FN Thomson Reuters Web of Science™ VR 1.0 PT J AU van Bergen, P Rauhala, P Spooner, C Chiueh, CC AF van Bergen, P Rauhala, P Spooner, C Chiueh, CC TI Pro- and anti-oxidative effects of hemoglobin and its metabolites in the brain SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIMH, Unit Neurodegenerat & Neuroprotect, Clin Sci Lab, Bethesda, MD 20892 USA. 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 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A481 EP A481 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033302772 ER PT J AU Vassell, R Glenn, G Udey, M Scharton-Kersten, T Alving, C Jakob, T AF Vassell, R Glenn, G Udey, M Scharton-Kersten, T Alving, C Jakob, T TI Activation of langerhans cells following transcutaneous immunization. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Iomai Corp, Walter Reed Army Inst Res, Washington, DC 20307 USA. NIH, Bethesda, MD 20892 USA. RI Jakob, Thilo/J-1621-2012 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 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A633 EP A633 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033303654 ER PT J AU Vieira, NE Goans, RE Weiss, GH Marini, JC Hopkins, E Yergey, AL AF Vieira, NE Goans, RE Weiss, GH Marini, JC Hopkins, E Yergey, AL TI Calcium kinetics in children with Osteogenesis Imperfecta Type III and IV: Response to growth hormone therapy SO FASEB JOURNAL LA English DT Meeting Abstract C1 NICHD & DCRT, NIH, Bethesda, MD 20892 USA. Oak Ridge Associated Univ, REACTS, Oak Ridge, TN 37716 USA. 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 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A244 EP A244 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033301406 ER PT J AU Wahlsten, J Gitchell, H Caspi, R AF Wahlsten, J Gitchell, H Caspi, R TI Exogenous IL-12 protects against experimental autoimmune encephalomyelitis (EAE). SO FASEB JOURNAL LA English DT Meeting Abstract C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. 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 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A285 EP A285 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033301645 ER PT J AU Walden, R Pritchard, JB AF Walden, R Pritchard, JB TI Mechanism of organic anion transport across the apical membrane of choroid plexus. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. 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 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A61 EP A61 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033300350 ER PT J AU Wang, RF Wang, X Atwood, A Rosenberg, SA AF Wang, RF Wang, X Atwood, A Rosenberg, SA TI Genetic engineering of antigen presentation of MHC class-II restricted antigens SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. 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 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A275 EP A275 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033301585 ER PT J AU Wang, WH Wang, SB Madara, P Cintron, AD Danner, RL AF Wang, WH Wang, SB Madara, P Cintron, AD Danner, RL TI Endothelial nitric oxide synthase upregulates TNF alpha production in transfected U937 cells through superoxide-dependent activation of P44/42 mitogen activated protein kinase. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. 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 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A132 EP A132 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033300760 ER PT J AU Weinstein, DL O'Neill, BL Miller, MJ Cuttitta, F Metcalf, ES AF Weinstein, DL O'Neill, BL Miller, MJ Cuttitta, F Metcalf, ES TI Adrenomedullin is induced in human small intestinal epithelial cells by Salmonella typhi. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. NCI, Biomarkers & Prevent Branch, NIH, Bethesda, MD 20892 USA. 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 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A290 EP A290 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033301677 ER PT J AU Welniak, LA Blazar, BR Wiltrout, R Murphy, WJ AF Welniak, LA Blazar, BR Wiltrout, R Murphy, WJ TI Intensity of conditioning regimen in GVHD models result in opposing outcomes in the absence of interferon gamma production by donor T cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Univ Minnesota, Ctr Canc, Minneapolis, MN 55455 USA. 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 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A614 EP A614 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033303542 ER PT J AU Weyer, C Bogardus, C Pratley, RE AF Weyer, C Bogardus, C Pratley, RE TI Metabolic factors contributing to the increase in resting metabolic rate (RMR) during the development of type 2 diabetes in Pima Indians. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIDDK, CDNS, Natl Inst Hlth, Phoenix, AZ 85016 USA. 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 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A54 EP A54 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033300308 ER PT J AU Whittaker, P San, RHC Seifried, HE Dunkel, VC AF Whittaker, P San, RHC Seifried, HE Dunkel, VC TI Genotoxicity of iron compounds. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. BioReliance, Rockville, MD 20850 USA. US FDA, Washington, DC 20204 USA. 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 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A574 EP A574 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033303311 ER PT J AU Wilson, CG Wong, S Koshiya, N Smith, JC AF Wilson, CG Wong, S Koshiya, N Smith, JC TI Real time imaging and patch clamp recording from hypoglossal pre-motoneurons in thin medullary slices in vitro SO FASEB JOURNAL LA English DT Meeting Abstract C1 NINDS, LNLC, 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 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A493 EP A493 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033302842 ER PT J AU Winkler-Pickett, R Lai, WC Mikovits, J Ruscetti, FW Ortaldo, JR AF Winkler-Pickett, R Lai, WC Mikovits, J Ruscetti, FW Ortaldo, JR TI Analysis of Ly-49H as an activating NK cell receptor SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Frederick Canc Res & Dev Ctr, SAIC, Expt Immunol Lab,DBS, Frederick, MD USA. NCI, Frederick Canc Res & Dev Ctr, SAIC, Lab Leuko Biol,DBS, Frederick, MD USA. SW Texas State Univ, Dallas, TX USA. 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 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A308 EP A308 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033301781 ER PT J AU Yamashita, M Glasgow, E Kusano, K Zhang, B Gainer, H AF Yamashita, M Glasgow, E Kusano, K Zhang, B Gainer, H TI Differential gene expression in magnocellular oxytocin and vasopressin neurons in rat hypothalamus. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. 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 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A477 EP A477 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033302752 ER PT J AU Yap, GS Hieny, S Souza, CRE Shear, A AF Yap, GS Hieny, S Souza, CRE Shear, A TI Preinjection with parasite antigen protects IL-10 deficient mice from lethal Th-1 associated immunopathology induced by toxoplasma gondii infections. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Imperial Canc Res Fund, London WC2A 3PX, England. NIAID, LPD, NIH, Bethesda, MD 20892 USA. 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 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A632 EP A632 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033303648 ER PT J AU Ying, H Zaks, TZ Wang, RF Irvine, KR Restifo, NP AF Ying, H Zaks, TZ Wang, RF Irvine, KR Restifo, NP TI Cancer therapy using a self-replicating nucleic acid vaccine SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. RI Restifo, Nicholas/A-5713-2008 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 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A299 EP A299 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033301726 ER PT J AU Zeller, JC Taylor, PA Panoskaltsis-Mortari, A Murphy, WJ Ruscetti, FW Narula, S Roncarolo, MG Blazar, BR AF Zeller, JC Taylor, PA Panoskaltsis-Mortari, A Murphy, WJ Ruscetti, FW Narula, S Roncarolo, MG Blazar, BR TI Ex vivo IL10 and TGF-beta act synergistically to induce CD4(+) alloantigen-specific tolerance resulting in diminished graft-versus-host disease in vivo. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA. NCI, Frederick Canc Res & Dev Ctr, DBS, Frederick, MD 21702 USA. Plough Res Inst, Kenilworth, NJ 07033 USA. DNAX Res Inst Mol & Cellular Biol Inc, Palo Alto, CA 93403 USA. TIGET, I-20132 Milan, Italy. 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 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A614 EP A614 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033303537 ER PT J AU Zhang, B Glasgow, E Murase, T Verbalis, JG Gainer, H AF Zhang, B Glasgow, E Murase, T Verbalis, JG Gainer, H TI Chronic hyponatremia induces a selective decrease in cell volume of magnocellular neurons in the hypothalamic supraoptic nucleus. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Div Endocrinol, Washington, DC 20007 USA. 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 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A477 EP A477 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033302751 ER PT J AU Zhou, P Seder, RA AF Zhou, P Seder, RA TI CD8+T cells have a role in primary immunity to H. capsulatum independent of IFN-g and perforin. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAID, NIH, Bethesda, MD 20892 USA. 