FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Mason, RP Trumbore, MW AF Mason, RP Trumbore, MW TI Differential membrane interactions of calcium channel blockers - Implications for antioxidant activity SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE antioxidants; calcium channel blockers; liposomes; X-ray diffraction ID LOW-DENSITY-LIPOPROTEIN; LIPID-PEROXIDATION; SARCOLEMMAL MEMBRANE; BIOLOGICAL-MEMBRANES; X-RAY; ANTAGONISTS; NIFEDIPINE; ATHEROSCLEROSIS; INHIBITION; VERAPAMIL AB Lipid peroxidation causes cellular damage during aging and various diseases, including atherosclerosis. Chronic administration of highly lipophilic calcium channel blockers (CCB) may reduce lipid peroxidation as a result of concentration in cell membranes and altering physico-chemical properties of the lipid bilayer. In this study, small angle X-ray scattering was used to examine reconstituted cardiac membrane lipid bilayers in the presence of CCB with various antioxidant activities, including nisoldipine, nifedipine, and diltiazem. Analysis of one-dimensional electron density profiles demonstrated that these compounds have different molecular distributions relative to the center of the membrane: diltiazem (+/- 14-22 Angstrom), nifedipine (+/- 12-22 Angstrom), and nisoldipine (+/- 7-22 Angstrom). The overall hydrocarbon core width for control samples was 44 Angstrom and was unaffected by the addition of drugs at these concentrations (< 1% by mass). High resolution differential scanning calorimetry indicated that CCB markedly perturbed the thermotropic properties of liposomes, including thermal phase transition temperature and enthalpy, relative to control samples. The effects of these compounds on membrane thermotropic properties correlate with their reported antioxidant activities. These data support the hypothesis that calcium channel blockers have potent physico-chemical interactions with the membrane lipid bilayer, which may underlie their antioxidant activity. C1 MED COLL PENN & HAHNEMANN UNIV,NEUROSCI RES CTR,DEPT BIOCHEM,PITTSBURGH,PA 15212. NCI,BETHESDA,MD 20892. RP Mason, RP (reprint author), MED COLL PENN & HAHNEMANN UNIV,NEUROSCI RES CTR,DEPT PSYCHIAT,320 E N AVE,10 S T,PITTSBURGH,PA 15212, USA. NR 28 TC 30 Z9 30 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD MAR 8 PY 1996 VL 51 IS 5 BP 653 EP 660 DI 10.1016/S0006-2952(95)02238-4 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TW991 UT WOS:A1996TW99100012 PM 8615902 ER PT J AU Gilbert, DL AF Gilbert, DL TI The eradication of the Phlogiston theory by book burning. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 177 EP 177 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28400178 ER PT J AU Dobbins, DE Premen, AJ AF Dobbins, DE Premen, AJ TI Mechanisms of bradykinin-mediated constriction of prenodal lymph vessels in the canine forelimb. SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIFORMED SERV UNIV HLTH SCI,DEPT PHYSIOL,BETHESDA,MD 20814. NIA,CARDIOVASC RES PROGRAM,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 295 EP 295 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28400293 ER PT J AU Long, RM AF Long, RM TI NIGMS program announcement: Factors that determine therapeutic drug bioavailability, PA-95-001 SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIGMS,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 488 EP 488 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28400487 ER PT J AU Evans, RL Turner, RJ AF Evans, RL Turner, RJ TI Activation of a non-specific cation channel (NSCC) at high [Ca2+](i) in rat parotid acinar cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDR,NIH,CIPCB,BETHESDA,MD 20892. NR 1 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 524 EP 524 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28400524 ER PT J AU Horton, ND Oeltgen, PR Kaftani, DJ Su, TP AF Horton, ND Oeltgen, PR Kaftani, DJ Su, TP TI Partial sequencing of hibernating woodchuck liver, cDNA associated with a hibernation-specific protein SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV KENTUCKY,COLL MED,GRAD CTR TOXICOL,DEPT PATHOL,LEXINGTON,KY 40511. VET ADM MED CTR,LEXINGTON,KY 40511. NIDA,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 668 EP 668 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28400668 ER PT J AU Park, C Baum, BJ Xu, T Oppenheim, FG OConnell, BC AF Park, C Baum, BJ Xu, T Oppenheim, FG OConnell, BC TI Construction of a replication-deficient, recombinant adenovirus encoding histatin 9 (H9). SO FASEB JOURNAL LA English DT Meeting Abstract C1 BOSTON UNIV,SGD,BOSTON,MA 02118. NIDR,NIH,CIPCB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 714 EP 714 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28400713 ER PT J AU Miller, DS Letcher, S Barnes, DM AF Miller, DS Letcher, S Barnes, DM TI Fluorescence imaging study of organic anion transport from renal proximal tubule cell to lumen SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS,CELLULAR & MOLEC PHARMACOL LAB,NIH,RES TRIANGLE PK,NC 27709. MT DESERT ISL BIOL LAB,SALSBURY COVE,ME 04672. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 726 EP 726 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28400725 ER PT J AU Masereeuw, R Russel, FGM Miller, DS AF Masereeuw, R Russel, FGM Miller, DS TI Active, Na-independent, organic anion secretion in killifish renal proximal tubules. SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV NIJMEGEN,DEPT PHARMACOL,NIJMEGEN,NETHERLANDS. NIEHS,CELLULAR & MOLEC PHARMACOL LAB,NIH,RES TRIANGLE PK,NC 27709. RI Russel, Frans/B-3184-2014; Masereeuw, Roos/N-3582-2014 OI Russel, Frans/0000-0002-7959-2314; NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 727 EP 727 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28400728 ER PT J AU Villalobos, AR Miller, DS Pritchard, JB AF Villalobos, AR Miller, DS Pritchard, JB TI Apical organic cation transport by primary cultures of rat choroid plexus. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS,CELLULAR & MOLEC PHARMACOL LAB,NIH,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 730 EP 730 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28400730 ER PT J AU Walsh, RC Sweet, DH Hall, LA Pritchard, JB AF Walsh, RC Sweet, DH Hall, LA Pritchard, JB TI Expression cloning and characterization of a novel organic cation transporter from rat kidney. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS,CELLULAR & MOLEC PHARMACOL LAB,NIH,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 732 EP 732 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28400731 ER PT J AU Jiang, QL vanRhee, AM Kim, JH Wess, J Jacobson, KA AF Jiang, QL vanRhee, AM Kim, JH Wess, J Jacobson, KA TI Hydrophilic side chains in the third and seventh transmembrane helical domains of human A(2A) adenosine receptors are required for ligand recognition SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK,NIH,LBC,MOL RECOGNIT SECT,BETHESDA,MD 20892. NIDDK,NIH,LBC,DRUG RECEPT INTERACT SECT,BETHESDA,MD 20892. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 781 EP 781 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28400781 ER PT J AU vanRhee, AM Siddiqi, SM Melman, N Shi, D Padgett, WL Daly, JW Jacobson, KA AF vanRhee, AM Siddiqi, SM Melman, N Shi, D Padgett, WL Daly, JW Jacobson, KA TI Tetrahydrobenzothiophenone derivatives as a novel class of adenosine receptor antagonists. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK,NIH,LBC,MOL RECOGNIT SECT,BETHESDA,MD 20892. NIDDK,NIH,LBC,PHARMACODYNAM SECT,BETHESDA,MD 20892. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 784 EP 784 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28400785 ER PT J AU Liu, J Blin, N Conklin, BR Wess, J AF Liu, J Blin, N Conklin, BR Wess, J TI Constitutively active mutant m2 muscarinic acetylcholine receptors suggest a possible mechanism of agonist-induced receptor activation. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK,NIH,BIOORGAN CHEM LAB,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,GLADSTONE INST CARDIOVASC DIS,SAN FRANCISCO,CA 94141. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 787 EP 787 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28400787 ER PT J AU Martens, JR Wang, D Sumners, C Posner, P Gelband, CH AF Martens, JR Wang, D Sumners, C Posner, P Gelband, CH TI Angiotensin II type 2 (AT(2)) receptor-mediated regulation of rat neuronal K+ channels. SO FASEB JOURNAL LA English DT Meeting Abstract C1 HANYANG UNIV,INST BIOMED SCI,SEOUL 133791,SOUTH KOREA. NINCDS,NEUROCHEM LAB,NIH,BETHESDA,MD 20892. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 801 EP 801 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28400802 ER PT J AU Reddy, NG Curtis, JF Mason, RP AF Reddy, NG Curtis, JF Mason, RP TI The effect of nitric oxide on prostaglandin H synthase: Prostaglandin formation was not stimulated by nitric oxide in studies with purified enzyme and with murine macrophages. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 845 EP 845 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28400845 ER PT J AU Vaughan, R Huff, R Uhl, G Kuhar, M AF Vaughan, R Huff, R Uhl, G Kuhar, M TI Phosphorylation of dopamine transporters in rat striatum. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDA,IRP,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 883 EP 883 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28400884 ER PT J AU Kreiss, DS Twery, MJ Walters, JR AF Kreiss, DS Twery, MJ Walters, JR TI Responses of subthalamic nucleus neurons to apomorphine and the D-1 receptor agonist SKF 38393 are altered in the dopamine-depleted rat. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NINCDS,EXPTL THERAPEUT BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 884 EP 884 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28400883 ER PT J AU Hokari, M Schwarcz, R Smith, QR AF Hokari, M Schwarcz, R Smith, QR TI Facilitated transport of 4-Cl-kynurenine into brain as possible prodrug for brain delivery of 7-Cl-kynurenic acid SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIA,NEUROSCI LAB,NIH,BETHESDA,MD 20892. MARYLAND PSYCHIAT RES CTR,BALTIMORE,MD 21228. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 888 EP 888 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28400887 ER PT J AU Acri, JB Wong, G Lyon, T Witkin, JM Basile, AS AF Acri, JB Wong, G Lyon, T Witkin, JM Basile, AS TI Localization and pharmacology of pigeon diazepam-insensitive gamma-aminobutyric acid(A) receptors SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDA,ADDICT RES CTR,DRUG DEV GRP,PSYCHOBIOL SECT,BALTIMORE,MD 21224. NIDDK,NEUROSCI LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 896 EP 896 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28400894 ER PT J AU Boyd, M Meshulam, Y Jacobson, K vonLubitz, D AF Boyd, M Meshulam, Y Jacobson, K vonLubitz, D TI Effect of A(1) adenosine receptor agonist and antagonist on [H-3]glutamic acid release from cortical tissue in vitro. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK,MOL RECOGNIT SECT,BIOORGAN CHEM LAB,NIH,BETHESDA,MD 20892. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 920 EP 920 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28400918 ER PT J AU Oriji, GK Keiser, HR AF Oriji, GK Keiser, HR TI Cyclosporine A-induced contractions and prostacyclin release are maintained by extracellular calcium in rat aortic rings: Role of protein kinase C. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,NIH,HYPERTENS ENDOCRINE BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 956 EP 956 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28400954 ER PT J AU Hunyady, B Mezey, E Pacak, K Harta, G Palkovits, M AF Hunyady, B Mezey, E Pacak, K Harta, G Palkovits, M TI Localization of muscarinic receptor mRNAs to different cell types in the stomach of normal or immobilized rats. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIMH,NINDS,NIH,BETHESDA,MD 20892. MED UNIV PECS,DEPT MED 1,PECS,HUNGARY. RI Palkovits, Miklos/F-2707-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 983 EP 983 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28400981 ER PT J AU Smith, PB Tiano, HF Langenbach, R Philpot, RM AF Smith, PB Tiano, HF Langenbach, R Philpot, RM TI 2-Aminoanthracene cytotoxicity in a cell line expressing rabbit lung cytochrome P-450 4B1 SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 1029 EP 1029 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28401027 ER PT J AU Kohno, Y Sei, Y Koshiba, M Kim, HO Jacobson, KA AF Kohno, Y Sei, Y Koshiba, M Kim, HO Jacobson, KA TI Induction of apoptosis in HL-60 human promyelocytic leukemia cells by selective adenosine A3 receptor agonists SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK,NEUROSCI LAB,BETHESDA,MD 20892. NIDDK,MOL RECOGNIT SECT,LBC,BETHESDA,MD 20892. NIAID,NIH,IMMUNOL LAB,BETHESDA,MD 20892. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 1037 EP 1037 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28401037 ER PT J AU Currens, MJ Mariner, JM McMahon, JB Boyd, MR AF Currens, MJ Mariner, JM McMahon, JB Boyd, MR TI Generation and characterization of resistance to calanolide A, a novel nonnucleoside RT inhibitor, by HIV-1 SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,NIH,DIV CAN TREATMENT DIAGNOSIS & CENTERS,DEV THERAPEUT PROGRAM,LAB DRUG DISCOVERY RES & DE,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 1055 EP 1055 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28401055 ER PT J AU Balaban, RS French, S AF Balaban, RS French, S TI Relation between mitochondrial NADH fluorescence and mitochondrial membrane potential SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,CARDIAC ENERGET LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 1224 EP 1224 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28401222 ER PT J AU Smith, QR Hokari, M Matharu, J Allen, DD Crooks, PA AF Smith, QR Hokari, M Matharu, J Allen, DD Crooks, PA TI Computer-derived molecular model of the binding site of the large neutral amino acid transporter (System L) of the blood-brain barrier. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIA,NEUROSCI LAB,NIH,BETHESDA,MD 20892. UNIV KENTUCKY,DIV MED CHEM,LEXINGTON,KY 40536. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 1304 EP 1304 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28401303 ER PT J AU Ziegler, RG Colavito, EA Hartge, P McAdams, MJ Schoenberg, JB Mason, TJ Fraumeni, JF AF Ziegler, RG Colavito, EA Hartge, P McAdams, MJ Schoenberg, JB Mason, TJ Fraumeni, JF TI The importance of alpha-carotene, beta-carotene, and other phytochemicals in the etiology of lung cancer. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NEW JERSEY STATE DEPT HLTH,TRENTON,NJ 08625. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 1385 EP 1385 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28401385 ER PT J AU VandenLangenberg, GM MaresPerlman, JM Brady, WE AF VandenLangenberg, GM MaresPerlman, JM Brady, WE TI Influence of using different sources of carotenoid data in epidemiologic studies. SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV WISCONSIN,MADISON,WI 53705. UNIV CALIF BERKELEY,BERKELEY,CA 94720. NCI,BETHESDA,MD 20892. UNIV ILLINOIS,CHICAGO,IL 60612. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 1397 EP 1397 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28401399 ER PT J AU Nebeling, LC Slesinski, MJ Ross, S Zhang, J Graubard, BI Yao, SX Snyder, RA Qiao, YL Taylor, P Forman, MR AF Nebeling, LC Slesinski, MJ Ross, S Zhang, J Graubard, BI Yao, SX Snyder, RA Qiao, YL Taylor, P Forman, MR TI Seasonal intake of foods in the Yunnan tin miners lung cancer study. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. INFORMAT MGMT SERV,SILVER SPRING,MD 20904. YUNNAN TIN CORP,GEJIU,PEOPLES R CHINA. RI Qiao, You-Lin/B-4139-2012 OI Qiao, You-Lin/0000-0001-6380-0871 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 1425 EP 1425 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28401427 ER PT J AU Shayakul, C Knepper, MA Smith, CP DiGiovanni, SR Hediger, MA AF Shayakul, C Knepper, MA Smith, CP DiGiovanni, SR Hediger, MA TI Different localization and physiologic response of two alternatively spliced urea transporter (UT) mRNAs in the rat kidney. SO FASEB JOURNAL LA English DT Meeting Abstract C1 BRIGHAM & WOMENS HOSP,BOSTON,MA 02115. HARVARD UNIV,SCH MED,BOSTON,MA 02115. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 1568 EP 1568 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28401568 ER PT J AU Kishore, BK Knepper, MA AF Kishore, BK Knepper, MA TI Absolute abundance of vasopressin-regulated renal urea transporter (RUT) and aquaporin-2 (AQP2) water channel in collecting ducts microdissected from rat kidney. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 1570 EP 1570 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28401569 ER PT J AU Chou, CL Ecelbarger, C Knepper, MA AF Chou, CL Ecelbarger, C Knepper, MA TI Differential effects of carbachol and vasopressin on activation of the phosphoinositide pathway in inner medullary collecting duct. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 1575 EP 1575 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28401577 ER PT J AU Misiewicz, B Poltorak, M Wright, R Raybourne, R Szczepanowski, R Freed, WJ Sternberg, EM AF Misiewicz, B Poltorak, M Wright, R Raybourne, R Szczepanowski, R Freed, WJ Sternberg, EM TI Intracerebroventricular transplantation of F344/N hypothalamic tissue alters the course of experimental allergic encephalomyelitis in LEW/N rats SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIMH,CNE,BETHESDA,MD 20892. GEORGE WASHINGTON UNIV,WASHINGTON,DC 20052. NIMH,PRECLIN NEUROSCI SECT,WASHINGTON,DC 20032. US FDA,IMMUNOBIOL BRANCH,LAUREL,MD 20708. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 1624 EP 1624 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28401622 ER PT J AU Kasserra, CE Arai, AE Balaban, RS AF Kasserra, CE Arai, AE Balaban, RS TI In vivo myocardium does not deoxygenate or increase NADH in response to increased work SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,CARDIAC ENERGET LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 1881 EP 1881 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28401880 ER PT J AU Mootha, VK Arai, A Kasserra, C Balaban, RS AF Mootha, VK Arai, A Kasserra, C Balaban, RS TI Maximum mitochondrial respiratory capacity of the mammalian heart. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,CARDIAC ENERGET LAB,NIH,BETHESDA,MD 20892. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 1886 EP 1886 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28401888 ER PT J AU Rywik, T OConnor, F Vaitkevicisu, P Nussbacher, A Wright, J Lakatta, E Fleg, J AF Rywik, T OConnor, F Vaitkevicisu, P Nussbacher, A Wright, J Lakatta, E Fleg, J TI Are there racial differences in the age-associated increase in arterial stiffness? SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,NIH,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 1921 EP 1921 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28401923 ER PT J AU Tate, JE Oriji, GK Keiser, HR AF Tate, JE Oriji, GK Keiser, HR TI Protein kinase C mediates angiotensin II-induced contractions and release of endothelin and prostacyclin in rat aortic rings. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,HYPERTENS ENDOCRINE BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 1962 EP 1962 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28401963 ER PT J AU Nolan, P Knepper, M Packer, R AF Nolan, P Knepper, M Packer, R TI Inhibition of inner medullary collecting duct (IMCD) 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) by low pH and acute metabolic acidosis. SO FASEB JOURNAL LA English DT Meeting Abstract C1 GEORGE WASHINGTON UNIV,WASHINGTON,DC 20052. NHLBI,NIH,BETHESDA,MD 20814. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 2132 EP 2132 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28402132 ER PT J AU Ferraris, JD Williams, CK Burg, MB GarciaPerez, A AF Ferraris, JD Williams, CK Burg, MB GarciaPerez, A TI Identification of an osmotic response element (ORE) in the rabbit aldose reductase (AR) gene. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,NIH,LKEM,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 2248 EP 2248 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28402248 ER PT J AU Kovbasnjuk, O Spring, KR AF Kovbasnjuk, O Spring, KR TI Regulation of tight junction sodium permeability in MDCK cells by PKA. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,NIH,LKEM,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 2319 EP 2319 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28402318 ER PT J AU Smith, JC Marks, WB Koshiya, N AF Smith, JC Marks, WB Koshiya, N TI Animation of the respiratory network. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NINCDS,NIH,NEURAL CONTROL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 2356 EP 2356 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28402356 ER PT J AU Coon, SL Roseboom, PH Baler, R Weller, JL Namboodiri, MAA Koonin, EV Klein, DC AF Coon, SL Roseboom, PH Baler, R Weller, JL Namboodiri, MAA Koonin, EV Klein, DC TI Pineal serotonin N-acetyltransferase: Expression cloning and molecular analysis. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NICHHD,NIH,BETHESDA,MD 20892. NCBI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 2381 EP 2381 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28402382 ER PT J AU Roseboom, PH Coon, SL Baler, R McCune, SK Weller, JL Klein, DC AF Roseboom, PH Coon, SL Baler, R McCune, SK Weller, JL Klein, DC TI Melatonin synthesis: Regulation of rat pineal serotonin N-acetyltransferase mRNA. SO FASEB JOURNAL LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD 21218. NICHHD,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 2382 EP 2382 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28402380 ER PT J AU Zhang, H Kim, HY AF Zhang, H Kim, HY TI Lipoxygenation and melatonin synthesis in rat pineal gland SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAAA,NIH,LAB MEMBRANE BIOCHEM & BIOPHYS,SECT MASS SPECTROMETRY,ROCKVILLE,MD 20852. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 2384 EP 2384 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28402384 ER PT J AU Kole, HK Garant, MJ Kole, S Bernier, M AF Kole, HK Garant, MJ Kole, S Bernier, M TI Tris-sulfotyrosyl dodecapeptide, a protein tyrosine phosphatase inhibitor, specifically enhances insulin receptor function in intact cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIA,NIH,GRC,DIABET UNIT,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 2426 EP 2426 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28402425 ER PT J AU Sudarshan, C Yaswen, L Kulkarni, A Raghow, R AF Sudarshan, C Yaswen, L Kulkarni, A Raghow, R TI Transforming growth factor beta 1 gene ablation leads to altered rates of cell proliferation and extracellular matrix biosynthesis. SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV TENNESSEE,DEPT MED,MEMPHIS,TN 38104. VET ADM MED CTR,MEMPHIS,TN 38104. NIDR,NIH,NINDS,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 2435 EP 2435 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28402435 ER PT J AU Snell, J Chernyshev, O Gilbert, D Colton, C AF Snell, J Chernyshev, O Gilbert, D Colton, C TI The induction of nitric oxide by polyribonucleotides in hamster and human glia. SO FASEB JOURNAL LA English DT Meeting Abstract C1 GEORGETOWN UNIV,SCH MED,WASHINGTON,DC 20007. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 2531 EP 2531 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28402532 ER PT J AU Alling, KL Katz, JL AF Alling, KL Katz, JL TI The effects of dopamine D-2/D-3 agonists and antagonists on behavior in squirrel monkeys. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDA,NIH,DIR,ARC,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 2582 EP 2582 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28402582 ER PT J AU Izenwasser, S Newman, AH Cox, BM Katz, JL AF Izenwasser, S Newman, AH Cox, BM Katz, JL TI The cocaine-like behavioral effects of meperidine are mediated by activity at the dopamine transporter. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDA,DIV INTRAMURAL RES,ADDICT RES CTR,PSYCHOBIOL SECT,BALTIMORE,MD 21224. UNIFORMED SERV UNIV HLTH SCI,DEPT PHARMACOL,BETHESDA,MD 20814. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 2584 EP 2584 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28402583 ER PT J AU Kunko, P Izenwasser, S AF Kunko, P Izenwasser, S TI Investigation of cocaine-induced changes in opioid receptors using selective monoamine uptake inhibitors SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDA,DIV INTRAMURAL RES,ADDICT RES CTR,PSYCHOBIOL SECT,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 2585 EP 2585 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28402586 ER PT J AU Ershow, AG AF Ershow, AG TI Dietary effects on lipoproteins and thrombogenic activity in subjects with markers for insulin resistance (DELTA-2): Study design and recruitment. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 2664 EP 2664 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28402664 ER PT J AU Smith, CB Sun, Y AF Smith, CB Sun, Y TI Effects of ''valine-flooding'' on leucine recycling. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIMH,LCM,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 2728 EP 2728 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28402730 ER PT J AU Denkins, YM Woods, J Hannigan, J Whitty, J Salem, N AF Denkins, YM Woods, J Hannigan, J Whitty, J Salem, N TI The fatty acid composition of the umbilical cord serum of infants exposed to alcohol in utero SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAAA,NIH,ROCKVILLE,MD 20852. WAYNE STATE UNIV,FETAL ALCOHOL RES CTR,DETROIT,MI 48201. WAYNE STATE UNIV,HERTZEL HOSP,DEPT OBSTET GYNECOL,DETROIT,MI 48201. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 2980 EP 2980 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28402981 ER PT J AU Preusch, PC AF Preusch, PC TI NIGMS program announcement: Structural biology of membrane proteins SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIGMS,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 3089 EP 3089 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28403088 ER PT J AU Reynolds, TH Brozinick, JT Rogers, MA Cushman, SW AF Reynolds, TH Brozinick, JT Rogers, MA Cushman, SW TI Transient enhancement of GLUT4 mRNA, GLUT4 protein, and glucose transport activity in rat skeletal muscle following short-term swim training SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV MARYLAND,COLLEGE PK,MD 20742. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 3163 EP 3163 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28403162 ER PT J AU Sinha, R Brown, E Rothman, N Swanson, C Knize, M Felton, J Levander, O AF Sinha, R Brown, E Rothman, N Swanson, C Knize, M Felton, J Levander, O TI Exposure assessment of heterocyclic amines (HCAs) in epidemiologic studies. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,NIH,BETHESDA,MD 20892. USDA,BHNRC,NRFL,BELTSVILLE,MD 20705. LAWRENCE LIVERMORE NATL LAB,LIVERMORE,CA 94550. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 3172 EP 3172 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28403172 ER PT J AU Neville, MC Toddywalla, VS Karit, FW Monks, J Gavigan, SJP AF Neville, MC Toddywalla, VS Karit, FW Monks, J Gavigan, SJP TI Drug and protein transfer into milk: A reevaluation SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV COLORADO,SCH MED,DENVER,CO 80262. INST RES REPROD,BOMBAY 400012,MAHARASHTRA,INDIA. NIEHS,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 3190 EP 3190 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28403190 ER PT J AU Yoshigi, M Keller, BB AF Yoshigi, M Keller, BB TI Frequency domain and time domain analysis of characteristic impedance in the embryonic SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV ROCHESTER,NIH,SCOR PEDIAT CARDIOVASC DIS,ROCHESTER,NY 14642. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 3248 EP 3248 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28403250 ER PT J AU Morio, D Lottenberg, R Schecter, A Tay, RST AF Morio, D Lottenberg, R Schecter, A Tay, RST TI Effects of PO2 and other physiological variables on the rheology of sickle red blood cell suspensions SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK,NIH,BIOL CHEM LAB,BETHESDA,MD 20892. UNIV FLORIDA,GAINESVILLE,FL 32611. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 3253 EP 3253 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28403253 ER PT J AU Tsutsui, M Milstien, S Katusic, ZS AF Tsutsui, M Milstien, S Katusic, ZS TI Tetrahydrobiopterin (BH4) and superoxide dismutase (SOD) synergistically augment endothelium-dependent relaxations in canine middle cerebral artery SO FASEB JOURNAL LA English DT Meeting Abstract C1 MAYO CLIN,ROCHESTER,MN 55905. NIMH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 3285 EP 3285 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28403286 ER PT J AU Pallone, TL Kishore, BK Nielsen, S Agre, P Knepper, MA AF Pallone, TL Kishore, BK Nielsen, S Agre, P Knepper, MA TI Small solute induced osmotic water transport across outer medullary descending vasa recta is water channel mediated. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,BETHESDA,MD 20892. UNIV MARYLAND,BALTIMORE,MD 21201. AARHUS UNIV,AARHUS,DENMARK. JOHNS HOPKINS UNIV,BALTIMORE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 3315 EP 3315 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28403316 ER PT J AU Tinney, JP Keller, BB AF Tinney, JP Keller, BB TI Ventricular/vascular coupling and uncoupling in the embryonic cardiovascular system. SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV ROCHESTER,NIH,SCOR PEDIAT CARDIOVASC DIS,ROCHESTER,NY 14642. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 3343 EP 3343 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28403343 ER PT J AU Keller, BB MacLennan, MJ Tinney, JP Yoshigi, M AF Keller, BB MacLennan, MJ Tinney, JP Yoshigi, M TI In vivo assessment of murine embryonic cardiovascular function. SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV ROCHESTER,NIH,SCOR PEDIAT CARDIOVASC DIS,ROCHESTER,NY 14642. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 3350 EP 3350 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28403351 ER PT J AU Kaya, M Chang, L Truong, A Brightman, M AF Kaya, M Chang, L Truong, A Brightman, M TI Reversible induction of fenestrae in vessels of the blood-brain barrier. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH,LN,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 3383 EP 3383 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28403385 ER PT J AU Gaynor, PM Zhang, WY Salehizadeh, B Kruth, HS AF Gaynor, PM Zhang, WY Salehizadeh, B Kruth, HS TI The human cornea: A model for lipid deposition in atherosclerosis. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 3550 EP 3550 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28403548 ER PT J AU Anasti, J Moy, E Kimzey, R George, M Nelson, LM AF Anasti, J Moy, E Kimzey, R George, M Nelson, LM TI Human follicle fluid vascular endothelial growth factor (VEGF) is correlated with serum LH and follicle fluid progesterone. SO FASEB JOURNAL LA English DT Meeting Abstract C1 ST LUKES HOSP,BETHLEHEM,PA 18015. NICHHD,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 3734 EP 3734 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28403734 ER PT J AU Johnson, LK Tilmont, EM Jay, SC Ingram, DK Roth, GS Lane, MA AF Johnson, LK Tilmont, EM Jay, SC Ingram, DK Roth, GS Lane, MA TI Effects of age and calorie restriction on reproductive function in female rhesus monkeys. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIA,NIH,GERONTOL RES CTR,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 3745 EP 3745 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28403745 ER PT J AU Chauthaiwale, JV Lockwich, T Sakai, T Ambudkar, IS AF Chauthaiwale, JV Lockwich, T Sakai, T Ambudkar, IS TI Characteristics of high and low affinity Ca2+ influx components in rat parotid acinar cells and basolateral plasma membrane vesicles. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDR,NIH,SECRETORY PHYSIOL SECT,CIPCB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 3751 EP 3751 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28403751 ER PT J AU Sakai, T Ambudkar, IS AF Sakai, T Ambudkar, IS TI Ca2+ regulates internal Ca2+ store depletion-activated Ca2+ influx in rat parotid acinar cells by Ca2+ store refill-dependent and -independent mechanisms. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDR,CLIN INVEST & PATIENT CARE BRANCH,SECRETORY PHYSIOL SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 3786 EP 3786 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28403786 ER PT J AU Fowler, MD Ryschon, TW Wysong, RE Balaban, RS AF Fowler, MD Ryschon, TW Wysong, RE Balaban, RS TI Muscle power per unit volume determines metabolism in dynamically contracting skeletal muscle. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH,LAB CARDIAC ENERGET,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 3855 EP 3855 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28403857 ER PT J AU Ryschon, TW Anthony, AR Fowler, MD Wysong, RE Balaban, RS AF Ryschon, TW Anthony, AR Fowler, MD Wysong, RE Balaban, RS TI Metabolic efficiency in isometric, concentric, and eccentric muscle action SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH,LAB CARDIAC ENERGET,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 3856 EP 3856 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28403855 ER PT J AU Rabin, O Grange, E Deutsch, J Chang, MCJ Rapoport, SI Purdon, AD AF Rabin, O Grange, E Deutsch, J Chang, MCJ Rapoport, SI Purdon, AD TI Brain acyl-CoA concentration in gerbil ischemia-reperfusion. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIA,NIH,LNS,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 3886 EP 3886 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28403887 ER PT J AU Henkin, RI Martin, BM AF Henkin, RI Martin, BM TI Carbonic anhydrase (CA) VI may be a protein that stimulates growth and development of taste buds. SO FASEB JOURNAL LA English DT Meeting Abstract C1 TASTE & SMELL CLIN,WASHINGTON,DC 20016. NIH,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 3900 EP 3900 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28403900 ER PT J AU Young, JK Baker, JH Muller, T AF Young, JK Baker, JH Muller, T TI Immunoreactivity for brain-fatty acid binding protein in gomori+ astrocytes SO FASEB JOURNAL LA English DT Meeting Abstract C1 HOWARD UNIV,DEPT ANAT,WASHINGTON,DC 20059. NINCDS,NIH,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 3916 EP 3916 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28403914 ER PT J AU Wess, J Liu, J AF Wess, J Liu, J TI Different single receptor domains determine the distinct G protein coupling profiles of members of the vasopressin receptor family. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK,NIH,BIOORGAN CHEM LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 3961 EP 3961 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28403962 ER PT J AU Allen, DD Matharu, JRS Crooks, PA Smith, OR AF Allen, DD Matharu, JRS Crooks, PA Smith, OR TI Characterization of the binding site of the blood-brain barrier (BBB) choline (OH) transporter. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIA,NIH,LNS,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 3989 EP 3989 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28403991 ER PT J AU Hill, MR Oriji, GK Keiser, HR AF Hill, MR Oriji, GK Keiser, HR TI Role of calcium in endothelin-induced contractions and prostacyclin release. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI,NIH,HYPERTENS ENDOCRINE BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 4006 EP 4006 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28404005 ER PT J AU Chiueh, CC Rauhala, P Sziraki, I AF Chiueh, CC Rauhala, P Sziraki, I TI Controversial issue: Nitric oxide radicals (NO) do not mediate neurotoxicity in the central nervous system. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIMH,CLIN SCI LAB,UNIT NEUROTOXICOL & NEUROPROTECT,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 4061 EP 4061 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28404062 ER PT J AU Rauhala, P Lin, AMY Mohanakumar, KP Sziraki, J Chiueh, CC AF Rauhala, P Lin, AMY Mohanakumar, KP Sziraki, J Chiueh, CC TI Nitric oxide (NO) as a neuroprotective antioxidant in vivo. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIMH,CLIN SCI LAB,UNIT NEUROTOXICOL & NEUROPROTECT,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 4062 EP 4062 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28404060 ER PT J AU Mohanakumar, KP Rauhala, P Sziraki, I Chiueh, CC AF Mohanakumar, KP Rauhala, P Sziraki, I Chiueh, CC TI Hydroxyl radicals (OH) but not nitric oxide (NO) mediate neurotoxicity produced by sodium nitroprusside (SNP) in vivo. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIMH,CLIN SCI LAB,UNIT NEUROTOXICOL & NEUROPROCTECT,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 4063 EP 4063 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28404063 ER PT J AU Zaveri, NT Mullet, DI Cox, GW Fertel, RH AF Zaveri, NT Mullet, DI Cox, GW Fertel, RH TI Effects of adenosine analogs plus gamma-IFN on the nitric oxide system in ANA-1 murine macrophages. SO FASEB JOURNAL LA English DT Meeting Abstract C1 OHIO STATE UNIV,COLL MED,DEPT PHARMACOL,COLUMBUS,OH 43210. NCI,FREDERICK CANC RES & DEV CTR,BRMP,EXPTL IMMUNOL LAB,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 4069 EP 4069 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28404069 ER PT J AU Rauhala, SIP Chiueh, CC AF Rauhala, SIP Chiueh, CC TI Iron and manganese: Two transition metals with opposite effects on brain dopaminergic neurons. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIMH,LCS,UNIT NEUROTOXICOL & NEUROPROTECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 4152 EP 4152 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28404152 ER PT J AU Salem, N Pawlosky, RJ Hibbeln, JR Wegher, B Mena, P Uauy, R AF Salem, N Pawlosky, RJ Hibbeln, JR Wegher, B Mena, P Uauy, R TI Arachidonate and docosahexaenoate biosynthesis in human adults and infants. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAAA,LMBB,NIH,ROCKVILLE,MD 20852. UNIV CHILE,INST NUTR & TECNOL ALIMENTOS,SANTIAGO 11,CHILE. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 4167 EP 4167 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28404166 ER PT J AU Kant, AK Thompson, FE AF Kant, AK Thompson, FE TI Measures of dietary variety from food frequency questionnaire (FFQ): National Health Interview Survey, 1992 (NHIS). SO FASEB JOURNAL LA English DT Meeting Abstract C1 CUNY QUEENS COLL,FLUSHING,NY 11367. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 4180 EP 4180 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28404179 ER PT J AU Munoz, K KrebsSmith, S BallardBarbash, R AF Munoz, K KrebsSmith, S BallardBarbash, R TI Dietary intake of children in the United States. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 4186 EP 4186 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28404184 ER PT J AU Hibbeln, JR Umhau, JC Linnoila, M Rawlings, R George, DT Salem, N AF Hibbeln, JR Umhau, JC Linnoila, M Rawlings, R George, DT Salem, N TI Plasma long chain polyunsaturated fatty acids predict cerebrospinal fluid (CSF) neurotransmitter metabolites associated with suicide and distinguish early onset alcoholics, late onset alcoholics and normals. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAAA,DICBR,CLIN STUDIES LAB,BETHESDA,MD 20892. NIAAA,DICBR,LAB MEMB BIOCHEM BIOPHYS,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 4249 EP 4249 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28404248 ER PT J AU Vannucci, SJ Simpson, IA AF Vannucci, SJ Simpson, IA TI Glucose transporters in the CNS: Development, injury and disease. SO FASEB JOURNAL LA English DT Meeting Abstract C1 PENN STATE UNIV,MILTON S HERSHEY MED CTR,HERSHEY,PA 17033. NIDDK,EDMNS,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 4252 EP 4252 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28404252 ER PT J AU Zhong, Z Connor, H Mason, RP Stachlewitz, RF Thurman, RG AF Zhong, Z Connor, H Mason, RP Stachlewitz, RF Thurman, RG TI Role of free radicals in alcohol-induced primary fatty liver graft failure. SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV N CAROLINA,DEPT PHARMACOL,CHAPEL HILL,NC 27599. UNIV N CAROLINA,DEPT CELL BIOL & ANAT,CHAPEL HILL,NC 27599. NIEHS,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 4282 EP 4282 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28404282 ER PT J AU Hong, HL Devereus, TR Boorman, GA Sills, RC AF Hong, HL Devereus, TR Boorman, GA Sills, RC TI Ras oncogene mutations in liver neoplasms of B6C3F1 mice exposed to tetrafluoroethylene for two years. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS,NTP,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 4365 EP 4365 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28404364 ER PT J AU Rumsh, L Gustchina, E Ginodman, L Majer, P Andreeva, N AF Rumsh, L Gustchina, E Ginodman, L Majer, P Andreeva, N TI Two structural forms of chymosin. The regulation of activity by the interaction with the native substrate fragment. SO FASEB JOURNAL LA English DT Meeting Abstract C1 RUSSIAN ACAD SCI,SHEMJAKIN & OVCHINNIKOV INST BIOORGAN CHEM,MOSCOW 117871,RUSSIA. NCI,STRUCT BIOCHEM PROGRAM,FREDERICK,MD 21702. RUSSIAN ACAD SCI,VA ENGELHARDT MOLEC BIOL INST,MOSCOW 117984,RUSSIA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 4482 EP 4482 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28404482 ER PT J AU Tilmont, EM Roth, GS Ingram, DK Johnson, LK Lane, MA AF Tilmont, EM Roth, GS Ingram, DK Johnson, LK Lane, MA TI Dual energy X-ray absorptiometry (DEXA) studies of bone loss during normal aging and calorie restriction in female rhesus monkeys. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIA,GERONTOL RES CTR,NIH,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 4503 EP 4503 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28404503 ER PT J AU Ross, S Lanza, E Forman, MR Graubard, BI Campbell, WS Beecher, GR AF Ross, S Lanza, E Forman, MR Graubard, BI Campbell, WS Beecher, GR TI Effect of black tea consumption on serum estradiol concentrations in healthy premenopausal, women. SO FASEB JOURNAL LA English DT Meeting Abstract C1 USDA,BELTSVILLE,MD 20705. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 4560 EP 4560 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28404558 ER PT J AU Pawlosky, RJ Salem, N AF Pawlosky, RJ Salem, N TI Alcohol-induced liver fibrosis in rhesus monkeys: The effects of a low essential fatty acid diet. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAAA,DIV INTRAMURAL CLIN & BIOL RES,ROCKVILLE,MD 20852. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 4607 EP 4607 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28404607 ER PT J AU Thurman, RG Iimuro, Y Gallucci, RM Luster, MI AF Thurman, RG Iimuro, Y Gallucci, RM Luster, MI TI Anti-TNF-alpha antibody prevents liver injury due to chronic intragastric ethanol exposure in the rat. SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV N CAROLINA,DEPT PHARMACOL,HEPATOBIOL & TOXICOL LAB,CHAPEL HILL,NC 27599. NIEHS,IMMUNOL & NEUROBIOL SECT,RES TRIANGLE PK,NC 27709. NR 0 TC 1 Z9 1 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 4612 EP 4612 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28404610 ER PT J AU Olsson, NU Harding, AJ Harper, C Salem, N AF Olsson, NU Harding, AJ Harper, C Salem, N TI Stability of brain lipid class patterns during alcohol exposure: HPLC analysis of brains from alcoholics. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAAA,NIH,LAB MEMBR BIOCHEM BIOPHYS,ROCKVILLE,MD 20852. UNIV SYDNEY,DEPT PATHOL,SYDNEY,NSW 2006,AUSTRALIA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 4618 EP 4618 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28404616 ER PT J AU Barbay, S Shi, B Stanfield, BB AF Barbay, S Shi, B Stanfield, BB TI Functional ipsilateral corticospinal projections extend from the hemisphere contralateral to a neonatal cortical lesion in the presence of either homotopic or heterotopic E17 transplants. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIMH,NIH,ANIM CTR,NEUROPHYSIOL LAB,POOLESVILLE,MD 20837. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 4654 EP 4654 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28404652 ER PT J AU Davis, CE Hunsberger, S Murray, D Skipper, B Caballero, B Stephenson, L AF Davis, CE Hunsberger, S Murray, D Skipper, B Caballero, B Stephenson, L TI Design and analysis issues in pathways SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. UNIV N CAROLINA,CHAPEL HILL,NC 27514. UNIV MINNESOTA,MINNEAPOLIS,MN 55454. UNIV NEW MEXICO,ALBUQUERQUE,NM 87131. JOHNS HOPKINS UNIV,BALTIMORE,MD 21205. GILA RIVER INDIAN COMMUNITY,SACATON,AZ 85247. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 4708 EP 4708 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28404710 ER PT J AU Lohman, T Himes, J Caballero, B Skipper, B Reid, R Stewart, D Hunsberger, S AF Lohman, T Himes, J Caballero, B Skipper, B Reid, R Stewart, D Hunsberger, S TI Body composition assessment in American Indian children. SO FASEB JOURNAL LA English DT Meeting Abstract C1 UNIV ARIZONA,TUCSON,AZ 85721. UNIV MINNESOTA,MINNEAPOLIS,MN 55454. JOHNS HOPKINS UNIV,BALTIMORE,MD 21205. UNIV NEW MEXICO,ALBUQUERQUE,NM 87131. UNIV N CAROLINA,CHAPEL HILL,NC 27514. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 1996 VL 10 IS 3 BP 4712 EP 4712 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA TZ284 UT WOS:A1996TZ28404712 ER PT J AU Denning, MF Dlugosz, AA Threadgill, DW Magnuson, T Yuspa, SH AF Denning, MF Dlugosz, AA Threadgill, DW Magnuson, T Yuspa, SH TI Activation of the epidermal growth factor receptor signal transduction pathway stimulates tyrosine phosphorylation of protein kinase C delta SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID H-RAS ONCOGENE; PHORBOL ESTER; DIFFERENTIATION MARKERS; MOUSE KERATINOCYTES; EXPRESSION; ALPHA; CELLS; OVEREXPRESSION; METABOLISM; ISOZYMES AB The expression of an oncogenic ras(Ha) gene in epidermal keratinocytes stimulates the tyrosine phosphorylation of protein kinase C delta and inhibits its enzymatic activity (Denning, M. F., Dlugosz, A. A., Howett, M. K., and Yuspa, S. H. (1993) J. Biol. Chem. 268, 26079-26081). Keratinocytes expressing an activated ras(Ha) gene secrete transforming growth factor alpha (TGF alpha) and have an altered response to differentiation signals involving protein kinase C (PKC), Because the neoplastic phenotype of v-ras(Ha) expressing keratinocytes can be partially mimicked in vitro by chronic treatment with TGF alpha and the G protein activator aluminum fluoride (AlF4-), we determined if TGF alpha or AlF4- could induce tyrosine phosphorylation of PKC delta. Treatment of primary keratinocyte cultures for 4 days with TGF alpha induced tyrosine phosphorylation of PKC delta, whereas AlF4- only slightly stimulated PKC delta tyrosine phosphorylation. The PKC delta that was tyrosine-phosphorylated in response to TGF alpha had reduced activity compared with the nontyrosine-phosphorylated PKC delta. Treatment of keratinocytes expressing a normal epidermal growth factor receptor (EGFR) with TGF alpha or epidermal growth factor for 5 min induced PKC delta tyrosine phosphorylation, This acute epidermal growth factor treatment did not induce tyrosine phosphorylation of PKC delta in keratinocytes isolated from waved-2 mice that have a defective epidermal growth factor receptor, In addition, the level of PKC delta tyrosine phosphorylation in v-ras(Ha)-transduced keratinocytes from EGFR null mice was substantially lower than in v-ras(Ha) transduced mild type cells, suggesting that activation of the EGFR is important for PKC delta tyrosine phosphorylation in ras transformation. However, purified EGFR did not phosphorylate recombinant PKC delta in vitro, whereas members of the Src family (c-Src, c-Fyn) and membrane preparations hom keratinocytes did, Furthermore, clearing c-Src or c-Fyn from keratinocyte membrane lysates decreased PKC delta tyrosine phosphorylation, and c-Src and c-Fyn isolated from keratinocytes treated with TGF alpha had increased kinase activity, Acute or chronic treatment with TGF alpha did not induce significant PKC delta translocation in contrast to the phorbol ester 12-O-tetradecanoylphorbol-13-acetate, which induced both translocation and tyrosine phosphorylation of PKC delta. This suggests that TGF alpha-induced tyrosine phosphorylation of PKC delta results from the activation of a tyrosine kinase rather than physical association of PKC delta with a membrane-anchored tyrosine kinase, Taken together, these results indicate that PKC delta activity is inhibited by tyrosine phosphorylation in response to EGFR-mediated signaling and activation of a member of the Src kinase family may be the proximal tyrosine kinase acting on PKC delta in keratinocytes. C1 NCI,LAB CELLULAR CARCINOGENESIS & TUMOR PROMOT,BETHESDA,MD 20892. CASE WESTERN RESERVE UNIV,DEPT GENET,CLEVELAND,OH 44106. RI Threadgill, David/N-4425-2013 OI Threadgill, David/0000-0003-3538-1635 NR 50 TC 169 Z9 171 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 MAR 8 PY 1996 VL 271 IS 10 BP 5325 EP 5331 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TZ286 UT WOS:A1996TZ28600010 PM 8621384 ER PT J AU Cara, A Cereseto, A Lori, F Reitz, MS AF Cara, A Cereseto, A Lori, F Reitz, MS TI HIV-1 protein expression from synthetic circles of DNA mimicking the extrachromosomal forms of viral DNA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; SPLEEN NECROSIS VIRUS; LONG TERMINAL REPEAT; POLY(A) SITE; CELLS; INFECTION; ACCUMULATION AB We have constructed circular forms of human immunodeficiency virus type 1 viral DNA in vitro that closely resemble the single and double long terminal repeat circular forms of unintegrated viral DNA formed in the nuclei of infected cells, We have analyzed viral protein expression after transient transfection of these circular DNAs into HeLa cells and compared it with expression from a transfected linearized plasmid containing an integrated provirus. Both circular forms are expressed, as judged by the appearance of extracellular p24, and expression is trans-activated by human immunodeficiency virus type 1 Tat, Viral p24 production, however, is approximately an order of magnitude lower than that obtained with transfected integrated viral DNA. Similar data were obtained when a luciferase reporter gene was substituted for the coding regions of the viral DNA. Positional effects of the transcriptional initiation and termination signals in the long terminal repeat appear to account for some of the low expression levels. These data suggest that unintegrated circular viral DNAs are transcriptionally active, although at low levels, and may contribute to overall viral replication in infected people under some conditions. RP Cara, A (reprint author), NCI,TUMOR CELL BIOL LAB,NIH,BLDG 37,RM 6A09,37 CONVENT DR,BETHESDA,MD 20892, USA. RI Cara, Andrea/M-4865-2015 OI Cara, Andrea/0000-0003-4967-1895 NR 29 TC 44 Z9 44 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 MAR 8 PY 1996 VL 271 IS 10 BP 5393 EP 5397 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TZ286 UT WOS:A1996TZ28600019 PM 8621393 ER PT J AU Dittrich, E Haft, CR Muys, L Heinrich, PC Graeve, L AF Dittrich, E Haft, CR Muys, L Heinrich, PC Graeve, L TI A di-leucine motif and an upstream serine in the interleukin-6 (IL-6) signal transducer gp130 mediate ligand-induced endocytosis and down-regulation of the IL-6 receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MANNOSE 6-PHOSPHATE RECEPTOR; ACUTE-PHASE RESPONSE; CYTOPLASMIC DOMAIN; MONOCLONAL-ANTIBODY; CARBOXYL-TERMINUS; MOLECULAR-CLONING; TYROSINE KINASE; PROTEIN; INTERNALIZATION; CELLS AB The interleukin-6 (IL-6) receptor complex is composed of two different subunits, the IL-6 binding protein (IL-6R, gp80) and the signal transducing component gp130. Our previous studies revealed that the 10-amino acid sequence TQPLLDSEER within the intracellular domain of gp130 is crucial for the efficient internalization of IL-6. Since this sequence contains a putative dileucine internalization motif, we further analyzed this region by constructing two additional deletions and a series of point mutants. Analyses of these mutants showed that the di-leucine pair (Leu-145 and Leu-146) is essential for ligand internalization, with leucine 145 being less resilient to exchanges. Furthermore, when a chimeric protein (Tac-STQPLL) composed of the Tac antigen fused to the hexapeptide STQPLL of gp130 was studied, we found that this sequence is sufficient to mediate endocytosis and lysosomal targeting of the chimera. Mutational analysis of three serine residues upstream of the di-leucine motif revealed that mutation of serine 139 to an alanine reduces the initial internalization rate by 50%. This finding suggests that a serine phosphorylation may be important for rapid endocytosis. C1 RHEIN WESTFAL TH AACHEN,INST BIOCHEM,D-52057 AACHEN,GERMANY. NIDDKD,DIABET BRANCH,NIH,BETHESDA,MD 20892. RHEIN WESTFAL TH AACHEN,INST PATHOL,D-52057 AACHEN,GERMANY. NR 52 TC 135 Z9 135 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 MAR 8 PY 1996 VL 271 IS 10 BP 5487 EP 5494 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TZ286 UT WOS:A1996TZ28600032 PM 8621406 ER PT J AU Tsoulfas, P Stephens, RM Kaplan, DR Parada, LF AF Tsoulfas, P Stephens, RM Kaplan, DR Parada, LF TI TrkC isoforms with inserts in the kinase domain show impaired signaling responses SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NERVE GROWTH-FACTOR; TETRADECANOYL PHORBOL ACETATE; SWISS 3T3 CELLS; TYROSINE KINASE; PC12 CELLS; PHOSPHATIDYLINOSITOL 3-KINASE; PHEOCHROMOCYTOMA CELLS; PROTOONCOGENE PRODUCT; RAT TRKC; RECEPTOR AB The genetic locus for the TrkC/neurotrophin 3 (NT-3) receptor tyrosine kinase encodes multiple isoforms including receptors with inserts in the catalytic domain. This study examines the signaling capabilities of TrkC and related kinase insert isoforms TrkC14 and TrkC25. We show that in PC12 cells expressing both TrkC and TrkA/nerve growth factor (NGF) receptors, different morphological changes occur upon addition of NGF or NT-3. NT-3-treated cells exhibit longer neurites and larger cell bodies as compared to NGF-treated cells. Both TrkC and TrkA mediate qualitatively similar increases in the tyrosine phosphorylation of phospholipase C (PLC)-gamma 1, Shc, SNT, and MAPK and the transcription of the c-fos, c-jun, NGFI-A, and NGFI-B immediate early genes. However, the TrkC kinase insert forms fail to stimulate these events. Furthermore, TrkC14 and TrkC25 have only a low intrinsic tyrosine kinase activity, and insertion of the TrkC14 kinase insert into TrkA at an equivalent position results in a dramatic reduction of the kinase activity and signaling capabilities of TrkA. The TrkC14 and -25 isoforms may fail to transmit signals due to their low intrinsic kinase activity and failure to activate and/or tyrosine phosphorylate targets shown to be involved in neurotrophin signal transduction pathways. C1 NCI,NIH,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,EUKARYOT SIGNAL TRANSDUCT SECT,FREDERICK,MD 21702. RI Parada, luis/B-9400-2014; OI Tsoulfas, Pantelis/0000-0003-1974-6366 NR 56 TC 54 Z9 54 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 MAR 8 PY 1996 VL 271 IS 10 BP 5691 EP 5697 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TZ286 UT WOS:A1996TZ28600060 PM 8621434 ER PT J AU Zhang, R Buczko, E Dufau, ML AF Zhang, R Buczko, E Dufau, ML TI Requirement of cysteine residues in exons 1-6 of the extracellular domain of the luteinizing hormone receptor for gonadotropin binding SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN THYROTROPIN RECEPTOR; SITE-DIRECTED MUTAGENESIS; FUNCTIONAL EXPRESSION; HIGH-AFFINITY; RAT; CELLS; MUTATION; GENE; CDNA; TSH AB The functional importance of cysteine residues in the extracellular domain and the extracellular loops (EL1 and EL2) to hormone binding of the rat luteinizing hormone receptor (LHR) was investigated. For this purpose, cysteines in the seven-transmembrane holoreceptor (Form A) and its hormone-binding splice variant (Form B) were replaced by serine residues, and mutant receptors were expressed in COS1 and/or insect cells. Within the extracellular domain, individual replacement of all four cysteines from Exon 1 abolished hormone binding activity, and replacement of Cys-109 and Cys-134 from exons 5 and 6 caused a 75% decrease in both cell surface and total cellular solubilized LHR hormone binding activity. Mutations of Cys-257 and -258 (Exon 9), Cys-321 and -331, and Cys-417 and -492 of EL1 and EL2, respectively (Exon 11), showed no surface hormone binding activity on intact cells, but exhibited wild type levels of total hormone binding activity when recovered from detergent-solubilized cellular extracts. This finding indicated that expression of high affinity LHR binding activity at the cell surface is independent of the acquisition of the high affinity binding conformation. Other cysteine residues, including Cys-282 (exon 10), and Cys-314 (exon 11) were not essential for hormone binding activity or plasma membrane insertion. This study demonstrates that the functional hormone binding domain utilizes all cysteines N-terminal to exon 7 and localizes the binding site to this N-terminal region of the extracellular domain. C1 NICHHD,NIH,SECT MOLEC ENDOCRINOL,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892. NR 27 TC 53 Z9 54 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 MAR 8 PY 1996 VL 271 IS 10 BP 5755 EP 5760 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TZ286 UT WOS:A1996TZ28600068 PM 8621442 ER PT J AU Yang, NY Shigeta, H Shi, HP Teng, CT AF Yang, NY Shigeta, H Shi, HP Teng, CT TI Estrogen-related receptor, hERR1, modulates estrogen receptor-mediated response of human lactoferrin gene promoter SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTION FACTOR; REPRODUCTIVE-TRACT; HORMONE RECEPTORS; ORPHAN RECEPTORS; BINDING-PROTEIN; DNA-BINDING; FACTOR-I; MOUSE; EXPRESSION; ACTIVATION AB We have shown previously that estrogen-stimulated transcription from the human lactoferrin gene in RL95-2 endometrium carcinoma cells is mediated through an imperfect estrogen response element (ERE) at the 5'-flanking region of the gene. Upstream from the ERE, a DNA sequence (-418 to -378, FP1) was selectively protected from DNase I digestion by nuclear extracts from endometrial and mammary gland cell lines. In this report, using the electrophoresis mobility shift assay, site-directed mutagenesis, and DNA methylation interference analyses, we show that three different nuclear proteins bind to the FP1 region (C1, C2, and C3 sites). The nuclear receptor, COUP-TF, binds to the C2 site. Mutations in the C1 binding region abolish C1 complex formation and reduce estrogen-dependent transcription from the lactoferrin ERE. When the imperfect ERE of the lactoferrin gene is converted to a perfect palindromic structure, the enhancing effect of the C1 binding element for estrogen responsiveness was abolished. me isolated a complementary DNA (cDNA) clone from an RL95-2 expression library that encodes the C1 site-binding protein. The encoded polypeptide maintains 99% amino acid identity with the previously described orphan nuclear receptor hERR1. A 2.2-kilobase mRNA was detected in RL95-2 cells by the newly isolated cDNA but not by the first 180 base pair of the published hERR1 sequence. By Western analysis, a major 42-kDa protein is detected in the RL95-2 nuclear extract with antibody generated against GST-hERR1 fusion protein. Finally, we show that the hERR1 interacts with the human estrogen receptor through protein-protein contacts. C1 NIEHS,NIH,GENE REGULAT GRP,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC 27709. NR 57 TC 160 Z9 169 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 MAR 8 PY 1996 VL 271 IS 10 BP 5795 EP 5804 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TZ286 UT WOS:A1996TZ28600074 PM 8621448 ER PT J AU Englander, EW Howard, BH AF Englander, EW Howard, BH TI A naturally occurring T(14)A(11) tract blocks nucleosome formation over the human neurofibromatosis type 1 (NF1)-Alu element SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RNA POLYMERASE-III; ALU REPEATED SEQUENCES; TRANSCRIPTION COMPLEXES; FAMILY MEMBERS; DNA; CHROMATIN; GENES; HISTONES; POLY(DA).POLY(DT); ORGANIZATION AB The nature of chromatin organization over Alu repetitive elements is of interest with respect to the maintenance of their transcriptional silencing as well as their potential to influence local chromatin structure. We previously demonstrated that the pattern of nucleosomal organization over Alu elements in native chromatin is specific and similar to the pattern observed with an in vitro reconstituted Alu template. This pattern, distinguished by a nucleosome centered over the 5'-end of the Alu element, is associated with repression of polymerase m-dependent transcription in vitro (Englander, E. W., Wolffe, A. P., and Howard, B. H. (1993) J. Biol. Chem. 268, 19565-19573; Englander, E. W., and Howard, B. H. (1995) J. Biol. Chem. 270, 10091-10096). In the current study, additional templates representing both evolutionarily old and young Alu subfamilies were found to direct a similar pattern of nucleosome assembly, consistent with the view that nucleosome positioning in vitro is shared by a majority of Alus. We discovered however, that the specific nucleosome positioning pattern was disrupted over one member of a young Alu subfamily, which recently transposed immediately downstream to a T(14)A(11) sequence in the neurofibromatosis type 1 locus (Wallace, M. R., Andersen, L. B., Saulino, A. M., Gregory, P. E., Glover, T. W., and Collins, F. S. (1991) Nature 353, 864-866). Upon removal of this sequence motif, the expected pattern of assembly was restored to the neurofibromatosis type 1-Alu template. This finding indicates that, at least in vitro, certain sequences can override the propensity for positioning nucleosomes that is inherent to Alu elements. The finding also raises the possibility that a similar situation may occur in vivo, with potential implications for understanding mechanisms by which certain Alu elements may evade chromatin-mediated transcriptional silencing. RP Englander, EW (reprint author), NICHHD,NIH,LAB MOLEC GROWTH REGULAT,BETHESDA,MD 20892, USA. NR 53 TC 12 Z9 12 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 8 PY 1996 VL 271 IS 10 BP 5819 EP 5823 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TZ286 UT WOS:A1996TZ28600077 PM 8621451 ER PT J AU Kajander, KC Madsen, AM Iadarola, MJ Draisci, G AF Kajander, KC Madsen, AM Iadarola, MJ Draisci, G TI Fos-like immunoreactivity increases in the lumbar spinal cord following a chronic constriction injury to the sciatic nerve of rat SO NEUROSCIENCE LETTERS LA English DT Article DE hyperalgesia; nerve compression syndromes; neuralgia; neuroma; neuronal plasticity; pain; proto-oncogene proteins c-fos ID PAINFUL PERIPHERAL NEUROPATHY; SUPERFICIAL DORSAL HORN; C-FOS; EXPRESSION; NEURONS; PROTEIN; STIMULATION; TRANSECTION AB A chronic constriction injury (CCI), transection injury, or sham injury to the sciatic nerve was induced in 30 rats. Rats were then sacrificed at 1, 3, 5, 10, and 20 days following injury, and the number of cells immunohistochemically labeled for Fos-like immunoreactivity (Fos-LI) was determined in random sections from the lumbar 4 and 5 (LA and 1,5) spinal segments. Non-parametric statistics (Wilcoxon) were used to compare the number of labeled cells ipsilateral to the injury to the number of labeled cells on the contralateral side. At 1 and 5 days following injury, in all treatment groups, significantly more labeled cells (P < 0.05) were observed ipsilaterally. In addition, at 3 and 10 days following injury, the CCI groups exhibited significantly more labeled cells ipsilaterally. The significant increases for the CCI groups ranged from 161% to 360%. Generally, increases were greater for the CCI groups. These results indicate that Fos-LI increases to a greater extent and for a longer duration following the CCI than following either a transection or sham injury. C1 UNIV MINNESOTA,DEPT CELL BIOL & NEUROANAT,MINNEAPOLIS,MN 55455. NIDR,NIH,NEUROBIOL & ANESTHESIOL BRANCH,BETHESDA,MD 20892. RP Kajander, KC (reprint author), UNIV MINNESOTA,DEPT ORAL SCI,515 DELAWARE ST SE,MINNEAPOLIS,MN 55455, USA. OI DRAISCI, Gaetano/0000-0003-0148-5073 FU NINDS NIH HHS [NS29567] NR 21 TC 60 Z9 61 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD MAR 8 PY 1996 VL 206 IS 1 BP 9 EP 12 DI 10.1016/0304-3940(96)12447-2 PG 4 WC Neurosciences SC Neurosciences & Neurology GA UB091 UT WOS:A1996UB09100003 PM 8848286 ER PT J AU Nissley, DV Garfinkel, DJ Strathern, JN AF Nissley, DV Garfinkel, DJ Strathern, JN TI HIV reverse transcription in yeast SO NATURE LA English DT Letter ID TY ELEMENTS; CEREVISIAE RP Nissley, DV (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,GENE REGULAT & CHROMOSOME BIOL LAB,POB B,FREDERICK,MD 21702, USA. NR 8 TC 11 Z9 11 U1 0 U2 2 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD MAR 7 PY 1996 VL 380 IS 6569 BP 30 EP 30 DI 10.1038/380030a0 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TY877 UT WOS:A1996TY87700038 PM 8598898 ER PT J AU Verheij, M Bose, R Lin, XH Yao, B Jarvis, WD Grant, S Birrer, MJ Szabo, E Zon, LI Kyriakis, JM HaimovitzFriedman, A Fuks, Z Kolesnick, RN AF Verheij, M Bose, R Lin, XH Yao, B Jarvis, WD Grant, S Birrer, MJ Szabo, E Zon, LI Kyriakis, JM HaimovitzFriedman, A Fuks, Z Kolesnick, RN TI Requirement for ceramide-initiated SAPK/JNK signalling in stress-induced apoptosis SO NATURE LA English DT Article ID KINASE; DEATH AB The induction of programmed cell death, or apoptosis, involves activation of a signalling system, many elements of which remain unknown(1). The sphingomyelin pathway, initiated by hydrolysis of the phospholipid sphingomyelin in the cell membrane to generate the second messenger ceramide(2,3), is thought to mediate apoptosis in response to tumour-necrosis factor (TNF)-alpha(2,3), to Fas ligand(4) and to X-rays(5). It is not known whether it plays a role in the stimulation of other forms of stress-induced apoptosis. Given that environmental stresses also stimulate a stress-activated protein kinase (SAPR/JNK)(6-12), the sphingomyelin and SAPK/ JNK signalling systems may be coordinated in induction of apoptosis. Here we report that ceramide initiates apoptosis through the SAPK cascade and provide evidence for a signalling mechanism that integrates cytokine- and stress-activated apoptosis. C1 MEM SLOAN KETTERING CANC CTR,LAB SIGNAL TRANSDUCT,NEW YORK,NY 10021. MEM SLOAN KETTERING CANC CTR,DEPT RADIAT ONCOL,NEW YORK,NY 10021. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT MED,DIV HEMATOL ONCOL,RICHMOND,VA 23298. NCI,DIV CANC PREVENT & CONTROL,BIOMARKERS & PREVENT RES BRANCH,ROCKVILLE,MD 20850. CHILDRENS HOSP,DIV HEMATOL ONCOL,BOSTON,MA 02115. HARVARD UNIV,SCH MED,HOWARD HUGHES MED INST,DEPT PEDIAT,DANA FARBER CANC INST,BOSTON,MA 02115. HARVARD UNIV,SCH MED,HOWARD HUGHES MED INST,DEPT PEDIAT,DANA FARBER CANC INST,CHILDRENS HOSP,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP EAST,MED SERV,DIABET RES LAB,BOSTON,MA 02129. NR 30 TC 1632 Z9 1671 U1 3 U2 47 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD MAR 7 PY 1996 VL 380 IS 6569 BP 75 EP 79 DI 10.1038/380075a0 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TY877 UT WOS:A1996TY87700060 PM 8598911 ER PT J AU Kim, S Brown, PH Birrer, MJ AF Kim, S Brown, PH Birrer, MJ TI The inhibitory activity of a transdominant c-jun mutant fused to the ligand binding domain of the estrogen receptor SO ONCOGENE LA English DT Article DE transcription factor; jun; fos; AP-1; dominant negative mutant; estrogen receptor ID FUSION PROTEIN; TRANSCRIPTIONAL ACTIVATION; EMBRYO FIBROBLASTS; GENE FAMILY; TRANSFORMATION; CELLS; DIFFERENTIATION; ONCOPROTEIN; SUPPRESSION; EXPRESSION AB Tam-67 is an amino-terminal deletion mutant of c-Jun (Delta 3-122) lacking most of the c-Jun transactivation domain, which has been shown previously to function in a transdominant fashion to inhibit c-Jun-induced transactivation and cellular transformation. In order to create a ligand-dependent dominant negative repressor of AP-1, we have constructed a fusion of the TAM-67 gene with the ligand binding domain of the estrogen receptor. Fusion of TAM-67 with the ligand binding domain of the estrogen receptor produced a 68 kD protein (TAM-67ER) which was immunoprecipitated by c-Jun-specific and estrogen receptor-specific antisera and shown by gel retardation assay to bind oligonucleotides containing an AP-1 sequence. Cotransfection of TAM-67ER and an AP-1-dependent reporter construct into rat embryo cells demonstrated ligand specific inhibition of AP-1 transactivation. In the absence of hormone, TAM-67ER produced complete inhibition of cJun-induced AP-1 transactivation. This inhibition was relieved by treatment with estradiol but not by treatment with tamoxifen. In addition, TAM-67ER inhibited activated c-Ha-ras- or c- raf-induced transformation of NTH3T3 cells. However, this inhibition of transformation was not relieved by the addition of estrogen. Thus, TAM-67ER inhibits transactivation in a ligand-dependent manner, but inhibits transformation in a ligand-independent manner. The results suggest that the ligand-dependent transactivation domain of the estrogen receptor (TAF-2) can substitute for the cJun transactivation domain absent in TAM-67 to stimulate transactivation. However, TAF-2 cannot substitute for the missing c-Jun transactivation domain to induce cellular transformation. C1 NCI,DIV CLIN SCI,BIOMARKERS & PREVENT RES BRANCH,ROCKVILLE,MD 20850. UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20814. NR 35 TC 9 Z9 9 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR 7 PY 1996 VL 12 IS 5 BP 1043 EP 1053 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA UA884 UT WOS:A1996UA88400012 PM 8649795 ER PT J AU Guerrero, C Rojas, JM Chedid, M Esteban, LM Zimonjic, DB Popescu, NC deMora, JF Santos, E AF Guerrero, C Rojas, JM Chedid, M Esteban, LM Zimonjic, DB Popescu, NC deMora, JF Santos, E TI Expression of alternative forms of Ras exchange factors GRF and SOS1 in different human tissues and cell lines SO ONCOGENE LA English DT Article DE Ras; hGRF; hSOS1; expression; alternative splicing ID NUCLEOTIDE-RELEASING FACTOR; RECEPTOR TYROSINE KINASES; SACCHAROMYCES-CEREVISIAE; DROSOPHILA SON; SEVENLESS GENE; IDENTIFICATION; HOMOLOGS; PROTEINS; GRB2; CDNAS AB DNA probes and antibodies specific for different coding regions of human SOS1 and GRF genes were used to screen expression of these genes in a variety of adult and fetal human tissues and cell lines. Despite previous reports of the exclusive expression of hGRF RNA in brain, we also observed expression of this gene in various other tissues including lung and pancreas, as web as several tumor cell lines. At least three different hGRF mRNA transcripts were observed depending on the probe used, with the larger transcripts being detected by probes corresponding to the 5' end of the gene while smaller transcripts were detected by probes corresponding to the 3' end. Expression of hSOS1-related transcripts was more ubiquitous and homogeneous than with hGRF, with similar levels of specific transcripts being detected in most tissues and cell lines tested. Three to five different transcripts were detected in human tissues when using probes for the 5' end and middle regions of this gene, whereas only two were detected with probes corresponding to the 3' end. Screening of multiple human tumor cell lines showed ubiquitous expression of three specific transcripts, although the level and ratio of each of these transcripts varied widely among individual cell lines. Consistent with the variety of transcripts detected, several protein forms were also identified in Western immunoblots with antisera raised against specific domains of hSOS1 and human Ras-GRF gene products. Fluorescence in situ chromosomal hybridization suggested that, in both cases, the multiple forms arise from single chromosomal loci. The heterogeneity of hGRF and hSOS1 gene products detected (which appear to retain in most cases a functional catalytic domain), suggests that differentially expressed, alternatively spliced hSOS1 and hGRF forms may contribute to fine regulation of Ras activation in different tissues or at different stages of development. C1 NCI,DBS,CELLULAR & MOLEC BIOL LAB,NATL INST HLTH,BETHESDA,MD 20892. NCI,DBS,BIOL LAB,NATL INST HLTH,BETHESDA,MD 20892. RI Font de Mora, Jaime/H-6304-2015; Guerrero, Carmen/F-1776-2010 OI Font de Mora, Jaime/0000-0002-6816-2095; Guerrero, Carmen/0000-0002-8747-6831 NR 34 TC 45 Z9 46 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR 7 PY 1996 VL 12 IS 5 BP 1097 EP 1107 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA UA884 UT WOS:A1996UA88400019 PM 8649802 ER PT J AU Rapola, JM Virtamo, J Haukka, JK Heinonen, OP Albanes, D Taylor, PR Huttunen, JK AF Rapola, JM Virtamo, J Haukka, JK Heinonen, OP Albanes, D Taylor, PR Huttunen, JK TI Effect of vitamin E and beta carotene on the incidence of angina pectoris - A randomized, double-blind, controlled trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CORONARY HEART-DISEASE; MYOCARDIAL-INFARCTION; DENSITY-LIPOPROTEIN; ROSE QUESTIONNAIRE; ALPHA-TOCOPHEROL; E CONSUMPTION; RISK; CHOLESTEROL; INHIBITION; HUMANS AB Objective.-To examine the effect of supplementation with vitamin E (alpha tocopherol), beta carotene, or both on the incidence of angina pectoris in men without known previous coronary heart disease. Design.-Randomized, double-blind, placebo-controlled trial. Setting and Participants.-Participants in the Alpha Tocopherol, Beta Carotene Cancer Prevention Study (N=29 133) were male smokers aged 50 through 69 years who were living in southern and western Finland. Of these men, 22 269 were considered free of coronary heart disease at baseline and were followed up for the incidence of angina pectoris. Intervention.-Participants were randomized to receive 50 mg/d of alpha tocopherol, 20 mg/d of beta carotene, both, or placebo in a 2x2 design. Outcome Measures.-An incident case was defined as the first occurrence of typical angina pectoris identified in administering the annually repeated World Health Organization (Rose) Chest Pain Questionnaire. Results.-During a median follow-up time of 4.7 years (96 427 person-years), 1983 new cases of angina pectoris were detected. Comparing alpha tocopherol-supplemented subjects with non-alpha tocopherol-supplemented subjects showed a relative risk (RR) of angina pectoris incidence of 0.91 (95% confidence interval [CI], 0.83 to 0.99; P=.04). The RR for incidence of angina pectoris for the beta carotene-supplemented subjects compared with those not receiving beta carotene was 1.06 (95% CI, 0.97 to 1.16; P=.19). Compared with those receiving placebo, the RRs for incidence of angina pectoris were 0.97 (95% CI, 0.85 to 1.10) and 0.96 (95% CI, 0.85 to 1.09) in the alpha tocopherol and alpha tocopherol plus beta carotene groups respectively, and 1.13 (95% CI, 1.00 to 1.27) in the beta carotene group (P=.06). Baseline dietary intakes and serum levels of alpha tocopherol and beta carotene did not predict incidence of angina pectoris. Conclusions.-Supplementation with alpha tocopherol was associated with only a minor decrease in the incidence of angina pectoris. Beta carotene had no preventive effect and was associated with a slight increase in the incidence of angina. C1 NCI,BETHESDA,MD 20892. RP Rapola, JM (reprint author), NATL PUBL HLTH INST,MANNERHEIMINTIE 166,SF-00300 HELSINKI,FINLAND. RI Albanes, Demetrius/B-9749-2015; Haukka, Jari/G-1484-2014 OI Haukka, Jari/0000-0003-1450-6208 FU NCI NIH HHS [N0I-CN-45165] NR 46 TC 151 Z9 156 U1 1 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 MAR 6 PY 1996 VL 275 IS 9 BP 693 EP 698 DI 10.1001/jama.275.9.693 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA TX174 UT WOS:A1996TX17400024 PM 8594266 ER PT J AU Rhyu, MS AF Rhyu, MS TI Molecular mechanisms underlying hereditary nonpolyposis colorectal carcinoma SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Review ID DNA MISMATCH CORRECTION; BASE-PAIR MISMATCHES; ESCHERICHIA-COLI K-12; UVRD GENE-PRODUCT; SACCHAROMYCES-CEREVISIAE; DEOXYRIBONUCLEIC-ACID; SPONTANEOUS MUTATION; CELL-LINES; REPAIR; CANCER AB MutS and MutL are bacterial genes that have critical roles in DNA repair and recombination. Mutations in homologues of these genes cause hereditary nonpolyposis colorectal carcinoma and are implicated in some sporadic (nonhereditary) colorectal cancers, Molecular functions of these genes have been defined through extensive work in bacteria and yeast. This article reviews and explores molecular events that require MutS and MutL, including mismatch repair, homologous recombination, and gene conversion. The mechanisms of action of eukaryotic MutS and MutL homologues are compared with those of their prokaryotic counterparts, and the relevance of these mechanisms to tumorigenesis is discussed. RP Rhyu, MS (reprint author), NCI,JOURNAL NATL CANC INST,BETHESDA,MD 20892, USA. NR 126 TC 77 Z9 78 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 MAR 6 PY 1996 VL 88 IS 5 BP 240 EP 251 DI 10.1093/jnci/88.5.240 PG 12 WC Oncology SC Oncology GA TY058 UT WOS:A1996TY05800010 PM 8614002 ER PT J AU Fitzsimmons, SA Workman, P Grever, M Paull, K Camalier, R Lewis, AD AF Fitzsimmons, SA Workman, P Grever, M Paull, K Camalier, R Lewis, AD TI Reductase enzyme expression across the national cancer institute tumor cell line panel: Correlation with sensitivity to mitomycin C and E09 SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID DT-DIAPHORASE; XANTHINE DEHYDROGENASE; BIOREDUCTIVE DRUGS; HYPOXIC CONDITIONS; GENE-EXPRESSION; CYTOTOXICITY; ACTIVATION; METABOLISM; MECHANISM; ACID AB Background: Many antitumor drugs require metabolic activation to exert their cytotoxic or cytostatic effects. The so-called bioreductive compounds, whose conversion into active antitumor agents is catalyzed by reductase enzymes, are examples of such drugs. The identification of specific enzymes involved in the activation of these compounds is important in understanding cellular factors that may influence drug antitumor activity. Purpose: We measured expression Levels of three different reductase enzymes-DT-diaphorase [NAD(P)H( i.e., reduced nicotinamide adenine dinucleotide, with or without phosphate):quinone oxidoreductase]; NADPH:cytochrome P-450 reductase; and NADH (i.e., reduced nicotinamide adenine dinucleotide): cytochrome-b(5) reductase-in 69 cell lines (most of the National Cancer Institute [NCI] human tumor cell panel) to see if relationships could be established between the activities of these enzymes and cellular sensitivities to the bioreductive compounds mitomycin C and EO9. Methods: For all 69 cell lines, the activity of each enzyme was determined using cellular extracts and photometric assays involving the reduction of cytochrome c. Western blot analysis was used to measure the relative amount of DT-diaphorase protein in each extract, and coupled reverse transcription and polymerase chain reactions were employed to assess DT-diaphorase and NADPH:cytochrome P-450 reductase messenger RNA (mRNA) levels in a subset of the cell lines. The cytotoxic and/or cytostatic activities of mitomycin C and EO9 toward the cell lines were determined under aerobic conditions. Relationships between enzyme activity levels and drug sensitivities were assessed by use of the COMPARE program and Pearson correlation coefficients. Results: In general, DT-diaphorase activity levels were higher than those observed for the other two reductases across the entire cell line panel. Measured activities for all three enzymes varied among cell lines derived from the same tissue as well as between lines derived from different tissues; however, tissue-specific patterns of expression could be discerned. Differences in the activity levels of individual enzymes appeared to reflect differences in corresponding enzyme protein and/or mRNA levels. A relationship between enzyme activity and chemosensitivities to mitomycin C and EO9 was observed only for DT-diaphorase (Pearson correlation coefficient = .424 [two-sided P<.0005] for mitomycin C and .446 [two-sided P less than or equal to.0013] for EO9). Conclusions: Reductase enzyme expression is heterogeneous across human tumor cell lines, and tissue-specific patterns of expression are apparent, DT-diaphorase activity levels correlate with sensitivities to mitomycin C and EO9, supporting a role for this enzyme in the bioactivation of these anticancer compounds. Implications: Comparison of biochemical, molecular biological, and chemosensitivity data obtained from screening a large number of cell lines (e.g., the NCI tumor cell line panel) may facilitate investigation of factors influencing drug antitumor activity. The knowledge gained may be of value in the development of new anticancer agents or in the selection of patients to receive specific therapies. C1 UNIV GLASGOW, CRC DEPT MED, CANC RES CAMPAIGN, BEATSON LABS, GLASGOW G61 1BD, LANARK, SCOTLAND. NCI, INFORMAT TECHNOL BRANCH, DIV CANC TREATMENT, BETHESDA, MD 20892 USA. NR 44 TC 202 Z9 206 U1 0 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAR 6 PY 1996 VL 88 IS 5 BP 259 EP 269 DI 10.1093/jnci/88.5.259 PG 11 WC Oncology SC Oncology GA TY058 UT WOS:A1996TY05800012 PM 8614004 ER PT J AU Hartge, P Devesa, SS Grauman, D Fears, TR Fraumeni, JF AF Hartge, P Devesa, SS Grauman, D Fears, TR Fraumeni, JF TI Non-Hodgkin's lymphoma and sunlight SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID TRENDS; RISK RP Hartge, P (reprint author), NCI,DIV CANC EPIDEMIOL & GENET,NIH,EXECUT PLAZA N,RM 443,BETHESDA,MD 20892, USA. NR 14 TC 82 Z9 82 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 MAR 6 PY 1996 VL 88 IS 5 BP 298 EP 300 DI 10.1093/jnci/88.5.298 PG 3 WC Oncology SC Oncology GA TY058 UT WOS:A1996TY05800017 PM 8614009 ER PT J AU Koenig, BW Kruger, S Orts, WJ Majkrzak, CF Berk, NF Silverton, JV Gawrisch, K AF Koenig, BW Kruger, S Orts, WJ Majkrzak, CF Berk, NF Silverton, JV Gawrisch, K TI Neutron reflectivity and atomic force microscopy studies of a lipid bilayer in water adsorbed to the surface of a silicon single crystal SO LANGMUIR LA English DT Article ID SUPPORTED PHOSPHOLIPID-BILAYERS; GLYCOL MONODODECYL ETHER; SPECULAR REFLECTION; PHOSPHATIDYLCHOLINE VESICLES; AQUEOUS-SOLUTION; GEL PHASE; FT-IR; X-RAY; INTERFACE; LAYER AB Specular reflection of neutrons has been used to characterize the structure of single lipid bilayers adsorbed to a planar silicon surface from aqueous solution. We used a novel experimental setup which significantly decreased the incoherent background scattering and allowed us to measure neutron reflectivities as low as 5 x 10(-7). Thicknesses and neutron scattering length densities were determined by a fitting procedure using (i) randomly generated smooth functions represented by parametric B-splines and (ii) stepped functions based on the theoretical lipid composition. The size of lipid domains at the surface and the degree of surface coverage were determined by atomic force microscopy. Chain-protonated and -deuterated dipalmitoylphosphatidylcholine (DPPC) bilayers were investigated in (H2O)-H-2 and a mixture of (H2O)-H-2 and H2O which matches the scattering density of silicon. Also, one measurement on a distearoylphosphatidylcholine bilayer which has longer acyl chains was performed for comparison. The lipid adsorbs to the silicon surface as a continuous layer interrupted by irregularly shaped uncovered areas which are 100-500 Angstrom in size. The surface coverage was estimated to be 70 +/- 20%. The reflectivity measurements on DPPC at 60 degrees C show a silicon oxide layer with a thickness of the order of 4 Angstrom, a rough silicon oxide/water layer between silicon oxide and lipid with a thickness between 2 and 8 Angstrom, and a single lipid bilayer. Fitting resolved a central membrane layer with a thickness of 28 +/- 2 Angstrom which represents the lipid hydrocarbon chains. This layer is sandwiched between interface membrane layers of lipid head groups and water which are 11.5 +/- 1 Angstrom in thickness. The angstrom-scale thickness changes of the central membrane layer as a function of the phase state of the lipid and of the length of the hydrocarbon chains are easily detected. C1 NIAAA,NIH,LAB MEMBRANE BIOCHEM & BIOPHYS,ROCKVILLE,MD 20852. NHLBI,NIH,BIOPHYS CHEM LAB,BETHESDA,MD 20892. NIST,MAT SCI & ENGN LAB,GAITHERSBURG,MD 20899. RI Koenig, Bernd/B-4315-2008 OI Koenig, Bernd/0000-0002-5300-6276 NR 39 TC 204 Z9 206 U1 2 U2 40 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0743-7463 J9 LANGMUIR JI Langmuir PD MAR 6 PY 1996 VL 12 IS 5 BP 1343 EP 1350 DI 10.1021/la950580r PG 8 WC Chemistry, Multidisciplinary; Chemistry, Physical; Materials Science, Multidisciplinary SC Chemistry; Materials Science GA TZ050 UT WOS:A1996TZ05000037 ER PT J AU Kuan, CT Pastan, I AF Kuan, CT Pastan, I TI Recombinant immunotoxin containing a disulfide-stabilized Fv directed at erbB2 that does not require proteolytic activation SO BIOCHEMISTRY LA English DT Article ID PSEUDOMONAS EXOTOXIN; MONOCLONAL-ANTIBODY; FORM; CANCER; TOXINS; RECEPTOR; LEUKEMIA; LYMPHOMA; TUMORS; CELLS AB PE35/e23(dsFv)KDEL is a recombinant immunotoxin composed of a recombinant form of Pseudomonas exotoxin that does not need proteolytic activation and a disulfide-stabilized Fv fragment of the anti-erbB2 monoclonal antibody e23. In this molecule, the variable heavy (V-H) domain is inserted near the carboxyl terminus of PE at position 607 and the variable light (V-L) domain is connected to the V-H domain by a disulfide bond engineered into the framework region. The disulfide bond forms between cysteines introduced at position 44 of V-H and position 99 of V-L [Reiter er al, (1994) J, Biol, Chem. 269, 18327-18331], In contrast to other PE-derived Fv fusion proteins, this type of recombinant toxin does not need proteolytic activation of the toxin domain, PE35/e23(dsFv)KDEL is very cytotoxic toward erbB2 antigen-expressing N87 cells (IC50 = 0.8 ng/mL) despite the fact that it binds to the erbB2 protein only 25% as well as e23(dsFv)PE38KDEL, in which the dsFv moiety is located at the amino terminus of the toxin. The lower binding affinity is probably due to interference by domain III of PE with the amino terminus of e23(V-H), possibly where the antigen binding sites are located. Nevertheless, the specificity of immunotoxin is still retained, and it is very stable at 37 degrees C, Because of its small size, stability, and activity without proteolytic processing, this immunotoxin may be advantageous for tumor treatment, PE35/ e23(dsFv)KDEL was also used to gain information about whether I reduction of the disulfide bonds connecting V-H and V-L occur in the endoplasmic reticulum (ER) or in a proximal compartment, To do this, we switched the ER retention sequence KDEL from the toxin-V-H subunit to the V-L subunit. Our results suggest that reduction of the disulfide bond connecting the dsFv heterodimer occurs before the immunotoxin reaches the ER, where translocation to the cytosol appears to occur. C1 NCI,NIH,DIV BASIC SCI,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 29 TC 9 Z9 9 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 5 PY 1996 VL 35 IS 9 BP 2872 EP 2877 DI 10.1021/bi952047g PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TZ118 UT WOS:A1996TZ11800009 PM 8608123 ER PT J AU Nomizu, M Utani, A Beck, K Otaka, A Roller, PP Yamada, Y AF Nomizu, M Utani, A Beck, K Otaka, A Roller, PP Yamada, Y TI Mechanism of laminin chain assembly into a triple-stranded coiled-coil structure SO BIOCHEMISTRY LA English DT Article ID BASEMENT-MEMBRANE PROTEINS; MULTIDOMAIN PROTEIN; PEPTIDE; DOMAIN; CELLS; BIOSYNTHESIS; CONFORMATION; SPECIFICITY; TROPOMYOSIN; HETERODIMER AB Laminin, a basement membrane glycoprotein, is a heterotrimer with alpha, beta, and gamma chains held together by a triple-stranded alpha-helical coiled-coil structure. Recently, a short peptide sequence at the C-terminus of the alpha-helical domain of each chain was identified as a critical site for the initiation of laminin chain assembly. Synthetic peptides, B1 and B2 (51-mers from the mouse laminin beta 1 and gamma 1 chains, respectively) and M (55-mer from the laminin alpha 2 chain), containing these sites were able to assemble into a triple-stranded coiled-coil structure with chain-specific interactions [Nomizu, M., Otaka, A., Utani, A., Roller, P. P., & Yamada, Y. (1994) J. Biol. Chern. 269, 30386-30392]. Here we focus on the mechanism of laminin assembly and examine the conformation and stability of the peptides under various conditions using circular dichroism (CD) spectroscopy. Dependence on chain length for the conformation and stability of trimers suggests that 51-mers for laminin beta 1 and gamma 1 chains and a 55-mer for the laminin alpha 2 chain are critical to attain high thermal stability (T-m = 62 degrees C), similar to the larger fragments (approximately 200-mers) and to intact laminins. Since the conformation and stability are dependent on pH and the B1 and B2 monomers and the B1-B2 dimer conformations are partially destroyed at neutral pH, it is likely that they contain intra- and/or interchain repulsions by acidic residues. Moreover, the B1-B2 dimer was significantly more stable under acidic conditions, while the B1-B2/M trimer appears to dissociate into separate B1-B2 and M peptides at pH 2. Urea-induced denaturation showed that the B1-B2/M was more stable than the B1-B2, while both complexes showed virtually identical guanidine hydrochloride denaturation curves. Our data indicate that ionic interactions between B1-B2 and M are critical for the specific trimer formation. We propose a mechanism for laminin assembly: (1) A heterodimer B1-B2 is preferentially formed and creates an acidic pocket which provides a less stable structure due to intra- and intermolecular repulsions between acidic amino acids. (2) A basic site in the M peptide interacts specifically with the acidic pocket of the B1-B2 dimer and results in assembly into a more stable triple-stranded coiled-coil structure. C1 NIDR,NIH,DEV BIOL LAB,BETHESDA,MD 20892. NCI,NIH,DIV BASIC SCI,MED CHEM LAB,BETHESDA,MD 20892. SHRINERS HOSP CRIPPLED CHILDRENS,PORTLAND,OR 97201. OI Beck, Konrad/0000-0001-5098-9484 NR 41 TC 35 Z9 35 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 5 PY 1996 VL 35 IS 9 BP 2885 EP 2893 DI 10.1021/bi951555n PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TZ118 UT WOS:A1996TZ11800011 PM 8608125 ER PT J AU Lee, S Chen, DYT Humphrey, JS Gnarra, JR Linehan, WM Klausner, RD AF Lee, S Chen, DYT Humphrey, JS Gnarra, JR Linehan, WM Klausner, RD TI Nuclear cytoplasmic localization of the von Hippel-Lindau tumor suppressor gene product is determined by cell density SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TRANSCRIPTION FACTOR-SIII; SEQUENCE; IDENTIFICATION; TRANSPORT; PROTEIN; SIGNAL AB The product of the von Hippel-Lindau (VHL) tumor suppressor gene, the gene inactivated in VHL disease and in sporadic clear-cell renal carcinomas, has recently been shown to have as a functional target the transcription elongation complex, elongin (also called SIII), Here it is shown that there is a tightly regulated, cell-density-dependent transport of VHL into and/or out of the nucleus. In densely grown cells, the VHL protein is predominantly in the cytoplasm, whereas in sparse cultures, most of the protein can be detected in the nucleus. We have identified a putative nuclear localization signal in the first 60 and first 28 amino acids of the human and rat VHL protein, respectively. Sequences in the C-terminal region of the VHL protein may also be required for localization to the cytosol. These findings provide the initial indication of a novel cell density-dependent pathway that is responsible for the regulation of VHL cellular localization. C1 NIH,NCI,OFF DIRECTOR,UROL ONCOL SECT,SURG BRANCH,BETHESDA,MD 20892. NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. NR 31 TC 125 Z9 128 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 5 PY 1996 VL 93 IS 5 BP 1770 EP 1775 DI 10.1073/pnas.93.5.1770 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TY964 UT WOS:A1996TY96400007 PM 8700833 ER PT J AU Berlett, BS Friguet, B Yim, MB Chock, PB Stadtman, ER AF Berlett, BS Friguet, B Yim, MB Chock, PB Stadtman, ER TI Peroxynitrite-mediated nitration of tyrosine residues in Escherichia coli glutamine synthetase mimics adenylylation: Relevance to signal transduction. SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE nitrotyrosine ID SUPEROXIDE-DISMUTASE AB Treatment of Escherichia coli glutamine synthetase (GS) with peroxynitrite leads to nitration of some tyrosine residues and conversion of some methionine residues to methionine sulfoxide (MSOX) residues, Nitration, but not MSOX formation, is stimulated by Fe-EDTA. In the absence of Fe-EDTA, nitration of only one tyrosine residue per subunit of unadenylylated GS leads to changes in divalent cation requirement, pH-activity profile, affinity for ADP, and susceptibility to feedback inhibition by end products (tryptophan, AMP, CTP), whereas nitration of one tyrosine residue per subunit in the adenylylated GS leads to complete loss of catalytic activity. In the presence of Fe-EDTA, nitration is a more random process: nitration of five to six tyrosine residues per subunit is needed to convert unadenylylated GS to the adenylylated configuration. These results and the fact that nitration of tyrosine residues is an irreversible process serve notice that the regulatory function of proteins that undergo phosphorylation or adenylylation in signal transduction cascades might be seriously compromised by peroxynitrite-promoted nitration. C1 NIH,NHLBI,BIOCHEM LAB,BETHESDA,MD 20892. NR 18 TC 150 Z9 154 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 5 PY 1996 VL 93 IS 5 BP 1776 EP 1780 DI 10.1073/pnas.93.5.1776 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TY964 UT WOS:A1996TY96400008 PM 8700834 ER PT J AU Minucci, S SaintJeannet, JP Toyama, R Scita, G De Luca, LM Taira, M Levin, AA Ozato, K Dawid, IB AF Minucci, S SaintJeannet, JP Toyama, R Scita, G De Luca, LM Taira, M Levin, AA Ozato, K Dawid, IB TI Retinoid X receptor-selective ligands produce malformations in Xenopus embryos SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Xenopus laevis; zebrafish; retinoids; retinoic acid receptor ID CENTRAL-NERVOUS-SYSTEM; ACID RECEPTORS; LAEVIS; EXPRESSION; PATTERN; DIFFERENTIATION; IDENTIFICATION; GENES; GAMMA; AXIS AB Retinoids exert pleiotropic effects on the development of vertebrates through the action of retinoic acid receptors (RAR) and retinoid X receptors (RXR). We have investigated the effect of synthetic retinoids selective for RXR and RAR on the development of Xenopus and zebrafish embryos. In Xenopus, both ligands selective for RAR and RXR caused striking malformations along the anterior-posterior axis, whereas in zebrafish only ligands specific for RAR caused embryonic malformations. In Xenopus, RAR- and RXR-selective ligands regulated the expression of the Xlim-1, gsc, and HoxA1 genes similarly as all-trans-retinoic acid. Nevertheless, RXR-selective ligands activated only an RXR responsive reporter but not an RAR responsive reporter introduced by microinjection into the Xenopus embryo, consistent with our failure to detect conversion of an RXR-selective ligand to different derivatives in the embryo. These results suggest that Xenopus embryos possess a unique response pathway in which liganded RXR can control gene expression. Our observations further illustrate the divergence in retinoid responsiveness between different vertebrate species. C1 NICHHD, LAB MOLEC GROWTH REGULAT, BETHESDA, MD 20892 USA. NICHHD, GENET MOLEC LAB, BETHESDA, MD 20892 USA. NIH, NCI, CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB, BETHESDA, MD 20892 USA. HOFFMANN LA ROCHE INC, DEPT TOXICOL & PATHOL, NUTLEY, NJ 07110 USA. RI Scita, GIORGIO/J-9670-2012; Minucci, Saverio/J-9669-2012; OI Scita, Giorgio/0000-0001-7984-1889 NR 31 TC 33 Z9 35 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 5 PY 1996 VL 93 IS 5 BP 1803 EP 1807 DI 10.1073/pnas.93.5.1803 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TY964 UT WOS:A1996TY96400013 PM 8700839 ER PT J AU Sun, XP Stanley, EF AF Sun, XP Stanley, EF TI An ATP-activated, ligand-gated ion channel on a cholinergic presynaptic nerve terminal SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE purinergic receptor; chicken ciliary ganglion; transmitter release; autoreceptor ID AVIAN CILIARY GANGLIA; TRANSMITTER RELEASE; SENSORY NEURONS; GUINEA-PIG; CELLS; ADENOSINE; CURRENTS; P2-PURINOCEPTOR; POTENTIATION; RECEPTORS AB ATP has recently been identified as a fast neurotransmitter in both the central and peripheral nervous systems. Several studies have suggested that ATP can also affect the release of classical neurotransmitters, including acetylcholine with which it is co-released. We have searched for ATP receptors on a cholinergic presynaptic nerve terminal using the calyx-type synapse of the chicken ciliary ganglion, ATP was pulsed onto the terminals under voltage clamp and induced a short latency cation current that exhibited inward rectification and marked desensitization. This current was not seen with adenosine but was mimicked by several sterically restricted ATP analogs and was blocked by suramin. ATP-activated single ion channels exhibited prominent flickering and had a conductance of approximate to 17 pS. Our results demonstrate a ligand-gated P-2X-like purinergic receptor on a cholinergic presynaptic nerve terminal. C1 NINCDS,NIH,SYNAPT MECHANISMS SECT,BETHESDA,MD 20892. NR 30 TC 56 Z9 56 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 5 PY 1996 VL 93 IS 5 BP 1859 EP 1863 DI 10.1073/pnas.93.5.1859 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TY964 UT WOS:A1996TY96400023 PM 8700849 ER PT J AU Vitale, N Moss, J Vaughan, M AF Vitale, N Moss, J Vaughan, M TI ARD1, a 64-kDa bifunctional protein containing an 18-kDa GTP-binding ADP-ribosylation factor domain and a 46-kDa GTPase-activating domain SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article AB The alpha subunits of the heterotrimeric guanine nucleotide-binding proteins (G proteins) hydrolyze GTP at a rate significantly higher than do most members of the Ras family of approximate to 20-kDa GTP-binding proteins, which depend on a GTPase-activating protein (GAP) for acceleration of GTP hydrolysis. It has been demonstrated that an inserted domain in the G-protein alpha subunit, not present in the much smaller Ras-like proteins, is responsible for this difference [Markby, D. W., Onrust, R. & Bourne, H. R. (1993) Science 262, 1895-1900]. We report here that ARD1, a 64-kDa protein with an 18-kDa carboxyl-terminal ADP-ribosylation factor (ARF) domain, exhibited significant GTPase activity, whereas the RF domain, expressed as a recombinant protein in Escherichia coli, did not. Addition of the 46-kDa amino-terminal extension (similarly synthesized in E. coli) to the GTP-binding ARF-domain of ARD1 enhanced GTPase activity and inhibited GDP dissociation. The kinetic properties of mixtures of the ARF and non-ARF domains were similar to those of an intact recombinant ARD1. Physical association of the two proteins was demonstrated directly by gel filtration and by using the immobilized non-ARF domain. Thus, like the alpha subunits of heterotrimeric G proteins, ARD1 appears to consist of two domains that interact to regulate the biological activity of the protein. RP Vitale, N (reprint author), NHLBI,NIH,PULM CRIT CARE MED BRANCH,BETHESDA,MD 20892, USA. RI Vitale, nicolas/G-5967-2014 OI Vitale, nicolas/0000-0002-4752-4907 NR 17 TC 32 Z9 32 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 5 PY 1996 VL 93 IS 5 BP 1941 EP 1944 DI 10.1073/pnas.93.5.1941 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TY964 UT WOS:A1996TY96400038 PM 8700863 ER PT J AU Accili, D Fishburn, CS Drago, J Steiner, H Lachowicz, JE Park, BH Gauda, EB Lee, EJ Cool, MH Sibley, DR Gerfen, CR Westphal, H Fuchs, S AF Accili, D Fishburn, CS Drago, J Steiner, H Lachowicz, JE Park, BH Gauda, EB Lee, EJ Cool, MH Sibley, DR Gerfen, CR Westphal, H Fuchs, S TI A targeted mutation of the D-3 dopamine receptor gene is associated with hyperactivity in mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID INSITU HYBRIDIZATION HISTOCHEMISTRY; MESSENGER-RNA; RAT-BRAIN; D3; SITES AB While most effects of dopamine in the brain are mediated by the D-1 and D-2 receptor subtypes, other members of this G protein-coupled receptor family have potentially important functions. D-3 receptors belong to the D-2-like subclass of dopamine receptors, activation of which inhibits adenylyl cyclase. Using targeted mutagenesis in mouse embryonic stem cells, we have generated mice lacking functional D-3 receptors. A premature chain-termination mutation was introduced in the D-3 receptor gene after residue Arg-148 in the second intracellular loop of the predicted protein sequence. Binding of the dopamine antagonist [I-125] iodosulpride to D-3 receptors was absent in mice homozygous for the mutation and greatly reduced in heterozygous mice. Behavioral analysis of mutant mice showed that this mutation is associated with hyperactivity in an exploratory test. Homozygous mice lacking D-3 receptors display increased locomotor activity and rearing behavior. Mice heterozygous for the D-3 receptor mutation show similar, albeit less pronounced, behavioral alterations. Our findings indicate that D-3 receptors play an inhibitory role in the control of certain behaviors. C1 WEIZMANN INST SCI,DEPT CLIN IMMUNOL,IL-76100 REHOVOT,ISRAEL. NICHHD,LAB MAMMALIAN GENES & DEV,BETHESDA,MD 20892. NIMH,LAB SYST NEUROSCI,BETHESDA,MD 20892. NINCDS,EXPTL THERAPEUT BRANCH,BETHESDA,MD 20892. RP Accili, D (reprint author), NIDDKD,DIABET BRANCH,BETHESDA,MD 20892, USA. NR 30 TC 375 Z9 379 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 5 PY 1996 VL 93 IS 5 BP 1945 EP 1949 DI 10.1073/pnas.93.5.1945 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TY964 UT WOS:A1996TY96400039 PM 8700864 ER PT J AU Friedman, MC Migone, TS Russell, SM Leonard, WJ AF Friedman, MC Migone, TS Russell, SM Leonard, WJ TI Different interleukin 2 receptor beta-chain tyrosines couple to at least two signaling pathways and synergistically mediate interleukin 2-induced proliferation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Jak1; Jak3; Stat5; protein phosphorylation ID HUMAN IL-2 RECEPTOR; GAMMA-CHAIN; FUNCTIONAL COMPONENT; PHOSPHORYLATION; ACTIVATION; EXPRESSION; CELLS; KINASE(S); CLONING; (IL)-2 AB One of the earliest events induced by interleukin 2 (IL-2) is tyrosine phosphorylation of cellular proteins, including the IL-2 receptor beta chain (IL-2R beta). Simultaneous mutation of three tyrosines (Y338, Y392, and Y510) in the IL-2R beta cytoplasmic domain abrogated IL-2-induced proliferation, whereas mutation of only Y338 or of Y392 and Y510 inhibited proliferation only partially. While Y392 and Y510 were critical for IL-2-induced activation of signal transducers and activators of transcription (STAT proteins), Y338 was required for Shc-IL-2R beta association and for IL-2-induced tyrosine phosphorylation of She. Thus, activation of both Jak-STAT and She-coupled signaling pathways requires specific IL-2R beta tyrosines that together act in concert to mediate maximal proliferation. In COS-7 cells, overexpression of Jak1 augmented phosphorylation of Y338 as well as Y392 and Y510, suggesting that the role for this Jak kinase may extend beyond the Jak-STAT pathway. C1 NHLBI,NIH,LAB MOL IMMUNOL,BETHESDA,MD 20892. RI Russell, Sarah/B-9341-2009 OI Russell, Sarah/0000-0001-5826-9641 NR 50 TC 138 Z9 141 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 5 PY 1996 VL 93 IS 5 BP 2077 EP 2082 DI 10.1073/pnas.93.5.2077 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TY964 UT WOS:A1996TY96400063 PM 8700888 ER PT J AU Giedd, JN Vaituzis, AC Hamburger, SD Lange, N Rajapakse, JC Kaysen, D Vauss, YC Rapoport, JL AF Giedd, JN Vaituzis, AC Hamburger, SD Lange, N Rajapakse, JC Kaysen, D Vauss, YC Rapoport, JL TI Quantitative MRI of the temporal lobe, amygdala, and hippocampus in normal human development: Ages 4-18 years SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE child; adolescent; neuroanatomy; sex; maturation ID FOOD-STORING BIRDS; SCHIZOPHRENIA; GLUCOCORTICOIDS; SPECIALIZATION; EPILEPSY; DISORDER; PARENT; BRAIN AB The volume of the temporal lobe, superior temporal gyrus, amygdala, and hippocampus was quantified from magnetic images of the brains of 99 healthy children and adolescents aged 4-18 years. Variability in volume was high for all structures examined. When adjusted for a 9% larger total cerebral volume in males, there were no significant volume differences between sexes. However, sex-specific maturational changes were noted in the volumes of medial temporal structures, with the left amygdala increasing significantly only in males and with the right hippocampus increasing significantly only in females. Right-greater-than-left laterality effects were found for temporal lobe, superior temporal gyrus, amygdala, and hippocampal volumes. These results are consistent with previous preclinical and human studies that have indicated hormonal responsivity of these structures and extend quantitative morphologic findings from the adult literature. In addition to highlighting the need for large samples and sex-matched controls in pediatric neuroimaging studies, the information from this understudied age group may be of use in evaluating developmental hypotheses of neuropsychiatric disorders. (C) 1996 Wiley-Liss, Inc. C1 NINCDS,BETHESDA,MD 20892. RP Giedd, JN (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,ROOM 6N240,10 CTR DR MSC 1600,BETHESDA,MD 20892, USA. RI Giedd, Jay/A-3080-2008; Rajapakse, Jagath/B-8485-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Rajapakse, Jagath/0000-0001-7944-1658; Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 50 TC 411 Z9 417 U1 2 U2 29 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 MAR 4 PY 1996 VL 366 IS 2 BP 223 EP 230 DI 10.1002/(SICI)1096-9861(19960304)366:2<223::AID-CNE3>3.0.CO;2-7 PG 8 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA TX435 UT WOS:A1996TX43500004 PM 8698883 ER PT J AU Ionescu, D Silverton, JV Dickinson, LC Miller, B AF Ionescu, D Silverton, JV Dickinson, LC Miller, B TI Stereochemistry and mechanisms of thermal cycloaddition reactions of conjugated enynes. The stereospecific formation of six tetrahedral centers in a single reaction SO TETRAHEDRON LETTERS LA English DT Article AB Thermal condensations of penta-1,5-dien-3-ynes with two molecules of olefinic dienophiles proceed stereospecifically with retention of the configurations of the dienophiles, and with both molecules of the dienophile in each reaction adding to the same face of the dienyne. C1 UNIV MASSACHUSETTS,LEDERLE GRAD RES LABS,DEPT CHEM,AMHERST,MA 01003. NIH,BIOPHYS CHEM LAB,BETHESDA,MD 20892. NR 19 TC 6 Z9 6 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD MAR 4 PY 1996 VL 37 IS 10 BP 1559 EP 1562 DI 10.1016/0040-4039(96)00103-7 PG 4 WC Chemistry, Organic SC Chemistry GA TY294 UT WOS:A1996TY29400011 ER PT J AU Supko, JG Phillips, LR Malspeis, L AF Supko, JG Phillips, LR Malspeis, L TI Specific high-performance liquid chromatographic assay with ultraviolet detection for the determination of 1-(2-chloroethyl)-3-sarcosinamide-1-nitrosourea in plasma SO JOURNAL OF CHROMATOGRAPHY B-BIOMEDICAL APPLICATIONS LA English DT Article DE 1-(2-chloroethyl)-3-sarcosinamide-1-nitrososurea ID AMINO-ACID AMIDES; BIOLOGICAL MEDIA; NITROSOUREAS; BCNU; PHARMACOKINETICS; FOTEMUSTINE; CARMUSTINE; RATS; CHLOROETHYLNITROSOUREA; MISONIDAZOLE AB A facile, sensitive and highly specific HPLC method for assaying 1-(2-chloroethyl)-3-sarcosinamide-1-nitrosourea (SarCNU) in plasma has been developed. The drug was efficiently isolated from plasma by extraction with tert,-butyl methyl ether. A structurally related compound with similar physicochemical properties served as the internal standard (I.S.). Following evaporation-of the organic solvent, the extract was reconstituted with 0.05 M ammonium acetate buffer, pH 5.0, and loaded onto a 4 mu m Nova-Pak C-18 column (15 cm X 3.9 mm), which was preceded by a 7 mu m Brownlee RP-18 precolumn (1.5 cm X 3.2 mm). Chromatography was performed at ambient temperature using a mobile phase of methanol-0.1 M ammonium formate buffer, pH 3.7 (25:75, v/v). UV absorbance of the effluent was monitored at 240 nm. A flow-rate of 1.0 ml/min was used for analyzing mouse and dog plasma extracts. Under these conditions, the drug eluted at 4.0 min and was followed by the I.S. at 6.1 min. An automatic switching valve was employed to allow the precolumn to be flushed 1.5 min into the run, without interrupting the flow of the mobile phase to the analytical column, thereby preventing the apparent build-up of extractable, strongly retained, UV-absorbing components present in mouse and dog plasma. Operating in this manner, more than 100 samples could be analyzed during a day using a refrigerated autosampler for overnight injection. The method was readily adapted to the determination of SarCNU in human plasma by simply decreasing the eluent flow-rate to 0.6 ml/min, whereby SarCNU and the I.S. eluted at approximately 5.8 and 9.1 min, respectively. Furthermore, the switching valve was not necessary for the analysis of human plasma samples. With a 50-mu l sample volume, the lowest concentration of SarCNU included in the plasma standard curves, 0.10 mu g/ml, was quantified with a 7.8% R.S.D. (n=27) over a 2 month period. Plasma standards, with concentrations Of 0.26 to 5.1 mu g/ml, exhibited R.S.D. values ranging from 1.3 to 4.7%. Thermospray-ionization MS detection was used to definitively establish the specificity of the method. The sensitivity of the assay was shown by application to be more than adequate for characterizing the plasma pharmacokinetics of SarCNU in mice. C1 NCI,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,LAB PHARMACEUT CHEM,FREDERICK,MD 21701. NR 33 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR B JI J. Chromatogr. B-Biomed. Appl. PD MAR 3 PY 1996 VL 677 IS 2 BP 351 EP 362 DI 10.1016/0378-4347(95)00430-0 PG 12 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA UE061 UT WOS:A1996UE06100019 PM 8704941 ER PT J AU Lehtinen, M Dillner, J Knekt, P Luostarinen, T Aromaa, A Kimbauer, R Koskela, P Paavonen, J Peto, R Schiller, JT Hakama, M AF Lehtinen, M Dillner, J Knekt, P Luostarinen, T Aromaa, A Kimbauer, R Koskela, P Paavonen, J Peto, R Schiller, JT Hakama, M TI Serologically diagnosed infection with human papillomavirus type 16 and risk for subsequent development of cervical carcinoma: Nested case-control study SO BRITISH MEDICAL JOURNAL LA English DT Article AB Objective-To study human papillomavirus type 16 in the aetiology of cervical c Design-Within a cohort of 18 814 Finnish women followed for up to 23 years a nested case-control study was conducted based on serological diagnosis of past infection with human papillomavirus type 16. Subjects-72 women (27 with invasive carcinoma and 45 with in situ carcinoma) and 143 matched controls were identified during the follow up. Main outcome measure- Relative risk of cervical carcinoma in presence of IgG antibodies to human papillomavirus type 16. Results-After adjustment for smoking and for antibodies to various other agents of sexually transmitted disease, such as herpes simplex virus type 2 and Chlamydia trachomatis, the only significant association was with infection with human papillomavirus type 16 (odds ratio 12.5; 95% confidence interval 2.7 to 57, 2P < 0.001). Conclusion-This prospective study provides epidemiological evidence that infection with human papillomavirus type 16 confers an excess risk for subsequent development of cervical carcinoma. C1 TAMPERE UNIV, TAMPERE SCH PUBL HLTH, SF-33101 TAMPERE, FINLAND. NATL PUBL HLTH INST, OULU, FINLAND. NATL PUBL HLTH INST, DEPT CHRON VIRAL DIS, SF-00300 HELSINKI, FINLAND. KAROLINSKA INST, MICROBIOL & TUMORBIOL CTR, STOCKHOLM, SWEDEN. SOCIAL INSURANCE INST, CTR RES & DEV, SF-00381 HELSINKI, FINLAND. FINNISH CANC REGISTRY, SF-00170 HELSINKI, FINLAND. UNIV VIENNA, SCH MED, DEPT IMMUNODERMATOL, VIENNA, AUSTRIA. HELSINKI UNIV, HELSINKI, FINLAND. UNIV OXFORD, CLIN TRIAL SERV UNIT, OXFORD, ENGLAND. UNIV OXFORD, IMPERIAL CANC RES FUND, CANC STUDIES UNIT, OXFORD, ENGLAND. NCI, CELLULAR ONCOL LAB, BETHESDA, MD 20892 USA. NR 14 TC 122 Z9 125 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0959-8138 J9 BRIT MED J JI Br. Med. J. PD MAR 2 PY 1996 VL 312 IS 7030 BP 537 EP 539 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA TY885 UT WOS:A1996TY88500021 PM 8595281 ER PT J AU SimonsMorton, DG AF SimonsMorton, DG TI Funding avenues for research in emergency medicine at the National Institutes of Health and the National Heart, Lung, and Blood Institute SO ACADEMIC EMERGENCY MEDICINE LA English DT Editorial Material DE emergency medicine; research; extramural support; federal government; funding RP SimonsMorton, DG (reprint author), NHLBI,PREVENT SCI RES GRP,DIV EPIDEMIOL & CLIN APPLICAT,ROCKLEDGE CTR 2,NIH,6701 ROCKLEDGE DR,BETHESDA,MD 20892, USA. NR 2 TC 4 Z9 4 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD MAR PY 1996 VL 3 IS 3 BP 202 EP 204 DI 10.1111/j.1553-2712.1996.tb03421.x PG 3 WC Emergency Medicine SC Emergency Medicine GA TX513 UT WOS:A1996TX51300006 PM 8673774 ER PT J AU Cohen, GH Sheriff, S Davies, DR AF Cohen, GH Sheriff, S Davies, DR TI Refined structure of the monoclonal antibody HyHEL-5 with its antigen hen egg-white lysozyme SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID 3-DIMENSIONAL STRUCTURE; CRYSTAL-STRUCTURE; MACROMOLECULAR STRUCTURES; PROTEIN STRUCTURES; R-FACTOR; COMPLEX; RESOLUTION; BINDING; BOND; SEQUENCES AB The crystal structure of the complex of the antibody Fab, HyHEL-5, with its antigen, hen egg-white lysozyme, has been refined at 2.65 Angstrom resolution to an R value of 0.196. The resulting model has significantly better stereochemistry than the previously reported model of the complex, PDB reference 2HFL, and sufficiently improved phases, permitting the reliable location of a number of water molecules. No major conformational differences are observed between this structure and that previously reported, although small differences occur throughout the complex. 