminoglycan mainly contains monosulfated chondroitin disaccharides and that oversulfation was not observed under the influence of IL-1 beta or TGF-beta, ruling out (d). The capacity to synthesize glycosaminoglycan chain in the presence of an artificial acceptor of chain elongation, beta-D-xylodide, was increased significantly by IL-1 beta but not obviously so by TGF-beta. Thus, an increased number of glycosaminoglycan chains (c) is possible for IL-1 beta. A preliminary northern blot analysis employing probes for mRNAs for various proteoglycan core proteins showed increased expression of versican and aggrecan in the presence of IL-1 beta or TGF-beta. This result supports the possibility of (a). In conclusion, IL-1 beta and TGF-beta increased [S-35]sulfate incorporation into proteoglycan by increasing the net increase of proteoglycan synthesis and possibly by increasing the number of glycosaminoglycan chains attached to core protein in the case of IL-1 beta. C1 NIDR,BONE RES BRANCH,BETHESDA,MD 20892. RP IMAI, Y (reprint author), TORANOMON GEN HOSP,DEPT MED,DIV ENDOCRINOL,MINATO KU,2-2-2 TORANOMON,TOKYO,JAPAN. NR 19 TC 9 Z9 13 U1 0 U2 0 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0804-4643 J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD DEC PY 1994 VL 131 IS 6 BP 630 EP 638 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PY185 UT WOS:A1994PY18500012 PM 7804447 ER PT J AU COCCO, P WARD, MH AF COCCO, P WARD, MH TI OCCUPATIONAL EXPOSURES AND GASTRIC-CANCER ETIOLOGY SO EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY LA English DT Review DE GASTRIC CANCER; OCCUPATIONAL CANCER; ASBESTOS; DUST; NITRIC OXIDE-NITROSO COMPOUNDS; NITROSAMINES; ETHYLENE OXIDE; POLYCYCLIC AROMATIC HYDROCARBONS AB Epidemiological studies have frequently reported that many occupations are associated with an increased risk of gastric cancer. However, the diversity of occupations and inconsistencies across studies have meant that positive findings are often explained by confounding dietary and life-style factors related to low socioeconomic status and manual work. Nevertheless, exposure to preformed nitrosamines and to precursors of endogenous nitrosation occurs via inhalation and dermal absorption in a number of occupations and industries. It is still unclear whether such exposures alone contribute to gastric cancer aetiology, or whether they act in combination with diet and life-style risk factors. N-nitroso compounds, may directly or through the formation of free radicals or nucleophilic intermediates, damage the nucleic acids of gastric mucosal cells and act as initiators of the carcinogenic process. Other physical agents, such as organic and inorganic dusts (including asbestos and other mineral dusts) may irritate the gastric mucosa and act as co-carcinogens when swallowed with mucus, causing superficial gastritis and increasing cell proliferation, which can promote initiated clones. Dusts can also act as carriers, delivering carcinogens to the gastric mucosa. Further research in this area is necessary to clarify dose-response curves and to elucidate the carcinogenic process. RP COCCO, P (reprint author), NCI,ENVIRONM EPIDEMIOL BRANCH,OCCUPAT STUDIES SECT,6130 EXECUT BLVD,EPN ROOM 418,BETHESDA,MD 20892, USA. NR 0 TC 6 Z9 7 U1 0 U2 0 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0954-691X J9 EUR J GASTROEN HEPAT JI Eur. J. Gastroenterol. Hepatol. PD DEC PY 1994 VL 6 IS 12 BP 1089 EP 1096 DI 10.1097/00042737-199412000-00004 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PU224 UT WOS:A1994PU22400004 ER PT J AU ACTOR, JK MARSHALL, MA ELTOUM, IA BULLER, RML BERZOFSKY, JA SHER, A AF ACTOR, JK MARSHALL, MA ELTOUM, IA BULLER, RML BERZOFSKY, JA SHER, A TI INCREASED SUSCEPTIBILITY OF MICE INFECTED WITH SCHISTOSOMA-MANSONI TO RECOMBINANT VACCINIA VIRUS - ASSOCIATION OF VIRAL PERSISTENCE WITH EGG GRANULOMA-FORMATION SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE SCHISTOSOMES; VACCINIA; GRANULOMA; CYTOKINES; CYTOTOXIC C LYMPHOCYTES ID HEPATITIS-B; ENVELOPE GLYCOPROTEIN; INTERFERON-GAMMA; T-CELLS; RESPONSES; INTERLEUKIN-4; CYTOKINES; HELMINTH; AREA AB BALB/c mice infected 7 weeks previously with Schistosoma mansoni and challenged with a recombinant vaccinia virus vPE16 expressing the human immunodeficiency virus envelope protein gp160 show a marked delay in hepatic viral clearance as compared to mice infected with vPE16 alone. This increase in viral persistence is accompanied by reduced gp120-specific Th1-associated cytokine responses as well as by impaired cytotoxic T lymphocyte (CTL) activity against targets expressing epitopes of the same antigen. To investigate the contribution of these defects to the observed delay in clearance of recombinant vaccinia virus, animals were challenged with vPE16 at different times following S. mansoni infection, and virus titers in tissues and viral-specific immune responses were measured simultaneously in the same animals. While normal resolution of virus occurred in schistosome-infected mice prior to parasite egg deposition, persistence within the liver was observed in animals challenged during the onset and peak phase of granuloma formation (6 to 8 weeks after S. mansoni infection). At later times,when schistosomiasis is in its chronic phase, normal viral clearance returned. This time course of viral resolution correlated in part with the observed pattern of decreased Th1 cytokine production toward viral antigens but was clearly less temporally related to the defect in virus-specific CTL activity. Immunohistochemical staining of liver sections from vaccinia/S. mansoni co-infected mice with polyclonal anti-vaccinia antibodies revealed that viral epitopes are localized primarily within granulomas. These experiments suggest that egg granulomas, by providing a microenvironment for viral expansion, in combination with the cytokine imbalance present during schistosome infection, can promote the expansion of vaccinia virus and possibly other viral agents. C1 NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. NIAID,VIRAL DIS LAB,BETHESDA,MD 20892. NCI,METAB BRANCH,BETHESDA,MD. OI Actor, Jeffrey/0000-0002-9265-7012 NR 33 TC 42 Z9 42 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD DEC PY 1994 VL 24 IS 12 BP 3050 EP 3056 DI 10.1002/eji.1830241220 PG 7 WC Immunology SC Immunology GA PZ242 UT WOS:A1994PZ24200020 PM 7805733 ER PT J AU DELAROSA, EJ BONDY, CA HERNANDEZSANCHEZ, C WU, X ZHOU, J LOPEZCARRANZA, A SCAVO, LM DEPABLO, F AF DELAROSA, EJ BONDY, CA HERNANDEZSANCHEZ, C WU, X ZHOU, J LOPEZCARRANZA, A SCAVO, LM DEPABLO, F TI INSULIN AND INSULIN-LIKE GROWTH-FACTOR SYSTEM COMPONENTS GENE-EXPRESSION IN THE CHICKEN RETINA FROM EARLY NEUROGENESIS UNTIL LATE DEVELOPMENT AND THEIR EFFECT ON NEUROEPITHELIAL CELLS SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE IGF-I RECEPTOR; IGF BINDING PROTEIN; INSULIN RECEPTOR; PM1 NEURAL PRECURSORS; RETINAL GANGLION CELL; RETINAL CULTURE ID I IGF-I; FACTOR BINDING PROTEIN-2; EARLY ORGANOGENESIS; CELLULAR-PATTERN; HYBRID RECEPTORS; PROGENITOR CELLS; BRAIN INSULIN; NEURAL RETINA; DNA-SYNTHESIS; RAT-BRAIN AB To better understand the role of insulin-related growth factors in neural development, we have characterized by in situ hybridization in chicken embryonic retina the patterns of gene expression for insulin, insulin-like growth factor I (IGF-I), their respective receptors and the IGF binding protein 5 (IGFBP5) from early stages (E6) until late stages (E18)-an analysis not performed yet in any species. In addition, we studied the effect of insulin and IGF-I on cultured neuroepithelial cells. Insulin receptor mRNA and IGF-I receptor mRNA were both present and showed a similar, widespread pattern throughout retina development Insulin mRNA could be detected only by reverse transcription coupled to polymerase chain reaction. IGF-I mRNA was concentrated in the ciliary processes and extraocular muscles early in development (embryonic day 6; E6) and in maturing retinal ganglion cells subsequently (E9-15). IGFBP5 mRNA was preferentially localized in the more differentiated central retinal zone and was maximally concentrated in the inner nuclear and ganglion cell layers at E9. These findings suggest a near constitutive expression of insulin receptor and IGF-I receptor genes, while IGF-I and IGFBP5 showed a highly focal spatiotemporal regulation of gene expression. Insulin and IGF-I, already at 10(-8) M, increased the proportion of PM1-positive neuroepithelial cells found in E5 retinal cultures without affecting significantly the total number of proliferating cells. Together, these data support the finding that, during early neurogenesis in chicken retina, insulin and IGF-I have a specific paracrine/autocrine action. This action, as well as possible effects elicited subsequently, may be dictated by restricted local synthesis of the ligands and limited access to the factors contained in the Vitreous humour. In the case of IGF's role, local IGFBPs expression can contribute to the fine modulation. C1 NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. RP DELAROSA, EJ (reprint author), CSIC,CTR INVEST BIOL,DEPT BIOL CELULAR & DESARROLLO,VELAZQUEZ 144,E-28006 MADRID,SPAIN. RI de la Rosa, Enrique/N-3689-2014; Hernandez Sanchez, Catalina/N-1737-2014 OI de la Rosa, Enrique/0000-0001-9984-9706; Hernandez Sanchez, Catalina/0000-0002-0846-5019 NR 58 TC 72 Z9 73 U1 1 U2 3 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD DEC 1 PY 1994 VL 6 IS 12 BP 1801 EP 1810 PG 10 WC Neurosciences SC Neurosciences & Neurology GA PY461 UT WOS:A1994PY46100004 PM 7535629 ER PT J AU VOORN, P BRADY, LS SCHOTTE, A BERENDSE, HW RICHFIELD, EK AF VOORN, P BRADY, LS SCHOTTE, A BERENDSE, HW RICHFIELD, EK TI EVIDENCE FOR 2 NEUROCHEMICAL DIVISIONS IN THE HUMAN NUCLEUS-ACCUMBENS SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Note DE STRIATUM; OPIOID RECEPTORS; DOPAMINE RECEPTORS; AUTORADIOGRAPHY; IN SITU HYBRIDIZATION ID KAPPA-OPIOID RECEPTORS; VENTRAL STRIATUM; OPIATE RECEPTORS; RAT-BRAIN; DOPAMINE; SHELL; CORE; LOCALIZATION; ORGANIZATION; ENKEPHALIN AB The neurochemical anatomy of the human nucleus accumbens was studied by comparing the distributional patterns of [H-3]DAMGE (mu opioid receptor), [H-3]bremazocine (kappa opioid receptor), [H-3]SCH-23390 (D-1-like dopamine receptor), [H-3]7-OH-DPAT (D-3 dopamine receptor) binding, preproenkephalin mRNA and acetylcholinesterase activity in sections of post mortem human striatum. Our results demonstrate the presence of at least two neurochemically distinct divisions within the human nucleus accumbens, which may be homologous to the 'shell' and 'core' divisions of the nucleus as found in the rat. C1 VRIJE UNIV,NEUROSCI RES INST,DEPT ANAT & EMBRYOL,1081 BT AMSTERDAM,NETHERLANDS. NIMH,FUNCT NEUROANAT SECT,BETHESDA,MD 20892. JANSSEN RES FDN,B-2340 BEERSE,BELGIUM. VRIJE UNIV AMSTERDAM,ACAD HOSP,DEPT NEUROL,1081 HV AMSTERDAM,NETHERLANDS. UNIV ROCHESTER,SCH MED & DENT,DEPT NEUROL,ROCHESTER,NY 14642. UNIV ROCHESTER,SCH MED & DENT,DEPT PHARMACOL,ROCHESTER,NY 14642. FU NIMH NIH HHS [MH 40381] NR 20 TC 47 Z9 47 U1 1 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD DEC 1 PY 1994 VL 6 IS 12 BP 1913 EP 1916 DI 10.1111/j.1460-9568.1994.tb00582.x PG 4 WC Neurosciences SC Neurosciences & Neurology GA PY461 UT WOS:A1994PY46100013 PM 7704301 ER PT J AU KUZUYA, M KINSELLA, JL AF KUZUYA, M KINSELLA, JL TI INDUCTION OF ENDOTHELIAL-CELL DIFFERENTIATION IN-VITRO BY FIBROBLAST-DERIVED SOLUBLE FACTORS SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; CAPILLARY-LIKE STRUCTURES; BASEMENT-MEMBRANE; EXTRACELLULAR-MATRIX; SCATTER FACTOR; PLASMINOGEN-ACTIVATOR; ANGIOGENESIS INVITRO; DNA-SYNTHESIS; MIGRATION; PROLIFERATION AB Recent studies have suggested that fibroblasts, widely distributed mesenchymal cells, not only function to sustain various organs and tissues as stroma cells but also act directly to regulate adjacent cell behavior including migration, proliferation, and differentiation. Since fibroproliferative diseases and lesions (fibroplasia) are accompanied by new capillary growth (angiogenesis), we hypothesized that fibroblasts may have direct effects on endothelial cell behavior, independent of the elaboration of extracellular matrix, that are relevant to complex process of angiogenesis. To test this hypothesis, bovine aortic endothelial cells were cocultured in collagen gels with human skin fibroblasts. This coculture system caused the endothelial cells to become spindle shaped and to organize into a capillary-like structure within the collagen gels. We found that fibroblast-conditioned medium (FCM) also induced endothelial cells initially to elongate and subsequently to organize into a capillary-like structure within collagen gels. While FCM had no significant effect on endothelial cell DNA synthesis, the soluble factor(s) in FCM increased endothelial cell motility in an in vitro wound assay and in a Boyden chamber assay. The chemoattractant(s) in FCM was alkaline (pH 9.0)-and acid (pH 3.0)-stable, relatively heat stable (stable at 60 degrees C for 30 min, unstable at 98 degrees C for 3 min), dithiothreitol (DTT)-sensitive, and bound to an anionic exchange resin (DEAE-cellulose). Another factor(s) stimulated endothelial cell reorganization into capillary-like structure both within a collagen gel and on a reconstituted basement membrane matrix, Matrigel. This factor(s) was alkaline (pH 9.0)- and acid (pH 3.0)-stable, heat (98 degrees C for 3 min)stable, and DTT-sensitive and bound an anionic exchange resin (DEAE-cellulose). These in vitro results suggest that fibroblasts secrete soluble factors that can influence endothelial cell behaviors relevant to the angiogenesis process with possible implications for vascularization in fibroproliferative conditions. (C) 1994 Academic Press, Inc. C1 NIA, FRANCIS SCOTT KEY MED CTR, GERONTOL RES CTR, CARDIOVASC SCI LAB, BALTIMORE, MD 21224 USA. RI Kuzuya, Masafumi/I-1583-2012 NR 50 TC 36 Z9 37 U1 0 U2 1 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD DEC PY 1994 VL 215 IS 2 BP 310 EP 318 DI 10.1006/excr.1994.1347 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA PW238 UT WOS:A1994PW23800009 PM 7526993 ER PT J AU SMITH, ML ZHAN, QM BAE, IS FORNACE, AJ AF SMITH, ML ZHAN, QM BAE, IS FORNACE, AJ TI ROLE OF RETINOBLASTOMA GENE-PRODUCT IN P53-MEDIATED DNA-DAMAGE RESPONSE SO EXPERIMENTAL CELL RESEARCH LA English DT Note ID TUMOR-SUPPRESSOR GENE; CELL-CYCLE; WILD-TYPE; P53; PROTEIN; EXPRESSION; PHOSPHORYLATION; MUTATIONS; CANCER AB The cellular response to DNA-damaging agents involves the activation of cell cycle checkpoints. Checkpoints provide a transient delay in cell cycle progression, presumably to allow time for the cell to repair the damage. A mesa important checkpoint, active in the G1 phase of the cell cycle, is mediated by the p53 tumor suppressor gene product. To investigate the role of downstream components of the cell cycle machinery in p53-mediated G1 arrest, the possible involvement of the RB gene product was examined. Rb and p53 proteins were studied by immunoprecipitation and Western blotting experiments in the presence and absence of DNA-damaging treatment. The phosphorylation status of Rb was altered following DNA damage in p53 wildtype cell lines, but was not altered in p53 mutant cell lines, nor in cell lines where p53 function was abrogated by viral gene products. These findings indicate that Rb probably plays a role in the activation of the p53-mediated checkpoint. (C) 1994 Academic Press, Inc. RP SMITH, ML (reprint author), NCI,DCT,DTP,MOLEC PHARMACOL LAB,ROOM 5C09,BLDG 37,BETHESDA,MD 20892, USA. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 27 TC 23 Z9 23 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD DEC PY 1994 VL 215 IS 2 BP 386 EP 389 DI 10.1006/excr.1994.1356 PG 4 WC Oncology; Cell Biology SC Oncology; Cell Biology GA PW238 UT WOS:A1994PW23800018 PM 7982477 ER PT J AU TSARFATY, G LONGO, DL MURPHY, WJ AF TSARFATY, G LONGO, DL MURPHY, WJ TI HUMAN INSULIN-LIKE GROWTH-FACTOR-I EXERTS HEMATOPOIETIC GROWTH-PROMOTING EFFECTS AFTER IN-VIVO ADMINISTRATION SO EXPERIMENTAL HEMATOLOGY LA English DT Article DE INSULIN-LIKE GROWTH FACTOR I; NEUROENDOCRINE; HEMATOPOIESIS; AZIDOTHYMIDINE; GROWTH HORMONE ID SOMATOMEDIN-C; CELLS; COLONY; ENHANCEMENT; HORMONE; AZIDOTHYMIDINE; SUPPRESSION; RECEPTORS; INVITRO; INVIVO AB Recombinant human insulin-like growth factor I (rhIGF-I) was administered to mice to determine its effect on hematopoiesis. Mice given intraperitoneal (IF) injections of 5 mu g rhIGF-I for 7 days exhibited a significant increase in bone marrow (BM) hematopoietic progenitor cells, suggesting that rhIGF-I acts as a hematopoietic growth factor. Treatment with rhIGF-I also resulted in increases in erythroid precursor cells. Mice were then placed on azidothymidine (AZT), which produces significant myelotoxic effects. Splenic and BM progenitor cell content and hematocrit values were all significantly increased if rhIGF-I (5 mu g injected IP every day for 28 days) was concurrently administered with AZT. Additionally, when mice were initially myelosuppressed by several weeks of AZT treatment, the subsequent administration of rhIGF-I resulted in an increase in hematopoietic progenitor cell content. No significant pathologic effects or weight changes were observed in mice receiving repeated injections of rhIGF-I at this dose and schedule. Thus, rhIGF-I exerts hematopoietic growth-promoting effects in vivo and may be of potential clinical use in promoting hematopoiesis in the face of myelotoxic therapy. C1 NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,LEUKOCYTE BIOL LAB,FREDERICK,MD 21702. NR 21 TC 33 Z9 34 U1 0 U2 2 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD DEC PY 1994 VL 22 IS 13 BP 1273 EP 1277 PG 5 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA PT541 UT WOS:A1994PT54100008 PM 7957713 ER PT J AU COOPER, GS HULKA, BS BAIRD, DD SAVITZ, DA HUGHES, CL WEINBERG, CR COLEMAN, RA SHIELDS, JM AF COOPER, GS HULKA, BS BAIRD, DD SAVITZ, DA HUGHES, CL WEINBERG, CR COLEMAN, RA SHIELDS, JM TI GALACTOSE CONSUMPTION, METABOLISM, AND FOLLICLE-STIMULATING-HORMONE CONCENTRATIONS IN WOMEN OF LATE REPRODUCTIVE AGE SO FERTILITY AND STERILITY LA English DT Article DE GALACTOSE METABOLISM; FOLLICLE-STIMULATING HORMONE; MENOPAUSAL STATUS; OVARIAN TOXICITY ID GALACTOSE-1-PHOSPHATE URIDYL TRANSFERASE; INHIBITION; MENOPAUSE; HISTORY; CANCER; RISK AB Objective: To test the hypothesis that high galactose consumption and low activity of galactose-1-phosphate uridyl transferase (transferase) is associated with early ovarian senescence among nongalactosemic women. Design: Cross-sectional study. Data collection consisted of a self-administered questionnaire with sections on diet (food frequency data to measure galactose consumption), reproductive, and medical histories. One blood sample was collected to measure FSH and transferase activity; FSH was used as a measure of ovarian senescence. Among women who were having menstrual periods at least every 8 weeks, the blood sample was drawn in the early follicular phase (days 2 to 4) of a menstrual cycle. Participants: Two hundred ninety-five women volunteers ages 38 to 49 years who had not had a hysterectomy or oophorectomy were recruited through posters and advertisements. Main Outcome Measure: Serum FSH concentrations. Results: Controlling for age, smoking, and body mass, transferase activity and FSH were unrelated. However, FSH levels were 29% higher (95% confidence intervals, 9% to 52%) among women who reported consuming greater than or equal to 6 g galactose/d. Conclusion: These data do not support the hypothesis that low transferase activity represents a genetic predisposition for early ovarian senescence, as measured by FSH levels in women ages 38 to 49 years. However, the hypothesized positive association between galactose consumption and FSH was supported. C1 UNIV N CAROLINA,CHAPEL HILL,NC. DUKE UNIV,MED CTR,DURHAM,NC. RP COOPER, GS (reprint author), NIEHS,EPIDEMIOL BRANCH MD A305,POB 12233,RES TRIANGLE PK,NC 27709, USA. OI Baird, Donna/0000-0002-5544-2653 FU NCI NIH HHS [5-T32-CA09330]; NCRR NIH HHS [RR00046] NR 25 TC 20 Z9 21 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 DEC PY 1994 VL 62 IS 6 BP 1168 EP 1175 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA PU445 UT WOS:A1994PU44500012 PM 7957979 ER PT J AU HEBERT, CD YUAN, J DIETER, MP AF HEBERT, CD YUAN, J DIETER, MP TI COMPARISON OF THE TOXICITY OF CINNAMALDEHYDE WHEN ADMINISTERED BY MICROENCAPSULATION IN FEED OR BY CORN-OIL GAVAGE SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article ID CHEMICAL MUTAGENESIS; FOOD-ADDITIVES; RATS; MUTAGENICITY; TOXICOLOGY; MICE; STRAIN AB The toxicity of cinnamaldehyde (CNMA) was compared after administration by gavage and in dosed feed. Rats and mice of both sexes received CNMA by daily corn oil gavage (for 2 wk), or in microencapsulated form in feed (2 wk for rats, 3 wk for mice). Feed formulations contained 0-10% CNMA microcapsules, equivalent to approximate daily doses of 0-3000 mg CNMA/kg body weight for rats and 0-10,000 mg CNMA/kg body weight for mice. Concentrations were chosen to deliver CNMA doses approximately equal to doses in the gavage study. Gavage doses of 2620 mg/kg/day and above in mice and 930 mg/kg/day and above in rats produced nearly 100% mortality; there were no deaths in animals receiving microencapsulated CNMA. Rats and mice receiving CNMA in feed showed a dose-related decrease in body weight gain, which was accompanied in rats by hypoplastic changes in reproductive organs and accessory sex glands. CNMA administration by either route caused hyperplasia of the forestomach mucosa. These results demonstrate that microencapsulation in feed can present a useful alternative to gavage dosing for repeated-dose or prolonged-exposure studies, in that (1) the toxic effects of CNMA were similar after gavage dosing and after administration in microencapsulated form in feed, (2) ingestion of chemical in the feed more closely approximates human exposures, and (3) microencapsulation allows the delivery of higher net doses of chemical, while avoiding the acutely toxic effects of a bolus dose. C1 NIEHS,RES TRIANGLE PK,NC 27709. NR 30 TC 13 Z9 13 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD DEC PY 1994 VL 32 IS 12 BP 1107 EP 1115 DI 10.1016/0278-6915(94)90126-0 PG 9 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA QE357 UT WOS:A1994QE35700002 PM 7813982 ER PT J AU AGUILERA, G AF AGUILERA, G TI REGULATION OF PITUITARY ACTH-SECRETION DURING CHRONIC STRESS SO FRONTIERS IN NEUROENDOCRINOLOGY LA English DT Review DE ADRENOCORTICOTROPIC HORMONE; HYPOTHALAMIC-PITUITARY ADRENAL AXIS; STRESS; VASOPRESSIN; CORTICOTROPIN RELEASING HORMONE; CRH RECEPTORS; VP RECEPTORS ID CORTICOTROPIN-RELEASING-FACTOR; HYPOPHYSEAL PORTAL BLOOD; RAT ANTERIOR-PITUITARY; FACTOR MESSENGER-RNA; STIMULATED ADRENOCORTICOTROPIN SECRETION; PARVOCELLULAR NEUROSECRETORY NEURONS; PROOPIOMELANOCORTIN GENE-EXPRESSION; PARAVENTRICULAR NUCLEUS NEURONS; ARGININE VASOPRESSIN; MEDIAN-EMINENCE AB Maintenance of adequate levels of response of the hypothalamic-pituitary-adrenal axis during chronic stress is important for survival. Three basic patterns of response can be identified depending on the type of stress: (a) desensitization of ACTH responses to the sustained stimulus, but hyperresponsiveness to a novel stress despite elevated plasma glucocorticoid levels, as occurs in physical-psychological paradigms; (b) no desensitization of ACTH response to the repeated stimulus and hyperresponsiveness to a novel stress, as occurs during repeated painful stress and insulin hypoglycemia; and (c) small and transient increases in ACTH, but sustained elevations of plasma corticosterone and diminished ACTH responses. The level of response of the pituitary corticotroph is determined by differential regulation of the hypothalamic regulators, corticotropin-releasing hormone (CRH) and vasopressin (VP), and the sensitivity of the negative glucocorticoid feedback. While osmotic stimulation increases VP expression in magnocellular neurons of the paraventricular (PVN) and supraoptic nuclei of the hypothalamus, chronic stress paradigms with high pituitary responsiveness are associated with activation of CRH and CRH/VP parvicellular neurons of the PVN, predominantly of the VP-containing population. While moderate increase of CRH output is important for stimulation of POMC transcription, the increase of the VP:CRH secretion ratio appears to be important in maintaining the secretory capacity of the pituitary corticotroph during chronic stimulation. Decreased sensitivity of the glucocorticoid feedback, probably due to interaction of glucocorticoid receptors with transcription factors induced by CRH and VP, is critical for the maintenance of ACTH responses in the presence of elevated plasma glucocorticoid levels during chronic stress. Although both CRH and VP receptors are activated and undergo regulatory variations during chronic stress, only the changes in VP receptor levels are parallel to the changes in pituitary ACTH responsiveness. The inhibitory effect of chronic osmotic stimulation on ACTH secretion in spite of high circulating levels of VP is probably the result of diminished activity of parvicellular PVN neurons and downregulation of pituitary VP receptors. Although the exact interaction between regulatory factors and the molecular mechanisms controlling the sensitivity of the corticotroph during adaptation to chronic stress remain to be determined, it is clear that regulation of the proportional secretion of CRH and VP in the PVN, modulation of pituitary VP receptors, and the sensitivity to feedback inhibition play a critical role. (C) 1994 Academic Press, Inc. RP AGUILERA, G (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,ENDOCRINE PHYSIOL SECT,BLDG 10,ROOM 10N262,10 CTR DR MCSC1862,BETHESDA,MD 20892, USA. NR 170 TC 346 Z9 350 U1 3 U2 32 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0091-3022 J9 FRONT NEUROENDOCRIN JI Front. Neuroendocrinol. PD DEC PY 1994 VL 15 IS 4 BP 321 EP 350 DI 10.1006/frne.1994.1013 PG 30 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA PY681 UT WOS:A1994PY68100002 PM 7895891 ER PT J AU GIMENO, M PALLAS, M NEWMAN, AH CAMARASA, J ESCUBEDO, E AF GIMENO, M PALLAS, M NEWMAN, AH CAMARASA, J ESCUBEDO, E TI THE ROLE OF CYCLIC-NUCLEOTIDES IN THE ACTION OF PERIPHERAL-TYPE BENZODIAZEPINE RECEPTOR LIGANDS IN RAT AORTA SO GENERAL PHARMACOLOGY LA English DT Article DE PO 5-4864; AHN-086; PK 11195; PK 14105; PHOSPHODIESTERASE; AORTA (RAT) ID SELECTIVE INHIBITORS; VAS-DEFERENS; RELAXING FACTOR; PHOSPHODIESTERASE; ADENOSINE AB 1. Peripheral-type benzodiazepine ligands (Ro 5-4864, AHN-086, PK 11195 and PK 14105) inhibit, in a concentration-dependent and non-competitive manner, noradrenaline-induced contractions in isolated rat aortic rings (IC50 values: 24 +/- 1.8, 49 +/- 2.5, 15 +/- 1.2, 49 +/- 3.2 mu M, respectively). 2. This effect is probably not mediated by peripheral-type benzodiazepine receptors and is not related to the presence of endothelium. 3. All compounds inhibited phosphodiesterase activity in vitro. 4. From the results obtained with nucleotide analogs, calcium antagonists and specific inhibitors of PDE isoenzymes, it can be concluded that the actions of AHN-086 and PK 11195 are related to effects on PDE I, III and IV. C1 UNIV BARCELONA,FAC PHARM,PHARMACOL & PHARMACOGNOSY LAB,E-08028 BARCELONA,SPAIN. NIDA,ADDICT RES CTR,DRUG DEV GRP,BALTIMORE,MD 21224. RI Pallas, Merce /H-3129-2016; OI Pallas, Merce /0000-0003-3095-4254; Escubedo, Elena/0000-0002-5078-366X NR 23 TC 7 Z9 7 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-3623 J9 GEN PHARMACOL JI Gen. Pharmacol. PD DEC PY 1994 VL 25 IS 8 BP 1553 EP 1561 DI 10.1016/0306-3623(94)90354-9 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QF051 UT WOS:A1994QF05100003 PM 7721028 ER PT J AU IMREH, S KHOLODNYUK, I ALLIKMETTS, R STANBRIDGE, EJ ZABAROVSKY, ER KLEIN, G AF IMREH, S KHOLODNYUK, I ALLIKMETTS, R STANBRIDGE, EJ ZABAROVSKY, ER KLEIN, G TI NONRANDOM LOSS OF HUMAN-CHROMOSOME-3 FRAGMENTS FROM MOUSE-HUMAN MICROCELL HYBRIDS FOLLOWING PROGRESSIVE GROWTH IN SCID MICE SO GENES CHROMOSOMES & CANCER LA English DT Article ID RENAL-CELL CARCINOMA; TUMOR-SUPPRESSOR GENE; SHORT ARM; LUNG-CANCER; HETEROZYGOSITY; DELETION; REGION; LOCUS; TUMORIGENICITY; TRANSLOCATION AB Microcell hybrid lines of A9 mouse fibrosarcoma containing complete or partially deleted human chromosomes 3 (chr. 3) were inoculated into SCID mice. Cell lines derived from the tumors were examined by fluorescent in situ hybridization for the status of the transferred human chromosome and by PCR for marker loss. The SCID tumors arising after the inoculation of 10(5) cells were passaged serially in vivo and regularly showed loss of four markers; D3S1029 (3p21.3-21.2), AP20R (3p22-21.3, D3S32 (3p21.3-p21.2), and THRB (3p24). This regularly deleted region is bordered by markers GNA12 (3p21.1-p21.3) and VHL (3p25) that were maintained in a fraction of tumors. Fragments derived from the long arm of chromosome 3 and corresponding markers in the 3q26-q28 region were retained in all tumors. Our findings may be related to the postulated presence of tumor suppressor genes in the 3p24-p21 region as indicated by the frequent deletion of this region in renal and small cell lung carcinomas and other solid tumors. The technically cumbersome identification of suppressor genes may be supplemented by an ''elimination test'' based on analogous principles. (C) 1994 Wiley-Liss, Inc. C1 NIH,VIRAL CARCINOGENESIS LAB,FREDERICK,MD. UNIV CALIF IRVINE,DEPT MICROBIOL & MOLEC GENET,IRVINE,CA 92717. RP IMREH, S (reprint author), KAROLINSKA INST,CTR MICROBIOL & TUMOR BIOL,BOX 280,S-17177 STOCKHOLM,SWEDEN. RI Zabarovsky, Eugene/A-6645-2010; OI Holodnuka, Irina/0000-0002-7208-4499 FU NCI NIH HHS [5RO1CA14054] NR 36 TC 42 Z9 46 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD DEC PY 1994 VL 11 IS 4 BP 237 EP 245 DI 10.1002/gcc.2870110406 PG 9 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA QF961 UT WOS:A1994QF96100005 PM 7533527 ER PT J AU COUCH, FJ KIOUSIS, S CASTILLA, LH XU, JH CHANDRASEKHARAPPA, SC CHAMBERLAIN, JS COLLINS, FS WEBER, BL AF COUCH, FJ KIOUSIS, S CASTILLA, LH XU, JH CHANDRASEKHARAPPA, SC CHAMBERLAIN, JS COLLINS, FS WEBER, BL TI CHARACTERIZATION OF 10 NEW POLYMORPHIC DINUCLEOTIDE REPEATS AND GENERATION OF A HIGH-DENSITY MICROSATELLITE-BASED PHYSICAL MAP OF THE BRCA1 REGION OF CHROMOSOME-17Q21 SO GENOMICS LA English DT Article ID FAMILIAL BREAST; OVARIAN-CANCER; GENETIC-ANALYSIS; LINKAGE AB A familial early onset breast cancer gene (BRCA1) has been localized to chromosome 17q21. To aid in the identification of this gene a number of new microsatellite markers from the D17S857 to D17S78 region were isolated and characterized. These markers, along with previously published markers from the region, were localized on a physical map by STS content mapping of cosmids from the BRCA1 interval. This high-density STS map of the BRCA1 region will be useful for linkage studies of families with apparent inherited breast cancer and for loss of heterozygosity analysis of breast tumor DNAs. (C) 1994 Academic Press,Inc. C1 UNIV PENN,DEPT INTERNAL MED,PHILADELPHIA,PA 19104. UNIV PENN,DEPT GENET,PHILADELPHIA,PA 19104. UNIV MICHIGAN,SCH MED,DEPT HUMAN GENET,ANN ARBOR,MI 48109. UNIV MICHIGAN,CTR HUMAN GENOME,ANN ARBOR,MI 48109. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. FU NCI NIH HHS [CA-57601] NR 19 TC 10 Z9 10 U1 0 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD DEC PY 1994 VL 24 IS 3 BP 419 EP 424 DI 10.1006/geno.1994.1647 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA PZ985 UT WOS:A1994PZ98500001 PM 7713491 ER PT J AU NEWTON, G WEREMOWICZ, S MORTON, CC COPELAND, NG GILBERT, DJ JENKINS, NA LAWLER, J AF NEWTON, G WEREMOWICZ, S MORTON, CC COPELAND, NG GILBERT, DJ JENKINS, NA LAWLER, J TI CHARACTERIZATION OF HUMAN AND MOUSE CARTILAGE OLIGOMERIC MATRIX PROTEIN SO GENOMICS LA English DT Article ID PLATELET THROMBOSPONDIN; EXTRACELLULAR-MATRIX; SEQUENCE ALIGNMENT; GENE; LOCALIZATION; CHROMOSOMES; EXPRESSION; FAMILY; GROWTH AB Cartilage oligomeric matrix protein (COMP) is a 524,000-Da protein that is expressed at high levels in the territorial matrix of chondrocytes. The sequences of rat and bovine COMP indicate that it is a member of the thrombospondin gene family. In this study, we have cloned and sequenced human COMP. Phylogenetic analysis using progressive sequence alignment and two parsimony-based algorithms indicates that the COMP gene and a precursor of the thrombospondin-3 and -4 genes were produced by a gene duplication that occurred 750 million years ago. An interspecific backcross mapping panel has been used to map the murine COMP gene to the central region of mouse chromosome 8. Southern blot analysis of a somatic cell hybrid DNA panel and in situ hybridization to human metaphase chromosomes indicate that the human COMP gene is located on chromosome 19 in band p13.1, These data confirm and extend the known regions of homology between human and mouse chromosomes and establish that COMP, like thrombospondin-1, -2, -3, and -4, is present in the human and mouse genomes. (C) 1994 Academic Press, Inc. C1 BRIGHAM & WOMENS HOSP,LMRC,DEPT PATHOL,DIV VASC RES,BOSTON,MA 02115. BRIGHAM & WOMENS HOSP,DEPT PATHOL,CYTOGENET LAB,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NCI,FREDERICK CANC RES & DEV CTR,MAMMALIAN GENET LAB,ABL,BASIC RES PROGRAM,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101]; NHLBI NIH HHS [HL28749, HL49081] NR 26 TC 123 Z9 127 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD DEC PY 1994 VL 24 IS 3 BP 435 EP 439 DI 10.1006/geno.1994.1649 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA PZ985 UT WOS:A1994PZ98500003 PM 7713493 ER PT J AU HUDSON, TJ COLBERT, AME REEVE, MP BAE, JS LEE, MK NUSSBAUM, RL BUDARF, ML EMANUEL, BS FOOTE, S AF HUDSON, TJ COLBERT, AME REEVE, MP BAE, JS LEE, MK NUSSBAUM, RL BUDARF, ML EMANUEL, BS FOOTE, S TI ISOLATION AND REGIONAL MAPPING OF 110 CHROMOSOME-22 STSS SO GENOMICS LA English DT Note ID HUMAN GENOME; LIBRARIES AB As part of a larger effort to create a complete physical map of the human genome, we have developed 110 new STSs specific for human chromosome 22. Clones isolated and sequenced from chromosome 22-enriched libraries provided a source of primers. These STSs were localized to regions of chromosome 22 using a panel of somatic cell hybrids. In building a refined physical map of chromosome 22, this set of STSs should provide a substantial backbone. (C) 1994 Academic Press, Inc. C1 NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. UNIV PENN,SCH MED,DEPT PEDIAT,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT GENET,PHILADELPHIA,PA 19104. CHILDRENS HOSP PHILADELPHIA,DIV HUMAN GENET & MOLEC BIOL,PHILADELPHIA,PA 19104. RP HUDSON, TJ (reprint author), MIT,WHITEHEAD INST BIOMED RES,CTR GENOME RES,1 KENDALL SQ,BLDG 300,CAMBRIDGE,MA 02139, USA. RI Foote, Simon/F-2802-2013; OI Foote, Simon/0000-0002-9142-2107 FU NHGRI NIH HHS [P50-HG00098] NR 13 TC 8 Z9 8 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD DEC PY 1994 VL 24 IS 3 BP 588 EP 592 DI 10.1006/geno.1994.1671 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA PZ985 UT WOS:A1994PZ98500025 PM 7713513 ER PT J AU YAMANAKA, S JOHNSON, ON LYU, MS KOZAK, CA PROIA, RL AF YAMANAKA, S JOHNSON, ON LYU, MS KOZAK, CA PROIA, RL TI THE MOUSE GENE ENCODING THE G(M2) ACTIVATOR PROTEIN (GM2A) - CDNA SEQUENCE, EXPRESSION, AND CHROMOSOME MAPPING SO GENOMICS LA English DT Note ID GM2-ACTIVATOR PROTEIN; LOCALIZATION; RECEPTOR; CLONING AB The G(M2) activator protein forms a substrate-complex with G(M2) ganglioside, which enables degradation of the ganglioside by beta-hexosaminidase A. Mutations in the human G(M2) activator protein gene (GM2A) result in the G(M2) gangliosidosis AB variant, a severe neurological disease. We have isolated and sequenced a mouse G(M2) activator protein (Gm2a) cDNA with complete protein coding and 3' untranslated regions. Expression of the Gm2a transcript (similar to 2.3 kb) was apparent in all tissues examined and was most abundant in kidney and testis. The Gm2a gene was mapped to a region on mouse chromosome (Chr) 11 that is homologous with a segment of human chromosome 5 containing the orthologous human gene. In addition, a Gm2a-related sequence (Gm2a-rs1) was mapped to mouse Chr 5. (C) 1994 Academic Press, Inc. C1 NIDDKD,BIOCHEM GENET SECT,GENET & BIOCHEM BRANCH,BETHESDA,MD 20892. NIAID,BETHESDA,MD 20892. RI Proia, Richard/A-7908-2012 NR 17 TC 5 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD DEC PY 1994 VL 24 IS 3 BP 601 EP 604 DI 10.1006/geno.1994.1674 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA PZ985 UT WOS:A1994PZ98500028 PM 7713516 ER PT J AU GERKEN, S FISH, K UYAR, D POLYMEROPOULOS, MH BRADLEY, P WHITE, R OVERHAUSER, J SILVERMAN, GA AF GERKEN, S FISH, K UYAR, D POLYMEROPOULOS, MH BRADLEY, P WHITE, R OVERHAUSER, J SILVERMAN, GA TI INTEGRATION OF 28 STSS INTO THE PHYSICAL MAP OF HUMAN-CHROMOSOME-18 SO GENOMICS LA English DT Note ID GENES C1 HARVARD UNIV,CHILDRENS HOSP,SCH MED,JOINT PROGRAM NEONATOL,BOSTON,MA 02115. UNIV UTAH,DEPT HUMAN GENET,SALT LAKE CITY,UT 84112. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. THOMAS JEFFERSON UNIV,DEPT BIOCHEM,PHILADELPHIA,PA 19107. FU NHGRI NIH HHS [HG00367, HG00167]; NICHD NIH HHS [HD28475] NR 9 TC 10 Z9 10 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD DEC PY 1994 VL 24 IS 3 BP 612 EP 613 DI 10.1006/geno.1994.1679 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA PZ985 UT WOS:A1994PZ98500034 PM 7713522 ER PT J AU TAKAI, S FERNANDEZSALGUERO, P KIMURA, S GONZALEZ, FJ YAMADA, K AF TAKAI, S FERNANDEZSALGUERO, P KIMURA, S GONZALEZ, FJ YAMADA, K TI ASSIGNMENT OF THE HUMAN DIHYDROPYRIMIDINE DEHYDROGENASE GENE (DPYD) TO CHROMOSOME REGION 1P22 BY FLUORESCENCE IN-SITU HYBRIDIZATION SO GENOMICS LA English DT Note ID FAMILIAL PYRIMIDINEMIA; PURIFICATION; TOXICITY; LIVER; 5-FLUOROURACIL C1 NCI,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. RP TAKAI, S (reprint author), INT MED CTR JAPAN,RES INST,DEPT GENET,SHINJUKU KU,1-21-1 TOYAMA CHO,TOKYO 162,JAPAN. OI Fernandez-Salguero, Pedro M./0000-0003-2839-5027 NR 14 TC 33 Z9 36 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD DEC PY 1994 VL 24 IS 3 BP 613 EP 614 DI 10.1006/geno.1994.1680 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA PZ985 UT WOS:A1994PZ98500035 PM 7713523 ER PT J AU QASBA, PK BALAJI, PV RAO, VSR AF QASBA, PK BALAJI, PV RAO, VSR TI MOLECULAR-DYNAMICS SIMULATIONS OF OLIGOSACCHARIDES AND THEIR CONFORMATION IN THE CRYSTAL-STRUCTURE OF LECTIN CARBOHYDRATE COMPLEX - IMPORTANCE OF THE TORSION ANGLE-PSI FOR THE ORIENTATION OF ALPHA-1,6-ARM SO GLYCOBIOLOGY LA English DT Article DE BISECTING GLCNAC; CARBOHYDRATES; GLYCOPROTEIN; LECTIN-SACCHARIDE COMPLEX ID MONOFUCOSYLATED BIANTENNARY GLYCAN; N-LINKED OLIGOSACCHARIDES; CONCANAVALIN-A; 3-DIMENSIONAL STRUCTURES; ACETYLLACTOSAMINE TYPE; ENERGY CALCULATIONS; FORCE-FIELD; DATA-BANK; OCTASACCHARIDE; GLYCOPROTEINS AB The conformation of the heptasaccharide Man-alpha 1,6(Man-alpha 1,3)(Xyl-beta 1,2)-Man-beta 1,4-GlcNAc(2)-beta 1,4-(L-Fuc-alpha 1,3)-GlcNAc(1), the carbohydrate moiety of Erythrina corallodendron lectin (EcorL), the hexasaccharide Man-alpha 1,6-(Man-alpha 1,3) (GlcNAc-beta 1,4)-Man-beta 1,4-GlcNAc-beta 1,4-GlcNAc and their disaccharide fragments have been studied by molecular dynamics (Mo) simulations for 1000 ps with different initial conformations, In the isolated heptasaccharide, the most frequently accessed conformation during Mn has a psi value of 180 degrees around Man-alpha 1,6-Man linkage, This conformation is stabilized by the formation of a hydrogen bond between the carbonyl oxygen of GlcNAc(2) with the O3/O4 hydroxyls of the alpha 1,6-linked mannose residue, The conformation of the heptasaccharide found in the crystal structure of the EcorL-lactose complex (Shaanan ed al., Science, 254, 862, 1991), that has a psi value of similar to 76 degrees around Man-alpha 1,6-Man linkage, is accessed, although less frequently, during Mn of the isolated oligosaccharide. The phi,psi,chi = 58 degrees, -134 degrees, -60 degrees conformation around Man-alpha(1),6-Man fragment observed in the crystal structure of the Lathyrus ochrus lectin complexed with a biantennary octasaccharide (Table I in Homans, S. W., Glycobiology, 3, 551, 1993) has also been accessed in the present Mn simulations, These psi values for the alpha 1,6-linkage, which are observed in the protein-carbohydrate crystal structures and are accessed in the Mn simulations,though occasionally, have not been predicted from NMR studies, Furthermore, these different values of psi lead to significantly different orientations of the alpha 1,6arm for the same value of chi. This contrasts,vith the earlier predictions that only different values of chi can bring about significant changes in the orientation of the alpha(1),6-arm. The MD simulations also show that the effects of bisecting GlcNAc or beta 1,2-xylose are very similar on the alpha(1),3-arm and slightly different on the alpha(1),6-arm. RP QASBA, PK (reprint author), NCI,MATH BIOL LAB,BLDG PK 5,ROOM 410,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 43 TC 19 Z9 19 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD DEC PY 1994 VL 4 IS 6 BP 805 EP 815 DI 10.1093/glycob/4.6.805 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA QF341 UT WOS:A1994QF34100008 PM 7734844 ER PT J AU CHRISTIAN, MC TRIMBLE, EL AF CHRISTIAN, MC TRIMBLE, EL TI SALVAGE CHEMOTHERAPY FOR EPITHELIAL OVARIAN-CARCINOMA SO GYNECOLOGIC ONCOLOGY LA English DT Article; Proceedings Paper CT NIH Consensus Development Conference on Ovarian Cancer: Screening, Treatment, and Follow-Up CY APR 05-07, 1994 CL BETHESDA, MD SP NIH ID GYNECOLOGIC-ONCOLOGY-GROUP; HIGH-DOSE CARBOPLATIN; PHASE-II TRIAL; COLONY-STIMULATING FACTOR; CANCER PATIENTS; CIS-DIAMMINEDICHLOROPLATINUM; COMBINATION CHEMOTHERAPY; ETOPOSIDE VP-16-213; 2ND-LINE TREATMENT; ORAL ETOPOSIDE AB Advanced epithelial ovarian cancer is a highly chemosensitive solid tumor with response rates of 70-80% to first-line chemotherapy, including a high proportion of complete responses. The majority of patients, however, eventually relapse and ultimately die of chemoresistant disease. Response rates to salvage agents are modest, and duration of response is relatively short. Important new agents have been identified in the salvage setting, however, and all patients with ovarian cancer recurring or persisting after front-line therapy should be encouraged to enroll in clinical trials. Phase II trials should include multiple adequately sized cohorts, for patients with platinum-sensitive disease and those with platinum-refractory disease. In addition, patients should be stratified by treatment-free interval. An effort should be made to report standard response endpoints, such as median duration of response, median time to progression, and median survival. Retreatment with a platinum-containing compound is appropriate in patients with platinum-sensitive disease. Trials of high-dose chemotherapy with hematologic support may be most appropriate for patients with minimal disease following first-line therapy, but are unlikely to benefit patients with platinum-resistant or bulky disease. Paclitaxel should figure prominently in consideration of salvage therapy for patients with platinum-resistant disease. Responses to other single agents or combination chemotherapy have been modest and generally of short duration. Efforts at hormonal therapy have been disappointing. Promising new agents include topoisomerase I inhibitors, such as topotecan, 9-aminocamptothecin, irinotecan (CPT-11), and pyrazoloacridine. Therapies focusing on novel molecular targets include antiangiogenesis agents, antimetastatic agents, and signal transduction inhibitors. Immunotherapy, including radioimmunotherapy, immunotoxins, and direct antitumor effects of monoclonal antibodies, may be useful. Greater understanding of the molecular pathology of ovarian cancer may help us develop more rational and effective treatment. (C) 1994 Academic Press, Inc. RP CHRISTIAN, MC (reprint author), NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,BETHESDA,MD 20892, USA. NR 74 TC 31 Z9 32 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD DEC PY 1994 VL 55 IS 3 BP S143 EP S150 DI 10.1006/gyno.1994.1354 PN 2 PG 8 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA QF352 UT WOS:A1994QF35200023 PM 7835799 ER PT J AU KRAMER, BS GOHAGAN, J PROROK, PC AF KRAMER, BS GOHAGAN, J PROROK, PC TI NIH CONSENSUS 1994 - SCREENING SO GYNECOLOGIC ONCOLOGY LA English DT Article; Proceedings Paper CT NIH Consensus Development Conference on Ovarian Cancer: Screening, Treatment, and Follow-Up CY APR 05-07, 1994 CL BETHESDA, MD SP NIH ID CANCER AB Frequently, the medical and lay community has assumed that earlier diagnosis of cancer of any type automatically confers benefit and that any diagnostic test that can identify early stages of disease must therefore be useful for screening. However, there is an emerging science of screening which affords a more rigorous approach to public health recommendations in the application of new technologies to screening and early detection. A number of public health groups and agencies are using an evidence-based approach in making recommendations. Using this approach, early detection methods for ovarian cancer would meet only the weakest level of evidence to support their routine application in asymptomatic women. For this reason, the National Cancer Institute has recently launched a large randomized clinical trial to test the effectiveness of screening for ovarian cancer. RP KRAMER, BS (reprint author), NCI,DIV CANC PREVENT & CONTROL,BETHESDA,MD 20892, USA. NR 5 TC 9 Z9 9 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD DEC PY 1994 VL 55 IS 3 BP S20 EP S21 DI 10.1006/gyno.1994.1335 PN 2 PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA QF352 UT WOS:A1994QF35200004 PM 7835804 ER PT J AU TRIMBLE, CL TRIMBLE, EL AF TRIMBLE, CL TRIMBLE, EL TI MANAGEMENT OF EPITHELIAL OVARIAN-TUMORS OF LOW MALIGNANT POTENTIAL SO GYNECOLOGIC ONCOLOGY LA English DT Article; Proceedings Paper CT NIH Consensus Development Conference on Ovarian Cancer: Screening, Treatment, and Follow-Up CY APR 05-07, 1994 CL BETHESDA, MD SP NIH ID CELLULAR DNA CONTENT; TERM FOLLOW-UP; FLOW CYTOMETRIC ANALYSIS; BORDERLINE MALIGNANCY; MUCINOUS TUMORS; PROGNOSTIC-SIGNIFICANCE; PSEUDOMYXOMA PERITONEI; BRENNER TUMORS; SEROUS TUMORS; NEOPLASMS AB The distinct pathologic and biologic nature of ovarian tumors of low malignant potential (LMP) has been officially recognized by FIGO and the World Health Organization. LMP tumors may comprise 10% of ovarian neoplasms; they occur at a mean age of 40 years. Pregnancy, breast-feeding, and the use of oral contraceptives are protective against the development of tumors of LMP. A history of infertility and use of infertility drugs appear to increase the risk of these tumors. No association with hereditary ovarian cancer syndromes has been reported. The survival associated with these tumors is 99% at mean follow-up of 7 years for patients with stage I disease, and 92% for those with stage II and II disease. Retrospectively, more patients appear to have died from complications associated with adjuvant therapy than from progressive disease. The recommended treatment is surgical, consisting of total abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic lymph node biopsies, peritoneal washings, and tumor debulking. In young patients with early-stage disease, conservative surgery, preserving the uterus and contralateral ovary, is acceptable. A role has not yet been established for adjuvant therapy, whether radiotherapy or chemotherapy. Laboratory investigations have not demonstrated that these tumors represent an intermediate step between benign ovarian tumors and carcinoma nor have they identified that small subset of tumors with aggressive clinical behavior. We should perhaps consider tumors of LMP in the same light as ''benign'' proliferative gynecologic conditions, such as endometriosis and leiomyomata. (C) 1994 Academic Press, Inc. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT GYNECOL & OBSTET,BALTIMORE,MD 21218. NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,BETHESDA,MD 20892. RP TRIMBLE, CL (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT PATHOL,BALTIMORE,MD 21218, USA. NR 77 TC 24 Z9 24 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD DEC PY 1994 VL 55 IS 3 BP S52 EP S61 DI 10.1006/gyno.1994.1342 PN 2 PG 10 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA QF352 UT WOS:A1994QF35200011 PM 7835812 ER PT J AU TRIMBLE, EL ARBUCK, SG MCGUIRE, WP AF TRIMBLE, EL ARBUCK, SG MCGUIRE, WP TI OPTIONS FOR PRIMARY CHEMOTHERAPY OF EPITHELIAL OVARIAN-CANCER - TAXANES SO GYNECOLOGIC ONCOLOGY LA English DT Article; Proceedings Paper CT NIH Consensus Development Conference on Ovarian Cancer: Screening, Treatment, and Follow-Up CY APR 05-07, 1994 CL BETHESDA, MD SP NIH ID PHASE-I TRIAL; HYPERSENSITIVITY REACTIONS; TAXOL; PACLITAXEL; AGENT; TOXICITIES; INFUSION AB The taxanes, a new class of anticancer agents, act by promoting the assembly of microtubules and stabilizing formed tubules. Two taxanes, paclitaxel and docetaxel, have clinical activity in epithelial ovarian carcinomas, including tumors with platinum resistance. Toxicities associated with the taxanes include hypersensitivity, leukopenia, neurotoxocity, and alopecia. Premedication with dexamethasone, diphenhydramine, and cimetidine decreases the incidence of severe anaphylactic reactions to less than 3%. In Phase II studies, response rates to paclitaxel in patients with previously treated ovarian cancer ranged from 20 to 48%. To date, only two Phase III study using paclitaxel in the treatment of ovarian cancer have mature data. In one trial in patients with suboptimally debulked stage III and IV ovarian cancer, conducted by the-Gynecologic Oncology Group, patients receiving paclitaxel/cisplatin had a significantly greater clinical response rate and surgical response rate and a significantly smaller risk of progression than those of patients receiving cisplatin/cyclophosphamide. In a Phase III study of paclitaxel in previously treated patients at two different schedules (3- and 24-hr infusions), conducted by the Canadian-European Taxol Cooperative Group, patients on the 24-hr infusion experienced significantly more grade 4 neutropenia than those receiving the 3-hr infusion. The optimal dose, schedule, and combination for paclitaxel in the treatment of patients with ovarian cancer have not yet been defined. In Phase II studies of docetaxel in patients with previously treated ovarian cancer, response rates of 33-35% were noted. Peripheral edema was noted to be a clinically significant toxicity. (C) 1994 Academic Press, Inc. C1 EMORY UNIV,DEPT HEMATOL ONCOL,ATLANTA,GA 30322. RP TRIMBLE, EL (reprint author), NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,BETHESDA,MD 20892, USA. NR 43 TC 7 Z9 7 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD DEC PY 1994 VL 55 IS 3 BP S114 EP S121 DI 10.1006/gyno.1994.1349 PN 2 PG 8 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA QF352 UT WOS:A1994QF35200018 PM 7835794 ER PT J AU TRIMBLE, EL AF TRIMBLE, EL TI THE NIH CONSENSUS CONFERENCE ON OVARIAN-CANCER - SCREENING, TREATMENT, AND FOLLOW-UP - INTRODUCTION SO GYNECOLOGIC ONCOLOGY LA English DT Editorial Material RP TRIMBLE, EL (reprint author), NCI,DEPT HLTH & HUMAN SERV,BETHESDA,MD 20894, USA. NR 0 TC 23 Z9 23 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD DEC PY 1994 VL 55 IS 3 BP S1 EP S3 DI 10.1006/gyno.1994.1332 PN 2 PG 3 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA QF352 UT WOS:A1994QF35200001 PM 7835792 ER PT J AU GLANZ, K PATTERSON, RE KRISTAL, AR DICLEMENTE, CC HEIMENDINGER, J LINNAN, L MCLERRAN, DF AF GLANZ, K PATTERSON, RE KRISTAL, AR DICLEMENTE, CC HEIMENDINGER, J LINNAN, L MCLERRAN, DF TI STAGES OF CHANGE IN ADOPTING HEALTHY DIETS - FAT, FIBER, AND CORRELATES OF NUTRIENT INTAKE SO HEALTH EDUCATION QUARTERLY LA English DT Article ID BEHAVIOR-CHANGE; NUTRITION; KNOWLEDGE; ATTITUDES; PREVENTION; REDUCTION; CAMPAIGN; MODELS; PEOPLE AB The stages of change construct, which addresses the readiness to change, has only recently been applied to dietary behavior, such as fat consumption. This article describes the application of the stages of change construct to dietary fat and fiber consumption and examines the association of dietary stages to eating practices and related demographic and psychosocial factors in a large, geographically diverse population of workers. We present results from the baseline survey of 17,121 employees in the Working Well Trial. We assessed stage from an algorithm based on seven items and measured dietary intake with an 88-item food frequency questionnaire. Findings indicated that a greater proportion of the population has actively tried to reduce fat intake than to consume more fiber. Stage of change was associated with fat, fiber, and fruit and vegetable intake in a stepwise manner, as predicted. In multivariate analyses that controlled for demographic characteristics, stage of change predicted between 8 and 13% of the variance in dietary intake, and more than demographic variables. These findings have implications for the design of nutrition interventions and for the evaluation of intermediate outcomes. C1 FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. UNIV WASHINGTON,FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98195. UNIV WASHINGTON,DEPT EPIDEMIOL,SEATTLE,WA 98195. UNIV HOUSTON,DEPT PSYCHOL,HOUSTON,TX 77004. NCI,BETHESDA,MD 20892. BROWN UNIV,MIRIAM HOSP,PROVIDENCE,RI 02912. UNIV HAWAII,DEPT PUBL HLTH,HONOLULU,HI 96813. RP GLANZ, K (reprint author), UNIV HAWAII,CANC RES CTR HAWAII,1236 LAUHALA ST,HONOLULU,HI 96813, USA. OI Kristal, Alan/0000-0002-7329-1617 FU NCI NIH HHS [U01 CA51671, U01 CA51686, U01 CA51687] NR 44 TC 167 Z9 172 U1 1 U2 17 PU SAGE PUBL INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 0195-8402 J9 HEALTH EDUC QUART JI Health Educ. Q. PD WIN PY 1994 VL 21 IS 4 BP 499 EP 519 DI 10.1177/109019819402100412 PG 21 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA QF978 UT WOS:A1994QF97800008 PM 7843980 ER PT J AU LEE, JH KLEIN, HG AF LEE, JH KLEIN, HG TI MONONUCLEAR CELL ADOPTIVE IMMUNOTHERAPY SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Review ID TUMOR-INFILTRATING LYMPHOCYTES; BONE-MARROW TRANSPLANTATION; ACTIVATED KILLER-CELLS; CHRONIC MYELOGENOUS LEUKEMIA; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; PERIPHERAL-BLOOD LYMPHOCYTES; RECURRENT SPONTANEOUS-ABORTION; DONOR LEUKOCYTE INFUSIONS; CHRONIC MYELOID-LEUKEMIA; T-CELL AB In contrast with red cells, platelets, and granulocytes, hemotherapy using lymphocytes and monocytes is only beginning to be explored. Blood banks and transfusion services, the traditional sources of expertise in sterile cell processing, storage, and transfusion, have played an integral role in the early technical development of mononuclear cell adoptive immunotherapy, and are logical partners in its future. This article reviews the clinical experience with this novel transfusion therapy. RP LEE, JH (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT TRANSFUS MED,BLDG 10,ROOM 1C-711,BETHESDA,MD 20892, USA. NR 109 TC 7 Z9 7 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD DEC PY 1994 VL 8 IS 6 BP 1203 EP 1221 PG 19 WC Oncology; Hematology SC Oncology; Hematology GA PT766 UT WOS:A1994PT76600011 PM 7860445 ER PT J AU MAHANEY, K TEDESCHI, V MAERTENS, G DIBISCEGLIE, AM VERGALLA, J HOOFNAGLE, JH SALLIE, R AF MAHANEY, K TEDESCHI, V MAERTENS, G DIBISCEGLIE, AM VERGALLA, J HOOFNAGLE, JH SALLIE, R TI GENOTYPIC ANALYSIS OF HEPATITIS-C VIRUS IN AMERICAN PATIENTS SO HEPATOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; 5' NONCODING REGION; SEQUENCE-ANALYSIS; NON-A; RNA; THERAPY AB We examined hepatitis C virus genotypes in 98 American patients with chronic hepatitis C virus infection by means of two methods; restriction fragment length polymorphism analysis and line probe assay, which is based on type-specific sequence variations in the 5' untranslated region. Type 1 was present in 73 patients (74%), type 2 in 15 (15%), type 3 in 6 (6%) and type 4 in 1 (1%). Line probe assay further subdivided type 1 into 1a (n = 35) and type 1b (n = 37) and type 2 into type 2a (n = 6) and 2b (n = 9). Two patients (2%) had both restriction fragment length polymorphism and line probe assay evidence of dual infection (with types 1 and type 2) while another ease had both type 1a and 1b by line probe assay. One patient was untypable by either technique. There was no correlation between infecting genotype and presumed cause, serum indexes of necroinflammatory activity, or age or sex of the patients studied or known duration of infection. Patients with type 2 hepatitis C virus had more severe liver disease histologically (p = 0.0027) compared with other genotypes but, paradoxically, had significantly lower levels of circulating hepatitis C virus RNA (12.1 +/- 12.8 x 10(5) genome equivalents/ml) than other types (36.4 +/- 44.8 x 10(5) genome equivalents/ml, p < 0.001). Response to interferon was less likely to be sustained in patients infected with type 1 than in those infected with other types (7% vs. 40%, p < 0.05). Thus hepatitis C virus genotype may have some influence on the clinical pattern of hepatitis, particularly with regard to the disease severity and response to interferon. The restriction fragment length polymorphism and line probe assays produced concordant results in 97 of 98 cases; however, whereas restriction fragment length polymorphism provides a relatively easy and reliable method for genotyping hepatitis C virus, the line probe assay assay is more rapid, uses standardized reagents, does not require radioisotopes and has the advantage of distinguishing the subtypes of genotype 1 and 2. C1 NIDDKD,LIVER DIS SECT,BETHESDA,MD 20892. US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. INNOGENET NV,B-9052 ZWIJNAARDE,BELGIUM. NR 22 TC 180 Z9 181 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD DEC PY 1994 VL 20 IS 6 BP 1405 EP 1411 DI 10.1002/hep.1840200605 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PV634 UT WOS:A1994PV63400004 PM 7982639 ER PT J AU CHAN, JKC BANKS, PM CLEARY, ML DELSOL, G DEWOLFPEETERS, C FALINI, B GATTER, KC GROGAN, TM HARRIS, NL ISAACSON, PG JAFFE, BS KNOWLES, DM MASON, DY MULLERHERMELINK, HK PILERI, SA PIRIS, MA RALFKIAER, E STEIN, H WARNKE, RA AF CHAN, JKC BANKS, PM CLEARY, ML DELSOL, G DEWOLFPEETERS, C FALINI, B GATTER, KC GROGAN, TM HARRIS, NL ISAACSON, PG JAFFE, BS KNOWLES, DM MASON, DY MULLERHERMELINK, HK PILERI, SA PIRIS, MA RALFKIAER, E STEIN, H WARNKE, RA TI A PROPOSAL FOR CLASSIFICATION OF LYMPHOID NEOPLASMS (BY THE INTERNATIONAL LYMPHOMA STUDY-GROUP) SO HISTOPATHOLOGY LA English DT Article DE LYMPHOMA; NON-HODGKINS LYMPHOMA; HODGKINS DISEASE; CLASSIFICATION AB A new classification of lymphoid neoplasms, mostly based on existing terminology, is proposed by the International Lymphoma Study Group. The proposed classification was reached through a consensus of the members, despite their diverse backgrounds, and consists of a listing of currently recognized clinicopathological entities. These tumours are divided into three major categories: B-cell neoplasms, T-cell and postulated natural killer cell neoplasms, and Hodgkin's disease. The characterization of each entity is based on a synthesis of all available information. This concept departs from a purely morphological approach to lymphoma classification, which is considered to be inadequate, because many biologically distinctive lymphoma types can exhibit a broad and overlapping morphological spectrum. Some entities are provisional, pending further data to confirm that their recognition is reproducible. The salient clinicopathological features of each entity are summarized in this review. C1 UNIV TEXAS,HLTH SCI CTR,SAN ANTONIO,TX. STANFORD UNIV,SCH MED,STANFORD,CA. UNIV TOULOUSE 3,FAC MED PURPAN,TOULOUSE,FRANCE. CATHOLIC UNIV LEUVEN,LOUVAIN,BELGIUM. UNIV PERUGIA,INST HAEMATOL,PERUGIA,ITALY. UNIV OXFORD,JOHN RADCLIFFE HOSP,OXFORD OX3 9DU,ENGLAND. UNIV ARIZONA,SCH MED,TUCSON,AZ. HARVARD UNIV,MASSACHUSETTS GEN HOSP,SCH MED,BOSTON,MA. UNIV COLL & MIDDLESEX HOSP,LONDON,ENGLAND. NCI,BETHESDA,MD 20892. CORNELL UNIV,MED CTR,NEW YORK HOSP,NEW YORK,NY. UNIV WURZBURG,W-8700 WURZBURG,GERMANY. UNIV BOLOGNA,BOLOGNA,ITALY. HOSP VIRGEN SALUD,TOLEDO,SPAIN. UNIV COPENHAGEN,HERLEV,DENMARK. FREE UNIV BERLIN,KLINIKUM STEGLITZ,W-1000 BERLIN,GERMANY. RP CHAN, JKC (reprint author), QUEEN ELIZABETH HOSP,DEPT PATHOL,WYLIE RD,KOWLOON,HONG KONG. OI Piris, Miguel A/0000-0001-5839-3634 NR 6 TC 88 Z9 89 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0309-0167 J9 HISTOPATHOLOGY JI Histopathology PD DEC PY 1994 VL 25 IS 6 BP 517 EP 536 DI 10.1111/j.1365-2559.1994.tb01371.x PG 20 WC Cell Biology; Pathology SC Cell Biology; Pathology GA PY476 UT WOS:A1994PY47600002 PM 7698729 ER PT J AU CHUAH, MKL VANDENDRIESSCHE, T CHANG, HK ENSOLI, B MORGAN, RA AF CHUAH, MKL VANDENDRIESSCHE, T CHANG, HK ENSOLI, B MORGAN, RA TI INHIBITION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 BY RETROVIRAL VECTORS EXPRESSING ANTISENSE-TAR SO HUMAN GENE THERAPY LA English DT Article ID TRANS-ACTIVATOR; GENE-TRANSFER; REPLICATION; SEQUENCES; PROTEIN; CELLS; HIV; TRANSACTIVATION; INVITRO; THERAPY AB The human immunodeficiency virus type-1 (HIV-1) Tat activation response (TAR) region is essential for Tat-mediated trans-activation of the HIV-I long terminal repeat (LTR), The TAR element is present on the 5' and 3' ends of all HIV-1 transcripts and is relatively conserved among different HIV-1 isolates. These properties make it an attractive target for anti-HIV-1 gene therapy strategies, We have constructed a Moloney murine leukemia-based retroviral vector that expresses a chimeric tRNA(i)Met-antisense TAR fusion transcript complementary to the HIV-1 TAR region. The potential of this anti-TAR retroviral vector to inhibit HIV-1 was initially tested by transient transfections with an HIV-1-LTR-Tat expression plasmid into HeLa-CAT cells, Anti-TAR inhibited Tat-mediated HIV-1 LTR-driven CAT reporter gene expression in a dose-dependent fashion, The antisense-TAR vector was then used to transduce the human SupT1 T cell line, Cotransfection of these SupT1 cells with a Tat expression plasmid plus an HIV-1 LTR-CAT reporter plasmid resulted in decreased CAT gene expression in comparison to control transduced SupT1 cells, The antisense-TAR engineered SupT1 cell line was then challenged with HIV-1(MN). HIV-1 viral production was inhibited in SupT1 cells transduced with the antisense-TAR retroviral vector, Greater inhibition of HIV-1 was observed with antisense-TAR as compared to antisense-Tat expressing retroviral vector, These observations suggest that antisense-TAR retroviral vectors are potentially useful for clinical anti-HIV-1 gene therapy. C1 NIH,NATL CTR HUMAN GENOME RES,CLIN GENE THERAPY BRANCH,BETHESDA,MD 20892. GENET THERAPY INC,GAITHERSBURG,MD 20878. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. RI Ensoli, Barbara/J-9169-2016 OI Ensoli, Barbara/0000-0002-0545-8737 NR 34 TC 33 Z9 34 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD DEC PY 1994 VL 5 IS 12 BP 1467 EP 1475 DI 10.1089/hum.1994.5.12-1467 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA PZ394 UT WOS:A1994PZ39400006 PM 7711139 ER PT J AU GUTIERREZ, MI BHATIA, KG BARREIRO, C SPANGLER, G SCHVARTZMANN, E MURIEL, FS MAGRATH, IT AF GUTIERREZ, MI BHATIA, KG BARREIRO, C SPANGLER, G SCHVARTZMANN, E MURIEL, FS MAGRATH, IT TI A DE-NOVO P53 GERMLINE MUTATION AFFECTING CODON-151 IN A 6-YEAR-OLD CHILD WITH MULTIPLE TUMORS SO HUMAN MOLECULAR GENETICS LA English DT Article ID CANCER-PRONE FAMILY; SPLICING MUTATION; LINE MUTATION; GENE; PATIENT; NEOPLASMS C1 NCI,PEDIAT BRANCH,LYMPHOMA BIOL SECT,BETHESDA,MD 20892. HOSP PEDIAT PROF DR JUAN P GARRAHAN,DEPT HEMATOL ONCOL,RA-1245 BUENOS AIRES,DF,ARGENTINA. HOSP PEDIAT PROF DR JUAN P GARRAHAN,DEPT GENET,RA-1245 BUENOS AIRES,DF,ARGENTINA. NR 15 TC 24 Z9 24 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD DEC PY 1994 VL 3 IS 12 BP 2247 EP 2248 DI 10.1093/hmg/3.12.2247 PG 2 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA PY481 UT WOS:A1994PY48100024 PM 7881428 ER PT J AU GREGOR, P HOFF, M HOLIK, J HADLEY, D FANG, N COON, H BYERLEY, W AF GREGOR, P HOFF, M HOLIK, J HADLEY, D FANG, N COON, H BYERLEY, W TI DINUCLEOTIDE REPEAT POLYMORPHISM IN THE HUMAN TAURINE TRANSPORTER GENE (TAUT) SO HUMAN MOLECULAR GENETICS LA English DT Note C1 NIDA,MOLEC NEUROBIOL BRANCH,BALTIMORE,MD 21224. UNIV UTAH,MED CTR,DEPT PSYCHIAT,SALT LAKE CITY,UT 84132. FU NIMH NIH HHS [5F32MH10168, MH44212, KO2 MH01089] NR 1 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 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD DEC PY 1994 VL 3 IS 12 BP 2263 EP 2263 DI 10.1093/hmg/3.12.2263 PG 1 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA PY481 UT WOS:A1994PY48100030 PM 7881434 ER PT J AU MOCHIZUKI, H PROCHAZKA, M AF MOCHIZUKI, H PROCHAZKA, M TI DINUCLEOTIDE REPEAT POLYMORPHISM AT THE PPP1CA LOCUS ON 11Q13 SO HUMAN MOLECULAR GENETICS LA English DT Note C1 NIDDKD,CLIN DIABET & NUTR SECT,PHOENIX,AZ 85016. NR 1 TC 7 Z9 7 U1 1 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD DEC PY 1994 VL 3 IS 12 BP 2265 EP 2265 DI 10.1093/hmg/3.12.2265 PG 1 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA PY481 UT WOS:A1994PY48100034 PM 7881439 ER PT J AU CLARK, DA VINCE, G FLANDERS, KC HIRTE, H STARKEY, P AF CLARK, DA VINCE, G FLANDERS, KC HIRTE, H STARKEY, P TI CD56(+) LYMPHOID-CELLS IN HUMAN 1ST-TRIMESTER PREGNANCY DECIDUA AS A SOURCE OF NOVEL TRANSFORMING GROWTH FACTOR-BETA(2)-RELATED IMMUNOSUPPRESSIVE FACTORS SO HUMAN REPRODUCTION LA English DT Article DE CD56(+) LYMPHOID CELLS; DECIDUA; IMMUNOSUPPRESSION; TGF-BETA(2) ID SUPPRESSOR CELLS; FLOW-CYTOMETRY; MURINE; TISSUE; LYMPHOCYTES; RELEASE AB The lymphomyeloid cells isolated from normal first trimester pregnancy decidua may be separated into a CD56(+) population of natural killer (NK)-lineage cells with the morphology of granulated lymphocytes, and a CD56(-) population which includes other cell types. Unlike CD56(+) NK cells in peripheral blood, decidual CD56(+) cells lack type III Fc receptors (CD16) and did not express significant levels of either type I FcR (CD64) or type II FcR (CDw32). By contrast to the decidual CD56(-) cells, CD56(+) cells could release biologically active transforming growth factor (TCF)-beta in vitro, detectable using an normal rat kidney fibroblast colony-forming assay. The CD56(+) cells could be stained using an antibody specific for TGF-beta(2), and similarly staining cells could be detected in intact biopsies of normal pregnancy decidua. Bioactive TGF-beta is known to suppress the generation of cytotoxic cells in vitro, and high performance liquid chromatography fractionation of supernatants conditioned by CD56(+) but not CD56(-) cells contained reproducible peaks of immunosuppressive activity at 40-45 and 15-20 kDa, similar to the TGF-beta(2) immunosuppressive activity in supernatants conditioned by unfractionated decidua. C1 MCMASTER UNIV,DEPT OBSTET & GYNAECOL,HAMILTON,ON L8N 3Z5,CANADA. MCMASTER UNIV,DEPT PATHOL,HAMILTON,ON L8N 3Z5,CANADA. UNIV OXFORD,JOHN RADCLIFFE HOSP,NUFFIELD DEPT OBSTET & GYNAECOL,DEPT OBSTET & GYNAECOL,OXFORD OX3 9DU,ENGLAND. NIH,CHEMOPREVENT LAB,BETHESDA,MD. RP CLARK, DA (reprint author), MCMASTER UNIV,DEPT MED,ROOM 3V39,1200 MAIN ST W,HAMILTON,ON L8N 3Z5,CANADA. NR 25 TC 70 Z9 70 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD DEC PY 1994 VL 9 IS 12 BP 2270 EP 2277 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA PZ462 UT WOS:A1994PZ46200019 PM 7536211 ER PT J AU UNSER, M ALDROUBI, A SCHIFF, SJ AF UNSER, M ALDROUBI, A SCHIFF, SJ TI FAST IMPLEMENTATION OF THE CONTINUOUS WAVELET TRANSFORM WITH INTEGER SCALES SO IEEE TRANSACTIONS ON SIGNAL PROCESSING LA English DT Letter ID SPLINE WAVELETS; EDGE-DETECTION; REPRESENTATION; DECOMPOSITION; CONVERGENCE; ALGORITHMS; DISCRETE AB We describe a fast noniterative algorithm for the evaluation of continuous spline wavelet transforms at any integer scale m. In this approach, the input signal and the analyzing wavelet are both represented by polynomial splines. The algorithm uses a combination of moving sum and zero-padded filters, and its complexity per scale is O(N), where N is the signal length. The computation is exact, and the implementation is noniterative across scales. We also present examples of spline wavelets exhibiting properties that are desirable for either singularity detection (first and second derivative operators) or Gabor-like time-frequency signal analysis. C1 CHILDRENS NATL MED CTR, DEPT NEUROSURG, WASHINGTON, DC 20010 USA. RP UNSER, M (reprint author), NIH, NATL CTR RES RESOURCES, BIOMED ENGN & INSTRUMENTAT PROGRAM, BETHESDA, MD 20892 USA. RI Unser, Michael/A-1550-2008; Aldroubi, Akram/J-7186-2012 NR 22 TC 50 Z9 54 U1 0 U2 2 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 1053-587X J9 IEEE T SIGNAL PROCES JI IEEE Trans. Signal Process. PD DEC PY 1994 VL 42 IS 12 BP 3519 EP 3523 DI 10.1109/78.340787 PG 5 WC Engineering, Electrical & Electronic SC Engineering GA PY299 UT WOS:A1994PY29900019 ER PT J AU TAYLOR, CE BAKER, PJ HRABA, T STASHAK, P FAUNTLEROY, MB AF TAYLOR, CE BAKER, PJ HRABA, T STASHAK, P FAUNTLEROY, MB TI EFFECTS OF INTERFERON-GAMMA ON THE ANTIBODY-RESPONSE TO PSEUDOMONAS-AERUGINOSA LIPOPOLYSACCHARIDE IN MICE SO IMMUNOBIOLOGY LA English DT Article ID III PNEUMOCOCCAL POLYSACCHARIDE; MURINE LEUKEMIA VIRUSES; PLAQUE-FORMING CELLS; SUPPRESSOR T-CELLS; CYSTIC-FIBROSIS; IMMUNOGLOBULIN ISOTYPE; PROTECTIVE IMMUNITY; PASSIVE TRANSFER; TYPE-2 ANTIGENS; IGG SUBCLASS AB Different strains of mice were examined for the capacity to produce an Ig subclass-specific antibody response to purified Pseudomonas aeruginosa lipopolysaccharide (PALPS). With the exception of the AKR strain, the predominant isotype for most of the strains tested was IgG3 whereas the least frequent isotype expressed was either IgG2b or IgG1. AKR mice were unique in that the predominant isotype produced was IgG2a, rather than IgG3; however, the administration of anti-interferon gamma antibody, at the time of immunization with PALPS caused a substantial decrease in the IgG2a antibody response. Selected B10 congenic strains were used to assess the relationship between the antibody responses and the major histocompatibility complex (MHC) genes. Here, the isotype-patterns for the antibody responses were essentially the same regardless of the MHC haplotype. Interestingly, an increase in IgG2a, with a concomitant decrease in IgM and IgG1 antibody was noted when C3H mice were given interferon gamma at the time of immunization. These studies indicate that, in general, the antibody response to PALPS consists of IgG3 antibody as the predominant isotype, and that the antibody response can be modified by interferon gamma. RP TAYLOR, CE (reprint author), NIAID,DMID,RESP DIS BRANCH,TWINBROOK 2 RES FACIL,SOLAR BLDG ROOM 3B11,ROCKVILLE,MD 20852, USA. NR 49 TC 3 Z9 3 U1 0 U2 1 PU GUSTAV FISCHER VERLAG PI STUTTGART PA WOLLGRASWEG 49 POSTFACH 72 01 43, D-70577 STUTTGART, GERMANY SN 0171-2985 J9 IMMUNOBIOLOGY JI Immunobiology PD DEC PY 1994 VL 192 IS 1-2 BP 106 EP 120 PG 15 WC Immunology SC Immunology GA QB876 UT WOS:A1994QB87600011 PM 7750985 ER PT J AU GREEN, DR MAHBOUBI, A NISHIOKA, W OJA, S ECHEVERRI, F SHI, YF GLYNN, J YANG, YL ASHWELL, J BISSONNETTE, R AF GREEN, DR MAHBOUBI, A NISHIOKA, W OJA, S ECHEVERRI, F SHI, YF GLYNN, J YANG, YL ASHWELL, J BISSONNETTE, R TI PROMOTION AND INHIBITION OF ACTIVATION-INDUCED APOPTOSIS IN T-CELL HYBRIDOMAS BY ONCOGENES AND RELATED SIGNALS SO IMMUNOLOGICAL REVIEWS LA English DT Review ID C-MYC PROTEIN; TRANSFORMING GROWTH FACTOR-BETA-1; DNA FRAGMENTATION; NEGATIVE SELECTION; HUMAN-LYMPHOCYTES; TYROSINE KINASE; B-CELL; DEATH; BCL-2; EXPRESSION C1 NCI,IMMUNE CELL BIOL LAB,BETHESDA,MD. RP GREEN, DR (reprint author), LA JOLLA INST ALLERGY & IMMUNOL,DIV CELLULAR IMMUNOL,LA JOLLA,CA 92037, USA. FU NIGMS NIH HHS [GM52735] NR 92 TC 54 Z9 55 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD DEC PY 1994 VL 142 BP 321 EP 342 DI 10.1111/j.1600-065X.1994.tb00895.x PG 22 WC Immunology SC Immunology GA QA309 UT WOS:A1994QA30900015 PM 7698799 ER PT J AU MANDY, S FENG, Z CANFIELD, LS MANDY, K QUAN, X ROWEHL, RA KHAN, MY AKIYAMA, SK GODFREY, HP AF MANDY, S FENG, Z CANFIELD, LS MANDY, K QUAN, X ROWEHL, RA KHAN, MY AKIYAMA, SK GODFREY, HP TI INHIBITION OF EXPRESSION OF DELAYED-HYPERSENSITIVITY BY NEUTRALIZING MONOCLONAL ANTI-T-CELL FIBRONECTIN ANTIBODY SO IMMUNOLOGY LA English DT Article ID MATRIX-DRIVEN TRANSLOCATION; SENSITIVE GUINEA-PIGS; LYMPHOKINE; INTEGRIN; GENE; MACROPHAGES; MODULATION; RESPONSES; PROTEINS; COMPLEX AB T-cell fibronectin (FN) is a unique cellular FN that is rapidly synthesized by memory T cells in response to antigen. Monoclonal anti-T-cell FN antibodies have been used to clarify the role of T-cell FN in the in vivo expression of delayed hypersensitivity. IgG1(kappa) mouse anti-human T-cell FN monoclonal antibodies 231 and 248 recognized epitopes on the FN cell-binding domain, were cross-reactive with plasma FN, and neutralized human and guinea-pig T-cell FN monocyte agglutinating activity. When injected intradermally together with tuberculin or 30 min before topical application of reactive sensitizer, antibody 231 significantly decreased macroscopic expression of guinea-pig delayed hypersensitivity at 24 hr in a dose-dependent manner. Similar doses of antibody 248 caused a slight statistically non-significant enhancement of delayed-type hypersensitivity (DTH) expression. Inhibition of visible skin responses was not associated with qualitative or quantitative changes in cellular infiltrates at the reaction site. Antibody 231 modulated expression of delayed hypersensitivity in a qualitatively and quantitatively similar manner to the FN-binding mycobacterial antigen 85 proteins. This is consistent with anti-T-cell FN and antigen 85 acting on the same molecule in vivo. C1 NEW YORK MED COLL,DEPT EXPTL PATHOL,VALHALLA,NY 10595. NEW YORK MED COLL,DEPT CELL BIOL & ANAT,VALHALLA,NY 10595. SUNY STONY BROOK,DEPT MICROBIOL,STONY BROOK,NY 11794. NIDR,DEV BIOL LAB,BETHESDA,MD 20892. OI Godfrey, Henry /0000-0002-7195-6363 FU NCI NIH HHS [CA34141] NR 35 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD DEC PY 1994 VL 83 IS 4 BP 582 EP 588 PG 7 WC Immunology SC Immunology GA PV342 UT WOS:A1994PV34200011 PM 7875739 ER PT J AU BLACKWELL, JM BARTON, CH WHITE, JK ROACH, TIA SHAW, MA WHITEHEAD, SH MOCK, BA SEARLE, S WILLIAMS, H BAKER, AM AF BLACKWELL, JM BARTON, CH WHITE, JK ROACH, TIA SHAW, MA WHITEHEAD, SH MOCK, BA SEARLE, S WILLIAMS, H BAKER, AM TI GENETIC-REGULATION OF LEISHMANIAL AND MYCOBACTERIAL INFECTIONS - THE LSH/ITY/BCG GENE STORY CONTINUES SO IMMUNOLOGY LETTERS LA English DT Article; Proceedings Paper CT 4th Elsinore Meeting on Infection Immunity - Macrophages in Infection Immunity CY MAY 20-24, 1994 CL ELSINORE, DENMARK SP EUROPEAN FEDERAT IMMUNOL SOC, STATENS SERUMINSTITUT, DENMARK, COMMISS EUROPEAN COMMUNITIES DE MACROPHAGE ACTIVATION; LSH/ITY/BCG (CANDIDATE NRAMP); RESISTANCE TO INFECTION ID MACROPHAGE PRIMING ACTIVATION; NATURAL-RESISTANCE; MEXICANA INFECTION; MAJOR INFECTION; MICE; LSH; MOUSE; PROTEIN; SUSCEPTIBILITY; DONOVANI AB A common basis to genetic regulation of leishmanial and mycobacterial infections is provided by the action of the murine Lsh/Ity/Bcg gene in controlling the priming/activation of macrophages for antimicrobial activity. This relies on the TNF-alpha-dependent sustained expression of the inducible nitric oxide synthase (iNOS) gene responsible for the generation of large amounts of toxic nitric oxide (NO). The Lsh/Ity/Bcg gene has many pleiotropic effects, including differential expression of the early response gene KC following stimulation of macrophages with bacterial lipopolysaccharide (LPS) and mycobacterial lipoarabinomannan (LAM). The major signal transduction pathway involved in KC induction requires the generation of low levels of NO via constitutive nitric oxide synthase (cNOS) activity, leading to activation of guanylate cyclase and the cGMP-dependent kinase pathway. NO therefore appears to provide a common link between the early influence of Lsh in regulating the expression of genes which mediate many pleiotropic effects, and the later production of NO as the final effector mechanism for kill. The recently cloned candidate for Lsh/Ity/Bcg, designated Nramp for Natural resistance associated macrophage protein, encodes a polytopic integral membrane protein that has structural features common to prokaryotic and eukaryotic transporters and includes a conserved binding-protein-dependent transport motif which may be involved in interaction with peripheral ATP-binding subunits. The N-terminal sequence also carries a proline/serine rich putative SH3 binding domain, consistent with a role for tyrosine kinases in regulating Nramp function. This is also supported by the demonstration that ligation of beta(1) integrins, which signal via tyrosine kinases, by plating of macrophages onto extracellular matrix proteins is sufficient to mediate differential TNF-alpha release by macrophages from congenic Lsh resistant and susceptible mice. Transfection studies with the resistant allele demonstrate that Nramp plays a role, either directly or as an additional pleiotropic effect, in interferon-gamma/LPS upregulated L-arginine transport across the macrophage membrane, thus providing the substrate required to generate NO for both signal transduction and antimicrobial activity. Nra,mp also shows 55-58% sequence similarity with the yeast genes SMF1 and SMF2, which influence protein import into mitochondria. A high degree of conservation over the region of Nramp which contains the susceptible Nramp mutation indicates a possible common function at the level of protein translocation across membranes of intracellular compartments. Analysis of human NRAMP has identified a novel 3X9 nucleotide repeat in the putative SH3 binding domain, with a rare second allele bearing a 2X9 nucleotide repeat occurring at low frequency in the Brazilian population. Studies in progress will attempt to determine the function of human NRAMP, and hence to identify its role in parallel activation pathways in man. This is of particular interest in the light of studies demonstrating (i) that NO generated by iNOS is not used for antimicrobial activity in human macrophages, and (ii) that the iNOS gene itself and the interferon-gamma-inducible JAK tyrosine kinases are candidates for two other major genes, Sell and Scl2, identified and mapped in mice for their role in controlling different leishmanial resistance phenotypes. Further analysis of genetic regulation of pathways leading to iNOS-mediated NO production may provide the key to understanding why human macrophages do not use this as an antimicrobial pathway, and may also provide the basis for development of novel immunotherapeutic strategies for disease control. C1 NCI,GENET LAB,BETHESDA,MD 20892. RP BLACKWELL, JM (reprint author), UNIV CAMBRIDGE,ADDENBROOKES HOSP,SCH CLIN,DEPT MED,LEVEL 5,HILLS RD,CAMBRIDGE CB2 2QQ,ENGLAND. RI Blackwell, Jenefer/H-3015-2015; xu, tao/K-6631-2016 FU Wellcome Trust NR 54 TC 100 Z9 103 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 J9 IMMUNOL LETT JI Immunol. Lett. PD DEC PY 1994 VL 43 IS 1-2 BP 99 EP 107 DI 10.1016/0165-2478(94)00161-8 PG 9 WC Immunology SC Immunology GA QA147 UT WOS:A1994QA14700014 PM 7737696 ER PT J AU CLERICI, M SHEARER, GM AF CLERICI, M SHEARER, GM TI THE TH1-TH2 HYPOTHESIS OF HIV-INFECTION - NEW INSIGHTS SO IMMUNOLOGY TODAY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; CD4+ T-CELLS; POLYMERASE CHAIN-REACTION; SCHISTOSOMA-MANSONI; CYTOKINE PROFILES; MEDIATED-IMMUNITY; INTERFERON-GAMMA; DOWN-REGULATION; HOMOSEXUAL MEN; IN-VITRO AB In their earlier, much quoted, viewpoint article, Mario Clerici and Gene Shearer examined the role of T helper 1 (Th1)- and Th2-type responses in immune dysregulation associated with human immunodeficiency virus (HIV) infection. In this article, they consider she complications of a Th1-Th2 model raised by the nomenclature, discuss the issue of cytokine production by non-T cells, and compare data obtained from T-cell clones with heterogeneous populations of leukocytes from patients. They define Th-cell responses and cytokine profiles as 'type 1' and 'type 2', and reemphasize the importance of strong cellular immune responses, along with the cytokines that augment and maintain such responses, in protective immunity against HIV infection and AIDS progression. Finally, they present a model of activation-induced, cytokine-modulated, programmed cell death as a major factor in the pathogenesis of HIV infection and AIDS. C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. RP CLERICI, M (reprint author), UNIV MILAN,CATTEDRA IMMUNOL,I-20133 MILAN,ITALY. NR 104 TC 606 Z9 611 U1 0 U2 6 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 DEC PY 1994 VL 15 IS 12 BP 575 EP 581 DI 10.1016/0167-5699(94)90220-8 PG 7 WC Immunology SC Immunology GA PV909 UT WOS:A1994PV90900007 PM 7848519 ER PT J AU SZU, SC BYSTRICKY, S HINOJOSAAHUMADA, M EGAN, W ROBBINS, JB AF SZU, SC BYSTRICKY, S HINOJOSAAHUMADA, M EGAN, W ROBBINS, JB TI SYNTHESIS AND SOME IMMUNOLOGICAL PROPERTIES OF AN O-ACETYL PECTIN [POLY(1-]4)-ALPHA-D-GALPA]-PROTEIN CONJUGATE AS A VACCINE FOR TYPHOID-FEVER SO INFECTION AND IMMUNITY LA English DT Article ID VI-CAPSULAR POLYSACCHARIDE; ESCHERICHIA-COLI; IMMUNOGENICITY; QUANTITATION; PREVENTION; ANTIGEN; MICE; ACID AB Pectin, a plant polysaccharide, is mostly a linear homopolymer of poly(1-->4)-alpha-D-GalpA with <5% neutral sugars: its molecular size has a broad distribution around 400 kDa, and the degree of esterification is <5%. The structure of the capsular polysaccharide of Salmonella typhi (Vi) differs from pectin in that it is N acetylated at C-2 and O acetylated at C-3, and has a molecular size of similar to 2 x 10(3) kDa. There is no serological cross-reaction between pectin and Vi. Pectin, when O acetylated at C-2 and C-3, is antigenically identical to Vi in double immunodiffusion. Unlike Vi, O-acetylated pectin (OAcPec) is not immunogenic in mice, probably because of its comparatively low molecular weight. After storage at 3 to 8 degrees C for 3 months, there was no change in the O-acetyl content or the M(r) of OAcPec. At 60 degrees C, the M(r) of OAcPec declined more rapidly than that of Vi. OAcPec conjugated to tetanus toroid elicited Vi antibodies in mice, and reinjection elicited a booster response. The levels of Vi antibodies elicited by OAcPec-tetanus toroid conjugates were lower than those elicited by Vi conjugates, but these differences were not statistically significant. OAcPec has some advantages because it can be measured by standardized colorimetric assays and because it forms more soluble conjugates with proteins than does Vi. One disadvantage is that its glycosidic bond is not as stable as that of Vi. The use of a plant polysaccharide, pectin, as an immunogen for prevention of a systemic infection caused by a capsulated pathogen (S. typhi) provides a novel approach to improve the preparation and immunogenicity of polysaccharide-based vaccines. C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. SLOVAK ACAD SCI,INST CHEM,BRATISLAVA,SLOVAKIA. RP SZU, SC (reprint author), NICHHD,DEV & MOLEC IMMUN LAB,BETHESDA,MD 20892, USA. NR 29 TC 22 Z9 22 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 1994 VL 62 IS 12 BP 5545 EP 5549 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA PT329 UT WOS:A1994PT32900046 PM 7960137 ER PT J AU KASLOW, DC BATHURST, IC LENSEN, T PONNUDURAI, T BARR, PJ KEISTER, DB AF KASLOW, DC BATHURST, IC LENSEN, T PONNUDURAI, T BARR, PJ KEISTER, DB TI SACCHAROMYCES-CEREVISIAE RECOMBINANT PFS25 ADSORBED TO ALUM ELICITS ANTIBODIES THAT BLOCK TRANSMISSION OF PLASMODIUM-FALCIPARUM SO INFECTION AND IMMUNITY LA English DT Article ID SURFACE PROTEIN; HUMAN MALARIA; SEXUAL STAGES; ANTIGENS; GALLINACEUM; EXPRESSION; IMMUNITY AB Antibodies to Pfs25, a cysteine-rich 25-KDa protein present on the surface of Plasmodium falciparum zygotes, can completely block the transmission of malaria parasites when mixed with infectious blood and fed to mosquitoes through a membrane feeding apparatus. Recently, a polypeptide analog, Pfs25-B, secreted from recombinant Saccharomyces cerevisiae was found to react with conformation-dependent, transmission-blocking monoclonal antibodies and to elicit transmission-blocking antibodies in experimental animals when emulsified in either Freund's or muramyl tripeptide adjuvant. In this study, Pfs25-B adsorbed to alum induced transmission-blocking antibodies in both rodents and primates. Bacterially produced Pfs25, however, did not elicit complete transmission-blocking antibodies in rodents. Furthermore, unlike monoclonal antibodies to Pfs25, which block transmission only after ookinete development, antisera to Pfs25-B adsorbed to alum appeared to block the in vivo development of zygotes to ookinetes as well. C1 CHIRON CORP,DIV MOLEC BIOL,EMERYVILLE,CA 94608. UNIV NIJMEGEN HOSP,DEPT MED MICROBIOL,6500 HB NIJMEGEN,NETHERLANDS. RP KASLOW, DC (reprint author), NIAID,MALARIA RES LAB,MOLEC VACCINE SECT,BLDG 4,ROOM B1-37,BETHESDA,MD 20892, USA. NR 18 TC 78 Z9 84 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD DEC PY 1994 VL 62 IS 12 BP 5576 EP 5580 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA PT329 UT WOS:A1994PT32900050 PM 7960139 ER PT J AU BLOOM, ME KANNO, H MORI, S WOLFINBARGER, JB AF BLOOM, ME KANNO, H MORI, S WOLFINBARGER, JB TI ALEUTIAN MINK DISEASE - PUZZLES AND PARADIGMS SO INFECTIOUS AGENTS AND DISEASE-REVIEWS ISSUES AND COMMENTARY LA English DT Review DE ALEUTIAN MINK DISEASE PARVOVIRUS; PARVOVIRUS INFECTIONS; CYTOKINES; INTERLEUKIN-6; PERSISTENT VIRUS INFECTIONS; IMMUNE COMPLEX DISEASES ID FOLLICULAR DENDRITIC CELLS; PARVOVIRUS MINUTE VIRUS; NONSTRUCTURAL PROTEIN NS2; RETROVIRUS-INDUCED IMMUNODEFICIENCY; ANTIBODY-DEPENDENT ENHANCEMENT; ACUTE INTERSTITIAL PNEUMONIA; RECOMBINANT VACCINIA VIRUS; FELINE PANLEUKOPENIA VIRUS; AMINO-ACID SUBSTITUTIONS; CANINE HOST RANGE AB Aleutian mink disease (AD) is a naturally occurring persistent virus infection of mink caused by the Aleutian mink disease parvovirus (ADV). The classical form of AD, which occurs in adult mink, is notable for high titers of antiviral antibodies, hypergammaglobulinemia, plasmacytosis, and immune complex disease. In addition, there is a progressive renal disease characterized by mesangial proliferative glomerulonephritis and severe interstitial nephritis. Development of AD depends on both host and viral factors, and mink of certain genotypes fail to develop progressive disease when inoculated with low-virulence strains of virus. In newborn mink kits, ADV causes a fatal, acute interstitial pneumonitis associated with permissive viral replication in alveolar type 2 cells, but treatment of newborn kits with anti-viral antibody aborts the acute disease and converts into one resembling the persistent infection observed in adults. In infected adult mink, ADV is sequestered as immune complexes in lymphoid organs, but actual viral replication is restricted at the level of the individual cell and can be detected in only a small population of macrophages and follicular dendritic cells. ADV infection of mink primary macrophages and the human macrophage cell line U937 is antibody dependent and leads to the production of the cytokine interleukin-6. Furthermore, levels of interleukin-6 are increased in lymph node culture supernatants from infected mink. Chronic production of interleukin-6 may promote development of the immune disorder characteristic of AD. C1 OSAKA UNIV,SCH MED,DEPT PATHOL,OSAKA 530,JAPAN. TOHOKU UNIV,SCH DENT,DEPT ORAL & MAXILLOFACIAL SURG,SENDAI,MIYAGI,JAPAN. RP BLOOM, ME (reprint author), NIAID,ROCKY MT LABS,PERSISTENT VIRAL DIS LAB,HAMILTON,MT 59840, USA. NR 222 TC 67 Z9 71 U1 0 U2 13 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1056-2044 J9 INFECT AGENT DIS JI Infect. Agents Dis.-Rev. Issues Comment. PD DEC PY 1994 VL 3 IS 6 BP 279 EP 301 PG 23 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA PY079 UT WOS:A1994PY07900002 PM 7889316 ER PT J AU COHEN, MS HOOK, EW HITCHCOCK, PJ AF COHEN, MS HOOK, EW HITCHCOCK, PJ TI INFECTIOUS-DISEASE CLINICS OF NORTH-AMERICA - SEXUALLY-TRANSMITTED DISEASES IN THE AIDS ERA .2. PREFACE SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 UNIV ALABAMA,SCH MED,BIRMINGHAM,AL 35294. NIH,DIV MICROBIOL & INFECT DIS,STD BRANCH,BETHESDA,MD 20892. RP COHEN, MS (reprint author), UNIV N CAROLINA,DEPT MED,DIV INFECT DIS,547 BURNETT WOMACK,CB 7030,CHAPEL HILL,NC 27599, USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD DEC PY 1994 VL 8 IS 4 BP R9 EP R10 PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA PX958 UT WOS:A1994PX95800001 ER PT J AU WEISS, PJ AF WEISS, PJ TI THE EXPERT CATALOGING ASSISTANT PROJECT AT THE NATIONAL-LIBRARY-OF-MEDICINE SO INFORMATION TECHNOLOGY AND LIBRARIES LA English DT Article AB Over the last few years, the National Library of Medicine (NLM) has pursued the development of an expert system to assist catalogers with personal name authority work. This article reviews the project, from project and tool selection through knowledge engineering to evaluation, and discusses the reasons for deciding to redirect NLM's energies from development of an operational system to modification of the cataloging rules. RP WEISS, PJ (reprint author), NATL LIB MED,DIV TECH SERV,BETHESDA,MD 20894, USA. NR 3 TC 4 Z9 4 U1 0 U2 3 PU AMER LIBRARY ASSN PI CHICAGO PA 50 E HURON ST, CHICAGO, IL 60611 SN 0730-9295 J9 INFORM TECHNOL LIBR JI Inf. Technol. Libr. PD DEC PY 1994 VL 13 IS 4 BP 267 EP 271 PG 5 WC Computer Science, Information Systems; Information Science & Library Science SC Computer Science; Information Science & Library Science GA PX230 UT WOS:A1994PX23000005 ER PT J AU KING, LB VACCHIO, MS ASHWELL, JD AF KING, LB VACCHIO, MS ASHWELL, JD TI TO BE OR NOT TO BE - MUTUALLY ANTAGONISTIC DEATH SIGNALS REGULATE THYMOCYTE APOPTOSIS SO INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY LA English DT Article DE ANTISENSE TRANSGENE; APOPTOSIS; GLUCOCORTICOID RECEPTOR; GLUCOCORTICOIDS; THYMOCYTE SELECTION ID T-CELL REPERTOIRE; THYMIC NURSE CELLS; FREE CORTICOSTERONE; SELECTION; ACTIVATION; COMPLEX; RAT AB Recognition of self-antigens by immature thymocytes results in either activation-induced apoptosis (negative selection) or survival (positive selection). While it is believed that T cell receptor avidity plays a role in determining the outcome, the mechanisms responsible for this life or death decision are not known. Recent data concerning the mutual antagonism between activation- and glucocorticoid-induced apoptosis have prompted an examination of the potential interaction of these two signaling pathways in the regulation of antigen-specific selection. RP KING, LB (reprint author), NCI,IMMUNE CELL BIOL LAB,BIOL RESPONSE MODIFIERS PROGRAM,BLDG 10,ROOM 1B-40,BETHESDA,MD 20892, USA. FU NCI NIH HHS [CA09162] NR 21 TC 9 Z9 10 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-2438 J9 INT ARCH ALLERGY IMM JI Int. Arch. Allergy Immunol. PD DEC PY 1994 VL 105 IS 4 BP 355 EP 358 PG 4 WC Allergy; Immunology SC Allergy; Immunology GA PW871 UT WOS:A1994PW87100007 PM 7981604 ER PT J AU KIRSHENBAUM, AS GOFF, JP ALBERT, JP KESSLER, SW METCALFE, DD AF KIRSHENBAUM, AS GOFF, JP ALBERT, JP KESSLER, SW METCALFE, DD TI FIBROBLASTS DETERMINE THE FATE OF FC(EPSILON)RI+ CELL-POPULATIONS IN-VITRO BY SELECTIVELY SUPPORTING THE VIABILITY OF MAST-CELLS WHILE INTERNALIZING AND DEGRADING BASOPHILS SO INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY LA English DT Article DE ALLERGY; BASOPHILS; FIBROBLASTS; IGE RECEPTOR; MAST CELLS ID C-KIT RECEPTOR; GROWTH-FACTOR; BONE-MARROW; PROGENITOR CELLS; GENE-PRODUCT; SI-LOCUS; CULTURE; INVITRO; LIGAND; CD34+ AB To determine the fate of Fc(epsilon)RI+ cells on fibroblasts in vitro, human bone marrow derived CD34+ cells were cultured in the presence of recombinant human interleukin 3 and recombinant human hematopoietic stem cell factor for 3 weeks, and Fc(epsilon)RI+ cells were purified by immunomagnetic selection. This enriched Fc(epsilon)RI+ cell population consisted of 92-94% basophils and 3-5% mast cells as determined by morphologic, immunohistochemical, and ultrastructural criteria. The Fc(epsilon)RI+ cells were then cocultured with 3T3 fibroblasts. Basophils decreased markedly by 1 week and were absent from cocultures by 2-3 weeks, while the mast cell numbers on the fibroblast monolayers remained constant. Ultrastructural examination of cocultures at 2 days demonstrated phagocytosis of basophils by fibroblasts. By 1 week, phagocytosed basophil membranes and granules gave fibroblasts the superficial appearance of mast cells by toluidine blue staining. Mast cells surviving in cocultures could be distinguished from granule-containing fibroblasts by IgE surface labeling and by ultrastructural demonstration of tryptase-positive granules. Thus, while mast cells remain viable in coculture with 3T3 fibroblasts, basophils do not survive and are internalized and degraded by the fibroblast monolayer. C1 GEORGETOWN UNIV,MED CTR,DIV MOLEC VIROL & IMMUNOL,ROCKVILLE,MD. USN,MED RES INST,DEPT IMMUNOBIOL & TRANSPLANTAT,BETHESDA,MD. RP KIRSHENBAUM, AS (reprint author), NIAID,CLIN INVEST LAB,ALLERG DIS SECT,BLDG 10,ROOM 11C212,BETHESDA,MD 20892, USA. NR 29 TC 7 Z9 7 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-2438 J9 INT ARCH ALLERGY IMM JI Int. Arch. Allergy Immunol. PD DEC PY 1994 VL 105 IS 4 BP 374 EP 380 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA PW871 UT WOS:A1994PW87100011 PM 7981608 ER PT J AU STERNBERG, KJ LAMB, ME GREENBAUM, C DAWUD, S CORTES, RM LOREY, F AF STERNBERG, KJ LAMB, ME GREENBAUM, C DAWUD, S CORTES, RM LOREY, F TI THE EFFECTS OF DOMESTIC VIOLENCE ON CHILDRENS PERCEPTIONS OF THEIR PERPETRATING AND NONPERPETRATING PARENTS SO INTERNATIONAL JOURNAL OF BEHAVIORAL DEVELOPMENT LA English DT Article ID ATTACHMENT AB The Family Relations Test was completed by 8- to 12-year-old children in order to assess the effects of various types of domestic violence on children's perceptions of their parents, all of whom were living with their children at the time of the study. Thirty-three of the children had been physically abused by their parents within the last 6 months, 16 had witnessed spouse abuse, 30 had been both victims and witnesses of domestic violence, and 31 of the children had experienced no known domestic violence. Groups were matched with respect to socioeconomic and demographic characteristics. Physically abused children more frequently reported negative perceptions of their perpetrating parents, but perceived nonabusive parents similarly to children in the comparison group. Children in the four groups did not differ with respect to the number of positive attributes assigned to their parents. In sum children who experienced different types of domestic violence discrimated between positive and negative aspects of their relationships with their parents and had different perceptions of perpetrating and nonperpetrating parents. C1 NICHHD,BETHESDA,MD 20892. HEBREW UNIV JERUSALEM,JERUSALEM,ISRAEL. JERUSALEM DEPT FAMILY SERV,JERUSALEM,ISRAEL. NR 33 TC 21 Z9 21 U1 0 U2 3 PU LAWRENCE ERLBAUM ASSOC LTD PI HOVE PA 27 PALMEIRA MANSIONS CHURCH RD, HOVE, E SUSSEX, ENGLAND BN3 2FA SN 0165-0254 J9 INT J BEHAV DEV JI Int. J. Behav. Dev. PD DEC PY 1994 VL 17 IS 4 BP 779 EP 795 PG 17 WC Psychology, Developmental SC Psychology GA PZ192 UT WOS:A1994PZ19200012 ER PT J AU TORTORA, G PEPE, S BIANCO, C DAMIANO, V RUGGIERO, A BALDASSARRE, G CORBO, C CHOCHUNG, YS BIANCO, AR CIARDIELLO, F AF TORTORA, G PEPE, S BIANCO, C DAMIANO, V RUGGIERO, A BALDASSARRE, G CORBO, C CHOCHUNG, YS BIANCO, AR CIARDIELLO, F TI DIFFERENTIAL-EFFECTS OF PROTEIN-KINASE A SUB-UNITS ON CHINESE-HAMSTER-OVARY CELL-CYCLE AND PROLIFERATION SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID HL-60 LEUKEMIA-CELLS; RI-ALPHA-SUBUNIT; REGULATORY SUBUNIT; GROWTH-INHIBITION; ANTISENSE OLIGODEOXYNUCLEOTIDE; DOWN-REGULATION; THYROID-CELLS; TRANSCRIPTION; MALIGNANCY; EXPRESSION AB It has been shown that a marked increase in the levels of RI alpha sub-units and a decrease in RII beta sub-unit levels correlate with neoplastic transformation or with the mitogenic response of normal cells to hormones and growth factors. The selective down-regulation of RI alpha and the following induction of RII beta determine cell-growth arrest and differentiation of several cancer cells. To directly address the question whether the 2 protein-kinase-A(PKA) isoforms play different roles in the control of proliferation and cell-cycle distribution, we introduced and over-expressed the different PKA sub-units in Chinese-hamster-ovary (CHO) cells via retroviral-vector-mediated gene transfer. Whereas CHO cells treated with RI alpha anti-sense oligodeoxynucleotides were growth arrested and accumulated in the G(0)/G(1) phases of the cell cycle, infection of CHO cells with a retroviral vector in order to over-express RI alpha determined growth advantages in monolayer conditions and substantially increased their cloning efficiency in soft agar. These events correlated with a sustained percentage of cells in S phase induced by RI alpha over-expression in the infected cells. In contrast, CHO cells infected with retroviral vectors over-expressing either a RII beta sub-unit or a C alpha catalytic sub-unit of PKA exhibited growth arrest within a few days of culture and accumulated in the G(2)-M phase of the cell cycle. The results of our study demonstrate that the different PKA sub-units play different and specific roles in the control of cell growth and cell-cycle distribution. (C) 1994 Wiley-Liss, Inc. C1 NCI,TUMOR IMMUNOL & BIOL LAB,BETHESDA,MD 20892. RP TORTORA, G (reprint author), UNIV NAPLES FEDERICO II,FAC MED & CHIRURG,ONCOL MED CATTEDRA,VIA S PANSINI 5,I-80131 NAPLES,ITALY. RI Baldassarre, Gustavo/K-1350-2016 OI Baldassarre, Gustavo/0000-0002-9750-8825 NR 22 TC 26 Z9 26 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD DEC 1 PY 1994 VL 59 IS 5 BP 712 EP 716 DI 10.1002/ijc.2910590521 PG 5 WC Oncology SC Oncology GA QF913 UT WOS:A1994QF91300020 PM 7960245 ER PT J AU SAINTJEANNET, JP KARAVANOV, AA DAWID, IB AF SAINTJEANNET, JP KARAVANOV, AA DAWID, IB TI EXPRESSION OF MESODERM MARKERS IN XENOPUS-LAEVIS KELLER EXPLANTS SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY LA English DT Article DE NEURAL INDUCTION; REGIONALIZATION; MESODERM; AMPHIBIA ID CENTRAL-NERVOUS-SYSTEM; HOMEO-BOX GENE; NEURAL INDUCTION; ANTEROPOSTERIOR PATTERN; PLANAR INDUCTION; ORGANIZER; PLATE; ACTIVIN; EMBRYOS; CELLS AB In an attempt to document at the molecular level the behavior of mesodermal cells in Keller explant preparation, we have analyzed the time course of expression of four molecular markers of mesoderm gsc, Xbra, Xnot and XLIM-1. Our findings demonstrate that, (i) all mesodermal markers tested were expressed in the explants, but patterning of the mesoderm appeared incomplete; (ii) during convergence and extension of the explants, mesodermal cells did not invade the ectodermal tissue at any time tested, supporting the view that mesoderm establishes exclusively planar contacts with the ectoderm in this preparation; (iii) planar contacts were not sufficient to promote the neural expression of XLIM-1 protein in these explants. C1 UNIV TOULOUSE 3,CTR BIOL DEV,CNRS,UNITE MIXTE RECH 9925,F-31062 TOULOUSE,FRANCE. NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892. NR 39 TC 6 Z9 6 U1 0 U2 0 PU UNIV BASQUE COUNTRY PRESS PI BILBAO PA POST BOX 1397, E-48080 BILBAO, SPAIN SN 0214-6282 J9 INT J DEV BIOL JI Int. J. Dev. Biol. PD DEC PY 1994 VL 38 IS 4 BP 605 EP 611 PG 7 WC Developmental Biology SC Developmental Biology GA PZ281 UT WOS:A1994PZ28100004 PM 7779682 ER PT J AU GUO, WD HSING, AW LI, JY CHEN, JS CHOW, WH BLOT, WJ AF GUO, WD HSING, AW LI, JY CHEN, JS CHOW, WH BLOT, WJ TI CORRELATION OF CERVICAL-CANCER MORTALITY WITH REPRODUCTIVE AND DIETARY FACTORS, AND SERUM MARKERS IN CHINA SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article ID RISK-FACTORS; INTRAEPITHELIAL NEOPLASIA; HUMAN PAPILLOMAVIRUS; UNITED-STATES; WHITE WOMEN; SINGAPORE; CARCINOMA; INSITU AB Background. Cervical cancer is the second leading cause of cancer death among Chinese women. Within China, a considerable geographical variation in mortality rates has been observed, but the reasons are not well understood. Methods. Cervical cancer rates were examined in relation to indices of reproductive factors, dietary habits, and selected serum biomedical markers in 65 rural Chinese counties. Results. Cervical cancer mortality rates correlated positively and significantly with antibodies to herpes simplex virus type 2 (HSV-2) (r = 0.40, P < 0.01), serum levels of ferritin (r = 0.33, P < 0.01), body mass index (BMI) (r = 0.42, P < 0.01) and cigarette smoking (r = 0.51, P < 0.05) and negatively and significantly with age at first birth (r = -0.51, P < 0.01), consumption of green vegetables (r = -0.40, P < 0.01) and animal foods (r = -0.40, P < 0.01), and serum levels of selenium (r = -0.26, P < 0.05). When these variables were considered in the multiple regression analysis, early age at first birth and higher BMI were positively associated with cervical cancer mortality, while consumption of green vegetables and animal foods were negatively correlated. In the serum model, infection with HSV-2 and low levels of sex hormone binding globulin (SHBG) were positively related to cervical cancer mortality. No relation was found for consumption of fruits. Conclusions. Although limitations of these ecologic data preclude causal inferences, findings in this study, including associations with HSV-2 infection, early age at first birth, consumption of green vegetables and animal foods, may provide C1 NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. CHINESE ACAD PREVENT MED,INST NUTR & FOOD HYG,BEIJING,PEOPLES R CHINA. CHINESE ACAD MED SCI,INST CANC,BEIJING,PEOPLES R CHINA. RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X NR 42 TC 26 Z9 26 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD DEC PY 1994 VL 23 IS 6 BP 1127 EP 1132 DI 10.1093/ije/23.6.1127 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA QD338 UT WOS:A1994QD33800003 PM 7721512 ER PT J AU RON, E BOICE, JD HAMBURGER, S STOVALL, M AF RON, E BOICE, JD HAMBURGER, S STOVALL, M TI MORTALITY FOLLOWING RADIATION TREATMENT FOR INFERTILITY OF HORMONAL ORIGIN OR AMENORRHEA SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article ID REPRODUCTIVE FACTORS; OVARIAN-CANCER; BREAST-CANCER; MYOCARDIAL-INFARCTION; UNITED-STATES; RISK-FACTORS; WOMEN; DISEASE; HISTORY; CERVIX AB Background. Between 1920 and 1965, radiation treatment to the ovaries and/or pituitary gland was used for refractory hormonal infertility and amenorrhoea. The potential carcinogenic effects of hormonal infertility, as well as exposure to relatively low doses of ovarian and pituitary radiation can be studied among patients receiving these treatments. Methods. A cohort of 816 patients treated between 1925 and 1961 was identified from the medical records of a New York City radiologist. The mortality experience for 84% of these women was determined and radiation doses for individual patients were estimated. Doses were, on average, 87, 64, 54, and 29 cGy to the ovary, brain, colon, and active bone marrow, respectively. Results. Compared with mortality rates in the US population, the risk of death was less than expected (standardized mortality ratio [SMR] = 0.87; 95% confidence interval [CI] : 0.75-1.00). Deaths due to circulatory and digestive diseases were significantly below expectation. Cancer mortality was about 10% higher than that expected based on New York City mortality rates. Based on a small number of cases, no increase was found for cancers of the ovary or brain, or leukaemia, sites for which direct radiation exposure occurred, but significant excesses of colon cancer and non-Hodgkin's lymphoma were observed. A deficit in mortality from female genital cancers was surprising, since nulliparity has been a consistently reported risk factor for cancers of the endometrium and ovary. Breast cancer mortality was close to expectation. Conclusions. Overall, this study provided little evidence that either infertility or its treatment with radiation increased the risk of total or cancer mortality. C1 US FDA,CTR DEVICES & RADIOL HLTH,ROCKVILLE,MD 20852. UNIV TEXAS,MD ANDERSON CANC CTR,DEPT RADIAT PHYS,HOUSTON,TX 77030. RP RON, E (reprint author), NCI,RADIAT EPIDEMIOL BRANCH,BETHESDA,MD, USA. NR 44 TC 11 Z9 11 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD DEC PY 1994 VL 23 IS 6 BP 1165 EP 1173 DI 10.1093/ije/23.6.1165 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA QD338 UT WOS:A1994QD33800009 PM 7721518 ER PT J AU GREENABATE, C TAFARI, N RAO, MR YU, KF CLEMENS, JD AF GREENABATE, C TAFARI, N RAO, MR YU, KF CLEMENS, JD TI COMPARISON OF HEATED WATER-FILLED MATTRESS AND SPACE-HEATED ROOM WITH INFANT INCUBATOR IN PROVIDING WARMTH TO LOW-BIRTH-WEIGHT NEWBORNS SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article ID BABIES AB Background. Prevention of excessive heat loss is fundamental to survival of low birthweight (LBW) newborns. The use of infant incubators (INC) is beyond the resources of developing countries, and the space-heated room (SHR) has been the only feasible means of providing thermal protection to LBW newborns. Recently a thermostatically controlled, heated, water-filled mattress (HWM) has been developed as a potentially simpler and affordable alternative. Methods. In a neonatal care ward of a referral hospital in Addis Ababa, 62 <1 week old newborns, weighing 1000-1999 g, who were well enough to breathe comfortably in room air and tolerate oral feeds, were randomly allocated to INC, HWM or SHR and followed for 3 weeks. The level of cold stress as assessed by core-to-skin temperature gradient and the rate of weight gain were the main outcome measures. Results. The level of cold stress was lowest in the INC, intermediate in the HWM and highest in the SHR. Relative to the INC group, the HWM group exhibited a modest increase in the occurrence of clinically important hyperthermic or hypothermic deviations in core temperature (rate ratio (RR) = 2.3; 95% CI : 0.9, 5.6), and the SHR displayed a definite increase (RR = 4.0; 95% CI : 1.7, 9.3). During the first week, the rate of weight gain was highest in the INC group (3.6 g/kg/day), lowest in the SHR group (-2.3 g/kg/day, P < 0.05 versus INC) and intermediate in the HWM group (1.6 g/kg/day, P > 0.1 versus INC). Conclusion. Care in the SHR produced clinically significant thermal stresses and was associated with deficient early neonatal growth, but the use of HWM may constitute a feasible and clinically acceptable alternative in providing warmth to LBW newborns during the neonatal period. C1 UNIV ADDIS ABABA,FAC MED,DEPT PAEDIAT & CHILD HLTH,ADDIS ABABA,ETHIOPIA. NICHHD,EPIDEMIOL BRANCH,BETHESDA,MD. NICHHD,BIOMETRY & MATH STAT BRANCH,BETHESDA,MD. NR 24 TC 9 Z9 9 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD DEC PY 1994 VL 23 IS 6 BP 1226 EP 1233 DI 10.1093/ije/23.6.1226 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA QD338 UT WOS:A1994QD33800017 PM 7721525 ER PT J AU FIKREE, FF GRAY, RH BERENDES, HW KARIM, MS AF FIKREE, FF GRAY, RH BERENDES, HW KARIM, MS TI A COMMUNITY-BASED NESTED CASE-CONTROL STUDY OF MATERNAL MORTALITY SO INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS LA English DT Article DE CLINICAL CAUSES; MATERNAL MORTALITY; NONCLINICAL CAUSES; RISK FACTORS ID EGYPT AB Objectives: Population-based information from Pakistan on maternal mortality is inadequate to define the magnitude of the problem or to contribute information on the distribution of clinical causes and risk factors. A population-based survey was conducted in eight urban squatter settlements of Karachi Pakistan, to address these key issues. Methods: Pre-coded questionnaires were administered to the 10 135 households to ascertain deaths of household members in the 5 years preceding the survey (1984-1989). A verbal autopsy questionnaire was administered to the 121 households where a female death between 15 and 49 years of age was reported. Results: The maternal mortality ratio was estimated as 281 per 100 000 livebirths with hemorrhage, eclampsia and puerperal sepsis as the major causes of maternal deaths. Important risk factors identified were maternal employment, paternal unemployment, and poor prior pregnancy history. Women did seek health care but the assistance sought was often inappropriate. Conclusion: Intervention programs for improving timely referral and upgrading of hospitals are suggested. C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT POPULAT DYNAM,BALTIMORE,MD 21202. NICHHD,DIV EPIDEMIOL STAT & PREVENT RES,BETHESDA,MD 20892. RP FIKREE, FF (reprint author), AGA KHAN UNIV,DEPT COMMUNITY HLTH SCI,KARACHI 74800,PAKISTAN. NR 21 TC 13 Z9 13 U1 0 U2 1 PU ELSEVIER SCI PUBL 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 DEC PY 1994 VL 47 IS 3 BP 247 EP 255 DI 10.1016/0020-7292(94)90569-X PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA PY297 UT WOS:A1994PY29700007 PM 7705530 ER PT J AU CHAH, JA RHIM, JS AF CHAH, JA RHIM, JS TI CURRENT STATUS OF PROSTATE-CANCER RESEARCH - DEVELOPMENT OF IN-VITRO MODEL SYSTEMS (REVIEW) SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Review DE PROSTATE CARCINOGENESIS; ONCOGENES; TUMOR SUPPRESSOR GENES; GROWTH FACTORS; PROSTATE CELL LINES ID POLYMERASE CHAIN-REACTION; FACTOR-BINDING PROTEIN-2; EPIDERMAL GROWTH-FACTOR; RAS ONCOGENE MUTATIONS; TUMOR-SUPPRESSOR GENE; CELL-LINE; HUMAN PAPILLOMAVIRUS; EPITHELIAL-CELLS; HIGH PREVALENCE; ACTIVATED RAS AB Prostate cancer is a major medical problem which is expected to affect over 200,000 US men in 1994. Despite its widespread prevalence and the difficulties in clinical diagnosis and treatment of the disease, the contribution of environmental factors and the etiological mechanism of prostate cancer are poorly understood. A brief update on recent progress in cellular and molecular research of prostate cancer is provided. Specific areas discussed include oncogenes (vas, myc, c-erbB-2 and bcl-2), tumor suppressor genes (p53, RB, DCC, putative suppressor genes), growth factors (EGF, FGF, IGF) and human papillomavirus (HPV) infections. The elucidation of a multistep mechanism of prostate tumorigenesis has been slowed by a lack of tumor tissue and the limited number of in vitro cell lines available for study. Reviewed here are the newly developed in vitro normal prostate cell systems which supply a base for addition of oncogenes and chemical mutagens and may provide insight into the molecular genetic events which accompany the stepwise induction of prostatic neoplasia. C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. NR 110 TC 2 Z9 2 U1 0 U2 0 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD DEC PY 1994 VL 5 IS 6 BP 1233 EP 1242 PG 10 WC Oncology SC Oncology GA PT933 UT WOS:A1994PT93300006 PM 21559703 ER PT J AU WESTERGAARD, GC AF WESTERGAARD, GC TI THE SUBSISTENCE TECHNOLOGY OF CAPUCHINS SO INTERNATIONAL JOURNAL OF PRIMATOLOGY LA English DT Article DE ABORIGINE; CAPUCHIN; CEBUS; CHIMPANZEE; TOOL MANUFACTURE; TOOL USE ID MONKEYS CEBUS-APELLA; TOOL USE; TUFTED CAPUCHIN; MANIPULATION AB Via Oswalt's system of classification, I compare the tool-kits of wild and captive capuchins with those of Tanzanian chimpanzees and Tasmanian aborigines. The results indicate that capuchins have tool-kits that are smaller, and have lower ratios of artifacts to naturefacts, than those of Tanzanian chimpanzees and Tasmanian aborigines. Accordingly, Oswalt's system can be used productively to assess the relative technological skills of monkeys versus those of apes and humans. RP WESTERGAARD, GC (reprint author), NICHHD,NIHAC,COMPARAT ETHOL,POB 529,POOLESVILLE,MD 20837, USA. NR 24 TC 21 Z9 22 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0164-0291 J9 INT J PRIMATOL JI Int. J. Primatol. PD DEC PY 1994 VL 15 IS 6 BP 899 EP 906 PG 8 WC Zoology SC Zoology GA PZ975 UT WOS:A1994PZ97500007 ER PT J AU KIRSCH, IR AF KIRSCH, IR TI V(D)J RECOMBINATION AND ATAXIA-TELANGIECTASIA - A REVIEW SO INTERNATIONAL JOURNAL OF RADIATION BIOLOGY LA English DT Article; Proceedings Paper CT 6th International Workshop on Ataxia-Telangiectasia CY MAY 22-25, 1994 CL UNIV BIRMINGHAM, BIRMINGHAM, ENGLAND HO UNIV BIRMINGHAM ID CHRONIC LYMPHOCYTIC-LEUKEMIA; T-CELL LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; SITE-SPECIFIC RECOMBINATION; STRAND BREAK REPAIR; 7-14 TRANSLOCATIONS; MOLECULAR ANALYSIS; PROLYMPHOCYTIC LEUKEMIA; CHROMOSOME-14 INVERSION; NONRANDOM OCCURRENCE AB I review one aspect of the A-T phenotype, the remarkable and fascinating increase of lymphocytes carrying chromosomal aberrations caused by V(D)J site-specific recombination. The review is organized to first present the facts of V(D)J recombination and the findings in this regard in A-T patients. Other populations that demonstrate similar increases in such chromosomal aberrations are then presented and a hypothesis is offered as to the basis and relevance of these increases vis-a-vis A-T. The contribution of V(D)J recombination to the clonal proliferations and frank lymphoid malignancies seen in A-T patients is briefly discussed. I conclude with some speculative comments extending the observations presented into a more global consideration of a possible function of an A-T gene. RP KIRSCH, IR (reprint author), NCI NAVY MED ONCOL BRANCH,BETHESDA,MD 20889, USA. NR 81 TC 28 Z9 28 U1 0 U2 0 PU TAYLOR & FRANCIS LTD LONDON PI LONDON PA ONE GUNDPOWDER SQUARE, LONDON, ENGLAND EC4A 3DE SN 0955-3002 J9 INT J RADIAT BIOL JI Int. J. Radiat. Biol. PD DEC PY 1994 VL 66 IS 6 SU S BP S97 EP S108 DI 10.1080/09553009414551921 PG 12 WC Biology; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA QD102 UT WOS:A1994QD10200013 PM 7836858 ER PT J AU KURRASCH, RHM WU, AJ FOX, PC AF KURRASCH, RHM WU, AJ FOX, PC TI ORAL-DISEASE ASSOCIATED WITH DRY EYES SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article RP KURRASCH, RHM (reprint author), NIH,BLDG 10,ROOM 1N-113,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD WIN PY 1994 VL 34 IS 1 BP 89 EP 100 DI 10.1097/00004397-199403410-00009 PG 12 WC Ophthalmology SC Ophthalmology GA MY964 UT WOS:A1994MY96400008 PM 8169075 ER PT J AU FUJITA, M ENOMOTO, T INOUE, M TANIZAWA, O OZAKI, M RICE, JM NOMURA, T AF FUJITA, M ENOMOTO, T INOUE, M TANIZAWA, O OZAKI, M RICE, JM NOMURA, T TI ALTERATION OF THE P53 TUMOR-SUPPRESSOR GENE OCCURS INDEPENDENTLY OF K-RAS ACTIVATION AND MORE FREQUENTLY IN SEROUS ADENOCARCINOMAS THAN IN OTHER COMMON EPITHELIAL TUMORS OF THE HUMAN OVARY SO JAPANESE JOURNAL OF CANCER RESEARCH LA English DT Article DE OVARIAN CANCER; P53; K-RAS; GENE MUTATION ID POLYMERASE CHAIN-REACTION; PROTO-ONCOGENE; COLORECTAL TUMORIGENESIS; ALLELIC DELETION; CANCER; MUTATIONS; AMPLIFICATION; ASSOCIATION; CARCINOMA; HETEROZYGOSITY AB To clarify the role of the p53 tumor suppressor gene in the development of human ovarian epithelial tumors and to study the association of p53 alterations with K-ras activation, a series of 70 common epithelial ovarian tumors from Japanese patients was studied. These included 31 serous adenocarcinomas, 12 mucinous adenocarcinomas, 5 mucinous tumors of borderline malignancy, 13 endometrioid adenocarcinomas, and 9 clear cell carcinomas. Allelic loss, recognized at the polymorphic site in codon 72 of the p53 gene, was detected in 14 of 36 (39%) informative cases by restriction fragment length polymorphism analysis and by single-strand conformation polymorphism (SSCP) analysis of polymerase chain reaction(PCR)-amplified DNA fragments. Mutations in the highly conserved regions of the p53 gene were detected by SSCP analysis of PCR-amplified fragments. Mutations were found in 22 of 70 (31%) ovarian tumors, including 1 of 5 mucinous tumors of borderline malignancy. Mutations were subsequently characterized by direct sequencing. Single missense base substitutions were detected in 13 ovarian carcinomas and in one case of mucinous tumor of borderline malignancy. Short (1-8 bp) deletions and insertions were found in 8 cases. Mutations in the p53 gene occurred more frequently in serous adenocarcinomas (14/31, 45%) than in all nonserous types of malignant epithelial tumors combined (7/34, 21%; P=0.032). Point mutations in K-ras were identified by dot blot hybridization analysis of PCR-amplified fragments with mutation-specific oligonucleotides and by direct sequencing. The overall frequency of K-ras mutations was 19/70 (27%). K-ras mutations were found in 12 of 17 (71%) mucinous tumors (8/12 mucinous carcinomas [67%] and 4/5 mucinous tumors of borderline malignancy [80%]), and occurred more frequently than in serous carcinomas (4/31, 13%; P=0.00009) or in all nonmucinous types of ovarian epithelial tumors combined (7/53, 13%; P=0.00002). These data suggest that different combinations of oncogenes and/or tumor suppresser genes may be involved in the genesis and development of histologically distinct categories of common epithelial tumors of the human ovary. C1 OSAKA UNIV,FAC MED,DEPT OBSTET & GYNECOL,SUITA,OSAKA 565,JAPAN. OSAKA UNIV,FAC MED,DEPT RADIAT BIOL,SUITA,OSAKA 565,JAPAN. CTR ADULT DIS,HIGASHINARI KU,OSAKA 537,JAPAN. KANAZAWA UNIV,FAC MED,DEPT OBSTET & GYNECOL,KANAZAWA,ISHIKAWA 920,JAPAN. NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. NR 50 TC 55 Z9 55 U1 0 U2 0 PU JAPANESE CANCER ASSOCIATION PI TOKYO PA EDITORIAL OFFICE 7TH FLOOR, JOHKOH BLDG 2-23-11, KOISHIKAWA, TOKYO 112, JAPAN SN 0910-5050 J9 JPN J CANCER RES JI Jpn. J. Cancer Res. PD DEC PY 1994 VL 85 IS 12 BP 1247 EP 1256 PG 10 WC Oncology SC Oncology GA PZ701 UT WOS:A1994PZ70100012 PM 7852189 ER PT J AU KAJIMURA, N KATO, M OKUMA, T SEKIMOTO, M WATANABE, T TAKAHASHI, K AF KAJIMURA, N KATO, M OKUMA, T SEKIMOTO, M WATANABE, T TAKAHASHI, K TI A COMPARATIVE-STUDY OF BENZODIAZEPINE HYPNOTICS AND ZOPICLONE IN SCHIZOPHRENIA - EFFECTS ON POLYSOMNOGRAMS AND BPRS SCORES SO JAPANESE JOURNAL OF PSYCHIATRY AND NEUROLOGY LA English DT Article DE SCHIZOPHRENIA; POLYSOMNOGRAM; ZOPICLONE; BENZODIAZEPINE; BRIEF PSYCHIATRIC RATING SCALE (BPRS); SLOW-WAVE SLEEP (SWS); NEGATIVE SYMPTOMS ID EYE-MOVEMENT SLEEP; DIAZEPAM; SYMPTOMS AB Sleep variables and psychiatric symptoms during benzodiazepine (BZD) hypnotic therapy and during zopiclone (ZPC) treatment were investigated in 6 male chronic schizophrenics. The amount of stage 1 was smaller and that of stage 2 was larger during treatment with ZPC than BZDs. However, no significant difference was shown in the amount of slow-wave sleep (SWS) between the treatments. Both the total and negatives-symptom scores in the Brief Psychiatric Rating Scale (BPRS) were lower, and the soundness of sleep in the subjective sleep assessments was better evaluated during treatment with ZPC than BZDs. These results suggest that ZPC may be more beneficial in treating schizophrenic insomnia than BZDs. C1 NATL CTR NEUROL & PSYCHIAT,TOKYO,JAPAN. NATL CTR HOSP MENTAL NERVOUS & MUSCULAR DISORDERS,DEPT PSYCHIAT,TOKYO,JAPAN. RP KAJIMURA, N (reprint author), NIMH,CLIN PSYCHOBIOL BRANCH,BLDG 10,ROOM 4S239,10 CTR DR MSC 1390,BETHESDA,MD 20892, USA. NR 30 TC 0 Z9 0 U1 2 U2 2 PU FOLIA PUBL SOC PI TOKYO PA ACADEMIC SOCIETIES BLDG 2-4-16 YAYOI, BUNKYO-KU, TOKYO 113, JAPAN SN 0912-2036 J9 JPN J PSYCHIAT NEUR PD DEC PY 1994 VL 48 IS 4 BP 815 EP 822 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA QL982 UT WOS:A1994QL98200010 ER PT J AU KLINE, RL VLAHOV, D QUINN, TC AF KLINE, RL VLAHOV, D QUINN, TC TI IMPROVED DETECTION OF HTLV-II ANTIBODY USING A WHOLE VIRAL LYSATE-BASED EIA SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Letter ID INTRAVENOUS-DRUG-USERS; INFECTION; ABUSERS C1 JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD. RP KLINE, RL (reprint author), NIAID,BETHESDA,MD, USA. NR 9 TC 4 Z9 4 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 DEC PY 1994 VL 7 IS 12 BP 1291 EP 1292 DI 10.1097/00126334-199412000-00016 PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA PV290 UT WOS:A1994PV29000016 PM 7965644 ER PT J AU ROGERS, AS YAFFE, S AF ROGERS, AS YAFFE, S TI PHARMACOKINETICS AND PHARMACODYNAMICS IN ADOLESCENTS JANUARY 20-21, 1994 - OVERVIEW SO JOURNAL OF ADOLESCENT HEALTH LA English DT Editorial Material RP ROGERS, AS (reprint author), NICHHD,CTR RES MOTHERS & CHILDREN,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD DEC PY 1994 VL 15 IS 8 BP 607 EP 608 DI 10.1016/S1054-139X(94)90625-4 PG 2 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA PZ256 UT WOS:A1994PZ25600001 ER PT J AU ROGERS, AS AF ROGERS, AS TI THE ROLE OF CYTOCHROME-P450 IN DEVELOPMENTAL PHARMACOLOGY SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE CYTOCHROME-P450; OXIDATIVE METABOLISM; BIOTRANSFORMATION; PUBERTY ID METABOLISM; GENE; CONSEQUENCES; EXPRESSION; MECHANISMS; INDUCTION; CAFFEINE; SYSTEM; ADULT; LIVER AB Numerous sources of human heterogeneity affect biotransformation of compounds. Cytochrome P450, the primary oxidative pathway of drug metabolism, is the dominant phase I oxidative system metabolizing, to some degree, most of the drugs used clinically in humans. The P450 pathway is a major site of drug-drug, drug-diet, and drug-disease/condition interactions. Functional variability in this system can have pronounced consequences in suboptimal therapeutic response or enhanced toxicity. Methods for cataloguing specific P450 enzymes are being developed and their identification will promote rational drug development, more efficient clinical trial evaluation, and improved therapeutic approaches to patients requiring special consideration. These methods will facilitate the study of the impact of pubertal development on function in this system. RP ROGERS, AS (reprint author), NICHHD,CTR RES MOTHERS & CHILDREN,BETHESDA,MD 20892, USA. NR 28 TC 12 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD DEC PY 1994 VL 15 IS 8 BP 635 EP 640 DI 10.1016/S1054-139X(94)90630-0 PG 6 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA PZ256 UT WOS:A1994PZ25600006 PM 7696283 ER PT J AU ROGERS, AS AF ROGERS, AS TI A RESEARCH AGENDA FOR THE STUDY OF THERAPEUTIC AGENTS IN ADOLESCENTS SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE RESEARCH; PHARMACOKINETICS; PHARMACODYNAMICS; ADOLESCENCE ID GROWTH-HORMONE; POSTMARKETING SURVEILLANCE; BREATH TEST; CIMETIDINE; MORTALITY; CHILDREN; CAFFEINE; SAFETY AB Without an understanding of the developmental factors which initiate functional changes in the adolescent's capacity for drug disposition, the choice of any developmental measure (e.g., Tanner stagging) to include in a focused research effort is premature. The role of growth and gender in pubertal functional change must be delineated. In addition, research must target clinically relevant pharmacokinetic changes resulting from this functional development and relate these to modifications of drug effect (i.e., using effect-controlled trials rather than concentration-controlled trials). Such studies could define population characteristics associated with pubertal development that produce pharmacodynamic changes. Drug effect in the adolescent, particularly at the receptor level, needs study. A strategy for the systematic evaluation of these issues is discussed. RP ROGERS, AS (reprint author), NICHHD,CTR RES MOTHERS & CHILDREN,BETHESDA,MD 20892, USA. NR 23 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE PUBL CO INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD DEC PY 1994 VL 15 IS 8 BP 672 EP 678 DI 10.1016/S1054-139X(94)90635-1 PG 7 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA PZ256 UT WOS:A1994PZ25600011 PM 7696288 ER PT J AU DICKLER, HB COLLIER, E AF DICKLER, HB COLLIER, E TI GENE-THERAPY IN THE TREATMENT OF DISEASE SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Editorial Material ID CYSTIC-FIBROSIS; ADENOVIRUSES; EPITHELIA; CORRECTS; DEFECT; CELLS; CFTR RP DICKLER, HB (reprint author), NIAID,DIV ALLERGY IMMUNOL & TRANSPLANTAT,SOLAR BLDG,ROOM 4A19,BETHESDA,MD 20892, USA. NR 25 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD DEC PY 1994 VL 94 IS 6 BP 942 EP 951 DI 10.1016/0091-6749(94)90111-2 PN 1 PG 10 WC Allergy; Immunology SC Allergy; Immunology GA PY230 UT WOS:A1994PY23000002 PM 7798542 ER PT J AU FISCHER, AR ROSENBERG, MA LILLY, CM CALLERY, JC RUBIN, P COHN, J WHITE, MV IGARASHI, Y KALINER, MA DRAZEN, JM ISRAEL, E AF FISCHER, AR ROSENBERG, MA LILLY, CM CALLERY, JC RUBIN, P COHN, J WHITE, MV IGARASHI, Y KALINER, MA DRAZEN, JM ISRAEL, E TI DIRECT EVIDENCE FOR A ROLE OF THE MAST-CELL IN THE NASAL RESPONSE TO ASPIRIN IN ASPIRIN-SENSITIVE ASTHMA SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE ASPIRIN; ASTHMA; MAST CELL; LEUKOTRIENES; ZILEUTON ID ARACHIDONIC-ACID METABOLITES; URINARY LEUKOTRIENE-E4; PEPTIDE LEUKOTRIENE; LYSINE-ASPIRIN; RELEASE; HISTAMINE; SECRETIONS; TRYPTASE; ANTAGONIST; CHALLENGE AB Background: A subset of patients with asthma experience adverse nasoocular reactions after ingestion of aspirin or agents that inhibit cyclooxygenase. Recent evidence has implicated the leukotrienes in the nasoocular reaction, but the cellullar sources and mechanism of activation are unknown. We used nasal lavage,vith and without a 5-lipoxygenase inhibitor, zileuton, to define the role of leukotrienes and to profile nasal cellular activation during this reaction. Methods: A group of eight patients with asthma shown to have adverse reactions to aspirin documented by a 15% or greater den ease in forced expiratory volume in 1 second, accompanied by an elevation in urinary leukotriene E(4) after ingestion of aspirin, received aspirin or placebo in a study with a crossover design. Nasal symptoms and nasal tryptase, histamine, leukotriene, and eosinophil cationic protein levels were evaluated. Serum tryptase and urinary histamine levels were also assessed. Subjects were then randomized to receive a week of treatment with zileuton or placebo according to a double-blind, crossover design followed by aspirin challenge and measurement of the same mediators. Results: Aspirin ingestion produced a marked increase in nasal symptoms from a baseline symptom score of 21 +/- 0.7 to a maximum of 8.4 +/- 1.2 (p < 0.0007). Aspirin ingestion produced a mean maximal increase in nasal tryptase of 3.5 +/- 26 ng/ml, whereas placebo ingestion produced a mean maximum increase of 0.1 +/- 0.2 ng/ml (p < 0.05, aspirin vs placebo). Mean maximal nasal histamine increased 1.73 +/- 1.26 ng/ml versus 0.08 +/- 0.08 ng/ml sm baseline (p < 0.05, aspirin vs placebo). Aspirin produced a mean maximal increase in nasal leukotriene value of 152 pg/ml versus a 16 pg/ml decrease after placebo ingestion (p < 0.05). Zileuton treatment blacked the increase in nasal symptoms after aspirin ingestion (maximum nasal symptom score of 1.6 +/- 0.6 with zileuton vs 5.5 +/- 0.9 with placebo [p < 0.0053]). It also blocked the rise in nasal tryptase (p = 0.011) and nasal leukotriene (p < 0.05) levels after aspirin ingestion. Zileluton treatment had no significant effect on the recovery of nasal histamine. Conclusion: The increase in nasal symptoms in aspirin-sensitive patients with asthma after aspirin ingestion is associated with increases in nasal tryptase, histamine, and cysteinyl leukotriene levels. This mediator profile is consistent with mast cell activation during the nasal response to aspirin and suggests that 5-lipoxygenase products are essential for the nasal response to aspirin. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT MED,DIV RESP,BOSTON,MA 02115. HARVARD UNIV,COMBINED PROGRAM PULM & CRIT CARE MED,BOSTON,MA 02115. LONGWOOD AREA ADULT ASTHMA CTR,BOSTON,MA. ABBOTT LABS,ABBOTT PK,IL. NIAID,ALLERG DIS SECT,BETHESDA,MD 20892. FU NCRR NIH HHS [M01-RR01032-17]; NHLBI NIH HHS [HL-T32-07633]; NIAID NIH HHS [AI-U01-31599] NR 39 TC 107 Z9 107 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD DEC PY 1994 VL 94 IS 6 BP 1046 EP 1056 DI 10.1016/0091-6749(94)90123-6 PN 1 PG 11 WC Allergy; Immunology SC Allergy; Immunology GA PY230 UT WOS:A1994PY23000013 PM 7798537 ER PT J AU SCHARENBERG, AM KINET, JP AF SCHARENBERG, AM KINET, JP TI INITIAL EVENTS IN FC-EPSILON-RI SIGNAL-TRANSDUCTION SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article ID PROTEIN-TYROSINE KINASE; TUMOR MAST-CELLS; BASOPHILIC LEUKEMIA-CELLS; HIGH-AFFINITY RECEPTOR; PHOSPHOLIPASE C-GAMMA-1; HISTAMINE-RELEASE; ANTIGEN RECEPTOR; IGE RECEPTORS; PHOSPHORYLATION; ACTIVATION C1 NIAID,MOLEC ALLERGY & IMMUNOL SECT,ROCKVILLE,MD 20852. NIH,BETHESDA,MD 20892. NR 42 TC 30 Z9 30 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD DEC PY 1994 VL 94 IS 6 SU S BP 1142 EP 1146 DI 10.1016/0091-6749(94)90323-9 PN 2 PG 5 WC Allergy; Immunology SC Allergy; Immunology GA QA020 UT WOS:A1994QA02000003 PM 7798551 ER PT J AU SEDER, RA AF SEDER, RA TI ACQUISITION OF LYMPHOKINE-PRODUCING PHENOTYPE BY CD4+ T-CELLS SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article ID INTERFERON-GAMMA PRODUCTION; STIMULATORY FACTOR; IFN-GAMMA; TRANSGENIC MICE; INTERLEUKIN-4; INVITRO; PRECURSORS; SECRETION; INDUCTION; CYTOKINE RP SEDER, RA (reprint author), NIAID,CLIN INVEST LAB,LYMPHOKINE REGULAT SECT,BETHESDA,MD 20892, USA. NR 22 TC 30 Z9 32 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD DEC PY 1994 VL 94 IS 6 SU S BP 1195 EP 1202 DI 10.1016/0091-6749(94)90332-8 PN 2 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA QA020 UT WOS:A1994QA02000012 PM 7798560 ER PT J AU GOUNNI, AS LAMKHIOUED, B DELAPORTE, E DUBOST, A KINET, JP CAPRON, A CAPRON, M AF GOUNNI, AS LAMKHIOUED, B DELAPORTE, E DUBOST, A KINET, JP CAPRON, A CAPRON, M TI THE HIGH-AFFINITY IGE RECEPTOR ON EOSINOPHILS - FROM ALLERGY TO PARASITES OR FROM PARASITES TO ALLERGY SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article ID RELEASE; CELLS C1 INST PASTEUR,CTR IMMUNOL & BIOL PARASITAIRE,INSERM,U167,CNRS 624,LILLE,FRANCE. CTR HOSP REG & UNIV LILLE,DERMATOL SERV,F-59037 LILLE,FRANCE. NIAID,MOLEC ALLERGY & IMMUNOL SECT,ROCKVILLE,MD 20852. NR 12 TC 48 Z9 49 U1 0 U2 3 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD DEC PY 1994 VL 94 IS 6 SU S BP 1214 EP 1216 DI 10.1016/0091-6749(94)90334-4 PN 2 PG 3 WC Allergy; Immunology SC Allergy; Immunology GA QA020 UT WOS:A1994QA02000014 PM 7798562 ER PT J AU BLEDSOE, HA CARROLL, JA WHELCHEL, TR FARMER, MA DORWARD, DW GHERARDINI, FC AF BLEDSOE, HA CARROLL, JA WHELCHEL, TR FARMER, MA DORWARD, DW GHERARDINI, FC TI ISOLATION AND PARTIAL CHARACTERIZATION OF BORRELIA-BURGDORFERI INNER AND OUTER MEMBRANES BY USING ISOPYCNIC CENTRIFUGATION SO JOURNAL OF BACTERIOLOGY LA English DT Article ID LYME-DISEASE SPIROCHETE; SURFACE PROTEIN-A; ESCHERICHIA-COLI; BACTEROIDES-FRAGILIS; POLYACRYLAMIDE GELS; LIPOPOLYSACCHARIDE; DEHYDROGENASE; LIPOPROTEIN; TREPONEMA; SUCCINATE AB In order to characterize the protein composition of the outer membrane of Borrelia burgdorferi, we have isolated inner and outer membranes by using discontinuous sucrose density step gradients. Outer and inner membrane fractions isolated by this method contained less than 1 and 2%, respectively, of the total lactate dehydrogenase activity (soluble marker) in cell lysate. More importantly, the purified outer membranes contained less than 4% contamination by the C subunit of F-1/F-0 ATPase (inner membrane marker). Very little flagellin protein was present in the outer membrane sample. This indicated that the outer membranes were relatively free of contamination by cytoplasmic, inner membrane or flagellar components. The outer membrane fractions (rho = 1.19 g/cm(3)) contained 0.15 mg (dry weight) of protein per mg. Inner membrane samples (rho = 1.12 g/cm(3)) contained 0.60 mg (dry weight) of protein per mg. Freeze-fracture electron microscopy revealed that the outer membrane vesicles contained about 1,700 intramembranous particles per mu m(2) while inner membrane vesicles contained about 6,600 intramembranous particles per mu m(2), similarly to previously observed particle densities for inner and outer membranes. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and nonequilibrium pH gel electrophoresis-SDS-PAGE analyses of inner and outer membrane samples revealed several proteins unique to the inner membrane and 20 proteins that localized specifically to the outer membrane. This analysis clearly shows that the inner and outer membranes isolated by this technique are unique structures. C1 UNIV GEORGIA,DEPT MICROBIOL,ATHENS,GA 30602. UNIV GEORGIA,ELECTRON MICROSCOPY LAB,ATHENS,GA 30602. NIH,ROCKY MT LABS,HAMILTON,MT 59840. FU NIAID NIH HHS [AI-23362] NR 43 TC 33 Z9 33 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD DEC PY 1994 VL 176 IS 24 BP 7447 EP 7455 PG 9 WC Microbiology SC Microbiology GA PX081 UT WOS:A1994PX08100005 PM 8002566 ER PT J AU NIMS, RW SIDHU, JS THOMAS, PE MELLINI, DW NELSON, VC OMIECINSKI, CJ LUBET, RA AF NIMS, RW SIDHU, JS THOMAS, PE MELLINI, DW NELSON, VC OMIECINSKI, CJ LUBET, RA TI ABSENCE OF ENANTIOSELECTIVITY IN THE PHARMACODYNAMICS OF P450 2B INDUCTION BY 5-ETHYL-5-PHENYLHYDANTOIN IN THE MALE-RAT LIVER OR IN CULTURED RAT HEPATOCYTES SO JOURNAL OF BIOCHEMICAL TOXICOLOGY LA English DT Article DE CYP2B, INDUCTION OF; CYP2B, PHARMACODYNAMICS OF; CYP2B, ENANTIOSELECTIVITY OF ID CYTOCHROME-P-450 GENE-EXPRESSION; DRUG-METABOLIZING-ENZYMES; PHENOBARBITAL INDUCTION; MESSENGER-RNAS; ACID; CYTOCHROMES-P-450; DISTINGUISH; MECHANISMS; ISOZYMES; INDUCER AB To explore the enantioselectivity of ligand interaction with the putative phenobarbital receptor, the pharmacodynamics of cytochrome P450 2B (CYP2B) induction by racemic 5-ethyl-5-phenylhydantoin and its two enantiomers were investigated in the male f344/NCr rat and in cultured adult male rat hepatocytes. Steady-state serum drug concentrations, measured following 14 days of administration of the compounds in the diet (0-1320 ppm, n = 3 rats per group), were used as an approximation of intrahepatocellular drug concentration. The serum xenobiotic concentrations associated with half-maximal hepatic CYP2B induction were 5-10 mu M, based on measurement of pentoxy- or benzyloxyresorufin O-dealkylation activities, or immunoreactive CYP2B1 protein. The corresponding potency values in the hepatocyte culture experiments were 8-12 mu M, based on measurement of total cellular RNA coding for CYP2B1. In both the in vivo and hepatocyte culture experiments, the potencies for CYP2B induction were essentially equivalent for the racemate and the individual enantiomers of 5-ethyl-5-phenylhydantoin. In the case of this compound, there would appear to be no enantioselectivity for CYP2B induction. this finding may be interpreted as evidence against receptor mediation in the induction of CYP2B activity, although it is also possible that a receptor is involved that does not exhibit enantioselectivity. C1 NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,CHEM SECT,FREDERICK,MD 21702. UNIV WASHINGTON,DEPT ENVIRONM HLTH,SEATTLE,WA 98195. RUTGERS STATE UNIV,COLL PHARM,DEPT BIOL CHEM,PISCATAWAY,NJ 08855. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,CHEM SYNTH & ANAL LAB,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74102]; NIGMS NIH HHS [GM 32281, R01 GM032281] NR 41 TC 11 Z9 11 U1 0 U2 0 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0887-2082 J9 J BIOCHEM TOXICOL JI J. Biochem. Toxicol. PD DEC PY 1994 VL 9 IS 6 BP 279 EP 288 DI 10.1002/jbt.2570090602 PG 10 WC Toxicology SC Toxicology GA PZ295 UT WOS:A1994PZ29500001 PM 7534352 ER PT J AU VALDIVIA, HH MARTIN, BM RAMIREZ, AN FLETCHER, PL POSSANI, LD AF VALDIVIA, HH MARTIN, BM RAMIREZ, AN FLETCHER, PL POSSANI, LD TI ISOLATION AND PHARMACOLOGICAL CHARACTERIZATION OF 4 NOVEL NA+ CHANNEL-BLOCKING TOXINS FROM THE SCORPION CENTRUROIDES NOXIUS HOFFMANN SO JOURNAL OF BIOCHEMISTRY LA English DT Article DE CENTRUROIDES NOXIUS; NA+ CHANNEL; SCORPION TOXINS; SCORPION VENOMS; TITYUS GAMMA-TOXIN ID TITYUS-SERRULATUS; SODIUM-CHANNEL; MEXICAN SCORPION; TRANSMITTER RELEASE; NERVE-TERMINALS; ALPHA-SCORPION; K+ CHANNELS; VENOM; SEQUENCE; ACTIVATION AB Four novel Na+ channel-blocking toxins (numbered 6 to 9) were purified from the venom of the scorpion Centruroides noxius Hoffmann by gel filtration and high-performance liquid chromatography and their chemical and pharmacological properties were characterized. Amino acid analysis and SDS-PAGE of the pure toxins showed them to be composed of approximately 65 amino acid residues with a molecular mass of similar to 7,500 Da. The amino acid sequences of the newly isolated toxins displayed substantial similarity to those of previously isolated and characterized C. noxius toxins, Toxin 7, the most active toxin from this venom, selectively blocked the whole-cell inward Na+ current (I-Na) from guinea pig ventricular myocytes without altering the K+ or Ca2+ currents, Using rat brain synaptosomes, the specific binding parameters of I-125-Toxin 7 were determined: K-D=40 pM and B-max=1.8 pmol/mg protein, The binding was independent of membrane potential and was displaced by all Na+ channel-toxins from C. noxius venom, with K(0.5)s ranging from 60 pM to 60 nM, Tityus gamma-toxin, a toxin representative of beta-scorpion toxins, totally displaced I-125-Toxin 7 binding, but AaH II and Lqq V toxins, representative of beta-scorpion toxins, had no effect. All four C. noxius toxins inhibited [H-3] GABA uptake by synaptosomes with IC50 similar to K-D s. The toxin effect was not synergistic with veratridine. From these results, it was concluded that the newly purified toxins exert their effects by binding to Site 4 of the voltage-sensitive Na+ channel and must, therefore, be classified as beta-scorpion toxins. C1 UNIV NACL AUTONOMA MEXICO,INST BIOTECHNOL,DEPT BIOQUIM,CUERNAVACA 62271,MORELOS,MEXICO. UNIV WISCONSIN,DEPT PHYSIOL,MADISON,WI 53706. NIMH,MOLEC NEUROGENET LAB,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. E CAROLINA UNIV,SCH MED,DEPT MICROBIOL & IMMUNOL,GREENVILLE,NC 27858. RI Possani, Lourival/J-2397-2013 NR 33 TC 12 Z9 15 U1 0 U2 0 PU JAPANESE BIOCHEMICAL SOC PI TOKYO PA ISHIKAWA BLDG-3F 25-16 HONGO-5-CHOME, TOKYO TOKYO 113, JAPAN SN 0021-924X J9 J BIOCHEM-TOKYO JI J. Biochem. (Tokyo) PD DEC PY 1994 VL 116 IS 6 BP 1383 EP 1391 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PW590 UT WOS:A1994PW59000032 PM 7706233 ER PT J AU BUCZEK, FL KEPPLE, TM SIEGEL, KL STANHOPE, SJ AF BUCZEK, FL KEPPLE, TM SIEGEL, KL STANHOPE, SJ TI TRANSLATIONAL AND ROTATIONAL JOINT POWER TERMS IN A 6-DEGREE-OF-FREEDOM MODEL OF THE NORMAL ANKLE COMPLEX SO JOURNAL OF BIOMECHANICS LA English DT Article ID PROSTHETIC FEET; BIOMECHANICAL ANALYSIS; STANCE PHASE; GAIT; KNEE; WALKING; WORK AB We hypothesized that defining joint power (JP) merely on the basis of joint rotations ignores important translational power terms, and may not adequately represent the energy flow profile for a given muscle group. A novel six degree-of-freedom (6 DOF) model of the ankle complex was implemented, accounting for previously ignored joint translations as well as traditional rotations. Foot and shank kinematic and kinetic data were collected over a stride cycle on five male and five female adults, walking five trials each at 0.69 statures s(-1). During intra-subject analyses, ensemble averages were calculated (n = 5) for JP associated with each DOF, and for related velocity and force/moment data. Translational joint velocities typically peaked below 10% of the mean walking velocity. The largest peak in JP occurred for the rotational DOF associated with dorsi/plantar flexion (360 W). The next largest peak in JP was for the vertical translational DOF, and was nearly 10% of the predominant peak. Positive work during push-off was significantly less p less than or equal to 0.05) for the 6 DOF model (27.9 J) than for either 1 or 3 DOF rotational models (30.3 and 29.9 J, respectively). Negative work during early stance was significantly less for the 6 DOF model (-10.3 J) than for either the 1 or 3 DOF models (-13.1 and -12.6 J, respectively). Inter-subject analyses (n = 50) were conducted for JP data only, with similar results. We conclude that translational JP terms are of practical importance in mechanical energy studies, and may be of particular concern when evaluating energy storing prostheses, when summing total power at several joints, and when studying pathologies that disturb joint geometry. C1 NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT REHABIL MED,BIOMECH LAB,BETHESDA,MD 20892. ADV BIOMECH INC,CLEARWATER,FL. RI Siegel, Karen Lohmann/B-5898-2008 NR 24 TC 24 Z9 24 U1 1 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0021-9290 J9 J BIOMECH JI J. Biomech. PD DEC PY 1994 VL 27 IS 12 BP 1447 EP 1457 DI 10.1016/0021-9290(94)90194-5 PG 11 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA PM712 UT WOS:A1994PM71200005 PM 7806552 ER PT J AU SESHADRI, K RAO, VSR VISHVESHWARA, S AF SESHADRI, K RAO, VSR VISHVESHWARA, S TI CHARACTERIZATION OF SUBSTRATE UPA BINDING TO RNASE-A - COMPUTER MODELING AND ENERGETICS APPROACH SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Article ID BOVINE PANCREATIC RIBONUCLEASE; MAGNETIC-RESONANCE SPECTROSCOPY; SITE-DIRECTED MUTAGENESIS; ACTIVE-SITE; NUCLEIC-ACIDS; CRYSTAL-STRUCTURE; AMINO-ACIDS; FORCE-FIELD; X-RAY; RESOLUTION AB In the past two decades RNase A has been the focus of diverse investigations in order to understand the nature of substrate binding and to know the mechanism of enzyme action. Although this system is reasonably well characterized from the view point of some of the binding sites, the details of interactions in the second base binding (B2) site is insufficient. Further, the nature of ligand-protein interaction is elucidated generally by studies on RNase A-substrate analog complexes (mainly with the help of X-ray crystallography). Hence, the details of interactions at atomic level arising due to substrates are inferred indirectly. In the present paper, the dinucleotide substrate UpA is fitted into the active site of RNase A Several possible substrate conformations are investigated and the binding modes have been selected based on Contact Criteria. Thus identified RNase A-UpA complexes are energy minimized in coordinate space and are analysed in terms of conformations, energetics and interactions. The best possible ligand conformations for binding to RNase A are identified by experimentally known interactions and by the energetics. Upon binding of UpA to RNase A the changes associated,with protein back bone, Side chains in general and at the binding sites in particular are described. Further, the detailed interactions between UpA and RNase A are characterized in terms of hydrogen bonds and energetics. An extensive study has helped in interpreting the diverse results obtained from a number of experiments and also in evaluating the extent of changes the protein and the substrate undergo in order to maximize their interactions. C1 INDIAN INST SCI,MOLEC BIOPHYS UNIT,BANGALORE 560012,KARNATAKA,INDIA. INDIAN INST SCI,JAWAHARLAL NEHRU CTR ADV SCI RES,BANGALORE 560012,KARNATAKA,INDIA. NCI,DIV CANC BIOL & DIAG,LMMB,BETHESDA,MD 20892. NR 65 TC 11 Z9 11 U1 0 U2 0 PU ADENINE PRESS INC PI GUILDERLAND PA PO BOX 355/340, GUILDERLAND, NY 12084 SN 0739-1102 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PD DEC PY 1994 VL 12 IS 3 BP 581 EP 603 PG 23 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA QD251 UT WOS:A1994QD25100005 PM 7727060 ER PT J AU WEWER, UM IBARAKI, K SCHJORRING, P DURKIN, ME YOUNG, MF ALBRECHTSEN, R AF WEWER, UM IBARAKI, K SCHJORRING, P DURKIN, ME YOUNG, MF ALBRECHTSEN, R TI A POTENTIAL ROLE FOR TETRANECTIN IN MINERALIZATION DURING OSTEOGENESIS SO JOURNAL OF CELL BIOLOGY LA English DT Article ID MATRIX GLA PROTEIN; BINDING-PROTEIN; ALKALINE-PHOSPHATASE; EXTRACELLULAR-MATRIX; PLASMA-TETRANECTIN; BONE-MATRIX; DEVELOPMENTAL EXPRESSION; GENE-EXPRESSION; HUMAN-TISSUES; GROWTH-FACTOR AB Tetranectin is a protein shared by the blood and the extracellular matrix. Tetranectin is composed of four identical, noncovalently bound polypeptides each with a molecular mass of similar to 21 kD. There is some evidence that tetranectin may be involved in fibrinolysis and proteolysis during tissue remodeling, but its precise biological function is not known. Tetranectin is enriched in the cartilage of the shark, but the gene expression pattern in the mammalian skeletal system has not been determined. In the present study we have examined the expression pattern and putative function of tetranectin during osteogenesis. In the newborn mouse, strong tetranectin immunoreactivity was found in the newly formed woven bone around the cartilage anlage in the future bone marrow and along the periosteum forming the cortex. No tetranectin immunoreactivity was found in the proliferating and hypertrophic cartilage or in the surrounding skeletal muscle. Using an in vitro mineralizing system, we examined osteoblastic cells at different times during their growth and differentiation. Tetranectin mRNA appeared in the cultured osteoblastic cells in parallel with mineralization, in a pattern similar to that of bone sialoprotein, which is regarded as one of the late bone differentiation markers. To explore the putative biological role of tetranectin in osteogenesis we established stably transfected cell lines (PC12-tet) overexpressing recombinant tetranectin as evidenced by Northern and Western blot analysis and immunoprecipitation. Both control PC12 cells and PC12-tet cells injected into nude mice produced tumors containing bone material, as evidenced by von Kossa staining for calcium and immunostaining with bone sialoprotein and alkaline phosphatase antiserum. Nude mice tumors established from PC12-tet cells contained approximately fivefold more bone material than those produced by the untransfected PC12 cell line or by the PC12 cells transfected with the expression vector with no insert (Mann Whitney rank sum test, p < 0.01), supporting the notion that tetranectin may play an important direct and/or indirect role during osteogenesis. In conclusion, we have established a potential role for tetranectin as a bone matrix protein expressed in time and space coincident with mineralization in vivo and in vitro. C1 NIDR,BETHESDA,MD 20892. RP WEWER, UM (reprint author), UNIV COPENHAGEN,INST PATHOL ANAT,MOLEC PATHOL LAB,FREDERIK VS VEJ 11,DK-2100 COPENHAGEN,DENMARK. NR 44 TC 66 Z9 69 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD DEC PY 1994 VL 127 IS 6 BP 1767 EP 1775 DI 10.1083/jcb.127.6.1767 PN 1 PG 9 WC Cell Biology SC Cell Biology GA PX308 UT WOS:A1994PX30800024 PM 7798325 ER PT J AU HAMMER, JA AF HAMMER, JA TI REGULATION OF DICTYOSTELIUM MYOSIN-II BY PHOSPHORYLATION - WHAT IS ESSENTIAL AND WHAT IS IMPORTANT SO JOURNAL OF CELL BIOLOGY LA English DT Review ID HEAVY-CHAIN PHOSPHORYLATION; CHEMOATTRACTANT-ELICITED INCREASES; KINASE; IDENTIFICATION; LOCALIZATION; FILAMENTS; GENE; PURIFICATION; REPLACEMENT; DISCOIDEUM RP HAMMER, JA (reprint author), NIH,CELL BIOL LAB,9000 ROCKVILLE PIKE,3 CTR DR,MSC 0301,BETHESDA,MD 20892, USA. NR 37 TC 18 Z9 18 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD DEC PY 1994 VL 127 IS 6 BP 1779 EP 1782 DI 10.1083/jcb.127.6.1779 PN 2 PG 4 WC Cell Biology SC Cell Biology GA PZ272 UT WOS:A1994PZ27200002 PM 7806558 ER PT J AU ZIMMERBERG, J BLUMENTHAL, R SARKAR, DP CURRAN, M MORRIS, SJ AF ZIMMERBERG, J BLUMENTHAL, R SARKAR, DP CURRAN, M MORRIS, SJ TI RESTRICTED MOVEMENT OF LIPID AND AQUEOUS DYES THROUGH PORES FORMED BY INFLUENZA HEMAGGLUTININ DURING CELL-FUSION SO JOURNAL OF CELL BIOLOGY LA English DT Article ID VIRAL ENVELOPE PROTEIN; INDUCED MEMBRANE-FUSION; PATCH-CLAMP; OPTICAL MEASUREMENTS; SURFACE-DENSITY; INITIAL-STAGES; MAST-CELLS; FLUORESCENCE; EVENTS; VIRUS AB The fusion of cells by influenza hemagglutinin (HA) is the best characterized example of protein-mediated membrane fusion. In simultaneous measurements of pairs of assays for fusion, we determined the order of detectable events during fusion. Fusion pore formation in HA-triggered cell-cell fusion was first detected by changes in cell membrane capacitance, next by a flux of fluorescent lipid, and finally by flux of aqueous fluorescent dye. Fusion pore conductance increased by small steps. A retardation of lipid and aqueous dyes occurred during fusion pore fluctuations. The flux of aqueous dye depended on the size of the molecule. The lack of movement of aqueous dyes while total fusion pore conductance increased suggests that initial HA-triggered fusion events are characterized by the opening of multiple small pores: the formation of a ''sieve''. C1 NCI,MEMBRANE STRUCT & FUNCT SECT,BETHESDA,MD 20892. UNIV DELHI,DEPT BIOCHEM,NEW DELHI 110021,INDIA. UNIV MISSOURI,SCH BIOL SCI,DIV BIOCHEM & MOLEC BIOL,KANSAS CITY,MO 64110. RP ZIMMERBERG, J (reprint author), NICHHD,THEORET & PHYS BIOL LAB,BLDG 10,ROOM 10D14,BETHESDA,MD 20892, USA. NR 44 TC 138 Z9 138 U1 1 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD DEC PY 1994 VL 127 IS 6 BP 1885 EP 1894 DI 10.1083/jcb.127.6.1885 PN 2 PG 10 WC Cell Biology SC Cell Biology GA PZ272 UT WOS:A1994PZ27200011 PM 7806567 ER PT J AU PAVLIN, D BEDALOV, A KRONENBERG, MS KREAM, BE ROWE, DW SMITH, CL PIKE, JW LICHTLER, AC AF PAVLIN, D BEDALOV, A KRONENBERG, MS KREAM, BE ROWE, DW SMITH, CL PIKE, JW LICHTLER, AC TI ANALYSIS OF REGULATORY REGIONS IN THE COL1A1 GENE RESPONSIBLE FOR 1,25-DIHYDROXYVITAMIN D-3-MEDIATED TRANSCRIPTIONAL REPRESSION IN OSTEOBLASTIC CELLS SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE TYPE I COLLAGEN; GENE REGULATION BY STEROID HORMONE; BONE CELLS IN CULTURE; VITAMIN-D; NUCLEOTIDES ID RAT OSTEOCALCIN GENE; GROWTH-FACTOR-I; ALPHA-1(I) COLLAGEN PROMOTER; HUMAN VITAMIN-D3 RECEPTOR; OSTEO-SARCOMA CELLS; RNA POLYMERASE-II; NEGATIVE REGULATION; BINDING-PROTEIN; DNA-SEQUENCES; MESSENGER-RNA AB The synthesis of type I collagen in bone cells is inhibited by the calcium-regulating hormone 1,25-dihydroxyvitamin D-3. Earlier work from our laboratories has indicated that vitamin D regulation is at the level of transcription, based on results from both nuclear run-off assays and functional promoter analysis of a hybrid gene consisting of a 3.6 kb COL1A1 promoter fragment fused to the chloramphenicol acetyltransferase reporter gene. In the present study, we investigated the molecular basis for vitamin D-mediated transcriptional repression of the COL1A1 gene and report the identification of a region within the COL1A1 upstream promoter (the HindIII-Pstl restriction fragment between nucleotides -2295 and -1670) which is necessary for 1,25-dihydroxyvitamin D-3 responsiveness in osteoblastic cells. This hormone-mediated inhibitory effect on the marker gene parallels the inhibition of the endogenous collagen gene. A 41 bp fragment from this region (between nucleotides -2256 and -2216) contains a sequence which is very similar to vitamin D-responsive elements identified in the osteocalcin gene. Extracts from cultured cells which express a high level of vitamin D receptor contain a hormone:receptor complex that binds specifically to this 41 bp fragment, as demonstrated by bandshift analysis. However, deletion of this vitamin D receptor binding region from either a -3.5 kb or a -2.3 kb promoter fragment did not abolish vitamin D responsiveness. These results indicate that a vitamin D response element similar to that described for other vitamin D responsive genes (osteocalcin and osteopontin) does not alone mediate the repression of COL1A1 by 1,25-dihydroxyvitamin D-3. (C) 1994 Wiley-Liss, Inc. C1 UNIV CONNECTICUT,CTR HLTH,DEPT PEDIAT,FARMINGTON,CT 06030. UNIV CONNECTICUT,CTR HLTH,DEPT MED,FARMINGTON,CT 06030. UNIV TEXAS,HLTH SCI CTR,DEPT CELLULAR & STRUCT BIOL,SAN ANTONIO,TX 78284. UNIV TEXAS,HLTH SCI CTR,DEPT ORTHODONT,SAN ANTONIO,TX 78284. NCI,MOLEC VIROL LAB,BETHESDA,MD 20892. LIGAND PHARMACEUT,SAN DIEGO,CA 92121. FU NIAMS NIH HHS [AR29850, AR29983, AR38933] NR 54 TC 26 Z9 27 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD DEC PY 1994 VL 56 IS 4 BP 490 EP 501 DI 10.1002/jcb.240560409 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA QF986 UT WOS:A1994QF98600008 PM 7890807 ER PT J AU ZIMERING, MB RILEY, DJ THAKKERVARIA, S WALKER, AM LAKSHMINARYAN, V SHAH, R BRANDI, ML EZZAT, S KATSUMATA, N FRIESEN, HG MARX, SJ ENG, J AF ZIMERING, MB RILEY, DJ THAKKERVARIA, S WALKER, AM LAKSHMINARYAN, V SHAH, R BRANDI, ML EZZAT, S KATSUMATA, N FRIESEN, HG MARX, SJ ENG, J TI CIRCULATING FIBROBLAST GROWTH FACTOR-LIKE AUTOANTIBODIES IN 2 PATIENTS WITH MULTIPLE ENDOCRINE NEOPLASIA TYPE-1 AND PROLACTINOMA SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CAPILLARY ENDOTHELIAL-CELLS; INSULIN-RECEPTOR; PITUITARY-TUMOR; FACTOR FGF; ANTIBODIES; PROTEIN; SEQUENCE; RELEASE; BINDING; SERA AB Basic fibroblast growth factor (bFGF) is a potent endothelial cell mitogen found in a variety of normal and tumor tissues. bFGF lacks a classical amino-terminal signal sequence and is not readily detectable in plasma from normal subjects. In earlier studies we showed increased bFGF-like mitogenic activity for parathyroid-derived endothelial cells and (increased) bFGF immunoreactivity (0.24-1.28 ng/mL) in plasma of subjects with multiple endocrine neoplasia type 1 (MEN-1). In the present study we examined the proliferative activity of MEN-1 and normal plasmas (applied to protein-A columns) in calf pulmonary artery endothelial cells. Protein-A-eluted activity in plasma from MEN-1 prolactinoma plasma exceeded activity from normal and MEN-1 nonprolactinoma plasma in three of eight MEN-1 subjects with untreated or recurrent prolactinoma. Protein-A-eluted active fractions from MEN-1 prolactinoma plasma had several properties of an immunoglobulin G, including affinity for antihuman immunoglobulin G (IgG) agarose, sensitivity to thiols, and (prepared by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions) apparent mor wt corresponding to those of the heavy and light chains of IgG. The IgG fraction of MEN-1 prolactinoma plasma had far mole activity in endothelial cells than did optimal concentrations of known growth factors or conditioned medium from prolactinoma cells. Endothelial cell bioactivity in protein-A-eluted fractions from MEN-1 prolactinoma plasma was neutralized 70% by rabbit antibodies to intact bFGF. These results imply novel growth stimulatory bFGF-like autoantibodies in a subset of MEN-1 patients with prolactinoma. C1 UNIV MED & DENT NEW JERSEY, ROBERT WOOD JOHNSON MED SCH, DIV PULM MED, PISCATAWAY, NJ 08854 USA. NIDDKD, METAB DIS BRANCH, BETHESDA, MD 20892 USA. UNIV CALIF RIVERSIDE, DIV BIOMED SCI, RIVERSIDE, CA 92521 USA. UNIV FLORENCE, SCH MED, DEPT PHYSIOPATHOL, I-60139 FLORENCE, ITALY. UNIV TORONTO, DIV ENDOCRINOL & METAB, TORONTO, ON M4Y 1J3, CANADA. UNIV MANITOBA, FAC MED, DEPT PHYSIOL, WINNIPEG, MB R3E 0W3, CANADA. VET AFFAIRS MED CTR, BRONX, NY 10468 USA. RP ZIMERING, MB (reprint author), VET AFFAIRS MED CTR, MED SERV 111, LYONS, NJ 07939 USA. NR 35 TC 10 Z9 10 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 EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 1994 VL 79 IS 6 BP 1546 EP 1552 DI 10.1210/jc.79.6.1546 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PX775 UT WOS:A1994PX77500005 PM 7989454 ER PT J AU IMAI, Y FUSCO, A SUZUKI, Y LESNIAK, MA DALFONSO, R SESTI, G BERTOLI, A LAURO, R ACCILI, D TAYLOR, SI AF IMAI, Y FUSCO, A SUZUKI, Y LESNIAK, MA DALFONSO, R SESTI, G BERTOLI, A LAURO, R ACCILI, D TAYLOR, SI TI VARIANT SEQUENCES OF INSULIN-RECEPTOR SUBSTRATE-1 IN PATIENTS WITH NONINSULIN-DEPENDENT DIABETES-MELLITUS SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SH2-CONTAINING PHOSPHOTYROSINE PHOSPHATASE; TYROSINE PHOSPHORYLATION; PIMA-INDIANS; GENE; RESISTANCE; MUTATIONS; PROTEIN; POLYMORPHISMS; PATHOGENESIS; CLONING AB The pathophysiology of noninsulin-dependent diabetes mellitus (NIDDM) is characterized by insulin resistance and insulin deficiency. To search for genetic defects causing NIDDM, we have screened for mutations in the gene encoding insulin receptor substrate-1 (IRS-1), an intracellular protein that is phosphorylated by the insulin receptor and is thought to play an important role in mediating insulin action. The coding sequence of the IRS-1 gene (divided into 12 overlapping fragments) was amplified by polymerase chain reaction and screened for the presence of single stranded conformational polymorphisms. This led to the identification of 6 variants in the nucleotide sequence. There were 3 nonconservative amino acids substitutions: Gly(819)-->Arg, Gly(972)-->Arg, and Arg(1221)-->Cys. In addition, there were three silent polymorphisms: GAC vs. GAT encoding Asp(90), GGG vs. GGA encoding Gly(235), and GCA us. GCG encoding Ala(805). The previously reported Arg(972) substitution was identified in 7 of 31 patients with NIDDM, 4 of 32 normal. subjects, and 4 of 16 nondiabetic obese individuals. The 2 novel amino acid substitutions (Arg(819) and Cys(1221)) were both detected in 1 patient with NIDDM, but not in either of the other 2 groups of nondiabetic individuals. All 3 amino acid residues are identically conserved in the amino acid sequences of human, mouse, and rat IRS-1, suggesting that Gly(819), Gly(972), and Arg(1221),, important for the normal function of IRS-1. Furthermore, the prevalence of amino acid substitutions in IRS-1 is increased in patients with NIDDM. These observations suggest that mutations in the IRS-1 gene may play a causal role in the pathogenesis of NIDDM. C1 NIDDKD, DIABET BRANCH, BETHESDA, MD 20892 USA. UNIV ROMA TOR VERGATA, DIPARTIMENTO MED INTERNA, ROME, ITALY. RI Sesti, Giorgio/B-1509-2012; OI Sesti, Giorgio/0000-0002-1618-7688 NR 24 TC 86 Z9 89 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 1994 VL 79 IS 6 BP 1655 EP 1658 DI 10.1210/jc.79.6.1655 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PX775 UT WOS:A1994PX77500023 PM 7989470 ER PT J AU ZHOU, J DSUPIN, BA GIUDICE, LC BONDY, CA AF ZHOU, J DSUPIN, BA GIUDICE, LC BONDY, CA TI INSULIN-LIKE GROWTH-FACTOR SYSTEM GENE-EXPRESSION IN HUMAN ENDOMETRIUM DURING THE MENSTRUAL-CYCLE SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FACTOR-BINDING PROTEIN-1; MESSENGER-RIBONUCLEIC-ACID; I IGF-I; STROMAL CELLS; RAT UTERUS; RECEPTOR; SECRETION; ESTROGEN; IDENTIFICATION; FOLLICLE AB To study the cellular patterns of gene expression of the insulin-like growth factor (IGF) system in human endometrium during the menstrual cycle, we used in situ hybridization histochemistry to localize messenger ribonucleic acids (mRNAs) encoding IGF-I and -II, their receptors, and their binding proteins (IGFBPs) in fresh-frozen endometrial tissue obtained from cycling women. IGF-I and IGF-II mRNAs are both expressed diffusely throughout endometrial stroma and are not detected in endometrial epithelium. Endometrial IGF-I mRNA is significantly more abundant during the proliferative than the secretory phase of the menstrual cycle, whereas the reverse is true for IGF-II. Type I and type II IGF receptor mRNAs are both present in endometrial stroma, but are relatively more abundant in endometrial epithelium, and neither shows distinctive cyclic changes. IGFBP-2, -4, -5, and -6 mRNAs demonstrate a diffuse stromal pattern of expression, whereas IGFBP-1 and -3 are more focally concentrated in selected subpopulations of endometrial cells. IGFBP-1 mRNA is not detected in proliferative endometrium and demonstrates a very heterogeneous pattern of expression in secretory endometrium, where it is intensely abundant in a patchy distribution of stromal and epithelial cells. IGFBP-3 mRNA is primarily concentrated in endometrial capillaries and is increased in the secretory phase, largely due to the intense vascularization of endometrial glands during this phase. IGFBP-5 mRNA is more abundant in the proliferative phase, but all other IGFBP mRNAs are relatively increased in the secretory phase of the menstrual cycle. These findings support the view that the IGF system plays a fundamental role in endometrial biology, acting via autocrine and/or paracrine mechanisms, with IGF-I and IGPBP-5 being dominant in the proliferative phase, and IGF-II and the other IGFBPs predominant in the secretory phase of the menstrual cycle. C1 STANFORD UNIV, MED CTR, DEPT GYNECOL & OBSTET, STANFORD, CA 94305 USA. RP ZHOU, J (reprint author), NICHHD, DEV ENDOCRINOL BRANCH, BLDG 10, ROOM 10N262, BETHESDA, MD 20892 USA. FU NICHD NIH HHS [HD-25220] NR 44 TC 133 Z9 138 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 1994 VL 79 IS 6 BP 1723 EP 1734 DI 10.1210/jc.79.6.1723 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PX775 UT WOS:A1994PX77500034 PM 7527408 ER PT J AU VELDHUIS, JD URBAN, RJ DUFAU, ML AF VELDHUIS, JD URBAN, RJ DUFAU, ML TI DIFFERENTIAL RESPONSES OF BIOLOGICALLY-ACTIVE LUTEINIZING-HORMONE SECRETION IN OLDER VERSUS YOUNG MEN TO INTERRUPTION OF ANDROGEN NEGATIVE FEEDBACK SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; LH-RELEASING HORMONE; ELDERLY MEN; AGING MEN; GONADOTROPIN-SECRETION; PITUITARY GONADOTROPINS; OVARIECTOMIZED EWES; CELL FUNCTION; TESTOSTERONE; SERUM AB To investigate the responsiveness of the healthy aging male hypothalamo-pituitary-gonadal axis to short term interruption of androgen negative feedback, we administered a selective nonsteroidal competitive antagonist of the androgen receptor, flutamide hydrochloride (250 mg, orally, three times daily for 3.5 days), to five older (aged 63-72 yr) and eight young (aged 21-30 yr) men. Pulsatile bioactive LH release was assessed by the rat interstitial cell testosterone bioassay in plasma sampled at 10-min intervals for 8 h overnight at baseline and after flutamide administration. Pituitary responsiveness was evaluated after two successive iv injections of 10 mu g GnRH. Deconvolution analysis was used to estimate the number, amplitude, duration, and mass of bioactive LH secretory bursts and the half-life of biologically active hormone. At baseline, older men exhibited a significantly lower spontaneous bioactive LH secretory burst frequency than young men, with a median of 5 events/8 h (older) vs. 7.5 bursts/8 h (younger, P < 0.05). In older men, mean 8-h plasma bioactive LH concentrations increased significantly in response to flutamide (P = 0.006), and the 8-h calculated secretion rate of bioactive LH rose concomitantly. These increases were similar to responses in young men. However, during antiandrogen administration, the frequency of bioactive LH secretory bursts failed to rise in older men to the baseline value seen in young men. Moreover, older (but not young) men showed a significant prolongation of the LH secretory burst duration in response to flutamide treatment. On the other hand, the estimated half-life of endogenous bioactive LH increased Significantly after flutamide ingestion in young compared to older individuals. After GnRH injections, older and young men secreted similar amounts of LH before flutamide administration, but during flutamide treatment, older men released more biologically active LH after the first GnRH stimulus [older men, 104 +/- 11 IU/L (median, 110); younger men, 44 +/- 8.4 IU/L (median, 40); P < 0.05]. Serum free testosterone concentrations rose significantly during flutamide exposure in both young and older men, but estradiol concentrations increased significantly only in young men. In summary, healthy older men exhibit a reduced (overnight) spontaneous bioactive LH secretory burst frequency. Pharmacological attenuation of androgen-mediated negative feedback increases mean serum free testosterone concentrations and plasma bioactive LH concentrations to a similar degree in older and young individuals, but different mechanisms operate in the two age groups. In older men, flutamide treatment amplifies the mass of bioactive LH secreted per burst by prolonging the LH secretory burst duration, whereas in young men, flutamide administration increases the apparent half-life of biologically active LH significantly relative to values in older men. We conclude that competitive nonsteroidal blockade of the androgen receptor unmasks qualitatively altered mechanisms of increased bioactive LH release in healthy older men. C1 UNIV VIRGINIA, HLTH SCI CTR, DEPT INTERNAL MED, DIV ENDOCRINOL & METAB, CHARLOTTESVILLE, VA 22908 USA. UNIV TEXAS, MED RES BRANCH, DEPT INTERNAL MED, GALVESTON, TX 77550 USA. NICHHD, MOLEC ENDOCRINOL SECT, BETHESDA, MD 20892 USA. FU NCRR NIH HHS [RR-00847, RR00847-15]; NICHD NIH HHS [1-KO4-HD-00634] NR 56 TC 35 Z9 35 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 EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 1994 VL 79 IS 6 BP 1763 EP 1770 DI 10.1210/jc.79.6.1763 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PX775 UT WOS:A1994PX77500041 PM 7989483 ER PT J AU YANO, K HIDAKA, A SAJI, M POLYMEROPOULOS, MH OKUNO, A KOHN, LD CUTLER, GB AF YANO, K HIDAKA, A SAJI, M POLYMEROPOULOS, MH OKUNO, A KOHN, LD CUTLER, GB TI A SPORADIC CASE OF MALE-LIMITED PRECOCIOUS PUBERTY HAS THE SAME CONSTITUTIVELY ACTIVATING POINT MUTATION IN LUTEINIZING-HORMONE CHORIOGONADOTROPIN RECEPTOR GENE AS FAMILIAL CASES SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID INOSITOL PHOSPHATE LEVELS; THYROTROPIN TSH RECEPTOR; 3RD CYTOPLASMIC LOOP; SEXUAL PRECOCITY; HORMONE RECEPTOR; LEYDIG; PHOSPHOINOSITIDE; TESTOTOXICOSIS; AUTOANTIBODIES; GENERATIONS AB Familial male-limited precocious puberty (FMPP) is an autosomal dominant disorder characterized by marked elevation of serum testosterone despite low levels of gonadotropin. Recently, a single point mutation in the LH/hCG receptor (LH/CGR) gene was found in FMPP families that constitutively activates the LH/CGR, causing Leydig cell activation and precocious puberty. Among the Japanese population, only four sporadic cases of male-limited precocious puberty have been reported. In the current study, we examined one of the four reported Japanese patients with sporadic male-limited precocious puberty and found the same mutation as that in the FMPP families. Genomic DNA was isolated, and the polymerase chain reaction (PCR) was performed to amplify a fragment of LH/ CGR DNA encoding amino acid residues that include transmembrane helixes 5 and 6. Sequencing of the PCR products revealed a heterozygous adenosine-guanine transition at nucleotide 1733 in codon 578. The mutation encodes an aspartic acid(678)-glycine substitution in transmembrane helix 6. The mutant LH/CGR, created by site-directed mutagenesis in vitro, exhibited constitutively higher cAMP levels in transfected COS-7 cells than the wild-type LH/CGR, as described previously; however, basal inositol phosphate levels were not increased by transfection with complementary DNA for the mutant receptor. The concentration and affinity of [I-125]hCG-binding sites were similar in cells transfected with the mutant and wild-type LH/CGR complementary DNAs, indicating that the mutant did not alter the production of receptor or its ability to bind human LH/CG. The sporadic occurrence of this case was confirmed by further studies. The mutation creates a recognition site for the restriction endonuclease MspI. Restriction digestion was positive for the mutant allele in the patient; however, the PCR products of his parents were not digested by MspI, indicating that the patient's mutant allele was not inherited from his parents. DNA analysis of the patient and the parents, using microsatellite repeat markers, was compatible with biological paternity and maternity. We conclude that the aspartic acid(578)-->glycine mutation in the LH/CGR has arisen in the Japanese population and is the cause of a sporadic case of male-limited precocious puberty. C1 NIDDKD, BIOCHEM & METAB LAB, CELL REGULAT SECT, BETHESDA, MD 20892 USA. NIH, NATL CTR HUMAN GENOME RES, BETHESDA, MD 20892 USA. ASAHIKAWA MED COLL, DEPT PEDIAT, ASAHIKAWA 078, HOKKAIDO, JAPAN. RP YANO, K (reprint author), NICHHD, DEV ENDOCRINOL BRANCH, BLDG 10, ROOM 10N262, BETHESDA, MD 20892 USA. NR 19 TC 54 Z9 54 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 1994 VL 79 IS 6 BP 1818 EP 1823 DI 10.1210/jc.79.6.1818 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PX775 UT WOS:A1994PX77500050 PM 7527413 ER PT J AU LIU, F HINTZ, RL KHARE, A DIAUGUSTINE, RP POWELL, DR LEE, PDK AF LIU, F HINTZ, RL KHARE, A DIAUGUSTINE, RP POWELL, DR LEE, PDK TI IMMUNOBLOT STUDIES OF THE IGF-RELATED ACID-LABILE SUBUNIT SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Note ID BINDING-PROTEIN COMPLEX; CHRONIC-RENAL-FAILURE; HUMAN-SERUM AB Insulin-like growth factors I and II (IGF-I and II) are present in serum primarily within a ternary complex consisting of IGF, IGF-binding protein-3 (IGF-3) and acid-labile subunit (ALS). Relatively little is known about ALS as compared to the other components of the complex. We report immunoblot studies of ALS using a new rabbit antiserum to human ALS(1-34). The antiserum shows high specificity for ALS, labelling only the intact 82-88 kDa doublet in whole serum. Treatment with endoglycosidase-F leads to only a partial deglycosylation of ALS in whole serum, while purified ALS is reduced to Mr similar to 58 kDa. Acidification of both whole serum and purified ALS leads to a complete loss of ALS ability to bind to cross-linked IGFBP-3:[I-125]IGF-II tracer; however, immunoblot studies show no change in the apparent Mr of the major ALS band. Immunoblot studies of human serum shows that intact ALS is decreased in growth-hormone (GH) deficiency, increases with GH treatment, is elevated in GH excess and is unchanged with IGF-I treatment. These data provide new information regarding the characteristics of ALS and demonstrate the research utility of a highly-specific antiserum for this protein. C1 DIAGNOST SYST LABS INC, WEBSTER, TX 77598 USA. NIEHS, RES TRIANGLE PK, NC 27709 USA. BAYLOR UNIV, DEPT PEDIAT, HOUSTON, TX 77030 USA. RP LIU, F (reprint author), STANFORD UNIV, DEPT PEDIAT, STANFORD, CA 94305 USA. NR 16 TC 22 Z9 23 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 EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC PY 1994 VL 79 IS 6 BP 1883 EP 1886 DI 10.1210/jc.79.6.1883 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PX775 UT WOS:A1994PX77500061 PM 7527417 ER PT J AU CHU, KC MILLER, BA FEUER, EJ HANKEY, BF AF CHU, KC MILLER, BA FEUER, EJ HANKEY, BF TI A METHOD FOR PARTITIONING CANCER MORTALITY TRENDS BY FACTORS ASSOCIATED WITH DIAGNOSIS - AN APPLICATION TO FEMALE BREAST-CANCER SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE INCIDENCE-BASED MORTALITY; BREAST CANCER MORTALITY RATES; STAGE-AT-DIAGNOSIS; AGE-AT-DIAGNOSIS; YEAR-OF-DIAGNOSIS; LEAD TIME BIAS ID MAMMOGRAPHY; RATES AB U.S. cancer mortality data derived from information recorded on death certificates are frequently relied upon as an indicator of progress against cancer. A limitation of this measure is the lack of information pertaining to the onset of disease, such as year-of-diagnosis, age-at-diagnosis, stage of disease at diagnosis and histology of lesions. However, population-based cancer registries collect these types of data and allow the calculation of an incidence-file based mortality rate. This incidence-based mortality rate allows a partitioning of mortality by variables associated with the cancer onset. Breast cancer incidence-based mortality measures are created and compared to mortality rates based on death certificates over a comparable time period. Novel mortality measures, such as mortality rates by stage-at-diagnosis, age-at-diagnosis and year-of-diagnosis, are used to illustrate the value of this approach. RP CHU, KC (reprint author), NCI,DIV CANC PREVENT & CONTROL,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 18 TC 37 Z9 38 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD DEC PY 1994 VL 47 IS 12 BP 1451 EP 1461 DI 10.1016/0895-4356(94)90089-2 PG 11 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA QB681 UT WOS:A1994QB68100016 PM 7730854 ER PT J AU WANG, GQ DAWSEY, SM ZHOU, MH LEWIN, KJ AF WANG, GQ DAWSEY, SM ZHOU, MH LEWIN, KJ TI GASTRIC HETEROTOPIA IN THE UPPER ESOPHAGUS (INLET PATCH) IN ENDOSCOPIC SURVEYS IN NORTHERN CHINA SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Review DE ENDOSCOPY; ESOPHAGUS; HETEROTOPIC GASTRIC MUCOSA; HELICOBACTER PYLORI; CHINA ID CAMPYLOBACTER-LIKE ORGANISMS; CERVICAL ESOPHAGUS; PROXIMAL ESOPHAGUS; MUCOSA; PYLORI; ADENOCARCINOMA; EPITHELIUM; PROFILE; ULCER AB Upper esophageal gastric heterotopia (inlet patch) has not been reported in endoscopic series from China. We describe the occurrence of endoscopically and histologically typical inlet patches in two endoscopic surveys of asymptomatic adults in northern China. Because rapid endoscopic protocols were used, the 0.3-0.4% prevalence of inlet patch in these surveys probably represents a minimum figure for adults in this population. C1 CHINESE ACAD MED SCI,HOSP CANC,DEPT CHEST SURG,BEIJING 100037,PEOPLES R CHINA. NCI,CANC PREVENT STUDIES BRANCH,BETHESDA,MD 20892. UNIV CALIF LOS ANGELES,CTR HLTH SCI,DEPT PATHOL,LOS ANGELES,CA 90024. NR 25 TC 13 Z9 13 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD DEC PY 1994 VL 19 IS 4 BP 321 EP 324 DI 10.1097/00004836-199412000-00014 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA PV011 UT WOS:A1994PV01100013 PM 7876515 ER PT J AU SCHWABE, M BRINI, AT BOSCO, MC RUBBOLI, F EGAWA, M ZHAO, JA PRINCLER, GL KUNG, HF AF SCHWABE, M BRINI, AT BOSCO, MC RUBBOLI, F EGAWA, M ZHAO, JA PRINCLER, GL KUNG, HF TI DISRUPTION BY INTERFERON-ALPHA OF AN AUTOCRINE INTERLEUKIN-6 GROWTH LOOP IN IL-6-DEPENDENT U266 MYELOMA CELLS BY HOMOLOGOUS AND HETEROLOGOUS DOWN-REGULATION OF THE IL-6 RECEPTOR ALPHA-CHAIN AND BETA-CHAIN SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE MULTIPLE MYELOMA; IL-6 DEPENDENCY; IL-6 RECEPTORS; IFN-ALPHA TREATMENT; RECEPTOR DOWN-REGULATION ID MULTIPLE-MYELOMA; GENE-EXPRESSION; SIGNAL TRANSDUCER; GAMMA-INTERFERON; RAT HEPATOCYTES; LINE; PROLIFERATION; INHIBITION; GP130; DIFFERENTIATION AB IL-6 is an autocrine growth factor for U266 myeloma cells and their growth is inhibited by IFN-alpha or IL-6 mAb. We asked, therefore, whether IFN-alpha-induced growth inhibition involved IL-6. IFN-alpha and mAb against IL-6, the IL-6R alpha-(gp80) or beta-chain (gp130) potently inhibited U266 cells. Remarkably, this effect occurred despite IFN-alpha-augmented secretion of endogenous IL-6. However, examining the IL-6R revealed that IFN-alpha drastically curtailed expression of the IL-6R alpha- and beta-chain. This effect occurred on two different levels (protein and mRNA) and by two different mechanisms (directly and indirectly through IL-6). First, IFN-alpha, but not IL-6, greatly decreased gp80 and, to a lesser extent, gp130 mRNA levels which resulted in a loss of IL-6 binding sites. Second, IFN-alpha-induced IL-6 predominantly downregulated membrane-bound gp130. IFN-alpha-mediated decrease of gp80 levels was not detected on IL-6-independent myeloma (RPMI 8226) or myeloid cells (U937). We conclude that IFN-alpha inhibited IL-6-dependent myeloma cell growth by depriving U266 cells of an essential component of their autocrine growth loop, a functional IL-6R. C1 NCI,FREDERICK CANC RES & DEV CTR,BIOCHEM PHYSIOL LAB,FREDERICK,MD 21701. NCI,FREDERICK CANC RES & DEV CTR,EXPTL IMMUNOL LAB,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21701. NIAID,MOLEC ALLERGY & IMMUNOL SECT,ROCKVILLE,MD 20852. UNIV MILAN,DIPARTIMENTO FARMACOL CHEMIOTERAPIA & TOSSICOL ME,I-20129 MILAN,ITALY. RI Bosco, Maria Carla/J-7928-2016 OI Bosco, Maria Carla/0000-0003-1857-7193 NR 57 TC 47 Z9 47 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 DEC PY 1994 VL 94 IS 6 BP 2317 EP 2325 DI 10.1172/JCI117596 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA PV810 UT WOS:A1994PV81000022 PM 7989587 ER PT J AU KLEIN, KO BARON, J COLLI, MJ MCDONNELL, DP CUTLER, GB AF KLEIN, KO BARON, J COLLI, MJ MCDONNELL, DP CUTLER, GB TI ESTROGEN-LEVELS IN CHILDHOOD DETERMINED BY AN ULTRASENSITIVE RECOMBINANT CELL BIOASSAY SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE PREPUBERTAL; YEAST; SACCHAROMYCES CEREVISIAE; ESTRADIOL; ESTROGEN ID SACCHAROMYCES-CEREVISIAE; TURNERS SYNDROME; ETHINYL ESTRADIOL; GROWTH-HORMONE; SHORT-TERM; RECEPTOR; PLASMA; RADIOIMMUNOASSAY; PUBERTY; GIRLS AB We hypothesized that estradiol levels are higher in prepubertal girls than in prepubertal boys and that this greater secretion of estradiol might drive the more rapid epiphyseal development and earlier puberty in girls. Since previous estradiol assays have lacked adequate sensitivity to test the hypothesis of higher estradiol levels in girls, we developed a new ultrasensitive assay to measure estrogen levels. The assay uses a strain of Saccharomyces cerevisiae genetically engineered for extreme sensitivity to estrogen. Yeast were transformed with plasmids encoding the human estrogen receptor and an estrogen-responsive promoter fused to the structural gene for beta-galactosidase. Ether extracts of 0.8 ml of serum were incubated with yeast for 8 h and the beta-galactosidase response was used to determine estrogen bioactivity relative to estradiol standards prepared in charcoal-stripped plasma. The assay was highly specific for estradiol with < 3% cross-reactivity with estrone, estriol, or estradiol metabolites. The detection limit was < 0.02 pg/ml estradiol equivalents (100-fold lower than existing assays). Using this assay, we measured estrogen levels in 23 prepubertal boys (9.4+/-2.0 yr) and 21 prepubertal girls (7.7+/-1.9 [SD] yr). The estrogen level in girls, 0.6+/-0.6 pg/ml estradiol equivalents, was significantly greater than the level in boys, 0.08+/-0.2 pg/ml estradiol equivalents (P < 0.05). We conclude that the ultrasensitive recombinant cell bioassay for estrogen is approximately 100-fold more sensitive than previous estradiol assays, that estrogen levels are much lower prepubertally, in both sexes, than reported previously, and that prepubertal girls have 8-fold higher estrogen levels than prepubertal boys. C1 DUKE UNIV,MED CTR,DEPT PHARMACOL,DURHAM,NC 27710. CHILDRENS HOSP ORANGE CTY,ORANGE,CA 92668. RP KLEIN, KO (reprint author), NICHHD,DEV ENDOCRINOL BRANCH,BLDG 10,ROOM 10N262,BETHESDA,MD 20892, USA. NR 46 TC 259 Z9 259 U1 1 U2 9 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 DEC PY 1994 VL 94 IS 6 BP 2475 EP 2480 DI 10.1172/JCI117616 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA PV810 UT WOS:A1994PV81000042 PM 7989605 ER PT J AU LATHEY, JL FISCUS, SA RASHEED, S KAPPES, JC GRIFFITH, BP ELBEIK, T SPECTOR, SA REICHELDERFER, PS AF LATHEY, JL FISCUS, SA RASHEED, S KAPPES, JC GRIFFITH, BP ELBEIK, T SPECTOR, SA REICHELDERFER, PS TI OPTIMIZATION OF QUANTITATIVE CULTURE ASSAY FOR HUMAN-IMMUNODEFICIENCY-VIRUS FROM PLASMA SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Note ID INFECTED INDIVIDUALS; VIREMIA; DISEASE; TYPE-1 AB Experimental conditions essential to a simple, reproducible, quantitative human immunodeficiency virus plasma assay were determined. Five parameters were evaluated: length of culture, reproducibility, assay dilution schema, washing procedures, and anticoagulant usage. The recommended quantitative plasma assay utilizes undiluted citrated plasma cultured with peripheral blood mononuclear cells for 14 days with fivefold dilutions and a medium change on day 1 with no washing. C1 UNIV N CAROLINA, DEPT MICROBIOL & IMMUNOL, CHAPEL HILL, NC 27599 USA. UNIV SO CALIF, VIRAL ONCOL & AIDS RES LAB, LOS ANGELES, CA 90032 USA. UNIV ALABAMA, DEPT MED, BIRMINGHAM, AL 35294 USA. YALE UNIV, SCH MED, DEPT LAB MED, NEW HAVEN, CT 06510 USA. UNIV CALIF SAN FRANCISCO, DEPT MED, SAN FRANCISCO, CA 94143 USA. NIAID, DIV AIDS, BETHESDA, MD 20892 USA. RP LATHEY, JL (reprint author), UNIV CALIF SAN DIEGO, DEPT PEDIAT, DIV INFECT DIS, 9500 GILMAN DR, LA JOLLA, CA 92093 USA. OI Elbeik, Tarek/0000-0001-5983-0867 FU NCRR NIH HHS [RR 00046]; NIAID NIH HHS [AI25868, AI27563] NR 11 TC 11 Z9 11 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 EI 1098-660X J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD DEC PY 1994 VL 32 IS 12 BP 3064 EP 3067 PG 4 WC Microbiology SC Microbiology GA PT187 UT WOS:A1994PT18700035 PM 7883903 ER PT J AU JOHNSTON, PG FISHER, ER ROCKETTE, HE FISHER, B WOLMARK, N DRAKE, JC CHABNER, BA ALLEGRA, CJ AF JOHNSTON, PG FISHER, ER ROCKETTE, HE FISHER, B WOLMARK, N DRAKE, JC CHABNER, BA ALLEGRA, CJ TI THE ROLE OF THYMIDYLATE SYNTHASE EXPRESSION IN PROGNOSIS AND OUTCOME OF ADJUVANT CHEMOTHERAPY IN PATIENTS WITH RECTAL-CANCER SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID DNA PLOIDY; COLORECTAL ADENOCARCINOMA; PROTOCOL R-01; SYNTHETASE; 5-FLUOROURACIL; CELLS; ANTIBODIES; THERAPY; BREAST; STAGE AB Purpose: We assessed the prognostic importance of the level of thymidylate synthase (TS) expression in patients with primary rectal cancer and whether, for Dukes' B and C cancer patients, the benefit of chemotherapy was associated with TS expression. Patients and Methods: The level of TS expression in the primary rectal cancers of 294 of 801 patients enrolled on protocol R-01 of the National Surgical Adjuvant Breast and Bowel Project (NSABP) was immuno histochemically assessed with the monoclonal antibody TS 106. Results: Forty-nine percent of patients whose tumors had low TS levels (n = 91) were disease free at 5 years compared with 27% of patients with high levels of TS (n = 203; P <.0.1). Moreover, 60% of patients with low TS levels were alive after 5 years compared with 40% of patients with high TS levels (P <.01). The level of TS protein wets significantly associated with Dukes' stage (P <.01); patients with a more advanced Dukes' stage had a significantly higher level of TS. The level of TS expression remained prognostic for both disease-free survival (P <.01) and survival (P <.05) independent of Dukes' stage and other pathologic characteristics evaluated. Thirty-eight percent and 54% of patients with high TS levels (n = 71) were disease free and alive, respectively, after 5 years when created with chemotherapy, compared with 17% and 31%, respectively, of similar patients when treated with surgery alone (n = 64) (P < .01). No difference was noted in disease-free survival (P =.46) or survival (P =.43) in patients with low TS levels. Conclusion: The expression of TS is an important independent prognosticator of disease-free survival and survival in patients with rectal cancer. Adjuvant fluorouracil (5-FU)-based chemotherapy demonstrated significa nt improvement in disease-free and overall survival for patients with high TS levels. Prospective studies measuring TS levels will be needed to understand further the role of TS as a prognosticator of survival and chemotherapeutic benefit. (C) 1994 by American Society of Clinical Oncology. C1 UNIV PITTSBURGH,SCH MED,NATL SURG ADJUVANT BREAST & BOWEL PROJECT,PITTSBURGH,PA. RP JOHNSTON, PG (reprint author), NCI,NAVY MED ONCOL BRANCH,DIV CANC TREATMENT,BLDG 8,ROOM 5101,BETHESDA,MD 20889, USA. NR 38 TC 365 Z9 371 U1 0 U2 3 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 DEC PY 1994 VL 12 IS 12 BP 2640 EP 2647 PG 8 WC Oncology SC Oncology GA PV811 UT WOS:A1994PV81100019 PM 7989939 ER PT J AU GULERIA, AS YANG, JC TOPALIAN, SL WEBER, JS PARKINSON, DR MACFARLANE, MP WHITE, RL STEINBERG, SM WHITE, DE EINHORN, JH SEIPP, CA AUSTIN, HA ROSENBERG, SA SCHWARTZENTRUBER, DJ AF GULERIA, AS YANG, JC TOPALIAN, SL WEBER, JS PARKINSON, DR MACFARLANE, MP WHITE, RL STEINBERG, SM WHITE, DE EINHORN, JH SEIPP, CA AUSTIN, HA ROSENBERG, SA SCHWARTZENTRUBER, DJ TI RENAL DYSFUNCTION ASSOCIATED WITH THE ADMINISTRATION OF HIGH-DOSE INTERLEUKIN-2 IN 199 CONSECUTIVE PATIENTS WITH METASTATIC MELANOMA OR RENAL-CARCINOMA SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RECOMBINANT INTERLEUKIN-2; CANCER-PATIENTS; IMMUNOTHERAPY; TOXICITY; NEPHROTOXICITY; EXCRETION; INFUSION; THERAPY AB Purpose: To describe the incidence and management of renal dysfunction associated with the use of high-dose interleukin-2 (IL-2) (as is currently approved) in the treatment of cancer patients. Patients and Methods: One hundred ninety-nine consecutive patients with metatstatic renal carcinoma or melanoma were treated with intravenous bolus infusions of IL-2 alone (720,000 IU/kg) every 8 hours. Results: Patients received 310 courses (589 cycles) of therapy and most experienced oliguria, hypotension, and weight gain; 13% of cycles were discontinued due to increased serum creatinine levels. Creatinine values (mean pretherapy, 1.2 mg/dL) increased during therapy and peaked (mean, 2.7 mg/dL) approximately 1 day after discontinuation of the second cycle of IL-2. Off therapy, toxicities reversed promptly and creatinine values returned to baseline. Higher peek creatinine values occurred in patients with renal carcinoma (v melanoma), older patients, males (v females), and those who had undergone prior nephrectomy. These same patient subsets received fewer doses of IL-2, but clinical responses were not associated with creatinine values or number of IL-2 doses administered. Urinalyses showed the appear ance of protein, bilirubin, RBCs, WBCs, and granular casts during therapy, which cleared completely on follow-up evaluation. Conclusion: High-dose IL-2 can be safely administered to cancer patients. The associated renal dysfunction is transient and without evidence of intrinsic long-term renal damage. Practical guidelines for patient management have been identified. C1 NCI,SURG BRANCH,BETHESDA,MD 20892. NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. NIDDKD,METAB DIS BRANCH,BETHESDA,MD 20892. NR 25 TC 32 Z9 33 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD DEC PY 1994 VL 12 IS 12 BP 2714 EP 2722 PG 9 WC Oncology SC Oncology GA PV811 UT WOS:A1994PV81100029 PM 7989949 ER PT J AU WALSH, SL PRESTON, KL SULLIVAN, JT FROMME, R BIGELOW, GE AF WALSH, SL PRESTON, KL SULLIVAN, JT FROMME, R BIGELOW, GE TI FLUOXETINE ALTERS THE EFFECTS OF INTRAVENOUS COCAINE IN HUMANS SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID PROGRESSIVE RATIO SCHEDULE; PUPILLARY RESPONSES; D-AMPHETAMINE; L-TRYPTOPHAN; SEROTONIN; DOPAMINE; BROMOCRIPTINE; COMBINATION; MAZINDOL; ABUSE AB Fluoxetine, a selective serotonin reuptake inhibitor, is currently being evaluated as a potential treatment for cocaine abuse. This 4-week inpatient study evaluated the pharmacologic interaction between fluoxetine and cocaine in healthy adult male volunteers (N = 5) with histories of cocaine abuse. Oral capsules were administered daily containing either placebo (weeks 1 and 4) or fluoxetine in a series of ascending doses (10, 20, 30, and 40 mg) where each dose was given for three to four consecutive days. Cocaine challenge sessions were conducted twice weekly, once at each active dose level and twice during both the placebo and washout phases. Subjects received three ascending intravenous doses of cocaine (0, 20, and 40 mg) 1.5 hours apart and were monitored on physiologic and subjective measures. Cocaine alone increased heart rate, blood pressure, and pupillary diameter and increased subjective reports reflecting positive mood effects and drug Liking. Fluoxetine (40 mg) significantly decreased subjective ratings of cocaine's positive mood effects on several visual analog measures. Fluoxetine also attenuated the mydriatic effect of cocaine. No adverse physiologic interactions between the two drugs were observed on cardiovascular measures. These data suggest that fluoxetine may be safely used in the presence of cocaine use and should be investigated further as a potential pharmacotherapy for cocaine abuse. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MED,BALTIMORE,MD 21224. NIDA,ADDICT RES CTR,TREATMENT BRANCH,BALTIMORE,MD 21224. RP WALSH, SL (reprint author), JOHNS HOPKINS UNIV,SCH MED,DEPT PSYCHIAT & BEHAV SCI,5510 NATHAN SHOCK DR,BALTIMORE,MD 21224, USA. RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 NR 66 TC 90 Z9 90 U1 2 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD DEC PY 1994 VL 14 IS 6 BP 396 EP 407 PG 12 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA PV514 UT WOS:A1994PV51400005 PM 7884020 ER PT J AU KRAMLINGER, KG PHILLIPS, KA POST, RM AF KRAMLINGER, KG PHILLIPS, KA POST, RM TI RASH COMPLICATING CARBAMAZEPINE TREATMENT SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID DRUG SURVEILLANCE PROGRAM; CUTANEOUS REACTIONS; ADVERSE REACTIONS; THERAPY; ALLERGY; DESENSITIZATION; EOSINOPHILIA AB Carbamazepine-widely used in the treatment of trigeminal neuralgia, seizure disorders, and more recently, manic-depressive illness-is generally safe and well tolerated. Although serious adverse reactions, such as hematologic toxicity, may occur rarely, we have found that carbamazepine-induced rash is common, occurring in 13 (12%) of 113 patients. We describe our experience with carbamazepine-induced rash, including clinical characteristics, demographic features, and associated laboratory findings. Integrating our findings with the literature, we also discuss incidence, possible mechanisms, and implications for treatment because these benign rashes can occasionally progress to more fulminant and life-threatening eruptions. C1 NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. NR 44 TC 34 Z9 34 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD DEC PY 1994 VL 14 IS 6 BP 408 EP 413 PG 6 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA PV514 UT WOS:A1994PV51400006 PM 7884021 ER PT J AU BEEMAN, M FRIEDMAN, RB GRAFMAN, J PEREZ, E DIAMOND, S LINDSAY, MB AF BEEMAN, M FRIEDMAN, RB GRAFMAN, J PEREZ, E DIAMOND, S LINDSAY, MB TI SUMMATION PRIMING AND COARSE SEMANTIC CODING IN THE RIGHT-HEMISPHERE SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID BRAIN-DAMAGED PATIENTS; CEREBRAL HEMISPHERES; SPATIAL RELATIONS; WORDS; DISSOCIATION; REPRESENTATIONS; SPECIALIZATION; COMPREHENSION; ORGANIZATION; APPRECIATION AB There are now numerous observations of subtle right hemisphere (RH) contributions to language comprehension. It has been suggested that these contributions reflect coarse semantic coding in the RH. That is, the RH weakly activates large semantic fields-including concepts distantly related to the input word-whereas the left hemisphere (LH) strongly activates small semantic fields-limited to concepts closely related to the input (Beeman, 1993a,b). This makes the RH less effective at interpreting single words, but more sensitive to semantic overlap of multiple words. To test this theory, subjects read target words preceded by either ''Summation'' primes (three words each weakly related to the target) or Unrelated primes (three unrelated words), and target exposure duration was manipulated so that subjects correctly named about half the target words in each hemifield. In Experiment 1, subjects benefited more from Summation primes when naming target words presented to the left visual field-RH (lvf-RH) than when naming target words presented to the right visual field-LH (rvf-LH), suggesting a RH advantage in coarse semantic coding. In Experiment 2, with a low proportion of related prime-target trials, subjects benefited more from ''Direct'' primes (one strong associate flanked by two unrelated words) than from Summation primes for rvf-LH target words, indicating that the LH activates closely related information much more strongly than distantly related information. Subjects benefited equally from both prime types for lvf-RH target words, indicating that the RH activates closely related information only slightly more strongly, at best, than distantly related information. This suggests that the RH processes words with relatively coarser coding than the LH, a conclusion consistent with a recent suggestion that the RH coarsely codes visual input (Kosslyn, Chabris, Marsolek, & Koenig, 1332). C1 GEORGETOWN UNIV,WASHINGTON,DC. NIH,BETHESDA,MD. RP BEEMAN, M (reprint author), RUSH PRESBYTERIAN ST LUKES MED CTR,RUSH NEUROSCI INST,1725 W HARRISON ST,CHICAGO,IL 60612, USA. OI Grafman, Jordan H./0000-0001-8645-4457 NR 59 TC 301 Z9 306 U1 1 U2 11 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD ST JOURNALS DEPT, CAMBRIDGE, MA 02142 SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD WIN PY 1994 VL 6 IS 1 BP 26 EP 45 DI 10.1162/jocn.1994.6.1.26 PG 20 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA MV321 UT WOS:A1994MV32100003 PM 23962328 ER PT J AU YAN, CH RESAU, JH HEWETSON, J WEST, M RILL, WL KENDE, M AF YAN, CH RESAU, JH HEWETSON, J WEST, M RILL, WL KENDE, M TI CHARACTERIZATION AND MORPHOLOGICAL ANALYSIS OF PROTEIN-LOADED POLY(LACTIDE-CO-GLYCOLIDE) MICROPARTICLES PREPARED BY WATER-IN OIL-IN-WATER EMULSION TECHNIQUE SO JOURNAL OF CONTROLLED RELEASE LA English DT Article DE MICROENCAPSULATION; POLY(LACTIDE-CO-GLYCOLIDE), VACCINE; CONFOCAL LASER SCAN MICROSCOPE ID BIODEGRADABLE MICROSPHERES; VACCINE DEVELOPMENT; DELIVERY SYSTEMS; RELEASE; ACID) AB Poly(lactide-co-glycolide) microparticles, containing ricin toroid or fluorescein isothiocyanate-labeled bovine serum albumin were prepared by a water-in-oil-in-water emulsion solvent extraction procedure with a high encapsulation efficiency (from 60% to 94%). Three agitation methods: vortex mixing, homogenization and sonication, were used to make the first inner w/o emulsion and the second w/o/w emulsion. The effects of process parameters on structure, surface condition, particle size, core loading and in vitro release properties of the protein-loaded microparticles were studied. SDS-PAGE analysis showed that none of the agitation methods damaged the structural integrity and stability of the encapsulated protein. Confocal laser scanning microscopic analysis and in vitro studies indicated that heterogeneous microparticles provided a fast release profile with a large protein burst (62%), and homogeneous microparticles released protein slower with a much lower protein burst (7%). These properties may influence the dynamics of the antibody response. C1 USA,MED RES INST INFECT DIS,FT DETRICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD. NR 23 TC 129 Z9 139 U1 0 U2 16 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-3659 J9 J CONTROL RELEASE JI J. Control. Release PD DEC 1 PY 1994 VL 32 IS 3 BP 231 EP 241 DI 10.1016/0168-3659(94)90233-X PG 11 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA PY402 UT WOS:A1994PY40200002 ER PT J AU HUFFMAN, LC AF HUFFMAN, LC TI CHILDRENS STRESS AND COPING - A FAMILY PERSPECTIVE - SORENSEN,ES SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Book Review RP HUFFMAN, LC (reprint author), NIMH,DIV NEUROSCI & BEHAV SCI,PERSONAL & EMOT PROGRAM,ROCKVILLE,MD 20857, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD DEC PY 1994 VL 15 IS 6 BP 443 EP 444 PG 2 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA PV521 UT WOS:A1994PV52100009 ER PT J AU SEMNANI, RT NUTMAN, TB HOCHMAN, P SHAW, S VANSEVENTER, GA AF SEMNANI, RT NUTMAN, TB HOCHMAN, P SHAW, S VANSEVENTER, GA TI COSTIMULATION BY PURIFIED INTERCELLULAR-ADHESION MOLECULE-1 AND LYMPHOCYTE FUNCTION-ASSOCIATED ANTIGEN-3 INDUCES DISTINCT PROLIFERATION, CYTOKINE AND CELL-SURFACE ANTIGEN PROFILES IN HUMAN NAIVE AND MEMORY CD4(+) T-CELLS SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID LOW-AFFINITY LIGAND; IFN-GAMMA; DIFFERENTIAL REGULATION; COUNTER-RECEPTOR; HOMING RECEPTOR; TRANSGENIC MICE; 2ND LIGAND; HUMAN CD2; CD4+; TH1 AB Activation of resting human CD4(+) ''naive'' (CD45RA(+) CD45RO(-)) and ''memory'' (CD45RA(-) CD45RO(+)) T cells requires costimulatory signal in addition to engagement of the T cell receptor/CD3 complex (TCR/CD3). The adhesion pathways mediated by lymphocyte function-associated antigen 1/intercellular adhesion molecule 1 (LFA-1/ICAM-1) and CD2/LFA-3 are capable of providing such costimulatory signals. Our work shows that these costimulatory adhesion pathways are critically involved in regulation of T cell differentiation/maturation. Evidence for subset-specific costimulatory requirements is demonstrated by the finding that only memory CD4(+) T cells were costimulated by LFA-3, whereas both naive and memory CD4(+) T cells were costimulated by ICAM-1. In addition, these costimulatory adhesion pathways regulated reciprocal cytokine secretion patterns for interleukin 5 (IL-5) and granulocyte/macrophage colony-simulating factor (GM-CSF). Repeated costimulation of CD4(+) memory T cells with LFA-3 led to secretion of high levels of IL-5, while repeated costimulation with ICAM-1 induced high levels of secreted GM-CSF. Significant interferon gamma (IFN-gamma) production was observed with either of the costimulatory ligands. Extensive cell surface analysis of these in vitro cultures of peripheral blood derived memory CD4(+) T cells, with monoclonal antibodies obtained from the 5th Leucocyte Typing Workshop, revealed differential expression of singular antigen, CD60. This antigen was preferentially expressed on LFA-3-costimulated cells suggesting a positive correlation between CD60 expression and a T helper type 2-like cytokine profile. In conclusion, this report demonstrates a new functional role for costimulatory adhesion molecules in regulating differential cytokine secretion in human memory CD4(+) T cells. C1 UNIV CHICAGO,DEPT PATHOL,DIV BIOL SCI,CHICAGO,IL 60637. NIAID,PARASIT DIS LAB,BETHESDA,MD 20892. BIOGEN INC,CAMBRIDGE,MA 02142. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. FU NCI NIH HHS [CA-14599-20]; NIAID NIH HHS [AI-34541-01] NR 67 TC 90 Z9 91 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 DEC 1 PY 1994 VL 180 IS 6 BP 2125 EP 2135 DI 10.1084/jem.180.6.2125 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA PU361 UT WOS:A1994PU36100012 PM 7525848 ER PT J AU GAO, JL BECKER, EL FREER, RJ MUTHUKUMARASWAMY, N MURPHY, PM AF GAO, JL BECKER, EL FREER, RJ MUTHUKUMARASWAMY, N MURPHY, PM TI A HIGH POTENCY NONFORMYLATED PEPTIDE AGONIST FOR THE PHAGOCYTE N-FORMYLPEPTIDE CHEMOTACTIC RECEPTOR SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CHEMOATTRACTANT RECEPTORS; DESENSITIZATION; LEUKOCYTES; EXPRESSION; DOMAINS; BINDING; CDNA AB Analysis of synthetic tri- and tetrapeptides has previously indicated that N-formylation is required for high biological activity when they react with the phagocyte N-formylpeptide receptor, suggesting that the natural ligand for the receptor is from bacterial and/or mitochondrial sources. To explore this requirement further, we synthesized the pentapeptide methionyl-norleucyl-leucyl-phenylalanylphenylalanine (MNleLFF) and studied the effects of different NH2-terminal modifications on its activity. N-formyl-MNleLFF induced transient alterations of [Ca2+](i) and superoxide production in human neutrophils with 10- and 100-fold greater potency, respectively, than the prototype N-formylpeptide, N-formylmethionyl-leucyl-phenylalanine (fMLF). Surprisingly, N-acetyl-MNleLFF was as potent as N-formyl-MNleLFE Moreover, the unacylated counterpart H-MNleLFF was also highly active, having an EC(50) for calcium mobilization of 10 nM, and for respiratory burst activation of 100 nM. All three pentapeptides could completely desensitize calcium transients elicited by stimulation of neutrophils with fMLF, whereas the neutrophil chemoattractants C5a and interleukin 8 only weakly affected fMLF-induced transients, suggesting that they activate neutrophils via the same receptor as fMLF Finally, all three pentapeptides activated the recombinant human N-formylpeptide receptor expressed in frog oocytes, but did not effectively activate related phagocyte receptors. These data broaden the potential sources of natural ligands for the N-formylpeptide receptor from N-formylated bacterial and mitochondrial products to other nonformylated endogenous peptides. C1 NIAID,HOST DEF LAB,BETHESDA,MD 20892. UNIV CONNECTICUT,CTR HLTH,DEPT PATHOL,FARMINGTON,CT 06032. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT BIOMED ENGN,RICHMOND,VA 23298. NR 18 TC 45 Z9 45 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 DEC 1 PY 1994 VL 180 IS 6 BP 2191 EP 2197 DI 10.1084/jem.180.6.2191 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA PU361 UT WOS:A1994PU36100019 PM 7964494 ER PT J AU GAZZINELLI, RT GIESE, NA MORSE, HC AF GAZZINELLI, RT GIESE, NA MORSE, HC TI IN-VIVO TREATMENT WITH INTERLEUKIN-12 PROTECTS MICE FROM IMMUNE ABNORMALITIES OBSERVED DURING MURINE ACQUIRED-IMMUNODEFICIENCY-SYNDROME (MAIDS) SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID RETROVIRUS-INDUCED IMMUNODEFICIENCY; CD4+ T-CELLS; STIMULATORY FACTOR INTERLEUKIN-12; INTERFERON-GAMMA PRODUCTION; LYMPHOCYTES-T; VIRUS; INDUCTION; ACTIVATION; DISEASE; AIDS AB Lymphoproliferation, chronic B cell activation resulting in hypergammaglobulinemia, and profound immunodeficiency are prominent features of a retrovirus-induced syndrome designated murine acquired immunodeficiency syndrome (MAIDS). In vivo treatment of infected mice with recombinant interleukin 12 (IL-12) beginning at the time of infection or up to 9 wk after virus inoculation markedly inhibited the development of splenomegaly and lymphadenopathy, as well as B cell activation and Ig secretion. Treatment with IL-12 also had major effects in preventing induction of several immune defects including impaired production of interferon gamma (IFN-gamma) and IL-2 and depressed proliferative responses to various stimuli. The therapeutic effects of IL-12 on the immune system of mice with MAIDS were also associated with reduced expression of the retrovirus that causes this disease (BM5def), with lesser effects on expression of ecotropic MuLV. IL-12 treatment was not effective in IFN-gamma knockout mice or in infected mice treated simultaneously with IL-12 and anti-IFN-gamma. These results demonstrate that induction and progression of MAIDS are antagonized by IL-12 through high-level expression of IFN-gamma and may provide an experimental basis for developing treatments of retrovirus-induced immune disorders with similar immunopathogenic mechanisms. RP GAZZINELLI, RT (reprint author), NIAID,PARASIT DIS LAB,IMMUNOL & CELL BIOL SECT,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. OI Morse, Herbert/0000-0002-9331-3705 FU NIAID NIH HHS [N01 AI-45203] NR 46 TC 121 Z9 122 U1 1 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 DEC 1 PY 1994 VL 180 IS 6 BP 2199 EP 2208 DI 10.1084/jem.180.6.2199 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA PU361 UT WOS:A1994PU36100020 PM 7964495 ER PT J AU MUSSO, T VARESIO, L ZHANG, XY ROWE, TK FERRARA, P ORTALDO, JR OSHEA, JJ MCVICAR, DW AF MUSSO, T VARESIO, L ZHANG, XY ROWE, TK FERRARA, P ORTALDO, JR OSHEA, JJ MCVICAR, DW TI IL-4 AND IL-13 INDUCE LSK, A CSK-LIKE TYROSINE KINASE, IN HUMAN MONOCYTES SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Note ID IFN-GAMMA; EXPRESSION; PHOSPHORYLATES; LYMPHOKINE; ENCODES; GENE; SITE AB Lsk is a protein tyrosine kinase with homology to the COOH-terminal Src kinase (Csk). Unlike Csk that is ubiquitously expressed, Lsk has limited tissue distribution. Here we have examined the expression and regulation of Lsk and Csk in peripheral human monocytes. We have found that Lsk mRNA and protein were not expressed in resting monocytes but were induced by treatment with interleukin 4 (IL-4) or IL-13 but not by interferon gamma (IFN-gamma) or IL-2. In fact, IFN-gamma, but not IL-2, efficiently blocked Lsk induction by IL-4 or IL-13. In contrast, Csk was constitutively present in human monocytes and was upregulated by IFN-gamma but not by IL-4 or IL-13. These results suggest that despite their structural similarities, Lsk and Csk may play distinct regulatory roles in monocyte functions elicited by cytokines, with Lsk functioning specifically within the context of a Th2-type immune response. C1 NCI,FREDERICK CANC RES & DEV CTR,MACROPHAGE CELL BIOL SECT,EXPTL IMMUNOL LAB,FREDERICK,MD 21702. SANOFI ELF BIO RECH,F-31676 LABEGE,FRANCE. RP MUSSO, T (reprint author), NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BIOL CARCINOGENSIS & DEV PROGRAM,PROGRAM RESOURCE,FREDERICK,MD 21702, USA. RI McVicar, Daniel/G-1970-2015; varesio, luigi/J-8261-2016 OI varesio, luigi/0000-0001-5659-2218 NR 29 TC 25 Z9 25 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 DEC 1 PY 1994 VL 180 IS 6 BP 2383 EP 2388 DI 10.1084/jem.180.6.2383 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA PU361 UT WOS:A1994PU36100042 PM 7964512 ER PT J AU SNYDER, HL YEWDELL, JW BENNINK, JR AF SNYDER, HL YEWDELL, JW BENNINK, JR TI TRIMMING OF ANTIGENIC PEPTIDES IN AN EARLY SECRETORY COMPARTMENT SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Note ID CLASS-I MOLECULES; TOXIC LYMPHOCYTES-T; GENE-PRODUCTS; MUTANT-CELLS; RECOGNITION; EXPRESSION; TRANSLOCATION; TRANSPORTER; PROTEIN AB Major histocompatibility complex (MHC) class I molecules bind peptides of 8-10 residues in the endoplasmic reticulum (ER) and convey them to the cell surface for inspection by CD8-expressing T cells (T-CD8+) Antigenic peptides are predominantly derived from a cytosolic pool of polypeptides. The proteolytic generation of peptides from polypeptides clearly begins in the cytosol, but it is uncertain whether the final proteolytic steps occur before or after peptides are transported into the ER by the MHC-encoded peptide transporter (TAP). To study the trimming of antigenic peptides in the secretory pathway in the absence of cytosolic processing, we used an NH2-terminal signal sequence to target to the ER of TAP-deficient cells, ''tandem'' peptides consisting of two defined T-CD8+ determinants arranged from head to tail. We find that in contrast to cytosolic proteases in TAP-expressing cells, which are able to liberate antigenic peptides from either end of a tandem peptide, proteases (probably aminopeptidases) present in an early secretory compartment preferentially liberate the COOH-terminal determinant. These findings demonstrate that proteolytic activities associated with antigen processing are not limited to the cytosol, but that they also exist in an early secretory compartment. Such secretory aminopeptidases may function to trim TAP-transported peptides to the optimal size for binding to class I molecules. RP SNYDER, HL (reprint author), NIAID,VIRAL DIS LAB,BETHESDA,MD 20892, USA. RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 30 TC 163 Z9 164 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 DEC 1 PY 1994 VL 180 IS 6 BP 2389 EP 2394 DI 10.1084/jem.180.6.2389 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA PU361 UT WOS:A1994PU36100043 PM 7964513 ER PT J AU ARISPE, N POLLARD, HB ROJAS, E AF ARISPE, N POLLARD, HB ROJAS, E TI BETA-AMYLOID CA2+-CHANNEL HYPOTHESIS FOR NEURONAL DEATH IN ALZHEIMER-DISEASE SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract ID BILAYER-MEMBRANES; CHANNELS C1 NIDDKD,CELL BIOL & GENET LAB,BETHESDA,MD 20892. NR 3 TC 1 Z9 1 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD DEC PY 1994 VL 104 IS 6 BP A31 EP A32 PG 2 WC Physiology SC Physiology GA PY569 UT WOS:A1994PY56900073 ER PT J AU COLLINS, FS AF COLLINS, FS TI WORLDS IN COLLUSION - PHYSIOLOGY AND THE GENOME PROJECT SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract C1 NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD DEC PY 1994 VL 104 IS 6 BP A1 EP A1 PG 1 WC Physiology SC Physiology GA PY569 UT WOS:A1994PY56900009 ER PT J AU GUY, HR DURELL, SR AF GUY, HR DURELL, SR TI STRUCTURAL AND FUNCTIONAL MODELS OF K+, NA+, AND CA2+ CHANNELS SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract C1 NCI,DIV CANC BIOL DIAG & CTR,MATH BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD DEC PY 1994 VL 104 IS 6 BP A3 EP A4 PG 2 WC Physiology SC Physiology GA PY569 UT WOS:A1994PY56900015 ER PT J AU POLLARD, JR ARISPE, N ROJAS, E POLLARD, HB AF POLLARD, JR ARISPE, N ROJAS, E POLLARD, HB TI A GEOMETRIC SEQUENCE WHICH ACCURATELY DESCRIBES ALLOWED MULTIPLE CONDUCTANCE LEVELS OF ION CHANNELS - THE 3-HALVES (3/2)-RULE. SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract C1 NIDDKD,CELL BIOL & GENET LAB,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 1 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD DEC PY 1994 VL 104 IS 6 BP A32 EP A33 PG 2 WC Physiology SC Physiology GA PY569 UT WOS:A1994PY56900074 ER PT J AU MARZANO, A SMEDILE, A ABATE, M OTTOBRELLI, A BRUNETTO, M NEGRO, F FARCI, P DURAZZO, M DAVID, E LAGGET, M VERME, G BONINO, F RIZZETTO, M AF MARZANO, A SMEDILE, A ABATE, M OTTOBRELLI, A BRUNETTO, M NEGRO, F FARCI, P DURAZZO, M DAVID, E LAGGET, M VERME, G BONINO, F RIZZETTO, M TI HEPATITIS TYPE-C AFTER ORTOTHOPIC LIVER-TRANSPLANTATION - REINFECTION AND DISEASE RECURRENCE SO JOURNAL OF HEPATOLOGY LA English DT Article DE HCV-RNA; HEPATITIS C VIRUS; LIVER TRANSPLANTATION ID VIRUS-INFECTION; VIRAL-INFECTION; RNA; RECIPIENTS; HCV AB We determined the prevalence of hepatitis C virus markers and the clinical course in patients transplanted for terminal type C or non-A, non-B cirrhosis. Hepatitis C virus infection recurred in 16 of 17 patients (94%) with type C cirrhosis (seropositive for hepatitis C virus prior to surgery) and in 10 of 11 patients (91%) with non-A, non-B cirrhosis whose hepatitis C virus status prior to surgery had not been determined. Markers of hepatitis C virus were detected in 4 of 16 liver transplants whose donors tested negative for hepatitis C virus prior to surgery; this figure represents the risk of hepatitis C virus acquisition from external sources at or after transplantation. In 18 of 26 reinfected patients aminotransferases increased after grafting and remained elevated throughout the 14 to 79 (mean 46.5) months of follow up. The histological findings varied from mild or moderate hepatitis in 15 patients to severe active hepatitis in two patients. Two patients developed cirrhosis; one of them died of intercurrent infection while she was receiving immunosuppressive therapy for chronic rejection. Patients transplanted for hepatitis C virus or non-A, non-B liver disease are at high risk of hepatitis C virus reinfection. However the course of recurrent hepatitis C is most often mild and compatible with a normal life and an excellent survival rate. (C) Journal of Hepatology. C1 MOLINETTE MAURIZIANO HOSP,DEPT GASTROENTEROL,I-10126 TURIN,ITALY. UNIV TURIN,DEPT BIOMED SCI & HUMAN ONCOL,I-10124 TURIN,ITALY. NIH,INFECT DIS LAB,HEPATITIS VIRUSES SECT,BETHESDA,MD 20892. UNIV TURIN,DEPT GASTROENTEROL,TURIN,ITALY. RI Negro, Francesco/E-2183-2012; OI Bonino, Ferruccio/0000-0001-9942-0328 NR 19 TC 27 Z9 27 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0169-5185 J9 J HEPATOL JI J. Hepatol. PD DEC PY 1994 VL 21 IS 6 BP 961 EP 965 DI 10.1016/S0168-8278(05)80602-6 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QA505 UT WOS:A1994QA50500006 PM 7699259 ER PT J AU DIBISCEGLIE, AM BACON, BR KLEINER, DE HOOFNAGLE, JH AF DIBISCEGLIE, AM BACON, BR KLEINER, DE HOOFNAGLE, JH TI INCREASE IN HEPATIC IRON STORES FOLLOWING PROLONGED THERAPY WITH RIBAVIRIN IN PATIENTS WITH CHRONIC HEPATITIS-C SO JOURNAL OF HEPATOLOGY LA English DT Article DE DRUG-INDUCED; HEMOLYSIS; HEMOSIDEROSIS; IRON OVERLOAD ID RECOMBINANT INTERFERON-ALFA; CONTROLLED TRIAL; HEMOCHROMATOSIS AB Ribavirin, an oral nucleoside analogue being evaluated as therapy for chronic hepatitis C, is associated with hemolysis. Other hemolytic conditions are known to be associated with accumulation of iron within the liver. We therefore examined hepatic iron stores before and after 6 to 12 months of therapy with ribavirin in 15 patients with chronic hepatitis C. Although there were no significant changes in serum iron or ferritin levels, hepatic iron staining increased in almost all patients. Using a ranking system to quantitate the amount of hepatic iron staining, we found that the mean rank increased from 3.9 to 8.5 after therapy (p<0.01). In six patients in whom hepatic tissue was available for determination of hepatic iron, concentrations also increased in all cases from a mean of 826 to 1857 mu g/g dry weight (p<0.01). The average rate of iron accumulation in these six patients was approximately 1500 mu g/g per year. Thus hepatic iron concentrations might enter the range clearly associated with hepatic fibrosis after approximately 15 years of continuous therapy. (C) Journal of Hepatology. C1 NIDDKD,DIGEST DIS BRANCH,LIVER DIS SECT,BETHESDA,MD 20892. ST LOUIS UNIV,SCH MED,DIV GASTROENTEROL & HEPATOL,ST LOUIS,MO. NCI,PATHOL LAB,BETHESDA,MD 20892. OI Kleiner, David/0000-0003-3442-4453 NR 14 TC 52 Z9 52 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0169-5185 J9 J HEPATOL JI J. Hepatol. PD DEC PY 1994 VL 21 IS 6 BP 1109 EP 1112 DI 10.1016/S0168-8278(05)80626-9 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA QA505 UT WOS:A1994QA50500030 PM 7699235 ER PT J AU GEORGE, A GUI, JX JENKINS, NA GILBERT, DJ COPELAND, NG VEIS, A AF GEORGE, A GUI, JX JENKINS, NA GILBERT, DJ COPELAND, NG VEIS, A TI IN-SITU LOCALIZATION AND CHROMOSOMAL MAPPING OF THE AG1 (DMP1) GENE SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Note DE DENTIN; PHOSPHOPROTEINS; AG1; MINERALIZATION; CHROMOSOMAL LOCALIZATION; DENTINOGENESIS IMPERFECTA ID INSITU HYBRIDIZATION; MESSENGER-RNA; EXPRESSION; PHOSPHOPROTEIN; PHOSPHOPHORYN; DIGOXIGENIN; EMBRYOS; MATRIX AB Dentinogenesis is being used as a model for understanding the biomineralization process. The odontoblasts synthesize a structural matrix comprised of Type I collagen fibrils which define the basic architecture of the tissue. The odontoblasts also synthesize and deliver a number of dentin-specific acidic macromolecules into the extracellular compartment. These acidic macromolecules may be involved in regulating the ordered deposition of hydroxyapatite crystals within the matrix. AG1 is the first tooth-specific acidic macromolecule to have been cloned and sequenced. To identify which cells of the rat incisor pulp/odontoblast complex were responsible for synthesis of AG1, in situ hybridization was used. Digoxigenin labeled sense and anti-sense AG1 riboprobes were prepared. The AG1 mRNA was found to be expressed in the mature secretory odontoblasts. Neither pulp cells nor pre-odontoblasts showed any staining with the anti-sense probes. Chromosomal localization studies placed the AG1 gene on mouse chromosome 5q21, in tight linkage with Fgf5. AG1 has been renamed Dmp1 (dentin matrix protein 1) in accordance with present chromosomal nomenclature. Mouse 5q21 corresponds to the 4q21 locus in humans. This is the locus for the human tooth mineralization disorder dentinogenesis imperfecta Type II (DI-II). These data suggest that the Dmp1 gene is involved in mineralization and is a candidate gene for DI-II. C1 NORTHWESTERN UNIV,DIV ORAL BIOL,CHICAGO,IL 60611. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD. OI GEORGE, ANNE/0000-0002-9008-7642 FU NIDCR NIH HHS [DE-01374] NR 26 TC 72 Z9 81 U1 0 U2 1 PU HISTOCHEMICAL SOC INC PI NEW YORK PA MT SINAI MEDICAL CENTER 19 EAST 98TH ST SUTIE 9G, NEW YORK, NY 10029 SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD DEC PY 1994 VL 42 IS 12 BP 1527 EP 1531 PG 5 WC Cell Biology SC Cell Biology GA PW589 UT WOS:A1994PW58900001 PM 7983353 ER PT J AU MORIOKA, H SUGANUMA, A TACHIBANA, M AF MORIOKA, H SUGANUMA, A TACHIBANA, M TI LOCALIZATION OF SUGAR-BINDING SITES IN STAPHYLOCOCCUS-AUREUS USING GOLD-LABELED NEOGLYCOPROTEIN SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE SUGAR-BINDING SITES; LECTIN; NEOGLYCOPROTEIN GOLD; N-ACETYLGLUCOSAMINIDE GOLD; ELECTRON MICROSCOPY; STAPHYLOCOCCUS AUREUS ID BOVINE MASTITIS; LECTINS; CELLS; HEMAGGLUTINATION; SAPROPHYTICUS; ADHERENCE; RECEPTOR; PROTEINS AB We studied post- and pre-embedding staining of sugar-binding sites on thin sections of Staphylococcus aureus with an electron microscopic neoglycoprotein-gold technique. Although gold particles of cellobiosyl bovine serum albumin (BSA)-glycosylated BSA-, lactosyl BSA-, and melibiosyl BSA-gold did not label, heavy labeling of N-acetylglucosaminide-BSA-gold was observed in both the cell wall and the cytoplasm on Spurr-embedded thin sections of S. aureus. Inhibition of labeling with wheat germ agglutinin-biotin and N-acetylglucosaminidase indicated that the labeling was due to N-acetylglucosamine These data suggested that molecules that bind specifically with N-acetylglucosamine occur in the cell wall and cytoplasm of S. aureus. Preembedding staining revealed that these molecules are abundant at the surface of the cell, mall and that the abundance differs depending on the bacterial strain. An N-acetylglucosamine-specific lectin-like substance, glucosaminidase, and toxins are proposed as candidates for molecules responsible for the labeling, and the possible functional significance of the findings is discussed briefly. C1 NAT INST DEAFNESS & OTHER COMMUNICAT DISORDERS,MOLEC GENET LAB,BETHESDA,MD 20892. KYOTO PREFECTURAL UNIV MED,ELECTRON MICROSCOPY LAB,KYOTO 602,JAPAN. KYOTO CENT SCH NURSING,KYOTO,JAPAN. NR 20 TC 1 Z9 1 U1 0 U2 1 PU HISTOCHEMICAL SOC INC PI NEW YORK PA MT SINAI MEDICAL CENTER 19 EAST 98TH ST SUTIE 9G, NEW YORK, NY 10029 SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD DEC PY 1994 VL 42 IS 12 BP 1609 EP 1613 PG 5 WC Cell Biology SC Cell Biology GA PW589 UT WOS:A1994PW58900010 PM 7983361 ER PT J AU WYNN, TA OSWALD, IP ELTOUM, IA CASPAR, P LOWENSTEIN, CJ LEWIS, FA JAMES, SL SHER, A AF WYNN, TA OSWALD, IP ELTOUM, IA CASPAR, P LOWENSTEIN, CJ LEWIS, FA JAMES, SL SHER, A TI ELEVATED EXPRESSION OF TH1 CYTOKINES AND NITRIC-OXIDE SYNTHASE IN THE LUNGS OF VACCINATED MICE AFTER CHALLENGE INFECTION WITH SCHISTOSOMA-MANSONI SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IRRADIATED CERCARIAE; PROTECTIVE IMMUNITY; IFN-GAMMA; T-CELL; INTERFERON-GAMMA; ACTIVATED MACROPHAGES; ATTENUATED CERCARIAE; PARASITE DEATH; PHASE IMMUNITY; CYTO-TOXICITY AB C57BL/6 mice were vaccinated with irradiated cercariae of Schistosoma mansoni, and, at various times after challenge infection, total lung mRNA was isolated to assess the induction of several cytokines that previously had been shown in in vitro studies to be involved in the activation of macrophages and/or endothelial cells for nitric oxide (NO) production and killing of schistosomula. Vaccinated mice demonstrated a highly significant increase in lFN-gamma mRNA upon subsequent infection when compared with infected nonvaccinated controls. A similar, although less dramatic, increase in two other macrophage-activating cytokines, TNF-alpha and IL-2, also was observed. In contrast, although the Th2 cytokines IL-4, IL-5, IL-10, and IL-13 were elevated in challenged vaccinated animals, only IL-10 and IL-13 showed increases that were significant with respect to the mRNA levels observed in challenged controls. Neutralization of IFN-gamma reduced immunity in vaccinated animals and resulted in decreased IFN-gamma, IL-2, IL-10, TNF-alpha, and IL-12 p40 but markedly increased IL-4, IL-5, and IL-13 mRNA expression and serum IgE levels. Pulmonary NO synthase expression was elevated in immunized mice at a time at which immune elimination of schistosomula is believed to occur. Moreover, suppression of NO synthase activity with the inhibitor aminoguanidine reduced immunity, as measured by a 32 to 33% increase in worm burden. Together, these data support previous in vitro studies that suggest a role for NO in schistosomulum killing. Furthermore, the observation that the down-regulatory cytokines IL-4, IL-10, and IL-13 are induced together with IFN-gamma may provide an explanation for the failure of this vaccine to provide complete protection. C1 NIAID,PARASIT DIS LAB,IMMUNOL & CELL BIOL SECT,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROSCI PHARMACOL & MOLEC SCI,BALTIMORE,MD 21205. BIOMED RES INST,ROCKVILLE,MD 20852. RI Wynn, Thomas/C-2797-2011; OSWALD, Isabelle/A-8497-2013; OI OSWALD, Isabelle/0000-0001-9918-277X NR 57 TC 87 Z9 93 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 1994 VL 153 IS 11 BP 5200 EP 5209 PG 10 WC Immunology SC Immunology GA PT301 UT WOS:A1994PT30100038 PM 7525727 ER PT J AU NERURKAR, VR SONG, KJ BASTIAN, IB GARIN, B FRANCHINI, G YANAGIHARA, R AF NERURKAR, VR SONG, KJ BASTIAN, IB GARIN, B FRANCHINI, G YANAGIHARA, R TI GENOTYPING OF HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE-I USING AUSTRALO-MELANESIAN TOPOTYPE-SPECIFIC OLIGONUCLEOTIDE PRIMER-BASED POLYMERASE CHAIN-REACTION - INSIGHTS INTO VIRAL EVOLUTION AND DISSEMINATION SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID PAPUA-NEW-GUINEA; COMPLETE NUCLEOTIDE-SEQUENCE; LEUKEMIA-VIRUS; SOLOMON-ISLANDS; MOLECULAR VARIANTS; LYMPHOMA; ISOLATE; PATIENT; ORIGIN; GENE AB Sequence variants of human T cell lymphotropic virus type I (HTLV-I), genetically distinct from cosmopolitan strains of HTLV-I from Japan, the Americas, the Caribbean, and Africa, have been discovered among Melanesians in Papua New Guinea and the Solomon Islands and among Australian aboriginals, By using oligonucleotide primer pairs derived from sequences unique to the gp46- and gp21-encoding regions of the env gene of the Melanesian HTLV-I variants, HTLV-I strains from widely separated geographic regions could be grouped into either of two major geographic-specific genotypes or topotypes: Australo-Melanesian and cosmopolitan. These primers did not permit amplification of the corresponding env gene regions in strains of simian T cell lymphotropic virus type I from Asia and Africa. Phylogenetic analysis also supported two distinct lineages, consistent with evolution of HTLV-I in Australia and Melanesia independent from that in other parts of the world. C1 NINCDS,CENT NERVOUS SYST STUDIES LAB,BETHESDA,MD. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. MENZIES SCH HLTH RES,DARWIN,NT,AUSTRALIA. INST PASTEUR,UNITE EPIDEMIOL VIRUS ONCOGENES,PARIS,FRANCE. NR 41 TC 17 Z9 17 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 DEC PY 1994 VL 170 IS 6 BP 1353 EP 1360 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA PW152 UT WOS:A1994PW15200001 PM 7995973 ER PT J AU LYMAN, CA GARRETT, KF PIZZO, PA WALSH, TJ AF LYMAN, CA GARRETT, KF PIZZO, PA WALSH, TJ TI RESPONSE OF HUMAN POLYMORPHONUCLEAR LEUKOCYTES AND MONOCYTES TO TRICHOSPORON BEIGELII - HOST-DEFENSE AGAINST AN EMERGING OPPORTUNISTIC PATHOGEN SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID COLONY-STIMULATING FACTOR; CRYPTOCOCCUS-NEOFORMANS; MURINE MACROPHAGES; HUMAN NEUTROPHILS; INFECTION; POLYSACCHARIDE; CYTOKINES; ANTIGEN; INHIBITION; DISEASE AB To further understand human host defenses against Trichosporon beigelii, functional responses were investigated of polymorphonuclear leukocytes (PMNL) and elutriated human monocytes (EHM) to this opportunistic fungal pathogen, There was significantly less PMNL phagocytosis (P < .001) and killing (P < .001) of T. beigelii isolates than of Candida albicans, However, levels of superoxide anions generated by PMNL in response to T. beigelii and C. albicans were comparable. Pretreatment of PMNL with granulocyte colony-stimulating factor or interferon-gamma (IFN-gamma) did not significantly enhance fungicidal activity. Killing of T. beigelii by EHM also was significantly impaired compared with killing of C. albicans (P < .001). However, pretreatment of EHM with macrophage colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, or IFN-gamma all resulted in enhanced fungicidal activity. Thus, phagocytosis and killing of T. beigelii by PMNL and EHM are significantly less efficient than that of C. albicans. However, monocytes may be more important in the control of Trichosporon species than previously shown. C1 NCI,PEDIAT BRANCH,INFECT DIS SECT,BETHESDA,MD 20892. NR 40 TC 30 Z9 32 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 DEC PY 1994 VL 170 IS 6 BP 1557 EP 1565 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA PW152 UT WOS:A1994PW15200026 PM 7995996 ER PT J AU THOMAS, DL ROMPALO, AM ZENILMAN, J HOOVER, D HOOK, EW QUINN, TC AF THOMAS, DL ROMPALO, AM ZENILMAN, J HOOVER, D HOOK, EW QUINN, TC TI ASSOCIATION OF HEPATITIS-C VIRUS-INFECTION WITH FALSE-POSITIVE TESTS FOR SYPHILIS SO JOURNAL OF INFECTIOUS DISEASES LA English DT Note ID ESSENTIAL MIXED CRYOGLOBULINEMIA; MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS; MEMBRANOUS GLOMERULONEPHRITIS AB The prevalence of false-positive reactions for syphilis (reactive rapid plasma reagin [RPR] test and nonreactive fluorescent treponemal antibody absorption [FTA-ABS] test) among patients at sexually transmitted disease (STD) clinics was assessed to evaluate the association between false-positive RPR reactions and hepatitis C virus (HCV) infections. Among 2672 patients, 400 (15.0%) had antibodies to HCV (anti-HCV) and 254 (9.5%) had a reactive RPR test. Of the 254 reactive RPR tests, 231 (90.1%) were also positive by FTA-ABS, leaving 23 false-positive RPR reactions. After excluding the 231 patients with positive FTA-ABS tests, false-positive RPR tests were found in 9 (2.7%) of 330 anti-HCV-positive patients compared with 14 (0.6%) of 2154 anti-HCV-negative participants (relative risk, 4.5; 95% confidence interval, 1.9-10.9; P = .0017). These data demonstrate that HCV infection is associated with false-positive RPR test results. However, because of the high prevalence of syphilis among STD patients, the RPR test remains a strong indicator of syphilis in this setting. C1 JOHNS HOPKINS UNIV,SCH PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD 21205. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. RP THOMAS, DL (reprint author), JOHNS HOPKINS UNIV,SCH MED PREVENT MED & EPIDEMIOL,DEPT BALTIMORE CITY HLTH,DIV INFECT DIS,BALTIMORE,MD 21205, USA. FU NIAID NIH HHS [AI-29508, AI-16959] NR 15 TC 15 Z9 15 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 DEC PY 1994 VL 170 IS 6 BP 1579 EP 1581 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA PW152 UT WOS:A1994PW15200030 PM 7527828 ER PT J AU KIMONIS, V DIGIOVANNA, JJ YANG, JM DOYLE, SZ BALE, SJ COMPTON, JG AF KIMONIS, V DIGIOVANNA, JJ YANG, JM DOYLE, SZ BALE, SJ COMPTON, JG TI A MUTATION IN THE V1-END DOMAIN OF KERATIN-1 IN NON-EPIDERMOLYTIC PALMAR-PLANTAR KERATODERMA SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID POINT MUTATIONS; BULLOSA SIMPLEX; GLYCINE LOOPS; HYPERKERATOSIS; DIFFERENTIATION; EXPRESSION; SUBDOMAIN; LINKAGE; GENES AB Mutations in keratin 9 have been found in families with an epidermolytic form of palmar-plantar keratoderma (PPK). In another form of PPK (Unna-Thost type), epidermolysis is not observed histologically. We studied a pedigree with this non-epidermolytic form of PPK. By gene linkage analysis, the type I keratin locus could be excluded but complete linkage with the type II keratin region was found. Sequence analysis identified a single base change in the amino-terminal V1 variable subdomain of keratin 1, which caused a lysine to isoleucine substitution. This non-conservative mutation completely cosegregated with the disease and was not observed in 50 unrelated unaffected individuals. An examination of keratin amino-terminal sequences revealed a previously unreported 22-residue window in the Vi subdomain that is conserved among most type II keratins. The altered lysine is an invariant residue in this conserved sequence. Previously described keratin mutations affect the central regions important for filament assembly and stability, and cause diseases characterized by cellular degeneration or disruption. This is the first disease mutation in a keratin chain variable end region. The observation that it is not associated with epidermolysis supports the concept that the amino-terminal domain of keratins may be involved in supramolecular interactions of keratin filaments rather than stability. Therefore, hyperkeratosis associated with this mutation may be due to perturbations in the interactions of the keratin end domain with other cellular components. C1 NIAMSD,SKIN BIOL LAB,BETHESDA,MD 20892. NCI,DERMATOL BRANCH,BETHESDA,MD 20892. NR 34 TC 104 Z9 108 U1 0 U2 2 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD DEC PY 1994 VL 103 IS 6 BP 764 EP 769 DI 10.1111/1523-1747.ep12412771 PG 6 WC Dermatology SC Dermatology GA QA803 UT WOS:A1994QA80300004 PM 7528239 ER PT J AU FINE, JD SUCHINDRAN, CM TIEN, H JOHNSON, LB MOSHELL, A AF FINE, JD SUCHINDRAN, CM TIEN, H JOHNSON, LB MOSHELL, A TI STATISTICAL CLASSIFICATION MODELS FOR INHERITED EPIDERMOLYSIS-BULLOSA (EB) - COMPARISON OF THE INFLUENCE OF DIFFERENT CLINICAL-VARIABLES ON SENSITIVITY AND SPECIFICITY SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 UNIV N CAROLINA,SCH PUBL HLTH,DEPT BIOSTAT,CHAPEL HILL,NC. UNIV N CAROLINA,SCH PUBL HLTH,DEPT DERMATOL,CHAPEL HILL,NC. UNIV N CAROLINA,SCH PUBL HLTH,DEPT EPIDEMIOL,CHAPEL HILL,NC. UNIV N CAROLINA,SCH MED,CHAPEL HILL,NC. NEBR,SE CLIN CTR,CHAPEL HILL,NC. NIH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 5 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD DEC PY 1994 VL 103 IS 6 BP 847 EP 847 PG 1 WC Dermatology SC Dermatology GA QA803 UT WOS:A1994QA80300034 ER PT J AU FINE, JD JOHNSON, LB TIEN, H SUCHINDRAN, C BROCK, L MOSHELL, A AF FINE, JD JOHNSON, LB TIEN, H SUCHINDRAN, C BROCK, L MOSHELL, A TI RISK OF PREMATURE DEATH AND INHERITED EPIDERMOLYSIS-BULLOSA (EB) - ASSESSMENT BY LIFETABLE ANALYSIS ACROSS MAJOR EB TYPES AND SUBTYPES OF PATIENTS WITHIN ONE REGIONAL CENTER OF THE NATIONAL EPIDERMOLYSIS-BULLOSA REGISTRY (NEBR) SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 UNIV N CAROLINA,NEBR SE CLIN CTR,SCH MED,DEPT DERMATOL,CHAPEL HILL,NC. UNIV N CAROLINA,NEBR SE CLIN CTR,SCH MED,DEPT BIOSTAT,CHAPEL HILL,NC. UNIV N CAROLINA,NEBR SE CLIN CTR,SCH MED,DEPT EPIDEMIOL,CHAPEL HILL,NC. UNIV N CAROLINA,NEBR SE CLIN CTR,SCH PUBL HLTH,CHAPEL HILL,NC. NIH,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 3 PU BLACKWELL SCIENCE PUBL INC CAMBRIDGE PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD DEC PY 1994 VL 103 IS 6 BP 848 EP 848 PG 1 WC Dermatology SC Dermatology GA QA803 UT WOS:A1994QA80300042 ER PT J AU OPPENHEIM, JJ AF OPPENHEIM, JJ TI SUMMARY OF THE FIFTH CONFERENCE ON THE MOLECULAR MECHANISMS AND PHYSIOLOGICAL ACTIVITIES OF CYTOKINES SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Editorial Material ID INTERFERON-GAMMA RECEPTOR; INFECTION; MICE; REARRANGEMENT; GENE RP OPPENHEIM, JJ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,POB B,BLDG 560,ROOM 21-89A,FREDERICK,MD 21702, USA. NR 38 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD DEC PY 1994 VL 56 IS 6 BP 687 EP 691 PG 5 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA PX336 UT WOS:A1994PX33600002 PM 7996044 ER PT J AU SAKANASHI, Y TAKEYA, M YOSHIMURA, T FENG, L MORIOKA, T TAKAHASHI, K AF SAKANASHI, Y TAKEYA, M YOSHIMURA, T FENG, L MORIOKA, T TAKAHASHI, K TI KINETICS OF MACROPHAGE SUBPOPULATIONS AND EXPRESSION OF MONOCYTE CHEMOATTRACTANT PROTEIN-1 (MCP-1) IN BLEOMYCIN-INDUCED LUNG INJURY OF RATS STUDIED BY A NOVEL MONOCLONAL-ANTIBODY AGAINST RAT MCP-1 SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE IMMUNOHISTOCHEMISTRY; AUTORADIOGRAPHY; NORTHERN BLOT HYBRIDIZATION ID INDUCED PULMONARY FIBROSIS; ALVEOLAR MACROPHAGES; GENE JE; CELLS; HETEROGENEITY; CYTOKINES; SECRETION; HAMSTERS; INVITRO; ORIGIN AB We investigated the kinetics of macrophage subpopulations and the expression of monocyte chemoattractant protein 1 (MCP-1) in a rat model of bleomycin-induced lung injury. Rat macrophage subpopulations were examined by immunohistochemistry using various anti-rat macrophage monoclonal antibodies (mAbs) and their proliferative capacity by [H-3]thymidine ((3)HTdR) autoradiography. To detect the localization of expressed MCP-1, we generated an mAb against rat MCP-1 for immunohistochemical staining. Expression of MCP-1 messenger RNA (mRNA) was detected by Northern blot hybridization. Shortly after intratracheal instillation of bleomycin, the number of exudate macrophages recognized by mAb TRPM-3 increased in the injured lungs, peaked 3 days later, and decreased thereafter, whereas tissue macrophages identified by mAb ED2 increased slowly and peaked 2 weeks after instillation. Northern blot analysis disclosed that the expression of MCP-1 mRNA in the lung was most prominent 1 day after instillation and declined thereafter, preceding the numerical change of the TRPM-3-positive exudate macrophages. Immunohistochemistry with anti-rat MCP-1 revealed that the main sources of MCP-1 production were alveolar and interstitial macrophages and polymorphonuclear leukocytes. Based on these results, MCP-1 produced by polymorphonuclear leukocytes and by alveolar and interstitial macrophages is thought to induce the infiltration of blood monocytes, and infiltrated exudate macrophages produce MCP-1 to enhance subsequent accumulation of macrophages. In contrast, the expression of MCP-1 did not correlate with the numerical changes of the EDP-positive macrophage. C1 KUMAMOTO UNIV, SCH MED, DEPT PATHOL 2, KUMAMOTO 860, JAPAN. KUMAMOTO UNIV, SCH MED, DEPT ANESTHESIOL, KUMAMOTO 860, JAPAN. NCI, IMMUNOBIOL LAB, IMMUNOPATHOL SECT, FREDERICK, MD 21701 USA. Scripps Res Inst, DEPT IMMUNOL, LA JOLLA, CA 92037 USA. NR 36 TC 64 Z9 65 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD DEC PY 1994 VL 56 IS 6 BP 741 EP 750 PG 10 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA PX336 UT WOS:A1994PX33600010 PM 7527830 ER PT J AU VERGES, B RADER, D SCHAEFER, J ZECH, L KINDT, M FAIRWELL, T GAMBERT, P BREWER, HB AF VERGES, B RADER, D SCHAEFER, J ZECH, L KINDT, M FAIRWELL, T GAMBERT, P BREWER, HB TI IN-VIVO METABOLISM OF APOLIPOPROTEIN A-IV IN SEVERE HYPERTRIGLYCERIDEMIA - A COMBINED RADIOTRACER AND STABLE-ISOTOPE KINETIC-STUDY SO JOURNAL OF LIPID RESEARCH LA English DT Article DE VERY LOW DENSITY LIPOPROTEIN; LOW DENSITY LIPOPROTEIN; VERY HIGH DENSITY LIPOPROTEIN; HIGH DENSITY LIPOPROTEIN; FRACTIONAL CATABOLIC RATE; FRACTIONAL SYNTHETIC RATE; LECITHIN-CHOLESTEROL ACYLTRANSFERASE ID HIGH-DENSITY-LIPOPROTEIN; ESTER TRANSFER PROTEIN; HUMAN-PLASMA; CHOLESTEROL ACYLTRANSFERASE; LIQUID-CHROMATOGRAPHY; DEUTERATED LEUCINE; INVIVO METABOLISM; BINDING; LYMPH; ACTIVATION AB Apolipoprotein (apo) A-IV is an intestinally derived apolipoprotein that plays a potentially important role in lipoprotein metabolism and reverse cholesterol transport. However, the factors that regulate its plasma concentrations are not well understood. Plasma apoA-IV levels have been previously shown to correlate with fasting triglyceride (TG) levels in humans with TG levels less than 300 mg/dl (Lagrost et al. 1989. J. Lipid Res. 30: 701-710). In this study, we established that apoA-IV levels were significantly elevated (mean 29.3 mg/dl) in a group of 15 hypertriglyceridemic patients (TG > 300 mg/dl) compared with normolipidemic controls (mean 13.4 mg/dl). In order to investigate the relationship between hypertriglyceridemia and apoA-IV metabolism, we then studied the in vivo kinetics of apoA-IV in two healthy hypertriglyceridemic patients (mean TG = 1297 mg/dl) compared with normolipidemic control subjects. Combined studies using endogenous stable isotope labeling (with a primed constant infusion of deuterated L-leucine) and exogenous radiolabeling (with I-125) of apoA-IV were performed. Both stable isotope and radiotracer studies demonstrated substantially decreased apoA-IV fractional catabolic rates (FCR) in the hypertriglyceridemic patients (1.24 +/- 0.13 day(-1)) compared with controls (2.33 +/- 0.08 day(-1)). The apoA-IV production rate was not significantly different between the two groups. Gel filtration chromatography of plasma indicated an increased proportion of apoA-IV in the triglyceride-rich lipoproteins (TRL) of the hypertriglyceridemic patients compared with controls and delayed catabolism of this TRL-associated apoA-IV. The rate of apoA-IV catabolism from the lipid deficient fraction was not different between the hypertriglyceridemic patients and controls. In summary, plasma levels of apoA-IV are significantly elevated in hypertriglyceridemic patients due to delayed catabolism of apoA-IV as demonstrated by both endogenous stable isotope labeling and exogenous radiotracer techniques. C1 NHLBI,MOLEC DIS BRANCH,BETHESDA,MD 20892. NR 50 TC 23 Z9 23 U1 0 U2 0 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 DEC PY 1994 VL 35 IS 12 BP 2280 EP 2291 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PZ293 UT WOS:A1994PZ29300018 PM 7897325 ER PT J AU BOUMENDJEL, A MILLER, SPF AF BOUMENDJEL, A MILLER, SPF TI SYNTHESIS OF SPHINGOSINE-1-PHOSPHATE AND DIHYDROSPHINGOSINE-1-PHOSPHATE SO JOURNAL OF LIPID RESEARCH LA English DT Article DE SPHINGANINE-1-PHOSPHATE; PHOSPHORAMIDITE; PHOSPHORYLATION ID C-13 NMR-SPECTROSCOPY; LONG-CHAIN BASES; PROTEIN-KINASE-C; CELL MOTILITY; SPHINGOSINE; LYSOSPHINGOLIPIDS; PROLIFERATION; DERIVATIVES AB The syntheses of D-erythro-sphingosine-1-phosphate ate and DL-erythro-sphinganine-1-phosphate are described starting from the commercially available D-erythro-sphingosine and DL-erythro-sphinganine. The phosphate group is introduced via phosphoramidite chemistry using bis(2-cyanoethyl)-N,N-diisopropylamino-phosphoramidite as the monophosphorylating reagent. The procedure generates the phosphorylated sphingoid bases in three steps and 32-39% overall yields. RP BOUMENDJEL, A (reprint author), NIH,BLDG 10,ROOM 3D-11,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 35 TC 14 Z9 14 U1 0 U2 5 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 DEC PY 1994 VL 35 IS 12 BP 2305 EP 2311 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA PZ293 UT WOS:A1994PZ29300020 PM 7897327 ER PT J AU MCNELLIS, D AF MCNELLIS, D TI A VIEW FROM BETHESDA - THE CLINICAL INVESTIGATOR DEVELOPMENT AWARD SO JOURNAL OF MATERNAL-FETAL INVESTIGATION LA English DT Editorial Material RP MCNELLIS, D (reprint author), NICHHD,CTR RES MOTHERS & CHILDREN,PREGNANCY & PERINATOL BRANCH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0939-6322 J9 J MATERN-FETAL INVES JI J. Matern.