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 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A322 EP A322 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033301862 ER PT J AU Ziegler, R Craft, N Fears, T Stemmermann, G Nomura, A AF Ziegler, R Craft, N Fears, T Stemmermann, G Nomura, A TI Individual carotenoids in the etiology of lung and upper aerodigestive tract cancers. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Craft Technol, Wilson, NC 27893 USA. Kuakini Med Ctr, Honolulu, HI 96817 USA. 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 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 12 PY 1999 VL 13 IS 4 SU S BP A210 EP A210 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 226QW UT WOS:000082033301213 ER PT J AU Jobbagy, Z Olah, Z Petrovics, G Eiden, MV Leverett, BD Dean, NM Anderson, WB AF Jobbagy, Z Olah, Z Petrovics, G Eiden, MV Leverett, BD Dean, NM Anderson, WB TI Up-regulation of the Pit-2 phosphate transporter retrovirus receptor by protein kinase C epsilon SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID APE LEUKEMIA-VIRUS; OSTEOBLAST-LIKE CELLS; NIH 3T3 CELLS; ECOTROPIC MURINE RETROVIRUSES; AMINO-ACID TRANSPORTER; PARATHYROID-HORMONE; SURFACE RECEPTOR; GROWTH; INVOLVEMENT; STIMULATION AB The membrane receptors for the gibbon ape leukemia retrovirus and the amphotropic murine retrovirus serve normal cellular functions as sodium-dependent phosphate transporters (Pit-1 and Pit-2, respectively). Our earlier studies established that activation of protein kinase C (PKC) by treatment of cells with phorbol 12-myristate 13-acetate (PMA) enhanced sodium-dependent phosphate (Na/P-i) uptake, Studies now have been carried out to determine which type of Na/P-i transporter (Pit-1 or Pit-2) is regulated by PKC and which PKC isotypes are involved in the up-regulation of Na/P-i uptake by the Na/P-i transporter/viral receptor. It was found that the activation of short term (2-min) Na/P-i uptake by PMA is abolished when cells are infected with amphotropic murine retrovirus (binds Pit-2 receptor) but not with gibbon ape leukemia retrovirus (binds Pit-1 receptor), indicating that Pit-2 is the form of Na/P-i, transporter/viral receptor regulated by PKC, The PKC-mediated activation of Pit-2 was blocked by pretreating cells with the pan-PKC inhibitor bisindolylmaleimide but not with the conventional PKC isotype inhibitor Go 6976, suggesting that a novel PKC isotype is required to regulate Pit-2. Overexpression of PKC epsilon, but not of PKC alpha, -delta, or -zeta was found to mimic the activation of Na/P-i uptake. To further establish that PKC epsilon is involved in the regulation of Pit-2, cells were treated with PKC epsilon-selective antisense oligonucleotides, Treatment with PKC epsilon antisense oligonucleotides decreased the PMA-induced activation of Na/P-i uptake. These results indicate that PMA-induced stimulation of Na/P-i uptake by Pit-2 is specifically mediated through activation of PKC epsilon. C1 NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. NIMH, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. ISIS Pharmaceut, Carlsbad Res Ctr, Dept Pharmacol, Carlsbad, CA 92008 USA. RP Anderson, WB (reprint author), NCI, Cellular Oncol Lab, NIH, Bldg 37,Rm 1E-14,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 34 TC 22 Z9 22 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 12 PY 1999 VL 274 IS 11 BP 7067 EP 7071 DI 10.1074/jbc.274.11.7067 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 175DV UT WOS:000079078400035 PM 10066763 ER PT J AU Stierum, RH Croteau, DL Bohr, VA AF Stierum, RH Croteau, DL Bohr, VA TI Purification and characterization of a mitochondrial thymine glycol endonuclease from rat liver SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HAMSTER OVARY CELLS; OXIDATIVE DNA-DAMAGE; ESCHERICHIA-COLI; ULTRAVIOLET-RADIATION; SACCHAROMYCES-CEREVISIAE; HUMAN HOMOLOG; POLYMERASE-I; BASE DAMAGE; REPAIR; GLYCOSYLASE AB Mitochondrial DNA is exposed to oxygen radicals produced during oxidative phosphorylation, Accumulation of several kinds of oxidative lesions in mitochondrial DNA may lead to structural genomic alterations, mitochondrial dysfunction, and associated degenerative diseases. The pyrimidine hydrate thymine glycol, one of many oxidative lesions, can block DNA and RNA polymerases and thereby exert negative biological effects. Mitochondrial DNA repair of this lesion is important to ensure normal mitochondrial DNA metabolism. Here, we report the purification of a novel rat liver mitochondrial thymine glycol endonuclease (mtTGendo), By using a radiolabeled oligonucleotide duplex containing a single thymine glycol lesion, damage-specific incision at the modified thymine was observed upon incubation with mitochondrial protein extracts. After purification using cation exchange, hydrophobic interaction, and size exclusion chromatography, the most pure active fractions contained a single band of similar to 37 kDa on a silver-stained gel. MtTGendo is active within a broad KCI concentration range and is EDTA-resistant. Furthermore, mtTGendo has an associated apurinic/apyrimidiniclyase activity. MtTGendo does not incise 8-oxodeoxyguanosine or uracil-containing duplexes or thymine glycol in single-stranded DNA. Based upon functional similarity, we conclude that mtTGendo may be a rat mitochondrial homolog of the Escherichia coli endonuclease III protein. C1 NIA, Genet Mol Lab, NIH, Baltimore, MD 21224 USA. RP Bohr, VA (reprint author), NIA, Genet Mol Lab, NIH, Box 01,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 44 TC 26 Z9 26 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 12 PY 1999 VL 274 IS 11 BP 7128 EP 7136 DI 10.1074/jbc.274.11.7128 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 175DV UT WOS:000079078400043 PM 10066771 ER PT J AU Candi, E Tarcsa, E Idler, WW Kartasova, T Marekov, LN Steinert, PM AF Candi, E Tarcsa, E Idler, WW Kartasova, T Marekov, LN Steinert, PM TI Transglutaminase cross-linking properties of the small proline-rich 1 family of cornified cell envelope proteins - Integration with loricrin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN EPIDERMAL-KERATINOCYTES; DIFFERENTIATION-SPECIFIC GENES; MALIGNANT KERATINOCYTES; SUBSTRATE-SPECIFICITY; PROTRANSGLUTAMINASE-E; EPITHELIAL-CELLS; BOND FORMATION; RETINOIC ACID; SPR1 GENE; EXPRESSION AB Small proline-rich 1 (SPR1) proteins are important for barrier function in stratified squamous epithelia, To explore their properties, we expressed in bacteria a recombinant human SPR1 protein and isolated native SPR1 proteins from cultured mouse keratinocytes. By circular dichroism, they possess no alpha or beta structure but have some organized structure associated with their central peptide repeat domain. The transglutaminase (TGase) 1 and 3 enzymes use the SPR1 proteins as complete substrates in vitro but in different ways: head domain A sequences at the amino terminus were used preferentially for cross-linking by TGase 3, whereas those in head domain B sequences were used for cross-linking by TGase 1. The TGase 2 enzyme cross-linked SPR1 proteins poorly. Together with our data base of 141 examples of in vivo cross-links between SPRs and loricrin, this means that both TGase 1 and 3 are required for cross-linking SPR1 proteins in epithelia in vivo. Double in vitro cross-linking experiments suggest that oligomerization of SPR1 into large polymers can occur only by further TGase 1 cross-linking of an initial TGase 3 reaction. Accordingly, we propose that TGase 3 first cross-links loricrin and SPRs together to form small interchain oligomers, which are then permanently affixed to the developing CE by further cross-linking by the TGase 1 enzyme. This is consistent with the known consequences of diminished barrier function in TGase 1 deficiency models. C1 NIAMS, Skin Biol Lab, NIH, Bethesda, MD 20892 USA. RP Steinert, PM (reprint author), NIAMS, Skin Biol Lab, NIH, Bldg 6,Rm 425,9000 Rockville Pike, Bethesda, MD 20892 USA. EM pemast@helix.nih.gov NR 58 TC 58 Z9 59 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 12 PY 1999 VL 274 IS 11 BP 7226 EP 7237 DI 10.1074/jbc.274.11.7226 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 175DV UT WOS:000079078400056 PM 10066784 ER PT J AU Dell'Angelica, EC Mullins, C Bonifacino, JS AF Dell'Angelica, EC Mullins, C Bonifacino, JS TI AP-4, a novel protein complex related to clathrin adaptors SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID VESICLE FORMATION; GOLGI MEMBRANES; SORTING SIGNALS; COAT PROTEINS; CELL-SURFACE; BINDING; RECEPTOR; SUBUNIT; IDENTIFICATION; RECRUITMENT AB Here we report the identification and characterization of AP-4, a novel protein complex related to the heterotetrameric AP-1, AP-2, and AP-3 adaptors that mediate protein sorting in the endocytic and late secretory pathways. The key to the identification of this complex was the cloning and sequencing of two widely expressed, mammalian cDNAs encoding new homologs of the adaptor beta and a subunits named beta 4 and sigma 4, respectively. An antibody to beta 4 recognized in human cells an similar to 83-kDa polypeptide that exists in both soluble and membrane-associated forms. Golgi filtration, sedimentation velocity, and immunoprecipitation experiments revealed that beta 4 is a component of a multisubunit complex (AP-4) that also contains the sigma 4 polypeptide and two additional adaptor subunit homologs named mu 4 (mu-ARP2) and epsilon. Immunofluorescence analyses showed that AP-4 is associated with the trans-Golgis network or an adjacent structure and that this association is sensitive to the drug brefeldin A. We propose that, like the related AP-1, AP-2, and AP-3 complexes, AP-4 plays a role in signal-mediated trafficking of integral membrane proteins in