82 water molecules have been assigned, of which three are in the antibody-antigen interface involved in a hydrogen-bonding network. Three other waters are trapped within the interface between VH and VL and a fourth water molecule is observed near the interface but buried below the lysozyme surface as observed in crystal structures of lysozyme alone. RP Cohen, GH (reprint author), NIDDK,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 66 TC 56 Z9 56 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD MAR 1 PY 1996 VL 52 BP 315 EP 326 DI 10.1107/S0907444995014855 PN 2 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA UF186 UT WOS:A1996UF18600009 PM 15299704 ER PT J AU Rodriguez, EM Mofenson, LM Chang, BH Rich, KC Fowler, MG Smeriglio, V Landesman, S Fox, HE Diaz, C Green, K Hanson, IC AF Rodriguez, EM Mofenson, LM Chang, BH Rich, KC Fowler, MG Smeriglio, V Landesman, S Fox, HE Diaz, C Green, K Hanson, IC TI Association of maternal drug use during pregnancy with maternal HIV culture positivity and perinatal HIV transmission SO AIDS LA English DT Article DE prenatal drug use; obstetrics gynecology; vertical HIV transmission; pregnancy; women; pediatrics; risk factors ID IMMUNODEFICIENCY-VIRUS TYPE-1; MONONUCLEAR CELL COCULTURES; COCAINE; WOMEN; REPLICATION; SUPPRESSION; INFANTS; GROWTH; AIDS AB Objective: To evaluate the relationship of drug use with maternal HIV culture positivity at delivery and perinatal HIV transmission. Design: Multicenter prospective cohort study. Setting: Obstetric and pediatric clinics in five cities in the United States. Participants: Five hundred and thirty HIV-infected pregnant women and their infants. Main outcome measures: Multivariate logistic regression was used to evaluate the association of 'hard drug' use (one or more of the following: cocaine, heroin/opiates, methadone, injecting drug use) assessed by self-report and urine toxicology with positive maternal HIV culture at delivery and perinatal HIV transmission. Results: Forty-two per cent of women used hard drugs during pregnancy. Increased probability of a positive maternal delivery HIV culture was significantly associated with prenatal hard drug use [odds ratio (OR), 3.08] and maternal cocaine use (OR, 2.98) among HIV-infected women with > 29% CD4+ lymphocytes. After adjusting for maternal culture positivity at delivery, CD4+ lymphocyte percentage and gestational age, significantly greater transmission risk was observed with hard drug use among women with membrane rupture > 4 h. Conclusions: On the basis of self-report and urine toxicology, overall maternal hard drug use and cocaine use in the WITS cohort were associated with maternal HIV culture positivity at delivery, and maternal hard drug use was associated with perinatal transmission. C1 NICHHD,PEDIAT ADOLESCENT & MATERNAL AIDS REDS,NIH,ROCKVILLE,MD. NEW ENGLAND RES INST,WATERTOWN,MA 02172. UNIV ILLINOIS,CHICAGO,IL. NIAID,DIV AIDS,NIH,ROCKVILLE,MD. NIDA,ROCKVILLE,MD. SUNY HLTH SCI CTR,BROOKLYN,NY 11203. COLUMBIA PRESBYTERIAN MED CTR,NEW YORK,NY 10032. UNIV PUERTO RICO,SAN JUAN,PR 00936. UNIV AMSTERDAM,SCH MED,WORCESTER,MA. BAYLOR COLL MED,HOUSTON,TX 77030. RP Rodriguez, EM (reprint author), HLTH RESOURCES SERV ADM,BUR HLTH RESOURCES DELIVERY,5600 FISHERS LANE,ROOM 7-13,ROCKVILLE,MD 20857, USA. OI Mofenson, Lynne/0000-0002-2818-9808 FU NIAID NIH HHS [AI-05072, AI-82505]; NICHD NIH HHS [HD-8-2913=] NR 45 TC 96 Z9 96 U1 0 U2 2 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0269-9370 J9 AIDS JI Aids PD MAR PY 1996 VL 10 IS 3 BP 273 EP 282 DI 10.1097/00002030-199603000-00006 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA UB187 UT WOS:A1996UB18700006 PM 8882667 ER PT J AU Ahlers, JD Dunlop, N Pendleton, CD Newman, M Nara, PL Berzofsky, JA AF Ahlers, JD Dunlop, N Pendleton, CD Newman, M Nara, PL Berzofsky, JA TI Candidate HIV type 1 multideterminant cluster peptide-P18MN vaccine constructs elicit type 1 helper T cells, cytotoxic T cells, and neutralizing antibody, all using the same adjuvant immunization SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; FREE SYNTHETIC PEPTIDE; TOXIC LYMPHOCYTES-T; ENVELOPE PROTEIN; IMMUNE-RESPONSES; LEISHMANIA-MAJOR; SEROPOSITIVE INDIVIDUALS; SUSCEPTIBLE MICE; RHESUS-MONKEYS; INDUCTION AB Cytotoxic T lymphocytes and Th1 cells have been suggested to play a critical role in the control of HIV infection, It is therefore considered that a vaccine that induces a strong Th1 response and CTL response would be more efficacious than one that does not in providing protection against infection and progression toward AIDS. In this study we show that immunization with vaccine constructs consisting of multideterminant cluster peptides containing Th epitopes from the HIV-1IIIB envelope colinearly synthesized to peptide 18MN, is capable of inducing a Th1 response in mice and, dependent on this help, both cytotoxic T cell responses and neutralizing antibody toward the homologous strain of HIV, Moreover, the cytotoxic T cell response elicited by immunization with a mixture of cluster peptide-P18MN vaccine constructs was at least as cross-reactive against known viral variant P18 target sequences as a CTL line produced by immunization with a vaccinia construct expressing recombinant gp160 MN. Four adjuvants were compared to optimize both CTL and antibody responses. A single adjuvant formulation of peptide in ISA 51 could elicit all three: Th1 cells, CTLs, and neutralizing antibody. Thus, immunization directed toward the development of a cytotoxic T cell response does not preclude the development of neutralizing antibody and vice versa, i.e., the responses are not mutually exclusive. The immunization protocol described here should be directly applicable for study in clinical trials aimed at HIV-1 immunotherapy or prophylaxis. C1 NCI,NIH,MOLEC IMMUNOGENET & VACCINE RES SECT,METAB BRANCH,BETHESDA,MD 20892. NCI,FREDERICK CANC RES FACIL,FREDERICK,MD 21701. NCI,PROGRAM RESOURCES INC,FREDERICK,MD 21701. CAMBRIDGE BIOTECH INC,WORCESTER,MA 01605. NR 72 TC 39 Z9 39 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 MAR 1 PY 1996 VL 12 IS 4 BP 259 EP 272 DI 10.1089/aid.1996.12.259 PG 14 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA UD140 UT WOS:A1996UD14000001 PM 8906986 ER PT J AU Hunt, WA AF Hunt, WA TI Role of acetaldehyde in the actions of ethanol on the brain - A review SO ALCOHOL LA English DT Review DE alcohol dehydrogenase; aldehyde dehydrogenase; catalase; 3-amino-1,2,4-triazole; thyroid function ID THYROTROPIN-RELEASING-HORMONE; ALCOHOL-PREFERRING RATS; CENTRAL-NERVOUS-SYSTEM; ALDEHYDE DEHYDROGENASE; ACATALASEMIC MICE; CATALASE ACTIVITY; 3-AMINO-1,2,4-TRIAZOLE; TRH; CONSUMPTION; PREFERENCE AB Over the last 30 years, acetaldehyde has been postulated to mediate various actions of ethanol on the brain. Experiments have studied ethanol consumption after acetaldehyde infusions into the brain, in rodents with high or low activities of hepatic and brain ethanol-metabolizing enzymes, and after treatment with drugs that alter the metabolism of acetaldehyde after ethanol ingestion. Evidence that acetaldehyde is involved in the actions of ethanol has been inconsistent because of the lack of knowledge of the brain acetaldehyde concentrations required to exert their effects, the lack of correlation between the activities of ethanol-metabolizing enzymes across strains of rodents and ethanol consumption, and the lack of specificity of drugs altering acetaldehyde metabolism. The formation of significant amounts of acetaldehyde the brain in vivo after ethanol ingestion and by what mechanism has not been clearly established, although catalase is a promising candidate. Future research needs to directly demonstrate in brain the formation of acetaldehyde in vivo, determine the concentrations in brain areas involved in ethanol consumption, and evaluate the possible actions of drugs other than an ability to block acetaldehyde metabolism. RP Hunt, WA (reprint author), NIAAA,DIV BASIC RES,NEUROSCI & BEHAV RES BRANCH,WILLCO BLDG,SUITE 402,6000 EXECUT BLVD,MSC 7003,BETHESDA,MD 20892, USA. NR 66 TC 124 Z9 124 U1 1 U2 14 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0741-8329 J9 ALCOHOL JI Alcohol PD MAR-APR PY 1996 VL 13 IS 2 BP 147 EP 151 DI 10.1016/0741-8329(95)02026-8 PG 5 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA UD073 UT WOS:A1996UD07300007 PM 8814648 ER PT J AU Nilsson, G Metcalfe, DD AF Nilsson, G Metcalfe, DD TI Contemporary issues in mast cell biology SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Article ID C-KIT LIGAND; FETAL LIVER-CELLS; RECOMBINANT HUMAN; BONE-MARROW; PROGENITOR CELLS; MEDIATOR RELEASE; HUMAN BASOPHILS; DIFFERENTIATION; INTERLEUKIN-3; PROLIFERATION AB Mast cells are the principal initial effect of cells in the modulation of allergic inflammation. They are now known to arise from CD34(+) pluripotential stem cells, circulate through the blood as CD34(+), Fc epsilon RI(-), Kit(+) committed but undifferentiated cells, and migrate into tissues where they mature in the presence of Kit-ligand (stem cell factor) and other locally produced cytokines. Mast cells undergo programmed cell death (apoptosis) when stem cell factor is not available. Mast cells adhere to specific connective tissue components such as fibronectin and laminin. This interaction localizes mast cells to specific sites while altering their biologic responsiveness. Mass cells, when activated through Fc epsilon RI, release and generate a wide variety of cytokines including IL-4 and IL-5. This information provides new insights on how allergic reactions may be modified by developing strategies to effect mast cell viability, survival and localization; and the production of inflammatory mediators. C1 NIAID,CLIN INVEST LAB,ALLERG DIS SECT,NIH,BETHESDA,MD 20892. NR 55 TC 21 Z9 22 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD MAR-APR PY 1996 VL 17 IS 2 BP 59 EP 63 DI 10.2500/108854196778645074 PG 5 WC Allergy SC Allergy GA UL903 UT WOS:A1996UL90300001 PM 8934794 ER PT J AU Cohen, SG AF Cohen, SG TI Asthma among the famous - A continuing series SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Article RP Cohen, SG (reprint author), NIAID,NIH,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD MAR-APR PY 1996 VL 17 IS 2 BP 103 EP 107 DI 10.2500/108854196778645065 PG 5 WC Allergy SC Allergy GA UL903 UT WOS:A1996UL90300010 ER PT J AU Chen, L Benjamin, EJ Larson, MG Evans, JC Levy, D AF Chen, L Benjamin, EJ Larson, MG Evans, JC Levy, D TI Doppler diastolic filling indexes in relation to disease states SO AMERICAN HEART JOURNAL LA English DT Article ID LEFT-VENTRICULAR HYPERTROPHY; ACUTE MYOCARDIAL-INFARCTION; CONGESTIVE HEART-FAILURE; M-MODE ECHOCARDIOGRAPHY; SYSTOLIC FUNCTION; NONINVASIVE ASSESSMENT; EXERCISE INTOLERANCE; DIABETES-MELLITUS; TRANSMITRAL FLOW; CARDIOMYOPATHY AB This study compares mean Doppler-derived diastolic filling indexes in a variety of disease states in a large, population-based sample. Pulse-wave Doppler was used to examine 880 eligible participants of the Framingham Heart Study. Peak velocity of early flow and late flow, ratio of early to late peak velocities, atrial filling fraction, and early filling wave acceleration and deceleration times were obtained. Multiple linear regression analyses were performed comparing mean values for individuals with hypertension, diabetes, coronary disease, cardiovascular disease, and pulmonary disease. Hypertension was associated with a greater peak velocity late flow (0.027 m/sec; 95% confidence interval, 0.006, 0.047; p = 0.011), and diabetes was associated with a larger mean deceleration time (0.12 sec, confidence interval, 0.002, 0.021; p = 0.016). In multivariate analyses, hypertension continued to show a strong association with altered Doppler diastolic filling patterns, p value 0.009, whereas in diabetes, the multivariate p value was 0.28. C1 FRAMINGHAM HEART DIS EPIDEMIOL STUDY, FRAMINGHAM, MA 01701 USA. NHLBI, BETHESDA, MD 20892 USA. BOSTON CITY HOSP, DEPT CARDIOL, BOSTON, MA 02118 USA. BETH ISRAEL HOSP, DIV CARDIOL, BOSTON, MA USA. BETH ISRAEL HOSP, DIV CLIN EPIDEMIOL, BOSTON, MA USA. OI Benjamin, Emelia/0000-0003-4076-2336 NR 62 TC 14 Z9 15 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD MAR PY 1996 VL 131 IS 3 BP 519 EP 524 DI 10.1016/S0002-8703(96)90531-1 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA TZ295 UT WOS:A1996TZ29500013 PM 8604632 ER PT J AU Hornung, RW Herrick, RF Stewart, PA Utterback, DF Feigley, CE Wall, DK Douthit, DE Hayes, RB AF Hornung, RW Herrick, RF Stewart, PA Utterback, DF Feigley, CE Wall, DK Douthit, DE Hayes, RB TI An experimental design approach to retrospective exposure assessment SO AMERICAN INDUSTRIAL HYGIENE ASSOCIATION JOURNAL LA English DT Article DE embalmers; epidemiologic studies; formaldehyde exposure; quantitative exposure levels ID FUNERAL DIRECTORS; MORTALITY; EMBALMERS; CANCER; DEATH AB There are several methods currently in use for retrospective estimation of quantitative exposure levels in occupational and environmental epidemiologic studies. The most popular is a job-exposure matrix approach using a combination of existing data and professional judgment. Another method is the use of statistical models based on available exposure data. The authors present an alternative approach using an experimental design in which several factors thought to affect exposure levels are identified and set at specific levels in a cross-classified design. This approach was used to estimate historical exposures to formaldehyde in a mortality study of embalmers. Exposures were estimated as a function of solution concentration, air exchange rate, and autopsied versus intact body. There were 12 combinations involving these 3 factors and a total of 25 embalming procedures (approximately 2 replicates of each combination) performed at a college of mortuary science. In addition to these design factors several covariates such as temperature, humidity, and the occurrence of spills were considered in an analysis of covariance statistical model. The results of the model prediction were validated against published measurements, and field samples were taken in several funeral homes. The overall accuracy of the model predictions was comparable to the variation found in replicate measurements of identical embalming procedures. C1 HARVARD UNIV,CAMBRIDGE,MA 02138. NCI,BETHESDA,MD 20892. UNIV S CAROLINA,COLUMBIA,SC 29208. CINCINNATI COLL MORTUARY SCI,CINCINNATI,OH. RP Hornung, RW (reprint author), NIOSH,MAILSTOP R-44,4676 COLUMBIA PKWY,CINCINNATI,OH 45226, USA. NR 18 TC 18 Z9 18 U1 1 U2 6 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 MAR PY 1996 VL 57 IS 3 BP 251 EP 256 DI 10.1202/0002-8894(1996)057<0251:AEDATR>2.0.CO;2 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA TY070 UT WOS:A1996TY07000006 PM 8776195 ER PT J AU BallardBarbash, R Swanson, CA AF BallardBarbash, R Swanson, CA TI Body weight: Estimation of risk for breast and endometrial cancers SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT Amercan-Health-Foundation Roundtable on Healthy Weight CY SEP 20, 1994 CL NEW YORK, NY SP Amer Hlth Fdn, Weight Watchers Int Inc DE breast neoplasms; endometrial neoplasms; body weight; weight gain; obesity; central adiposity; risk; prognosis ID FAT DISTRIBUTION; ANTHROPOMETRIC INDICATORS; RELATIVE WEIGHT; 570,000 WOMEN; HEIGHT; SIZE; ASSOCIATION; GAIN; MASS; EPIDEMIOLOGY AB Consistent, positive, and independent associations between body weight or body mass index (BMI), weight gain, and various measures of central adiposity and the incidence of endometrial cancer exist. Increases in relative risks of 2-3.5 are reported for women with BMIs (in kg/m(2)) greater than or equal to 28-30, for women in the fourth compared with the first quartile of measures of central adiposity, and for women with weight gains from young adulthood to middle age of greater than or equal to 27 kg. Furthermore, endometrial cancer mortality is increased in heavier and taller women. Associations between breast cancer incidence and these measures of adiposity vary by age and menopausal status at the time of diagnosis. Heavier women appear to be at decreased risk for developing premenopausal breast cancer; relative risks of approximate to 0.6 were reported for women with BMIs greater than or equal to 26-27. Conversely, heavier women are at increased risk of developing and dying from postmenopausal breast cancer. Although contradictory findings have been observed in cohort studies, modest increases in relative risks on the order of 1.2-1.5 were reported in older postmenopausal women with BMIs of greater than or equal to 28-30. Furthermore, adult weight gain and increased central adiposity have been consistently and independently associated with an increased risk for postmenopausal breast cancer. No significant associations have been observed between weight loss and postmenopausal breast cancer incidence. These findings indicate that avoidance of weight gain and accumulation of central body fat during adult life may reduce risk of both endometrial and postmenopausal breast cancer. C1 NCI, NIH, ENVIRONM EPIDEMIOL BRANCH, DIV CANC ETIOL, BETHESDA, MD 20892 USA. RP BallardBarbash, R (reprint author), NCI, DIV CANC PREVENT & CONTROL,APPL RES BRANCH, 6130 EXECUT BLVD,MSC 7344,EXECUT PLAZA N, ROOM 34, BETHESDA, MD 20892 USA. NR 38 TC 29 Z9 33 U1 1 U2 3 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD MAR PY 1996 VL 63 IS 3 SU S BP 437 EP 441 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA TZ683 UT WOS:A1996TZ68300009 ER PT J AU Iribarren, C Sharp, D Burchfiel, CM Sun, P Dwyer, JH AF Iribarren, C Sharp, D Burchfiel, CM Sun, P Dwyer, JH TI Association of serum total cholesterol with coronary disease and all-cause mortality: Multivariate correction for bias due to measurement error SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE bias (epidemiology); cohort studies; coronary disease; mortality; regression analysis; risk factors ID HONOLULU-HEART-PROGRAM; LOW BLOOD CHOLESTEROL; CONFIDENCE-INTERVALS; JAPANESE ANCESTRY; 20-YEAR MORTALITY; NUTRIENT INTAKE; RISK-FACTORS; FOLLOW-UP; DIET; MEN AB Measurement error in the exposure under investigation is an important but often ignored source of bias in observational studies. The authors examined the impact of measurement error in the association between total serum cholesterol and 16-year coronary heart disease and all-cause mortality in a cohort of 6,137 middle-aged men of Japanese descent in the Honolulu Heart Program (1973-1988). A Cox regression model that enables modeling of survival time with correction for measurement errors in multiple covariates was employed. After controlling for age, body mass index, systolic blood pressure, smoking status, alcohol consumption, dietary cholesterol, and total calorie intake, a difference of one standard deviation (38 mg/dL) in total cholesterol was associated with a significant increase in the risk of coronary disease death (uncorrected hazard ratio = 1.35). After correction for measurement errors in total cholesterol and covariates (except smoking and age), the estimated hazard ratio increased to 1.65 (a 22% increase). A U-shaped relation was observed between total cholesterol levels and the risk of all-cause mortality. This association was then examined with a quadratic model and with a two-slope or V-shaped regression model. In the quadratic fit, the magnitude of the quadratic total cholesterol term increased threefold after the adjustment for measurement error. In the V fit, the hazard ratio of all-cause death corresponding to a change in one standard deviation above 214 mg/dL (the nadir of the V) was 1.15, and increased to 1.49 (by 29%) after the correction. The corresponding hazard ratio of a change in one standard deviation below 214 mg/dL was 1.11, and increased to 1.37 (by 23%) after the correction. The authors conclude that the impact of elevated total cholesterol on the risk of coronary disease and all-cause mortality may be greater than previously estimated with standard methods of analysis. In addition, the correction for measurement error in total cholesterol and covariates did not explain the excess mortality associated with low total cholesterol. More research is needed to elucidate the fundamental issues underlying the U-shaped association, i.e., confounding versus causal implications. C1 UNIV SO CALIF,SCH MED,DEPT PREVENT MED,INST HLTH PROMOT & DIS PREVENT RES,LOS ANGELES,CA 90033. NHLBI,DIV EPIDEMIOL & CLIN APPLICAT,HONOLULU EPIDEMIOL RES UNIT,BETHESDA,MD 20892. FU NHLBI NIH HHS [N01-HV-02901, N01-HC-02901] NR 45 TC 17 Z9 17 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 MAR 1 PY 1996 VL 143 IS 5 BP 463 EP 471 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA TZ598 UT WOS:A1996TZ59800006 PM 8610661 ER PT J AU Mark, SD Thomas, DG Decarli, A AF Mark, SD Thomas, DG Decarli, A TI Measurement of exposure to nutrients: An approach to the selection of informative foods SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE diet; epidemiologic methods; measurement error; misclassification; nutrition; questionnaires ID DIET; QUESTIONNAIRE; CANCER AB Frequently, epidemiologic questionnaires are designed to measure several individual level exposures, including exposure to one or more nutrients, Although most nutrients are contained in a large number of foods, constraints on questionnaire length permit the inclusion of only a subset of these, In this paper, the authors review the two common methods of food selection, and they propose two new methods. When the intent is to estimate the effect of the nutrient on disease risk using a logistic regression model, the authors show that their Max_r method is optimal, With the use of case-control data, they examine the assumption of non-differential measurement error that is essential to the validity of all analyses that rely on shortened questionnaires, They conclude by combining the statistical considerations developed for judging adequacy of a selection method with their empirical results and suggest new goals for dietary questionnaires and a new approach to questionnaire construction consistent with those goals. C1 UNIV MILAN,IST STAT MED & BIOMETRIA,I-20122 MILAN,ITALY. IST NATL TUMORE,MILAN,ITALY. RP Mark, SD (reprint author), NCI,BIOSTAT BRANCH,EXECUT PLAZA N,ROOM 403,6130 EXECUT BLVD,MSC 7368,BETHESDA,MD 20892, USA. RI Decarli, Adriano/C-3129-2017 OI Decarli, Adriano/0000-0003-1451-8292 NR 20 TC 20 Z9 22 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 MAR 1 PY 1996 VL 143 IS 5 BP 514 EP 521 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA TZ598 UT WOS:A1996TZ59800012 PM 8610667 ER PT J AU Levy, EN Shen, Y Kupelian, A Kruglyak, L Aksentijevich, I Pras, E Balow, JE Linzer, B Chen, XG Shelton, DA Gumucio, D Pras, M Shohat, M Rotter, JI FischelGhodsian, N Richards, RI Kastner, DL AF Levy, EN Shen, Y Kupelian, A Kruglyak, L Aksentijevich, I Pras, E Balow, JE Linzer, B Chen, XG Shelton, DA Gumucio, D Pras, M Shohat, M Rotter, JI FischelGhodsian, N Richards, RI Kastner, DL TI Linkage disequilibrium mapping places the gene causing familial mediterranean fever close to D16S246 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID DINUCLEOTIDE REPEAT POLYMORPHISMS; MOROCCAN JEWS; HOMOZYGOSITY; CHROMOSOME-16; ARMENIANS; MAP AB This report presents refined genetic mapping data for the gene causing familial Mediterranean fever (FMF), a recessively inherited disorder of inflammation. We sampled 65 Jewish, Armenian, and Arab families and typed them for eight markers from chromosome 16p. Using a new algorithm that permits multipoint calculations for a dense map of markers in consanguineous families, we obtained a maximal LOD score of 49.2 at a location 1.6 cM centromeric to D16S246. A specific haplotype at D16S283-D16S94-D16S246 was found in 76% of Moroccan and 32% of non-Moroccan Jewish carrier chromosomes, but this haplotype was not overrepresented in Armenian or Arab FMF carriers. Moreover, the 2.5-kb allele at D16S246 was significantly associated with FMF in Moroccan and non-Moroccan Jews but not in Armenians or Arabs. Since the Moroccan Jewish community represents a relatively recently established and genetically isolated founder population, we analyzed the Moroccan linkage-disequilibrium data by using Luria-Delbruck formulas and simulations based on a Poisson branching process. These methods place the FMF susceptibility gene within 0.305 cM of D16S246 (2-LOD-unit range 0.02-0.64 cM). C1 NIAMSD,ARTHRIT & RHEUMATISM BRANCH,BETHESDA,MD 20892. ADELAIDE WOMENS & CHILDRENS HOSP,DEPT CYTOGENET & MOLEC GENET,ADELAIDE,SA,AUSTRALIA. CEDARS SINAI MED CTR,DEPT PEDIAT,LOS ANGELES,CA 90048. CEDARS SINAI MED CTR,DEPT MED GENET,LOS ANGELES,CA 90048. WHITEHEAD INST BIOMED RES,CAMBRIDGE,MA 02142. UNIV MICHIGAN,DEPT ANAT & CELL BIOL,ANN ARBOR,MI 48109. CHAIM SHEBA MED CTR,HELLER INST MED RES,IL-52621 TEL HASHOMER,ISRAEL. BEILINSON MED CTR,DEPT MED GENET,IL-49100 PETAH TIQWA,ISRAEL. FU NHGRI NIH HHS [HG00017] NR 41 TC 23 Z9 23 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 MAR PY 1996 VL 58 IS 3 BP 523 EP 534 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA TV564 UT WOS:A1996TV56400011 PM 8644712 ER PT J AU Yin, SN Hayes, RB Linet, MS Li, GL Dosemeci, M Travis, LB Li, CY Zhang, ZN Li, DG Chow, WH Wacholder, S Wang, YZ Jiang, ZL Dai, TR Zhang, WY Chao, XJ Ye, PZ Kou, QR Zhang, XC Lin, XF Meng, JF Ding, CY Zho, JS Blot, WJ AF Yin, SN Hayes, RB Linet, MS Li, GL Dosemeci, M Travis, LB Li, CY Zhang, ZN Li, DG Chow, WH Wacholder, S Wang, YZ Jiang, ZL Dai, TR Zhang, WY Chao, XJ Ye, PZ Kou, QR Zhang, XC Lin, XF Meng, JF Ding, CY Zho, JS Blot, WJ TI A cohort study of cancer among benzene-exposed workers in China: Overall results SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE benzene; leukemia; lymphoma; epidemiology ID OCCUPATIONAL EXPOSURE; RETROSPECTIVE COHORT; CHEMICAL-EXPOSURE; LEUKEMIA; MORTALITY; CYTOGENETICS; DISORDERS; SUBTYPE AB A large cohort study of 74,825 benzene-exposed and 35,805 unexposed workers employed between 1972 and 1987 in 12 cities in China were followed to determine mortality from all causes and the incidence of lymphohematopoietic malignancies and other hematologic disorders. Benzene-exposed study subjects were employed in a variety of occupations, including painting, printing, and the manufacture of footwear, paint, and other chemicals. All-cause mortality was similar in the benzene-exposed and unexposed comparison group. Statistically significant excess deaths were noted among benzene-exposed subjects for leukemia (RR = 2.3, 95% CI: 1.1-5.0), malignant lymphoma (RR = 4.5, 95% CI: 1.3-28.4), and nonneoplastic diseases of the blood (RR = infinity, 95% CI: 2.5-infinity), and a marginally significant excess was noted for lung cancel (RR = 1.4, 95% CI: 1.0-2.0). Risk was significantly elevated for the incidence of all lymphohematopoietic malignancies (RR = 2.6, 95% CI: 1.5-5.0), malignant lymphoma (RR = 3.5, 95% CI: 1.2-14.9), and leukemia (RR = 2.6, 95% CI: 1.3-5.7). Among the leukemia subtypes, only acute myelogenous leukemia (AML) incidence was significantly elevated (RR = 3.1, 95% CI: 1.2-10.7), although nonsignificant excesses were also noted for chronic myelogenous leukemia (CML) (RR = 2.6, 95% CI: 0.7-16.9) and lymphocytic leukemias (RR = 2.8, 95% CI: 0.5-54.5). Significant excesses were found for aplastic anemia (RR = infinity, 95% CI: 2.5-infinity) and myelodysplastic syndrome (RR = infinity, 95% CI: 1.7-infinity). Employment in benzene-associated occupations in China is associated with a wide spectrum of myelogenous and lymphocytic malignant diseases and related disorders. Investigations continue to assess the nature of these associations. (C) 1996 Wiley-Liss, Inc. C1 NCI, NIH, EPIDEMIOL & BIOSTAT PROGRAM, BETHESDA, MD 20892 USA. MAYO CLIN, HEMATOPATHOL SECT, ROCHESTER, MN USA. CHINESE ACAD MED SCI, PEKING UNION MED HOSP, DIV HEMATOL, BEIJING 100037, PEOPLES R CHINA. CHINESE ACAD MED SCI, INST OCCUPAT MED, BEIJING 100037, PEOPLES R CHINA. STN PUBL HLTH & PREVENT INFECT, SHANGHAI, PEOPLES R CHINA. STN PUBL HLTH & PREVENT INFECT, CHENGDU, PEOPLES R CHINA. STN PUBL HLTH & PREVENT INFECT, CHONGQING, PEOPLES R CHINA. INST LABOR HLTH & OCCUPAT DIS, TIANJIN, PEOPLES R CHINA. INST LABOR HLTH & OCCUPAT DIS, SHENYANG, PEOPLES R CHINA. INST LABOR HLTH & OCCUPAT DIS, NANCHANG, PEOPLES R CHINA. INST LABOR HLTH & OCCUPAT DIS, CANTON, PEOPLES R CHINA. INST LABOR HLTH & OCCUPAT DIS, JINZHOU, PEOPLES R CHINA. INST LABOR HLTH & OCCUPAT DIS, HEILONGJIANG, PEOPLES R CHINA. INST LABOR HLTH & OCCUPAT DIS, HENAN, PEOPLES R CHINA. INST LABOR HLTH & OCCUPAT DIS, SICHUAN, PEOPLES R CHINA. INST LABOR HLTH & OCCUPAT DIS, JIANGXI, PEOPLES R CHINA. NR 46 TC 121 Z9 129 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0271-3586 EI 1097-0274 J9 AM J IND MED JI Am. J. Ind. Med. PD MAR PY 1996 VL 29 IS 3 BP 227 EP 235 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA TX830 UT WOS:A1996TX83000002 PM 8833775 ER PT J AU Rothman, N Li, GL Dosemeci, M Bechtold, WE Marti, GE Wang, YZ Linet, M Xi, LQ Lu, W Smith, MT TitenkoHolland, N Zhang, LP Blot, W Yin, SN Hayes, RB AF Rothman, N Li, GL Dosemeci, M Bechtold, WE Marti, GE Wang, YZ Linet, M Xi, LQ Lu, W Smith, MT TitenkoHolland, N Zhang, LP Blot, W Yin, SN Hayes, RB TI Hematotoxicity among Chinese workers heavily exposed to benzene SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE benzene; hematotoxicity; phenol; muconic acid; hydroquinone; catechol ID HUMAN-LYMPHOCYTES; METABOLITES; TOXICITY; HYDROQUINONE; MICE; CHROMOSOME; TOLUENE; INVITRO; MYELOTOXICITY; STIMULATION AB Benzene is a well-established hematotoxin. However, reports of its effects on specific blood cells have been somewhat inconsistent and the relative toxicity of benzene metabolites on peripheral blood cells in humans has not been evaluated. We compared hematologic outcomes in a cross-sectional study of 44 workers heavily exposed to benzene (median: 31 parts permillion [ppm] as an 8-hr time-weighted average [TWA] and 44 age and gender-matched unexposed controls from Shanghai, China. All hematologic parameters (total white blood cells [WBC], absolute lymphocyte count, platelets, red blood cells, and hematocrit) were decreased among exposed workers compared to controls, with the exception of the red blood cell mean corpuscular volume (MCV), which was higher among exposed subjects. In a subgroup of workers who were not exposed to more than 31 ppm benzene on any of 5 sampling days (n = 11, median 8 hr TWA = 7.6 ppm, range = 1-20 ppm), only the absolute lymphocyte count was significantly different between exposed workers (mean [sd] 1.6 [0.4] x 10(3) mu L) and controls (1.9 [0.4] x 10(3) mu L, p = 0.03). Among exposed subjects, a dose-response relationship with various measures of current benzene exposure (i.e., personal air monitoring, benzene metabolites in urine) was present only for the total WBC count, the absolute lymphocyte count, and the MCV. Correlations between benzene metabolites and hematologic parameters were generally similar, although hydroquinone was somewhat more strongly associated with a decrease in the absolute lymphocyte count, and catechol was more strongly associated with an increase in MCV. Morphologic review of peripheral blood slides demonstrated and excess of red blood cell abnormalities (i.e., stomatocytes and target cells) only in the most heavily exposed workers, with no differences in granulocyte, lymphocyte, or platelet morphology noted. Although benzene can affect all the major peripheral blood elements, our results support the use of the absolute lymphocyte count as the most sensitive indicator of benzene-induced hematotoxicity. (C) 1995 Wiley-Liss, Inc. C1 CHINESE ACAD PREVENT MED,INST OCCUPAT MED,BEIJING 100050,PEOPLES R CHINA. LOVELACE INHALAT TOXICOL RES INST,ALBUQUERQUE,NM. US FDA,CTR BIOL RES & EVALUAT,BETHESDA,MD. SHANGHAI HYG & ANTIEPIDEM CTR,DEPT OCCUPAT HLTH,SHANGHAI,PEOPLES R CHINA. UNIV CALIF BERKELEY,SCH PUBL HLTH,BERKELEY,CA 94720. RP Rothman, N (reprint author), NCI,NIH,EPIDEMIOL & BIOSTAT PROGRAM 418,BETHESDA,MD 20892, USA. FU NIEHS NIH HHS [P30ES01896, P42ES04705] NR 50 TC 114 Z9 121 U1 1 U2 10 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD MAR PY 1996 VL 29 IS 3 BP 236 EP 246 DI 10.1002/(SICI)1097-0274(199603)29:3<236::AID-AJIM3>3.0.CO;2-O PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA TX830 UT WOS:A1996TX83000003 PM 8833776 ER PT J AU Schaeffer, MH Krantz, DS Wichman, A Masur, H Reed, E Vinicky, JK AF Schaeffer, MH Krantz, DS Wichman, A Masur, H Reed, E Vinicky, JK TI The impact of disease severity on the informed consent process in clinical research SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID BIOMEDICAL-RESEARCH; INFORMATION; CANCER; CARE AB PURPOSE: To assess the efficacy of informed consent in subjects differing in disease severity, ranging from those with immediately life-threatening disease to healthy volunteers. SUBJECTS AND METHODS: A total of 127 subjects, enrolled in four types of clinical research protocols, were tested. Subjects completed questionnaires before entry into the protocol, within 24 hours of signing the primary protocol's consent document, and 4 to 6 weeks after entry. RESULTS: Healthy volunteers retained the most information about risks and side effects, and severely ill Phase I subjects retained the least (P < 0.0001). Phase I and II subjects had the best long-term retention of information about procedures, whereas Phase III subjects and healthy volunteers retained the least (P < 0.001). Information about the scientific purpose and confidentiality of data were retained best by symptom-free, Phase III subjects (P < 0.05). Phase I subjects entered the study primarily for treatment purposes, and the consent document was rated less useful by subjects with more advanced disease (P < 0.05). CONCLUSIONS: Subjects with differing disease processes and illness severities focused on and retained different aspects of experimental protocols for dissimilar reasons. During the informed consent process, research staff should inquire of potential subjects' personal goals for participating in experimental protocols and develop means for ensuring subjects' understanding of the inherent risks and alternative interventions available. C1 WASHINGTON HOSP CTR,DEPT BIOETH,WASHINGTON,DC 20010. NIH,BIOETH PROGRAM,BETHESDA,MD 20892. NIH,WARREN G MAGNUSON CLIN CTR,DEPT CRIT CARE MED,BETHESDA,MD 20892. NIH,OFF HUMAN SUBJECTS RES,OFF DIRECTOR,BETHESDA,MD 20892. NCI,MED BRANCH,NIH,MED OVARIAN CANC SECT,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,DEPT MED & CLIN PSYCHOL,BETHESDA,MD 20814. RI Krantz, David/L-5364-2015 OI Krantz, David/0000-0002-1671-1355 NR 30 TC 106 Z9 109 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9343 J9 AM J MED JI Am. J. Med. PD MAR PY 1996 VL 100 IS 3 BP 261 EP 268 DI 10.1016/S0002-9343(97)89483-1 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA TZ975 UT WOS:A1996TZ97500003 PM 8629670 ER PT J AU Sturgeon, SR Curtis, RE Johnson, K Ries, L Brinton, LA AF Sturgeon, SR Curtis, RE Johnson, K Ries, L Brinton, LA TI Second primary cancers after vulvar and vaginal cancers SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE vulvar cancer; vaginal cancer; cervical cancer; second primary cancer ID CERVICAL-CANCER; SMOKING; CARCINOMA; RISK AB OBJECTIVE: Our objective was to examine the occurrence of second primary cancers after vaginal and vulvar cancers. STUDY DESIGN: Women in whom cancers of the vagina (in situ, n = 461; invasive, n = 888) and vulva (in situ, n = 2898; invasive, n = 2685) were diagnosed between 1973 and 1988 were identified from nine population-based cancer registries. Subjects were followed through 1989 for the development of a subsequent primary cancer. RESULTS: We found increased risks of all second cancers combined among women with cancer of the vulva (observed/expected in situ = 1.5; observed/expected invasive = 1.3) and vagina (observed/expected invasive = 1.2). Most of the excess second cancers were smoking related (e.g., cancers of the lung, buccal cavity and pharynx, esophagus, nasal cavity and larynx) or related to infection with human papillomavirus (e.g., cervix, vulva, vagina, and anus). CONCLUSION: These associations indicate that the follow-up care of women with cancers of the vulva and vagina should involve efforts to promote smoking cessation. The data are also consistent with a common sexually related cause for cancers of the cervix, vulva, vagina, and anus. C1 NCI,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892. NCI,RADIAT EPIDEMIOL BRANCH,BETHESDA,MD 20892. NCI,COMMUNITY ONCOL & REHABIL BRANCH,BETHESDA,MD 20892. NCI,CANC STAT BRANCH,BETHESDA,MD 20892. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 21 TC 23 Z9 24 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAR PY 1996 VL 174 IS 3 BP 929 EP 933 DI 10.1016/S0002-9378(96)70328-9 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA UC866 UT WOS:A1996UC86600026 PM 8633671 ER PT J AU Baumrind, S Korn, EL Boyd, RL Maxwell, R AF Baumrind, S Korn, EL Boyd, RL Maxwell, R TI The decision to extract .1. Interclinician agreement SO AMERICAN JOURNAL OF ORTHODONTICS AND DENTOFACIAL ORTHOPEDICS LA English DT Article AB As part of an ongoing prospective clinical trial of conventional orthodontic treatment, the decision making patterns of a representative group of orthodontic clinicians were examined. Data were available for 148 subjects (100 adolescents and 48 adults) who had presented at the University of California San Francisco Graduate Orthodontic Clinic requesting treatment for correction of a Class I or Class II malocclusion. The records for each subject were evaluated independently by each of five members of the clinical faculty, making available a total of 740 independent patient evaluations. With regard to the primary decision as to whether extraction or nonextraction treatment was to be preferred, agreement among clinicians was higher than had been anticipated. In almost two thirds of the cases, the decisions of all five clinicians were in agreement as to whether extraction or nonextraction was the preferred treatment modality. (This figure included 59 cases of complete agreement for extraction therapy (40%) and 38 cases of complete agreement for nonextraction therapy (26%)). In only 51 cases (34%), did the reviewing clinicians disagree as to whether extraction or nonextraction was the preferred modality of treatment. The clinicians were also asked to indicate their opinions as to whether orthognatic surgery was likely to be a part of the ultimate treatment course for each individual subject. Nine percent of the 740 patient evaluations contained a clinician judgement that surgery would be a probable or definite component of the orthodontic treatment plan. For 29% of the adult subjects (14 cases) and 23% of the adolescent subjects (23 cases), one or more of the five examining clinicians believed that adjunctive surgical intervention would probably or definitely be appropriate. These high values were unexpected, particularly because the sample had been prescreened by a single clinician to exclude subjects who might require orthognathic surgery. Clinician agreement of Angle classification was also evaluated. Disagreements were observed in 14 adult subjects (29%) and 27 adolescent subjects (27%). Little association was observed between clinician agreement on Angle classification and clinician agreement on whether or not to extract. C1 NCI,BIOMETRY RES BRANCH,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,DEPT GROWTH & DEV,DIV ORTHODONT,SAN FRANCISCO,CA 94143. FU NIDCR NIH HHS [DE08713] NR 40 TC 29 Z9 33 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0889-5406 J9 AM J ORTHOD DENTOFAC JI Am. J. Orthod. Dentofac. Orthop. PD MAR PY 1996 VL 109 IS 3 BP 297 EP 309 DI 10.1016/S0889-5406(96)70153-1 PG 13 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TZ457 UT WOS:A1996TZ45700012 PM 8607475 ER PT J AU Washiyama, K Muragaki, Y Rorke, LB Lee, VMY Feinstein, SC Radeke, MJ Blumberg, D Kaplan, DR Trojanowski, JQ AF Washiyama, K Muragaki, Y Rorke, LB Lee, VMY Feinstein, SC Radeke, MJ Blumberg, D Kaplan, DR Trojanowski, JQ TI Neurotrophin and neurotrophin receptor proteins in medulloblastomas and other primitive neuroectodermal tumors of the pediatric central nervous system SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR; FIBRILLARY ACIDIC PROTEIN; INTERMEDIATE FILAMENT PROTEINS; CHILDHOOD BRAIN-TUMORS; MONOCLONAL-ANTIBODIES; NEUROFILAMENT PROTEIN; HUMAN NEUROBLASTOMA; GLIAL FILAMENT; PALE ISLANDS; CELL-LINES AB Primitive neuroectodermal tumors (PNETs) of the central nervous system (CNS) are poorly understood childhood neoplasms, and medulloblastomas are the most common pediatric PNETs. Neoplastic cells in medulloblastomas and other PNETs resemble progenitor cells of the developing central nervous system, but they also may exhibit the molecular phenotype of immature neurons or glia, As neurotrophins play a role itt regulating differentiation, proliferation, and cell death in the normal developing central nervous system, and recent evidence suggests that neurotrophins may influence the behavior of medullablostomas, we studied 29 PNET biopsy samples (27 of which were posterior fossa medulloblastomas) by immunohistochemistry using antibodies specific for each of the major high affinity neurotrophin receptor proteins, ie, TrkA, TrkB, and TrkC. A subset of these tumors also was examined by Western blot. Immunoreactive TrkA, TrkB, and TrkC were observed in neoplastic cells in 8 (27%), 18 (62%), and 14 (48%) of these PNETs, respectively. Additional immunohistochemical studies of a subset of these PNETs using antibodies to neurotrophins that primarily activate TrkB and TrkC, ie, brain-derived neurotrophic factor neurotrophin-3, and neurotrophin-4/5, showed that immunoreactive brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4/5 were detected in 22, 9, and 19% of these PNET biopsies, respectively. Finally, 19 pediatric brain tumors other than these PNETs also were studied here, and they expressed these neurotrophins and their receptors to a variable extent. The demonstration here that neurotrophins and their cognate receptor proteins ape expressed in PNETs as well as in other pediatric brain tumors may imply that signal transduction pathways mediated by neurotrophins and/or their receptors influence the induction or progression of these common childhood neoplasms. C1 UNIV PENN,SCH MED,DEPT PATHOL & LAB MED,PHILADELPHIA,PA 19104. CHILDRENS HOSP PHILADELPHIA,DEPT PATHOL,PHILADELPHIA,PA 19104. UNIV CALIF SANTA BARBARA,NEUROSCI RES INST,SANTA BARBARA,CA 93106. UNIV CALIF SANTA BARBARA,DEPT MOLEC CELLULAR & DEV BIOL,SANTA BARBARA,CA 93106. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD. FU NCI NIH HHS [CA-36245-13] NR 63 TC 53 Z9 54 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 MAR PY 1996 VL 148 IS 3 BP 929 EP 940 PG 12 WC Pathology SC Pathology GA TY074 UT WOS:A1996TY07400026 PM 8774147 ER PT J AU Rosenbaum, M Ravussin, E Matthews, DW Gilker, C Ferraro, R Heymsfield, SB Hirsch, J Leibel, RL AF Rosenbaum, M Ravussin, E Matthews, DW Gilker, C Ferraro, R Heymsfield, SB Hirsch, J Leibel, RL TI A comparative study of different means of assessing long-term energy expenditure in humans SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE obesity; body composition; caloric titration; chamber calorimetry; differential isotope excretion ID DOUBLY LABELED WATER; INDIRECT-CALORIMETRY; BODY-COMPOSITION; BALANCE AB We compared three independent techniques for measurement of total energy expenditure (TEE) in human subjects: 1) weight-maintaining energy intake (dietTEE), 2) 24-h chamber calorimetry (chamberTEE), and 3) differential elimination rates (H2O)-H-2 and (H2O)-O-18 (isotopeTEE). Twenty-three healthy adult in-patients [19 never obese (NO), 2 obese (OB), and 2 formerly-obese (RO); 9 female, 14 male] ingested a liquid formula diet (40% of calories as fat, 45% carbohydrate, 15% protein), the volume of which was adjusted until body weight was stable for at least 14 days. Body composition was then determined by hydrodensitometry, isotope dilution, and dual photon beam absorptiometry (DXA). The thermic effect of feeding (TEF) and resting energy expenditure [REE; measured before arising (dietREE) and after arising (chamberREE)] were determined by indirect calorimetry. Non-resting energy expenditure (NREE) was calculated as NREE = TEE - (REE + TEF). Subjects then gained or lost 10% of their body weight and were restudied as described above. All measures of TEE were significantly correlated (dietTEE vs. chamberTEE r(2) = 0.75; dietTEE vs. isotopeTEE r(2) = 0.88; isotopeTEE vs. chamberTEE r(2) = 0.73; P < 0.0001). ChamberTEE (mean +/- SE = 2,107 +/- 64 kcal/day) was similar to 20% lower than either dietTEE (2,536 +/- 94 kcal/day, P < 0.0001) or isotopeTEE (2,564 +/- 83 kcal/day, P < 0.0001). When data were normalized to metabolic mass, weight gain of 10% was associated with significant increases in dietTEE (P < 0.005) and isotopeTEE (P < 0.05) but not chamberTEE; weight loss of 10% was associated with significant reductions in dietTEE (P < 0.005) and isotopeTEE (P < 0.05) but not chamberTEE. We conclude that measures of energy expenditure obtained in a highly controlled environment by caloric titration (dietTEE) or differential excretion rates of (H2O)-H-2 and (H2O)-O-18 (isotopeTEE) are not significantly different and that measurements of TEE obtained in a respiratory chamber (chamberTEE) are significantly lower than dietTEE or isotopeTEE, probably largely due to limitations on physical activity in the chamber. C1 ST LUKES ROOSEVELT HOSP, DEPT MED, OBES RES CTR, NEW YORK, NY 10025 USA. CORNELL UNIV, MED CTR, NEW YORK HOSP, NEW YORK, NY 10021 USA. NIDDKD, NIH, CLIN DIABET & NUTR SECT, PHOENIX, AZ 85016 USA. RP Rosenbaum, M (reprint author), ROCKEFELLER UNIV, HUMAN BEHAV & METAB LAB, 1230 YORK AVE, NEW YORK, NY 10021 USA. RI Biguzzi, Felipe/E-4724-2015 FU NIDDK NIH HHS [DK-30583, DK-01983, DK-26687] NR 23 TC 41 Z9 41 U1 2 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD MAR PY 1996 VL 270 IS 3 BP R496 EP R504 PG 9 WC Physiology SC Physiology GA TZ876 UT WOS:A1996TZ87600002 PM 8780213 ER PT J AU Jacobsen, LK Giedd, JN Vaituzis, AC Hamburger, SD Rajapakse, JC Frazier, JA Kaysen, D Lenane, MC McKenna, K Gordon, CT Rapoport, JL AF Jacobsen, LK Giedd, JN Vaituzis, AC Hamburger, SD Rajapakse, JC Frazier, JA Kaysen, D Lenane, MC McKenna, K Gordon, CT Rapoport, JL TI Temporal lobe morphology in childhood-onset schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID GENDER DIFFERENCES; BRAIN; ABNORMALITIES; POSTMORTEM; HIPPOCAMPUS; PATHOLOGY; DISORDER; VOLUME AB Objective: Neurodevelopmental models of schizophrenia imply that a more severe early brain lesion may produce earlier onset of psychotic symptoms. The menial temporal lobes have been proposed as possible locations for such a lesion. The authors tested this hypothesis in a group of children and adolescents with childhood-onset schizophrenia who had severe, chronic symptoms and who were refractory to treatment with typical neuroleptics. Method: Anatomic brain magnetic resonance imaging scans were acquired with a 1.5-T scanner for 21 patients (mean age=14.6 years, SD=2.1) who had onset of schizophrenia by age 12 (mean age at onset=10.2, SD=1.5) and 41 normal children. Volumes of the temporal lobe, superior temporal gyrus, amygdala, and hippocampus were measured by manually outlining these structures on contiguous 2-mm thick coronal slices. Results: Patients with childhood-onset schizophrenia had significantly smaller cerebral volumes. With no adjustment for brain volume, no diagnostic differences were observed for any temporal lobe structure. Unexpectedly, with adjustment for total cerebral volume, larger volumes of the superior temporal gyrus ann its posterior segment and a trend toward larger temporal lobe volume emerged for the patients with schizophrenia. These patients lacked the normal (right-greater-than-left) hippocampal asymmetry. Conclusions: These findings do not indicate a more severe medial temporal lobe lesion as the basis of very early onset of schizophrenia. C1 UNIV MARYLAND,SCH MED,BALTIMORE,MD 21201. NORTHWESTERN UNIV,SCH MED,CHICAGO,IL. RP Jacobsen, LK (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,RM 6N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. RI Giedd, Jay/A-3080-2008; Rajapakse, Jagath/B-8485-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Rajapakse, Jagath/0000-0001-7944-1658; Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 59 TC 86 Z9 88 U1 2 U2 4 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAR PY 1996 VL 153 IS 3 BP 355 EP 361 PG 7 WC Psychiatry SC Psychiatry GA TY356 UT WOS:A1996TY35600008 PM 8610822 ER PT J AU Zubenko, GS Teply, I Winwood, E Huff, FJ Moossy, J Sunderland, T Martinez, AJ AF Zubenko, GS Teply, I Winwood, E Huff, FJ Moossy, J Sunderland, T Martinez, AJ TI Prospective study of increased platelet membrane fluidity as a risk factor for Alzheimer's disease: Results at 5 years SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID DEMENTIA; DIAGNOSIS; RELATIVES; HISTORY; AGE AB Objective: The primary goal of this study was to evaluate increased platelet membrane fluidity as a putative risk factor for Alzheimer's disease. Method: This report describes the initial results of a prospective, longitudinal study of 330 initially asymptomatic, first-degree relatives of probands with Alzheimer's disease. Results: Five incident cases of Alzheimer's disease were detected during the first 1,582 subject-years of the follow-up period. The age-specific incidence of Alzheimer's disease was several-fold higher than corresponding figures that were obtained in two prospective community studies. Most important, both age and increased platelet membrane fluidity made significant independent contributions to the risk of developing Alzheimer's disease. Conclusions: These results validate age and a family history of Alzheimer's disease as risk factors for this disorder and provide the first prospective evidence of increased platelet membrane fluidity as a biological risk factor for Alzheimer's disease. C1 UNIV PITTSBURGH,SCH MED,DEPT PSYCHIAT,PITTSBURGH,PA. UNIV PITTSBURGH,SCH MED,DEPT PATHOL NEUROPATHOL,PITTSBURGH,PA. UNIV MED & DENT NEW JERSEY,PISCATAWAY,NJ 08854. NIMH,CLIN SCI LAB,SECT GERIATR PSYCHIAT,BETHESDA,MD 20892. FU NIA NIH HHS [AG-05133]; NIMH NIH HHS [MH-43261, MH-30915] NR 24 TC 18 Z9 18 U1 1 U2 1 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAR PY 1996 VL 153 IS 3 BP 420 EP 423 PG 4 WC Psychiatry SC Psychiatry GA TY356 UT WOS:A1996TY35600021 PM 8610834 ER PT J AU Evans, VJ AF Evans, VJ TI Fertility: Past, present, and future SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Article; Proceedings Paper CT 6th International Congress of Reproductive Immunology CY JUL 19-23, 1995 CL WASHINGTON, DC DE fertility RP Evans, VJ (reprint author), NICHHD,DBSB,POPULAT RES CTR,6100 EXECUT BLVD,ROOM 8B13,BETHESDA,MD 20892, USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 8755-8920 J9 AM J REPROD IMMUNOL JI Am. J. Reprod. Immunol. PD MAR PY 1996 VL 35 IS 3 BP 131 EP 139 PG 9 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA UA033 UT WOS:A1996UA03300002 PM 8962638 ER PT J AU Levine, SJ Logun, C Chopra, DP Rhim, JS Shelhamer, JH AF Levine, SJ Logun, C Chopra, DP Rhim, JS Shelhamer, JH TI Protein kinase C, interleukin-1 beta, and corticosteroids regulate shedding of the type I, 55 kDa TNF receptor from human airway epithelial cells SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; FACTOR-ALPHA; SOLUBLE RECEPTORS; MACROPHAGES; EXPRESSION; CYTOKINES; SECRETION; RELEASE; ASTHMA; NEUTROPHILS AB Tumor necrosis factor (TNF) may contribute to the pathogenesis of inflammatory airway disorders via the regulation of inflammatory and cellular immune responses. Shed cell surface TNF receptors can act as soluble TNF binding proteins and modulate TNF biological activity. We report that normal human airway epithelial cells, as well as two human airway epithelial cell lines, shed soluble type I TNF receptors (sTNF-RI) in a concentration-dependent fashion following protein kinase C (PKC) activation by PMA. Interleukin (IL)-1 beta also induced concentration-dependent sTNF-RI shedding from NCI-H292 cells, which could be inhibited by the PKC inhibitor calphostin C. Since corticosteroids are commonly utilized as antiinflammatory agents in airway disorders, the effect of dexamethasone on STNF-RI release was assessed. Dexamethasone inhibited constitutive, as well as PMA- and IL-1 beta-mediated STNF-RI release from NCI-H292 cells in a concentration-dependent fashion. Furthermore, dexamethasone increased while PMA decreased total cellular 55 kDa TNF-RI protein as detected by immunoblotting. These changes in total cellular 55 kDa TNF-RI protein did not appear to be mediated at the mRNA level, as assessed by ribonuclease protection assays. This suggests that sTNF-RI shedding represents a mechanism by which airway epithelial cells can actively participate in local cytokine networks and modulate TNF-mediated inflammation. Furthermore, since corticosteroids inhibit sTNF-RI release and are known to downregulate TNF synthesis, this may represent a mechanism by which equilibrium between TNF ligand and soluble binding protein is maintained in the airway microenvironment. C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT CRIT CARE MED,BETHESDA,MD 20892. NIH,NCI,BETHESDA,MD 20892. WAYNE STATE UNIV,INST CHEM TOXICOL,DETROIT,MI 48201. NR 49 TC 38 Z9 38 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD MAR PY 1996 VL 14 IS 3 BP 254 EP 261 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA TY727 UT WOS:A1996TY72700007 PM 8845176 ER PT J AU Choyke, PL Putnam, BJ Koby, M Mossy, G Feuerstein, IM Summers, R AF Choyke, PL Putnam, BJ Koby, M Mossy, G Feuerstein, IM Summers, R TI Morphing radiologic images: Applications on a desktop computer SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article AB OBJECTIVE. Morphing is an image processing technology that transforms one image into another by generating a series of intermediate synthetic images. The ability to perform morphing, once restricted to high-end graphics workstations, is now widely available for desktop computers. We investigated the potential use of morphing for displaying radiographic images. MATERIALS AND METHODS. Morphing was performed with commercially available software (Morph 2.5; Gryphon Software, San Diego, CA) on a Macintosh (Apple Computer, Cupertino, CA) computer. Images from 26 patients with serial radiologic studies were selected, digitized, and morphed. Key points and key surfaces were identified on the images to improve the quality of the morph movie, a process that took approximately 15 min. The images were then morphed into a continuous Quick Time (Apple) movie lasting 5-7 sec. When a sequence contained more than two images, a single movie incorporating all the images was created. The intervals between segments of the movie were made proportional to the actual time elapsed between the images. Images obtained with different techniques (positron emission tomography and MR imaging) were also morphed. Three observers judged the quality of the morph movies as satisfactory, good, or excellent. RESULTS. Twenty of 26 movies were judged to be of good or excellent quality. The movie format allowed the rapid display of multiple images in a concise 5- to 7-sec time frame. Moreover, the movie allowed the recognition of several simultaneous processes more easily than was possible with static images. Morphing two images of the same anatomic site using different techniques (MR imaging and positron emission tomography) proved to be a simple method of superimposing images. CONCLUSION. Morphing is a readily available and easily learned technique for displaying serial studies. The movie format is a more interesting, intuitive, and concise summary of events than can be provided by serial static images. Morphing may be useful for displaying large numbers of serial images in a short time for occasions such as clinical conferences or teaching purposes. RP Choyke, PL (reprint author), NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT RADIOL,HENRY M JACKSON FDN,BLDG 10,RM 1C660,BETHESDA,MD 20892, USA. NR 4 TC 2 Z9 2 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAR PY 1996 VL 166 IS 3 BP 527 EP 529 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TW774 UT WOS:A1996TW77400007 PM 8623621 ER PT J AU Martinez, A Allegra, CJ Kovacs, JA AF Martinez, A Allegra, CJ Kovacs, JA TI Efficacy of epiroprim (Ro11-8958), a new dihydrofolate reductase inhibitor, in the treatment of acute Toxoplasma infection in mice SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID LIPID-SOLUBLE ANTIFOLATE; PYRIMETHAMINE; ENCEPHALITIS; THERAPY; POTENT; SULFADIAZINE; TRIMETREXATE; COMBINATION; INVITRO; GONDII AB Toxoplasma gondii is a major cause of focal encephalitis in patients with acquired immunodeficiency syndrome. Epiroprim, an inhibitor of dihydrofolate reductase, was evaluated in vitro and in a mouse model of acute infection for activity against T. gondii. The 50% inhibitory concentration (IC50) of epiroprim for T. gondii dihydrofolate reductase was 0.9 mu M, similar to that of pyrimethamine, but epiroprim was 650-fold more selective than pyrimethamine for T. gondii compared with human dihydrofolate reductase. While intraperitoneally administered epiroprim (300 mg/kg/day for 14 days) alone was ineffective in mice acutely infected with the RH strain of T. gondii, 100% survival was seen when it was combined with orally administered sulfadiazine (375 mg/kg/day), which alone was also ineffective. Increases in survival were seen in combination with doses of sulfadiazine as low as 0.375 mg/kg/day. Orally administered epiroprim combined with dapsone also prolonged survival. Thus, epiroprim is an active and potentially less toxic alternative to pyrimethamine for the treatment of toxoplasmosis. C1 NCI,DEPT CRIT CARE MED,CTR CLIN,NATL INST HLTH,BETHESDA,MD 20892. ST AGNES HOSP,DEPT CRIT CARE,BALTIMORE,MD 21229. NCI,NAVY MED ONCOL BRANCH,BETHESDA,MD 20889. NR 13 TC 10 Z9 11 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DRIVE SUITE 130, MCLEAN, VA 22101 SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD MAR PY 1996 VL 54 IS 3 BP 249 EP 252 PG 4 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA UE418 UT WOS:A1996UE41800006 PM 8600759 ER PT J AU Hasin, DS Tsai, WY Endicott, J Mueller, TI Coryell, W Keller, M AF Hasin, DS Tsai, WY Endicott, J Mueller, TI Coryell, W Keller, M TI The effects of major depression on alcoholism - Five-year course SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID FOLLOW-UP; AFFECTIVE-DISORDER; DRUG-ABUSE; RELIABILITY; PERSISTENCE; SYMPTOMS; FAMILY AB Some patients come into treatment with clear cases of both major depression (MDD) and alcoholism. Although assumptions are often made about the relationships of these two conditions, little empirical information exists on the effects of changes in MDD on the course of alcoholism in patients presenting at psychiatric facilities. The authors used survival analysis with time-dependent covariates to investigate the effects of remissions and relapses of MDD on the 5-year course of alcoholism in 127 dual diagnosis patients. Changes in the status of MDD had strong, significant effects on the course of alcoholism. Improvement in MDD status increased the chances of remission in alcoholism and reduced the chances of alcoholism relapse. The status of MDD appears to have an effect on the course of alcoholism in patients with severe affective disorders. C1 NATL INST MENTAL HLTH,COLLABORAT PROGRAM PSYCHOBIOL DEPRESS CLIN STUDIE,BETHESDA,MD 20892. NR 31 TC 35 Z9 35 U1 0 U2 2 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 SPR PY 1996 VL 5 IS 2 BP 144 EP 155 PG 12 WC Substance Abuse SC Substance Abuse GA UH172 UT WOS:A1996UH17200006 ER PT J AU Strupp, HH Parloff, MB AF Strupp, HH Parloff, MB TI Julius Segal (1924-1994) SO AMERICAN PSYCHOLOGIST LA English DT Item About an Individual C1 NIMH,PSYCHOSOCIAL RES BRANCH,BETHESDA,MD 20892. RP Strupp, HH (reprint author), VANDERBILT UNIV,DEPT PSYCHOL,NASHVILLE,TN 37240, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0003-066X J9 AM PSYCHOL JI Am. Psychol. PD MAR PY 1996 VL 51 IS 3 BP 263 EP 263 PG 1 WC Psychology, Multidisciplinary SC Psychology GA UB198 UT WOS:A1996UB19800019 ER PT J AU Liu, KJ Shi, XL Jiang, JJ Goda, F Dalal, N Swartz, HM AF Liu, KJ Shi, XL Jiang, JJ Goda, F Dalal, N Swartz, HM TI Low frequency electron paramagnetic resonance investigation on metabolism of chromium (VI) by whole live mice SO ANNALS OF CLINICAL AND LABORATORY SCIENCE LA English DT Article ID CARCINOGEN CHROMATE; REDUCTION; MECHANISM; GLUTATHIONE; DAMAGE AB Detection of Cr(V) in the reduction of Cr(VI) by whole live mice and its characterization were carried out by low frequency electron paramagnetic resonance (EPR). Intravenous injection of Cr(VI) to mice generated Cr(V). The Cr(V) was found predominantly in the liver with a small amount in the blood. Liver homogenates from Cr(VI) heated mice generated essentially the same Cr(V) spectrum as that obtained from the whole live mice. This Cr(V) species was identified to be a Cr(V)-nicotinamide adenine dinucleotide (NAD) (P)H complex with an oxygen bond to Cr(V). Pretreatment of the mice with ascorbic acid and glutathione reduced the Cr(V) formation, while pretreatment with reduced nicotinamide adenine dinucleotide (NADH) enhanced it. Metal chelators, ethylenediaminetetraacetic acid (EDTA), 1,10-phenanthroline, and diethylenetriaminepentaacetic acid (DTPA) inhibited the intensity of the Cr(V) signal. The results suggest that Cr(V) generated in the whole body of a live animal is a Cr(V)-NAD(P)H complex and NAD(P)H/flavoenzymes and not glutathione or ascorbate as the major one-electron Cr(VI) reductant responsible for observed formation of Cr(V)-NAD(P)H complex in vivo. C1 NCI,NIH,LAB EXPTL PATHOL,BETHESDA,MD 20892. DARTMOUTH COLL SCH MED,DEPT RADIOL,HANOVER,NH 03755. W VIRGINIA UNIV,DEPT CHEM,MORGANTOWN,WV 26506. RI Shi, Xianglin/B-8588-2012 FU NCRR NIH HHS [RR-01811] NR 29 TC 40 Z9 41 U1 0 U2 0 PU INST CLINICAL SCIENCE INC PI PHILADELPHIA PA 1833 DELANCEY PLACE, PHILADELPHIA, PA 19103 SN 0091-7370 J9 ANN CLIN LAB SCI JI Ann. Clin. Lab. Sci. PD MAR-APR PY 1996 VL 26 IS 2 BP 176 EP 184 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA TY797 UT WOS:A1996TY79700010 PM 8852427 ER PT J AU Luo, H Lu, YD Shi, XL Mao, Y Dalal, NS AF Luo, H Lu, YD Shi, XL Mao, Y Dalal, NS TI Chromium(IV)-mediated Fenton-like reaction causes DNA damage: Implication to genotoxicity of chromate SO ANNALS OF CLINICAL AND LABORATORY SCIENCE LA English DT Article ID ONE-ELECTRON REDUCTION; CARCINOGEN CHROMATE; GLUTATHIONE-REDUCTASE; CHROMIUM(V) AB This paper describes our deoxyribonucleic acid (DNA) damage and Fenton activity studies on Cr(IV) that were undertaken to examine a role of Cr(IV) in the biochemical mechanism of genotoxicity of Cr(VI) compounds. A Cr(IV)-containing compound, a Cr(IV)-ester, was synthesized and used as the first model compound for Cr(IV) studies. Electron spin resonance measurements demonstrated that in the presence of H2O2, this Cr(IV) compound acts as a potent Fenton-like reagent, i.e., it generates (OH)-O-. radical and a Cr(V) species (g = 1.9787) via: Cr(IV) + H2O2 --> Cr(V) + (OH)-O-. + OH-. Measurements of (OH)-O-. yield as a function of H2O2 concentration showed that Cr(IV) is more potent than Cr(V) in generating (OH)-O-.. DNA damage assays demonstrate that Cr(IV) and the Cr(IV)/H2O2-generated (OH)-O-. radical can cause DNA strand breaks. The DNA damage caused by (OH)-O-. radical can be effectively blocked by (OH)-O-. radical scavengers. These results thus constitute the first. direct evidence for DNA damage by Cr(IV) and Cr(IV)-mediated Fenton-like reaction and support the conjecture that Cr(IV) plays a significant role in the biochemical mechanism of the genotoxic reactions of Cr(VI) compounds and that this effect can be modulated by suitable antiradical agents. C1 NCI,NIH,LAB EXPTL PATHOL,BETHESDA,MD 20892. W VIRGINIA UNIV,DEPT CHEM,MORGANTOWN,WV 26506. RI Shi, Xianglin/B-8588-2012 FU ODCDC CDC HHS [U60-CC306149-01-1] NR 22 TC 51 Z9 56 U1 0 U2 2 PU INST CLINICAL SCIENCE INC PI PHILADELPHIA PA 1833 DELANCEY PLACE, PHILADELPHIA, PA 19103 SN 0091-7370 J9 ANN CLIN LAB SCI JI Ann. Clin. Lab. Sci. PD MAR-APR PY 1996 VL 26 IS 2 BP 185 EP 191 PG 7 WC Medical Laboratory Technology SC Medical Laboratory Technology GA TY797 UT WOS:A1996TY79700011 PM 8852428 ER PT J AU Burchfiel, CM Reed, DM Strong, JP Sharp, DS Chyou, PH Rodriguez, BL AF Burchfiel, CM Reed, DM Strong, JP Sharp, DS Chyou, PH Rodriguez, BL TI Predictors of myocardial lesions in men with minimal coronary atherosclerosis at autopsy - The Honolulu Heart Program SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE Asian-Americans; autopsy; cigarette smoking; cardiovascular diseases; fish oils; risk factors ID HIGH-DENSITY-LIPOPROTEIN; RISK-FACTORS; CIGARETTE-SMOKING; FISH CONSUMPTION; FATTY-ACIDS; LIFESTYLE CHARACTERISTICS; ALCOHOL-CONSUMPTION; DIABETES-MELLITUS; PLASMA-FIBRINOGEN; PLATELET-FUNCTION AB Some cardiovascular risk factors are associated with clinical coronary heart disease but not with autopsy evidence of coronary atherosclerosis. To determine whether these risk factors might operate through mechanisms other than atherosclerosis, we examined associations between cardiovascular risk factors and subsequent intramural myocardial lesions assessed by protocol autopsy between 1965 and 1984 in 120 Japanese-American men from the Honolulu Heart Program who had minimal coronary atherosclerosis (American Heart Association (AHA) panel score < 3 on scale of 1 to 7). Age-adjusted Prevalence of myocardial lesions was related to smoking status (P < 0.01), as well as amount, duration, and pack-years of smoking (P < 0.03). In a multiple logistic model, smoking (20 pack-years) was directly associated and fsh intake (greater than or equal to 2 times/wk) was inversely associated with myocardial lesions independently of age, cholesterol, systolic blood pressure, body mass index, alcohol, diabetes, total calories, and animal protein intake (odds ratio (OR) = 1.5, 95% confidence intervals (CI) = 1.1 to 2.0 and OR = 0.35, 95% CI = 0.2 to 0.9, respectively). The protective effect of fish intake was most evident among men who did not have hypertension at baseline. Indices of obesity, body fat distribution, and physical activity and levels of triglyceride and alcohol intake were not associated with myocardial lesions. Thus, the adverse effects of smoking and the protective effects of fish consumption may extend to individuals relatively free of coronary atherosclerosis, possibly through hemostatic mechanisms or effects on small intramural arteries. C1 NHLBI, HONOLULU EPIDEMIOL RES SECT, FIELD STUDIES & BIOMETRY BRANCH, DIV EPIDEMIOL & CLIN APPLICAT, HONOLULU, HI USA. UNIV HAWAII MANOA, HONOLULU, HI 96822 USA. BUCK CTR RES AGING, NOVATO, CA USA. LOUISIANA STATE UNIV, MED CTR, DEPT PATHOL, NEW ORLEANS, LA 70112 USA. RP Burchfiel, CM (reprint author), KUAKINI MED CTR, HONOLULU HEART PROGRAM, 347 N KUAKINI ST, HONOLULU, HI 96817 USA. FU NHLBI NIH HHS [HC-95009] NR 60 TC 20 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD MAR PY 1996 VL 6 IS 2 BP 137 EP 146 DI 10.1016/1047-2797(95)00125-5 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UC780 UT WOS:A1996UC78000007 PM 8775594 ER PT J AU Faden, VB Graubard, BI AF Faden, VB Graubard, BI TI Untitled SO ANNALS OF EPIDEMIOLOGY LA English DT Letter ID MATERNAL ALCOHOL-CONSUMPTION; BIRTH-WEIGHT; PREGNANCY C1 NCI,NIH,BETHESDA,MD 20892. RP Faden, VB (reprint author), NIAAA,DIV BIOMETRY & EPIDEMIOL,NIH,BETHESDA,MD 20892, USA. NR 7 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD MAR PY 1996 VL 6 IS 2 BP 170 EP 170 DI 10.1016/S1047-2797(96)90010-1 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA UC780 UT WOS:A1996UC78000013 ER PT J AU TalarWilliams, C Hijazi, YM Walther, MM Linehan, WM Hallahan, CW Lubensky, L Kerr, CS Hoffman, GS Fauci, AS Sneller, MC AF TalarWilliams, C Hijazi, YM Walther, MM Linehan, WM Hallahan, CW Lubensky, L Kerr, CS Hoffman, GS Fauci, AS Sneller, MC TI Cyclophosphamide-induced cystitis and bladder cancer in patients with wegener granulomatosis SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID ULCERATIVE-COLITIS; RHEUMATOID-ARTHRITIS; TOXICITY AB Objective: To describe the incidence of, clinical manifestations of, and risk factors for cyclophosphamide-induced urinary bladder toxicity in patients treated for nonmalignant disease. Design: Retrospective analysis of patients followed at the National Institutes of Allergy and Infectious Diseases from 1967 to 1993. Setting: The Warren G. Magnuson Clinical Center of the National Institutes of Health (NIH). Patients: 145 patients who received cyclophosphamide for the treatment of Wegener granulomatosis and were followed for 0.5 to 27 years (median, 8.5 years), for a total of 1333 patient-years. Measurements: Clinical characteristics, cystoscopic findings, results of cytologic examination of urine, surgical pathology. and total dose and duration of cyclophosphamide therapy were recorded and analyzed using a computer-based information retrieval system. Results: Nonglomerular hematuria occurred in 73 of 145 patients treated with cyclophosphamide (50%). Sixty of the 73 patients with nonglomerular hematuria (82%) had cystoscopy at the NIH. Forty-two of the 60 patients (70%) who had cystoscopy had macroscopic changes consistent with cyclophosphamide-induced bladder injury. Seven patients (5%) developed transitional-cell carcinoma of the urinary bladder. In 6 of these 7 patients, the total cumulative cyclophosphamide dose exceeded 100 g, and the cumulative duration of cyclophosphamide therapy exceeded 2.7 years. Before they were given a diagnosis of bladder cancer, all 7 patients had had one or more episodes of microscopic or gross nonglomerular hematuria. In contrast, none of the 72 patients who had never had nonglomerular hematuria developed bladder cancer. Cox proportional hazards regression analysis showed that only microscopic nonglomerular hematuria was a significant risk factor for the development of bladder cancer (P < 0.01). Conclusion: Long-term oral cyclophosphamide therapy is associated with substantial urotoxicity, including the development of transitional-cell carcinoma of the urinary bladder. In this cohort of patients, the estimated incidence of bladder cancer after the first exposure to cyclophosphamide was 5% at 10 years and 16% at 15 years. Nonglomerular hematuria was a frequent manifestation of cyclophosphamide-induced cystitis, and it identified a subgroup of patients at high risk for the development of bladder cancer. C1 NIAID,NIH,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NR 24 TC 311 Z9 317 U1 0 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAR 1 PY 1996 VL 124 IS 5 BP 477 EP & PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA TW773 UT WOS:A1996TW77300003 PM 8602705 ER PT J AU Johnson, RT Glass, JD McArthur, JC Chesebro, BW AF Johnson, RT Glass, JD McArthur, JC Chesebro, BW TI Quantitation of human immunodeficiency virus in brains of demented and nondemented patients with acquired immunodeficiency syndrome SO ANNALS OF NEUROLOGY LA English DT Article AB We measured human immunodeficiency virus (HIV) DNA in brains of 15 patients who died with acquired immunodeficiency syndrome (AIDS). All had been followed prospectively prior to death; 7 were demented and 8 were not demented. HIV was detected in 13 of 15 brains by polymerase chain reaction (PCR) and in the remaining 2 by presence of viral RNA or viral antigen. Quantitative PCR showed a wide range in amounts of HIV DNA with no significant difference between brains of demented and nondemented patients. These results suggest that qualitative features of the virus, rather than increased virus load per se, may be responsible for the clinical differences between HIV-infected patients with and without dementia. C1 JOHNS HOPKINS UNIV, DEPT NEUROL, BALTIMORE, MD 21218 USA. JOHNS HOPKINS UNIV, DEPT PATHOL, BALTIMORE, MD 21218 USA. JOHNS HOPKINS UNIV, DEPT EPIDEMIOL, BALTIMORE, MD 21218 USA. NIAID, ROCKY MT LABS, PERSISTENT VIRAL DIS LAB, HAMILTON, MT 59840 USA. FU NINDS NIH HHS [NS26643] NR 16 TC 111 Z9 113 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD MAR PY 1996 VL 39 IS 3 BP 392 EP 395 DI 10.1002/ana.410390319 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA UC473 UT WOS:A1996UC47300018 PM 8602761 ER PT J AU Doherty, GM Alexander, HR Merino, MJ Venzon, DJ Norton, JA AF Doherty, GM Alexander, HR Merino, MJ Venzon, DJ Norton, JA TI Role of endogenous interferon gamma in murine tumor growth and tumor necrosis factor alpha antitumor efficacy SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article DE interferon gamma; tumor necrosis factor; mouse; sarcoma ID RECOMBINANT HUMAN; IFN-GAMMA; MALIGNANCIES; COMBINATION; MELANOMA; TOXICITY; INVIVO; CELLS; DNA AB Background: The anticancer role of tumor necrosis factor-alpha (TNF-alpha) has been limited by toxicity. These experiments evaluate blocking endogenous interferon-gamma (IFN-gamma) activity to abrogate TNF-alpha toxicity, Methods: C57B1/6 mice bearing MCA 105 tumor were treated with TNF-alpha and anti-IFN-gamma antibody (Ab) to evaluate the effect on the acute lethality of TNF-alpha and their efficacy as evaluated by tumor growth rate, tumor histology, and survival, Results: Anti-IFN-gamma Ab decreased TNF-alpha lethality, Anti-IFN-gamma Ab alone increased tumor growth significantly more than did nonimmune IgG (p(2) < 0.0001), Tumor-bearing mice that received nonimmune IgG and TNF-alpha had slower tumor growth (p(2) < 0.02) and a trend toward improved survival (p = 0.07) compared with saline-treated controls. Anti-IFN-gamma Ab abrogated the antitumor effect of TNF-alpha, prevented acute tumor necrosis histologically, and resulted in tumor growth rate and host survival similar to that of controls. The findings in mice that received anti-IFN-gamma Ab and high-dose TNF-alpha were comparable with those in mice that received a lower, equitoxic dose of TNF-alpha alone. Conclusions: Blocking endogenous IFN-gamma accelerates tumor growth in this model and partially abrogates the toxic and antitumor activity of exogenous TNF-alpha equally. This suggests that blocking endogenous IFN-gamma activity is not a useful strategy for limiting TNF-alpha treatment toxicity. C1 NCI,NIH,SURG METAB SECT,SURG BRANCH,BETHESDA,MD 20892. NCI,NIH,PATHOL LAB,BETHESDA,MD 20892. NCI,NIH,BIOSTAT & DATA MANAGEMENT BRANCH,BETHESDA,MD 20892. RP Doherty, GM (reprint author), WASHINGTON UNIV,DEPT SURG,LAB BIOL THERAPY,BOX 8109,1 BARNES HOSP PLAZA,ST LOUIS,MO 63110, USA. RI Venzon, David/B-3078-2008 NR 19 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD MAR PY 1996 VL 3 IS 2 BP 198 EP 203 DI 10.1007/BF02305801 PG 6 WC Oncology; Surgery SC Oncology; Surgery GA TX815 UT WOS:A1996TX81500015 PM 8646522 ER PT J AU Breen, N AF Breen, N TI Bound by our Constitution: Women, workers, and the minimum wage - Hart,V SO ANNALS OF THE AMERICAN ACADEMY OF POLITICAL AND SOCIAL SCIENCE LA English DT Book Review RP Breen, N (reprint author), NCI,BETHESDA,MD 20892, USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SAGE SCIENCE PRESS PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 SN 0002-7162 J9 ANN AM ACAD POLIT SS JI Ann. Am. Acad. Polit. Soc. Sci. PD MAR PY 1996 VL 544 BP 223 EP 223 DI 10.1177/0002716296544001030 PG 1 WC Political Science; Social Sciences, Interdisciplinary SC Government & Law; Social Sciences - Other Topics GA TW045 UT WOS:A1996TW04500034 ER PT J AU Chio, LC Bolyard, LA Nasr, M Queener, SF AF Chio, LC Bolyard, LA Nasr, M Queener, SF TI Identification of a class of sulfonamides highly active against dihydropteroate synthase from Toxoplasma gondii, Pneumocystis carinii, and Mycobacterium avium SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID DIHYDROFOLATE-REDUCTASE; IN-VITRO; INVITRO; DRUGS; INHIBITORS; GROWTH; INVIVO AB Sulfanilanilides with 3',5'-halogen substitutions had K-i values 6- to 57-fold lower than the K-i of sulfamethoxazole when tested against dihydropteroate synthase from Toxoplasma gondii. The compounds acted as competitive inhibitors. These compounds were also active against dihydropteroate synthase from Pneumocystis carinii. Mycobacterium avium, and Escherichia coli but were not significantly more active than sulfamethoxazole. The compounds were significantly more active in culture than were standard agents. Against T. gondii in culture, 50% inhibitory concentrations were 7- to 30-fold lower than that of sulfadiazine; against P. carinii in culture, a concentration of 100 mu M caused 33 to 95% inhibition of growth, compared with 9% inhibition with 100 mu M sulfamethoxazole. C1 INDIANA UNIV,SCH MED,DEPT PHARMACOL & TOXICOL,INDIANAPOLIS,IN 46202. NIAID,DIV AIDS,ROCKVILLE,MD 20892. FU NIAID NIH HHS [N01-AI-55256, N01 AI-35171, N01 AI-87240] NR 22 TC 25 Z9 27 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 MAR PY 1996 VL 40 IS 3 BP 727 EP 733 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA TY366 UT WOS:A1996TY36600036 PM 8851601 ER PT J AU Turpin, JA Schaeffer, CA Bu, M Graham, L Buckheit, RW Clanton, D Rice, WG AF Turpin, JA Schaeffer, CA Bu, M Graham, L Buckheit, RW Clanton, D Rice, WG TI Human immunodeficiency virus type-1 (HIV-1) replication is unaffected by human secretory leukocyte protease inhibitor SO ANTIVIRAL RESEARCH LA English DT Article DE secretory leukocyte protease inhibitor (SLPI); lymphocytes; monocytes; human immunodeficiency virus type-1 (HIV-1); antivirals; saliva ID HUMAN LYMPHOCYTES-T4+; SALIVARY INHIBITION; INFECTIVITY; MEMBRANE AB Human secretory leukocyte protease inhibitor (SLPI); a serine protease inhibitor found concentrated in secretory fluids, has been postulated to participate in the body's natural defense against infection by the human immunodeficiency virus type-1 (HIV-1) by affecting trypsin-like enzymes on the surface of target cells. SLPI was evaluated for potential antiviral activity against laboratory, clinical and monocytotropic strains of HIV-1 in human T-cell lines, peripheral blood lymphocytes and monocyte/macrophage cultures. SLPI was tested in a single cycle of infection assay and under conditions in which SLPI was preincubated both with target cells and with virus and then maintained during the virus-to-cell adsorption phase and throughout the entire culture period. However, SLPI did not exert anti-HIV activity under any experimental conditions; and mechanistic studies showed SLPI to have no inhibitory activity on HIV-1 binding, reverse transcriptase or protease. Thus, SLPI exhibited no suggestive anti-HIV-1 activity. C1 NCI,FREDERICK CANC RES & DEV CTR,LAB ANTIVIRAL DRUG MECHANISMS,SAIC FREDERICK,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,ANTI AIDS VIRUS DRUG SCREENING LAB,SAIC FREDERICK,FREDERICK,MD 21702. FREDERICK RES CTR,SO RES INST,VIROL RES GRP,FREDERICK,MD 21701. NR 19 TC 36 Z9 36 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD MAR PY 1996 VL 29 IS 2-3 BP 269 EP 277 DI 10.1016/0166-3542(95)00907-8 PG 9 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA UJ976 UT WOS:A1996UJ97600013 PM 8739605 ER PT J AU Shen, L Huang, KP Chen, HC Huang, FL AF Shen, L Huang, KP Chen, HC Huang, FL TI Molecular cloning and characterization of a novel casein kinase II substrate, HASPP28, from rat brain SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID DEPENDENT PROTEIN-KINASE; AMINO-ACID-SEQUENCE; GLYCOGEN-SYNTHASE; C SUBSTRATE; TROPONIN-T; PHOSPHORYLATION; BINDING; CELLS; NEUROGRANIN; SITES AB HASPP28 (heat- and acid-stable phosphoprotein of 28 kDa) has been purified to near homogeneity from the acid-stable protein fraction of rat brain extract, Based on the N-terminal 40 amino acid sequence, a pair of highly degenerate primers was used to generate a 107-bp probe from rat brain RNA by RT-PCR, From the rat brain lambda gt11 library, this probe identified two positive clones that together provided a cDNA of 837 bp with an open reading frame of 546 bp. This cDNA was extended by 3 'RACE to 1.2 kb that included a polyadenylation signal and a poly(A) tail. The 180-amino-acid sequence derived from the open reading frame, which did not correspond to any known protein, was predicted to have phosphorylation sites for protein kinase C, casein kinase II (CKII), and protein kinase A. Indeed, both the purified rat brain HASPP28 and the recombinant HASPP28 (rHASPP28) can be phosphorylated by these kinases, Northern blot analysis indicated that HASPP28 was present in all rat tissues tested, including those from the brain, lung, spleen, kidney, liver, heart, and muscle, in decreasing order of abundance. Phosphopeptide analysis of rHASPP28 phosphorylated in vitro by various kinases showed different tryptic peptide patterns on two-dimensional mapping and isoelectric focusing gels, From [P-32]PO4-labeled N1E115 neuroblastoma cells, HASPP28 can be immunoprecipitated with a polyclonal antiserum raised against rHASPP28. The immunoprecipitated protein showed a phosphopeptide pattern similar to that of rHASPP28 phosphorylated by CK II in vitro. Furthermore, the immunoprecipitates from cells treated with phorbol 12-myristate 13-acetate or 8-bromo-cAMP did not show any increased phosphorylation over those of untreated ones, and the phosphopeptide patterns of the immunoprecipitates again were similar to that of CK II phosphorylated protein. These results suggest that HASPP28 is a novel phosphoprotein that can be phosphorylated by several kinases in vitro. In intact cells, CK II seems to be solely responsible for the phosphorylation of HASPP28. (C) 1996 Academic Press, Inc. C1 NICHHD, ENDOCRINOL & REPROD RES BRANCH, NIH, BETHESDA, MD 20892 USA. NR 41 TC 7 Z9 9 U1 1 U2 5 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 MAR 1 PY 1996 VL 327 IS 1 BP 131 EP 141 DI 10.1006/abbi.1996.0101 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA TY716 UT WOS:A1996TY71600017 PM 8615683 ER PT J AU Gordis, E AF Gordis, E TI Alcohol research - At the cutting edge SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Editorial Material ID NALTREXONE; DEPENDENCE; IMPAIRMENT; DRINKING; AGE RP Gordis, E (reprint author), NIAAA,SUITE 400,6000 EXECUT BLVD,BETHESDA,MD 20892, USA. NR 25 TC 9 Z9 9 U1 4 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD MAR PY 1996 VL 53 IS 3 BP 199 EP 201 PG 3 WC Psychiatry SC Psychiatry GA TZ010 UT WOS:A1996TZ01000001 PM 8611055 ER PT J AU FilsAime, ML Eckardt, MJ George, DT Brown, GL Mefford, I Linnoila, M AF FilsAime, ML Eckardt, MJ George, DT Brown, GL Mefford, I Linnoila, M TI Early-onset alcoholics have lower cerebrospinal fluid 5-hydroxyindoleacetic acid levels than late-onset alcoholics SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID PLATELET MAO ACTIVITY; FAMILY HISTORY; DISORDERS; VIOLENT; PERFORMANCE; INSTRUMENT; SUBGROUPS; OFFENDERS; CRITERIA; AGE AB Background: We investigated the interrelationships of age at onset of excessive alcohol consumption, family history of alcoholism, psychiatric comorbidity, and cerebrospinal fluid monoamine metabolite concentrations in abstinent, treatment-seeking alcoholics. Methods: We studied 131 recently abstinent alcoholics. Supervised abstinence was maintained on a research ward at the National Institutes of Health Clinical Center for a minimum of 3 weeks. All alcoholics received a low-monoamine diet for a minimum of 3 days before lumbar puncture. Lumbar punctures were performed in the morning after an overnight fast. Monoamine metabolites and tryptophan in cerebrospinal fluid were quantified with liquid chromatography by means of electrochemical detection. Psychiatric diagnoses were established from blind-rated Schedule for Affective Disorders and Schizophrenia-Lifetime version interviews administered by a research social worker. Severity and age at onset of excessive alcohol consumption were documented with a structured lifetime drinking history questionnaire and with selected alcoholism screening questionnaires (CAGE and Michigan Alcoholism Screening Test). Family history of alcoholism was obtained from the probands. Results: A majority of the treatment-seeking, primarily white male alcoholics had a lifetime history of psychiatric disorders other than alcoholism None fulfilled criteria for antisocial personality disorder. Early-onset alcoholics (onset of excessive consumption before 25 years of age) had a more severe course of alcoholism and lower mean cerebrospinal fluid 5-hydroxyindoleacetic acid concentration than late-onset alcoholics. Patients who reported both parents to be alcoholics had particularly low mean cerebrospinal fluid 5-hydroxyindoleacetic acid, homovanillic acid, and tryptophan concentrations. Conclusion: Among treatment-seeking alcoholics, early age at onset is generally associated with a more severe course of alcoholism and lower cerebrospinal fluid 5-hydroxyindoleacetic acid concentration. C1 NIAAA,DIV INTRAMURAL CLIN & BIOL RES,CLIN STUDIES LAB,BETHESDA,MD 20892. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. NR 36 TC 136 Z9 136 U1 4 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD MAR PY 1996 VL 53 IS 3 BP 211 EP 216 PG 6 WC Psychiatry SC Psychiatry GA TZ010 UT WOS:A1996TZ01000003 PM 8611057 ER PT J AU Mazor, M Hershkowitz, R Ghezzi, F Cohen, J Chaim, W Wiznitzer, A Levy, J Leiberman, JR AF Mazor, M Hershkowitz, R Ghezzi, F Cohen, J Chaim, W Wiznitzer, A Levy, J Leiberman, JR TI Prolactin concentrations in preterm and term pregnancy and labour SO ARCHIVES OF GYNECOLOGY AND OBSTETRICS LA English DT Article DE labor; prolactin; amniotic fluid; plasma; preterm labour ID AMNIOTIC-FLUID; PROSTAGLANDINS; INITIATION; WOMEN; 13,14-DIHYDRO-15-KETO-PROSTAGLANDIN-F2-ALPHA; PARTURITION AB Maternal plasma and amniotic fluid (AF) were obtained for measurement of prolactin concentrations from: 1) 20 patients with preterm labor and intact membranes who delivered within one week of amniocentesis; 2) 20 patients with preterm labor who responded to tocolysis and delivered at term; 3) 20 women at term who were not in labor and 4) from 20 women in active labor at term. No significant differences were found between: 1) maternal plasma prolactin concentrations in women with preterm labor who delivered prematurely and those who delivered at term (155 ng/ml vs 176.5 ng/ml); 2) patients at term who were not in labor (188 ng/ml) and those who were in labor (155 ng/ml); 3) AF prolactin concentrations in the two preterm labor groups (1987.5 vs 1282.5 ng/ml) and 4) AF prolactin concentration in the two term groups (562 ng/ml vs 701 ng/ml). Prolactin concentrations were generally significantly higher preterm than at term. We concluded that no significant changes in maternal plasma and amniotic fluid prolactin levels were found in preterm and term parturition. C1 BEN GURION UNIV NEGEV,FAC HLTH SCI,SOROKA MED CTR KUPAT HOLIM,SEPT CLIN BIOCHEM UNIT,IL-84101 BEER SHEVA,ISRAEL. NICHHD,PERINATOL RES BRANCH,BETHESDA,MD 20892. RP Mazor, M (reprint author), BEN GURION UNIV NEGEV,FAC HLTH SCI,SOROKA MED CTR,DEPT OBSTET & GYNECOL,POB 151,IL-84101 BEER SHEVA,ISRAEL. OI Ghezzi, Fabio/0000-0003-3949-5410 NR 25 TC 3 Z9 6 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0932-0067 J9 ARCH GYNECOL OBSTET JI Arch. Gynecol. Obstet. PD MAR PY 1996 VL 258 IS 2 BP 69 EP 74 DI 10.1007/BF00626026 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA UB163 UT WOS:A1996UB16300003 PM 8779613 ER PT J AU Mazor, M Hershkowitz, R Ghezzi, F Cohen, J Silber, A Levy, J Leiberman, JR Glezerman, M AF Mazor, M Hershkowitz, R Ghezzi, F Cohen, J Silber, A Levy, J Leiberman, JR Glezerman, M TI Maternal plasma and amniotic fluid 17 beta-estradiol, progesterone and cortisol concentrations in women with successfully and unsuccessfully treated preterm labor SO ARCHIVES OF GYNECOLOGY AND OBSTETRICS LA English DT Article DE labor-amniotic fluid; plasma-17 beta-estradiol; progesterone; cortisol ID HUMAN-FETAL MEMBRANES; HUMAN PARTURITION; CELLS; TERM; GLUCOCORTICOIDS; PROSTAGLANDINS; INCREASE; DECIDUA; RATIO AB Maternal plasma and amniotic fluid (AF) were obtained for measurement of 17 beta-estradiol, progesterone and cortisol concentrations from 40 patients with preterm labor and intact membranes at 28-32 weeks of gestation: 20 delivered preterm and the remaining 20 patients responded to tocolytic treatment and delivered at term. Maternal plasma and AF concentrations of these hormones were measured with specific commercially available radioimmunoassay kits. Maternal plasma and AF 17 beta-estradiol concentrations were significantly higher in women who delivered preterm than in those who delivered at term, 8.0 ng/ml vs 3.5 ng/ml and 0.85 ng/ml vs. 0.6 ng/ml, respectively. No significant differences were found between groups in maternal plasma and AF progesterone concentrations. Maternal plasma cortisol concentrations were higher in the preterm delivery group than in the term group (235 ng/ml vs. 55 ng/ml, respectively). No significant differences were found in AF cortisol concentrations between groups. C1 BEN GURION UNIV NEGEV,FAC HLTH SCI,SOROKA MED CTR KUPAT HOLIM,DEPT OBSTET & GYNECOL,BEER SHEVA,ISRAEL. BEN GURION UNIV NEGEV,FAC HLTH SCI,SOROKA MED CTR KUPAT HOLIM,CLIN BIOCHEM UNIT,BEER SHEVA,ISRAEL. NICHHD,PERINATOL RES BRANCH,BETHESDA,MD 20892. OI Ghezzi, Fabio/0000-0003-3949-5410 NR 27 TC 13 Z9 14 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0932-0067 J9 ARCH GYNECOL OBSTET JI Arch. Gynecol. Obstet. PD MAR PY 1996 VL 258 IS 2 BP 89 EP 96 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA UB163 UT WOS:A1996UB16300006 PM 8779616 ER PT J AU Sperduto, RD Hiller, R Podgor, MJ Freidlin, V Milton, RC Wolf, PA Myers, RH DAgostino, RB Roseman, MJ Stockman, ME Wilson, PW AF Sperduto, RD Hiller, R Podgor, MJ Freidlin, V Milton, RC Wolf, PA Myers, RH DAgostino, RB Roseman, MJ Stockman, ME Wilson, PW TI Familial aggregation and prevalence of myopia in the framingham offspring eye study SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID EDUCATION; HEREDITY; CHILDREN AB Objectives: To examine familial relationships for myopia among siblings and the distribution of myopia in an adult population aged 23 to 78 years. Methods and Participants: Eye examinations were conducted in a cross-sectional study on the offspring of the Framingham Eye Study cohort. Between 1989 and 1991, 1585 persons, the offspring of 1319 parents, underwent refraction and were tested for best corrected visual acuity. A person was considered myopic if at least one eye had a spherical equivalent refractive error of at least -1.00 diopter. Results: For both sexes, prevalence of myopia decreased with increasing age, from about 60% for ages 23 to 34 years to about 20% for ages 65 years and older. Among men, both age and years of education were related to myopia. Among women, age was related to myopia, but years of education were not. Age-, sex-, and education-adjusted analyses, using the second-order generalized estimating equations approach, showed a strong association of myopia between siblings. The association between siblings decreased with increasing between-siblings age difference: the estimated odds ratio was about 5 for an age difference of 2 years and half that for an age difference of 10 years. Conclusions: The relative importance of genetic and environmental factors in explaining familial relationships for myopia remains unclear. Nevertheless, the large increase in myopia prevalence for more recent birth cohorts and the decrease in the strength of the between siblings association for myopia with increasing between siblings age difference suggest an important role for environmental factors in the cause of myopia. RP Sperduto, RD (reprint author), NEI, DIV BIOMETRY & EPIDEMIOL, BLDG 31, ROOM 6A52, 31 CTR DR MSC 2510, BETHESDA, MD 20892 USA. NR 53 TC 69 Z9 69 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0003-9950 EI 1538-3601 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD MAR PY 1996 VL 114 IS 3 BP 326 EP 332 PG 7 WC Ophthalmology SC Ophthalmology GA TZ301 UT WOS:A1996TZ30100014 ER PT J AU Hagiwara, E Gourley, MF Lee, S Klinman, DM AF Hagiwara, E Gourley, MF Lee, S Klinman, DM TI Disease severity in patients with systemic lupus erythematosus correlates with an increased ratio of interleukin-10:Interferon-gamma-secreting cells in the peripheral blood SO ARTHRITIS AND RHEUMATISM LA English DT Article ID GROWTH-FACTOR; B-CELLS; IL-6; PATHOGENESIS; EXPRESSION; RESPONSES; MICE; SLE; TH1 AB Objective. To compare the phenotype and frequency of cells that actively secrete type 1 and type 2 cytokines in systemic lupus erythematosus (SLE) patients (n = 46), versus normal controls (n = 60). Methods. ELISPOT analysis of freshly isolated peripheral blood mononuclear cells (PBMC). Results. T cells were the major source of interleukin-2 (IL-2), IL-4, and interferon-gamma (IFN gamma), whereas monocytes were the primary source of IL-6 and IL-10 in the PB of lupus patients. Significantly fewer PBMC spontaneously secreted IFN gamma and IL-2 (P less than or equal to 0.03), while significantly more PBMC produced IL-6 and IL-10 (P < 0.001), in lupus patients versus controls. Disease severity in lupus patients correlated with an elevated ratio of IL-10:IFN gamma-secreting cells (P < 0.001). Conclusion. SLE is characterized by an imbalance in the ratio of type 1:type 2 cytokine-secreting PBMC. C1 US FDA,CTR BIOL EVALUAT & RES,DIV VIRAL PROD,BETHESDA,MD 20892. NIAMSD,NIH,BETHESDA,MD 20892. NR 36 TC 245 Z9 262 U1 0 U2 5 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD MAR PY 1996 VL 39 IS 3 BP 379 EP 385 DI 10.1002/art.1780390305 PG 7 WC Rheumatology SC Rheumatology GA TZ599 UT WOS:A1996TZ59900004 PM 8607886 ER PT J AU Alarcon, GS Willkens, RF Ward, JR Clegg, DO Morgan, JG Ma, KN Singer, JZ Steen, VD Paulus, HE Luggen, ME Polisson, RP Ziminski, CM Yarboro, C Williams, HJ AF Alarcon, GS Willkens, RF Ward, JR Clegg, DO Morgan, JG Ma, KN Singer, JZ Steen, VD Paulus, HE Luggen, ME Polisson, RP Ziminski, CM Yarboro, C Williams, HJ TI Early undifferentiated connective tissue disease SO ARTHRITIS AND RHEUMATISM LA English DT Article ID RHEUMATOID-ARTHRITIS; FOLLOW-UP; REVISED CRITERIA; ONSET; SEVERITY; HLA-DR4; DERMATOMYOSITIS; CLASSIFICATION; SUSCEPTIBILITY; POLYMYOSITIS AB Objective. To examine the musculoskeletal manifestations in a large cohort of patients (n = 410) diagnosed with either a well-established connective tissue disease (CTD) (n = 197) or an early undifferentiated CTD (n = 213) with a symptom duration of <1 year. This study was aimed at determining the predictive value of demographic, clinical, and laboratory features on outcome in patients with unexplained polyarthritis (UPA) (from the early undifferentiated CTD cohort; n 67) or rheumatoid arthritis (RA) (from the well-established CTD cohort; n = 57), over a 5-year followup period. Methods. Patients from both cohorts were assessed at years 1, 3, and 5. At the study visits, clinical data were collected in a standardized manner, and sera were obtained and stored. A priori criteria were established for patient ascertainment and diagnosis over the duration of the study, Standard statistics were used for comparisons of baseline characteristics in patients diagnosed as having systemic lupus erythematosus, RA, undifferentiated CTD, and UPA at entry into the cohorts. Baseline features in patients with UPA were examined according to the different subsequent outcomes (RA, CTD, or undifferentiated CTD, remission [nonpersistent], or persistent or active UPA). Baseline features in patients with RA whose disease remained active versus those in whom remission was attained were also examined. Two multivariable analyses, classification trees and polychotomous logistic regression, were performed to predict disease outcomes over time. Results. The overall rate of ascertainment for the 410 patients ranged from 90% at year 1 to 71% at year 5. Patients with established CTDs showed a tendency for more stable diagnoses than those with early undifferentiated CTDs (90-100% versus 45-70%). Consistent baseline predictors of persistent active disease among patients with RA, in both univariate and multivariable analyses, were higher joint counts for pain and tenderness and higher erythrocyte sedimentation rate (ESR). In similar to 20% of patients who were classified as having RA when they originally entered the cohort, the disease was in remission at 5 years. Twenty percent of the patients originally classified as having UPA developed RA over the duration of the study. These patients tended to be older and to have swelling of small joints at baseline. However, a consistent pattern of predictive variables could not be identified in the multivariable analyses, other than at year 1 (higher small joint counts for swelling and higher ESR). Conclusion. Baseline features (joint counts and ESR) among RA patients were variously predictive of persistently active disease at years 1-5. Consistent baseline predictors of outcome among the patients with UPA only emerged at year 1. Remission occurred in similar to 20% of RA patients, whereas a similar percentage of patients with UPA developed RA. These findings have implications with regard to treatment decisions in patients with early RA and/or UPA. C1 UNIV UTAH,SALT LAKE CITY,UT. SUNY HLTH SCI CTR,BROOKLYN,NY 11203. UNIV PITTSBURGH,PITTSBURGH,PA. UNIV CALIF LOS ANGELES,LOS ANGELES,CA. UNIV CINCINNATI,CINCINNATI,OH. DUKE UNIV,DURHAM,NC. JOHNS HOPKINS UNIV,BALTIMORE,MD. NIH,BETHESDA,MD 20892. RP Alarcon, GS (reprint author), UNIV ALABAMA,UAB STN-615 MEB,BIRMINGHAM,AL 35294, USA. FU NIADDK NIH HHS [N01-AM6-2218] NR 55 TC 40 Z9 44 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD MAR PY 1996 VL 39 IS 3 BP 403 EP 414 DI 10.1002/art.1780390308 PG 12 WC Rheumatology SC Rheumatology GA TZ599 UT WOS:A1996TZ59900007 PM 8607889 ER PT J AU Dalakas, MC Cupler, EJ AF Dalakas, MC Cupler, EJ TI Neuropathies in HIV infection SO BAILLIERES CLINICAL NEUROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS-INFECTION; IMMUNE-DEFICIENCY SYNDROME; GUILLAIN-BARRE-SYNDROME; AIDS-RELATED COMPLEX; PERIPHERAL NEUROPATHY; 2',3'-DIDEOXYCYTIDINE DDC; SENSORY NEUROPATHY; ATAXIC NEUROPATHY; NERVE BIOPSIES; GRACILE TRACT C1 NIDS, NIH, BETHESDA, MD 20892 USA. RP Dalakas, MC (reprint author), NINCDS, NIH,BLDG 10,ROOM 4N248,10 CTR DR, MSC 1382, BETHESDA, MD 20892 USA. NR 63 TC 29 Z9 29 U1 0 U2 0 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0961-0421 J9 BAILLIERE CLIN NEUR JI Baillieres Clin. Neurol. PD MAR PY 1996 VL 5 IS 1 BP 199 EP 218 PG 20 WC Clinical Neurology SC Neurosciences & Neurology GA UH336 UT WOS:A1996UH33600012 PM 8732208 ER PT J AU Guyton, KZ Xu, QB Holbrook, NJ AF Guyton, KZ Xu, QB Holbrook, NJ TI Induction of the mammalian stress response gene GADD153 by oxidative stress: Role of AP-1 element SO BIOCHEMICAL JOURNAL LA English DT Article ID GROWTH ARREST; DNA DAMAGE; BINDING; GLUTATHIONE; ACTIVATION; CELLS; EXPRESSION; MESSENGER; ARSENITE; ENZYMES AB GADD153 is a CCAAT/enhancer-binding-protein-related gene that may function to control cellular growth in response to stress signals. In this study, a variety of oxidant treatments were shown to stimulate endogenous GADD153 mRNA expression and to transcriptionally activate a GADD153 promoter-reporter gene construct in transfected HeLa cells. Both commonalities and distinctions in the induction of GADD153 by H2O2 and the thiol-reactive compound arsenite were demonstrated. GADD153 mRNA induction by both H2O2 and arsenite was potentiated by GSH depletion, and completely inhibited by N-acetyl-cysteine. o-Phenanthroline and mannitol blocked GADD153 induction by H2O2, indicating that iron-generated hydroxyl radical mediates this induction. Concordantly, GSH peroxidase overexpression in WI38 cells attenuated GADD153 mRNA induction by H2O2. However, GADD153 induction by arsenite was only modestly reduced in the same cells, suggesting a lesser contribution of peroxides to gene activation by arsenite. We also demonstrated that oxidative stress participates in the induction of GADD153 by UVC (254 nm) irradiation. Finally, both promoter-deletion analysis and point mutation of the AP-1 site in an otherwise intact promoter support a significant role for AP-1 in transcriptional activation of GADD153 by UVC or oxidant treatment. Indeed, exposure of cells to oxidants or UVC stimulated binding of Fos and Jun to the GADD153 AP-1 element. Together, these results demonstrate that both free-radical generation and thiol modification can transcriptionally activate GADD153, and that AP-1 is critical to oxidative regulation of this gene. This study further supports a role for the GADD153 gene product in the cellular response to oxidant injury. C1 NIA,GERONTOL RES CTR,SECT GENE EXPRESS & AGING,BALTIMORE,MD 21224. NR 38 TC 166 Z9 169 U1 0 U2 1 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD MAR 1 PY 1996 VL 314 BP 547 EP 554 PN 2 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UA368 UT WOS:A1996UA36800027 PM 8670069 ER PT J AU Innamorati, G Lolait, SJ Birnbaumer, M AF Innamorati, G Lolait, SJ Birnbaumer, M TI Sequence identity between the rat and human vasopressin V1a receptors SO BIOCHEMICAL JOURNAL LA English DT Letter ID MOLECULAR-CLONING; HORMONE; EXPRESSION C1 UNIV CALIF LOS ANGELES,SCH MED,DEPT ANESTHESIOL,LOS ANGELES,CA 90095. UNIV CALIF LOS ANGELES,SCH MED,INST MOLEC BIOL,LOS ANGELES,CA 90095. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. NR 12 TC 7 Z9 8 U1 0 U2 1 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD MAR 1 PY 1996 VL 314 BP 710 EP 711 PN 2 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UA368 UT WOS:A1996UA36800049 PM 8670090 ER PT J AU Mazuruk, K Schoen, TJ Chader, GJ Iwata, T Rodriguez, IR AF Mazuruk, K Schoen, TJ Chader, GJ Iwata, T Rodriguez, IR TI Structural organization and chromosomal localization of the human ribosomal protein L9 gene SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION LA English DT Article DE rpL9; ribosomal protein; gene structure ID PROCESSED PSEUDOGENE; CAP SITE; EXPRESSION; PROMOTER; TRANSCRIPTION; INTRON; RAT; IDENTIFICATION; SEQUENCE; LOCATION AB The intron-containing gene for the human ribosomal protein L9 has been cloned, sequenced and localized. The gene is approximately 5.5 kb in length and contains 8 exons. Splice sites follow the AG/GT consensus rule. The message for human rpL9 is 712 nt in length and is detected in all tissues examined. In the adult, expression is highest in retina and liver while brain shows highest expression among the fetal tissues tested. The transcription start site contains an oligopyrimidine tract, TTCTTTCTT, similar to those found in other ribosomal protein genes. As in other previously characterized ribosomal protein genes, a TATA box is absent from the 5' flanking region but a number of elements recognized by common transcription factors are present including Spl sites, CACCC boxes, inverted CCAAT boxes, and GATA elements. Another possible element of interest in the rpL9 5' flanking region is RFX1 also found in the well characterized rat rpL30 promoter. The gene was mapped by fluorescent in situ hybridization to band 13p of chromosome 4. At least 8 possible pseudogenes are present in the human genome, one of which is on Xp. As assessed by Southern 'Zoo-blot' analysis and direct cDNA sequence comparison, the human ribosomal protein L9 gene, like other ribosomal protein genes, is highly conserved among mammals. C1 NEI,NIH,RETINAL CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. NEI,NIH,LAB MECHANISMS OCULAR DIS,BETHESDA,MD 20892. NR 50 TC 15 Z9 16 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4781 J9 BBA-GENE STRUCT EXPR JI Biochim. Biophys. Acta-Gene Struct. Expression PD MAR 1 PY 1996 VL 1305 IS 3 BP 151 EP 162 DI 10.1016/0167-4781(95)00201-4 PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA TY814 UT WOS:A1996TY81400011 PM 8597601 ER PT J AU Collier, AJ Elsegood, KA Yeudall, WA Paterson, IC Prime, SS Sandy, JR AF Collier, AJ Elsegood, KA Yeudall, WA Paterson, IC Prime, SS Sandy, JR TI TGF-beta isoforms fail to modulate inositol phosphates and cAMP in normal and tumour-derived human oral keratinocytes SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE LA English DT Article DE inositol phosphate; cyclic AMP; keratinocyte; transforming growth factor-beta; isoform ID GROWTH-FACTOR-BETA; TRANSFORMING GROWTH-FACTOR-BETA-1; AKR-2B CELLS; II RECEPTOR; FIBROBLASTS; DIFFERENTIATION; EXPRESSION; INHIBITION; METABOLISM; CARCINOMA AB This study examined inositol phosphate and cAMP regulation by TGF-beta 1, -beta 2 and -beta 3 in normal and tumour-derived human oral keratinocytes. Previous findings indicated that the cell lines expressed TGF-beta cell surface receptors and had a range of response to exogenous TGF-beta 1, -beta 2 and -beta 3 from being refractory to the ligand to marked inhibition. Basal levels of inositol phosphates broadly reflected the differentiation status of the cells as demonstrated by involucrin expression, but did not correlate with responsiveness to TGF-beta 1, as measured previously by thymidine incorporation. Treatment of cells with bradykinin or serum caused up-regulation of inositol phosphate levels; by contrast, TGF-beta 1, -beta 2 and -beta 3 failed to modulate inositol phosphates. In two tumour-derived cell lines, the TGF-beta isoforms had no effect on cAMP levels, despite a significant increase in cAMP using a potent agonist of adenylate cyclase (forskolin). Furthermore, the cAMP analogue, dibutyryl cAMP, failed to mimic the inhibitory or refractory responses of TGF-beta in these cell lines. The results demonstrate that in normal and tumour-derived human oral keratinocytes, TGF-beta signal transduction is not mediated by inositol phosphates or cAMP. C1 UNIV BRISTOL,DEPT ORAL & DENT SCI,BRISTOL,AVON,ENGLAND. UNIV BRISTOL,DEPT MED,BRISTOL,AVON,ENGLAND. NIH,CELLULAR DEV & ONCOL LAB,BETHESDA,MD 20892. RI Paterson, Ian/G-8688-2011 NR 28 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4439 J9 BBA-MOL BASIS DIS JI Biochim. Biophys. Acta-Mol. Basis Dis. PD MAR 1 PY 1996 VL 1315 IS 2 BP 117 EP 122 DI 10.1016/0925-4439(95)00109-3 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA TY945 UT WOS:A1996TY94500007 PM 8608168 ER PT J AU Gowda, DC Ambekar, SY Gupta, P Lecchi, P Pannell, LK Davidson, EA AF Gowda, DC Ambekar, SY Gupta, P Lecchi, P Pannell, LK Davidson, EA TI Benzoylecgonine hydrazides: Synthesis, coupling to horseradish peroxidase, and characterization of the conjugates SO BIOCONJUGATE CHEMISTRY LA English DT Article ID OLIGOSACCHARIDE MOIETIES; MONOCLONAL-ANTIBODIES; IMMOBILIZATION; CARBOHYDRATE AB Benzoylecgonine-horseradish peroxidase conjugate (BE-HRP) can be used as a diagnostic reagent for the detection of cocaine in illicit drug samples and in biological fluids. This paper describes the preparation and characterization of BE-HRP. Two hydrazide derivatives of benzoylecgonine, N-2-(tert-butyloxycarbonyl)benzoylecgonine hydrazide and mono(N-2'-benzoylecgoninoyl)adipic dihydrazide, were synthesized by carbodiimide-activated coupling of benzoylecgonine to N-2-(tert-butyloxycarbonyl) hydrazide and adipic dihydrazide, respectively. Removal of the tert-butyloxycarbonyl protecting group in N-2-(tert-butyloxycarbonyl)benzoylecgonine hydrazide with anhydrous HCl yielded benzoylecgonine hydrazide hydrochloride. NMR and high-resolution mass spectral analyses demonstrated that the benzoyl group of benzoylecgonine remained intact under the conditions of both carbodiimide coupling and anhydrous HCl treatment. By aldehyde-hydrazide condensation, the hydrazides were covalently conjugated to the carbohydrate residues of horseradish peroxidase (HRP). Dot blot analysis of the conjugates employing antibodies specific to benzoylecgonine demonstrated the presence of bound benzoylecgonine in HRP. The stoichiometry of benzoylecgonine residues to HRP was determined by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). Mono(N-2'-benzoylecgoninoyl)adipic dihydrazide gave a 2.5-3-fold higher coupling compared with benzoylecgonine hydrazide. Conjugates were also prepared by the coupling of the carbodiimide-activated benzoylecgonine to HRP that was derivatized with adipic dihydrazide. C1 NIDDKD,NIH,BETHESDA,MD 20892. RP Gowda, DC (reprint author), GEORGETOWN UNIV,MED CTR,DEPT BIOCHEM & MOLEC BIOL,3900 RESERVOIR RD NW,WASHINGTON,DC 20007, USA. NR 20 TC 5 Z9 5 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD MAR-APR PY 1996 VL 7 IS 2 BP 265 EP 270 DI 10.1021/bc960009j PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA UC417 UT WOS:A1996UC41700012 PM 8983349 ER PT J AU Kawczynski, W Czochralska, B Lindqvist, L Torrence, PF AF Kawczynski, W Czochralska, B Lindqvist, L Torrence, PF TI Reaction intermediates of a dihydropyridine derivative of 2',3'-dideoxycytidine related to AIDS dementia studied by laser flash photolysis SO BIOELECTROCHEMISTRY AND BIOENERGETICS LA English DT Article DE cytidine derivative; flash photolysis; AIDS dementia; radical intermediate ID HUMAN IMMUNODEFICIENCY VIRUS; CHEMICAL DELIVERY SYSTEM; AQUEOUS-SOLUTION; ZIDOVUDINE; EXCITATION; INVITRO; METABOLISM; MECHANISM; NADH; NM AB A derivative of 2',3'-dideoxycytidine (ddC), carrying one 1,4-dihydro-1-methyl-3-pyridinyl-carbonyl group at the cytidine exocyclic amino group and one at the ribose 5-hydroxyl group, was exposed in water-ethanol solution to high-power pulsed laser emission at a wavelength of 354.7 nm. Measurement of the transient absorption spectra. with nanosecond time resolution shows that the photoejection of an electron occurs due to stepwise two-photon absorption by the dihydropyridine via its fluorescent state. The spectrum of the cation radical formed in this reaction was determined, together with that of the neutral radical appearing following deprotonation of the cation. The electron is apparently abstracted only from the pyridine group attached to the ribose, since a comparative study on ddC carrying a dihydropyridine only at the exocyclic amino group showed no evidence for photoionization in the same experimental conditions. C1 UNIV WARSAW,INST EXPTL PHYS,DEPT BIOPHYS,PL-02089 WARSAW,POLAND. UNIV PARIS 11,CNRS,PHOTOPHYS MOLEC LAB,F-91405 ORSAY,FRANCE. NIDDKD,SECT BIOMED CHEM,MED CHEM LAB,NIH,BETHESDA,MD 20892. NR 18 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE SA LAUSANNE PI LAUSANNE 1 PA PO BOX 564, 1001 LAUSANNE 1, SWITZERLAND SN 0302-4598 J9 BIOELECTROCH BIOENER JI Bioelectrochem. Bioenerg. PD MAR PY 1996 VL 39 IS 2 BP 263 EP 266 DI 10.1016/0302-4598(95)01889-1 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UG704 UT WOS:A1996UG70400017 ER PT J AU Chu, E Allegra, CJ AF Chu, E Allegra, CJ TI The vole of thymidylate synthase as an RNA binding protein SO BIOESSAYS LA English DT Review ID 3' UNTRANSLATED REGION; MESSENGER-RNA; ESCHERICHIA-COLI; NUCLEOTIDE-SEQUENCE; MOUSE FIBROBLASTS; R17-COAT PROTEIN; COAT PROTEIN; POLY(A) TAIL; CELL-LINE; TRANSLATION AB Thymidylate synthase plays a central role in the biosynthesis of thymidylate, an essential precursor for DNA biosynthesis. in addition to its role in catalysis and cellular metabolism, it is now appreciated that thymidylate synthase functions as an RNA binding protein. Specifically, thymidylate synthase binds with high affinity to its own mRNA, resulting in translational repression. An extensive series of experiments has been performed to elucidate the molecular elements underlying the interaction between thymidylate synthase and its own mRNA. In addition to characterization of the underlying cis- and trans-acting elements, recent studies have shown that thymidylate synthase has the capacity to bind specifically to other cellular RNA species. While the biological significance of these other RNA/thymidylate synthase interactions remains to be defined, this work suggests a potential role for TS in coordinately regulating several critical aspects of cellular metabolism. RP Chu, E (reprint author), USN,NCI,MED ONCOL BRANCH,BETHESDA,MD 20889, USA. NR 65 TC 85 Z9 86 U1 1 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0265-9247 J9 BIOESSAYS JI Bioessays PD MAR PY 1996 VL 18 IS 3 BP 191 EP 198 DI 10.1002/bies.950180306 PG 8 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA UA994 UT WOS:A1996UA99400005 PM 8867733 ER PT J AU Chanturiya, AN AF Chanturiya, AN TI A comparative study of planar lipid membranes formed by Montal-Mueller and Mueller-Rudin techniques SO BIOLOGICHESKIE MEMBRANY LA English DT Article ID BILAYER-MEMBRANES; FUSION; CONDUCTANCE; MONOLAYERS; THICKNESS AB Planar phospholipid bilayer membranes formed by two techniques, Montal-Mueller and Mueller-Rudin, were compared in order to determine the differences between these two types of BLM. The specific capacitance and the morphology of membranes formed from different lipid/solvent combinations were examined using a ramp of voltage and high resolution interference contrast and fluorescence microscopy. It was found that the specific capacitance depends more upon the choice of lipids and hydrocarbons used for membrane formation than upon the method of formation. For diphytanoyl-phosphocholine membranes, capacitance increases with the increase in molecular weight of the hydrocarbon used either for hole pretreatment or for making a membrane forming solution. For phosphatidylethanolamine membranes. No differences were found in the morphology of membranes formed using these techniques. Both led to membranes having tort, and the membranes often contained lenses and/or linear structures. Examination of these structures in membranes formed with the addition of fluorescent lipid indicates that they contain substantial amount of lipid. C1 AV PALLADIN BIOCHEM INST,DEPT NEUROCHEM,KIEV,UKRAINE. RP Chanturiya, AN (reprint author), NICHHD,THEORET & PHYS BIOL LAB,NIH,BLDG 10,ROOM 6C101,BETHESDA,MD 20892, USA. NR 14 TC 3 Z9 3 U1 0 U2 3 PU MEZHDUNARODNAYA KNIGA PI MOSCOW PA 39 DIMITROVA UL., 113095 MOSCOW, RUSSIA SN 0233-4755 J9 BIOL MEMBRANY JI Biol. Membr. PD MAR-APR PY 1996 VL 13 IS 2 BP 216 EP 221 PG 6 WC Cell Biology SC Cell Biology GA UF300 UT WOS:A1996UF30000011 ER PT J AU Heindel, JJ Sneeden, J Powell, CJ Davis, B Culler, MD AF Heindel, JJ Sneeden, J Powell, CJ Davis, B Culler, MD TI A novel hypothalamic peptide, pituitary adenylate cyclase-activating peptide, regulates the function of rat granulosa cells in vitro SO BIOLOGY OF REPRODUCTION LA English DT Article ID VASOACTIVE-INTESTINAL-PEPTIDE; BINDING-SITES; MOLECULAR-IDENTIFICATION; POLYPEPTIDE PACAP; VIP; RECEPTOR; STEROIDOGENESIS; RESPONSIVENESS; ANTAGONIST; FOLLICLES AB Pituitary adenylate cyclase-activating peptide (PACAP) is a novel peptide that was isolated from ovine hypothalamic tissue on the basis of its ability to stimulate cAMP accumulation in cultured rat pituitary cells. Recently we demonstrated that PACAP can stimulate cAMP accumulation and secretory function in cultured rat Sertoli cells. Since ovarian granulosa cells share many properties with Sertoli cells, we have examined the effect of PACAP (consisting of 38 or 27 amino acid residues) on cultured granulosa cell function. Granulosa cells were obtained from the ovaries of 25-day-old rats implanted with a silastic capsule containing diethylstilbestrol 5 days prior to culture. PACAP 38 (0.1 mu M-0.01 pM), both alone and in the presence of the phosphodiesterase inhibitor, methylisobutylxanthine, stimulated cAMP accumulation 4-8-fold with an ED(50) of similar to 100 pM. Maximal PACAP 38 or PACAP 27 stimulation of granulosa cell cAMP was significantly greater than that produced by a maximally effective concentration of FSH. Because PACAP 38 and 27 have 68% sequence homology with vasoactive intestinal peptide (VIP), and since VIP stimulates granulosa cell cAMP accumulation and estradiol and progesterone secretion, we examined the possibility that PACAP could be acting via the VIP receptor. VIP stimulated cAMP only at concentrations of 10 nM or greater, whereas the PACAP stimulation was evident at 10 pM. Moreover, only one of th ree potent VIP antagonists inhibited VIP stimulation of cAMP accumulation, and only at 1 mu M or greater. This VIP antagonist did not inhibit PACAP 38 action at 2000-fold excess concentration. Interestingly PACAP 38 was more effective than PACAP 27 with regard to steroid secretion and the ability to induce LH responsiveness. PACAP and VIP stimulation of granulosa cell cAMP accumulation or estradiol or progesterone secretion was not additive. Thus, these data support the hypothesis that granulosa cells have specific PACAP 38 receptors and that VIP acts via these receptors. In addition, PACAPs 38 and 27 are more potent stimulators of cAMP accumulation in luteinized granulosa cells than LH. These results both pre- and postovulation, along with previous data indicating that the PACAPs are found in the ovaries, suggest a role for PACAP in the regulation of ovarian function. C1 NIEHS, MOLEC & INTEGRAT NEUROSCI LAB, RES TRIANGLE PK, NC 27709 USA. N CAROLINA STATE UNIV, DEPT MICROBIOL PARASITOL & PATHOL, RALEIGH, NC 27603 USA. RP NIEHS, ENVIRONM TOXICOL PROGRAM, REPROD TOXICOL GRP, POB 12233, MD 3-02, RES TRIANGLE PK, NC 27709 USA. FU NIEHS NIH HHS [ES00233] NR 40 TC 43 Z9 44 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA SN 0006-3363 EI 1529-7268 J9 BIOL REPROD JI Biol. Reprod. PD MAR PY 1996 VL 54 IS 3 BP 523 EP 530 DI 10.1095/biolreprod54.3.523 PG 8 WC Reproductive Biology SC Reproductive Biology GA TV989 UT WOS:A1996TV98900001 PM 8835372 ER PT J AU Baker, SG AF Baker, SG TI The analysis of categorical case-control data subject to nonignorable nonresponse SO BIOMETRICS LA English DT Article DE composite linear models; missing data; MP transformation; partially observed covariates ID VARIABLES; MODELS AB In analyzing partially observed categorical case-control data, Williamson and Haber (1994, Biometrics 50, 194-203) assumed ignorable nonresponse. We reanalyzed the data allowing for nonignorable nonresponse while explicitly incorporating case-control sampling. RP Baker, SG (reprint author), NCI,DIV CANC PREVENT & CONTROL,BIOMETRY BRANCH,EPN 344,6130 EXECUT BLVD,MSC 7354,BETHESDA,MD 20892, USA. NR 19 TC 10 Z9 10 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 MAR PY 1996 VL 52 IS 1 BP 362 EP 369 DI 10.2307/2533174 PG 8 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA UF292 UT WOS:A1996UF29200036 PM 8934603 ER PT J AU Schuck, P AF Schuck, P TI Kinetics of ligand binding to receptor immobilized in a polymer matrix, as detected with an evanescent wave biosensor .1. A computer simulation of the influence of mass transport SO BIOPHYSICAL JOURNAL LA English DT Article ID SURFACE-PLASMON RESONANCE; BIOSPECIFIC INTERACTION ANALYSIS; TYROSINE-PHOSPHORYLATED PEPTIDES; NONLINEAR LEAST-SQUARES; MONOCLONAL-ANTIBODIES; SH2 DOMAINS; DIFFUSION; PROTEIN; SYSTEM; SEDIMENTATION AB The influence of mass transport on ligand binding to receptor immobilized in a polymer matrix, as detected with an evanescent wave biosensor, was investigated. A one-dimensional computer model for the mass transport of ligand between the bulk solution and the polymer gel and within the gel was employed, and the influence of the diffusion coefficient, the partition coefficient, the thickness of the matrix, and the distribution of immobilized receptor were studied for a variety of conditions. Under conditions that may apply to many published experimental studies, diffusion within the matrix was found to decrease the overall ligand transport significantly. For relatively slow reactions, small spatial gradients of free and bound ligand in the gel are found, whereas for relatively rapid reactions strong inhomogeneities of ligand within the gel occur before establishment of equilibrium. Several types of deviations from ideal pseudo-first-order binding progress curves are described that resemble those of published experimental data. Extremely transport limited reactions can in some cases be fitted with apparently ideal binding progress curves, although with apparent reaction rates that are much lower than the true reaction rates. Nevertheless, the ratio of the apparent rate constants can be semiquantitatively consistent with the true equilibrium constant. Apparently ''cooperative'' binding can result from high chemical on rates at high receptor saturation. Dissociation in the presence of transport limitation was found to be well described empirically by a single or a double exponential, with both apparent rate constants considerably lower than the intrinsic chemical rate constant, Transport limitations in the gel can introduce many generally unknown factors into the binding progress curve. The simulations suggest that unexpected deviations from ideal binding progress curves may be due to highly transport influenced binding kinetics. The use of a thinner polymer matrix could significantly increase the range of detectable rate constants. RP Schuck, P (reprint author), NIDDK,NIH,BIOCHEM PHARMACOL LAB,SECT PHYS BIOCHEM,BLDG 8,RM 220,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. OI Schuck, Peter/0000-0002-8859-6966 NR 74 TC 180 Z9 184 U1 0 U2 14 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD MAR PY 1996 VL 70 IS 3 BP 1230 EP 1249 PG 20 WC Biophysics SC Biophysics GA UB817 UT WOS:A1996UB81700013 PM 8785280 ER PT J AU Steinbach, PJ AF Steinbach, PJ TI Two-dimensional distributions of activation enthalpy and entropy from kinetics by the maximum entropy method SO BIOPHYSICAL JOURNAL LA English DT Article ID BARRIER HEIGHT DISTRIBUTIONS; CARBON-MONOXIDE BINDING; HEME-PROTEINS; LIGAND-BINDING; DYNAMICS; MYOGLOBIN; MODEL; RELAXATION; ALGORITHM; DECAY AB The maximum entropy method (MEM) is used to numerically invert the kinetics of ligand rebinding at low temperatures to obtain the underlying two-dimensional distribution of activation enthalpies and entropies, g(H,S). A global analysis of the rebinding of carbon monoxide (CO) to myoglobin (Mb), monitored in the Soret band at temperatures from 60 to 150 K, is performed using a Newton-Raphson optimization algorithm. The MEM approach describes the data much better than traditional least-squares analyses, reducing chi(2) by an order of magnitude, The MEM resolves two barrier distributions suggestive of rebinding to different bound conformations of MbCO, the so-called A, and A, substates, whose activation barriers have been independently estimated from kinetics monitored in the infrared. The distribution corresponding to A, possesses higher activation entropies, also consistent with infrared measurements. Within an A substate, correlations of S and H are recovered qualitatively from simulated data but can be difficult to obtain from experimental data. When the rebinding measured at 60 K is excluded from the inversion, two peaks are no longer clearly resolved, Thus, data of very high quality are required to unambiguously determine the kinetic resolvability of subpopulations and the shape of the barrier distribution for a single A substate. RP Steinbach, PJ (reprint author), NIH, DIV COMP RES & TECHNOL,STRUCT BIOL LAB,BLDG 12A, RM 2041,12 SOUTH DR, MSC 5626, BETHESDA, MD 20892 USA. NR 31 TC 24 Z9 24 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD MAR PY 1996 VL 70 IS 3 BP 1521 EP 1528 PG 8 WC Biophysics SC Biophysics GA UB817 UT WOS:A1996UB81700042 PM 8785309 ER PT J AU Vodovotz, Y AF Vodovotz, Y TI Modified microassay for serum nitrite and nitrate SO BIOTECHNIQUES LA English DT Article ID OXIDE RELEASE; ASSAY RP Vodovotz, Y (reprint author), NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892, USA. NR 13 TC 58 Z9 59 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD MAR PY 1996 VL 20 IS 3 BP 390 EP & PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TY801 UT WOS:A1996TY80100014 PM 8679195 ER PT J AU Medin, JA Migita, M Pawliuk, R Jacobson, S Amiri, M KluepfelStahl, S Brady, RO Humphries, RK Karlsson, S AF Medin, JA Migita, M Pawliuk, R Jacobson, S Amiri, M KluepfelStahl, S Brady, RO Humphries, RK Karlsson, S TI A bicistronic therapeutic retroviral vector enables sorting of transduced CD34(+) cells and corrects the enzyme deficiency in cells from gaucher patients SO BLOOD LA English DT Article ID MEDIATED GENE-TRANSFER; HEMATOPOIETIC STEM-CELLS; HUMAN MDR1; MULTIDRUG RESISTANCE; NUCLEOTIDE-SEQUENCE; PROGENITOR CELLS; MAMMALIAN-CELLS; DRUG-RESISTANCE; GROWTH-FACTORS; EXPRESSION AB Corrective gene transfer for therapeutic intervention in metabolic and hematopoietic disorders has been hampered by the relatively inefficient transduction of human hematopoietic stem cells. To overcome this, a bicistronic recombinant retrovirus has been generated that delivers both a therapeutic glucocerebrosidase (GC) cDNA for the treatment of Gaucher disease, and a small murine cell surface antigen (heat-stable antigen [HSA]) as a selectable marker. An amphotropic retroviral-producing cell clone was created, and filtered supernatant was used to transduce NIH 3T3 cells. Sorting of transduced cells by flow cytometry enabled separation into populations based on cell surface fluorescence intensity derived from the expressed HSA. Significant increases in GC enzyme activity were seen for the transduced and especially the transduced and sorted cells. Similarly, increases in GC specific activity were seen in transduced and sorted skin fibroblasts from a patient with Gaucher disease. To streamline future transfer and sorting protocols for hematopoietic cells, transformed B-cell lines from Gaucher patients were created. Type I B cells were transduced and sorted, and large increases in GC specific activity occurred with concomitant increases in integrated retroviral copy numbers. In addition, toward the goal of using this selectable approach for corrective gene transfer to bone marrow stem cells, CD34(+) cells were isolated from normal BM donors, transduced, and sorted based on cell surface expression of HSA. Proviral DNA was detected in approximately 40% of clonogenic progenitor colonies derived from unsorted, transduced CD34(+) cells, demonstrating the high titer of the vector. However, after sorting, 100% of the colonies had the corrective GC cDNA, demonstrating the efficiency of this selective system for human hematopoietic progenitors. It is expected that strategies based on this approach will allow sorting of transduced cells of many types before implantation of transduced cells to animals or patients. This vector system may also be used to simplify manipulations and studies on retroviral-mediated gene delivery in vitro and for in vivo models. C1 BRITISH COLUMBIA CANC AGCY,TERRY FOX LAB,VANCOUVER,BC V5Z 1L3,CANADA. RP Medin, JA (reprint author), NINCDS,NIH,MMGS,DMND,NEUROIMMUNOL BRANCH,BLDG 10,ROOM 3D04,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. OI Humphries, Richard/0000-0003-0540-7005 NR 47 TC 37 Z9 37 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 MAR 1 PY 1996 VL 87 IS 5 BP 1754 EP 1762 PG 9 WC Hematology SC Hematology GA TY339 UT WOS:A1996TY33900012 PM 8634421 ER PT J AU Lowell, CA Niwa, M Soriano, P Varmus, HE AF Lowell, CA Niwa, M Soriano, P Varmus, HE TI Deficiency of the Hck and Src tyrosine kinases results in extreme levels of extramedullary hematopoiesis SO BLOOD LA English DT Article ID EXPRESS HIGH-LEVELS; SIGNAL-TRANSDUCTION; BONE-MARROW; PROTEIN-KINASES; STROMAL CELLS; MUTANT MICE; C-FOS; OSTEOCLASTS; FAMILY; OSTEOPETROSIS AB Expression of the Src-family kinases-Src, Hck, and Fgr-increases dramatically during myeloid cell development. Src-deficient mice exhibit functional abnormalities in only one myeloid cell type, the osteoclast, resulting in impaired bone remodeling and osteopetrosis, while hck-/- or fgr-/- mice have few and subtle myeloid cell deficiencies. To determine whether these limited phenotypes are due to the coexpression of multiple Src-family kinases with overlapping functions, we have intercrossed src(-/-) mice to hck(-/-) and fgr(-/-) mutants to produce double mutants. Two thirds of hck(-/-)src(-/-) double mutants die at birth; surviving animals develop a severe form of osteopetrosis, resulting in extreme levels of splenic extramedullary hematopoiesis, anemia, and leukopenia. These hematopoietic defects are caused by abnormalities in the bone marrow environment because hck(-/-)src(-/-) mutant stem cells reconstitute a normal hematopoietic system in irradiated wild-type mice. In contrast, fgr(-/-)src(-/-) double mutants have no defects beyond those observed in src(-/-) animals. Cultured normal murine osteoclasts express abundant amounts of Src, Hck, and Fgr and Hck levels are increased in src(-/-) osteoclasts. These observations suggest that Hck and Src serve partially overlapping functions in osteoclasts and that the expression of Hck in src-/- osteoclasts ameliorates their functional defects. (C) 1996 by The American Society of Hematology. C1 FRED HUTCHINSON CANC RES CTR,PROGRAM MOLEC MED,SEATTLE,WA 98104. NIH,OFF DIRECTOR,BETHESDA,MD. RP Lowell, CA (reprint author), UNIV CALIF SAN FRANCISCO,DEPT MICROBIOL & IMMUNOL,SAN FRANCISCO,CA 94143, USA. RI Soriano, Philippe/E-5797-2015 OI Soriano, Philippe/0000-0002-0427-926X NR 45 TC 84 Z9 85 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 MAR 1 PY 1996 VL 87 IS 5 BP 1780 EP 1792 PG 13 WC Hematology SC Hematology GA TY339 UT WOS:A1996TY33900015 PM 8634424 ER PT J AU Benedetti, L Grignani, F Scicchitano, BM Jetten, AM Diverio, D LoCoco, F Avvisati, G GambacortiPasserini, C Adamo, S Levin, AA Pelicci, G Nervi, C AF Benedetti, L Grignani, F Scicchitano, BM Jetten, AM Diverio, D LoCoco, F Avvisati, G GambacortiPasserini, C Adamo, S Levin, AA Pelicci, G Nervi, C TI Retinoid-induced differentiation of acute promyelocytic leukemia involves PRL-RAR alpha-mediate increase of type II transglutaminase SO BLOOD LA English DT Article ID PROGRAMMED CELL-DEATH; ACID RECEPTORS; X-RECEPTOR; TISSUE TRANSGLUTAMINASE; T(15-17) TRANSLOCATION; NUCLEAR RECEPTOR; BETA-SUBUNIT; HL-60 CELLS; BINDING; EXPRESSION AB All-trans retinoic acid (t-RA) administration leads to complete remission in acute promyelocytic leukemia (APL) patients by inducing growth arrest and differentiation of the leukemic clone. In the present study, we show that t-RA treatment dramatically induced type II transglutaminase (type II TGase) expression in cells carrying the t(15;17) translocation and expressing the PML-RAR alpha product such as the APL-derived NB4 cell line and fresh leukemic cells from APL patients. This induction correlated with the t-RA-induced growth arrest, granulocytic differentiation, and upregulation of the leukocyte adherence receptor beta subunit (CD18) gene expression. The increase in type II TGase was not abolished by cycloheximide treatment, suggesting that synthesis of a protein intermediate was not required for the induction. t-RA did not significantly alter the rate of growth arrest and did not stimulate differentiation and type II TGase activity in NB4.306 cells, a t-RA-resistant subclone of the NB4 cell line, or in leukemic cells derived from two patients morphologically defined as APL but lacking the t(15;17). However, in NB4.306 cells, t-RA treatment was able to increase CD18 mRNA expression in a manner similar to NB4 cells. The molecular mechanisms involved in the induction of these genes were investigated. In NB4 cells, using novel receptor-selective ligands such as 9-cis-RA, TTNPB, AM580, and SR11217. we found that RAR- and RAR alpha-selective retinoids were able to induce growth arrest, granulocytic differentiation, and type II TGase, whereas the RXR-selective retinoid SR11217 was inactive. Moreover, an RAR alpha-antagonist completely inhibited the expression of type II TGase and CD18 induced by these selective retinoids in NB4 cells. In NB4.306 cells, an RAR alpha-dependent signaling pathway was found involved in the modulation of CD18 expression. In addition, expression of the PML-RAR alpha gene in myeloid U937 precursor cells resulted in the ability of these cells to induce type II TGase in response to t-RA. On the basis of these results we hypothesize a specific involvement of a signaling pathway involving PML-RAR alpha for the induction of growth arrest, granulocytic differentiation, and type II TGase by retinoids in APL cells. (C) 1996 by The American Society of Hematology. C1 UNIV ROMA LA SAPIENZA,INST HISTOL & GEN EMBRYOL,I-00161 ROME,ITALY. UNIV ROMA LA SAPIENZA,DEPT HUMAN BIOPATHOL,SECT HEMATOL,ROME,ITALY. UNIV PERUGIA,DEPT MED,I-06100 PERUGIA,ITALY. NIEHS,NIH,LPP,CELL BIOL SECT,RES TRIANGLE PK,NC. IST NAZL TUMORI,DIV EXPTL ONCOL D,I-20133 MILAN,ITALY. HOFFMANN LA ROCHE INC,DEPT TOXICOL & PATHOL,NUTLEY,NJ 07110. EUROPEAN INST ONCOL,DEPT EXPTL ONCOL,MILAN,ITALY. RI Adamo, Sergio/E-9058-2012 OI Adamo, Sergio/0000-0002-1409-0452 NR 65 TC 79 Z9 79 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD MAR 1 PY 1996 VL 87 IS 5 BP 1939 EP 1950 PG 12 WC Hematology SC Hematology GA TY339 UT WOS:A1996TY33900033 PM 8634442 ER PT J AU Huh, HY Pearce, SF Yesner, LM Schindler, JL Silverstein, RL AF Huh, HY Pearce, SF Yesner, LM Schindler, JL Silverstein, RL TI Regulated expression of CD36 during monocyte-to-macrophage differentiation: Potential role of CD36 in foam cell formation SO BLOOD LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; PARASITIZED ERYTHROCYTES; MEDIATES CYTOADHERENCE; GLYCOPROTEIN-IV; MELANOMA-CELLS; RECEPTOR; THROMBOSPONDIN; INVITRO; MATURATION; BINDING AB CD36 is an 88-kD integral membrane glycoprotein expressed on monocytes, platelets, and certain microvascular endothelium serving distinct cellular functions both as an adhesive receptor for thrombospondin, collagen, and Plasmodium falciparom-infected erythrocytes, and as a scavenger receptor for oxidized low-density lipoprotein and apoptotic neutrophils. In this study, we examined the expression of CD36 during in vitro differentiation of peripheral blood monocytes into culture-derived macrophages. Steady-state mRNA levels of CD36 showed a transient eightfold increase during monocyte-to-macrophage differentiation, peaking at the early macrophage stage (days 3 or 4 in culture), following a gradual decrease back to baseline levels by the mature macrophage stage (days 7 or 8 in culture). Immunoblotting with monoclonal antibodies to CD36 supported this transient, yet significant (8- to 10-fold) increase in total protein levels of CD36. The increased CD36 protein was observed at the plasma membrane, whereas an intracellular pool of CD36 was also detected from day 2 to day 6 in culture through indirect immunofluorescence. A concomitant twofold increase in the cells' ability to bind I-125-thrombospondin at the early macrophage stage (day 4) verified the functional competency of the plasma membrane localized CD36, and supported the presence of an intracellular pool of CD36. The in vitro differentiated macrophages as well as alveolar macrophages remained responsive to macrophage colony-stimulating factor (M-CSF), a known transcriptional regulator of monocyte CD36. The M-CSF-induced macrophages resulted in enhanced foam cell formation, which was inhibitable with monoclonal antibodies to CD36, Thus, the transient expression of CD36 during monocyte-to-macrophage differentiation, and the ability of M-CSF to maintain macrophage CD36 at elevated levels, may serve as a critical process in dictating the functional activity of CD36 during inflammatory responses and atherogenesis. (C) 1996 by The American Society of Hematology. C1 CORNELL UNIV,COLL MED,DIV HEMATOL ONCOL,DEPT MED,NEW YORK,NY 10021. CORNELL UNIV,COLL MED,CELL BIOL & GENET PROGRAM,NEW YORK,NY 10021. CORNELL UNIV,COLL MED,NIH,SPECIALIZED CTR RES THROMBOSIS,NEW YORK,NY 10021. FU NHLBI NIH HHS [HL42540, HL18828, HL46403] NR 40 TC 197 Z9 201 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 MAR 1 PY 1996 VL 87 IS 5 BP 2020 EP 2028 PG 9 WC Hematology SC Hematology GA TY339 UT WOS:A1996TY33900044 PM 8634453 ER PT J AU Iwamoto, Y Nomizu, M Yamada, Y Ito, Y Tanaka, K Sugioka, Y AF Iwamoto, Y Nomizu, M Yamada, Y Ito, Y Tanaka, K Sugioka, Y TI Inhibition of angiogenesis, tumour growth and experimental metastasis of human fibrosarcoma cells HT1080 by a multimeric form of the laminin sequence Tyr-IIe-Gly-Ser-Arg (YIGSR) SO BRITISH JOURNAL OF CANCER LA English DT Article DE laminin; metastasis; angiogenesis; synthetic peptide ID RECONSTITUTED BASEMENT-MEMBRANE; SYNTHETIC PEPTIDE; A-CHAIN; MULTIDOMAIN PROTEIN; IKVAV SEQUENCE; B1 CHAIN; MIGRATION; IDENTIFICATION; PENTAPEPTIDE; ENHANCEMENT AB A multimeric peptide, Ac-Y16, consisting of 16 YIGSR sequences from laminin was evaluated for its effect on experimental metastasis, angiogenesis and tumour growth of HT1080 human fibrosarcoma cells. Go-injection of 0.5 mg per mouse of Ac-Y16 i.v. with HT1080 cells inhibited lung colonisation by 100%, whereas 0.5 mg per mouse of monomeric Ac-YIGSR-NH2(Ac-Y1) inhibited by 94%. Ac-Y16 did not show any direct cytotoxicity on tumour cells in vivo. The effect of the peptides on angiogenesis and tumour growth respectively were evaluated by counting areas of neovessels and weighing tumours after the s.c. implantation of HT1080 cells with basement membrane extracts and the peptide into nude mice. Go-injection of 0.5 mg per mouse of Ac-Y16 s.c. with HT1080 cells inhibited angiogenesis and tumour growth by 92% (P<0.05) and 76% (P<0.05) respectively, whereas 0.5 mg per mouse of monomeric Ac-YIGSR-NH2(Ac-YI) inhibited angiogenesis and tumour growth by 40% (P<0.05) and 9% (P>0.05) respectively. It can be inferred from these data that anti-tumour effects of Ac-Y16 are likely to result from anti-angiogenesis. Intraperitoneal administration of Ac-Y16 was also effective in inhibiting angiogenesis, tumour growth and lung colonisation of HT1080 cells. It was concluded that the multimeric YIGSR-containing peptide, Ac-Y16, inhibits angiogenesis, tumour growth and experimental metastasis more than the monomeric form and that it is active when administered i.p., i.v, and s.c. C1 NIDR,NIH,DEV BIOL LAB,BETHESDA,MD 20892. RP Iwamoto, Y (reprint author), KYUSHU UNIV,FAC MED,DEPT ORTHOPAED SURG,HIGASHI KU,MAIDASHI 3-1-1,FUKUOKA 812,JAPAN. NR 36 TC 38 Z9 38 U1 0 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD MAR PY 1996 VL 73 IS 5 BP 589 EP 595 DI 10.1038/bjc.1996.102 PG 7 WC Oncology SC Oncology GA TV827 UT WOS:A1996TV82700006 PM 8605091 ER PT J AU Wu, AH Ziegler, RG Pike, MC Nomura, AMY West, DW Kolonel, LN HornRoss, PL Rosenthal, JF Hoover, RN AF Wu, AH Ziegler, RG Pike, MC Nomura, AMY West, DW Kolonel, LN HornRoss, PL Rosenthal, JF Hoover, RN TI Menstrual and reproductive factors and risk of breast cancer in Asian-Americans SO BRITISH JOURNAL OF CANCER LA English DT Article DE breast cancer; menstrual factor; reproductive factor; Asian-Americans; migrants; US-born ID FULL-TERM PREGNANCY; CHINESE-WOMEN; 1ST BIRTH; AGE; MENARCHE; POPULATION; MENOPAUSE; INCREASE; ASSOCIATIONS; EPIDEMIOLOGY AB We conducted a population-based case-control study of breast cancer among Chinese-, Japanese- and Filipino-American women in Los Angeles County Metropolitan Statistical Area (MSA), San Francisco-Oakland MSA and Oahu, Hawaii. One objective of the study was to quantify breast cancer risks in relation to menstrual and reproductive histories in migrant and US-born Asian-Americans and to establish whether the gradient of risk in Asian-Americans can be explained by these factors. Using a common study design and questionnaire in the three study areas, we successfully conducted in-person interviews with 597 Asian-American women diagnosed with incident, primary breast cancer during the period 1983-87 (70% of those eligible) and 966 population-based controls (75% of those eligible). Controls were matched to cases on age, ethnicity and area of residence. In the present analysis, which included 492 cases and 768 controls, we observed a statistically non-significant 4% reduction in risk of breast cancer with each year delay in onset of menstruation. Independent of age at menarche risk of breast cancer was lower (odds ratio; OR= 0.77) among women with menstrual cycles greater than 29 days. Parous Asian-American women showed a significantly lower risk of breast cancer than nulliparous women (OR = 0.54). An increasing number of livebirths and a decreasing age at first livebirth were both associated with a lower risk of breast cancer, although the effect of number of livebirths was no longer significant after adjustment for age at first livebirth. Women with a pregnancy (spontaneous or induced abortions) but no livebirth had a statistically non-significant increased risk (OR = 1.84), but there was no evidence that one type of abortion was particularly harmful. A positive history of breastfeeding was associated with non-significantly lower risk of breast cancer (OR = 0.78). There are several notable differences in the menstrual and reproductive factors between Asian-Americans in this study and published data on US whites. US-born Asian-Americans had an average age at menarche of 12.2 years-no older than has been found in comparable studies of US whites, but 1.4 years earlier than Asian women who migrated to the US. Asian-American women, particularly those born in the US and those who migrated before age 36, also had a later age at first birth and fewer livebirths than US whites. A slightly higher proportion of Asian-American women breastfed, compared with US whites. The duration of breastfeeding was similar in US-born Asians and US whites, but was longer in Asian migrants, especially those who migrated al a later age. Menstrual and reproductive Factors in Asian-American women are consistent with their boast cancer rates being at least as high as in US whites, and they are. However, the effects of these menstrual and reproductive factors were small and the ORs for migration variables changed only slightly after adjustment for these menstrual and reproductive factors. These results suggest that the lower rates of breast cancer in Asians must be largely as a result of other environmental/lifestyle factors. C1 NCI,DIV CANC ETIOL,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD 20892. UNIV HAWAII,CTR CANC RES,PROGRAM EPIDEMIOL,HONOLULU,HI 96817. NO CALIF CANC CTR,UNION CITY,CA 94587. WESTAT CORP,ROCKVILLE,MD 20892. RP Wu, AH (reprint author), UNIV SO CALIF,DEPT PREVENT MED,1420 SAN PABLO ST,PMB B300,LOS ANGELES,CA 90033, USA. NR 42 TC 76 Z9 77 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD MAR PY 1996 VL 73 IS 5 BP 680 EP 686 DI 10.1038/bjc.1996.118 PG 7 WC Oncology SC Oncology GA TV827 UT WOS:A1996TV82700022 PM 8605107 ER PT J AU deBerker, D Windebank, K Sviland, L Kingma, DW Carter, R Rees, JL AF deBerker, D Windebank, K Sviland, L Kingma, DW Carter, R Rees, JL TI Spontaneous regression in angiocentric T-cell lymphoma SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article ID EPSTEIN-BARR-VIRUS; IMMUNOPROLIFERATIVE LESIONS; VIRAL GENOMES; PAPULOSIS; LOCALIZATION; SPECTRUM; SKIN AB An 8-year-old boy presented with a 10-week history of ulcerating lesions which were histologically and immunocytochemically consistent with the diagnosis of angiocentric T-cell lymphoma. The disease was limited to the skin and resolved with no chemotherapy. Angiocentric T-cell lymphoma is commonly a disease with considerable morbidity and is often fatal. Epstein-Barr virus (EBV) could not be identified in involved tissue by immunostaining or by in situ hybridization. We consider whether the uncharacteristic absence of EBV in this case has prognostic significance. C1 ROYAL VICTORIA INFIRM,DEPT DERMATOL,NEWCASTLE TYNE NE1 4LP,TYNE & WEAR,ENGLAND. ROYAL VICTORIA INFIRM,DEPT CHILD HLTH,NEWCASTLE TYNE NE1 4LP,TYNE & WEAR,ENGLAND. ROYAL VICTORIA INFIRM,DEPT PATHOL,NEWCASTLE TYNE NE1 4LP,TYNE & WEAR,ENGLAND. NCI,PATHOL LAB,HEMATOPATHOL SECT,BETHESDA,MD 20892. ROYAL MARSDEN HOSP,DEPT HISTOPATHOL,LONDON,ENGLAND. NR 29 TC 8 Z9 8 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD MAR PY 1996 VL 134 IS 3 BP 554 EP 558 PG 5 WC Dermatology SC Dermatology GA UA905 UT WOS:A1996UA90500032 PM 8731688 ER PT J AU Schwartz, GN Hakim, F Zujewski, J Szabo, JM Cepada, R Riseberg, D Warren, MK Mackall, CL Setzer, A Noone, M Cowan, KH OShaughnessy, J Gress, RE AF Schwartz, GN Hakim, F Zujewski, J Szabo, JM Cepada, R Riseberg, D Warren, MK Mackall, CL Setzer, A Noone, M Cowan, KH OShaughnessy, J Gress, RE TI Early suppressive effects of chemotherapy and cytokine treatment on committed versus primitive haemopoietic progenitors in patient bone marrow SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE GM-CSF; PIXY321; bone marrow long-term cultures; colony-forming units for granulocytes and macrophages; CD34(+) cells ID COLONY-STIMULATING FACTOR; TUMOR NECROSIS FACTOR; GRANULOCYTE-MACROPHAGE; CORD BLOOD; PRECURSOR CELLS; GROWTH-FACTORS; TARGET-CELLS; FACTOR-ALPHA; INTERLEUKIN-3; CANCER AB These studies investigated the effectiveness of in vivo administration of cytokines in ameliorating potential marrow damage induced by chemotherapy. Breast cancer patients received 5-fluorouracil, leucovorin, doxorubicin and cyclophosphamide (FLAC) followed by either GM-CSF, PIXY321, or no cytokine. Marrow was obtained before and after one or two cycles of FLAC once blood cell counts had recovered. Colony-forming units for granulocytes and macrophages (CFU-GM) were used to indicate the effect of therapy on recovery of committed progenitor cells responsible for early blood cell recovery. The frequency and number of CFU-GM in marrow obtained after FLAC + PIXY321 were significantly lower than in marrow obtained after FLAC + GM-CSF or FLAC without cytokine. CD34(+) cell numbers were also reduced after FLAC + PIXY321. CFU-GM production in marrow long-term cultures (LTC) was used to assess the effect of therapy on primitive progenitors. After 5 weeks the number of CFU-GM in LTC of post-therapy marrow from all three treatment arms was < 15% of the number in pre-therapy LTC. Suppressive effects of FLAC on primitive progenitors were observed even when committed progenitors and CD34(+) cells had recovered to pre-therapy levels. These results demonstrate that cytokine treatment did not ameliorate suppressive or toxic effects of FLAC on the functional integrity of the marrow. C1 OTSUKA PHARMACEUT CO LTD,ROCKVILLE,MD. NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. RP Schwartz, GN (reprint author), NCI,MED BRANCH,TRANSPLANTAT THERAPY SECT,BLDG 10,ROOM 12N226,BETHESDA,MD 20892, USA. NR 49 TC 6 Z9 6 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD MAR PY 1996 VL 92 IS 3 BP 537 EP 547 DI 10.1046/j.1365-2141.1996.00387.x PG 11 WC Hematology SC Hematology GA TY265 UT WOS:A1996TY26500005 PM 8616014 ER PT J AU Lewalle, P Hensel, N Guimaraes, A Couriel, D Jiang, YZ Mavroudis, D Barrett, AJ AF Lewalle, P Hensel, N Guimaraes, A Couriel, D Jiang, YZ Mavroudis, D Barrett, AJ TI Helper and cytotoxic lymphocyte responses to chronic myeloid leukaemia: Implications for adoptive immunotherapy with T cells SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE chronic myeloid leukaemia; cytotoxic T cells; helper T cells; antileukaemia cytotoxicity; adoptive immunotherapy ID CHRONIC MYELOGENOUS LEUKEMIA; BONE-MARROW TRANSPLANTATION; DONOR; GENERATION; FREQUENCY; INVITRO AB We studied 19 patients with chronic myeloid leukaemia (CML) to characterize T-cell autologous responses to leukaemia. Third party stimulated alloresponses in mixed lymphocyte reactions were normal in all patients. Using the helper T-lymphocyte precursor frequency (HTLPf) assay we demonstrated a low frequency of T helper cells recognizing autologous leukaemia cells from CML blood (1/850 000) and marrow (1/965 000). However, similar frequencies to autologous bone marrow and lymphoid cells were also found in normal individuals. In 11 patients studied, HLA-matched siblings had a higher HTLPf to leukaemia than the patient's autologous response (P < 0.004). Alloresponse in mixed lymphocyte reactions (MLR), and autologous HTLPf to leukaemia, were comparable at all stages of disease progression and time from diagnosis, and independent of treatment given. In order to generate autologous cytotoxic lymphocyte responses to CML, lymphocytes were stimulated with CML cells. Cultures were fed again with CML cells and examined for cytotoxicity after 21 d. Strong lymphokine-activated killer (LAK) cytotoxicity was found against K562 and Daudi cell lines, and to Epstein-Barr virus-transformed allogeneic and autologous lymphoblastoid cell lines. Autologous leukaemia cells were lysed to a lesser extent in only 3/13 patients tested. The findings indicate that immune reactivity in CML is normal but suggest that CML cells are relatively resistant to lysis by cytotoxic T cells. The results do ndt support the existence of a leukaemia-specific T-cell response in CML. C1 NHLBI,NIH,BONE MARROW TRANSPLANT UNIT,HEMATOL UNIT,BETHESDA,MD 20892. INST PORTUGUES ONCOL FRANCISCO GENTIL,SERV HEMATOL,LISBON,PORTUGAL. NR 27 TC 11 Z9 12 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD MAR PY 1996 VL 92 IS 3 BP 587 EP 594 PG 8 WC Hematology SC Hematology GA TY265 UT WOS:A1996TY26500013 PM 8616022 ER PT J AU Schmidt, AM Crandall, J Hori, O Cao, R Lakatta, E AF Schmidt, AM Crandall, J Hori, O Cao, R Lakatta, E TI Elevated plasma levels of vascular cell adhesion molecule-1 (VCAM-1) in diabetic patients with microalbuminuria: A marker of vascular dysfunction and progressive vascular disease SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE glycation; diabetes; adhesion molecule; microalbuminuria; vasculopathy ID MELLITUS; ALBUMIN AB Advanced glycation endproducts (AGEs), which accumulate in diabetic vasculature, result in enhanced expression of endothelial cell-associated vascular cell adhesion molecule-1 (VCAM-1) as well release of a soluble form of VCAM-1 (sVCAM-1) into culture supernatants. We hypothesized that sVCAM-1 in diabetic plasma might reflect early vascular perturbation in diabetic vasculopathy. Diabetic patients with microalbuminuria, a group with a high incidence of vascular complications, had increased plasma levels of sVCAM-1, similar to 1.5-fold greater than diabetic patients without microalbuminuria: P<0.05. sVCAM-1 map be an indicator of ongoing cellular dysfunction in diabetes, as well as a dynamic surrogate marker for the effectiveness of therapeutic interventions. C1 COLUMBIA UNIV COLL PHYS & SURG,DEPT SURG,NEW YORK,NY 10032. COLUMBIA UNIV COLL PHYS & SURG,DEPT PHYSIOL,NEW YORK,NY 10032. ST LUKES ROOSEVELT HOSP,DEPT MED,JOSLIN DIABET CTR,NEW YORK,NY 10025. NIA,GERONTOL RES CTR,CARDIOVASC RES LAB,BALTIMORE,MD. RP Schmidt, AM (reprint author), COLUMBIA UNIV COLL PHYS & SURG,DEPT MED,630 W 168TH ST,P&S 11-518,NEW YORK,NY 10032, USA. FU NHLBI NIH HHS [HL 21006, HL 42507]; NIA NIH HHS [AG00602] NR 12 TC 85 Z9 87 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD MAR PY 1996 VL 92 IS 3 BP 747 EP 750 DI 10.1046/j.1365-2141.1996.379915.x PG 4 WC Hematology SC Hematology GA TY265 UT WOS:A1996TY26500039 PM 8616048 ER PT J AU AlDamluji, S Kopin, IJ AF AlDamluji, S Kopin, IJ TI Binding and competitive inhibition of amine uptake at postsynaptic neurones (transport-P) by tricyclic antidepressants SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE uptake; biological transport; tricyclic antidepressants; noradrenaline; prazosin ID HIGH-AFFINITY UPTAKE; RAT-BRAIN; ANTI-DEPRESSANTS; NORADRENALINE; EXPRESSION; DRUGS; CATECHOLAMINES; PHARMACOLOGY; RECEPTORS; CLONING AB 1 We have provided evidence for a novel amine uptake process for which prazosin is a substrate in postsynaptic neurones, characterized by a paradoxical increase in accumulation of the radioligand when the concentration of the unlabelled drug is increased above 10(-7) M. This increase is due to activation of a proton-dependent, vacuolar type-ATPase-linked uptake process which is blocked by desipramine but is resistant to reserpine. We have now examined the effects of tricyclic antidepressants on this uptake system in a cell line derived from hypothalamic peptidergic neurones, known to be innervated by noradrenergic nerve terminals in vivo. 2 [H-3]-imipramine bound to the cells and was displaced by unlabelled imipramine, desipramine, amitriptyline and nortriptyline. The data fitted a single binding site model. This is the first demonstration of antidepressant binding sites in postsynaptic neurones. 3 There was no increase in the binding of [H-3]-imipramine at high concentrations of unlabelled imipramine, suggesting that antidepressants inhibit uptake but are not themselves accumulated by peptidergic gonadotrophin releasing hormone neurones. 4 Accumulation of prazosin was competitively inhibited by antidepressants. Tertiary amines were slightly more potent than secondary amines and the presence of a nitrogen atom in the heterocyclic ring enhanced blocking activity. 5 The affinities of the antidepressants for the uptake process are within the range of plasma concentrations that are observed during therapeutic use of these compounds. Since it is likely that this uptake process has a physiological function, its inhibition by antidepressants may provide a new avenue for investigating the mechanism of action of these compounds. C1 NINCDS,CLIN NEUROSCI BRANCH,NIH,BETHESDA,MD 20892. NR 44 TC 10 Z9 10 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD MAR PY 1996 VL 117 IS 5 BP 811 EP 816 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TZ112 UT WOS:A1996TZ11200008 PM 8851495 ER PT J AU Hou, X Wehrle, J Menge, W Ciccarelli, E Wess, J Mutschler, E Lambrecht, G Timmerman, H Waelbroeck, M AF Hou, X Wehrle, J Menge, W Ciccarelli, E Wess, J Mutschler, E Lambrecht, G Timmerman, H Waelbroeck, M TI Influence of monovalent cations on the binding of a charged and an uncharged ('carbo'-)muscarinic antagonist to muscarinic receptors SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE muscarinic receptors; quaternary nitrogen; uncharged muscarinic antagonist; coulombic interaction; affinity; BS-6181 ID SITE-DIRECTED MUTAGENESIS; GUINEA-PIG ILEUM; TYROSINE RESIDUES; RAT-HEART; PH; M3-MUSCARINIC-RECEPTOR; THREONINE; AGONISTS; AFFINITY AB 1 The effect of the buffer concentration on binding of [H-3]-N-methylscopolamine to muscarinic receptors M(2) was tested in rat heart. Tracer binding was of low affinity in a 20 mM imidazole buffer (pK(D) 8.3), inhibited by an increase from 10 to 100 mM of the sodium phosphate buffer concentration (pK(D) 9.92 to 9.22), slightly inhibited by an increase of the Tris/HCl buffer concentration from 20 to 100 mM (pK(D) 9.70 to 9.47) and unaffected by an increase of the histidine/HCl buffer concentration from 20 to 100 mM (pK(D) 9.90 to 9.82). We chose the last buffer to analyse the effect of ions on antagonists binding to cardiac M(2) receptors and to transiently expressed wild-type and (Y533-->F) mutant m3 muscarinic receptors in COS-7 cells. 2 Equilibrium [H-3]-N-methylscopolamine binding to cardiac M(2) receptors was inhibited, apparently competitively, by monovalent salts (LiCl greater than or equal to NaCl greater than or equal to KCl). In contrast, binding of the uncharged 3,3-dimethylbutan-1-ol ester of diphenylglycolic acid (BS-6181) was facilitated by addition of monovalent salts (LiCl greater than or equal to NaCl greater than or equal to KCl) to the binding buffer. This cation binding pattern is consistent with interaction with a large, negative field strength binding site, such as, for instance, a carboxylic acid. 3 In the presence of 100 mM NaCl, [H-3]-N-methylscopolamine had a similar affinity for the wild-type m3 receptor (pK(D) 9.85) and for a (Y533-->F) mutant m3 receptor (pK(D) 9.68). However, in the absence of added salts, the tracer had a significantly lower affinity for the mutated (pK(D) 10.19) as compared to the wild-type (pK(D) 10.70) m3 receptor. BS-6181 had a significantly lower affinity for the (Y533-->F) mutant m3 muscarinic receptor, as compared to the wild-type m3 receptor, both in the absence (pK(D) 6.19-6.72) in the presence (pK(D) 6.48-7.40) of 100 mM NaCl. The effects of NaCl on binding of the uncharged ester and of [H-3]-N-methylscopolamine to the m3 receptor were decreased by the mutation. 4 Taken together, these results support the hypothesis that monovalent cations from the buffer may interact with the cation binding site of the receptors (an aspartate residue in the third transmembrane helix of muscarinic receptors). Buffer cations may inhibit competitively the binding of (charged) muscarinic ligands having a tertiary amine or ammonium group, while facilitating the receptor recognition by uncharged, isosteric 'carbo-analogues'. Mutation of the (Y533-->F) of the m3 receptor decreased the affinity of the receptor for positive charges, including the sodium ion. C1 FREE UNIV BRUSSELS,SCH MED,LAB BIOCHEM & NUTR,B-1070 BRUSSELS,BELGIUM. NIDDK,NIH,BIOORGAN CHEM LAB,BETHESDA,MD 20892. UNIV FRANKFURT,BIOCTR NIEDERURSEL,DEPT PHARMACOL,D-60439 FRANKFURT,GERMANY. FREE UNIV AMSTERDAM,DEPT PHARMACOCHEM,LEIDEN AMSTERDAM CTR DRUG RES,1081 HV AMSTERDAM,NETHERLANDS. NR 24 TC 8 Z9 8 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD MAR PY 1996 VL 117 IS 5 BP 955 EP 961 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TZ112 UT WOS:A1996TZ11200030 PM 8851517 ER PT J AU Jordan, NJ Watson, ML Yoshimura, T Westwick, J AF Jordan, NJ Watson, ML Yoshimura, T Westwick, J TI Differential effects of protein kinase C inhibitors on chemokine production in human synovial fibroblasts SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE protein kinase C inhibitors; chemokine; synovial fibroblasts; interleukin 1 alpha; tumour necrosis factor alpha; bisindolylmaleimide; Ro 31-8220; GF 109203X; staurosporine; chelerythrine chloride ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; NEUTROPHIL CHEMOTACTIC FACTOR; RHEUMATOID-ARTHRITIS; CYTOKINE RANTES; MONOCLONAL-ANTIBODIES; GENE-EXPRESSION; LYMPHOCYTES-T; GROWTH-FACTOR; CELLS; INTERLEUKIN-8 AB 1 Rheumatoid arthritis is associated with the accumulation and activation of selected populations of inflammatory cells within the arthritic joint. One putative signal for this process is the production, by resident cells, of a group of inflammatory mediators known as the chemokines. 2 The chemokines interleukin-8 (IL-8), monocyte chemotactic protein-1 (MCP-I) and RANTES (regulated on activation normal T-cell expressed and presumably secreted) are target-cell specific chemoattractants produced by synovial fibroblasts in response to stimulation with interleukin-1 alpha (IL-1 alpha) or tumour necrosis factor alpha (TNF alpha). The signalling pathways involved in their production are not well defined. We therefore used four different protein kinase C inhibitors to investigate the role of this kinase in the regulation of chemokine mRNA and protein expression in human cultured synovial fibroblasts. 3 The non-selective PKC inhibitor, staurosporine (1-300 nM) significantly increased the production of IL-1 alpha-induced IL-8 mRNA and protein. A specific PKC inhibitor, chelerythrine chloride (0.1-3 mu M), also caused a small concentration-dependent increase in IL-8 mRNA and protein production. In contrast, 3-[1-[3-(amidinothio)propyl]-3-indoly]-4-(1-methyl-3-indolyl)-1H-pyrrole-2,5-dione methanesulphonate (Ro 31-8220) and 2[1-(3-dimethylaminopropyl)-1H-indol-3-yl]-3-(1H-indol-3-yl)-maleimide (GF 109203X), two selective PKC inhibitors of the substituted bisindolylmaleimide family had a concentration-dependent biphasic effect on IL-1 alpha or TNF alpha-induced chemokine expression. At low concentrations they caused a stimulation in chemokine production, which was especially evident at the mRNA level. At higher concentrations both inhibited IL-1 alpha or TNF alpha-induced chemokine mRNA and protein production. Ro 31-8220 was 10 fold more potent than GF 109203X, with an IC50 of 1.6+/-0.08 mu M (mean+/-s.e.mean, n=4) for IL-1 alpha induced IL-8 production. Ro 31-8220 also inhibited the expression of IL-1 alpha or TNF alpha-induced MCP-1 and RANTES mRNA with a similar potency. 4 The stimulatory effect of staurosporine is discussed in relation to the known poor selectivity of this inhibitor for PKC. It is proposed that activation of an isoform of PKC, possibly PKC epsilon or zeta, which is inhibited by higher concentrations of the bisinodolylmaleimides, plays a role in the regulation of chemokine expression induced by IL-1 alpha or TNF alpha in synovial cells. 5 The inhibition of chemokine production by bisindolylmaleimide compounds heralds a novel approach for future anti-inflammatory therapies. C1 NCI, FREDERICK CANC RES & DEV CTR, FREDERICK, MD USA. RP Jordan, NJ (reprint author), UNIV BATH, SCH PHARM & PHARMACOL, DEPT PHARMACOL, BATH BA2 7AY, AVON, ENGLAND. RI Jordan, Nicola/B-3341-2013 FU Wellcome Trust NR 47 TC 21 Z9 21 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD MAR PY 1996 VL 117 IS 6 BP 1245 EP 1253 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UB816 UT WOS:A1996UB81600036 PM 8882622 ER PT J AU Kramlinger, KG Post, RM AF Kramlinger, KG Post, RM TI Ultra-rapid and ultradian cycling in bipolar affective illness SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID DEPRESSIVE CYCLES; UNIPOLAR; RELIABILITY; DISORDERS; PATIENT AB Background. Rapid-cycling bipolar disorder is defined as four or more affective episodes yearly. the conventionally recognised limit in episode duration is usually considered 24 hours (i.e. a cycle duration of 48 hours). We report a small series of intensively observed bipolar patients who showed much faster patterns of mood oscillation. Methods. Detailed, systematic, longitudinal assessment of five bipolar patients during extended in-patient psychiatric evaluation were conducted, including retrospective life charting and prospective evaluation of daily mood by self and blinded observer ratings, and motor activity recording. Results. Our data demonstrate a spectrum of cycling frequencies in rapid-cyclers, including distinct, clinically robust mood shifts that occur at frequencies faster than once per 24 hours. Affective oscillations spanned a range of cycling frequencies from four episodes per year (rapid cycling) to those occurring within the course of weeks to several days (ultra-rapid cycling), to distinct abrupt mood shifts of less than 24 hours duration (ultra-ultra rapid or ultradian cycling). The time of onset and duration of these ultradian affective fluctuations are highly variable and they are observed in bipolar patients without evidence of personality disorder. Conclusions. The potential clinical and theoretical implications of these first systematic observations of ultra-rapid and ultradian cycling in the context of the evolution of otherwise classical bipolar affective illness are discussed. C1 NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. NR 30 TC 111 Z9 113 U1 2 U2 4 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON, ENGLAND SW1X 8PG SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD MAR PY 1996 VL 168 IS 3 BP 314 EP 323 DI 10.1192/bjp.168.3.314 PG 10 WC Psychiatry SC Psychiatry GA UA077 UT WOS:A1996UA07700010 PM 8833685 ER PT J AU Solary, E Dubrez, L Eymin, B Bertrand, R Pommier, Y AF Solary, E Dubrez, L Eymin, B Bertrand, R Pommier, Y TI Apoptosis induction in human leukemic cells by topoisomerase I and II inhibitors. SO BULLETIN DU CANCER LA French DT Article DE apoptosis; topoisomerases; leukemia; proteases; cell cycle ID HL-60 CELLS; DEATH; BCL-2; GENE; DNA; HOMOLOG AB Comparison between five human leukemic lines (BV173, HL60, U937, K562, KCL22) suggest that the main determinant of their sensitivity to topoisomerase I (camptothecin) and II (VP-16) inhibitors is their ability to regulate cell cycle progression in response to specific DNA damage, then to die through apoptosis: the more the cells inhibit cell cycle progression, the less sensitive they are. The final pathway of apoptosis induction involves a cytoplasmic signal, active at neutral pH, needing magnesium, sensitive to various protease inhibitors and activated directly by staurosporine. Modulators of intracellular signaling (calcium chelators, calmoduline inhibitors, PKC modulators, kinase and phosphatase inhibitors) have no significant influence upon apoptosis induction. Conversely, apoptosis induction pathway is modified during monocytic differentiation of HL60 cells induced by phorbol esters. Lastly, poly(ADP-ribosyl)ation and chromatine structure should regulate apoptotic DNA fragmentation that is prevented by 3-aminobenzamide and spermine, respectively. C1 INST CANC MONTREAL,MONTREAL,PQ,CANADA. NCI,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. RP Solary, E (reprint author), UFR MED PHARM,LAB ONCOHEMATOL & PHARMACOL,GRP BIOL & THERAPIE CANC,7 BD JEANNE DARC,F-21033 DIJON,FRANCE. RI Eymin, Beatrice/M-1962-2013; Dubrez, Laurence/I-4971-2016 OI Dubrez, Laurence/0000-0002-7030-2181 NR 25 TC 11 Z9 11 U1 0 U2 2 PU EDITIONS SCIENTIFIQUES ELSEVIER PI PARIS CEDEX 15 PA 141 RUE JAVEL, 75747 PARIS CEDEX 15, FRANCE SN 0007-4551 J9 B CANCER JI Bull. Cancer PD MAR PY 1996 VL 83 IS 3 BP 205 EP 212 PG 8 WC Oncology SC Oncology GA UR899 UT WOS:A1996UR89900005 PM 8695922 ER PT J AU Porter, JP AF Porter, JP TI Informed consent issues in international research concerns SO CAMBRIDGE QUARTERLY OF HEALTHCARE ETHICS LA English DT Article ID CLINICAL RESEARCH; ETHICS C1 DEPT HLTH & HUMAN SERV,OPRR,NIH,BETHESDA,MD. NR 18 TC 2 Z9 2 U1 0 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0963-1801 J9 CAMB Q HEALTHC ETHIC JI Camb. Q. Healthc. Ethics PD SPR PY 1996 VL 5 IS 2 BP 237 EP 243 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Social Sciences, Biomedical SC Health Care Sciences & Services; Biomedical Social Sciences GA UG115 UT WOS:A1996UG11500006 PM 8718730 ER PT J AU Biesecker, LG AF Biesecker, LG TI Orphan tests SO CAMBRIDGE QUARTERLY OF HEALTHCARE ETHICS LA English DT Article RP Biesecker, LG (reprint author), NIH,NATL CTR HUMAN GENOME RES,LAB GENET DIS RES,BETHESDA,MD 20892, USA. NR 17 TC 3 Z9 3 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0963-1801 J9 CAMB Q HEALTHC ETHIC JI Camb. Q. Healthc. Ethics PD SPR PY 1996 VL 5 IS 2 BP 300 EP 306 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Social Sciences, Biomedical SC Health Care Sciences & Services; Biomedical Social Sciences GA UG115 UT WOS:A1996UG11500017 PM 8718739 ER PT J AU Blaxton, TA Bookheimer, SY Zeffiro, TA Figlozzi, CM Gaillard, WD Theodore, WH AF Blaxton, TA Bookheimer, SY Zeffiro, TA Figlozzi, CM Gaillard, WD Theodore, WH TI Functional mapping of human memory using PET: Comparisons of conceptual and perceptual tasks SO CANADIAN JOURNAL OF EXPERIMENTAL PSYCHOLOGY-REVUE CANADIENNE DE PSYCHOLOGIE EXPERIMENTALE LA English DT Article ID IMPLICIT MEMORY; PREFRONTAL CORTEX; WORD; DISSOCIATIONS; ORGANIZATION; RETENTION; RETRIEVAL; ANATOMY; TESTS AB An experiment is reported in which regional cerebra blood flow (rCBF) was measured using positron emission tomography (PET) as participants performed conceptual and perceptual memory tasks. Blood flow during two conceptual tests of semantic cued recall and semantic association was compared to a control condition in which participants made semantic associations to nonstudied words. Analogously, rCBF during two perceptual tasks of word fragment cued recall and word fragment completion was compared to a word fragment nonstudied control condition. A direct comparison of conceptual and perceptual tasks showed that conceptual tasks activated media and lateral left hemisphere in frontal and temporal regions as well as the lateral aspect; of bilateral inferior parietal lobule. Perceptual tasks, in contrast, produced relatively greater activation in right frontal and temporal cortex as well as bilateral activation in more posterior regions. Comparisons of the memory tasks with their control conditions revealed memory-specific deactivations in left media and superior temporal cortex as well as left frontal cortex for both conceptual tasks. In contrast, memory-specific deactivations for both perceptual fragment completion tests were localized in posterior regions including occipital cortex. Results from this and other functional imaging experiments provide evidence that conceptual and perceptual memory processes are subserved, at least in part, by different neurological structures in the human brain. RP Blaxton, TA (reprint author), NIH,BLDG 10,ROOM 5C205,BETHESDA,MD 20892, USA. NR 53 TC 119 Z9 120 U1 0 U2 0 PU CANADIAN PSYCHOL ASSOC PI QUEBEC CITY PA RUE VINCENT RD OLD CHELSEA, QUEBEC CITY J0X 2N0, CANADA SN 1196-1961 J9 CAN J EXP PSYCHOL JI Can. J. Exp. Psychol.-Rev. Can. Psychol. Exp. PD MAR PY 1996 VL 50 IS 1 BP 42 EP 56 DI 10.1037/1196-1961.50.1.42 PG 15 WC Psychology, Experimental SC Psychology GA UG130 UT WOS:A1996UG13000005 PM 8653097 ER PT J AU Goldspiel, BR Curt, GA AF Goldspiel, BR Curt, GA TI Issues in antiemetic therapy SO CANCER LA English DT Editorial Material ID ITALIAN-ONCOLOGY-GROUP; CANCER; METHYLPREDNISOLONE; METOCLOPRAMIDE; DEXAMETHASONE; ONDANSETRON; ALCOHOL; EMESIS; NAUSEA C1 NCI,DIV CLIN SCI,BETHESDA,MD 20892. WARREN G MAGNUSON CLIN CTR,BETHESDA,MD. NR 19 TC 3 Z9 3 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD MAR 1 PY 1996 VL 77 IS 5 BP 823 EP 826 DI 10.1002/(SICI)1097-0142(19960301)77:5<823::AID-CNCR3>3.0.CO;2-F PG 4 WC Oncology SC Oncology GA TW395 UT WOS:A1996TW39500003 PM 8608470 ER PT J AU Glynn, SA Albanes, D Pietinen, P Brown, CC Rautalahti, M Tangrea, JA Taylor, PR Virtamo, J AF Glynn, SA Albanes, D Pietinen, P Brown, CC Rautalahti, M Tangrea, JA Taylor, PR Virtamo, J TI Alcohol consumption and risk of colorectal cancer in a cohort of Finnish men SO CANCER CAUSES & CONTROL LA English DT Review DE alcohol; cohort studies; colorectal cancer; Finland; men ID LARGE-BOWEL CANCER; RECTAL-CANCER; COLON-CANCER; BEVERAGE CONSUMPTION; PREVENTION; ETIOLOGY; POLYPS AB We investigated the association between self-reported alcohol ingestion and colorectal cancer in a cohort of male smokers in Finland. Among 27,109 men aged 50 to 69 years, 87 colon and 53 rectal cases were diagnosed during the five to eight years of follow-up. Among drinkers, colorectal cancer risk increased with the amount of alcohol consumed (P trend = 0.01) with risk increasing by 17 percent for each drink consumed. Both beer and spirits contributed to this increased risk. Further analyses revealed that the positive association with alcohol was primarily for colon cancer (P trend = 0.01). Interestingly, risk of colorectal cancer associated with drinking (cf self-reported abstinence) changed with follow-up time, suggesting an inverse association for alcohol early in follow-up, and a positive association after about three-and-a-half years of follow-up. Follow-up time did not modify the positive association with amount of alcohol among drinkers, however. Results also indicated that p-carotene supplementation may attenuate the effect of alcohol on colorectal cancer risk among drinkers. In conclusion, this study supports a role for alcohol in colon carcinogenesis and suggests that similar studies should evaluate carefully the effects of lifetime drinking habits and recent abstinence. C1 NATL PUBL HLTH INST,HELSINKI,FINLAND. RP Glynn, SA (reprint author), NCI,DIV CANC PREVENT & CONTROL,CANC PREVENT STUDIES BRANCH,CPRP,EXECUT PLAZA N,SUITE 211,BETHESDA,MD 20892, USA. RI Albanes, Demetrius/B-9749-2015 FU NCI NIH HHS [N01-CN-45165] NR 52 TC 43 Z9 43 U1 1 U2 4 PU RAPID SCIENCE PUBLISHERS PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8NH SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD MAR PY 1996 VL 7 IS 2 BP 214 EP 223 DI 10.1007/BF00051297 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA UJ455 UT WOS:A1996UJ45500004 PM 8740734 ER PT J AU Enger, SM Longnecker, MP Chen, MJ Harper, JM Lee, ER Frankl, HD Haile, RW AF Enger, SM Longnecker, MP Chen, MJ Harper, JM Lee, ER Frankl, HD Haile, RW TI Dietary intake of specific carotenoids and vitamins A, C, and E, and prevalence of colorectal adenomas SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; CANCER PREVENTION; SIGMOID COLON; POLYPS; RISK; VEGETABLES; RECURRENCE; REPRODUCIBILITY; SUPPLEMENTATION; EPIDEMIOLOGY AB We determined whether intakes of the main dietary carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein plus zeaxanthin, and lycopene) and of vitamins A, C, and E were associated with the prevalence of colorectal adenomas among male and female members of a prepaid health plan in Los Angeles who underwent sigmoidoscopy (n = 488 matched pairs). Participants, ages 50-74 years, completed a 126-item semiquantitative food-frequency questionnaire and a nondietary questionnaire from 1991 to 1993. In the univariate-matched analysis, alpha-carotene, beta-carotene (with and without supplements), beta-cryptoxanthin, lutein plus zeaxanthin, vitamin A (with and without supplements), and vitamin C (with and without supplements) were associated with a decreased prevalence of colorectal adenomas. After adjustment for intake of calories, saturated fat, folate, fiber, and alcohol, and for current smoking status, body mass index, race, physical activity, and use of nonsteroidal anti-inflammatory drugs, only beta-carotene including supplements was inversely associated with adenomas [odds ratio (OR), 0.6; 95% confidence interval (CI), 0.4-1.1; trend, P = 0.04; ORs compare highest to lowest quartiles]; vitamin C showed a weaker inverse association (OR, 0.8; 95% CI, 0.5-1.5; trend, P = 0.08); and the remaining compounds were no longer clearly associated with risk. After including beta-carotene with supplements and vitamin C simultaneously in the multivariate model, the association of beta-carotene with supplements with adenomas was weakened (OR, 0.8; 95% CI, 0.5-1.3; trend P = 0.15), and vitamin C was no longer associated with risk. These data provide only modest support for a protective association of beta-carotene with colorectal adenomatous polyps. C1 UNIV CALIF LOS ANGELES,SCH PUBL HLTH,DEPT EPIDEMIOL,LOS ANGELES,CA 90024. BELLFLOWER MED CTR,DIV GASTROENTEROL,LOS ANGELES,CA 90027. KAISER PERMANENTE MED CTR,DIV GASTROENTEROL,LOS ANGELES,CA 90027. SUNSET MED CTR,DIV GASTROENTEROL,LOS ANGELES,CA 90027. NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC 27709. RP Enger, SM (reprint author), UNIV SO CALIF,SCH MED,DEPT PREVENT MED,1420 SAN PABLO ST,PMB A202,LOS ANGELES,CA 90033, USA. OI Longnecker, Matthew/0000-0001-6073-5322 FU NCI NIH HHS [1-RO1 CA51923-01A1, CA-49565] NR 46 TC 48 Z9 49 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 MAR PY 1996 VL 5 IS 3 BP 147 EP 153 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA TZ891 UT WOS:A1996TZ89100001 PM 8833613 ER PT J AU McKeever, PE Dennis, TR Burgess, AC Meltzer, PS Marchuk, DA Trent, JM AF McKeever, PE Dennis, TR Burgess, AC Meltzer, PS Marchuk, DA Trent, JM TI Chromosome breakpoint at 17q11.2 and insertion of DNA from three different chromosomes in a glioblastoma with exceptional glial fibrillary acidic protein expression SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID MALIGNANT HUMAN GLIOMAS; CELL-LINES; INSITU HYBRIDIZATION; CYTOGENETIC ANALYSIS; ASTROCYTOMAS; ESTABLISHMENT; KARYOTYPE; TUMORS; MARKER; GENE AB A glioblastoma that retained glial fibrillary acidic protein (GFAP) in culture has a break in the long arm of chromosome 17 at band 17q11.2. DNA inserted at this breakpoint came from chromosome bands 3p21, 3q23, 16q11.2, and 22q11.2. These chromosome fragments were inserted in band 17q11.2 proximal to the neurofibromatosis-1 (NF-1) gene and neu (HER2; erbB2) oncogene loci. The glioblastoma also contained a reciprocal translocation between 16p12 and 20p12. These structural abnormalities, previously undescribed in gliomas, were demonstrated by high-resolution chromosome banding, microdissection, and fluorescence in situ hybridization (FISH). Numerical changes typical of glioblastoma were present: gain of chromosome 7 and losses of chromosomes 10, 13, and 22. The complex chromosome origin of DNA inserted in this glioma chromosome is described. The association of two infrequent events in this single glioblastoma line, this complex insertion and retention of GFAP expression, is not likely to be a chance occurrence. If raises the possibility of an association between the two events. C1 UNIV MICHIGAN,SCH MED,DEPT RADIAT ONCOL,ANN ARBOR,MI 48109. NATL INST HLTH,NATL CTR HUMAN GENOME RES,BETHESDA,MD. RP McKeever, PE (reprint author), UNIV MICHIGAN,SCH MED,DEPT PATHOL,BOX 0602,1301 CATHERINE ST,ANN ARBOR,MI 48109, USA. FU NCI NIH HHS [CA47558] NR 40 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD MAR PY 1996 VL 87 IS 1 BP 41 EP 47 DI 10.1016/0165-4608(95)00237-5 PG 7 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA UD431 UT WOS:A1996UD43100010 PM 8646740 ER PT J AU Thompson, FH Nelson, MA Trent, JM Guan, XY Liu, Y Yang, JM Emerson, J Adair, L Wymer, J Balfour, C Massey, K Weinstein, R Alberts, DS Taetle, R AF Thompson, FH Nelson, MA Trent, JM Guan, XY Liu, Y Yang, JM Emerson, J Adair, L Wymer, J Balfour, C Massey, K Weinstein, R Alberts, DS Taetle, R TI Amplification of 19q13.1-q13.2 sequences in ovarian cancer - G-band, FISH, and molecular studies SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID CLONAL CHROMOSOME-ABNORMALITIES; HUMAN BREAST CARCINOMAS; MALIGNANT-MELANOMA; N-MYC; GENERATION; DNA; MICRODISSECTION; NEUROBLASTOMA; ABERRATIONS; DISEASE AB In this study of ovarian carcinoma, we extended previous findings by performing FISH using chromosome 19 paint and microFISH probes and patient samples with and without abnormalities of chromosome 19 identified by G-banding. Karyotype interpretations of der(19) were confirmed, while additional 19 translocations were also detected by FISH with 19WCP in some cases. Similar FISH studies of ovarian carcinoma cell lines found chromosome 19 abnormalities even after extensive in vitro culture. MicroFISH probes were generated by chromosome microdissection from two cases with hsr(l9) and mapped to 19q13.2 and 19q13.1-.2, respectively. FISH with these microFISH probes alone or in combination with a 19 WCP probe to four patient samples and seven cell lines showed that 65% of chromosome 19 structural abnormalities contained 19q13.1-q13.2 sequences, sometimes as large hsrs. Ovarian cancer cell lines showed amplification and overexpression of the AKT2 putative oncogene, but not the ERCC-2 DNA repair gene in this chromosomal region. In addition to AKT2, amplification and overexpression of other yet-unidentified genes in the 19q13.1-q13.2 region may contribute to ovarian carcinoma pathogenesis or progression. C1 UNIV ARIZONA,ARIZONA CANC CTR,TUCSON,AZ 85724. NATL INST HLTH,NATL CTR HUMAN GENOME RES,BETHESDA,MD. RI Guan, Xin-Yuan/A-3639-2009 OI Guan, Xin-Yuan/0000-0002-4485-6017 FU NCI NIH HHS [CA 41183, CA 23074] NR 32 TC 67 Z9 69 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD MAR PY 1996 VL 87 IS 1 BP 55 EP 62 DI 10.1016/0165-4608(95)00248-0 PG 8 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA UD431 UT WOS:A1996UD43100013 PM 8646743 ER PT J AU Gutierrez, MI Judde, JG Magrath, IT Bhatia, KG AF Gutierrez, MI Judde, JG Magrath, IT Bhatia, KG TI Switching viral latency to viral lysis: A novel therapeutic approach for Epstein-Barr virus-associated neoplasia SO CANCER RESEARCH LA English DT Article ID BURKITTS-LYMPHOMA; LYMPHOCYTES; REPLICATION; EXPRESSION; ORIGIN; CELLS; DNA AB We describe an EBV-driven lytic system (LySED) that can be used to specifically target therapy to EBV-containing tumors. This system takes advantage of the transactivating properties of EBNA-1, a latency protein expressed in all EBV-containing cells, to drive the expression of Zta, a gene sufficient for inducing the EBV lytic cycle. Thus, EBV provides both the target and the executor for mediating tumor-specific cell death, markedly increasing the specificity of the system. Transfection of EBV-positive cell lines with the LySED construct resulted in a switch to lytic cycle and subsequent cell death, even in the presence of an inhibitor of EBV thymidine kinase (acyclovir) without an increase in virion production. In contrast, growth of EBV-negative B-cell lines was not affected. C1 NCI,PEDIAT BRANCH,NIH,LYMPHOMA BIOL SECT,BETHESDA,MD 20892. NR 20 TC 41 Z9 41 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 MAR 1 PY 1996 VL 56 IS 5 BP 969 EP 972 PG 4 WC Oncology SC Oncology GA TX173 UT WOS:A1996TX17300009 PM 8640787 ER PT J AU Nishi, T Yoshizato, K Yamashiro, S Takeshima, H Sato, K Hamada, K Kitamura, I Yoshimura, T Saya, H Kuratsu, J Ushio, Y AF Nishi, T Yoshizato, K Yamashiro, S Takeshima, H Sato, K Hamada, K Kitamura, I Yoshimura, T Saya, H Kuratsu, J Ushio, Y TI High-efficiency in vivo gene transfer using intraarterial plasmid DNA injection following in vivo electroporation SO CANCER RESEARCH LA English DT Article ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; LIPOSOME COMPLEXES; TRANSFER INVIVO; MICE; THERAPY; CELLS; ELECTROCHEMOTHERAPY; ELECTROPERMEABILIZATION; IMMUNIZATION; ANTIBODIES AB A novel method for high-efficiency and region-controlled in vivo gene transfer was developed by combining in vivo electroporation and intraarterial plasmid DNA injection. A mammalian expression plasmid for the Escherichia coli lacZ gene (driven with a SV40 early promoter) was injected into the internal carotid artery of rats whose brain tumors (from prior inoculation) had been electroporated between two electrodes. The lacZ gene was efficiently transferred and expressed in the tumor cells 3 days after plasmid injection. However, neither any gene transfers nor any elevated lacZ activity was detected in tissues outside the electrodes. The plasmid was not transferred without electroporation. Human monocyte chemoattractant protein-1 cDNA was also transferred by this method, and its long-lasting (3 weeks) expression was confirmed by using the Epstein-Barr virus episomal replicon system. The expressed monocyte chemoattractant protein-1 protein was functional, as evident by the presence of a large number of monocytes in the tumor tissue. This method, ''electrogene therapy,'' which does not require viral genes or particles, allows genes to be transferred and expressed in desired organs or tissues, and it may lead to the development of a new type of highly effective gene therapy. C1 KUMAMOTO UNIV,SCH MED,DEPT TUMOR GENET & BIOL,KUMAMOTO 860,JAPAN. NCI,IMMUNOBIOL LAB,IMMUNOPATHOL SECT,FREDERICK,MD 21702. RP Nishi, T (reprint author), KUMAMOTO UNIV,SCH MED,DEPT NEUROSURG,1-1-1 HONJO,KUMAMOTO 860,JAPAN. RI Saya, Hideyuki/J-4325-2013 NR 37 TC 228 Z9 247 U1 2 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 1 PY 1996 VL 56 IS 5 BP 1050 EP 1055 PG 6 WC Oncology SC Oncology GA TX173 UT WOS:A1996TX17300021 PM 8640760 ER PT J AU Wigginton, JM Kuhns, DB Back, TC Brunda, MJ Wiltrout, RH Cox, GW AF Wigginton, JM Kuhns, DB Back, TC Brunda, MJ Wiltrout, RH Cox, GW TI Interleukin 12 primes macrophages for nitric oxide production in vivo and restores depressed nitric oxide production by macrophages from tumor-bearing mice: Implications for the antitumor activity of interleukin 12 and/or interleukin 2 SO CANCER RESEARCH LA English DT Article ID CELL STIMULATORY FACTOR; LYMPHOCYTE MATURATION FACTOR; L-ARGININE; ACTIVATED MACROPHAGES; MURINE MACROPHAGES; INTERFERON-GAMMA; TUMORICIDAL FUNCTION; EFFECTOR MECHANISM; NITROGEN-OXIDES; CYTO-TOXICITY AB Interleukin-12 (IL-12) is a recently described immunoregulatory cytokine with potent therapeutic activity in various preclinical models of infectious or malignant disease, As part of our ongoing evaluation of potential mechanisms accounting for the potent antitumor activity of IL-12, we have investigated the influence of IL-12 administration on total serum nitrate/nitrite (NOx-) levels and the production of nitric oxide (NO) by peritoneal macrophages from normal and tumor-bearing mice. We report here that IL-12 administration to either normal or tumor-bearing mice for periods of time ranging from 7-19 days induced progressive increases in serum NOx- levels and primed peritoneal macrophages for NO production on subsequent exposure to lipopolysaccharide or IL-2 ex vivo. Treatment of resident peritoneal macrophages of the macrophage cell line ANA-1 with IL-12 alone or IL-12 in combination with various other stimuli failed to induce NO production, suggesting that the effects of IL-12 occurred via an indirect mechanism. Furthermore, we have shown that not only was the production of NO by macrophages from untreated long-term, tumor-bearing mice suppressed compared with control mice treated with vehicle or IL-12, but also that IL-12 administration overcame this suppression and delayed tumor growth. Lastly, we have shown that administration of weekly pulses of IL-2 in combination with IL-12 additively enhanced the priming of macrophages for NO production ex vivo and delayed tumor growth far more effectively than either agent alone. These observations and reports in the literature regarding the potential influence of NO on development of the immune response and on the regulation of tumor growth and vascularization suggest that NO may play a significant role in the antitumor activity of IL-12 and IL-2. C1 SCI APPLICAT INT CORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD. SCI APPLICAT INT CORP,CLIN SERV PROGRAM,FREDERICK,MD. NCI,FREDERICK CANC RES & DEV CTR,EXPTL IMMUNOL LAB,DIV BASIC SCI,FREDERICK,MD 21701. HOFFMANN LA ROCHE INC,DEPT ONCOL,NUTLEY,NJ 07110. NR 59 TC 63 Z9 63 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 1 PY 1996 VL 56 IS 5 BP 1131 EP 1136 PG 6 WC Oncology SC Oncology GA TX173 UT WOS:A1996TX17300033 PM 8640772 ER PT J AU Middleman, MN Lush, RM Sartor, O Reed, E Figg, WD AF Middleman, MN Lush, RM Sartor, O Reed, E Figg, WD TI Treatment approaches for metastatic cancer of the prostate based on recent molecular evidence SO CANCER TREATMENT REVIEWS LA English DT Review ID PROGRAMMED CELL-DEATH; RAT VENTRAL PROSTATE; FLUTAMIDE WITHDRAWAL SYNDROME; COMBINATION THERAPY; ANDROGEN RECEPTOR; CASTRATION; ACTIVATION; CARCINOMA; TRANSCRIPTION; ORCHIECTOMY C1 NCI,NIH,DIV CLIN SCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. RI Figg Sr, William/M-2411-2016 NR 61 TC 11 Z9 11 U1 0 U2 1 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0305-7372 J9 CANCER TREAT REV JI Cancer Treat. Rev. PD MAR PY 1996 VL 22 IS 2 BP 105 EP 118 DI 10.1016/S0305-7372(96)90030-4 PG 14 WC Oncology SC Oncology GA UT733 UT WOS:A1996UT73300002 PM 8665563 ER PT J AU Hill, BA Brown, PC Preisegger, KH Silverman, JA AF Hill, BA Brown, PC Preisegger, KH Silverman, JA TI Regulation of mdrlb gene expression in Fischer, Wistar and Sprague-Dawley rats in vivo and in vitro SO CARCINOGENESIS LA English DT Article ID MULTIDRUG-RESISTANCE GENE; P-GLYCOPROTEIN EXPRESSION; YA-SUBUNIT GENE; INDUCIBLE EXPRESSION; TRANSCRIPTIONAL REGULATION; PHENOLIC ANTIOXIDANTS; HEPATOCYTE CULTURES; RESPONSIVE ELEMENT; CELL-LINES; LIVER AB Administration of 2-acetylaminofluorene (2-AAF) to rats increased mdr1b expression in Fischer, Wistar and Sprague-Dawley rat livers; however, the response was much smaller in Sprague-Dawley livers, To investigate the basis of this difference we further examined the regulation of the mdr1b gene in hepatocytes isolated from Fischer, Sprague-Dawley and Wistar rats, A time-dependent increase in basal expression of mdr1b but not mdr2 was observed in hepatocytes isolated from all three strains of rats, After 4 days in culture, a larger increase in mdr1b mRNA levels was observed in Fischer and Wistar rat hepatocytes (3.5- and 4.6-fold respectively) than Sprague-Dawley hepatocytes (2-fold), Treatment of primary hepatocytes with 2-AAF caused an induction of mdr1b expression that varied among the three strains, Notably, Sprague-Dawley hepatocytes were not responsive to 2-AAF, In contrast to the parent compound, the electrophilic metabolites N-hydroxy-2-acetylaminofluorene and N-acetoxy-2-acetylaminofluorene caused a dose-dependent induction of mdr1b expression in both Fischer and Sprague-Dawley hepatocytes, indicating that differences in the metabolic activation of 2-AAF between the strains may account for the differences in mdr1b induction by 2-AAF, Hepatocytes isolated from all three strains of rats showed an equivalent induction of mdr1b after treatment with cycloheximide, Nuclear run-on assays demonstrated that the increases in mdr1b expression with time in culture and after xenobiotic treatment were due to increased transcription. C1 NCI,EXPTL CARCINOGENESIS LAB,BETHESDA,MD 20892. NR 57 TC 27 Z9 27 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 MAR PY 1996 VL 17 IS 3 BP 451 EP 457 DI 10.1093/carcin/17.3.451 PG 7 WC Oncology SC Oncology GA UC150 UT WOS:A1996UC15000011 PM 8631130 ER PT J AU Harvat, BL Jetten, AM AF Harvat, BL Jetten, AM TI gamma-Interferon induces an irreversible growth arrest in mid-G(1) in mammary epithelial cells which correlates with a block in hyperphosphorylation of retinoblastoma SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID C-MYC; BINDING PROTEIN; OVARIAN-CANCER; GENE-PRODUCT; ALPHA; TRANSCRIPTION; EXPRESSION; ACTIVATION; LEUKEMIA; PROMOTER AB In this study, we analyze effects of IFN-gamma on the proliferation of normal human mammary epithelial cells (MECs) and several mammary carcinoma cell lines. We demonstrate that IFN-gamma blocks the proliferation of MECs in a time- and concentration-dependent manner. This growth arrest is irreversible and occurs at a specific stage in the G(1) phase of the cell cycle, 1FM-gamma caused a rapid (within 12-24 h) down-regulation of cyclin A, c-myc, and cdc2 proteins, as well as a disappearance of hyperphosphorylated forms of the retinoblastoma family proteins, Rb and p130. The synthesis of several other growth control proteins, p53, p21/Waf1, and proliferating cell nuclear antigen, was down-regulated between 24 and 48 h. In MECs synchronized by epidermal growth factor deprivation and released for cell cycle traverse by re-addition of epidermal growth factor to the medium, lFN-gamma was able to block DNA synthesis only if added in the first 6 to 7 h after epidermal growth factor. The block in Rb phosphorylation and cyclin A expression was coordinately regulated during the same narrow window of G(1). Several mammary carcinoma cell lines demonstrated resistance to the growth-inhibitory effects of lFN-gamma and did not exhibit down-regulation of cdc2 and cyclin A expression or a change in hyperphosphorylation of Rb when treated with IFN-gamma. Initial studies suggest, in some carcinoma cell lines, that resistance to lFN-gamma may be caused by defects in the IFN-gamma signal transduction pathway (measured by expression of the IFN-gamma-responsive gene GBP), while resistance in others may be due to defects in cell cycle regulatory proteins that are the targets of lFN-gamma action. C1 NIEHS, NIH, RES TRIANGLE PK, NC 27709 USA. OI Jetten, Anton/0000-0003-0954-4445 NR 73 TC 57 Z9 58 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD MAR PY 1996 VL 7 IS 3 BP 289 EP 300 PG 12 WC Cell Biology SC Cell Biology GA TY628 UT WOS:A1996TY62800002 PM 8838859 ER PT J AU Mills, KJ Vollberg, TM Nervi, C Grippo, JF Dawson, MI Jetten, AM AF Mills, KJ Vollberg, TM Nervi, C Grippo, JF Dawson, MI Jetten, AM TI Regulation of retinoid-induced differentiation in embryonal carcinoma PCC4.aza1R cells: Effects of retinoid-receptor selective ligands SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID ACID RECEPTOR; X-RECEPTOR; NUCLEAR RECEPTORS; THYROID-HORMONE; RESPONSE ELEMENTS; BETA-GENE; EXPRESSION; RXR; IDENTIFICATION; BINDING AB Retinoic acid (RA) is a potent inducer of differentiation of embryonal carcinoma PCC4.aza1R cells into mesenchymal stem cells, Induction of Hoxa-1, Hoxa-5, cellular retinoic acid-binding protein (CRABP) I and II, and retinoic acid receptor (RAR)-beta expression occurs early in this multistage program of differentiation. RA is also a potent inducer of these genes in the differentiation-defective mutant PCC4(RA)-1; however, RA is much less effective in the mutant cell line PCC4(RA)-2. the up-regulation of several of these genes by RA is, at least in part, due to increased transcription, It is likely that some of these changes are mediated either directly or indirectly by nuclear retinoid receptors, Previously, we characterized the expression of RARs in PCC4.aza1R and (RA)-1 and (RA)-2 cells, In this study, we show that these cells also express retinoid X receptor (RXR)-alpha, RXR-beta, and RXR-gamma and that RA treatment down-regulates the expression of RXR-gamma. No large differences were found in RXR mRNA expression between parental and mutant cell lines except that PCC4(RA)-1 cells expressed an 8-fold higher level of RXR gamma mRNA than the parental cells, To obtain more insight into the retinoid signaling pathways involved in the regulation of this pathway of differentiation, we examined the action of two retinoid receptor-selective agonists and one antagonist, The RAR-selective retinoid SRI-6751-84 is a very effective inducer of transactivation of beta RARE-tk-LUC, but not of RXRE-tk-CAT, in PCC4.aza1R cells and is a very potent inducer of morphological differentiation and Hoxa-1, Hoxa-2, CRABP II, and RAR-beta expression. In contrast, the RXR-selective retinoid SR11,217, which transactivates the RXRE-tk-CAT effectively, but beta RARE-tk-LUC poorly, is unable to induce differentiation and has little effect on the expression of these early genes, The RAR-alpha-selective antagonist Ro 41-5253, which inhibits RARE-dependent transcriptional activation, has by itself no effect on the differentiation of PCC4.aza1R cells. However, this antagonist is able to block the induction of morphological differentiation by the RAR-selective retinoid as well as the expression of Hoxa-1, Hoxa-5, CRABP II, and RAR-beta. Our data suggest that the activation of RAR signaling pathways