-Fetal Invest. PD WIN PY 1994 VL 4 IS 1 BP 3 EP 4 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA ND028 UT WOS:A1994ND02800002 ER PT J AU NAVARRO, EE ALMARIO, JS KING, C BACHER, J PIZZO, PA WALSH, TJ AF NAVARRO, EE ALMARIO, JS KING, C BACHER, J PIZZO, PA WALSH, TJ TI DETECTION OF CANDIDA CASTS IN EXPERIMENTAL RENAL CANDIDIASIS - IMPLICATIONS FOR THE DIAGNOSIS AND PATHOGENESIS OF UPPER URINARY-TRACT INFECTION SO JOURNAL OF MEDICAL AND VETERINARY MYCOLOGY LA English DT Article ID AMPHOTERICIN-B; INVASIVE CANDIDIASIS; ALBICANS; BLADDER; IRRIGATION; RABBITS AB The distinction between upper versus lower urinary tract infection in patients with candiduria is a commonly encountered and therapeutically important diagnostic dilemma. Candida casts have been reported in the urine of several individual case reports of human renal candidiasis. The specificity of Candida casts would identify unequivocally a patient with upper urinary tract disease. Little is known, however, about the sensitivity and the formation of Candida casts. We therefore studied the diagnostic yield, methods for detection and pathogenesis of Candida cast formation in serially collected urine specimens from immunologically intact and granulocytopenic rabbit models of haematogenous disseminated candidiasis. Refractile blastoconidia and pseudohyphae of Candida encased in the granular matrix were seen on wet mounts while Candida stained a brilliant red in the fuschia pink tubular matrix on periodic acid Schiff(PAS) stained cytopathology filters. Among 24 rabbits with disseminated candidiasis, 11 (46%) had Candida casts detectable by wet mount and PAS-stained urine filters in comparison to none of 10 non-infected immunologically normal controls (P=0.014). Fifteen (70%) of 21 episodes of Candida casts were detected within the first 3 days of infection, indicating possible utility in the early diagnosis of renal candidiasis. No Candida casts were detected in the urine of granulocytopenic rabbits, possibly due to the rapid destruction of tubules and abrogation of cast formation. This absence of detectable Candida in eight infected granulocytopenic rabbits differed significantly from that of 24 non-granulocytopenic infected rabbits, in which Candida casts were detected in 11 (46%) (P=0.029). Candida cast formation occurred predominantly in the cortex. Histopathological examination demonstrated invasion of Candida into the glomerular tufts and peritubular capillaries, followed by development of Candida casts in the proximal and distal tubules, respectively. Detection of renal Candida casts may be a useful diagnostic marker in distinguishing upper versus lower urinary tract candidiasis. C1 NCI,PEDIAT BRANCH,INFECT DIS SECT,BETHESDA,MD 20892. GEORGETOWN UNIV HOSP,DEPT INTERNAL MED,NEPHROL SECT,WASHINGTON,DC 20007. NIH,DIV CANC BIOL,PATHOL LAB,BETHESDA,MD 20892. NIH,VET RESOURCES PROGRAM,BETHESDA,MD 20892. NR 26 TC 12 Z9 13 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0268-1218 J9 J MED VET MYCOL JI J. Med. Vet. Mycol. PD DEC PY 1994 VL 32 IS 6 BP 415 EP 426 PG 12 WC Mycology SC Mycology GA QJ945 UT WOS:A1994QJ94500002 PM 7738724 ER PT J AU BATTEGAY, M SIMPSON, LH HOOFNAGLE, JH SALLIE, R DIBISCEGLIE, AM AF BATTEGAY, M SIMPSON, LH HOOFNAGLE, JH SALLIE, R DIBISCEGLIE, AM TI ELIMINATION OF HEPATITIS-DELTA VIRUS-INFECTION AFTER LOSS OF HEPATITIS-B SURFACE-ANTIGEN IN PATIENTS WITH CHRONIC DELTA-HEPATITIS SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE POLYMERASE CHAIN REACTION; INTERFERON THERAPY; HBV; HDV ID SERUM; PRIMER; LIVER; DNA AB The aim of this study was to evaluate whether patients with chronic hepatitis delta virus (HDV) infection treated with alpha interferon and subsequent loss of hepatitis B surface antigen (HB-sAg) eliminate HDV. HDV RNA was detected in 26 of 28 patients with chronic delta hepatitis using the polymerase chain reaction. Seventeen patients in whom HDV RNA was detected were treated with alpha interferon; in 65%, HDV RNA remained detectable during treatment or reappeared after stopping therapy whereas in three patients HDV RNA remained absent (17.5%). HDV RNA became and remained undetectable in serum and liver of two of these three patients who lost HBsAg from serum and in one patient who was intermittently HBsAg negative during therapy. After loss of HBsAg, hepatitis B virus (HBV) DNA was still detectable in the liver, but not HBV RNA, indicating absent or very low HBV replication. Three patients were lost to follow up (17.5%). Two nontreated patients with chronic HDV infection also lost HBsAg during follow up; HDV RNA also became undetectable in their serum. Thus, HDV replication does not persist after the loss of HBsAg. Clearance of HBsAg may be a useful guide to when therapy can be stopped. (C) 1994 Wiley-Liss, Inc. C1 NIDDKD,LIVER DIS SECT,BETHESDA,MD 20892. NR 16 TC 30 Z9 31 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD DEC PY 1994 VL 44 IS 4 BP 389 EP 392 DI 10.1002/jmv.1890440413 PG 4 WC Virology SC Virology GA QM895 UT WOS:A1994QM89500012 PM 7897369 ER PT J AU GRADY, C AF GRADY, C TI HIV PREVENTIVE VACCINE RESEARCH - SELECTED ETHICAL ISSUES SO JOURNAL OF MEDICINE AND PHILOSOPHY LA English DT Article DE BEHAVIORAL INTERVENTIONS; HIV; SUBJECT PROTECTION; TRIAL DESIGN; VACCINES ID AIDS; TRIALS AB This paper explores three selected issues which present ethical challenges unique to the development and testing of preventive HIV vaccines. The issues are: when to move forward with large scale efficacy testing of vaccines, how to incorporate behavioral interventions into the study of vaccine efficacy, and how to plan for and mitigate social harms associated with participation in an HIV vaccine trial. Careful and ongoing consideration must be given to the ethical implications of these decisions. Proposed solutions include planning for a more complex prevention trial which would integrate the evaluation of behavioral interventions and vaccine efficacy; scrupulous attention to the process of individual informed consent and community participation; and serious and deliberate attempts to plan for, educate about, and minimize the social harms. RP GRADY, C (reprint author), NINR,CLIN THERAPEUT LAB,BLDG 31,ROOM 5B10,BETHESDA,MD 20892, USA. NR 39 TC 3 Z9 3 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0360-5310 J9 J MED PHILOS JI J. Med. Philos. PD DEC PY 1994 VL 19 IS 6 BP 595 EP 612 PG 18 WC Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Biomedical Social Sciences GA QF152 UT WOS:A1994QF15200005 PM 7738453 ER PT J AU LAUGHLIN, MR HEINEMAN, FW AF LAUGHLIN, MR HEINEMAN, FW TI THE RELATIONSHIP BETWEEN PHOSPHORYLATION POTENTIAL AND REDOX STATE IN THE ISOLATED WORKING RABBIT HEART SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE NADH; LACTATE; PYRUVATE; BETA-HYDROXYBUTYRATE; AMINOOXY-ACETATE; FLUORESCENCE; NMR; REDOX STATE ID PERFUSED RAT-HEART; OXYGEN-CONSUMPTION; EQUILIBRIUM RELATIONS; OXIDATIVE-METABOLISM; LACTATE PYRUVATE; CREATINE-KINASE; INVIVO; CYCLE; NMR; DEHYDROGENASE AB The effects of the cytosolic and mitochondrial redox state on the function and phosphorylation potential of working perfused rabbit hearts were studied. Hearts were perfused with glucose, while lactate, aminooxy-acetate (an inhibitor of the malate-aspartate shuttle), beta-hydroxybutyrate, and pyruvate were sequentially added to the perfusate to manipulate the cytosolic and mitochondrial NAD(+)/NADH ratio. The phosphorylation potential and product of ADP and P-i were both found to be proportional to mitochondrial redox state. There was no overall relationship between cytosolic redox potential and the ATP/ADP x P-i ratio, although at high mitochondrial NADH, there was a tendency for the states with more reduced cytoplasm to be associated with a lower phosphorylation potential. Cardiac output and dP/dt were decreased after 75 mu M aminooxy-acetate was present for 15 min, and remained low when 0.5-1.0 mM beta-hydroxybutyrate was added, even though the B-hydroxybutyrate period was characterized by both very low cytosolic NAD(+)/NADH and high mitochondrial NADH. Function returned to normal when the cytoplasm was oxidized by addition of 10 mM pyruvate, and although MVO(2) rose from 4.0+/-0.4 to 5.0+/-0.5, this was not accompanied by statistical changes in either mitochondrial NADH or phosphorylation potential. Therefore, the cytosolic redox state may play a role in cardiac function, but has only a minor contribution to the regulation of the phosphorylation potential in the working perfused rabbit heart. C1 NHLBI, CARDIAC ENERGET LAB, BETHESDA, MD 20892 USA. NR 41 TC 30 Z9 30 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 DEC PY 1994 VL 26 IS 12 BP 1525 EP 1536 DI 10.1006/jmcc.1994.1173 PG 12 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA QB856 UT WOS:A1994QB85600001 PM 7731048 ER PT J AU ISHITANI, R KIMURA, M TAKEICHI, M CHUANG, DM AF ISHITANI, R KIMURA, M TAKEICHI, M CHUANG, DM TI TRYPTAMINE INDUCES PHOSPHOINOSITIDE TURNOVER AND MODULATES ADRENERGIC AND MUSCARINIC CHOLINERGIC RECEPTOR FUNCTION IN CULTURED CEREBELLAR GRANULE CELLS SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE TRYPTAMINE; CEREBELLAR GRANULE CELLS; PHOSPHOINOSITIDE TURNOVER; NEUROMODULATOR; ADRENERGIC AND MUSCARINIC CHOLINERGIC RECEPTORS ID AFFINITY TRYPTAMINE BINDING; C6 GLIOMA-CELLS; RAT-BRAIN; PHARMACOLOGICAL CHARACTERIZATION; PHOSPHOLIPASE-C; SITES; NEUROTRANSMITTER; STIMULATION; HYDROLYSIS; AGONISTS AB Tryptamine dose-dependently increased phosphoinositide (PI) hydrolysis by approximately fourfold in primary cultures of rat cerebellar granule cells (EC(50) = 56 mu M). The PI response stimulated by tryptamine was dependent on the presence of extracellular Ca2+ and Na+. Tryptamine-induced PI breakdown could be partially inhibited by pretreatment with 4 beta-phorbol 12-myristate 13-acetate but not pertussis toxin. The presence of tryptamine markedly attenuated PI responses induced by norepinephrine (NE) and carbachol, with no apparent effect on the responses to 5-hydroxytryptamine and glutamate. The inhibition of NE- and carbachol-induced PI turnover by tryptamine was dose dependent with IC50 values of similar to 0.4 and similar to 2.5 mM, respectively. Pretreatment of cells with tryptamine (0.5 mM) also attenuated NE- and carbachol-induced PI turnover, but failed to affect 5-hydroxytryptamine- and glutamate-induced responses. Furthermore, ketanserin, atropine, and prazosin did not have any effect on inositol phosphate formation induced by tryptamine. These observations indicate that tryptamine markedly increased Ca2+- and Na+-dependent PI turnover in cerebellar neurons and selectively inhibited NE- and carbachol-induced PI hydrolysis. C1 NIMH,BIOL PSYCHIAT BRANCH,MOLEC NEUROPHARMACOL SECT,BETHESDA,MD 20892. RP ISHITANI, R (reprint author), JOSAI UNIV,CELLULAR NEUROPHARMACOL GRP,SAKADO,SAITAMA 35002,JAPAN. NR 25 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD DEC PY 1994 VL 63 IS 6 BP 2080 EP 2085 PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA PT409 UT WOS:A1994PT40900011 PM 7964726 ER PT J AU ELHANANY, E JAFFE, H LINK, WT SHEELEY, DM GAINER, H PANT, HC AF ELHANANY, E JAFFE, H LINK, WT SHEELEY, DM GAINER, H PANT, HC TI IDENTIFICATION OF ENDOGENOUSLY PHOSPHORYLATED KSP SITES IN THE HIGH-MOLECULAR-WEIGHT RAT NEUROFILAMENT PROTEIN SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE HIGH-MOLECULAR-WEIGHT NEUROFILAMENT PROTEIN; ENDOGENOUS PHOSPHORYLATION SITES; CARBOXY-TERMINAL TAIL DOMAIN; KSP REPEATS ID MONOCLONAL-ANTIBODIES DISTINGUISH; NEURONAL INTERMEDIATE FILAMENTS; ACUTE PROMYELOCYTIC LEUKEMIA; SQUID GIANT-AXON; MAMMALIAN NEUROFILAMENTS; NF-H; TRIPLET PROTEINS; GENE FAMILY; SEQUENCE; SUBUNIT AB The high-molecular-weight neurofilament protein (NF-H) is highly phosphorylated in vivo, with estimates as high as 16-51 mol of P-i/mol of protein. Most of the phosphorylation sites are thought to be located on Ser residues in multiple KSP repeats, in the carboxyterminal tail region of the molecule. Because the extent and site-specific patterns of tail domain phosphorylation are believed to modulate neurofilament structure and function, it becomes essential to identify the endogenous sites of phosphorylation. In this study, we have used selective proteolytic cleavage procedures, P-i determinations, microsequencing, and mass-spectral analysis to determine the endogenously phosphorylated sites in the NF-H tail isolated from rat spinal cord. Twenty Ser residues in NF-H carboxy-terminal tail were analyzed; nine of these, all located in KSP repeats, were phosphorylated. No detectable phosphorylation could be identified in any of the 11 ''non-KSP'' Ser residues that were examined. KSPXKX, KSPXXX, and KSPXXK motifs were found to be phosphorylated. In addition, a 27-kDa KSP-rich domain, containing 43 virtually uninterrupted KSPXXX repeats, was isolated from the tail domain and found to contain between 30 and 35 mol of P-i/mol of protein. This domain appeared to be highly resistant to endoproteinase Glu-C digestion, although it contains a large number of glutamate residues. It could be proteolyzed, however, after dephosphorylation. This suggests that phosphorylation of the tail domain may contribute to neurofilament stability in vivo. A neuronal-derived protein kinase that specifically phosphorylates only KSPXKX motifs in neurofilaments has been reported. The presence of extensively phosphorylated KSPXXX repeats in NF-H in vivo suggests the existence of yet another, unidentified kinase(s) with specificity for KSPXXX motifs. C1 NINCDS,NEUROCHEM LAB,BETHESDA,MD 20892. NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. NR 55 TC 77 Z9 78 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD DEC PY 1994 VL 63 IS 6 BP 2324 EP 2335 PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA PT409 UT WOS:A1994PT40900041 PM 7964754 ER PT J AU WILLIAMSON, LC NEALE, EA AF WILLIAMSON, LC NEALE, EA TI BAFILOMYCIN A1 INHIBITS THE ACTION OF TETANUS TOXIN IN SPINAL-CORD NEURONS IN CELL-CULTURE SO JOURNAL OF NEUROCHEMISTRY LA English DT Note DE BAFILOMYCIN AL; ENDOSOMES; TETANUS TOXIN; BREFELDIN A; ACIDIC COMPARTMENTS; GOLGI APPARATUS ID NEUROTRANSMITTER RELEASE; BREFELDIN-A; CLOSTRIDIAL NEUROTOXINS; SYNAPTOBREVIN; MECHANISM; MONENSIN; GOLGI AB Tetanus toxin (TeNT) is one of the clostridial neurotoxins that act intracellularly to block neurotransmitter release. However, neither the route of entry nor the mechanism by which these toxins gain access to the neuronal cytoplasm has been established definitively. In murine spinal cord cell cultures, release of the neurotransmitter glycine is particularly sensitive to blockade by TeNT. To test whether TeNT enters neurons through acidic endosomes or is routed through the Golgi apparatus, toxin action on potassium-evoked glycine release was assayed in cultures pretreated with bafilomycin A1 (baf A1) or brefeldin A (BFA). baf A1, which inhibits the vacuolar-type H+-ATPase responsible for endosome acidification, diminishes the staining of acidic compartments and interferes with the action of TeNT in a dose-dependent manner. TeNT blockade of evoked glycine release is inhibited by 50 and 90% in cultures pretreated with 50 and 100 nM bat A1, respectively, compared with cultures treated with the inhibitor alone. The effects of baf A1 are fully reversible. In contrast, BFA, which disrupts Golgi function, has no effect on TeNT action. These findings provide evidence that TeNT enters the neuronal cytoplasm through bai A1-sensitive acidic compartments and that TeNT is not trafficked through the Golgi apparatus before its translocation into the neuronal cytosol. RP WILLIAMSON, LC (reprint author), NICHHD,DEV NEUROBIOL LAB,BLDG 49,ROOM 5A38,BETHESDA,MD 20892, USA. NR 23 TC 47 Z9 48 U1 0 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD DEC PY 1994 VL 63 IS 6 BP 2342 EP 2345 PG 4 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA PT409 UT WOS:A1994PT40900043 PM 7964755 ER PT J AU CHEN, G MANJI, HK HAWVER, DB WRIGHT, CB POTTER, WZ AF CHEN, G MANJI, HK HAWVER, DB WRIGHT, CB POTTER, WZ TI CHRONIC SODIUM VALPROATE SELECTIVELY DECREASES PROTEIN KINASE-C-ALPHA AND KINASE-EPSILON IN-VITRO SO JOURNAL OF NEUROCHEMISTRY LA English DT Note DE VALPROIC ACID; VALPROATE; PROTEIN KINASE C; ANTICONVULSANT; MANIC-DEPRESSIVE ILLNESS ID PHOSPHORYLATION; HIPPOCAMPUS; CELLS AB Valproic acid (VPA) is a fatty acid antiepileptic with demonstrated antimanic properties, but the molecular mechanism or mechanisms underlying its therapeutic efficacy remain to be elucidated. in view of the increasing evidence demonstrating effects of the first-line antimanic drug, lithium, on protein kinase C (PKC), we investigated the effects of VPA on various aspects of this enzyme. Chronic exposure (6-7 days) of rat C6 glioma cells to ''therapeutic'' concentrations (0.6 mM) of VPA resulted in decreased PKC activity in both membrane and cytosolic fractions and increased the cytosol/membrane ratio of PKC activity. Western blot analysis revealed isozyme-selective decreases in the levels of PKC alpha and epsilon (but not delta or zeta) in both the membrane and cytosolic fractions after chronic VPA exposure; VPA added to reaction mixtures did not alter PKC activity or H-3-phorbol ester binding. Together, these data suggest that chronic VPA indirectly lowers the levels of specific isozymes of PKC in C6 cells. Given the pivotal role of PKC in regulating neuronal signal transduction and modulating intracellular cross-talk between neurotransmitter systems, the specific decreases in PKC alpha and epsilon may play a role in the antimanic effects of VPA. RP NIMH, EXPTL THERAPEUT BRANCH,CLIN PHARMACOL SECT, BLDG 10,ROOM 2D46, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. RI Chen, Guang/A-2570-2017 NR 21 TC 133 Z9 139 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 DEC PY 1994 VL 63 IS 6 BP 2361 EP 2364 PG 4 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA PT409 UT WOS:A1994PT40900048 PM 7964759 ER PT J AU LUO, X KISS, A MAKARA, G LOLAIT, SJ AGUILERA, G AF LUO, X KISS, A MAKARA, G LOLAIT, SJ AGUILERA, G TI STRESS-SPECIFIC REGULATION OF CORTICOTROPIN-RELEASING HORMONE-RECEPTOR EXPRESSION IN THE PARAVENTRICULAR AND SUPRAOPTIC NUCLEI OF THE HYPOTHALAMUS IN THE RAT SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE STRESS; HYPOTHALAMUS-PITUITARY-ADRENAL AXIS; CRH RECEPTORS; IN SITU HYBRIDIZATION; OSMOTIC STIMULATION ID ULTRASHORT LOOP FEEDBACK; PITUITARY-ADRENAL AXIS; MILK-EJECTION REFLEX; OSMOTIC STIMULATION; OXYTOCIN NEURONS; MESSENGER-RNA; CRF RECEPTOR; VASOPRESSIN; SECRETION; BRAIN AB Corticotropin releasing hormone (CRH), a major regulator of pituitary ACTH secretion, also acts as a neurotransmitter in the brain. To determine whether CRH is involved in the regulation of hypothalamic function during stress, CRH receptor binding and CRH receptor mRNA levels were studied in the hypothalamus of rats subjected to different stress paradigms: immobilization, a physical-psychological model; water deprivation and 2% saline intake, osmotic models; and i.p. hypertonic saline injection, a combined physical-psychological and osmotic model. In agreement with the distribution of CRH receptor binding in the brain, in situ hybridization studies using S-35-labeled cRNA probes revealed low levels of CRH receptor mRNA in the anterior hypothalamic area, which were unaffected after acute or chronic exposure to any of the stress paradigms used. Under basal conditions, there was no CRH binding or CRH receptor mRNA in the supraoptic (SON) or paraventricular (PVN) nuclei. However, 2 h after the initiation of acute immobilization, CRH receptor mRNA hybridization became evident in the parvicellular division of the PVN, with levels substantially increasing from 2 to 4 h, decreasing at 8 h and disappearing by 24 h. identical hybridization patterns of CRH receptor mRNA were found in the parvicellular PVN after repeated immobilization; levels were similar to those after 2 h single stress following immobilization at 8-hourly intervals for 24 h (3 times), and very low, but clearly detectable 24 h after 8 or 14 days daily immobilization for 2 h. On the other hand, water deprivation for 24 or 60 h and intake of 2% NaCl for 12 days induced expression of CRH receptor mRNA in the SON and magnocellular PVN, but not in the parvicellular pars of the PVN. Both parvicellular and magnocellular hypothalamic areas showed CRH receptor mRNA following i.p. hypertonic saline injection, single (4 h after) or repeated at 8-hourly intervals for 24 h (3 injections), or one injection daily for 8 or 14 days. Consistent with the expression of CRH receptor mRNA, autoradiographic studies showed binding of I-125-Tyr-oCRH in the parvicellular division of the PVN after immobilization; in the magnocellular division of the PVN after osmotic stimulation, and in the PVN and SON after i.p. hypertonic saline injection. The data show that stress-specific activation of the parvicellular and magnocellular systems is associated with CRH receptor expression, and suggest a role for CRH in the autoregulation of hypothalamic function. C1 NICHHD, DEV ENDOCRINOL BRANCH, PHYSIOL & ENDOCRINOL SECT, BETHESDA, MD 20892 USA. NIMH, CELL BIOL LAB, BETHESDA, MD 20892 USA. RI Makara, Gabor/H-8397-2013 OI Makara, Gabor/0000-0001-9220-0373 NR 51 TC 119 Z9 119 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD DEC PY 1994 VL 6 IS 6 BP 689 EP 696 DI 10.1111/j.1365-2826.1994.tb00636.x PG 8 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA PX573 UT WOS:A1994PX57300014 PM 7894472 ER PT J AU DRAGO, J KILPATRICK, TJ KOBLAR, SA TALMAN, PS AF DRAGO, J KILPATRICK, TJ KOBLAR, SA TALMAN, PS TI GROWTH-FACTORS - POTENTIAL THERAPEUTIC APPLICATIONS IN NEUROLOGY SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Review ID CILIARY NEUROTROPHIC FACTOR; LEUKEMIA INHIBITORY FACTOR; RETROGRADE AXONAL-TRANSPORT; PROGRESSIVE MOTOR NEURONOPATHY; FOREBRAIN CHOLINERGIC NEURONS; FACTOR PREVENTS DEGENERATION; FIMBRIA FORNIX TRANSECTION; CENTRAL-NERVOUS-SYSTEM; ROOT GANGLION NEURONS; GLIAL PROGENITOR-CELL C1 ROYAL MELBOURNE HOSP,WALTER & ELIZA HALL INST MED RES,MELBOURNE,VIC 3050,AUSTRALIA. SALK INST BIOL STUDIES,LA JOLLA,CA 92037. NIH,MAMMALIAN GENES & DEV LAB,BETHESDA,MD 20892. OI Koblar, Simon/0000-0002-8667-203X; Kilpatrick, Trevor/0000-0003-3999-085X NR 120 TC 19 Z9 19 U1 0 U2 2 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD DEC PY 1994 VL 57 IS 12 BP 1445 EP 1450 DI 10.1136/jnnp.57.12.1445 PG 6 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA PW356 UT WOS:A1994PW35600001 PM 7798970 ER PT J AU COWIE, RJ ROBINSON, DL AF COWIE, RJ ROBINSON, DL TI SUBCORTICAL CONTRIBUTIONS TO HEAD MOVEMENTS IN MACAQUES .1. CONTRASTING EFFECTS OF ELECTRICAL-STIMULATION OF A MEDIAL PONTOMEDULLARY REGION AND THE SUPERIOR COLLICULUS SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID ORIENTING GAZE SHIFTS; MESENCEPHALIC RETICULAR-FORMATION; SACCADIC EYE-MOVEMENTS; ALERT CAT; SPINAL-CORD; TECTORETICULOSPINAL SYSTEM; DESCENDING PATHWAYS; RHESUS-MONKEY; BURST NEURONS; SYNERGIC EYE AB 1. These studies were initiated to understand the neural sites and mechanisms controlling head movements during gaze shifts. Gaze shifts are made by saccadic eye movements with and without head movements. Sites were stimulated electrically within the brain stem of awake, trained monkeys relatively free to make head movements to study the head-movement components of gaze shifts. 2. Electrical stimulation in and around the gigantocellular reticular nucleus evoked head movements in the ipsilateral direction. Gaze shifts were never evoked from these sites, presumably because the vestibule-ocular reflex compensated. The rough topography of this region included large head movements laterally, small movements medially, downward movements from dorsal sites, and upward movements more ventrally. 3. The initial position of the head influenced the magnitude of the elicited movement with larger movements produced when the head was directed to the contralateral side. Attentive fixation was associated with larger and faster head movements when compared with those evoked during spontaneous behavior. 4. The superior colliculus makes a significant contribution to gaze shifts and has been shown to contribute to head movements. Because the colliculus is a major source of afferents to the gigantocellular reticular nucleus, comparable stimulation studies of the superior colliculus were conducted. When the colliculus was excited, shifts of gaze in the contralateral direction were predominant. These were most often accomplished by saccadic eye movements, however, we frequently elicited head movements that had an average latency 10 ms longer than those elicited from the reticular head movement region. Sites evoking head movements tended to be deeper and more caudal than loci eliciting eye movements. Neither the onset latencies, amplitudes, nor peak velocities of head movements and eye movements were correlated. Gaze shifts evoked from the caudal colliculus with the head free were larger than those elicited from the same site with the head fixed. 5. These studies demonstrate that both the superior colliculus and gigantocellular reticular nucleus mediate head movements. The colliculus plays a role in orienting to external events, and so collicular head movements predominantly were associated with gaze shifts, with the eye and head movements uncoupled. The medullary reticular system may play a role in the integration of a wider range of movements. Head movements from the medullary reticular sites probably participate in several forms of head movements, such as those that are related to postural reflexes, started volitionally, and/or oriented to external events. C1 HOWARD UNIV, COLL MED, DEPT ANAT, WASHINGTON, DC 20059 USA. RP COWIE, RJ (reprint author), NEI, SENSORIMOTOR RES LAB, VISUAL BEHAVIOR SECT, BLDG 49, RM 2A50, BETHESDA, MD 20892 USA. NR 73 TC 108 Z9 108 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD DEC PY 1994 VL 72 IS 6 BP 2648 EP 2664 PG 17 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA PX464 UT WOS:A1994PX46400011 PM 7897481 ER PT J AU COWIE, RJ SMITH, MK ROBINSON, DL AF COWIE, RJ SMITH, MK ROBINSON, DL TI SUBCORTICAL CONTRIBUTIONS TO HEAD MOVEMENTS IN MACAQUES .2. CONNECTIONS OF A MEDIAL PONTOMEDULLARY HEAD-MOVEMENT REGION SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID CONJUGATED HORSERADISH-PEROXIDASE; MESENCEPHALIC RETICULAR-FORMATION; STEM RETICULOSPINAL NUCLEI; SUPERIOR COLLICULUS; BRAIN-STEM; SPINAL-CORD; DESCENDING PROJECTIONS; TOPOGRAPHICAL REPRESENTATION; FUNCTIONAL-ORGANIZATION; BEHAVIORAL ORGANIZATION AB 1. In the companion article, a variety of head movements were elicited by stimulation in, and adjacent to, the gigantocellular reticular nucleus (Cowie and Robinson 1994). We refer to this area, caudal to the abducens nucleus, as the gigantocellular head movement region. In the present paper, the anatomical connections of this region, as determined by injections of wheat-germ agglutinin conjugated horseradish peroxidase (WGA-HRP), are reported. The majority of efferent and afferent connections were with areas related to head movements. 2. Efferent fibers from the region projected via two paths to the caudal medulla and upper cervical spinal cord. Labeled fibers descended in the anterolateral funiculus of the ipsilateral spinal cord to terminate in lateral parts of the ventral horn. A second pathway descended bilaterally in the medial longitudinal fasciculus to the anterior funiculi and medial portions of the ventral gray. These efferents paralleled the head-movement topography demonstrated physiologically. Other projections included efferents to the interstitial nucleus of Cajal, caudal field H of Forel, paramedian pontine reticular formation, and caudal vestibular nuclei. Other efferent fibers projected to the trigeminal, facial, and hypoglossal nuclei, as well as to the parvocellular reticular field, which contains interneurons for these motor groups. However, no efferent or afferent labeling involved the ocular motor nuclei. 3. Afferents to the gigantocellular head movement region arose mainly from head-movement areas. In all animals, labeled cells were found in the intermediate and deep layers of the caudal superior colliculus. Labeled neurons also were found in the caudal field H of Forel, interstitial nucleus of Cajal, pontine medial tegmentum including the pontine paramedian reticular formation, nucleus subcoeruleus, and vestibular nuclear complex. Caudally, filled cells were located in the parvocellular, magnocellular, dorsal, and ventral reticular nuclei, the supraspinal nucleus, and the upper cervical ventral horn. 4. In one animal, the ipsilateral frontal cortex contained retrogradely labeled neurons. These cells were found in layer V of cortical areas 4 and 6. Other afferent cells were found consistently in the periventricular and periaqueductal gray matter. 5. A control injection into the caudal vestibular nuclear complex showed projections to the gigantocellular reticular formation and labeled cells in the vestibular and parvocellular reticular nuclei. These observations show that the connections of the gigantocellular region are not typical of all head movement sites. 6. These data indicate that the gigantocellular head-movement region has the requisite efferent and afferent connections to function in the subcortical control of head, but not eye, movements. Efferent connections to the appropriate motor and premotor nuclei are present to support the other body movements elicited by our stimulation. In addition, the region receives afferents that could mediate the behavioral modulations of movement that we have demonstrated. We hypothesize that the gigantocellular region integrates a variety of afferent signals to generate the synergistic patterns of motor activity that often accompany head movements. C1 HOWARD UNIV,COLL MED,DEPT ANAT,WASHINGTON,DC 20059. RP COWIE, RJ (reprint author), NEI,SENSORIMOTOR RES LAB,VISUAL BEHAVIOR SECT,BLDG 49,RM 2A50,BETHESDA,MD 20892, USA. NR 85 TC 59 Z9 59 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD DEC PY 1994 VL 72 IS 6 BP 2665 EP 2682 PG 18 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA PX464 UT WOS:A1994PX46400012 PM 7534824 ER PT J AU MCBAIN, CJ AF MCBAIN, CJ TI HIPPOCAMPAL INHIBITORY NEURON ACTIVITY IN THE ELEVATED POTASSIUM MODEL OF EPILEPSY SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID ACTIVITY-DEPENDENT DISINHIBITION; GUINEA-PIG HIPPOCAMPUS; PYRAMIDAL CELLS; EPILEPTIFORM ACTIVITY; ORIENS-ALVEUS; CA3; INVITRO; RECEPTOR; MEMBRANE; SLICES AB 1. Whole cell patch-clamp recordings were made from CA1 stratum oriens inhibitory neurons of rat hippocampal slices in vitro to determine their contribution to the epileptiform activity elicited by elevating the extracellular potassium ion concentration ([K+](o)) from 3.5 to 8.5 mm. 2. Under current-clamp conditions, spontaneous action potential activity in inhibitory neurons normally occurs in a sustained repetitive firing mode paced by nonsynaptic, intrinsic mechanisms. On elevation of [K+](o) to 8.5 mm the pattern of activity is altered such that clusters of action potentials occur interrupted by periods of silence without an appreciable afterhyperpolarization (AHP). In addition, elevation of [K+](o) caused a large reduction in the action potential AHP amplitude and duration concomitant with a 20-mV shift in the reversal potential of the AHP. 3. In voltage clamp a small persistent inward current was observed after the introduction of elevated potassium concomitant with an increase in the frequency of spontaneous excitatory postsynaptic currents (EPSCs) in all interneurons studied. After a short period of time (similar to 1 min) temporal summation of synchronously occurring EPSCs contributed a periodic inward current (PIC; 10-40 pA, 0.8 Hz) that persisted for the duration of the [K+](o) elevation. Analysis of the charge transfer associated with the PIC suggests that they comprise the temporal summation of similar to 35 EPSCs. This PIC was synchronous with the extracellular field potential recorded from the CA1 pyramidal neuron layer. 4. The PIC was responsible for the clustering of action potential activity because blockade of EPSC activity by the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) abolished PICs and reverted action potential activity to single sustained firing, despite the continued application of 8.5 mm [K+](o). Antagonists of N-methyl-D-aspartate receptors were without effect on either the PICs or the action potential activity. 5. Addition of the metabotropic glutamate receptor (mGluR) antagonist (+)-2-methyl-4-carboxyphenylglycine (MCPG) reversibly abolished the PIC without affecting the increase in EPSC frequency. 6. Recordings from CA3 pyramidal neurons in 8.5 mm [K+](o) demonstrated that interictal activity occurred at a frequency identical to the PICs observed in interneurons. Interictal activity in CA3 pyramidal neurons was attenuated but never abolished by MCPG, suggesting a role for mGluR receptors in the maintenance of interictal activity in area CA3. 7. Flurries of synchronous inhibitory postsynaptic currents (IPSCs) were observed on a small number of CA1 pyramidal neurons on elevation of [K+]o, consistent with these neurons being the synaptic target of stratum oriens/alveus interneurons. Unexpectedly, a rundown of this IPSC activity was observed during the transition to CA1 pyramidal neuron epileptiform activity. 8. In CA1 pyramidal neurons, current-voltage relationships measured at the peak response to gamma-aminobutyric acid (GABA) were identical in both normal or elevated [K+](o). However, subsequent current-voltage relationships determined during the fade of the GABA response revealed a positive shift in the reversal potential in both control and 8.5 mm [K+](o) conditions. The mechanism for this positive shift in reversal potential is at present un known but may occur due to the intracellular accumulation of Cl- after sustained GABA receptor activation. 9. These experiments suggest that the ongoing intrinsic action potential activity of the CA1 interneuron population is ''overridden'' during electrographic activity resulting from [K+](o) elevation. The resulting activity is paced by interictal events occurring in the CA3 pyramidal neuron population. A role for mGluRs in the interictal activity of the CA3 pyramidal neuron population is also described. After the establishment of epileptiform activity, synaptic inhibition onto CA1 pyramidal neurons is severly attenuated. This results not from the [K+](o) elevation per se but possibly from an activity-dependent Cl- redistribution across the CA1 pyramidal neurons after sustained IPSC activity. RP MCBAIN, CJ (reprint author), NICHHD,LCMN,CELLULAR & SYNAPT PHYSIOL UNIT,RM 5A72,BLDG 49,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 35 TC 48 Z9 48 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD DEC PY 1994 VL 72 IS 6 BP 2853 EP 2863 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA PX464 UT WOS:A1994PX46400027 PM 7897494 ER PT J AU GOLOMB, D KLEINFELD, D REID, RC SHAPLEY, RM SHRAIMAN, BI AF GOLOMB, D KLEINFELD, D REID, RC SHAPLEY, RM SHRAIMAN, BI TI ON TEMPORAL CODES AND THE SPATIOTEMPORAL RESPONSE OF NEURONS IN THE LATERAL GENICULATE-NUCLEUS SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID TWO-DIMENSIONAL PATTERNS; CAT STRIATE CORTEX; PRIMARY VISUAL-CORTEX; SINGLE UNITS; SIMPLE CELLS; RECEPTIVE-FIELDS; BEHAVING PRIMATES; TRANSMITTED INFORMATION; DIRECTIONAL SELECTIVITY; 2-DIMENSIONAL PATTERNS AB 1. The present work relates recent experimental studies of the temporal coding of visual stimuli (McClurkin, Optican, Richmond, and Gawne, Science 253: 675, 1991) to the measurements of the spatiotemporal receptive fields of neurons within the lateral geniculate of primate. 2. We analyze both new and previously described magnocellular and parvocellular single units. The spatiotemporal impulse response function of the unit, defined as the time-resolved average firing rate in response to a weak stimulus flashed at a given location and time, is characterized by the singular value decomposition. This analysis allows one to represent the impulse response by a small number, two to three, of spatial and temporal modes. Both magnocellular and parvocellular units are weakly nonseparable, with major and minor modes that account, respectively, for similar to 78 and 22% of the response. The major temporal mode for both types is essentially identical for the first 100 ms. At later times the response of magnocellular units changes sign and decays slowly, whereas the response of parvocellular units decays relatively rapidly. 3. The spatiotemporal impulse response function completely determines the response of a unit to an arbitrary stimulus when linear response theory is valid. Using the measured impulse response, combined with a rectifying neuronal input-output relation, we calculate the responses to a complete set of spatial luminance patterns constructed of ''Walsh'' functions. Our predicted temporal responses are in qualitative agreement with those reported for parvocellular units (McClurkin, Optican, Richmond, and Gawne, J. Neurophysiol. 66: 794, 1991). Under the additional assumptions of Poisson statistics for the probability of spiking and a plausible background firing rate, we predict the performance of a unit in the Walsh pattern discrimination task as quantified by mutual information. Our prediction is again consistent with the reported results. 4. Last, we consider the issue of temporal coding within linear response. For stimuli presented for fixed time intervals, the singular value decomposition provides a natural relation between the temporal modes of the neuronal response and the spatial pattern of the stimulus. Although it is tempting to interpret each temporal mode as an independent channel that encodes orthogonal features of the stimulus, successively higher order modes are increasingly unreliable and do not significantly increase the discrimination capabilities of the unit. C1 AT&T BELL LABS,MURRAY HILL,NJ 07974. NIDDKD,MATH RES BRANCH,BETHESDA,MD 20892. ROCKEFELLER UNIV,NEUROBIOL LAB,NEW YORK,NY 10021. NYU,CTR NEURAL SCI,NEW YORK,NY 10003. FU NEI NIH HHS [EY-01472, EY-10115] NR 42 TC 35 Z9 35 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD DEC PY 1994 VL 72 IS 6 BP 2990 EP 3003 PG 14 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA PX464 UT WOS:A1994PX46400038 PM 7897504 ER PT J AU SCOTT, AM MACAPINLAC, HA DIVGI, CR ZHANG, JJ KALAIGIAN, H PENTLOW, K HILTON, S GRAHAM, MC SGOUROS, G PELIZZARI, C CHEN, G SCHLOM, J GOLDSMITH, SJ LARSON, SM AF SCOTT, AM MACAPINLAC, HA DIVGI, CR ZHANG, JJ KALAIGIAN, H PENTLOW, K HILTON, S GRAHAM, MC SGOUROS, G PELIZZARI, C CHEN, G SCHLOM, J GOLDSMITH, SJ LARSON, SM TI CLINICAL VALIDATION OF SPECT AND CT/MRI IMAGE REGISTRATION IN RADIOLABELED MONOCLONAL-ANTIBODY STUDIES OF COLORECTAL-CARCINOMA SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE IMAGE REGISTRATION; MONOCLONAL ANTIBODIES; COLORECTAL CARCINOMA ID F-18 FDG PET; EMISSION TOMOGRAPHY; CT; MR; FUSION; METASTASES; CANCER; RECURRENCE; DIAGNOSIS; RESECTION AB Registration methods combine the anatomic localizing ability of CT or MRI with SPECT images of radiolabeled monoclonal antibodies (Mabs), allowing the accurate staging of patients prior to surgery or following treatment. Methods: Twenty-four patients (15 males and 9 females, mean age 55 yr, range 29-70 yr) were studied with this technique. Ten patients had suspected colorectal cancer recurrence and were infused with 10 mCi of I-131-CC49 prior to staging laparotomy. Fourteen patients treated in a Phase I radioimmunotherapy study with I-131-CC49 were also studied. All patients underwent SPECT imaging of the abdomen and pelvis 5-7 days following infusion of Mab. Results: Phantom studies demonstrated a 3.6-mm surface fitting mean accuracy of datasets for the liver and 1.8 mm for an intrahepatic tumor. In the presurgical group, SPECT and CT/MRI registration allowed more accurate identification of uptake abnormal sites. Areas of metastatic disease >1 cm confirmed at surgery were found in six of nine patients with liver lesions and in two patients with extrahepatic (including one patient with pelvic) disease. In patients imaged following radioimmunotherapy, all lesions >1.5 cm seen on CT/MRI were identified, and activity distribution in tumor and normal tissue could be more accurately assessed. Conclusions: Routine registration of SPECT and CT/MRI images is feasible and allows more accurate anatomic assessment of sites of abnormal uptake in radiolabeled Mab studies. C1 UNIV CHICAGO,CHICAGO,IL 60637. NIH,BETHESDA,MD 20892. RP SCOTT, AM (reprint author), MEM SLOAN KETTERING CANC CTR,NUCL MED SERV,H213,1275 YORK AVE,NEW YORK,NY 10021, USA. FU NCI NIH HHS [CA-97609] NR 41 TC 50 Z9 51 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD DEC PY 1994 VL 35 IS 12 BP 1976 EP 1984 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PW035 UT WOS:A1994PW03500021 PM 7989980 ER PT J AU GOLDSMITH, SJ AF GOLDSMITH, SJ TI YEAR OF THE BRAIN SO JOURNAL OF NUCLEAR MEDICINE LA English DT Editorial Material C1 UNIV CHICAGO,CHICAGO,IL 60637. NIH,BETHESDA,MD 20892. RP GOLDSMITH, SJ (reprint author), MEM SLOAN KETTERING CANC CTR,1275 YORK AVE,NEW YORK,NY 10021, USA. NR 0 TC 0 Z9 0 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 DEC PY 1994 VL 35 IS 12 BP N15 EP N15 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PW035 UT WOS:A1994PW03500001 ER PT J AU SULLIVAN, KE MULLEN, CA BLAESE, RM WINKELSTEIN, JA AF SULLIVAN, KE MULLEN, CA BLAESE, RM WINKELSTEIN, JA TI A MULTIINSTITUTIONAL SURVEY OF THE WISKOTT-ALDRICH SYNDROME SO JOURNAL OF PEDIATRICS LA English DT Article ID BONE-MARROW TRANSPLANTATION; X-LINKED THROMBOCYTOPENIA; T-CELL LYMPHOMA; TERM FOLLOW-UP; CHROMOSOME INACTIVATION; PLATELET SIZE; LYMPHOCYTES; SPLENECTOMY; HEREDITARY; MANAGEMENT AB The Wiskott-Aldrich syndrome is an X-linked primary immunodeficiency originally characterized by the clinical triad of thrombocytopenia, eczema, and immunodeficiency, We collected clinical and laboratory information on 154 unselected patients with Wiskott-Aldrich syndrome to define better the clinical expression of this disorder. The classic triad of thrombocytopenia with small platelets, recurrent otitis media, and eczema was seen in only 27% of the study population; 5% of the study population had only infectious manifestations, and 20% of the study group had only hematologic manifestations before diagnosis, The results of immunologic evaluations varied from one patient to another and the course of the disorder varied tremendously, even within a single kindred, We conclude that many patients with Wiskott-Aldrich syndrome have an atypical presentation and that a panel of diagnostic tests is often required to establish the diagnosis, Two high-risk subgroups were identified in the study population: patients with platelet counts < 10 X 10(9)/L (< 10,000/mm(3)) at the time of diagnosis were at high risk of bleeding, and patients with autoimmune disorders were at increased risk of having a malignancy, C1 JOHNS HOPKINS UNIV, SCH MED, DEPT PEDIAT, BALTIMORE, MD 21205 USA. NCI, METAB BRANCH, BETHESDA, MD 20892 USA. RP SULLIVAN, KE (reprint author), CHILDRENS HOSP, DEPT PEDIAT, DIV ALLERGY IMMUNOL & INFECT DIS, 34TH ST & CIVIC CTR BLVD, PHILADELPHIA, PA 19104 USA. OI Sullivan, Kathleen/0000-0003-4018-1646 FU NIAID NIH HHS [AI 07007]; NICHD NIH HHS [HD 28815] NR 50 TC 349 Z9 361 U1 0 U2 6 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 DEC PY 1994 VL 125 IS 6 BP 876 EP 885 DI 10.1016/S0022-3476(05)82002-5 PN 1 PG 10 WC Pediatrics SC Pediatrics GA PW572 UT WOS:A1994PW57200006 PM 7996359 ER PT J AU WOLFE, JL LEE, GE POTTI, GK GALLELLI, JF AF WOLFE, JL LEE, GE POTTI, GK GALLELLI, JF TI DEGRADATION OF ANTIFLAMMIN-2 IN AQUEOUS-SOLUTION SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Letter ID PHARMACEUTICAL PREPARATIONS; PEPTIDE DEGRADATION; CHEMICAL-STABILITY; DEAMIDATION; ASPARAGINYL; UTEROGLOBIN; ENDOTOXIN; RESIDUES; PATHWAYS; INSULIN C1 NIH,CLIN CTR PHARM,PHARMACEUT DEV SECT,BETHESDA,MD 20892. RP WOLFE, JL (reprint author), UNIV TENNESSEE,DEPT PHARMACEUT SCI,MEMPHIS,TN 38163, USA. NR 11 TC 4 Z9 4 U1 0 U2 0 PU AMER PHARMACEUTICAL ASSN PI WASHINGTON PA 2215 CONSTITUTION AVE NW, WASHINGTON, DC 20037 SN 0022-3549 J9 J PHARM SCI JI J. Pharm. Sci. PD DEC PY 1994 VL 83 IS 12 BP 1762 EP 1764 DI 10.1002/jps.2600831223 PG 3 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA PW786 UT WOS:A1994PW78600022 PM 7891309 ER PT J AU BAUMANN, MH CHAR, GU DECOSTA, BR RICE, KC ROTHMAN, RB AF BAUMANN, MH CHAR, GU DECOSTA, BR RICE, KC ROTHMAN, RB TI GBR12909 ATTENUATES COCAINE-INDUCED ACTIVATION OF MESOLIMBIC DOPAMINE NEURONS IN THE RAT SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID VENTRAL TEGMENTAL AREA; UPTAKE INHIBITOR; INVIVO MICRODIALYSIS; EXTRACELLULAR DOPAMINE; NUCLEUS ACCUMBENS; GBR-12909; AMPHETAMINE; BUPROPION; STRIATUM; BINDING AB Previous studies have shown that the dopamine (DA) reuptake inhibitor 1-{2-[bis(4-fluorophenyl)-[methoxy]ethyl}-4-(3-phenyl-propyl)piperazine (GBR12909) antagonizes the increase in extracellular DA evoked by local perfusion of cocaine into the striatum. In the present work, in vivo microdialysis methods were used to examine the effects of i.v. cocaine, GBR12909 and combinations of the two drugs on DA overflow in the nucleus accumbens of awake rats. Both cocaine and GBR12909 (0.3, 1.0 and 3.0 mg/kg) caused dose-related elevations in extracellular DA when given alone. However, the temporal profile of DA overflow was different with each drug. Cocaine caused a rapid and short-lived increase in DA, whereas GBR12909 caused a slow and sustained elevation of transmitter. In drug combination studies, the rise in extracellular DA after a modest dose of cocaine (1.0 mg/kg) was significantly reduced from 250% to 175% of baseline by pretreatment with a subthreshold dose of GBR12909 (0.3 mg/kg). A high dose of cocaine (3.0 mg/kg) increased dialysate DA by 600%; this rise in DA was decreased to 450% and 325% of baseline by pretreatment with 0.3 and 1.0 mg/kg of GBR12909, respectively. The neurochemical effect of the combination of GBR12909 plus cocaine was clearly not additive. GBR12909 also blocked the DA-releasing action of amphetamine (1.0 mg/kg). Our findings show that GBR12909 antagonizes the rise in extracellular DA produced by systemic cocaine and these results provide further evidence that DA reuptake inhibitors may be useful pharmacological adjuncts in the treatment of cocaine addiction and withdrawal in human patients. C1 NIDDKD,MED CHEM LAB,BETHESDA,MD 20892. RP BAUMANN, MH (reprint author), NIDA,ADDICT RES CTR,INTRAMURAL RES PROGRAM,CLIN PSYCHOPHARMACOL SECT,POB 5180,BALTIMORE,MD 21224, USA. NR 40 TC 105 Z9 105 U1 1 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD DEC PY 1994 VL 271 IS 3 BP 1216 EP 1222 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PX343 UT WOS:A1994PX34300013 PM 7996429 ER PT J AU NOURJAH, P HOROWITZ, AM WAGENER, DK AF NOURJAH, P HOROWITZ, AM WAGENER, DK TI FACTORS ASSOCIATED WITH THE USE OF FLUORIDE SUPPLEMENTS AND FLUORIDE DENTIFRICE BY INFANTS AND TODDLERS SO JOURNAL OF PUBLIC HEALTH DENTISTRY LA English DT Article DE FLUORIDE DENTIFRICES; DIETARY FLUORIDE SUPPLEMENTS; FLUOROSIS; INFANTS AND TODDLERS; ORAL HEALTH KNOWLEDGE ID DENTAL FLUOROSIS; ENAMEL FLUOROSIS; CHILDREN; CARIES; PREVALENCE; INGESTION; WATER; TOOTHPASTE; COMMUNITY; RISK AB Dental fluorosis may be associated with the inappropriate use of fluoride dentifrices and/or dietary fluoride supplements by young children, especially for those who consume optimally fluoridated water. Studies to date have used retrospective designs that rely on anamnestic responses of adults to determine fluoride exposures in their children. The 1986 National Health Interview Survey (NHIS) collected information on current use of fluoride-containing dental products (dentifrices, drops, tablets, and mouth rinses) by all household members during home interviews. This report contains information obtained from adults for 1,996 children younger than two years of age. Nearly haff of the children used fluoride dentifrices or dietary fluoride supplements. Eleven percent of the children younger than one year of age and nearly 60 percent of children between one and two years of age reportedly used a fluoride toothpaste. Dietary fluoride supplements were used about equally in these age groups (about 16%). The use of a fluoride dentifrice was similar across racial-ethnic groups, but the use of dietary fluoride supplements was less among blacks and Hispanics. A significantly higher proportion of children whose respondent knew the purpose of water fluoridation used some type of fluoride product. Because young children tend to swallow dentifrices, the findings of this study suggest the need for educational programs targeted to parents and health care providers regarding the appropriate use of fluorides and the risk of fluorosis when they are used inappropriately. C1 NIDR,EPIDEMIOL & ORAL DIS PREVENT PROGRAM,WESTWOOD BLDG,BETHESDA,MD 20892. CTR DIS CONTROL & PREVENT,NATL CTR HLTH STAT,OFF ANAL & EPIDEMIOL,HYATTSVILLE,MD. NR 45 TC 9 Z9 9 U1 1 U2 1 PU AAPHD NATIONAL OFFICE PI RICHMOND PA J PUBLIC HEALTH DENT 10619 JOUSTING LANE, RICHMOND, VA 23235 SN 0022-4006 J9 J PUBLIC HEALTH DENT JI J. Public Health Dent. PD WIN PY 1994 VL 54 IS 1 BP 47 EP 54 DI 10.1111/j.1752-7325.1994.tb01178.x PG 8 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA MZ507 UT WOS:A1994MZ50700007 PM 8164191 ER PT J AU NOURJAH, P WAGENER, DK EBERHARDT, M HOROWITZ, AM AF NOURJAH, P WAGENER, DK EBERHARDT, M HOROWITZ, AM TI KNOWLEDGE OF RISK-FACTORS AND RISK BEHAVIORS RELATED TO CORONARY HEART-DISEASE AMONG BLUE AND WHITE-COLLAR MALES SO JOURNAL OF PUBLIC HEALTH POLICY LA English DT Article ID SMOKING CESSATION; DETERMINANTS AB In this report the data regarding coronary heart disease (CHD) from the 1990 Health Promotion and Disease Prevention Supplement of the National Health Interview Survey are used to examine the relationship between risk factor knowledge and health related behaviors among currently employed white collar(N = 5,349) and blue collar(N = 4,158) men workers. Blue collar employees have less knowledge about CHD risk factors, less favorable risk factors status, and poorer health practices than their white collar workers. Despite these findings within each occupational group, the relationship of knowledge to either risk factor status or health practices is similar. Knowledge is generally related to the attempts to change behaviors. However, for the different risk factors, the associations vary. For example, knowledge of cigarette smoking as a risk factor of CHD is negatively associated with reported ever smoking or current smoking, but not with heavy smoking. In contrast, knowledge of overweight, high serum cholesterol, and high blood pressure as CHD risk factors is not associated with risk factor status. These result suggest that while difference in level of knowledge and risk profiles remain between blue collar and white collar employees, the associations between knowledge and risk profiles are similar. Programs located at worksites must continue to provide education opportunities about the risk factors, especially among blue collar workers. C1 CTR DIS CONTROL & PREVENT NATL CTR HLTH STAT,OFF ANAL & EPIDEMIOL,HYATTSVILLE,MD 20782. NIDR,EPIDEMIOL & ORAL DIS PREVENT PROGRAM,BETHESDA,MD 20892. RP NOURJAH, P (reprint author), WESTAT CORP,1650 RES BLVD,ROCKVILLE,MD 20850, USA. NR 25 TC 26 Z9 26 U1 1 U2 1 PU JOURNAL PUBLIC HEALTH POLICY PI S BURLINGTON PA 208 MEADOWOOD DR, S BURLINGTON, VT 05403 SN 0197-5897 J9 J PUBLIC HEALTH POL JI J. Public Health Policy PD WIN PY 1994 VL 15 IS 4 BP 443 EP 459 DI 10.2307/3343026 PG 17 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA QF751 UT WOS:A1994QF75100007 PM 7883945 ER PT J AU MICHELSON, D PAGE, SW CASEY, R TRUCKSESS, MW LOVE, LA MILSTIEN, S WILSON, C MASSAQUOI, SG CROFFORD, LJ HALLETT, M GOLD, PW STERNBERG, EM AF MICHELSON, D PAGE, SW CASEY, R TRUCKSESS, MW LOVE, LA MILSTIEN, S WILSON, C MASSAQUOI, SG CROFFORD, LJ HALLETT, M GOLD, PW STERNBERG, EM TI AN EOSINOPHILIA-MYALGIA-SYNDROME RELATED DISORDER ASSOCIATED WITH EXPOSURE TO L-5-HYDROXYTRYPTOPHAN SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE EOSINOPHILIA MYALGIA SYNDROME; L-5-HYDROXYTRYPTOPHAN; EOSINOPHILIA; L-TRYPTOPHAN ID L-TRYPTOPHAN; SCLERODERMA-LIKE; FASCIITIS; CARBIDOPA AB Objective. To determine whether L-5-hydroxytryptophan (L-5-HTP) associated with eosinophilia-myalgia syndrome (EMS) like illness contains impurities in a fashion similar to that described in L-tryptophan associated with EMS. Methods. Members of a family who became ill after exposure to L-5-HTP were evaluated at the National Institutes of Health. Data from patients with extended exposure to L-5-HTP were also examined. Samples of L-5-HTP were examined using high performance liquid chromatography. Results. One member of the family had EMS, and 2 others had eosinophilia. No patient in the other group reviewed developed the syndrome, although 2 patients developed eosinophilia. The L-5-HTP used by the family contained an impurity not present in samples from the other patient group. After replacement with L-5-HTP not containing this impurity, eosinophilia in 2 family members resolved. Conclusion. Some L-5-HTP contains impurities that may be related to L-5-HTP associated EMS. C1 NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. US FDA,CTR FOOD SAFETY & APPL NUTR,BETHESDA,MD 20892. NIMH,NEUROCHEM LAB,BETHESDA,MD 20892. NIAMS,ARTHRIT & RHEUMATISM BRANCH,BETHESDA,MD. NINCDS,MED NEUROL BRANCH,BETHESDA,MD 20892. NIMH,WASHINGTON,DC. KINSMEN CHILDRENS CTR,SASKATOON,SK,CANADA. RI Crofford, Leslie/J-8010-2013 NR 12 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 DEC PY 1994 VL 21 IS 12 BP 2261 EP 2265 PG 5 WC Rheumatology SC Rheumatology GA PX446 UT WOS:A1994PX44600017 PM 7699627 ER PT J AU BOYER, GS TEMPLIN, DW CORNONIHUNTLEY, JC EVERETT, DE LAWRENCE, RC HEYSE, SE MILLER, MM GORING, WP AF BOYER, GS TEMPLIN, DW CORNONIHUNTLEY, JC EVERETT, DE LAWRENCE, RC HEYSE, SE MILLER, MM GORING, WP TI PREVALENCE OF SPONDYLOARTHROPATHIES IN ALASKAN ESKIMOS SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE SPONDYLOARTHROPATHIES; EPIDEMIOLOGY; ESKIMO ID ANKYLOSING-SPONDYLITIS; REITERS-SYNDROME; RHEUMATOID-ARTHRITIS; PRELIMINARY CRITERIA; POPULATION; CLASSIFICATION; GREENLAND; HLA-B27; INDIANS AB Objective. To estimate the prevalence of spondyloarthropathies (SpA) in 2 Alaskan Eskimo populations, using improved methodology for case ascertainment and new, more inclusive classification criteria. Methods, Through existing rheumatic disease registries, health care providers and the Alaska Area Native Health Service (AANHS) computerized patient information system, we identified ail native residents of the 2 study regions with a diagnosis of any inflammatory arthritis or problems characteristic of SpA, such as iritis or persistent back pain. Individuals with such diagnoses or problems were evaluated in clinic, according to a standardized protocol (interview, examination), and by medical record review, pelvic radiography and laboratory tests. Each case was evaluated according to standard diagnostic criteria for the individual disease entities and by the Amor and European Spondylarthropathy Study Group (ESSG) preliminary classification criteria for SpA. Results. We identified 104 cases of SpA in the combined Eskimo populations, an overall prevalence of 2.5% in adults aged 20 and over. Both undifferentiated (USpA) and reactive SpA were more common than ankylosing spondylitis (AS). Conclusion, Using the new criteria and a more effective approach to case ascertainment we found the prevalence of SpA to be about twice that found in our earlier studies of adult Eskimo populations. The prevalence of SpA was very similar in men and women. Despite the known high prevalence (25-40 %) of HLA-B27 in the study populations we did not find the prevalence of any form of SpA to be as strikingly high as that of AS (6-10%) for the Canadian Haida. C1 DUKE UNIV,SCH PUBL HLTH,ALASKA AREA NATIVE HLTH SERV,DURHAM,NC 27706. NEI,BETHESDA,MD. NIAMS,BETHESDA,MD. UNIV ARIZONA,TUCSON,AZ 85721. FU NIAMS NIH HHS [Y02-AR-00005-02] NR 27 TC 65 Z9 67 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 DEC PY 1994 VL 21 IS 12 BP 2292 EP 2297 PG 6 WC Rheumatology SC Rheumatology GA PX446 UT WOS:A1994PX44600022 PM 7699631 ER PT J AU LYTLE, LA JOHNSON, CC BACHMAN, K WAMBSGANS, K PERRY, CL STONE, EJ BUDMAN, S AF LYTLE, LA JOHNSON, CC BACHMAN, K WAMBSGANS, K PERRY, CL STONE, EJ BUDMAN, S TI SUCCESSFUL RECRUITMENT STRATEGIES FOR SCHOOL-BASED HEALTH PROMOTION - EXPERIENCES FROM CATCH SO JOURNAL OF SCHOOL HEALTH LA English DT Article AB School-based research designs in the 1990s often require that a large number of schools be recruited to participate in studies. Therefore, effective recruitment and maintenance of schools becomes an important activity for ensuring the integrity of the study design. The Child and Adolescent Trial for Cardiovascular Health (CATCH) is the largest school-based health promotion research project yet undertaken; 96 schools (24 per field site) were successfully recruited and retained for this cardiovascular disease risk reduction project. This article describes general recruitment strategies used at the four CATCH sites, a description of how Social Learning Theory guided these activities, a discussion of logistical considerations, and recommended recruitment strategies for future school-based research. C1 TULANE UNIV,SCH PUBL HLTH & TROP MED,DEPT APPL HLTH SCI,NEW ORLEANS,LA 70112. UNIV CALIF SAN DIEGO,DEPT PEDIAT CHILD & FAMILY HLTH STUDIES,LA JOLLA,CA 92093. UNIV TEXAS,CTR HLTH PROMOT,AUSTIN,TX 78712. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. NEW ENGLAND RES INST INC,WATERTOWN,MA 02172. RP LYTLE, LA (reprint author), UNIV MINNESOTA,SCH PUBL HLTH,DIV EPIDEMIOL,1300 S 2ND ST,SUITE 300,MINNEAPOLIS,MN 55455, USA. NR 12 TC 27 Z9 27 U1 0 U2 0 PU AMER SCHOOL HEALTH ASSOC PI KENT PA PO BOX 708, KENT, OH 44240 SN 0022-4391 J9 J SCHOOL HEALTH JI J. Sch. Health PD DEC PY 1994 VL 64 IS 10 BP 405 EP 409 PG 5 WC Education & Educational Research; Education, Scientific Disciplines; Health Care Sciences & Services; Public, Environmental & Occupational Health SC Education & Educational Research; Health Care Sciences & Services; Public, Environmental & Occupational Health GA QA887 UT WOS:A1994QA88700003 PM 7707715 ER PT J AU DONOVAN, DM MATTSON, ME AF DONOVAN, DM MATTSON, ME TI ALCOHOLISM-TREATMENT MATCHING RESEARCH - METHODOLOGICAL AND CLINICAL ISSUES SO JOURNAL OF STUDIES ON ALCOHOL LA English DT Editorial Material ID EMPIRICALLY DERIVED TYPOLOGY; SEVERITY; ABUSE AB Client-treatment matching is an area receiving increased attention both in clinical practice and research with alcoholism. While the notion of potentially improving treatment outcomes by matching has been suggested for some time, there are a number of methodological and practical barriers that have impeded progress in the development of theoretically and clinically relevant matching models. This article provides an overview of the potential benefits of matching, the methodological factors that increase the complexity of research in this area, and some of overview also serves to introduce this special issue of the Journal of Studies on Alcohol, which examines in more detail each of the methodological issues involved in clinical research on treatment matching. While these methodological issues present unique challenges to the clinical researcher, the potential benefits of matching appear promising and should serve to motivate clinicians and researchers to pursue continued work in this area. C1 UNIV WASHINGTON,DEPT PSYCHIAT & BEHAV SCI,SEATTLE,WA 98195. UNIV WASHINGTON,INST ALCOHOL & DRUG ABUSE,SEATTLE,WA 98195. RP DONOVAN, DM (reprint author), NIAAA,ROCKVILLE,MD 20852, USA. NR 27 TC 1 Z9 1 U1 0 U2 0 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA PO BOX 969, PISCATAWAY, NJ 08855-0969 SN 0096-882X J9 J STUD ALCOHOL JI J. Stud. Alcohol PD DEC PY 1994 SU 12 BP 5 EP 14 PG 10 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA QA016 UT WOS:A1994QA01600001 ER PT J AU MATTSON, ME AF MATTSON, ME TI AN INTRODUCTION TO MULTICENTER CLINICAL-TRIALS IN CLIENT TREATMENT MATCHING RESEARCH - HISTORY, RATIONALE AND DESIGN SO JOURNAL OF STUDIES ON ALCOHOL LA English DT Editorial Material RP MATTSON, ME (reprint author), NIAAA,DIV CLIN & PREVENT RES,6000 EXECUT BLVD,ROCKVILLE,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA PO BOX 969, PISCATAWAY, NJ 08855-0969 SN 0096-882X J9 J STUD ALCOHOL JI J. Stud. Alcohol PD DEC PY 1994 SU 12 BP 15 EP 15 PG 1 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA QA016 UT WOS:A1994QA01600002 ER PT J AU MATTSON, ME ALLEN, JP LONGABAUGH, R NICKLESS, CJ CONNORS, GJ KADDEN, RM AF MATTSON, ME ALLEN, JP LONGABAUGH, R NICKLESS, CJ CONNORS, GJ KADDEN, RM TI A CHRONOLOGICAL REVIEW OF EMPIRICAL-STUDIES MATCHING ALCOHOLIC CLIENTS TO TREATMENT SO JOURNAL OF STUDIES ON ALCOHOL LA English DT Article ID APTITUDE TREATMENT INTERACTION; SUBSTANCE-ABUSE TREATMENT; COPING SKILLS; FOLLOW-UP; THERAPY; STRESS; MODEL; PSYCHOTHERAPY; ORIENTATION; POPULATIONS AB During the past 20 years researchers have become increasingly interested in exploring the benefits of differential assignment of alcoholics Co treatments based on client-specific characteristics, rather than searching for a single ''most effective'' intervention for all clients. Thirty-one empirical studies on ''client-treatment matching'' are reviewed, particularly from the perspective of how research methodology in this area has evolved. In addition, general observations are provided on how research methodology on this topic can be further enhanced. Finally, several promising interactions between client characteristics and particular interventions are noted, based on empirical studies to date. RP MATTSON, ME (reprint author), NIAAA,600 EXECUT BLVD,SUITE 505-DCPR,ROCKVILLE,MD 20892, USA. NR 67 TC 1 Z9 1 U1 1 U2 1 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA PO BOX 969, PISCATAWAY, NJ 08855-0969 SN 0096-882X J9 J STUD ALCOHOL JI J. Stud. Alcohol PD DEC PY 1994 SU 12 BP 16 EP 29 PG 14 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA QA016 UT WOS:A1994QA01600003 ER PT J AU FULLER, RK MATTSON, ME ALLEN, JP RANDALL, CL ANTON, RF BABOR, TF AF FULLER, RK MATTSON, ME ALLEN, JP RANDALL, CL ANTON, RF BABOR, TF TI MULTISITE CLINICAL-TRIALS IN ALCOHOLISM-TREATMENT RESEARCH - ORGANIZATIONAL, METHODOLOGICAL AND MANAGEMENT ISSUES SO JOURNAL OF STUDIES ON ALCOHOL LA English DT Article AB Multisite clinical trials have two major advantages over single-site studies: the large sample size of multisite studies allows for adequate statistical power and better representativeness of the population being studied. However, they are more complex to implement than single-site studies. This article reviews previous multisite clinical trials of alcohol abuse and alcoholism, reasons for selecting a multisite design, management of such studies, and some statistical issues. RP FULLER, RK (reprint author), NIAAA,SUITE 505,WILLCO BLDG,6000 EXECUT BLVD,ROCKVILLE,MD 20892, USA. NR 18 TC 0 Z9 0 U1 2 U2 2 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA PO BOX 969, PISCATAWAY, NJ 08855-0969 SN 0096-882X J9 J STUD ALCOHOL JI J. Stud. Alcohol PD DEC PY 1994 SU 12 BP 30 EP 37 PG 8 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA QA016 UT WOS:A1994QA01600004 ER PT J AU MATTSON, ME DONOVAN, DM AF MATTSON, ME DONOVAN, DM TI CLINICAL-APPLICATIONS - THE TRANSITION FROM RESEARCH TO PRACTICE SO JOURNAL OF STUDIES ON ALCOHOL LA English DT Article AB As validated and improved alcoholism treatment methods emerge from Project MATCH and other studies, a dedicated and systematic effort will be needed to incorporate them into ongoing programs, to monitor their success. in real world settings and to make adjustments and refinements as needed. Accomplishing this involves responsibilities for both researchers and practitioners. A complex continuum of activities designed to move interventions from research to practice is common to all therapeutic areas, with a fundamental component being researcher-provider interactions. Challenges include ''debunking'' myths; realistic evaluations of the feasibility of making changes in the treatment system; effective communication between providers and researchers; and proactive guidance from leaders who set standards of practice. Findings from relevant studies in alcoholism research can be assimilated into the treatment system with as little delay as possible as linkages between researchers and providers are strengthened. These linkages will be further strengthened by research in organizational, management and delivery mechanisms conducted by emerging applied research areas such as health services. RP MATTSON, ME (reprint author), NIAAA,DIV CLIN & PREVENT RES,6000 EXECUT BLVD,ROCKVILLE,MD 20892, USA. NR 22 TC 0 Z9 0 U1 0 U2 2 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA PO BOX 969, PISCATAWAY, NJ 08855-0969 SN 0096-882X J9 J STUD ALCOHOL JI J. Stud. Alcohol PD DEC PY 1994 SU 12 BP 163 EP 166 PG 4 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA QA016 UT WOS:A1994QA01600022 ER PT J AU MATTSON, ME AF MATTSON, ME TI ALCOHOLISM-TREATMENT MATCHING RESEARCH - METHODOLOGICAL AND CLINICAL APPROACHES - EPILOGUE SO JOURNAL OF STUDIES ON ALCOHOL LA English DT Editorial Material RP MATTSON, ME (reprint author), NIAAA,ROCKVILLE,MD 20852, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA PO BOX 969, PISCATAWAY, NJ 08855-0969 SN 0096-882X J9 J STUD ALCOHOL JI J. Stud. Alcohol PD DEC PY 1994 SU 12 BP 167 EP 168 PG 2 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA QA016 UT WOS:A1994QA01600023 ER PT J AU GILLIGAN, DM SACK, MN GUETTA, V CASINO, PR QUYYUMI, AA RADER, DJ PANZA, JA CANNON, RO AF GILLIGAN, DM SACK, MN GUETTA, V CASINO, PR QUYYUMI, AA RADER, DJ PANZA, JA CANNON, RO TI EFFECT OF ANTIOXIDANT VITAMINS ON LOW-DENSITY-LIPOPROTEIN OXIDATION AND IMPAIRED ENDOTHELIUM-DEPENDENT VASODILATION IN PATIENTS WITH HYPERCHOLESTEROLEMIA SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID FOREARM RESISTANCE VESSELS; CORONARY-ARTERIES; LOWERING THERAPY; L-ARGININE; ALPHA-TOCOPHEROL; SUPEROXIDE ANION; RABBIT AORTA; ATHEROSCLEROSIS; ACETYLCHOLINE; CHOLESTEROL AB Objectives. The aims of this study were to determine whether antioxidant vitamins could reduce the susceptibility of low density lipoprotein (LDL) to oxidation and improve endothelium-dependent vasodilator responsiveness in patients with hypercholesterolemia. Background. Animals and humans with hypercholesterolemia have exhibited impaired endothelium-dependent vasodilation. In vitro studies suggest that oxidatively modified LDL can impair nitric oxide production. Methods. Forearm blood flow was measured with strain gauge plethysmography and brachial artery drug infusions in 19 patients, aged 52 +/- 9 sears, with hypercholesterolemia (mean +/- SD total cholesterol 283 +/- 22 mg/dl, LDL 197 +/- 31 mg/dl) and in 14 subjects, aged 48 +/- 8 years, with normal cholesterol levels (total cholesterol 169 +/- 20 mg/dl, LDL 102 +/- 25 mg/dl). Acetylcholine (7.5, 15 and 30 mu g/min) was utilized as an endothelium-dependent vasodilator, and sodium nitroprusside (0.8, 1.6 and 3.2 mu g/min) was used to test endothelium-independent vasodilation. Oxidative susceptibility of LDL was measured by a spectrophotometric assay of conjugated diene production after the addition of copper chloride. Hypercholesterolemic patients then received daily anti-oxidant vitamin supplements (beta carotene [30 mg], ascorbic acid [vitamin C] [1,000 mg], vitamin E [800 IU]) for 1 month, with repeat measurement of both forearm blood flow responsiveness to the same agonists and LDL oxidizability. Results. The maximal flow in response to acetylcholine was impaired in patients compared with that in normal subjects (9.8 +/- 7.8 vs. 15.9 +/- 8.1 ml/min per 100 ml, p = 0.03), with similar maximal flow responses to sodium nitroprusside (9.5 +/- 4.2 vs. 9.0 +/- 2.8 ml/min per 100 ml, p = 0.72). After 1 month of vitamin therapy, the onset of LDL oxidation was prolonged over baseline measurements by 71 +/- 67%, and the maximal rate of oxidation was decreased by 26 +/- 25% (both p < 0.001). However, the maximal forearm blood flow response to acetylcholine remained unchanged horn baseline values (maximal how after acetylcholine 9.0 +/- 6.2 vs. 9.8 +/- 7.8 ml/min per 100 ml, p = 0.57). This study had 80% power (alpha 0.05) to exclude a 45% increase over baseline value in acetylcholine-stimulated flow during vitamin therapy. Conclusions. Although 1 month of administration of antioxidant vitamin supplements in hypercholesterolemic patients reduced the susceptibility of LDL to oxidation, impairment in endothelial function tion remained unaltered. The use of nonvitamin antioxidants or concomitant reduction in LDL levels, as well as more sensitive techniques for measuring vascular responsiveness, may be required to show a beneficial effect on endothelial vasodilator function. C1 NHLBI,CARDIOL BRANCH,BETHESDA,MD 20892. NR 41 TC 143 Z9 144 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD DEC PY 1994 VL 24 IS 7 BP 1611 EP 1617 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA PT858 UT WOS:A1994PT85800003 PM 7963105 ER PT J AU TATARANNI, PA LARSON, DE RAVUSSIN, E AF TATARANNI, PA LARSON, DE RAVUSSIN, E TI BODY-FAT DISTRIBUTION AND ENERGY-METABOLISM IN OBESE MEN AND WOMEN SO JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION LA English DT Article DE UPPER BODY OBESITY; LOWER BODY OBESITY; ENERGY EXPENDITURE; RESPIRATORY QUOTIENT; INDIRECT CALORIMETRY ID ADIPOSE-TISSUE CELLULARITY; WEIGHT-REDUCTION; VISCERAL FAT; COMPUTED-TOMOGRAPHY; EXPENDITURE; INSULIN; AGE; THERMOGENESIS; PROGNOSIS; IMPACT AB Objective: Upper body obesity seems to be associated with a better prognosis for weight loss than does lower body obesity. However, the impact of body fat distribution on energy metabolism is not clear. Subjects: One hundred fifteen non-diabetic obese Caucasians (64 males and 51 females) and 108 Caucasian lean controls (82 males and 26 females) were studied. Methods: Body composition was assessed by hydrodensitometry and body fat distribution was estimated by the waist-to-thigh circumference ratio (W/T). Values of 24-hour energy expenditure (24h-EE), basal metabolic rate (BMR), sleeping metabolic rate (SMR) and respiratory quotient (RQ) were measured in a respiration chamber. Results: BMR, adjusted for differences in fat-free mass, fat mass, age and sex, correlated with W/T in obese males (r = 0.40; p < 0.01), but not in obese females. Obese male subjects with upper body obesity had BMR significantly higher than those with lower body obesity (2189 +/- 268 vs 1974 +/- 141 kcal/day; p < 0.01), independently of differences in fat-free mass, fat mass and age. No correlations were found between W/T and adjusted 24h-EE, SMR or RQ in all examined groups. Conclusion: These findings indicate that in obese males, upper body obesity is associated with increased metabolic rate, possibly related to higher levels of lipid turnover in visceral fat. RP TATARANNI, PA (reprint author), NIDDKD,CLIN DIABET & NUTR SECT,4212 N 16TH ST,PHOENIX,AZ 85016, USA. NR 42 TC 27 Z9 27 U1 0 U2 1 PU AMER COLL NUTRITION PI NEW YORK PA C/O HOSP. JOINT DIS. 301 E. 17TH ST., NEW YORK, NY 10003 SN 0731-5724 J9 J AM COLL NUTR JI J. Am. Coll. Nutr. PD DEC PY 1994 VL 13 IS 6 BP 569 EP 574 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA PW326 UT WOS:A1994PW32600007 PM 7706588 ER PT J AU DUGONI, AA BROWN, LJ DEPAOLA, DP PRIDE, JR NIESSEN, LC AF DUGONI, AA BROWN, LJ DEPAOLA, DP PRIDE, JR NIESSEN, LC TI SPOTLIGHT ON TODAYS MAJOR ISSUES - 5 SHARE THEIR VIEWS SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article C1 BAYLOR COLL DENT,DEPT PUBL HLTH SCI,DALLAS,TX 75246. NIDR,EPIDEMIOL & ORAL DIS PREVENT PROGRAM,BETHESDA,MD 20892. PRIDE INST,GREENBRAE,CA. RP DUGONI, AA (reprint author), UNIV PACIFIC,SCH DENT,SAN FRANCISCO,CA 94115, USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD DEC PY 1994 VL 125 IS 12 BP 1591 EP 1596 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA PW567 UT WOS:A1994PW56700013 ER PT J AU CAROME, MA STRIKER, LJ PETEN, EP ELLIOT, SJ YANG, CW STETLERSTEVENSON, WG REPONEN, P TRYGGVASON, K STRIKER, GE AF CAROME, MA STRIKER, LJ PETEN, EP ELLIOT, SJ YANG, CW STETLERSTEVENSON, WG REPONEN, P TRYGGVASON, K STRIKER, GE TI ASSESSMENT OF 72-KILODALTON GELATINASE AND TIMP-1 GENE-EXPRESSION IN NORMAL AND SCLEROTIC MURINE GLOMERULI SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article DE METALLOPROTEINASE; EXTRACELLULAR MATRIX; INHIBITOR; COMPETITIVE POLYMERASE CHAIN REACTION; KIDNEY ID POLYMERASE CHAIN-REACTION; DEGRADING NEUTRAL PROTEINASE; GROWTH FACTOR-I; MESSENGER-RNA; TISSUE INHIBITOR; MESANGIAL CELLS; COLLAGENASE INHIBITOR; METALLOPROTEINASES-2; PURIFICATION; HORMONE AB Mice transgenic for bovine growth hormone (bGH) develop progressive diffuse glomerulosclerosis. Because murine mesangial cells in vitro were found to express the genes for 72-kd gelatinase and the metalloproteinase inhibitor TIMP-1, the expression of these genes in vivo in isolated whole glomeruli from bGH mice and normal control littermates was examined. Intact glomeruli were isolated by microdissec tion and subjected to reverse transcription. TIMP-1 cDNA was not detected by standard polymerase chain reaction (PCR) in glomeruli from bGH or control mice. In contrast, cDNA for 72-kd gelatinase was detected by standard PCR in both bGH and control mice, and the level was subsequently measured by quantitative competitive PCR. The gelatinase cDNA lever was 14.7 +/- 2.8 x 10(-4) attomoles/glomerulus in 2-to 3-month-old control mice and was unchanged in 6-month-old controls. The bGH mice had 3.5-fold and 4.5-fold higher cDNA levels at 2 to 3 months and 6 months of age, respectively. Finally, zymography of glomerular extracts revealed increased levels of 72-kd and 96 to 100-kd gelatinase activity in bGH glomeruli in comparison to that in controls. In summary, whereas the genes for both TIMP-1 and 72-kd gelatinase are expressed in vitro in cultured mesangial cells, only the gelatinase gene appeared to be expressed in vivo in intact glomeruli. In addition, there was an up-regulation in the glomerular expression of the 72-kd gelatinase in bGH mice, a murine model of glomerulosclerosis. C1 NIDDK,METAB DIS BRANCH,RENAL CELL BIOL SECT,BETHESDA,MD 20892. WALTER REED ARMY MED CTR,DEPT MED,WASHINGTON,DC 20307. WALTER REED ARMY MED CTR,DEPT CLIN INVEST,WASHINGTON,DC 20307. NCI,PATHOL LAB,BETHESDA,MD 20892. UNIV OULU,BIOCTR OULU,HELSINKI,FINLAND. UNIV OULU,DEPT BIOCHEM,HELSINKI,FINLAND. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 36 TC 31 Z9 31 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD DEC PY 1994 VL 5 IS 6 BP 1391 EP 1399 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA PY134 UT WOS:A1994PY13400016 PM 7894006 ER PT J AU HUNSBERGER, S AF HUNSBERGER, S TI SEMIPARAMETRIC REGRESSION IN LIKELIHOOD-BASED MODELS SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE KERNEL SMOOTHERS; PARTIAL LINEAR MODEL; WEIGHTED LIKELIHOOD ID PARTLY LINEAR-MODEL; CONVERGENCE-RATES AB A weighted likelihood is used to estimate the parameters in a semiparametric model involving two covariates and allowing an association between the covariates. The development is for arbitrary but specified densities of the observations. The estimators are consistent and asymptotically normal. Hypothesis testing of the parametric component can be performed using a Wald test. Simulations and analysis of data with Bernoulli observations demonstrate the estimators' application. Speckman developed kernel estimators where the conditional density of the observations is normal with p parametric covariates. Speckman's estimators and the new estimators are asymptotically equivalent, with the bias of Speckman's estimators being smaller. As an example, we study the relationship between a binary response indicating the occurrence of an intraoperative cardiac complication (ICC) in vascular surgery patients and two risk factors: duration of the operation (OR) and ASA score, which is an evaluation of the patient's overall health prior to surgery. ASA score is modeled in the parametric portion, because it appears valid to assume that ASA is linearly related to the legit of the probability of an ICC. The functional relationship between OR duration and the legit of the probability of an ICC is unknown, so it is modeled nonparametrically. RP HUNSBERGER, S (reprint author), NHLBI,BIOSTAT RES BRANCH,BLDG 10,BETHESDA,MD 20892, USA. NR 24 TC 28 Z9 29 U1 1 U2 2 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD DEC PY 1994 VL 89 IS 428 BP 1354 EP 1365 DI 10.2307/2290997 PG 12 WC Statistics & Probability SC Mathematics GA PU330 UT WOS:A1994PU33000020 ER PT J AU BORRAJERO, I PEREZ, JL DOMINGUEZ, C CHONG, A CORO, RM RODRIGUEZ, H GOMEZ, N ROMAN, GC NAVARROROMAN, L AF BORRAJERO, I PEREZ, JL DOMINGUEZ, C CHONG, A CORO, RM RODRIGUEZ, H GOMEZ, N ROMAN, GC NAVARROROMAN, L TI EPIDEMIC NEUROPATHY IN CUBA - MORPHOLOGICAL CHARACTERIZATION OF PERIPHERAL-NERVE LESIONS IN SURAL NERVE BIOPSIES SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE AXONAL NEUROPATHY; BERI BERI; CUBA; EPIDEMIC NEUROPATHY; MORPHOMETRY; MYELIN; NEUROTOXICITY; NUTRITIONAL NEUROPATHY; SURAL NERVE BIOPSY; TROPICAL MYELONEUROPATHIES AB More than 50 000 patients were affected in Cuba during an epidemic outbreak of peripheral neuropathy from January 1992 until September 1993. The disease presented as either a retrobulbar optic neuropathy, a predominantly sensory peripheral neuropathy, a dorsolateral myeloneuropathy, or as mixed forms. The morphological findings in sural nerve biopsies from 34 patients with various forms of the disease are presented here. Frozen, paraffin and semi-thin sections were prepared for light and electron microscopy, immunohistochemistry and morphometric analysis. Every case presented morphological alterations ranging from mild axonal dystrophy (9 cases, or 27%) to moderate and severe atonal damage (25 cases, or 73%). In 6 cases (18%), axonal damage was accompanied by perineural fibrosis and vascular abnormalities. Axonal regeneration was noted in 8 cases (23%) and remyelination in 9 (26%). Morphometric analysis showed a predominant loss of myelinated fibers in 92% of the patients. Quantification of myelinated fiber loss in 11 patients revealed a remarkable decrease in large caliber fibers. Scarce mononuclear cells were observed in 17 cases. No virus-like elements were seen. The morphological features found in this study indicate that, regardless of the clinical presentation, peripheral nerve lesions of the epidemic neuropathy in Cuba correspond to an axonal neuropathy. These lesions are compatible with nutritional, toxic, or metabolic etiologies. An inflammatory etiology would be unusual with these lesions. C1 NATL REF CTR PATHOL ANAT,PATHOL LAB,HAVANA,CUBA. DEPT INTERNAL MED,HAVANA,CUBA. HERMANOS AMEIJEIRAS HOSP,HAVANA,CUBA. NINCDS,NEUROEPIDEMIOL BRANCH,BETHESDA,MD. NCI,HEMATOPATHOL SECT,PATHOL LAB,BETHESDA,MD 20892. NR 25 TC 34 Z9 35 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD DEC 1 PY 1994 VL 127 IS 1 BP 68 EP 76 DI 10.1016/0022-510X(94)90137-6 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA PX672 UT WOS:A1994PX67200009 PM 7699394 ER PT J AU WALTHER, MM CHOYKE, PL HAYES, W SHAWKER, TH ALEXANDER, RB LINEHAN, WM AF WALTHER, MM CHOYKE, PL HAYES, W SHAWKER, TH ALEXANDER, RB LINEHAN, WM TI EVALUATION OF COLOR DOPPLER INTRAOPERATIVE ULTRASOUND IN PARENCHYMAL SPARING RENAL SURGERY SO JOURNAL OF UROLOGY LA English DT Article DE KIDNEY NEOPLASMS; ULTRASONOGRAPHY; HIPPEL-LINDAU DISEASE; NEPHRECTOMY ID VONHIPPEL-LINDAU DISEASE; CELL CARCINOMA; ULTRASONOGRAPHY; MANIFESTATIONS; SONOGRAPHY; MEMBERS AB A renal parenchymal sparing surgical approach may be recommended in select patients with von Hippel-Lindau disease and renal cancer or in those with sporadic renal cancer and limited normal renal function. We performed 27 partial nephrectomies or enucleations in 17 patients with the use of intraoperative ultrasound to examine a subset of all renal lesions identified on preoperative examination. Of 24 lesions deep in the renal parenchyma that were examined, localized or identified with intraoperative ultrasound 18 were characterized as cystic and 6 as solid. The deep cystic lesions were characterized with ultrasound as benign simple cysts. Intraoperative ultrasound was used to locate and mark the line of incision over 2 impalpable solid renal cell carcinomas. Four solid renal cell tumors extended deep into the renal parenchyma where color Doppler intraoperative ultrasound helped to define the plane of dissection adjacent to vital vascular structures. Renal hypothermia was not used in 3 renal operations based on intraoperative ultrasound findings. C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BETHESDA,MD. RP WALTHER, MM (reprint author), NCI,SURG BRANCH,UROL ONCOL SECT,BETHESDA,MD, USA. NR 21 TC 26 Z9 26 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-5347 J9 J UROLOGY JI J. Urol. PD DEC PY 1994 VL 152 IS 6 BP 1984 EP 1987 PN 1 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA PR245 UT WOS:A1994PR24500015 PM 7966656 ER PT J AU GALLINELLA, G YOUNG, NS BROWN, KE AF GALLINELLA, G YOUNG, NS BROWN, KE TI IN-SITU HYBRIDIZATION AND IN-SITU POLYMERASE CHAIN-REACTION DETECTION OF PARVOVIRUS B19 DNA WITHIN CELLS SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE PARVOVIRUS B19; IN SITU HYBRIDIZATION; IN SITU PCR; DIAGNOSIS; POLYMERASE CHAIN REACTION ID BONE-MARROW; INSITU HYBRIDIZATION; APLASTIC CRISIS; INFECTION; DIGOXIGENIN; PROBE AB Modification of an in situ polymerase chain reaction (ISPCR) technique is described for the detection of B19 parvovirus infection. Specific amplification of B19 DNA inside fixed cells was followed by hybridisation with a digoxigenin-labelled probe and then visualised by immunochemical reaction. The assay had higher sensitivity compared to direct in situ hybridisation and still allowed cellular localisation and characterisation of infected cells. This assay can be used as a confirmatory method for PCR in tissues and will allow further identification of tissues permissive for B19 parvovirus infection. C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 19 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD DEC PY 1994 VL 50 IS 1-3 BP 67 EP 74 DI 10.1016/0166-0934(94)90164-3 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA QE939 UT WOS:A1994QE93900007 PM 7714060 ER PT J AU COPELAND, KFT HAAKSMA, AGM DERSE, D HEENEY, JL AF COPELAND, KFT HAAKSMA, AGM DERSE, D HEENEY, JL TI DETECTION OF HUMAN T-CELL LEUKEMIA-VIRUS-1 PERMISSIVE CELLS USING CELL-LINES PRODUCING SELECTABLE RECOMBINANT VIRIONS SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE HTLV-1; IN VITRO TROPISM; NEOMYCIN RESISTANCE ID HTLV TYPE-I; LEUKEMIA-VIRUS; LYMPHOMA VIRUS; RETROVIRUS; INFECTION; EXPRESSION; PATIENT AB A selectable retrovirus vector based on a full length HTLV-1 provirus clone, pCS-HTLV-1, was constructed by replacing the coding regions for true, rex and the 3' region of enu with the prokaryotic neomycin resistance gene under the control of the CMV promoter. This vector, pHTLV-1-CMVneo, was transfected into HTLV-1 infected human lymphocytes and fibroblasts. The production of recombinant virus by these cells was measured by the transfer of G418 resistance to target cells. Infection of target cells showed a preference for human lymphocytes in addition to two human fibroblast cell lines, Hos7 and RD4, and the African green monkey kidney cell line, Cos7. This system provides a method to study the cellular tropism of HTLV-1 and additionally provides a model to facilitate molecular studies of the natural events of HTLV-1 infection and integration. C1 TNO,VIRAL PATHOGENESIS LAB,2280 HV RIJSWIJK,NETHERLANDS. NCI,FREDERICK CANC RES FACIL,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21701. NR 19 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD DEC PY 1994 VL 50 IS 1-3 BP 219 EP 225 DI 10.1016/0166-0934(94)90178-3 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA QE939 UT WOS:A1994QE93900021 PM 7714045 ER PT J AU FUJITA, K MALDARELLI, F PURCELL, DFJ SILVER, J AF FUJITA, K MALDARELLI, F PURCELL, DFJ SILVER, J TI MURINE RETROVIRAL VECTOR THAT INDUCES LONG-TERM EXPRESSION OF HIV-1 ENVELOPE PROTEIN SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE HIV-1; RETROVIRAL VECTOR; ENVELOPE PROTEIN ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 VPU PROTEIN; CELL-SURFACE CD4; LEUKEMIA-VIRUS; MUTATIONAL ANALYSIS; FV-4 RESISTANCE; DOWN-REGULATION; GENE-PRODUCTS; MESSENGER-RNA; ENV GENE AB A retroviral vector was constructed that induces long-term expression of human immunodeficiency virus type 1 (HIV-1) rev, vpu and env genes. The vector contains the neo gene and a cytomegalovirus (CMV) immediate early promoter followed by HIV-1 sequence. When HeLa cells were infected with viral stocks derived from this vector, about 25% of the resulting G418-resistant clones expressed HIV-1 envelope protein (Env), easily detectable by Western blot analysis, metabolic labelling, and syncytium formation after co-cultivation with HeLa-CD4 cells. In most cases the level of Env expression was higher than in a T cell line (H9) chronically infected with HIV-1. Env-expressing HeLa cell lines also expressed Rev, detected by transfection with a Rev-dependent CAT gene construct, and Vpu, detected by immunoprecipitation with a Vpu-specific antiserum. The 75% of G418-resistant HeLa cell lines that did not express Env were found to contain proviruses that had undergone deletion of env sequences corresponding to a known intron; presumably these cell lines arose as a result of infection with virions derived from spliced RNAs. This vector should be useful for studying non-transient effects of HIV Env, Rev and Vpu in tissue culture, and for the production of Env- and/or Rev-expressing cell lines. C1 NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. OI Silver, Jonathan/0000-0001-9231-6368 NR 58 TC 3 Z9 3 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD DEC PY 1994 VL 50 IS 1-3 BP 293 EP 311 DI 10.1016/0166-0934(94)90185-6 PG 19 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA QE939 UT WOS:A1994QE93900028 PM 7714053 ER PT J AU TREANOR, J PERKINS, M BATTAGLIA, R MURPHY, BR AF TREANOR, J PERKINS, M BATTAGLIA, R MURPHY, BR TI EVALUATION OF THE GENETIC STABILITY OF THE TEMPERATURE-SENSITIVE PB2 GENE MUTATION OF THE INFLUENZA A/ANN ARBOR/6/60 COLD-ADAPTED VACCINE VIRUS SO JOURNAL OF VIROLOGY LA English DT Article ID A VIRUS; WILD-TYPE; EXTRAGENIC SUPPRESSION; SEQUENCE CHANGES; PROTEIN GENES; ATTENUATION; PHENOTYPE; MUTANTS; H2N2; POLYMERASE AB A single-gene reassortant bearing the PB2 gene of the A/Ann Arbor/6/60 cold-adapted virus in the background of the A/Korea/82 (H3N2) wild-type virus is a temperature-sensitive (ts) virus with an in vitro shutoff temperature of 38 degrees C. A single mutation at amino acid (aa) at 265 (Asp-Ser) of the PB2 protein is responsible for the ts phenotype. This ts single-gene PB2 reassortant virus was serially passaged at elevated temperatures in Madin-Darby canine kidney cells to generate ts(+) phenotypic revertant viruses. Four ts(+) phenotypically revertant viruses were derived independently, and each possessed a shutoff temperature for replication in vitro of >40 degrees C. Each of the four phenotypically revertant viruses replicated efficiently in the upper and lower respiratory tracts of mice and hamsters, unlike the PB2 single-gene reassortant virus, confirming that the ts phenotype was responsible for the attenuation of this virus in rodents. Mating the ts(+) revertants with wild-type virus yielded ts progeny in high frequency, indicating that the loss of ts phenotype was due to a suppressor mutation which was mapped to the PA gene in each of the four independently derived ts phenotypic revertants. Nucleotide sequence analysis confirmed the absence of new mutations on the PB2 gene and the presence of predicted amino acid changes in the PA proteins of the revertant viruses. These studies suggest that single amino acid changes at aa 245 (Glu-Lys) or 337 (Asp-Asn) of the PA protein can completely suppress the ts and attenuation phenotypes specified by the Asp-Ser mutation at aa 265 of the PB2 protein of the A/Ann Arbor/6/60 cold-adapted virus. C1 NIAID,INFECT DIS LAB,BETHESDA,MD 20892. RP TREANOR, J (reprint author), UNIV ROCHESTER,MED CTR,DEPT MED,INFECT DIS UNIT,BOX 689,ROCHESTER,NY 14642, USA. NR 20 TC 25 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 DEC PY 1994 VL 68 IS 12 BP 7684 EP 7688 PG 5 WC Virology SC Virology GA PR432 UT WOS:A1994PR43200003 PM 7966557 ER PT J AU WILSON, CA FARRELL, KB EIDEN, MV AF WILSON, CA FARRELL, KB EIDEN, MV TI PROPERTIES OF A UNIQUE FORM OF THE MURINE AMPHOTROPIC LEUKEMIA-VIRUS RECEPTOR EXPRESSED ON HAMSTER-CELLS SO JOURNAL OF VIROLOGY LA English DT Article ID SUBGROUP-B; INTERFERENCE; INFECTION; RETROVIRUSES; LINES AB Identification and cloning of the receptors for amphotropic murine leukemia virus (A-MuLV) and gibbon ape leukemia virus (GaLV) have both enabled the determination of the normal function of these virus receptors in cells and initiated experimental examination of how these receptors interact with their respective viruses. GaLV and A-MuLV have distinct host ranges and use different receptors to infect human cells. It was therefore surprising to find that the human GaLV and A-MuLV receptors were not only structurally similar but performed similar cellular functions (B. O'Hara, S. V. Johann, H. P. Klinger, D. G. Flair, H. Rubinson, K. J. Dunn, P. Sass, S. M. Vitek, and T. Robbins, Cell Growth Differ. 1:119-127, 1990; M. van Zeijl, S. V. Johann, E. Closs, J. Cunningham, R. Eddy, T. B. Shows, and B. O'Hara, Proc. Natl. Acad. Sci. USA 91:1168-1172, 1994; M. P. Kavanaugh, D. G. Miller, W. Zhang, W. Law, S. L. Kozak, D. Kabat, and A. D. Miller, Proc. Natl. Acad. Sci. USA 91:7071-7075, 1994; and Z. Olah, C. Lehel, W. B. Anderson, M. V. Eiden, and C. A. Wilson, J. Biol. Chum., in press). We have now determined that the murine retrovirus 10A1 can use both the human GaLV receptor and the human A-MuLV receptor to infect cells. Furthermore, we have cloned and functionally characterized a unique form of the amphotropic receptor homolog expressed in E36 hamster cells. This receptor (EAR) can serve as both a GaLV receptor and an A-MuLV receptor, and it therefore differs from the receptors expressed in human cells, which function exclusively as either GaLV or A-MuLV receptors. C1 NIMH,CELL BIOL LAB,MOLEC VIROL UNIT,BETHESDA,MD 20892. NR 24 TC 64 Z9 66 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 DEC PY 1994 VL 68 IS 12 BP 7697 EP 7703 PG 7 WC Virology SC Virology GA PR432 UT WOS:A1994PR43200005 PM 7966559 ER PT J AU COHEN, JI SEIDEL, K AF COHEN, JI SEIDEL, K TI VARICELLA-ZOSTER VIRUS (VZV) OPEN READING FRAME-10 PROTEIN, THE HOMOLOG OF THE ESSENTIAL HERPES-SIMPLEX VIRUS PROTEIN-VP16, IS DISPENSABLE FOR VZV REPLICATION IN-VITRO SO JOURNAL OF VIROLOGY LA English DT Article ID IMMEDIATE-EARLY GENE; COMPLETE DNA-SEQUENCE; EXPRESSION; TYPE-1; TRANSCRIPTION; ACTIVATOR; GANGLIA AB Varicella-zoster virus (VZV) open reading frame 10 (ORF10) protein is the homolog of the herpes simplex virus type 1 (HSV-1) protein VP16. VZV ORF10 transactivates the VZV IE62 gene and is a tegument protein present in the virion. HSV-1 VP16, a potent transactivator of HSV-1 immediate early genes and tegument protein, is essential for HSV-1 replication in vitro. To determine whether VZV ORF10 is required for viral replication in vitro, we constructed two VZV mutants which were unable to express ORF10. One mutant had a stop codon after the 61st codon of the ORF10 gene, and the other mutant was deleted for all but the last five codons of the gene. Both VZV mutants grew in cell culture to titers similar to that of the parental virus. To determine whether HSV-1 VP16 alters the growth of VZV, we constructed a VZV mutant in which VP16 was inserted in place of ORF10. Using immune electron microscopy, we found that HSV-1 VP16 was present in the tegument of the recombinant VZV virions. The VZV VP16 substitution mutant produced smaller plaques and grew to a lower titer than parental virus. Thus, VZV ORF10 is not required for growth of the virus in vitro, and substitution of HSV-1 VP16 for VZV ORF10 impairs the growth of VZV. RP COHEN, JI (reprint author), NIAID,CLIN INVEST LAB,MED VIROL SECT,BLDG 10,RM 11N214,BETHESDA,MD 20892, USA. NR 33 TC 33 Z9 36 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1994 VL 68 IS 12 BP 7850 EP 7858 PG 9 WC Virology SC Virology GA PR432 UT WOS:A1994PR43200022 PM 7966575 ER PT J AU BESSEN, RA MARSH, RF AF BESSEN, RA MARSH, RF TI DISTINCT PRP PROPERTIES SUGGEST THE MOLECULAR-BASIS OF STRAIN VARIATION IN TRANSMISSIBLE MINK ENCEPHALOPATHY SO JOURNAL OF VIROLOGY LA English DT Review ID CREUTZFELDT-JAKOB-DISEASE; SCRAPIE PRION PROTEIN; GERSTMANN-STRAUSSLER SYNDROME; FATAL FAMILIAL INSOMNIA; INFECTED BRAIN; MOUSE SCRAPIE; ALZHEIMERS-DISEASE; MASS-SPECTROMETRY; AGENT REPLICATION; ABNORMAL ISOFORM AB The molecular basis of strain variation in scrapie diseases is unknown. The only identified component of the agent is the posttranslationally modified host prion protein (PrPSc). The biochemical and physical properties of PrP from two strains of transmissible mink encephalopathy (TME), called hyper (HY) and drowsy (DY), were compared to investigate if PrP heterogeneity could account for Strain diversity. The degradation rate of PrPTME digested with proteinase K was found to be strain specific and correlated with inactivation of the TME titer. Edman protein sequencing revealed that the major N-terminal end of HY PrPTME commenced at least 10 amino acids prior to that of DP PrPTME after digestion with proteinase K. Analysis of the brain distribution of PrPTME exhibited a strain-specific pattern and localization of PrPTME to the perikarya of specific neuron populations. Our findings are consistent with HY and DY PrPTME having distinct protein conformations and/or strain-specific ligand interactions that influence PrPTME properties. We propose that PrPTME conformation could play a role in targeting TME strains to different neuron populations in which strain-specific formation occurs. These data are consistent with the idea that PrPTME protein structure determines the molecular basis of strain variation. C1 UNIV WISCONSIN, MADISON, WI 53706 USA. RP BESSEN, RA (reprint author), NIAID, ROCKY MT LABS, PERSISTENT VIRAL DIS LAB, HAMILTON, MT 59840 USA. FU NIA NIH HHS [R01 AG10669-03] NR 101 TC 459 Z9 463 U1 0 U2 13 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1994 VL 68 IS 12 BP 7859 EP 7868 PG 10 WC Virology SC Virology GA PR432 UT WOS:A1994PR43200023 PM 7966576 ER PT J AU VICENZI, E DIMITROV, DS ENGELMAN, A MIGONE, TS PURCELL, DFJ LEONARD, J ENGLUND, G MARTIN, MA AF VICENZI, E DIMITROV, DS ENGELMAN, A MIGONE, TS PURCELL, DFJ LEONARD, J ENGLUND, G MARTIN, MA TI AN INTEGRATION-DEFECTIVE U5 DELETION MUTANT OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REVERTS BY ELIMINATING ADDITIONAL LONG TERMINAL REPEAT SEQUENCES SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; NF-KAPPA-B; ENVELOPE GLYCOPROTEIN; EFFICIENT INITIATION; DNA INTEGRATION; RETROVIRAL DNA; AVIAN-SARCOMA; VIRAL GROWTH; POL GENE; RNA AB Nonoverlapping deletions that eliminated the 5' (HIV-1(U5/603del)), middle (HIV-1(U5/206del)), and 3' (HIV-1(U5/604del)) thirds of the U5 region of the human immunodeficiency virus type I (HIV-1) long terminal repeat (LTR) were studied for their effects on virus replication (transient transfection of HeLa cells) and infectivity (T-cell lines and peripheral blood mononuclear cells). All three mutants exhibited a wild-type phenotype in directing the production and release of virus particles from transfected HeLa cells. In infectivity assays, HIV-1(U5/206del) was usually indistinguishable from wild-type virus whereas HIV-1(U5/603del) was unable to infect human peripheral blood mononuclear cells or MT4 and CEM cells. Investigations of HIV-1(U5/603del) particles revealed a packaging defect resulting in a 10-fold reduction of encapsidated genomic RNA. The HIV-1(U5/604del) mutant either was noninfectious or exhibited delayed infection kinetics, depending on the cell type and multiplicity of infection. Quantitative competitive PCR indicated that HIV-1(U5/604del) synthesized normal amounts of viral DNA in newly infected cells. During the course of a long-term infectivity assay, a revertant of the HIV-1(U5/604del) mutant that displayed rapid infection kinetics emerged. Nucleotide sequence analysis indicated that the original 26-nucleotide deletion present in HIV-1(U5/604del) had been extended an additional 19 nucleotides in the revertant virus. Characterization of the HIV-1(U5/604del) mutant LTR in in vitro integration reactions revealed defective 3' processing and strand transfer activities that were partially restored when the revertant LTR substrate was used, suggesting that the reversion corrected a similar defect in the mutant virus. C1 NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. NCI,MATH BIOL LAB,BETHESDA,MD 20892. NIDDKD,MOLEC BIOL LAB,BETHESDA,MD 20892. RI Purcell, Damian/G-5068-2011; OI Vicenzi, Elisa/0000-0003-0051-3968 NR 61 TC 55 Z9 55 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1994 VL 68 IS 12 BP 7879 EP 7890 PG 12 WC Virology SC Virology GA PR432 UT WOS:A1994PR43200025 PM 7966578 ER PT J AU ZOLOTUKHIN, AS VALENTIN, A PAVLAKIS, GN FELBER, BK AF ZOLOTUKHIN, AS VALENTIN, A PAVLAKIS, GN FELBER, BK TI CONTINUOUS PROPAGATION OF RRE(-) AND REV(-)RRE(-) HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 MOLECULAR CLONES CONTAINING A CIS-ACTING ELEMENT OF SIMIAN RETROVIRUS TYPE-1 IN HUMAN PERIPHERAL-BLOOD LYMPHOCYTES SO JOURNAL OF VIROLOGY LA English DT Article ID REV-RESPONSIVE ELEMENT; VIRAL MESSENGER-RNA; HTLV-I REX; HIV-1 REV; TARGET SEQUENCE; FUNCTIONAL-ANALYSIS; SECONDARY STRUCTURE; VIRION EXPRESSION; GENE-EXPRESSION; PROTEIN AB Molecular clones of human immunodeficiency virus type 1 that contained either 37 point mutations in the Rev-responsive element (RRE) that did not affect the overlapping env reading frame or both a mutated RRE and two mutations that eliminated Rev were constructed. The mutations in the RRE were shown to remove both negative and Rev-inducible positive effects of the RRE on gene expression (G. Nasioulas, A. S. Zolotukhin, C. Tabernero, L. Solomin, C. P. Cunningham, G. N. Pavlakis, and B. K. Felber, J. Virol. 68:2986-2993, 1994). Upon insertion of a cis-acting element of simian retrovirus type 1 (SRV-1) into these clones, both RRE(-) and Rev(-)RRE(-) clones were expressed efficiently. The element of SRV-1 has properties similar to those of the recently identified element of Mason-Pfizer monkey virus (M. Pray, S. Prasad, J. W. Dubay, E. Hunter, K.-T. Jeang, D. Rekosh, and M.-L. Hammarskjold, Proc. Natl. Acad. Sci. USA 4:1256-1260, 1994). We demonstrated that virus preparations produced after transfections of these SRV-1 element-containing molecular clones in human cells were infectious after cell-free transmission, that they replicated about 5 to 10 times less efficiently than wild-type virus, and that they were propagated continuously for more than 7 months in human peripheral blood mononuclear cells. Growth characteristics and sequence analysis of these viruses after long-term culture demonstrated that no RRE(+)Rev(+) revertants developed. These data demonstrate that human immunodeficiency virus type 1 Rev and RRE can be replaced by heterologous regulatory systems, resulting in efficient virus production. The resulting Rev(-)RRE(-) virus can be prepared and propagated efficiently in tissue culture and can be used for further studies of the life cycle of the virus. The data also suggest that Rev acts exclusively through the RRE interaction and that it does not have any additional essential function in the life cycle of the virus. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,HUMAN RETROVIRUS PATHOGENESIS GRP,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,HUMAN RETROVIRUS SECT,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101] NR 54 TC 161 Z9 161 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 DEC PY 1994 VL 68 IS 12 BP 7944 EP 7952 PG 9 WC Virology SC Virology GA PR432 UT WOS:A1994PR43200032 PM 7966585 ER PT J AU GIRI, A MARKHAM, P DIGILIO, L HURTEAU, G GALLO, RC FRANCHINI, G AF GIRI, A MARKHAM, P DIGILIO, L HURTEAU, G GALLO, RC FRANCHINI, G TI ISOLATION OF A NOVEL SIMIAN T-CELL LYMPHOTROPIC VIRUS FROM PAN-PANISCUS THAT IS DISTANTLY RELATED TO THE HUMAN T-CELL LEUKEMIA LYMPHOTROPIC VIRUS TYPE-I AND TYPE-II SO JOURNAL OF VIROLOGY LA English DT Note ID COMPLETE NUCLEOTIDE-SEQUENCE; HTLV-II; RETROVIRUS; PYGMIES; AFRICA; SEROPREVALENCE; TRANSMISSION; INFECTION; VARIANT; GENOME AB An unusual serological profile against human T-cell leukemia/lymphotropic virus type I and II (HTLV-I and -II) proteins was reported in several human Pygmy tribes in Zaire and Cameroon with serum antibodies reactive with gp21 and p24. Here we describe a similar pattern of serum antibodies in a colony of captive pygmy chimpanzees and the isolation of a novel retrovirus, simian T-cell lymphotropic virus from Pan paniscus (STLV(pan-p)), from the peripheral blood mononuclear cells of several seropositive animals. Cocultures of peripheral blood mononuclear cells from three seropositive pygmy chimpanzees with human cord blood mononuclear cells led to the expression of an HTLV-I- and HTLV-II-related virus initially demonstrated by electron microscopy. Furthermore, several of these cocultures became immortalized T-cell lines expressing the CD4(+) CD8(+) DR(+) phenotype of mature activated T cells. Southern blotting and DNA sequencing of a PCR fragment of viral DNA from these cell cultures demonstrated a distant evolutionary relationship of these viruses to HTLV-I and -II and distinct from the known STLV isolates. We designated this virus STLV(pan-p). A genealogical analysis of the captive pygmy chimpanzees colony, originated from wild caught animals, revealed a prevalence of seropositive offspring from infected mothers, as also observed with HTLVs. The presence in this old African Great Ape species of a virus which is genetically quite distinct from HTLV-I and -II could provide new insights in the phylogenesis of STLVs and HTLVs and be instrumental in the discovery of related human viruses. C1 NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. ADV BIOSCI LABS INC,KENSINGTON,MD 20895. NR 24 TC 58 Z9 58 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1994 VL 68 IS 12 BP 8392 EP 8395 PG 4 WC Virology SC Virology GA PR432 UT WOS:A1994PR43200084 PM 7966632 ER PT J AU MOMOEDA, M WONG, S KAWASE, M YOUNG, NS KAJIGAYA, S AF MOMOEDA, M WONG, S KAWASE, M YOUNG, NS KAJIGAYA, S TI A PUTATIVE NUCLEOSIDE TRIPHOSPHATE-BINDING DOMAIN IN THE NONSTRUCTURAL PROTEIN OF B19 PARVOVIRUS IS REQUIRED FOR CYTOTOXICITY SO JOURNAL OF VIROLOGY LA English DT Note ID VIRUS REP GENE; TRANS-ACTIVATION; DNA-REPLICATION; MINUTE VIRUS; CELL-LINE; SITE; TRANSFORMATION; EXPRESSION; MUTATION; SEQUENCE AB Cytotoxicity secondary to B19 parvovirus infection is due to expression of the viral nonstructural protein. Nonstructural proteins of many parvoviruses contain a well-conserved nucleoside triphosphate (NTP)-binding motif, which has been shown to be essential for a variety of protein functions. We show here that cytotoxicity of the B19 parvovirus nonstructural protein was abolished by single mutations of amino acids within the NTP-binding domain, especially within the A motif, implicating NTP-binding in virus-induced cell death. C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. NR 29 TC 65 Z9 66 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 1994 VL 68 IS 12 BP 8443 EP 8446 PG 4 WC Virology SC Virology GA PR432 UT WOS:A1994PR43200095 PM 7966641 ER PT J AU HUNYADY, L TIAN, Y SANDBERG, K BALLA, T CATT, KJ AF HUNYADY, L TIAN, Y SANDBERG, K BALLA, T CATT, KJ TI DIVERGENT CONFORMATIONAL REQUIREMENTS FOR ANGIOTENSIN-II RECEPTOR INTERNALIZATION AND SIGNALING SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT Symposium on Molecular and Cellular Mechanisms of Renin-Angiotensin Synthesis and Release - Forefronts in Nephrology CY MAR 27-30, 1994 CL PORT DOUGLAS, AUSTRALIA ID ADRENAL GLOMERULOSA CELLS; POTENTIAL MECHANISM; ENDOCYTIC PATHWAY; CARBOXYL-TERMINUS; SEQUESTRATION; CLATHRIN; DYNAMIN; MUTANT RP HUNYADY, L (reprint author), NICHHD,ENDOCRINOL & REPROD RES BRANCH,BLDG 49,ROOM 6A36,BETHESDA,MD 20892, USA. OI Balla, Tamas/0000-0002-9077-3335 NR 24 TC 20 Z9 20 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD DEC PY 1994 VL 46 IS 6 BP 1496 EP 1498 DI 10.1038/ki.1994.428 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA PT272 UT WOS:A1994PT27200006 PM 7699988 ER PT J AU BAYNE, KAL STRANGE, GM DEXTER, SL AF BAYNE, KAL STRANGE, GM DEXTER, SL TI INFLUENCE OF FOOD ENRICHMENT ON CAGE SIDE PREFERENCE SO LABORATORY ANIMAL SCIENCE LA English DT Article ID CAPTIVE RHESUS-MONKEYS; CHIMPANZEES; PRIMATES AB A preference test paradigm was used to assess the value of two enrichment techniques for rhesus macaques (Macaca mulatta): 1) a Kong(R) toy stuffed with food treats and 2) a fleece board covered with particulate food. The duration of time spent in the enriched cage side was compared with that spent in the unenriched cage side. Additionally, the number of cage side changes made during an observation interval and the duration and frequency of occurrence of select behaviors were recorded. Half the subjects altered their cage side preference during the experimental condition, and a fifth animal reversed side preference in the postex-perimental phase. Subjects spent a mean time of 14% of a session engaged with the foraging devices. The occurrence of several behaviors, including self-directed and locomotor activities, varied significantly with the experimental condition. These results were compared with data from a previous preference study of nonnutritive enrichments, and a hypothesis regarding the relative value of different types of enrichment was developed. RP BAYNE, KAL (reprint author), NIH,NATL CTR RES RESOURCES,VET RESOURCES PROGRAM,BEHAV & NUTR UNIT,BETHESDA,MD 20892, USA. NR 19 TC 7 Z9 7 U1 0 U2 1 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI CORDOVA PA 70 TIMBERCREEK DR, SUITE 5, CORDOVA, TN 38018 SN 0023-6764 J9 LAB ANIM SCI JI Lab. Anim. Sci. PD DEC PY 1994 VL 44 IS 6 BP 624 EP 629 PG 6 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA QB522 UT WOS:A1994QB52200015 PM 7898037 ER PT J AU SCHEINOWITZ, M SHOU, M BANAI, S GERTZ, SD LAZAROUS, DF UNGER, EF AF SCHEINOWITZ, M SHOU, M BANAI, S GERTZ, SD LAZAROUS, DF UNGER, EF TI NEOINTIMAL PROLIFERATION IN CANINE CORONARY-ARTERIES - A MODEL OF RESTENOSIS PERMITTING LOCAL AND CONTINUOUS DRUG-DELIVERY SO LABORATORY INVESTIGATION LA English DT Article DE SMOOTH MUSCLE CELLS; VASCULAR DISEASE; RESTENOSIS; CORONARY CIRCULATION ID MUSCLE CELL-PROLIFERATION; INTIMAL PROLIFERATION; BALLOON ANGIOPLASTY; CLINICAL-TRIALS; PORCINE MODEL; ANIMAL-MODEL; INJURY; SYSTEM; DIPYRIDAMOLE; PREVENTION AB BACKGROUND: A number of experimental preparations have been used to elucidate the pathophysiology of restenosis after percutaneous transluminal coronary angioplasty; however, few models have been advanced that address restenosis in coronary arteries, and none provides an effective means of continuous-focal drug delivery. In this report, we describe a model of restenosis in coronary arteries with the provision for local, continuous delivery of cytotoxic and/ or anti-proliferative agents. EXPERIMENTAL DESIGN: An ameroid constrictor was placed on the left circumflex coronary artery of 17 normocholesterolemic dogs. One month later, after substantial collateral development had ensued, a segment of the left circumflex coronary artery distal to the ameroid was mechanically compressed using surgical forceps for 10 (N = 4), 15 (N = 4), 20 (N = 2), or 30 minutes (N = 5). In two dogs, an indwelling left circumflex catheter and implanted pump maintained a continuous infusion of saline at the injury site. In addition, the pump side port provided transcutaneous access for serial, selective coronary arteriography. The animals were maintained on a normal diet, without cholesterol or fat supplementation. RESULTS: Three weeks after vascular injury, significant neointimal proliferation was observed in all dogs that was morphologically similar to the proliferation seen after percutaneous transluminal coronary angioplasty in human coronary arteries. The extent of neointimal formation was linearly related to the duration of injury: neointimal/medial area ratios were 0.35 +/- 0.10, 0.46 +/- 0.10, 0.58 +/- 0.03, and 1.16 +/- 0.26 (mean +/- SE) after 10, 15, 20, and 30 minutes of mechanical compression injury, respectively. CONCLUSIONS: This model produces striking neointimal proliferation in the coronary arteries of normocholesterolemic dogs, morphologically similar to that seen in human coronary restenosis specimens. The model appears suitable to test the efficacy of agents with the potential to inhibit neointimal formation, providing continuous intracoronary drug delivery, as well as transcutaneous access for serial, selective arteriography. C1 NHLBI,CARDIOL BRANCH,EXPTL PHYSIOL & PHARMACOL SECT,BETHESDA,MD 20892. HEBREW UNIV JERUSALEM,HADASSAH MED SCH,DEPT ANAT & EMBRYOL,IL-91010 JERUSALEM,ISRAEL. NR 29 TC 9 Z9 10 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 DEC PY 1994 VL 71 IS 6 BP 813 EP 819 PG 7 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA PZ175 UT WOS:A1994PZ17500003 PM 7632203 ER PT J AU STRIKER, LJ PETEN, EP HE, CJ STRIKER, GE AF STRIKER, LJ PETEN, EP HE, CJ STRIKER, GE TI RENAL FIBROSIS SO M S-MEDECINE SCIENCES LA French DT Article AB Progressive glomerulosclerosis or interstitial fibrosis may occur in most chronic renal disorders and result in decreasing kidney function, eventuating in endstage renal failure. The pathogenesis of progressive renal disease is still largely unknown but there is considerable evidence that there is heterogeneity in the glomerular response to a sclerotic stimulus in the general population. For instance, in diabetes mellitus, despite similar levels of glycemia, only a fraction develops renal disease. The same is true for patients with AIDS nephropathy, where the propensity to the development of progressive glomerulosclerosis seems restricted to certain ethnic groups without regard to the severity of the underlying disease. The causes of this wide variation in response has led to the speculation that there may be an underlying genetic basis which determines the glomerular sclerotic response to particular stimuli. The normal glomerular extracellular matrix (ECM) contains multiple components, synthetized by the resident glomerular cells. The role of the mesangial cells, the smooth muscle component of the glomerulus, is critical in the development of glomerulosclerosis. Glomerular cells respond to various stimuli such as cytokines, or to metabolic derangements by an exaggerated synthesis of ECM, a phenomenon well established in vitro, and to a certain degree, in vivo. These data led us to evaluate the levels of ECM mRNAs in isolated microdissected glomeruli, in normal mice as well as in several models of glomerulosclerosis. We studied matrix synthesis at the level of gene expression and ECM composition in the intact glomerulus using a competitive PCR assay. To determine whether the rate of ECM synthesis and the composition of sclerosis were similar among diseases, we examined a normal mouse strain and compared them with transgenic mice or with strains which spontaneously developed glomerulosclerosis. Mice transgenic for growth hormone provide a good model of progressive glomerulosclerosis leading to terminal renal failure. In these mice, the levels of ECM matrix mRNAs were elevated at all time points studied. The elevation occurred prior to the histologic appearance of glomerulosclerosis, and high mRNA levels persisted until the animals died in renal failure. We also examined these levels in a model of mouse which has a reduction in the number of glomeruli at birth (OS) and severe glomerulosclerosis, as well as in mice with more slowly progressive renal disease. The baseline levels of basement membrane collagen mRNAS Varied between different mouse strains, and correlated with their propensity to develop glomerulosclerosis. In addition, the baseline ECM mRNA level predicted the subsequent outcome. Less is known about the factors that lead to interstitial fibrosis although it represents a critical determinant of renal fibrosis in human diseases. Three candidate cells can contribute to the excess of ECM in the interstitial compartment : fibroblasts, endothelial cells lining the interstitial capillaries and tubular cells. RP STRIKER, LJ (reprint author), NIDDK,RENAL CELL BIOL SECT,BLDG 10,ROOM 3N110,BETHESDA,MD 20892, USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU JOHN LIBBEY EUROTEXT LTD PI MONTROUGE PA 127 AVE DE LA REPUBLIQUE, 92120 MONTROUGE, FRANCE SN 0767-0974 J9 M S-MED SCI JI M S-Med. Sci. PD DEC PY 1994 VL 10 IS 12 BP 1263 EP 1273 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA PZ357 UT WOS:A1994PZ35700007 ER PT J AU DEVEREUX, TR WISEMAN, RW KAPLAN, N GARREN, S FOLEY, JF WHITE, CM ANNA, C WATSON, MA PATEL, A JARCHOW, S MARONPOT, RR ANDERSON, MW AF DEVEREUX, TR WISEMAN, RW KAPLAN, N GARREN, S FOLEY, JF WHITE, CM ANNA, C WATSON, MA PATEL, A JARCHOW, S MARONPOT, RR ANDERSON, MW TI ASSIGNMENT OF A LOCUS FOR MOUSE LUNG-TUMOR SUSCEPTIBILITY TO PROXIMAL CHROMOSOME-19 SO MAMMALIAN GENOME LA English DT Article ID RAS PROTOONCOGENE; LINKAGE MAP; MICE; ACTIVATION; GENES; ADDUCTS; ADENOMA; GENOME; STRAIN; LIVER AB Previous studies have hypothesized that at least three genetic loci contribute to differences in pulmonary adenoma susceptibility between mouse strains A/J and C57BL/6J. One gene that may confer susceptibility to lung tumorigenesis is the Kras protooncogene. To identify other relevant loci involved in this polygenic trait, we determined tumor multiplicity in 56 randomly chosen N-ethyl-N-nitrosourea-treated (A/J X C57BL/6J) N1 X C57BL/6 backcross (AB6N2) progeny and correlated it with genotypes at 77 microsatellite markers spanning the genome. A correlation of lung tumor multiplicity phenotypes with genotypes of microsatellite markers on distal Chromosome (Chr) 6 in the Kras region (Pas1) was confirmed, and a new region on Chr 19 (designated Pad) was identified that also contributes to susceptibility. Linkage analysis on Chr 19 with 270 AB6N2 mice localized the region flanked by D19Mit42 and D19Mit19 that is most closely associated with lung tumor susceptibility. The Pas3 locus may be an enhancer of the susceptibility locus on Chr 6. C1 NIEHS,EXPTL BIOL PROGRAM,RES TRIANGLE PK,NC 27709. RP DEVEREUX, TR (reprint author), NIEHS,ENVIRONM CARCINOGENESIS PROGRAM,RES TRIANGLE PK,NC 27709, USA. NR 34 TC 56 Z9 56 U1 1 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD DEC PY 1994 VL 5 IS 12 BP 749 EP 755 DI 10.1007/BF00292007 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA PZ352 UT WOS:A1994PZ35200002 PM 7894154 ER PT J AU ISHIKAWA, H SILOS, SA TAMAI, K COPELAND, NG GILBERT, DJ JENKINS, NA UITTO, J AF ISHIKAWA, H SILOS, SA TAMAI, K COPELAND, NG GILBERT, DJ JENKINS, NA UITTO, J TI CDNA CLONING AND CHROMOSOMAL ASSIGNMENT OF THE MOUSE GENE FOR DESMOGLEIN-3 (DSG3), THE PEMPHIGUS-VULGARIS ANTIGEN SO MAMMALIAN GENOME LA English DT Note ID AUTOANTIBODIES; CADHERIN C1 THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,JEFFERSON INST MOLEC MED,DEPT DERMATOL,PHILADELPHIA,PA 19107. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,JEFFERSON INST MOLEC MED,DEPT BIOCHEM,PHILADELPHIA,PA 19107. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,JEFFERSON INST MOLEC MED,DEPT MOLEC BIOL,PHILADELPHIA,PA 19107. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO74101]; NIAMS NIH HHS [P01-AR38923, T32-AR07561] NR 14 TC 21 Z9 22 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD DEC PY 1994 VL 5 IS 12 BP 803 EP 804 DI 10.1007/BF00292018 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA PZ352 UT WOS:A1994PZ35200013 PM 7894164 ER PT J AU HIMMELBAUER, H HARVEY, RP COPELAND, NG JENKINS, NA SILVER, LM AF HIMMELBAUER, H HARVEY, RP COPELAND, NG JENKINS, NA SILVER, LM TI HIGH-RESOLUTION GENETIC-ANALYSIS OF A DELETION ON MOUSE CHROMOSOME-17 EXTENDING OVER THE FUSED, TUFTED, AND HOMEOBOX NKX2-5 LOCI SO MAMMALIAN GENOME LA English DT Note ID T-HAPLOTYPES; LINKAGE MAP; LIBRARY; GENOME C1 PRINCETON UNIV,DEPT MOLEC BIOL,PRINCETON,NJ 08544. ROYAL MELBOURNE HOSP,WALTER & ELIZA HALL INST MED RES,MELBOURNE,VIC 3050,AUSTRALIA. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-74101]; NICHD NIH HHS [HD20275] NR 17 TC 6 Z9 6 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD DEC PY 1994 VL 5 IS 12 BP 814 EP 816 DI 10.1007/BF00292022 PG 3 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA PZ352 UT WOS:A1994PZ35200017 PM 7894168 ER PT J AU ROBINSON, GW MAHON, KA AF ROBINSON, GW MAHON, KA TI DIFFERENTIAL AND OVERLAPPING EXPRESSION DOMAINS OF DLX-2 AND DLX-3 SUGGEST DISTINCT ROLES FOR DISTAL-LESS HOMEOBOX GENES IN CRANIOFACIAL DEVELOPMENT SO MECHANISMS OF DEVELOPMENT LA English DT Article DE DISTAL-LESS (DLX); HOMEOBOX GENES; BRANCHIAL ARCHES; NEURAL CREST; TOOTH DEVELOPMENT; EAR DEVELOPMENT; CONSERVED GENE FAMILIES; CRANIOFACIAL DEVELOPMENT ID NEURAL CREST CELLS; DEVELOPING FOREBRAIN; LIMB DEVELOPMENT; RESTRICTED EXPRESSION; TARGETED DISRUPTION; ECTOPIC EXPRESSION; PATTERN-FORMATION; CRANIAL NERVES; RETINOIC ACID; MOUSE EMBRYO AB During the development of the vertebrate head, cranial neural crest cells migrate into the branchial arches to form many of the structures of the facial skeleton. These cells follow defined developmental pathways and their fates are determined early. We have isolated and characterized the murine Distal-less homeobox gene Dlx-3 and have performed a comparative analysis of Dlx-3 and Dlx-2 expression during craniofacial development. In contrast to Dlx-2 and other vertebrate Distal-less genes, Dlx-3 is not expressed in the central nervous system and is expressed in a highly restricted region of the branchial arches. Dlx-2 and -3 display temporal and spatial differences in expression in the arches and their derivatives. In later development, these two genes are expressed in both complementary and partially overlapping domains in regions whose development is dependent on epithelial-mesenchymal interactions, such as the developing middle and inner ear, teeth and whisker follicles. The differential expression of Dlx genes in the branchial region suggests that they play key roles in craniofacial patterning and morphogenesis. C1 NICHHD,MAMMALIAN GENES & DEV LAB,BETHESDA,MD 20892. RI Robinson, Gertraud/I-2136-2012 NR 69 TC 205 Z9 208 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD DEC PY 1994 VL 48 IS 3 BP 199 EP 215 DI 10.1016/0925-4773(94)90060-4 PG 17 WC Developmental Biology SC Developmental Biology GA QC457 UT WOS:A1994QC45700006 PM 7893603 ER PT J AU SORBARA, LR TANG, ZC CAMA, A XIA, JR SCHENKER, E KOHANSKI, RA PORETSKY, L KELLER, E TAYLOR, SI DUNAIF, A AF SORBARA, LR TANG, ZC CAMA, A XIA, JR SCHENKER, E KOHANSKI, RA PORETSKY, L KELLER, E TAYLOR, SI DUNAIF, A TI ABSENCE OF INSULIN-RECEPTOR GENE-MUTATIONS IN 3 INSULIN-RESISTANT WOMEN WITH THE POLYCYSTIC-OVARY-SYNDROME SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID TYROSINE KINASE DOMAIN; IMPAIRED GLUCOSE-TOLERANCE; ACANTHOSIS NIGRICANS; CULTURED LYMPHOCYTES; DECREASED LEVELS; MUTANT ALLELES; MESSENGER-RNA; SUBSTITUTION; MECHANISMS; TRANSPORT AB Women with polycystic ovary syndrome (PCOS) are markedly insulin-resistant, but the molecular mechanisms of these changes and their relationship to the hyperandrogenic state remain to be clarified. Mutations have recently been identified in the insulin receptor gene of patients with extreme forms of insulin resistance associated with hyperandrogenism leg, type A insulin resistance), and these mutations account for the insulin resistance in such patients. We performed this study to determine whether mutations in the coding portion of the insulin receptor gene were responsible for insulin resistance in PCOS. Insulin binding studies using cultured skin fibroblasts of three obese (body mass index > 27 kg/m(2)) women with PCOS tie, mild hyperandrogenemia and chronic anovulation of unknown etiology) and documented insulin resistance showed no apparent abnormalities in either the number or affinity of insulin binding sites. Direct sequencing of all 22 exons of the insulin receptor gene from two of the women with PCOS did not reveal any mutations. Furthermore, both alleles of the gene were expressed at equal levels. In a third insulin-resistant PCOS woman, there was no evidence for a mutation in the coding portion of the insulin receptor gene as determined by denaturing gradient gel electrophoresis (DGGE). We conclude that the insulin resistance in these PCOS women was caused by a defect extrinsic to the insulin receptor. Copyright (C) 1994 by W.B. Saunders Company C1 PENN STATE UNIV,COLL MED,DEPT MED,DIV ENDOCRINOL DIABET & METAB,HERSHEY,PA 17033. CUNY MT SINAI SCH MED,DEPT MED,DIV ENDOCRINOL,NEW YORK,NY 10029. CUNY MT SINAI SCH MED,DEPT BIOCHEM,NEW YORK,NY 10029. NIDDKD,DIABET BRANCH,BETHESDA,MD 20892. FU NIDDK NIH HHS [R01 DK40605] NR 48 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 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD DEC PY 1994 VL 43 IS 12 BP 1568 EP 1574 DI 10.1016/0026-0495(94)90018-3 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA PW062 UT WOS:A1994PW06200018 PM 7990713 ER PT J AU BEATTY, WL MORRISON, RP BYRNE, GI AF BEATTY, WL MORRISON, RP BYRNE, GI TI PERSISTENT CHLAMYDIAE - FROM CELL-CULTURE TO A PARADIGM FOR CHLAMYDIAL PATHOGENESIS SO MICROBIOLOGICAL REVIEWS LA English DT Review ID OUTER-MEMBRANE PROTEIN; MOUSE PERITONEAL-MACROPHAGES; TUBAL FACTOR INFERTILITY; HUMAN GAMMA-INTERFERON; FIBROBLASTS L-CELLS; LIFE-CYCLE FORMS; MIP-LIKE PROTEIN; TRACHOMATIS INFECTION; ULTRASTRUCTURAL ANALYSIS; DEVELOPMENTAL REGULATION AB Chlamydiae are medically important bacteria responsible for a wide range of human infections and diseases. Repeated episodes of infection promote chronic inflammation associated with detrimental immune system-mediated pathologic changes. However, the true nature of chlamydial pathogenesis may encompass repeated infection superimposed upon persistent infection which would allow for heightened iummune reactivity. During the course of chlamydial infection, numerous host-elaborated factors with inhibitory or modifying effects may cause alterations in the chlamydia-host cell relationship such that the organism is maintained in a nonproductive stage of growth. Abnormal or persistent chlamydiae have been recognized under a variety of cell culture systems. The numerous factors associated with altered growth suggest an innate flexibility in the developmental cycle of chlamydiae. This review evaluates in vitro studies of chlamydial persistence and correlates these model systems to features of natural chlamydial disease. C1 UNIV WISCONSIN,DEPT MED MICROBIOL & IMMUNOL,MADISON,WI 53706. NIAID,ROCKY MT LABS,INTRACELLULAR PARASITES LAB,HAMILTON,MT 59840. FU NIAID NIH HHS [P01 AI034617, R01 AI019782] NR 129 TC 430 Z9 438 U1 0 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0146-0749 J9 MICROBIOL REV JI Microbiol. Rev. PD DEC PY 1994 VL 58 IS 4 BP 686 EP 699 PG 14 WC Microbiology SC Microbiology GA PV324 UT WOS:A1994PV32400005 PM 7854252 ER PT J AU CHOI, WJ SANTOS, B DURAN, A CABIB, E AF CHOI, WJ SANTOS, B DURAN, A CABIB, E TI ARE YEAST CHITIN SYNTHASES REGULATED AT THE TRANSCRIPTIONAL OR THE POSTTRANSLATIONAL LEVEL SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; SYNTHESIS INVIVO; CELL-SEPARATION; GENE; ENZYME; CYCLE; CAL1; PURIFICATION; SYNTHETASE; PHEROMONE AB The three chitin synthases of Saccharomyces cerevisiae, Chs1, Chs2, and Chs3, participate in septum and cell wall formation of vegetative cells and in wall morphogenesis of conjugating cells and spores. Because df the differences in the nature and in the time of execution of their functions, the synthases must be specifically and individually regulated. The nature of that regulation has been investigated by measuring changes in the levels of the three synthases and of the messages of the three corresponding genes, CHS1, CHS2, and CAL1/CSD2/DIT101/KT12 (referred to below as CAL1/CSD2), during the budding and sexual cycles. By transferring cells carrying CHS2 under the control of a GAL1 promoter from galactose-containing medium to glucose-containing medium, transcription of CHS2 was shut off. This resulted in a rapid disappearance of Chs2, whereas the mRNA decayed much more slowly. Furthermore, Chs2 levels experienced pronounced oscillations during the budding cycle and were decreased in the sexual cycle, indicating that this enzyme is largely regulated by a process of synthesis and degradation. For CHS1 and CAL1/CSD2, however, a stop in transcription was followed by a slow decrease in the level of zymogen (Chs1) or an increase in the level of activity (Chs3), despite a rapid drop in message level in both cases. In synchronized cultures, Chs1 levels were constant during the cell cycle. Thus, for Chs1 and Chs3, posttranslational regulation, probably by activation of latent forms, appears to be predominant. Since Chs2, like Chs1, is found in the cell in the zymogenic form, a posttranslational activation step appears to be necessary for this synthase also. C1 NIDDKD,BIOCHEM & METAB LAB,BETHESDA,MD 20892. CSIC,FAC BIOL,INST MICROBIOL BIOQUIM,SALAMANCA,SPAIN. UNIV SALAMANCA,E-37008 SALAMANCA,SPAIN. RI Santos, Beatriz/D-3102-2015 OI Santos, Beatriz/0000-0002-0781-0378 NR 39 TC 86 Z9 88 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 DEC PY 1994 VL 14 IS 12 BP 7685 EP 7694 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PV674 UT WOS:A1994PV67400001 PM 7969112 ER PT J AU DEALDANA, CRV WEK, RC SANSEGUNDO, P TRUESDELL, AG HINNEBUSCH, AG AF DEALDANA, CRV WEK, RC SANSEGUNDO, P TRUESDELL, AG HINNEBUSCH, AG TI MULTICOPY TRANSFER-RNA GENES FUNCTIONALLY SUPPRESS MUTATIONS IN YEAST EIF-2-ALPHA KINASE GCN2 - EVIDENCE FOR SEPARATE PATHWAYS COUPLING GCN4 EXPRESSION TO UNCHARGED TRANSFER-RNA SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSFER-RNA-SYNTHETASES; NUCLEOTIDE-EXCHANGE FACTOR; AMINOACYL-TRANSFER-RNA; POLYPEPTIDE-CHAIN INITIATION; SACCHAROMYCES-CEREVISIAE; TRANSLATIONAL CONTROL; PROTEIN-KINASE; MESSENGER-RNA; ACID AVAILABILITY; ACTIVATOR AB GCN2 is a protein kinase that stimulates translation of GCN4 mRNA in amino acid-starved cells by phosphorylating the alpha subunit of translation initiation factor 2 (eIF-2). We isolated multicopy plasmids that overcome the defective derepression of GCN4 and its target genes caused by the leaky mutation gcn2-507. One class of plasmids contained tRNA(His) genes and conferred efficient suppression only when cells were starved for histidine; these plasmids suppressed a gcn2 deletion much less efficiently than they suppressed gcn2-507. This finding indicates that the reduction in GCN4 expression caused by gcn2-507 can be overcome by elevating tRNA(His) expression under conditions in which the excess tRNA cannot be fully aminoacylated. The second class of suppressor plasmids all carried the same gene encoding a mutant form of tRNA(Val)(AAC) with an A-to-G transition at the 3' encoded nucleotide, a mutation shown previously to reduce aminoacylation of tRNA(Val) in vitro. In contrast to the wild-type tRNA(His) genes, the mutant tRNA(Val) gene efficiently suppressed a gcn2 deletion, and this suppression was independent of the phosphorylation site on eIF-2 alpha (Ser-51). Overexpression of the mutant tRNA(Val) did, however, stimulate GCN4 expression at the translational level. We propose that the multicopy mutant tRNA(Val) construct leads to an accumulation of uncharged tRNA(Val) that derepresses GCN4 translation through a pathway that does not involve GCN2 or eIF-2 alpha phosphorylation. This GCN2-independent pathway was also stimulated to a lesser extent by the multicopy tRNA(His) constructs in histidine-deprived cells. Because the mutant tRNA(Val) exacerbated the slow-growth phenotype associated with eIF-2 alpha hyperphosphorylation by an activated GCN2(c) kinase, me suggest that the GCN2-independent derepression mechanism involves down-regulation of eIF-2 activity. C1 NICHHD,MOLEC GENET LAB,MOLEC GENET LOWER EUKARYOTES SECT,BETHESDA,MD 20892. INDIANA UNIV,SCH MED,DEPT MOLEC BIOL & BIOCHEM,INDIANAPOLIS,IN 46202. RI Vazquez de Aldana, Carlos/B-7772-2008; San-Segundo, Pedro/L-4539-2014 OI Vazquez de Aldana, Carlos/0000-0002-4513-3654; NR 58 TC 29 Z9 29 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 DEC PY 1994 VL 14 IS 12 BP 7920 EP 7932 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PV674 UT WOS:A1994PV67400022 ER PT J AU BRYAN, RG LI, YG LAI, JH VAN, M RICE, NR RICH, RR TAN, TH AF BRYAN, RG LI, YG LAI, JH VAN, M RICE, NR RICH, RR TAN, TH TI EFFECT OF CD28 SIGNAL-TRANSDUCTION ON C-REL IN HUMAN PERIPHERAL-BLOOD T-CELLS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NF-KAPPA-B; ACCESSORY MOLECULE CD28; TRANSCRIPTION FACTORS; RESPONSE ELEMENT; LYMPHOCYTES-T; TYROSINE PHOSPHORYLATION; ACTIVATION SIGNALS; GENE-TRANSCRIPTION; CYCLOSPORINE-A; PATHWAY AB Optimal T-cell activation requires both an antigen-specific signal delivered through the T-cell receptor and a costimulatory signal which can be delivered through the CD28 molecule. CD28 costimulation induces the expression of multiple lymphokines, including interleukin 2 (IL-2). Because the c-Rel transcription factor bound to and activated the CD28 response element within the IL-2 promoter, we focused our study on the mechanism of CD28-mediated regulation of c-Rel in human peripheral blood T cells. We showed that CD28 costimulation accelerated the kinetics of nuclear translocation of c-Rel (and its phosphorylated form), p50 (NFKB1), and p65 (RelA). The enhanced nuclear translocation of c-Rel correlated with the stimulation of IL-2 production and T-cell proliferation by several distinct anti-CD28 monoclonal antibodies. This is explained at least in part by the long-term downregulation of I kappa B alpha following CD28 signalling as opposed to phorbol myristate acetate alone. Furthermore, we showed that the c-Rel-containing CD28-responsive complex is enhanced by, but not specific to, CD28 costimulation. Our results indicate that c-Rel is one of the transcription factors targeted by CD28 signalling. C1 BAYLOR COLL MED,DEPT MICROBIOL & IMMUNOL,HOUSTON,TX 77030. BAYLOR COLL MED,DEPT MED,HOUSTON,TX 77030. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. RI Tan, Tse-Hua/E-3983-2010 OI Tan, Tse-Hua/0000-0003-4969-3170 FU NIAID NIH HHS [AI-15394]; NIGMS NIH HHS [R01 GM-49875] NR 63 TC 84 Z9 84 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 1994 VL 14 IS 12 BP 7933 EP 7942 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PV674 UT WOS:A1994PV67400023 PM 7969133 ER PT J AU NIKLINSKA, BB HOU, D JUNE, C WEISSMAN, AM ASHWELL, JD AF NIKLINSKA, BB HOU, D JUNE, C WEISSMAN, AM ASHWELL, JD TI CD45 TYROSINE PHOSPHATASE-ACTIVITY AND MEMBRANE ANCHORING ARE REQUIRED FOR T-CELL ANTIGEN RECEPTOR SIGNALING SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID LEUKOCYTE-COMMON ANTIGEN; LYMPHOCYTES-T; ZETA-CHAIN; B-CELLS; PROTEIN; ACTIVATION; PHOSPHORYLATION; KINASE; TRANSDUCTION; STIMULATION AB T cells that lack the CD45 transmembrane tyrosine phosphatase have a variety of T-cell receptor (TCR) signaling defects that are corrected by reexpression of wild-type CD45 or its intracytoplasmic domains. In this study, a chimeric molecule containing the myristylation sequence of Src and the intracellular portion of CD45, previously shown to restore function in CD45(-) T cells, was mutagenized to determine if membrane-associated CD45 tyrosine phosphatase activity is required to restore TCR-mediated signaling in CD45(-) T cells. Abolition of enzymatic activity by substitution of a serine for a critical cysteine in the first catalytic domain resulted in failure of this molecule to restore TCR signaling. Another mutation, in which a single amino acid substitution destroyed the myristylation site, resulted in failure of the chimeric molecule to partition to the plasma membrane. Although expressed at high levels and enzymatically active, this form of intracellular CD45 also failed to restore normal signaling in CD45(-) T cells. These findings strongly suggest that CD45's function in TCR signaling requires its proximity to membrane-associated tyrosine phosphatase substrates. C1 NCI,IMMUNE CELL BIOL LAB,BIOL RESPONSE MODIFIERS PROGRAM,BETHESDA,MD 20892. USN,MED RES INST,IMMUNE CELL BIOL PROGRAM,BETHESDA,MD 20889. NR 44 TC 13 Z9 13 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 1994 VL 14 IS 12 BP 8078 EP 8084 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PV674 UT WOS:A1994PV67400037 PM 7526153 ER PT J AU DEY, A MINUCCI, S OZATO, K AF DEY, A MINUCCI, S OZATO, K TI LIGAND-DEPENDENT OCCUPANCY OF THE RETINOIC ACID RECEPTOR BETA-2 PROMOTER IN-VIVO SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID EMBRYONAL CARCINOMA-CELLS; THYROID-HORMONE; RESPONSE ELEMENT; TRANSCRIPTION FACTOR; GLUCOCORTICOID RECEPTOR; GENE-EXPRESSION; MMTV PROMOTER; RXR-ALPHA; INVIVO; BINDING AB Retinoic acid (RA) activates transcription of the RA receptor beta 2 (RAR beta 2) gene in embryonal carcinoma (EC) cells. This activation involves binding of the RAR/retinoid X receptor (RAR/RXR) heterodimer to the RA-responsive element (beta RARE). Dimethyl sulfate-based genomic footprinting was performed to examine occupancy of this promoter in P19 EC cells. No footprint was detected at the beta RARE prior to RA treatment, but a footprint was detected within the first hour of RA treatment. Concomitantly, other elements in the promoter, the cyclic AMP-responsive element and tetradecanoyl phorbol acetate-like-responsive element became footprinted. Footprints at these elements were induced by RA without requiring new protein synthesis and remained for the entire duration of RA treatment but rapidly reversed upon withdrawal of RA. A delayed protection observed at the initiator site was also reversed upon RA withdrawal. The RA-inducible footprint was not due to induction of factors that bind to these element, since in vitro assays showed that these factors are present in P19 cell extracts before RA treatment. Significantly, no RA-induced footprint was observed at any of these elements in P19 cells expressing a dominant negative RXR beta, in which RXR heterodimers are unable to bind to the beta RARE. Results indicate that binding of a liganded heterodimer receptor to the beta RARE is the initial event that allows other elements to gain access to the factors. In accordance, reporter analyses showed that a mutation in the beta RARE, but not those in other elements, abrogates RA activation of the promoter. It is likely that the RAR beta 2 promoter opens in a hierarchically ordered manner, signalled by the occupancy of liganded heterodimers. C1 NICHHD,MOLEC GROWTH REGULAT LAB,BLDG 6,RM 2A01,BETHESDA,MD 20892. RI Minucci, Saverio/J-9669-2012 NR 66 TC 60 Z9 61 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 1994 VL 14 IS 12 BP 8191 EP 8201 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PV674 UT WOS:A1994PV67400049 PM 7969156 ER PT J AU MELILLO, RM HELIN, K LOWY, DR SCHILLER, JT AF MELILLO, RM HELIN, K LOWY, DR SCHILLER, JT TI POSITIVE AND NEGATIVE REGULATION OF CELL-PROLIFERATION BY E2F-1 - INFLUENCE OF PROTEIN LEVEL AND HUMAN PAPILLOMAVIRUS ONCOPROTEINS SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSCRIPTION FACTOR E2F; RETINOBLASTOMA GENE-PRODUCT; KINASE-II PHOSPHORYLATION; TYPE-16 E7 ONCOPROTEIN; LARGE T-ANTIGEN; HUMAN KERATINOCYTES; BINDING PROTEIN; CYCLIN-A; TRANSFORMING ACTIVITY; ADENOVIRUS E1A AB E2F-1 is a member of a family of transcription factors implicated in the activation of genes required for the progression through the S phase of the cell cycle. We have examined the biological activities of E2F-1 with short-term colony-forming assays and long-term immortalization assays. High levels of E2F-1, produced by transfection of the E2F-1 cDNA under the control of a strong promoter, reduced colony formation in normal human foreskin keratinocytes (NHFKs). This inhibition could not be overcome by wild-type human papillomavirus type 16 (HPV16) E6 and E7, two proteins which cooperate to immortalize NHFKs, or by a transdominant p53 mutant. High levels of E2F-1 also inhibited growth of primary and established fibroblasts. The growth-inhibitory activity required the DNA binding function of E2F-1 but not its transactivation or pRB binding activities. A positive role for lower levels of E2F-1 in NHFK immortalization was established by examining the ability of E2F-1 to complement HPV16 E7 mutants that were unable to cooperate with HPV16 E6 to immortalize NHFKs. Although E2F-1 was unable by itself to cooperate with E6, it did, in conjunction with E6, complement a p24GLY mutant of E7 that is defective for immortalization and binding of pRB and pRB-related proteins. By contrast, E2F-1 was unable to complement two other E7 mutants, p2PRO and p31/ 32ARG/PRO, which are also defective in the immortalization assay, although their proteins display wild-type binding of pRB in vitro. Since the binding of E7 to pRB results in disruption of pRB-E2F interaction and release of transcriptionally active E2F, the data support the hypothesis that binding of pRB by E7 and the consequent increase in E2F activity are important but not sufficient for E7-induced keratinocyte immortalization. C1 NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. DANISH CANC SOC,DIV CANC BIOL,DK-2100 COPENHAGEN,DENMARK. OI MELILLO, Rosa Marina/0000-0002-9233-5275 NR 59 TC 38 Z9 38 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD DEC PY 1994 VL 14 IS 12 BP 8241 EP 8249 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA PV674 UT WOS:A1994PV67400054 PM 7969161 ER PT J AU FRENCH, JE LIBBUS, BL HANSEN, L SPALDING, J TICE, RR MAHLER, J TENNANT, RW AF FRENCH, JE LIBBUS, BL HANSEN, L SPALDING, J TICE, RR MAHLER, J TENNANT, RW TI CYTOGENETIC ANALYSIS OF MALIGNANT SKIN TUMORS INDUCED IN CHEMICALLY TREATED TG-CENTER-DOT-AC TRANSGENIC MICE SO MOLECULAR CARCINOGENESIS LA English DT Article DE CYTOGENETICS ID HA-RAS GENE; MOUSE SKIN; ONCOGENE ACTIVATION; PHORBOL ESTERS; CELL-LINES; PROGRESSION; CHROMOSOME-7; PAPILLOMAS; CARCINOMA; CARCINOGENESIS AB TG AC mice (which carry a v-Ha-ras transgene) rapidly develop papillomas in response to 12-O-tetradecanoylphorbol-13-acetate (TPA). Approximately 30% of the papillomas are associated with subsequent development of malignancies. Early-passage spindle-shaped tumor cells arising from explant cultures of TPA-induced tumors in TG-AC mice were tumorigenic when transplanted to syngeneic recipients. The v-Ha-ras transgene in the transplanted tumors was expressed at a high level. To identify possible genetic changes associated with the development of malignant tumors, explanted cells were cultured in vitro and assessed for karyotypic changes between the second and third passages by analyzing G-banded metaphase chromosomes. For comparison, skin malignancies were induced in nontransgenic FVB/N mice (parent strain) by 7,12-dimethylbenz[a]anthracene (DMBA) initiation and TPA promotion, and their G-banded metaphase chromosomes were analyzed. Trisomy (in at least 50% of about 30 metaphases) of chromosome 15 (in five of 15 tumors) and chromosome 6 (four of 15 tumors) was observed in TG-AC mice, independent of chemical treatment or tumor type. Of six tumors from DMBA/TPA-treated FVB/N mice, three had trisomy 10 or 15 (or both), and two appeared normal. The absence of trisomy 7 is notable because c-Ha-ras maps to that chromosome. The absence of trisomy 7 in the six FVB/N DMBA/TPA-induced skin malignancies contrasts with DMBA/TPA-induced karyotypic effects in SENCAR mice. Expression of the v-Ha-ras transgene may have precluded the requirement for endogenous mutant ras and allelic imbalance involving chromosome 7 in TG-AC mice, but it could not have in FVB/N mice. These results suggest the possibility that the observed trisomies are consequential, rather than causal, events in the development of TG-AC or FVB/N skin malignancies. Molecular genetic analysis will be required to understand the changes associated with tumorigenesis in this transgenic line as well as in the parent mouse line. (C) 1994 Wiley-Liss, Inc.* C1 INTEGRATED LAB SYST,RES TRIANGLE PK,NC 27709. RP FRENCH, JE (reprint author), NIEHS,POB 12233,MD C1-10,RES TRIANGLE PK,NC 27709, USA. NR 34 TC 14 Z9 15 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD DEC PY 1994 VL 11 IS 4 BP 215 EP 226 DI 10.1002/mc.2940110407 PG 12 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA QG457 UT WOS:A1994QG45700006 PM 7999263 ER PT J AU LEE, YC KOMATSU, K DRISCOLL, WJ STROTT, CA AF LEE, YC KOMATSU, K DRISCOLL, WJ STROTT, CA TI STRUCTURAL AND FUNCTIONAL-CHARACTERIZATION OF ESTROGEN SULFOTRANSFERASE ISOFORMS - DISTINCT CATALYTIC AND HIGH-AFFINITY BINDING ACTIVITIES SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID HEAT-STABLE FACTOR; SULFATASE ACTIVITY; MOLECULAR-CLONING; PROTEIN-ACTIVITY; BREAST-CANCER; PHOSPHORYLATION; METABOLISM; INHIBITION; CELLS AB Estrogen sulfotransferase (EST) purified from the guinea pig (gp) adrenal gland consists of multiple charge isoforms with isoelectric points (pls) ranging from 6.5 to 5.2. Four individual isoforms were isolated for use in antibody production, as well as for tryptic fragmentation analysis. The multiple charge isoforms manifested a high degree of relatedness as evidenced by complete immunocross-reactivity. This relatedness was further demonstrated by peptide mapping analysis, which revealed essentially identical elution profiles for three of the isoforms, whereas the fourth most acidic isoform, although similar to the other three isoforms, demonstrated same differences. To further explore the nature of the charge isoforms, native gpEST and EST expressed by CHO-K1 cells transfected with the gpEST cDNA were subjected to additional biochemical characterization. An interesting finding was that, in addition to EST activity, gpEST bound estradiol with a high affinity [dissociation constant (K-d) 10 nM]; furthermore, the binding activity was absolutely dependent on the cofactor, adenosine-3',5'-diphosphate (3', 5'-ADP). An unexpected and novel finding was that only the most basic pi 6.5 isoform was catalytically active, while estradiol-binding activity was associated with a more acidic isoform (pi 5.5-5.2); however, it has not as yet been possible to definitively assign the binding activity to a specific isoform. Although a complete understanding of the molecular basis for the gpEST isoformation is lacking, evidence is presented that indicates the isoformation is caused, at least in part, by the binding of the nucleotide cofactor, 3',5'-ADP, which converts the pi 6.5 isoform to a high affinity estradiol-binding protein and, by virtue of its negative charges, shifts the binding activity to the more acidic region of the isoelectric focusing gel. C1 NICHHD, ENDOCRINOL & REPROD RES BRANCH, STEROID REGULAT SECT, BETHESDA, MD 20892 USA. NR 30 TC 3 Z9 4 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD DEC PY 1994 VL 8 IS 12 BP 1627 EP 1635 DI 10.1210/me.8.12.1627 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QA530 UT WOS:A1994QA53000004 PM 7708052 ER PT J AU HIROSE, T FUJIMOTO, W YAMAAI, T KIM, KH MATSUURA, H JETTEN, AM AF HIROSE, T FUJIMOTO, W YAMAAI, T KIM, KH MATSUURA, H JETTEN, AM TI TAK1 - MOLECULAR-CLONING AND CHARACTERIZATION OF A NEW MEMBER OF THE NUCLEAR RECEPTOR SUPERFAMILY SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID RETINOIC ACID RECEPTOR; MOUSE SPERMATOGENIC CELLS; MALE GERM-CELL; THYROID-HORMONE; STAGE-SYNCHRONIZATION; SEMINIFEROUS TUBULES; TRANSCRIPTION FACTOR; ESTROGEN-RECEPTOR; STEROID-RECEPTOR; BINDING DOMAINS AB Using polymerase chain reaction and two degenerate primers whose designs were based on the two best conserved regions of the DNA-binding domain of the nuclear receptor superfamily, we identified and cloned a novel orphan receptor, named TAK1, The open reading frame of TAK1 encodes a protein of 596 amino acid residues, Based on the modular structure and the presence of a DNA-binding domain containing two zinc fingers TAK1 belongs to the steroid/thyroid hormone receptor superfamily, The amino acid sequence of TAK1 is most closely related to the orphan receptor TR2-11, Their overall sequence homology is 64%, with the highest similarity (82%) being observed in the DNA-binding domain, Northern blot analysis using RNA from multiple human tissues showed that a 9.4 kilobase TAK1 transcript was expressed ubiquitously and that the presence of a 2.8 kilobase mRNA was largely restricted to the testis, In situ hybridization using sections of rat and mouse testes and Northern blot analysis using RNA from testes of rats at various ages revealed that TAK1 is most abundantly expressed in spermatocytes whereas little expression was observed in other germ cells or somatic cells. In situ hybridization using other mouse and rat tissues revealed cell type-specific expression of TAK1 in several tissues. Our observations suggest a role for this putative transcription factor in the regulation of gene expression in specific cell types, In the testis, TAK1 appears to control gene expression during spermatogenesis, particularly during the meiotic phase. C1 NIEHS, PULM PATHOBIOL LAB, CELL BIOL SECT, RES TRIANGLE PK, NC 27709 USA. OKAYAMA UNIV, SCH MED, DEPT DERMATOL, OKAYAMA 700, JAPAN. OKAYAMA UNIV, SCH DENT, DEPT ORAL ANAT, OKAYAMA 700, JAPAN. WASHINGTON STATE UNIV, DEPT GENET & CELL BIOL, PULLMAN, WA 99164 USA. RI Hirose, Takahisa /E-6117-2011; OI Jetten, Anton/0000-0003-0954-4445 NR 65 TC 76 Z9 78 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD DEC PY 1994 VL 8 IS 12 BP 1667 EP 1680 DI 10.1210/me.8.12.1667 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA QA530 UT WOS:A1994QA53000008 PM 7708055 ER PT J AU WANG, M CHAMPION, LE BIESSMANN, H MASON, JM AF WANG, M CHAMPION, LE BIESSMANN, H MASON, JM TI MAPPING A MUTATOR, MU2, WHICH INCREASES THE FREQUENCY OF TERMINAL DELETIONS IN DROSOPHILA-MELANOGASTER SO MOLECULAR & GENERAL GENETICS LA English DT Article DE DEFICIENCY MAPPING; MUTATION; TELOMERE; CHROMOSOME STRUCTURE ID PHOSPHORIBOSYLTRANSFERASE STRUCTURAL GENE; CHROMOSOME ENDS; DNA-SEQUENCES; ORGANIZATION; TELOMERES; MUTATIONS; REGION AB A mutator, mu2, in Drosophila melanogaster has been identified recently that potentiates the recovery of terminal deficiencies. The deleted chromosomes behave as if they had been capped; that is, they are protected from degradation and from fusion with other chromosome fragments. The mutator maps near the telomere on the left arm of chromosome 3. Using the selectable marker Aprt, 150 deficiencies for region 62 of the cytological map have been recovered. These deficiencies identify the map position of mu2 as 62B11-C1. A yeast artificial chromosome spanning this region has been subcloned into lambda phage, and the positions of deficiency breakpoints on either side of the mu2 gene have been identified within the subclones. These positions limit the location of the left end of the gene to a 23 kb region. In the course of these experiments, three additional, presumptive mutant alleles were identified, suggesting that other mutator alleles remain undiscovered in many standard laboratory stocks. C1 NIEHS,MOLEC GENET LAB,RES TRIANGLE PK,NC 27709. NIEHS,EXPTL CARCINOGENESIS & MUTAGENESIS BRANCH,RES TRIANGLE PK,NC 27709. UNIV CALIF IRVINE,CTR DEV BIOL,IRVINE,CA 92717. FU NIGMS NIH HHS [GM46211] NR 30 TC 12 Z9 12 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0026-8925 J9 MOL GEN GENET JI Mol. Gen. Genet. PD DEC 1 PY 1994 VL 245 IS 5 BP 598 EP 607 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA PX720 UT WOS:A1994PX72000008 PM 7808410 ER PT J AU WONG, G LYON, T SKOLNICK, P AF WONG, G LYON, T SKOLNICK, P TI CHRONIC EXPOSURE TO BENZODIAZEPINE RECEPTOR LIGANDS UNCOUPLES THE GAMMA-AMINOBUTYRIC-ACID TYPE-A RECEPTOR IN WSS-1 CELLS SO MOLECULAR PHARMACOLOGY LA English DT Article ID CEREBRAL CORTICAL-NEURONS; GABA-A RECEPTORS; DOWN-REGULATION; MOLECULAR-BIOLOGY; MESSENGER-RNAS; PHARMACOLOGY; SUBTYPES; COMPLEX; SENSITIVITY; FLURAZEPAM AB Chronic exposure to benzodiazepines can result in an ''uncoupling'' of gamma-aminobutyric acid (GABA) receptors and benzodiazepine receptors (BzR) both in primary neuronal cell cultures and in vivo. The effect of chronic exposure to BzR ligands was examined in an engineered cell line (WSS-1) stably expressing ''type I'' GABA(A) receptors. Chronic exposure to flurazepam produced a concentration- (EC(50), similar to 1.1 mu M after a 48-hr exposure) and time-dependent(t(1/2), similar to 3 hr at 100 mu M) reduction in the efficacy (E(max)) of GABA to enhance [H-3]flunitrazepam binding to BzR, a characteristic of uncoupling in native GABA(A) receptor isoforms. Uncoupling of GABA(A) receptors and BzR without concomitant changes in BzR density was also produced by chronic exposure to other, structurally diverse, BzR ligands, including Ro 15-1788 and methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate, but was not manifested after exposure to the 5-hydroxytryptamine reuptake blocker fluoxetine. Chronic (12-48-hr) exposure to flurazepam did not remarkably alter levels of alpha 1 and gamma 2 mRNAs, which constitute GABA(A) receptors in this cell line. Based on these findings, it is hypothesized that uncoupling of GABA(A) receptors and BzR in this engineered cell line can proceed without the elaboration of additional novel subunits and could involve either post-translational modification of GABA(A) receptor proteins or changes in subunit stoichiometry. C1 NIDDK,NEUROSCI LAB,BETHESDA,MD 20892. NR 34 TC 35 Z9 36 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD DEC PY 1994 VL 46 IS 6 BP 1056 EP 1062 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QA533 UT WOS:A1994QA53300007 PM 7808424 ER PT J AU ZHANG, H COONEY, DA SREENATH, A ZHAN, QM AGBARIA, R STOWE, EE FORNACE, AJ JOHNS, DG AF ZHANG, H COONEY, DA SREENATH, A ZHAN, QM AGBARIA, R STOWE, EE FORNACE, AJ JOHNS, DG TI QUANTITATION OF MITOCHONDRIAL-DNA IN HUMAN LYMPHOBLASTS BY A COMPETITIVE POLYMERASE CHAIN-REACTION METHOD - APPLICATION TO THE STUDY OF INHIBITORS OF MITOCHONDRIAL-DNA CONTENT SO MOLECULAR PHARMACOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS-INFECTION; DEOXYRIBONUCLEIC-ACID; 2',3'-DIDEOXYCYTIDINE; CELLS; REPLICATION; EXPRESSION; TOXICITY; COMPOUND; HIV-1 AB With increasing awareness of the mitochondrial toxicity associated with certain 2',3'-dideoxynucleosides used in anti-human immunodeficiency virus therapy, procedures for quantitative analyses of drug effects on mitochondrial DNA (mtDNA) have assumed enhanced importance. For this reason we have developed a method to measure the copy numbers of mtDNA in cultured MOLT-4 cells. First a hybrid competitive DNA template was synthesized by conventional polymerase chain reaction (PCR), using two custom-synthesized 40-mer composite primers incorporating mitochondrial displacement loop sequences linked by a non-mitochondrial cDNA template (a 76-base pair sequence from the tat/rev region of human immunodeficiency virus cDNA). For the competitive assay, increasing known copy numbers of the hybrid competitive template were added as an internal control to samples containing total cellular DNA. With this approach, two competitive PGR products were generated, 1) a mitochondrial displacement loop-derived fragment (182 base pairs) and 2) a competitive DNA template-derived fragment (156 base pairs). Absolute quantitation was achieved by radiometric comparison of the relative amounts of the two products. To test the versatility of this method, varying amounts of competitive template (6.6 x 10(4) to 6.6 X 10(9) copies) were used with a fixed quantity of total cellular DNA taken from cells cultured for 9 days in the presence or absence of selected pyrimidine and purine dideoxynucleosides. The results showed that the copy number of cellular mtDNA is 823 +/- 71 copies/cell in MOLT-4 cells. Little selective depletion of mtDNA, compared with total cellular DNA, was seen with the purine dideoxynucleosides examined; however, when the cells were exposed to the pyrimidine dideoxynucleoside 2',3'-dideoxycytidine (50 nM) for 9 days, mtDNA content was specifically depleted, although total cellular DNA decreased by only 10%. Thus, in addition to the presently used methods of assessing mitochondrial impairment, i.e., Southern blot analysis and electron microscopy, the competitive PCR method provides a third and convenient assay, with particular applicability to determination of mtDNA in very small numbers of cells. C1 NCI,MED CHEM LAB,BETHESDA,MD 20892. NCI,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 21 TC 32 Z9 32 U1 0 U2 4 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD DEC PY 1994 VL 46 IS 6 BP 1063 EP 1069 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QA533 UT WOS:A1994QA53300008 PM 7808425 ER PT J AU GRIMM, SW DYROFF, MC PHILPOT, RM HALPERT, JR AF GRIMM, SW DYROFF, MC PHILPOT, RM HALPERT, JR TI CATALYTIC SELECTIVITY AND MECHANISM-BASED INACTIVATION OF STABLY EXPRESSED AND HEPATIC CYTOCHROMES P450 2B4 AND 2B5 - IMPLICATIONS OF THE CYTOCHROME-P450 2B5 POLYMORPHISM SO MOLECULAR PHARMACOLOGY LA English DT Article ID PHENOBARBITAL-INDUCIBLE FORMS; RABBIT LIVER; RAT-LIVER; FUNCTIONAL EXPRESSION; METABOLISM; ACID; PHENCYCLIDINE; INDUCTION; SYSTEM; STEREOSPECIFICITY AB Cytochrome P450 (P450) 2B5 was recently found to be functionally distinct from three other rabbit P450 2B forms, based on androstenedione hydroxylase activities. In this investigation, we examined the frequency of the P450 285-null phenotype and the functional consequences of polymorphic P450 2B5 expression in hepatic microsomes from phenobarbital-treated rabbits. Four of the 10 animals examined did not have detectable levels of P450 2B5 mRNA and exhibited much lower microsomal androstenedione 15 alpha- and 16 alpha-hydroxylase activities. The 15 alpha-hydroxylase activity was found to correlate (r = 0.91) with liver P450 2B5 mRNA. P450 2B4 and 2B5 were stably expressed in human kidney 293 cells to further characterize substrate specificities and to investigate mechanism-based inactivation by phencyclidine. P450 2B4 was 4-16-fold more active than 2B5 towards benzphetamine, 7-ethoxycoumarin, methylenedioxybenzene, and pentoxyresorufin. Benzyloxyresorufin O-debenzylase activity was 160-fold higher for P450 2B4 than P450 2B5. Anti-P450 2B4 IgG inhibited benzyloxyresorufin O-debenzylation nearly completely in untreated and phenobarbital-induced liver microsomes. Phencyclidine selectively inactivated P450 2B4, compared with 2B5, in both human kidney 293 cell and liver microsomes. Poor inactivation of P450 2B5 by phencyclidine was found to be a result of its low maximal rate constant. Results of this study establish the idea that the metabolic consequences of phenobarbital induction depend on the potential of animals to express functionally variant P450 2B forms. Furthermore, we conclude that one or more of the 11 amino acid differences between these highly related P450 forms are critical to their substrate specificities and selective inactivation. C1 UNIV ARIZONA,COLL PHARM,DEPT PHARMACOL & TOXICOL,TUCSON,AZ 85721. NIEHS,CELLULAR & MOLEC PHARMACOL LAB,RES TRIANGLE PK,NC 27709. RP GRIMM, SW (reprint author), ZENECA INC,ZENECA PHARMACEUT GRP,LW253,WILMINGTON,DE 19897, USA. FU NIEHS NIH HHS [ES03619] NR 39 TC 25 Z9 25 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD DEC PY 1994 VL 46 IS 6 BP 1090 EP 1099 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA QA533 UT WOS:A1994QA53300012 PM 7808429 ER PT J AU VALLSSOLE, J LOU, JS HALLETT, M AF VALLSSOLE, J LOU, JS HALLETT, M TI BRAIN-STEM REFLEXES IN PATIENTS WITH OLIVOPONTOCEREBELLAR ATROPHY SO MUSCLE & NERVE LA English DT Article DE OLIVOPONTOCEREBELLAR ATROPHY; MYOCLONUS; BRAIN-STEM; BLINK REFLEX; FACIAL NERVE; TRIGEMINAL NERVE ID BLINK REFLEX; FACIAL-NERVE; MASSETER; SPASM; CAT AB In 4 patients with familiar olivopontocerebellar atrophy (OPCA) we have recently described an abnormal movement of facial muscles characterized by rhythmic muscle twitching during voluntary activation (facial action myoclonus). In the present article, we present the results of a neurophysiological study of brainstem reflexes in those 4 patients, in 4 other patients with OPCA but without facial action myoclonus, in 3 patients with pure cerebellar cortical atrophy, and in 6 normal volunteers used as control subjects. All patients had similar clinical features, but only the patients with facial action myoclonus and only one of the other patients with OPCA had brainstem atrophy detected on magnetic resonance imaging. Electrophysiological abnormalities were found in all patients with facial action myoclonus and consisted of myokymia in perioral muscles at rest, spread of spontaneous and reflex blinking to the orbicularis oris, and enhanced long-latency facial reflex responses to stimuli applied to the facial or trigeminal nerve. Other relevant electrophysiological abnormalities were the absence of jaw jerk in 2 patients, the absence of an R1 response of the blink reflex in 1 patient, and a markedly reduced compound muscle action potential of the facial nerve in another patient. Comparable electrophysiological abnormalities were found in only 1 of the patients with OPCA but without facial action myoclonus, and in none of the patients with pure cerebellar cortical atrophy. Facial action myoclonus is a clinical manifestation of a global brainstem functional derangement that may characterize a subgroup of patients with OPCA or constitute a distinctive step in the natural evolution of some forms of the disease. (C) 1994 John Wiley & Sons, Inc. C1 NINCDS,MED NEUROL BRANCH,HUMAN MOTOR CONTROL SECT,BETHESDA,MD 20892. NR 25 TC 12 Z9 13 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD DEC PY 1994 VL 17 IS 12 BP 1439 EP 1448 DI 10.1002/mus.880171213 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA PT145 UT WOS:A1994PT14500010 PM 7969244 ER PT J AU CASTILLA, LH COUCH, FJ ERDOS, MR HOSKINS, KF CALZONE, K GARBER, JE BOYD, J LUBIN, MB DESHANO, ML BRODY, LC COLLINS, FS WEBER, BL AF CASTILLA, LH COUCH, FJ ERDOS, MR HOSKINS, KF CALZONE, K GARBER, JE BOYD, J LUBIN, MB DESHANO, ML BRODY, LC COLLINS, FS WEBER, BL TI MUTATIONS IN THE BRCA1 GENE IN FAMILIES WITH EARLY-ONSET BREAST AND OVARIAN-CANCER SO NATURE GENETICS LA English DT Article ID CHROMOSOME-17Q21; LINKAGE; REGION; DNA AB We analysed 50 probands with a family history of breast and/or ovarian cancer for germline mutations in the coding region of the BRCA1 candidate gene, using single-strand conformation polymorphism (SSCP) analysis on PCR-amplified genomic DNA. A total Of eight putative disease-causing alterations were identified: four of these are frameshifts and two are nonsense mutations. In addition, we found two missense mutations, one of which changes the final cysteine of the BRCA1 zinc finger motif to glycine. These data are consistent with a tumour suppressor model, and support the notion that this candidate gene is in fact BRCA1. The heterogeneity of mutations, coupled with the large size of the gene, indicates that clinical application of BRCA1 mutation testing will be technically challenging. C1 UNIV PENN,DEPT INTERNAL MED,PHILADELPHIA,PA 19104. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. UNIV MICHIGAN,DEPT BIOL,ANN ARBOR,MI 48109. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,DIV CANC EPIDEMIOL & CONTROL,BOSTON,MA 02115. UNIV PENN,DEPT OBSTET & GYNECOL,PHILADELPHIA,PA 19104. STRANG CANC PREVENT CTR,NEW YORK,NY 10021. UNIV PENN,DEPT GENET,PHILADELPHIA,PA 19104. FU NCI NIH HHS [R01 CA-61231, R01-CA-57601] NR 26 TC 337 Z9 341 U1 1 U2 6 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 1994 VL 8 IS 4 BP 387 EP 391 DI 10.1038/ng1294-387 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA PV682 UT WOS:A1994PV68200021 PM 7894491 ER PT J AU FRIEDMAN, TC GARCIABORREGUERO, D HARDWICK, D AKUETE, CN DOPPMAN, JL DORN, LD BARKER, CN YANOVSKI, JA CHROUSOS, GP AF FRIEDMAN, TC GARCIABORREGUERO, D HARDWICK, D AKUETE, CN DOPPMAN, JL DORN, LD BARKER, CN YANOVSKI, JA CHROUSOS, GP TI DECREASED DELTA-SLEEP AND PLASMA DELTA-SLEEP-INDUCING PEPTIDE IN PATIENTS WITH CUSHING SYNDROME SO NEUROENDOCRINOLOGY LA English DT Article DE DELTA SLEEP IN CUSHING SYNDROME; CUSHING SYNDROME; SLEEP; CORTICOTROPIN RELEASING HORMONE; CLINICAL NEUROENDOCRINOLOGY ID HORMONE-RELEASING HORMONE; MAJOR DEPRESSIVE DISORDER; GROWTH-HORMONE; DSIP; CORTISOL; RADIOIMMUNOASSAY; EEG; CORTICOTROPIN; SECRETION; DISEASE AB To evaluate the sleep disturbances of patients with Cushing syndrome and to examine the relationship between the sleep disturbances and plasma levels of delta-sleep-inducing peptide-like immunoreactivity (DSIP-LI), we performed three polysomnographic/endocrinological studies in patients with Cushing syndrome. In study 1, polysomnography was studied in 12 patients and 12 matched normal volunteers. In addition, DSIP-LI was measured every 30 min for 24 h in 9 patients with Cushing syndrome and 12 normal volunteers. The percentage of time spent in delta sleep (stages 3 and 4) was significantly reduced in patients with Cushing syndrome(5.8 +/- 1.4%; mean +/- SEM) compared to normal volunteers (14.0 +/- 2.5%) (p < 0.01). REM sleep indices, however, were not significantly different between the two groups. There was a significant negative correlation between amount of delta sleep and 08.00 h DSIP-LI (r = -0.43, p < 0.05), which is against the notion of a causal relationship between DSIP-LI and delta sleep. The circadian rhythm of plasma DSIP-LI was found to be similar in Cushing patients and normal volunteers. In study 2, we measured plasma levels of delta-sleep-inducing peptide-like immunoreactivity (DSIP-LI) at 08.00 h in 65 patients with Cushing syndrome and 49 normal volunteers. The 08.00 h DSIP-LI concentrations of 797 +/- 57 pmol/l (mean +/- SEM) in the patients with Cushing syndrome were significantly reduced compared to the level of 1,062 +/- 99 pmol/l found in the normal volunteers (p < 0.05). In study 3, plasma was drawn simultaneously from the petrosal sinuses and peripheral veins of Cushing patients. No central-toperipheral gradient for plasma DSIP-LI was noted and neither peripheral, nor central plasma DSIP-LI was affected by administration of intravenous ovine CRH. We conclude that patients with Cushing syndrome have less delta sleep and lower plasma concentrations of DSIP-LI than normal controls, however a causal relationship between the two appears to be unlikely. The pituitary does not appear to be the site of synthesis of plasma DSIP, whose source remains unknown. C1 NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NIMH,CLIN PSYCHOBIOL BRANCH,BETHESDA,MD 20892. NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. UNIV PITTSBURGH,SCH NURSING,PITTSBURGH,PA 15261. RP FRIEDMAN, TC (reprint author), NICHHD,DEV NEUROBIOL LAB,BLDG 49,RM 5A-38,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 41 TC 19 Z9 19 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PD DEC PY 1994 VL 60 IS 6 BP 626 EP 634 DI 10.1159/000126806 PG 9 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA PW190 UT WOS:A1994PW19000010 PM 7700506 ER PT J AU BIRCH, NP HAKES, DJ DIXON, JE MEZEY, E AF BIRCH, NP HAKES, DJ DIXON, JE MEZEY, E TI DISTRIBUTION AND REGULATION OF THE CANDIDATE PROHORMONE PROCESSING ENZYMES SPC2 AND SPC3 IN ADULT-RAT BRAIN SO NEUROPEPTIDES LA English DT Article ID ALPHA-AMIDATING MONOOXYGENASE; INSITU HYBRIDIZATION HISTOCHEMISTRY; INTESTINAL POLYPEPTIDE VIP; MESSENGER-RNA DISTRIBUTION; CULTURED ASTROCYTES; GENE-EXPRESSION; YEAST KEX2; PROPROTEIN CONVERTASES; FUNCTIONAL EXPRESSION; MAGNOCELLULAR NEURONS AB A number of candidate mammalian prohormone processing enzymes related to the yeast Kex2 endoprotease have been cloned and demonstrated to cleave several prohormone precursors at single, pairs and tetra basic amino acid processing sites. We have mapped the distribution of the mRNAs encoding two of these endoproteases in adult rat brain. SPC3 message levels showed a more restricted distribution and generally lower levels than SPC2 transcripts. The highest levels of SPC2 mRNA were found in the pyramidal cells of the hippocampus, several thalamic nuclei, the habenula and selected nuclei in the hypothalamus. SPC3 mRNA was most abundant in dentate gyrus granule cells, the habenula and selected hypothalamic nuclei. In the hypothalamus overlapping and unique distributions of the two transcripts were seen in the paraventricular nucleus with SPC3 mRNA predominantly expressed in lateral magnocellular cells. Both SPC2 and SPC3 mRNA were upregulated in the paraventricular and supraoptic hypothalamic nuclei following chronic salt loading. Combined immunocytochemistry/in situ hybridization histochemistry demonstrated that SPC2 and SPC3 transcripts were both expressed in the vasopressinergic subpopulation of magnocellular neurons in the supraoptic nucleus. SPC3 mRNA, but not SPC2 transcripts, also colocalized with immunoreactive vasopressin-associated neurophysin in the suprachiasmatic nucleus. These results remain consistent with roles for SPC2 and SPC3 in the biosynthesis of neuropeptides and for a specific role for SPC3 in the processing of provasopressin. Increased levels of SPC2 and SPC3 transcripts following a chronic osmotic stimulus suggests these proteases are coregulated with prohormone substrates and may be useful as an indicator of peptidergic activity. C1 NICHHD,DEV NEUROBIOL LAB,CELLULAR NEUROBIOL SECT,BETHESDA,MD 20892. UNIV MICHIGAN,SCH MED,DEPT BIOL CHEM,ANN ARBOR,MI 48109. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. RP BIRCH, NP (reprint author), UNIV AUCKLAND,SCH BIOL SCI,PRIVATE BAG 92019,AUCKLAND,NEW ZEALAND. RI Birch, Nigel/H-2498-2011 OI Birch, Nigel/0000-0002-8417-3587 NR 64 TC 17 Z9 17 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0143-4179 J9 NEUROPEPTIDES JI Neuropeptides PD DEC PY 1994 VL 27 IS 6 BP 307 EP 322 DI 10.1016/0143-4179(94)90057-4 PG 16 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA PX842 UT WOS:A1994PX84200001 PM 7898639 ER PT J AU FAN, P WEIGHT, FF AF FAN, P WEIGHT, FF TI PROCAINE IMPAIRS THE FUNCTION OF 5-HT3 RECEPTOR-ION CHANNEL COMPLEX IN RAT SENSORY GANGLION NEURONS SO NEUROPHARMACOLOGY LA English DT Article DE 5-HT; RECEPTOR; LOCAL ANESTHETICS; PROCAINE; PATCH-CLAMP ID REINFORCING PROPERTIES; LOCAL-ANESTHETICS; RHESUS-MONKEYS; ACETYLCHOLINE-RECEPTORS; NEUROBLASTOMA-CELLS; INHIBITION; CURRENTS; BINDING; PENICILLIN; MEMBRANES AB Previous studies have shown that local anesthetics block voltage-dependent Nai channels and nicotinic acetylcholine receptors. The present study investigated the effect of the local anesthetic, procaine on another ligand-gated ion channel, the 5-HT3 receptor, in rat nodose ganglion neurons. Procaine (0.01-100 mu M) inhibited the 5-HT3 receptor-mediated inward current in the whole-cell patch clamp recording. The inhibition was fully reversible, concentration-dependent but not sensitive to changes in membrane potential. Concentration-response curves indicated that procaine appears to produce a competitive inhibition on 5-HT3 receptors with a K-D of 1.7 mu M. These observations suggest that one of the actions of procaine in nervous system is on 5-HT3 receptors. RP FAN, P (reprint author), NIAAA, MOLEC & CELLULAR NEUROBIOL LAB, 1250 WASHINGTON AVE, MSC 8205, BETHESDA, MD 20892 USA. NR 35 TC 15 Z9 15 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD DEC PY 1994 VL 33 IS 12 BP 1573 EP 1579 DI 10.1016/0028-3908(94)90132-5 PG 7 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA QE508 UT WOS:A1994QE50800009 PM 7539114 ER PT J AU MARTIN, A WIGGS, CL LALONDE, F MACK, C AF MARTIN, A WIGGS, CL LALONDE, F MACK, C TI WORD RETRIEVAL TO LETTER AND SEMANTIC CUES - A DOUBLE DISSOCIATION IN NORMAL SUBJECTS USING INTERFERENCE TASKS SO NEUROPSYCHOLOGIA LA English DT Article DE LANGUAGE; VERBAL FLUENCY; SEMANTIC MEMORY; FRONTAL LOBE; TEMPORAL LOBE; COGNITION ID ALZHEIMERS-DISEASE; MEMORY; IMPAIRMENT; DEMENTIA; KNOWLEDGE; PICTURES; OBJECT AB Recent evidence suggests that letter and semantic category verbal fluency tasks may use different component processes of a distributed word retrieval system. We hypothesized that the retrieval of words that begin with the same letter places greater demands on frontal lobe mediated strategic search processes than on temporal lobe mediated semantic knowledge. Conversely, generation of words from the same semantic category places greater demands on semantic knowledge than on strategic search. This hypothesis was tested by requiring subjects to generate lists of words to letter and semantic cues alone and while performing an interference task. A motor sequencing task (developed by Moscovitch, Neuropsychology of Memory, pp. 5-22, 1992) was used to activate frontal regions and an object decision task was used to activate posterior temporal cortex. In support of the hypothesis, letter fluency was reduced to a greater extent by concurrent performance of the motor sequencing task than by the object decision task. The opposite interference pattern was found for semantic category fluency. RP NIMH, CLIN SCI LAB, BLDG 10, ROOM 3D-41, BETHESDA, MD 20892 USA. RI martin, alex/B-6176-2009 NR 28 TC 138 Z9 140 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 EI 1873-3514 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD DEC PY 1994 VL 32 IS 12 BP 1487 EP 1494 DI 10.1016/0028-3932(94)90120-1 PG 8 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA PW698 UT WOS:A1994PW69800005 PM 7885578 ER PT J AU WESTLAKE, TM HOWLETT, AC BONNER, TI MATSUDA, LA HERKENHAM, M AF WESTLAKE, TM HOWLETT, AC BONNER, TI MATSUDA, LA HERKENHAM, M TI CANNABINOID RECEPTOR-BINDING AND MESSENGER-RNA EXPRESSION IN HUMAN BRAIN - AN IN-VITRO RECEPTOR AUTORADIOGRAPHY AND IN-SITU HYBRIDIZATION HISTOCHEMISTRY STUDY OF NORMAL AGED AND ALZHEIMERS BRAINS SO NEUROSCIENCE LA English DT Article ID RAT-BRAIN; SENILE DEMENTIA; BASAL GANGLIA; DISEASE; HIPPOCAMPUS; LOCALIZATION; CORTEX AB The distribution and density of cannabinoid receptor binding and messenger RNA expression in aged human brain were examined in several forebrain and basal ganglia structures. In vitro binding of [H-3]CP-55,940, a synthetic cannabinoid, was examined by autoradiography in fresh frozen brain sections from normal aged humans (n = 3), patients who died with Alzheimer's disease (n = 5) and patients who died with other forms of cortical pathology (n = 5). In the structures examined-hippocampal formation, neocortex, basal ganglia and parts of the brainstem-receptor binding showed a characteristic pattern of high densities in the dentate gyrus molecular layer, globus pallidus and substantia nigra pars reticulata, moderate densities in the hippocampus, neocortex, amygdala and striatum, and low densities in the white matter and brainstem. In situ hybridization histochemistry of human cannabinoid receptor, a ribonucleotide probe for the human cannabinoid receptor messenger RNA, showed a pattern of extremely dense transcript levels in subpopulations of cells in the hippocampus and cortex, moderate levels in hippocampal pyramidal neurons and neurons of the striatum, amygdala and hypothalamus, and no signal over dentate gyrus granule cells and most of the cells of the thalamus and upper brainstem, including the substantia nigra. In Alzheimer's brains, compared to normal brains, [3H]CP-55,940 binding was reduced by 37-45% in all of the subfields of the hippocampal formation and by 49% in the caudate. Lesser reductions (20-24%) occurred in the substantia nigra and globus pallidus, internal segment. Other neocortical and basal ganglia structures were not different from control levels. Levels of messenger RNA expression did not differ between Alzheimer's and control brains, but there were regionally discrete statistically significant losses of the intensely expressing cells in the hippocampus. The reductions in binding did not correlate with or localize to areas showing histopathology, estimated either on the basis of overall tissue quality or silver staining of neuritic plaques and neurofibrillary tangles. Reduced [H-3]CP-55,940 binding was receptor losses are related to the generalized aging and/or disease process and are not selectively associated with the pathology characteristic of Alzheimer's disease, nor with overall decrements in levels of cannabinoid receptor gene expression. C1 NIMH,FUNCT NEUROANAT SECT,BETHESDA,MD 20892. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. ST LOUIS UNIV,SCH MED,DEPT PHARMACOL & PHYSIOL SCI,ST LOUIS,MO 63104. OI Herkenham, Miles/0000-0003-2228-4238; Howlett, Allyn/0000-0002-2810-0164 FU NIDA NIH HHS [R01 DA03690, R01 DA06912]; NINDS NIH HHS [T32-NS07254] NR 51 TC 158 Z9 164 U1 0 U2 3 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 DEC PY 1994 VL 63 IS 3 BP 637 EP 652 DI 10.1016/0306-4522(94)90511-8 PG 16 WC Neurosciences SC Neurosciences & Neurology GA PV798 UT WOS:A1994PV79800002 PM 7898667 ER PT J AU CADET, JL KAHLER, LA AF CADET, JL KAHLER, LA TI FREE-RADICAL MECHANISMS IN SCHIZOPHRENIA AND TARDIVE-DYSKINESIA SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS LA English DT Review DE FREE RADICALS; ANTIOXIDANTS; SUPEROXIDE DISMUTASE; GLUTATHIONE; GLUTATHIONE PEROXIDASE; CATALASE; CATECHOLAMINES; SCHIZOPHRENIA; NEUROLEPTICS; TARDIVE DYSKINESIA; NITRIC OXIDE; GLUTAMATE ID GLUTAMIC-ACID DECARBOXYLASE; CENTRAL-NERVOUS-SYSTEM; VITAMIN-E TREATMENT; RAT-BRAIN; ISODENDRITIC CORE; OXYGEN RADICALS; NITRIC-OXIDE; L-DOPA; GLUTATHIONE PEROXIDASE; AMPHETAMINE PSYCHOSIS AB The present article discusses the distribution of free radical processes in the central nervous system (CNS). Specifically, we discuss the involvement of oxyradicals in the normal metabolism of catecholamine. We also review some proposals related to the possible importance of these compounds in the development of neuropsychiatric and movement disorders such as schizophrenia and neuroleptic-induced tardive dyskinesia (TD), respectively. Clinical studies have shown that antioxidant treatment can attenuate the movement abnormalities observed in TD. Further studies are necessary to evaluate the status of specific scavenging systems in these two disorders. The prophylactic use of antioxidants in patients who are treated with neuroleptics needs also to be considered. RP NIDA, ADDICT RES CTR, MOLEC NEUROPSYCHIAT SECT, POB 5180, BALTIMORE, MD 21224 USA. NR 203 TC 80 Z9 81 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0149-7634 EI 1873-7528 J9 NEUROSCI BIOBEHAV R JI Neurosci. Biobehav. Rev. PD WIN PY 1994 VL 18 IS 4 BP 457 EP 467 DI 10.1016/0149-7634(94)90001-9 PG 11 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA PZ112 UT WOS:A1994PZ11200001 PM 7708360 ER PT J AU ZAWIA, NH EVERS, LB KODAVANTI, PRS HARRY, GJ AF ZAWIA, NH EVERS, LB KODAVANTI, PRS HARRY, GJ TI MODULATION OF DEVELOPMENTAL CEREBELLAR ORNITHINE DECARBOXYLASE ACTIVITY BY LEAD ACETATE SO NEUROTOXICOLOGY LA English DT Article DE LEAD; CALCIUM; DEVELOPMENT; ORNITHINE DECARBOXYLASE (ODC); CEREBELLUM ID CENTRAL NERVOUS-SYSTEM; RAT-BRAIN; GENE-EXPRESSION; NUCLEIC-ACIDS; EXPOSURE; NEUROTOXICITY; CALCIUM; MECHANISMS; PROTEIN; HIPPOCAMPUS AB The developing brain is particularly susceptible to the neurotoxic effects of lead exposure. The ontological profile of ornithine decarboxylase (ODC) activity in the cerebellum was examined following lactational exposure of rats to 0.2% lead acetate (Pb). Relative to controls, Pb-exposure induced ODC activity levels in a transient manner with a 50% increase at postnatal day (PND) 6, a 20% increase at PND 9, returning to control basal levels by PND 15. These effects were seen at exposure levels of Pb that did not alter the normal growth and body weight of either the lactating dam or the developing pups. Basal cerebellar ODC activity in homogenates was increased with addition of low concentrations of Pb acetate (0.01 mu M and 0.1 mu M), while concentrations of 1 mu M or greater were inhibitory. The effects of Pb acetate on tissue ODC activity in vitro were not mimicked by the addition of calcium chloride. Unlike tissue ODC activity, incubation of these metals with a pure ODC protein preparation exhibited fluctuations in ODC activity possibly due to the ionic interactions of Pb or calcium chloride. Calcium homeostatic mechanisms appeared to be unchanged with Pb exposure, at this dose, in that neither Ca-45-uptake (both mitochondrial and microsomal) nor synaptosomal Ca2+ ATPase activity was altered. These data suggest that alterations in ODC activity may be indicative of subtle toxicant induced perturbations during early development. Although the precise mechanism by which Pb may induce ODC activity in developing tissue is unknown, our results suggest that Pb may specifically alter ODC activity via cytosolic in teractions. (C) 1994 Intox Press, Inc. C1 NIEHS,INTEGRATED BIOL LAB,RES TRIANGLE PK,NC 27707. US EPA,HLTH EFFECTS RES LAB,DIV NEUROTOXICOL,RES TRIANGLE PK,NC 27711. NR 53 TC 9 Z9 9 U1 0 U2 0 PU INTOX PRESS INC PI LITTLE ROCK PA PO BOX 24865, LITTLE ROCK, AR 72221 SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD WIN PY 1994 VL 15 IS 4 BP 903 EP 911 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA QD366 UT WOS:A1994QD36600012 PM 7715861 ER PT J AU BENOWITZ, NL HENNINGFIELD, J AF BENOWITZ, NL HENNINGFIELD, J TI REGULATION OF THE NICOTINE CONTENT OF CIGARETTES - REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NIDA,BALTIMORE,MD 21224. RP BENOWITZ, NL (reprint author), UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94110, 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 DEC 1 PY 1994 VL 331 IS 22 BP 1531 EP 1532 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA PU866 UT WOS:A1994PU86600033 ER PT J AU SPIRTAS, R HEINEMAN, EF BERNSTEIN, L BEEBE, GW KEEHN, RJ STARK, A HARLOW, BL BENICHOU, J AF SPIRTAS, R HEINEMAN, EF BERNSTEIN, L BEEBE, GW KEEHN, RJ STARK, A HARLOW, BL BENICHOU, J TI MALIGNANT MESOTHELIOMA - ATTRIBUTABLE RISK OF ASBESTOS EXPOSURE SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article DE ASBESTOS; EPIDEMIOLOGIC FACTORS; MESOTHELIOMA; OCCUPATIONAL EXPOSURE; PERITONEAL; PLEURAL ID PLEURAL MESOTHELIOMA; UNITED-STATES; OCCUPATIONAL EXPOSURE; EPIDEMIOLOGY; PATTERNS; TRENDS; COMBINATION; AUSTRALIA; REGISTER; WORKERS AB Objectives-To evaluate a case-control study of malignant mesothelioma through-patterns of exposure to asbestos based upon information from telephone interviews with next of kin. Methods-Potential cases, identified from medical files and death certificates, included all people diagnosed with malignant mesothelioma and registered during 1975-1980 by the Los Angeles County Cancer Surveillance Program, the New York State Cancer Registry (excluding New York City), and 39 large Veterans Administration hospitals. Cases whose diagnosis was confirmed in a special pathology review as definite or probable mesothelioma (n = 208) were included in the analysis. Controls (n = 533) had died of other causes, excluding cancer, respiratory disease, suicide, or violence. mined from responses to three types of questions: specific queries as to any exposure to asbestos; occupational or non-vocational participation in any of nine specific activities thought to entail exposure to asbestos; and analysis of lifetime work histories. Indirect exposures were assessed through residential histories and reported contact with family members exposed to asbestos. Results-Among men with pleural mesothelioma the attributable risk (AR) for exposure to asbestos was 88% (95% confidence interval (95% CI) 76-95%). For men, the AR of peritoneal cancer was 58% (95% CI 20-89%). For women (both sites combined), the AR was 23% (95% CI 3-72%). The large differences in AR by sex are compatible with the explanations: a lower background incidence rate in women, lower exposure to asbestos, and greater misclassification among women. Conclusions-Most of the pleural and peritoneal mesotheliomas in the men studied were attributable to exposure to asbestos. The situation in women was less definitive. C1 NCI,DIV CANC ETIOL,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892. UNIV SO CALIF,SCH MED,LOS ANGELES,CA. NATL ACAD SCI,INST MED,MED FOLLOW UP AGCY,WASHINGTON,DC 20418. NEW YORK STATE DEPT HLTH,ALBANY,NY 12201. WESTAT CORP,ROCKVILLE,MD. NR 66 TC 155 Z9 157 U1 4 U2 8 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 1351-0711 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD DEC PY 1994 VL 51 IS 12 BP 804 EP 811 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA PV495 UT WOS:A1994PV49500003 PM 7849863 ER PT J AU CHOW, LML DAVIDSON, D FOURNEL, M GOSSELIN, P LEMIEUX, S LYU, MS KOZAK, CA MATIS, LA VEILLETTE, A AF CHOW, LML DAVIDSON, D FOURNEL, M GOSSELIN, P LEMIEUX, S LYU, MS KOZAK, CA MATIS, LA VEILLETTE, A TI 2 DISTINCT PROTEIN ISOFORMS ARE ENCODED BY NTK, A CSK-RELATED TYROSINE PROTEIN-KINASE GENE SO ONCOGENE LA English DT Article ID SRC FAMILY KINASES; RECEPTOR; P56LCK; AUTOPHOSPHORYLATION; PHOSPHORYLATES; ASSOCIATION; ACTIVATION; EXPRESSION; P50(CSK); P56(LCK) AB Recently, we and others have cloned cDNAs encoding a second member of the Csk family of inhibitory tyrosine protein kinases, which we have termed Ntk. Intriguingly, the mouse ntk cDNA sequences published by two independent groups differed by the presence or absence of a 136 nucleotide-insert near their 5' ends. In this report, we demonstrate that this 136 nucleotide-sequence likely corresponds to a complete exon in the ntk gene (termed exon 2), and that the two types of cDNAs/transcripts are produced by alternative splicing. Using ribonuclease protection assays, it was also established that brain and lymphoid organs, as well as most hemopoietic cells, predominantly expressed ntk transcripts lacking exon 2. In contrast, selected hemopoietic cell lines, such as the immature myeloid cell lines 32D cl3(G) and WEHI-3B, exclusively possessed exon 2-bearing RNAs. Interestingly, exon 2 introduced a novel in-frame upstream AUG in the ntk transcript, which is in the appropriate context for translation initiation. Evidence was obtained that this AUG is utilized in vivo, and that it extends the amino-terminal sequence of Ntk by 40 amino acids. Indeed, while exon 2-deficient ntk RNAs were translated into a 52 kilodalton (kDa) polypeptide (p52(ntk)), those bearing exon 2 produced a 56 kDa protein (p56(ntk)). Furthermore, p56(ntk), but not p52(ntk), was recognized by an antiserum directed against the novel amino-terminal sequence encoded by exon 2. Additional biochemical characterizations showed that p52(ntk) and p56(ntk) were localized to the cytoplasm, and that they partially accumulated in the detergent-insoluble cellular fraction. This last finding suggested that the Ntk proteins can associate with the cytoskeleton. Finally, through linkage analysis of two multilocus crosses, the ntk gene was mapped to Chromosome 10 in the mouse. Taken together, these data showed that ntk, a csk-related tyrosine protein kinase gene, encodes two protein isoforms expressed in distinct cell types. Moreover, they raised the possibility that Ntk may be involved in the regulation of Src-Like enzymes in detergent-insoluble cellular compartments. C1 MCGILL UNIV,CTR CANC,MONTREAL H3G 1Y6,PQ,CANADA. MCGILL UNIV,DEPT BIOCHEM,MONTREAL H3G 1Y6,PQ,CANADA. MCGILL UNIV,DEPT MED,MONTREAL H3G 1Y6,PQ,CANADA. MCGILL UNIV,DEPT ONCOL,MONTREAL H3G 1Y6,PQ,CANADA. UNIV QUEBEC,INST ARMAND FRAPPIER,CTR RECH IMMUNOL,LAVAL H7V 1B7,PQ,CANADA. NIAID,BETHESDA,MD 20892. ALEXION PHARMACEUT INC,NEW HAVEN,CT 06511. MONTREAL GEN HOSP,DEPT MED,MONTREAL H3G 1A4,PQ,CANADA. MONTREAL GEN HOSP,DEPT ONCOL,MONTREAL H3G 1A4,PQ,CANADA. NR 41 TC 32 Z9 34 U1 1 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD DEC PY 1994 VL 9 IS 12 BP 3437 EP 3448 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA PT392 UT WOS:A1994PT39200005 PM 7970703 ER PT J AU RIMESSI, P GUALANDI, F MORELLI, C TRABANELLI, C WU, Q POSSATI, L MONTESI, M BARRETT, JC BARBANTIBRODANO, G AF RIMESSI, P GUALANDI, F MORELLI, C TRABANELLI, C WU, Q POSSATI, L MONTESI, M BARRETT, JC BARBANTIBRODANO, G TI TRANSFER OF HUMAN-CHROMOSOME-3 TO AN OVARIAN-CARCINOMA CELL-LINE IDENTIFIES 3 REGIONS ON 3P INVOLVED IN OVARIAN-CANCER SO ONCOGENE LA English DT Article ID NONPOLYPOSIS COLORECTAL-CANCER; YEAST ARTIFICIAL CHROMOSOME; TUMOR-SUPPRESSOR GENE; FREQUENT LOSS; LUNG-CANCER; SHORT ARM; BREAST-CANCER; GROWTH-FACTOR; LOW-GRADE; HETEROZYGOSITY AB The molecular pathogenesis of ovarian carcinoma involves altered expression of growth factors, activation of oncogenes and loss of tumor suppressor genes. Loss of heterozygosity on chromosomes 3p, 6q, 11p, 17 and 18q was reported as a significant alteration in ovarian cancer. However, no functional proof has been provided of tumor suppressor activity located in these chromosomal regions. We therefore introduced normal human chromosomes 3 and 11 into an ovarian carcinoma cell line by microcell mediated chromosome transfer. Transfer of chromosome 3 induced senescence acid growth arrest as well as suppression of tumorigenicity. Tumors induced by chromosome 3 monochromosomic hybrids consistently lost three small regions on 3p, two of which located in 3p23-24.2 and one located in 3p21.1-21.2, suggesting that these chromosomal regions are important for suppression of tumorigenicity of ovarian carcinoma cells. Transfer of chromosome 11 reduced the in vitro growth properties of ovarian cancer cells but did not significantly affect tumorigenicity. These results provide functional evidence for chromosome 3 tumor suppressor activity in ovarian cancer and define the chromosomal regions on 3p involved in the pathogenesis of this tumor. This experimental system, based on functional effects, may be useful for further delimitation and isolation of critical regions on 3p involved in tumor suppression. C1 UNIV FERRARA,SCH MED,INST MICROBIOL,I-44100 FERRARA,ITALY. UNIV FERRARA,SCH MED,INTERDEPT CTR BIOTECHNOL,I-44100 FERRARA,ITALY. UNIV ANCONA,INST BIOMED SCI,I-60131 ANCONA,ITALY. NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. RI Gualandi, Francesca/K-7513-2016 OI Gualandi, Francesca/0000-0001-9551-057X NR 65 TC 68 Z9 70 U1 1 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD DEC PY 1994 VL 9 IS 12 BP 3467 EP 3474 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA PT392 UT WOS:A1994PT39200008 PM 7970706 ER PT J AU RAPP, UR TROPPMAIR, J BECK, T BIRRER, MJ AF RAPP, UR TROPPMAIR, J BECK, T BIRRER, MJ TI TRANSFORMATION BY RAF AND OTHER ONCOGENES RENDERS CELLS DIFFERENTIALLY SENSITIVE TO GROWTH-INHIBITION BY A DOMINANT-NEGATIVE C-JUN MUTANT SO ONCOGENE LA English DT Article ID MAP KINASE-KINASE; PROTEIN-KINASE; V-RAF; SIGNAL TRANSDUCTION; EMBRYO CELLS; MYC PROTEIN; TRANSCRIPTION; EXPRESSION; ACTIVATION; PHOSPHORYLATION AB In NIH3T3 cells expressing active Raf-1 protein serine/threonine kinase (PSK) c-jun expression is constitutive while c-fos expression is attenuated. This alteration prompted us to determine whether oncogene transformation would render cells differentially sensitive to growth inhibition by a dominant negative mutant of c-jun, TAM 67. Growth inhibition was observed in three types of assays: (1) transfection of TAM 67 into cells stably transformed by a variety of oncogenes, (2) cotransfection of TAM 67 with oncogene expression plasmids into NIH3T3 cells and (3) titration of oncogene-expressing retroviruses on cells stably expressing TAM 67. The results clearly demonstrate that Raf-1 dependent oncogenes, which include receptor protein tyrosine kinases (PTKs)-, intracellular PTKs- and Ras-derived genes share the Raf phenotype of constitutive c-jun expression, attenuated c-fos induction, and high sensitivity to growth suppression by TAM 67. Additionally, the intracellular PSK oncogene, mos and the nuclear oncogenes c-myc, c-fos, and SV40 T antigen were TAM 67-sensitive for transformation This universal pattern of altered growth regulation in oncogene transformed fibroblast cell lines highlights the potential usefulness of c-jun based inhibitors for control of tumor cell growth. C1 NCI,DIV CANC PREVENT & CONTROL,BIOMARKERS & PREVENT RES BRANCH,ROCKVILLE,MD 20850. NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. UNIV WURZBURG,INST STRAHLEN & ZELLFORSCH,WURZBURG,GERMANY. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC,BCDP,FREDERICK,MD. NR 52 TC 59 Z9 59 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD DEC PY 1994 VL 9 IS 12 BP 3493 EP 3498 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA PT392 UT WOS:A1994PT39200011 PM 7970709 ER PT J AU PRASAD, DDK OUCHIDA, M LEE, L RAO, VN REDDY, ESP AF PRASAD, DDK OUCHIDA, M LEE, L RAO, VN REDDY, ESP TI TLS FUS FUSION DOMAIN OF TLS FUS-ERG CHIMERIC PROTEIN RESULTING FROM THE T(1621) CHROMOSOMAL TRANSLOCATION IN HUMAN MYELOID-LEUKEMIA FUNCTIONS AS A TRANSCRIPTIONAL ACTIVATION DOMAIN SO ONCOGENE LA English DT Article ID ETS-RELATED GENE; SERUM RESPONSE FACTOR; RNA-BINDING PROTEIN; DNA-BINDING; FLI-1 GENE; FAMILY; ELK-1; C-ETS-1; MEMBER; ERYTHROLEUKEMIA AB EWS and TLS/FUS genes, which code for RNA binding proteins are involved in a wide variety of human solid tumors. The TLS/FUS gene is involved both in human myxoid liposarcomas which carry a characteristic chromosomal translocation, t(12;16)(q13;p11) and in human myeloid leukemias with recurrent chromosomal translocation, t(16;21)(p11:q22). The TLS/FUS gene is fused to a transcriptional repressor, CHOP (in human myxoid liposarcomas) or transcriptional activator, erg (in human myeloid leukemias). To understand better the functional role of TLS/FUS-erg in human myeloid leukemias, we have cloned the TLS/FUS and TLS/FUS-erg cDNAs and studied the functional properties of their gene products. TLS/FUS protein binds to RNA in vitro and shows preferential binding to poly G. Both the amino- and the carboxy- terminal regions of TLS/FUS containing the conserved RNA binding motifs are needed for poly G specific RNA binding activity. The TLS/FUS fusion domain (TFD) appears to regulate the DNA binding activity of TLS/FUS-erg chimeric protein which shows weaker transcriptional activation properties compared to normal erg proteins. Mutational analysis of the TLS/FUS-erg chimeric protein reveals TFD to function as a transcriptional activation domain thus replacing the amino terminal transcriptional activation domain of the erg protein. Therefore alterations in both DNA binding and transcriptional activation properties of aberrant erg proteins may be responsible for the genesis of t(16;21) chromosomal translocation-bearing human myeloid leukemias. C1 THOMAS JEFFERSON UNIV,JEFFERSON CANC INST,DEPT MICROBIOL & IMMUNOL,PHILADELPHIA,PA 19107. NCI,FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC,FREDERICK,MD 21702. FU NCI NIH HHS [CA 51083, CA 57157, CA 58642] NR 51 TC 125 Z9 127 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD DEC PY 1994 VL 9 IS 12 BP 3717 EP 3729 PG 13 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA PT392 UT WOS:A1994PT39200038 PM 7970732 ER PT J AU ZHAN, QM FAN, SJ BAE, I GUILLOUF, C LIEBERMANN, DA OCONNOR, PM FORNACE, AJ AF ZHAN, QM FAN, SJ BAE, I GUILLOUF, C LIEBERMANN, DA OCONNOR, PM FORNACE, AJ TI INDUCTION OF BAX BY GENOTOXIC STRESS IN HUMAN-CELLS CORRELATES WITH NORMAL P53 STATUS AND APOPTOSIS SO ONCOGENE LA English DT Article ID WILD-TYPE P53; ATAXIA-TELANGIECTASIA; IONIZING-RADIATION; NITROGEN-MUSTARD; BINDING-SITE; CYCLE ARREST; PROTEIN; BCL-2; DEATH; GENE AB DNA-damaging agents such as ionizing radiation (IR) activate the tumor suppressor p53 and in some cases can cause apoptosis. M1 cells, which do not express the endogenous tumor suppressor gene p53, undergo apoptosis following activation of a temperature sensitive p53 transgene, where it has been shown that bax, an important mediator of apoptosis, is a p53 target gene (Selvakumaran et al, Oncogene 9, 1791-8, 1994). Since p53 can function as a transcription factor after activation by IR, the genetic response to this stress was examined in a panel of human cells with defined p53 status. Like the p53-regulated gene gadd45, bax was rapidly induced, as measured by increased mRNA levels,in the p53 wt (wild type) human myeloid line ML-1, and it was not induced in cells lacking functional p53. However, unlike other p53-regulated genes, bax was only induced in p53 wt cells in which IR also triggered apoptosis. In the case of bc12, which opposes bax function, mRNA levels were reduced in ML-1 cells after IR. Thus, bax appears to be an unique p53-regulated gene in that its induction by IR not only requires functional p53 but also requires that the cells be apoptosis ''proficient.'' C1 NCI, DIV CANC TREATMENT, MOLEC PHARMACOL LAB, DEV THERAPEUT PROGRAM, BETHESDA, MD 20892 USA. TEMPLE UNIV, SCH MED, FELS INST CANC RES & MOLEC BIOL, PHILADELPHIA, PA 19140 USA. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X FU NCI NIH HHS [1RO1CA43618] NR 45 TC 398 Z9 406 U1 1 U2 6 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD DEC PY 1994 VL 9 IS 12 BP 3743 EP 3751 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA PT392 UT WOS:A1994PT39200041 PM 7970735 ER PT J AU RHEW, K FIEDLER, DA LUDLOW, CL AF RHEW, K FIEDLER, DA LUDLOW, CL TI TECHNIQUE FOR INJECTION OF BOTULINUM TOXIN THROUGH THE FLEXIBLE NASOLARYNGOSCOPE SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID ADDUCTOR SPASMODIC DYSPHONIA; MUSCLE AB A new endoscopic method of injecting botulinum toxin into the thyroarytenoid muscles for treatment of adductor spasmodic dysphonia was evaluated. Twelve patients with adductor spasmodic dysphonia were given injections in the thyroarytenoid muscle under video visualization with a flexible catheter needle that was passed through the working channel of a flexible nasolaryngoscope. Six patients received unilateral injections, and six received bilateral injections. Preinjection and postinjection speech samples were compared by use of spectrographic analysis. Significant decreases in voice breaks and sentence duration were found after treatment with both unilateral and bilateral injections. Patient interviews and diaries documented the reported degree and duration of symptom reduction. All 12 patients reported that the injections were of significant benefit and that the endoscopic procedure was tolerable. We concluded that this is a safe and effective technique for injecting botulinum toxin into laryngeal muscles for treatment of spasmodic dysphonia. C1 NIDOCD,VOICE & SPEECH SECT,BETHESDA,MD. OI Ludlow, Christy/0000-0002-2015-6171 NR 15 TC 38 Z9 38 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD DEC PY 1994 VL 111 IS 6 BP 787 EP 794 DI 10.1016/S0194-5998(94)70569-0 PG 8 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA PX413 UT WOS:A1994PX41300016 PM 7991260 ER PT J AU FUJITA, K SILVER, J AF FUJITA, K SILVER, J TI SINGLE-STRAND CONFORMATIONAL POLYMORPHISM SO PCR-METHODS AND APPLICATIONS LA English DT Article ID POLYMERASE CHAIN-REACTION; POINT MUTATIONS; SSCP ANALYSIS; PCR-SSCP; GEL-ELECTROPHORESIS; DNA; RNA; OPTIMIZATION; EFFICACY; GENE RP FUJITA, K (reprint author), NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892, USA. NR 31 TC 10 Z9 10 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 1054-9803 J9 PCR METH APPL JI PCR-Methods Appl. PD DEC PY 1994 VL 4 IS 3 BP S137 EP S140 PG 4 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA RM626 UT WOS:A1994RM62600013 PM 7580895 ER PT J AU REICHELDERFER, PS JACKSON, JB AF REICHELDERFER, PS JACKSON, JB TI QUALITY ASSURANCE AND USE OF PCR IN CLINICAL-TRIALS SO PCR-METHODS AND APPLICATIONS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; POLYMERASE CHAIN-REACTION; MONONUCLEAR-CELLS; HIV-INFECTION; DNA; PLASMA; QUANTITATION; INDIVIDUALS; THERAPY; QUANTIFICATION C1 CASE WESTERN RESERVE UNIV,INST PATHOL,CLEVELAND,OH 44106. UNIV HOSP CLEVELAND,CLEVELAND,OH 44106. RP REICHELDERFER, PS (reprint author), NIAID,DIV AIDS,BETHESDA,MD 20892, USA. NR 44 TC 6 Z9 7 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 1054-9803 J9 PCR METH APPL JI PCR-Methods Appl. PD DEC PY 1994 VL 4 IS 3 BP S141 EP S149 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA RM626 UT WOS:A1994RM62600014 PM 7580896 ER PT J AU STRATTON, P AF STRATTON, P TI TREATMENT OPTIONS AND CARE OF HIV-INFECTED PREGNANT-WOMEN SO PEDIATRIC AIDS AND HIV INFECTION-FETUS TO ADOLESCENT LA English DT Article RP STRATTON, P (reprint author), NICHHD,POPULAT RES CTR,CONTRACEPT DEV BRANCH,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1045-5418 J9 PEDIATR AIDS HIV INF JI Pediatr. AIDS HIV Infect.-Fetus Adolesc. PD DEC PY 1994 VL 5 IS 6 BP 333 EP 343 PG 11 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA PZ880 UT WOS:A1994PZ88000001 PM 11361374 ER PT J AU NOZYCE, M HITTELMAN, J MUENZ, L DURAKO, SJ FISCHER, ML WILLOUGHBY, A AF NOZYCE, M HITTELMAN, J MUENZ, L DURAKO, SJ FISCHER, ML WILLOUGHBY, A TI EFFECT OF PERINATALLY ACQUIRED HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION ON NEURODEVELOPMENT IN CHILDREN DURING THE FIRST 2 YEARS OF LIFE SO PEDIATRICS LA English DT Article DE HUMAN IMMUNODEFICIENCY VIRUS; CHILD DEVELOPMENT ID IMMUNE-DEFICIENCY SYNDROME; INFANTS; WOMEN; HISTORY; BORN AB Objective. To determine the timing, extent, and magnitude of neurodevelopmental problems in children with perinatal HIV infection compared to similar uninfected children of HIV-infected women and controls. Methods. Neurodevelopmental assessments during the first 24 months of life for 21 HIV-infected children born to HIV-infected mothers, 65 seroreverted children born to HIV-infected mothers, and 95 non-HIV-infected children born to non-HIV-infected mothers were analyzed. Neurodevelopment was assessed by using the Bayley Scales of Infant Development beginning at 3 months of age. Kent Scoring Adaptation was also utilized. A two-stage Hierarchical Linear Model was used for analysis of neurodevelopmental scores. Results. In the initial comparison of these three groups, infected children had significantly lower scores on the Mental Development Index (MDI) and Psychomotor Development Index (PDI) than the other two groups. The HIV-infected children were further classified into HIV-infected without Centers for Disease Control-defined AIDS, those with lymphoid interstitial pneumonitis (LIP) only as their AIDS-defining illness, and children with an AIDS-defining diagnosis other than LIP in the first 24 months. The children with LIP-only AIDS and the infected children without AIDS on average were not significantly different from the seroreverters or the controls on MDI or PDI, while the children with non-LIP AIDS had significantly lower scores after 3 months of age. Analysis of the Kent scores indicated that the decrement in the non-LIP AIDS children was seen in all five functional domains. Conclusion. Children with serious HIV symptomatology appear to be at very high risk for serious developmental impairments, HIV-infected children not highly symptomatic have relatively normal neurodevelopment, and uninfected children of HIV-infected mothers do not appear to be adversely affected by the mother's HIV infection. C1 NICHHD,CTR RES MOTHERS & CHILDREN,ROCKVILLE,MD 20852. BRONX LEBANON HOSP CTR,DEPT PEDIAT,BRONX,NY 10457. SUNY DOWNSTATE MED CTR,DEPT PSYCHIAT,BROOKLYN,NY 11203. WESTAT CORP,ROCKVILLE,MD 20850. NR 17 TC 74 Z9 76 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD DEC PY 1994 VL 94 IS 6 BP 883 EP 891 PN 1 PG 9 WC Pediatrics SC Pediatrics GA PU835 UT WOS:A1994PU83500016 PM 7971006 ER PT J AU FRIEDMAN, SL BROOKSGUNN, J VANDELL, D WEINRAUB, M AF FRIEDMAN, SL BROOKSGUNN, J VANDELL, D WEINRAUB, M TI EFFECTS OF CHILD-CARE ON PSYCHOLOGICAL-DEVELOPMENT - ISSUES AND FUTURE-DIRECTIONS FOR RESEARCH SO PEDIATRICS LA English DT Article; Proceedings Paper CT International Conference on Child Day Care Health: Science, Prevention, and Practice CY JUN 15-17, 1992 CL ATLANTA, GA SP CTR DISEASE CONTROL AND PREVENTION, ADM CHILDREN & FAMILIES, AMER ACAD PEDIAT, AMER PUBLIC HLTH ASSOC, ASSOC STATE & TERRITORIAL HLTH OFFICIALS, HLTH RESOURCES & SERV ADM, INTER PEDIAT ASSOC, NATL ASSOC EDUC YOUNG CHILDREN, NATL CTR CLIN INFANT PROGRAMS, NIH, TASK FORCE CHILD SURVIVAL & DEV, UNITED NATL CHILDRENS FUND, WHO ID NATIONAL LONGITUDINAL SURVEY; YOUTH RP FRIEDMAN, SL (reprint author), NICHHD,CTR RES MOTHERS & CHILDREN,HUMAN LEARNING & BEHAV BRANCH,BETHESDA,MD 20892, USA. NR 18 TC 1 Z9 1 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD DEC PY 1994 VL 94 IS 6 SU S BP 1069 EP 1070 PG 2 WC Pediatrics SC Pediatrics GA PW229 UT WOS:A1994PW22900045 PM 7971061 ER PT J AU CAIN, VS AF CAIN, VS TI CHILD-CARE AND CHILD HEALTH - USE OF POPULATION SURVEYS SO PEDIATRICS LA English DT Article; Proceedings Paper CT International Conference on Child Day Care Health: Science, Prevention, and Practice CY JUN 15-17, 1992 CL ATLANTA, GA SP CTR DISEASE CONTROL AND PREVENTION, ADM CHILDREN & FAMILIES, AMER ACAD PEDIAT, AMER PUBLIC HLTH ASSOC, ASSOC STATE & TERRITORIAL HLTH OFFICIALS, HLTH RESOURCES & SERV ADM, INTER PEDIAT ASSOC, NATL ASSOC EDUC YOUNG CHILDREN, NATL CTR CLIN INFANT PROGRAMS, NIH, TASK FORCE CHILD SURVIVAL & DEV, UNITED NATL CHILDRENS FUND, WHO ID ILLNESS RP CAIN, VS (reprint author), NICHHD,BETHESDA,MD 20892, USA. NR 14 TC 2 Z9 2 U1 1 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD, ELK GROVE VILLAGE, IL 60007-1098 SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD DEC PY 1994 VL 94 IS 6 SU S BP 1096 EP 1098 PG 3 WC Pediatrics SC Pediatrics GA PW229 UT WOS:A1994PW22900057 PM 7971073 ER PT J AU GOLDSTEIN, JA DEMORAIS, SMF AF GOLDSTEIN, JA DEMORAIS, SMF TI BIOCHEMISTRY AND MOLECULAR-BIOLOGY OF THE HUMAN CYP2C SUBFAMILY SO PHARMACOGENETICS LA English DT Review ID HUMAN-LIVER CYTOCHROME-P-450; MEPHENYTOIN HYDROXYLATION DEFICIENCY; OXIDATIVE DRUG-METABOLISM; S-MEPHENYTOIN; GENETIC-POLYMORPHISM; DIAZEPAM METABOLISM; TOLBUTAMIDE HYDROXYLATION; INTERETHNIC DIFFERENCES; OMEPRAZOLE METABOLISM; SLOW METABOLIZERS AB The cytochromes P450 (CYP) are a superfamily of hemoproteins which metabolize foreign chemicals as well as a number of endogenous compounds such as steroids, The human CYP2C subfamily appears to principally metabolize a number of clinically used drugs, Four members of this subfamily have been identified in humans: CYP2C8, CYP2C9, CYP2C18, and CYP2C19. CYP2C9 is important in the metabolism certain of therapeutically used drugs including the anticoagulant drug warfarin and a number of nonsteroidal antiinflammatory drugs, A number of allelic variants of CYP2C9 exist in humans, but the effects of these allelic variants on metabolism in vivo remain to be determined. A well-characterized genetic polymorphism occurs in the 2C subfamily which is associated with the metabolism of the anticonvulsant drug mephenytoin, In population studies, individuals can be segregated into extensive and poor metabolizers of mephenytoin. Poor metabolizers are unable to 4'-hydroxylate the S-enantiomer of mephenytoin. There are marked interracial variations in the frequency of the poor metabolizer phenotype which represents 3-5% of Caucasians, but 18-23% of Oriental populations, The mechanism of this polymorphism has been recently elucidated, The enzyme responsible for S-mephenytoin metabolism has been shown to be CYP2C19, and two defects in the CYP2C19 gene have been described in poor metabolizers, The first defect, CYP2C19(m1) consists of the creation of an aberrant splice site in exon 5, This defect accounts for similar to 75-85% of Caucasian and Japanese poor metabolizers, A second defect, CYP2C19(m2) has been found only in Oriental populations and accounts for the remaining 25% of poor metabolizers in Japanese populations, The availability of genotyping tests for this polymorphism will enhance the assessment of the role of this pathway in clinical studies. RP GOLDSTEIN, JA (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 99 TC 434 Z9 446 U1 1 U2 18 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD DEC PY 1994 VL 4 IS 6 BP 285 EP 299 DI 10.1097/00008571-199412000-00001 PG 15 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA PZ832 UT WOS:A1994PZ83200001 PM 7704034 ER PT J AU DEERAUSQUIN, GA COSTA, E HANBAUER, I AF DEERAUSQUIN, GA COSTA, E HANBAUER, I TI CALCIUM HOMEOSTASIS, FREE-RADICAL FORMATION, AND TROPHIC FACTOR DEPENDENCE MECHANISMS IN PARKINSONS-DISEASE SO PHARMACOLOGICAL REVIEWS LA English DT Review ID MESENCEPHALIC DOPAMINERGIC-NEURONS; PROGRESSIVE SUPRANUCLEAR PALSY; GANGLIOSIDE-INDUCED RECOVERY; CEREBELLAR GRANULE NEURONS; FIBROBLAST GROWTH-FACTOR; MONOAMINE-DEPLETED RATS; D-ASPARTATE ANTAGONISTS; PROGRAMMED CELL-DEATH; SUBSTANTIA-NIGRA; NEUROTROPHIC FACTOR C1 NHLBI,MOLEC IMMUNOL LAB,BETHESDA,MD 20892. YALE UNIV,SCH MED,W HAVEN,CT 06516. NATHAN S KLINE INST PSYCHIAT RES,CTR NEUROPHARMACOL,ORANGEBURG,NY. RI de Erausquin, Gabriel/G-5840-2010 OI de Erausquin, Gabriel/0000-0001-6423-4461 NR 145 TC 30 Z9 30 U1 1 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-6997 J9 PHARMACOL REV JI Pharmacol. Rev. PD DEC PY 1994 VL 46 IS 4 BP 467 EP 482 PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA PY825 UT WOS:A1994PY82500003 PM 7899474 ER PT J AU MAURICE, T SU, TP PARISH, DW NABESHIMA, T PRIVAT, A AF MAURICE, T SU, TP PARISH, DW NABESHIMA, T PRIVAT, A TI PRE-084, A SIGMA SELECTIVE PCP DERIVATIVE, ATTENUATES MK-801-INDUCED IMPAIRMENT OF LEARNING IN MICE SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE SIGMA SITES; PRE-084; N-METHYL-D-ASPARTATE RECEPTOR; MK-801-INDUCED AMNESIA; CHRONIC TREATMENT; PASSIVE AVOIDANCE TEST; Y-MAZE TEST; MECAMYLAMINE; AMNESIA MODELS ID EXTRACELLULAR ACETYLCHOLINE LEVEL; INDUCED NEURONAL ACTIVATION; ELEVATED PLUS-MAZE; RAT FRONTAL-CORTEX; ANTIPSYCHOTIC-DRUGS; RECEPTORS; PHENCYCLIDINE; RELEASE; LIGAND; ASPARTATE AB We investigated the effect of the a selective PCP derivative PRE-084 on the impairment of learning induced in mice by the noncompetitive NMDA antagonist MK-801. Learning capacities were evaluated using the spontaneous alternation in a Y-maze test for spatial working memory, the step-down passive avoidance and the elevated plus-maze test for long-term memory. At doses about 1 mg/kg IP, PRE-084 significantly attenuated MK-801 (0.2 mg/kg IP) induced impairment of learning. The dose-response curve was bell-shaped which is typical for cognition enhancers. The effect of PRE-084 was antagonized by BMY-14802 (10 mg/kg IP) and suppressed by a chronic treatment with haloperidol (4 mg/kg/day SC for 7 days). Furthermore, PRE-084 did not affect scopolamine (1 mg/kg SC) induced amnesia but significantly attenuated mecamylamine (10 mg/kg IP) induced amnesia. These results show that a sites mediate a modulation of the NMDA receptor complex-dependent learning processes and may similarly affect the cholinergic nicotinic memory processes. Moreover, the PCP derivative PRE-084, acting selectively at a sites, reverses the amnesia induced by a drug acting at the PCP site. C1 NIDA,INTRAMURAL RES PROGRAM,BALTIMORE,MD 21224. BIOCAD CORP,SUNNYVALE,CA 94086. NAGOYA UNIV,SCH MED,DEPT NEUROPSYCHOPHARMACOL,SHOWA KU,NAGOYA,AICHI 466,JAPAN. NAGOYA UNIV,SCH MED,HOSP PHARM,SHOWA KU,NAGOYA,AICHI 466,JAPAN. RP MAURICE, T (reprint author), ECOLE NATL SUPER CHIM MONTPELLIER,INSERM,U336,8 RUE ECOLE NORMALE,F-34053 MONTPELLIER 1,FRANCE. NR 42 TC 77 Z9 80 U1 5 U2 8 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 DEC PY 1994 VL 49 IS 4 BP 859 EP 869 DI 10.1016/0091-3057(94)90235-6 PG 11 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA PU333 UT WOS:A1994PU33300014 PM 7886099 ER PT J AU MASSIOT, G DIJOUX, MG LAVAUD, C LEMENOLIVIER, L CONNOLLY, JD SHEELEY, DM AF MASSIOT, G DIJOUX, MG LAVAUD, C LEMENOLIVIER, L CONNOLLY, JD SHEELEY, DM TI SECO-GLYCOSIDES OF OLEANOLIC ACID FROM BETA-VULGARIS SO PHYTOCHEMISTRY LA English DT Article DE BETA VULGARIS; CHENOPODIACEAE; SUGAR BEET; TRITERPENE SAPONINS ID MOLLUSCICIDAL SAPONINS; CONSTITUENTS AB Two new oleanolic acid saponins were isolated from the leaves and roots of Beta vulgaris. Both contained the unusual feature of a 3,4 seco-glycopyranosyl moiety. Their structures were established by a combination of 2D NMR experiments and of Californium plasma desorption mass spectrometry. C1 UNIV GLASGOW,DEPT CHEM,GLASGOW G12 8QQ,LANARK,SCOTLAND. NHLBI,BIOPHYS CHEM LAB,BETHESDA,MD 20892. RP MASSIOT, G (reprint author), FAC PHARM REIMS,CNRS,URA 492,PHARMACOGNOSIE LAB,51 RUE COGNACQ JAY,F-51096 REIMS,FRANCE. NR 9 TC 24 Z9 25 U1 2 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0031-9422 J9 PHYTOCHEMISTRY JI Phytochemistry PD DEC PY 1994 VL 37 IS 6 BP 1667 EP 1670 DI 10.1016/S0031-9422(00)89589-8 PG 4 WC Biochemistry & Molecular Biology; Plant Sciences SC Biochemistry & Molecular Biology; Plant Sciences GA QN609 UT WOS:A1994QN60900023 PM 7766003 ER PT J AU TABACOVA, S BAIRD, DD BALABAEVA, L LOLOVA, D PETROV, I AF TABACOVA, S BAIRD, DD BALABAEVA, L LOLOVA, D PETROV, I TI PLACENTAL ARSENIC AND CADMIUM IN RELATION TO LIPID PEROXIDES AND GLUTATHIONE LEVELS IN MATERNAL-INFANT PAIRS FROM A COPPER SMELTER AREA SO PLACENTA LA English DT Article AB Arsenic exposure may enhance oxidative damage causing adverse health effects in pregnant women. The purposes of this paper are: (i) to evaluate placental arsenic concentration as a biomarker of arsenic exposure for pregnant women; and (ii) to examine the relationship between metal exposure from a copper smelter area in Bulgaria and oxidative damage during pregnancy (as measured by glutathione and lipid peroxides) in 49 maternal-infant pairs. Placental levels of arsenic were highest in areas with the highest environmental contamination, and environmental variables (residency, smoking and occupational exposure) explained a large portion of the observed variability placental arsenic levels (linear regression R(2) = 0.71). The combined exposures of smoking and living in the smelter area were associated with lower glutathione antioxidant protection. The per Gent maternal and cord blood glutathione in reduced for was significantly lower for smokers compared to nonsmokers in the smelter area (47 versus 66 per cent in maternal blood, P < 0.01, and 60 versus 75 per cent in cord blood, P < 0.05). Higher concentrations of lipid peroxides in maternal blood cord blood and placenta, though not statistically significant, suggested that pregnant women with both exposures may be at higher risk of oxidative damage. C1 NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC 27709. NATL CTR HYG ECOL & NUTR,BU-1431 SOFIA,BULGARIA. OI Baird, Donna/0000-0002-5544-2653 NR 13 TC 48 Z9 48 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0143-4004 J9 PLACENTA JI Placenta PD DEC PY 1994 VL 15 IS 8 BP 873 EP 881 DI 10.1016/S0143-4004(05)80188-2 PG 9 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA PY770 UT WOS:A1994PY77000008 PM 7886027 ER PT J AU HERMAN, EM LI, XH SU, RT LARSEN, P HSU, HT SZE, H AF HERMAN, EM LI, XH SU, RT LARSEN, P HSU, HT SZE, H TI VACUOLAR-TYPE H+-ATPASES ARE ASSOCIATED WITH THE ENDOPLASMIC-RETICULUM AND PROVACUOLES OF ROOT-TIP CELLS SO PLANT PHYSIOLOGY LA English DT Article ID PROTON-TRANSLOCATING ATPASE; CLATHRIN-COATED VESICLES; SUBUNIT COMPOSITION; OAT ROOTS; HIGHER-PLANT; BIOLOGICAL-MEMBRANES; TONOPLAST; PROTEIN; LOCALIZATION; ORGANIZATION AB To understand the origin of vacuolar H+-ATPases (V-ATPases) and their cellular functions, the subcellular location of V-H+-ATPases was examined immunologically in root cells of oat seedlings. A V-ATPase complex from oat roots consists of a large peripheral sector (V-1) that includes the 70-kD (A) catalytic and the 60-kD (B) regulatory subunits. The soluble V, complex, thought to be synthesized in the cytoplasm, is assembled with the membrane integral sector (V-0) at a yet undefined location. In mature cells, V-ATPase subunits A and B, detected in immunoblots with monoclonal antibodies (Mab) (7A5 and 2E7), were associated mainly with vacuolar membranes (20-22% sucrose) fractionated with an isopycnic sucrose gradient. However, in immature root tip cells, which lack large vacuoles, most of the V-ATPase was localized with the endoplasmic reticulum (ER) at 28 to 31% sucrose where a major ER-resident binding protein equilibrated. The peripheral subunits were also associated with membranes at 22% sucrose, at 31 to 34% sucrose (Golgi), and in plasma membranes at 38% sucrose. Immunogold labeling of root tip cells with Mab 2E7 against subunit B showed gold particles decorating the ER as well as numerous small vesicles (0.1-0.3 mu m diameter), presumably provacuoles. The immunological detection of the peripheral subunit B on the ER supports a model in which the V-1 sector is assembled with the V-0 on the ER. These results support the model in which the central vacuolar membrane originates ultimately from the ER. The presence of V-ATPases on several endomembranes indicates that this pump could participate in diverse functional roles. C1 UNIV MARYLAND,DEPT BOT,COLLEGE PK,MD 20742. USDA ARS,PLANT MOLEC BIOL LAB,BELTSVILLE,MD 20705. USDA ARS,FLORIST & NURSERY CROPS LAB,BELTSVILLE,MD 20705. NIH,DIV RES GRANTS,BETHESDA,MD 20892. NR 58 TC 78 Z9 80 U1 0 U2 0 PU AMER SOC PLANT PHYSIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 SN 0032-0889 J9 PLANT PHYSIOL JI Plant Physiol. PD DEC PY 1994 VL 106 IS 4 BP 1313 EP 1324 PG 12 WC Plant Sciences SC Plant Sciences GA PY046 UT WOS:A1994PY04600010 ER PT J AU CHARY, KVR RASTOGI, V GOVIL, G HOWARD, FB MILES, HT AF CHARY, KVR RASTOGI, V GOVIL, G HOWARD, FB MILES, HT TI H-1 AND P-31 RESONANCE ASSIGNMENTS AND SECONDARY STRUCTURE OF HAIRPIN CONFORMER OF IA MISMATCHED OLIGONUCLEOTIDE D-GGTACIAGTACC SO PROCEEDINGS OF THE INDIAN ACADEMY OF SCIENCES-CHEMICAL SCIENCES LA English DT Article DE CONFORMERS OF D-GGTACIAGTACC; NMR ASSIGNMENTS; MISMATCHED OLIGONUCLEOTIDE ID DOUBLE HELIX; DEOXYINOSINE; MACROMOLECULES; PROBE AB Almost complete H-1 and P-31 resonance assignments of two coexisting conformers (duplex and an hairpin) of d-GGTACIAGTACC at 1.25 mM concentration and 305 K have been achieved. The results demonstrate that the hairpin conformer has a structure with two purines I6 and A7 forming a two-base loop on a B-DNA stem. Stacking is continued on the 5'-side of the loop, with the 16 stacked upon C5. The base A7, on the 3'-side of the loop stacks partially with I6. The glycosidic angle for G8 is in the anti domain and it maintains normal Watson-Crick base-pairing with the opposite C5. C1 TATA INST FUNDAMENTAL RES,CHEM PHYS GRP,BOMBAY 400005,MAHARASHTRA,INDIA. NIDDKD,BETHESDA,MD 20892. NR 28 TC 5 Z9 5 U1 0 U2 0 PU INDIAN ACADEMY SCIENCES PI BANGALORE PA P B 8005 C V RAMAN AVENUE, BANGALORE 560 080, INDIA SN 0253-4134 J9 P INDIAN AS-CHEM SCI JI Proc. Indian Acad. Sci.-Chem. Sci. PD DEC PY 1994 VL 106 IS 7 BP 1491 EP 1504 PG 14 WC Chemistry, Multidisciplinary SC Chemistry GA RA719 UT WOS:A1994RA71900008 ER PT J AU VANGELDEREN, P DUYN, JH LIU, GY MOONEN, CTW AF VANGELDEREN, P DUYN, JH LIU, GY MOONEN, CTW TI OPTIMAL T-2-ASTERISK WEIGHTING FOR BOLD-TYPE FUNCTIONAL MRI OF THE HUMAN BRAIN SO PROCEEDINGS OF THE INDIAN ACADEMY OF SCIENCES-CHEMICAL SCIENCES LA English DT Article DE ECHO TIME; NEURONAL ACTIVITY; INDUCED GRADIENTS; DIFFUSION EFFECTS; RF SPOILING; COHERENT PHASE; SPIN DENSITY ID BLOOD OXYGENATION AB Optimal T-2* weighting in BOLD functional MRI depends on the local field homogeneity. In areas with relatively poor shimming, the size of the BOLD effect decreases and the optimum echo time becomes smaller. T-2* weighting can be accomplished with echo-planar imaging and conventional gradient-echo imaging. Neither method is optimal, since part of the data is either acquired with short echo times (in case of EPI), or substantial time is lost due to delayed acquisition (in case of long echo time FLASH). To improve efficiency. Echo-Shifted gradient echo imaging can be used. For 2-D BOLD, a T-2* preparation period can be used as an alternative. C1 NIH,NCRR,BEIP,IN VIVO NMR RES CTR,BETHESDA,MD 20892. NIH,OIR,DIAGNOST RADIOL RES LAB,BETHESDA,MD 20892. RI Duyn, Jozef/F-2483-2010; Moonen, Chrit/K-4434-2016 OI Moonen, Chrit/0000-0001-5593-3121 NR 12 TC 5 Z9 5 U1 0 U2 1 PU INDIAN ACADEMY SCIENCES PI BANGALORE PA P B 8005 C V RAMAN AVENUE, BANGALORE 560 080, INDIA SN 0253-4134 J9 P INDIAN AS-CHEM SCI JI Proc. Indian Acad. Sci.-Chem. Sci. PD DEC PY 1994 VL 106 IS 7 BP 1617 EP 1624 PG 8 WC Chemistry, Multidisciplinary SC Chemistry GA RA719 UT WOS:A1994RA71900019 ER PT J AU SHEN, Y SPECHT, SM DESAINTGHISLAIN, I LI, R AF SHEN, Y SPECHT, SM DESAINTGHISLAIN, I LI, R TI THE HIPPOCAMPUS - A BIOLOGICAL MODEL FOR STUDYING LEARNING AND MEMORY SO PROGRESS IN NEUROBIOLOGY LA English DT Review ID LONG-TERM POTENTIATION; NICTITATING-MEMBRANE RESPONSE; HIGH-FREQUENCY STIMULATION; GRANULE CELL SYNAPSE; PYRAMIDAL CELLS; RAT HIPPOCAMPUS; PERFORANT PATH; LASTING POTENTIATION; GLUTAMATE RECEPTORS; NEURONAL PLASTICITY C1 NINCDS,EXPTL THERAPEUT BRANCH,BETHESDA,MD 20892. LEBANON VALLEY COLL,DEPT PSYCHOL,ANNVILLE,PA 17003. NIMH,NEUROSCI CTR ST ELIZABETHS,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032. UNIV LOUISVILLE,SCH MED,DEPT PSYCHIAT,LOUISVILLE,KY 40292. NR 124 TC 53 Z9 62 U1 2 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0301-0082 J9 PROG NEUROBIOL JI Prog. Neurobiol. PD DEC PY 1994 VL 44 IS 5 BP 485 EP 496 DI 10.1016/0301-0082(94)90008-6 PG 12 WC Neurosciences SC Neurosciences & Neurology GA QB252 UT WOS:A1994QB25200004 PM 7886236 ER PT J AU BENHAR, I PASTAN, I AF BENHAR, I PASTAN, I TI CLONING, EXPRESSION AND CHARACTERIZATION OF THE FV FRAGMENTS OF THE ANTICARBOHYDRATE MABS B1 AND B5 AS SINGLE-CHAIN IMMUNOTOXINS SO PROTEIN ENGINEERING LA English DT Article DE CANCER THERAPY; PSEUDOMONAS EXOTOXIN ID ESCHERICHIA-COLI; CARCINOMA; B3 AB The mAbs B1 (IgG1 kappa) and B5 (IgM kappa) recognize carbohydrate epitopes on human carcinoma cells. The Fv regions of these antibodies were separately cloned from hybridoma RNA using reverse transcription and PCR with oligonucleotide primers designed according to the amino acid sequences of the N-termini. The Fv regions also provide sequences for translation initiation in Escherichia coli (Fr1 oligos) and sequences of the constant region of the heavy and light domains (CH1 or C-kappa oligos). Following the determination of the DNA sequence of the Fvs, primers were designed according to the 3' ends of the V-H and V-L domains. These also provided for a peptide linker at the C-terminus of the V-H and a short connector at the C-terminus of the V-L (Fr4 oligos). The V-H and V-L were then each PCR-amplified using their corresponding Fr1 and phosphorylated Fr4 oligos. The resulting PCR products were annealed as 'mutagenic primers' to a uracil-containing single-stranded template obtained from an expression plasmid encoding a single-chain immunotoxin in which the B3 single-chain Fv is fused to a truncated form of Pseudomonas exotoxin (PE). Thus, the B1 and B5 variable domains replaced their corresponding B3 domains in the expression plasmid by 'variable domain shuffling' without subcloning. The resulting B1(Fv)-PE38 and B5(Fv)-PE38 were expressed in E. coli and purified to near homogeneity. Both show specific cytotoxicities to human carcinoma cell lines, but B1(Fv)-PE38 is much more active, reflecting its higher affinity to the target cells. C1 NCI,DIV CANC BIOL DIAG & CTR,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 23 TC 21 Z9 21 U1 0 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0269-2139 J9 PROTEIN ENG JI Protein Eng. PD DEC PY 1994 VL 7 IS 12 BP 1509 EP 1515 DI 10.1093/protein/7.12.1509 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA PY771 UT WOS:A1994PY77100014 PM 7716163 ER PT J AU OKOROKOV, AL HARTLEY, RW PANOV, KI AF OKOROKOV, AL HARTLEY, RW PANOV, KI TI AN IMPROVED SYSTEM FOR RIBONUCLEASE BA EXPRESSION SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article ID BARNASE AB The extracellular ribonuclease from Bacillus amyloliquefaciens (barnase, RNase Ba) is a well-characterized enzyme extensively used in structure-function studies. A new system for efficient expression and purification of barnase has been developed. The strong regulated expression cassette with the Pr promoter of lambda phage and the cooperative expression of barnase and barstar under its control have been applied to expression of these proteins in Escherichia coli. The expression cassette containing the Pr promoter of E. coli lambda phage under cI repressor regulation and the nucleotide sequence coding for barnase and barstar structural genes were merged into the plasmid pTN441, which was used for large-scale barnase production. The phoA signal peptide was used to express the target protein into cell periplasm. The purification of RNase Pa was carried out in two steps: the initial sample was concentrated followed by RP-HPLC. The system provides a stable yield of homogeneous protein of about 100-150 mg per liter of culture medium. (C) 1994 Academic Press, Inc. C1 NIDDK,BETHESDA,MD 20892. RP OKOROKOV, AL (reprint author), RUSSIAN ACAD SCI,VA ENGELHARDT MOLEC BIOL INST,VAVILOV STR 32,MOSCOW 117984,RUSSIA. NR 10 TC 13 Z9 13 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 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD DEC PY 1994 VL 5 IS 6 BP 547 EP 552 DI 10.1006/prep.1994.1075 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA PU343 UT WOS:A1994PU34300004 PM 7858423 ER PT J AU BORK, P KOONIN, EV AF BORK, P KOONIN, EV TI A P-LOOP-LIKE MOTH IN A WIDESPREAD ATP PYROPHOSPHATASE DOMAIN - IMPLICATIONS FOR THE EVOLUTION OF SEQUENCE MOTIFS AND ENZYME-ACTIVITY SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS LA English DT Article DE ATP HYDROLYSIS; HOMOLOGY; SULFATE METABOLISM; MOTIF EVOLUTION ID TRANSFER RNA-SYNTHETASE; BACILLUS-SUBTILIS; NUCLEOTIDE-SEQUENCE; SUGAR KINASES; DATA-BANK; PROTEIN; BINDING; COMMON; ALIGNMENT; GENE AB A conserved amino acid sequence motif was identified in four distinct groups of enzymes that catalyze the hydrolysis of the alpha-beta phosphate bond of ATP, namely GMP synthetases, argininosuccinate synthetases, asparagine synthetases, and ATP sulfurylases, The motif is also present in Rhodobacter capsulata AdgA, Escherichia coli NtrL, and Bacillus subtilis OutB, for which no enzymatic activities are currently known. The observed pattern of amino acid residue conservation and predicted secondary structures suggest that this motif may be a modified version of the P-loop of nucleotide binding domains, and that it is likely to be involved in phosphate binding. We call it PP-motif, since it appears to be a part of a previously uncharacterized ATP pyrophophatase domain. ATP sulfurylases, NtrL, and OutB consist of this domain alone, In other proteins, the pyrophosphatase domain is associated with amidotransferase domains (type I or type II), a putative citrulline-aspartate ligase domain or a nitrilase/amidase domain, Unexpectedly, statistically significant overall sequence similarity was found between ATP sulfurylase and 3'-phosphoadenosine 5'-phosphosulfate (PAPS) reductase, another protein of the sulfate activation pathway, The PP-motif is strongly modified in PAPS reductases, but they share with ATP sulfurylases another conserved motif which might be involved in sulfate binding, We propose that PAPS reductases may have evolved from ATP sulfurylases; the evolution of the new enzymatic function appears to be accompanied by a switch of the strongest functional constraint from the PP-motif to the putative sulfate-binding motif. (C) 1994 Wiley-Liss, Inc. C1 NATL LIB MED, NATL CTR BIOTECHNOL INFORMAT, BETHESDA, MD 20894 USA. EUROPEAN MOLEC BIOL LAB, D-69012 HEIDELBERG, GERMANY. MAX DELBRUCK CTR, D-13189 BERLIN, GERMANY. RI Bork, Peer/F-1813-2013 OI Bork, Peer/0000-0002-2627-833X NR 45 TC 87 Z9 88 U1 0 U2 3 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 DEC PY 1994 VL 20 IS 4 BP 347 EP 355 DI 10.1002/prot.340200407 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA QH321 UT WOS:A1994QH32100006 PM 7731953 ER PT J AU GEORGE, MS AF GEORGE, MS TI INTRODUCTION - THE EMERGING NEUROANATOMY OF DEPRESSION SO PSYCHIATRIC ANNALS LA English DT Editorial Material RP GEORGE, MS (reprint author), NIMH,BLDG 10,RM 3N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 0 TC 9 Z9 9 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD DEC PY 1994 VL 24 IS 12 BP 635 EP 636 PG 2 WC Psychiatry SC Psychiatry GA PX436 UT WOS:A1994PX43600003 ER PT J AU KETTER, TA GEORGE, MS RING, HA PAZZAGLIA, P MARANGELL, L KIMBRELL, TA POST, RM AF KETTER, TA GEORGE, MS RING, HA PAZZAGLIA, P MARANGELL, L KIMBRELL, TA POST, RM TI PRIMARY MOOD DISORDERS - STRUCTURAL AND RESTING FUNCTIONAL-STUDIES SO PSYCHIATRIC ANNALS LA English DT Article; Proceedings Paper CT Emerging Neuroanatomy of Depression Symposium, at the 1994 Annual Meeting of the American-Psychiatric-Association CY 1994 CL PHILADELPHIA, PA SP AMER PSYCHIAT ASSOC ID CEREBRAL BLOOD-FLOW; COGNITIVE IMPAIRMENT; EMISSION TOMOGRAPHY; DEPRESSED-PATIENTS; REDUCTION; CORTEX C1 UCL, NATL HOSP NERVOUS DIS, RAYMOND WAY NEUROPSYCHIAT RES GRP, LONDON, ENGLAND. RP KETTER, TA (reprint author), NIMH, BIOL PSYCHIAT BRANCH,W CLIN RES UNIT 3,BLDG 10, RM 3N212, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. RI Ring, Howard/G-6684-2011 NR 31 TC 17 Z9 18 U1 1 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD DEC PY 1994 VL 24 IS 12 BP 637 EP 642 PG 6 WC Psychiatry SC Psychiatry GA PX436 UT WOS:A1994PX43600004 ER PT J AU GEORGE, MS KETTER, TA POST, RM AF GEORGE, MS KETTER, TA POST, RM TI ACTIVATION STUDIES IN MOOD DISORDERS SO PSYCHIATRIC ANNALS LA English DT Article; Proceedings Paper CT Emerging Neuroanatomy of Depression Symposium, at the 1994 Annual Meeting of the American-Psychiatric-Association CY 1994 CL PHILADELPHIA, PA SP AMER PSYCHIAT ASSOC ID DORSOLATERAL PREFRONTAL CORTEX; POSITRON EMISSION TOMOGRAPHY; CEREBRAL BLOOD-FLOW; HUMAN-BRAIN; SCHIZOPHRENIA; DYSFUNCTION; MECHANISM RP GEORGE, MS (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,RM 3N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 34 TC 10 Z9 11 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD DEC PY 1994 VL 24 IS 12 BP 648 EP 652 PG 5 WC Psychiatry SC Psychiatry GA PX436 UT WOS:A1994PX43600006 ER PT J AU JOYCE, EM RIO, DE RUTTIMANN, UE ROHRBAUGH, JW MARTIN, PR RAWLINGS, RR ECKARDT, MJ AF JOYCE, EM RIO, DE RUTTIMANN, UE ROHRBAUGH, JW MARTIN, PR RAWLINGS, RR ECKARDT, MJ TI DECREASED CINGULATE AND PRECUNEATE GLUCOSE-UTILIZATION IN ALCOHOLIC KORSAKOFFS-SYNDROME SO PSYCHIATRY RESEARCH LA English DT Article DE ALCOHOL DEPENDENCE; POSITRON EMISSION TOMOGRAPHY; COMPUTED TOMOGRAPHY; ELECTROENCEPHALOGRAPHY; CINGULATE CORTEX ID CEREBRAL BLOOD-FLOW; POSITRON EMISSION TOMOGRAPHY; ALZHEIMERS-DISEASE; PSYCHOSIS; IMPAIRMENT; AMNESIA; DEFICIT AB Localized cerebral glucose utilization was determined for nine abstinent alcoholic men with Korsakoff's syndrome and 10 age-matched normal men who underwent positron emission tomography with [F-18]2-fluoro-2-deoxyglucose (FDG). Patients with Korsakoff's syndrome showed relatively decreased glucose utilization in cingulate and precuneate areas. These decreases persisted even after correction for group differences in ventricular and sulcal cerebrospinal fluid measured on computed tomography. Electroencephalographic recordings at the time of FDG uptake showed no group differences, a finding that demonstrates that the metabolic differences could not be explained by differences in physiological arousal at the time of scanning. It is concluded that the decreased glucose utilization in the patients reflects a disruption of memory circuitry, the Papez circuit, caused by diencephalic lesions induced by thiamine deficiency. C1 NIAAA,CLIN STUDIES LAB,BETHESDA,MD 20892. WASHINGTON UNIV,DEPT PSYCHIAT,ST LOUIS,MO. VANDERBILT UNIV,SCH MED,DEPT PSYCHIAT,NASHVILLE,TN 37212. RP JOYCE, EM (reprint author), CHARING CROSS & WESTMINSTER MED SCH,DEPT PSYCHIAT,ST DUNSTANS RD,LONDON W6 8RP,ENGLAND. RI Martin, Peter/A-7738-2008 NR 39 TC 35 Z9 36 U1 1 U2 1 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD DEC PY 1994 VL 54 IS 3 BP 225 EP 239 DI 10.1016/0165-1781(94)90017-5 PG 15 WC Psychiatry SC Psychiatry GA QK587 UT WOS:A1994QK58700001 PM 7792327 ER PT J AU GEORGE, MS ROBERTSON, MM COSTA, DC ELL, PJ TRIMBLE, MR PILOWSKY, L VERHOEFF, NPLG AF GEORGE, MS ROBERTSON, MM COSTA, DC ELL, PJ TRIMBLE, MR PILOWSKY, L VERHOEFF, NPLG TI DOPAMINE-RECEPTOR AVAILABILITY IN TOURETTES-SYNDROME SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY; NEUROLEPTICS; (123)IODO-6-METHOXYBENZAMIDE; TICS ID OBSESSIVE-COMPULSIVE DISORDER; BASAL GANGLIA; CHILDREN; HUMANS; I-123; SPECT; MRI AB A large body of evidence suggests that abnormal dopaminergic activity is present in Gilles de la Tourette Syndrome (GTS). To investigate whether dopamine dysregulation involving the D-2/D-3 receptor occurs in GTS, we performed single slice dynamic single photon emission computed tomography (SPECT) with (123)iodo-6-methoxybenzamide (I-123-IBZM) in 15 GTS patients (eight unmedicated) and six healthy volunteers. After intravenous administration of 5 mCi (185 MBq) of I-123-IBZM, dynamic SPECT (5 minutes per slice) studies were performed at the level of the basal ganglia for 55 minutes. The mean activity per pixel in the basal ganglia was compared with the mean activity per pixel in the visual cortex. Unmedicated GTS patients showed no differences from control subjects. However, GTS patients taking D-2 blocking medications had significantly decreased I-123-IBZM binding compared with control subjects in both the right and left basal ganglia. Thus, D-2/D-3 receptor availability, as measured by I-123-IBZM SPECT, is not abnormal in GTS. C1 MED UNIV S CAROLINA,DEPT PSYCHIAT & BEHAV SCI,CHARLESTON,SC 29425. UNIV COLL & MIDDLESEX SCH MED,DEPT PSYCHIAT,LONDON,ENGLAND. INST NUCL MED,LONDON,ENGLAND. INST NEUROL,DEPT CLIN NEUROL,RAYMOND WAY READER RES GRP,LONDON WC1N 3BG,ENGLAND. INST PSYCHIAT,LONDON,ENGLAND. TECH UNIV EINDHOVEN,5600 MB EINDHOVEN,NETHERLANDS. RP GEORGE, MS (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,ROOM 3N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 37 TC 48 Z9 48 U1 1 U2 1 PU ELSEVIER SCI PUBL IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD DEC PY 1994 VL 55 IS 4 BP 193 EP 203 DI 10.1016/0165-1781(95)91245-9 PG 11 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA QL571 UT WOS:A1994QL57100002 PM 7701034 ER PT J AU WIGGS, CL MARTIN, A AF WIGGS, CL MARTIN, A TI AGING AND FEATURE-SPECIFIC PRIMING OF FAMILIAR AND NOVEL STIMULI SO PSYCHOLOGY AND AGING LA English DT Article; Proceedings Paper CT Annual Meeting of the Eastern-Psychological-Association CY APR, 1993 CL ARLINGTON, VA SP E PSYCHOL ASSOC AB English and Turkish words in 2 fonts were presented to young and elderly Ss, and memory was assessed directly with recognition tests and indirectly with reading time. Young and elderly Ss showed repetition priming on English words and showed larger priming effects when the study and test fonts were the same rather than different. Elderly Ss were impaired, however, on recognition of feature-specific information in comparison with young Ss. When Turkish words were shown, only young Ss evidenced priming, despite recognition performance above chance for both young and elderly Ss. A 2nd experiment replicated these findings with different materials. RP WIGGS, CL (reprint author), NIMH, CLIN SCI LAB, BLDG 10, ROOM 3D41, BETHESDA, MD 20892 USA. RI martin, alex/B-6176-2009 NR 62 TC 18 Z9 18 U1 5 U2 6 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0882-7974 J9 PSYCHOL AGING JI Psychol. Aging PD DEC PY 1994 VL 9 IS 4 BP 578 EP 588 DI 10.1037/0882-7974.9.4.578 PG 11 WC Gerontology; Psychology, Developmental SC Geriatrics & Gerontology; Psychology GA QG007 UT WOS:A1994QG00700009 PM 7893429 ER PT J AU OREN, DA SCHULKIN, J ROSENTHAL, NE AF OREN, DA SCHULKIN, J ROSENTHAL, NE TI 1,25 (OH)(2) VITAMIN-D-3 LEVELS IN SEASONAL AFFECTIVE-DISORDER - EFFECTS OF LIGHT SO PSYCHOPHARMACOLOGY LA English DT Article DE VITAMIN-D; BLOOD; SEASONAL AFFECTIVE DISORDER; DEPRESSION; WINTER ID THERAPY; SOLTRIOL AB 1,25 (OH)7 vitamin D-3 levels were assessed in nine females and six males with winter seasonal affective disorder and in 15 age- and gender-matched controls in winter during periods with and without treatment with light therapy. No difference was found between groups or across conditions, though wide variations within each group make the presence of a type II error possible. RP OREN, DA (reprint author), NIMH,CLIN PSYCHOBIOL & NEUROENDOCRINOL BRANCHES,BLDG 10,ROOM 4S-239,10 CTR DR MSC 1390,BETHESDA,MD 20892, USA. NR 7 TC 18 Z9 18 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD DEC PY 1994 VL 116 IS 4 BP 515 EP 516 DI 10.1007/BF02247486 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA PW712 UT WOS:A1994PW71200020 PM 7701056 ER PT J AU VILLALOBOSMOLINA, R JOSEPH, JA RABIN, BM KANDASAMY, SB DALTON, TK ROTH, GS AF VILLALOBOSMOLINA, R JOSEPH, JA RABIN, BM KANDASAMY, SB DALTON, TK ROTH, GS TI FE-56 IRRADIATION DIMINISHES MUSCARINIC BUT NOT ALPHA(1)-ADRENERGIC-STIMULATED LOW-K-M GTPASE IN RAT-BRAIN SO RADIATION RESEARCH LA English DT Article ID STRIATAL DOPAMINE; SIGNAL TRANSDUCTION; G-PROTEINS; RECEPTOR; MEMBRANES; AGE; STIMULATION; SENESCENCE; DIVERSITY; FLUIDITY AB Initial findings from our laboratory have indicated that muscarinic enhancement of K+-evoked release of dopamine from perifused striatal slices is reduced after exposure to Fe-56-particle irradiation. This finding suggested that there is a radiation-induced deficit in muscarinic receptor sensitivity. Subsequent findings have indicated that at least part of the loss in sensitivity may occur as a result of alterations in the initial steps of the signal transduction process and involve muscarinic receptor-G protein coupling/uncoupling. The present study was carried out to localize this deficit further by determining carbachol-stimulated low-Km guanosine triphosphatase (GTPase) activity in striatal and hippocampal tissue obtained from rats exposed to 0, 0.1 or 1.0 Gy of Fe-56-particle irradiation. In addition, to examine the specificity of the effect of Fe-56-particle irradiation, alpha(1)-adrenergic-stimulated low-K-m GTPase activity was also examined in these tissues. The results showed that there was a high degree of specificity in the effects of Fe-56 particles. Decrements were observed in muscarinic-stimulated low-K-m GTPase in striatum but not in hippocampus, and Fe-56-particle irradiation did not affect alpha(1)-adrenergic low-K-m GTPase activity in either brain tissue. C1 NIA,GERONTOL RES CTR,BALTIMORE,MD 21224. ARMED FORCES RADIOBIOL RES INST,BETHESDA,MD 20889. NR 24 TC 17 Z9 17 U1 1 U2 1 PU RADIATION RESEARCH SOC PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD DEC PY 1994 VL 140 IS 3 BP 382 EP 386 DI 10.2307/3579116 PG 5 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA PV082 UT WOS:A1994PV08200011 PM 7972691 ER PT J AU WAHL, RL HAWKINS, RA LARSON, SM HENDEE, WR COLEMAN, RE HOLDEN, RW FRICK, MP GATSONIS, C BROWN, GS SHTERN, F AF WAHL, RL HAWKINS, RA LARSON, SM HENDEE, WR COLEMAN, RE HOLDEN, RW FRICK, MP GATSONIS, C BROWN, GS SHTERN, F TI PROCEEDINGS OF A NATIONAL-CANCER-INSTITUTE WORKSHOP - PET IN ONCOLOGY - A CLINICAL RESEARCH AGENDA SO RADIOLOGY LA English DT Editorial Material DE EDITORIALS; EMISSION CT (ECT); NEOPLASMS, EMISSION CT (ECT) ID POSITRON EMISSION TOMOGRAPHY; FDG-PET; MUSCULOSKELETAL TUMORS; GLUCOSE-UTILIZATION; BREAST-CANCER; 2--FLUORO-2-DEOXY-D-GLUCOSE; FLUORODEOXYGLUCOSE; RECURRENCE; CARCINOMA; CT AB On November 28, 1992, the National Cancer Institute sponsored a workshop to discuss the current state of positron emission tomography (PET) applications in clinical oncology and to identify areas of consensus regarding a targeted research agenda in this growing field. Workshop members concluded that PET with the use of the glucose analog 18-F-fluoro-2-deoxy-D-glucose (FDG) has demonstrated substantial clinical potential as a method to (a) depict and characterize masses, (b) depict regional metastatic disease involving lymph nodes, (c) depict systemic metastases of cancer, and (d) help assess the response of cancers to a variety of therapies. More broad-based research directed at advancing our ability to apply the PET method to cancer diagnosis and treatment monitoring is needed. There was also a consensus that rigorous prospective trials of the PET method should be performed with current technology, transverse attenuation-corrected PET scans to determine the accuracy of PET in the characterization and regional staging of primary lung and breast cancers. Rational application of the PET method to cancer management will be accomplished better after the results of these research studies become available. C1 UNIV CALIF LOS ANGELES,DIV NUCL MED,LOS ANGELES,CA. CORNELL UNIV,SCH MED,DEPT RADIOL,NEW YORK,NY. MEM SLOAN KETTERING CANC CTR,DIV NUCL MED,NEW YORK,NY. MED COLL WISCONSIN,MILWAUKEE,WI. DUKE UNIV,SCH MED,DEPT RADIOL,DIV NUCL MED,DURHAM,NC. INDIANA UNIV,SCH MED,DEPT RADIOL,INDIANAPOLIS,IN. CREIGHTON UNIV,SCH MED,DEPT RADIOL,OMAHA,NE. HARVARD UNIV,SCH MED,DEPT HLTH CARE POLICY,BOSTON,MA. NCI,RADIAT RES PROGRAM,ROCKVILLE,MD. NCI,DIAGNOST IMAGING RES BRANCH,ROCKVILLE,MD. RP WAHL, RL (reprint author), UNIV MICHIGAN,MED CTR,DEPT INTERNAL MED,DIV NUCL MED,BIG505C,UH24,1500 E MED CTR DR,ANN ARBOR,MI 48109, USA. NR 27 TC 32 Z9 33 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 SN 0033-8419 J9 RADIOLOGY JI Radiology PD DEC PY 1994 VL 193 IS 3 BP 604 EP 606 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA PT553 UT WOS:A1994PT55300005 PM 7972793 ER PT J AU KNIERMAN, MD COLIGAN, JE PARKER, KC AF KNIERMAN, MD COLIGAN, JE PARKER, KC TI PEPTIDE FINGERPRINTS AFTER PARTIAL ACID-HYDROLYSIS - ANALYSIS BY MATRIX-ASSISTED LASER-DESORPTION IONIZATION MASS-SPECTROMETRY SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article ID PROTEIN AB A method is described by which a sequence-dependent peptide fingerprint can be rapidly obtained upon partial hydrolysis of peptides with hydrochloric acid and subsequent analysis by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). When synthetic peptides are treated with 3M HCl for 5 min at 110 degrees C, amino acids are released in turn from the C-terminus or, depending on the peptide, from the N-terminus. Sequence information can be deduced by identifying the amino acid whose mass corresponds to the difference in MW between the major hydrolysis products, beginning from the MW of the starting peptide. A similar pattern exclusively from the C-terminus has been obtained using pentafluoropropionic acid as a hydrolyzing agent (Tsugita et al. Eur. J. Biochem. 206, 691 (1992)), but required longer hydrolysis time and more handling prior to analysis. The technique we have developed could be used to obtain a sequence-dependent 'fingerprint' for a peptide cheaply and rapidly, starting with picomole amounts of peptide, because the hydrolysate can be directly analyzed by MALDI. This methodology might be especially useful for confirming the identity of peptides during peptide mapping. C1 NIAID,MOLEC STRUCT LAB,BETHESDA,MD 20892. RP KNIERMAN, MD (reprint author), FREDERICK CANC RES & DEV CTR,PROGRAM RESOURCES INC,FREDERICK,MD 21701, USA. OI Parker, Kenneth/0000-0002-6282-2478 NR 5 TC 15 Z9 15 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0951-4198 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PD DEC PY 1994 VL 8 IS 12 BP 1007 EP 1010 DI 10.1002/rcm.1290081220 PG 4 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA QF622 UT WOS:A1994QF62200018 PM 7696698 ER PT J AU ROOT, J SMITH, KR WHELAN, EA SANDLER, D VODA, AM AF ROOT, J SMITH, KR WHELAN, EA SANDLER, D VODA, AM TI TRACING WOMEN OVER HALF A CENTURY - STRATEGIES TO LOCATE SUBJECTS LOST TO FOLLOW-UP IN A LONGITUDINAL HEALTH STUDY SO RESEARCH ON AGING LA English DT Article AB Cohort studies typically require repeated contacts with the same study participants over many years. In large-scale follow-up studies of women, it can be difficult to locate and maintain contact with participants because women are more likely to experience name changes through marriage and divorce and may be less visible in public records, particularly contemporary elderly women. This article reports on the methods used in 1990 and 1991 to trace 998 participants of the Women's Health Study (WHS) who were enrolled during the 1930s in the Menstruation and Reproductive History study, a longitudinal study on menstruation and reproduction. Some of these women had been lost to follow-up for nearly 50 years. This article reviews the strategies used to locate the WHS participants. C1 NIEHS,RES TRIANGLE PK,NC 27709. UNIV UTAH,SALT LAKE CITY,UT 84112. NIOSH,CINCINNATI,OH 45226. NR 6 TC 10 Z9 10 U1 1 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 0164-0275 J9 RES AGING JI Res. Aging PD DEC PY 1994 VL 16 IS 4 BP 375 EP 388 DI 10.1177/0164027594164002 PG 14 WC Gerontology SC Geriatrics & Gerontology GA PT560 UT WOS:A1994PT56000002 ER PT J AU KOHN, MC LUCIER, GW PORTIER, CJ AF KOHN, MC LUCIER, GW PORTIER, CJ TI THE IMPORTANCE OF BIOLOGICAL REALISM IN DIOXIN RISK ASSESSMENT MODELS SO RISK ANALYSIS LA English DT Article DE 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN; MATHEMATICAL MODELS; GENE EXPRESSION; CARCINOGENESIS ID EPIDERMAL GROWTH-FACTOR; RECEPTOR-BINDING; FACTOR-ALPHA; CELL-PROLIFERATION; TUMOR PROMOTION; GENE-EXPRESSION; RAT-LIVER; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN; MECHANISM; TCDD AB Mechanistic mathematical models of hepatocarcinogenesis in the female rat were constructed to investigate possible relationships among the Ah, estrogen, and EGF receptors in TCDD hepato-carcinogenicity. Each model generates dose-response curves for the expression of biomarker liver proteins CYP1A1, CYP1A2, and residual plasma membrane EGF receptor consequent to exposure to TCDD. The shapes of the response curves were strongly dependent on the assumed mechanisms of constitutive expression of these proteins. Assuming a constant level of the hepatic Ah receptor, a sigmoidal dose-response of hepatic CYP1A1 to total liver TCDD was computed. However, inclusion of induction of the Ah receptor by TCDD in a physiologically realistic dosimetric model produced a linear low-dose response of CYP1A1. This behavior was was computed to arise from the net effect of sublinear response of CYP1A1 mRNA to the concentration of the Ah-TCDD complex and supralinear response of the protein concentration to the mRNA level, illustrating the importance of biological realism in dose-response modeling. The dosimetric model also computed effects of TCDD on the hepatic estradiol concentration and consequent effects on the binding capacity of the EGF receptor and suggests plausible mechanisms for tumor promotion by TCDD. Setting circulating estradiol levels in the model to values typical of the male rat indicated possible sources of the differences in the responses of the EGF receptor and in development of tumors in the two sexes. C1 NIEHS,BIOCHEM RISK ANAL LAB,RES TRIANGLE PK,NC 27709. RP KOHN, MC (reprint author), NIEHS,QUANTITAT & COMPUTAT BIOL LAB,POB 12233,RES TRIANGLE PK,NC 27709, USA. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 31 TC 15 Z9 15 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0272-4332 J9 RISK ANAL JI Risk Anal. PD DEC PY 1994 VL 14 IS 6 BP 993 EP 1000 PG 8 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA PZ760 UT WOS:A1994PZ76000020 PM 7846331 ER PT J AU SHERMAN, CD PORTIER, CJ KOPPSCHNEIDER, A AF SHERMAN, CD PORTIER, CJ KOPPSCHNEIDER, A TI MULTISTAGE MODELS OF CARCINOGENESIS - AN APPROXIMATION FOR THE SIZE AND NUMBER-DISTRIBUTION OF LATE-STAGE CLONES SO RISK ANALYSIS LA English DT Article DE CARCINOGENESIS; MULTISTAGE MODELS; LATE-STAGE CLONES ID ENZYME-ALTERED FOCI; QUANTITATIVE-ANALYSIS; 2-STAGE MODEL; RAT-LIVER; CANCER; HEPATOCARCINOGENESIS AB Multistage models have become the basic paradigm for modeling carcinogenesis. One model, the two-stage model of carcinogenesis, is now routinely used in the analysis of cancer risks from exposure to environmental chemicals. In its most general form, this model has two states, an initiated state and a neoplastic state, which allow for growth of cells via a simple linear birth-death process. In all analyses done with this model, researchers have assumed that tumor incidence is equivalent to the formation of a single neoplastic cell and the growth kinetics in the neoplastic state have been ignored. Some researchers have discussed the impact of this assumption on their analyses, but no formal methods were available for a more rigorous application of the birth-death process. In this paper, an approximation is introduced which allows for the application of growth kinetics in the neoplastic state. The adequacy of the approximation against simulated data is evaluated and methods are developed for implementing the approximation using data on the number and size of neoplastic clones. C1 GERMAN CANC RES CTR,W-6900 HEIDELBERG 1,GERMANY. RP SHERMAN, CD (reprint author), NIEHS,QUANTITAT & COMPUTAT BIOL LAB,MAIL DROP A306,POB 12233,RES TRIANGLE PK,NC 27709, USA. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 23 TC 12 Z9 14 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0272-4332 J9 RISK ANAL JI Risk Anal. PD DEC PY 1994 VL 14 IS 6 BP 1039 EP 1048 DI 10.1111/j.1539-6924.1994.tb00074.x PG 10 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA PZ760 UT WOS:A1994PZ76000026 PM 7846311 ER PT J AU KOPPSCHNEIDER, A PORTIER, CJ SHERMAN, CD AF KOPPSCHNEIDER, A PORTIER, CJ SHERMAN, CD TI THE EXACT FORMULA FOR TUMOR-INCIDENCE IN THE 2-STAGE MODEL SO RISK ANALYSIS LA English DT Article DE CANCER; RISK ASSESSMENT; CARCINOGENICITY DATA ID CARCINOGENESIS AB An exact formula for the tumor incidence rate in the usual two-stage model of carcinogenesis is presented. This formula is simple and easily implemented on calculators and computers. C1 GERMAN CANC RES CTR,BIOSTAT ABT,HEIDELBERG 1,GERMANY. NIEHS,QUANTITAT & COMPUTAT BIOL LAB,RES TRIANGLE PK,NC 27709. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 8 TC 42 Z9 44 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0272-4332 J9 RISK ANAL JI Risk Anal. PD DEC PY 1994 VL 14 IS 6 BP 1079 EP 1080 DI 10.1111/j.1539-6924.1994.tb00078.x PG 2 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA PZ760 UT WOS:A1994PZ76000030 PM 7846315 ER PT J AU ISHIZUYAOKA, A SHIMOZAWA, A TAKEDA, H SHI, YB AF ISHIZUYAOKA, A SHIMOZAWA, A TAKEDA, H SHI, YB TI CELL-SPECIFIC AND SPATIOTEMPORAL EXPRESSION OF INTESTINAL FATTY-ACID-BINDING PROTEIN GENE DURING AMPHIBIAN METAMORPHOSIS SO ROUXS ARCHIVES OF DEVELOPMENTAL BIOLOGY LA English DT Note DE FATTY-ACID-BINDING PROTEIN; INTESTINAL EPITHELIUM; IN SITU HYBRIDIZATION; ANURAN METAMORPHOSIS; REGIONAL DIFFERENCE ID CONNECTIVE-TISSUE; THYROID-HORMONE; XENOPUS-LAEVIS; LARVAL; INVITRO; DIFFERENTIATION; PATTERNS; MICE AB Intestinal fatty acid-binding protein (IFABP) gene is known to be regulated during Xenopus metamorphosis. To determine the relationship between its regulation and cellular differentiation during metamorphosis, we have examined the distribution of IFABP mRNA in the Xenopus digestive tract by in situ hybridization techniques. Throughout all stages examined, transcripts of IFABP gene were observed exclusively in absorptive epithelial cells of the small intestine, and they decreased in amount towards the posterior intestine. Around stage 58, just before metamorphic climax, IFABP mRNA level began to decrease in larval absorptive cells that still remained intact morphologically. Thereafter, IFABP mRNA was no longer detected among larval cells. In turn, at stage 62, IFABP mRNA became detectable in some of the newly formed adult epithelium that had not yet developed a brush border, but not in the remaining larval cells. By the end of metamorphosis, IFABP mRNA became more abundant towards the crest of intestinal folds. These results suggest that IFABP gene expression is specific for absorptive epithelial cells of the small intestine and is regionally regulated along the intestinal anterior-posterior axis in both tadpoles and frogs and also along the trough-crest axis of frog intestinal folds. In addition, our present study directly shows that IFABP mRNA level decreases in larval absorptive cells but increases in adult ones during metamorphosis, preceding morphological changes of both types of cells. Therefore, the regulation of IFABP gene is an early event during both larval epithelial cell death and adult epithelial cell differentiation. C1 NAGOYA UNIV,FAC SCI,DEPT MOLEC BIOL,CHIGUSA KU,NAGOYA,AICHI 46401,JAPAN. NICHHD,MOLEC EMBRYOL LAB,BETHESDA,MD 20892. RP ISHIZUYAOKA, A (reprint author), DOKKYO UNIV,SCH MED,DEPT ANAT,MIBU,TOCHIGI 32102,JAPAN. NR 33 TC 20 Z9 20 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0930-035X J9 ROUX ARCH DEV BIOL JI Rouxs Arch. Dev. Biol. PD DEC PY 1994 VL 204 IS 2 BP 150 EP 155 DI 10.1007/BF00361110 PG 6 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA PY849 UT WOS:A1994PY84900009 PM 28305939 ER PT J AU YAKAR, S KAPLAN, B LIVNEH, A MARTIN, B MIURA, K ALIKHAN, Z SHTRASBURG, S PRAS, M AF YAKAR, S KAPLAN, B LIVNEH, A MARTIN, B MIURA, K ALIKHAN, Z SHTRASBURG, S PRAS, M TI DIRECT EVIDENCE FOR SAA DEPOSITION IN TISSUES DURING MURINE AMYLOIDOGENESIS SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY LA English DT Article ID SERUM AMYLOID-A; POLYACRYLAMIDE-GEL ELECTROPHORESIS; PERFORMANCE LIQUID-CHROMATOGRAPHY; AMINO-ACID SEQUENCE; PROTEIN-AA; FIBRIL PROTEIN; MOUSE; PURIFICATION; COMPONENT; PRECURSOR AB To study the mechanism of amyloid deposition, the nature of amyloid proteins formed in experimental murine amyloidosis, was examined. Spleen specimens, 15-60 mg, were homogenized and extracted using aqueous acidic acetonitrile, in a recently developed procedure, making it possible to obtain amyloid proteins from minute amounts of tissue. The extracted material, 1.5-4mg, was analysed by Western blotting and ELISA using antibodies recognizing differentially proteins AA and SAA. Two immunoreactive proteins of 8 and 12 KDa were isolated and subjected to amino acid analysis and N-terminal sequence determination. The results of immunochemical and chemical examination showed that the 8 and 12 KDa proteins represented proteins AA and SAA, respectively. The data obtained provide new direct evidence for SAA deposition in tissues during murine amyloidogenesis. C1 CHAIM SHEBA MED CTR, HELLER INST MED RES, IL-52621 TEL HASHOMER, ISRAEL. NIMH, CLIN NEUROSCI BRANCH, BETHESDA, MD 20892 USA. HAMAMATSU UNIV SCH MED, DEPT PATHOL, HAMAMATSU, SHIZUOKA, JAPAN. MCGILL UNIV, DEPT MICROBIOL & IMMUNOL, MONTREAL, PQ, CANADA. NR 33 TC 23 Z9 23 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0300-9475 J9 SCAND J IMMUNOL JI Scand. J. Immunol. PD DEC PY 1994 VL 40 IS 6 BP 653 EP 658 DI 10.1111/j.1365-3083.1994.tb03519.x PG 6 WC Immunology SC Immunology GA PV668 UT WOS:A1994PV66800014 PM 7527934 ER PT J AU JASKIW, GE JULIANO, DM GOLDBERG, TE HERTZMAN, M UROWHAMELL, E WEINBERGER, DR AF JASKIW, GE JULIANO, DM GOLDBERG, TE HERTZMAN, M UROWHAMELL, E WEINBERGER, DR TI CEREBRAL VENTRICULAR ENLARGEMENT IN SCHIZOPHRENIFORM DISORDER DOES NOT PROGRESS - A 7 YEAR FOLLOW-UP-STUDY SO SCHIZOPHRENIA RESEARCH LA English DT Article DE SCHIZOPHRENIFORM; COMPUTERIZED TOMOGRAPHY; CHRONIC SCHIZOPHRENIA; VENTRICULAR BRAIN RATIO ID BRAIN MORPHOLOGICAL-CHANGES; COMPUTED-TOMOGRAPHY; PSYCHOSIS; ONSET; STABILITY; SIZE AB Ten patients, who underwent computerized tomography (CT) study during evaluation for first episode schizophreniform psychosis were restudied an average of 7 years later. Of the 10 patients, 7 were found to carry a diagnosis of schizophrenia at follow-up. In this subgroup, there was no significant change in the mean ventricular brain ratio measure of cerebral. ventricular size between the index and follow-up scans. These findings are consistent with the hypothesis that ventricular enlargement is present at the onset of schizophrenia and does not progress with duration of illness or treatment. C1 ST ELIZABETH HOSP,NIMH,INTRAMURAL RES PROGRAM,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. GEORGE WASHINGTON UNIV HOSP,DEPT PSYCHIAT,WASHINGTON,DC. PSYCHIAT INST WASHINGTON DC,WASHINGTON,DC. NR 25 TC 87 Z9 88 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD DEC PY 1994 VL 14 IS 1 BP 23 EP 28 DI 10.1016/0920-9964(94)90005-1 PG 6 WC Psychiatry SC Psychiatry GA PY224 UT WOS:A1994PY22400004 PM 7893618 ER PT J AU PARKINSON, DR AF PARKINSON, DR TI EXPANDING ROLE OF INTERFERON-ALFA IN THE TREATMENT OF CANCER - INTRODUCTION SO SEMINARS IN ONCOLOGY LA English DT Editorial Material RP PARKINSON, DR (reprint author), NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,INVEST DRUG BRANCH,BETHESDA,MD 20892, USA. NR 0 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 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD DEC PY 1994 VL 21 IS 6 SU 14 BP 1 EP 1 PG 1 WC Oncology SC Oncology GA PY194 UT WOS:A1994PY19400001 ER PT J AU SHEARER, GM CLERICI, M LUCEY, DR AF SHEARER, GM CLERICI, M LUCEY, DR TI CYTOKINES AND HIV-INFECTION SO SEMINARS IN VIROLOGY LA English DT Article DE AIDS CYTOKINES; HIV INFECTION; T HELPER CELLS; TYPE 1 VERSUS TYPE 2 ID HUMAN-IMMUNODEFICIENCY-VIRUS; NECROSIS-FACTOR-ALPHA; CD4+ T-CELLS; INTERFERON-GAMMA; IMMUNE-RESPONSES; IN-VITRO; EXPRESSION; MONOCYTES; INTERLEUKIN-10; MECHANISMS AB Infection with the human immunodeficiency virus (HIV) results in the production of cytokines by cells that comprise the immune system. Such cytokines regulate both immune function and viral replication, and thereby complicate their contribution to the progression to AIDS. Certain cytokines that regulate immune function exert opposing effects, such that some promote mainly cellular immune function, whereas others enhance antibody production. It has been suggested that an imbalance in cytokine production is responsible ist part for the immune dysregulation characteristic of progression to AIDS. Different cytokines can also have different effects on HIV expression and replication. Cytokine-based therapy has been suggested for preventing or delaying progression to AIDS. If such therapy is to be successful, it will be necessary to identify the correlate of immune protection, as well as to determine which cytokines enhance or suppress protective immunity, and the effects of these cytokines on viral replication. C1 UNIV MILAN,CATTEDRA IMMUNOL,I-20133 MILAN,ITALY. RP SHEARER, GM (reprint author), NCI,EXPTL IMMUNOL BRANCH,BLDG 10,BETHESDA,MD 20892, USA. NR 63 TC 6 Z9 6 U1 1 U2 1 PU ACADEMIC PRESS (LONDON) LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1044-5773 J9 SEMIN VIROL JI Semin. Virol. PD DEC PY 1994 VL 5 IS 6 BP 449 EP 455 DI 10.1006/smvy.1994.1051 PG 7 WC Virology SC Virology GA QJ548 UT WOS:A1994QJ54800007 ER EF