mammalian cells. C1 NICHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Bonifacino, JS (reprint author), NICHD, Cell Biol & Metab Branch, NIH, Bldg 18T,Rm 101, Bethesda, MD 20892 USA. OI Bonifacino, Juan S./0000-0002-5673-6370 NR 41 TC 166 Z9 171 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 12 PY 1999 VL 274 IS 11 BP 7278 EP 7285 DI 10.1074/jbc.274.11.7278 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 175DV UT WOS:000079078400062 PM 10066790 ER PT J AU Strumberg, D Nitiss, JL Rose, A Nicklaus, MC Pommier, Y AF Strumberg, D Nitiss, JL Rose, A Nicklaus, MC Pommier, Y TI Mutation of a conserved serine residue in a quinolone-resistant type II topoisomerase alters the enzyme-DNA and drug interactions SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EUKARYOTIC TOPOISOMERASE; ESCHERICHIA-COLI; CLEAVAGE; YEAST; DERIVATIVES; INHIBITORS; MECHANISM; COMPLEX; BINDING; GYRASE AB A Ser(740) --> Trp mutation in yeast topoisomerase II (top2) and of the equivalent Ser(83) in gyrase results in resistance to quinolones and confers hypersensitivity to etoposide (VP-16), We characterized the cleavage complexes induced by the top2(S740W) in the human c-myc gene. In addition to resistance to the fluoroquinolone CP-115,953, top2(S740W) induced novel DNA cleavage sites in the presence of VP-16, azatoxin, amsacrine, and mitoxantrone, Analysis of the VP-16 sites indicated that the changes in the cleavage pattern were reflected by alterations in base preference. C at position -2 and G at position +6 were observed for the top(2S740W) in addition to the previously reported C-1 and G+5 for the wildtype top2, The VP-16-induced top(2S740W) cleavage complexes were also more stable. The most stable sites had strong preference for C-l, whereas the most reversible sites showed no base preference at positions -1 or -2, Different patterns of DNA cleavage were also observed in the absence of drug and in the presence of calcium. These results indicate that the Ser(740) --> Trp mutation alters the DNA recognition of top2, enhances its DNA binding, and markedly affects its interactions with inhibitors. Thus, residue 740 of top2 appears critical for both DNA and drug interactions. C1 NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. NCI, Med Chem Lab, Div Basic Sci, NCI, Bethesda, MD 20892 USA. St Jude Childrens Res Hosp, Dept Mol Pharmacol, Memphis, TN 38105 USA. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, NIH, Blg 37,Rom 5D02, Bethesda, MD 20892 USA. RI Nitiss, John/E-9974-2010; Nicklaus, Marc/N-4183-2014; OI Nitiss, John/0000-0002-1013-4972 FU NCI NIH HHS [CA52814] NR 48 TC 19 Z9 19 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 12 PY 1999 VL 274 IS 11 BP 7292 EP 7301 DI 10.1074/jbc.274.11.7292 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 175DV UT WOS:000079078400064 PM 10066792 ER PT J AU Park, SH Liu, XW Hennighausen, L Davey, HW Waxman, DJ AF Park, SH Liu, XW Hennighausen, L Davey, HW Waxman, DJ TI Distinctive roles of STAT5a and STAT5b in sexual dimorphism of hepatic P450 gene expression - Impact of Stat5a gene disruption SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TESTOSTERONE 16-ALPHA-HYDROXYLASE I-P-45016-ALPHA; GROWTH-HORMONE STIMULATION; DNA-BINDING; TYROSINE PHOSPHORYLATION; MAMMARY-GLAND; MOUSE-LIVER; RAT HEPATOCYTES; PROLACTIN; CYTOCHROME-P450; TRANSCRIPTION AB Stat5b gene disruption leads to an apparent growth hormone (GH) pulse insensitivity associated with loss of male-characteristic body growth rates and male-specific liver gene expression (Udy, G, B,, Towers, R. P,, Snell, R. G,, Wilkins, R, J,, Park, S, H,, Ram, P, A., Waxman, D, J,, and Davey, H, W, (1997) Proc. Natl. Acad. Sci. U.S.A. 94, 7239-7244). In the present study, disruption of the mouse Stat5a gene, whose coding sequence is similar to 90% identical to the Stat5b gene, resulted in no loss of expression in male mice of several sex-dependent, GH-regulated liver cytochrome P450 (CYP) enzymes. By contrast, the loss of STAT5b feminized the livers of males by decreasing expression of male-specific CYPs (CYP2D9 and testosterone 16 alpha-hydroxylase) while increasing to female levels several female-predominant liver CYPs (CYP3A, CYP2B, and testosterone 6 beta-droxylase). Since STAT5a is thus nonessential for these male GH responses, STAT5b homodimers, but not STAT5a-STAT5b heterodimers, probably mediate the sexually dimorphic effects of male GH pulses on liver CYP expression. In female mice, however, disruption of either Stat5a or Stat5b led to striking decreases in several liver CYP-catalyzed testosterone hydroxylase activities. Stat5a or Stat5b gene disruption also led to the loss of a female-specific, GH-regulated hepatic CYP2B enzyme. STAT5a, which is much less abundant in liver than STAT5b, and STAT5b are therefore both required for constitutive expression in female but not male mouse liver of certain GH-regulated CYP steroid hydroxylases, suggesting that STAT5 protein heterodimerization is an important determinant of the sex-dependent and gene-specific effects that GH has on the liver. C1 Boston Univ, Dept Biol, Div Cell & Mol Biol, Boston, MA 02215 USA. NIDDK, NIH, Bethesda, MD 20892 USA. AgResearch, Hamilton, New Zealand. RP Boston Univ, Dept Biol, Div Cell & Mol Biol, 5 Cummington St, Boston, MA 02215 USA. EM djw@bio.bu.edu FU NIDDK NIH HHS [R01 DK033765] NR 55 TC 85 Z9 86 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 12 PY 1999 VL 274 IS 11 BP 7421 EP 7430 DI 10.1074/jbc.274.11.7421 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 175DV UT WOS:000079078400079 PM 10066807 ER PT J AU Gupta, N Scharenberg, AM Fruman, DA Cantley, LC Kinet, JP Long, EO AF Gupta, N Scharenberg, AM Fruman, DA Cantley, LC Kinet, JP Long, EO TI The SH2 domain-containing inositol 5 '-phosphatase (SHIP) recruits the p85 subunit of phosphoinositide 3-kinase during Fc gamma RIIb1-mediated inhibition of B cell receptor signaling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FC-GAMMA-RIIB; PHOSPHATIDYLINOSITOL 3-KINASE; POLYPHOSPHATE 5-PHOSPHATASE; TYROSINE PHOSPHORYLATION; PHOSPHATASE SHIP; ACTIVATION; ANTIGEN; KINASE; IMMUNOGLOBULIN; LYMPHOCYTES AB Coligation of Fc gamma RIIb1 with the B cell receptor (BCR) or Fc epsilon RI on mast cells inhibits B cell or mast cell activation, Activity of the inositol phosphatase SHIP is required for this negative signal. In vitro, SHIP catalyzes the conversion of the phosphoinositide 3-kinase (PI3K) product phosphatidylinositol 3,4,5-trisphosphate (PIP3) into phosphatidylinositol 3,4-bisphosphate. Recent data demonstrate that coligation of Fc gamma RIIb1 with BCR inhibits PIP3-dependent Btk (Bruton's tyrosine kinase) activation and the Btk-dependent generation of inositol trisphosphate that regulates sustained calcium influx, In this study, we provide evidence that coligation of Fc gamma RIIb1 with BCR induces binding of PI3K to SHIP, This interaction is mediated by the binding of the SH2 domains of the p85 subunit of PI3K to a tyrosine-based motif in the C-terminal region of SHIP. Furthermore, the generation of phosphatidylinositol 3,4-bisphosphate was only partially reduced during coligation of BCR with Fc gamma RIIb1 despite a drastic reduction in PIP3. In contrast to the complete inhibition of Tec kinase-dependent calcium signaling, activation of the serine/threonine kinase Akt was partially preserved during BCR and Fc gamma RIIb1 coligation, The association of PI3K with SHIP may serve to activate PI3K and to regulate downstream events such as B cell activation-induced apoptosis. C1 NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. Beth Israel Deaconess Med Ctr, Lab Allergy & Immunol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Lab Signal Transduct, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP NIAID, Immunogenet Lab, NIH, Twinbrook II,12441 Parklawn Dr, Rockville, MD 20852 USA. EM elong@nih.gov RI Long, Eric/G-5475-2011; Cantley, Lewis/D-1800-2014 OI Long, Eric/0000-0002-7793-3728; Cantley, Lewis/0000-0002-1298-7653 FU NIGMS NIH HHS [R01 GM041890] NR 40 TC 46 Z9 46 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 12 PY 1999 VL 274 IS 11 BP 7489 EP 7494 DI 10.1074/jbc.274.11.7489 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 175DV UT WOS:000079078400087 PM 10066815 ER PT J AU Kruth, HS Zhang, WY Skarlatos, SI Chao, FF AF Kruth, HS Zhang, WY Skarlatos, SI Chao, FF TI Apolipoprotein B stimulates formation of monocyte-macrophage surface-connected compartments and mediates uptake of low density lipoprotein-derived liposomes into these compartments SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MOUSE PERITONEAL-MACROPHAGES; RECEPTOR-RELATED PROTEIN; RICH LIPID PARTICLES; HUMAN ATHEROSCLEROTIC LESIONS; UNESTERIFIED CHOLESTEROL; FAMILIAL HYPERCHOLESTEROLEMIA; MONOCLONAL-ANTIBODIES; HYPERLIPIDEMIC RABBIT; BETA-VLDL; ACCUMULATION AB Much of the cholesterol that accumulates in atherosclerotic plaques is found within monocyte-macrophages transforming these cells into "foam cells." Native low density lipoprotein (LDL) does not cause foam cell formation. Treatment of LDL with cholesterol esterase converts LDL into cholesterol-rich liposomes having >90% cholesterol in unesterified form. Similar cholesterol-rich liposomes are found in early developing atherosclerotic plaques surrounding foam cells. We now show that cholesterol-rich liposomes produced from cholesterol esterase-treated LDL can cause human monocyte-macrophage foam cell formation inducing a 3-5-fold increase in macrophage cholesterol content of which >60% is esterified. Although cytochalasin D inhibited LDL liposome-induced macrophage cholesteryl ester accumulation, LDL liposomes did not enter macrophages by phagocytosis. Rather, the