is important in initiating the cascade of changes in gene expression that result in the differentiation of PCC4.aza1R into mesenchymal stem cells. In addition, we demonstrate that the two mutant cell lines, PCC4(RA)-1 and PCC4(RA)-2, are defective at different stages of the differentiation program. C1 NIEHS,NIH,PULM PATHOBIOL LAB,CELL BIOL SECT,RES TRIANGLE PK,NC 27709. ROCHE INST MOLEC BIOL,ROCHE RES CTR,DEPT METAB DIS,NUTLEY,NJ 07110. SRI INT,MENLO PK,CA 94025. OI Jetten, Anton/0000-0003-0954-4445; NERVI, Clara/0000-0001-9341-0188 NR 51 TC 10 Z9 10 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 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD MAR PY 1996 VL 7 IS 3 BP 327 EP 337 PG 11 WC Cell Biology SC Cell Biology GA TY628 UT WOS:A1996TY62800006 PM 8838863 ER PT J AU Tornatore, C BakerCairns, B Yadid, G Hamilton, R Meyers, K Atwood, W Cummins, A Tanner, V Major, E AF Tornatore, C BakerCairns, B Yadid, G Hamilton, R Meyers, K Atwood, W Cummins, A Tanner, V Major, E TI Expression of tyrosine hydroxylase in an immortalized human fetal astrocyte cell line; In vitro characterization and engraftment into the rodent striatum SO CELL TRANSPLANTATION LA English DT Article; Proceedings Paper CT 2nd Annual Meeting of the American-Society-for-Neural-Transplantation CY APR 27-29, 1995 CL CLEARWATER, FL SP Amer Soc Neural Transplantat DE neural transplantation; human fetal glial cell line; Parkinson's disease; tyrosine hydroxylase ID NERVE GROWTH-FACTOR; DOPAMINERGIC-NEURONS INVITRO; GENETICALLY MODIFIED CELLS; PRODUCE L-DOPA; PARKINSONS-DISEASE; CHOLINERGIC NEURONS; MESENCEPHALIC GLIA; PUTAMINAL IMPLANTS; LUMBAR PUNCTURE; SEPTAL NEURONS AB The use of primary human fetal tissue in the treatment of neurodegenerative disorders, while promising, faces several difficult technical and ethical issues. An alternative approach that would obviate these problems would be to use immortalized cell lines of human fetal central nervous system origin. An immortalized human fetal astrocyte cell line (SVG) has been established (45) and herein we describe the in vitro and in vivo characteristics of this cell line which suggest that it may be a useful vehicle for neural transplantation. The SVG cell line is vimentin, GFAP, Thy 1.1 and MHC class I positive, and negative for neurofilament and neuron specific enolase, consistent with its glial origin. To determine whether the cell line could be used as a drug delivery system, a cDNA expression vector for tyrosine hydroxylase was constructed (phTH/Neo) and stably expressed in the SVG cells for over 18 months as demonstrated by immunohistochemistry and Western blotting of the stable transfectants. HPLC analysis of the supernatant from these cells, termed SVG-TH, consistently found 4-6 pmol/ml/min of 1-dopa produced with the addition of BH4 to the media. Furthermore, in cocultivation experiments with hNT neurons, PC-12 cells and primary rat fetal mesencephalic tissue, both the SVG and SVG-TH tells demonstrated neurotrophic potential, suggesting that they constituitively express factors with neuroregenerative potential. To determine the viability of these cells in vivo, SVG-TH cells were grafted into the striatum of Sprague-Dawley rats and followed over time. A panel of antibodies was used to unequivocally differentiate the engrafted cells from the host parenchyma, including antibodies to: SV40 large T antigen (expressed in the SVG-TH cells), human and rat MHC class 1, vimentin, GFAP, and tyrosine hydroxylase. While the graft was easily identified with the first week, over the course of a four week period of time the engrafted cells decreased in number. Concomittantly, rat CD4 and CD8 expression in the vicinity of the graft increased, consistent with xenograft rejection. When the SVG-TH cells were grafted to the lesioned striatum of a 6-hydroxydopamine lesioned rats, rotational behavior of the rat decreased as much as 80% initially, then slowly returned to baseline over the next four weeks, parallelling graft rejection. Thus, the SVG-TH cells can induce a functional recovery in an animal model of Parkinson's disease, however as a xenograft, the SVG cells are recognized by the immune system. C1 NINCDS, NIH, MOL MED & VIROL SECT, BETHESDA, MD 20892 USA. BAR ILAN UNIV, RAMAT GAN, ISRAEL. NINCDS, NIH, ELECTRON MICROSCOPY CORE FACIL, BETHESDA, MD 20892 USA. NINCDS, NIH, CNR, IMPLANTAT UNIT, BETHESDA, MD 20892 USA. RP NINCDS, NIH,MOL THERAPEUT SECT,BLDG 36,ROOM 5W21, 36 CONVENT DR, MSC 4164, BETHESDA, MD 20892 USA. NR 74 TC 48 Z9 50 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI PUTNAM VALLEY PA 18 PEEKSKILL HOLLOW RD, PO BOX 37, PUTNAM VALLEY, NY 10579 USA SN 0963-6897 EI 1555-3892 J9 CELL TRANSPLANT JI Cell Transplant. PD MAR-APR PY 1996 VL 5 IS 2 BP 145 EP 163 DI 10.1016/0963-6897(95)02041-1 PG 19 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA UB957 UT WOS:A1996UB95700004 PM 8689028 ER PT J AU Misiewicz, B Poltorak, M Gomez, M Glowa, JR Gold, PW Sternberg, EM AF Misiewicz, B Poltorak, M Gomez, M Glowa, JR Gold, PW Sternberg, EM TI Intracerebroventricularly transplanted embryonic neuronal tissue from inflammatory-resistant F344/N rats decreases acoustic startle responses in inflammatory-susceptible LEW/N rats SO CELL TRANSPLANTATION LA English DT Article; Proceedings Paper CT 2nd Annual Meeting of the American-Society-for-Neural-Transplantation CY APR 27-29, 1995 CL CLEARWATER, FL SP Amer Soc Neural Transplantat DE acoustic startle response; hypothalamus; neural transplantation; inflammation; stress ID CORTICOTROPIN-RELEASING FACTOR; PITUITARY-ADRENAL AXIS; INTERLEUKIN-1; HYPOTHALAMUS; HORMONE; SYSTEM; CELLS; CRF AB Recently, we have shown that intracerebral transplantation of fetal F344/N hypothalamic tissue into LEW/N rats converts the LEW/N inflammatory-susceptible phenotype into an inflammatory-resistant phenotype in LEW/N hosts, Because LEW/N rats also exhibit relatively high acoustic startle responses (ASRs) compared to F344/N rats, in the present study we examined the effects on ASR of transplantation of F344/N hypothalamic tissue into the third ventricle of LEW/N rats, Dissected neuronal tissue from F344/N rats (Day E15-16) was implanted into the third ventricle of LEW/N rats, After 4 wk of postoperative survival, the animals' responses to acoustic startle stimuli were tested. Compared to naive and sham-operated animals, LEW/N rats transplanted with hypothalamic tissue exhibited significant decreases in ASR amplitudes, A similar decrease in ASR amplitude was observed in the group of LEW/N rats transplanted with embryonic striatal tissue, Our results indicate that the third ventricular neuronal grafts may modulate behavioral responses in the LEW/N rats. Although the mechanism of this effect is unknown, these studies suggest that intracerebral neuronal transplantation is a viable method with which to explore mechanisms of behavioral, neuroendocrine, and inflammatory response associations. C1 NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032. RP Misiewicz, B (reprint author), NIMH,CLIN NEUROENDOCRINOL BRANCH,SECT NEUROENDOCRINE IMMUNOL & BEHAV,BLDG 10,RM 3S 231,BETHESDA,MD 20892, USA. NR 27 TC 6 Z9 6 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PD MAR-APR PY 1996 VL 5 IS 2 BP 287 EP 291 DI 10.1016/0963-6897(95)02027-6 PG 5 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA UB957 UT WOS:A1996UB95700015 PM 8689039 ER PT J AU Hermouet, S Aznavoorian, S Spiegel, AM AF Hermouet, S Aznavoorian, S Spiegel, AM TI In vitro and in vivo growth inhibition of murine melanoma K-1735 cells by a dominant negative mutant alpha subunit of the G(i2) protein SO CELLULAR SIGNALLING LA English DT Article DE melanoma; G(i2) proteins; malignant cell growth; tumor formation ID BETA-GAMMA-SUBUNITS; MATRIX-MEDIATED MOTILITY; GTP-BINDING PROTEINS; NIH 3T3 CELLS; SIGNAL-TRANSDUCTION; PERTUSSIS TOXIN; GS-ALPHA; POSSIBLE INVOLVEMENT; ADENYLYL CYCLASE; RECEPTOR AB In murine and rat fibroblasts, activation of several G proteins (G(i2), G(q), G(12)) can stimulate cell growth or transformation, and can induce tumor formation in nude mice; contrastingly, inactivation of G(i2) inhibits fibroblast proliferation in vitro. We investigated whether it is possible to modulate malignant cell growth in vitro and in vivo through alteration of G(i2) protein function. To do so, we introduced mutated a subunits of G(i2) (alpha(i2)) in CL19 cells, a clone of the murine melanoma cell line K-1735. When we did this, a constitutively activated mutant (alpha(i2)-R205L) and a dominant negative mutant (alpha(i2)-G204A) of alpha(i2) were stably expressed in CL19 cells. We found that the in vitro motility of all alpha(i2)-transfected CL19 cells was increased; however, overexpression and alteration of the function of G(i2) did not increase metastasis formation by CL19 cells in nude mice. Expression of alpha(i2)-R205L conferred a limited growth advantage to CL19 cells in vitro; in vivo, tumor formation and size, and overall survival of animals injected with CL19 cells expressing alpha(i2)-R205L, were similar to controls. In contrast, expression of the inactive alpha(i2)-G204A mutant inhibited CL19 growth in vitro by at least 50% in all conditions tested, and mice injected with cells expressing the alpha(i2)-G204A mutant showed delayed tumor formation, reduced tumor size, and longer survival. We conclude that G(i2) proteins contribute to malignant cell growth, and more importantly, that inactivation of G(i2) proteins can inhibit proliferation of melanoma cells and possibly of other malignant cells both in vitro and in vivo. C1 NIDDKD,METAB DIS BRANCH,NIH,BETHESDA,MD 20892. NCI,PATHOL LAB,DIV CANC BIOL & DIAG,NIH,BETHESDA,MD 20892. NR 39 TC 19 Z9 19 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD MAR PY 1996 VL 8 IS 3 BP 159 EP 166 DI 10.1016/0898-6568(95)02049-7 PG 8 WC Cell Biology SC Cell Biology GA UK212 UT WOS:A1996UK21200002 PM 8736698 ER PT J AU Basi, NS Okuya, S Rebois, RV AF Basi, NS Okuya, S Rebois, RV TI GTP binding to G(s) does not promote subunit dissociation SO CELLULAR SIGNALLING LA English DT Article DE adenylylcyclase; GTP gamma S; immunoprecipitation; magnesium ID BETA-GAMMA-SUBUNITS; STIMULATORY REGULATORY COMPONENT; ADENYLATE-CYCLASE; G-PROTEINS; ADRENERGIC-RECEPTOR; LIGAND-BINDING; RESOLUTION; INTERACT AB The stimulatory G protein (G,) mediates activation of adenylyl cyclase. G, is a heterotrimeric protein (alpha beta gamma) that is activated when guanosine triphosphate (GTP) or a non-hydrolyzable GTP analogue displaces tightly bound guanosine diphosphate (GDP) from the guanine nucleotide-binding site of the alpha-subunit (G(s) alpha). Divalent cations such as magnesium are also required for G(s) activation. Subunit dissociation can accompany G(s) activation and is thought to be critical for this process. We investigated the effects of MgCl2, and various purine nucleotides on G(s)-subunit dissociation and activation. Subunit dissociation was assayed by measuring the amount of G protein beta-subunit that was co-precipitated by G(s) alpha-specific antiserum. G(s) activation was determined by its ability to reconstitute adenylyl cyclase activity in S49 cyc(-) membranes that lack G(s) alpha. High concentrations of MgCl2 caused bound GDP to dissociate from G(s) and inactivated the protein unless high concentrations of GDP or GTP were present in solution. MgCl2 caused: a concentration-dependent dissociation of G(s) subunits. GTP gamma S (a non-hydrolyzable GTP analogue) shifted the MgCl2 concentration-response curve for subunit dissociation to lower concentrations of MgCl2, suggesting that GTP IS promoted subunit dissociation. On the other hand, GDP and GTP were equally effective in shifting the curve to higher concentration of MgCl2. These results suggest that GTP, the compound that activates G(s) in vivo, was no more effective at promoting G(s) subunit dissociation than was GDP. C1 NINCDS,MEMBRANE BIOCHEM SECT,LAB MOL & CELLULAR NEUROBIOL,NIH,BETHESDA,MD 20892. NR 25 TC 12 Z9 12 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD MAR PY 1996 VL 8 IS 3 BP 209 EP 215 DI 10.1016/0898-6568(95)02056-X PG 7 WC Cell Biology SC Cell Biology GA UK212 UT WOS:A1996UK21200009 PM 8736705 ER PT J AU DenisHenriot, D deMazancourt, P Goldsmith, PK Giudicelli, Y AF DenisHenriot, D deMazancourt, P Goldsmith, PK Giudicelli, Y TI G proteins in adipocytes and preadipocytes: Characterization, subcellular distribution, and potential roles for G(i2) and/or G(i3) in the control of cell proliferation SO CELLULAR SIGNALLING LA English DT Article DE adipocyte; preadipocyte; fat cell; G protein; raf; proliferation ID GTP-BINDING PROTEINS; MESSENGER-RNA LEVELS; PERTUSSIS TOXIN; ALPHA-SUBUNIT; SIGNAL-TRANSDUCTION; ADENYLATE-CYCLASE; RAT ADIPOCYTES; 3T3-L1 CELLS; ENDOPLASMIC-RETICULUM; ADP-RIBOSYLATION AB Guanosine triphosphate (GTP) binding protein subunits were studied by immunoblot analysis in particulate fractions from mature adipocytes, confluent preadipocytes, and in vitro-differentiated preadipocytes. Mature adipocytes express Gi alpha 1, Gi alpha 2, Gi alpha 3, Go alpha, Gq/11 alpha, G13 alpha and the long and shore isoforms of Gsa, but no Gz alpha or G12 alpha. Confluent and differentiated preadipocytes differ in having a higher content of Gi alpha 3 and G13 alpha and expressing G12 alpha. In contrast, they lack Gi alpha 1, Go alpha, and the short form of Gs alpha. The G-protein alpha subunits Gi alpha 2, Gs alpha (long isoform), and Gq/11 alpha, and G-protein beta subunits were unchanged throughout the differentiation process. By immunoblot and indirect immunofluorescence studies on confluent preadipocytes, we showed that Gi alpha 2 is present in the endoplasmic reticulum and marginally in plasma membranes and nuclei. In contrast, antibodies to Gi alpha 3 stained the Golgi apparatus. The role of G proteins on preadipocyte proliferation was studied using Bordetella pertussis toxin. Exposure of growing cells to this toxin in the presence of fetal calf serum (FCS) decreased [H-3]thymidine incorporation by 40% and induced a 40% increase in doubling time. This resulted in a 30% decrease in cell number per well after 48 h. These effects of B. pertussis toxin did not appear to be related to an increase in cyclic adenosine monophosphaee (cAMP) concentration, because forskolin had the opposite effect on cell proliferation. Finally, B. pertussis toxin prevented serum-induced Raf1 association to the plasma membrane, possibly by disrupting FCS-induced G beta gamma effects on the Ras/Raf1 pathway. Since Go alpha and Gi alpha 1 subunits were absent in preadipocytes, we conclude that Gi2 and/or Gi3 proteins transduce some mitogenic signals of FCS through release of G beta gamma subunits. The subcellular distribution of Gi alpha 2 and Gi alpha 3 suggests that part of their functions result from interactions with components other than the plasma membrane. C1 UNIV PARIS 05,INSERM CJF 9402,BIOCHIM LAB,FAC MED PARIS QUEST,HOP POISSY,F-78303 POISSY,FRANCE. NIDDKD,METAB DIS BRANCH,NIH,BETHESDA,MD 20892. NR 62 TC 16 Z9 16 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD MAR PY 1996 VL 8 IS 3 BP 225 EP 234 DI 10.1016/0898-6568(95)02058-6 PG 10 WC Cell Biology SC Cell Biology GA UK212 UT WOS:A1996UK21200011 PM 8736707 ER PT J AU Distler, C Bachevalier, J Kennedy, C Mishkin, M Ungerleider, LG AF Distler, C Bachevalier, J Kennedy, C Mishkin, M Ungerleider, LG TI Functional development of the corticocortical pathway for motion analysis in the macaque monkey: A C-14-2-deoxyglucose study SO CEREBRAL CORTEX LA English DT Review ID SUPERIOR TEMPORAL SULCUS; DORSAL TERMINAL NUCLEUS; ACCESSORY OPTIC TRACT; VISUAL AREA MT; CEREBRAL GLUCOSE-UTILIZATION; POSITRON EMISSION TOMOGRAPHY; RECEPTIVE-FIELD PROPERTIES; CENTRAL NERVOUS-SYSTEM; STRIATE CORTEX; CORTICAL CONNECTIONS AB The corticocortical pathway for motion analysis transmits visual information from striate cortex (V1) via V2, V3d, superior temporal sulcal areas MT, MST, and FST to motion-sensitive areas in the poor and upper bank of the anterior part of the superior temporal sulcus (AST). We studied the functional development of this pathway by applying the C-14-deoxyglucose method to rhesus monkeys (Macaca mulatta) ranging in age from 2 d to 3-4 years. A comparison of local cerebral glucose utilization (LCGU) in an intact and a visually deafferented hemisphere in each animal across the age range revealed that this pathway, immature at birth, reaches adult-like levels at 3 months of age. This developmental time course is reflected both in absolute LCGU and in the interhemispheric LGGU differences in all the areas of the pathway. At all ages. the interhemispheric difference in LCGU is largest in Vt and gradually declines along the pathway until a minimum is reached in AST. This decline likely reflects an increasing proportion of nonvisual inputs to the higher-order areas of the pathway. Measurements like those above taken in areas of inferior parietal cortex indicate that they mature at the same rate as those in the motion analysis pathway. However, comparison with findings on the functional development of the temporal areas of the occipitotemporal pathway for object vision (Bachevalier et al., 1991) suggests that areas along the motion analysis pathway and those in parietal cortex mature about 1 month earlier. C1 NIMH,NEUROPSYCHOL LAB,BETHESDA,MD 20892. NIMH,CEREBRAL METAB LAB,BETHESDA,MD 20892. NR 109 TC 51 Z9 51 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD MAR-APR PY 1996 VL 6 IS 2 BP 184 EP 195 DI 10.1093/cercor/6.2.184 PG 12 WC Neurosciences SC Neurosciences & Neurology GA UC121 UT WOS:A1996UC12100010 PM 8670649 ER PT J AU Turesky, RJ Gremaud, E Markovic, J Snyderwine, EG AF Turesky, RJ Gremaud, E Markovic, J Snyderwine, EG TI DNA adduct formation of the food-derived mutagen 2-amino-3-methylimidazo[4,5-f]quinoline in nonhuman primates undergoing carcinogen bioassay SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID IDENTIFICATION; ACTIVATION; INDUCTION; MONKEYS; IQ; CANCER; PHIP; RAT; 2-AMINO-3-METHYLIMIDAZOLO<4,5-F>QUINOLINE; N-(DEOXYGUANOSIN-8-YL)-IQ AB DNA adduct formation of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) was investigated in cynomolgus monkeys. The pattern and distribution of DNA adducts examined by P-32-postlabeling were similar in all tissues 24 h after a single oral dose of IQ (20 mg/kg). The highest DNA adduct levels were found in the liver (3.67-11.19 adducts per 10(7) bases), followed by kidney (0.53-1.16 adducts per 10(7) bases), with comparable adduct levels detected in colon, heart, and pancreas (0.15-0.40 adducts per 10(7) leases). Two 2'-deoxyguanosine (dG) adducts accounted for approximately 90% of the observed lesions in all tissues. N-(Deoxyguanosin-8- yl)-2-amino-3-methylimidazo[4,5-f]quinoline (dG-C8-IQ) was the major adduct and accounted for approximately 50-80% of the adducts, followed by 5-(deoxyguanosin-N-2-yl)-amino-3-methylimidazo[4,5-f]quinoline (dG-N-2-IQ) which accounted for 20-40% of the adducts. DNA adduct formation was also investigated in animals undergoing carcinogen bioassay with IQ administered at 10 or 20 mg/kg, 5 days per week for up to 9.2 years. In chronically treated animals, the DNA adduct levels in pancreas, kidney, and heart increased on average by 40- to 90-fold over those observed in animals given a single dose, while only 3- to 10-fold increases in adducts were observed in colon and liver. A sharp increase in the contribution of dG-N-2-IQ to total DNA adducts occurred in all slowly dividing tissues during chronic treatment, and dG-N-2-IQ became the predominant lesion. There was no preferential accumulation of dG-N-2-IQ in the colon, a tissue with a high rate of cell division, and dG-C8-IQ remained the predominant lesion. These findings point to a preferential removal of the dG-C8-IQ adduct by enzyme repair system(s) in slowly dividing tissues. The respective roles of dG-N-2-IQ and dG-C8-IQ, and the involvement of adduct repair in the potent hepatocarcinogenicity of IQ, merit further investigation. C1 NCI, DIV BASIC SCI, EXPTL CARCINOGENESIS LAB, BETHESDA, MD 20892 USA. RP Turesky, RJ (reprint author), NESTEC LTD, NESTLE RES CTR, VERS CHEZ LES BLANC, CH-1000 LAUSANNE 26, SWITZERLAND. NR 48 TC 26 Z9 26 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X EI 1520-5010 J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD MAR PY 1996 VL 9 IS 2 BP 403 EP 408 DI 10.1021/tx950132j PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA TY393 UT WOS:A1996TY39300008 PM 8839042 ER PT J AU Smith, MBK Schmidt, BF Czerwinski, G Taneyhill, LA Snyder, EJ Kline, AM Michejda, CJ Smith, RH AF Smith, MBK Schmidt, BF Czerwinski, G Taneyhill, LA Snyder, EJ Kline, AM Michejda, CJ Smith, RH TI Specificity of DNA alkylation by 1-(2-chloroethyl)-3-alkyl-3-acyltriazenes depends on the structure of the acyl group: Kinetic and product studies SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID 1,3-DIALKYL-3-ACYLTRIAZENES; DECOMPOSITION; AGENTS; GASTRIN; RATES AB The reactions of calf thymus DNA with ten 1-(2-chloroethyl)-3-alkyl-3-acyltriazenes of varying acyl side chain structure were studied alone, or in the presence of porcine liver esterase in pH 7.0 phosphate buffer. In several. of the key triazenes, the acyl substituent contained a free carboxylic acid group. With esterase present in the reaction mixture, the resultant levels of DNA alkylation could be correlated with the kinetic rates of decomposition of the triazenes. Under these conditions, the predominant pathway of decomposition involved deacylation of the parent triazene and eventual production of an alkanediazonium ion. This intermediate subsequently alkylated DNA-guanine to give 7-alkylguanine as the principal reaction product. In the absence of esterase, the order of DNA alkylation for all of the acyltriazenes did not correlate with their respective rates of decomposition, leading to the conclusion that the triazenes did not decompose by the expected mode of uncatalyzed N(2)-N(3) heterolyic cleavage. The major DNA alkylation product from the N(3)-methyltriazenes was 7-methylguanine, instead of the expected 7-(chloroethyl)- and 7-(hydroxyethyl)guanine products, which suggested that the acyl group was being hydrolyzed. However, acyltriazenes with an N(3)-benzyl group rather than a methyl in this position produced very Little 7-benzylguanine product, contrary to prediction. An alternative mechanism involving internally assisted hydrolysis of the side chain ester is proposed to explain these results. NMR product analysis and computational studies were carried out to lend support to the postulated mechanism. C1 WESTERN MARYLAND COLL,DEPT CHEM,WESTMINSTER,MD 21157. RP Smith, MBK (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MOLEC ASPECTS DRUG DESIGN SECT,FREDERICK,MD 21702, USA. RI Taneyhill, Lisa/K-1815-2013 FU NCI NIH HHS [N01-CO-46000] NR 19 TC 4 Z9 4 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD MAR PY 1996 VL 9 IS 2 BP 466 EP 475 PG 10 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA TY393 UT WOS:A1996TY39300017 PM 8839051 ER PT J AU Bal, W Lukszo, J Kasprzak, KS AF Bal, W Lukszo, J Kasprzak, KS TI Interactions of Nickel(II) with histones: Enhancement of 2'-deoxyguanosine oxidation by Ni(II) complexes with CH3CO-Cys-Ala-Ile-His-NH2, a putative metal binding sequence of histone H3 SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID HYDROGEN-PEROXIDE; HYDROXYLATION; OXYGEN; DNA AB Studies of 2'-deoxyguanosine oxidation by hydrogen peroxide in the presence of CH3CO-Cys-Ala-Ile-His-NH2 (CAIH) and/or NiCl2 have been carried out in 100 mM phosphate buffer (pH 7.4) at 37 degrees C. The dimeric CAIH oxidation product, CAIH disulfide, and its weak, octahedral Ni(II) complex, rather than the monomeric CAIH and its strong, square-planar Ni(II) complex, were found to be major catalysts of 8-oxo-2'-deoxyguanosine (8-oxo-dG) formation, The presence of Ni(II) largely enhanced 8-oxo-dG yield, especially at submillimolar concentrations of H2O2. The reaction was found not to involve detectable amounts of free radicals or Ni(III). These results, together with those published previously [Bal, W. et al, (1995) Chem. Res. Toxicol. 8, 683-692], lay a framework for the detailed investigations of the interactions of histone octamer with Ni(II) and other metal ions. They also suggest that molecular mechanisms of nickel carcinogenesis may involve oxidative damage processes catalyzed by weak Ni(II) complexes with cellular components. C1 NIAID,MOLEC STRUCT LAB,ROCKVILLE,MD 20852. RP Bal, W (reprint author), NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,BLDG 538,ROOM 205,FREDERICK,MD 21702, USA. NR 22 TC 38 Z9 38 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD MAR PY 1996 VL 9 IS 2 BP 535 EP 540 DI 10.1021/tx950157i PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA TY393 UT WOS:A1996TY39300025 PM 8839059 ER PT J AU Halmes, NC Hinson, JA Martin, BM Pumford, NR AF Halmes, NC Hinson, JA Martin, BM Pumford, NR TI Glutamate dehydrogenase covalently binds to a reactive metabolite of acetaminophen SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID SUBCELLULAR LIVER FRACTIONS; PROTEIN ADDUCTS; MOUSE-LIVER; MICE; HEPATOTOXICITY; RESPIRATION; INVITRO; ASSAY AB The mechanism of the hepatotoxicity of the analgesic acetaminophen is believed to be mediated by covalent binding to protein; however, critical targets which effect the toxicity are unknown. It has been shown that mitochondrial respiration in vivo is inhibited in mice as early as 1 h following a hepatotoxic dose of acetaminophen, and it is postulated that covalent binding to critical mitochondrial proteins may be important. A time course of mitochondrial proteins stained with anti-acetaminophen in an immunoblot detected two major adducts of 50 and 67 kDa as early as 30 min after a hepatotoxic dose of acetaminophen in mice. To further understand the role of covalent binding to mitochondrial proteins and acetaminophen hepatotoxicity, we have purified and identified a 50 kDa mitochondrial protein which becomes covalently bound to a reactive metabolite of acetaminophen. An N-terminal sequence of the 50 kDa adduct was 100% homologous with the deduced amino acid sequence of glutamate dehydrogenase. In addition, the purified protein was immunochemically reactive with rat liver anti-glutamate dehydrogenase. Enzyme activity of glutamate dehydrogenase was significantly decreased in mice 1 h following hepatotoxic treatment with acetaminophen. These data suggest that acetaminophen hepatotoxicity may in part be mediated by covalent binding to glutamate dehydrogenase. C1 UNIV ARKANSAS,DIV TOXICOL,LITTLE ROCK,AR 72205. NIMH,NIH,BETHESDA,MD 20892. FU NIGMS NIH HHS [GM48749] NR 28 TC 51 Z9 53 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD MAR PY 1996 VL 9 IS 2 BP 541 EP 546 DI 10.1021/tx950158a PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA TY393 UT WOS:A1996TY39300026 PM 8839060 ER PT J AU Zhao, WY Kloczkowski, A Mark, JE Erman, B Bahar, I AF Zhao, WY Kloczkowski, A Mark, JE Erman, B Bahar, I TI Make tough plastic films from gelatin SO CHEMTECH LA English DT Article C1 BOGAZICI UNIV,POLYMER RES CTR,ISTANBUL,TURKEY. UNIV CINCINNATI,DEPT CHEM,POLYMER RES CTR,CINCINNATI,OH 45221. NIH,MATH BIOL LAB,BETHESDA,MD 20892. RP Zhao, WY (reprint author), SRI INT,MENLO PK,CA 94025, USA. RI Kloczkowski, Andrzej/B-9868-2012; OI ERMAN, BURAK/0000-0002-2496-6059 NR 22 TC 12 Z9 15 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0009-2703 J9 CHEMTECH JI Chemtech PD MAR PY 1996 VL 26 IS 3 BP 32 EP 38 PG 7 WC Chemistry, Applied SC Chemistry GA TY399 UT WOS:A1996TY39900010 ER PT J AU Devereux, TR Taylor, JA Barrett, JC AF Devereux, TR Taylor, JA Barrett, JC TI Molecular mechanisms of lung cancer - Interaction of environmental and genetic factors SO CHEST LA English DT Article; Proceedings Paper CT Symposium on Environmental Lung Disease in Exposures and Mechanisms, at the Thomas-L-Petty-Aspen-Lung-Conference 38th Annual Meeting CY JUL 07-10, 1995 CL ASPEN, CO SP Thomas L Petty Aspen Lung Conf ID SQUAMOUS-CELL CARCINOMA; TUMOR SUPPRESSOR GENE; CIGARETTE-SMOKING; URANIUM MINERS; P53 MUTATIONS; 3P DELETION; RAS; CHROMOSOME-3; CARCINOGENESIS; SUSCEPTIBILITY C1 NIEHS, ENVIRONM CARCINOGENESIS PROGRAM, RES TRIANGLE PK, NC 27709 USA. NR 80 TC 29 Z9 32 U1 1 U2 3 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD MAR PY 1996 VL 109 IS 3 SU S BP S14 EP S19 DI 10.1378/chest.109.3_Supplement.14S PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA UA472 UT WOS:A1996UA47200009 PM 8598134 ER PT J AU Lasky, JA Bonner, JC Tonthat, B Brody, AR AF Lasky, JA Bonner, JC Tonthat, B Brody, AR TI Chrysotile asbestos induces PDGF-A chain-dependent proliferation in human and rat lung fibroblasts in vitro SO CHEST LA English DT Article; Proceedings Paper CT Symposium on Environmental Lung Disease in Exposures and Mechanisms, at the Thomas-L-Petty-Aspen-Lung-Conference 38th Annual Meeting CY JUL 07-10, 1995 CL ASPEN, CO SP Thomas L Petty Aspen Lung Conf ID GROWTH-FACTOR; PULMONARY MACROPHAGES; RECEPTORS C1 NIEHS,PULM PATHOBIOL LAB,RES TRIANGLE PK,NC 27709. RP Lasky, JA (reprint author), TULANE UNIV,SCH MED,PULM & CRIT CARE MED SECT,1430 TULANE AVE,NEW ORLEANS,LA 70112, USA. FU NHLBI NIH HHS [HL03374]; NIEHS NIH HHS [ES06766] NR 12 TC 6 Z9 6 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 MAR PY 1996 VL 109 IS 3 SU S BP S26 EP S28 DI 10.1378/chest.109.3_Supplement.02S6-a PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA UA472 UT WOS:A1996UA47200014 PM 8598140 ER PT J AU Allen, JW Dix, DJ Collins, BW Merrick, BA He, C Selkirk, JK PoormanAllen, P Dresser, ME Eddy, EM AF Allen, JW Dix, DJ Collins, BW Merrick, BA He, C Selkirk, JK PoormanAllen, P Dresser, ME Eddy, EM TI HSP70-2 is part of the synaptonemal complex in mouse and hamster spermatocytes SO CHROMOSOMA LA English DT Article ID HEAT-SHOCK PROTEINS; SPERMATOGENIC CELLS; EXPRESSION; IDENTIFICATION; MEIOSIS; NUCLEI; GENE AB Mouse spermatogenic cells are known to express HSP70-2, a member of the HSP70 family of heat-shock proteins. The purpose of the present study was to characterize further the expression and localization of HSP70-2 in meiotic cells of mice and hamsters. After separating mouse spermatogenic cells into cytoplasmic and nuclear fractions, proteins were separated by two-dimensional gel electrophoresis and detected with HSP-specific antibodies. Of several HSP70 proteins identified in the cytoplasm, only HSC70 and HSP70-2 were also detected in the nucleus. Immunocytological analyses of spermatocyte prophase cells revealed that HSP70-2 was associated with the synaptonemal complex. Surface-spread synaptonemal complexes at pachytene and diplotene stages labeled distinctly with the antiserum to HSP70-2. Synaptonemal complexes from fetal mouse oocytes failed to show any evidence of HSP70-2. Reverse-transcriptase-polymerase chain reaction (RT-PCR) analyses of gene expression confirmed this sex specificity; Hsp70-2 mRNA was detected in mouse testes, but not ovaries. These findings are suggestive of a previously unsuspected sexual dimorphism in structure and/or function of the synaptonemal complex. C1 NIEHS,MOLEC CARCINOGENESIS LAB,RES TRIANGLE PK,NC 27709. GLAXO WELLCOME INC,DIV MED SAFETY EVALUAT,RES TRIANGLE PK,NC 27709. OKLAHOMA MED RES FDN,PROGRAM MOLEC & CELL BIOL,OKLAHOMA CITY,OK 73104. NIEHS,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC 27709. RP Allen, JW (reprint author), US EPA,HLTH EFFECTS RES LAB,RES TRIANGLE PK,NC 27711, USA. FU NIGMS NIH HHS [GM45250] NR 32 TC 75 Z9 77 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0009-5915 J9 CHROMOSOMA JI Chromosoma PD MAR PY 1996 VL 104 IS 6 BP 414 EP 421 DI 10.1007/BF00352265 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA UD786 UT WOS:A1996UD78600003 PM 8601336 ER PT J AU Takimoto, CH Lu, ZH Zhang, RW Liang, MD Larson, LV Cantilena, LR Grem, JL Allegra, CJ Diasio, RB Chu, E AF Takimoto, CH Lu, ZH Zhang, RW Liang, MD Larson, LV Cantilena, LR Grem, JL Allegra, CJ Diasio, RB Chu, E TI Severe neurotoxicity following 5-fluorouracil-based chemotherapy in a patient with dihydropyrimidine dehydrogenase deficiency SO CLINICAL CANCER RESEARCH LA English DT Article ID FAMILIAL PYRIMIDINEMIA; BIOCHEMICAL BASIS; TOXICITY; THYMIDINE; LIVER AB Patients with decreased dihydropyrimidine dehydrogenase (DPD) activity are at increased risk for experiencing serious adverse reactions following 5-fluorouracil (5-FU)-based chemotherapy. Symptoms include severe and potentially life-threatening gastrointestinal toxicity, myelosuppression, and neurological toxicity. In the present study, we describe a 50-year-old Caucasian man who developed severe encephalopathy during his second cycle of 5-FU chemotherapy. The patient remained in a comatose state for 4 days but then showed dramatic improvement in his neurological status following continuous i.v. infusion of thymidine at 8 g/m(2)/day. Laboratory studies revealed the patient to be severely DPD deficient, as demonstrated by DPD enzyme activity from peripheral blood mononuclear cells being below the lower limit of the 95th percentile of a control population and by Western immunoblot analysis showing undetectable levels of DPD protein. Additional studies revealed a significant defect in pyrimidine catabolism with a 3.3- and 365-fold increase in the levels of uracil in plasma and urine, respectively, compared to normal subjects. Family studies suggest that the inheritance pattern of this syndrome is complex and most consistent with an autosomal recessive trait. This study demonstrates that cancer patients with DPD deficiency are at increased risk for developing severe neurological toxicity secondary to 5-FU chemotherapy, and that infusional thymidine should be considered as a potential rescue agent against this particular host toxicity. C1 NCI, NAVY MED ONCOL BRANCH, NIH, BETHESDA, MD 20889 USA. UNIV ALABAMA, DEPT PHARMACOL & TOXICOL, BIRMINGHAM, AL 35294 USA. UNIFORMED SERV UNIV HLTH SCI, DIV CLIN PHARMACOL, BETHESDA, MD 20814 USA. FU NCI NIH HHS [CA-64214] NR 20 TC 116 Z9 119 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR PY 1996 VL 2 IS 3 BP 477 EP 481 PG 5 WC Oncology SC Oncology GA TY620 UT WOS:A1996TY62000006 PM 9816193 ER PT J AU Thibault, A Samid, D Tompkins, AC Figg, WD Cooper, MR Hohl, RJ Trepel, J Liang, B Patronas, N Venzon, DJ Reed, E Myers, CE AF Thibault, A Samid, D Tompkins, AC Figg, WD Cooper, MR Hohl, RJ Trepel, J Liang, B Patronas, N Venzon, DJ Reed, E Myers, CE TI Phase I study of lovastatin, an inhibitor of the mevalonate pathway, in patients with cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID COENZYME-A REDUCTASE; COMPETITIVE INHIBITOR; MEVINOLIN AB Lovastatin, an inhibitor of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (the major regulatory enzyme of the mevalonate pathway of cholesterol synthesis), displays antitumor activity in experimental models. We therefore conducted a Phase I trial to characterize the tolerability of lovastatin administered at progressively higher doses to cancer patients. From January 1992 to July 1994, 88 patients with solid tumors (median age, 57 +/- 14 years) were treated p.o. with 7-day courses of lovastatin given monthly at doses ranging from 2 to 45 mg/kg/day. The inhibitory effects of lovastatin were monitored through serum concentrations of cholesterol and ubiquinone, two end products of the mevalonate pathway. Concentrations of lovastatin and its active metabolites were also determined, by bioassay, in the serum of selected patients. Cyclical treatment with lovastatin markedly inhibited the mevalonate pathway, evidenced by reductions in both cholesterol acid ubiquinone concentrations, by up to 43 and 49% of pretreatment values, respectively. The effect was transient, however, and its magnitude appeared to be dose independent. Drug concentrations reached up to 3.9 mu M and were in the range associated with antiproliferative activity in vitro. Myopathy was the dose-limiting toxicity. Other toxicities included nausea, diarrhea, and fatigue. Treatment with ubiquinone was associated with reversal of lovastatin-induced myopathy, and its prophylactic administration prevented the development of this toxicity in a cohort of 56 patients. One minor response was documented in a patient with recurrent high-grade glioma. Lovastatin given p.o. at a dose of 25 mg/kg daily for 7 consecutive days is well tolerated. The occurrence of myopathy, the dose-limiting toxicity, can be prevented by ubiquinone supplementation. To improve on the transient inhibitory activity of this dosing regimen on the mevalonate pathway, alternative schedules based on uninterrupted administration of lovastatin should also be studied. C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT NEURORADIOL,BETHESDA,MD 20892. NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. NCI,BIOMETR SECT,BETHESDA,MD 20892. UNIV IOWA,COLL MED,DIV HEMATOL ONCOL,IOWA CITY,IA 52242. UNIV IOWA,COLL MED,DIV CLIN PHARMACOL,IOWA CITY,IA 52242. RI Venzon, David/B-3078-2008; Figg Sr, William/M-2411-2016 NR 27 TC 289 Z9 297 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 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR PY 1996 VL 2 IS 3 BP 483 EP 491 PG 9 WC Oncology SC Oncology GA TY620 UT WOS:A1996TY62000007 PM 9816194 ER PT J AU Kopp, WC Urba, WJ Rager, HC Alvord, WG Oppenheim, JJ Smith, JW Longo, DL AF Kopp, WC Urba, WJ Rager, HC Alvord, WG Oppenheim, JJ Smith, JW Longo, DL TI Induction of interleukin 1 receptor antagonist after interleukin 1 therapy in patients with cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID IL-1 RECEPTOR; SIGNAL TRANSDUCTION; II RECEPTOR; BINDING; CELLS; ENDOTOXEMIA; ARTHRITIS; BLOCKADE; PROTEIN; HUMANS AB The interleukin 1 receptor antagonist (IL-1ra) is a naturally occurring molecule that shares homology with IL-1 alpha and IL-1 beta and binds competitively to IL-1 receptors. Serum concentrations of IL-1ra mere measured by ELISA in patients enrolled in Phase I clinical trials of IL-1 alpha and IL-1 beta given by 15-min infusion. Pretreatment levels of IL-lra were <1500 (mean, 453 +/- 57) pg/ml. IL-1ra levels were increased in some patients within 1 h of completing the IL-1 infusion. By 2 h after infusion, serum levels of IL-1ra had increased dramatically, and they remained stable 4 h after infusion. There was evidence that peak IL-1ra levels were IL-1 dose dependent. Seven patients treated with IL-1 alpha had IL-1ra levels that exceeded 1 mu g/ml. In contrast, serum levels of IL-1 declined rapidly and were undetectable 1 h after completing IL-1 infusion in most patients receiving <1.0 mu g/kg. IL-1ra levels remained slightly elevated over pretreatment values in serum obtained 18-24 h after IL-1 infusion, but there was no evidence for progressive accumulation over repeated days of therapy. A similar pattern of IL-lra elevation was observed after the last IL-1 infusion on day 6. This study shows that cancer patients produce 2 to >6 log incremental increases in IL-1ra rapidly following treatment with IL-1, a response that has implications for the design of future clinical trials with IL-1 and with agents thought to induce IL-1 production. C1 NCI,FREDERICK CANC RES & DEV CTR,DYNCORP,PROGRAM RESOURCES INC,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,DATA MANAGEMENT SERV INC,FREDERICK,MD 21702. RP Kopp, WC (reprint author), NCI,FREDERICK CANC RES & DEV CTR,SCI APPLICAT INT CORP,CLIN SERV PROGRAM,POB B,FREDERICK,MD 21702, USA. NR 43 TC 13 Z9 15 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 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR PY 1996 VL 2 IS 3 BP 501 EP 506 PG 6 WC Oncology SC Oncology GA TY620 UT WOS:A1996TY62000009 PM 9816196 ER PT J AU Normanno, N Bianco, C Damiano, V deAngelis, E Selvam, MP Grassi, M Magliulo, G Tortora, G Bianco, AR Mendelsohn, J Salomon, DS Ciardiello, F AF Normanno, N Bianco, C Damiano, V deAngelis, E Selvam, MP Grassi, M Magliulo, G Tortora, G Bianco, AR Mendelsohn, J Salomon, DS Ciardiello, F TI Growth inhibition of human colon carcinoma cells by combinations of anti-epidermal growth factor-related growth factor antisense oligonucleotides SO CLINICAL CANCER RESEARCH LA English DT Article ID RECEPTOR MONOCLONAL-ANTIBODIES; FACTOR-ALPHA; COLORECTAL TUMORS; CANCER-CELLS; EXPRESSION; AMPHIREGULIN; LINE; PROLIFERATION; GENE; MICE AB GEO is a well-differentiated colon cancer cell line that coexpresses the epidermal growth factor-like growth factors CRTPTO (CR), amphiregulin (AR), and transforming growth factor alpha. (TGF-alpha). Antisense 20-mer phosphorothioate oligodeoxynucleotides (AS S-oligos) directed against CR, AR, and TGF-alpha mRNAs were equipotent in their ability to inhibit both the anchorage-dependent growth and the anchorage-independent growth (AIG) of GEO cells, with a 50% inhibitory concentration of about 5 mu M in the AIG assay. A supraadditive effect was observed when a combination of S-oligos was used. For example, a combination of two different AS S-oligos (either AR + CR, or TGF-alpha + CR, or TGF-alpha + AR) at a concentration of 1 mu M each (total concentration, 2 mu M) resulted in 50% inhibition of GEO cells AIG, whereas the use of each AS S-Oligo at a 1 or 2 mu M concentration resulted respectively in about 10 and 20% growth inhibition. A combination of the three AS S-oligos was even more effective, resulting in about 60% inhibition of GEO cells AIG at a concentration of 1 mu M each (3 mu M total concentration). The AS S-oligos were also able to inhibit specifically the expression of either AR, CR, or TGF-alpha proteins in GEO cells, as assessed using immunocytochemistry or Western blot analysis. Finally, a supraadditive growth inhibitory effect of the AS S-oligos and an epidermal growth factor receptor-blocking antibody (monoclonal antibody 528) was observed. These data suggest that the use of a combination of AS S-oligos directed against different growth factors and antibodies directed against their receptors might result in an efficient inhibition of colon carcinoma cell growth. C1 UNIV FREDERICO II, FAC MED & CHIRURG, DIPARTIMENTO ENDOCRINOL & ONCOL MOL & CLIN, I-80131 NAPLES, ITALY. NCI, TUMOR IMMUNOL & BIOL LAB, TUMOR GROWTH FACTOR SECT, NIH, BETHESDA, MD USA. US FDA, ROCKVILLE, MD 20852 USA. MEM SLOAN KETTERING CANC CTR, DEPT MED, NEW YORK, NY 10021 USA. RP Normanno, N (reprint author), FDN PASCALE, ITN, I-80131 NAPLES, ITALY. OI Ciardiello, Fortunato/0000-0002-3369-4841; Normanno, Nicola/0000-0002-7158-2605 NR 53 TC 59 Z9 60 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR PY 1996 VL 2 IS 3 BP 601 EP 609 PG 9 WC Oncology SC Oncology GA TY620 UT WOS:A1996TY62000022 PM 9816209 ER PT J AU Saravolatz, L Neaton, JD Sacks, L Deyton, L Rhame, F Sherer, R AF Saravolatz, L Neaton, JD Sacks, L Deyton, L Rhame, F Sherer, R TI CD4(+) T lymphocyte counts and patterns of mortality among patients infected with human immunodeficiency virus who were enrolled in community programs for clinical research on AIDS SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID PNEUMOCYSTIS-CARINII PNEUMONIA; HIV-INFECTION; NATURAL-HISTORY; ANTIRETROVIRAL THERAPY; DISEASE; RISK; PROGRESSION; ZIDOVUDINE; TYPE-1; PREDICTORS AB CD4(+) T lymphocyte measurements are used frequently in clinical practice and have important prognostic implications. In this study, we describe mortality patterns for 5,204 human immunodeficiency virus (HIV)-infected patients classified in different CD4(+) cell strata; patients with and patients without a history of disease progression were included, Patients were enrolled in studies sponsored by the Terry Beirn Community Programs for Clinical Research on AIDS of the National Institute of Allergy and Infectious Diseases between September 1990 and December 1993. Over a median follow-up period of 23.6 months, 1,703 of the 5,204 patients died, For those with CD4(+) cell counts (/mm(3)) of <25, 25-49, 50-99, 100-199, and 200-499, the cumulative mortality rates after 24 months were 72%, 58%, 47%, 27%, and 10%, respectively. The median survival time was 15 months for those with CD4(+) cell counts of <25 cells/mm(3); 21 months for those with CD4(+) cell counts of 25-49 cells/mm(3); and 40 months for patients with CD4(+) cell counts of 100-199/mm(3), In each CD4(+) cell stratum, mortality rates were higher for those with a history of disease progression at entry into the study; across all CD4(+) cell strata, mortality was 60% greater (relative risk = 1.6; 95% confidence interval = 1.5-1.8). These data should be useful in planning clinical trials, and they have implications in terms of the frequency with which CD4(+) cell counts should be measured to monitor the progression of HIV infection. C1 UNIV MINNESOTA,SCH PUBL HLTH,DIV BIOSTAT,MINNEAPOLIS,MN 55455. UNIV MINNESOTA,DEPT MED,DIV INFECT DIS,MINNEAPOLIS,MN 55455. VET AFFAIRS MED CTR,WASHINGTON REG AIDS PROGRAM,INFECT DIS SECT,WASHINGTON,DC 20422. NIAID,DIV AIDS,HIV RES BRANCH,BETHESDA,MD 20892. COOK CTY HOSP,COOK CTY HIV PRIMARY CARE CTR,CHICAGO,IL 60612. RP Saravolatz, L (reprint author), HENRY FORD HOSP,DIV INFECT DIS,2799 W GRAND BLVD,CFP-103,DETROIT,MI 48202, USA. FU NIAID NIH HHS [N01-AI-45229] NR 54 TC 13 Z9 13 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAR PY 1996 VL 22 IS 3 BP 513 EP 520 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA TY732 UT WOS:A1996TY73200019 PM 8852972 ER PT J AU Andrich, MP Chen, CC AF Andrich, MP Chen, CC TI Bone scan injection artifacts SO CLINICAL NUCLEAR MEDICINE LA English DT Article C1 NIH,WARREN G MAGNUSON CLIN CTR,DEPT NUCL MED,BETHESDA,MD 20892. NR 0 TC 5 Z9 6 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0363-9762 J9 CLIN NUCL MED JI Clin. Nucl. Med. PD MAR PY 1996 VL 21 IS 3 BP 260 EP 262 DI 10.1097/00003072-199603000-00021 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA TZ555 UT WOS:A1996TZ55500021 PM 8846581 ER PT J AU Vaquero, JJ Rahms, H Green, MV delPozo, F AF Vaquero, JJ Rahms, H Green, MV delPozo, F TI Dynamic circular buffering: A technique for equilibrium gated blood pool imaging SO COMPUTERS IN BIOLOGY AND MEDICINE LA English DT Article DE gated blood pool imaging function; real time; computer processing; ventricular ID VENTRICULAR-FUNCTION AB We have devised a software technique called ''dynamic circular buffering'' (DCB) with which we create a gated blood pool image sequence of the heart in real time using the best features of LIST and FRAME mode methods of acquisition/processing. The routine is based on the concept of independent ''agents'' acting on the timing and position data continuously written into the DCB. This approach allows efficient asynchronous operation on PC-type machines and enhanced capability on systems capable of true multiprocessing and multithreading. C1 NATL INST HLTH,DEPT NUCL MED,CLIN CTR,BETHESDA,MD 20892. RP Vaquero, JJ (reprint author), UNIV POLITECN MADRID,ETSI TELECOMMUNICAC,GRP BIOINGN & TELEMED,CIUDAD UNIV S-N,E-28040 MADRID,SPAIN. RI Vaquero, Juan Jose/D-3033-2009; DEL POZO GUERRERO, FRANCISCO/H-6668-2015 OI Vaquero, Juan Jose/0000-0001-9200-361X; DEL POZO GUERRERO, FRANCISCO/0000-0001-9919-9125 NR 8 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0010-4825 J9 COMPUT BIOL MED JI Comput. Biol. Med. PD MAR PY 1996 VL 26 IS 2 BP 113 EP 121 PG 9 WC Biology; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Computer Science; Engineering; Mathematical & Computational Biology GA TZ151 UT WOS:A1996TZ15100002 PM 8904285 ER PT J AU Sirigu, A Grafman, J AF Sirigu, A Grafman, J TI Selective impairments within episodic memories SO CORTEX LA English DT Article ID DISEASE AB We report the case of a patient (T.R.) who developed a severe and selective amnesia for names and dates associated with events. His amnesia was temporally limited, affecting only the last two to three decades of his life. When recalling an event he was able to evoke both its content and place, while he could not provide any information about people (names or their physical features) and the time (date/period) of its occurrence. His performance on event-memory tests was consistent across the type of material used (personal and public events) or the period of life investigated. These results suggest that knowledge of an episode is specified across multiple representations. C1 NINCDS,COGNIT NEUROSCI SECT,MED NEUROL BRANCH,BETHESDA,MD. OI Grafman, Jordan H./0000-0001-8645-4457 NR 12 TC 11 Z9 11 U1 0 U2 0 PU MASSON DIVISIONE PERIODICI PI MILAN PA VIA STATUTO 2/4, 20121 MILAN, ITALY SN 0010-9452 J9 CORTEX JI Cortex PD MAR PY 1996 VL 32 IS 1 BP 83 EP 95 PG 13 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA UB975 UT WOS:A1996UB97500005 PM 8697754 ER PT J AU Vukmir, RB Bircher, NG Radovsky, A AF Vukmir, RB Bircher, NG Radovsky, A TI Cardiac arrest and sodium bicarbonate - Reply SO CRITICAL CARE MEDICINE LA English DT Letter C1 UNIV PITTSBURGH,MED CTR,DEPT ANESTHESIOL CRIT CARE MED,PITTSBURGH,PA. NIEHS,RES TRIANGLE PK,NC 27709. RP Vukmir, RB (reprint author), SAFAR CTR RESUSCITAT RES,PITTSBURGH,PA, USA. NR 10 TC 0 Z9 0 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 MAR PY 1996 VL 24 IS 3 BP 547 EP 548 DI 10.1097/00003246-199603000-00030 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA UB546 UT WOS:A1996UB54600030 ER PT J AU Wolffe, AP Pruss, D AF Wolffe, AP Pruss, D TI Chromatin: Hanging on to histones SO CURRENT BIOLOGY LA English DT Article ID TRANSCRIPTION AB Transcriptional control at a number of promoters has been found to involve the highly selective recognition of individual core histones by regulatory proteins, showing how the eukaryotic transcriptional machinery is adapted to function in a chromosomal environment. RP Wolffe, AP (reprint author), NICHHD,NIH,MOLEC EMBRYOL LAB,BLDG 6,ROOM B1A13,BETHESDA,MD 20892, USA. NR 9 TC 19 Z9 20 U1 0 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD MAR 1 PY 1996 VL 6 IS 3 BP 234 EP & DI 10.1016/S0960-9822(02)00465-7 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UC440 UT WOS:A1996UC44000009 PM 8805244 ER PT J AU Tatusov, RL Mushegian, AR Bork, P Brown, NP Hayes, WS Borodovsky, M Rudd, KE Koonin, EV AF Tatusov, RL Mushegian, AR Bork, P Brown, NP Hayes, WS Borodovsky, M Rudd, KE Koonin, EV TI Metabolism and evolution of Haemophilus influenzae deduced from a whole-genome comparison with Escherichia coli SO CURRENT BIOLOGY LA English DT Article ID HEMOPHILUS-INFLUENZAE; BACILLUS-SUBTILIS; ORGANIZATION; PROTEINS; BACTERIA AB Background: The 1.83 Megabase (Mb) sequence of the Haemophilus influenzae chromosome, the first completed genome sequence of a cellular life form, has been recently reported, Approximately 75% of the 4.7 Mb genome sequence of Escherichia coli is also available. The life styles of the two bacteria are very different - H. influenzae is an obligate parasite that lives in human upper respiratory mucosa and can be cultivated only on rich media, whereas E. coli is a saprophyte that can grow on minimal media, A detailed comparison of the protein products encoded by these two genomes is expected to provide valuable insights into bacterial cell physiology and genome evolution. Results: We describe the results of computer analysis of the amino-acid sequences of 1703 putative proteins encoded by the complete genome of H. influenzae, We detected sequence similarity to proteins in current databases for 92% of the H. influenzae protein sequences, and at least a general functional prediction was possible for 83%, A comparison of the H. influenzae protein sequences with those of 3010 proteins encoded by the sequenced 75% of the E. coli genome revealed 1128 pairs of apparent orthologs, with an average of 59% identity, In contrast to the high similarity between orthologs, the genome organization and the functional repertoire of genes in the two bacteria were remarkably different, The smaller genome size of H. influenzae is explained, to a large extent, by a reduction in the number of paralogous genes. There was no long range colinearity between the E. coli and H. influenzae gene orders, but over 70% of the orthologous genes were found in short conserved strings, only about half of which were operons in E. coli. Superposition of the H. influenzae enzyme repertoire upon the known E. coli metabolic pathways allowed us to reconstruct similar and alternative pathways in H. influenzae and provides an explanation for the known nutritional requirements. Conclusions: By comparing proteins encoded by the two bacterial genomes, we have shown that extensive gene shuffling and variation in the extent of gene paralogy are major trends in bacterial evolution; this comparison has also allowed us to deduce crucial aspects of the largely uncharacterized metabolism of H. influenzae. C1 NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,NIH,BETHESDA,MD 20894. EUROPEAN MOLEC BIOL LAB,W-6900 HEIDELBERG,GERMANY. GEORGIA INST TECHNOL,SCH BIOL,ATLANTA,GA 30322. RI Bork, Peer/F-1813-2013; OI Bork, Peer/0000-0002-2627-833X; Mushegian, Arcady/0000-0002-6809-9225 FU NHGRI NIH HHS [HG00783] NR 58 TC 234 Z9 241 U1 0 U2 5 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON, ENGLAND W1P 6LB SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD MAR 1 PY 1996 VL 6 IS 3 BP 279 EP 291 DI 10.1016/S0960-9822(02)00478-5 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UC440 UT WOS:A1996UC44000022 PM 8805245 ER PT J AU Blake, DA Whikehart, DR Yu, HN Vogel, T Roberts, DD AF Blake, DA Whikehart, DR Yu, HN Vogel, T Roberts, DD TI Common cryopreservation media deplete corneal endothelial cell plasma membrane Na+,K+ ATPase activity SO CURRENT EYE RESEARCH LA English DT Article DE corneal endothelial cells; cattle (bovine); cryopreservation; Na+, K+ ATPase; endothelial cell fluid pump ID FLUID TRANSPORT; PUMP; DIMETHYLSULFOXIDE; GLYCEROL; INVITRO AB This study describes the effects of three cryopreservation media on the specific activity of corneal endothelial plasma membrane Na+,K+ ATPase activity, a transporter required for the fluid pump in the cornea. Bovine corneal endothelial cell cultures were used as a model system for these studies. Cryopreserved primary cells were thawed and passaged once to increase cell number. The specific activity plasma membrane Na+,K+ ATPase activity was subsequently measured on 4-6 replicate cultures. One freeze/thaw cycle depleted the Na+,K+ ATPase specific activity of corneal endothelial cell cultures by approximately 90%, as compared to cells of equivalent passage which had not been cryopreserved. Cell morphology of the cryopreserved cultures was indistinguishable from that of control cultures. In other experiments, first passage cultures which had not been subjected to cryopreservation were incubated with a dimethyl sulfoxide-, glycerol-, or propane diol-based freezing medium and Na+,K+ ATPase was measured on plasma membranes subsequently isolated from the cultures. Incubation of cells with cryopreservation media in the absence of the freezing process also depleted Na+,K+ ATPase by approximately 90%. Radiolabeled ouabain was used to measure Na+,K+ ATPase sites on cell cultures pretreated with dimethyl sulfoxide-based freezing media. A 4 h treatment with DMSO-based freezing medium had no effect on ouabain binding; treatment for 18 h reduced binding by only 50%. Thus, the method used to assess pump function (determination of Na+,K+ ATPase specific activity versus ouabain binding) may provide conflicting data concerning the level of pump function cultured cells. The cryoprotectants present in many common media used to freeze tissue culture cells appear to inhibit corneal endothelial Na+,K+ ATPase. Since the fluid pump of corneal endothelial cells is coupled to Na+,K+ ATPase activity, care must be taken to insure that pump function is not impaired during cryopreservation of cell cultures. C1 UNIV ALABAMA,VIS SCI RES CTR,BIRMINGHAM,AL 35294. BIOTECHNOL GEN LTD,REHOVOT,ISRAEL. NCI,NIH,PATHOL LAB,BETHESDA,MD 20892. RP Blake, DA (reprint author), TULANE UNIV,SCH MED,DEPT OPHTHALMOL,1430 TULANE AVE,NEW ORLEANS,LA 70112, USA. RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 FU NEI NIH HHS [EY02949, EY09092] NR 30 TC 2 Z9 3 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0271-3683 J9 CURR EYE RES JI Curr. Eye Res. PD MAR PY 1996 VL 15 IS 3 BP 263 EP 271 DI 10.3109/02713689609007620 PG 9 WC Ophthalmology SC Ophthalmology GA UB548 UT WOS:A1996UB54800005 PM 8654106 ER PT J AU Aran, JM Germann, UA Gottesman, MM Pastan, I AF Aran, JM Germann, UA Gottesman, MM Pastan, I TI Construction and characterization of a selectable multidrug resistance glucocerebrosidase fusion gene SO CYTOKINES AND MOLECULAR THERAPY LA English DT Article DE p-glycoprotein; glucocerebrosidase; lysosomes; gene fusion; cryptic splicing ID GAUCHER DISEASE; P-GLYCOPROTEIN; MONOCLONAL-ANTIBODIES; RETROVIRAL TRANSFER; MOLECULAR-BIOLOGY; EXPRESSION; CELLS; VECTORS; BIOSYNTHESIS; THERAPY AB Gene fusions can be employed to ensure concomitant expression of two different proteins under the same transcriptional control elements, We have synthesized a retroviral expression vector (pHaMG1) containing a human multidrug resistance (MDR1)-glucocerebrosidase (GC) chimeric gene inserted between the long terminal repeats of the Harvey murine sarcoma virus, When introduced into psi-CRE mouse fibroblasts, pHaMG1 conferred the drug-selectable multidrug resistance phenotype, and drug-resistant clones produced active human GC of about 60 kDa, Percoll gradient fractionation of homogenates prepared from transfectants confirmed correct targeting of P-glycoprotein to the plasma membrane and of GC to lysosomes, Although this construction was designed as a translational fusion of the MDR1 gene product, P-glycoprotein, and human GC, no evidence for a fusion protein was found in transfected cells, and an analysis of the RNAs transcribed from the integrated pHaMG1 retroviral vector suggests that either P-glycoprotein and GC are translated from one mRNA and rapidly processed into two proteins or they are translated separately from different mRNAs, These results reveal the feasibility of using fusion genes, which are smaller than alternative constructions with two promoters or with an internal ribosome entry site, for coexpression of selectable and nonselectable cDNAs In retroviral vectors. C1 NCI,MOLEC BIOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. VERTEX PHARMACEUT INC,CAMBRIDGE,MA. NCI,CELL BIOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NR 39 TC 6 Z9 6 U1 0 U2 0 PU MARTIN DUNITZ LTD PI LONDON PA 7-9 PRATT ST, LONDON, ENGLAND NW1 0AE SN 1355-6568 J9 CYTOKINES MOL THER JI Cytokines Mol. Ther. PD MAR PY 1996 VL 2 IS 1 BP 47 EP 57 PG 11 WC Biotechnology & Applied Microbiology; Cell Biology; Hematology; Immunology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Cell Biology; Hematology; Immunology; Research & Experimental Medicine GA UB670 UT WOS:A1996UB67000006 PM 9384689 ER PT J AU Elahl, D AF Elahl, D TI In praise of the hyperglycemic clamp - A method for assessment of beta-cell sensitivity and insulin resistance SO DIABETES CARE LA English DT Article; Proceedings Paper CT 2nd International Insulin Resistance and Atherosclerosis Symposium CY NOV 19-19, 1994 CL FT WORTH, TX SP Merck Human Hlth Div;, Merck Int, Merck Frosst, Canada ID TRANSPLANTED PANCREAS; GLUCOSE-METABOLISM; SECRETION; RESPONSES; OBESITY; MODEL; GIP AB The most widely used methods for the assessment of beta-cell response and peripheral tissue sensitivity to insulin include the oral glucose tolerance test (OGTT), the frequently sampled intravenous glucose tolerance lest, and the hyperinsulinemic-euglycemic clamp technique. During an OGTT, glucose levels increase after a variable lag period, then reach a peak and fall variably among individuals. The response even varies in the same subject upon repeat testing. A more reproducible glucose curve is achieved with an intravenous glucose tolerance test in which the plasma glucose levels rise rapidly to a very high level and fall exponentially. In neither of the two methods is a steady-state glucose level achieved. In the hyperinsulinemic-euglycemic clamp technique, a steady-state glucose level can be maintained al any level of hyperinsulinemia. However, an assessment of beta-cell sensitivity is not obtained. The less used hyperglycemic clamp technique can assess beta-cell sensitivity as well as peripheral tissue sensitivity. Moreover, a measure of glucose effectiveness or non-insulin-mediated glucose uptake can also be determined. With this technique the beta-cells of all subjects are stimulated with the same arterial glucose concentration, thus enabling assessment of beta-cell response to identical plasma glucose levels. Comparison of responses to stable hyperglycemic stimuli can be made in glucose-tolerant and -intolerant states with the addition of various substances, either alone or in combination. The use of the hyperglycemic clamp and several of its variant forms is reviewed as an alternative method for assessment of glucose homeostasis. C1 UNIV MARYLAND, SCH MED, CTR GERIATR RES EDUC & CLIN, BALTIMORE, MD 21201 USA. NIA, NIH, CTR GERONTOL RES, BALTIMORE, MD 21224 USA. RP Elahl, D (reprint author), VET ADM MED CTR, GERIATR SERV, GRECC 18, 10 N GREENE ST, BALTIMORE, MD 21201 USA. FU NIA NIH HHS [P60AG12583] NR 26 TC 95 Z9 99 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD MAR PY 1996 VL 19 IS 3 BP 278 EP 286 DI 10.2337/diacare.19.3.278 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TX233 UT WOS:A1996TX23300023 PM 8742583 ER PT J AU Majer, M Mott, DM Mochizuki, H Rowles, JC Pedersen, O Knowler, WC Bogardus, C Prochazka, M AF Majer, M Mott, DM Mochizuki, H Rowles, JC Pedersen, O Knowler, WC Bogardus, C Prochazka, M TI Association of the glycogen synthase locus on 19q13 with NIDDM in Pima Indians SO DIABETOLOGIA LA English DT Article DE non-insulin-dependent diabetes mellitus; insulin resistance; skeletal muscle glycogen synthase gene; association; Pima Indians ID DEPENDENT DIABETES-MELLITUS; INVIVO INSULIN ACTION; MYOTONIC-DYSTROPHY; AMERICAN-INDIANS; SKELETAL-MUSCLE; GENE; ADMIXTURE; GLUCOSE; POLYMORPHISM; SENSITIVITY AB Skeletal muscle glycogen synthase (encoded by GYS1 on chromosome 19q13.3) is the rate-limiting enzyme in insulin-mediated non-oxidative glucose disposal. Our previous studies have demonstrated an impairment of insulin-stimulated GYS1 activities in insulin-resistant Pima Indians, and associations of non-insulin-dependent diabetes mellitus (NIDDM) with the GYS1 locus were reported recently in Finnish and Japanese populations. We have performed linkage and association analyses of GYS1 and seven additional DNA markers on 19q with NIDDM, and with parameters of insulin action in the Pima Indians. We have found a significant association of NIDDM with GYS1 genotypes (p = 0.009), and with common GYS1 alleles (p = 0.022) in the Pima Indians. We have performed a detailed comparative analysis of the GYS1 gene, mRNA, and protein product in insulin-sensitive and insulin-resistant Pima Indians. No mutations in GYS1 coding sequences were detected; nor did we find alterations of CYS1 mRNA expression or of its basal enzymatic activity in insulin-resistant Pima Indians. These results contrasted with a 25% reduction of immunoreactive protein in insulin-resistant subjects as detected by Western blotting with an antibody specific for the C-terminal end of GYS1 (t-test p = 0.024; Wilcoxon's ranksum test, p = 0.04). Because no mutations were detected in the DNA encoding this epitope, the difference in immunoreactivity may reflect post-translational modification(s) of the protein rather than a difference in the gene itself, or it could have occurred by chance, We conclude that our data do not indicate alterations in the GYS1 gene as the cause for the observed association, and that a different locus near GYS1 may be the contributing genetic element. C1 NIDDKD,NIH,CLIN DIABET & NUTR SECT,PHOENIX,AZ 85016. NIDDKD,NIH,DIABET & ARTHRITIS EPIDEMIOL SECT,PHOENIX,AZ 85016. STENO DIABET CTR,GENTOFTE,DENMARK. FU NCRR NIH HHS [1P41RR03655] NR 31 TC 48 Z9 48 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD MAR PY 1996 VL 39 IS 3 BP 314 EP 321 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TX951 UT WOS:A1996TX95100010 PM 8721777 ER PT J AU Wang, J Medeiros, LJ Longo, DL Mansoor, A Raffeld, M Duffey, PL Jaffe, ES StetlerStevenson, M AF Wang, J Medeiros, LJ Longo, DL Mansoor, A Raffeld, M Duffey, PL Jaffe, ES StetlerStevenson, M TI Use of the polymerase chain reaction technique to determine c-myc expression in follicular center cell lymphoma SO DIAGNOSTIC MOLECULAR PATHOLOGY LA English DT Article DE c-myc expression; follicular center cell lymphoma; reverse transcription; polymerase chain reaction; cDNA; RNA ID REARRANGEMENTS; HYPERPLASIA; PROTEIN; BCL-2 AB We determined, in a semiquantitative fashion, the level of expression of c-myc in 18 follicular center cell lymphomas and five non-neoplastic lymph nodes using reverse transcription and the polymerase chain reaction technique (RT-PCR), With this method, RNA is extracted from lymph node specimens and reverse-transcribed to produce cDNA, which is then amplified using primers specific for c-myc sequences that span introns, thus precluding amplification of genomic DNA. Amplified products are compared with beta(2)-microglobulin sequences coamplified in each case as a control for the quality of RNA extracted, RT, and PCR amplification. Using cell lines derived from Burkitt's lymphomas, the RT-PCR method yielded results equivalent to standard Northern blot analysis yet required smaller quantities of tissue. The c-myc transcripts were detected in all lymphoma cases studied (seven high, 11 low expression) and in all non-neoplastic lymph nodes. High or low c-myc expression was based on comparison with non-neoplastic lymph nodes, We conclude that the RT-PCR method is a sensitive, reliable method for measuring gene expression in lymphoma tissues and may be useful for studying the role of c-myc in follicular lymphomas. C1 NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. NCI,BIOL RESPONSE MODIFIERS PROGRAM,NIH,FREDERICK,MD. NR 15 TC 18 Z9 18 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1052-9551 J9 DIAGN MOL PATHOL JI Diagn. Mol. Pathol. PD MAR PY 1996 VL 5 IS 1 BP 20 EP 25 DI 10.1097/00019606-199603000-00004 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology GA TW642 UT WOS:A1996TW64200004 PM 8919541 ER PT J AU Reid, AH Tsai, MM Venzon, DJ Wright, CF Lack, EE OLeary, TJ AF Reid, AH Tsai, MM Venzon, DJ Wright, CF Lack, EE OLeary, TJ TI MDM2 amplification, P53 mutation, and accumulation of the P53 gene product in malignant fibrous histiocytoma SO DIAGNOSTIC MOLECULAR PATHOLOGY LA English DT Article DE MDMZ; P53; MFH; mutation; amplification ID SOFT-TISSUE SARCOMAS; PROSPECTIVE RANDOMIZED EVALUATION; POLYMERASE CHAIN-REACTION; LIMB-SPARING SURGERY; ADJUVANT CHEMOTHERAPY; RADIATION-THERAPY; BREAST CANCERS; PROTEIN; EXTREMITIES; EXPRESSION AB Fifty-two cases of malignant fibrous histiocytoma (MFH) were evaluated for amplification of the MDM2 gene, mutation of the P53 gene, accumulation of the P53 gene product, and their relation to disease-free and overall survival. All tests were carried out on formalin-fixed, paraffin-embedded tissue samples. Amplification of the MDM2 gene was detected in 15 of 52 cases (29%). Six of 52 cases (12%) demonstrated abnormalities of the P53 gene. Sequence analysis detected point mutations in four cases and a 1-base pair deletion in one case, whereas differential polymerase chain reaction (dPCR) indicated that the P53 gene had been entirely deleted in one case. Eight of 52 cases (15%) demonstrated staining for the P53 protein in >10% of tumor cells. The presence of MDM2 amplification did not have a significant effect on either disease-free or overall survival. Patients with accumulation of the P53 gene product did not differ in disease-free or overall survival from patients without P53 accumulation. Survival also was not significantly different in patients with genetic aberration in P53. However, when the patients were stratified by histologic grade, the results indicated that patients with alterations in the P53 gene may have shorter overall survival. C1 NCI,BIOSTAT & DATA MANAGEMENT SECT,NIH,BETHESDA,MD 20892. GEORGETOWN UNIV,SCH MED,DEPT PATHOL,WASHINGTON,DC. NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. RP Reid, AH (reprint author), ARMED FORCES INST PATHOL,DEPT CELLULAR PATHOL,WASHINGTON,DC 20306, USA. RI Venzon, David/B-3078-2008 NR 40 TC 55 Z9 55 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1052-9551 J9 DIAGN MOL PATHOL JI Diagn. Mol. Pathol. PD MAR PY 1996 VL 5 IS 1 BP 65 EP 73 DI 10.1097/00019606-199603000-00010 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology GA TW642 UT WOS:A1996TW64200010 PM 8919547 ER PT J AU Biesecker, LG AF Biesecker, LG TI Molecular pathology, informed consent, and the paraffin block SO DIAGNOSTIC MOLECULAR PATHOLOGY LA English DT Letter RP Biesecker, LG (reprint author), NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892, USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1052-9551 J9 DIAGN MOL PATHOL JI Diagn. Mol. Pathol. PD MAR PY 1996 VL 5 IS 1 BP 74 EP 74 DI 10.1097/00019606-199603000-00011 PG 1 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology GA TW642 UT WOS:A1996TW64200011 PM 8919548 ER PT J AU Orbuch, M Venzon, DJ Lubensky, IA Weber, HC Gibril, F Jensen, RT AF Orbuch, M Venzon, DJ Lubensky, IA Weber, HC Gibril, F Jensen, RT TI Prolonged hypergastrinemia does not increase the frequency of colonic neoplasia in patients with Zollinger-Ellison syndrome SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Zollinger-Ellison syndrome; colon cancer; colon polyps; hypergastrinemia; omeprazole ID OMEPRAZOLE-INDUCED HYPERGASTRINEMIA; MULTIPLE ENDOCRINE NEOPLASIA; PEPTIC-ULCER DISEASE; OCCULT BLOOD-TESTS; LARGE-BOWEL CANCER; GASTRIN RECEPTORS; PERNICIOUS-ANEMIA; SERUM GASTRIN; CLINICAL-SIGNIFICANCE; HELICOBACTER-PYLORI AB Whereas considerable experimental evidence suggests chronic hypergastrinemia can increase the occurrence of colonic neoplasia, the risks in man remain unclear, Zollinger-Ellison syndrome (ZES) is associated with marked plasma elevation of all forms of gastrin and, because of its prolonged course, has been shown to be an excellent model disease to study the effects of chronic hypergastrinemia in man, To determine whether profound chronic hypergastrinemia affects the occurrence of colonic dysplasia and neoplasia, 97 consecutive patients with ZES were studied, All patients underwent colonoscopic examination to the cecum, and the location, size: and type of polyps/tumors were determined, The patients had a mean fasting gastrin level 31 times above normal and a mean disease duration of 10 years, 17/97 (18%) had adenomatous polyps, 67/97 (69%) no adenomatous polyps, and 2/97 (2%) had adenocarcinoma of the colon, These rates were within ranges reported in a number of colonoscopy and/or autopsy studies for asymptomatic controls. Stratification by age or gender, presence of MEN-I, tumor extent, and duration or degree of hypergastrinemia did not increase prevalence. This stud!: shows that despite prolonged? profound hypergastrinemia, no increased rate of colonic neoplasia (polyps or cancer) was noted, These data suggest that the development of hypergastrinemia secondary to continuous use of H+,K+-ATPase inhibitors for as long as 10 years is unlikely to cause an increased risk of developing colonic neoplasia in man. C1 NIDDK,DDB,NIH,BETHESDA,MD 20892. NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20814. NCI,PATHOL LAB,BETHESDA,MD 20892. RI Venzon, David/B-3078-2008 NR 89 TC 44 Z9 44 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD MAR PY 1996 VL 41 IS 3 BP 604 EP 613 DI 10.1007/BF02282349 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA UB267 UT WOS:A1996UB26700033 PM 8617144 ER PT J AU Vasiliou, V Kozak, CA Lindahl, R Nebert, DW AF Vasiliou, V Kozak, CA Lindahl, R Nebert, DW TI Mouse microsomal class 3 aldehyde dehydrogenase: AHD3 cDNA sequence, inducibility by dioxin and clofibrate, and genetic mapping SO DNA AND CELL BIOLOGY LA English DT Article ID RAT-LIVER; MOLECULAR-CLONING; RECEPTOR; EXPRESSION; TRANSCRIPTION; CYTOCHROME-B5; SUPERFAMILY; ACTIVATION; EUKARYOTES; OXIDATION AB We have cloned and sequenced the mouse AHD3 cDNA, which codes for the Class 3 microsomal aldehyde dehydrogenase (ALDH3m), The cDNA is 2,997 bp in length excluding the poly(A)(+) tail, and has 5' and 3' nontranslated regions of 113 bp and 1,429 bp, respectively, The deduced amino acid sequence consists of 484 amino acids, including the first methionine (M(r) = 53,942), and contains a hydrophobic segment at the carboxyl terminus which is the putative membrane anchor, The mouse AHD3 protein was found to be: 95% similar to the rat microsomal ALDH3m protein, 65% identical to the mouse, rat and human cytosolic ALDH3c protein, and <28% similar to the rat Class 1 and Class 2 ALDH and methylmalonate-semialdehyde dehydrogenase proteins, Southern hybridization analysis of mouse cDNA probed with the full-length AHD3 cDNA revealed that the Ahd3 gene likely spans less than a total of 25 kb, The mouse Ahd3 gene is very tightly linked to the Ahd4 gene on chromosome 11, Mouse AHD3 mRNA levels are increased by dioxin in mouse Hepa1c1c7 hepatoma wild-type (wt) cells but not in the Ah receptor nuclear translocator (ARNT)-defective (c4) mutant line, indicating that the induction process is mediated by the Ah (aromatic hydrocarbon) dioxin-binding receptor, AHD3 mRNA levels are also inducible by clofibrate in both the wt and c4 lines, AHD3 mRNA levels are not elevated in the CYP1A1 metabolism-deficient c37 mutant line or as part of the oxidative stress response found in the untreated 14CoS/14CoS mouse cell line, These data indicate that, although inducible by dioxin, the Ahd3 gene does not qualify as a member of the aromatic hydrocarbon [Ah] gene battery. C1 UNIV CINCINNATI,MED CTR,DEPT ENVIRONM MED,CINCINNATI,OH 45267. NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. UNIV S DAKOTA,SCH MED,DEPT BIOCHEM & MOLEC BIOL,VERMILLION,SD 57069. FU NCI NIH HHS [R01 CA21103]; NIA NIH HHS [R01 AG09235]; NIEHS NIH HHS [P30 ES06096] NR 75 TC 40 Z9 41 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 MAR PY 1996 VL 15 IS 3 BP 235 EP 245 DI 10.1089/dna.1996.15.235 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA UC256 UT WOS:A1996UC25600006 PM 8634152 ER PT J AU Giambra, LM Jung, RE Grodsky, A AF Giambra, LM Jung, RE Grodsky, A TI Age changes in dream recall in adulthood SO DREAMING LA English DT Article DE dreams; dream recall; age; aging AB Dream recall was measured retrospectively with the Night Dreaming Scale of the Imaginal Processes Inventory. Evidence supports a high degree of correspondence among methods which assess dreaming frequency. A cross-sectional sample (17-92 years old, n = 2328) found fewer dreams recalled with increasing age. Women recalled move dreams and showed a less vapid decrease in frequency than men. Longitudinal changes (n = 333) over 6 to 8 years were not wholly consistent with cross-sectional age differences. We found many fewer recalled dreams in senescence. However, the reduction in recalled dreams began well before senescence. Explanations based on dream saliency, long- and short-term memory failure, levels of REM sleep, and degree of spontaneous information processing were considered. C1 UNIV NEW MEXICO,ALBUQUERQUE,NM 87131. NO VIRGINIA COMMUNITY COLL,ANNANDALE,VA 22003. RP Giambra, LM (reprint author), NIA,LAB PERSONAL & COGNIT,NIH,GERONTOL RES CTR,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 21 TC 22 Z9 22 U1 0 U2 0 PU HUMAN SCI PRESS INC PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 SN 1053-0797 J9 DREAMING JI Dreaming PD MAR PY 1996 VL 6 IS 1 BP 17 EP 31 PG 15 WC Psychology, Multidisciplinary SC Psychology GA UG981 UT WOS:A1996UG98100002 ER PT J AU Chrambach, A AF Chrambach, A TI Quantitative and automated electrophoresis in sieving media SO ELECTROPHORESIS LA English DT Article; Proceedings Paper CT International Meeting Electrophoresis 95 CY AUG 30-SEP 02, 1995 CL PARIS, FRANCE SP Int Council Electrophoresis Soc, Soc Francaise Electrophorese DE quantitative electrophoresis; automation; dispersion; resolution ID POLYACRYLAMIDE-GEL ELECTROPHORESIS; DNA ELECTROPHORESIS; POLYMER-SOLUTIONS; FERGUSON PLOT; MOBILITY DATA; EFFICIENCY; COMPUTERS; FRAGMENTS; PROTEIN; BUFFER RP Chrambach, A (reprint author), NICHHD,MACROMOLEC ANAL SECT,THEORET & PHYS BIOL LAB,NIH,BLDG 10,RM 6C215,BETHESDA,MD 20892, USA. NR 67 TC 9 Z9 9 U1 0 U2 1 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD MAR PY 1996 VL 17 IS 3 BP 454 EP 464 DI 10.1002/elps.1150170304 PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA UP015 UT WOS:A1996UP01500003 PM 8740158 ER PT J AU Lemkin, PF Chipperfield, M Merril, C Zullo, S AF Lemkin, PF Chipperfield, M Merril, C Zullo, S TI A world wide web (WWW) server database engine for an organelle database, MitoDat SO ELECTROPHORESIS LA English DT Article; Proceedings Paper CT International Meeting Electrophoresis 95 CY AUG 30-SEP 02, 1995 CL PARIS, FRANCE SP Int Council Electrophoresis Soc, Soc Francaise Electrophorese DE mitochondrial proteins; World Wide Web Internet; two-dimensional polyacrylamide gel wis; databases; chromosome idiograms ID MITOCHONDRIAL PROTEINS; CELLS AB We describe a simple database search engine ''dbEngine'' which may be used to quickly create a searchable database on a World Wide Web (WWW) server. Data may be prepared from spreadsheet programs (such as Excel, etc.) or from tables exported from relational database systems. This Common Gateway Interface (CGI-BIN) program is used with a WWW server such as available commercially, or from National Center for Supercomputer Algorithms (NCSA) or CERN. Its capabilities include: (i) searching records by combinations of terms connected with ANDs or ORs; (ii) returning search results as hypertext links to other WWW database servers; (iii) mapping lists of literature reference identifiers to the full references; (iv) creating bidirectional hypertext links between pictures and the database. DbEngine has been used to support the MitoDat database (Mendelian and non-Mendelian inheritance associated with the Mitochondrion) on the WWW. C1 JOHNS HOPKINS UNIV,GDB,BALTIMORE,MD. NIMH,LBG,WASHINGTON,DC. RP Lemkin, PF (reprint author), NCI,IMAGE PROC SECT,LMMB,FCRDC,NIH,BLDG 469,RM 150,FREDERICK,MD 21702, USA. NR 7 TC 15 Z9 15 U1 0 U2 1 PU VCH PUBLISHERS INC PI DEERFIELD BEACH PA 303 NW 12TH AVE, DEERFIELD BEACH, FL 33442-1788 SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD MAR PY 1996 VL 17 IS 3 BP 566 EP 572 DI 10.1002/elps.1150170327 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA UP015 UT WOS:A1996UP01500026 PM 8740181 ER PT J AU Hackstadt, T Rockey, DD Heinzen, RA Scidmore, MA AF Hackstadt, T Rockey, DD Heinzen, RA Scidmore, MA TI Chlamydia trachomatis interrupts an exocytic pathway to acquire endogenously synthesized sphingomyelin in transit from the Golgi apparatus to the plasma membrane SO EMBO JOURNAL LA English DT Article DE Chlamydia trachomatis; exocytosis; Golgi apparatus; sphingolipids ID FLUORESCENT CERAMIDE ANALOG; INTRACELLULAR-TRANSPORT; BREFELDIN-A; CULTURED FIBROBLASTS; HOST-CELLS; METABOLISM; PARASITISM; PROTEINS; COMPLEX AB Chlamydia trachomatis acquires C-6-NBD-sphingomyelin endogenously synthesized from C-6-NBD-ceramide and transported to the vesicle (inclusion) in which they multiply. Here we explore the mechanisms of this unusual trafficking and further characterize the association of the chlamydial inclusion with the Golgi apparatus, Endocytosed chlamydiae are trafficked to the Golgi region and begin to acquire sphingolipids from the host within a few hours following infection. The transport of NBD-sphingolipid to the inclusion is energy- and temperature-dependant with the characteristics of an active, vesicle-mediated process, Photo-oxidation of C-5-DMB-ceramide, in the presence of diaminobenzidine, identified DMB-lipids in vesicles in the process of fusing to the chlamydial inclusion membrane, C-6-NBD-sphingomyelin incorporated into the plasma membrane is not trafficked to the inclusion to a significant degree, suggesting the pathway for sphingomyelin trafficking is direct from the Golgi apparatus to the chlamydial inclusion, Lectins and antibody probes for Golgi-specific glycoproteins demonstrate the close association of the chlamydial inclusion with the Golgi apparatus but do not detect these markers in the inclusion membrane, Collectively, the data are consistent with a model in which C.trachomatis inhabits a unique vesicle which interrupts an exocytic pathway to intercept host sphingolipids in transit from the Golgi apparatus to the plasma membrane. RP Hackstadt, T (reprint author), NIAID,NIH,ROCKY MT LABS,LAB INTRACELLULAR PARASITES,HOST PARASITE INTERACT SECT,HAMILTON,MT 59840, USA. NR 40 TC 255 Z9 257 U1 1 U2 4 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD MAR 1 PY 1996 VL 15 IS 5 BP 964 EP 977 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TZ981 UT WOS:A1996TZ98100002 PM 8605892 ER PT J AU Ozeri, V Tovi, A Burstein, I NatansonYaron, S Caparon, MG Yamada, KM Akiyama, SK Vlodavsky, I Hanski, E AF Ozeri, V Tovi, A Burstein, I NatansonYaron, S Caparon, MG Yamada, KM Akiyama, SK Vlodavsky, I Hanski, E TI A two-domain mechanism for group A streptococcal adherence through protein F to the extracellular matrix SO EMBO JOURNAL LA English DT Article DE bacterial adherence; extracellular matrix; fibronectin; group A streptococcus; protein F ID FIBRONECTIN-BINDING PROTEIN; GROUP-A STREPTOCOCCUS; STAPHYLOCOCCUS-AUREUS; NUCLEOTIDE-SEQUENCE; EPITHELIAL-CELLS; PYOGENES JRS4; INFECTIONS; EXPRESSION; GENE; PURIFICATION AB Streptococcus pyogenes binds to the extracellular matrix (ECM) and a variety of host cells and tissues, causing diverse human diseases. Protein F, a S.pyogenes adhesin that binds fibronectin (Fn), contains two binding domains, A repeated domain (RD2) and an additional domain (UR), located immediately N-terminal to RD2, Both domains are required for maximal Fn binding, In this study, we characterize RD2 and UR precisely and compare their functions and binding sites in Fn, The minimal functional unit of RD2 is of 44 amino acids, with contributions from two adjacent RD2 repeats flanked by a novel 'MGGQSES' moth, RD2 binds to the N-terminal fibrin binding domain of Fn, UR contains 49 amino acids, of which six are from the first repeat of RD2, It binds to Fn with higher affinity than RD2, and recognizes a larger fragment that contains fibrin and collagen binding domains, Expression of UR and RD2 independently on the surface-exposed region of unrelated streptococcal protein demonstrates that both mediate adherence of the bacteria to the ECM, We describe here a mechanism of adherence of a pathogen that involves two pairs of sites located on a single adhesin molecule and directed at the same host receptor. C1 HEBREW UNIV JERUSALEM,HADASSAH MED SCH,DEPT CLIN MICROBIOL,IL-91010 JERUSALEM,ISRAEL. WASHINGTON UNIV,SCH MED,DEPT MOLEC MICROBIOL,ST LOUIS,MO 63110. NIDR,NIH,DEV BIOL LAB,BETHESDA,MD 20892. HADASSAH UNIV HOSP,DEPT ONCOL & MED B,IL-91120 JERUSALEM,ISRAEL. OI Yamada, Kenneth/0000-0003-1512-6805 NR 29 TC 79 Z9 79 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 MAR 1 PY 1996 VL 15 IS 5 BP 989 EP 998 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TZ981 UT WOS:A1996TZ98100004 PM 8605894 ER PT J AU Yoshimura, A Ichihara, M Kinjyo, I Moriyama, M Copeland, NG Gilbert, DJ Jenkins, NA Hara, T Miyajima, A AF Yoshimura, A Ichihara, M Kinjyo, I Moriyama, M Copeland, NG Gilbert, DJ Jenkins, NA Hara, T Miyajima, A TI Mouse oncostatin M: An immediate early gene induced by multiple cytokines through the JAK-STAT5 pathway SO EMBO JOURNAL LA English DT Article DE cytokine receptor; erythropoietin; hematopoiesis; interleukin; signal transduction ID LEUKEMIA INHIBITORY FACTOR; SIGNAL-TRANSDUCTION; TYROSINE PHOSPHORYLATION; HUMAN CHROMOSOME-22; GROWTH-REGULATOR; LIGAND-BINDING; FACTOR LIF; M OSM; RECEPTOR; CELLS AB Oncostatin M (OSM) is a member of the interleukin-6 (IL6)-related cytokine subfamily that includes IL6, IL11, leukemia inhibitory factor (LIF), ciliary neurotrophic factor and cardiotrophin-1. While human OSM has been characterized and the bovine OSM gene was recently cloned, the murine counterpart had not been identified, Here we describe molecular cloning of murine OSM as an immediate early gene induced by a subset of cytokines including IL2, IL3 and erythropoietin (EPO) in myeloid and lymphoid cell lines, The induction kinetics of OSM are rapid and transient, reaching a maximal level within 30-60 min and decreasing thereafter, Induction of OSM depends on the signals generated by the membrane-proximal region of the EPO receptor as well as that of the beta chain of the IL3/GM-CSF receptor, which activate JAK2 and STAT5, About 100 bases upstream of the transcription initiation site of the OSM gene contains a possible STAT5 binding site which is essential for IL2, IL3 and EPO-dependent promoter activity of the OSM gene. Expression of STAT5 and the EPO receptor in COS cells conferred EPO-dependent activation of the OSM promoter. Moreover, the mutant IL2 receptor lacking the ability to activate STAT5 induced c-myc but failed to induce OSM, Thus, OSM is one of the common targets of a subset of cytokines that activate STAT5, The murine OSM gene is located near to the LIF gene, expressed at high levels in bone marrow and possesses similar biological activity to human OSM, Identification of murine OSM as a cytokine-inducible immediate early gene provides a new insight into the physiological function of this unique cytokine. C1 DNAX RES INST MOLEC & CELLULAR BIOL INC,PALO ALTO,CA 94304. KURUME UNIV,INST LIFE SCI,KURUME,FUKUOKA 839,JAPAN. KAGOSHIMA UNIV,FAC MED,CANC RES INST,KAGOSHIMA 890,JAPAN. UNIV TOKYO,INST MOLEC & CELLULAR BIOSCI,BUNKYO KU,TOKYO 113,JAPAN. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. RI Yoshimura, Akihiko/K-5515-2013 FU NCI NIH HHS [N01-CO-46000] NR 53 TC 185 Z9 189 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 MAR 1 PY 1996 VL 15 IS 5 BP 1055 EP 1063 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TZ981 UT WOS:A1996TZ98100012 PM 8605875 ER PT J AU Radnedge, L Davis, MA Austin, SJ AF Radnedge, L Davis, MA Austin, SJ TI P1 and P7 plasmid partition: ParB protein bound to its partition site makes a separate discriminator contact with the DNA that determines species specificity SO EMBO JOURNAL LA English DT Article DE discriminator; P1; ParB; partition; plasmid ID INTEGRATION HOST FACTOR; UNIT-COPY MINIPLASMIDS; CENTROMERE-LIKE SITE; DAUGHTER CELLS; BINDING; COMPLEX; REGION; SYSTEM AB The cis-acting P1 and P7 parS sites are responsible for active partition of P1 and P7 plasmids to daughter cells, The two sites are similar but function only with ParB proteins from the correct species, Using hybrid ParB proteins and hybrid parS sites, we show that specificity is determined by contacts between bases that lie within two parS hexamer boxes and a region in the ParB C-terminus. We refer to these contacts as discriminator contacts, The P7 discriminator contacts were mapped to 3 and 2 bp respectively within the two parS hexamer boxes, and a 10 amino acid region of P7 ParB, Similarly placed residues of different sequence are responsible for the P1 discriminator contact. The discriminator contacts are distinct from previously identified DNA binding contacts which involve different ParB and parS regions, Deletion of the ParB C-terminus that makes the discriminator contact does not diminish in vitro binding but renders it species independent, The discriminator contact is therefore a negative function, interfering with binding of the wrong ParB, but not providing energy for the binding of the correct one. Similar discriminator contacts might be responsible for specificities seen among families of eukaryotic DNA binding proteins that share common binding motifs. RP Radnedge, L (reprint author), NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,LAB CHROMOSOME BIOL,FREDERICK,MD 21702, USA. NR 22 TC 42 Z9 43 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 MAR 1 PY 1996 VL 15 IS 5 BP 1155 EP 1162 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA TZ981 UT WOS:A1996TZ98100023 PM 8605886 ER PT J AU Mulroney, SE Koenig, JI Csikos, T Pesce, C Striker, L LeRoith, D Haramati, A AF Mulroney, SE Koenig, JI Csikos, T Pesce, C Striker, L LeRoith, D Haramati, A TI Temporal changes in insulin-like growth factor I, c-fos, and c-jun gene expression during hyperplastic kidney growth in weanling rats SO ENDOCRINOLOGY LA English DT Article ID COMPENSATORY RENAL GROWTH; HORMONE-RELEASING-FACTOR; IGF-I; UNILATERAL NEPHRECTOMY; IMMATURE RATS; MESSENGER-RNA; CELLS; HYPERTROPHY; INITIATION; RECEPTORS AB We have previously determined that compensatory renal growth (CRG) during the initial 24-48 h after uninephrectomy (UNX) is GH independent in weanling animals, but associated with significant increases in insulin-like growth factor I (IGF-I) and IGF-I receptor gene expression. The purpose of the present study was to determine the temporal sequence of molecular and cellular events that occur at various time points (1, 6, 12, 18, 24, 48, and 72 h post-UNX) during this early period of accelerated renal growth in the weanling (21- to 25-day-old) rat. Rapid and sustained increases in steady state renal IGF-I receptor and IGF-I messenger RNA (mRNA) were observed at 1 and 6 h, respectively, and remained elevated in the remnant kidneys until 72 h post-UNX. The mRNAs for the early response genes, c-ibs and c-jun, were not induced in the remnant kidneys from weanling rats until between 12-18 h, but were also sustained through 48 h post-UNX. Increases in remnant kidney DNA content and [H-3]thymidine incorporation also occurred from 18-48 h post-UNX and returned to baseline levels by 72 h post-UNX, indicating that the hy perplastic response in the weanling remnant kidney occurs over a discrete period early after UNX. Neither IGF-I nor early response genes were elevated in kidneys from adult animals, which exhibited only hypertrophic renal growth at those early time points after UNX. These findings suggest that early CRG in the weanling rat is associated with rapid increases in IGF-I mRNA followed by a rise in c-fos and c-jun gene expression and a mitogenic response. Furthermore, when the mRNA levels of IGF-I and early response genes returned to baseline levels, mitogenic growth stopped, and slower prolonged hy pertrophic renal growth ensued. C1 NIDDKD, NIH, MBD, RENAL CELL BIOL GRP, BETHESDA, MD 20892 USA. NIDDKD, NIH, SECT CELL & MOLEC PHYSIOL, DIABET BRANCH, BETHESDA, MD 20892 USA. RP GEORGETOWN UNIV, SCH MED, DEPT PHYSIOL & BIOPHYS, 3900 RESERVOIR RD NW, WASHINGTON, DC 20007 USA. FU NIDDK NIH HHS [DK-36111, DK-40788] NR 24 TC 17 Z9 17 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD MAR PY 1996 VL 137 IS 3 BP 839 EP 845 DI 10.1210/en.137.3.839 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TW606 UT WOS:A1996TW60600007 PM 8603593 ER PT J AU LeRoith, D Yanowski, J Kaldjian, EP Jaffe, ES LeRoith, T Purdue, K Cooper, BD Pyle, R Adler, W AF LeRoith, D Yanowski, J Kaldjian, EP Jaffe, ES LeRoith, T Purdue, K Cooper, BD Pyle, R Adler, W TI The effects of growth hormone and insulin-like growth factor I on the immune system of aged female monkeys SO ENDOCRINOLOGY LA English DT Article ID TRANSGENIC MICE; SERUM; CELLS; PROLIFERATION; ENHANCEMENT; STIMULATION AB The aging process is associated with a significant reduction in circulating GH and insulin-like growth factor I(IGF-I) levels. During this period, immune function also declines. Rodent data suggest that treatment with recombinant human GH (rhGH) or rhIGF-I enhances immune function in normal adult mice. To determine whether rhGH and/or rhIGF-I treatment could improve immune function in aged female rhesus monkeys, we administered rhIGF-I(120 mu g/kg . day), rhGH (100 mu g/kg . day), a combination of therapies, or excipient alone by sc infusion using Alzet pumps over a 7-week period. At 28 days, the pumps were replaced, and the animals were bled and immunized with tetanus toroid. At the end of the 7-week period, the animals were killed. rhGH and rhIGF-I increased serum GH and IGF-I levels, respectively; rhGH and rhIGF-I in combination induced the highest serum IGF-I levels (906 +/- 261 ng/ml us. control, 185 +/- 36 ng/ml at death). rhGH and rhIGF-I also increased IGFBP-3 levels. rhGH infusion resulted in the most marked changes in lymph node and splenic reactivity, as determined by histological assessment. Lymph nodes from the rhGH-treated animals showed changes from baseline indicating a stimulated reactive state. Both rhGH and rhIGF-I had effects on lymphocyte phenotype, but there were different responses in blood compared to spleen and lymph nodes. In the peripheral blood, the percent B cells and percent CD8 cell count rose after rhIGF-I therapy, with a fall in the CD4/CD8 ratio. In the spleen, on the other hand, the CD4/CD8 ratio nearly doubled (0.33 +/- 0.12 us. 0.53 +/- 0.12) after rhIGF-I therapy. In the spleen, the combination of rhGH and rhIGF-I increased the percent T cells from 26.7 +/- 2.3 to 42.4 +/- 4.4 and the CD4/CD8 ratio to 0.71 +/- 0.11. Both rhGH and rhIGF-I increased in vivo (antibody titer to tetanus toroid) responses by lymphocytes, and rhGH increased Con-A-induced DNA synthesis in vitro. These results confirm the rodent data showing that rhGH and rhIGF-I cause beneficial changes in immune function and suggest that further investigation is warranted to assess their therapeutic potential. C1 OFF DIRECTOR, BETHESDA, MD 20892 USA. NCI, PATHOL LAB, BETHESDA, MD 20892 USA. NCRR, NIH, VET RESOURCE PROGRAM, BETHESDA, MD 20892 USA. NIA, NIH, BALTIMORE, MD 21224 USA. RP NIDDKD, NIH, DIABET BRANCH, BLDG 10, ROOM 8S235A, BETHESDA, MD 20892 USA. OI LeRoith, Tanya/0000-0002-1196-6949 NR 36 TC 64 Z9 68 U1 0 U2 0 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD MAR PY 1996 VL 137 IS 3 BP 1071 EP 1079 DI 10.1210/en.137.3.1071 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TW606 UT WOS:A1996TW60600039 PM 8603576 ER PT J AU Kleinman, D Karas, M Danilenko, M Arbeli, A Roberts, CT LeRoith, D Levy, J Sharoni, Y AF Kleinman, D Karas, M Danilenko, M Arbeli, A Roberts, CT LeRoith, D Levy, J Sharoni, Y TI Stimulation of endometrial cancer cell growth by tamoxifen is associated with increased insulin-like growth factor (IGF)-I induced tyrosine phosphorylation and reduction in IGF binding proteins SO ENDOCRINOLOGY LA English DT Article ID BREAST-CANCER; FACTOR-I; POSTMENOPAUSAL WOMEN; RECEPTORS; ADENOCARCINOMA; PROLIFERATION; MODULATION; ESTROGEN; MOUSE; CARCINOMA AB A significant increase in endometrial cancer incidence in tamoxifen-treated breast cancer patients has been reported in many recent studies. The major growth stimulators of endometrial tumors are estrogens, but paradoxically, tamoxifen, a known aritiestrogen, also stimulates their growth. The mode of action of estrogen can be partially explained by the modulation of insulin-like growth factor (IGF) autocrine or paracrine action. The purpose of the present study was to examine the involvement of the IGF system in the tamoxifen-stimulated growth of Ishikawa endometrial cancer cells by quantitating the IGF-I receptors and their phosphorylation, as well as membrane-associated and secreted IGF-binding proteins (IGFBPs). Tamoxifen did not affect the number Or affinity of IGF-I receptors. On the other hand, tamoxifen, similar to estradiol, increased IGF-I-stimulated tyrosine phosphorylation of cellular substrates. In contrast, in MCF-7 mammary cancer cells, tamoxifen reduced IGF-induced tyrosine phosphorylation in the presence of estradiol. The pure antiestrogen LY156758 did not affect Ishikawa basal cell growth but inhibited estradiol- and tamoxifen-induced growth. Growth inhibition by LY156758 of tamoxifen and estradiol-stimulated cells was accompanied by a corresponding inhibition of IGF-stimulated tyrosine phosphorylation. Tamoxifen caused a 3-fold decrease in membrane-associated IGFBPs. Moreover, a reduction in soluble IGFBPs was also observed, making the IGF peptides more available to the receptors. A parallel decrease in IGFBP-3 mRNA was also detected. These experiments suggest that tamoxifen, like estradiol, directly sensitizes endometrial cancer cells to the effects of IGFs that act through the type I receptor. Furthermore, the decrease in IGFBPs and the increase in tyrosine phosphorylation in the presence of tamoxifen provides a molecular mechanism that accounts for the uterotropic effects that are seen with tamoxifen therapy. C1 BEN GURION UNIV NEGEV, FAC HLTH SCI, DEPT CLIN BIOCHEM, SOROKA MED CTR, IL-84105 BEER SHEVA, ISRAEL. NIDDK, NIH, DIABET BRANCH, BETHESDA, MD 20892 USA. RI DANILENKO, MICHAEL/F-2283-2012; OI Roberts, Charles/0000-0003-1756-5772; Danilenko, Michael/0000-0001-9466-6169 NR 50 TC 48 Z9 49 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD MAR PY 1996 VL 137 IS 3 BP 1089 EP 1095 DI 10.1210/en.137.3.1089 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TW606 UT WOS:A1996TW60600041 PM 8603578 ER PT J AU Becker, DV Robbins, J Beebe, GW Bouville, AC Wachholz, BW AF Becker, DV Robbins, J Beebe, GW Bouville, AC Wachholz, BW TI Childhood thyroid cancer following the Chernobyl accident - A status report SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Article ID RADIATION; HYPERTHYROIDISM; IRRADIATION; BELARUS; THERAPY; TUMORS; I-131 AB Cross-species models of simple behaviors can provide critical information regarding the neural substrates for sexual dimorphism and the neuroendocrine regulation of information processing. This article reviews evidence that one such behavioral measure, prepulse inhibition of the startle reflex, may help us to understand the endocrine substrates that regulate sensorimotor gating and the contribution of these substrates to sex differences in the clinical characteristics of schizophrenia. C1 CORNELL UNIV, MED CTR, NEW YORK HOSP, DEPT MED, NEW YORK, NY 10021 USA. NIDDKD, GENET & BIOCHEM BRANCH, BETHESDA, MD 20892 USA. NCI, RADIAT EPIDEMIOL BRANCH, BETHESDA, MD 20892 USA. NCI, RADIAT EFFECTS BRANCH, BETHESDA, MD 20892 USA. RP Becker, DV (reprint author), CORNELL UNIV, MED CTR,NEW YORK HOSP,DEPT RADIOL,DIV NUCL MED, 520 E 68TH ST, ROOM ST-221, NEW YORK, NY 10021 USA. NR 55 TC 34 Z9 37 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8529 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD MAR PY 1996 VL 25 IS 1 BP 197 EP + DI 10.1016/S0889-8529(05)70319-4 PG 0 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TZ614 UT WOS:A1996TZ61400011 PM 8907687 ER PT J AU Goehl, TJ AF Goehl, TJ TI Reviews in environmental health, 1996 - Introduction SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material RP Goehl, TJ (reprint author), NIEHS,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 0 Z9 0 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 MAR PY 1996 VL 104 SU 1 BP 3 EP 3 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA UE548 UT WOS:A1996UE54800001 ER PT J AU Darden, TA Bartolotti, L Pedersen, LG AF Darden, TA Bartolotti, L Pedersen, LG TI Selected new developments in computational chemistry SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE molecular dynamics; particle mesh Ewald; quantum mechanics; transition states; rate constants; potential energy surfaces; fast multipole expansion ID MOLECULAR-DYNAMICS SIMULATION; MULTIPOLE METHOD; EWALD AB Molecular dynamics is a general technique for simulating the time-dependent properties of molecules and their environments. Quantum mechanics, as applied to molecules or clusters of molecules, provides a prescription for predicting properties exactly (in principle). It is reasonable to expect that both will have a profound effect on our understanding of environmental chemistry in the future. In this review, we consider several recent advances and applications in computational chemistry. C1 NIEHS,RES TRIANGLE PK,NC 27709. N CAROLINA SUPERCOMP CTR,RES TRIANGLE PK,NC. UNIV N CAROLINA,DEPT CHEM,CHAPEL HILL,NC. RI Pedersen, Lee/E-3405-2013 OI Pedersen, Lee/0000-0003-1262-9861 NR 56 TC 2 Z9 2 U1 1 U2 7 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 MAR PY 1996 VL 104 SU 1 BP 69 EP 74 DI 10.2307/3432697 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA UE548 UT WOS:A1996UE54800006 PM 8722111 ER PT J AU Melnick, RL Kohn, MC Portier, CJ AF Melnick, RL Kohn, MC Portier, CJ TI Implications for risk assessment of suggested nongenotoxic mechanisms of chemical carcinogenesis SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Review DE nongenotoxic carcinogenic mechanisms; regenerative hyperplasia; mitogenesis; receptor-mediated carcinogenesis; peroxisome proliferators; alpha(2)-microglobulin nephropathy ID HEPATIC PEROXISOME PROLIFERATORS; EPIDERMAL GROWTH-FACTOR; INDUCED HEPATOCYTE PROLIFERATION; FEMALE FISCHER-344 RATS; THYROID-HORMONE LEVELS; CELL-PROLIFERATION; UNLEADED GASOLINE; ALPHA-2U-GLOBULIN NEPHROPATHY; 2,2,4-TRIMETHYLPENTANE-INDUCED NEPHROTOXICITY; DI(2-ETHYLHEXYL) PHTHALATE AB Nongenotoxic carcinogens are chemicals that induce neoplasia without it or its metabolites reacting directly with DNA. Chemicals classified as nongenotoxic carcinogens have been assumed to act as tumor promoters and exhibit threshold tumor dose-responses. This is in contrast to genotoxic carcinogens that are DNA reactive, act as tumor initiators, and are assumed to exhibit proportional responses at low doses. In this perspective, we examine the basic tenets and utility of this classification for evaluating human cancer risk. Two classes of so-called nongenotoxic chemical carcinogens selected for review include cytotoxic agents that induce regenerative hyperplasia (trihalomethanes and inducers of alpha(2)-microglobulin nephropathy) and agents that act via receptor-mediated mechanisms (peroxisome proliferators and dioxin). Major conclusions of this review include: a) many chemicals considered to be nongenotoxic carcinogens actually possess certain genotoxic activities, and limiting evaluations of carcinogenicity to their nongenotoxic effects can be misleading; b) some nongenotoxic activities may cause oxidative DNA damage and thereby initiate carcinogenesis; c) although cell replication is involved in tumor development. cytotoxicity and mitogenesis do not reliably predict carcinogenesis; d) a threshold tumor response is not an inevitable result of a receptor-mediated mechanism. There are insufficient data on the chemicals reviewed here to justify treating their carcinogenic effects in animals as irrelevant for evaluating human risk. Research findings that characterize the multiple mechanisms of chemical carcinogenesis should be used quantitatively to clarify human dose-response relationships, leading to improved scientifically based public health decisions. Excessive reliance on over-simplified classification schemes that do not consider all potential contributing effects of a toxicant can obscure the actual causal relationships between exposure and cancer outcome. RP Melnick, RL (reprint author), NIEHS,LAB QUANTITAT & COMPUTAT BIOL,POB 12233,RES TRIANGLE PK,NC 27709, USA. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 122 TC 70 Z9 70 U1 0 U2 2 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 MAR PY 1996 VL 104 SU 1 BP 123 EP 134 DI 10.2307/3432702 PG 12 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA UE548 UT WOS:A1996UE54800011 PM 8722116 ER PT J AU Kohn, MC AF Kohn, MC TI Developing confidence in risk assessments based on physiological toxicokinetic models SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material RP Kohn, MC (reprint author), NIEHS,LAB QUANTITAT & COMPUTAT BIOL,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 0 TC 0 Z9 0 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 MAR PY 1996 VL 104 IS 3 BP 242 EP 243 DI 10.2307/3432873 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA UC092 UT WOS:A1996UC09200001 PM 8919755 ER PT J AU Carpenter, DO Suk, WA Blaha, K Cikrt, M AF Carpenter, DO Suk, WA Blaha, K Cikrt, M TI Hazardous wastes in Eastern and Central Europe SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE hazardous wastes; hospital wastes; incineration; landfills; municipal wastes; persistent organics; military wastes ID CANCER MORTALITY; COUNTIES; HEALTH; SITES AB The countries of Eastern and Central Europe have emerged from a political system which for decades has ignored protection of human health from hazardous wastes. While the economies of the countries in this region are stretched, awareness and concern about hazardous waste issues are a part of the new realities. At a recent conference sponsored in part by the National Institute of Environmental Health Sciences, representatives of seven countries in the region described the status of hazardous waste programs, issues of major concern, and steps being taken to protect human health. This report summarizes the deliberations, outlines some of the problems remaining in dealing with the legacy of the past, addressing the problems of the present, and providing a framework for future research and collaborative efforts. C1 NIEHS,SUPERFUND BASIC RES PROGRAM,RES TRIANGLE PK,NC 27709. NATL PUBL HLTH INST,PRAGUE 10,CZECH REPUBLIC. RP Carpenter, DO (reprint author), SUNY ALBANY,SCH PUBL HLTH,EXECUT PK S,ROOM 185,ALBANY,NY 12203, USA. NR 30 TC 5 Z9 5 U1 2 U2 3 PU NATL INST ENVIRON HEALTH SCI PI RES TRIANGLE PK PA PO BOX 12233, RES TRIANGLE PK, NC 27709 SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAR PY 1996 VL 104 IS 3 BP 244 EP 248 DI 10.2307/3432874 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA UC092 UT WOS:A1996UC09200002 PM 8919756 ER PT J AU Cantor, KP AF Cantor, KP TI Arsenic in drinking water: How much is too much? SO EPIDEMIOLOGY LA English DT Editorial Material ID CANCER RP Cantor, KP (reprint author), NCI,DIV CANC EPIDEMIOL & GENET,EPN 443,BETHESDA,MD 20892, USA. NR 19 TC 17 Z9 18 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAR PY 1996 VL 7 IS 2 BP 113 EP 115 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA TW362 UT WOS:A1996TW36200001 PM 8834547 ER PT J AU Doody, MM Linet, MS Glass, AG Rochelle, RE Pottern, LM Rush, BB Boice, JD Fraumeni, JF Friedman, GD AF Doody, MM Linet, MS Glass, AG Rochelle, RE Pottern, LM Rush, BB Boice, JD Fraumeni, JF Friedman, GD TI Risks of non Hodgkin's lymphoma, multiple myeloma, and leukemia associated with common medications SO EPIDEMIOLOGY LA English DT Article DE non-Hodgkin's lymphoma; multiple myeloma; leukemia; prescriptions (drug); drugs (nonprescription); health maintenance organizations; case control studies ID BONE-MARROW TRANSPLANTATION; ENDOMETRIAL CARCINOMA; RHEUMATOID-ARTHRITIS; BREAST-CANCER; CONJUGATED ESTROGENS; EXOGENOUS ESTROGEN; THERAPY; CARCINOGENICITY; DRUGS; AGRANULOCYTOSIS AB We utilized data from two Kaiser Permanente medical care programs to evaluate risks of hematopoietic and lymphoproliferative (HLP) malignancies after use of 14 common medications. The subjects were adult cases of non-Hodgkin's lymphoma (NHL) (N = 94), multiple myeloma (N = 159), and leukemia (N = 257) and individually matched controls (N = 695). Abstractors reviewed medical records and recorded med ication notations. Using a minimum 5-year exposure lag be tween first notation and malignancy diagnosis, the risk of NHL was greater among plan members who were prescribed amphet amines [odds ratio (OR) = 2.2; 95% confidence interval (CI) = 1.1-4.8], lidocaine (OR = 2.6; 95% CI = 1.2-5.5), and meprobamate (OR = 2.1; 95% CI = 1.03-4.3). The risk of NHL rose with increasing number of medical record notations for amphetamines; however, there was no association with number of notations for lidocaine or meprobamate. The odds ratio for total leukemia was decreased among patients who took chloramphenicol (OR = 0.4; 95% CI = 0.2-0.97). RP Doody, MM (reprint author), NCI,RADIAT EPIDEMIOL BRANCH,EPIDEMIOL & BIOSTAT PROGRAM,EXECUT PLAZA N,ROOM 408,BETHESDA,MD 20892, USA. FU NCI NIH HHS [N01-CP-01047, N01-CP-01054, N01-CP-11009] NR 61 TC 26 Z9 26 U1 1 U2 4 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAR PY 1996 VL 7 IS 2 BP 131 EP 139 DI 10.1097/00001648-199603000-00005 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA TW362 UT WOS:A1996TW36200005 PM 8834551 ER PT J AU Wacholder, S AF Wacholder, S TI The case-control study as data missing by design: Estimating risk differences SO EPIDEMIOLOGY LA English DT Article DE bias; biometry; epidemiologic methods; logistic regression; missing data; study design ID REGRESSION-MODELS; SELECTION; EXPOSURE; DISEASE; PROBABILITIES; CANCER AB There are advantages to viewing the case-control design as a missing-data problem instead of as a sampling problem. In the simplest setup, cases are those members of a population who develop disease; controls can be a small random sample of the large number who do not; and covariates, including exposures and other important variables, are available only for cases and controls and are assumed to be missing at random for the remaining large fraction of the population. This approach allows estimation of the joint distribution of all variables in the population. Thus, when the size of the population is known, analysis is not restricted to logistic and other multiplicative intercept models. Methods based on this approach can obtain estimates and confidence intervals for parameters representing the effect of exposure on disease, with multivariate adjustment for other factors. Thus, case-control data can be used to estimate the risk difference, a parameter with great public health value. The missing-data perspective offers an additional advantage by linking the ''study base principle'' of control selection with the statistical concept of ''missing at random.'' As an illustration, 1 use a subset of data from a case-control study to obtain estimates of the difference between annual risk of bladder cancer for various levels of smoking and lifetime non smokers, adjusted for occupational exposure. RP Wacholder, S (reprint author), NCI,DIV CANC EPIDEMIOL & GENET,BIOSTAT BRANCH,EPN 403,6130 EXECUT BLVD,BETHESDA,MD 20892, USA. NR 42 TC 19 Z9 20 U1 1 U2 7 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAR PY 1996 VL 7 IS 2 BP 144 EP 150 DI 10.1097/00001648-199603000-00007 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA TW362 UT WOS:A1996TW36200007 PM 8834553 ER PT J AU Friedman, DR Hatch, EE Tarone, R Kaune, WT Kleinerman, RA Wacholder, S Boice, JD Linet, MS AF Friedman, DR Hatch, EE Tarone, R Kaune, WT Kleinerman, RA Wacholder, S Boice, JD Linet, MS TI Childhood exposure to magnetic fields: Residential area measurements compared to personal dosimetry SO EPIDEMIOLOGY LA English DT Article DE electromagnetic fields; environmental monitoring; epidemiologic measurements; data collection; children ID LEUKEMIA AB We examined the relation between area measurements of residential magnetic fields and personal dosimetry measurements among 64 control children age 2-14 years from the National Cancer Institute-Children's Cancer Group's nine state case-control study of childhood leukemia. During a typical weekday, an activity diary was completed, and a 24-hour measurement was obtained in each child's bedroom. According to the activity diaries, children spent more than 40% of the 24 hours in their bedrooms, and 68% of their time at home. We found that at-home personal dosimetry levels were highly correlated with total personal dosimetry levels in children under 9 years (Spearman correlation coefficient, R = 0.94), whereas the correlation was lower in older children (R = 0.59). For all children combined, bedroom 24-hour measurements correlated well with at-home personal dosimetry levels (R = 0.76). The 24-hour bedroom measurement was a useful predictor of both at-home and total personal dosimetry measurements. Particularly for younger children, our data suggest that in-home area measurements predict both current residential and current total magnetic field exposures. This information will be valuable for assessing the validity of exposure assessment in previous and ongoing studies and for developing measurement protocols for future studies. C1 NCI,DIV CANC EPIDEMIOL & GENET,ROCKVILLE,MD. OI Kleinerman, Ruth/0000-0001-7415-2478 NR 18 TC 35 Z9 35 U1 1 U2 6 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAR PY 1996 VL 7 IS 2 BP 151 EP 155 DI 10.1097/00001648-199603000-00008 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA TW362 UT WOS:A1996TW36200008 PM 8834554 ER PT J AU Hirvonen, A Taylor, JA Wilcox, A Berkowitz, G Schachter, B Chaparro, C Bell, DA AF Hirvonen, A Taylor, JA Wilcox, A Berkowitz, G Schachter, B Chaparro, C Bell, DA TI Xenobiotic metabolism genes and the risk of recurrent spontaneous abortion SO EPIDEMIOLOGY LA English DT Article DE glutathione S-transferase M1; N-acetyltransferase 2; spontaneous abortion; genetic polymorphism; polymerase chain reaction technique; gender ID CANCER; COMMON; MISCARRIAGE AB We examined the relation between spontaneous abortion and polymorphisms in two genes, glutathione S-transferase (GSTM1) and N-acetyltransferase (NAT2), which are involved in the metabolism of xenobiotics. In a case-control study of 29 women, we found that, among women with the GSTM1 null genotype, the odds ratio (OR) was 3.1 [95% confidence interval (CI) = 1.3-7.0]. There was less evidence of a relation with NAT2 [Mantel-Haenszel adjusted OR (OR(MH)) = 1.4; 95% CI = 0.45-4.3]. We sought to replicate the CSTZ1 finding in an independent case control study from New York involving 89 cases. We found an inverse association (OR = 0.8; 95% CI = 0.4-2.4). Taken together, these data provide little evidence of an association between GSTM1 or NAT2 genotype and risk of spontaneous abortion. C1 NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC 27709. OI Wilcox, Allen/0000-0002-3376-1311; taylor, jack/0000-0001-5303-6398 NR 15 TC 16 Z9 20 U1 0 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAR PY 1996 VL 7 IS 2 BP 206 EP 208 DI 10.1097/00001648-199603000-00018 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA TW362 UT WOS:A1996TW36200018 PM 8834564 ER PT J AU Malow, BA Blaxton, TA Sato, S Bookheimer, SY Kufta, CV Figlozzi, CM Theodore, WH AF Malow, BA Blaxton, TA Sato, S Bookheimer, SY Kufta, CV Figlozzi, CM Theodore, WH TI Cortical stimulation elicits regional distinctions in auditory and visual naming SO EPILEPSIA LA English DT Article DE cortical stimulation; subdural electrodes; language; anomia; epilepsy ID TEMPORAL LANGUAGE AREA; LOBE EPILEPSY; ELECTRICAL-STIMULATION; CORTEX; LOCALIZATION; IMPAIRMENT; LOBECTOMY; SPEECH; MEMORY AB We used electrical stimulation mapping to compare performance on auditory and visual naming tasks in inferotemporal, lateral temporal, frontal, and parietal cortex in 8 temporal lobe epilepsy (TLE) patients with subdural electrodes placed for preoperative language localization. Performance on auditory responsive naming (ARN) and visual confrontation naming (VCN) was best during stimulation of parietal cortex and was equally impaired during stimulation of inferotemporal and frontal cortex. In contrast, ARN performance was significantly poorer than VCN performance during stimulation of anterior and posterior lateral temporal cortex. In most patients, stimulation of inferotemporal cortex at relatively low stimulus intensities (less than or equal to 5 mA) during either ARN or VCN elicited reproducible errors in which patients could describe, gesture, spell, or draw, but not name, in response to auditory or visual cues. Inferotemporal and frontal cortex appear to be multimodality language regions distinct from lateral temporal cortex. C1 NINCDS,NIH,EEG SECT,EPILEPSY RES BRANCH,BETHESDA,MD. NINCDS,NIH,SURG NEUROL BRANCH,BETHESDA,MD. NR 39 TC 54 Z9 54 U1 0 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD MAR PY 1996 VL 37 IS 3 BP 245 EP 252 DI 10.1111/j.1528-1157.1996.tb00020.x PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA TX890 UT WOS:A1996TX89000005 PM 8598182 ER PT J AU Ketter, TA Malow, BA Flamini, R Ko, D White, SR Post, RM Theodore, WH AF Ketter, TA Malow, BA Flamini, R Ko, D White, SR Post, RM Theodore, WH TI Felbamate monotherapy has stimulant-like effects in patients with epilepsy SO EPILEPSY RESEARCH LA English DT Article DE anticonvulsant; psychotropic medication; drug withdrawal; anxiety; depression ID PARTIAL-ONSET SEIZURES; CONTROLLED TRIAL; CLINICAL-TRIAL; RATING-SCALE; ANTICONVULSANT AB The objective of this study was to assess the psychiatric effects of the antiepileptic drug (AED) felbamate (FBM) in patients with epilepsy. FBM is a new AED with a novel putative (antiglutaminergic) mechanism. Older AEDs such as carbamazepine and valproate have psychotropic properties, but the psychiatric effects of FBM and other new antiglutamatergic AEDs remain to be determined. Thirty inpatients with refractory epilepsy were openly tapered off all AEDs in conjunction with intensive presurgical monitoring prior to a two week randomized double-blind parallel trial of FBM monotherapy versus placebo, followed by open FBM therapy. Psychopathology was rated with weekly psychiatric rating scales. Anxiety, depression and seizures increased significantly with AED discontinuation. Acute blind FBM monotherapy yielded antiepileptic and stimulant-like effects (insomnia, anorexia, and anxiety), but failed to influence AED withdrawal-emergent psychopathology. Restarting original AEDs resolved such pathology in FBM drop outs. Chronic open FBM also had stimulant-like effects, with half of the patients displaying psychiatric deterioration and the other half modest improvement compared to baseline therapies. Baseline insomnia and anxiety may be markers for poorer psychiatric responses to chronic open FBM. FBM had stimulant-like effects, lacked anxiolytic effects, and failed to attenuate AED withdrawal-emergent psychopathology. Baseline insomnia or anxiety may predict poorer psychiatric responses to FBM. Further studies are required to assess whether the novel psychiatric effects observed with FBM also occur with other new antiglutamatergic AEDs. C1 NINCDS,EPILEPSY RES BRANCH,NIH,BETHESDA,MD 20892. RP Ketter, TA (reprint author), NIMH,BIOL PSYCHIAT BRANCH,BLDG 10,ROOM 3N212,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 28 TC 33 Z9 33 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD MAR PY 1996 VL 23 IS 2 BP 129 EP 137 DI 10.1016/0920-1211(95)00089-5 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA UE005 UT WOS:A1996UE00500005 PM 8964274 ER PT J AU Blackford, J Reid, HW Pappin, DJC Bowers, FS Wilkinson, JM AF Blackford, J Reid, HW Pappin, DJC Bowers, FS Wilkinson, JM TI A monoclonal antibody, 3/22, to rabbit CD11c which induces homotypic T cell aggregation: Evidence that ICAM-1 is a ligand for CD11c/CD18 SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE rabbit; CD11c; adhesion; integrin; monoclonal antibody ID MALIGNANT CATARRHAL FEVER; LEUKOCYTE ADHESION GLYCOPROTEIN; COMPLEMENT RECEPTOR TYPE-3; ALPHA-SUBUNIT; SURFACE-ANTIGENS; MOLECULES; IDENTIFICATION; INTEGRIN; EXPRESSION; DISTINCT AB The rabbit CD11c molecule has been characterized by use of 3 new monoclonal antibody, mAb 3/22. Expression of the p150.95 integrin (CD11c/CD18) has been shown by flow cytometry and immunohistochemistry to be restricted to monocytes, macrophages, dendritic cells and a small population of lymphocytes in peripheral blood. No expression on neutrophils could be demonstrated. Incubation of the newly derived CD8(+) T cell line. BJ/873, with mAb 3/22 causes homotypic aggregation, which has been shown to be a cell surface event that is not dependent on intracellular signaling or on receptor cross-linking. Inhibition studies show that the ligands responsible for this aggregation are CD11c/CD18 and ICAM-1, both of which are expressed on BJ/873. One other rabbit T cell line, K34, that also expresses p150.95 and ICAM-1, shows a similar aggregation response when stimulated with 3/22. Cell lines that express p150.95 but not ICAM-1 do not aggregate. These observations suggest that ICAM-1 is a ligand for activated p150.95. C1 UCL EASTMAN DENT INST, MAXILLOFACIAL SURG UNIT, LONDON, ENGLAND. MOREDUN RES INST, EDINBURGH EH17 7JH, MIDLOTHIAN, SCOTLAND. IMPERIAL CANC RES FUND, LONDON, ENGLAND. NIAID, IMMUNOGENET LAB, NIH, ROCKVILLE, MD 20852 USA. WELLCOME TRUST RES LABS, LONDON NW1 2BE, ENGLAND. OI Pappin, Darryl/0000-0002-8981-8401 FU Wellcome Trust NR 49 TC 20 Z9 20 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD MAR PY 1996 VL 26 IS 3 BP 525 EP 531 DI 10.1002/eji.1830260304 PG 7 WC Immunology SC Immunology GA UJ768 UT WOS:A1996UJ76800003 PM 8605916 ER PT J AU Bush, GA Miles, FA AF Bush, GA Miles, FA TI Short-latency compensatory eye movements associated with a brief period of free fall SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE eye movement; vestibular; otolith; latency; monkey ID LINEAR HEAD MOTION; VIEWING DISTANCE; OCULAR RESPONSES; SQUIRREL-MONKEY; REFLEX; ACCELERATION; POSITION AB The vertical eye movements induced by a brief period of free fall were recorded from three monkeys (Macaca mulatta) using the electromagnetic search-coil technique. Free fall was initiated in total darkness immediately following binocular fixation of one of six target lights located at viewing distances ranging from 20 to 107 cm. Responses consisted of an initial transient downward eye movement (anticompensatory direction) with a latency of a few milliseconds at most followed by a sustained upward (compensatory) eye movement. The early transient was independent of viewing distance and attributed to an artifact, whereas the later component was a linear function of the inverse of the prior viewing distance and attributed to the translational vestibule-ocular reflex (TVOR). Response latencies for the four nearer viewing distances were determined from the individual eye velocity traces using a computerized algorithm: after removing the initial transient by subtracting the mean response obtained with the most distant viewing, a regression line was fitted to the initial rising phase of the residual response and then extrapolated back to the baseline to determine the onset. When so determined, median latencies for the nearest viewing ranged from 16.4 to 18.5 ms, values appreciably shorter than any in the literature. RP Bush, GA (reprint author), NIH,SENSORIMOTOR RES LAB,BLDG 49,ROOM 2A50,BETHESDA,MD 20892, USA. NR 20 TC 42 Z9 42 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD MAR PY 1996 VL 108 IS 2 BP 337 EP 340 PG 4 WC Neurosciences SC Neurosciences & Neurology GA UD776 UT WOS:A1996UD77600014 PM 8815042 ER PT J AU Garland, DL DouglasTabor, Y JimenezAsensio, J Datiles, MB Magno, B AF Garland, DL DouglasTabor, Y JimenezAsensio, J Datiles, MB Magno, B TI The nucleus of the human lens: Demonstration of a highly characteristic protein pattern by two-dimensional electrophoresis and introduction of a new method of lens dissection SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE lens; human; sutures; crystallins; lens proteins ID AGE-RELATED-CHANGES; ADULT HUMAN LENS; WATER; FETAL; CELL AB A practical method for dissection of human lenses is described. The method utilizes the suture patterns as a guide to identify the developmental stage in which fiber cells were formed. Lenses were separated into cortex and adult, infantile, fetal and embryonic nuclear regions. Analysis of the proteins in each of these regions in adult lenses shows that the lens nucleus has a highly characteristic two-dimensional protein pattern distinct from that of the cortex. Each of the nuclear regions has essentially the same protein pattern. The data suggest that the conversion of cortical fibers to mature nuclear fibers involves well controlled processes. (C) 1996 Academic Press Limited C1 NEI,LAB MECHANISMS OCULAR DIS,BETHESDA,MD 20892. NEI,OPHTHALM GENET & CLIN SERV BRANCH,BETHESDA,MD 20892. OI Datiles, Manuel III B./0000-0003-4660-1664 NR 26 TC 53 Z9 54 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD MAR PY 1996 VL 62 IS 3 BP 285 EP 291 DI 10.1006/exer.1996.0034 PG 7 WC Ophthalmology SC Ophthalmology GA UE297 UT WOS:A1996UE29700010 PM 8690038 ER PT J AU Chanock, SJ Faust, LRP Barrett, D Christensen, B Newburger, PE Babior, BM AF Chanock, SJ Faust, LRP Barrett, D Christensen, B Newburger, PE Babior, BM TI Partial reconstitution of the respiratory burst oxidase in lymphoblastoid B cell lines lacking p67-phox after transfection with an expression vector containing wild-type and mutant p67-phox cDNAs: Deletions of the carboxy and amino terminal residues of p67-phox are not required for activity SO EXPERIMENTAL HEMATOLOGY LA English DT Article DE respiratory burst; p67-phox; chronic granulomatous disease ID CHRONIC GRANULOMATOUS-DISEASE; SUPEROXIDE GENERATION; LYMPHOCYTES-B; CHROMOSOMAL LOCATION; CYTOSOLIC COMPONENTS; NADPH OXIDASE; GENE; ACTIVATION; MEMBRANE; CLONING AB The respiratory burst oxidase of phagocytes and B lymphocytes is a multicomponent enzyme that catalyzes the reduction of oxygen by NADPH. It is responsible for O-2(-) production in response to stimulation with phorbol 12-myristate 13-acetate (PMA). The study of patients with chronic granulomatous disease (CGD), an inherited disorder characterized by deficient or absent respiratory burst activity, has contributed greatly to our understanding of the NADPH-oxidase. The absence of any one of four components results in the clinical expression of CGD: the two membrane-bound components of the cytochrome b-558, gp91-phox and p22-phox, or the cytosolic factors, p47-phox and p67-phox. We used a system to investigate the activity of mutant p67-phox proteins expressed in a reconstitution assay. This system is characterized by the partial reconstitution of O-2(-) production in an Epstein-Barr virus (EBV)-transformed lymphoblastoid B cell line from a patient with p67-phox-deficient CGD by transfection with an expression plasmid containing the p67-phox cDNA in the sense orientation. No O-2(-) production was detectable in p67-phox-deficient lymphoblastoid B cell lines transfected with an antisense plasmid or in untransfected p67-phox lymphoblastoid cells stimulated by PMA. We tested two mutants, pEBOp67 Delta 1-22 and pEBOp67 Delta 512-526, and found that both recombinant proteins are active in our system. Thus, we conclude that the first 22 amino acid residues and the last 14 amino acid residues are not critical for initiation of O-2(-) production. C1 UNIV MASSACHUSETTS, SCH MED, DEPT PEDIAT, WORCESTER, MA 01605 USA. SCRIPPS RES INST, DEPT MOLEC & EXPTL MED, LA JOLLA, CA 92037 USA. RP Chanock, SJ (reprint author), NCI, PEDIAT BRANCH, BLDG 10, 13N240, BETHESDA, MD 20892 USA. FU NIAID NIH HHS [AI-24838, AI-24879, AI-24227] NR 30 TC 9 Z9 9 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 MAR PY 1996 VL 24 IS 4 BP 531 EP 536 PG 6 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA UD280 UT WOS:A1996UD28000008 PM 8608803 ER PT J AU Preusch, PC AF Preusch, PC TI No crystals - No grant - Response SO FASEB JOURNAL LA English DT Letter RP Preusch, PC (reprint author), NIGMS,BIOCHEM & BIORELATED CHEM PROGRAM BRANCH,PHARMACOL PHYSIOL & BIOL CHEM DIV,NIH,BETHESDA,MD 20892, USA. NR 0 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1996 VL 10 IS 4 BP 529 EP 529 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA UE557 UT WOS:A1996UE55700019 ER PT J AU Johnson, MC Devoto, L Retamales, I Kohen, P Troncoso, JL Aguilera, G AF Johnson, MC Devoto, L Retamales, I Kohen, P Troncoso, JL Aguilera, G TI Localization of insulin-like growth factor (IGF-I) and IGF-I receptor expression in human corpora lutea: Role on estradiol secretion SO FERTILITY AND STERILITY LA English DT Article DE corpus luteum; insulin-like growth factor mRNA; luteal cell culture ID CELL-MEMBRANE RECEPTOR; GRANULOSA-CELLS; GENE-EXPRESSION; HUMAN OVARY; RAT OVARY; BINDING AB Objective: To determine whether insulin-like growth factor (IGF-I) and its receptors are expressed by human corpus luteum (CL) and to establish the effect of IGF-I on E(2) biosynthesis in human luteal cell cultures. Design: Middle corpora lutea were obtained from women undergoing surgical sterilization. The tissue was frozen for binding and in situ studies or dispersed for cell cultures. Setting: Procedures were performed at the San Borja-Arriaran Hospital, National Health Service, and Institute of Maternal and Child Research, Faculty of Medicine, University of Chile. Patients: Twelve patients aged 30 to 40 years requesting surgical sterilization in our institution. The laparotomy was scheduled 6 to 8 days after ovulation. Main Outcome Measures: Expression of IGF-I and IGF-I receptor messenger RNAs (mRNAs) by in situ hybridization. Concentration of IGF-I receptor and binding characteristics. Production of E(2) by luteal cells. Results: The binding of IGF-I was detected in middle human CL membranes. In addition, this tissue expressed the mRNAs of IGF-I and its receptor. In culture, IGF-I caused a progressive increase on E(2) production. Conclusion: These data suggest that the IGF-I system is present in middle human CL. The topographic distribution of IGF-I and its receptors and the ability of IGF-I to stimulate E(2) secretion strongly suggest that IGF-I has a role as a paracrine or autocrine regulator of the human luteal function. C1 UNIV CHILE, HOSP SAN BORJA ARRIARAN, NATL HLTH SERV, INST INVEST MATERNO INFANTIL, SANTIAGO, CHILE. NICHHD, NIH, BETHESDA, MD USA. NR 25 TC 21 Z9 21 U1 1 U2 5 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 MAR PY 1996 VL 65 IS 3 BP 489 EP 494 PG 6 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA TW842 UT WOS:A1996TW84200006 PM 8774275 ER PT J AU Batista, MC Cartledge, TP Zellmer, AW Merino, MJ Nieman, LK Loriaux, DL Merriam, GR AF Batista, MC Cartledge, TP Zellmer, AW Merino, MJ Nieman, LK Loriaux, DL Merriam, GR TI A prospective controlled study of luteal and endometrial abnormalities in an infertile population SO FERTILITY AND STERILITY LA English DT Article DE endometrial biopsy; progesterone; placental protein 14; human chorionic gonadotropin ID PLACENTAL PROTEIN-14; PHASE DEFICIENCY; NORMAL FERTILITY; CYCLING WOMEN; BIOPSY; GONADOTROPIN; SERUM AB Objective: To investigate whether luteal and endometrial abnormalities occur more frequently in an infertile population and thus contribute to infertility. Design: Prospective controlled clinical study. Setting: Outpatient clinic in an academic research institution. Participants: Thirty-three fertile controls and 31 infertile women without ovulatory disorders, tubal disease, or male factors. Interventions: All women underwent an endometrial biopsy 9 days after the LH surge followed by an IM injection of 5,000 TU hCG. Blood samples were drawn immediately before hCG administration for serum P and placental protein 14 (:PP14) measurements, at 6 hours after hCG stimulation for serum P concentrations, and on day 5 after hCG administration for serum PP14 levels. Main Outcome Measures: Histologic dating of the endometrium and serum P and PP14 measurements. Results: Abnormal endometrial biopsies occurred more frequently in infertile (43%) than in fertile women (9%). Except for one case, these specimens were not associated with low hCG-stimulated P levels. Serum PP14 measurements varied widely and did not discriminate subjects with abnormal endometrial development. Conclusions: Disruption of endometrial maturation without a concomitant defect of the corpus luteum occurs more frequently in an infertile population and thus may contribute to infertility. C1 NICHHD,NIH,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT NURSING,BETHESDA,MD 20892. NCI,NIH,DIV CANC BIOL & DIAGNOST,PATHOL LAB,BETHESDA,MD 20892. NR 25 TC 6 Z9 6 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 MAR PY 1996 VL 65 IS 3 BP 495 EP 502 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA TW842 UT WOS:A1996TW84200007 PM 8774276 ER PT J AU Zinaman, MJ Clegg, ED Brown, CC OConnor, J Selevan, SG AF Zinaman, MJ Clegg, ED Brown, CC OConnor, J Selevan, SG TI Estimates of human fertility and pregnancy loss SO FERTILITY AND STERILITY LA English DT Article DE human fertility; pregnancy loss ID HUMAN CHORIONIC-GONADOTROPIN; MONOCLONAL-ANTIBODIES; WOMEN AB Objective: To examine the fertility and pregnancy wastage rates in a group of presumably fertile couples. Design: Prospective observational study of 200 couples desiring to achieve pregnancy over 12 menstrual cycles coupled with pregnancy outcome follow-up. Setting: A university-based obstetrics and gynecological center. Patients: Personal interviews and questionnaires were used to screen couples for entry into the study. Couples were counseled to have intercourse centered on predicted day of ovulation. Phase 1 included the first three cycles in which women collected daily morning urine samples, underwent midcycle postcoital tests, and, if late for their menses, presented for serum hCG testing. Phase 2 encompassed the next nine cycles in which women were contacted monthly by phone and underwent serum hCG testing if menses was delayed. Urine samples from cycles in which clinical (serum hCG) pregnancy did not occur underwent sensitive hCG testing to detect occult pregnancies. Pregnancies were followed until delivery to ascertain outcome. Results: Eighty-two percent of the 200 couples followed for the entire study period conceived. The maximal fertility rate was approximately 30% per cycle in the first two cycles. This rate quickly tapered over the remainder of the study. Pregnancy wastage during phase 1 accounted for 31% of the pregnancies detected. Forty-one percent (15/36) of these losses were seen only by urine hCG testing and were categorized as occult. Eleven of these same patients later achieved clinically recognized conceptions during the study. Conclusions: These results support the concept that the efficiency of human reproduction is maximum at approximately 30% per cycle. A very significant number of these pregnancies end in spontaneous abortion. In addition, pregnancy loss before missed menses occurs in a significant proportion of women. C1 GEORGETOWN UNIV,MED CTR,DEPT OBSTET & GYNECOL,WASHINGTON,DC 20007. US EPA,OFF RES & DEV,WASHINGTON,DC 20460. NATL CANC CTR,BETHESDA,MD. COLUMBIA UNIV,IRVING CTR CLIN RES,NEW YORK,NY. RP Zinaman, MJ (reprint author), LOYOLA UNIV,MED CTR,DEPT OBSTET & GYNECOL,2160 S 1ST AVE,MAYWOOD,IL 60153, USA. NR 21 TC 226 Z9 235 U1 2 U2 19 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 MAR PY 1996 VL 65 IS 3 BP 503 EP 509 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA TW842 UT WOS:A1996TW84200008 PM 8774277 ER PT J AU Sayle, AE Cooper, GS Savitz, DA AF Sayle, AE Cooper, GS Savitz, DA TI Menstrual and reproductive history of mothers of galactosemic children SO FERTILITY AND STERILITY LA English DT Article DE heterozygous galactosemia carriers; menopausal status; infertility; ovarian toxicity ID CIGARETTE-SMOKING; OVARIAN-CANCER; FECUNDABILITY; MENOPAUSE; WOMEN AB Objective: To test the hypothesis that female carriers of the galactosemia gene (mothers of galactosemic children) experience impaired fecundability and earlier age at natural menopause. Design: Retrospective cohort study comparing experiences of mothers of galactosemic children with mothers of children with phenylketonuria (PKU). Data collection consisted of a structured telephone interview with sections on menstrual, reproductive, and medical histories. Participants: One hundred three galactosemia carriers and 116 PKU carriers (mean age 35.0 and 38.4 years, respectively), recruited from 38 metabolic disease clinics throughout the United States. Main Outcome Measures: Time-to-pregnancy (a measure of fecundability), menstrual cycle patterns, and natural menopause. Results: No difference was seen between carriers of the galactosemia and the PKU gene in history of greater than or equal to 12 months of unprotected intercourse without a pregnancy, physician-diagnosed infertility, or amenorrhea lasting >6 weeks. The fecundability ratio, adjusting for age and smoking before most recent pregnancy, was 1.17 (95% confidence interval [CI] 0.85 to 1.61). By age 45, 11% of galactosemia carriers who had not had a hysterectomy reported a natural menopause compared with 4% of PKU carriers (risk difference 7.2%, 95% CI - 12.7% to 27.1%). Conclusion: Fecundability and other measures of fertility did not differ between mothers of galactosemic children and mothers of children with PKU. Suggestions of an earlier age at natural menopause can not be addressed definitively in this cohort because of the small number of participants who were currently age 45 years or older but may warrant additional assessment as the cohort ages. C1 UNIV N CAROLINA,DEPT EPIDEMIOL,CHAPEL HILL,NC 27599. NIEHS,EPIDEMIOL BRANCH,RES TRIANGLE PK,NC 27709. NR 12 TC 5 Z9 5 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 MAR PY 1996 VL 65 IS 3 BP 534 EP 538 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA TW842 UT WOS:A1996TW84200013 PM 8774282 ER PT J AU Brown, M Rudicel, S Esquenazi, A AF Brown, M Rudicel, S Esquenazi, A TI Measurement of dynamic pressures at the shoe-foot interface during normal walking with various foot orthoses using the FSCAN system SO FOOT & ANKLE INTERNATIONAL LA English DT Article ID FORCES AB Foot orthoses are routinely used in clinical practice to redistribute pressure at the shoe-foot interface, although there is very little scientific evidence to support the efficacy of their use. In this study, the FSCAN sensor (an ultrathin in-shoe transducer) was used to determine the efficacy of pressure redistribution with a Plastizote, Spence, cork, and a plastic foot orthosis as compared with control (no orthosis). Measurement variations of up to 18% occurred between sensors, and changes in stance time of up to 5% occurred between the orthoses and the control conditions. In spite of these potentially confounding variables, statistically significant differences in peak pressure between the orthotic types and the control condition (range, 9-146%) were noted. We conclude that Plastizote, cork, and plastic foot orthoses can be beneficial in relieving pressure in certain regions of the shoe-foot interface, but that they may do so at the cost of increasing pressure in other areas of the plantar surface. C1 TUFTS UNIV,NEW ENGLAND MED CTR,BOSTON,MA 02111. TEMPLE UNIV,MOSS REHABIL HOSP,PHILADELPHIA,PA 19122. RP Brown, M (reprint author), NIAMSD,NIH,BLDG 10,ROOM 6S235,BETHESDA,MD 20892, USA. NR 18 TC 45 Z9 46 U1 1 U2 5 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1071-1007 J9 FOOT ANKLE INT JI Foot Ankle Int. PD MAR PY 1996 VL 17 IS 3 BP 152 EP 156 PG 5 WC Orthopedics SC Orthopedics GA UC432 UT WOS:A1996UC43200006 PM 8919619 ER PT J AU Irwin, RD Chhabra, R Eustis, S Pinter, A Prejean, JD AF Irwin, RD Chhabra, R Eustis, S Pinter, A Prejean, JD TI Tumors of the bladder, kidney, and intestine of F344 rats and liver of B6C3F(1) mice administered o-nitroanisole in feed SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID DOSE-RESPONSE; CARCINOGENESIS; TESTS AB o-Nitroanisole, a mutagenic intermediate used in the manufacture of azo dyes, was administered in feed for 2 years at concentrations of 0, 222, 666, or 2000 ppm to groups of 60 male and 60 female F344 rats. No significant increase in neoplasms occurred in these groups of rats. Additional (stop exposure) groups of 60 male and 60 female F344 rats received diets containing 0, 6000, or 18,000 ppm for 27 weeks followed by maintenance on control diets for up to an additional 77 weeks. Survival of the stop exposure groups was reduced because of the development of chemical related neoplasms of the urinary bladder. After 13, 28, 40, and 65 weeks on study, 10 rats per group were necropsied and evaluated for the presence of chemical associated lesions. Hyperplasia of the epithelium of the urinary bladder was significantly increased at all interim evaluations. A transitional cell carcinoma was observed at the 13-week evaluation in one male rat that received 18,000 ppm and thereafter transitional cell neoplasms of the bladder were present in male and female rats at each interim evaluation. Adenomatous polyps of the large intestine were significantly increased in groups that received 6000 or 18,000 ppm. In addition carcinomas of the large intestine were present in four males and two females that received 18,000 ppm. Hyperplasia of the transitional epithelium of the renal pelvis was significantly increased in groups of rats that received 6000 or 18,000 ppm and transitional cell papillomas were observed in three males and one female that received 18,000 ppm. Transitional cell carcinomas of the kidney occurred in one male that received 6000 ppm and six males and one female that received 18,000. Groups of 60 male and 60 female B6C3F(1) mice received dietary concentrations of 0, 666, 2000, or 6000 ppm o-nitroanisole for 2 years. No stop exposure study was conducted with mice. The only neoplastic response observed in mice was in the liver of males; hepatocellular adenomas or carcinomas were increased in groups of male mice that received 2000 or 6000 ppm. No increase in neoplasms associated with chemical exposure occurred in female mice. (C) 1996 Society of Toxicology C1 SO RES INST,BIRMINGHAM,AL 35255. NATL INST HYG,H-1966 BUDAPEST,HUNGARY. RP Irwin, RD (reprint author), NIEHS,RES TRIANGLE PK,NC 27709, USA. NR 12 TC 4 Z9 4 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD MAR PY 1996 VL 30 IS 1 BP 1 EP 12 DI 10.1006/faat.1996.0037 PG 12 WC Toxicology SC Toxicology GA TY224 UT WOS:A1996TY22400001 PM 8812201 ER PT J AU Travlos, GS Mahler, J Ragan, HA Chou, BJ Bucher, JR AF Travlos, GS Mahler, J Ragan, HA Chou, BJ Bucher, JR TI Thirteen-week inhalation toxicity of 2- and 4-chloronitrobenzene in F344/N rats and B6C3F1 mice SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID ZERO DOSE CONTROL; VIRAL-INFECTIONS; TUMOR PREVALENCE; BODY-WEIGHT; CARCINOGENICITY; SURVIVAL AB Toxicity studies were performed by exposing F344/N rats and B6C3F1 mice to 2- and 4-chloronitrobenzene (CNB) by whole-body inhalation 6 hr/day, 5 days/week, for 13 weeks. Animals were evaluated for clinical chemistry (rats), hematology (rats), histopathology, and body/organ weights. Exposure concentrations were 0, 1.1, 2.3, 4.5, 9, and 18 ppm for 2-CNB and 0, 1.5, 3, 6, 12, and 24 ppm for 4-CNB. All rats in the 2-CNB study survived until the end of the study. Two male mice in the 18-ppm group in the 2-CNB study, however, died during Week 12; no deaths attributable to 4-CNB exposure occurred in rats or mice. In both studies, the mean body weight gains of exposed animals were similar to those of the respective controls. In rats, inhalation exposure to 2- or 4-CNB resulted in methemoglobinemia leading to a regenerative anemia and a variety of tissue changes secondary to the oxidative erythrocyte injury. In the 2-CNB study, methemoglobinemia resulted in a normocytic, normochromic, responsive anemia, whereas with 4-CNB, the methemoglobinemia was more severe and resulted in a macrocytic, hyperchromic, responsive anemia. Alterations of erythrocyte morphology were observed in both studies; changes included Heinz bodies, poikilocytes, and polychromasia. In rats, both isomers caused increases in serum activities of alanine aminotransferase and sorbitol dehydrogenase and increased bile acid concentrations. Microscopic liver changes included hemosiderin deposition in Kupffer cells (rats and mice exposed to 4-CNB), hepatocytomegaly (mice), and cytoplasmic basophilia (rats). Hepatocellular necrosis and chronic inflammation observed in mice were rather specific to the 2-CNB isomer, as only slight evidence of focal necrosis in the liver was observed in mice exposed to 4-CNB. Splenic lesions included hemosiderin accumulation, capsular fibrosis, and increased hematopoietic cell proliferation. Increased bone marrow hemosiderin and hematopoietic cell proliferation and kidney tubule hemosiderin deposition were also observed. Other findings, attributed to chemical exposure but not to the hematotoxicity, were described. Lesions included hyaline droplet nephropathy and degeneration of the testis in male rats exposed to 4-CNB, inflammation of the harderian gland in rats exposed to 4-CNB, hyperplasia of the nasal cavity epithelium in rats exposed to 2-CNB, and hyperplasia of the forestomach epithelium in mice exposed to 4-CNB; these lesions have not been described previously in studies with these chemicals. Based on the exposure concentrations evaluated, A no-observed-adverse-effect level (NOAEL) for histopathological injury in mice was 4.5 ppm for 2-chloronitrobenzene and 6 ppm for 4-chloronitrobenzene; a NOAEL was not determined for rats. (C) 1996 Society of Toxicology C1 PACIFIC NW LAB, RICHLAND, WA 99352 USA. RP Travlos, GS (reprint author), NIEHS, POB 12233, RES TRIANGLE PK, NC 27709 USA. NR 46 TC 27 Z9 39 U1 1 U2 7 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD MAR PY 1996 VL 30 IS 1 BP 75 EP 92 DI 10.1006/faat.1996.0045 PG 18 WC Toxicology SC Toxicology GA TY224 UT WOS:A1996TY22400009 PM 8812232 ER PT J AU Chan, PC Sills, RC Braun, AG Haseman, JK Bucher, JR AF Chan, PC Sills, RC Braun, AG Haseman, JK Bucher, JR TI Toxicity and carcinogenicity of Delta(9)-tetrahydrocannabinol in Fischer rats and B6C3F1 mice SO FUNDAMENTAL AND APPLIED TOXICOLOGY LA English DT Article ID STATISTICAL ISSUES; CANNABINOIDS; DELTA-9-TETRAHYDROCANNABINOL; DELTA9-TETRAHYDROCANNABINOL; PERIODS AB Delta(9)-Tetrahydrocannabinol (Delta(9)-THC) was studied for potential carcinogenicity in rodents because it is the principal psychoactive ingredient in marihuana and it has potential medicinal uses. Delta(9)-THC in corn oil was administered by gavage to groups of male and female Fischer rats and B6C3F1 mice at 0, 5, 15, 50, 150, or 500 mg/kg, 5 days a week for 13 weeks and for 13-week plus a 9-week recovery period, and to groups of rats at 0, 12.5, 25, or 50 mg/kg and mice at 0, 125, 250, or 500 mg/kg, 5 times a week for 2 years. In all studies, mean body weights of dosed male and female rats and mice were lower than controls but feed consumptions were similar. Convulsions and hyperactivity were observed in dosed rats and mice; the onset and frequency were dose related. Serum FSH and LH levels in all dosed male rats and corticosterone levels in 25 mg/kg female rats were significantly higher than controls at 15 months in the 2-year studies. Delta(9)-THC administration for 13 weeks induced testicular atrophy and uterine and ovarian hypoplasia; the lesions persisted in a 9-week recovery period. In the 2-year studies, survival of dosed rats was higher than controls; that of mice was similar to controls. Incidences of testicular interstitial cell, pancreas and pituitary gland adenomas in male rats, mammary gland fibroadenoma and uterus stromal polyp in female rats, and hepatocellular adenoma/carcinoma in male and female mice were reduced in a dose-related manner. Decreased tumor incidences may be at least in part due to reduced body weights of dosed animals. Incidences of thyroid gland follicular cell hyperplasia were increased in all dosed groups of male and female mice, and follicular cell adenomas were significantly increased in the 125 mg/kg group of males, but there was no evidence of a dose-related trend in proliferative lesions of the thyroid. There was no evidence that Delta(9)-THC was carcinogenic in rats or mice. (C) 1996 Society of Toxicology C1 TSI MASON RES INST,WORCESTER,MA 01608. RP Chan, PC (reprint author), NIEHS,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 26 TC 49 Z9 49 U1 0 U2 5 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0272-0590 J9 FUND APPL TOXICOL JI Fundam. Appl. Toxicol. PD MAR PY 1996 VL 30 IS 1 BP 109 EP 117 DI 10.1006/faat.1996.0048 PG 9 WC Toxicology SC Toxicology GA TY224 UT WOS:A1996TY22400012 PM 8812248 ER PT J AU Lyon, GR AF Lyon, GR TI Learning disabilities SO FUTURE OF CHILDREN LA English DT Article ID DYSLEXIA; CHILDREN; PROGRAM AB Approximately 5% of all public school students are identified as having a learning disability (LD). LD is not a single disorder, but includes disabilities in any of seven areas related to reading, language, and mathematics. These separate types of learning disabilities frequently co-occur with one another and with social skill deficits and emotional of behavioral disorders. Most of the available information concerning learning disabilities relates to reading disabilities, and the majority of children with learning disabilities have their primary deficits in basic reading skills. An important part of the definition of LD is its exclusions: learning disabilities cannot be attributed primarily to mental retardation, emotional disturbance, cultural difference, or disadvantage. Thus, the concept of LD focuses on the notion of a discrepancy between a child's academic achievement and his or her apparent capacity to learn. Recent research indicates, however, that disability in basic reading skills is primarily caused by deficits in phonological awareness, which is independent of any achievement-capacity discrepancy. Deficits in phonological awareness can be identified in late kindergarten and first grade using inexpensive, straightfonvard testing protocol. Interventions have varying effectiveness, depending largely on the severity of the individual child's disability. The prevalence of learning disability identification has increased dramatically in the past 20 years. The ''real'' prevalence of LD is subject to much dispute because of the lack of an agreed-upon definition of LD with objective identification criteria. Some researchers have argued that the currently recognized 5% prevalence rate is inflated; others argue that LD is still underidentified. In fact, it appears that there are both sound and unsound reasons for the increase in identification rates. Sound reasons for the increase include better research, a broader definition of disability in reading, focusing on phonological awareness, and greater identification of girls with learning disabilities. Unsound reasons for the increase include broad and vague definitions of learning disability, financial incentives to identify students for speciaI education, and inadequate preparation of teachers by colleges of education, leading to overreferral of students with any type of special need. There is no clear demarcation between students with normal reading abilities and those with mild reading disability. The majority of children with reading disabilities have relatively mild reading disabilities, with a smaller number having extreme reading disabilities. The longer children with disability in basic reading skills, at any level of severity, go without identification and intervention, the more difficult the task of remediation and the lower the rate of success. Children with extreme deficits in basic reading skills are much more difficult to remediate than children with mild or moderate deficits. It is unclear whether children in the most severe range can achieve age- and grade-approximate reading skills, even with normal intelligence and with intense, informed intervention provided over a protracted period of time. Children with severe learning disabilities are likely to manifest an increased number of and increased severity of social and behavioral deficits. When children with disabilities in reading also manifest attention deficit disorder, their reading deficits are typically exacerbated, more severe, and more resistant to intervention. While severe reading disorders are clearly a major concern, even mild deficits in reading skills are likely to portend significant difficulties in academic learning. These deficits, too, are worthy of early identification and intervention. Even children with relatively subtle linguistic and reading deficits require the expertise of a teacher who is well trained and informed about the relationships between language development and reading development. Unfortunately, such teachers are in short supply, primarily because of a lack of professional certification programs providing this training. This article focuses primarily on deficits in basic reading skills, both because of their critical importance to academic success and because relatively more is known about these deficiencies. However, other academic, social, and behavioral manifestations of learning disability are also important and cannot be assumed to be adequately addressed by programs to improve basic reading skills. While early intervention is necessary, it should not be assumed to be sufficient to address the multiple manifestations of learning disability. RP Lyon, GR (reprint author), NICHHD, NIH, BETHESDA, MD 20892 USA. NR 71 TC 96 Z9 98 U1 7 U2 45 PU PRINCETON UNIV PI PRINCETON PA 277 WALLACE HALL, PRINCETON, NJ 08544 USA SN 1054-8289 EI 1550-1558 J9 FUTURE CHILD JI Future Child. PD SPR PY 1996 VL 6 IS 1 BP 54 EP 76 DI 10.2307/1602494 PG 23 WC Family Studies; Health Policy & Services; Social Sciences, Interdisciplinary SC Family Studies; Health Care Sciences & Services; Social Sciences - Other Topics GA UT689 UT WOS:A1996UT68900005 PM 8689262 ER PT J AU Pruchno, RA Johnson, KW AF Pruchno, RA Johnson, KW TI Research on grandparenting: Review of current studies and future needs SO GENERATIONS-JOURNAL OF THE AMERICAN SOCIETY ON AGING LA English DT Review ID ADULT GRANDCHILDREN; FAMILY; GRANDMOTHERS; PERCEPTIONS; DIVORCE; IMPACT; HEALTH; ROLES; LIFE C1 NIA,OLDER PEOPLE & SOC SECT,BEHAV & SOCIAL RES PROGRAM,BETHESDA,MD 20892. RP Pruchno, RA (reprint author), BRADLEY UNIV,CTR AGING,PEORIA,IL 61625, USA. NR 88 TC 12 Z9 12 U1 0 U2 2 PU AMER SOC AGING PI SAN FRANCISCO PA 833 MARKET ST STE 511, SAN FRANCISCO, CA 94103-1824 SN 0738-7806 J9 GENERATIONS JI Generations-J. Am. Soc. Aging PD SPR PY 1996 VL 20 IS 1 BP 65 EP 70 PG 6 WC Gerontology SC Geriatrics & Gerontology GA UG370 UT WOS:A1996UG37000015 ER PT J AU Cleghon, V Gayko, U Copeland, TD Perkins, LA Perrimon, N Morrison, DK AF Cleghon, V Gayko, U Copeland, TD Perkins, LA Perrimon, N Morrison, DK TI Drosophila terminal structure development is regulated by the compensatory activities of positive and negative phosphotyrosine signaling sites on the Torso RTK SO GENES & DEVELOPMENT LA English DT Article DE receptor tyrosine kinase; drosophila; Torso; Corkscrew ID RECEPTOR TYROSINE KINASE; EMBRYONIC TERMINI; GENE TAILLESS; BODY PATTERN; PHOSPHATASE; TRANSDUCTION; ACTIVATION; ENCODES AB Specification of cell fates in the nonsegmented terminal regions of developing Drosophila embryos is under the control of a signal transduction pathway mediated by the receptor tyrosine kinase Torso (Tor). Here, we identify tyrosines (Y) 630 and 918 as the major sites of Tor autophosphorylation. We demonstrate that mutation of Y630, a site required for association with and tyrosine phosphorylation of the tyrosine phosphatase Corkscrew, decreases the efficiency of Tor signaling. In contrast, mutation of Y918, a site capable of binding mammalian rasGAP and PLC-gamma 1, increases Tor signaling. Interestingly, when receptors contain mutations in both the Y630 and Y918 sites, Tor signaling is restored to wild-type levels. These results identify a novel mechanism whereby Tor function is regulated using compensatory signals generated from distinct autophosphorylation sites and reveal an underlying signaling pathway for terminal development. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,CELLULAR GROWTH MECHANISMS SECT,FREDERICK,MD 21702. HARVARD UNIV,SCH MED,HOWARD HUGHES MED INST,DEPT GENET,BOSTON,MA 02115. MASSACHUSETTS GEN HOSP,PEDIAT SURG RES LAB,BOSTON,MA 02114. RI Perrimon, Norbert/F-9766-2011 NR 44 TC 40 Z9 40 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAR 1 PY 1996 VL 10 IS 5 BP 566 EP 577 DI 10.1101/gad.10.5.566 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA TZ839 UT WOS:A1996TZ83900005 PM 8598287 ER PT J AU Gellert, M AF Gellert, M TI A new view of V(D)J recombination SO GENES TO CELLS LA English DT Review ID STRAND-BREAK-REPAIR; DEPENDENT PROTEIN-KINASE; COMBINED IMMUNE-DEFICIENCY; BROKEN DNA-MOLECULES; SCID MUTATION; GENE REARRANGEMENT; CATALYTIC SUBUNIT; MOUSE THYMOCYTES; CODING SEGMENTS; MICE AB The DNA rearrangement that assembles antibody and T cell receptor genes is beginning to be understood. New work shows that the first step is a site-specific cleavage which can be performed by purified RAG1 and RAG2 proteins. The later steps largely overlap with the repair of radiation-induced DNA double-strand breaks, as indicated by the identity of several newly cloned factors. These developments open the way for a thorough biochemical study of V(D)J recombination. C1 NIDDKD,MOL BIOL LAB,BETHESDA,MD 20892. NR 40 TC 20 Z9 20 U1 1 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 1356-9597 J9 GENES CELLS JI Genes Cells PD MAR PY 1996 VL 1 IS 3 BP 269 EP 275 DI 10.1046/j.1365-2443.1996.22023.x PG 7 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA VC844 UT WOS:A1996VC84400001 PM 9133660 ER PT J AU Rinckel, LA Garfinkel, DJ AF Rinckel, LA Garfinkel, DJ TI Influences of histone stoichiometry on the target site preference of retrotransposons Ty1 and Ty2 in Saccharomyces cerevisiae SO GENETICS LA English DT Article ID UBIQUITIN-CONJUGATING ENZYME; TRANSFER-RNA GENES; CHROMATIN STRUCTURE; INTEGRATION SPECIFICITY; HYPERSENSITIVE SITES; S-CEREVISIAE; CAN1 LOCUS; SPT3 GENE; YEAST; TRANSPOSITION AB In Saccharomyces cerevisiae, the target site specificity of the retrotransposon Ty1 appears to involve the Ty integration complex recognizing chromatin structures. To determine whether changes in chromatin structure affect Ty1 and Ty2 target site preference, we analyzed Ty transposition at the CAN1 locus in mutants containing altered levels of histone proteins. A Delta hta1-htb1 mutant with decreased levels of H2A and H2B histone proteins showed a pattern of Ty1 and Ty2 insertions at CAN1 that was significantly different from that of both the wild-type and a Delta hta2-htb2 mutant, which does not have altered histone protein levels. Altered levels of H2A and H2B proteins disrupted a dramatic orientation bias in the CAN1 promoter region. In the wild-type strains, few Ty1 and Ty2 insertions in the promoter region were oriented opposite to the direction of CAN1 transcription. In the Delta hta1-htb1 background, however, numerous Ty1 and Ty2 insertions were in the opposite orientation clustered within the TATA region. This altered insertion pattern does not appear to be due to a bias caused by selecting canavanine resistant isolates in the different HTA1-HTB1 backgrounds. Our results suggest that reduced levels of histone proteins alter Ty target site preference and disrupt an asymmetric Ty insertion pattern. C1 NCI,FREDERICK CANC RES & DEV CTR,GENE REGULAT & CHROMOSOME BIOL LAB,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NR 51 TC 26 Z9 26 U1 0 U2 0 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD MAR PY 1996 VL 142 IS 3 BP 761 EP 776 PG 16 WC Genetics & Heredity SC Genetics & Heredity GA TX455 UT WOS:A1996TX45500011 PM 8849886 ER PT J AU Bedell, MA Copeland, NG Jenkins, NA AF Bedell, MA Copeland, NG Jenkins, NA TI Multiple pathways for Steel regulation suggested by genomic and sequence analysis of the murine Steel gene SO GENETICS LA English DT Article ID CELL GROWTH-FACTOR; C-KIT RECEPTOR; TYROSINE KINASE RECEPTOR; W-LOCUS; ENHANCER ELEMENTS; MESSENGER-RNA; SI-LOCUS; PROTO-ONCOGENE; EXPRESSION; LIGAND AB The Steel (Sl) locus encodes mast cell growth factor (Mgf) that is required for the development of germ cells, hematopoietic cells and melanocytes. Although the expression patterns of the Mgf gene are well characterized, little is known of the factors which regulate its expression. Here, we describe the cloning and sequence of the full-length transcription unit and the 5' flanking region of the murine Mgf gene. The full-length Mgf mRNA consists of a short 5' untranslated region (UTR), a 0.8-kb ORF and a long 3' UTR. A single transcription initiation site is used in a number of mouse tissues and is located just downstream of binding sites for several known transcription factors. In the 5' UTR, two ATGs were found upstream ol the initiator methionine and are conserved among different species, suggesting that Mgf may be translationally regulated. At least two Mgf mRNAs are produced by alternative use of polyadenylation sites, but numerous other potential polyadenylation sites were found in the 3' UTR. In addition, the 3' UTR contains numerous sequence motifs that may regulate Mgf mRNA stability. These studies suggest multiple ways in which expression of Mgf may be regulated. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. NR 39 TC 19 Z9 21 U1 0 U2 0 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD MAR PY 1996 VL 142 IS 3 BP 927 EP 934 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA TX455 UT WOS:A1996TX45500023 PM 8849898 ER PT J AU Bedell, MA Cleveland, LS OSullivan, TN Copeland, NG Jenkins, NA AF Bedell, MA Cleveland, LS OSullivan, TN Copeland, NG Jenkins, NA TI Deletion and interallelic complementation analysis of Steel mutant mice SO GENETICS LA English DT Article ID TYROSINE KINASE RECEPTOR; GENETIC-LINKAGE MAP; CELL GROWTH-FACTOR; KIT LIGAND; W-LOCUS; MOUSE CHROMOSOME-10; PROTO-ONCOGENE; SI-LOCUS; TRANSMEMBRANE; PRODUCT AB Mutations at the Steel (Sl) locus produce pleiotropic effects on viability as well as hematopoiesis, pigmentation and fertility. Several homozygous viable Sl alleles have previously been shown to contain either structural alterations in mast cell growth factor (Mgf) or regulatory mutations that affect expression of the Mgf gene. More severe Sl alleles cause lethality to homozygous embryos and all lethal Sl alleles examined to dare contain deletions that remove the entire Mgf coding region. As the timing of the lethality varies from early to late in gestation, it is possible that some deletions may affect other closely linked genes in addition to Mgf. We have analyzed the extent of deleted sequences in seven homozygous lethal Sl alleles. The results of this analysis suggest that late gestation lethality represents the Sl null phenotype and that peri-implantation lethality results from the deletion of at least one essential gene that maps proximal to Sl. We have also examined gene dosage effects of Sl by comparing the phenotypes of mice homozygous and hemizygous for each of four viable Sl alleles. Lastly, we show that certain combinations of the viable Sl alleles exhibit interallelic complementation. Possible mechanisms by which such complementation could occur are discussed. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. NR 39 TC 23 Z9 24 U1 1 U2 1 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 SN 0016-6731 J9 GENETICS JI Genetics PD MAR PY 1996 VL 142 IS 3 BP 935 EP 944 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA TX455 UT WOS:A1996TX45500024 PM 8849899 ER PT J AU Brinkmann, U Gallo, M Polymeropoulos, MH Pastan, I AF Brinkmann, U Gallo, M Polymeropoulos, MH Pastan, I TI The human CAS (cellular apoptosis susceptibility) gene mapping on chromosome 20q13 is amplified in BT474 breast cancer cells and part of aberrant chromosomes in breast and colon cancer cell lines SO GENOME RESEARCH LA English DT Article AB The CAS (cellular apoptosis susceptibility) gene is the human homolog of the yeast chromosome segregation gene CSE1. CAS may have a dual Function in mammalian cells, one in apoptosis and another in cell proliferation. We have now mapped the CAS gene to chromosome 20q13. This region is known to harbor amplifications that correlate with aggressive breast cancer. Southern hybridizations with a CAS cDNA fragment and Fluorescent in situ hybridization (FISH) with a P1 clone containing the CAS gene show elevated copy numbers in one leukemia, three of four colon, and in three of seven breast cancer cell lines. Elevated CAS copy number in CEM leukemia and COLO201 colon cancer cells was attributable to additional copies of chromosome 20. In SW480 and COLO205 colon cancer cells CAS is part of aberrant chromosomes containing large parts of 20q. In breast cancer cells CAS is also part of aberrant 20q chromosomes (MDA-MB-157 and UACC-812) or of additional 20q isochromosome in MDA-MB-134. In MDA-MB361 and BT-474 breast cancer cells CAS is separated from other markers centromeric and telomeric of CAS on 20q. MDA-MB 361 contains one additional copy of GAS, separated from the centromeric 20q control probe. BT-474 cells have up to 12 additional CAS copies that we separated from nearby telomeric and centromeric probes on 20q and that are translocated to abnormal chromosomes. C1 NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. RP Brinkmann, U (reprint author), NCI,NIH,DIV BASIC SCI,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 17 TC 93 Z9 94 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 1054-9803 J9 GENOME RES JI Genome Res. PD MAR PY 1996 VL 6 IS 3 BP 187 EP 194 DI 10.1101/gr.6.3.187 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA UD146 UT WOS:A1996UD14600003 PM 8963895 ER PT J AU Hoglund, P Haila, S Scherer, SW Tsui, LC Green, ED Weissenbach, J Holmberg, C delaChapelle, A Kere, J AF Hoglund, P Haila, S Scherer, SW Tsui, LC Green, ED Weissenbach, J Holmberg, C delaChapelle, A Kere, J TI Positional candidate genes for congenital chloride diarrhea suggested by high-resolution physical mapping in chromosome region 7q31 SO GENOME RESEARCH LA English DT Article ID HUMAN GENOME; YEAST; DNA; IDENTIFICATION; LOCALIZATION; LIBRARY; CLONING; PROTEIN; CHAIN; MAP AB Congenital chloride diarrhea affects intestinal transportation of electrolytes, resulting in potentially Fatal diarrhea. Linkage disequilibrium analyses have suggested the congenital chloride diarrhea gene (CLD) to lie within 0.37 cM from D7S496 in human chromosome 7q31. To clone the CLD gene, we have constructed and refined a physical map based on a 2.7-Mb YAC contig around D7S496 and identified two candidate genes. The physical positions of 4 known genes (DRA, PRKAR2B, LAMB1, DLD), 7 polymorphic repeat markers, and 13 CpG islands were established. DRA (down-regulated in adenoma) is expressed in the gut and encodes a protein with sequence homology to anion transporters, whereas PRKAR2B encodes a regulatory subunit for protein kinase A. Both genes map within 450 kb from D7S496, making them functionally and positionally relevant candidates for CLD. C1 UNIV TORONTO,DEPT MOLEC & MED GENET,TORONTO,ON M5S 1A1,CANADA. HOSP SICK CHILDREN,DEPT GENET,TORONTO,ON M5G 1X8,CANADA. NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. GENETHON,CNRS URA 1922,F-91000 EVRY,FRANCE. UNIV HELSINKI,CHILDRENS HOSP,SF-00290 HELSINKI,FINLAND. RP Hoglund, P (reprint author), UNIV HELSINKI,DEPT MED GENET,SF-00014 HELSINKI,FINLAND. RI Kere, Juha/A-9179-2008; Tsui, Lap-chee/A-1081-2010; Howe, Jennifer/I-9013-2012; Scherer, Stephen /B-3785-2013 OI Kere, Juha/0000-0003-1974-0271; Scherer, Stephen /0000-0002-8326-1999 FU NIGMS NIH HHS [GM46641] NR 33 TC 26 Z9 26 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 1054-9803 J9 GENOME RES JI Genome Res. PD MAR PY 1996 VL 6 IS 3 BP 202 EP 210 DI 10.1101/gr.6.3.202 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA UD146 UT WOS:A1996UD14600005 PM 8963897 ER PT J AU Huh, TL Kim, YO Oh, IU Song, BJ Inazawa, J AF Huh, TL Kim, YO Oh, IU Song, BJ Inazawa, J TI Assignment of the human mitochondrial NAD(+)-specific isocitrate dehydrogenase alpha subunit (IDH3A) gene to 15q25.1->q25.2 by in situ hybridization SO GENOMICS LA English DT Article ID PIG-HEART; INSITU HYBRIDIZATION; CHROMOSOME-15; LOCALIZATION; SEQUENCES; CLONING; REGION C1 NIAAA,NEUROGENET LAB,ROCKVILLE,MD 20852. KYOTO PREFECTURAL UNIV MED,DEPT HYG,KAMIGYO KU,KYOTO 602,JAPAN. RP Huh, TL (reprint author), KYUNGPOOK NATL UNIV,COLL NAT SCI,DEPT GENET ENGN,TAEGU 702701,SOUTH KOREA. NR 19 TC 11 Z9 11 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD MAR 1 PY 1996 VL 32 IS 2 BP 295 EP 296 DI 10.1006/geno.1996.0120 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA TZ197 UT WOS:A1996TZ19700018 PM 8833160 ER PT J AU Young, JK Baker, JH Muller, T AF Young, JK Baker, JH Muller, T TI Immunoreactivity for brain-fatty acid binding protein in Gomori-positive astrocytes SO GLIA LA English DT Article DE hypothalamus; glia; Alzheimer's; Apo E; lipids; DBI ID NORMAL RAT-BRAIN; APOLIPOPROTEIN-E; GLIAL-CELLS; DISEASE; NEURONS AB Gomori-positive (GP) astrocytes are a subset of brain astrocytes with highly stained cytoplasmic granules that arise from the degradation of mitochondria. The GP granules of these astrocytes are most prominent in the arcuate nucleus of the hypothalamus, but can also be detected in the olfactory bulbs, hippocampus, habenula, and other selected brain regions. The cause and functional effects of this mitochondrial pathology in these glia are not yet known with certainty. In other tissues, mitochondrial dysfunction is associated with elevations in cytoplasmic lipids and lipid-binding proteins, due to impaired mitochondrial oxidation of lipids. To see if GP astrocytic mitochondrial pathology is also associated with an elevation in lipid binding proteins, rat brain sections were stained for brain fatty acid binding protein (B-FABP), using immunocytochemistry. Astrocytes immunoreactive for B-FABP were much more abundant in brain regions enriched in GP astrocytes than in other brain regions. Semi-thin sections revealed that astrocytic B-FABP immunoreactivity was often, but not always, associated with GP cytoplasmic granules. These data suggest that GP astrocytes have an unusual lipid metabolism, which may relate to degenerative processes occurring in the selected brain regions that contain GP astrocytes. (C) 1996 Wiley-Liss, Inc. C1 NINCDS,NIH,MOLEC BIOL LAB,BETHESDA,MD 20892. MAX DELBRUCK CTR MOLEC MED,BERLIN,GERMANY. RP Young, JK (reprint author), HOWARD UNIV,DEPT ANAT,520 W ST NW,WASHINGTON,DC 20059, USA. OI Young, John/0000-0002-1294-942X FU NIGMS NIH HHS [SO6GM08016] NR 25 TC 21 Z9 21 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 0894-1491 J9 GLIA JI Glia PD MAR PY 1996 VL 16 IS 3 BP 218 EP 226 PG 9 WC Neurosciences SC Neurosciences & Neurology GA TY427 UT WOS:A1996TY42700004 PM 8833192 ER PT J AU Peehl, DM Wong, ST Rubin, JS AF Peehl, DM Wong, ST Rubin, JS TI KGF and EGF differentially regulate the phenotype of prostatic epithelial cells SO GROWTH REGULATION LA English DT Article DE epidermal growth factor; keratinocyte growth factor; prostate; retinoic acid; keratin; differentiation; fibroblast growth factor ID EPIDERMAL GROWTH-FACTOR; SERUM-FREE; HUMAN KERATINOCYTES; MESSENGER-RNA; RAT PROSTATE; FACTOR-ALPHA; CANCER; EXPRESSION; CARCINOMA; BENIGN AB Previous studies indicate that keratinocyte growth factor (KGF) acts as a paracrine factor in the prostatic epithelium and epidermal growth factor (EGF) acts as an autocrine factor. In serum-free medium, KGF or EGF promoted similar growth of human prostatic epithelial cells. Response to two growth-inhibitory factors (suramin and transforming growth factor-beta), and expression of keratins and prostate-specific antigen (PSA), were similar with either mitogen. However, colonies in medium with KGF were very compact with extensive intercellular bonds, whereas colonies with EGF consisted of widely-separated cells. Growth was decreased to a greater extent by deletion of growth factors from medium with KGF versus EGF, and retinoic acid was 10-foid more potent at inducing growth inhibition and differentiation-associated keratin with KGF compared to ECP. We conclude that regulation of growth and differentiation in the prostate might vary depending on the availability of KGF versus EGF. C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. RP Peehl, DM (reprint author), STANFORD UNIV,SCH MED,DEPT UROL,STANFORD,CA 94305, USA. FU NIDDK NIH HHS [DK47551] NR 51 TC 36 Z9 36 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0956-523X J9 GROWTH REGULAT JI Growth Regul. PD MAR PY 1996 VL 6 IS 1 BP 22 EP 31 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UK510 UT WOS:A1996UK51000004 PM 8717447 ER PT J AU Lin, CJ Kohn, E Reed, E AF Lin, CJ Kohn, E Reed, E TI The relationship between borderline ovarian tumors and epithelial ovarian carcinoma: Epidemiologic, pathologic, and molecular aspects SO GYNECOLOGIC ONCOLOGY LA English DT Review ID MALIGNANT POTENTIAL BORDERLINE; CELLULAR DNA CONTENT; LOW-GRADE; PERITONEAL IMPLANTS; FALLOPIAN-TUBE; GROWTH-FACTOR; CANCER; EXPRESSION; RISK; HETEROZYGOSITY AB Borderline ovarian tumors (BOT) are a low-grade form of ovarian malignancy with significantly less aggressive behavior than classical epithelial ovarian carcinoma (EOC). Yet, a subset of these tumors can progress and be lethal. Prognostic factors related to the development of BOT are similar to those for EOC. BOT with aneuploid DNA content have a worse prognosis; this trend is similar to that found in EOC. Patterns of loss of heterozygosity of some chromosomal abnormalities suggest that some, but not all BOT may evolve into more invasive tumors. Molecular biology has provided some clues to the pathogenesis of this entity. Increasing frequency of K-ras mutations are associated with EOC compared to BOT or benign lesions of the ovary. Platelet-derived growth factor and PDGF-alpha receptor are overexpressed in some BOT and EOC, but not in benign tumors or normal ovaries. These genetic markers suggest a closer relationship between a subset of BOT and invasive EOC. Further analysis of genetic abnormalities may delineate the relationship between BOT and EOC better, and will hopefully lead to a unifying hypothesis as to the origin of these important ovarian lesions. (C) 1996 Academic Press, Inc. C1 NCI,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. RP Lin, CJ (reprint author), HUMAN GENE THERAPY RES INST,1415 WOODLAND AVE,DES MOINES,IA 50325, USA. NR 64 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 1996 VL 60 IS 3 BP 347 EP 354 PG 8 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA TY216 UT WOS:A1996TY21600004 ER PT J AU Cecchini, S Ciatto, S Bonardi, R Mazzotta, A Grazzini, G Pacini, P Muraca, MG AF Cecchini, S Ciatto, S Bonardi, R Mazzotta, A Grazzini, G Pacini, P Muraca, MG TI Screening by ultrasonography for endometrial carcinoma in postmenopausal breast cancer patients under adjuvant tamoxifen SO GYNECOLOGIC ONCOLOGY LA English DT Article AB Seven-hundred thirty-seven asymptomatic postmenopausal breast cancer patients under long-term adjuvant tamoxifen therapy (average, 50 months) were screened by endometrial ultrasonography. Abnormal endometrial thickness (6 mm or larger) was observed in 209 subjects and was significantly associated with patients' age and duration of tamoxifen therapy. Outpatient endometrial biopsy was recommended in presence of abnormal endometrial thickness: 25 subjects refused biopsy, whereas 76 were not biopsied because of cervical stenosis and were followed-up by repeat sonography. Of 108 biopsied subjects, one case of endometrial carcinoma (as expected in the screened cohort according to age-specific incidence rates provided by the regional cancer registry) and one case of endometrial hyperplasia were histologically confirmed, whereas endometrial atrophy was evident in the remaining cases. No other case of endometrial carcinoma has been recorded so far in the studied cohort according to the local cancer registry and no further change of the endometrium has been observed at sonographic follow-up. The cohort will be followed-up by repeat annual endometrial sonography. Thus far, we did not find evidence of increased prevalence of endometrial pathology (carcinoma or hyperplasia) which may be ascribed to tamoxifen therapy. The apparent increase in endometrial thickness observed at sonography might be explained by tamoxifen-induced changes of endometrial stroma and myometrium, misinterpreted as hyperplasia, while causing no real epithelial disease. (C) 1996 Academic Press, Inc. C1 NATL CANC INST,GENOA,ITALY. CAREGGI HOSP,DEPT RADIOTHERAPY,FLORENCE,ITALY. RP Cecchini, S (reprint author), CTR STUDIO & PREVENZ ONCOL,VIALE A VOLTA 171,I-50131 FLORENCE,ITALY. RI Grazzini, Grazia/K-8503-2016 OI Grazzini, Grazia/0000-0002-9713-3007 NR 14 TC 42 Z9 42 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 1996 VL 60 IS 3 BP 409 EP 411 DI 10.1006/gyno.1996.0064 PG 3 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA TY216 UT WOS:A1996TY21600014 PM 8774648 ER PT J AU Likhtarev, IA Kovgan, LN Vavilov, SE Gluvchinsky, RR Perevoznikov, ON Litvinets, LN Anspaugh, LR Kercher, JR Bouville, A AF Likhtarev, IA Kovgan, LN Vavilov, SE Gluvchinsky, RR Perevoznikov, ON Litvinets, LN Anspaugh, LR Kercher, JR Bouville, A TI Internal exposure from the ingestion of foods contaminated by Cs-137 after the Chernobyl accident. Report 1. General model: Ingestion doses and countermeasure effectiveness for the adults of Rovno Oblast of Ukraine SO HEALTH PHYSICS LA English DT Article DE Cs-137; Chernobyl; accidents, reactor; dose assessment ID RADIONUCLIDE INGESTION; CHAIN MODEL; PATHWAY AB The Chernobyl accident, which occurred in April 1986, resulted in the atmospheric release of about 70-100 PBq of Cs-137. This paper examines the doses to the adult population of the northern part of Rovno Oblast, Ukraine, from ingestion of Cs-137, Fallout of Cs-137 in these regions was lower than in other regions of Ukraine, However, the transfer of Cs-137 from soil to milk in the region considered is high (up to 20 Bq L(-1) per kBq m(-2)) and results in the predominance of internal doses compared to those from external exposure, Numerous measurements of Cs-137 soil deposition, Cs-137 milk contamination, and Cs-137 body burden have been made in the area and form the basis of a general model of internal exposure from the ingestion of foods contaminated by Cs-137. This paper has two main purposes. The first is to develop the general phenomenological description of the process leading to internal exposure from the ingestion of Cs-137 contaminated foods in the situation where different countermeasures are realized, The second is to apply the model for the adult population of the northern part of the Rovno Oblast (first report) for the limited time period of up to six years after the accident, The doses actually received by the adults are estimated to be four to eight times smaller than the doses calculated for the situation without countermeasures. C1 LAWRENCE LIVERMORE NATL LAB, DOSE RECONSTRUCT PROGRAM, LIVERMORE, CA 94550 USA. NCI, BETHESDA, MD 20892 USA. RP Likhtarev, IA (reprint author), UKRAINIAN ACAD TECHNOL SCI, RADIAT PROTECT INST, KIEV 252050, UKRAINE. NR 36 TC 20 Z9 20 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD MAR PY 1996 VL 70 IS 3 BP 297 EP 317 DI 10.1097/00004032-199603000-00001 PG 21 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA TW547 UT WOS:A1996TW54700002 PM 8609023 ER PT J AU Pellinen, P Stenback, F Kojo, A Honkakoski, P Gelboin, HV Pasanen, M AF Pellinen, P Stenback, F Kojo, A Honkakoski, P Gelboin, HV Pasanen, M TI Regenerative changes in hepatic morphology and enhanced expression of CYP2B10 and CYP3A during daily administration of cocaine SO HEPATOLOGY LA English DT Article ID HUMAN LIVER-MICROSOMES; RAT-LIVER; INDUCED HEPATOTOXICITY; CYTOCHROME-P450 ISOZYMES; STRAIN DIFFERENCES; N-DEMETHYLATION; MOUSE; MICE; NECROSIS; SEX AB The effects of daily cocaine administration for up to 14 days were studied in terms of hepatic morphology and the expression of cytochrome P450 (CYP) enzymes in the mouse liver. Daily intraperitoneal doses of 60 mg/kg of cocaine for 3 days induced severe hepatocellular necrosis in the pericentral zone and decreased activities of CYP1A2, CYP2A4/5, and CYP2Cx. The microsomal CYP2B10 protein content was increased by about 2.5-fold, but 2B10-dependent 7-pentoxyresorufin O-dealkylase (PROD) activity was barely detectable. Five or seven daily cocaine doses caused prominent pericentral inflammation and a significant (up to 14-fold) increase in the microsomal protein content and PROD activity. An increase in microsomal CYP3A was also evident, but CYP2A5 and CYP1A2 still remained at a low level. Immunohistochemical examination showed that the relative induction of CYP2B10 and CYP3A after treatment with cocaine was strongest in perivenous hepatocytes. Immunoinhibition experiments showed that CYP2B10 accounted for catalysis of only 15% to 20% of the enhanced microsomal cocaine N-demethylase (CNDM) activity, which correlated well with immunoreactive 3A protein, and could be blocked 70% to 90% by triacetyloleandomycin. After 10 or 14 daily doses of cocaine, regenerative changes with hepatocyte ballooning were observed, co-inciding with increases in CYP1A2, CYP2A4/5, and CYP3A These results suggest the following: (1) cocaine enhances its own cytochrome P450-dependent metabolism; (2) increased production of norcocaine in microsomes is catalyzed mainly by CYP3A enzyme(s), whereas 2B10, although markedly increased by cocaine treatment, has only a minor role in cocaine hepatotoxicity; and (3) despite increased microsomal CNDM activity, cocaine-induced liver injury is reversible in mice. C1 UNIV KUOPIO,DEPT PHARMACOL & TOXICOL,SF-70211 KUOPIO,FINLAND. UNIV OULU,DEPT PATHOL,OULU,FINLAND. NCI,NIH,MOLEC CARCINOGENESIS LAB,BETHESDA,MD 20892. OI Honkakoski, Paavo/0000-0002-4332-3577 NR 60 TC 30 Z9 31 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 MAR PY 1996 VL 23 IS 3 BP 515 EP 523 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA TZ788 UT WOS:A1996TZ78800016 PM 8617431 ER PT J AU Lindor, KD Hoofnagle, J Maddrey, WC MacKay, IR Dickson, ER AF Lindor, KD Hoofnagle, J Maddrey, WC MacKay, IR Dickson, ER TI Primary biliary cirrhosis clinical research single-topic conference SO HEPATOLOGY LA English DT Article ID CONTROLLED TRIAL; LIVER-TRANSPLANTATION; D-PENICILLAMINE; DIHYDROLIPOAMIDE ACETYLTRANSFERASE; URSODEOXYCHOLIC ACID; COLCHICINE THERAPY; BONE-DISEASE; CHOLESTASIS; PRURITUS; METHOTREXATE C1 NIH, BETHESDA, MD 20892 USA. UNIV TEXAS SW, DALLAS, TX USA. MONASH UNIV, CLAYTON, VIC 3168, AUSTRALIA. RP Lindor, KD (reprint author), MAYO CLIN & MAYO FDN, DIV GASTROENTEROL, ROCHESTER, MN 55905 USA. RI Mackay, Ian/A-7228-2010 NR 80 TC 9 Z9 9 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD MAR PY 1996 VL 23 IS 3 BP 639 EP 644 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA TZ788 UT WOS:A1996TZ78800032 PM 8617447 ER PT J AU RICHARDS, SL KLEIN, LJ AF RICHARDS, SL KLEIN, LJ TI NATIONAL-LIBRARY-OF-MEDICINE AUDIOVISUAL-COLLECTIONS + BETHESDA, MARYLAND SO HISTORICAL JOURNAL OF FILM RADIO AND TELEVISION LA English DT Article RP RICHARDS, SL (reprint author), NATL LIB MED,BETHESDA,MD 20209, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0143-9685 J9 HIST J FILM RADIO TV JI Hist. J. Film Radio Telev. PD MAR PY 1996 VL 16 IS 1 BP 69 EP 71 DI 10.1080/01439689600260101 PG 3 WC Film, Radio, Television SC Film, Radio & Television GA UJ546 UT WOS:A1996UJ54600010 ER PT J AU Kim, TG Carrington, M Choi, HB Kim, HY Han, H AF Kim, TG Carrington, M Choi, HB Kim, HY Han, H TI Three HLA-DMB variants in Korean patients with autoimmune diseases SO HUMAN IMMUNOLOGY LA English DT Article C1 CATHOLIC UNIV MED COLL,DEPT IMMUNOL & MICROBIOL,SEOCHO KU,SEOUL 137701,SOUTH KOREA. NCI,FREDERICK CANC RES & DEV CTR,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD. CATHOLIC UNIV MED COLL,RHEUMATISM CTR,DEPT INTERNAL MED,KANGNAM ST MARYS HOSP,SEOUL 137701,SOUTH KOREA. NR 5 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD MAR PY 1996 VL 46 IS 1 BP 58 EP 60 DI 10.1016/0198-8859(95)00171-9 PG 3 WC Immunology SC Immunology GA UH136 UT WOS:A1996UH13600009 PM 9157091 ER PT J AU Simpson, JL Mills, JL Kim, H Holmes, LB Lee, J Metzger, B Knopp, R JovanovicPeterson, L AArons, J Conley, M AF Simpson, JL Mills, JL Kim, H Holmes, LB Lee, J Metzger, B Knopp, R JovanovicPeterson, L AArons, J Conley, M TI Infectious processes: An infrequent cause of first trimester spontaneous abortions SO HUMAN REPRODUCTION LA English DT Article DE spontaneous abortion; first trimester losses; infectious processes ID CHLAMYDIA-TRACHOMATIS; DIABETIC MOTHERS; EARLY-PREGNANCY; INFANTS; RATES; WOMEN AB A systematic assessment of infections beginning early in pregnancy is necessary to determine the true role of infections in pregnancy loss, given that infections could readily arise only after fetal demise. To this end, we have prospectively determined the frequency of infections in pregnant women who were subjects in a multi-centre US study, Insulin-dependent diabetic subjects and controlled subjects were recruited either before conception (86%) or at the latest within 21 days of conception (14%), We collected data prospectively on all important risk factors and potential confounding variables, seeing 386 diabetic subjects weekly and 432 control subjects every other week during the first trimester, At each visit we inquired about untoward events and explicitly about fever or infections, We found no clinical evidence that infection occurred more often in the 116 subjects experiencing pregnancy loss as compared to the 702 having successful pregnancies, This held both for the 2 week interval in which a given loss was recognized clinically as well as in the prior 2 week interval, Similar findings were not only observed for both the control as well as diabetic subjects but also when data were stratified by genital infection only or by systemic infection only. Our prospective data suggest that the attributable risk of infection in first trimester spontaneous abortion is small. C1 UNIV TENNESSEE,DEPT OBSTET & GYNECOL,MEMPHIS,TN 38103. NICHHD,DIV EPIDEMIOL STAT & PREVENT RES,BETHESDA,MD. BRIGHAM & WOMENS HOSP,DEPT OBSTET & GYNECOL,BOSTON,MA 02115. NORTHWESTERN UNIV,DEPT MED,CHICAGO,IL 60611. UNIV WASHINGTON,DEPT MED,SEATTLE,WA. SANSUM MED RES FDN,SANTA BARBARA,CA 93105. UNIV PITTSBURGH,MAGEE WOMENS HOSP,DEPT MED,PITTSBURGH,PA 15213. RP Simpson, JL (reprint author), BAYLOR COLL MED,DEPT OBSTET & GYNECOL,DEPT MOLEC & HUMAN GENET,HOUSTON,TX 77030, USA. NR 23 TC 13 Z9 14 U1 0 U2 1 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 MAR PY 1996 VL 11 IS 3 BP 668 EP 672 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA UF145 UT WOS:A1996UF14500044 PM 8671289 ER PT J AU Unser, M Thevenaz, P Aldroubi, A AF Unser, M Thevenaz, P Aldroubi, A TI Shift-orthogonal wavelet bases using splines SO IEEE SIGNAL PROCESSING LETTERS LA English DT Article ID MULTIRESOLUTION AB We present examples of a new type of wavelet basis functions that are orthogonal across shifts but not across scales. The analysis functions are piecewise linear while the synthesis functions are polynomial splines of degree n (odd). The approximation power of these representations is essentially as good as that of the corresponding Battle-Lemarie orthogonal wavelet transform, with the difference that the present wavelet synthesis filters have a much faster decay. This last property, together with the fact that these transformations are almost orthogonal, may be useful for image coding applications. 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 15 TC 13 Z9 13 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 SN 1070-9908 J9 IEEE SIGNAL PROC LET JI IEEE Signal Process. Lett. PD MAR PY 1996 VL 3 IS 3 BP 85 EP 88 DI 10.1109/97.481163 PG 4 WC Engineering, Electrical & Electronic SC Engineering GA UB277 UT WOS:A1996UB27700009 ER PT J AU Unser, M AF Unser, M TI Approximation power of biorthogonal wavelet expansions SO IEEE TRANSACTIONS ON SIGNAL PROCESSING LA English DT Article ID COMPACTLY SUPPORTED WAVELETS; ORTHONORMAL BASES; SPLINE WAVELETS; ONDELETTES AB This paper looks at the effect of the number of vanishing moments on the approximation power of wavelet expansions, The Strang-Fix conditions imply that the error for an orthogonal wavelet approximation at scale alpha = 2(-i) globally decays as alpha(N), where N is the order of the transform, This is why, for a given number of scales, higher order wavelet transforms usually result in better signal approximations, We prove that this result carries over for the general biorthogonal case and that the rate of decay of the error is determined by the order properties of the synthesis scaling function alone, We also derive asymptotic error formulas and show that biorthogonal wavelet transforms are equivalent to their corresponding orthogonal projector as the scale goes to;zero, These results strengthen Sweldens' earlier analysis and confirm that the approximation power of biorthogonal and (semi-)orthogonal wavelet expansions is essentially the same, Finally, we compare the asymptotic performance of various wavelet transforms and briefly discuss the advantages of splines, We also indicate how the smoothness of the basis functions is beneficial in reducing the approximation error. RP Unser, M (reprint author), NIH, NATL CTR RES RESOURCES, BIOMED ENGN & INSTRUMENTAT PROGRAM, BETHESDA, MD 20892 USA. RI Unser, Michael/A-1550-2008 NR 31 TC 64 Z9 67 U1 2 U2 7 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 MAR PY 1996 VL 44 IS 3 BP 519 EP 527 DI 10.1109/78.489025 PG 9 WC Engineering, Electrical & Electronic SC Engineering GA UF713 UT WOS:A1996UF71300006 ER PT J AU Henkart, PA AF Henkart, PA TI ICE family proteases: Mediators of all apoptotic cell death? SO IMMUNITY LA English DT Review ID GENE CED-3; ENZYME; ENCODES RP Henkart, PA (reprint author), NCI,EXPTL IMMUNOL BRANCH,NIH,BETHESDA,MD 20892, USA. NR 52 TC 391 Z9 393 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD MAR PY 1996 VL 4 IS 3 BP 195 EP 201 DI 10.1016/S1074-7613(00)80428-8 PG 7 WC Immunology SC Immunology GA UC018 UT WOS:A1996UC01800001 PM 8624810 ER PT J AU Giese, NA Gazzinelli, RT Actor, JK Morawetz, RA Sarzotti, M Morse, HC AF Giese, NA Gazzinelli, RT Actor, JK Morawetz, RA Sarzotti, M Morse, HC TI Retrovirus-elicited interleukin-12 and tumour necrosis factor-alpha as inducers of interferon-gamma-mediated pathology in mouse AIDS SO IMMUNOLOGY LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; MURINE LEUKEMIA VIRUSES; DEFECTIVE VIRUS; T-CELLS; EXPRESSION; MICE; INDUCTION; INFECTION; MAIDS; GENES AB Spleen cells from mice resistant or sensitive to mouse acquired immune deficiency syndrome (MAIDS) were examined for cytokine mRNA. In MAIDS-resistant BALB/c mice, cytokine transcripts peaked at 1 week after infection with Type 1 cytokines [interleukin-2 (IL-2), tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), IL-12], dominating over Type 2 cytokines (IL-4, IL-10). Expression of cytokines other than IL-2 later declined to levels seen in uninfected mice. In MAIDS-sensitive B6 mice, transcripts for all cytokines were increased at 1 week and, except for IL-2, increased progressively. Spontaneous production of IFN-gamma protein was associated with enhanced mRNA expression at 1 week after infection of either strain, but none was detectable in association with even higher levels of transcripts at later times after infection of B6 mice. Spleen cells from longer-term-infected B6 mice, however, produced substantial amounts of IFN-gamma following treatment with lipopolysaccharide (LPS) or IL-12. Inclusion of anti-IL-12 or anti-TNF-alpha antibodies blocked induction of IFN-gamma by LPS. Induction of IFN-gamma by IL-12 was potentiated by TNF-alpha following stimulation of intact spleen cells and purified CD4(+) or CD8(+) T cells, as well as-negatively selected CD4(-)8(-) cells from infected B6 mice. Further studies showed that IFN-gamma knockout mice on a B6 background developed MAIDS with a prolonged time-course, whereas BALB/c knockout mice were unchanged in their resistance to MAIDS. These studies suggest that continuing low-level expression of IFN-gamma, stimulated by IL-12 and TNF-alpha, contributes to the susceptibility of B6 mice to MAIDS but is not required for the resistance of BALB/c mice to disease. C1 NIAID,PARASIT DIS LAB,NIH,IMMUNOL & CELL BIOL SECT,BETHESDA,MD 20892. VET ADM MED CTR,BALTIMORE,MD 21218. RP Giese, NA (reprint author), NIAID,IMMUNOPATHOL LAB,NIH,BLDG 7,ROOM 302,7 CTR DR,MSC 0760,BETHESDA,MD 20892, USA. OI Actor, Jeffrey/0000-0002-9265-7012; Morse, Herbert/0000-0002-9331-3705 FU NIAID NIH HHS [N01-AI-45203] NR 31 TC 26 Z9 26 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD MAR PY 1996 VL 87 IS 3 BP 467 EP 474 DI 10.1046/j.1365-2567.1996.492569.x PG 8 WC Immunology SC Immunology GA UB061 UT WOS:A1996UB06100020 PM 8778035 ER PT J AU Jiang, YZ Couriel, D Mavroudis, DA Lewalle, P Malkovska, V Hensel, NF Dermime, S Molldrem, J Barrett, AJ AF Jiang, YZ Couriel, D Mavroudis, DA Lewalle, P Malkovska, V Hensel, NF Dermime, S Molldrem, J Barrett, AJ TI Interaction of natural killer cells with MHC class II: Reversal of HLA-DR1-mediated protection of K562 transfectant from natural killer cell-mediated cytolysis by brefeldin-A SO IMMUNOLOGY LA English DT Article ID NK-CELLS; ANTIGEN EXPRESSION; SUSCEPTIBILITY; MOLECULES; LYSIS; RESISTANCE; ANTIBODIES; PEPTIDES; INVITRO; GENES AB Major histocompatibility complex (MHC) class I antigens on tumour cell surfaces have been shown to modulate target susceptibility to natural killer (NK) cell-mediated lysis in some, although not all, systems investigated. MHC class II expression may also affect NK cell function, but the mechanism by which MHC class II antigen regulates NK cell activity has not been fully examined. In this study we induced HLA-DR1 expression by gene transfection into the classic NK-sensitive K562 cell line to study the interaction of NK cells with MHC class II molecules and the effect of brefeldin-A (BFA), an endogenous antigen-processing pathway blocker, on NK-target cell interaction. We demonstrated that the expression of HLA-DR1 on the cell surface reduced K562 cell susceptibility to NK lysis by peripheral blood monuclear cells and a NK cell line. The effect was demonstrable in prolonged (8 hr) cytotoxicity assays and was blocked by pretreatment of target cells with anti-HLA-DR antibody. Treatment of K562 DR transfectant with BFA abrogated the resistance of K562 transfectant to NK-mediated cytolysis. These findings indicate that HLA class II molecules regulate NK cell function and target recognition, and suggest that endogenous peptides presented through MHC molecules are responsible for regulating NK cytolysis. C1 CHILDRENS NATL MED CTR,CTR CANC & TRANSPLANTAT BIOL,WASHINGTON,DC 20010. RP Jiang, YZ (reprint author), NHLBI,HEMATOL BRANCH,BONE MARROW TRANSPLANTAT UNIT,NIH,BLDG 10,ROOM 7C-103,BETHESDA,MD 20892, USA. RI Dermime, Said/C-6235-2009 OI Dermime, Said/0000-0002-5526-7496 FU NCI NIH HHS [R01CA55623] NR 28 TC 17 Z9 17 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 MAR PY 1996 VL 87 IS 3 BP 481 EP 486 DI 10.1046/j.1365-2567.1996.483556.x PG 6 WC Immunology SC Immunology GA UB061 UT WOS:A1996UB06100022 PM 8778037 ER PT J AU Shahabuddin, M Lemos, FJA Kaslow, DC JacobsLorena, M AF Shahabuddin, M Lemos, FJA Kaslow, DC JacobsLorena, M TI Antibody-mediated inhibition of Aedes aegypti midgut trypsins blocks sporogonic development of Plasmodium gallinaceum SO INFECTION AND IMMUNITY LA English DT Article ID BLOOD MEAL; MOSQUITO; TRANSMISSION AB The peritrophic matrix (PM) that forms around a blood meal is a potential barrier for Plasmodium development in mosquitoes. Previously, we have shown that to traverse the PM, Plasmodium ookinetes secrete a prochitinase and that an inhibitor of chitinase blocks further parasite development, Here we report that it is the mosquito trypsin that activates the Plasmodium prochitinase. Trypsin was identified as the chitinase-activating enzyme by two criteria: (i) trypsin activity and activating activity comigrated on one-dimensional gels, and (ii) activating activity and penetration of the PM by Plasmodium parasites were both hindered by trypsin-specific inhibitors, Subsequently, we examined the effect of antitrypsin antibodies on the parasite life cycle, Antibodies prepared against a recombinant blackfly trypsin effectively and specifically inhibited mosquito trypsin activity, Moreover, when incorporated into an infective blood meal, the antitrypsin antibodies blocked infectivity of Aedes aegypti mosquitoes by Plasmodium gallinaceum. This block of infectivity could be reversed by exogenously provided chitinase, strongly suggesting that the antibodies act by inhibiting prochitinase activation and not on the parasite itself, This work led to the identification of a mosquito antigen, i.e., midgut trypsin, as a novel target for blocking malaria transmission. C1 CASE WESTERN RESERVE UNIV,SCH MED,DEPT GENET,CLEVELAND,OH 44106. RP Shahabuddin, M (reprint author), NIAID,NIH,LPD,MOL VACCINE SECT,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 17 TC 61 Z9 62 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 MAR PY 1996 VL 64 IS 3 BP 739 EP 743 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA TX566 UT WOS:A1996TX56600009 PM 8641775 ER PT J AU Heinzen, RA Scidmore, MA Rockey, DD Hackstadt, T AF Heinzen, RA Scidmore, MA Rockey, DD Hackstadt, T TI Differential interaction with endocytic and exocytic pathways distinguish parasitophorous vacuoles of Coxiella burnetii and Chlamydia trachomatis SO INFECTION AND IMMUNITY LA English DT Article ID LYSOSOMAL MEMBRANE-GLYCOPROTEINS; L-CELLS; MACROPHAGES; PROTEIN; PSITTACI; IDENTIFICATION; PURIFICATION; FIBROBLASTS; PARASITISM; ENTRY AB Coxiella burnetii and Chlamydia trachomatis are bacterial obligate intracellular parasites that occupy distinct vacuolar niches within eucaryotic host cells. We have employed immunofluorescence, cytochemistry, fluorescent vital stains, and fluid-phase markers in conjunction with electron, confocal, and conventional microscopy to characterize the vacuolar environments of these pathogens. The acidic nature of the C. burnetii-containing vacuole was confirmed by its acquisition of the acidotropic base acridine orange (AO). The presence of the vacuolar-type (H+) ATPase (V-ATPase) within the Coxiella vacuolar membrane was demonstrated by indirect immunofluorescence, and growth of C. burnetii was inhibited by bafilomycin A(1) (Baf A), a specific inhibitor of the V-ATPase. In contrast, AO did not accumulate in C. trachomatis inclusions nor was the V-ATPase found in the inclusion membrane. Moreover, chlamydial growth was not inhibited by Baf A or the lysosomotropic amines methylamine, ammonium chloride, and chloroquine. Vacuoles harboring C. burnetii incorporated the fluorescent fluid-phase markers, fluorescein isothiocyanate-dextran (FITC-dex) and Lucifer yellow (LY), indicating trafficking between that vacuole and the endocytic pathway. Neither FITC-dex nor LY was sequestered by chlamydial inclusions. The late endosomal-prelysosomal marker cation-independent mannose 6-phosphate receptor was not detectable in the vacuolar membranes encompassing either parasite. However, the lysosomal enzymes acid phosphatase and cathepsin D and the lysosomal glycoproteins LAMP-1 and LAMP-2 localized to the C. burnetii vacuole but not the chlamydial vacuole. Interaction of C. trachomatis inclusions with the Golgi-derived vesicles was demonstrated by the transport of sphingomyelin, endogenously synthesized from C-6-NBD-ceramide, to the chlamydial inclusion and incorporation into the bacterial cell wall. Similar trafficking of C-6-NBD-ceramide was not evident in C. burnetii-infected cells. Collectively, the data indicate that C. trachomatis replicates within a nonacidified vacuole that is disconnected from endosome-lysosome trafficking but may receive lipid from exocytic vesicles derived from the trans-Golgi network. These observations are in sharp contrast to those for C. burnetii, which by all criteria resides in a typical phagolysosome. C1 NIAID,ROCKY MT LABS,INTRACELLULAR PARASITES LAB,HOST PARASITE INTERACT SECT,HAMILTON,MT 59840. FU NICHD NIH HHS [N01-HD-2-3144] NR 45 TC 242 Z9 248 U1 1 U2 6 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 MAR PY 1996 VL 64 IS 3 BP 796 EP 809 PG 14 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA TX566 UT WOS:A1996TX56600018 PM 8641784 ER PT J AU Li, Q Luyo, D Hikita, N Whitcup, SM Chan, CC AF Li, Q Luyo, D Hikita, N Whitcup, SM Chan, CC TI Compound 48/80-induced conjunctivitis in the mouse: Kinetics, susceptibility, and mechanism SO INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY LA English DT Article DE allergic mouse, conjunctivitis; compound 48/80; conjunctivitis, compound 48/80 induced; goblet cell; late-phase inflammatory reactions; mast cell degranulation ID INDUCED OCULAR ANAPHYLAXIS; LATE-PHASE REACTION; GOBLET CELL MUCUS; MAST-CELLS; DOSE-RESPONSE; RAT; RELEASE; STIMULATION; ALLERGY; MODEL AB A mouse model of conjunctivitis has been developed by topical application of compound 48/80 (C48/80), an agent that triggers mast cell degranulation. We examined the responsiveness of C57BL/6, C3H/HeN, and ASW/J mouse strains to C48/80 stimulation, and of a mutant strain with mast cell depletion (WBB6F1/J and its sham control). Conjunctivae were collected and examined histopathologically at 15 min and 1,6,24,48, and 72 h after topical C48/80 administration. Conjunctival inflammation developed in all strains, although the severity varied. The conjunctivitis was characterized clinically by irritation, discharge, erythema, and chemosis. Pathology showed conjunctival infiltration with neutrophils, macrophages, CD4+ T lymphocytes, and a few eosinophils. Degranulation of mast cells and evacuation of goblet cells were also observed. Late-phase inflammatory reactions peaked 6-24 h after C48/80 administration and resolved by 48-72 h. WBB6F1/J mice had much less inflammation than their sham controls. In conclusion, topical C48/80 induced a conjunctival inflammatory response similar to allergen-induced conjunctivitis. The depletion of mast cells significantly reduced the inflammation. This model which consistently mimics the clinical signs and histopathological processes of allergic conjunctivitis in humans, is practical and reliable for the evaluation of new anti-allergic medications and for the investigation of conjunctival cellular responses in the allergic inflammatory cascade. C1 NEI,IMMUNOL LAB,BETHESDA,MD. NEI,CLIN BRANCH,BETHESDA,MD. RP Li, Q (reprint author), NEI,IMMUNOL LAB,BLDG 10,ROOM 10N 103,BETHESDA,MD 20892, USA. NR 30 TC 17 Z9 17 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 MAR PY 1996 VL 109 IS 3 BP 277 EP 285 PG 9 WC Allergy; Immunology SC Allergy; Immunology GA TX329 UT WOS:A1996TX32900012 PM 8620098 ER PT J AU Verreck, FAW Vermeulen, C vanderPoel, A Jorritsma, P Amons, R Coligan, JE Drijfhout, JW Koning, F AF Verreck, FAW Vermeulen, C vanderPoel, A Jorritsma, P Amons, R Coligan, JE Drijfhout, JW Koning, F TI The generation of SDS-stable HLA DR dimers is independent of efficient peptide binding SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE anchor residue; DR beta 86 dimorphism; natural peptides; SDS stability ID CLASS-II STRUCTURE; SURFACE EXPRESSION; MHC; MOLECULES; HLA-DR1; IDENTIFICATION; DISTINCT; MOTIF; INHIBITION AB MHC class II molecules can exist in two conformations which can be distinguished on the basis of their stability in SDS. The formation of SDS-stable dimers has been shown to correlate with persistent expression of antigenic MHC class II-peptide complexes by murine antigen-presenting cells. HLA DR molecules contain either a Vat or a Gly at position 86 of the beta chain, which is located in a conserved and prominent hydrophobic pocket in the peptide binding site, Here we show that Val86-containing DR molecules more frequently select peptides which induce the formation of SDS-stable dimers than Gly86 variants. Using analogues of the influenza virus haemagglutinin epitope 307-319 we found that the replacement of the aromatic hydrophobic anchor residue (Tyr) at position 309 by amino acids with an aliphatic hydrophobic side chain resulted in the specific formation of high numbers of SDS-stable Val86-DR but not Gly86-DR dimers. These results indicate that the fit between the first anchor residue and the hydrophobic pocket around DR beta 86 plays a critical role in the formation of SDS-stable DR dimers, Synthetic analogues of naturally processed DR-associated peptides displayed promiscuity in their capacity to bind to several DR specificities and in their ability to induce the SDS-stable conformation. However, no correlation was observed between binding capacity and the ability to induce the SDS-stable conformation, Since it has been shown that SDS stability can relate to the kinetics of peptide-MHC class II interactions, the definition of the requirements for the formation of SDS-stable HLA class II molecules may be important for the design of effective peptide-based immunomodulation protocols. C1 LEIDEN UNIV HOSP,BLOOD BANK,2333 AA LEIDEN,NETHERLANDS. SYLVIUS LABS,DEPT MED BIOCHEM,2333 AL LEIDEN,NETHERLANDS. NIAID,MOLEC STRUCT LAB,NIH,ROCKVILLE,MD 20852. RP Verreck, FAW (reprint author), LEIDEN UNIV HOSP,DEPT IMMUNOHAEMATOL,RIJNSBURGERWEG 10,2333 AA LEIDEN,NETHERLANDS. NR 32 TC 17 Z9 17 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD MAR PY 1996 VL 8 IS 3 BP 397 EP 404 DI 10.1093/intimm/8.3.397 PG 8 WC Immunology SC Immunology GA TZ608 UT WOS:A1996TZ60800013 PM 8671626 ER PT J AU Mizuta, I ZahnWaxler, C Cole, PM Hiruma, N AF Mizuta, I ZahnWaxler, C Cole, PM Hiruma, N TI A cross-cultural study of preschoolers' attachment: Security and sensitivity in Japanese and US dyads SO INTERNATIONAL JOURNAL OF BEHAVIORAL DEVELOPMENT LA English DT Article ID BEHAVIOR; PATTERNS; MOTHER; ADAPTATION; COMPETENCE AB Japanese and US 4- and 5-year-old children and their mothers were studied in situations designed to examine attachment-related behaviours, feelings, and representations. Separation and reunion behaviours, conversations about separation, and child-rearing patterns were examined in relation to culture, gender, and internalising symptoms. Japanese and US dyads did not differ in overall levels of