LDL liposomes induced and entered surface-connected compartments within the macrophages, a unique endocytic pathway in these cells that we call patocytosis, LDL liposome apoB rather than LDL liposome lipid mediated LDL liposome uptake by macrophages, This was shown by the findings that: 1) protease treatment of the LDL liposomes prevented macrophage cholesterol accumulation; 2) liposomes prepared from LDL lipid extracts did not cause macrophage cholesterol accumulation; and 3) purified apoB induced and accumulated within macrophage surface-connected compartments. Although apoB mediated the macrophage uptake of LDL liposomes, this uptake did not occur through LDL, LDL receptor-related protein, or scavenger receptors, Also, LDL liposome uptake was not sensitive to treatment of macrophages with trypsin or heparinase, Cholesterol esterase-mediated transformation of LDL into cholesterol-rich liposomes is an LDL modification that: 1) stimulates uptake of LDL cholesterol by apoB-dependent endocytosis into surface-connected compartments, and 2) causes human monocyte-macrophage foam cell formation. C1 NHLBI, Sect Expt Atherosclerosis, NIH, Bethesda, MD 20892 USA. RP Kruth, HS (reprint author), NHLBI, Sect Expt Atherosclerosis, NIH, Bldg 10,Rm 5N-113,10 Ctr Dr,MSC 1422, Bethesda, MD 20892 USA. NR 46 TC 20 Z9 20 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 12 PY 1999 VL 274 IS 11 BP 7495 EP 7500 DI 10.1074/jbc.274.11.7495 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 175DV UT WOS:000079078400088 PM 10066816 ER PT J AU Du, QZ Wu, CJ Qian, GJ Wu, PD Ito, Y AF Du, QZ Wu, CJ Qian, GJ Wu, PD Ito, Y TI Relationship between the flow-rate of the mobile phase and retention of the stationary phase in counter-current chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE counter-current chromatography; flow-rate; retention of stationary phase AB The retention percentages of the stationary phase (S-F) at various flow-rates (F-c) of 15 two-phase solvent systems were determined in three types of counter-current chromatographic apparatus equipped with small-, middle- and large-bore coiled columns. The regression analysis of S-F showed a linear relationship between the square root of the flow-rate and the retention percentage of the stationary phase, i.e. S-F=A-B root F-C where A indicates the difference in the solvent composition of the solvent system and B indicates the difference in the volume ratio of the solvents for the same composition of the solvent system. (C) 1999 Published by Elsevier Science B.V. All rights reserved. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. Chinese Acad Agr Sci, Tea Res Inst, Chinesse Minist Agr, Key Lab Tea Chem Engn, Hangzhou 310008, Zhejiang, Peoples R China. Zhejiang Univ, Dept Chem Engn, Hangzhou 310027, Zhejiang, Peoples R China. RP Ito, Y (reprint author), NHLBI, Biophys Chem Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 5 TC 60 Z9 64 U1 3 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD MAR 12 PY 1999 VL 835 IS 1-2 BP 231 EP 235 DI 10.1016/S0021-9673(98)01066-8 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 179GN UT WOS:000079318300021 ER PT J AU Weeks, RA Aziz-Sultan, A Bushara, KO Tian, B Wessinger, CM Dang, N Rauschecker, JP Hallett, M AF Weeks, RA Aziz-Sultan, A Bushara, KO Tian, B Wessinger, CM Dang, N Rauschecker, JP Hallett, M TI A PET study of human auditory spatial processing SO NEUROSCIENCE LETTERS LA English DT Article DE space perception; sound localization; inferior parietal lobule; sound frequency discrimination; H2O-PET; human brain mapping ID SOUND-LOCALIZATION; CEREBRAL-CORTEX; MEMORY; AREA AB To learn more about human auditory spatial processing, we used positron emission tomography (PET) to measure regional cerebral blood flow in human volunteers engaged in sound localization tasks. Spectral and binaural cues of localized sound were reproduced by a sound system and delivered via headphones. During localization tasks, subjects activated inferior parietal lobules (IPL) bilaterally. In a second experiment, matched in design to the first, subjects made non-spatial auditory discriminations based on frequency, activating the IPL bilaterally with left hemispheric predominance. A between-study comparison revealed that the right IPL was significantly more activated during the sound localization task compared with the feature discrimination task, suggesting a preferential role for the right IPL in auditory spatial processing. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Inst Cognit & Computat Sci, Washington, DC 20007 USA. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bldg 10,Room 5N226,10 Ctr Dr,MSC 1428, Bethesda, MD 20892 USA. EM hal-lett@codon.nih.gov RI Rauschecker, Josef/A-4120-2013 NR 14 TC 148 Z9 150 U1 1 U2 6 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 12 PY 1999 VL 262 IS 3 BP 155 EP 158 DI 10.1016/S0304-3940(99)00062-2 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 176UZ UT WOS:000079171400003 PM 10218879 ER PT J AU Carrington, M Nelson, GW Martin, MP Kissner, T Vlahov, D Goedert, JJ Kaslow, R Buchbinder, S Hoots, K O'Brien, SJ AF Carrington, M Nelson, GW Martin, MP Kissner, T Vlahov, D Goedert, JJ Kaslow, R Buchbinder, S Hoots, K O'Brien, SJ TI HLA and HIV-1: Heterozygote advantage and B*35-Cw*04 disadvantage SO SCIENCE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CYTOTOXIC T-CELL; HEPATITIS-B VIRUS; CLASS-I MOLECULES; TYPE-1 INFECTION; DISEASE PROGRESSION; CHEMOKINE RECEPTOR; GENETIC-VARIATION; AIDS; COMPLEX AB A selective advantage against infectious disease associated with increased heterozygosity at the human major histocompatibility complex [human Leukocyte antigen (HLA) class I and class II] is believed to play a major role in maintaining the extraordinary allelic diversity of these genes. Maximum HLA heterozygosity of class I loci (A, B, and C) delayed acquired immunodeficiency syndrome (AIDS) onset among patients infected with human immunodeficiency virus-type 1 (HIV-1), whereas individuals who were homozygous for one or more Loci progressed rapidly to AIDS and death. The HLA class I alleles B*35 and Cw*04 were consistently associated with rapid development of: AIDS-defining conditions in Caucasians. The extended survival of 28 to 40 percent of HIV1-infected Caucasian patients who avoided AIDS for ten or more years can be attributed to their being Fully heterozygous at HLA class I Loci, to their Lacking the AIDS-associated alleles B*35 and Cw*04, or to both. C1 NCI, Lab Genom Divers, Frederick, MD 21702 USA. NCI, Sci Applicat Corp Frederick, Intramural Res Support Program, Frederick, MD 21702 USA. Johns Hopkins Sch Hyg & Publ Hlth, Baltimore, MD 21205 USA. NCI, Viral Epidemiol Branch, Bethesda, MD 20892 USA. Univ Alabama, Multictr Hemophilia Cohort Study, Birmingham, AL 35294 USA. San Francisco City Clin Cohort, San Francisco, CA 94102 USA. Univ Texas, Hlth Sci Ctr, Gulf States Hemophilia Ctr, Houston, TX 77030 USA. RP O'Brien, SJ (reprint author), NCI, Lab Genom Divers, Frederick, MD 21702 USA. EM obrien@mail.ncifcrf.gov FU NCI NIH HHS [N01-CO-56000] NR 66 TC 811 Z9 845 U1 5 U2 41 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD MAR 12 PY 1999 VL 283 IS 5408 BP 1748 EP 1752 DI 10.1126/science.283.5408.1748 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 175PF UT WOS:000079102800056 PM 10073943 ER PT J AU Luzzio, FA Zacherl, DP Figg, WD AF Luzzio, FA Zacherl, DP Figg, WD TI A facile scheme for phthalimide reversible arrow phthalimidine conversion SO TETRAHEDRON LETTERS LA English DT Article DE oxidation; protecting groups; reduction; sonochemistry ID ISOINDOLINONE DERIVATIVES; LACTAMS; CYCLIZATION; REDUCTION; EFFICIENT; MILD AB Desulfurization of phenylthiolactams using an ultrasound-promoted Raney nickel protocol yields the corresponding N-substituted phthalimidines. Benzylic oxidation of the N-substituted phthalimidines by treatment with 2,2'-bipyridinium chlorochromate/m-chloroperbenzoic acid (BPCC/MCPBA) affords the original phthalimides. The reduction-desulfurization is applied to the preparation of a deoxythalidomide derivative which is a TNF-alpha inhibitor. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Univ Louisville, Dept Chem, Louisville, KY 40292 USA. NCI, Med Branch, Bethesda, MD 20892 USA. RP Luzzio, FA (reprint author), Univ Louisville, Dept Chem, Louisville, KY 40292 USA. EM FALUZZ01@athena.louisville.edu NR 36 TC 24 Z9 24 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD MAR 12 PY 1999 VL 40 IS 11 BP 2087 EP 2090 DI 10.1016/S0040-4039(99)00152-5 PG 4 WC Chemistry, Organic SC Chemistry GA 171WN UT WOS:000078887300016 ER PT J AU Musoke, P Guay, LA Bagenda, D Mirochnick, M Nakabiito, C Fleming, T Elliott, T Horton, S Dransfield, K Pav, JW Murarka, A Allen, M Fowler, MG Mofenson, L Hom, D Mmiro, F Jackson, JB AF Musoke, P Guay, LA Bagenda, D Mirochnick, M Nakabiito, C Fleming, T Elliott, T Horton, S Dransfield, K Pav, JW Murarka, A Allen, M Fowler, MG Mofenson, L Hom, D Mmiro, F Jackson, JB TI A phase I/II study of the safety and pharmacokinetics of nevirapine in HIV-1-infected pregnant Ugandan women and their neonates (HIVNET 006) SO AIDS LA English DT Article DE HIV vertical transmission; nevirapine; pharmacokinetics; Uganda ID HUMAN-IMMUNODEFICIENCY-VIRUS; TRANSMISSION; INFECTION; TYPE-1 AB Objective: To determine the safety, pharmacokinetics, tolerance, antiretroviral activity, and infant HIV infection status after giving a single dose of nevirapine to HIV-1-infected pregnant women during labor and their newborns during the first week of life. Design: An open label phase I/II study. Setting: Tertiary care hospital, Kampala, Uganda. Patients and interventions: Nevirapine, 200 mg, was given as a single dose during labor to 21 HIV-1-infected pregnant Ugandan women. In cohort 1, eight infants did not receive nevirapine whereas in cohort 2, 13 infants received a single dose of nevirapine, 2 mg/kg, at 72 h of age. Outcomes: The number and type of adverse events; nevirapine concentrations in the plasma and breast milk; maternal plasma HIV-1 RNA copy number before and up to 6 weeks after delivery and HIV-1 infection status of the infants were monitored. Results: Nevirapine was well tolerated by women and infants; no serious adverse events that were related to nevirapine were observed. Median nevirapine concentration in the women at delivery was 1623 ng/ml (range 238-2356 ng/ml); median cord/maternal blood ratio of 0.75 (0.37-0.93). The median half-life in women was 61.3 h (27-90 h) and the transplacental nevirapine half-life in infants who did not receive a neonatal dose was 54 h. The median half-life after a single dose at 72 h in infants was 46.5 h. During the first week of life, the median colostrum/breast milk to maternal plasma nevirapine concentration was 60.5% (25-122%). The median nevirapine concentration in breast milk 1 week after delivery was 103 ng/ml (25-309 ng/ml). Plasma nevirapine concentrations were above 100 ng/ml in all infants from both cohorts tested at age 7 days. Maternal HIV-1 RNA levels decreased by a median of 1.3 logs at 1 week postpartum, and returned to baseline by 6 weeks postpartum. Detectable plasma HIV-1 RNA was observed in one out of 22 (4.5%) infants at birth; three out of 21 (14%) at 6 weeks; and four out of 21 (19%) at 6 months of age. Conclusion: The administration of a single dose of nevirapine to women during labor and to their newborns at 72 h was well tolerated and showed potent antiretroviral activity in the women at 1 week after dosing without rebound above baseline 6 weeks after a single dose. The nevirapine concentration was maintained above the target of 100 ng/ml in infants at age 7 days, even in those infants not receiving a neonatal dose. This regimen has promise as prophylaxis against intrapartum and early breast milk transmission in a breastfeeding population. (C) 1999 Lippincott Williams & Wilkins. C1 Makerere Univ, Dept Paediat, Kampala, Uganda. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. Makerere Univ, Dept Obstet & Gynaecol, Kampala, Uganda. Boston Univ, Sch Med, Dept Pediat, Boston, MA 02118 USA. Univ Washington, HIVNET Stat Ctr, Seattle, WA 98195 USA. Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA. Family Hlth Int, Durham, NC USA. NIAID, Div AIDS, NIH, Bethesda, MD 20892 USA. NICHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Bethesda, MD USA. Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA. RP Jackson, JB (reprint author), Johns Hopkins Sch Med, Carnegie Bldg,Room 420,600 N wolfe St, Baltimore, MD 21287 USA. OI Mofenson, Lynne/0000-0002-2818-9808 FU NIAID NIH HHS [AI-35173-121, N01-AI-35173] NR 17 TC 151 Z9 153 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAR 11 PY 1999 VL 13 IS 4 BP 479 EP 486 DI 10.1097/00002030-199903110-00006 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 177EN UT WOS:000079196100006 PM 10197376 ER PT J AU Boeke, JD Pickeral, OK AF Boeke, JD Pickeral, OK TI Genome structure - Retroshuffling the genomic deck SO NATURE LA English DT Editorial Material ID RETROTRANSPOSITION; RNA C1 Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA. NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Boeke, JD (reprint author), Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA. NR 11 TC 23 Z9 24 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 11 PY 1999 VL 398 IS 6723 BP 108 EP + DI 10.1038/18118 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 176DG UT WOS:000079135200023 PM 10086353 ER PT J AU Walsh, TJ Finberg, RW Arndt, C Hiemenz, J Schwartz, C Bodensteiner, D Pappas, P Seibel, N Greenberg, RN Dummer, S Schuster, M Holcenberg, JS AF Walsh, TJ Finberg, RW Arndt, C Hiemenz, J Schwartz, C Bodensteiner, D Pappas, P Seibel, N Greenberg, RN Dummer, S Schuster, M Holcenberg, JS CA Natl Inst Allergy Infect Dis Mycoses Study Grp TI Liposomal amphotericin B for empirical therapy in patients with persistent fever and neutropenia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID INVASIVE FUNGAL-INFECTIONS; IMMUNOCOMPROMISED PATIENTS; RISK-FACTORS; TOXICITY; AMBISOME; MANAGEMENT; INFUSION; GRANULOCYTOPENIA; EXPERIENCE; EFFICACY AB Background In patients with persistent fever and neutropenia, amphotericin B is administered empirically for the early treatment and prevention of clinically occult invasive fungal infections. However, breakthrough fungal infections can develop despite treatment, and amphotericin B has substantial toxicity. Methods We conducted a randomized, double-blind, multicenter trial comparing liposomal amphotericin B with conventional amphotericin B as empirical antifungal therapy. Results The mean duration of therapy was 10.8 days for liposomal amphotericin B (343 patients) and 10.3 days for conventional amphotericin B (344 patients). The composite rates of successful treatment were similar (50 percent for liposomal amphotericin B and 49 percent for conventional amphotericin B) and were independent of the use of antifungal prophylaxis or colony-stimulating factors. The outcomes were similar with liposomal amphotericin B and conventional amphotericin B with respect to survival (93 percent and 90 percent, respectively), resolution of fever (58 percent and 58 percent), and discontinuation of the study drug because of toxic effects or lack of efficacy (14 percent and 19 percent). There were fewer proved breakthrough fungal infections among patients treated with liposomal amphotericin B (11 patients [3.2 percent]) than among those treated with conventional amphotericin B (27 patients [7.8 percent], P = 0.009). With the liposomal preparation significantly fewer patients had infusion-related fever (17 percent vs. 44 percent), chills or rigors (18 percent vs. 54 percent), and other reactions, including hypotension, hypertension, and hypoxia. Nephrotoxic effects (defined by a serum creatinine level two times the upper limit of normal) were significantly less frequent among patients treated with liposomal amphotericin B (19 percent) than among those treated with conventional amphotericin B (34 percent, P<0.001). Conclusions Liposomal amphotericin B is as effective as conventional amphotericin B for empirical antifungal therapy in patients with fever and neutropenia, and it is associated with fewer breakthrough fungal infections, less infusion-related toxicity, and less nephrotoxicity. (N Engl J Med 1999;340:764-71.) (C)1999, Massachusetts Medical Society. C1 NCI, Div Clin Sci, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Div Infect Dis, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Mayo Clin & Mayo Fdn, Dept Pediat, Sect Pediat Hematol Oncol, Rochester, MN 55905 USA. H Lee Moffitt Canc Ctr, Div Bone Marrow Transplantat, Tampa, FL USA. Johns Hopkins Med Inst, Div Pediat Hematol Oncol, Baltimore, MD 21205 USA. Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. Univ Alabama, Div Infect Dis, Birmingham, AL USA. Childrens Hosp, Natl Med Ctr, Div Hematol Oncol, Washington, DC 20010 USA. Vanderbilt Univ, Div Infect Dis, Nashville, TN USA. Hosp Univ Penn, Div Infect Dis, Philadelphia, PA 19104 USA. Childrens Hosp & Med Ctr, Seattle, WA 98105 USA. RP Walsh, TJ (reprint author), NCI, Div Clin Sci, Bldg 10,Rm 13N-240, Bethesda, MD 20892 USA. RI Finberg, Robert/E-3323-2010 FU NIAID NIH HHS [N01-AI-65296] NR 32 TC 723 Z9 758 U1 1 U2 14 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 11 PY 1999 VL 340 IS 10 BP 764 EP 771 DI 10.1056/NEJM199903113401004 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 174KJ UT WOS:000079034100004 PM 10072411 ER PT J AU Elia, J Ambrosini, PJ Rapoport, JL AF Elia, J Ambrosini, PJ Rapoport, JL TI Treatment of attention-deficit-hyperactivity disorder SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID SUSTAINED-RELEASE METHYLPHENIDATE; TERM STIMULANT TREATMENT; 4-YEAR FOLLOW-UP; PSYCHIATRIC STATUS; DOPAMINE TRANSPORTER; TOURETTES-SYNDROME; DOUBLE-BLIND; DIAGNOSTIC-CRITERIA; GENERAL-POPULATION; CLINICAL-RESPONSE C1 Childrens Hosp Philadelphia, Dept Child & Adolescent Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. MCP Hahnemann Univ, Div Child & Adolescent Psychiat, Dept Psychiat, Philadelphia, PA 19103 USA. NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RP Elia, J (reprint author), Childrens Hosp Philadelphia, Dept Child & Adolescent Psychiat, Main Bldg,Rm 3636,34th St & Civ Ctr Blvd, Philadelphia, PA 19104 USA. NR 85 TC 214 Z9 220 U1 3 U2 11 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 11 PY 1999 VL 340 IS 10 BP 780 EP 788 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 174KJ UT WOS:000079034100007 PM 10072414 ER PT J AU Bolan, CD Leitman, SF AF Bolan, CD Leitman, SF TI Hematopoietic stem-cell transplantation for acute leukemia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID COLONY-STIMULATING FACTOR; DONORS; COLLECTION; COUNTS C1 NIH, Bethesda, MD 20892 USA. RP Bolan, CD (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 11 PY 1999 VL 340 IS 10 BP 810 EP 810 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 174KJ UT WOS:000079034100017 PM 10075529 ER PT J AU Jang, JS Lee, SJ Choi, YH Nguyen, P Lee, J Hwang, SG Wu, ML Takano, E Maki, M Henkart, PA Trepel, JB AF Jang, JS Lee, SJ Choi, YH Nguyen, P Lee, J Hwang, SG Wu, ML Takano, E Maki, M Henkart, PA Trepel, JB TI Posttranslational regulation of the retinoblastoma gene family member p107 by calpain protease SO ONCOGENE LA English DT Article DE proteolysis; p107; calpain; proteasome