security and sensitivity in separation and reunion behaviours, based on a rating system developed by Crowell, Feldman, and Ginsberg, (1988). However, Japanese children showed more amae (desire for bodily closeness) behaviour than US children. Amae was positively correlated with internalising symptoms for US children but not for Japanese children. Cultural differences in dyads' discussions of separation issues and in maternal child-rearing patterns also were identified. C1 NIMH,BETHESDA,MD 20892. PENN STATE UNIV,UNIVERSITY PK,PA 16802. KEIO UNIV,SCH MED,TOKYO 108,JAPAN. RP Mizuta, I (reprint author), OSAKA UNIV,SCH MED,DEPT NEUROPSYCHIAT,2-2 YAMADAOKA,SUITA,OSAKA 565,JAPAN. NR 43 TC 38 Z9 38 U1 2 U2 4 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE, EAST SUSSEX, ENGLAND BN3 2FA SN 0165-0254 J9 INT J BEHAV DEV JI Int. J. Behav. Dev. PD MAR PY 1996 VL 19 IS 1 BP 141 EP 159 PG 19 WC Psychology, Developmental SC Psychology GA UE035 UT WOS:A1996UE03500011 ER PT J AU Wolffe, AP Meric, F AF Wolffe, AP Meric, F TI Coupling transcription to translation: A novel site for the regulation of eukaryotic gene expression SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY LA English DT Review DE translational control; transcriptional control; hnRNPs; Y-box proteins; nuclear compartmentalization; mRNA processing ID TRACT-BINDING-PROTEIN; RNA POLYMERASE-III; XENOPUS-LAEVIS OOCYTES; MESSENGER-RNA; Y-BOX; DNA-BINDING; RIBONUCLEOPROTEIN-PARTICLES; MOLECULAR-CLONING; CYTOPLASMIC MRNP; NUCLEAR-RNA AB Recent experiments using Xenopus oocytes demonstrate that the history of a particular mRNA in the nucleus can influence the efficiency with which that mRNA will be utilized by the translational machinery. Individual promoter elements, specific protein-RNA interactions and the splicing process within the nucleus can all influence translational fate within the cytoplasm. Central to the regulatory mechanisms influencing the translation process is the packaging of mRNA by a highly conserved family of Y-box proteins. These Y-box proteins are found in cytoplasmic messenger ribonucteoprotein particles where they have a causal role in restricting the recruitment of mRNA to the translational machinery. Nuclear processes influence the packaging of mRNA by the Y-box proteins in the cytoplasm and in consequence mRNA translation. This functional coupling provides a novel site for the regulation of eukaryotic gene expression. RP Wolffe, AP (reprint author), NICHHD,MOLEC EMBRYOL LAB,NIH,BLDG 6,RM B1A-13,BETHESDA,MD 20892, USA. NR 102 TC 35 Z9 35 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 1357-2725 J9 INT J BIOCHEM CELL B JI Int J. Biochem. Cell Biol. PD MAR PY 1996 VL 28 IS 3 BP 247 EP 257 DI 10.1016/1357-2725(95)00141-7 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UD546 UT WOS:A1996UD54600001 PM 8920634 ER PT J AU Schaffhauser, MA Sato, S Kador, PF AF Schaffhauser, MA Sato, S Kador, PF TI NADPH-dependent reductases in dog thyroid: Comparison of a third enzyme ''glyceraldehyde reductase'' to dog thyroid aldehyde reductase SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY LA English DT Article DE glyceraldehyde reductase; aldose reductase; aldehyde reductase; aldose reductase inhibitors; thyroid ID ALDOSE REDUCTASE; KIDNEY ALDOSE; INHIBITION; CATARACT AB The increased incidence of thyroiditis reported to occur in diabetes has also been. observed in long-term galactose-fed dogs where it is reduced by the administration of aldose reductase inhibitors. Since this suggests that thyroidal changes are linked to the abnormal accumulation of sugar alcohols (polyols), present studies were conducted to confirm the presence of aldose and aldehyde reductases in dog thyroid through isolation and characterization. Aldose and aldehyde reductases were isolated from dog thyroid by a series of chromatographic steps which included gel filtration on Sephadex G-100, affinity chromatography on Matrex Gel Orange A and chromatofocusing on Mono P. A third, labile NADPH-reductase was partially purified by gel filtration on Sephadex G-100, affinity chromatography on Matrex Green A and hydroxylapatite chromatography on BIG-GEL HT. The kinetic properties of aldose and aldehyde reductases and their susceptibility to inhibition by aldose reductase inhibitors are similar to those of dog kidney aldose and aldehyde reductases. However, the levels of aldose reductase present in thyroid are extremely low compared to the levels of aldehyde reductase. A third NADPH-dependent reductase, tentatively identified as glyceraldehyde reductase, is also present in dog thyroid. This novel enzyme utilizes NADPH to reduce DL-glyceraldehyde and is clearly distinct from the other aldo-keto reductases in molecular weight, substrate specificity, inhibition by aldose reductase inhibitors and immunological properties. In summary aldose reductase, aldehyde reductase and a third novel glyceraldehyde reductase, all of which can utilize glyceraldehyde as substrate, have been identified and characterized in dog thyroid. Only aldose and aldehyde reductases, which can catalyze the production of polyols and were inhibited by aldose reductase inhibitors, appear to be linked to thyroiditis. C1 NEI,OCULAR THERAPEUT LAB,NIH,BETHESDA,MD 20892. NR 18 TC 3 Z9 3 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 1357-2725 J9 INT J BIOCHEM CELL B JI Int J. Biochem. Cell Biol. PD MAR PY 1996 VL 28 IS 3 BP 275 EP 284 DI 10.1016/1357-2725(95)00147-6 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UD546 UT WOS:A1996UD54600003 PM 8920636 ER PT J AU Williams, AO Knapton, AD Ifon, ET Saffiotti, U AF Williams, AO Knapton, AD Ifon, ET Saffiotti, U TI Transforming growth factor beta expression and transformation of rat lung epithelial cells by crystalline silica (quartz) SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID II CELLS; ALVEOLAR; LOCALIZATION AB Crystalline silica (quartz) induces silicosis and associated peripheral lung carcinomas in rats. The role and pattern of expression of transforming growth factor (TGF)-beta 1/beta 2 mRNA transcripts were investigated in the fetal rat lung epithelial cell line FRLE, its neoplastic transformants and derived tumors in athymic nude mice. FRLE cells, treated with 100 mu g/cm(2) of quartz in serum-free medium, gave rise to phenotypically altered, tumorigenic cells. Quartz-treated, transformed and tumorigenic cells, subcultured directly (QTT-C1) or after growth in soft agar (QTT-C2), formed tumors in athymic nude mice (QTT-T1). Cells subcultured from the tumors (QTT-T1C) were also tumorigenic in nude mice (QTT-T2). QTT-T1 and QTT-T2 tumors were poorly differentiated carcinomas with variable amounts of extracellular matrix-associated TGF-beta 1 and desmoplasia. For comparison, a tumorigenic cell line derived from FRLE cells transformed with a mutated K-ras plasmid (RT-C1) and cells subcultured from a corresponding nude mouse tumor (RT-T1) and designated RT-T1C were used. Whereas TGF-beta 1 and TGF-beta 2 inhibited the growth of QTT-TIC and FRLE cells in a dose-dependent fashion, RT-T1C cells, containing an activated ros gene, were relatively unaffected. TGF-beta 1 and TGF-beta 2 mRNAs were expressed at higher levels in QTT-T1C cells than in FRLE and RT-TIC cells, and there was an increase in TGF-beta type II receptor (TGF-beta R) mRNA expression in QTT-T1C and RT-T1C cells compared to FRLE cells. Carcinomas in nude mice derived from QTT and RT cells and silicosis-associated lung carcinomas induced in rats by intra-tracheal quartz did not express either active or latent forms of TGF-beta 1 protein on immunohistochemistry. The disparity between TGF-beta 1 mRNA and TGF-beta 1 protein expression in QTT tumors may be due to post-transcriptional regulation of TGF-beta 1. (C) 1996 Wiley-Liss, Inc. RP Williams, AO (reprint author), NCI,DIV CANC ETIOL,LAB EXPTL PATHOL,BLDG 41,ROOM C105,BETHESDA,MD 20892, USA. NR 25 TC 14 Z9 15 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAR 1 PY 1996 VL 65 IS 5 BP 639 EP 649 DI 10.1002/(SICI)1097-0215(19960301)65:5<639::AID-IJC14>3.0.CO;2-2 PG 11 WC Oncology SC Oncology GA TX822 UT WOS:A1996TX82200014 PM 8598316 ER PT J AU Londos, C GruiaGray, J Brasaemle, DL Rondinone, CM Takeda, T Dwyer, NK Barber, T Kimmel, AR BlanchetteMackie, EJ AF Londos, C GruiaGray, J Brasaemle, DL Rondinone, CM Takeda, T Dwyer, NK Barber, T Kimmel, AR BlanchetteMackie, EJ TI Perilipin: Possible roles in structure and metabolism of intracellular neutral lipids in adipocytes and steroidogenic cells SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE hormone-sensitive lipase; adipocyte; lipolysis; steroidogenesis; adrenal cortical; Leydig cells; neutral lipids ID HORMONE-SENSITIVE LIPASE; ADIPOSE-TISSUE; LIPOLYSIS; DROPLET; PROTEIN AB Perilipins are a family of unique proteins intimately associated with the limiting surface of neutral lipid storage droplets in adipocytes and in steroidogenic cells, Lipid hydrolysis in these cells is initiated by cAMP, which leads to phosphorylation of hormone-sensitive lipase in adipocytes and cholesteryl esterase in steroidogenic cells by protein kinase A, Although the concurrent phosphorylation of perilipin by this kinase suggests a role for these proteins in lipid breakdown, a role for these proteins in lipid packaging or in maintaining the lipid droplet structure cannot be excluded. RP Londos, C (reprint author), NIDDKD,CELLULAR & DEV BIOL LAB,NIH,BLDG 6,ROOM B1-32A,BETHESDA,MD 20892, USA. NR 13 TC 31 Z9 32 U1 1 U2 4 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD MAR PY 1996 VL 20 SU 3 BP S97 EP S101 PG 5 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA UE541 UT WOS:A1996UE54100016 PM 8680486 ER PT J AU Porras, A Santos, E AF Porras, A Santos, E TI The insulin Ras pathway of adipocytic differentiation of 3T3 L1 cells: Dissociation between Raf-1 kinase and the MAPK/RSK cascade SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE Ras; insulin; 3T3 L1; adipocytic differentiation; MAP kinase; Raf-1 kinase ID ACTIVATED PROTEIN-KINASE; NERVE GROWTH-FACTOR; SIGNAL-TRANSDUCTION PATHWAY; MAP KINASE; S6 KINASE; PHOSPHORYLATION; RECEPTOR; SERINE; P21RAS; STIMULATION AB Insulin-induced differentiation of 3T3 LZ cells can be mimicked by expression of transfected ras oncogenes but is completely blocked by expression of dominant negative Ras mutants, demonstrating that Pas proteins mediate insulin signaling in these mammalian cells, In contrast, transfection of tyrosine kinase oncogenes including trk and src does not result in adipocytic differentiation. Transfected raf-1 oncogenes induce partial adipocytic differentiation, while dominant negative raf mutants block partially the insulin-induced differentiation process. Exposure of 3T3 L1 cells to insulin results in formation of the active Ras-GTP complex without GAP tyrosine phosphorylation, Insulin treatment of untransfected 3T3 L1 cells also induced quick activation of cytosolic 42 kDa mitogen-activated protein kinase (MAPK) and a 90 kDa S6 kinase (RSK), The activation of these cytosolic serine-threonine kinases was also mimicked by Ras expression (in the absence of insulin) in the same cells transfected with inducible ras oncogenes, Furthermore, insulin-induced activation of MAPK and RSK could be blocked by expression of a transfected. inducible dominant negative pas mutant (N17). These results indicate that Ras proteins are obligatory intermediates in the activation of cytostolic ERKs by insulin. Insulin treatment of 3T3 L1 cells or expression of transfected ras oncogenes resulted also in hyperphosphorylation of cellular Raf-1. Insulin-induced Raf hyperphosphorylation was inhibited by expression of an inducible, dominant negative Ras mutant (N17), interestingly however, expression of transfected raf oncogenes did not induce MAPK or RSK activation, and the insulin-induced activation of these kinases was not blocked by expression of transfected dominant negative raf mutants, These results suggest a functional dissociation between Raf-1 and MAPK/RSK activation in insulin/Ras signaling pathways leading to 3T3 L1 differentiation and are consistent with Raf-1 kinase acting in a parallel pathway to the MAPK/RSK pathway after Res activation in these cells. C1 NEI,CELLULAR & MOLEC BIOL LAB,NIH,BETHESDA,MD 20892. RI Porras, Almudena/N-2121-2015 OI Porras, Almudena/0000-0002-6495-3308 NR 47 TC 18 Z9 18 U1 0 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD MAR PY 1996 VL 20 SU 3 BP S43 EP S51 PG 9 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA UE541 UT WOS:A1996UE54100008 PM 8680477 ER PT J AU Yoshizato, K Kuratsu, J Takeshima, H Nishi, T Yoshimura, T Ushio, Y AF Yoshizato, K Kuratsu, J Takeshima, H Nishi, T Yoshimura, T Ushio, Y TI Increased monocyte chemoattractant protein-1 expression by tumor necrosis factor-alpha can mediate macrophage infiltration in gliomas SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE monocyte chemoattractant protein-1; tumor necrosis factor-alpha; macrophage infiltration; glioma ID MONOCLONAL-ANTIBODIES; MALIGNANT GLIOMA; GENE-TRANSFER; SUPPRESSION; MCP-1; CELLS; JE AB We compared the in vitro effects of various cytokines on the expression of monocyte chemoattractant protein-1 (MCP-1) in glioma cell lines and found that MCP-1 expression was highly induced by tumor necrosis factor-alpha (TNF alpha) and interleukin-1 beta. The intra-tumoral injection of TNF alpha in rat glioma model increased the in vivo expression of MCP-1 at 1 to 12 h after the injection and induced macrophage infiltration into tumor tissue. The injection of TNF alpha into post-operative tumor cavity of human malignant glioma also increased the concentration of MCP-1 in the cavity fluid at 24 to 38 h after injection. These data, together with the previous finding that the growth of transplanted MCP-1-transfected cells was significantly inhibited by infiltrated macrophages, suggest that injection of TNF alpha inhibits turner growth via the induction of MCP-1 expression. C1 NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,IMMUNOPATHOL SECT,FREDERICK,MD 21701. NR 22 TC 3 Z9 3 U1 0 U2 1 PU INT JOURNAL ONCOLOGY PI ATHENS PA C/O PROFESSOR D A SPANDIDOS, EDITORIAL OFFICE, 1, S MERKOURI ST, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD MAR PY 1996 VL 8 IS 3 BP 493 EP 497 PG 5 WC Oncology SC Oncology GA TY669 UT WOS:A1996TY66900011 PM 21544387 ER PT J AU Johnstone, PAS Laskin, WB DeLuca, AM Barnes, M Kinsella, TJ Sindelar, WF AF Johnstone, PAS Laskin, WB DeLuca, AM Barnes, M Kinsella, TJ Sindelar, WF TI Tumors in dogs exposed to experimental intraoperative radiotherapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE canine; carcinogenesis; intraoperative radiotherapy; radiation oncology ID RADIATION-THERAPY; TOLERANCE; IRRADIATION; IORT; SARCOMAS; BEAM AB Purpose: The frequency of radiation-induced neoplasms was determined in dogs enrolled in the National Cancer Institute canine trials of intraoperative radiotherapy (IORT). Methods and Materials: Twelve protocols assessing normal tissue response to IORT involved 238 dogs in a 15-year trial. Eighty-one dogs were followed for > 24 months postoperatively and were assessed for tumor development; 59 of these animals received IORT. Results: Twelve tumors occurred in the 59 dogs receiving IORT, Nine were in the IORT portals and were considered to be radiation induced. No tumors occurred in 13 sham animals or in 9 animals treated with external beam radiotherapy alone, The frequency of radiation-induced malignancies in dogs receiving IORT was 15%, and was 25% in animals receiving greater than or equal to 25 Gy IORT. Frequency of all tumors, including spontaneous lesions, was 20%. Conclusions: Intraoperative radiotherapy contributed to a high frequency of sarcoma induction in these dogs, Unknown to date in humans involved in clinical trials of IORT, this potential complication should be looked for as long-term survivors are followed. C1 NCI, NIH, RBB, BETHESDA, MD 20892 USA. NCI, NIH, SURG BRANCH, BETHESDA, MD 20892 USA. NATL NAVAL MED CTR, DIV PATHOL, BETHESDA, MD 20814 USA. HOSP UNIV PENN, DEPT RADIAT ONCOL, PHILADELPHIA, PA 19104 USA. UNIV WISCONSIN, CTR CANC, DEPT HUMAN ONCOL, MADISON, WI 53792 USA. USN, MED CTR, DIV RADIAT ONCOL, SAN DIEGO, CA 92134 USA. NR 25 TC 20 Z9 20 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAR 1 PY 1996 VL 34 IS 4 BP 853 EP 857 DI 10.1016/0360-3016(95)02118-3 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA UA185 UT WOS:A1996UA18500012 PM 8598362 ER PT J AU Kalebic, T Judde, JG VelezYanguas, M Knutsen, T Helman, LJ AF Kalebic, T Judde, JG VelezYanguas, M Knutsen, T Helman, LJ TI Metastatic human rhabdomyosarcoma: Molecular, cellular and cytogenetic analysis of a novel cellular model SO INVASION & METASTASIS LA English DT Article DE rhabdomyosarcoma ID TUMOR-CELL; CHILDHOOD RHABDOMYOSARCOMA; CANCER METASTASIS; GENE-EXPRESSION; C-MYC; INVASION; ONCOGENES; PROGRESSION; GROWTH; CARCINOMAS AB A new human metastatic rhabdomyosarcoma (RMS) model was established and analyzed for a number of biologic, cytogenetic and molecular parameters. Consistent with previous studies, the metastatic capacity of different RMS cell variants did not correlate with their tumorigenic or proliferative capacities. Interestingly, a highly metastatic variant was diploid, while a nonmetastatic variant was tetraploid, which parallels previous clinical observations. Genes whose expression had been found to be associated with either low-or high-metastatic capacity in carcinoma or melanoma did not show a similar association with different metastatic variants of RMS, derived from a mesenchymal tumor. We also found, in transient reporter gene assays, that several promoters had higher transcriptional activity in highly metastatic than in nonmetastatic RMS cell variants. This novel human RMS metastatic model may be instrumental for a better understanding of the regulatory pathways that control the metastatic phenotype of tumors of mesenchymal origin. C1 NATL CANC INST,CYTOGENET ONCOL SECT,MED BRANCH,BETHESDA,MD. RP Kalebic, T (reprint author), NCI,MOL ONCOL SECT,PEDIAT BRANCH,9000 ROCKVILLE PIKE,BLDG 10-13N240,BETHESDA,MD 20892, USA. NR 52 TC 4 Z9 4 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0251-1789 J9 INVAS METAST JI Invasion Metastasis PD MAR-APR PY 1996 VL 16 IS 2 BP 83 EP 96 PG 14 WC Oncology SC Oncology GA WE607 UT WOS:A1996WE60700005 PM 9030243 ER PT J AU Miller, RW AF Miller, RW TI The US-Japan cooperative cancer research program: Some highlights of seminars, interdisciplinary program area, 1981-1996 SO JAPANESE JOURNAL OF CANCER RESEARCH LA English DT Review DE cancer; genetics; neoplastic syndromes; demography; racial stock ID UNITED-STATES; CARCINOMA; DISEASES AB Thirty-one seminars have been held in the 16 years since 1981. A principal interest from the beginning was the genetics of cancer, well before this subject became widely popular. This interest arose in part because of marked binational differences in type-specific cancer rates, such as the very low rates among Japanese for Hodgkin's disease in the young, testicular cancer, Ewing's sarcoma, superficial spreading melanoma, chronic lymphocytic leukemia, and Wilms' tumor (half the U.S. frequency). Three seminars were devoted to the seeming reciprocal relationship between B-cell lymphoma (low in Japan) and certain autoimmune diseases (high in Japan), which is perhaps similar in origin to the male/female differences in the rates for these diseases. A seminar on Li-Fraumeni syndrome led to the recognition of cases among Japanese pedigrees brought to the meeting, and generated a study of its occurrence in Japanese families with adrenocortical carcinoma in a child. Another seminar revealed a marked clustering of rare cancers in Werner's (premature aging) syndrome in Japan, and led to a binational study and analysis of case-reports worldwide. Three seminars on pathology heightened appreciation of the importance of subclassifying cancer by subsite and subtype for racial and other comparisons. Four seminars on biostatistics in cancer research generated a substantial exchange of specialists and trainees in this field. RP Miller, RW (reprint author), NCI,GENET EPIDEMIOL BRANCH,EPN-400,BETHESDA,MD 20892, USA. NR 21 TC 4 Z9 4 U1 0 U2 1 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 MAR PY 1996 VL 87 IS 3 BP 221 EP 226 PG 6 WC Oncology SC Oncology GA UE777 UT WOS:A1996UE77700002 PM 8613422 ER PT J AU Cone, EJ Kato, K Hillsgrove, M AF Cone, EJ Kato, K Hillsgrove, M TI Cocaine excretion in the semen of drug users SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Letter ID ALCOHOLICS; MOTILITY; SONS RP Cone, EJ (reprint author), NIDA,ADDICT RES CTR,INTRAMURAL RES PROGRAM,NIH,POB 5180,BALTIMORE,MD 21224, USA. NR 11 TC 8 Z9 8 U1 0 U2 2 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD MAR-APR PY 1996 VL 20 IS 2 BP 139 EP 140 PG 2 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA TZ698 UT WOS:A1996TZ69800012 PM 8868408 ER PT J AU Donaldson, KM Tong, SYC Washburn, T Lubahn, DB Eddy, EM Hutson, JM Korach, KS AF Donaldson, KM Tong, SYC Washburn, T Lubahn, DB Eddy, EM Hutson, JM Korach, KS TI Morphometric study of the gubernaculum in male estrogen receptor mutant mice SO JOURNAL OF ANDROLOGY LA English DT Article DE ERKO; estrogen; estrogen receptor; cremaster; processus vaginalis; testis; gubernaculum ID TESTICULAR DESCENT; HORMONAL-CONTROL; FETAL; CRYPTORCHIDISM; EXPRESSION AB To determine role of estrogen receptors in testicular descent, a morphometric study of the testis and structures derived from the gubernaculum was made in sexually mature male mice having an estrogen receptor disrupted gene mutation (ERKO). Macroscopic dissections and sagittal serial sections were made of the pelvis of four wild-type mice, four mice heterozygous for the ERKO mutation, and four homozygous ERKO males. By external morphological examination the testes appeared to be descended in all three genotypes. All mice had development of a cremaster sac, which is derived from the gubernaculum, but this was twice as large in wildtype mice than in both the heterozygote or homozygote ERKO groups. The cause for the smaller cremaster sac appeared to be excessive development of the cremaster muscle in ERKO mice. The thickened muscle was associated with postmortem retraction of the testes into the inguinal canal or abdomen. Spermatogenesis and testicular volume were deficient in homozygous ERKO mice at this age. This study demonstrates that estrogen has a previously unknown role in masculine sexual development of the gubernaculum and the structures derived from it, such as the cremaster muscle. C1 ROYAL CHILDRENS HOSP,RES FDN,F DOUGLAS STEPHENS SURG RES LAB,MELBOURNE,VIC,AUSTRALIA. NIEHS,REPROD & DEV TOXICOL LAB,NIH,RES TRIANGLE PK,NC 27709. OI Tong, Steven/0000-0002-1368-8356; Korach, Kenneth/0000-0002-7765-418X NR 22 TC 41 Z9 42 U1 0 U2 0 PU AMER SOC ANDROLOGY, INC PI LAWRENCE PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 SN 0196-3635 J9 J ANDROL JI J. Androl. PD MAR-APR PY 1996 VL 17 IS 2 BP 91 EP 95 PG 5 WC Andrology SC Endocrinology & Metabolism GA UH287 UT WOS:A1996UH28700002 PM 8723431 ER PT J AU Mechold, U Cashel, M Steiner, K Gentry, D Malke, H AF Mechold, U Cashel, M Steiner, K Gentry, D Malke, H TI Functional analysis of a relA/spoT gene homolog from Streptococcus equisimilis SO JOURNAL OF BACTERIOLOGY LA English DT Article ID GUANOSINE 5'-DIPHOSPHATE 3'-DIPHOSPHATE; ESCHERICHIA-COLI; STRINGENT RESPONSE; PROTEIN-SYNTHESIS; SPOT GENE; RIBONUCLEIC-ACID; RELA GENE; PPGPP; TETRAPHOSPHATE; DEGRADATION AB We examined the functional attributes of a gene encountered by sequencing the streptokinase gene region of Streptococcus equisimilis H46A. This gene, originally called rel, here termed rel(S.equisimilis), is homologous to two related Escherichia coli genes, spoT and relA, that function in the metabolism of guanosine 5',3' polyphosphates [(p)ppGpp]. Studies with a variety of E. coli mutants led us to deduce that the highly expressed rel(S.equisimilis) gene encodes a strong (p)ppGppase and a weaker (p)ppGpp synthetic activity, much like the spoT gene, with a net effect favoring degradation and no complementation of the absence of the relA gene. We verified that the Rel(S.equisimilis) protein, purified from an E. coli relA spoT double mutant, catalyzed a manganese-activated (p)ppGpp 3'-pyrophosphohydrolase reaction similar to that of the SpoT enzyme. This Rel(S.equisimilis) protein preparation also weakly catalyzed a ribosome-independent synthesis of (p)ppGpp by an ATP to GTP 3'-pyrophosphoryltransferase reaction when degradation was restricted by the absence of manganese ions. An analogous activity has been deduced for the SpoT protein from genetic evidence. In addition, the Rel(S.equisimilis) protein displays immunological cross-reactivity with polyclonal antibodies specific for SpoT but not for RelA. Despite assignment of rel(S.equisimilis) gene function in E. coli as being similar to that of the native spoT gene, disruptions of rel(S.equisimilis) in S. equisimilis abolish the parental (p)ppGpp accumulation response to amino acid starvation in a manner expected for relA mutants rather than spoT mutants. C1 UNIV JENA,INST MOLEC BIOL,D-07745 JENA,GERMANY. NICHHD,MOLEC GENET LAB,BETHESDA,MD 20892. NR 66 TC 85 Z9 86 U1 0 U2 3 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 MAR PY 1996 VL 178 IS 5 BP 1401 EP 1411 PG 11 WC Microbiology SC Microbiology GA TX752 UT WOS:A1996TX75200022 PM 8631718 ER PT J AU David, M Petricoin, E Larner, AC AF David, M Petricoin, E Larner, AC TI Activation of protein kinase A inhibits interferon induction of the Jak/Stat pathway in U266 cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ALPHA; RECEPTOR; CAMP AB Activation of early response genes by interferons (IFNs) requires tyrosine phosphorylation of the Stat transcription factors and is mediated by the Jak family of tyrosine kinases, Recent evidence suggests that ERK2 serine/threonine kinase modulates the IFN-stimulated Jak/Stat pathway. In this report we show that in the myeloma cell line U266 protein kinase A specifically interacts with the cytoplasmic domain of the IFN alpha/beta receptor, Treatment of cells with the adenylate cyclase activator forskolin inhibits IFN beta-, IFN gamma-, and hydrogen peroxide/vanadate-induced formation of complexes that bind to enhancers known to stimulate the expression of IFN-regulated genes. Immunoprecipitations followed by anti-phosphotyrosine immunoblots indicate that tyrosine phosphorylation of the alpha chain of the IFN alpha/beta receptor, Jak1, Trk2, as well as Stat1 and Stat2 is reduced as a consequence of incubation of cells with forskolin. In contrast, dideoxyforskolin, which fails to activate adenylate cyclase, has no effect on IFN induction of the Jak/Stat pathway. These results indicate a novel regulatory mechanism by which protein kinase A can modulate the Jak/Stat signaling cascade. C1 NIH,DIV CYTOKINE BIOL,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. NR 20 TC 62 Z9 64 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 1 PY 1996 VL 271 IS 9 BP 4585 EP 4588 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TX697 UT WOS:A1996TX69700005 PM 8617715 ER PT J AU Ridky, TW Cameron, CE Cameron, J Leis, J Copeland, T Wlodawer, A Weber, IT Harrison, RW AF Ridky, TW Cameron, CE Cameron, J Leis, J Copeland, T Wlodawer, A Weber, IT Harrison, RW TI Human immunodeficiency virus, type 1 protease substrate specificity is limited by interactions between substrate amino acids bound in adjacent enzyme subsites SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ROUS-SARCOMA VIRUS; RETROVIRAL PROTEASE; MOLECULAR-DYNAMICS; FORCE-FIELD; INHIBITOR; PROTEINS; SIMULATIONS; CLEAVAGE; GAG AB The specificity of the retroviral protease is determined by the ability of substrate amino acid side chains to bind into eight individual subsites within the enzyme, Although the subsites are able to act somewhat independently in selection of amino acid side chains that fit into each pocket, significant interactions exist between individual subsites that substantially limit the number of cleavable amino acid sequences, The substrate peptide binds within the enzyme in an extended anti-parallel beta sheet conformation with substrate amino acid side chains adjacent in the linear sequence extending in opposite directions in the enzyme-substrate complex, From this geometry, we have defined both cis and trans steric interactions, which have been characterized by a steady state kinetic analysis of human immunodeficiency virus, type-1 protease using a series of peptide substrates that are derivatives of the avian leukosis/sarcoma virus nucleocapsid-protease cleavage site, These peptides contain both single and double amino acid substitutions in seven positions of the minimum length substrate required by the retroviral protease for specific and efficient cleavage, Steady state kinetic data from the single amino acid substituted peptides were used to predict effects on protease-catalyzed cleavage of corresponding double substituted peptide substrates, The calculated Gibbs' free energy changes were compared with actual experimental values in order to determine how the fit of a substrate amino acid in one subsite influences the fit of amino acids in adjacent subsites, Analysis of these data shows that substrate specificity is limited by steric interactions between pairs of enzyme subsites, Moreover, certain enzyme subsites are relatively tolerant of substitutions in the substrate and exert little effect on adjacent subsites, whereas others are more restrictive and have marked influence on adjacent cis and trans subsites. C1 CASE WESTERN RESERVE UNIV,SCH MED,CLEVELAND,OH 44106. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. THOMAS JEFFERSON UNIV,JEFFERSON CANC INST,PHILADELPHIA,PA 19107. FU NCI NIH HHS [CA52047, CA58166]; PHS HHS [N01 C01 46000] NR 25 TC 49 Z9 49 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 1 PY 1996 VL 271 IS 9 BP 4709 EP 4717 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TX697 UT WOS:A1996TX69700026 PM 8617736 ER PT J AU Shen, F Triezenberg, SJ Hensley, P Porter, D Knutson, JR AF Shen, F Triezenberg, SJ Hensley, P Porter, D Knutson, JR TI Critical amino acids in the transcriptional activation domain of the herpesvirus protein VP16 are solvent-exposed in highly mobile protein segments - An intrinsic fluorescence study SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TIME-RESOLVED FLUORESCENCE; DNA-BINDING DOMAIN; TRANSACTIVATION DOMAIN; ALCOHOL-DEHYDROGENASE; BASAL TRANSCRIPTION; GAL4 DERIVATIVES; TRYPTOPHAN; VMW65; DECAY; RENATURATION AB Eukaryotic transcriptional regulatory proteins typically comprise both a DNA binding domain and a regulatory domain. Although the structures of many DNA binding domains have been elucidated, no detailed structures are yet available for transcriptional activation domains. The activation domain of the herpesvirus protein VP16 has been an important model in mutational and biochemical studies. Here, we characterize the VP16 activation domain using time-resolved and steady-state fluorescence. Unique intrinsic fluorescent probes were obtained by replacing phenylalanine residues with tryptophan at position 442 or 473 of the activation domain of VP16 (residues 413-490, or subdomains thereof), linked to the DNA binding domain of the yeast protein GAL4. Emission spectra and quenching properties of Trp at either position were characteristic of fully exposed Trp. Time-resolved anisotropy decay measurements suggested that both Trp residues were associated with substantial segmental motion. The Trp residues at either position showed nearly identical fluorescence properties in either the full-length activation domain or relevant subdomains, suggesting that the two subdomains are similarly unstructured and have little effect on each other. As this domain may directly interact with several target proteins, it is likely that a significant structural transition accompanies these interactions. C1 SMITHKLINE BEECHAM PHARMACEUT,DEPT MACROMOLEC SCI,KING OF PRUSSIA,PA 19406. NHLBI,NIH,CELL BIOL LAB,BETHESDA,MD 20892. RP Shen, F (reprint author), MICHIGAN STATE UNIV,DEPT BIOCHEM,E LANSING,MI 48824, USA. FU NIAID NIH HHS [R01-AI27323, K04-AI01284] NR 60 TC 29 Z9 30 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 MAR 1 PY 1996 VL 271 IS 9 BP 4819 EP 4826 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TX697 UT WOS:A1996TX69700041 PM 8617751 ER PT J AU Shen, F Triezenberg, SJ Hensley, P Porter, D Knutson, JR AF Shen, F Triezenberg, SJ Hensley, P Porter, D Knutson, JR TI Transcriptional activation domain of the herpesvirus protein VP16 becomes conformationally constrained upon interaction with basal transcription factors SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-BINDING PROTEINS; FACTOR-TFIIB; TRANSACTIVATION DOMAIN; MAMMALIAN-CELLS; AMINO-ACIDS; FLUORESCENCE; VMW65; 5-HYDROXYTRYPTOPHAN; SEQUENCE; RECOGNITION AB The transcriptional activation domain of the herpesvirus protein VP16 resides in the carboxyl-terminal 78 amino acids (residues 413-490). Fluorescence analyses of this domain indicated that critical amino acids are solvent-exposed in highly mobile segments. To examine interactions between VP16 and components of the basal transcriptional machinery, we incorporated (at position 442 or 473 of VP16) tryptophan analogs that can be selectively excited in complexes with other Trp-containing proteins. TATA-box binding protein (TBP) (but not transcription factor B (TFIIB)) caused concentration-dependent changes in the steady-state anisotropy of VP16, from which equilibrium binding constants were calculated. Quenching of the fluorescence from either position (442 or 473) was significantly affected by TBP, whereas TFIIB affected quenching only at position 473. 7-aza-Trp residues at either position showed a emission spectral shift in the presence of TBP (but not TFIIB), indicating a change to a more hydrophobic environment. In anisotropy decay experiments, TBP reduced the segmental motion at either position; in contrast, TFIIB induced a slight change only at position 473. Our results support models of TBP as a target protein for transcriptional activators and suggest that ordered structure in the VP16 activation domain is induced upon interaction with target proteins. C1 MICHIGAN STATE UNIV,DEPT BIOCHEM,E LANSING,MI 48824. SMITHKLINE BEECHAM PHARMACEUT,DEPT MACROMOLEC SCI,KING OF PRUSSIA,PA 19406. NHLBI,NIH,CELL BIOL LAB,BETHESDA,MD 20892. FU NIAID NIH HHS [R01-AI27323, K04-AI01284] NR 64 TC 86 Z9 87 U1 3 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 MAR 1 PY 1996 VL 271 IS 9 BP 4827 EP 4837 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TX697 UT WOS:A1996TX69700042 PM 8617752 ER PT J AU HermidaMatsumoto, ML Chock, PB Curran, T Yang, DCH AF HermidaMatsumoto, ML Chock, PB Curran, T Yang, DCH TI Ubiquitinylation of transcription factors c-Jun and c-Fos using reconstituted ubiquitinylating enzymes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AFFINITY PURIFICATION; PROTOONCOGENES FOS; PROTEIN LIGASE; SYSTEM; DEGRADATION; EXPRESSION; RESOLUTION; PROTEASOME; COMPONENTS; INVIVO AB Recombinant c-Jun and c-Fos were ubiquitinylated by the ubiquitin carrier enzymes E2(14K), E2(20K), or E2(32K) in the presence of the ubiquitin-activating enzyme, E1. Addition of ubiquitin protein ligase E3 substantially enhanced the E2(14K)-mediated ubiquitinylation of c-Jun and c-Fos, Truncated c-Jun and c-Fos mutant proteins including wbJun and wbFos were also ubiquitinylated under the same conditions, suggesting the sites of ubiquitinylation are located within the dimerization and DNA binding domains of c-Jun and c-Fos. The E3-dependent ubiquitinylation of c-Jun was inhibited upon the heterodimerization of c-Jun with c-Fos. Further addition of E2(20K) significantly enhanced ubiquitinylation of c-Jun in the heterodimer suggesting a regulatory role of E2(20K). Polyubiquitinylated c-Jun, wbFos, and wbJun, but not E2(20K)-ubiquitinylated c-Jun, were readily degraded by the ATP-dependent 26 S multicatalytic proteases. These results suggest that the temporal control of c-Jun and c-Fos may be regulated through the ubiquitinylation pathways, and the ubiquitinylation of c-Jun and c-Fos may in turn be regulated in response to the heterodimerization between them and the cooperation between E2(20K) and E3 mediated polyubiquitinylation. C1 GEORGETOWN UNIV, DEPT CHEM, WASHINGTON, DC 20057 USA. NHLBI, NIH, BIOCHEM LAB, BETHESDA, MD 20892 USA. ST JUDE CHILDRENS RES HOSP, DEPT DEV NEUROBIOL, MEMPHIS, TN 38105 USA. RI Curran, Tom/C-1164-2008; Curran, Tom/D-7515-2011; Yang, David/A-7294-2009 OI Curran, Tom/0000-0003-1444-7551; FU NIGMS NIH HHS [GM-25848] NR 31 TC 41 Z9 41 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 1 PY 1996 VL 271 IS 9 BP 4930 EP 4936 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TX697 UT WOS:A1996TX69700056 PM 8617766 ER PT J AU Chavany, C Mimnaugh, E Miller, P Bitton, R Nguyen, P Trepel, J Whitesell, L Schnur, R Moyer, JD Neckers, L AF Chavany, C Mimnaugh, E Miller, P Bitton, R Nguyen, P Trepel, J Whitesell, L Schnur, R Moyer, JD Neckers, L TI p185(erbB2) binds to GRP94 in vivo - Dissociation of the p185(erbB2)/GRP94 heterocomplex by benzoauinone ansamycins precedes depletion of p185(erbB2) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEAT-SHOCK PROTEIN; ENDOPLASMIC-RETICULUM; KINASE-ACTIVITY; HSP90; GLYCOPROTEIN AB Treatment of SKBr3 cells with benzoquinone ansamycins, such as geldanamycin (GA), depletes p185(erbB2), the receptor tyrosine kinase encoded by the erbB2 gene. In the same cells, a biologically active benzoquinone photoaffinity label specifically binds a protein of about 100 kDa, and the ability of various GA derivatives to reduce the intracellular level of p185(erbB2) correlates with their ability to compete with the photoaffinity label for binding to this protein. In this report, we present evidence that the similar to 100-kDa ansamycin-binding protein is GRP94. Membrane-associated p185(erbB2) exists in a stable complex with GRP94. GA binding to GRP94 disrupts this complex, leading to degradation of pre-existing p185(erbB2) protein, and resulting in an altered subcellular distribution of newly synthesized p185(erbB2). C1 NCI,NIH,CLIN PHARMACOL BRANCH,BETHESDA,MD 20892. NCI,NIH,MED BRANCH,BETHESDA,MD 20892. PFIZER INC,CENT RES,GROTON,CT 06340. UNIV ARIZONA,HLTH SCI CTR,STEELE MEM RES CTR,DEPT PEDIAT,TUCSON,AZ 85724. NR 28 TC 184 Z9 195 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 MAR 1 PY 1996 VL 271 IS 9 BP 4974 EP 4977 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TX697 UT WOS:A1996TX69700062 PM 8617772 ER PT J AU Biswas, I Hsieh, P AF Biswas, I Hsieh, P TI Identification and characterization of a thermostable MutS homolog from Thermus aquaticus SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA MISMATCH CORRECTION; ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; SALMONELLA-TYPHIMURIUM; STREPTOCOCCUS-PNEUMONIAE; NUCLEOTIDE-SEQUENCE; REPAIR; BINDING; PROTEIN; RECOMBINATION AB Recognition of mispaired or unpaired bases during DNA mismatch repair is carried out by the MutS protein family. Here, we describe the isolation and characterization of a thermostable MutS homolog from Thermus aquaticus YT-1. Sequencing of the mutS gene predicts an 89.3-kDa polypeptide sharing extensive amino acid sequence homology with MutS homologs from both prokaryotes and eukaryotes. Expression of the T. aquaticus mutS gene in Escherichia coli results in a dominant mutator phenotype. Initial biochemical characterization of the thermostable MutS protein, which was purified to apparent homogeneity, reveals two thermostable activities, an ATP hydrolysis activity in which ATP is hydrolyzed to ADP and P-i and a specific DNA mismatch binding activity with affinities for heteroduplex DNAs containing either an insertion/deletion of one base or a GT mismatch. The ATPase activity exhibits a temperature optimum of approximately 80 degrees C. Heteroduplex DNA binding by the T. aquaticus MutS protein requires Mg2+ and occurs over a broad temperature range from 0 degrees C to at least 70 degrees C. The thermostable MutS protein may be useful for further biochemical and structural studies of mismatch binding and for applications involving mutation detection. C1 NIDDK,NIH,GENET & BIOCHEM BRANCH,BETHESDA,MD 20892. NR 47 TC 49 Z9 51 U1 2 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 MAR 1 PY 1996 VL 271 IS 9 BP 5040 EP 5048 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TX697 UT WOS:A1996TX69700071 PM 8617781 ER PT J AU Bryant, SS Mitchell, AL Collins, F Miao, WY Marshall, M Jove, R AF Bryant, SS Mitchell, AL Collins, F Miao, WY Marshall, M Jove, R TI N-terminal sequences contained in the Src homology 2 and 3 domains of p120 GTPase-activating protein are required for full catalytic activity toward Ras SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NEUROFIBROMATOSIS TYPE-1 GENE; TYROSINE KINASES; SACCHAROMYCES-CEREVISIAE; SH3 DOMAINS; P21 GTPASE; GAP; BINDING; TRANSFORMATION; IDENTIFICATION; CLONING AB The p120 GTPase-activating protein (GAP) is a negative regulator of Ras, which has a central role in signal transduction pathways that control cell proliferation. p120 GAP accelerates the conversion of activated Ras-GTP to its inactive form, Ras-GDP, thereby inhibiting mitogenic signaling. To examine potential contributions of p120 N-terminal sequences to regulation of its C-terminal catalytic domain, we constructed deletion mutants lacking defined regions, including the variable hydrophobic region as well as the Src homology 2 (SH2) and 3 (SH3) domains. These mutant proteins were expressed in infected Sf9 insect cells from recombinant baculoviruses and assayed in vitro for their ability to stimulate the intrinsic GTPase activity of purified Ras. While deletion of the variable hydrophobic region had no effect on p120 GAP activity, deletion of the entire SH2/SH3/SH2 region severely impaired catalytic activity toward Ras. Deletion of individual SH2 and SH3 domains within this region partially inhibited p120 GAP activity. Moreover, p120 N-terminal sequences enhanced the Ras GTPase-stimulating activity of the neurofibromin GAP-related domain. These results demonstrate that sequences in the SH2/SH3/SH2 region of p120 GAP are required for full catalytic activity toward Ras. Together with earlier findings that the p120 GAP SH2 domains mediate interactions with several GAP-associated proteins, our results suggest multiple roles for the N-terminal sequences in regulating p120 GAP catalytic activity and mitogenic signaling pathways. In addition, our results raise the possibility that SH2 domain point mutations in p120 GAP detected in some basal cell carcinomas reduce catalytic activity toward Ras and thereby contribute to oncogenesis. C1 UNIV MICHIGAN,SCH MED,MOLEC & CELLULAR BIOL PROGRAM,ANN ARBOR,MI 48109. UNIV MICHIGAN,SCH MED,DEPT HUMAN GENET,ANN ARBOR,MI 48109. UNIV MICHIGAN,SCH MED,DEPT MICROBIOL & IMMUNOL,ANN ARBOR,MI 48109. UNIV MICHIGAN,SCH MED,CTR COMPREHENS CANC,ANN ARBOR,MI 48109. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. INDIANA UNIV,MED CTR,DEPT MED,WALTHER ONCOL CTR,INDIANAPOLIS,IN 46202. FU NCI NIH HHS [CA55652] NR 48 TC 12 Z9 12 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 1 PY 1996 VL 271 IS 9 BP 5195 EP 5199 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TX697 UT WOS:A1996TX69700092 PM 8617802 ER PT J AU Howell, RM Woodford, KJ Weitzmann, MN Usdin, K AF Howell, RM Woodford, KJ Weitzmann, MN Usdin, K TI The chicken beta-globin gene promoter forms a novel ''cinched'' tetrahelical structure SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HIV-1 REVERSE-TRANSCRIPTASE; DNA-REPLICATION INVITRO; ESCHERICHIA-COLI; INTERNAL REGIONS; BINDING PROTEIN; SUPERCOILED DNA; STRAND TRANSFER; SEQUENCE; TERMINUS; ARREST AB We have previously shown that the G-rich sequence G(16)CG(GGT)(2)GG in the promoter region of the chicken beta-globin gene poses a formidable barrier to DNA synthesis in vitro (Woodford et al., 1994, J. Biol. Chem. 269, 27029-27035). The K+ requirement, template-strand specificity, template concentration independence, and involvement of Hoogsteen bonding suggested that the underlying basis of this new type of DNA synthesis arrest site might be an intrastrand tetrahelical structure. However, the arrest site lacks the four G-rich repeats that are a hallmark of previously described intramolecular tetraplexes and contains a number of noncanonical bases that would be expected to greatly destabilize such a structure. Here we report evidence for an unusual K+-dependent intrastrand ''cinched'' tetraplex. This structure has several unique features including the incorporation of bases other than guanine into the stem of the tetraplex, interaction between loop bases and bases in the flanking region, and base pairing between bases 3' and 5' of the tetrahelix-forming region to form a molecular ''cinch.'' This finding extends the range of sequences capable of tetraplex formation as well as our appreciation of the conformational complexity of the chicken beta-globin promoter. RP Howell, RM (reprint author), NIDDK,BIOCHEM PHARMACOL LAB,SECT GENOM STRUCT & FUNCT,BLDG 8,ROOM 202,8 CTR DR MSC 0830,BETHESDA,MD 20892, USA. NR 32 TC 44 Z9 45 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 MAR 1 PY 1996 VL 271 IS 9 BP 5208 EP 5214 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TX697 UT WOS:A1996TX69700094 PM 8617804 ER PT J AU Baulida, J Kraus, MH Alimandi, M DiFiore, PP Carpenter, G AF Baulida, J Kraus, MH Alimandi, M DiFiore, PP Carpenter, G TI All ErbB receptors other than the epidermal growth factor receptor are endocytosis impaired SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TYROSINE KINASE-ACTIVITY; SIGNAL TRANSDUCTION; HUMAN-FIBROBLASTS; INTERNALIZATION; PROTEIN; CELLS; GENE; AUTOPHOSPHORYLATION; PHOSPHORYLATION; DEGRADATION AB Four transmembrane tyrosine kinases constitute the ErbB receptor family: the epidermal growth factor (EGF) receptor, ErbB-2, ErbB-3, and ErbB-4. We have measured the endocytic capacities of all four members of the EGF receptor family, including ErbB-3 and ErbB-4, which have not been described previously. EGF-responsive chimeric receptors containing the EGF receptor extracellular domain and different ErbB cytoplasmic domains (EGFR/ErbB) have been employed. The capacity of these growth factor-receptor complexes to mediate I-125-EGF internalization, receptor down-regulation, receptor degradation, and receptor co-immunoprecipitation with AP-2 was assayed. In contrast to the EGF receptor, all EGFR/ErbB receptors show impaired ligand-induced rapid internalization, down-regulation, degradation, and AP-2 association. Also, we have analyzed the heregulin-responsive wild-type ErbB-4 receptor, which does not mediate the rapid internalization of I-125-heregulin, demonstrates no heregulin-regulated receptor degradation, and fails to form association complexes with AP-2. Despite the substantial differences in ligand-induced receptor trafficking between the EGF and ErbB-4 receptors, EGF and heregulin have equivalent capacities to stimulate DNA synthesis in quiescent cells. These results show that the ligand-dependent down-regulation mechanism of the EGF receptor, surprisingly, is not a property of any other known ErbB receptor family member. Since endocytosis is thought to be an attenuation mechanism for growth factor-receptor complexes, these data imply that substantial differences in attenuation mechanisms exist within one family of structurally related receptors. C1 VANDERBILT UNIV,SCH MED,DEPT BIOCHEM,NASHVILLE,TN 37232. VANDERBILT UNIV,SCH MED,DEPT MED,NASHVILLE,TN 37232. NCI,NIH,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. RI Di Fiore, Pier Paolo/K-2130-2012 OI Di Fiore, Pier Paolo/0000-0002-2252-0950 FU NCI NIH HHS [CA24071] NR 46 TC 324 Z9 328 U1 1 U2 11 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 MAR 1 PY 1996 VL 271 IS 9 BP 5251 EP 5257 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TX697 UT WOS:A1996TX69700100 PM 8617810 ER PT J AU Basic, N Basic, V Bulic, K Grgic, M Kleinman, HK Luyten, FP Vukicevic, S AF Basic, N Basic, V Bulic, K Grgic, M Kleinman, HK Luyten, FP Vukicevic, S TI TGF-beta and basement membrane Matrigel stimulate the chondrogenic phenotype in osteoblastic cells derived from fetal rat calvaria SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID X COLLAGEN-SYNTHESIS; GROWTH-FACTOR-BETA; HYPERTROPHIC CHONDROCYTES; INVITRO DEVELOPMENT; GENE-EXPRESSION; BONE; DIFFERENTIATION; CULTURE; OSTEOGENIN; TRANSDIFFERENTIATION AB Primary cultures of fetal rat calvarial cells contain a spectrum of osteogenic phenotypes including undifferentiated mesenchymal cells, osteoprogenitor cells, and osteoblasts. We recently demonstrated that rat calvarial osteoblastlike cells grown on basement membrane undergo profound morphological changes resembling a canalicular network in bone, In the present study, we examined the effect of reconstituted basement membrane Matrigel on chondroblastic versus osteoblastic differentiation of different cell subpopulations obtained by five consecutive enzymatic digestions of rat calvarial cell populations, We found that the appearance of canalicular cell processes decreased with the later digests, When cells from the fourth and fifth digest were grown on top of Matrigel for 7 days, the majority of the cell aggregates displayed chondrocytic characteristics but none of the cells became hypertrophic, When individual chondroblastic cell aggregates were subsequently transferred from Matrigel to plastic, they started expressing types I and X collagens, alkaline phosphatase, and osteocalcin, Within the next 7 days (days 8-14 of the experiment), the majority of cells increased in size, and at day 17 on plastic (day 24 of the experiment) mineralized bone nodules formed, The chondroblastic differentiation of calvarial cells grown on Matrigel could be inhibited by a specific transforming growth factor-beta 1 (TGF-beta 1) but not by a TGF-beta 2 antibody, Addition of recombinant TGF-beta 1 to similar cultures promoted the appearance of chondroblastic cell aggregates, The cartilage phenotype could not, on the contrary, be promoted by growing the cells on other extracellular matrices such as a collagen I gel, We suggest that TGF-beta 1 in concert with the basement membrane extracellular matrix induces chondroblastic differentiation of rat calvarial osteoprogenitor cells. C1 UNIV ZAGREB,SCH MED,DEPT ANAT,ZAGREB 10000,CROATIA. NIDR,NIH,DEV BIOL LAB,BETHESDA,MD 20892. NIDR,NIH,BONE RES BRANCH,BETHESDA,MD 20892. NR 49 TC 16 Z9 16 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD MAR PY 1996 VL 11 IS 3 BP 384 EP 391 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TY261 UT WOS:A1996TY26100011 PM 8852949 ER PT J AU Karanian, JW Ramwell, PW AF Karanian, JW Ramwell, PW TI Effect of gender and sex steroids on the contractile response of canine coronary and renal blood vessels SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY LA English DT Article DE gender; sex steroids; vascular reactivity; dogs ID SMOOTH-MUSCLE CELLS; RAT AORTA; ANDROGEN TREATMENT; TESTOSTERONE; RECEPTORS; PROSTAGLANDIN; MEN; PROGESTERONE; THROMBOXANE; REACTIVITY AB The effect of gender, gonadal steroids, and antiandrogen/antiestrogen-treatment on the iso to nic response of isolated preparations of the left anterior descending coronary artery (LAD), left circumflex coronary artery, and renal artery and vein of sexually mature dogs was investigated. The maximum isotonic response of the coronary and renal vasculature to the thromboxane A(2) (TXA(2))-mimetic U46619 was significantly greater, and the EC(50) value was significantly lower in males as compared with females. Moreover, similar gender differences in the contractile response of the coronary vasculature to norepinephrine were observed. Pretreatment of male dogs with the antiandrogens flutamide or cyproterone acetate reduced the maximum contractile response of the LAD to the TXA(2)-mimetic. Pretreatment of female dogs with testosterone resulted in an increase in both the maximum contractile response and EC(50) value to U46619. Antiestrogen treatment of female dogs with tamoxifen was associated with an increase in the maximum contractile response of the LAD to U46619. Estrogen pretreatment of male dogs decreased both the maximum contractile response and the EC(50) value to U46619. Therefore, there is a sex difference in LAD and LCX contractile responses to both U46619 and norepinephrine. These results suggest that smooth muscle reactivity of dog coronary artery to the TXA(2)-mimetic U46619 may be susceptible to regulation by both androgens and estrogens. The observed gender differences in the catecholamine response may be similarly altered by changes in the hormonal milieu. C1 GEORGETOWN UNIV,MED CTR,DEPT PHYSIOL & BIOPHYS,WASHINGTON,DC 20007. RP Karanian, JW (reprint author), NIAAA,NIH,LAB MEMBRANE BIOCHEM & BIOPHYS,450-HFZ,9200 CORP BLVD,ROCKVILLE,MD 20852, USA. NR 37 TC 32 Z9 33 U1 2 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0160-2446 J9 J CARDIOVASC PHARM JI J. Cardiovasc. Pharmacol. PD MAR PY 1996 VL 27 IS 3 BP 312 EP 319 DI 10.1097/00005344-199603000-00002 PG 8 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA TW522 UT WOS:A1996TW52200002 PM 8907791 ER PT J AU Ferns, M Deiner, M Hall, Z AF Ferns, M Deiner, M Hall, Z TI Agrin-induced acetylcholine receptor clustering in mammalian muscle requires tyrosine phosphorylation SO JOURNAL OF CELL BIOLOGY LA English DT Article ID EXTRACELLULAR-MATRIX; PROTEIN; DYSTROPHIN; MEMBRANE; FORMS; SURFACE; DIFFER AB Agrin is thought to be the nerve-derived factor that initiates acetylcholine receptor (AChR) clustering at the developing neuromuscular junction. We have investigated the signaling pathway in mouse C2 myotubes and report that agrin induces a rapid but transient tyrosine phosphorylation of the AChR beta subunit. As the beta-subunit tyrosine phosphorylation occurs before the formation of AChR clusters, it may serve as a precursor step in the clustering mechanism. Consistent with this, we observed that tyrosine phosphorylation of the beta subunit correlated precisely with the presence or absence of clustering under several experimental conditions. Moreover, two tyrosine kinase inhibitors, herbimycin and staurosporine, that blocked beta-subunit phosphorylation also blocked agrin-induced clustering. Surprisingly, the inhibitors also dispersed preformed AChR clusters, suggesting that the tyrosine phosphorylation of other proteins may be required for the maintenance of receptor clusters. These findings indicate that in mammalian muscle, agrin-induced AChR clustering occurs through a mechanism that requires tyrosine phosphorylation and may involve tyrosine phosphorylation of the AChR itself. C1 UNIV CALIF SAN FRANCISCO,DEPT PHYSIOL,SAN FRANCISCO,CA 94143. NIMH,NIH,BETHESDA,MD 20892. MONTREAL GEN HOSP,RES INST,DEPT NEUROSURG,MONTREAL,PQ H3G 1A4,CANADA. NR 35 TC 131 Z9 133 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD MAR PY 1996 VL 132 IS 5 BP 937 EP 944 DI 10.1083/jcb.132.5.937 PG 8 WC Cell Biology SC Cell Biology GA UA360 UT WOS:A1996UA36000015 PM 8603924 ER PT J AU Ross, AH Daou, MC McKinnon, CA Condon, PJ Lachyankar, MB Stephens, RM Kaplan, DR Wolf, DE AF Ross, AH Daou, MC McKinnon, CA Condon, PJ Lachyankar, MB Stephens, RM Kaplan, DR Wolf, DE TI The neurotrophin receptor, gp75, forms a complex with the receptor tyrosine kinase TrkA SO JOURNAL OF CELL BIOLOGY LA English DT Article ID NERVE GROWTH-FACTOR; AFFINITY NGF RECEPTOR; NEURONAL DIFFERENTIATION; SIGNAL TRANSDUCTION; LIGAND-BINDING; GENE-TRANSFER; CELLS; PROTOONCOGENE; ASSOCIATION; EXPRESSION AB The high-affinity NGF receptor is thought to be a complex of two receptors, gp75 and the tyrosine kinase TrkA, but direct biochemical evidence for such an association has been lacking. In this report, we demonstrate the existence of such a gp75-TrkA complex by a copatching technique. Gp75 on the surface of intact cells is patched with an anti-gp75 antibody and fluorescent secondary antibody, the cells are then fixed to prevent further antibody-induced redistributions, and the distribution of TrkA is probed with an anti-TrkA antibody and fluorescent secondary antibody. We utilize a baculovirus-insect cell expression system which allows high level expression of wild-type and mutated NGF receptors. TrkA and gp75 copatch in both the absence and presence of NGF. This association is specific, since gp75 does not copatch with other tyrosine kinase receptors, including TrkB, platelet-derived growth factor receptor-beta, and Torso (Tor). To determine which domains of TrkA are required for copatching, we used a series of TrkA-Tor chimeric receptors and show that the extracellular domain of TrkA is sufficient for copatching with gp75. A chimeric receptor with TrkA transmembrane and intracellular domains shows partial copatching with gp75. Deletion of the intracellular domain of gp75 decreases but does not eliminate copatching. A point mutation which inactivates the TrkA kinase has no effect on copatching, indicating that this enzymatic activity is not required for association with gp75. Hence, although interactions between the gp75 and TrkA extracellular domains are sufficient for complex formation, interactions involving other receptor domains also play a role. C1 UNIV MASSACHUSETTS,MED CTR,WORCESTER,MA 01655. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21701. RP Ross, AH (reprint author), WORCESTER FDN BIOMED RES,222 MAPLE AVE,SHREWSBURY,MA 01545, USA. FU NINDS NIH HHS [NS28760, NS21716] NR 54 TC 66 Z9 66 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD MAR PY 1996 VL 132 IS 5 BP 945 EP 953 DI 10.1083/jcb.132.5.945 PG 9 WC Cell Biology SC Cell Biology GA UA360 UT WOS:A1996UA36000016 PM 8603925 ER PT J AU Hagen, SJ Eaton, WA AF Hagen, SJ Eaton, WA TI Nonexponential structural relaxations in proteins SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID HIERARCHICALLY CONSTRAINED DYNAMICS; RANDOM ENERGY-MODEL; MOLECULAR-DYNAMICS; LIGAND-BINDING; GLASSY RELAXATION; SINGLE MOLECULES; MYOGLOBIN; SPECTROSCOPY; HEMOGLOBIN; SIMULATION AB Conformational changes in proteins have been observed to exhibit a nonexponential time course. In myoglobin the conformational relaxation that follows photodissociation of the heme ligand is a very extended process that stretches from less than 1 picosecond to nearly 1 microsecond. We explain these kinetics with a model in which the initial protein conformational substates are connected to the final substates and to each other via transition states of a single energy. (C) 1996 American Institute of Physics. RP Hagen, SJ (reprint author), NIDDKD,NIH,CHEM PHYS LAB,BLDG 5,BETHESDA,MD 20892, USA. NR 37 TC 64 Z9 65 U1 0 U2 7 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD MAR 1 PY 1996 VL 104 IS 9 BP 3395 EP 3398 DI 10.1063/1.471044 PG 4 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA TW809 UT WOS:A1996TW80900027 ER PT J AU Margolis, RN Canalis, E Partridge, NC AF Margolis, RN Canalis, E Partridge, NC TI Invited review of a workshop: Anabolic hormones in bone: Basic research and therapeutic potential SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PARATHYROID-HORMONE; RECEPTOR; CELLS; GENE; EXPRESSION; PEPTIDE; BINDING AB Age-, postmenopause-, and disease-related conditions that result in low bone mass represent important public health issues. Maintenance of bone mass is a balance between bone resorption and formation and is influenced by diet, body composition, activity level, and the interactions between and among a large number of hormones, growth factors, and cytokines. Recent research has emphasized establishing a more complete understanding of the hormonal regulation of bone and developing anabolic agents with therapeutic potential for the treatment of low bone mass. The NIDDK at the NIH recently sponsored a Workshop, entitled Anabolic Hormones in Bone: Basic Research and Therapeutic Potential, that attempted to define the current state of the art knowledge of hormones, growth factors, and cytokines that affect bone mass, with particular emphasis on those that could potentially have a role as anabolic agents in bone. This review presents a condensed proceedings of that workshop along with a summary of the optimal requisites for the development of anabolic agents with therapeutic potential in bone. C1 ST FRANCIS HOSP & MED CTR, DEPT RES, HARTFORD, CT 06105 USA. UNIV CONNECTICUT, SCH MED, FARMINGTON, CT 06030 USA. ST LOUIS UNIV, SCH MED, DEPT PHARMACOL, ST LOUIS, MO 63104 USA. ST LOUIS UNIV, SCH MED, DEPT PHYSIOL SCI, ST LOUIS, MO 63104 USA. RP Margolis, RN (reprint author), NIDDKD, NIH,ENDOCRINOL SECT,BLDG 45,ROOM 5AN12J, 45 CTR DR, MSC 6600, BETHESDA, MD 20892 USA. NR 60 TC 38 Z9 38 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 MAR PY 1996 VL 81 IS 3 BP 872 EP 877 DI 10.1210/jc.81.3.872 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TZ906 UT WOS:A1996TZ90600002 PM 8772542 ER PT J AU Ross, JL McCauley, E Roeltgen, D Long, L Kushner, H Feuillan, P Cutler, GB AF Ross, JL McCauley, E Roeltgen, D Long, L Kushner, H Feuillan, P Cutler, GB TI Self-concept and behavior in adolescent girls with Turner syndrome: Potential estrogen effects SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SKILLS AB Data on self-concept and behavior were gathered from 31 girls with Turner syndrome (TS) followed longitudinally between the ages of 12 and 16 and from 89 normal control girls recruited from public schools and assessed cross-sectionally. The two groups of girls were similar in age and racial composition. The girls with TS were treated with estrogen replacement therapy in increasing doses between the ages of 12 and 16 (100-400 ng/kg day ethinyl estradiol). Their self-reported self-esteem and psychological well-being (Piers-Harris Self-Concept Scale) revealed significant improvement over time for most scales as well as the total score (P < 0.001). Parents reported improvement in problem behaviors, as reflected in the Child Behavior Checklist (CBCL) scales: Behavior Total, Externalizing Behavior, Aggressive Behavior, and Social Problems Behavior scales (all P < 0.001). Analysis of covariance comparing normal controls to the TS subjects revealed that at age 12 yr, TS and normal subjects differed significantly for the School Social Competency subscale and the Social Problems Behavior subscale (all P < 0.001). Girls with TS resembled the normal controls on all CBCL scales by ages 14-15 yr. Thus, we found improved self-concept both by self- and parental report in estrogen-treated girls with TS followed longitudinally through adolescence. An analogous correlation with age was not seen in the cross-sectional normal control sample. These findings support positive effects of estrogen on psychological well-being in girls with TS and underscores the need to initiate estrogen replacement therapy by ages 12-14 yr in this population. C1 UNIV WASHINGTON, CHILDRENS HOSP & MED CTR, DEPT PSYCHIAT & BEHAV SCI, SEATTLE, WA 98105 USA. UNIV WASHINGTON, CHILDRENS HOSP & MED CTR, DEPT PEDIAT, SEATTLE, WA 98105 USA. HAHNEMANN UNIV, DEPT BIOSTAT, PHILADELPHIA, PA 19107 USA. WILLIAMSPORT HOSP, WILLIAMSPORT, PA 17701 USA. NICHHD, DEV ENDOCRINOL BRANCH, NIH, BETHESDA, MD 20892 USA. RP Ross, JL (reprint author), THOMAS JEFFERSON UNIV, JEFFERSON MED COLL, DEPT PEDIAT, 1025 WALNUT ST, PHILADELPHIA, PA 19107 USA. FU NINDS NIH HHS [NS-29857] NR 15 TC 53 Z9 56 U1 2 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 MAR PY 1996 VL 81 IS 3 BP 926 EP 931 DI 10.1210/jc.81.3.926 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TZ906 UT WOS:A1996TZ90600012 PM 8772552 ER PT J AU Mastorakos, G Scopa, CD Kao, LC Vryonidou, A Friedman, TC Kattis, D Phenekos, C Rabin, D Chrousos, GP AF Mastorakos, G Scopa, CD Kao, LC Vryonidou, A Friedman, TC Kattis, D Phenekos, C Rabin, D Chrousos, GP TI Presence of immunoreactive corticotropin-releasing hormone in human endometrium SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID RAT SPINAL-CORD; PHARMACOKINETIC PROPERTIES; FACTOR RECEPTORS; BETA-ENDORPHIN; NERVOUS-SYSTEM; FACTOR CRF; SECRETION; CELLS; OVINE; GENE AB Immunoreactive CRH (IrCRH) is produced locally in experimentally induced and spontaneous inflammation, where it exerts autocrine or paracrine proinflammatory effects. In addition, CRH is secreted by the human placenta, rat Leydig cells, and rat and human ovaries, where it may participate in the inflammatory processes of ovulation and luteolysis, and/or the regulation of steroidogenesis. Finally, CRH is secreted in vitro by cultured human epithelial and decidualized stromal endometrial cells. To investigate the presence of CRH in human endometrium in. vivo, we examined this tissue immunohistochemically and by extraction/RIA using a polyclonal, highly specific antirat/human CRH antibody. Endometrial biopsies from 33 women, aged 23-43 yr (median age, 33.5 yr), were performed by linear endometrial curettage for diagnostic purposes at different stages of the cycle. Intense IrCRH staining was localized in the cytoplasm of cells of the endometrial glands in all samples examined. IrCRH was also found in endometrial stromal cells exhibiting decidual reaction and in local immune accessory cells. The mobility of the endometrial IrCRH molecule was similar to that of r/hCRH in reverse phase high pressure liquid chromatography. The presence of CRH in the endometrium, and more specifically in the glandular epithelium, during the proliferative and secretory phases of the menstrual cycle together with its known proinflammatory properties, suggest that this neuropeptide might participate in the inflammatory-like phenomena of endometrial physiology, such as menstrual shedding, surface epithelium repair, and/or implantation of the blastocyst. The presence of CRH in decidualized stromal cells is in accordance with its previously reported production by in vitro decidualized cultured endometrial stromal cells as well as by the placental decidua. C1 NICHHD, DEV ENDOCRINOL BRANCH, NATL INST HLTH, BETHESDA, MD 20892 USA. NICHHD, DEV NEUROBIOL LAB, NATL INST HLTH, BETHESDA, MD 20892 USA. UNIV PATRAS, SCH MED, DEPT PATHOL, GR-26110 PATRAI, GREECE. RED CROSS HOSP, DEPT ENDOCRINOL, ATHENS, GREECE. NR 48 TC 61 Z9 61 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 MAR PY 1996 VL 81 IS 3 BP 1046 EP 1050 DI 10.1210/jc.81.3.1046 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TZ906 UT WOS:A1996TZ90600034 PM 8772574 ER PT J AU Rose, SR Municchi, G Barnes, KM Cutler, CB AF Rose, SR Municchi, G Barnes, KM Cutler, CB TI Overnight growth hormone concentrations are usually normal in pubertal children with idiopathic short stature - A Clinical Research Center Study SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BODY-MASS; SECRETION; DEFICIENCY; LEUKEMIA; THERAPY; BOYS AB To estimate the incidence of low growth hormone (GH) concentration in children and adolescents with idiopathic short stature, overnight GH levels were measured in 167 subjects. The results were compared with data from 132 normal children of similar pubertal stage, bone age, or body mass index. The majority of short children had normal overnight GH concentrations in a distribution not significantly different from that observed in normal children. However, in 6% of children grouped by pubertal stage and in 13% of children grouped by bone age, overnight GH levels were below the 95% confidence limits of normal. The overnight GH levels were above normal in 6%. The observed frequencies of both low and high GH levels were significantly greater than expected (P < 0.001). However, when body mass index was included in the analysis, only 5% of the children had low GH measures, and only 4% had high GH measures (both not significant). This frequency of low overnight GH levels in short children is considerably less than that reported by others. Thus, these data do not support the hypothesis that a deficiency of spontaneous GH secretion is a common cause of short stature. We conclude that standard GH stimulation tests, despite their limitations, remain the best definitive test of GH secretion. Subsequent overnight GH studies may be useful, however, in selected clinical settings such as previous cranial irradiation or other central nervous system disorder. C1 UNIV TENNESSEE, DEPT PEDIAT, MEMPHIS, TN 38103 USA. NICHHD, DEV ENDOCRINOL BRANCH, NATL INST HLTH, BETHESDA, MD 20892 USA. FU NCRR NIH HHS [5 M01 RR00997] NR 29 TC 12 Z9 12 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 MAR PY 1996 VL 81 IS 3 BP 1063 EP 1068 DI 10.1210/jc.81.3.1063 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TZ906 UT WOS:A1996TZ90600037 PM 8772577 ER PT J AU Dong, QH BruckerDavis, F Weintraub, BD Smallridge, RC Carr, FE Battey, J Spiegel, AM Shenker, A AF Dong, QH BruckerDavis, F Weintraub, BD Smallridge, RC Carr, FE Battey, J Spiegel, AM Shenker, A TI Screening of candidate oncogenes in human thyrotroph tumors: Absence of activating mutations of the G alpha(q), G alpha(11), G alpha(s), or thyrotropin-releasing hormone receptor genes SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PROTEIN-KINASE-C; SECRETING PITUITARY-ADENOMAS; HUMAN ENDOCRINE TUMORS; NIH 3T3 CELLS; G-ALPHA-Q; PHOSPHOLIPASE-C; ADENYLYL CYCLASE; MALIGNANT TRANSFORMATION; PRIMARY HYPOTHYROIDISM; REGULATORY PROTEINS AB Activating mutations encoding substitutions at positions Arg(201) and Gln(227) of the alpha-subunit of the stimulatory C protein, G(s), have been found in about 40% of pituitary somatotroph tumors. Although the etiology of thyrotroph adenomas is unknown, their autonomous behavior and blunted response to stimulatory hypothalamic hormone superficially resemble those of somatotroph tumors. We hypothesized that a subset of thyrotroph tumors might be caused by dominant somatic mutations that lead to inappropriate activation of the G(q)/phospholipase C beta/Ca2+/protein kinase C pathway normally triggered by occupancy of the TRH receptor (TRHR). We, therefore, screened samples from nine thyrotroph tumors for the presence of activating mutations of the alpha(q), alpha(11), and TRHR genes. Fragments of alpha(q) and alpha(11) complementary DNA encompassing residues (Arg(183) and Gln(209)) that correspond to Arg(201) and Gln(227) of alpha(s) were amplified and sequenced. Temperature gradient gel electrophoresis was used to screen for heterozygous mutations in the TRHR coding sequence as well as for known alpha(s) mutations. No mutations were detected. We conclude that mutations in these regions of the alpha(q), alpha(11), alpha(s), and TRHR genes occur infrequently, if at all, in human thyrotroph tumors. Alternative mechanisms underlying thyrotroph tumorigenesis, including changes in the expression levels of G protein alpha-subunits or TRHR, dysregulation of downstream components, inappropriate activation of other stimulatory pathways, or loss of inhibitory inputs, remain to be explored. C1 NIDDKD, MOLEC & CELLULAR ENDOCRINOL BRANCH, NATL INST DEAFNESS & OTHER COMMUN DISORDERS, BETHESDA, MD 20892 USA. NIDDKD, METAB DIS BRANCH, NATL INST DEAFNESS & OTHER COMMUN DISORDERS, NATL INST HLTH, BETHESDA, MD 20892 USA. WALTER REED ARMY MED CTR, WALTER REED ARMY INST RES, DIV MED, WASHINGTON, DC 20307 USA. WALTER REED ARMY MED CTR, DEPT CLIN INVEST, WASHINGTON, DC 20307 USA. NR 69 TC 48 Z9 49 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAR PY 1996 VL 81 IS 3 BP 1134 EP 1140 DI 10.1210/jc.81.3.1134 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TZ906 UT WOS:A1996TZ90600048 PM 8772588 ER PT J AU Hussain, A Zimmerman, CA Boose, JA Froehlich, J Richardson, A Horowitz, RS Collins, MT Lash, RW AF Hussain, A Zimmerman, CA Boose, JA Froehlich, J Richardson, A Horowitz, RS Collins, MT Lash, RW TI Large scale synthesis of recombinant human thyrotropin using methotrexate amplification: Chromatographic, immunological, and biological characterization SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HAMSTER OVARY CELLS; THYROID-STIMULATING HORMONE; GONADOTROPIN-BETA-SUBUNIT; CHORIONIC-GONADOTROPIN; DIHYDROFOLATE-REDUCTASE; SELECTABLE MARKER; ALPHA-SUBUNIT; EXPRESSION; CLONING; SEQUENCE AB Studies of human TSH (hTSH) structure and function have been limited by difficulties in producing large quantities of recombinant hormone. We describe a system for the stable expression of high levels of recombinant human TSH (rec hTSH) using a mutant form of dihydrofolate reductase (dhfr) as an amplifiable dominant selectable marker. A vector expressing both the hTSH alpha-subunit and the mutant dhfr was cotransfected with a hTSH beta-subunit expression vector into dhfr-deficient cells. Amplification of the transfected sequences by methotrexate selection, followed by cell culture in a hollow fiber perfusion system, yielded rec hTSH production as high as 100,000 mu U/mt. Immunoradiometric assays using five different antibodies revealed no differences in the immunological activities of rec hTSH and pituitary hTSH. Bioactivity was measured in a novel TSH bioassay coupling the generation of cAMP by a transfected hTSH receptor to the cAMP-dependent regulation of a luciferase reporter gene. The ED(50) for bovine TSH in this bioassay was 1.4 ng/mL (3.5 x 10(-11) mol/L). The ratio of the ED(50) values for rec hTSH and pituitary hTSH was 1.0:1.1 (P = NS), indicating that the two TSHs were of equivalent potency. In conclusion, we have developed techniques for the high level production of rec hTSH that is immunologically and biologically equivalent to pituitary hTSH. The ability to produce large quantities of rec hTSH using standard laboratory techniques should facilitate future studies, such as the development of clinically useful TSH analogs. C1 UNIV MARYLAND, SCH MED, CTR CANC, DEPT MED, DIV ENDOCRINOL, BALTIMORE, MD 21201 USA. UNIV MARYLAND, CTR CANC, BALTIMORE, MD 21201 USA. VET ADM MED CTR, BALTIMORE, MD 21201 USA. NICHHD, DEV ENDOCRINOL BRANCH, NIH, BETHESDA, MD 20892 USA. FU NIDDK NIH HHS [5-K08-DK-02107-02] NR 30 TC 9 Z9 9 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 MAR PY 1996 VL 81 IS 3 BP 1184 EP 1188 DI 10.1210/jc.81.3.1184 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA TZ906 UT WOS:A1996TZ90600058 PM 8772598 ER PT J AU Quarles, RH Dalakas, MC AF Quarles, RH Dalakas, MC TI Do anti-ganglioside antibodies cause human peripheral neuropathies? SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID POLYNEUROPATHY; PATIENT; IGM C1 NINCDS,NIH,NEUROMUSCULAR DIS SECT,BETHESDA,MD 20892. RP Quarles, RH (reprint author), NINCDS,NIH,MOLEC & CELLULAR NEUROBIOL LAB,BETHESDA,MD 20892, USA. NR 9 TC 8 Z9 8 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR 1 PY 1996 VL 97 IS 5 BP 1136 EP 1137 DI 10.1172/JCI118526 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA TZ805 UT WOS:A1996TZ80500002 PM 8636423 ER PT J AU He, CJ Esposito, C Phillips, C Zalups, RK Henderson, DA Striker, GE Striker, LJ AF He, CJ Esposito, C Phillips, C Zalups, RK Henderson, DA Striker, GE Striker, LJ TI Dissociation of glomerular hypertrophy, cell proliferation, and glomerulosclerosis in mouse strains heterozygous for a mutation (Os) which induces a 50% reduction in nephron number SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE nephron number; glomerular hypertrophy; glomerular extracellular matrix mRNAs ID UNILATERAL RENAL AGENESIS; DIABETIC NEPHROPATHY; GROWTH-HORMONE; SEGMENTAL GLOMERULOSCLEROSIS; TRANSGENIC MICE; SCLEROSIS; RAT; PROGRESSION; DISEASE; LESIONS AB We reported that the Os mutation in ROP mice induced a 50% reduction in nephron number, glomerular hypertrophy, and severe glomerulosclerosis, We examined two mouse strains with the Os mutation, ROP Os/+ and C57 Os/+ mice, to determine whether the genetic background influenced the development of glomerulosclerosis, Nephron number was decreased by 50% in both ROP Os/+ and C57 Os/+ mice, and a glomerular volume and labeling index were two- to threefold increased in both, Whereas glomerulosclerosis was severe in ROP Os/+ mice, it was absent or minimal in C57 Os/+ mice. ROP Os/+ glomeruli had two- to threefold more type TV collagen, laminin, and tenascin than C57 Os/+ by immunofluorescence microscopy. Glomerular alpha 1IV collagen and tenascin mRNA levels were increased (2.8- and 1.7-fold) in ROP Os/+ and in C57 Os/+ (1.7- and 1.4-fold) mice, Both ROP Os/+ and C57 Os/+ mice had a slight increase (1.5- and 1.7-fold) in 72-kD collagenase mRNA levels. Whereas laminin B1 mRNA levels were twofold higher in ROP +/+ than in C57 +/+ mice, there was no further change in the presence of the Os mutation, Thus, the response to the Os mutation depended on the mouse strain, since severe glomerulosclerosis occurred only in ROP Os/+ mice, even though cell proliferation and glomerular hypertrophy also were present in C57 Os/+ mice. C1 NIDDK,METAB DIS BRANCH,RENAL CELL BIOL SECT,NIH,BETHESDA,MD 20892. MERCER UNIV,SCH MED,DIV BASIC MED SCI,MACON,GA 31207. OKLAHOMA STATE UNIV,COLL OSTEOPATH MED,RES DEPT,TULSA,OK 74107. OI Phillips, Carrie/0000-0002-0256-0736 FU NIEHS NIH HHS [ES-05157] NR 50 TC 67 Z9 67 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR 1 PY 1996 VL 97 IS 5 BP 1242 EP 1249 DI 10.1172/JCI118539 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA TZ805 UT WOS:A1996TZ80500015 PM 8636436 ER PT J AU Salmon, JE Millard, S Schachter, LA Arnett, FC Ginzler, EM Gourley, MF RamseyGoldman, R Peterson, MGE Kimberly, RP AF Salmon, JE Millard, S Schachter, LA Arnett, FC Ginzler, EM Gourley, MF RamseyGoldman, R Peterson, MGE Kimberly, RP TI Fc gamma RIIA alleles are heritable risk factors for lupus nephritis in African Americans SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE Fc gamma receptors; immunoglobulin; nephritis; phagocytes; systemic lupus erythematosus ID MONONUCLEAR PHAGOCYTE SYSTEM; COLLAGEN-LIKE REGION; CIRCULATING IMMUNE-COMPLEXES; SINGLE AMINO-ACID; RECEPTOR-II; MONOCLONAL-ANTIBODY; HUMAN MONOCYTES; RESPONDER FORM; HUMAN IGG2; ERYTHEMATOSUS AB Allelic variants of Fc gamma R confer distinct phagocytic capacities providing a mechanism for heritable susceptibility to immune complex disease, Human Fc gamma RIIa has two codominantly expressed alleles, R131 and H131, which differ substantially in their ability to ligate human IgG2. The Fc gamma RIIa-H131 is the only human Fc gamma R which recognizes IgG2 efficiently and optimal IgG2 handling occurs only in the homozygous state. Therefore, since immune complex clearance is essential in SLE, we hypothesized that Fc gamma RIIA genes are important disease susceptibility factors for SLE, particularly lupus nephritis, In a two-stage cross-sectional study, we compared the distribution of Fc gamma RIIA alleles in African Americans with SLE to that in African American non-SLE controls. A pilot study of 43 SLE patients and 39 controls demonstrated a skewed distribution of Fc gamma RIIA alleles, with only 9% of SLE patients homozygous for Fc gamma RIIa-H131 compared with 36% of controls (odds ratio, 0.18; 95% CI, 0.05-0.69, P = 0.009). This was confirmed with a multicenter study of 214 SLE patients and 100 non-SLE controls. The altered distribution of Fc gamma RIIA alleles was most striking in lupus nephritis. Trend analysis of the genotype distribution showed a highly significant decrease in Fc gamma RIIA-H131 as the likelihood for lupus nephritis increased (P = 0.0004) consistent with a protective effect of the Fc gamma RIIA-H131 gene, The skewing in the distribution of Fc gamma RIIA alleles identifies this gene as a risk factor with pathophysiologic importance for the SLE diathesis in African Americans. C1 CORNELL UNIV,COLL MED,NEW YORK HOSP,GRAD PROGRAM IMMUNOL,NEW YORK,NY 10021. UNIV TEXAS,HLTH SCI CTR,DEPT MED,HOUSTON,TX 77225. SUNY HLTH SCI CTR,DEPT MED,BROOKLYN,NY 11203. NIAMSD,NIH,BETHESDA,MD 20892. NORTHWESTERN UNIV,SCH MED,DEPT MED,CHICAGO,IL 60611. RP Salmon, JE (reprint author), HOSP SPECIAL SURG,DEPT MED,535 E 70TH ST,NEW YORK,NY 10021, USA. RI Millard, Sean/A-8522-2013; OI Millard, Sean/0000-0001-8573-4625 FU NIAMS NIH HHS [P50-AR42588, R01-AR333062, R01-AR38889] NR 48 TC 346 Z9 354 U1 0 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR 1 PY 1996 VL 97 IS 5 BP 1348 EP 1354 DI 10.1172/JCI118552 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA TZ805 UT WOS:A1996TZ80500028 PM 8636449 ER PT J AU Munderloh, UG Madigan, JE Dumler, JS Goodman, JL Hayes, SF Barlough, JE Nelson, CM Kurtti, TJ AF Munderloh, UG Madigan, JE Dumler, JS Goodman, JL Hayes, SF Barlough, JE Nelson, CM Kurtti, TJ TI Isolation of the equine granulocytic ehrlichiosis agent, Ehrlichia equi, in tick cell culture SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID CAUSATIVE AGENT; INFECTION AB The equine granulocytic ehrlichiosis agent, Ehrlichia equi, is closely related or identical to the human granulocytic ehrlichiosis (HGE) agent, Both are suspected of being transmitted by ticks, We have successfully isolated E. equi in a cell line, IDE8, derived from a putative vector, the tick Ixodes scapularis, Peripheral blood leukocytes from an experimentally infected horse were inoculated onto IDE8 monolayers. Cultures were incubated in a candle jar at 34 degrees C in tick cell culture medium with NaHCO3 and an organic buffer [3-(N-morpholino)-propanesulfonic acid] (MOPS). Within 2 weeks, infected cells were detected in Giemsa-stained culture samples, and the organisms subsequently spread to uninfected cells in the cultures, E. equi was passaged serially by transferring a portion of an infected culture to new cell layers every 2 to 3 weeks. The identity of the organisms was confirmed by PCR using oligonucleotide primers specific for E. equi and the HGE agent and by immunocytology, Homologous equine antibodies and human anti-HGE convalescent serum recognized E. equi grown in tick cell culture, Electron microscopy revealed electron-lucent and -dense ehrlichia-like forms developing within host cell endosomes. E. equi passaged twice in tick cell culture retained infectivity and pathogenicity for the equine host, as demonstrated by intravenous inoculation of a suspension of infected tick cells and subsequent reisolation from peripheral blood, in fulfillment of Koch's postulates, The horse developed severe clinical signs, i.e., fever, inappetence. thrombocytopenia, icterus, and limb edema, typical of granulocytic equine ehrlichiosis, within 1 week. C1 UNIV MINNESOTA, DEPT MED, MINNEAPOLIS, MN 55455 USA. UNIV CALIF DAVIS, SCH VET MED, DEPT MED & EPIDEMIOL, DAVIS, CA 95616 USA. UNIV MARYLAND, SCH MED, DEPT PATHOL, BALTIMORE, MD 21201 USA. NATL INST HLTH, ROCKY MT LABS, HAMILTON, MT 59840 USA. RP Munderloh, UG (reprint author), UNIV MINNESOTA, DEPT ENTOMOL, 1980 FOLWELL AVE, ST PAUL, MN 55108 USA. FU NIAID NIH HHS [AI37772]; NIAMS NIH HHS [AR37909] NR 48 TC 87 Z9 88 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAR PY 1996 VL 34 IS 3 BP 664 EP 670 PG 7 WC Microbiology SC Microbiology GA UD137 UT WOS:A1996UD13700035 PM 8904434 ER PT J AU Fisherman, JS Cowan, KH Noone, M Denicoff, A Berg, S Poplack, D Balis, F Venzon, D McCabe, M Goldspiel, B Chow, C Ognibene, FP OShaughnessy, J AF Fisherman, JS Cowan, KH Noone, M Denicoff, A Berg, S Poplack, D Balis, F Venzon, D McCabe, M Goldspiel, B Chow, C Ognibene, FP OShaughnessy, J TI Phase I/II study of 72-hour infusional paclitaxel and doxorubicin with granulocyte colony-stimulating factor in patients with metastatic breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CELL-LINES; TAXOL; ADRIAMYCIN; TOXICITY; COMBINATION; RESISTANCE AB Purpose: We conducted a phase I/II trial of concurrently administered 72-hour infusional paclitaxel and doxorubicin in combination with granulocyte colony-stimulating factor (G-CSF) in patients with previously untreated metastatic breast cancer and bidimensionally measurable disease. Patients and Methods: We defined the maximum-tolerated dose (MTD) of concurrent paclitaxel and doxorubicin administration and then studied potential pharmacokinetic interactions between the two drugs. Forty-two patients who had not received prior chemotherapy for metastatic breast cancer received 296 total cycles of paclitaxel and doxorubicin with G-CSF. Results: The MTD was determined to be paclitaxel 180 mg/m(2) and doxorubicin 60 mg/m(2) each by 72-hour infusion with G-CSF. Diarrhea was the dose-limiting toxicity (DLT) of this combination, with three of three patients developing abdominal computed tomographic (CT) scan evidence of typhlitis (cecal thickening) at the dose level above the MTD. All patients developed grade 4 neutropenia (absolute neutrophil count [ANC] < 500/mu L), generally less than 5 days in duration. This combination was generally safely administered at dose levels at or below the MTD. The overall response rate was 72% (28 of 39 patients; 95% confidence interval [CI], 55% to 85%), with 8% complete responses (CRs) (three of 39; 95% CI, 2% to 21%) and a median response duration of 9 months. The median overall survival time for all patients is 23 months, with a median follow-up duration of 28 months. Pharmacokinetic studies showed that administration of paclitaxel and doxorubicin together by 72-hour infusion did not affect the steady-state concentrations of either drug. Conclusion: Concurrent 72-hour infusional paclitaxel nd doxorubicin can be administered safely, but is associated with significant toxicity. The overall response rate of this combination in untreated metastatic breast cancer patients is similar to that achieved with other doxorubicin-based combination regimens. The modest complete response rate achieved suggests that this schedule of paclitaxel and doxorubicin administration does not produce significant additive or synergistic cytotoxicity against breast cancer. C1 NCI,CANC THERAPY EVALUAT PROGRAM,BIOSTAT & DATA MANAGEMENT SECT,PEDIAT BRANCH,MED BRANCH,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT CRIT CARE MED,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT PHARM,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT RADIOL,BETHESDA,MD 20892. RI Venzon, David/B-3078-2008 NR 32 TC 70 Z9 70 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 MAR PY 1996 VL 14 IS 3 BP 774 EP 782 PG 9 WC Oncology SC Oncology GA TZ732 UT WOS:A1996TZ73200012 PM 8622023 ER PT J AU Johnson, BE Bridges, JD Sobczeck, M Gray, J Linnoila, RI Gazdar, AF Hankins, L Steinberg, SM Edison, M Frame, JN Pass, H Nesbitt, J Holden, D Mulshine, JL Glatstein, E Ihde, DC AF Johnson, BE Bridges, JD Sobczeck, M Gray, J Linnoila, RI Gazdar, AF Hankins, L Steinberg, SM Edison, M Frame, JN Pass, H Nesbitt, J Holden, D Mulshine, JL Glatstein, E Ihde, DC TI Patients with limited-stage small-cell lung cancer treated with concurrent twice-daily chest radiotherapy and etoposide cisplatin followed by cyclophosphamide, doxorubicin, and vincristine SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID NERVOUS-SYSTEM LEUKEMIA; THORACIC RADIOTHERAPY; RADIATION-THERAPY; ONCOLOGY GROUP; LOCAL-CONTROL; CHEMOTHERAPY; CARCINOMA; SURVIVAL; IRRADIATION; SENSITIVITY AB Purpose: A phase II trial in patients with limited-stage small-cell lung cancer treated with induction etoposide/cisplatin plus twice-daily chest radiotherapy was conducted in an attempt to increase response rates and prolong survival. Patients and Methods: Fifty-four previously untreated patients with limited-stage small-cell cancer were treated with etoposide/cisplatin and concurrent radiotherapy at 1.5 Gy twice daily for 3 weeks to a total dose of 45 Gy. Patients then received three more cycles of etoposide/cisplatin followed by four cycles of vincristine, doxorubicin, and cyclophosphamide or an individualized chemotherapy regimen. Results: Nine patients are alive and free of cancer a median of 4 years (range, 2 to 7) from the start of treatment. Thirty-eight have held progression of their cancer at a median of 1.2 years (range, 0.5 to 5.4) and all have died of small-cell cancer. Thirteen of these 38 patients' (34%) only site of initial relapse was in the CNS and all died of CNS metastases. Five patients died during therapy or from its complications and two patients died of causes other than relapsed small-cell lung cancer and toxicity. The median survival rime is 21.3 months, with an actual survival rate of 83% at 1 year, and actuarial survival rates of 43% at 2 years and 19% at 5 years. Conclusion: This combined modality regimen for patients with limited-stage small-cell lung cancer results in a a-year survival rate of 43%, but the principal cause of death in these patients is still relapse of the original cancer. Isolated CNS metastases caused more than 30% of the cancer deaths. C1 NCI,NAVY MED ONCOL BRANCH,BETHESDA,MD 20892. NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. NCI,SURG BRANCH,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,NATL NAVAL MED CTR,DEPT MED,BETHESDA,MD 20814. UNIFORMED SERV UNIV HLTH SCI,NATL NAVAL MED CTR,DEPT SURG,BETHESDA,MD 20814. UNIFORMED SERV UNIV HLTH SCI,NATL NAVAL MED CTR,DEPT RADIOL,BETHESDA,MD 20814. RP Johnson, BE (reprint author), NCI,NATL NAVAL MED CTR,NAVY MED ONCOL BRANCH,BLDG 8,ROOM 5101,BETHESDA,MD 20889, USA. NR 26 TC 77 Z9 81 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR PY 1996 VL 14 IS 3 BP 806 EP 813 PG 8 WC Oncology SC Oncology GA TZ732 UT WOS:A1996TZ73200017 PM 8622028 ER PT J AU Wexler, LH WeaverMcClure, L Steinberg, SM Jacobson, J Jarosinski, P Avila, N Pizzo, PA Horowitz, ME AF Wexler, LH WeaverMcClure, L Steinberg, SM Jacobson, J Jarosinski, P Avila, N Pizzo, PA Horowitz, ME TI Randomized trial of recombinant human granulocyte-macrophage colony-stimulating factor in pediatric patients receiving intensive myelosuppressive chemotherapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BONE-MARROW TRANSPLANTATION; NON-HODGKINS-LYMPHOMAS; EWINGS-SARCOMA; INDUCED NEUTROPENIA; DOSE-INTENSITY; DOUBLE-BLIND; PHASE-I/II; CANCER; MALIGNANCIES AB Purpose: To evaluate whether recombinant human graulocyte-macrophage colony-stimulating factor (GM-CSF) reduces the hematologic toxicities and supportive care requirements of an intensive combination chemoradiotherapy regimen in pediatric and young adult sarcoma patients. Patients and Methods: Thirty-seven newly diagnosed patients age 1 to 25 years were randomised to receive 18 cycles of chemotherapy alone or with GM-CSF beginning in cycle 3. GM-CSF (5 to 15 mu g/kg/d subcutaneously) was begun 24 hours after the completion of chemotherapy and continued through day 19 of each cycle or until the absolute granulocyte count (AGC) was greater than or equal to 500/mu L on 2 consecutive days. Results: GM-CSF reduced the median duration of grade 4 granulocytopenia from 9.0 days (range, 2 to 24) to 7.0 days (range, 1 to 21) (P <.0001), but did not significantly affect the grade of granulocyte nadir. No differences were seen in the incidence or types of infectious complications, incidence or duration of hospitalization and antimicrobial therapy, response to chemotherapy, or event-free or overall survival. GM-CSF was associated with more severe and protracted thrombocytopenia (median platelet nadir, 29,500/mu L [range, 3,000 to 288,000] v 59,000/mu L [range, 3,000 to 309,000], P <.0001; median time to recovery > 75,000/mu L, 16.0 days [range, 0 to 61] v 14.0 days [range, 0 to 38], P <.0001). Conclusion: GM-CSF does not produce clinically meaningful reductions in the degree or duration of severe granulocytopenia following intensive multiagent chemotherapy, but is associated with worsened thrombocytopenia. GM-CSF also does not reduce the need for hospitalization or the incidence of febrile neutropenia and infectious complications. We conclude that the costs and increased toxicities associated with the use of this agent are not justified by its minimal clinical benefit for regimens of this level of intensity. C1 NCI,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT PHARM,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT RADIOL,BETHESDA,MD 20892. RP Wexler, LH (reprint author), NCI,PEDIAT BRANCH,9000 ROCKVILLE PIKE,BLDG 10,ROOM 13N240,10 CTR DR,BETHESDA,MD 20892, USA. NR 37 TC 34 Z9 35 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR PY 1996 VL 14 IS 3 BP 901 EP 910 PG 10 WC Oncology SC Oncology GA TZ732 UT WOS:A1996TZ73200027 PM 8622038 ER PT J AU Magrath, I Adde, M Shad, A Venzon, D Seibel, N Gootenberg, J Neely, J Arndt, C Nieder, M Jaffe, E Wittes, RA Horak, ID AF Magrath, I Adde, M Shad, A Venzon, D Seibel, N Gootenberg, J Neely, J Arndt, C Nieder, M Jaffe, E Wittes, RA Horak, ID TI Adults and children with small non-cleaved-cell lymphoma have a similar excellent outcome when treated with the same chemotherapy regimen SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; NON-HODGKINS-LYMPHOMA; INTENSIVE CHEMOTHERAPY; PEDIATRIC-ONCOLOGY; BURKITTS; CYTARABINE; CHILDHOOD; SURVIVAL; SOCIETY; THERAPY AB Purpose: We have used identical treatment protocols for adults and children with small non-cleaved-cell lymphoma (SNCL) for many years and report here the results of two successive treatment regimens in these age groups. Patients and Methods: Seventy-two patients (39 adults and 33 children) were treated with protocol 77-04 between 1977 and 1985. All patients, except those with resected abdominal disease, received 15 cycles of a combination of cyclophosphamide (CTX), doxorubicin (ADR), prednisone (PRED), vincristine (VCR), high-dose methotrexate (MTX), and intrathecal (IT) therapy. Forty-one patients (20 adults and 21 children) were treated with protocol 89-C-41, which has been used since 1989. High-risk patients received four alternating cycles (with a total duration of 12 to 15 weeks) of an intensified version of protocol 77-04 without PRED (CODOX-M), and a new drug combination consisting of ifosfamide, etoposide, high-dose cytarabine (ara-C), and IT MTX (IVAC). Low-risk patients received three cycles of the CODOX-M regimen, High-risk patients were randomized to either receive or nor receive granulocyte-macrophage colony-stimulating factor (GM-CSF). Results: Event-free survival (EFS) in protocol 77-04 wets 56% at 2 years and beyond, EFS in protocol 89-C-41 was 92% at 2 years and beyond, GM-CSF was associated with increased thrombocytopenia. Conclusion: Adults and children with SNCL have a similar Prognosis when treated with the same chemotherapy. EFS in high-risk patients has been markedly improved by including IVAC in protocol 89-C-41, and excellent results can be achieved with only four cycles of therapy. In protocol 89-C-41,GM-CSF was not beneficial. C1 CHILDRENS NATL MED CTR,DEPT HEMATOL ONCOL,WASHINGTON,DC 20010. GEORGETOWN UNIV,SCH MED,DIV PEDIAT HEMATOL ONCOL,WASHINGTON,DC. PENN STATE UNIV,CHILDRENS HOSP,DIV HEMATOL ONCOL,HERSHEY,PA. MAYO CLIN & MAYO FDN,DEPT PEDIAT ADOLESCENT MED,ROCHESTER,MN 55905. RAINBOW BABIES & CHILDRENS HOSP,DIV HEMATOL & ONCOL,CLEVELAND,OH 44106. RP Magrath, I (reprint author), NCI,NIH,PEDIAT BRANCH,BLDG 10,ROOM 13N240,BETHESDA,MD 20892, USA. RI Venzon, David/B-3078-2008 NR 26 TC 245 Z9 252 U1 0 U2 2 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 MAR PY 1996 VL 14 IS 3 BP 925 EP 934 PG 10 WC Oncology SC Oncology GA TZ732 UT WOS:A1996TZ73200030 PM 8622041 ER PT J AU Weintraub, M Adde, MA Venzon, DJ Shad, AT Horak, ID Neely, JE Seibel, NL Gootenberg, J Arndt, C Nieder, ML Magrath, IT AF Weintraub, M Adde, MA Venzon, DJ Shad, AT Horak, ID Neely, JE Seibel, NL Gootenberg, J Arndt, C Nieder, ML Magrath, IT TI Severe atypical neuropathy associated with administration of hematopoietic colony-stimulating factors and vincristine SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CLINICAL-TRIAL; NEUROTOXICITY; TOXICITY; THERAPY; ACID AB Purpose: We have observed a severe atypical neuropathy (SAN) in patients with small non-cleaved-cell (SNCL) and large-cell lymphoma (LCL) treated with intensive chemotherapy and hematopoietic colony-stimulating factors (CSFs). The present analysis was undertaken in an attempt to identify factors associated with the development of this syndrome. Patients and Methods: Fifty-four adult and pediatric patients consecutively treated according to the same chemotherapy protocol were included in the analysis. Low-risk patients received three cycles of cyclophosphamide, vincristine, doxorubicin, and high-dose methotrexate (CODOX-M) while in high-risk patients this drug combination was alternated with high-dose cytarabine (ara-C), etoposide, and ifosfamide (IVAC) for a total of four cycles, Twenty-eight patients received a CSF (granulocyte [G]- or granulocyte-macrophage [GM]-CSF), and 26 patients received no CSF, A statistical analysis, which included a logistic regression model, was undertaken to examine the importance of potential contributing factors to the development of SAN. Results: SAN, which consisted of excruciating foot pain, usually associated with marked motor weakness, was observed in 12 patients, There was a highly significant association between the occurrence of this syndrome and the administration of CSFs, and on independent association with the cumulative dose of vincristine given in the first cycle of chemotherapy. Furthermore, the analysis suggested a synergistic effect between administration of the CSFs and vincristine in the genesis of this neuropathy. Conclusion: Our results indicate that CSFs can precipitate SAN when given in conjunction with vincristine. The development of SAN was associated most strongly with the cumulative dose of vincristine-the size of individual doses and the number of doses given in cycle 1 were important to the extent that they influenced the cumulative dose. C1 NCI,PEDIAT BRANCH,LYMPHONA BIOL SECT,NIH,BETHESDA,MD 20892. CHILDRENS NATL MED CTR,DEPT HEMATOL ONCOL,WASHINGTON,DC 20010. GEORGETOWN UNIV,DIV PEDIAT HEMATOL ONCOL,WASHINGTON,DC. PENN STATE UNIV,CHILDRENS HOSP,DIV HEMATOL ONCOL,HERSHEY,PA. MAYO CLIN & MAYO FDN,DEPT PEDIAT ADOLESCENT MED,ROCHESTER,MN 55905. RAINBOW BABIES & CHILDRENS HOSP,DIV HEMATOL & ONCOL,CLEVELAND,OH 44106. RI Venzon, David/B-3078-2008 NR 24 TC 34 Z9 34 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR PY 1996 VL 14 IS 3 BP 935 EP 940 PG 6 WC Oncology SC Oncology GA TZ732 UT WOS:A1996TZ73200031 PM 8622042 ER PT J AU Nayfield, SG Gorin, MB AF Nayfield, SG Gorin, MB TI Tamoxifen-associated eye disease: A review SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID HIGH-DOSE TAMOXIFEN; OCULAR MANIFESTATIONS; BREAST-CARCINOMA; RETINOPATHY; CANTHAXANTHIN; REGRESSION; METASTASES; TOXICITY; THERAPY; DOSAGE AB Purpose: The oral antiestrogen tamoxifen has demonstrated efficacy in the treatment of metastatic breast cancer and as adjuvant therapy in early-stage disease, Clinical trials of tamoxifen in chemoprevention of breast cancer among high-risk women have focused attention on potential adverse effects of long-term tamoxifen use, including the possibility of ocular toxicity. This review evaluates the published case reports, clinical series, and clinical trial data on ocular toxicities attributed to tamoxifen. Clinical issues of surveillance, differential diagnosis, and management of tamoxifen-related eye disease are discussed. Design: National Library of Medicine online bibliographic services were used to identify case reports and clinical studies of ocular adverse effects that occurred in patients receiving tamoxifen published through the fall of 1994. The medical literature relevant to issues raised by the reports and studies was similarly identified and reviewed. Results: Case reports and case series identify crystalline retinal deposits, macular edema, and corneal changes as potential tamoxifen ocular toxicities, Extensive retinal lesions and macular edema with visual impairment have been reported in a few patients receiving high-dose tamoxifen, Less extensive retinal changes may occur in patients receiving low doses for long periods, and isolated retinal crystals may be observed in patients without visual symptoms. Conclusion: Ocular toxicity is uncommon in the current clinical setting of long-term, low-dose tamoxifen use, Physicians should be aware of the potential for ocular toxicity among patients receiving the drug and should assure appropriate surveillance and prompt evaluation of visual complaints. C1 UNIV PITTSBURGH, SCH MED, DEPT OPHTHALMOL, PITTSBURGH, PA 15261 USA. RP Nayfield, SG (reprint author), NCI, DIV CANC PREVENT & CONTROL, CHEMOPREVENT BRANCH, EXECUT PLAZA N, ROOM 201A, BETHESDA, MD 20892 USA. NR 58 TC 85 Z9 87 U1 1 U2 6 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR PY 1996 VL 14 IS 3 BP 1018 EP 1026 PG 9 WC Oncology SC Oncology GA TZ732 UT WOS:A1996TZ73200042 PM 8622006 ER PT J AU Castellanos, FX Ritchie, GF Marsh, WL Rapoport, JL AF Castellanos, FX Ritchie, GF Marsh, WL Rapoport, JL TI DSM-IV stereotypic movement disorder: Persistence of stereotypies of infancy in intellectually normal adolescents and adults SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 147th Annual Meeting of the American-Psychiatric-Association CY MAY 21-26, 1994 CL PHILADELPHIA, PA SP Amer Psychiat Assoc ID OBSESSIVE-COMPULSIVE DISORDER; FLUOXETINE TREATMENT; AUTISTIC DISORDER; SELF-INJURY; CHILDREN; CLOMIPRAMINE; DESIPRAMINE; BEHAVIOR; ROCKING; HISTORY AB Background: As part of a broader series of studies on unwanted repetitive behaviors, DSM-IV stereotypic movement disorder (SMD) was examined in an intellectually normal population. Repetitive nonfunctional behaviors, or stereotypies, are expressed during early normal development but have not been described in adults without severe psychiatric or intellectual impairment. Method: Lifetime and current psychiatric Axis I diagnoses were determined by structured and clinical interviews in subjects who responded to a newspaper advertisement that specifically mentioned rocking and head banging. Results: Of 52 potential subjects who were screened by telephone, 32 had been previously diagnosed with an Axis I psychiatric disorder, which presumably accounted for the repetitive behavior, or were otherwise excluded. Of 20 who were interviewed in person, 12 met DSM-IV criteria for SMD; rocking or thumb sucking was present in 8 of these 12. Four of 8 rockers had a first-degree relative who had a lifetime history of a similar repetitive behavior. A lifetime history of an affective or anxiety disorder was found for 11 of 12 SMD subjects. Conclusion: DSM-IV stereotypic movement disorder can be diagnosed in intellectually normal individuals. Although sampling bias was probable, prominent stereotypies in individuals meeting the DSM-IV criteria for stereotypic movement disorder, which are narrower than the DSM-III-R criteria for stereotypy/habit disorder, seem Likely to include rocking and thumb sucking. The likelihood of persistence of these behaviors, which are developmentally appropriate in infancy, may be enhanced by comorbidity with anxiety or affective disorders. RP Castellanos, FX (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,ROOM 6N240,10 CTR DR,MSC 1600,BETHESDA,MD 20892, USA. NR 