ID LARGE T-ANTIGEN; ACTIVATED NEUTRAL PROTEASE; CELL-CYCLE; PROTEINS P130; KAPPA-B; IN-VIVO; C-JUN; UBIQUITIN; DEGRADATION; PATHWAY AB The retinoblastoma protein plays a critical role in regulating the G1/S transition. Less is known about the function and regulation of the homologous pocket protein p107. Here we present evidence for the posttranslational regulation of p107 by the Ca2+-activated protease calpain. Three negative growth regulators, the HMG-CoA reductase inhibitor lovastatin, the antimetabolite 5-fluorouracil, and the cyclic nucleotide dibutyryl cAMP were found to induce cell type-specific loss of p107 protein which was reversible by the calpain inhibitor leucyl-leucyl-norleucinal but not by the serine protease inhibitor phenylmethylsulfonylfluoride, caspase inhibitors, or lactacystin, a specific inhibitor of the 26S proteasome, Purified calpain induced Ca2+-dependent p107 degradation in cell lysates. Transient expression of the specific calpain inhibitor calpastatin blocked the loss of p107 protein in lovastatin-treated cells, and the half-life of p107 was markedly lengthened in lovastatian-treated cells stably transfected with a calpastatin expression vector versus cells transfected with vector alone. The data presented here demonstrate downregulation of p107 protein in response to various antiproliferative signals, and implicate calpain in p107 posttranslational regulation. C1 NCI, Med Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. NCI, Expt Immunol Branch, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Natl Kyoto Hosp, Kyoto 612, Japan. Nagoya Univ, Nagoya, Aichi 46401, Japan. RP Trepel, JB (reprint author), NCI, Med Branch, Div Clin Sci, NIH, Bldg 10,Room 12N226, Bethesda, MD 20892 USA. NR 68 TC 22 Z9 23 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR 11 PY 1999 VL 18 IS 10 BP 1789 EP 1796 DI 10.1038/sj.onc.1202497 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 175JM UT WOS:000079090000002 PM 10086333 ER PT J AU Ettenberg, SA Keane, MM Nau, MM Frankel, M Wang, LM Pierce, JH Lipkowitz, S AF Ettenberg, SA Keane, MM Nau, MM Frankel, M Wang, LM Pierce, JH Lipkowitz, S TI cbl-b inhibits epidermal growth factor receptor signaling SO ONCOGENE LA English DT Article DE cbl proteins; EGF receptor; signal transduction ID PROTEIN-COUPLED RECEPTORS; PROTOONCOGENE C-CBL; EGF RECEPTOR; TYROSINE PHOSPHORYLATION; V-CBL; PHOSPHATIDYLINOSITOL 3-KINASE; HEMATOPOIETIC-CELLS; T-CELLS; KINASE; ACTIVATION AB The role of cbl-b in signaling by the epidermal growth factor receptor (EGFR),vas studied and compared with c-cbl, We demonstrate in vivo, that chl-b, like c-cbl, is phosphorylated and recruited to the EGFR upon EGF stimulation and both cbl proteins can bind to the Grb2 adaptor protein, To investigate the functional role of chi proteins in EGFR signaling, we transfected cbl-b or c-cbl into 32D cells overexpressing the EGFR (32D/EGFR), This cell line is absolutely dependent on exogenous IL-3 or EGF for sustained growth. 32D/EGFR cells overexpressing cbl-b showed markedly inhibited growth in EGF compared to c-cbl transfectants and vector controls, This growth inhibition by cbl-b was the result of a dramatic increase in the number of cells undergoing apoptosis, Consistent with this finding, chl-b overexpression markedly decreased the amplitude and duration of AKT activation upon EGF stimulation compared to either vector controls or c-cbl overexpressing cells. In addition, the duration of EGF mediated MAP kinase and Jun kinase activation in cells overespressing cbl-b is shortened. These data demonstrate that cbl-b inhibits EGF-induced cell growth and that cbl-b and c-cbl have distinct roles in EGF mediated signaling. C1 USN Hosp, NCI, Med Branch, Dept Genet, Bethesda, MD 20889 USA. Mt Sinai Sch Med, Dept Microbiol, New York, NY 10029 USA. NCI, Mol & Cellular Biol Lab, Div Basic Sci, Bethesda, MD 20892 USA. RP Lipkowitz, S (reprint author), USN Hosp, NCI, Med Branch, Dept Genet, Bethesda, MD 20889 USA. NR 46 TC 85 Z9 91 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR 11 PY 1999 VL 18 IS 10 BP 1855 EP 1866 DI 10.1038/sj.onc.1202499 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 175JM UT WOS:000079090000009 PM 10086340 ER PT J AU Emanuel, EJ Daniels, ER Fairclough, DL Clarridge, BR AF Emanuel, EJ Daniels, ER Fairclough, DL Clarridge, BR TI Oncologists' practice of euthanasia and physician-assisted suicide - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NIH, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Amer Med Ctr, Denver, CO USA. Univ Massachusetts, Boston, MA 02125 USA. RP Emanuel, EJ (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 10 PY 1999 VL 281 IS 10 BP 898 EP 899 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 172XH UT WOS:000078950600030 ER PT J AU Henderson, DK AF Henderson, DK TI Postexposure chemoprophylaxis for occupational exposures to the human immunodeficiency virus SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HEALTH-CARE WORKERS; DENDRITIC CELLS; ZIDOVUDINE TREATMENT; HIV-INFECTION; LANGERHANS CELLS; RHESUS MACAQUES; SIV INFECTION; 3'-AZIDO-3'-DEOXYTHYMIDINE; TRANSMISSION; PROPHYLAXIS C1 NIH, Off Deputy Director Clin Care, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Henderson, DK (reprint author), NIH, Off Deputy Director Clin Care, Warren G Magnuson Clin Ctr, Bldg 10,Room 2C146,10 Ctr Dr,MSC-1504, Bethesda, MD 20892 USA. NR 63 TC 33 Z9 33 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 10 PY 1999 VL 281 IS 10 BP 931 EP 936 DI 10.1001/jama.281.10.931 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 172XH UT WOS:000078950600039 PM 10078491 ER PT J AU Huster, D Gawrisch, K AF Huster, D Gawrisch, K TI NOESY NMR crosspeaks between lipid headgroups and hydrocarbon chains: Spin diffusion or molecular disorder? SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; UNILAMELLAR VESICLES; SPECTRA; SPECTROSCOPY; RELAXATION; CHOLESTEROL; MEMBRANES; DYNAMICS; EXCHANGE; MODEL C1 NIAAA, Lab Membrane Biochem & Biophys, Rockville, MD 20852 USA. RP Gawrisch, K (reprint author), NIAAA, Lab Membrane Biochem & Biophys, 12420 Parklawn Dr,Rm 158, Rockville, MD 20852 USA. NR 14 TC 77 Z9 77 U1 2 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD MAR 10 PY 1999 VL 121 IS 9 BP 1992 EP 1993 DI 10.1021/ja9838413 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 176GR UT WOS:000079143700044 ER PT J AU Ghabra, MB Hallett, M Wassermann, EM AF Ghabra, MB Hallett, M Wassermann, EM TI Simultaneous repetitive transcranial magnetic stimulation does not speed fine movement in PD SO NEUROLOGY LA English DT Article AB Objective: To reevaluate the effect of subthreshold repetitive transcranial magnetic stimulation (rTMS) on concurrent fine movement in PD. Background: A previous study showed a beneficial effect of rTMS on the performance of six patients with PD on the Grooved Pegboard test. Methods: The authors repeated this experiment in 11 patients with idiopathic PD who performed the test while the stimulating coil discharged continuously at 5 Hz, either over the contralateral motor cortex at just below the threshold for movement, or in the air near the head as a control. Patients were tested twice under both conditions. Results: Although some patients performed faster with rTMS, others showed the opposite effect. There was no significant effect of rTMS in the group, nor did baseline performance or the order of conditions interact with the effect of rTMS. Conclusions: Based on this larger and more comprehensive study, simultaneous, 5-Hz subthreshold rTMS over the motor cortex does not have consistent or potentially therapeutic effects on movement in PD. C1 NINDS, Off Clin Director, Bethesda, MD 20892 USA. RP Wassermann, EM (reprint author), 10 Ctr Dr,MSC 1428, Bethesda, MD 20892 USA. NR 8 TC 76 Z9 80 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 10 PY 1999 VL 52 IS 4 BP 768 EP 770 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 175ZR UT WOS:000079126400019 PM 10078725 ER PT J AU Syed, NA Delgado, A Sandbrink, F Schulman, AE Hallett, M Floeter, MK AF Syed, NA Delgado, A Sandbrink, F Schulman, AE Hallett, M Floeter, MK TI Blink reflex recovery in facial weakness - An electrophysiologic study of adaptive changes SO NEUROLOGY LA English DT Article ID ESSENTIAL BLEPHAROSPASM; EYELID MOVEMENTS; NERVE PALSY; DYSTONIA; NUCLEUS; REGENERATION; TORTICOLLIS; CLOSURE; CURVES; SYSTEM AB Objective: To study the electrophysiologic effects of unilateral facial weakness on the excitability of the neuronal circuitry underlying blink. reflex, and to localize the site of changes in blink reflex excitability that occur after facial weakness. Background: Eyelid kinematic studies suggest that adaptive modification of the blink reflex occurs after facial weakness. Such adaptations generally optimize eye closure. A report of blepharospasm following Bell's palsy suggests that dysfunctional adaptive changes can also occur. Methods: Blink reflex recovery was evaluated with paired stimulation of the supraorbital ner-ve at different interstimulus intervals. Comparisons were made between normal control subjects and patients with Bell's palsy who either recovered facial strength or who had persistent weakness. Results: Blink reflex recovery was enhanced in patients with residual weakness but not in patients who recovered facial strength. Facial muscles on weak and unaffected sides showed enhancement. In patients with residual weakness, earlier blink reflex recovery occurred when stimulating the supraorbital nerve on the weak. side. Sensory thresholds were symmetric. Conclusion: Enhancement of blink reflex recovery is dependent on ongoing facial weakness. Faster recovery when stimulating the supraorbital nerve on the paretic side suggests that sensitization may be lateralized, and suggests a role for abnormal afferent input in maintaining sensitization. Interneurons in the blink reflex pathway are the best candidates for the locus of this plasticity. C1 NINDS, EMG Sect, NIH, Bethesda, MD 20892 USA. Natl Naval Med Ctr, Dept Neurol, Bethesda, MD USA. Aga Khan Univ, Neurol Sect, Karachi, Pakistan. RP Floeter, MK (reprint author), NINDS, EMG Sect, NIH, 10 Ctr Dr,MSC 1404, Bethesda, MD 20892 USA. NR 23 TC 37 Z9 41 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 10 PY 1999 VL 52 IS 4 BP 834 EP 838 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 175ZR UT WOS:000079126400029 PM 10078735 ER PT J AU Otero, ADS Doyle, MB Hartsough, MT Steeg, PS AF Otero, ADS Doyle, MB Hartsough, MT Steeg, PS TI Wild-type NM23-H1, but not its S120 mutants, suppresses desensitization of muscarinic potassium current SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE NM23; G protein-activated inward rectifier potassium channel; I-KACh; desensitization ID NUCLEOSIDE-DIPHOSPHATE KINASE; BREAST-CARCINOMA CELLS; RECTIFYING K+-CHANNEL; MEDIATED MODULATION; CRYSTAL-STRUCTURE; TUMOR-METASTASIS; MELANOMA-CELLS; I-KACH; PROTEIN; MUTATION AB NM23 (NDP kinase) modulates the gating of muscarinic K+ channels by agonists through a mechanism distinct from GTP regeneration. To better define the function of NM23 in this pathway and to identify sites in NM23 that are important for its role in muscarinic Ki channel function, we utilized MDA-MB-435 human breast carcinoma cells that express low levels of NM23-H1. M2 muscarinic receptors and GIRK1/GIRK4 channel subunits were co-expressed in cells stably transfected with vector only (control), wild-type NM23-H1, or several NM13-H1 mutants. Lysates from all cell lines tested exhibit comparable nucleoside diphosphate (NDP) kinase activity. Whole cell patch clamp recordings revealed a substantial reduction of the acute desensitization of muscarinic K+ currents in cells overexpressing NM23-H1, The mutants NM23-H1(P96S) and NM23-H1(S44A) resembled wild-type NM23-H1 in their ability to reduce desensitization. In contrast, mutants NM23-H1(S120G) and NM23-H1(S120A) completely abolished the effect of NM23-H1 on desensitization of muscarinic K+ currents. Furthermore, NM23-H1(S120G) potentiated acute desensitization, indicating that this mutant retains the ability to interact with the muscarinic pathway, but has properties antithetical to those of the wild-type protein. We conclude that NM23 acts as a suppressor of the processes leading to the desensitization of muscarinic K+ currents, and that Ser-120 is essential for its actions. (C) 1999 Published by Elsevier Science B.V. All rights reserved. C1 Univ Virginia, Sch Med, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22906 USA. NCI, Womens Canc Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Otero, ADS (reprint author), Univ Virginia, Sch Med, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22906 USA. FU NHLBI NIH HHS [HL48726, HL37127]; NIGMS NIH HHS [GM57833] NR 63 TC 16 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD MAR 8 PY 1999 VL 1449 IS 2 BP 157 EP 168 DI 10.1016/S0167-4889(99)00009-9 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 179QT UT WOS:000079340700006 PM 10082974 ER PT J AU Van Koughnet, K Smirnova, O Hyman, SE Borsook, D AF Van Koughnet, K Smirnova, O Hyman, SE Borsook, D TI Proenkephalin transgene regulation in the paraventricular nucleus of the hypothalamus by lipopolysaccharide and interleukin-1 beta SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Review DE phosphocyclic amino-3-hydroxy-5-methyl-4-isoxazole-propionate response element-binding protein; naltrexone; stress; mice ID CORTICOTROPIN-RELEASING HORMONE; CENTRAL-NERVOUS-SYSTEM; MESSENGER-RNA EXPRESSION; PARVOCELLULAR NEUROSECRETORY NEURONS; PITUITARY-ADRENOCORTICAL ACTIVITY; GALACTOSIDASE FUSION GENE; IN-SITU HYBRIDIZATION; IMMEDIATE-EARLY GENES; RAT-BRAIN; SUPRAOPTIC NUCLEI AB Immunologic challenge with lipopolysaccharide (LPS) or interleukin-1 beta (IL-1 beta) produces a functional response within the paraventricular nucleus of the hypothalamus (PVN) and leads to changes in gene expression within PVN neurons. Regulated expression of neuropeptide genes within neurons of the PVN is a potential mechanism by which an organism can adapt to stressful challenges. Here, the authors used a transgenic mouse model in which expression of a readily measurable beta-galactosidase reporter was driven in PVN neurons by human proenkephalin regulatory sequences. This proenkephalin-beta-galactosidase transgene has been demonstrated previously to respond appropriately to a variety of stressors. It is demonstrated that expression of the proenkephalin transgene product was up-regulated significantly in a subset of PVN neurons 6 hours following intraperitoneal LPS (16-400 mu g/kg) administration, remained elevated at 12 hours, and fell below basal levels by 24 hours. A more rapid and transient pattern of transgene up-regulation in the PVN followed administration of intraperitoneal IL-1 beta (10 mu g/kg) with significant induction by 2 hours, peak levels reached by 4 hours, and a return toward basal levels by 6 hours. IL-1 beta (10-50 ng/mouse) administered intracerebroventricularly also led to up-regulation of the transgene 6 hours following infusion. Transgene expression was not up-regulated in hypothalamic slice cultures treated directly with IL-1 beta (5-10 ng/ml media). Up-regulation of transgene expression does not appear to result from local action of IL-1 beta at the level of the PVN but, rather, through as yet unidentified intermediates. The authors demonstrate phosphorylation of the cyclic amino-3-hydroxy-5-methyl-4-isoxazole-propionate response element binding protein, a transcription factor known to interact with proenkephalin regulatory sequences within the transgene, in the PVN following LPS administration. LPS induced up-regulation of the transgene was blocked by pretreatment with naltrexone, indicating an additional role for endogenous opioid systems in regulation of the PVN response to immune challenge. J. Comp. Neurol. 405:199-215, 1999. (C) 1999 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. NINDS, Mol Plast Sect, Rockville, MD 20892 USA. Massachusetts Gen Hosp, Neural Plast Res Grp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. RP Borsook, D (reprint author), Massachusetts Gen Hosp E, Neural Plast Res Grp, Bldg 149,13th St,CNY4, Charlestown, MA 02129 USA. FU NIDA NIH HHS [DA0956501] NR 119 TC 8 Z9 8 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD MAR 8 PY 1999 VL 405 IS 2 BP 199 EP 215 PG 17 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 163NM UT WOS:000078411900005 PM 10023810 ER PT J AU Hong, JY Wang, YY Bondoc, FY Yang, CS Gonzalez, FJ Pan, ZY Cokonis, CD Hu, WY Bao, ZP AF Hong, JY Wang, YY Bondoc, FY Yang, CS Gonzalez, FJ Pan, ZY Cokonis, CD Hu, WY Bao, ZP TI Metabolism of methyl tert-butyl ether and other gasoline ethers in mouse liver microsomes lacking cytochrome P450 2E1 SO TOXICOLOGY LETTERS LA English DT Article DE methyl tert-butyl ether; gasoline ethers; metabolism; knock-out mice; cytochrome P450 2E1 ID N-NITROSODIMETHYLAMINE DEMETHYLASE AB To reduce the production of pollutants in motor vehicle exhaust, methyl tert-butyl ether (MTBE) and other ethers such as ethyl tert-butyl ether (ETBE) and tert-amyl methyl ether (TAME) are added to gasoline as oxygenates for more complete combustion. Metabolism of these gasoline ethers is catalyzed by cytochrome P450 (P450) enzymes. P450 2E1, which metabolizes diethyl ether, was suggested to be an enzyme involved. The present study used 2E1 knock-out mice (2E1(-/-)) to assess the contribution of 2E1 to the metabolism of MTBE, ETBE and TAME. Liver microsomes prepared from the 2E1 knock-out mice lacked 2E1 activity (assayed as N-nitrosodimethylamine demethylation), but were still active in metabolizing all three gasoline ethers. The levels of ether-metabolizing activity (nmol/min per mg) in the liver microsomes from 7 week old female 2E1 knock-out mice were 0.54 +/- 0.17 for MTBE, 0.51 +/- 0.24 for ETBE and 1.14 +/- 0.25 for TAME at a 1 mM substrate concentration. These activity levels were not significantly different from those of the sex- and age-matched C57BL/6N and 129/Sv mice, which are the parental lineage strains of the 2E1 knock-out mice and are both 2E1(+/+). Our results clearly demonstrate that 2E1 plays a negligible role in the metabolism of MTBE, ETBE and TAME in mouse livers. (C) 1999 Published by Elsevier Science Ireland Ltd. All rights reserved. C1 Rutgers State Univ, Coll Pharm, Dept Biol Chem, Canc Res Lab, Piscataway, NJ 08854 USA. NCI, Lab Metab, Bethesda, MD 20892 USA. RP Rutgers State Univ, Coll Pharm, Dept Biol Chem, Canc Res Lab, 164 Frelinghuysen Rd, Piscataway, NJ 08854 USA. EM jyhong@rci.rutgers.edu FU NIEHS NIH HHS [ES03938, ES05022] NR 18 TC 20 Z9 21 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 EI 1879-3169 J9 TOXICOL LETT JI Toxicol. Lett. PD MAR 8 PY 1999 VL 105 IS 1 BP 83 EP 88 DI 10.1016/S0378-4274(98)00389-0 PG 6 WC Toxicology SC Toxicology GA 177CL UT WOS:000079189800011 PM 10092060 ER PT J AU Mofenson, LM AF Mofenson, LM TI Short-course zidovudine for prevention of perinatal infection SO LANCET LA English DT Editorial Material ID CLINICAL-TRIAL; TRANSMISSION; AFRICA C1 NICHHD, Pediat Adolescent & Maternal AIDS Branch, Ctr Res Mothers & Children, NIH, Rockville, MD 20852 USA. RP Mofenson, LM (reprint author), NICHHD, Pediat Adolescent & Maternal AIDS Branch, Ctr Res Mothers & Children, NIH, Rockville, MD 20852 USA. OI Mofenson, Lynne/0000-0002-2818-9808 NR 16 TC 47 Z9 