44 TC 45 Z9 45 U1 2 U2 6 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAR PY 1996 VL 57 IS 3 BP 116 EP 122 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA UA873 UT WOS:A1996UA87300005 PM 8617696 ER PT J AU Rajapakse, JC DeCarli, C McLaughlin, A Giedd, JN Krain, AL Hamburger, SD Rapoport, JL AF Rajapakse, JC DeCarli, C McLaughlin, A Giedd, JN Krain, AL Hamburger, SD Rapoport, JL TI Cerebral magnetic resonance image segmentation using data fusion SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE brain; magnetic resonance imaging; white matter; gray matter; cerebrospinal fluid; magnetic resonance imaging, physics and instrumentation ID CEREBROSPINAL-FLUID; TISSUE CLASSIFICATION; ANALYSIS SYSTEM; WHITE MATTER; BRAIN IMAGES; GRAY-MATTER; MR; VALIDATION; VOLUMES; MATURATION AB Objective: A semiautomated method is described for segmenting dual echo MR head scans into gray and white matter and CSF. The method is applied to brain scans of 80 healthy children and adolescents. Materials and Methods: A probabilistic data fusion equation was used to combine simultaneously acquired T2-weighted and proton density head scans for tissue segmentation. The fusion equation optimizes the probability of a voxel being a particular tissue type, given the corresponding probabilities from both images. The algorithm accounts for the intensity inhomogeneities present in the images by fusion of local regions of the images. Results: The method was validated using a phantom (agarose gel with iron oxide particles) and hand-segmented images. Gray and white matter volumes for subjects aged 20-30 years were close to those previously published. White matter and CSF volume increased and gray matter volume decreased significantly across ages 4-18 years. White matter, gray matter, and CSF volumes were larger for males than for females. Males and females showed similar change of gray and white matter volumes with age. Conclusion: This simple, reliable, and valid method can be employed in clinical research for quantification of gray and white matter and CSF volumes in MR head scans. Increase in white matter volume may reflect ongoing axonal growth and myelination, and gray matter reductions may reflect synaptic pruning or cell death in the age span of 4-18 years. C1 NEUROL DISORDERS & STROKES INST,EPILEPSY BRANCH,BETHESDA,MD. NIMH,NIH,CLIN BRAIN DISORDERS BRANCH,BETHESDA,MD 20892. RP Rajapakse, JC (reprint author), NIMH,CHILD PSYCHIAT BRANCH,BLDG 10,RM 6N240,10 CTR DR,MSC 1600,BETHESDA,MD 20982, USA. RI Giedd, Jay/A-3080-2008; DeCarli, Charles/B-5541-2009; Rajapakse, Jagath/B-8485-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Rajapakse, Jagath/0000-0001-7944-1658; Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 41 TC 31 Z9 31 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD MAR-APR PY 1996 VL 20 IS 2 BP 206 EP 218 DI 10.1097/00004728-199603000-00007 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UE246 UT WOS:A1996UE24600006 PM 8606224 ER PT J AU Lenardo, MJ AF Lenardo, MJ TI Fas and the art of lymphocyte maintenance SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID T-CELLS; APOPTOSIS; SUICIDE RP Lenardo, MJ (reprint author), NIAID,IMMUNOL LAB,NIH,BLDG 10,ROOM 11N311,10 CTR DR,MSC 1892,BETHESDA,MD 20892, USA. NR 31 TC 149 Z9 152 U1 1 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAR 1 PY 1996 VL 183 IS 3 BP 721 EP 724 DI 10.1084/jem.183.3.721 PG 4 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA UC775 UT WOS:A1996UC77500003 PM 8642275 ER PT J AU John, S Marais, R Child, R Light, Y Leonard, WJ AF John, S Marais, R Child, R Light, Y Leonard, WJ TI Importance of low affinity Elf-1 sites in the regulation of lymphoid-specific inducible gene expression SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID DNA-BINDING SPECIFICITIES; SERUM RESPONSE FACTOR; ETS-RELATED PROTEIN; TRANSCRIPTION FACTORS; ACTIVATION; ENHANCER; FAMILY; DOMAIN AB Elf-1 is an Ets family transcription factor that regulates a number of inducible lymphoid-specific genes, including those encoding interleukin 3 (IL-3), granulocyte/macrophage colony-stimulating factor (GM-CSF), and the IL-2 receptor (IL-2R) alpha chain. A minimal oligonucleotide spanning the IL-2R alpha Elf-1 site (-97/-84) bound Elf-1 poorly, but binding activity markedly increased when this oligonucleotide was multimerized or flanking sequences were added. This result is consistent with the requirement of accessory proteins for efficient Elf-1 binding, as has been demonstrated for the GM-CSF and IL-3 promoters. A binding site selection analysis revealed the optimal Elf-1 consensus motif to be A(A/t)(C/a)CCGGAAGT(A/S), which is similar to the consensus motif for the related Drosophila E74 protein. This minimal high affinity site could bind Elf-1 and functioned as a stronger transcription element than the -97/-84 IL-2R alpha oligonucleotide when cloned upstream of a heterologous promoter. In contrast, in the context of the IL-2R alpha promoter, conversion of the naturally occurring low affinity Elf-1 site to an optimal site decreased inducible activation of a reporter construct in Jurkat cells. This finding may be explained by the observation that another Ets family protein, ERGB/Fli-1, can efficiently bind only to the optimal site, and in this context, interferes with Elf-1 binding. Therefore, high affinity Elf-1 sites may lack sufficient binding specificity, whereas naturally occurring low affinity sites presumably favor the association of Elf-1 in the context of accessory proteins. These findings offer an explanation for the lack of optimal sites in any of the known Elf-1-regulated genes. C1 NHLBI,LAB MOL IMMUNOL,NIH,BETHESDA,MD 20892. INST CANC RES,CHESTER BEATTY LABS,CANC RES CAMPAIGN,CTR CELL & MOL BIOL,LONDON SW3 6JB,ENGLAND. NR 30 TC 30 Z9 30 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAR 1 PY 1996 VL 183 IS 3 BP 743 EP 750 DI 10.1084/jem.183.3.743 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA UC775 UT WOS:A1996UC77500006 PM 8642278 ER PT J AU Takahashi, H Nakagawa, Y Leggatt, GR Ishida, Y Saito, T Yokomuro, K Berzofsky, JA AF Takahashi, H Nakagawa, Y Leggatt, GR Ishida, Y Saito, T Yokomuro, K Berzofsky, JA TI Inactivation of human immunodeficiency virus (HIV)-1 envelope-specific CD8(+) cytotoxic T lymphocytes by free antigenic peptide: A self-veto mechanism? SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CLASS-I MHC; CYTOLYTIC LYMPHOCYTES; MONOCLONAL-ANTIBODIES; CELL RECEPTOR; COGNATE PEPTIDES; HLA MOLECULES; H-2D ANTIGENS; RECOGNITION; INDUCTION; EXPRESSION AB Free peptide has been found to inhibit cytotoxic T lymphocyte (CTL) activity, and veto cells bearing peptide-major histocompatibility complex (MHC) complexes have been found to inactivate CTL, but the two phenomena have not been connected. Here we show that a common mechanism may apply to both. CD8(+) CTL lines or clones specific for a determinant of the human immunodeficiency virus (HIV) 1 IIIB envelope protein gp160, P18IIIB, are inhibited by as little as 10 min exposure to the minimal 10-mer peptide, I-10, within P18IIIB, free in solution, in contrast to peptide already bound to antigen-presenting cells (APC), which does not inhibit. Several lines of evidence suggest that the peptide must be processed and presented by H-2D(d) on the CTL itself to the specific T cell receptor (TCR) to be inhibitory. The inhibition was not killing, in that CTL did not kill Cr-51-labeled sister CTL in the presence of free peptide, and in mixing experiments with CTL lines of different specificities restricted by the same MHC molecule, D-d, the presence of free peptide recognized by one CTL line did not inhibit the activity of the other CTL line that could present the peptide. Also, partial recovery of activity could be elicited by restimulation with cell-bound peptide, supporting the conclusion that neither fratricide nor suicide (apoptosis) was involved. The classic veto phenomenon was ruled out by failure of peptide-bearing CTL to inactivate others. Using pairs of CTL lines of differing specificity but similar MHC restriction, each pulsed with the peptide for which the other is specific, we showed that the minimal requirement is simultaneous engagement of the TCR and class I MHC molecules of the same cell. This could occur in single cells or pairs of cells presenting peptide to each other. Thus, mechanistically the inhibition is analogous to veto, and might be called self-veto. As a clue to a possible mechanism, we found that free I-10 peptide induced apparent downregulation of expression of specific TCR as well as interleukin 2 receptor, CD69, lymphocyte function-associated antigen 1, and CD8. This self-veto effect also has implications for in vivo immunization and mechanisms of viral escape from CTL immunity. C1 NCI,MOLEC IMMUNOGENET & VACCINE RES SECT,METAB BRANCH,NIH,BETHESDA,MD 20892. CHIBA UNIV,SCH MED,CTR BIOMED SCI,DIV MOLEC GENET,CHIBA 280,JAPAN. RP Takahashi, H (reprint author), NIPPON MED COLL,DEPT MICROBIOL & IMMUNOL,BUNKYO KU,1-1-5 SENDAGI,TOKYO 113,JAPAN. RI Leggatt, Graham/G-1924-2010; Saito, Takashi/C-9684-2009; OI Saito, Takashi/0000-0001-9495-3547; Leggatt, Graham/0000-0002-4078-5653 NR 50 TC 47 Z9 47 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAR 1 PY 1996 VL 183 IS 3 BP 879 EP 889 DI 10.1084/jem.183.3.879 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA UC775 UT WOS:A1996UC77500020 PM 8642292 ER PT J AU Stuber, E Strober, W AF Stuber, E Strober, W TI The T cell B cell interaction via OX40-OX40L is necessary for the T cell-dependent humoral immune response SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID ANTIBODY-FORMING-CELLS; X-LINKED IMMUNODEFICIENCY; HYPER-IGM SYNDROME; CD40 LIGAND; EXPRESSION; ACTIVATION; SITES; LYMPHOCYTES; ANTIGENS; MOLECULE AB Recent in vitro studies have established that activated B cells express OX40 ligand (L), a member of the tumor necrosis factor/nerve growth factor family of cytokines, and become stimulated to proliferate and secrete immunoglobulin (Ig) after cross-linking of OX40L by its counterreceptor OX40, which is expressed on activated T cells. In the present study we investigated the in vivo role of this receptor-ligand pair for the interaction of T and B cells in the course of the T-dependent B cell response against 2,4,6 trinitro-phenyl-keyhole limpet hemocyanin. First, we showed that OX40 is maximally expressed by T cells in the periarteriolar lymphoid sheath (PALS) 3 d after primary immunization. These OX40(+) cells are located in close proximity to antigen-specific, activated B cells. Second, we demonstrated that blocking of OX40-OX40L interaction with a polyclonal anti-OX40 antibody or with antibodies against certain peptide sequences within its extracellular domain resulted in a profound decrease of the antihapten IgG response, whereas the antihapten IgM, response was grossly unchanged. Third, we showed that this antibody treatment leads to an inhibition of the development of PALS-associated B cell foci, whereas the formation of germinal centers remained intact. Finally, our data suggest that, whereas B cell memory development was not impaired by anti-OX40 administration, OX40-OX40L interaction seems to be crucial in the secondary immune response. We conclude from these data that the OX40-OX40L interaction in vivo is necessary for the differentiation of activated B cells into highly Ig-producing cells, but is not involved in other pathways of antigen-driven B cell differentiation such as memory cell development in the germinal centers. C1 NIH,CLIN INVEST LAB,MUCOSAL IMMUN SECT,BETHESDA,MD 20892. NR 36 TC 207 Z9 212 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAR 1 PY 1996 VL 183 IS 3 BP 979 EP 989 DI 10.1084/jem.183.3.979 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA UC775 UT WOS:A1996UC77500029 PM 8642301 ER PT J AU Wang, RF Parkhurst, MR Kawakami, Y Robbins, PF Rosenberg, SA AF Wang, RF Parkhurst, MR Kawakami, Y Robbins, PF Rosenberg, SA TI Utilization of an alternative open reading frame of a normal gene in generating a novel human cancer antigen SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; MESSENGER-RNA; HUMAN-MELANOMA; TRANSLATION; PROTEIN; MELANOCYTES; VIRUS; INTERLEUKIN-2; IMMUNOTHERAPY; TRANSCRIPTION AB Tumor infiltrating lymphocytes (TILs) derived from tumor-bearing patients recognize tumor-associated antigens presented by major histocompatibility complex (MHC) class I molecules. The infusion of TIL586 along with interleukin (IL) 2 into an autologous patient with metastatic melanoma resulted in the objective regression of tumor. A gene encoding a tumor anti-recognized by TIL586 was recently isolated and shown to encode gp75. Here we report that an antigenic peptide, MSLQRQFLR, recognized by TIL586 was not derived from the normal gp75 protein. Instead, this nonamer peptide resulted from translation of an alternative open reading frame of the same gene. Thus, the gp75 gene encodes two completely different polypeptides, gp75 as an antigen recognized by immunoglobulin G antibodies in sera from a patient with cancer, and a 24-amino acid product as a tumor rejection antigen recognized by T cells. This represents the first demonstration that a human tumor rejection antigen can be generated from a normal cellular gene using an open reading frame other than that used to encode the normal protein. These findings revealed a novel mechanism for generating tumor antigens, which may be useful as vaccines to induce tumor-specific cell-mediated immunity against cancer. C1 NCI,SURG BRANCH,NIH,BETHESDA,MD 20892. RI Kawakami, Yutaka /E-7429-2013 OI Kawakami, Yutaka /0000-0003-4836-2855 NR 41 TC 183 Z9 184 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAR 1 PY 1996 VL 183 IS 3 BP 1131 EP 1140 DI 10.1084/jem.183.3.1131 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA UC775 UT WOS:A1996UC77500045 PM 8642255 ER PT J AU Robbins, PF ElGamil, M Li, YF Kawakami, Y Loftus, D Appella, E Rosenberg, SA AF Robbins, PF ElGamil, M Li, YF Kawakami, Y Loftus, D Appella, E Rosenberg, SA TI A mutated beta-catenin gene encodes a melanoma-specific antigen recognized by tumor infiltrating lymphocytes SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID PEPTIDE; CANCER; CELLS AB A number of antigens recognized by tumor-reactive T cells have recently been identified. The antigens identified in mouse model systems appear, with one exception, to represent the products of mutated genes. In contrast, most of the antigens recognized by human tumor-reactive T cells reported to date appear to represent the products of non-mutated genes. Here we report the isolation of a cDNA clone encoding beta-catenin, which was shown to be recognized by the tumor-infiltrating lymphocyte (TIL) 1290, a HLA-A24 restricted melanoma-specific CTL line from patient 888. The cDNA clone, which was isolated from the autologous melanoma cDNA library, differed by a single base pair from the published beta-catenin sequence, resulting in a change from a serine to a phenylalanine residue at position 37. Normal tissues from this patient did not express the altered sequence, nor did 12 allogeneic melanomas, indicating that this represented a unique mutation in this patient's melanoma. A peptide corresponding to the sequence between amino acids 29 and 37 of the mutant gene product was identified as the T cell epitope recognized by TIL 1290. The observation that HLA-A24 binding peptides contain an aromatic or hydrophobic residue at position 9 suggested that the change at position 37 may have generated a peptide (SYLDSGIHF) which was capable of binding to HLA-A24, and a competitive binding assay confirmed this hypothesis. The beta-catenin protein has been shown previously to be involved in cell adhesion mediated through the cadherin family of cell surface adhesion molecules. The high frequency of mutations found in members of cellular adhesion complexes in a variety of cancers suggests that these molecules may play a role in development of the malignant phenotype. C1 NCI,NIH,CELL BIOL LAB,BETHESDA,MD 20892. RP Robbins, PF (reprint author), NCI,NIH,SURG BRANCH,BLDG 10 RM 2B42,BETHESDA,MD 20892, USA. RI Kawakami, Yutaka /E-7429-2013 OI Kawakami, Yutaka /0000-0003-4836-2855 NR 28 TC 384 Z9 387 U1 0 U2 6 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAR 1 PY 1996 VL 183 IS 3 BP 1185 EP 1192 DI 10.1084/jem.183.3.1185 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA UC775 UT WOS:A1996UC77500050 PM 8642260 ER PT J AU Angus, CW Tu, A Vogel, P Qin, M Kovacs, JA AF Angus, CW Tu, A Vogel, P Qin, M Kovacs, JA TI Expression of variants of the major surface glycoprotein of Pneumocystis carinii SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID ANTIGEN; PURIFICATION; ATTACHMENT; PNEUMONIA; PROTEIN; CELLS AB Previously, we have shown that a multicopy family of related but unique genes encodes the major surface glycoprotein (MSG) of Pneumocystis carinii. To examine whether different members of this gene family are expressed by P. carinii, antisera were prepared against peptides whose sequences were determined from the deduced amino acid sequences of variants of rat-derived MSG. Immunohistochemical staining of serial sections of rat lungs of infected infected animals showed that at least three variants of MSG were expressed in an individual lobe, that there was a focal expression of these variants within the lung, and that the relative numbers of these foci were different. Indirect immunofluorescent staining of purified P. carinii organisms using these antisera revealed that at least three variants of MSG were present in organisms isolated from an individual rat and that both cysts and trophozoites reacted with each antiserum. A substantial difference in the fraction of organisms reacting with a specific antipeptide antiserum was seen when comparing organisms isolated from rats raised in a single colony over a period of two years as well as organisms isolated at one time point from rats raised in different colonies. This demonstration of antigenic variation in P. carinii supports the hypothesis that P. carinii utilizes such variation for evading host defense mechanisms. C1 USA,MED RES INST INFECT DIS,DIV PATHOL,FREDERICK,MD 21702. RP Angus, CW (reprint author), NIH,DEPT CRIT CARE MED,CTR CLIN,BLDG 10,ROOM 7D43,MSC 1662,BETHESDA,MD 20892, USA. NR 27 TC 42 Z9 42 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAR 1 PY 1996 VL 183 IS 3 BP 1229 EP 1234 DI 10.1084/jem.183.3.1229 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA UC775 UT WOS:A1996UC77500054 PM 8642264 ER PT J AU Goping, G Kuijpers, GAJ Vinet, R Pollard, HB AF Goping, G Kuijpers, GAJ Vinet, R Pollard, HB TI Comparison of LR White and Unicryl as embedding media for light and electron immunomicroscopy of chromaffin cells SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE LR White; Unicryl; postembedding; immunocytochemistry; chromaffin cells ID TYROSINE-HYDROXYLASE; SECRETORY GRANULES; ADRENAL-MEDULLA; MICROSCOPY AB LR White and Unicryl are members of the same family of acrylic embedding resins and are very suitable for ''on grid'' postembedding immunogold labeling, We studied the ultrastructure of LR White- and Unicryl-embedded cultured chromaffin cells and the immunolocalization of three chromaffin cell proteins, the enzymes dopamine-P-hydroxylase (DPH) and tyrosine hydroxylase (TH), and the membrane fusion and Ca2+ channel protein synexin (annexin VII). We report here that Unicryl is preferable to LR White as an embedding medium for electron microscopy when osmium tetroxide fixation is omitted, The basis for this distinction is better ultrastructural preservation and improved immunodetection efficiency. C1 NIDDKD,NIH,CELL BIOL & GENET LAB,BETHESDA,MD 20892. NR 20 TC 13 Z9 13 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 MAR PY 1996 VL 44 IS 3 BP 289 EP 295 PG 7 WC Cell Biology SC Cell Biology GA TY743 UT WOS:A1996TY74300012 PM 8648090 ER PT J AU Fleury, S Huang, B Zerbib, A Croteau, G Long, EO Sekaly, RP AF Fleury, S Huang, B Zerbib, A Croteau, G Long, EO Sekaly, RP TI Mutations in human CD4 impair the functional interaction with different human and mouse class II isotypes and alleles SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL HYBRIDOMA; HISTOCOMPATIBILITY COMPLEX-MOLECULES; MHC CLASS; STRUCTURAL-ANALYSIS; ENVELOPE GLYCOPROTEIN; CRYSTAL-STRUCTURE; BINDING-SITE; HIV; IDENTIFICATION; RESIDUES AB The structure-function of the CD4-class II MHC interaction was investigated, Two functional assays were used to assess the responses of the 3DT52,5,8 murine T cell hybridoma expressing human CD4 (h-CD4) or murine CD4 (m-CD4), First, we determined the responses of the CD4(+) and CD4(-) effector cells toward DAP-3 cells co-expressing the cognate alloantigen H-2D(d) together with several human (DRw52b, DR4-Dw4, DR2A, and DPw2) and murine (I-A(b), I-A(k), I-A alpha(b)I-A beta(k) and I-E(k)) class II alleles and isotypes, We found that h-CD4 and m-CD4 strongly enhance the T cell response to H-2D(d), demonstrating that interspecies CD4/class II interactions occur efficiently, Furthermore, mutations in h-CD4 at positions 19, 89, and 165 markedly reduced the interaction with both human class II and mouse class II, indicating that the structural features of this cross-species interaction are strongly conserved, This was further supported by the finding that a h-CD4 deletion mutant (deletion F43-S49) interacted with both human and murine class II, Moreover, as 3DT cells express the responsive V beta element for the bacterial superantigen staphylococcal enterotoxin 8, a co-receptor assay was conducted, DAP-3 cells expressing only class II molecules were used as APCs to present staphylococcal enterotoxin B to h-CD4(+) and m-CD4(+) T cells, h-CD4 and m-CD4 were able to enhance the T cell response to staphylococcal enterotoxin B, further demonstrating the conservation of the CD4-class ii MHC interaction. C1 CLIN RES INST MONTREAL,IMMUNOL LAB,MONTREAL,PQ H2W 1R7,CANADA. UNIV MONTREAL,DEPT MICROBIOL & IMMUNOL,MONTREAL,PQ H3C 3J7,CANADA. MCGILL UNIV,DEPT EXPTL MED,MONTREAL,PQ,CANADA. UNIV TOULOUSE 3,F-31062 TOULOUSE,FRANCE. NIAID,IMMUNOGENET LAB,NIH,ROCKVILLE,MD 20852. RI Long, Eric/G-5475-2011 OI Long, Eric/0000-0002-7793-3728 NR 51 TC 10 Z9 10 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 1996 VL 156 IS 5 BP 1848 EP 1855 PG 8 WC Immunology SC Immunology GA TW699 UT WOS:A1996TW69900020 PM 8596036 ER PT J AU Crowley, RW Secchiero, P Zella, D Cara, A Gallo, RC Lusso, P AF Crowley, RW Secchiero, P Zella, D Cara, A Gallo, RC Lusso, P TI Interference between human herpesvirus 7 and HIV-1 in mononuclear phagocytes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CENTRAL NERVOUS-SYSTEM; LYMPHOTROPIC VIRUS; T-CELLS; INFECTION; TROPISM; MACROPHAGES; CHILDREN; ADULTS AB Human herpesvirus 7 (HHV-7) uses CD4 as a cellular membrane receptor and thereby interferes with infection of CD4(+) T cells by HIV-1, We studied the interactions between HHV-7 and a macrophage-tropic HIV-1 isolate (HIV-1(BAL)) in terminally differentiated human peripheral blood monocyte-derived macrophages, another critical target for infection by HIV-1 in vivo, Exposure of macrophages to HHV-7 alone yielded no signs of virus replication or cytopathic effects, Nevertheless, when macrophages were pre-exposed to either live or UV-inactivated HHV-7 and Subsequently infected with HIV-1(BAL), a significant dose-dependent inhibition of HIV-1 replication was documented, At day 7 postinfection, the average level of HIV-1 p24 Ag in cultures from five different donors was reduced by 91.7 +/- 8.3% by pretreatment with live HHV-7 and by 91.8 +/- 8.2% by pretreatment with UV-inactivated HHV-7, Moreover, the synthesis of HIV-1 proviral DNA in macrophages pretreated with HHV-7 was completely inhibited during the early stages after infection, suggesting that HHV-7 blocks HIV-1 at the level of interaction with the CD4 receptor, Consistent with this concept, both macrophage and CD4+ T cell cultures with pre-established HIV-1 infection were not susceptible to inhibitory effects of HHV-7. The proliferative response of PBMC to mitogens was only marginally inhibited by exposure to HHV-7 before mitogen stimulation, indicating that the inhibition of HIV-1 infection was not due to a negative effect on cell proliferation, These data demonstrate that HHV-7 is a powerful inhibitor of HIV-1 infection in cells of the mononuclear phagocytic lineage, despite its inability to replicate actively in such cells. RP Crowley, RW (reprint author), NCI,TUMOR CELL BIOL LAB,NIH,BLDG 37,ROOM 6A11,37 CONVENT DR,BETHESDA,MD 20892, USA. RI secchiero, paola/G-9689-2015; Cara, Andrea/M-4865-2015 OI secchiero, paola/0000-0003-4101-7987; Cara, Andrea/0000-0003-4967-1895 NR 32 TC 29 Z9 30 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 MAR 1 PY 1996 VL 156 IS 5 BP 2004 EP 2008 PG 5 WC Immunology SC Immunology GA TW699 UT WOS:A1996TW69900040 PM 8596056 ER PT J AU Neville, DM Scharff, J Hu, HZ Rigaut, K Shiloach, J Slingerland, W Jonker, M AF Neville, DM Scharff, J Hu, HZ Rigaut, K Shiloach, J Slingerland, W Jonker, M TI A new reagent for the induction of T-cell depletion, anti-CD3-CRM9 SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE immunotoxin; TCR; CD3 epsilon; rhesus; transplantation; autoimmune ID BONE-MARROW TRANSPLANTATION; RHESUS-MONKEY LYMPHOCYTES; PHASE-I TRIAL; DIPHTHERIA-TOXIN; MONOCLONAL-ANTIBODY; DIFFERENTIATION ANTIGENS; ALLOGRAFT SURVIVAL; CD3; REGENERATION; MUTATIONS AB We have developed a new reagent for inducing in vivo T-cell depletion and have tested this reagent in rhesus monkeys. The reagent is an anti-CDSE immunotoxin based on a diphtheria toxin binding-site mutant, CRM9. After administration to monkeys, T cells are depleted from both the blood and lymph node compartments to <1% of their initial values. T-cell depletion is associated with transient immunosuppression, as judged by delayed rejection of RhLA-mismatched skin allografts. T cells are repopulated in both compartments; however, the rate of repopulation is age dependent. The rate is rapid in juvenile animals (12 days) and requires >30 days in old animals. The correlation between repopulation rate and age suggests that the repopulation is thymus dependent and that the repopulated T cells are probably naive T cells. This reagent should be a valuable tool in studying the role of memory T cells in rhesus models of autoimmune diseases and protocols of tolerance induction after organ transplantation. C1 NIDDK,BIOTECHNOL UNIT,CELLULAR & DEV BIOL LAB,NIH,BETHESDA,MD. BIOMED PRIMATE RES CTR,RIJSWIJK,NETHERLANDS. RP Neville, DM (reprint author), NIMH,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 37 TC 70 Z9 70 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD MAR PY 1996 VL 19 IS 2 BP 85 EP 92 DI 10.1097/00002371-199603000-00001 PG 8 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA UH707 UT WOS:A1996UH70700001 PM 8732691 ER PT J AU Funakoshi, S Longo, DL Murphy, WJ AF Funakoshi, S Longo, DL Murphy, WJ TI Differential in vitro and in vivo antitumor effects mediated by anti-CD40 and anti-CD20 monoclonal antibodies against human B-cell lymphomas SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE anti-CD40; B lymphoma; anti-CD20; human/mouse; immunotherapy ID SEVERE COMBINED IMMUNODEFICIENCY; TUMOR-GROWTH; MICE; CD40; ACTIVATION; INHIBITION AB The antitumor effects of CD40 and CD20 monoclonal antibodies (mAbs) were compared on various human B-cell lymphomas by using both in vitro and in vivo assays. Anti-CD40 directly inhibited the proliferation of human B-cell lymphomas in vitro, whereas anti-CD20 exerted no inhibitory effects on the growth of any lymphoma tested. These lymphomas were then injected into immunodeficient mice to examine the antitumor efficacy of these unconjugated mAbs in vivo. This xenogeneic model was used in the evaluation of various potential therapeutic agents against human cancers in an in vivo setting. Surprisingly, in contras to its negligible effects on lymphoma growth in vitro, anti-CD20 was more efficacious than anti-CD40 in promoting the survival of mice bearing some but not all lymphoma lines. To determine whether the antitumor effects of these mAbs were direct or indirect in vivo, we concurrently treated tumor-bearing mice with mAbs to the murine Fc receptor to block antibody-dependent cell-mediated cytotoxicity (ADCC), When these neutralizing antibodies against Fc receptors were administered at the same time as mAb treatment, the antitumor effects of anti-CD20 in vivo were completely abrogated, whereas anti-CD40 treatment, although also diminished, still provided significant antitumor effects, These results indicate that the in vivo antitumor activity of the murine anti-human CD20 mAb was primarily due to ADCC by murine effector cells, which may not translate into comparable effects in humans. By contrast, anti-CD40 may be of potential clinical use in the treatment of lymphomas in humans because of its additional direct antiproliferative effects. The results also demonstrate a possible difficulty in accurately evaluating the potential clinical efficacy of murine antibodies against human tumors in a human/mouse model system. Murine monoclonal antihuman antibodies may produce greater effects in human/mouse xenogeneic models, in which they are more likely to elicit host effector systems than when used in vivo in humans. C1 NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,LEUKOCYTE BIOL LAB,FREDERICK,MD 21702. NR 18 TC 37 Z9 37 U1 0 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD MAR PY 1996 VL 19 IS 2 BP 93 EP 101 DI 10.1097/00002371-199603000-00002 PG 9 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA UH707 UT WOS:A1996UH70700002 PM 8732692 ER PT J AU Curti, BD Urba, WJ Longo, DL Janik, JE Sharfman, WH Miller, LL Cizza, G Shimizu, M Oppenheim, JJ Alvord, WG Smith, JW AF Curti, BD Urba, WJ Longo, DL Janik, JE Sharfman, WH Miller, LL Cizza, G Shimizu, M Oppenheim, JJ Alvord, WG Smith, JW TI Endocrine effects of IL-1 alpha and beta administered in a phase I trial to patients with advanced cancer SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE interleukin-1; cortisol; testosterone; pituitary hormones ID TUMOR-NECROSIS-FACTOR; INTERLEUKIN-1; RELEASE; HORMONE; HYPOTHALAMUS; PITUITARY; PLASMA; CELLS; MICE; RATS AB Previous primate and rodent studies suggested that interleukin-1 alpha (IL-1 alpha) caused changes in the secretion of pituitary, adrenal, thyroid, and gonadal hormones, as well as acute-phase reactants. Plasma samples were obtained after IL-1 alpha and beta treatment in cancer patients to document the changes in endocrine function suggested by the animal models. Successive groups of patients were treated at IL-1 alpha doses of 0.01, 0.03, 0.1, 0.3, and 1.0 mu g/kg, given daily as a 15-min intravenous bolus. IL-1 beta was given at 0.1 mu g/kg by the same route and time course. After the first dose of IL-1, statistically significant elevations of a.m. and p.m. cortisol, growth hormone (GH), and prolactin (PRL) occurred. Thyroid-stimulating hormone (TSH) and C-reactive protein (CRP) were elevated by the sixth treatment day. Testosterone decreased significantly in male patients. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were more variable but decreased in most patients. The changes in cortisol, GH, PRL, TSH, CRP, FSH, LH, and testosterone resolved after treatment and did not result in clinically apparent endocrinopathies. Bolus doses of IL-1 alpha and beta cause significant changes in many endocrine laboratory parameters and influence the in vivo activities of multiple homeostatic endocrine functions in human beings. C1 FREDERICK MEM HOSP,FREDERICK,MD. PROVIDENCE MED CTR,EARLE CHILES RES INST,PORTLAND,OR. NCI,DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM,INVEST DRUG BRANCH,BETHESDA,MD 20892. NIMH,NIH,BETHESDA,MD 20892. DAINIPPON PHARMACEUT CO LTD,OSAKA,JAPAN. NCI,FREDERICK CANC RES & DEV CTR,DATA MANAGEMENT SERV,FREDERICK,MD. RP Curti, BD (reprint author), NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAMME,501 W 7TH ST,SUITE 3,FREDERICK,MD 21701, USA. FU NCI NIH HHS [N01-CO-74102] NR 27 TC 17 Z9 17 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD MAR PY 1996 VL 19 IS 2 BP 142 EP 148 DI 10.1097/00002371-199603000-00007 PG 7 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA UH707 UT WOS:A1996UH70700007 PM 8732697 ER PT J AU Emerson, SU Tsarev, SA Govindarajan, S Shapiro, M Purcell, RH AF Emerson, SU Tsarev, SA Govindarajan, S Shapiro, M Purcell, RH TI A simian strain of hepatitis a virus, AGM-27, functions as an attenuated vaccine for chimpanzees SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID A VIRUS; CELL-CULTURE; GROWTH; SITE AB The AGM-27 strain of hepatitis A virus (HAV) was originally isolated from an African green monkey with hepatitis and appears to represent a true simian strain, The virus caused acute hepatitis after intravenous inoculation into African green monkeys, rhesus monkeys, and marmosets. Cynomolgus monkeys inoculated with the virus did not develop hepatitis, probably because of prior exposure to HAV. Chimpanzees inoculated with a high dose of the virus did not develop signs of hepatitis, although the virus replicated and the animals seroconverted. Marmosets and chimpanzees convalescent from infection with the AGM-27 strain of HAV were rechallenged with the virulent HM-175 strain of human HAV. They were partially or totally protected from disease. C1 BIOQUAL INC,GAITHERSBURG,MD. RANCHO LOS AMIGOS MED CTR,CLIN LAB,DOWNEY,CA. RANCHO LOS AMIGOS MED CTR,PATHOL LAB,DOWNEY,CA. RP Emerson, SU (reprint author), NIAID,NIH,LID,HEPATITIS VIRUSES SECT,BLDG 7,ROOM 209,7 CTR DR MSC-0740,BETHESDA,MD 20892, USA. FU NIAID NIH HHS [AI-05069] NR 16 TC 14 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 MAR PY 1996 VL 173 IS 3 BP 592 EP 597 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA TW806 UT WOS:A1996TW80600011 PM 8627022 ER PT J AU Rattray, C Strickler, HD Escoffery, C Cranston, B Brown, C Manns, A Schiffman, MH Palefsky, JM Hanchard, B Blattner, WA AF Rattray, C Strickler, HD Escoffery, C Cranston, B Brown, C Manns, A Schiffman, MH Palefsky, JM Hanchard, B Blattner, WA TI Type-specific prevalence of human papillomavirus DNA among Jamaican colposcopy patients SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID CERVICAL INTRAEPITHELIAL NEOPLASIA; INFECTION; CANCER; AFRICA AB Human papillomavirus (HPV) types differ in their association with cervical cancer. Therefore, the types of HPV in precancerous lesions are important. In many regions with high cancer incidence, the HPV types in precancerous lesions have not been well studied. In Jamaica, a country that has high cervical cancer incidence, 174 colposcopy patients were tested for HPV DNA using polymerase chain reaction. HPV DNA detection was strongly related to presence and grade of cervical neoplasia (P < .001). Furthermore, severe neoplastic change was most highly associated with HPV DNA types also considered high-risk for severe neoplasia in other populations, HPV-45 DNA, a high-risk type uncommon in most previously tested countries, was detected in 12% of patients who had neoplasia. Thus, cervical neoplasia in Jamaica, as elsewhere, is linked to HPV, The high prevalence of HPV-45 DNA was notable, and its relation to high cervical cancer incidence in Jamaica must be assessed. C1 NCI,NIH,VIRAL EPIDEMIOL BRANCH,EPN 434,BETHESDA,MD 20892. UNIV HOSP W INDIES,DEPT OBSTET GYNECOL,KINGSTON,JAMAICA. UNIV HOSP W INDIES,DEPT PATHOL,KINGSTON,JAMAICA. NCI,NIH,ENVIRONM EPIDEMIOL BRANCH,BETHESDA,MD. UNIV CALIF SAN FRANCISCO,DEPT LAB MED,SAN FRANCISCO,CA 94143. NR 15 TC 9 Z9 9 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 MAR PY 1996 VL 173 IS 3 BP 718 EP 721 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA TW806 UT WOS:A1996TW80600027 PM 8627038 ER PT J AU Simpson, RM Leno, M Hubbard, BS Kindt, TJ AF Simpson, RM Leno, M Hubbard, BS Kindt, TJ TI Cutaneous manifestations of human T cell leukemia virus type I infection in an experimental model SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID RETROVIRUS; DISEASE; LINES AB Skin diseases ranging from infective dermatitis to cutaneous lymphoma have been associated with human T cell leukemia virus (HTLV) type I, A generalized exfoliative papillated dermatopathy occurred in a rabbit 20 months into a course of chronic HTLV-I infection, Biopsies revealed epidermotropic T cell infiltrates, including Sezary-like cells, that resulted in a pattern mimicking cutaneous T cell lymphoma. HTLV-I was isolated from affected skin, and virus expression was detected in cutaneous cultures. Sezary-like cells also occurred in circulation, Interleukin-2-independent lymphocyte cultures, established from blood exhibiting elevated CD8 T cell levels and CD25 expression, had polyclonal integration of provirus. The findings are similar to those in evolving adult T cell leukemia lymphoma and may represent a prelymphomatous change. The cutaneous lymphoproliferative lesion resulted from HTLV-I infection and further establishes the New Zealand White rabbit inoculated with the RH/K34 T cell line as a suitable model for investigation of HTLV-I pathogenesis. RP Simpson, RM (reprint author), NIAID,NIH,IMMUNOGENET LAB,TWINBROOK 2 FACIL,12441 PARKLAWN DR,ROCKVILLE,MD 20852, USA. NR 17 TC 20 Z9 20 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 MAR PY 1996 VL 173 IS 3 BP 722 EP 726 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA TW806 UT WOS:A1996TW80600028 PM 8627039 ER PT J AU Egan, AF Morris, J Barnish, G Allen, S Greenwood, BM Kaslow, DC Holder, AA Riley, EM AF Egan, AF Morris, J Barnish, G Allen, S Greenwood, BM Kaslow, DC Holder, AA Riley, EM TI Clinical immunity to Plasmodium falciparum malaria is associated with serum antibodies to the 19-kDa C-terminal fragment of the merozoite surface antigen, PfMSP-1 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID WEST-AFRICA; MORBIDITY; PROTEIN; RECOGNITION; INVASION; CHILDREN; MONKEYS AB The development of an effective malaria vaccine depends upon identification of antigens that are targets of protective immune responses, An immunoepidemiologic approach has been used to investigate the relationship between antibody responses to a defined region of the major merozoite surface protein of Plasmodium falciparum (PfMSP-1(19)) and resistance to clinical malaria in 2 populations of children from West Africa, After allowing for the confounding effects of age, antibodies to PfMSP-1(19) were shown to provide similar to 40% protection against clinical malaria in children in Sierra Leone, In Gambian children, antibodies to one of the epidermal growth factor-like motifs of PfMSP-1(19) were strongly associated with resistance to both clinical malaria and high levels of parasitemia. C1 UNIV EDINBURGH,INST CELL ANIM & POPULAT BIOL,DIV BIOL SCI,EDINBURGH EH9 3JT,MIDLOTHIAN,SCOTLAND. LONDON SCH HYG & TROP MED,LONDON WC1,ENGLAND. NATL INST MED RES,LONDON NW7 1AA,ENGLAND. MRC LABS,BO,SIERRA LEONE. MRC LABS,FAJARA,GAMBIA. NIH,MALARIA RES LAB,BETHESDA,MD 20892. RI Holder, Anthony/A-7554-2013 OI Holder, Anthony/0000-0002-8490-6058 FU Medical Research Council [MC_U117532067]; Wellcome Trust NR 15 TC 248 Z9 252 U1 1 U2 5 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 MAR PY 1996 VL 173 IS 3 BP 765 EP 769 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA TW806 UT WOS:A1996TW80600039 PM 8627050 ER PT J AU Mahanty, S Mollis, SN Ravichandran, M Abrams, JS Kumaraswami, V Jayaraman, K Ottesen, EA Nutman, TB AF Mahanty, S Mollis, SN Ravichandran, M Abrams, JS Kumaraswami, V Jayaraman, K Ottesen, EA Nutman, TB TI High levels of spontaneous and parasite antigen-driven interleukin-10 production are associated with antigen-specific hyporesponsiveness in human lymphatic filariasis SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID INFECTIONS; IL-10 AB To determine whether counterregulation by interleukin (IL)-10 plays a role in the generation or maintenance of the antigen-specific hyporesponsiveness seen in asymptomatic microfilaremic (MF) patients, parasite antigen (PAg)- and nonparasite antigen (NPAg)-driven IL-10 production by peripheral blood mononuclear cells (PBMC) was studied in 10 MF patients and in 11 patients with chronic lymphatic pathology (CP), PBMC from MF patients spontaneously secreted similar to 10-fold more IL-10 than did PBMC from patients with CP, PAg also induced significantly more IL-10 production by PBMC from MF than from CP patients, There was a negative correlation between PAg-driven IL-10 production by PBMC and PAg-specific T cell proliferation in the MF group. IL-10 secretion by plastic adherent cells from MF persons was higher in response to PAg than to NPAg, whereas IL-6 and tumor necrosis factor-alpha secretion were equivalent for PAg and NPAg, suggesting that PAg preferentially induces IL-10 secretion in these cells, Thus, PAg-induced IL-10 likely plays an important role in down-regulating antigen-specific proliferative responses in MF patients. C1 ANNA UNIV,CTR BIOTECHNOL,MADRAS 600025,TAMIL NADU,INDIA. TB RES CTR,MADRAS,TAMIL NADU,INDIA. DNAX RES INST MOLEC & CELLULAR BIOL INC,DEPT IMMUNOL,PALO ALTO,CA 94304. RP Mahanty, S (reprint author), NIAID,NIH,PARASIT DIS LAB,CLIN PARASITOL SECT,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. RI Ravichandran, Manickam/A-7128-2011; OI Mahanty, Siddhartha/0000-0003-1068-0524 NR 12 TC 121 Z9 121 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAR PY 1996 VL 173 IS 3 BP 769 EP 773 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA TW806 UT WOS:A1996TW80600040 PM 8627051 ER PT J AU Nutman, TB Parredes, W Kubofcik, J Guderian, RH AF Nutman, TB Parredes, W Kubofcik, J Guderian, RH TI Polymerase chain reaction-based assessment after macrofilaricidal therapy in Onchocerca volvulus infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID AMOCARZINE; SEQUENCE; CGP-6140; REGIMENS; DRUG AB A recently developed polymerase chain reaction (PCR)-based assay is significantly more sensitive than current methods for diagnosing Onchocerca volvulus infection, and it overcomes many difficulties in identifying active onchocerciasis. Since chemotherapy is widely used to treat onchocerciasis, the utility of PCR in assessing responses to treatment and in predicting recrudescence is important, Twenty-eight patients who had skin snips positive for microfilariae (Mf) were studied 120 days after receiving amocarzine, when each was negative for Mf: 16 (57%) were positive for O. volvulus DNA in the PCR-based assay. Of these, 14 (88%) were Mf positive when reassessed parasitologically on day 240, and all were Mf positive on day 365. Equally important was the finding that 12 patients had cleared both Mf and Mf DNA; only 1 was Mf positive at day 240, This suggests that the PCR-based assay provides a sensitive means for assessing infection status after macrofilaricidal chemotherapy and is an early predictor of persons likely to have a recurrence of Mf. C1 HOSP VOZANDES,DEPT CLIN INVEST,QUITO,ECUADOR. RP Nutman, TB (reprint author), NIAID,NIH,PARASIT DIS LAB,BLDG 4,ROOM 126,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 15 TC 8 Z9 8 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 MAR PY 1996 VL 173 IS 3 BP 773 EP 776 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA TW806 UT WOS:A1996TW80600041 PM 8627052 ER PT J AU Chipev, CC Steinert, PM Woodworth, CD AF Chipev, CC Steinert, PM Woodworth, CD TI Characterization of an immortalized cell line from a patient with epidermolytic hyperkeratosis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE RT-PCR allele specific assay; immunohistochemistry; submerged and organotypic cultures; Arg to His mutation; keratin 10 ID SKIN DISEASES; GENETIC-BASIS; KERATIN; DIFFERENTIATION; MUTATIONS AB The most frequent mutation that causes the autosomal dominant skin disease epidermolytic hyperkeratosis (EHK) is an arginine to histidine substitution at position 10 in the 1A segment of the rod domain of keratin 10. As an initial step toward developing a strategy for treating EHK, a cell line, EH18-1, was established after keratinocytes derived from an EHK patient with this mutation were immortalized by a recombinant retrovirus encoding the E6 and E7 genes of human papillomavirus type 18. EH18-1 cells synthesize considerable amounts of keratin 10 mRNA and protein when maintained in either submerged cultures or in organotypic cultures. When grown in organotypic culture, EH18-1 cells form multiple layers and express keratin 10 and filaggrin predominantly in the upper layers. Thus, the EH18-1 cell line exhibits several morphological and biochemical markers of terminal epidermal differentiation. A semiquantitative reverse transcriptase polymerase chain reaction assay for keratin 10 mRNA was developed to distinguish between expression of the normal and the mutant alleles. The EH18-1 keratinocyte cell line will be useful in developing protocols for gene therapy of EHK that may be monitored by reverse transcriptase polymerase chain reaction of either allele. C1 NIAMS,NIH,SKIN BIOL BRANCH,BETHESDA,MD 20892. NCI,NIH,BIOL LAB,BETHESDA,MD 20892. NR 23 TC 9 Z9 9 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAR PY 1996 VL 106 IS 3 BP 385 EP 390 DI 10.1111/1523-1747.ep12343322 PG 6 WC Dermatology SC Dermatology GA UB968 UT WOS:A1996UB96800001 PM 8648165 ER PT J AU Stanwell, C Denning, MF Rutberg, SE Cheng, C Yuspa, SH Dlugosz, AA AF Stanwell, C Denning, MF Rutberg, SE Cheng, C Yuspa, SH Dlugosz, AA TI Staurosporine induces a sequential program of mouse keratinocyte terminal differentiation through activation of PKC isozymes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE keratinocytes; protein kinase C; staurosporine ID PROTEIN-KINASE-C; EPIDERMAL-CELLS; GENE-EXPRESSION; HUMAN-NEUTROPHILS; PHORBOL ESTERS; CALCIUM; INHIBITOR; IDENTIFICATION; INVITRO; POTENT AB Staurosporine (stsp) induces assembly of cornified envelopes in mouse keratinocyte cultures, To clarify whether this effect is the consequence of a coordinated differentiation program similar to that observed in epidermis, we assessed the expression of multiple differentiation-specific markers in stsp-treated keratinocytes, In medium containing 0.05 mM Ca2+, in which the basal cell phenotype is normally maintained, stsp induced dose-dependent increases in keratin 1, epidermal and keratinocyte transglutaminases, SPR-1, loricrin, and profilaggrin mRNA, Based on nuclear run-on analysis, stsp-mediated marker expression was found to be due at least in part to increased transcription, Since protein kinase C (PKC) activation is required for keratinocyte differentiation, we tested whether stsp influenced this signaling pathway, Stsp induced the translocation of multiple PKC isoforms from the cytosol to membrane and/or cytoskeletal fractions, inducing isozyme downregulation within 24 h, Moreover, AP-1 DNA binding activity was elevated in stsp-treated keratinocytes, consistent with the notion that this agent influences keratinocyte-specific gene expression via the PKC pathway, Stsp-mediated marker expression was inhibited by the PKC inhibitor GF 109203X, In cells pre-treated with bryostatin 1 to selectively down-modulate specific PKC isoforms, stsp-induced loricrin, filaggrin, and SPR-1 expression was suppressed when PKC alpha, epsilon, and/or delta were downregulated, suggesting that these isozymes may be necessary for marker expression in response to this agent, Thus, in addition to its effects on cornified envelope assembly, stsp induces a coordinate program of differentiation-specific keratinocyte gene expression that is mediated at least in part by the PKC signaling pathway. C1 NCI,NIH,DIV BASIC SCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. NR 54 TC 34 Z9 34 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAR PY 1996 VL 106 IS 3 BP 482 EP 489 DI 10.1111/1523-1747.ep12343690 PG 8 WC Dermatology SC Dermatology GA UB968 UT WOS:A1996UB96800017 PM 8648181 ER PT J AU Schwarzenberger, K Udey, MC AF Schwarzenberger, K Udey, MC TI Contact allergens and epidermal proinflammatory cytokines modulate langerhans cell E-cadherin expression in situ SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE leukocyte; activation; adhesion; migration ID IMMUNOSTIMULATORY DENDRITIC CELLS; COLONY-STIMULATING FACTOR; DRAINING LYMPH-NODES; PROTEIN ANTIGENS; INDUCTION-PHASE; IA-ANTIGEN; SKIN; SENSITIVITY; MATURATION; MIGRATION AB After exposure to antigen, Langerhans cells (LC) migrate from the epidermis to lymph nodes, where they initiate primary immune responses in T cells, The adhesion molecule E-cadherin mediates adhesion of LC to keratinocytes in vitro and may be responsible for localization of LC in epidermis. To determine if levels of LC E-cadherin are modulated during LC emigration from epidermis, we utilized flow cytometry to evaluate E-cadherin expression on BALB/c LC exposed in situ to the contact allergen 2,4,6-trinitrochlorobenzene (TNCB), TNCB induced increased I-A/E antigen and decreased E-cadherin expression on a subpopulation of LC as early as 12 h, and as late as 48 h, after application. At 24 h, similar to 30% of LC in TNCB-treated skin expressed increased I-A/E antigens; of these activated LC, similar to 40% expressed decreased levels of E-cadherin. E-cadherin levels on this latter subset were similar to 15% of those expressed by LC in normal skin, and were similar to levels on cultured LC and LC that migrated from skin explants, The effect was specific for allergens; no changes occurred in LC following treatment with several contact irritants or the tolerogen dinitrothiocyanobenzene. To determine if cytokines modulated LC E-cadherin expression, we introduced various cytokines into BALB/c ear skin and assayed I-A/E antigen and E-cadherin levels, Of the cytokines tested, only interleukin-1 and tumor necrosis factor alpha reproduced the effects of TNCB. We propose that downmodulation of E-cadherin expression occurs as a consequence of local cytokine production during antigen-induced LC activation, facilitating LC emigration and the initiation of immune responses against antigens encountered in epidermis. C1 NCI, DERMATOL BRANCH, NIH, BETHESDA, MD 20892 USA. NR 30 TC 130 Z9 134 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAR PY 1996 VL 106 IS 3 BP 553 EP 558 DI 10.1111/1523-1747.ep12344019 PG 6 WC Dermatology SC Dermatology GA UB968 UT WOS:A1996UB96800029 PM 8648193 ER PT J AU Asico, LD Accili, D Fuchs, S Eisner, GM Jose, PA AF Asico, LD Accili, D Fuchs, S Eisner, GM Jose, PA TI Increased blood pressure in mutant mice lacking D-3 dopamine receptors. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NIDDKD,DIABET BRANCH,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,DEPT PEDIAT,WASHINGTON,DC 20057. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A307 EP A307 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700642 ER PT J AU Baram, D Culpepper, S Madara, P Danner, RL AF Baram, D Culpepper, S Madara, P Danner, RL TI Human neutrophils (PMNs) differentially regulate monocyte and endothelial cell (EC) cytokine production SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NIH,DEPT CRIT CARE MED,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A277 EP A277 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700468 ER PT J AU Bergsagel, PL Chesi, M Brents, LA Kuehl, WM AF Bergsagel, PL Chesi, M Brents, LA Kuehl, WM TI Promiscuous translocations into IgH switch regions: The genetic hallmark of multiple myeloma. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 CORNELL UNIV MED COLL,DIV HEMATOL ONCOL,NEW YORK,NY. NATL CANC INST,NAVY MED ONCOL BRANCH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A233 EP A233 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700216 ER PT J AU Boguski, MS AF Boguski, MS TI Adventures in information space: Genbank, genomes and a turning point in biomedical research. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NIH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A323 EP A323 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700725 ER PT J AU Bruening, JC Winnay, J BonnerWeir, S Accili, D Kahn, CR AF Bruening, JC Winnay, J BonnerWeir, S Accili, D Kahn, CR TI Creating polygenic models of insulin resistance and diabetes mellitus. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. JOSLIN DIABET CTR,BOSTON,MA 02215. NR 0 TC 1 Z9 1 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A258 EP A258 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700362 ER PT J AU Bui, MN Caulfield, MT Katz, P Cannon, RO Rackley, CE AF Bui, MN Caulfield, MT Katz, P Cannon, RO Rackley, CE TI Autoantibodies to oxidized LDL in hyperlipidemic patients treated with HMG-CoA reductase inhibitors SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 GEORGETOWN UNIV,MED CTR,WASHINGTON,DC 20007. NHLBI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A296 EP A296 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700578 ER PT J AU Castro, M Kino, T Elliot, S Bamberger, C Karl, M Webster, E Chrousos, GP AF Castro, M Kino, T Elliot, S Bamberger, C Karl, M Webster, E Chrousos, GP TI The nonligand-binding isoform of the human glucocorticoid receptor (hGRD) may define target tissue sensitivity to glucocorticoids SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NICHHD,DEB,BETHESDA,MD 20892. RI Castro, Margaret/A-4918-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A266 EP A266 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700405 ER PT J AU ChoChung, YS Nesterova, M Noguchi, K Srivastava, R AF ChoChung, YS Nesterova, M Noguchi, K Srivastava, R TI Type 1 protein kinase A - Directed antisense restrains tumor growth: Sequence specific inhibition of gene expression SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A198 EP A198 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700007 ER PT J AU Cizza, G Brady, LS Esclapes, M Blackman, MR Gold, PW Chrousos, GP AF Cizza, G Brady, LS Esclapes, M Blackman, MR Gold, PW Chrousos, GP TI Age and gender influence basal and stress-modulated hypothalamic-pituitary-thyroid in Fischer 344/N rats. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A326 EP A326 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700744 ER PT J AU Cizza, G Nieman, LK Doppman, JL Passaro, MD Czerwiec, FS Chrousos, GP Cutler, GB AF Cizza, G Nieman, LK Doppman, JL Passaro, MD Czerwiec, FS Chrousos, GP Cutler, GB TI Factitious Cushing syndrome SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NIH,WARREN G MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A261 EP A261 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700380 ER PT J AU Cohen, O Lam, G Pantaleo, G Schwartzentruber, D Baird, BF Fauci, AS AF Cohen, O Lam, G Pantaleo, G Schwartzentruber, D Baird, BF Fauci, AS TI Incomplete expression of rev/nef mRNAs in lymph node mononuclear cells from HIV-infected long term non-progressors. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. NCI,SURG BRANCH,BETHESDA,MD 20892. RI Pantaleo, Giuseppe/K-6163-2016 NR 0 TC 0 Z9 0 U1 1 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A320 EP A320 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700717 ER PT J AU Ding, I Zhang, RL Zhang, K Okunieff, P AF Ding, I Zhang, RL Zhang, K Okunieff, P TI mRNA expression of fibroblast growth factors and receptors in human colon adenocarcinomas SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NCI,RADIAT ONCOL BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A278 EP A278 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700469 ER PT J AU Druey, KM Blumer, KJ Kang, VH Kehrl, JH AF Druey, KM Blumer, KJ Kang, VH Kehrl, JH TI Inhibition of G protein-mediated MAP kinase activation by members of a novel mammalian gene family SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 WASHINGTON UNIV,SCH MED,ST LOUIS,MO. NIAID,NIH,BETHESDA,MD 20892. RI Blumer, Kendall/C-5268-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A271 EP A271 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700429 ER PT J AU Dunn, E Yu, J Nagarajan, S Devetten, M Medof, ME Young, NS Liu, JM AF Dunn, E Yu, J Nagarajan, S Devetten, M Medof, ME Young, NS Liu, JM TI A PIG-A knock-out model of PNH: Rescue of hematopoiesis follows transfer of GPI-anchored proteins SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NHLBI,HEMATOL BRANCH,BETHESDA,MD 20892. CASE WESTERN RESERVE UNIV,INST PATHOL,CLEVELAND,OH 44106. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A233 EP A233 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700212 ER PT J AU Frucht, DM Holland, SM AF Frucht, DM Holland, SM TI Abnormal peptidoglycan-induced response in monocytes from familial disseminated Mycobacterium avium complex patients. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NIAID,NIH,HOST DEF LAB,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A217 EP A217 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700123 ER PT J AU Fuss, I Strober, W Pearlstein, G Wanidworanun, C Dale, J Fritz, S Puck, J Lenardo, M Straus, S AF Fuss, I Strober, W Pearlstein, G Wanidworanun, C Dale, J Fritz, S Puck, J Lenardo, M Straus, S TI Patients with autoimmune lymphoproliferative syndrome (ALPS) and defective apoptosis manifest a TH2 cytokine profile. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NIAID,NCHGR,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A254 EP A254 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700338 ER PT J AU Giattina, M Miller, JL AF Giattina, M Miller, JL TI Intercellular transfer of GPI-anchored proteins. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NIDDK,NIH,BIOL CHEM LAB,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A244 EP A244 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700276 ER PT J AU Giuliano, M Marinacci Messina, E Capogrossi, MC Cirielli, C Pass, HI Modesti, A Carbone, M Procopio, A AF Giuliano, M Marinacci Messina, E Capogrossi, MC Cirielli, C Pass, HI Modesti, A Carbone, M Procopio, A TI Adenovirus-mediated wild-type p53 gene transfer induces apoptosis and inhibits in vivo tumor growth of human mesothelioma cells. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 UNIV G DANNUNZIO,GENE THERAPY CTR,CHIETI,ITALY. NIA,GENE THERAPY UNIT,LCS,NIH,BALTIMORE,MD 21224. NCI,NIH,BETHESDA,MD 20892. UNIV CHICAGO,DEPT PATHOL,CHICAGO,IL 60637. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A280 EP A280 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700485 ER PT J AU Himmelmann, A Wilson, GL Lucas, B Thevenin, C Kehrl, J AF Himmelmann, A Wilson, GL Lucas, B Thevenin, C Kehrl, J TI B cell and developmental stage specific expression of the human CD20 gene is achieved via a novel PU.1/PIP site. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NIAID,LIR,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A237 EP A237 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700238 ER PT J AU Hirschhorn, R Yang, DR Puck, JM Huie, ML Jiang, CK Kurlandsky, LE AF Hirschhorn, R Yang, DR Puck, JM Huie, ML Jiang, CK Kurlandsky, LE TI Spontaneous in vivo reversion to normal of an inherited mutation in a patient with adenosine deaminase deficiency. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NYU,DEPT MED,MED CTR,NEW YORK,NY 10016. NIH,HUMAN GENOME RES CTR,BETHESDA,MD 20892. MICHIGAN STATE HLTH CTR,DEPT PEDIAT,GRAND RAPIDS,MI. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A235 EP A235 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700222 ER PT J AU Huh, CG Yamaguchi, S Collins, A Karlsson, S AF Huh, CG Yamaguchi, S Collins, A Karlsson, S TI Cystatin C null mice have abnormal behavior and increased susceptibility to mouse corona virus infection. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NINCDS,NIH,DEV & METAB NEUROL BRANCH,MOL & MED GENET SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A206 EP A206 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700054 ER PT J AU Humphrey, RW Davis, DA Mitsuya, H Yarchoan, R AF Humphrey, RW Davis, DA Mitsuya, H Yarchoan, R TI HIV virions produced by cells treated with the HIV-1 protease inhibitor KNI-272 do not acquire infectivity after viral budding. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NCI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A252 EP A252 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700323 ER PT J AU Imai, Y Philippe, N Sesti, G Accili, D Taylor, SI AF Imai, Y Philippe, N Sesti, G Accili, D Taylor, SI TI Transfection studies of insulin receptor substrate-1 with variant sequences found in patients with noninsulin-dependent diabetes mellitus. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NIDDK,DIABET BRANCH,NIH,BETHESDA,MD. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A259 EP A259 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700363 ER PT J AU Jackson, SH Gallin, JI Miller, GF Holland, SM AF Jackson, SH Gallin, JI Miller, GF Holland, SM TI Prophylactic interferon-gamma is effective in the P47(PHOX) deficient mouse model of chronic granulomatous disease (CGD). SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NIAID,HOST DEF LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A320 EP A320 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700715 ER PT J AU Kaler, SG AF Kaler, SG TI Expression of the menkes disease gene homologue in rodent brain and astrocytes from cortex, cerebellum and corpus striatum. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NINCDS,CLIN NEUROSCI BRANCH,NIH,BETHESDA,MD 20892. CHILDRENS HOSP,WASHINGTON,DC 20010. NR 0 TC 2 Z9 2 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A203 EP A203 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700038 ER PT J AU Kreitman, RJ Pastan, I AF Kreitman, RJ Pastan, I TI Recombinant toxins containing human GM-CSF and Pseudonomas exotoxin (PE) or diphtheria toxin (DT) kill colon cancer and leukemia cells. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NCI,MOLEC BIOL LAB,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A231 EP A231 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700202 ER PT J AU Lee, J Brantly, M AF Lee, J Brantly, M TI A conformational change in the reactive site loop of alpha 1-antitrypsin promotes rapid intracellular degradation. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NHLBI,PULM CRIT CARE MED BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A270 EP A270 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700428 ER PT J AU Leto, TL Shi, J Ross, CR Blecha, F AF Leto, TL Shi, J Ross, CR Blecha, F TI PR-39: A proline-rich antimicrobial peptide from neutrophils that inhibits NADPH oxidase by binding to a SH3 domain of P47PHOX SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 KANSAS STATE UNIV,COLL VET MED,MANHATTAN,KS 66506. NIAID,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A268 EP A268 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700414 ER PT J AU Li, J Peters, B Fibach, E Schechter, AN Noguchi, CT AF Li, J Peters, B Fibach, E Schechter, AN Noguchi, CT TI Mechanism of silencing of the human epsilon globin gene. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NIDDK,NIH,BIOL CHEM LAB,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A215 EP A215 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700111 ER PT J AU Licinio, J Wong, ML Bongiorno, PB Gold, PW AF Licinio, J Wong, ML Bongiorno, PB Gold, PW TI Localization of interleukin in 1 beta (IL-1 beta) converting enzyme mRNA in rat brain vasculature: Evidence that the genes encoding the IL-1 system are constitutively expressed in brain blood vessels. Pathophysiological implications. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NIMH,CLIN NEUROENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892. RI Licinio, Julio/L-4244-2013 OI Licinio, Julio/0000-0001-6905-5884 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A277 EP A277 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700467 ER PT J AU Liu, C Yu, K Chin, K Shen, K Liu, Z Noguchi, CT AF Liu, C Yu, K Chin, K Shen, K Liu, Z Noguchi, CT TI Human erythropoietin receptor gene expression in the brain of transgenic mice. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NIDDK,BIOL CHEM LAB,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A205 EP A205 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700053 ER PT J AU Medin, JA Pawliuk, R Amiri, M Brooks, C KluepfelStahl, S Migita, M Humphries, RK Karlsson, S AF Medin, JA Pawliuk, R Amiri, M Brooks, C KluepfelStahl, S Migita, M Humphries, RK Karlsson, S TI Selection and metabolic correction of normal and Gaucher patient CD34+ hematopoietic progenitors with a therapeutic and selectable retrovirus. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NINCDS,DEV & METAB NEUROL BRANCH,NIH,BETHESDA,MD 20892. TERRY FOX LAB,VANCOUVER,BC,CANADA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A279 EP A279 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700478 ER PT J AU Murphy, WJ Tian, Z Asai, O Hornung, R Longo, DL AF Murphy, WJ Tian, Z Asai, O Hornung, R Longo, DL TI Activated natural killer (NK) cells mediate graft-versus-tumor (GVT) effects but inhibit graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,DES,LAB LEUKOCYTE BIOL,FREDERICK,MD 21701. NCI,FREDERICK CANC RES & DEV CTR,SAIC,BCDP,FREDERICK,MD 21701. NIA,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A232 EP A232 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700209 ER PT J AU OGrady, NP Preas, HL Tropea, M Culpepper, S Reda, S Suffredini, AF AF OGrady, NP Preas, HL Tropea, M Culpepper, S Reda, S Suffredini, AF TI Bronchial instillation of endotoxin in normal humans results in localized but not systemic activation of neutrophils. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NIH,DEPT CRIT CARE MED,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A256 EP A256 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700347 ER PT J AU Okazaki, IJ Miller, JS Moss, J AF Okazaki, IJ Miller, JS Moss, J TI Regulation of immune function by ADP-ribosylation: IL-2-mediated induction in human NK cells of an NAD:arginine ADP-ribosyltransferase. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NHLBI,NIH,PULM CRIT CARE MED BRANCH,BETHESDA,MD 20892. UNIV MINNESOTA,DEPT MED,DIV HEMATOL,MINNEAPOLIS,MN 55455. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A241 EP A241 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700257 ER PT J AU Papanicolaou, DA Tsigos, C Torpy, D Defensor, R Thompson, B Chrousos, GP AF Papanicolaou, DA Tsigos, C Torpy, D Defensor, R Thompson, B Chrousos, GP TI Recombinant interleukin-6 effects on pituitary secretion in humans SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NICHHD,DEV ENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 4 Z9 5 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A266 EP A266 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700402 ER PT J AU Philpott, CC Iwai, Y Klausner, R Dancis, A AF Philpott, CC Iwai, Y Klausner, R Dancis, A TI The toxicity of AFT1-1(UP), a dominant mutant allele of an iron regulator, is enhanced by the Delta rad52 mutation in yeast. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NICHHD,CELL BIOL & METAB BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A325 EP A325 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700739 ER PT J AU Rosen, R Winestock, K Liu, X Hennighausen, L Finbloom, DS AF Rosen, R Winestock, K Liu, X Hennighausen, L Finbloom, DS TI Differential activation of STAT5A and STAT5B by granulocyte-macrophage colony stimulating factor (GMCSF) in human peripheral blood monocytes. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NIDDK,NIH,BETHESDA,MD. US FDA,DIV CYTOKINE BIOL,BETHESDA,MD 20014. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A230 EP A230 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700198 ER PT J AU Schachter, LA Wisnieski, JJ Denburg, M Michael, AR Gourley, MF Kimberly, RP Salmon, JE AF Schachter, LA Wisnieski, JJ Denburg, M Michael, AR Gourley, MF Kimberly, RP Salmon, JE TI Antibodies to the collagen like region of C1q in systemic lupus erythematosus: Likely contributors to renal disease. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 CORNELL UNIV,MED CTR,NEW YORK,NY 10021. CASE WESTERN RESERVE UNIV,CLEVELAND VA MED CTR,CLEVELAND,OH 44106. NIAMS,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A298 EP A298 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700591 ER PT J AU Schwartz, LB Sakai, K Bradford, TR Ren, S Worobec, AS Metcalfe, DD AF Schwartz, LB Sakai, K Bradford, TR Ren, S Worobec, AS Metcalfe, DD TI The alpha form of human tryptase predominates in blood at baseline in normal subjects, and is elevated in those with systemic mastocytosis SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 VIRGINIA COMMONWEALTH UNIV,DEPT MED,RICHMOND,VA 23284. NIAID,CLIN INVEST LAB,ALLERG DIS SECT,NATL INST HLTH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A298 EP A298 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700588 ER PT J AU Smith, MC Pendleton, CD Kelley, MJ Carbone, DP Berzofsky, JA AF Smith, MC Pendleton, CD Kelley, MJ Carbone, DP Berzofsky, JA TI Candidate cancer vaccines: Oncogenic mutations in RAS create HLA-A2.1 binding peptides SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NCI,METAB BRANCH,MOLEC IMMUNOGENET & VACCINE RES SECT,BETHESDA,MD 20892. NCI,NAVY MED ONCOL BRANCH,BETHESDA,MD 20892. UNIV TEXAS,SW MED CTR,DALLAS,TX 75235. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A247 EP A247 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700297 ER PT J AU Stewart, DM TreiberHeld, S Kurman, CC Nelson, DL AF Stewart, DM TreiberHeld, S Kurman, CC Nelson, DL TI Studies of the expression of the Wiskott-Aldrich syndrome protein. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NCI,METAB BRANCH,NIH,BETHESDA,MD 20892. UNIV BRESCIA,BRESCIA,ITALY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A254 EP A254 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700334 ER PT J AU Straus, SE Puck, J Dale, JK Sneller, M Lin, A Fleisher, T Strober, WT Lenardo, M AF Straus, SE Puck, J Dale, JK Sneller, M Lin, A Fleisher, T Strober, WT Lenardo, M TI Autoimmune lymphoproliferative syndrome (ALPS): Clinical, immunologic, and genetic aspects of defective lymphocyte apoptosis. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NIAID,NCHGR,NCI,CC NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A254 EP A254 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700339 ER PT J AU Tagaya, Y Burton, JD Miyamoto, Y Waldmann, TA AF Tagaya, Y Burton, JD Miyamoto, Y Waldmann, TA TI Interleukin-15/T is a novel growth factor for mast cells. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NCI,METAB BRANCH,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A230 EP A230 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700199 ER PT J AU Tang, DC Pope, SH Wang, M Fibach, E Rodgers, GP AF Tang, DC Pope, SH Wang, M Fibach, E Rodgers, GP TI Thyroid hormone increases hemoglobin F and A(2) levels in human adult erythroid cells. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NIDDK,MOLEC HEMATOL SECT,BIOL CHEM LAB,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A329 EP A329 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700759 ER PT J AU Timmers, KI Cushman, SW AF Timmers, KI Cushman, SW TI Characterization of apparent vesicular components of the insulin-regulated subcellular trafficking pathway for GLUT4 in rat adipose cells. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NIDDK,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A224 EP A224 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700162 ER PT J AU TreiberHeld, SA Stewart, DM Kurman, CC Barraclough, HA Nelson, DL AF TreiberHeld, SA Stewart, DM Kurman, CC Barraclough, HA Nelson, DL TI Interleukin 15 activates human peripheral blood mononuclear cells in the absence of other exogenous stimuli. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NCI,METAB BRANCH,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A231 EP A231 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700200 ER PT J AU Tsai, SC Ding, M Vitale, N Adamik, R Ogasawara, M Moss, J Vaughan, M AF Tsai, SC Ding, M Vitale, N Adamik, R Ogasawara, M Moss, J Vaughan, M TI Characterization of a GTPase activating protein (GAP) for ADP-ribosylation factors (ARFS) and ARF-like proteins (ARLS): Substrate specificity of the ARF-GAP from spleen cytosol. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NHLBI,NIH,PULM CRIT CARE MED BRANCH,BETHESDA,MD 20892. RI Vitale, nicolas/G-5967-2014 OI Vitale, nicolas/0000-0002-4752-4907 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A241 EP A241 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700258 ER PT J AU Tullio, AN Accili, D Corria, Z Preston, YA Bertuzzi, S Westphal, H Adelstein, RS AF Tullio, AN Accili, D Corria, Z Preston, YA Bertuzzi, S Westphal, H Adelstein, RS TI Targeted disruption of the gene encoding nonmuscle myosin heavy chain II-B results in developmental abnormalities in the brain and heart. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A227 EP A227 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700183 ER PT J AU Tuscano, JM Kehrl, JH AF Tuscano, JM Kehrl, JH TI Signal transduction via the human B lymphocyte antigen CD22 results in a potent B cell stimulatory signal and the association of CD22 with a complex of effector molecules. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NIAID,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A241 EP A241 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700261 ER PT J AU Ulery, P Martin, BM Henkin, RI AF Ulery, P Martin, BM Henkin, RI TI Carbonic anhydrase (CA) VI action differs from that of CA I and II. CA VI inhibition induces human taste dysfunction. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 TASTE & SMELL CLIN,WASHINGTON,DC 20016. NIMH,CLIN NEUROSCI BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 3 Z9 3 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A272 EP A272 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700435 ER PT J AU Wang, SB Yan, LA Wesley, RA Danner, RL AF Wang, SB Yan, LA Wesley, RA Danner, RL TI Nitric oxide(NO) increases TNF production in differentiated U937 cells by decreasing cyclic AMP. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NIH,CTR CLIN,DEPT CRIT CARE MED,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A240 EP A240 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700255 ER PT J AU Wenkert, D Schoneberg, T Merendino, JJ Pena, MSR Vinitsky, R Goldsmith, PK Wess, J Spiegel, AM AF Wenkert, D Schoneberg, T Merendino, JJ Pena, MSR Vinitsky, R Goldsmith, PK Wess, J Spiegel, AM TI Expression and functional characterization of five V2 vasopressin receptor gene mutations identified in families with X-linked nephrogenic diabetes insipidus. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NIDDK,NIH,BETHESDA,MD. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A225 EP A225 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700171 ER PT J AU Wong, ML Bongiorno, PB Gold, PW Licinio, J AF Wong, ML Bongiorno, PB Gold, PW Licinio, J TI The gene encoding for the novel transacting factor proopiomelanocortin corticotropin-releasing hormone responsive element binding protein 1 (PCRH-REB-1)is constitutively expressed in rat pituitary and in discrete brain regions containing CRH or CRH receptors Pathophysiological implications. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NIMH,CLIN NEUROENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892. RI Licinio, Julio/L-4244-2013 OI Licinio, Julio/0000-0001-6905-5884 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A260 EP A260 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700373 ER PT J AU Yao, XL Logun, C Shelhamer, JH AF Yao, XL Logun, C Shelhamer, JH TI Cytokine effects on epithelial cell CC 10 KD protein production. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NIH,CTR CLIN,DEPT CRIT CARE MED,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A244 EP A244 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700275 ER PT J AU Zhou, YF Leon, MB Waclawiw, MA Yu, ZX Finkel, T Epstein, SE AF Zhou, YF Leon, MB Waclawiw, MA Yu, ZX Finkel, T Epstein, SE TI Prior infection with cytomegalovirus markedly increases the risk of restenosis following directional coronary atherectomy. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 NHLBI,CARDIOL BRANCH,NATL INST HLTH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1996 VL 44 IS 3 BP A287 EP A287 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA UG207 UT WOS:A1996UG20700522 ER PT J AU Barna, BP Thomassen, MJ Zhou, P Pettay, J SinghBurgess, S Deodhar, SD AF Barna, BP Thomassen, MJ Zhou, P Pettay, J SinghBurgess, S Deodhar, SD TI Activation of alveolar macrophage TNF and MCP-1 expression in vivo by a synthetic peptide of C-reactive protein SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE tumor necrosis factor; monocyte chemoattractant protein 1; integrin ID TUMOR-NECROSIS-FACTOR; MURAMYL TRIPEPTIDE; LIPOSOMES; CELLS; METASTASES; INHIBITION; GENERATION; DIPEPTIDE; CYTOKINE; INVIVO AB Administration of multilamellar vesicles (MLV) encapsulating a synthetic peptide (RS-83277) derived from human C-reactive protein (CRP) augments anti-tumor activity of murine alveolar macrophages and reduces established pulmonary metastases of experimental tumors. To explore mechanisms involved in these phenomena, we investigated cytokine and integrin (CD11b) expression of bronchoalveolar lavage (BAL)-derived alveolar macrophages in control (blank MLV) and RS-83277-MLV-treated C57B1 mice, Alveolar macrophage production of tumor necrosis factor alpha (TNF-alpha) and monocyte chemoattractant bioactivity increased at 48 h after treatment with RS-83277-MLV but not control MLV, Chemoattractant activity was neutralized by antibody to monocyte chemoattractant protein-1 (MCP-1), brit not irrelevant immunoglobulin G (IgG). Changes were reflected by augmented TNF-alpha and MCP-1 mRNA levels in pulmonary tissue and enhanced CD11b expression on mononuclear leukocytes derived from total lung tissue, but not on BAL-derived alveolar macrophages. Results suggest that RS-83277-MLV treatment is associated with activation of alveolar macrophage TNF-alpha and MCP-1 production and up-regulation of adhesion molecules on pulmonary mononuclear leukocytes but not on alveolar macrophages. C1 CLEVELAND CLIN FDN,DEPT PULM & CRIT CARE MED,CLEVELAND,OH 44195. CLEVELAND CLIN FDN,RES INST,CLEVELAND,OH 44195. NIAID,CLIN INVEST LAB,NIH,BETHESDA,MD 20892. RP Barna, BP (reprint author), CLEVELAND CLIN FDN,DEPT CLIN PATHOL,L-12,9500 EUCLID AVE,CLEVELAND,OH 44195, USA. FU NCI NIH HHS [CA49950] NR 33 TC 25 Z9 26 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 MAR PY 1996 VL 59 IS 3 BP 397 EP 402 PG 6 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA UD921 UT WOS:A1996UD92100012 PM 8604018 ER PT J AU Rouis, M Lohse, P Dugi, KA Lohse, P Beg, OU Ronan, R Talley, GD Brunzell, JD SantamarinaFojo, S AF Rouis, M Lohse, P Dugi, KA Lohse, P Beg, OU Ronan, R Talley, GD Brunzell, JD SantamarinaFojo, S TI Homozygosity for two point mutations in the lipoprotein lipase (LPL) gene in a patient with familial LPL deficiency: LPL(Asp(9)->Asn, Tyr(262)->His) SO JOURNAL OF LIPID RESEARCH LA English DT Article DE glycosaminoglycans; heparin binding; hypertriglyceridemia; lipoprotein lipase deficiency; LPL monomer; pancreatitis ID SITE-DIRECTED MUTAGENESIS; HYPERCHYLOMICRONEMIA SYNDROME; POSTHEPARIN PLASMA; MOLECULAR-CLONING; MISSENSE MUTATION; HEPARIN BINDING; SPLICE SITE; SINGLE COPY; SEQUENCE; DNA AB Familial lipoprotein lipase (LPL) deficiency is an inherited disorder of lipoprotein metabolism characterized by hypertriglyceridemia and recurrent episodes of abdominal pain and pancreatitis. We have studied the genetic basis of LPL deficiency in a 62-year-old black male with undetectable pre- and post-heparin plasma LPL mass and activity. DNA sequence analysis of the patient's LPL cDNA and gene as well as digestion with Bcl I and Asu I revealed that the proband is a homozygote for two separate gene defects. One mutation changed a G to an A, resulting in the conversion of amino acid 9 of the mature protein, aspartic acid (GAG), to asparagine (AAC). The second substitution, a C for a T, replaced tyrosine (TAC) at residue 262 with histidine (CAC). Northern blot analysis of monocyte-derived macrophage RNA demonstrated the presence of LPL mRNA of approximately normal size and quantity when compared to control. Expression of both mutations separately (pCMV-9 and pCMV-262) or in combination (pCMV-9+262) in human embryonal kidney-293 cells demonstrated that LPL-9 had approximately 80% the specific activity of wild type LPI,. but LPL-262 and LPL-9+262 had no enzymic activity, thus establishing the functional significance of the LPL-262 defect. Despite an absolute deficiency of LPL mass and activity demonstrated by analysis of patient post-heparin plasma, in vitro expression of both LPL mutants was normal, suggesting that the absence of LPL in patient post-heparin plasma was a result of altered in vivo processing. Analysis of the heparin binding properties of the mutant enzymes by heparin-Sepharose affinity chromatography indicated that most of the LPL-262 mass was present in an inactive peak, which like the normal LPL monomer, eluted at 0.8 M NaCl. Thus, the Tyr(262) --> His mutation may alter the stability of the LPL dimer, leading to the formation of inactive LPL-262 monomer which exhibits reduced heparin affinity. Based on these results, we propose that, in vivo, enhanced formation of LPL-9+262 monomer leads to abnormal binding of the mutant lipase to endothelial glycosaminoglycans ultimately resulting in enhanced catabolism of the mutant enzyme and lower enzyme mass in post-heparin plasma. C1 NHLBI,MOLEC DIS BRANCH,NIH,BETHESDA,MD 20892. UNIV WASHINGTON,DEPT MED,DIV METAB ENDOCRINOL & NUTR,SEATTLE,WA 98195. RI Rouis, Mustapha/E-4993-2016 FU NIDDK NIH HHS [DK02456] NR 54 TC 27 Z9 28 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 MAR PY 1996 VL 37 IS 3 BP 651 EP 661 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UG085 UT WOS:A1996UG08500018 PM 8728326 ER PT J AU Bax, A Farley, KA Walker, GS AF Bax, A Farley, KA Walker, GS TI Increased HMBC sensitivity for correlating poorly resolved proton multiplets to carbon-13 using selective or semi-selective pulses SO JOURNAL OF MAGNETIC RESONANCE SERIES A LA English DT Article ID COUPLING-CONSTANTS 3JHN-ALPHA; POLARIZATION TRANSFER; IMPROVED RESOLUTION; NMR-SPECTRA; SPECTROSCOPY; PROTEINS; PHASE; ENHANCEMENT; NUCLEI C1 PHARMACIA & UPJOHN INC,ANALYT RES & SPECIFICAT DEV,KALAMAZOO,MI 49001. RP Bax, A (reprint author), NIDDKD,NIH,CHEM PHYS LAB,BETHESDA,MD 20892, USA. NR 22 TC 31 Z9 31 U1 1 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1064-1858 J9 J MAGN RESON SER A JI J. Magn. Reson. Ser. A PD MAR PY 1996 VL 119 IS 1 BP 134 EP 138 DI 10.1006/jmra.1996.0063 PG 5 WC Physics, Atomic, Molecular & Chemical SC Physics GA UB175 UT WOS:A1996UB17500020 ER PT J AU Burke, TR Ye, B Akamatsu, M Ford, H Yan, XJ Kole, HK Wolf, G Shoelson, SE Roller, PP AF Burke, TR Ye, B Akamatsu, M Ford, H Yan, XJ Kole, HK Wolf, G Shoelson, SE Roller, PP TI 4'-O-[2-(2-fluoromalonyl)]-L-tyrosine: A phosphotyrosyl mimic for the preparation of signal transduction inhibitory peptides SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID SOLID-PHASE SYNTHESIS; ANALOGS; ACIDS AB Development of phosphotyrosyl (pTyr) mimetics which are stable to protein-tyrosine phosphatases (PTPs), yet can retain biological potency when incorporated into peptides, is an active area of drug development. Since a majority of pTyr mimetics derive their ''phosphofunctionality'' from phosphorus-containing moieties, such as phosphonates, evolution of new inhibitors and modes of prodrug derivatization have been restricted to chemistries appropriate for phosphorus-containing moieties. A new, nonphosphorus-containing pTyr mimetic has recently been reported, L-O-(2-malonyl)tyrosine (OMT, 5), which can be incorporated into peptides that exhibit good PTP and Src homology 2 (SH2) domain inhibitory potency. For phosphonate-based pTyr mimetics such as phosphonomethyl phenylalanine (Pmp, 2), introduction of fluorines a to the phosphorus has provided higher affinity pTyr mimetics. This strategy has now been applied to OR IT, and herein is reported 4'-O-[2-(2-fluoromalonyl)]-L-tyrosine (FOMT) 6), a new fluorine-containing nonphosphorus pTyr mimetic. Incorporation of FOMT into appropriate peptides results in good inhibition of both PTP and SH2 domains. In an assay measuring the inhibition of PTP 1B-mediated dephosphorylation of phosphorylated insulin receptor, the peptide Ac-DA-D-E-X-L-amide exhibited a 10-fold enhancement in inhibitory potency for X = FOMT (19) (IC50 = 1 mu M) relative to the unfluorinated peptide, X = OMT (18) (IC50 = 10 mu M). Molecular modeling indicated that this increased affinity may be attributable to new hydrogen-bonding interactions between the fluorine and the enzyme catalytic site, and not due to lowering of pK(a) values. In a competition binding assay using the p85 PI 3-kinase C-terminal SH2 domain GST fusion construct, the inhibitory peptide, Ac-D-X-V-P-M-L-amide, showed no enhancement of inhibitory potency for X = FOMT (22) (IC50 = 18 mu M) relative to the unfluorinated peptide, X = OMT (21) (IC50 = 14 mu M). The use of FOMT would therefore appear to have particular potential for the development of PTP inhibitors. C1 NIA,GERONTOL RES CTR,NIH,DIABET UNIT,LAB CLIN PHYSIOL,BALTIMORE,MD 21224. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,BOSTON,MA 02215. HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02215. RP Burke, TR (reprint author), NCI,NIH,MED CHEM LAB,DIV BASIC SCI,BLDG 37,ROOM 5C06,BETHESDA,MD 20892, USA. RI Burke, Terrence/N-2601-2014 NR 34 TC 93 Z9 94 U1 0 U2 9 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 MAR 1 PY 1996 VL 39 IS 5 BP 1021 EP 1027 PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA TY544 UT WOS:A1996TY54400004 PM 8676336 ER PT J AU Smith, DJ Chakravarthy, D Pulfer, S Simmons, ML Hrabie, JA Citro, ML Saavedra, JE Davies, KM Hutsell, TC Mooradian, DL Hanson, SR Keefer, LK AF Smith, DJ Chakravarthy, D Pulfer, S Simmons, ML Hrabie, JA Citro, ML Saavedra, JE Davies, KM Hutsell, TC Mooradian, DL Hanson, SR Keefer, LK TI Nitric oxide-releasing polymers containing the [N(O)NO](-) group SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID CONTROLLED BIOLOGICAL RELEASE; SMOOTH-MUSCLE CELLS; NUCLEOPHILE COMPLEXES; VASODILATORS; THROMBOSIS; AGENTS; PROLIFERATION; INHIBIT; BABOONS; RABBIT AB Ions of structure X[N(O)NO](-) display broad-spectrum pharmacological activity that correlates with the rate and extent of their spontaneous, first-order decomposition to nitric oxide when dissolved. We report incorporation of this functional group into polymeric matrices that can be used for altering the time course of nitric oxide release and/or targeting it to tissues with which the polymers are in physical contact. Structural types prepared include those in which the [N(O)NO]- group is attached to heteroatoms in low molecular weight species that are noncovalently distributed throughout the polymeric matrix, in groupings pendant to the polymer backbone, and in the polymer backbone itself. They range in physical form from films that can be coated onto other surfaces to microspheres, gels, powders, and moldable resins. Chemiluminescence measurements confirm that polymers to which the [N(O)NO](-) group is attached can serve as localized sources of nitric oxide, with one prototype providing sustained NO release for 5 weeks in pH 7.4 buffer at 37 degrees C. The latter composition, a cross-linked poly(ethylenimine) that had been exposed to NO, inhibited the in vitro proliferation of rat aorta smooth muscle cells when added as a powder to the culture medium and showed potent antiplatelet activity when coated on a normally thrombogenic vascular graft situated in an arteriovenous shunt in a baboon's circulatory system. The results suggest that polymers containing the [N(O)NO]- functional group may hold considerable promise for a variety of biomedical applications in which local delivery of NO is desired. C1 SAIC,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD. NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,CHEM SECT,FREDERICK,MD 21702. GEORGE MASON UNIV,DEPT CHEM,FAIRFAX,VA 22030. COMEDICUS INC,COLUMBIA HEIGHTS,MN 55421. UNIV MINNESOTA,DEPT LAB MED & PATHOL,CTR BIOMED ENGN,MINNEAPOLIS,MN 55455. EMORY UNIV,YERKES REG PRIMATE RES CTR,ATLANTA,GA 30322. EMORY UNIV,DIV HEMATOL,ATLANTA,GA 30322. RP Smith, DJ (reprint author), UNIV AKRON,DEPT CHEM,AKRON,OH 44325, USA. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU NCI NIH HHS [CA26731]; NHLBI NIH HHS [HL31469, HL48667] NR 39 TC 154 Z9 159 U1 2 U2 28 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 MAR 1 PY 1996 VL 39 IS 5 BP 1148 EP 1156 DI 10.1021/jm950652b PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA TY544 UT WOS:A1996TY54400020 PM 8676352 ER PT J AU Kaplan, D Bungay, P Sullivan, J Zimmerberg, J AF Kaplan, D Bungay, P Sullivan, J Zimmerberg, J TI A rapid-flow perfusion chamber for high-resolution microscopy SO JOURNAL OF MICROSCOPY-OXFORD LA English DT Article DE cell fusion; exocytosis; flow chamber; kinetics; stopped-flow ID CELL FLUORESCENCE MEASUREMENTS; SINGLE; TEMPERATURE; CULTURE; TOOL AB Perfusion chambers employing laminar flow have dead volumes and unstirred layers which limit the minimum time required to effect a change in the local chemical environment of the sample, We have fabricated and tested a chamber capable of developing turbulent flow at reasonable now rates of aqueous solutions. Transition to turbulence occurred at approximate to 1 mL s(-1). To minimize dead space, a dual-exit cross-now pattern was employed. The chamber was designed to mount on optical microscope stages for visual sample observation supplemented by a variety of techniques, such as fluorescence, light scattering and electrochemical monitoring. As indicated by fluorescence from a fluorescein-labelled protein film adherent to the chamber wall, local pH changes were produced within 200 ms. Use of the chamber is illustrated by measurements of stopped-flow kinetics in both calcium-triggered cortical granule exocytosis and influenza virus haemagglutinin-mediated cell-cell fusion. C1 NICHHD,LTPB,BETHESDA,MD 20892. ISRAEL INST BIOL RES,IL-70450 NESS ZIONA,ISRAEL. NCRR,BIOMED ENGN & INSTRUMENTAT PROGRAM,BETHESDA,MD 20892. NR 29 TC 6 Z9 7 U1 0 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA OSNEY MEAD, OXFORD, OXON, ENGLAND OX2 0EL SN 0022-2720 J9 J MICROSC-OXFORD JI J. Microsc.-Oxf. PD MAR PY 1996 VL 181 BP 286 EP 297 DI 10.1046/j.1365-2818.1996.103383.x PN 3 PG 12 WC Microscopy SC Microscopy GA UF448 UT WOS:A1996UF44800007 PM 8642587 ER PT J AU Miyazawa, S Jernigan, RL AF Miyazawa, S Jernigan, RL TI Residue-residue potentials with a favorable contact pair term and an unfavorable high packing density term, for simulation and threading SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE hydrophobicity; contact energy; residue packing energy; sequence threading; sequence sampling weights ID AMINO-ACID-SEQUENCE; GLOBULAR-PROTEINS; 3-DIMENSIONAL STRUCTURE; MEAN FORCE; MODELS; STABILITY; CONFORMATIONS; FOLD; IDENTIFICATION; HYDROPHOBICITY AB Attractive inter-residue contact energies for proteins have been re-evaluated with the same assumptions and approximations used originally by us in 1985, but with a significantly larger set of protein crystal structures. An additional repulsive packing energy term, operative at higher densities to prevent overpacking, has also been estimated for all 20 amino acids as a function of the number of contacting residues, based on their observed distributions. The two terms of opposite sign are intended to be used together to provide an estimate of the overall energies of inter-residue interactions in simplified proteins without atomic details. To overcome the problem of how to utilize the many homologous proteins in the Protein Data Bank, a new scheme has been devised to assign different weights to each protein, based on similarities among amino acid sequences. A total of 1168 protein structures containing 1661 subunit sequences are actually used here. After the sequence weights have been applied, these correspond to an effective number of residue-residue contacts of 113,914, or about six times more than were used in the old analysis. Remarkably, the new attractive contact energies are nearly identical to the old ones, except for those with Leu and the rarer amino acids Trp and Met. The largest change found for Leu is surprising. The estimates of hydrophobicity from the contact energies for non-polar side-chains agree well with the experimental values. In an application of these contact energies, the sequences of 88 structurally distinct proteins in the Protein Data Bank are threaded at all possible positions without gaps into 189 different folds of proteins whose sequences differ from each other by at least 35% sequence identity. The native structures for 73 of 88 proteins, excluding 15 exceptional proteins such as membrane proteins, are all demonstrated to have the lowest alignment energies. (C) 1996 Academic Press Limited C1 GUNMA UNIV,FAC TECHNOL,KIRYU,GUMMA 376,JAPAN. NCI,NIH,DBS,MATH BIOL LAB,BETHESDA,MD 20892. RI Jernigan, Robert/A-5421-2012 NR 37 TC 751 Z9 772 U1 8 U2 50 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 MAR 1 PY 1996 VL 256 IS 3 BP 623 EP 644 DI 10.1006/jmbi.1996.0114 PG 22 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TW702 UT WOS:A1996TW70200019 PM 8604144 ER PT J AU Modi, WS Gallagher, DS Womack, JE AF Modi, WS Gallagher, DS Womack, JE TI Evolutionary histories of highly repeated DNA families among the artiodactyla (mammalia) SO JOURNAL OF MOLECULAR EVOLUTION LA English DT Article DE mammalia; artiodactyla; evolutionary history ID RIBOSOMAL DNA; SATELLITE DNA; BOVIDAE; SEQUENCES; TRANSLOCATIONS; ORGANIZATION; RETROPOSONS; CHROMOSOMES; DIVERGENCE; PHYLOGENY AB Six highly repeated DNA families were analyzed using Southern blotting and fluorescence in situ hybridization in a comparative study of 46 species of artiodactyls belonging to seven of the eight extant taxonomic families. Two of the repeats, the dispersed bovine-Pst family and the localized 1.715 component, were found to have the broadest taxonomic distributions, being present in all pecoran ruminants (Giraffidae, Cervidae, Antilocapridae, and Bovidae), indicating that these repeats may be 25-40 million years old. Different 1.715 restriction patterns were observed in different taxonomic families, indicating that independent concerted evolution events have homogenized different motifs in different lineages. The other four satellite arrays were restricted to the Bovini and sometimes to the related Boselaphini and Tragelaphini. Results reveal that among the two compound satellites studied, the two components of the 1.711a originated simultaneously, whereas the two components of the 1.711b originated at two different historical times, perhaps as many as 15 million years apart. Systematic conclusions support the monophyly of the infraorder Pecora, the monophyly of the subfamily Bovinae (containing the Boselaphini, Bovini, and Tragelaphini), an inability to resolve any interrelationships among the other tribes of bovids, paraphyly of the genus Bos with respect to Bison, and a lack of molecular variation among two morphologically and ecologically distinct subspecies of African buffaloes (Syncerus caffer cafer and S. c. nanus). Cytogenetically, a reduction in diploid chromosome numbers through centric fusion in derived karyotypes is accompanied by a loss of centromeric satellite DNA. The nilgai karyotype contains an apparent dicentric chromosome as evidenced by the sites of 1.715 hybridization. Telomeric sequences have been translocated to the centromeres without concomitant chromosomal rearrangement in Thompson's gazelle. C1 TEXAS A&M UNIV, TEXAS VET MED CTR, DEPT VET PATHOBIOL, COLLEGE STN, TX 77843 USA. TEXAS A&M UNIV, INST BIOSCI & TECHNOL, COLLEGE STN, TX 77843 USA. RP Modi, WS (reprint author), NCI, FREDERICK CANC RES & DEV CTR, SAIC FREDERICK, BIOL CARCINOGENESIS & DEV PROGRAM, FREDERICK, MD 21702 USA. NR 49 TC 73 Z9 76 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0022-2844 J9 J MOL EVOL JI J. Mol. Evol. PD MAR PY 1996 VL 42 IS 3 BP 337 EP 349 PG 13 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA UE491 UT WOS:A1996UE49100002 PM 8661995 ER PT J AU Ishitani, R Sunaga, K Hirano, A Saunders, P Katsube, N Chuang, DM AF Ishitani, R Sunaga, K Hirano, A Saunders, P Katsube, N Chuang, DM TI Evidence that glyceraldehyde-3-phosphate dehydrogenase is involved in age-induced apoptosis in mature cerebellar neurons in culture SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE glyceraldehyde-3-phosphate dehydrogenase; overexpression; neuronal apoptosis; antisense oligodeoxynucleotide; cerebellar granule cells ID RECEPTOR MESSENGER-RNA; PROGRAMMED CELL-DEATH; GRANULE CELLS; SKELETAL-MUSCLE; NERVOUS-SYSTEM; NITRIC-OXIDE; PROTEIN; SURVIVAL; RAT; IDENTIFICATION AB Under typical culture conditions, cerebellar granule cells die abruptly after 17 days in vitro. This burst of neuronal death involves ultrastructural changes and internucleosomal DNA fragmentations characteristic of apoptosis and is effectively arrested by pretreatment with actinomycin-D and cycloheximide. The level of a 38-kDa protein in the particulate fraction is markedly increased during age-induced cell death and by pretreatment with NMDA, which potentiates this cell death. Conversely, the age-induced increment of the 38-kDa particulate protein is suppressed by actinomycin-D and cycloheximide. N-terminal microsequencing of the 38-kDa protein revealed sequence identity with glyceraldehyde-3-phosphate dehydrogenase (GAPDH). A GAPDH antisense oligodeoxyribonucleotide blocks age-induced expression of the particulate 38-kDa protein and effectively inhibits neuronal apoptosis. In contrast, the corresponding sense oligonucleotide of GAPDH was completely ineffective in preventing the age-induced neuronal death and the 38-kDa protein overexpression. Moreover, the age-induced expression of the 38-kDa protein is preceded by a pronounced increase in the GAPDH mRNA level, which is abolished by actinomycin-D, cycloheximide, or the GAPDH antisense, but not sense, oligonucleotide, Thus, our results suggest that overexpression of GAPDH in the particulate fraction has a direct role in age-induced apoptosis of cerebellar neurons. C1 ONO PHARMACEUT CO LTD,MINASE RES INST,OSAKA,JAPAN. NIMH,BIOL PSYCHIAT BRANCH,MOLEC NEUROBIOL SECT,BETHESDA,MD 20892. RP Ishitani, R (reprint author), JOSAI UNIV,GRP CELLULAR NEUROBIOL,SAKADO,SAITAMA 35002,JAPAN. NR 43 TC 174 Z9 184 U1 0 U2 5 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 1996 VL 66 IS 3 BP 928 EP 935 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA TV786 UT WOS:A1996TV78600006 PM 8769851 ER PT J AU Tang, T Hirata, Y Whalin, M Guroff, G AF Tang, T Hirata, Y Whalin, M Guroff, G TI Nerve growth factor-stimulated nuclear S6 kinase in PC12 cells SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE PC12 cells; nerve growth factor; nuclear S6 kinase ID RIBOSOMAL-PROTEIN S6; PHOSPHORYLATION SITES; TYROSINE KINASE; RAT-LIVER; ACTIVATION; RAPAMYCIN; IDENTIFICATION; EXPRESSION; RECEPTOR; GENE AB Previous work has shown that nerve growth factor (NGF) stimulates the phosphorylation of the ribosomal protein S6 in PC12 cells. In this study, we show that S6 kinase activity is also present in purified PC12 cell nuclei. This activity was increased by treatment of the cells with NGF and, to a lesser extent, by treatment with epidermal growth factor. The NGF-stimulated activity was obtained from nuclear extracts and some of its characteristics described. The increase in activity was prevented by treatment of the cells with rapamycin or with wortmannin, and the overall activity could be precipitated by antibodies directed against the p85(S6K). These data indicate that p85(S6K) is the NGF-stimulated S6 kinase in PC12 cell nuclei. The presence of S6 protein in the nucleus of PC12 cells has been confirmed and evidence is presented that suggests that it is identical to a protein called SMP reported some years ago. C1 NICHHD, NIH, GROWTH FACTORS SECT, BETHESDA, MD 20892 USA. NR 48 TC 8 Z9 8 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 MAR PY 1996 VL 66 IS 3 BP 1198 EP 1206 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA TV786 UT WOS:A1996TV78600039 PM 8769884 ER PT J AU Schreurs, BG Oh, MM Alkon, DL AF Schreurs, BG Oh, MM Alkon, DL TI Pairing-specific long-term depression of Purkinje cell excitatory postsynaptic potentials results from a classical conditioning procedure in the rabbit cerebellar slice SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID NICTITATING-MEMBRANE RESPONSE; PARALLEL FIBER SYNAPSES; SYNAPTIC DEPRESSION; CLIMBING FIBER; INFERIOR OLIVE; LOBULE HVI; RECEPTORS; CORTEX; STIMULATION; INVITRO AB 1. Using a rabbit cerebellar slice preparation, we simulated a classical conditioning procedure by stimulating parallel fiber inputs to Purkinje cells with the use of a brief, high-frequency train of eight constant-current pulses 80 ms before climbing fiber inputs to the same Purkinje cell were stimulated with the use of a brief, lower frequency train of three constant-current pulses. In all experiments, we assessed the effects of stimulation by measuring the peak amplitude of Purkinje cell excitatory postsynaptic potentials (EPSPs) to single parallel fiber test pulses. 2. Intradendritically recorded Purkinje cell EPSPs underwent a long-term (>20 min) reduction in peak amplitude (30%) after paired stimulation of the parallel and climbing fibers but not after unpaired or parallel fiber alone stimulation. We call this phenomenon pairing-specific long-term depression (PSD). 3. Facilitation of the peak amplitude of a second EPSP elicited by a parallel fiber train occurred both before and after paired stimulation, suggesting that the locus of depression was not presynaptic. Depression of the peak amplitude of a depolarizing response to focal application of glutamate following pairings of parallel and climbing tiber stimulation added support to a suggested postsynaptic locus of the PSD effect. 4. The application of aniracetam potentiated EPSP peak amplitude by 40%, but these values returned to baseline as a result of pairings. With the removal of aniracetam from the bath 20 min after pairings, normal levels of pairing-specific EPSP depression were observed, indicating that the effect did not result from direct desensitization of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-proprionic acid (AMPA) receptors. 5. Incubation of slices in the protein kinase inhibitor H-7 potentiated EPSP peak amplitudes slightly (9%), but peak amplitudes returned to baseline levels after pairings. The net reduction in EPSP peak amplitude of < 10% after pairings suggested that H-7 partially blocked PSD and that, in turn, PSD involved protein kinases. 6. The means of induction and the specificity of those means suggest that the phenomenology of PSD is fundamentally different from that of long-term depression. PSD only occurs with pairings of trains of parallel fiber and climbing fiber stimulation; it occurs without the need for bicuculline; and it can overcome the blocking effects of aniracetam. 7. Nevertheless, the involvement of protein kinases and the potential role of calcium suggest that the mechanisms involved in the induction of PSD and long-term depression have a number of features in common. 8. Because of the pairing-specific nature of the long-term synaptic depression observed in these experiments, PSD provides a mechanism that may contribute to the role of the cerebellar cortex in classical conditioning. RP Schreurs, BG (reprint author), NINCDS,NIH,LAB ADAPT SYST,BLDG 36,RM B205,BETHESDA,MD 20892, USA. OI Schreurs, Bernard/0000-0002-5776-0807; Oh, Matthew/0000-0002-6702-5785 NR 44 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 MAR PY 1996 VL 75 IS 3 BP 1051 EP 1060 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA UA062 UT WOS:A1996UA06200008 PM 8867117 ER PT J AU Bowman, EM Aigner, TG Richmond, BJ AF Bowman, EM Aigner, TG Richmond, BJ TI Neural signals in the monkey ventral striatum related to motivation for juice and cocaine rewards SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID TWO-DIMENSIONAL PATTERNS; INFERIOR TEMPORAL CORTEX; NUCLEUS-ACCUMBENS NEURONS; SINGLE UNITS; TEGMENTAL AREA; VISUAL-CORTEX; D-AMPHETAMINE; INFORMATION; RESPONSES; STIMULATION AB 1. The results of neuropsychological, neuropharmacological, and neurophysiological experiments have implicated the ventral striatum in reward-related processes. We designed a task to allow us to separate the effects of sensory, motor, and internal signals so that we could study the correlation between the activity of neurons in the ventral striatum and different motivational states. In this task, a visual stimulus was used to cue the monkeys as to their progress toward earning a reward. The monkeys performed more quickly and with fewer mistakes in the rewarded trials. After analyzing the behavioral results from three monkeys, we recorded from 143 neurons from two of the monkeys while they performed the task with either juice or cocaine reward. 2. In this task the monkey was required to release its grip on a bar when a small visual response cue changed colors from red (the wait signal) to green (the go signal). The duration of the wait signal was varied randomly. The cue became blue whenever the monkey successfully responded to the go signal within 1 s of its appearance. A reward was delivered after the monkey successfully completed one, two, or three trials. The schedules were randomly interleaved. A second visual stimulus that progressively brightened or dimmed signaled to the monkeys their progress toward earning a reward. This discriminative cue allowed the monkeys to judge the proportion of work remaining in the current ratio schedule of reinforcement. Data were collected from three monkeys while they performed this task. 3. The average reaction times became faster and error rates declined as the monkeys progressed toward completing the current schedule of reinforcement and thereby earning a reward, whereas the modal reaction time did not change. As the duration of the wait period before the go signal increased, the monkeys reacted more quickly but their error rates scarcely changed. From these results we infer that the effects of motivation and motor readiness in this task are generated by separate mechanisms rather than by a single mechanism subserving generalized arousal. 4. The activity of 138 ventral striatal neurons was sampled in two monkeys while they performed the task to earn juice reward. We saw tonic changes in activity throughout the trials, and we saw phasic activity following the reward. The activity of these neurons was markedly different during juice-rewarded trials than during correctly performed trials when no reward was forthcoming (or expected). The responses also were weakly, but significantly, related to the proximity of the reward in the schedules requiring more than one trial. 5. The monkeys worked to obtain intravenous cocaine while we recorded 62 neurons. For 57 of the neurons, we recorded activity while the monkeys worked in blocks of trials during which they self-administered cocaine after blocks during which they worked for juice. Although fewer neurons responded to cocaine than to juice reward (19 vs. 33%), this difference was not significant. The neuronal response properties to cocaine and juice rewards were independent; that is, the responses when one was the reward one failed to predict the response when the other was the reward. In addition, the neuronal activity lost most of its selectivity for rewarded trials, i.e, the activity did not distinguish nearly as well between cocaine and sham rewards as between juice and sham rewards. 6. Our results show that mechanisms by which cocaine acts do not appear to be the same as the ones activated when the monkeys were presented with an oral juice reward. This finding raises the intriguing possibility that the effects of cocaine could be reduced selectively without blocking the effects of many natural rewards. C1 NIMH,NIH,NEUROPSYCHOL LAB,BETHESDA,MD 20892. RI Bowman, Eric/A-3780-2010 NR 45 TC 181 Z9 182 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAR PY 1996 VL 75 IS 3 BP 1061 EP 1073 PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA UA062 UT WOS:A1996UA06200009 PM 8867118 ER PT J AU Meunier, M Hadfield, W Bachevalier, J Murray, EA AF Meunier, M Hadfield, W Bachevalier, J Murray, EA TI Effects of rhinal cortex lesions combined with hippocampectomy on visual recognition memory in rhesus monkeys SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID INFERIOR TEMPORAL CORTEX; BRAIN-LESIONS; TERM-MEMORY; AMYGDALA; ASSOCIATION; IMPAIRMENT; ANTERIOR; CORTICES; MACAQUES; RECENCY AB 1. We assessed the visual recognition abilities, as measured by delayed nonmatching-to-sample with trial-unique objects, of rhesus monkeys with hippocampectomy (i.e., removal of the hippocampal formation plus parahippocampal gyrus) combined with ablations of the rhinal cortex (i.e., entorhinal cortex plus perirhinal cortex). 2. Relative to unoperated controls, monkeys with combined hippocampectomy and rhinal cortex ablation (H+Rh) were significantly impaired in visual recognition. 3. Comparison of the scores of the monkeys in the present H+Rh group, which sustained near-complete rhinal cortex damage, with the scores of monkeys in an earlier H+Rh group in which the rostral part of the rhinal cortex had been spared indicates that the magnitude of the impairment is greater in the group with the more complete rhinal cortex damage. This finding is consistent with the idea that the rhinal cortex is critical for visual recognition. 4. Comparison of the present results with those from an earlier study on visual recognition that employed lesions limited to the rhinal cortex (Rh group) shows, paradoxically, that adding removal of the hippocampal formation and parahippocampal gyrus to a rhinal cortex lesion significantly reduces the recognition impairment produced by rhinal cortex lesions atone. 5. Our findings do not fit the view that the hippocampal formation, parahippocampal gyrus, and rhinal cortex constitute parts of a single functional system, such that the greater the damage to the entire system, the more severe the impairment. Instead, the results are consistent with the view thar there are multiple functional subdivisions within the medial temporal lobe. C1 NIMH, NEUROPSYCHOL LAB, BETHESDA, MD 20892 USA. RI MEUNIER, Martine/C-2611-2015; OI MEUNIER, Martine/0000-0002-9380-9372; Murray, Elisabeth/0000-0003-1450-1642 NR 44 TC 104 Z9 104 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 MAR PY 1996 VL 75 IS 3 BP 1190 EP 1205 PG 16 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA UA062 UT WOS:A1996UA06200019 PM 8867128 ER PT J AU Morris, PLP Robinson, RG deCarvalho, ML Albert, P Wells, JC Samuels, JF EdenFetzer, D Price, TR AF Morris, PLP Robinson, RG deCarvalho, ML Albert, P Wells, JC Samuels, JF EdenFetzer, D Price, TR TI Lesion characteristics and depressed mood in the stroke data bank study SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID HEMISPHERIC CEREBRAL INFARCTION; POSTSTROKE DEPRESSION; DISORDERS; LOCATION; RECOVERY; RAT AB This study examined the relationship between poststroke lesion size and location and depressed mood by using data from the multicenter National Stroke Data Bank. For inpatients with first-ever cerebral infarction, lesions were characterized by location and size from CT scans. Forty-seven (24%) of the 193 patients studied were depressed. In the complete sample, neither lesion size nor location was associated with depression. However, among patients with comparable small-sized lesions (n = 124), depression was more frequent among those with left hemisphere stroke than those with right hemisphere stroke (31% vs. 16%; P = 0.04). Among patients with larger lesions, brain edema was common and may have obscured lateralized findings. Different biogenic amine neurotransmitter responses to right and left hemisphere brain injury may underlie this mood asymmetry. C1 UNIV IOWA,COLL MED,DEPT PSYCHIAT,IOWA CITY,IA 52242. UNIV MELBOURNE,DEPT PSYCHIAT,PARKVILLE,VIC 3052,AUSTRALIA. NIH,DIV BIOMETRY,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,DEPT PSYCHIAT,BALTIMORE,MD. UNIV MARYLAND,DEPT NEUROL,COLLEGE PK,MD 20742. OI Samuels, Jack/0000-0002-6715-7905 FU NIMH NIH HHS [MH00165, MH40355]; NINDS NIH HHS [NS15128] NR 29 TC 49 Z9 50 U1 0 U2 1 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD SPR PY 1996 VL 8 IS 2 BP 153 EP 159 PG 7 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA UG910 UT WOS:A1996UG91000004 PM 9081550 ER PT J AU George, MS Wassermann, EM Williams, WA Steppel, J PascualLeone, A Basser, P Hallett, M Post, RM AF George, MS Wassermann, EM Williams, WA Steppel, J PascualLeone, A Basser, P Hallett, M Post, RM TI Changes in mood and hormone levels after rapid-rate transcranial magnetic stimulation (rTMS) of the prefrontal cortex SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID CEREBRAL BLOOD-FLOW; BRAIN INJURY; EMISSION TOMOGRAPHY; MAJOR DEPRESSION; INDUCTION; DISORDERS; SAFETY; MANIA AB Rapid-rate transcranial magnetic stimulation (rTMS) tons administered to 10 healthy volunteers on different days over the right or left prefrontal cortex, midfrontal cortex, occipital cortex, or cerebellum. Mood (self-rated), reaction time, and hormone levels were serially measured. Consistent with a previous study, comparison of hemispheres revealed significant associations with decreased happiness after left prefrontal rTMS and decreased sadness after right prefrontal rTMS. Stimulation of all three prefrontal regions, but not the occipital or cerebellar regions, was associated with increases in serum thyroid-stimulating hormone. There was no effect on serum prolactin. rTMS applied to prefrontal cortex is safe and well tolerated and produces regionally and laterally specific changes in mood and neuroendocrine measures in healthy adults. rTMS is a promising tool for investigating prefrontal cortex functions. C1 MED UNIV S CAROLINA, DEPT PSYCHIAT, CHARLESTON, SC 29425 USA. MED UNIV S CAROLINA, DEPT NEUROL, CHARLESTON, SC 29425 USA. NIMH, BIOL PSYCHIAT BRANCH, ROCKVILLE, MD 20857 USA. NINCDS, HUMAN MOTOR CONTROL SECT, NIH, BETHESDA, MD 20892 USA. NIH, BIOMED ENGN & INSTRUMENTAT PROGRAM, NATL CTR RES & RESOURCES, BETHESDA, MD USA. RP George, MS (reprint author), MED UNIV S CAROLINA, DEPT RADIOL, 171 ASHLEY AVE, CHARLESTON, SC 29425 USA. RI Pascual-Leone, Alvaro/G-6566-2011; Basser, Peter/H-5477-2011 NR 61 TC 224 Z9 229 U1 5 U2 14 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD SPR PY 1996 VL 8 IS 2 BP 172 EP 180 PG 9 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA UG910 UT WOS:A1996UG91000007 PM 9081553 ER PT J AU Behar, TN Li, YX Tran, HT Ma, W Dunlap, V Scott, C Barker, JL AF Behar, TN Li, YX Tran, HT Ma, W Dunlap, V Scott, C Barker, JL TI GABA stimulates chemotaxis and chemokinesis of embryonic cortical neurons via calcium-dependent mechanisms SO JOURNAL OF NEUROSCIENCE LA English DT Article DE migration; development; cerebral cortex; GABA receptor; calcium; rat ID GROWTH-FACTOR; PRENATAL DEVELOPMENT; CEREBRAL-CORTEX; CELL-MIGRATION; A-RECEPTOR; RAT-BRAIN; EXPRESSION; NEUTROPHIL; NEOCORTEX; CHEMOATTRACTANTS AB During rat cortical development, when neurons migrate from the ventricular zone to the cortical plate, GABA localizes within the target destinations of migratory neurons. At this time, cells in germinal zones and along migratory pathways express GABA receptor subunit transcripts, implying that in vivo, GABA may be a chemoattractant. We used an in vitro strategy to study putative chemotropic effects of GABA on embryonic rat cortical cells. GABA stimulated neuronal migration in vitro at embryonic day 15 (E15). From E16 onward, two concentration ranges (fM and mu M) induced motility. Femtomolar GABA primarily stimulated chemotaxis (migration along a chemical gradient), whereas micromolar GABA predominantly initiated chemokinesis (increased random movement). These effects were mimicked by structural analogs of GABA with relative specificity at GABA(A) (muscimol), GABA(B) (R-baclofen), and GABA(C) (trans- or cis-4-aminocrotonic acid) receptors. Antagonists of GABA(B) (saclofen) and GABA(C) (picrotoxin) receptors partially inhibited responses to both femto- and micromolar GABA; however, only responses to femtomolar GABA were partially blocked by bicuculline, a well established antagonist of GABA at GABA(A) receptors. Hence, chemotactic responses to femtomolar GABA seem to involve all three classes of GABA receptor proteins, whereas chemokinetic responses to micromolar GABA involve GABA(B) and GABA(C) receptor proteins. GABA-induced motility was blocked by loading the cells with the Ca2+-chelating molecule bis(2-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid, suggesting that intracellular Ca2+ mediates GABA-induced cell movement. Optical recordings of cells loaded with Ca2+ indicator dye revealed that both femto- and micromolar GABA evoked increases in intracellular Ca2+ Thus, GABA-stimulated increases in intracellular Ca2+ may mediate both chemotactic and chemokinetic responses in embryonic cortical cells. RP Behar, TN (reprint author), NINCDS,NEUROPHYSIOL LAB,NIH,BLDG 36,ROOM 2C02,BETHESDA,MD 20892, USA. NR 45 TC 286 Z9 287 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAR 1 PY 1996 VL 16 IS 5 BP 1808 EP 1818 PG 11 WC Neurosciences SC Neurosciences & Neurology GA TW143 UT WOS:A1996TW14300022 PM 8774448 ER PT J AU Bartoszewicz, ZP Lauter, CJ Quarles, RH AF Bartoszewicz, ZP Lauter, CJ Quarles, RH TI The myelin-associated glycoprotein of the peripheral nervous system in trembler mutants contains increased alpha 2-3 sialic acid and galactose SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE glycoprotein; myelin; myelin-associated glycoprotein; sialic acid; trembler mice ID QUAKING MOUSE; PROTEIN; MICE; BRAIN; ANTIBODIES; EXPRESSION; MUTATION; CARRIES; GENE; P0 AB The myelin-associated glycoprotein (MAG) exhibits an abnormally high apparent molecular weight in sciatic nerve, but not in brain, of dysmyelinating trembler mutants (Inuzuka et al.: J Neurochem 44:793-797, 1985). Antibodies to the large and small isoforms of MAG (L- and S-MAG) and probes for oligosaccharide structure were used to determine if this was due to overexpression of L-MAG or increased glycosylation. Nerves from both control and trembler 36-day-old mice contained primarily S-MAG with only traces of L-MAG. The distribution of the two isoforms appeared normal in trembler mice, and both isoforms exhibited the higher apparent molecular weight, Lectin binding showed that, in contrast to brain in which most glycoproteins contain primarily alpha 2-3 linked sialic acid, most glycoproteins of both control and trembler nerve contained primarily alpha 2-6 linked sialic acid, Lectin binding and glycosidase treatments demonstrated that the higher molecular weight of MAG in trembler nerves was due to an increased content of alpha 2-3 linked sialic acid and galactose, The abnormal glycosylation of MAG in trembler mutants may contribute to the myelin pathology. (C) 1996 Wiley-Liss, Inc. C1 NINCDS,NIH,MOLEC & CELLULAR NEUROBIOL LAB,MYELIN & BRAIN DEV SECT,BETHESDA,MD 20892. NR 29 TC 11 Z9 11 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD MAR 1 PY 1996 VL 43 IS 5 BP 587 EP 593 PG 7 WC Neurosciences SC Neurosciences & Neurology GA TY122 UT WOS:A1996TY12200008 PM 8833093 ER PT J AU Zunkeler, B Carson, RE Olson, J Blasberg, RG Girton, M Bacher, J Herscovitch, P Oldfield, EH AF Zunkeler, B Carson, RE Olson, J Blasberg, RG Girton, M Bacher, J Herscovitch, P Oldfield, EH TI Hyperosmolar blood-brain barrier disruption in baboons: An in vivo study using positron emission tomography and rubidium-82 SO JOURNAL OF NEUROSURGERY LA English DT Article DE blood-brain barrier disruption; positron emission tomography; capillary permeability; plasma volume; mathematical models; mannitol; baboon ID TO-TUMOR TRANSPORT; EXPERIMENTAL RG-2 GLIOMAS; RB-82; FLOW; PERMEABILITY; CHEMOTHERAPY; METHOTREXATE; PHARMACOKINETICS; DEXAMETHASONE; CAPILLARY AB Hyperosmolar blood-brain barrier (BBB) disruption remains controversial as an adjuvant therapy to increase delivery of water-soluble compounds to extracellular space in the brain in patients with malignant brain tumors. To understand the physiological effects of BBB disruption more clearly, the authors used positron emission tomography (PET) to study the time course of BBB permeability in response to the potassium analog rubidium-82 (Rb-82, halflife 75 seconds) following BBB disruption in anesthetized adult baboons. Mannitol (25%) was injected into the carotid artery and PET scans were performed before and serially at 8- to 15-minute intervals after BBB disruption. The mean influx constant (K-1), a measure of permeability-surface area product, in ipsilateral, mannitol-perfused mixed gray and white-matter brain regions was 4.9 +/- 2.4 mu l/min/ml (+/- standard deviation) at baseline and increased more than 100% (Delta K-1 = 9.4 +/- 5.1 mu l/min/ml, 18 baboons) in brain perfused by mannitol. The effect of BBB disruption on K-1 correlated directly with the total amount of mannitol administered (p < 0.005). Vascular permeability returned to baseline with a halftime of 24.0 +/- 14.3 minutes. The mean brain plasma volume rose by 0.57 +/- 0.34 ml/100 mi in ipsilateral perfused brain following BBB disruption. This work provides a basis for the in vivo study of permeability changes induced by BBB disruption in human brain and brain tumors. C1 NINCDS, NIH, SURG NEUROL BRANCH, BETHESDA, MD 20892 USA. NIH, POSITRON EMISS TOMOG DEPT, BETHESDA, MD USA. NIH, CTR CLIN, DEPT DIAGNOST RADIOL, BETHESDA, MD USA. NIH, VET RESOURCES PROGRAM, BETHESDA, MD USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 38 TC 17 Z9 17 U1 1 U2 2 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD MAR PY 1996 VL 84 IS 3 BP 494 EP 502 DI 10.3171/jns.1996.84.3.0494 PG 9 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA TW713 UT WOS:A1996TW71300019 PM 8609564 ER PT J AU Mills, JL Scott, JM Kirke, PN McPartlin, JM Conley, MR Weir, DG Molloy, AM Lee, YJ AF Mills, JL Scott, JM Kirke, PN McPartlin, JM Conley, MR Weir, DG Molloy, AM Lee, YJ TI Homocysteine and neural tube defects SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Ceres Forum Program on Making Health Claims Work, Fortifying Policy with Science - The Case of Folate CY JUN 04, 1995 CL GEORGETOWN UNIV, WASHINGTON, DC SP Ceres Forum, Amer Inst Nutr HO GEORGETOWN UNIV DE neural tube defect; folic acid; folate; homocysteine; birth defect ID PERICONCEPTIONAL VITAMIN SUPPLEMENTATION; AMNIOTIC-FLUID; FOLATE; PREGNANCIES; METHIONINE; PREVENTION; METABOLISM; INFANTS; SERUM AB It is now well established that folic acid, when taken periconceptionally, can prevent many neural tube defects. It is also becoming clear that folic acid does not work by correcting a nutritional deficiency in pregnant women. Rather, it appears that a metabolic defect is responsible for these neural tube defects and that this defect or defects can be corrected by a sufficiently large dose of folic acid. Our recent work demonstrates that homocysteine metabolism is likely to be the critical pathway affected by folic acid. We have demonstrated significantly higher homocysteine levels in women carrying affected fetuses than in control women. These findings indicate that one of the enzymes responsible for homocysteine metabolism is likely to be abnormal in affected pregnancies. Animal studies suggest that the conversion of homocysteine to methionine could be the critical step. Rat embryos in culture require methionine for neural tube closure. Methionine synthase, cystathionine synthase, and 5,10 methylene tetrahydrofolate reductase are all important in the metabolism of homocysteine in humans. If methionine synthase is the critical enzyme, it would raise the interesting public health issue that vitamin B-12 might be able to stimulate the abnormal enzyme as folic acid does. Adding vitamin B-12 might make it possible to reduce the dose of folic acid required in fortified food, thus allaying concerns about overexposure to folic acid. C1 TRINITY COLL DUBLIN,DEPT BIOCHEM,DUBLIN,IRELAND. HLTH RES BOARD IRELAND,DUBLIN,IRELAND. TRINITY COLL DUBLIN,DEPT CLIN MED,DUBLIN,IRELAND. RP Mills, JL (reprint author), NICHHD,NIH,PEDIAT EPIDEMIOL SECT,DIV EPIDEMIOL STAT & PREVENT RES,6100 BLDG,ROOM 7B03,BETHESDA,MD 20892, USA. NR 28 TC 28 Z9 29 U1 0 U2 2 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3166 J9 J NUTR JI J. Nutr. PD MAR PY 1996 VL 126 IS 3 BP S756 EP S760 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA TZ111 UT WOS:A1996TZ11100020 PM 8598561 ER PT J AU McCrae, RR Zonderman, AB Bond, MH Costa, PT Paunonen, SV AF McCrae, RR Zonderman, AB Bond, MH Costa, PT Paunonen, SV TI Evaluating replicability of factors in the revised NEO personality inventory: Confirmatory factor analysis versus procrustes rotation SO JOURNAL OF PERSONALITY AND SOCIAL PSYCHOLOGY LA English DT Article; Proceedings Paper CT 102nd Annual Convention of the American-Psychological-Association CY AUG 12-16, 1994 CL LOS ANGELES, CA SP Amer Psychol Assoc ID COMMON FACTOR-ANALYSIS; 5-FACTOR MODEL; FACET SCALES; SAMPLE-SIZE; TRAITS; NUMBER; CONSCIENTIOUSNESS; AGREEABLENESS; DIMENSIONS; CONGRUENCE AB Despite the empirical robustness of the 5-factor model of personality, recent confirmatory factor analyses (CFAs) of NEO Personality Inventory (NEO-PI) data suggest they do not fit the hypothesized model. In a replication study of 229 adults, a series of CFAs showed that Revised NEO-PI scales are not simple-structured but do approximate the normative 5-factor structure. CFA goodness-of-fit indices, however, were not high. Comparability analyses showed that no more than 5 factors were replicable, which calls into question some assumptions underlying the use of CFA. An alternative method that uses targeted rotation was presented and illustrated with data from Chinese and Japanese versions of the Revised NEO-PI that clearly replicated the 5-factor structure. C1 CHINESE UNIV HONG KONG,DEPT PSYCHOL,HONG KONG,HONG KONG. UNIV WESTERN ONTARIO,DEPT PSYCHOL,LONDON,ON,CANADA. RP McCrae, RR (reprint author), NIA,GERONTOL RES CTR,NIH,PERSONAL STRESS & COPING SECT,LAB PERSONAL & COGN,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. OI Costa, Paul/0000-0003-4375-1712; Zonderman, Alan B/0000-0002-6523-4778 NR 77 TC 457 Z9 462 U1 4 U2 26 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0022-3514 J9 J PERS SOC PSYCHOL JI J. Pers. Soc. Psychol. PD MAR PY 1996 VL 70 IS 3 BP 552 EP 566 DI 10.1037/0022-3514.70.3.552 PG 15 WC Psychology, Social SC Psychology GA TZ883 UT WOS:A1996TZ88300011 ER PT J AU Morita, K Teraoka, K Oka, M Levine, M AF Morita, K Teraoka, K Oka, M Levine, M TI Inhibitory action of palytoxin on ascorbic acid transport into cultured bovine adrenal chromaffin cells SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID NOREPINEPHRINE BIOSYNTHESIS; HUMAN-NEUTROPHILS; GLUCOSE; FIBROBLASTS; MECHANISM; RELEASE; DEPOLARIZATION; MEMBRANE; SODIUM; AXONS AB The effect of palytoxin on the transport of ascorbic acid into cultured bovine adrenal chromaffin cells was examined by measuring the accumulation of radiolabeled ascorbic acid within cells. Ascorbic acid transport into these cells was inhibited by palytoxin in a concentration-dependent manner, and this inhibitory action of palytoxin was shown to be noncompetitive and irreversible. Neither the Na+/K+-pump activity in the intact cells nor the Na+,K+-adenosine 5'-triphosphatase activity in the plasma membranes was significantly influenced by this toxin at concentrations inhibiting ascorbic acid transport. In contrast to the effect of palytoxin on ascorbic acid transport, glucose transport into these cells was not significantly affected by this toxin. These findings indicate that palytoxin can inhibit ascorbic acid transport into adrenal chromaffin cells without affecting the Na+,K+-adenosine 5'-triphosphatase activity in the plasma membranes. Furthermore, because palytoxin discriminated between ascorbic acid transport and glucose transport, the data provide new evidence that the transport of ascorbic acid and that of glucose may be mediated by different mechanisms in the adrenal medullary cell. C1 UNIV TOKUSHIMA,SCH MED,DEPT PHARMACOL,KURAMOTO,TOKUSHIMA,JAPAN. NIDDKD,NIH,CELL BIOL & GENET LAB,BETHESDA,MD 20892. NR 32 TC 3 Z9 3 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD MAR PY 1996 VL 276 IS 3 BP 996 EP 1001 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TZ544 UT WOS:A1996TZ54400019 PM 8786581 ER PT J AU Jeong, TC Jordan, SD Matulka, RA Stanulis, ED Park, SS Holsapple, MP AF Jeong, TC Jordan, SD Matulka, RA Stanulis, ED Park, SS Holsapple, MP TI Immunosuppression induced by acute exposure to cocaine is dependent on metabolism by cytochrome P-450 SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID INDUCED HEPATIC-NECROSIS; INDUCED HEPATOTOXICITY; N-NITROSODIMETHYLAMINE; MONOCLONAL-ANTIBODIES; REACTIVE METABOLITES; HUMORAL IMMUNITY; PROTEIN-BINDING; RAT-LIVER; MICE; ETHANOL AB The primary objective of this paper was to characterize the role of metabolism in immunosuppression by acute exposure to cocaine. beta-Ionone has been used to study the role of metabolism in hepatotoxicity associated with acute exposure to cocaine, and was shown to produce a greater effect than other cytochrome P-450 (P-450) inducers. When beta-ionone (600 mg/kg s.c.) was pretreated 72 and 48 hr before the acute administration of cocaine (30 mg/kg i.p.) in B6C3F1 female mice, the antibody response to sheep red blood cells was significantly suppressed, Exposure to cocaine alone produced little or no suppression. The immunosuppression in cocaine + beta-ionone-treated mice was accompanied by a decrease in thymus weight and an increase in liver weight. Administration of metyrapone (40 mg/kg i.p.) 30 min before cocaine administration (40 mg/kg) blocked completely the suppression of the antibody response by cocaine in beta-ionone-pretreated mice. The reversal by metyrapone was additional evidence that a P-450 pathway was the critical metabolic pathway of cocaine to be immunosuppressive, and the inhibitory effect of metyrapone on cocaine N-demethylase was confirmed in liver microsomes. The inductive effects of beta-ionone were also characterized further. Cocaine N-demethylase activity was significantly induced by beta-ionone. The induction of P-450IIB1/2, the only isozyme shown previously to be associated with the hepatotoxicity by cocaine, was demonstrated by Western immunoblotting to be induced by beta-ionone at doses as low as 300 mg/kg; but was less than the induction associated with phenobarbital. Studies confirmed that acute exposure to cocaine also was immunosuppressive in phenobarbital-pretreated mice. Taken together, our present results suggest that the immunosuppression by acute exposure to cocaine is associated with the increased metabolism of cocaine to toxic metabolites by P-450, probably P-450IIB1/2, as demonstrated previously for its hepatotoxicity. C1 VIRGINIA COMMONWEALTH UNIV, MED COLL VIRGINIA, DEPT PHARMACOL & TOXICOL, RICHMOND, VA 23298 USA. KOREA RES INST CHEM TECHNOL, TAEJON 305606, SOUTH KOREA. NCI, FREDERICK CANC RES & DEV CTR, COMPARAT CARCINOGENESIS LAB, FREDERICK, MD 21702 USA. FU NIDA NIH HHS [DA 08161]; NIEHS NIH HHS [ES 07087] NR 41 TC 16 Z9 16 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD MAR PY 1996 VL 276 IS 3 BP 1257 EP 1265 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA TZ544 UT WOS:A1996TZ54400050 PM 8786558 ER PT J AU Gift, HC AF Gift, HC TI Quality of life - An outcome of oral health care? SO JOURNAL OF PUBLIC HEALTH DENTISTRY LA English DT Editorial Material ID INDICATORS; RATINGS; IMPACT RP Gift, HC (reprint author), NIDR,NIH,45 CTR DR,3AN-44D,BETHESDA,MD 20892, USA. NR 13 TC 13 Z9 13 U1 0 U2 0 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 SPR PY 1996 VL 56 IS 2 BP 67 EP 68 DI 10.1111/j.1752-7325.1996.tb02398.x PG 2 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA VB866 UT WOS:A1996VB86600001 PM 8863288 ER PT J AU Gift, HC Drury, TF NowjackRaymer, RE Selwitz, RH AF Gift, HC Drury, TF NowjackRaymer, RE Selwitz, RH TI The state of the nation's oral health: Mid-decade assessment of Healthy People 2000 SO JOURNAL OF PUBLIC HEALTH DENTISTRY LA English DT Article DE Healthy People 2000; Third National Health and Nutrition Examination Survey; prevention; dental caries; dental sealants; tooth loss; edentulousness; dental utilization ID PUBLIC KNOWLEDGE AB Objectives: This communication reviews the history and process of establishing and assessing national health objectives, presents the status of oral health objectives in Healthy People 2000, and summarizes major issues related to the outlook for the nation's oral health from the perspectives of participants in a July 1995 briefing session with the US Assistant Secretary for Health. Methods: Data obtained from sources such as the third National Health and Nutrition Examination Survey-Phase I, the 1991 Indian Health Service Survey, and 1989-92 National Health Interview Surveys were examined in relation to specific indicators and populations defined at baseline using mid-1980s data. Results: Examination of baseline measures and progress data shows that the indicators for objectives are, for the most part, stable or improving slightly. Deaths due to oral cancer have decreased. Edentulousness is declining. Placement of dental sealants on children's teeth is increasing. Adult dental visits are on the expected course. Little change has been observed in water fluoridation. Apparent declines in dental visits and increases in untreated dental decay for young children are potential concerns. Four objectives have no data for progress evaluation. Conclusions: The persistent and often dramatic race-ethnicity and socioeconomic differences on many objectives, in combination with possible alterations in the public health infrastructure, indicate that concentrated and collaborative efforts are needed to achieve Healthy People 2000 targets. C1 NIDR,NIH,DIV EPIDEMIOL & ORAL DIS PREVENT,DIS PREVENT & HLTH PROMOT BRANCH,BETHESDA,MD 20892. RP Gift, HC (reprint author), NIDR,NIH,BLDG 45,3AN-44D,BETHESDA,MD 20892, USA. NR 29 TC 20 Z9 21 U1 0 U2 2 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 SPR PY 1996 VL 56 IS 2 BP 84 EP 91 DI 10.1111/j.1752-7325.1996.tb02402.x PG 8 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA VB866 UT WOS:A1996VB86600005 PM 8863292 ER PT J AU Wilder, RL AF Wilder, RL TI Adrenal and gonadal steroid hormone deficiency in the etiopathogenesis of rheumatoid arthritis SO JOURNAL OF RHEUMATOLOGY LA English DT Article; Proceedings Paper CT Meeting on Rheumatoid Arthritis - The Status and Future of Combination Therapy CY JUL 13-15, 1995 CL CHATHAM, MA SP Sandoz Pharm DE cortisol; progesterone; dehydroepiandrosterone; testosterone; estrogen; pregnancy AB Rheumatoid arthritis (RA) is a multifactorial disease in which both environmental and genetic factors play a role. Data also suggest that neuroendocrine factors are involved, I briefly summarize observations that support this hypothesis. RA is characterized by striking age-sex disparities, The incidence of disease in women increases steadily from the age of menarche to its maximal incidence around menopause. The disease is uncommon in men under age 45, but its incidence increases rapidly in older men and approaches the incidence in women. These observations strongly suggest that androgens play a major suppressive role, and, in fact, testosterone levels are depressed in most men with RA. Mechanistically, many data indicate that testosterone suppresses both cellular and humoral immune: responses, Dehydroepiandrosterone (DHEA), an adrenal product, is the major androgen in women. Its production is strikingly dependent upon age, Peak production is in the 2nd and 3rd decades, but levels decline precipitously thereafter. DHEA levels are low in both men and women with RA, and recent data show that levels of this hormone may be depressed before the onset of disease, The role of DHEA in immune diseases, however, is controversial. The menopausal peak of RA onset suggests estrogen and/or progesterone deficiency play a role in the disease, and many data indicate that estrogens suppress cellular immunity but stimulate humoral immunity, i.e., deficiency promotes cellular (Th1-type) immunity. Recent data also indicate that progesterone stimulates a switch for Th1 to Th2-type immune responses. RA often develops or flares in the postpartum period, particularly if the mother breastfeeds. This is again consistent with gonadal steroid deficiency playing a role in the onset of disease. Breastfeeding is associated with blunted hypothalamic-pituitary-adrenal function and elevated prolactin synthesis, Gonadal and adrenal steroid hormone deficiency, plus elevated prolactin, probably greatly facilitates the expression of Th1-type immunity, which is widely believed to be critical in the pathogenesis of RA, By contrast, RA typically remits during pregnancy, in parallel with the increasing levels of corticosteroids, estrogens, and progesterone. Pregnancy is characterized by a shift in immune function from Th1-type to Th2-type. Oral contraceptives, which generate a condition of pseudopregnancy, also decrease the risk of RA. These data argue that adrenal and gonadal steroid hormones suppress the development of RA. Several studies indicate that corticosteroid production is inappropriately low in patients with RA, and are reminiscent of observations in Lewis rat models of chronic erosive arthritis, In summary, a growing body of data indicate that RA develops as a consequence of a deficiency in both adrenal and gonadal steroid hormone production. This hypothesis clearly has potential clinical implications. RP Wilder, RL (reprint author), NIAMS,NIH,INFLAMMATORY JOINT DIS SECT,BLDG 10,ROOM 9N240,BETHESDA,MD 20892, USA. NR 9 TC 15 Z9 16 U1 1 U2 1 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 MAR PY 1996 VL 23 SU 44 BP 10 EP 12 PG 3 WC Rheumatology SC Rheumatology GA TZ688 UT WOS:A1996TZ68800004 ER PT J AU Steven, AC Baumeister, W AF Steven, AC Baumeister, W TI Untitled SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Editorial Material C1 MAX PLANCK INST BIOCHEM,D-82152 MARTINSRIED,GERMANY. RP Steven, AC (reprint author), NIAMSD,STRUCT BIOL LAB,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD MAR-APR PY 1996 VL 116 IS 2 BP 251 EP 252 DI 10.1006/jsbi.1996.0039 PG 2 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA UG933 UT WOS:A1996UG93300001 ER PT J AU Heck, DV Trus, BL Steven, AC AF Heck, DV Trus, BL Steven, AC TI Three-dimensional structure of Bordetella pertussis fimbriae SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article ID FILAMENTOUS HEMAGGLUTININ; GENE; PILI; PURIFICATION; CLONING; SUBUNIT AB We describe the helical structure of Bordetella pertussis fimbriae of serotype 3/6 as determined to a resolution of similar to 2.5 nm by three-dimensional reconstruction of negatively stained electron micrographs, The fimbria has a distinctly polar structure whose axial repeat of 13 nm contains five copies of the fim3 gene product (22 kDa) in two complete turns, These subunits are connected by interactions along the fimbrial backbone which, unlike other classes of bacterial fimbriae, has no axial channel, Its outer diameter is similar to 5.7 nm, and the most pronounced feature is a radially protruding domain that gives the fimbria its characteristic serrated appearance. Serotype 2 fimbriae, composed of the fim2 subunit which is 60% homologous with fim3, have essentially the same quaternary structure, These observations are discussed in relation to fimbrial phase variation and structure-based classification of fimbriae/pili. (C) 1996 Academic Press, Inc. C1 NIAMSD,NIH,STRUCT BIOL LAB,BETHESDA,MD 20892. NIH,DIV COMP RES & TECHNOL,COMPUTAT BIOSCI & ENGN LAB,BETHESDA,MD 20892. NR 37 TC 14 Z9 16 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD MAR-APR PY 1996 VL 116 IS 2 BP 264 EP 269 DI 10.1006/jsbi.1996.0041 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA UG933 UT WOS:A1996UG93300003 PM 8812982 ER PT J AU Putnam, FW AF Putnam, FW TI The multiple personality debate - Reply SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Letter RP Putnam, FW (reprint author), NIMH,BETHESDA,MD 20892, 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 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAR PY 1996 VL 35 IS 3 BP 262 EP 263 DI 10.1097/00004583-199603000-00005 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA TW743 UT WOS:A1996TW74300005 ER PT J AU Dorn, LD Burgess, ES Dichek, HL Putnam, FW Chrousos, GP Gold, PW AF Dorn, LD Burgess, ES Dichek, HL Putnam, FW Chrousos, GP Gold, PW TI Thyroid hormone concentrations in depressed and nondepressed adolescents: Group differences and behavioral relations SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE thyroid; depression; adolescents ID THYROTROPIN-RELEASING-HORMONE; STIMULATING HORMONE; PSYCHIATRIC-PATIENTS; L-TRIIODOTHYRONINE; AFFECTIVE-ILLNESS; THYROXINE; POTENTIATION; DISORDERS; TRH; PERSPECTIVE AB Objective: To examine thyroid hormone concentrations and the influence of these hormones on mood and problem behaviors in adolescents with depression. Method: The sample included 21 depressed adolescents and 20 matched control adolescents. Blood was drawn to measure thyroid-stimulating hormone (TSH), free thyroxine (FT4), thyroxine (T4), and triiodothyronine (T3). Major depression (MD), attention deficit (AD), and obsessive-compulsive (OC) symptom scores were abstracted from the Diagnostic Interview Schedule for Children. Total behavior problem scores from the Youth Self-Report also were obtained. Results: Paired analysis revealed there were no significant group or gender differences or group by gender interactions for TSH, T4, or T3. For FT4, however, there were significant group differences (p=.008) showing lower concentrations in depressed adolescents than control subjects, suggesting that the former might be functionally hypothyroid. Although there were no significant correlations of TSH with any of the psychological measures obtained, in the depressed group correlations were negative (although not always significant) with FT4 and total behavior problems (r=-.40, p=.09), as well as with symptom scores of MD (r=-.25, p=.288), OC (r=-.56, p=.011), and AD behaviors (r=-.57, p=.008). Higher numbers of symptom scores of OG and AD were related to lower concentrations of FT4. Conclusions: FT4 concentrations were lower in depressed adolescents. These findings suggest a relationship between negative behaviors and dysfunction of the hypothalamic-pituitary-thyroid axis in adolescents with depression. C1 NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD. NHLBI,MOLEC DIS BRANCH,BETHESDA,MD 20892. NIMH,LAB DEV PSYCHOL,BETHESDA,MD 20892. NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892. UNIV PITTSBURGH,SCH NURSING,PITTSBURGH,PA 15260. BROWN UNIV,BUTLER HOSP,PROVIDENCE,RI 02912. NR 48 TC 14 Z9 14 U1 1 U2 6 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAR PY 1996 VL 35 IS 3 BP 299 EP 306 DI 10.1097/00004583-199603000-00010 PG 8 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA TW743 UT WOS:A1996TW74300010 PM 8714317 ER PT J AU Brown, LJ Kaste, LM Selwitz, RH Furman, LJ AF Brown, LJ Kaste, LM Selwitz, RH Furman, LJ TI Dental caries and sealant usage in US children, 1988-1991 - Selected findings from the Third National Health and Nutrition Examination Survey SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article AB This article provides estimates of dental caries and dental sealant use among U.S. children and adolescents, obtained from Phase 1 (1988-1991) of the Third National Health and Nutrition Examination Survey. More than 60 percent of children under the age of 10 years had a caries-free primary dentition; among children and adolescents aged 5 to 17 years, about 55 percent had a caries-free Permanent dentition. The highest percentages of dental caries among children and adolescents continue to be distributed disproportionally among about 25 percent of the U.S. population. Fewer than one in five U.S. children and adolescents aged 5 to 17 years had one or more sealed permanent teeth. RP Brown, LJ (reprint author), NIDR,DIV EPIDEMIOL & ORAL DIS PREVENT,NATCHER BLDG,ROOM 4AS-13E,45 CTR DR,MSC-6401,BETHESDA,MD 20892, USA. NR 19 TC 56 Z9 57 U1 0 U2 2 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 MAR PY 1996 VL 127 IS 3 BP 335 EP 343 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TY549 UT WOS:A1996TY54900015 PM 8819780 ER PT J AU Slavkin, HC AF Slavkin, HC TI Are we ready for clinical gene therapy? SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article RP Slavkin, HC (reprint author), NIDR,31 CTR DR,MSC 2290,BLDG 31,ROOM 2C39,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR PY 1996 VL 127 IS 3 BP 396 EP 397 PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA TY549 UT WOS:A1996TY54900023 PM 8819788 ER PT J AU Ferrucci, L Guralnik, JM Salive, ME Pahor, M Corti, MC Baroni, A Havlik, RJ AF Ferrucci, L Guralnik, JM Salive, ME Pahor, M Corti, MC Baroni, A Havlik, RJ TI Cognitive impairment and risk of stroke in the older population SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID BLOOD-PRESSURE; LEUKO-ARAIOSIS; DEMENTIA; LEUKOARAIOSIS AB OBJECTIVE: Recent studies have suggested that vascular dementia in older persons is more common than previously hypothesized. A substantial proportion of dementia in old age may be an early manifestation of cerebrovascular disease (CVD), that eventually becomes clinically evident as an acute cerebrovascular accident. This study was aimed at assessing whether cognitive impairment and cognitive decline in older persons free of stroke are associated with higher risk of future stroke, independently of other risk factors. DESIGN: Population-based prospective study. PARTICIPANTS: A total of 5024 subjects from the Established Populations for Epidemiologic Studies of the Elderly, who were alive and had no history of previous stroke at the sixth follow-up visit. Subjects who had reported a stroke in a previous interview or with a diagnosis of cerebrovascular disease in a hospitalization record during the previous 3 years were excluded. MEASUREMENTS: Cognitive function was assessed by the Short Portable Mental Status Questionnaire (SPMSQ). Occurrence of a stroke was prospectively assessed by examining hospital discharge diagnoses and death certificates. RESULTS: During 19,533 person-years of follow-up, 259 strokes were recorded (13.3/1000 person-years). Stroke incidence was lowest in those with normal SPMSQ score (12.1/1000 person-years), intermediate in those with moderate impairment (16.3/1000 person-years), and highest in those with severe impairment (30.9/1000 person-years). Adjusting for age, education, smoking, history of hypertension, blood pressure, heart attack, diabetes, and disability, the relative risks of stroke for moderate and severe cognitive impairment were 1.2 (0.9-1.6) and 2.2 (1.2-3.8), respectively. The association between cognitive impairment and incident stroke was not mediated by hypertension or diabetes. Compared with subjects with stable or improved SPMSQ score in the previous 3 years, those who declined had higher risk of stroke. CONCLUSIONS: The elevated risk of subsequent strokes in older persons with cognitive impairment suggests that CVD may play a larger role in causing cognitive impairment then previously suspected. It remains to be demonstrated whether reducing modifiable risk factors for CVD decreases the burden of cognitive impairment in older persons without stroke. C1 UNIV CATTOLICA SACRO CUORE, DEPT INTERNAL MED & GERIATR, I-00168 ROME, ITALY. NATL RES CTR, DEPT GERIATR, FLORENCE, ITALY. RP Ferrucci, L (reprint author), NIA, EPIDEMIOL DEMOG & BIOMETRY PROGRAM, 7201 WISCONSIN AVE, GATEWAY BLDG, SUITE 3C-309, BETHESDA, MD 20892 USA. NR 38 TC 120 Z9 121 U1 7 U2 9 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 1996 VL 44 IS 3 BP 237 EP 241 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA TZ893 UT WOS:A1996TZ89300002 PM 8600190 ER PT J AU Spitzer, V Ackerman, MJ Scherzinger, AL Whitlock, D AF Spitzer, V Ackerman, MJ Scherzinger, AL Whitlock, D TI The visible human male: A technical report SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article AB The National Library of Medicine's Visible Human Male data set consists of digital magnetic resonance (MR), computed tomography (CT), and anatomic images derived from a single male cadaver. The data set is 15 gigabytes in size and is available from the National Library of Medicine under a no-cost license agreement. The history of the Visible Human Male cadaver and the methods and technology to produce the data set are described. C1 NATL LIB MED,VIS HUMAN PROJECT,BETHESDA,MD 20894. UNIV COLORADO,SCH MED,DENVER,CO. FU NLM NIH HHS [N01-LM1-3543] NR 4 TC 351 Z9 411 U1 1 U2 18 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD MAR-APR PY 1996 VL 3 IS 2 BP 118 EP 130 PG 13 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA TY741 UT WOS:A1996TY74100003 PM 8653448 ER PT J AU Wang, TCL Cornio, LJ Markey, SP AF Wang, TCL Cornio, LJ Markey, SP TI Liquid chromatography particle beam mass spectrometry with massive cluster impact SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article ID AEROSOL GENERATION INTERFACE; PERFORMANCE AB A new liquid chromatography-mass spectrometry technique is described that utilizes a particle beam interface to transport and deposit desolvated analyte molecules onto a target surface that is bombarded by a primary beam of massive multiply charged glycerol cluster ions to generate secondary ions for mass analysis. The massive cluster ion beam is generated by electrohydrodynamic emission from a solution of 1.5-M ammonium acetate in glycerol. In the present instrumental configuration the massive cluster ion gun is placed above the target probe and the particle beam interface is connected through a side port of the mass spectrometer. The massive cluster ion beam and particle beam are intercepted by a target surface substituted for a conventional ion volume. The target surface is positioned such that it is similar to 45 degrees to the primary cluster ion beam, the particle beam, and the mass analyzer axis. This geometric orientation represents a compromise among the performances of these three elements. The feasibility of this liquid chromatography-particle beam on-line with massive cluster impact is demonstrated by flow injections of acetylcholine chloride and gramicidin S. Spectra generated from this preliminary study indicate promise for routine liquid chromatography-mass spectrometry of polar compounds by using a robust inlet and an effective generation of secondary ions without an added matrix. C1 NIMH,NIH,ANALYT BIOCHEM SECT,BETHESDA,MD 20892. NR 16 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD MAR PY 1996 VL 7 IS 3 BP 293 EP 297 DI 10.1016/1044-0305(95)00703-2 PG 5 WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA TY358 UT WOS:A1996TY35800009 PM 24203301 ER PT J AU Elliot, S Goldsmith, P Knepper, M Haughey, M Olson, B AF Elliot, S Goldsmith, P Knepper, M Haughey, M Olson, B TI Urinary excretion of aquaporin-2 in humans: A potential marker of collecting duct responsiveness to vasopressin SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article DE osmotic; wafer channel; collecting duct; urinary excretion ID WATER CHANNEL; RAT-KIDNEY; BINDING AB The vasopressin-sensitive water channel (aquaporin 2; AQP-2) mediates water transport across the apical plasma membrane of the renal collecting ducts and is excreted in human urine. This study presents the hypothesis that measurements of the AQP-2 excretion rate might be used as a marker of collecting-duct responsiveness to vasopressin, and therefore could be useful in the clinical evaluation of various water-balance disorders. This study presents information about the development of an antibody to human AQP-2, and measures the urinary excretion of AQP-2 by quantitative Western analysis. A standard curve of band densities was generated by using known quantities of the modified immunizing peptide to derive the amount of AQP-2 contained in aliquots of urine. AQP-2 urinary excretion changed with short-term alterations in hydration status produced either by water loading (76% decrease, P < 0.01) or by 3% sodium chloride (760% increase, P < 0.01). Steady-state 24-h urinary excretion of AQP-2 was 43 +/- 10 nmol/24 h (or 28.5 +/- 6.9 pmol/mg creatinine), and 20 +/- 6 nmol/24 h (or 18.3 +/- 7.9 pmol/mg creatinine) in men and women, respectively. Therefore, urinary AQP-2 excretion can be quantified by using Western analysis, and may serve as a marker of collecting-duct responsiveness to vasopressin in different physiologic settings. C1 NHLBI,NIH,KIDNEY & ELECTROLYTE METAB BRANCH,BETHESDA,MD 20892. NICHHD,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. NIDDKD,METAB DIS BRANCH,BETHESDA,MD 20892. NIH,CTR CLIN,DEPT NURSING,BETHESDA,MD 20892. NR 13 TC 76 Z9 77 U1 0 U2 0 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 MAR PY 1996 VL 7 IS 3 BP 403 EP 409 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA UC397 UT WOS:A1996UC39700004 PM 8704105 ER PT J AU Gail, MH AF Gail, MH TI Statistics in action SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Editorial Material RP Gail, MH (reprint author), NCI,BIOSTAT BRANCH,BETHESDA,MD 20892, USA. NR 61 TC 9 Z9 9 U1 1 U2 2 PU AMER STATIST ASSN PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD MAR PY 1996 VL 91 IS 433 BP 1 EP 13 DI 10.2307/2291378 PG 13 WC Statistics & Probability SC Mathematics GA UB272 UT WOS:A1996UB27200001 ER PT J AU DeVito, MJ Beebe, LE Menache, M Birnbaum, LS AF DeVito, MJ Beebe, LE Menache, M Birnbaum, LS TI Relationship between CYP1A enzyme activities and protein levels in rats treated with 2,3,7,8-teirachlorodibenzo-p-dioxin SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH LA English DT Article ID AH-RECEPTOR; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN TCDD; 2-HYDROXYLASE ACTIVITY; CYTOCHROME P-450D; BINDING; MOUSE; TOXICITY; CLONING; LIVER; IDENTIFICATION AB Induction of CYP1A1 is one of the best characterized responses to 2,3,7,8-tetrachloro dibenzo-p-dioxin (TCDD). EROD activity has been used as an enzymatic marker for CYP1A1 following TCDD treatment. Enzymatic markers for the induction of CYP1A2 by TCDD are not as well characterized. The present study examines the relationship between CYP1A1 and CYP1A2 protein and the corresponding enzymatic markers. Induction of hepatic ethoxyresorufin O-deethylase (EROD) activity and methoxyresorufin O-demethylase (MEROD) and acetanilide 4-hydroxylase (ACOH) activity (both markers for CYP1A2) were analyzed in 8-wk-old male and female Fischer 344 rats treated orally with either 0, 0.1, 0.3, 1.0, or 3.0 mu g TCDD/kg. There were no sex differences in basal EROD or ACOH activity. MEROD activity was significantly greater in control males than in control females. Significant induction oi EROD activity in females occurred at slightly lower doses of TCDD compared to males (0.1 vs. 0.3 mu g/kg, respectively); However, a greater absolute and a larger fold induction of EROD activity was seen in males compared to females at all doses tested except 0.1 mu g/kg. EROD activity did not attain a maximum in either sex. Similarly, MEROD activity was induced at lower doses of TCDD in females than in males (0.1 vs. 0.3 mu g/kg, respectively). MEROD activity was maximally induced at 0.3 mu g/kg in males. ln females, MEROD did not attain maximum induction at the doses rested. ACOH activity was induced at doses as low as 0.3 mu g/kg in both sexes, and the dose-dependent increases in activity were equivalent in males and females. Both ACOH and MEROD activity correlated well with CYP1A2 levels as determined Dy Western blot analysis, although there was a greater fold induction of protein than either MEROD or ACOH. Although MEROD and ACOH are both markers for the same response, MEROD activity may be a more useful marker because it is the quicker and more sensitive of the two assays. C1 NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. DUKE UNIV,CTR EXTRAPOLAT MODELING,DURHAM,NC. RP DeVito, MJ (reprint author), US EPA,NATL HLTH & ENVIRONM EFFECTS RES LAB,DIV ENVIRONM TOXICOL,MD-74,RES TRIANGLE PK,NC 27711, USA. NR 33 TC 20 Z9 21 U1 0 U2 0 PU TAYLOR & FRANCIS PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0098-4108 J9 J TOXICOL ENV HEALTH JI J. Toxicol. Environ. Health PD MAR PY 1996 VL 47 IS 4 BP 379 EP 394 DI 10.1080/009841096161717 PG 16 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA UA178 UT WOS:A1996UA17800006 PM 8600290 ER PT J AU Jin, H Subbarao, K Bagai, S Leser, GP Murphy, BR Lamb, RA AF Jin, H Subbarao, K Bagai, S Leser, GP Murphy, BR Lamb, RA TI Palmitylation of the influenza virus hemagglutinin (H3) is not essential for virus assembly or infectivity SO JOURNAL OF VIROLOGY LA English DT Article ID VESICULAR STOMATITIS-VIRUS; CYTOPLASMIC DOMAIN; MEMBRANE-FUSION; A VIRUS; GLYCOPROTEIN; RESTRICTION; CYSTEINE; ANTIBODY; BINDING; PROTEIN AB The C terminus of the influenza virus hemagglutinin (HA) contains three cysteine residues that are highly conserved among HA subtypes, two in the cytoplasmic tail and one in the transmembrane domain. All of these C-terminal cysteine residues are modified by the covalent addition of palmitic acid through a thio-ether linkage, To investigate the role of HA. palmitylation in virus assembly, we used reverse genetics techniques to introduce substitutions and deletions that affected the three conserved cysteine residues into the H3 subtype HA, The rescued viruses contained the HA of subtype H3 (A/Udorn/72) in a subtype H1 helper virus (A/WSN/33) background, Rescued viruses which do not contain a site for palmitylation (by residue substitution or substitution combined with deletion of the cytoplasmic tail) were obtained, Rescued virions had a normal polypeptide composition, Analysis of the kinetics of HA low-pH-induced fusion of the mutants showed no major change from that of virus with wild-type (wt) HA. The PFU/HA ratio of the rescued viruses grown in eggs ranged from that of virus with wt HA to 16-fold lower levels, whereas the PFU/HA ratio of the rescued viruses grown in MDCK cells varied only 2-fold from that of virus with mt HA. However, except for one rescued mutant virus (CAC), the mutant viruses were attenuated in mice, as indicated by a greater than or equal to 400-fold increase in the 50% lethal dose, Interestingly, except for one mutant virus (CAC), all of the rescued mutant viruses were restricted for replication in the upper respiratory tract but much less restricted in the lungs, Thus, the WA cytoplasmic tail may play a very important role in the generation of virus that can replicate in multiple cell types. C1 NORTHWESTERN UNIV,DEPT BIOCHEM MOLEC BIOL & CELL BIOL,EVANSTON,IL 60208. NORTHWESTERN UNIV,HOWARD HUGHES MED INST,EVANSTON,IL 60208. NIAID,INFECT DIS LAB,BETHESDA,MD 20892. FU NIAID NIH HHS [AI-20201] NR 39 TC 63 Z9 64 U1 2 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 1996 VL 70 IS 3 BP 1406 EP 1414 PG 9 WC Virology SC Virology GA TV696 UT WOS:A1996TV69600010 PM 8627657 ER PT J AU Voevodin, A Samilchuk, E Schatzl, H Boeri, E Franchini, G AF Voevodin, A Samilchuk, E Schatzl, H Boeri, E Franchini, G TI Interspecies transmission of macaque simian T-cell leukemia/lymphoma virus type 1 in baboons resulted in an outbreak of malignant lymphoma SO JOURNAL OF VIROLOGY LA English DT Article ID HTLV-I VARIANT; LEUKEMIA-VIRUS; SEQUENCE; DNA; ANTIBODIES; INFECTION; COLONY AB An outbreak of malignant lymphoma has been observed in one of the baboon (Papio hamadryas) stocks of Sukhumi Primate Center. More than 300 cases in this ''high-lymphoma stock'' have been registered since 1967. Human T-cell lymphotropic virus type 1 (HTLV-1)-related virus was implicated as the etiologic agent of Sukhumi baboon lymphoma. The origin of this virus remained unclear. Two possibilities were originally considered: the origin could be baboon simian T-cell leukemia/lymphoma virus type 1 (STLV-1) or HTLV-1 (before the outbreak started, some Sukhumi baboons were inoculated with human leukemic material). The third possibility emerged recently: interspecies transmission of rhesus macaque STLV-1 to baboons. It was prompted by the finding of very close similarity between STLV-1 991-1cc (the strain isolated from a non-Sukhumi baboon inoculated with material from a Sukhumi lymphomatous baboon) and rhesus STLV-1. To test this hypothesis, we investigated 37 Sukhumi STLV-1 isolates from baboons of high-lymphoma stock by PCR discriminating rhesus type and baboon type STLV-1 isolates. All of them were proved to be rhesus type STLV-1. In contrast, all six STLV-1 isolates from baboons belonging to other stocks or populations were of baboon type. The PCR results were fully confirmed by DNA sequence data. The partial env gene sequences of all four STLV-1 isolates from Sukhumi lymphomatous baboons were 97 to 100% similar to the sequence of known rhesus STLV-1 and only 85% homologous with the sequence of conventional baboon STLV-1. Thus, interspecies transmission of STLV-1 from rhesus macaques (or closely related species) to baboons occurred at Sukhumi Primate Center. Most probably this event initiated the outbreak of lymphoma in Sukhumi baboons. C1 MINIST HLTH,KUWAIT MED GENET CTR,SAFAT 13110,KUWAIT. UNIV MUNICH,MAX VON PETTENKOFER INST HYG & MED MICROBIOL,W-8000 MUNICH 2,GERMANY. NCI,TUMOR CELL BIOL LAB,BETHESDA,MD 20892. RP Voevodin, A (reprint author), KUWAIT UNIV,FAC MED,DEPT MICROBIOL,POB 24923,SAFAT 13110,KUWAIT. RI Schatzl, Hermann/G-4958-2011 NR 42 TC 44 Z9 45 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 MAR PY 1996 VL 70 IS 3 BP 1633 EP 1639 PG 7 WC Virology SC Virology GA TV696 UT WOS:A1996TV69600037 PM 8627684 ER PT J AU Gao, F Morrison, SG Robertson, DL Thornton, CL Craig, S Karlsson, G Sodroski, J Morgado, M GalvaoCastro, B vonBriesen, H Beddows, S Weber, J Sharp, PM Shaw, GM Hahn, BH Osmanov, S Heyward, WL Esparza, J vandePerre, P Karita, E Sempala, S Tugume, B Biryahwaho, B Wasi, C RubsamenWaigmann, H Holmes, H Newberry, A Ranjbar, S Tomlinson, P Bradac, J Mullins, JI Delwart, EL CheingsongPopov, R Kaleebu, P Myers, G Korber, BTM Chiphangwi, J Taha, T Desormeaux, J Eiumtrakul, S Natpratan, C Khamboonruang, C Miotti, P Halsey, NA Vlahov, D Nelson, KE Phair, J Cao, Y Moore, JP Ho, DD Matocha, M Fowler, A Dilworth, S Sharma, O Brown, R Dusing, S Whitman, J Hoekzema, D Vogel, F AF Gao, F Morrison, SG Robertson, DL Thornton, CL Craig, S Karlsson, G Sodroski, J Morgado, M GalvaoCastro, B vonBriesen, H Beddows, S Weber, J Sharp, PM Shaw, GM Hahn, BH Osmanov, S Heyward, WL Esparza, J vandePerre, P Karita, E Sempala, S Tugume, B Biryahwaho, B Wasi, C RubsamenWaigmann, H Holmes, H Newberry, A Ranjbar, S Tomlinson, P Bradac, J Mullins, JI Delwart, EL CheingsongPopov, R Kaleebu, P Myers, G Korber, BTM Chiphangwi, J Taha, T Desormeaux, J Eiumtrakul, S Natpratan, C Khamboonruang, C Miotti, P Halsey, NA Vlahov, D Nelson, KE Phair, J Cao, Y Moore, JP Ho, DD Matocha, M Fowler, A Dilworth, S Sharma, O Brown, R Dusing, S Whitman, J Hoekzema, D Vogel, F TI Molecular cloning and analysis of functional envelope genes from human immunodeficiency virus type 1 sequence subtypes A through G SO JOURNAL OF VIROLOGY LA English DT Review ID HIGHLY CYTOPATHIC STRAIN; CYTOPLASMIC DOMAIN; NUCLEOTIDE-SEQUENCES; PROTEIN SEQUENCES; AIDS VIRUS; HIV-1; DIVERSITY; ENV; GAG; IDENTIFICATION AB Present knowledge of human immunodeficiency virus type 1 (HIV-1) envelope immunobiology has been derived almost exclusively from analyses of subtype B viruses, yet such viruses represent only a minority of strains currently spreading worldwide. To generate a more representative panel of genetically diverse envelope genes, we PCR amplified, cloned, and sequenced complete gp160 coding regions of 35 primary (peripheral blood mononuclear cell-propagated) HTV-1 isolates collected at major epicenters of the current AIDS pandemic. Analysis of their deduced amino acid sequences revealed several important differences from prototypic subtype B strains, including changes in the number and distribution of cysteine residues, substantial length differences in hypervariable regions, and premature truncations in the gp41 domain. Moreover, transiently expressed glycoprotein precursor molecules varied considerably in both size and carbohydrate content. Phylogenetic analyses of full-length env sequences indicated that the panel included members of all major sequence subtypes of HTV-1 group M (clades A to G), as well as an intersubtype recombinant (FIB) from an infected individual in Brazil. In addition, all subtype E and three subtype G viruses initially classified on the basis of partial env sequences were found to cluster in subtype A in the 3' half of their gp41 coding region, suggesting that they are also recombinant. The biological activity of PCR-derived env genes was examined in a single-round virus infectivity assay, This analysis identified 20 clones, including 1 from each subtype (or recombinant), which expressed fully functional envelope glycoproteins. One of these, derived from a patient with rapid CD4 cell decline, contained an amino acid substitution in a highly conserved endocytosis signal (Y721C), as well as a premature truncation of its gp41 domain, which lacked 17 amino acids. Several other env constructs mediated virus entry with very poor efficiency, although they did not contain sequence changes predicted to alter protein function. These results indicate that the env genes of primary HTV-1 isolates collected worldwide can vary considerably in their genetic, phylogenetic, and biological properties. The panel of env constructs described here should prove valuable for future structure-function studies of naturally occurring envelope glycoproteins as well as AIDS vaccine development efforts targeted against a broader spectrum of viruses. C1 UNIV ALABAMA,DEPT MED,BIRMINGHAM,AL 35294. UNIV ALABAMA,DEPT MICROBIOL,BIRMINGHAM,AL 35294. UNIV NOTTINGHAM,QUEENS MED CTR,DEPT GENET,NOTTINGHAM NG7 2RD,ENGLAND. UNIV LONDON IMPERIAL COLL SCI TECHNOL & MED,ST MARYS HOSP,SCH MED,DEPT COMMUNICABLE DIS,LONDON W2 1PG,ENGLAND. DANA FARBER CANC INST,DEPT PATHOL,BOSTON,MA 02115. FIOCRUZ MS,INST OSWALDO CRUZ,DEPT IMMUNOL,RIO JANEIRO,BRAZIL. FIOCRUZ MS,CTR PESQUISA GONCALO MONIZ,ADV LAB PUBL HLTH,SALVADOR,BA,BRAZIL. GEORG SPEYER HAUS,CHEMOTHERAPEUT FORSCHUNGSINST,FRANKFURT,GERMANY. WHO,GLOBAL PROGRAMME AIDS,GENEVA,SWITZERLAND. NATL AIDS CONTROL PROGRAM,KIGALI,RWANDA. INST TROP MED,B-2000 ANTWERP,BELGIUM. UGANDA VIRUS RES INST,ENTEBBE,UGANDA. MAHIDOL UNIV,SIRIRAJ HOSP,BANGKOK 10700,THAILAND. NATL INST BIOL STAND & CONTROLS,LONDON NW3 6RB,ENGLAND. UNIV WASHINGTON,SEATTLE,WA 98195. LOS ALAMOS NATL LAB,LOS ALAMOS,NM 87545. MALAWI COLL MED,BLANTYRE,MALAWI. CTR DEV & SANTE,PORT AU PRINCE,HAITI. ROYAL THAI ARMY HOSP,CHIANG MAI,THAILAND. ROYAL THAI MINIST PUBL HLTH,CHIANG MAI,THAILAND. CHIANG MAI UNIV,CHIANG MAI 50000,THAILAND. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,BALTIMORE,MD. NORTHWESTERN UNIV,CHICAGO,IL 60611. AARON DIAMOND AIDS RES CTR,NEW YORK,NY. NIAID,AIDS RES & REFERENCE REAGENT PROGRAM,BETHESDA,MD 20892. NIAID,AIDS VACCINE REAGENT PROGRAM,BETHESDA,MD 20892. RI Sharp, Paul/F-5783-2010; Van de Perre, Philippe/B-9692-2008 OI Sharp, Paul/0000-0001-9771-543X; Van de Perre, Philippe/0000-0002-3912-0427 FU NIAID NIH HHS [N01AI35170, P30 AI27767, R01AI25291] NR 104 TC 248 Z9 261 U1 2 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 1996 VL 70 IS 3 BP 1651 EP 1667 PG 17 WC Virology SC Virology GA TV696 UT WOS:A1996TV69600039 PM 8627686 ER PT J AU Nihrane, A Fujita, K Willey, R Lyu, MS Silver, J AF Nihrane, A Fujita, K Willey, R Lyu, MS Silver, J TI Murine leukemia virus envelope protein in transgenic-mouse serum blocks infection in vitro (Retracted article. See vol 72, pg 8462, 1998) SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; RECOMBINANT GP160; CELL-SURFACE; SOLUBLE CD4; FV-4 GENE; GLYCOPROTEIN; TYPE-1; MICE; EXPRESSION; IMMUNOGENICITY AB Transgenic mice bearing a murine retroviral envelope transgene (Fv4) have Fv4 gp70(env) (SU) in their serum in amounts sufficient to block infection by ecotropic virus in vitro. Fv4 Env in serum is derived largely but not exclusively from hematopoietic cells. Tail cells from Fv4 mice and cell lines transduced with the Fv4 env transgene synthesize both components of the envelope protein (gp70 SU and p15E TM) but secrete the gp70 moiety, in the absence of retroviral particles. Blocking of the ecotropic viral receptor by secreted gp70 SU may contribute to resistance to retroviral infection in these mice. C1 NIAID, MOLEC MICROBIOL LAB, BETHESDA, MD 20892 USA. NR 42 TC 17 Z9 17 U1 2 U2 5 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 MAR PY 1996 VL 70 IS 3 BP 1882 EP 1889 PG 8 WC Virology SC Virology GA TV696 UT WOS:A1996TV69600066 PM 8627713 ER PT J AU Lech, WJ Wang, G Yang, YL Chee, Y Dorman, K McCrae, D Lazzeroni, LC Erickson, JW Sinsheimer, JS Kaplan, AH AF Lech, WJ Wang, G Yang, YL Chee, Y Dorman, K McCrae, D Lazzeroni, LC Erickson, JW Sinsheimer, JS Kaplan, AH TI In vivo sequence diversity of the protease of human immunodeficiency virus type 1: Presence of protease inhibitor-resistant variants in untreated subjects SO JOURNAL OF VIROLOGY LA English DT Article ID REVERSE-TRANSCRIPTASE; GENETIC DIVERSITY; VIRAL INFECTIVITY; ENVELOPE PROTEIN; V3 LOOP; HIV-1; MUTATION; IDENTIFICATION; SENSITIVITY; INVIVO AB We have evaluated the sequence diversity of the protease of human immunodeficiency virus type 1 in vivo. Our analysis of 246 protease coding domain sequences obtained from 12 subjects indicates that amino acid substitutions predicted to give rise to protease inhibitor resistance mag be present in patients who have not received protease inhibitors, In addition, we demonstrated that amino acid residues directly involved in enzyme-substrate interactions may be varied in infected individuals. Several of these substitutions occurred in combination either more or less frequently than would be expected if their appearance was independent, suggesting that one substitution may compensate for the effects of another. Taken together, our analysis indicates that the human immunodeficiency virus type 1 protease has flexibility sufficient to vary critical subsites in vivo, thereby retaining enzyme function and viral pathogenicity. C1 UNIV CALIF LOS ANGELES, SCH MED, DEPT MED, LOS ANGELES, CA 90024 USA. STANFORD UNIV, DEPT STAT, STANFORD, CA 94305 USA. NCI, FREDERICK CANC RES & DEV CTR, PRI DYNCORP, STRUCT BIOCHEM PROGRAM, FREDERICK, MD 21702 USA. UNIV CALIF LOS ANGELES, DEPT BIOMATH, LOS ANGELES, CA 90024 USA. UNIV CALIF LOS ANGELES, DEPT IMMUNOL & MICROBIOL, LOS ANGELES, CA 90024 USA. RI Lazzeroni, Laura/F-2903-2010; OI Dorman, Karin/0000-0003-3650-0018; Lazzeroni, Laura/0000-0002-1846-6920 FU NCI NIH HHS [5R01 CA 59039-20]; NIAID NIH HHS [K11 AI01107, R29 AI36702] NR 50 TC 136 Z9 137 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD MAR PY 1996 VL 70 IS 3 BP 2038 EP 2043 PG 6 WC Virology SC Virology GA TV696 UT WOS:A1996TV69600086 PM 8627733 ER PT J AU Sundberg, JP Montali, RJ Bush, M Phillips, LG OBrien, SJ Jenson, AB Burk, RD VanRanst, M AF Sundberg, JP Montali, RJ Bush, M Phillips, LG OBrien, SJ Jenson, AB Burk, RD VanRanst, M TI Papillomavirus-associated focal oral hyperplasia in wild and captive Asian lions (Panthera leo persica) SO JOURNAL OF ZOO AND WILDLIFE MEDICINE LA English DT Article DE papillomavirus; Asian lion; Panthera leo persica; felidae; PIPV ID FELINE HERPESVIRUS TYPE-1; PYGMY CHIMPANZEE; INFECTION; CHEETAH; VIRUS; SKIN; MICE; LESIONS; CAT AB Four Asian lions (Panthera leo persica), two wild and two captive, were diagnosed with focal oral hyperplasia affecting the ventral surface of their tongues. Focal, flat, sessile lesions consisted of hyperplastic, stratified squamous epithelium. Koilocytotic atypia was evident in the upper layers of cells, some of which contained characteristic intranuclear papillomavirus particles visible by electron microscopy. In addition, large amphophilic cytoplasmic inclusions were evident in the koilocytes and were considered to be a product of the viral E4 gene. Papillomavirus group-specific antigens were detected by immunohistochemistry in the atypical cell nuclei. Conserved papillomavirus antigenic epitopes differed from epitopes found in cutaneous papillomavirus-induced lesions from domestic cats. An 8,000-base pair DNA fragment, linearized by Bam HI digestion, was detected by Southern blot hybridization probed with a mixed human papillomavirus genomic probe. Limited restriction endonuclease studies of DNA prepared using an oral hyperplastic lesion from an Asian lion indicate that this is a novel feline papillomavirus different from the domestic cat cutaneous papillomavirus. This new virus has been designated ''PLPV.'' C1 SMITHSONIAN INST,NATL ZOOL PK,WASHINGTON,DC 20008. UNIV CALIF DAVIS,SCH VET MED,DAVIS,CA 92112. NCI,NIH,FREDERICK,MD 21702. GEORGETOWN UNIV,SCH MED,WASHINGTON,DC 20007. CATHOLIC UNIV LEUVEN,REGA INST MED RES,B-3000 LOUVAIN,BELGIUM. YESHIVA UNIV ALBERT EINSTEIN COLL MED,NEW YORK,NY 10461. RP Sundberg, JP (reprint author), JACKSON LAB,600 MAIN ST,BAR HARBOR,ME 04609, USA. NR 37 TC 15 Z9 16 U1 0 U2 4 PU AMER ASSOC Z00 VETERINARIANS PI MEDIA PA 6 NORTH PENNELL ROAD, MEDIA, PA 19063 SN 1042-7260 J9 J ZOO WILDLIFE MED JI J. Zoo Wildl. Med. PD MAR PY 1996 VL 27 IS 1 BP 61 EP 70 PG 10 WC Veterinary Sciences SC Veterinary Sciences GA WK434 UT WOS:A1996WK43400008 ER PT J AU Ship, JA Pearson, JD Cruise, LJ Brant, LJ Metter, EJ AF Ship, JA Pearson, JD Cruise, LJ Brant, LJ Metter, EJ TI Longitudinal changes in smell identification SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID OF-PENNSYLVANIA SMELL; ODOR IDENTIFICATION; OLFACTORY FUNCTION; ELDERLY PERSONS; NASAL PUNGENCY; AGE; UNIVERSITY; PERCEPTION; TASTE; ABILITY AB Background. Cross-sectional studies have demonstrated that olfactory function diminishes with increasing age, which may impact on the safety and quality of life of older persons. To date, however, there have been no published longitudinal studies on olfaction. The purpose of this study was to examine the influence of age and gender on smell identification over a 3-year period in a group of generally healthy men and women. Methods. Males (n = 85) and females (n = 76) between the ages of 19 and 95 years were administered the University of Pennsylvania Smell identification Test (SIT) over a 3-year span as part of the oral physiology component of the Baltimore Longitudinal Study of Aging. A linear mixed-effects regression model was used to determine how longitudinal changes in SIT scores differ with respect to gender, history of medical problems, and use of prescription medications. Results. Over the 3-year period, SIT scores diminished progressively with increased age. Women and men in the eighth decade of life experienced a decline of greater than one SIT point per year. Females consistently performed better than males in smell identification. Similar results were obtained regardless of medical problems or medication usage. Conclusions. These results extend the conclusions of previous cross-sectional olfactory studies and indicate that smell identification deteriorates progressively with greater age. Furthermore, age-related declines in olfaction occur even in the absence of overt medical problems. C1 NIA, NIH, CTR GERONTOL RES, BALTIMORE, MD 21224 USA. RP UNIV MICHIGAN, SCH DENT, 1011 N UNIV, ROOM 2010, ANN ARBOR, MI 48109 USA. NR 54 TC 53 Z9 54 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 EI 1758-535X J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAR PY 1996 VL 51 IS 2 BP M86 EP M91 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA UB199 UT WOS:A1996UB19900016 PM 8612109 ER PT J AU Nielsen, S Knepper, M Agre, P AF Nielsen, S Knepper, M Agre, P TI Water channels in the kidney. SO KIDNEY INTERNATIONAL LA English DT Meeting Abstract C1 AARHUS UNIV,AARHUS,DENMARK. NIH,BETHESDA,MD 20892. JOHNS HOPKINS UNIV,BALTIMORE,MD. NR 0 TC 0 Z9 0 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 MAR PY 1996 VL 49 IS 3 BP 918 EP 918 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA TW637 UT WOS:A1996TW63700042 ER PT J AU Simpson, RM Zhao, TM Hubbard, BS Sawasdikosol, S Kindt, TJ AF Simpson, RM Zhao, TM Hubbard, BS Sawasdikosol, S Kindt, TJ TI Experimental acute adult T cell leukemia-lymphoma is associated with thymic atrophy in human T cell leukemia virus type I infection SO LABORATORY INVESTIGATION LA English DT Article ID POLYMERASE CHAIN-REACTION; HTLV-I; TRANSGENIC MICE; LYMPHOCYTES-T; GENE; RABBITS; DISEASE; MALIGNANCIES; INTEGRATION; ACTIVATION AB Human T cell leukemia virus type I (HTLV-I) infection may lead to an acutely fatal adult T cell leukemia-lymphoma (ATLL), but HTLV-l-infected people usually remain asymptomatic, Why only certain HTLV-I infections lead to acute ATLL, which is characterized by leukemic infiltration of multiple organs and immune suppression, remains unknown. A readily accessible animal model in which the spectrum of consequences resulting from HTLV-I infection can be observed would greatly aid studies of this retrovirus. New Zealand White rabbits inoculated with either HTLV-I-infected CD25(+) T cells or cell-free virus, were serially necropsied at different intervals after death or humane sacrifice. Tissues were preserved at necropsy or cultured in vitro and subsequently prepared for morphologic or molecular examination. Rabbits inoculated with RH/K34, a productively infected rabbit T cell line that contains a monoclonally integrated full-length HTLV-I provirus, developed acute ATLL-like biologically malignant lymphoproliferative disease with lymphocyte infiltration of viscera; lymphomas consisting primarily of monoclonal expansions of RH/K34 manifested a variety of diffuse pleomorphic histologic types. Concurrently, lymphoproliferative disease was associated with onset of thymic atrophy in the presence of rapidly increasing thymic proviral load. In contrast, rabbits given two other HTLV-I inocula, originally derived (as was RH/K34) using the human T cell line MT-2 as virus source, also became infected but did not develop thymic atrophy or the ATLL-like disease, HTLV-I infection, thymic atrophy, and leukemic infiltration similar to acute ATLL occurred reproducibly in a New Zealand White rabbit model independent of RH/K34 inoculum and host histocompatibility. Thymic atrophy in RH/K34-inoculated rabbits, but not in rabbits given other similar HTLV-I, was consistent with immunosuppression sufficient to prevent rejection of the inoculum. Although the short, 8-day course of the experimental ATLL precludes its having a molecular pathogenesis identical to the human condition, the systemic consequences of acute ATLL, including its association with thymic atrophy, are closely modeled. RP Simpson, RM (reprint author), NIAID,IMMUNOGENET LAB,TWINBROOK FACIL,12441 PARKLAWN DR,ROCKVILLE,MD 20852, USA. NR 64 TC 26 Z9 26 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD MAR PY 1996 VL 74 IS 3 BP 696 EP 710 PG 15 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA UB443 UT WOS:A1996UB44300014 PM 8600320 ER PT J AU Magrath, IT Haddy, TB Adde, MA AF Magrath, IT Haddy, TB Adde, MA TI Treatment of patients with high grade non-Hodgkin's lymphomas and central nervous system involvement: Is radiation an essential component of therapy? SO LEUKEMIA & LYMPHOMA LA English DT Article DE central nervous system; cranial neuropathy; lymphoma; high grade non-Hodgkin's; paraplegia; radiotherapy ID ACUTE LYMPHOBLASTIC-LEUKEMIA; COMBINED MODALITY TREATMENT; AMERICAN BURKITTS-LYMPHOMA; CRANIAL IRRADIATION; CELL LYMPHOMA; BRAIN-TUMORS; CHILDHOOD; CHILDREN; DISEASE; GROWTH AB We have retrospectively examined the outcome of 41 patients with high grade non-Hodgkin's lymphomas (NHL) and central nervous system (CNS) involvement who were treated with and without radiation at a single institution. Group I consisted of 25 patients with CNS involvement at presentation and Group II, of 16 with CNS involvement at first relapse. All 41 had systemic disease at diagnosis and received systemic and intrathecal chemotherapy. Response to therapy did not differ whether patients received concomitant radiation or no CNS radiation. Thirteen of 16 non-irradiated (81%) and 8 of 9 irradiated Group I patients (89%) achieved complete responses. Three of 4 non-irradiated (75%) and 7 of 12 irradiated (58%) Group II patients achieved complete responses. CNS relapse patterns were similar whether or not patients were irradiated, and regardless of radiation dose. Most patients (18) failed systemically; there were few (6) isolated CNS relapses. Survival was not improved by the addition of radiation. Of the 15 patients who achieved long term survival, 13 remained disease-free throughout their clinical course: 7 of these 13 patients (all Group I) did not receive CNS radiation and 6 (4 Group I, 2 Group II) did. In this series, in which 44% of patients who presented with CNS disease and 13% of those who relapsed with CNS became long term disease-free survivors, there was no discernable benefit from radiation, but increased toxicity was observed. RP Magrath, IT (reprint author), NCI,NIH,PEDIAT BRANCH,DIV CANC TREATMENT,CLIN ONCOL PROGRAM,BLDG 10,ROOM 13N240,BETHESDA,MD 20892, USA. NR 32 TC 9 Z9 9 U1 0 U2 0 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD MAR PY 1996 VL 21 IS 1-2 BP 99 EP 105 DI 10.3109/10428199609067586 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA TX941 UT WOS:A1996TX94100015 PM 8907276 ER PT J AU Holte, LL Separovic, F Gawrisch, K AF Holte, LL Separovic, F Gawrisch, K TI Nuclear magnetic resonance investigation of hydrocarbon chain packing in bilayers of polyunsaturated phospholipids SO LIPIDS LA English DT Article; Proceedings Paper CT 2nd Congress of the International-Society-for-the-Study-of-Fatty-Acids-and-Lipids CY JUN 07-10, 1995 CL NIH, NATCHER CONF CTR, BETHESDA, MD SP Int Soc Study Fatty Acids & Lipids HO NIH, NATCHER CONF CTR ID LIPID-PROTEIN INTERACTIONS; X-RAY-DIFFRACTION; UNSATURATED PHOSPHATIDYLETHANOLAMINE; NEUTRON-DIFFRACTION; ORIENTATIONAL ORDER; MEMBRANES; EQUILIBRIUM; CHOLESTEROL; RHODOPSIN; VESICLES AB H-2 nuclear magnetic resonance (NMR) on chain-deuterated phospholipids has been used to study the influence of the degree of unsaturation on lipid chain packing and on area per molecule at the lipid water interface. Order and motions of deuterated stearic acid in position sn-1 of phosphatidylcholines (PC) containing 18:0, 18:1n-9, 18:2n-6, 18:3n-3, 20:4n-6, 20:5n-3, or 22:6n-3 in position sn-2 were investigated in pure PC and in mixtures of PC in a phosphatidylethanolamine (PE) matrix. Results reveal that lipid packing in bilayers is mainly controlled by packing requirements at the lipid water interface. Increasing degrees of unsaturation lower chain order and increase area per PC molecule, whereas inclusion of PE in model membranes has the opposite effect. Chain order and motions in highly unsaturated lipid membranes are less sensitive to changes in temperature. Temperature sensitivity decreases further upon incorporation of PC into a PE matrix. Unsaturation induces chain disordering, which may be interpreted as an increase in area per molecule of lipids toward the center of the bilayer. This may result in a lower packing density of unsaturated lipids at the lipid water interface. We hypothesize that these differences in lipid packing and dynamics may influence activity of membrane proteins. C1 NIAAA,NIH,LAB MEMBRANE BIOCHEM & BIOPHYS,ROCKVILLE,MD 20852. RI Separovic, Frances/D-9698-2011 OI Separovic, Frances/0000-0002-6484-2763 NR 38 TC 34 Z9 34 U1 0 U2 2 PU AMER OIL CHEMISTS SOC PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 SN 0024-4201 J9 LIPIDS JI Lipids PD MAR PY 1996 VL 31 SU S BP S199 EP S203 DI 10.1007/BF02637076 PG 5 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA UB908 UT WOS:A1996UB90800035 PM 8729119 ER PT J AU Karanian, JW Kim, HY Salem, N AF Karanian, JW Kim, HY Salem, N TI The structure-activity relationship of lipoxygenase products of long-chain polyunsaturated fatty acids: Effects on human platelet aggregation SO LIPIDS LA English DT Article; Proceedings Paper CT 2nd Congress of the International-Society-for-the-Study-of-Fatty-Acids-and-Lipids CY JUN 07-10, 1995 CL NIH, NATCHER CONF CTR, BETHESDA, MD SP Int Soc Study Fatty Acids & Lipids HO NIH, NATCHER CONF CTR ID DOCOSAHEXAENOIC ACID; PROSTAGLANDIN-H2 RECEPTOR; SMOOTH-MUSCLE; INHIBITION; 12-HETE AB The effect of hydroperoxy and hydroxy derivatives of various fatty acids on human platelet aggregation was determined to delineate potencies and structure-activity function. In this regard, the 22-carbon n-3 fatty acids are the most potent inhibitors in comparison to the n-6 lipoxygenase derivatives. Submicromolar levels of the docosapentaenoic (22:5) and especially docosahexaenoic (22:6) n-3 hydroperoxy and hydroxy derivatives specifically antagonize the platelet aggregating effect to arachidonic acid (AA, 20:4n-6) but not that of ADP or collagen. Chain length (22-C > 20-C), double-bond position (n-3 > n-6), and double-bond number (6 > 5 > 4) influence the degree of inhibition of AA-induced aggregation of human platelets. Moreover, significant differences in potency were associated with specific structural aspects of 22:6n-3 lipoxygenase derivatives of 22:6n-3 as follows: functional group (OOH > OH) and positional isomer (14-OOH, 14-OH, 20-OOH > 11-OOH, 17-OOH > 10-OOH > 11-OH, 8-OOH, 7-OOH > 4-OOH). C1 NIAAA, NIH, LAB MEMBRANE BIOCHEM & BIOPHYS, ROCKVILLE, MD 20852 USA. NR 26 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0024-4201 EI 1558-9307 J9 LIPIDS JI Lipids PD MAR PY 1996 VL 31 SU S BP S305 EP S308 DI 10.1007/BF02637097 PG 4 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA UB908 UT WOS:A1996UB90800056 PM 8729140 ER PT J AU Kim, HY Edsall, L Ma, YC AF Kim, HY Edsall, L Ma, YC TI Specificity of polyunsaturated fatty acid release from rat brain synaptosomes SO LIPIDS LA English DT Article; Proceedings Paper CT 2nd Congress of the International-Society-for-the-Study-of-Fatty-Acids-and-Lipids CY JUN 07-10, 1995 CL NIH, NATCHER CONF CTR, BETHESDA, MD SP Int Soc Study Fatty Acids & Lipids HO NIH, NATCHER CONF CTR ID PHOSPHOLIPASE-A2; SELECTIVITY; INHIBITORS AB Release of specific polyunsaturated fatty acids from cell membranes may have a significant implication in biological function, considering the involvement of various fatty acids in cell signal transduction. In the present study, release of polyunsaturated fatty acids from rat brain synaptosomes by endogenous synaptosomal lipase activity was examined in comparison to that by cobra venom phospholipase A(2) (Naja naja naja). Cobra venom phospholipase A(2) (Naja naja naja) preferentially hydrolyzed docosahexaenoic acid (22:6n-3) from both synaptosomes and lipid mixtures containing similar classes of lipids commonly found in the brain. Arachidonic acid (20:4n-6) and oleic acid (18:1n-9) were also hydrolyzed; however, monoene species was hydrolyzed slower than were polyenoic species in synaptosomes. Phosphatidylethanolamine was the most preferred phospholipid class for release of 22:6n-3 fatty acid from both lipid mixtures and synaptosomes. In contrast to hydrolysis by cobra venom phospholipase A(2), endogenous synaptosomal lipase activity preferentially hydrolyzed 20:4n-6 from rat brain synaptosomes, despite the high abundance of 22:6n-3 in synaptosomal membranes. Preferential release of 20:4n-6 was observed over a wide range of pH values and calcium concentrations. Synaptosomal 22:6 species appeared to be resistant to hydrolysis even after stimulation with various agents such as phorbolmyristate, suggesting that physiological importance of 22:6n-3 in neuronal membranes may not be as the release fatty acid. RP Kim, HY (reprint author), NIAAA,NIH,LAB MEMBRANE BIOCHEM & BIOPHYS,SECT MASS SPECTROMETRY,12501 WASHINGTON AVE,ROCKVILLE,MD 20892, USA. NR 23 TC 8 Z9 11 U1 0 U2 0 PU AMER OIL CHEMISTS SOC PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 SN 0024-4201 J9 LIPIDS JI Lipids PD MAR PY 1996 VL 31 SU S BP S229 EP S233 DI 10.1007/BF02637081 PG 5 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA UB908 UT WOS:A1996UB90800040 PM 8729124 ER PT J AU Litman, BJ Mitchell, DC AF Litman, BJ Mitchell, DC TI A role for phospholipid polyunsaturation in modulating membrane protein function SO LIPIDS LA English DT Article; Proceedings Paper CT 2nd Congress of the International-Society-for-the-Study-of-Fatty-Acids-and-Lipids CY JUN 07-10, 1995 CL NIH, NATCHER CONF CTR, BETHESDA, MD SP Int Soc Study Fatty Acids & Lipids HO NIH, NATCHER CONF CTR ID CHAIN PHOSPHATIDYLCHOLINE VESICLES; HIGHER-ORDER ANALYSIS; FLUORESCENCE ANISOTROPY; METARHODOPSIN-I; BILAYER LIPIDS; FATTY-ACID; CHOLESTEROL; EQUILIBRIUM; DECAY; UNILAMELLAR AB Visual transduction is one of the best characterized G protein-coupled signalling systems. In addition, about 50% of the disk membrane phospholipid acyl chains are 22:6n-3, making this system ideal for determining the role of polyunsaturation in modulating membrane-signalling systems. The extent of formation of metarhodopsin II (MII), the G protein-activating photointermediate of rhodopsin, was studied in phospholipid vesicles composed of a variety of phosphatidylcholines, differing in their acyl chain composition at the sn-2 position. The amount of MII formed increased progressively with the level of acyl chain unsaturation at the sn-2 position. The effect of added cholesterol was to reduce the amount of MII formed. The acyl chain packing free volume of the rhodopsin containing lipid vesicles was characterized by a fractional volume parameter f(v) derived from measurements of the time-resolved fluorescence anisotropy decay of the hydrophobic membrane probe 1,6-diphenyl-1,3,5-hexatriene. The relationship among sn-2 acyl chain unsaturation, cholesterol content, and MII formation is explained on the basis of variation in f(v) with bilayer lipid composition and a novel model for the packing of phospholipids containing polyenoic acyl chains, such as 22:6n-3. RP Litman, BJ (reprint author), NIAAA,NIH,LAB MEMBRANE BIOCHEM & BIOPHYS,SECT FLUORESCENCE STUDIES,FLOW BLDG,RM 2,ROCKVILLE,MD 20852, USA. NR 18 TC 100 Z9 103 U1 1 U2 4 PU AMER OIL CHEMISTS SOC PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 SN 0024-4201 J9 LIPIDS JI Lipids PD MAR PY 1996 VL 31 SU S BP S193 EP S197 DI 10.1007/BF02637075 PG 5 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA UB908 UT WOS:A1996UB90800034 PM 8729118 ER PT J AU Pawlosky, RJ Ward, G Salem, N AF Pawlosky, RJ Ward, G Salem, N TI Essential fatty acid uptake and metabolism in the developing rodent brain SO LIPIDS LA English DT Article; Proceedings Paper CT 2nd Congress of the International-Society-for-the-Study-of-Fatty-Acids-and-Lipids CY JUN 07-10, 1995 CL NIH, NATCHER CONF CTR, BETHESDA, MD SP Int Soc Study Fatty Acids & Lipids HO NIH, NATCHER CONF CTR ID CHAIN ELONGATION-DESATURATION; VEGETABLE-OIL FORMULA; LINOLEIC-ACID; RAT-BRAIN; LIVER; PRODUCTS; PIGLETS; RETINA; RICH; PIG AB Studies were carried out to determine whether the brain takes up and metabolizes essential fatty acids during early postnatal development in rodents. Rats and mice were dosed with deuterium-labeled linoleic and linolenic acids either by intraperitoneal injection or by gavage. Animals were killed at different times thereafter, and organs were removed. Brains, livers, and blood were analyzed by gas chromatography-negative-ion-mass spectrometry for labeled fatty acids. To determine whether fatty acids were present in the brain apart from cerebral blood, a subset of animals was exsanguinated by perfusion with buffered saline, and the brain was then fractionated into subcellular components. Results demonstrated that the brain took up both labeled essential fatty acids within 8 h from the time of dosing. There was on average a greater uptake of linolenic acid into the cerebellum than into the cerebral cortex during the first 8 d of life in rats. The amount of linoleic acid taken into either region was similar, however. Docosahexaenoic acid intermediates, 20:5n-3 and 22:5n-3, were also found labeled in the brain. Time-course labeling experiments indicated that these intermediates may be converted to 22:6n-3 within the brain. A rise of labeled 22:6n-3 in the brain at 24 h appeared to be due to uptake of this fatty acid from the blood. The amount of labeled 22:6n-3 in the brain continued to increase beyond 24 h, and this did not appear to be correlated with its blood concentration. These results suggest that, during development in the rodent, different regions within the brain may vary in their capacity to synthesize 22:6n-3, and this may be correlated with regional growth rates. C1 NIAAA,DIV INTRAMURAL CLIN & BIOL RES,LAB MEMBRANE BIOCHEM & BIOPHYS,ROCKVILLE,MD 20852. NR 19 TC 22 Z9 22 U1 0 U2 1 PU AMER OIL CHEMISTS SOC PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 SN 0024-4201 J9 LIPIDS JI Lipids PD MAR PY 1996 VL 31 SU S BP S103 EP S107 DI 10.1007/BF02637060 PG 5 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA UB908 UT WOS:A1996UB90800019 PM 8729103 ER PT J AU Rapoport, SI AF Rapoport, SI TI In vivo labeling of brain phospholipids by long-chain fatty acids: Relation to turnover and function SO LIPIDS LA English DT Article; Proceedings Paper CT 2nd Congress of the International-Society-for-the-Study-of-Fatty-Acids-and-Lipids CY JUN 07-10, 1995 CL NIH, NATCHER CONF CTR, BETHESDA, MD SP Int Soc Study Fatty Acids & Lipids HO NIH, NATCHER CONF CTR ID CEREBRAL PALMITATE INCORPORATION; NUCLEUS BASALIS MAGNOCELLULARIS; RAT; ACTIVATION; PROTEINS AB An experimental method and model are described to quantitate kinetics of in vivo incorporation of fatty acids (FA) into stable brain phospholipids. When a radiolabeled long-chain FA is injected intravenously in a rat, it rapidly equilibrates with brain FA-CoA, the precursor pool for phospholipids. As different labeled FA enter different sn positions of specific phospholipids, a combination of labels can be used to investigate roles of different phospholipids in brain function and structure. By taking into account dilution lambda of specific activity of brain FA-CoA, compared with specific activity of FA in plasma, half-lives of FA in individual brain phospholipids can be calculated. Values for lambda less than 0.02 suggest marked recycling, and give half-lives two orders of magnitude smaller than literature values. A half-life of arachidonate in phosphatidylinositol of 0.66 h (turnover = 105 %h) is consistent with active participation of this FA in phospholipase A(2) mediated signal transduction. RP Rapoport, SI (reprint author), NIA,NIH,NEUROSCI LAB,BETHESDA,MD 20892, USA. NR 27 TC 25 Z9 25 U1 0 U2 0 PU AMER OIL CHEMISTS SOC PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 SN 0024-4201 J9 LIPIDS JI Lipids PD MAR PY 1996 VL 31 SU S BP S97 EP S101 DI 10.1007/BF02637059 PG 5 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA UB908 UT WOS:A1996UB90800018 PM 8729102 ER PT J AU Salem, N Reyzer, M Karanian, J AF Salem, N Reyzer, M Karanian, J TI Losses of arachidonic acid in rat liver after alcohol inhalation SO LIPIDS LA English DT Article; Proceedings Paper CT 2nd Congress of the International-Society-for-the-Study-of-Fatty-Acids-and-Lipids CY JUN 07-10, 1995 CL NIH, NATCHER CONF CTR, BETHESDA, MD SP Int Soc Study Fatty Acids & Lipids HO NIH, NATCHER CONF CTR AB This paper presents an animal model of alcoholism in which rats were exposed to alcohol by inhalation and were fed a diet that simulated the poor diet of some alcoholics. It is hypothesized that some of the pathophysiological effects of alcohol are related to its effects on essential fatty acid metabolism and composition of vital organs. A diet that contains no 20- and 22-carbon essential fatty acids and has low levels of 18-carbon essential fatty acids was used as a dietary challenge. Addition of a second metabolic challenge, i.e., alcohol, led to loss of tissue polyunsaturates, particularly liver arachidonate. A method of cycling alcohol inhalation for 12 h/d was also presented, which was also shown to lower liver arachidonic acid content. RP Salem, N (reprint author), NIAAA,LAB MEMBRANE BIOCHEM & BIOPHYS,12501 WASHINGTON AVE,ROCKVILLE,MD 20852, USA. NR 11 TC 45 Z9 46 U1 0 U2 1 PU AMER OIL CHEMISTS SOC PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 SN 0024-4201 J9 LIPIDS JI Lipids PD MAR PY 1996 VL 31 SU S BP S153 EP S156 DI 10.1007/BF02637068 PG 4 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA UB908 UT WOS:A1996UB90800027 PM 8729111 ER PT J AU Tataranni, PA Baier, LJ Paolisso, G Howard, BV Ravussin, E AF Tataranni, PA Baier, LJ Paolisso, G Howard, BV Ravussin, E TI Role of lipids in development of noninsulin-dependent diabetes mellitus: Lessons learned from Pima Indians SO LIPIDS LA English DT Article; Proceedings Paper CT 2nd Congress of the International-Society-for-the-Study-of-Fatty-Acids-and-Lipids CY JUN 07-10, 1995 CL NIH, NATCHER CONF CTR, BETHESDA, MD SP Int Soc Study Fatty Acids & Lipids HO NIH, NATCHER CONF CTR ID FATTY-ACID METABOLISM; INSULIN-RESISTANCE; GLUCOSE; OBESITY; OXIDATION AB We studied the role of lipids in the pathogenesis of noninsulin-dependent diabetes mellitus (NIDDM) in Pima Indians. High plasma levels of nonesterified fatty acid (NEFA) predicted development of NIDDM, but this effect cannot entirely be explained by the glucose-fatty acid cycle. Dyslipidemia, although often associated with diabetes, did not seem to predict NIDDM and might rather be associated with, or the consequence of insulin resistance. In some individuals, a single amino acid substitution in the intestinal fatty acid binding protein could result in increased rates of intestinal absorption of dietary NEFA and thereby contribute to increased lipid-oxidation rates and insulin resistance. RP Tataranni, PA (reprint author), NIDDKD, NIH, CLIN DIABET & NUTR SECT, 4212 N 16TH STR, ROOM 541-A, PHOENIX, AZ 85016 USA. OI Paolisso, Giuseppe/0000-0002-2137-455X NR 31 TC 11 Z9 11 U1 0 U2 0 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0024-4201 EI 1558-9307 J9 LIPIDS JI Lipids PD MAR PY 1996 VL 31 SU S BP S267 EP S270 DI 10.1007/BF02637088 PG 4 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA UB908 UT WOS:A1996UB90800047 PM 8729131 ER PT J AU Alavanja, MCR Brownson, RC Benichou, J AF Alavanja, MCR Brownson, RC Benichou, J TI Estimating the effect of dietary fat on the risk of lung cancer in nonsmoking women SO LUNG CANCER LA English DT Article; Proceedings Paper CT International Symposium on Lifestyle Factors and Human Lung Cancer CY DEC 12-16, 1994 CL GUANGZHOU, PEOPLES R CHINA SP Guangzhou Med Coll, China, New York Med Coll, US DE lung cancer; nonsmoking women; dietary fat; saturated fat; Missouri; risk factors for lung cancer ID ATTRIBUTABLE RISK; PASSIVE SMOKING; CHOLESTEROL; HAWAII; POPULATION; MISSOURI; MEN AB In 1992, approximately 13 000 lung cancers occurred in nonsmoking U.S. women but the cause of these highly fatal tumors is not well understood. As the rate of smoking declines in many developed countries, the interest in identifying lung cancer risk factors other than tobacco smoking is increasing. A population-based, case-control study of incident lung cancer among nonsmoking women in Missouri was conducted between 1986 and 1992 to assess the effect of a comprehensive list of potential risk factors. Dietary information on 429 case subjects and 1021 control subjects was obtained by personal interview, or next-of-kin interviews (36% and 64%, respectively) and the relationship of diet to lung cancer risk is the focus of this investigation. Odds ratios and population attributable risks (PAR) for dietary fat and dietary saturated fat were computed among lifetime nonsmokers and long-term ex-smokers. The mean age at lung cancer diagnosis was 71 years old, and nearly 50% of the lung cancers were histologically confirmed adenocarcinomas. Dietary intake of saturated fat was the leading identified cause of lung cancer among lifetime nonsmokers and former smokers in Missouri. The etiologic link between dietary saturated fat and lung cancer has not been examined in many other studies and the studies published to date are not completely consistent with the hypothesis so a cautious interpretation of the population attributable risks for these exposures is warranted. Nonetheless, a growing number of studies arising from around the world purport to show a link between fat, saturated fat and/or cholesterol or food groups containing relatively high amounts of these macronutrients (i.e. dairy products, eggs and/or red meat consumption) and lung cancer, and these recent studies add support to this hypothesis. If the results from Missouri are valid and applicable to other Americans, 23% of lung cancer cases among lifetime nonsmokers in the United States could be prevented if the saturated fat consumption of the upper half of saturated fat intake continuum could be reduced to the level consumed by the lower half. Even greater reductions in risk could be achieved if saturated fat consumption were reduced to even lower levels (i.e. 20th percentile of consumption as shown in this paper). However, additional etiologic research and evaluation is needed before specific dietary recommendations concerning fat and saturated fat and lung cancer prevention can be made. C1 ST LOUIS UNIV,SCH PUBL HLTH,DEPT COMMUNITY HLTH,ST LOUIS,MO. RP Alavanja, MCR (reprint author), NCI,EPIDEMIOL & BIOSTAT PROGRAM,BETHESDA,MD 20892, USA. NR 32 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD MAR PY 1996 VL 14 SU 1 BP S63 EP S74 PG 12 WC Oncology; Respiratory System SC Oncology; Respiratory System GA UE523 UT WOS:A1996UE52300006 PM 8785668 ER PT J AU Xu, ZY Brown, L Pan, GW Li, G Feng, YP Guan, DX Liu, TF Liu, LM Chao, RM Sheng, JH Gao, GC AF Xu, ZY Brown, L Pan, GW Li, G Feng, YP Guan, DX Liu, TF Liu, LM Chao, RM Sheng, JH Gao, GC TI Lifestyle, environmental pollution and lung cancer in cities of Liaoning in northeastern China SO LUNG CANCER LA English DT Article; Proceedings Paper CT International Symposium on Lifestyle Factors and Human Lung Cancer CY DEC 12-16, 1994 CL GUANGZHOU, PEOPLES R CHINA SP Guangzhou Med Coll, China, New York Med Coll, US DE lung cancer; occupational exposure; environmental pollution; lifestyle factors ID AIR-POLLUTION AB Several studies were conducted in cities of Liaoning Province, one of the areas of China with heavy concentrations of industry, to investigate the effects of life-style factors and environmental pollutants on lung cancer causation. A case-control study involving 1249 lung cancer patients and 1345 population-based controls was conducted in 1985-1988 in Shenyang, the capital of Liaoning. Cigarette smoking was found to be the principal cause of lung cancer in this population, accounting for 55% of the disease in males and 37% in females. There was also a significant increase in lung cancer risk associated with an overall index of indoor air pollution due to coal-burning emission. The population attributable risk (PAR) for indoor air pollution was 13% for males and 17% for females. Risks were significantly increased for workers in the non-ferrous smelter (odds ratio (OR) = 2.6, 95% CI, 1.3-5.1), chemical and drug manufacturing (OR = 3.0, 95% Cr, 1.0-8.0), and the glass and pottery industry (OR = 1.6, 95% CI, 1.0-2.5). Studies in the Anshan Iron-Steel Complex showed a significant excess of lung cancer for workers exposed to a variety of dusts. A standardized proportional mortality ratio (SPMR) study of 8887 deaths during 1980-1989 among male workers of the complex indicated a 37% excess risk of lung cancer compared to residents of the city. A nested case-control study was then conducted in that complex. A total of 610 cases of lung cancer diagnosed during 1987-1993 and 959 randomly selected controls from 196 993 active and retired employees of the complex were interviewed. Historical monitoring records for dust and benzo(a)pyrene (B(a)P) were collected from 1956-1992 to calculate cumulative exposure for each person. Results suggested that risks were increased for all occupations in which there was exposure to dusts, with the highest risks seen among coke oven workers (OR = 3.5, 95% CI, 2.0-6.4) and fire-resistant brick makers (OR = 2.9, 95% CI, 1.9-4.4). Significant dose-response patterns between cumulative total dust, cumulative total B(a)P and lung cancer risk were observed. The findings suggest that smoking and environmental pollution combine to account for elevated rates of lung cancer in cities of northeastern China. C1 NCI,BETHESDA,MD 20892. ANSHAN IRON STEEL COMPLEX,PUBL HLTH STN,SHENYANG,PEOPLES R CHINA. INST LABOR HYG ANSHAN IRON STEEL COMPLEX,SHENYANG,PEOPLES R CHINA. RP Xu, ZY (reprint author), LIAONING PUBL HLTH & ANTIEPIDEM STN,SHENYANG,PEOPLES R CHINA. NR 11 TC 19 Z9 22 U1 3 U2 8 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD MAR PY 1996 VL 14 SU 1 BP S149 EP S160 DI 10.1016/S0169-5002(96)90220-2 PG 12 WC Oncology; Respiratory System SC Oncology; Respiratory System GA UE523 UT WOS:A1996UE52300015 PM 8785660 ER EF