48 U1 0 U2 1 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD MAR 6 PY 1999 VL 353 IS 9155 BP 766 EP 767 DI 10.1016/S0140-6736(99)90028-4 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 175JC UT WOS:000079089100002 PM 10459952 ER PT J AU Gueyffier, F Bulpitt, C Boissel, JP Schron, E Ekbom, T Fagard, R Casiglia, E Kerlikowske, A Coope, J AF Gueyffier, F Bulpitt, C Boissel, JP Schron, E Ekbom, T Fagard, R Casiglia, E Kerlikowske, A Coope, J CA INDANA Grp TI Antihypertensive drugs in very old people: a subgroup meta-analysis of randomised controlled trials SO LANCET LA English DT Article ID ELDERLY TRIAL; SYSTOLIC HYPERTENSION; CLINICAL-TRIALS; BLOOD-PRESSURE; MORTALITY; METAANALYSIS; MORBIDITY; HYVET AB Background Beneficial clinical effects of treatment with antihypertensive drugs have been shown in middle-aged patients and in those hypertensive patients over 60 years old, but whether treatment is beneficial in patients over 80 years old is not known. Methods We collected data from all participants aged 80 years and over in randomised controlled trials of antihypertensive drugs through direct contact with study investigators. Our primary outcome was fatal and non-fatal stroke. Secondary outcomes were death from all causes, cardiovascular death, fatal and non-fatal major coronary and cardiovascular events, and heart failure. Findings There were 57 strokes and 34 deaths among 874 actively treated patients, compared with 77 strokes and 28 stroke deaths among 796 controls, representing 1 non-fatal stroke prevented for about 100 patients treated each year. The meta-analysis of data from 1670 participants aged 80 years or older suggested that treatment prevented 34% (95% CI 8-52) of strokes. Rates of major cardiovascular events and heart failure were significantly decreased, by 22% and 39%, respectively. However, there was no treatment benefit for cardiovascular death, and a non-significant 6% (-5 to 18) relative excess of death from all causes. Interpretations The inconclusive findings for mortality contrast with the benefit of treatment for non-fatal events. Results of a large-scale specific trial are needed for definite conclusion that antihypertensive treatment is beneficial in very elderly hypertensive patients. Meanwhile, an age threshold beyond which hypertension should not be treated cannot be justified. C1 Univ Lyon 1, Lyon Hosp, Dept Clin Pharmacol, F-69622 Villeurbanne, France. Hammersmith Hosp, Imperial Coll Sch Med, London, England. NHLBI, NIH, Bethesda, MD 20892 USA. Dept Community Hlth Sci, Lund, Sweden. Hypertens & Cardiovasc Rehabil Unit, Louvain, Belgium. Univ Padua, Dept Clin & Expt Med, I-35100 Padua, Italy. Vet Adm Med Ctr, San Francisco, CA 94121 USA. Bollington Med Ctr, Macclesfield, Cheshire, England. RP Gueyffier, F (reprint author), Serv Pharmacol Clin, EA 643,BP 3041, F-69394 Lyon 03, France. EM fg@upcl.univ-lyon1.fr RI Gueyffier, Francois/B-8545-2008 OI Gueyffier, Francois/0000-0002-9921-0977 NR 32 TC 372 Z9 398 U1 2 U2 8 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD MAR 6 PY 1999 VL 353 IS 9155 BP 793 EP 796 DI 10.1016/S0140-6736(98)08127-6 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 175JC UT WOS:000079089100010 PM 10459960 ER PT J AU Gong, DW He, YF Reitman, ML AF Gong, DW He, YF Reitman, ML TI Genomic organization and regulation by dietary fat of the uncoupling protein 3 and 2 genes SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE thermogenesis; diet induced obesity; uncoupling proteins ID BROWN ADIPOSE-TISSUE; NUCLEOTIDE-BINDING-SITE; THYROID-HORMONE; OBESITY; EXPRESSION; THERMOGENESIS; MEDIATOR; CLONING; HOMOLOG; MEMBER AB Uncoupling protein-1 (UCP1) dissipates the transmitochondrial proton gradient as heat. UCP2 and UCP3 are two recently discovered homologues that also have uncoupling activity and thus presumably have a role in energy homeostasis. We now report the genomic structure of murine UCP3 (7 exons) and UCP2 (8 exons). UCP3 is similar to 8 kilobases upstream of UCP2. An UCP3 variant mRNA, UCP3S, was also found and characterized. The effect of a high fat diet (45% versus 10%) on UCP3 and UCP2 mRNA levels was measured. Eating the 45% fat diet for eight weeks caused greater weight gain in AKR and C57BL/6J mice than in the obesity-resistant A/J mice. The high fat diet increased muscle UCP3 expression twofold in C57BL/6J animals. UCP2 expression increased slightly on the 45% fat diet in white adipose of AKR mice, but not in A/J or C57BL/6J mice. In skeletal muscle, UCP2 expression showed little variation with diet. Thus, UCP2 and UCP3 expression levels change in response to diet-induced obesity, but the changes are modest and depend on the tissue and genotype. The data suggest that it is not a reduction in UCP2 or UCP3 expression that causes obesity in the susceptible mice. (C) 1999 Academic Press. C1 NIDDK, Diabet Branch, NIH, Bethesda, MD 20892 USA. RP Gong, DW (reprint author), NIDDK, Diabet Branch, NIH, Bldg 10,Room 8N-250,10 Ctr Dr,MSC 1770, Bethesda, MD 20892 USA. RI Reitman, Marc/B-4448-2013 OI Reitman, Marc/0000-0002-0426-9475 NR 33 TC 54 Z9 58 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 5 PY 1999 VL 256 IS 1 BP 27 EP 32 DI 10.1006/bbrc.1999.0239 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 175JA UT WOS:000079088900005 PM 10066417 ER PT J AU Huh, JR Park, JM Kim, M Carlson, BA Hatfield, DL Lee, BJ AF Huh, JR Park, JM Kim, M Carlson, BA Hatfield, DL Lee, BJ TI Recruitment of TBP or TFIIB to a promoter proximal position leads to stimulation of RNA polymerase II transcription without activator proteins both in vivo and in vitro SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE transcriptional activation; recruitment assay; TBP; TFIIB; GAL4; Xenopus ID TATA-BINDING PROTEIN; BASAL TRANSCRIPTION; IN-VIVO; MOLECULAR-CLONING; GENE ACTIVATION; TERMINAL DOMAIN; HOLOENZYME; DROSOPHILA; VP16; EXPRESSION AB Eukaryotic transcriptional activators may function, at least in part, to facilitate the assembly of the RNA polymerase II (pol II) preinitiation complex at the core promoter region through their interaction with a subset of components of the basal transcription machinery. Previous studies have shown that artificial tethering of TATA-binding protein (TBP) to the promoter region is sufficient to stimulate pol II transcription in yeast. To test whether this phenomenon is a general one in eukaryotic pol II transcription, the DNA-binding domain of yeast GAL4 was fused to either Xenopus laevis TBP or TFIIB in order to enable these factors to be efficiently positioned near the transcription start site in a GAL4-binding site-dependent manner. We found that GAL4-xTBP as well as GAL4-xTFIIB directed an increased level of transcription without involvement of the transcriptional activator, suggesting that incorporation of these basal factors into a preinitiation complex (PIC) is a major rate-limiting step accelerated by activator proteins in metazoans. These results show that transcription activation by artificial recruitment of basal transcription machinery can be observed in general among eukaryotic transcription both in vivo and in vitro. Furthermore, failure of recovery of transcription by adding GAL4-xTFIIB after depletion of endogenous TBP with TATA oligo competitor suggests that recruitment of TBP cannot be bypassed for Pol II transcription. (C) 1999 Academic Press. C1 Seoul Natl Univ, Inst Mol Biol & Genet, Mol Genet Lab, Seoul 151742, South Korea. NCI, Sect Mol Biol Selenium, Lab Basic Sci, Div Basic Sci,NIH, Bethesda, MD 20892 USA. RP Lee, BJ (reprint author), Seoul Natl Univ, Inst Mol Biol & Genet, Mol Genet Lab, Seoul 151742, South Korea. EM imbglmg@plaza.snu.ac.kr NR 41 TC 8 Z9 8 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 5 PY 1999 VL 256 IS 1 BP 45 EP 51 DI 10.1006/bbrc.1999.0280 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 175JA UT WOS:000079088900008 PM 10066420 ER PT J AU Selmane, T Wittung-Stafshede, P Maraboeuf, F Voloshin, ON Norden, B Camerini-Otero, DR Takahashi, M AF Selmane, T Wittung-Stafshede, P Maraboeuf, F Voloshin, ON Norden, B Camerini-Otero, DR Takahashi, M TI The L2 loop peptide of RecA stiffens and restricts base motions of single-stranded DNA similar to the intact protein SO FEBS LETTERS LA English DT Article DE RecA protein; homologous recombination; DNA binding; peptide; DNA base motion ID ESCHERICHIA-COLI RECA; LINEAR DICHROISM; ELECTRON-MICROSCOPY; RAD51 PROTEIN; BINDING; FLUORESCENCE; COMPLEXES; RECOMBINATION; SPECTROSCOPY; MOLECULES AB The L2 loop in the RecA protein is the catalytic center for DNA strand exchange, Here we investigate the DMA binding properties of the L2 loop peptide using optical spectroscopy with polarized light. Both fluorescence intensity and anisotropy of an etheno-modified poly(dA) increase upon peptide binding, indicate that the base motions of single-stranded DNA are restricted in the complex. In agreement with this conclusion, the peptide-poly(dT) complex exhibits a significant linear dichroism signal. The peptide is also found to modify the structure of double-stranded DNA, but does not denature it. It is inferred that strand separation may not be required for the formation of a joint molecule, (C) 1999 Federation of European Biochemical Societies. C1 Inst Curie, Unite Mixte Rech 216, F-91405 Orsay, France. CNRS, F-91405 Orsay, France. Chalmers Univ Technol, Dept Phys Chem, S-41296 Gothenburg, Sweden. NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. RP Takahashi, M (reprint author), Inst Curie, Unite Mixte Rech 216, F-91405 Orsay, France. EM masa.takahashi@curie.u-psud.fr OI wittung-stafshede, pernilla/0000-0003-1058-1964 NR 27 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD MAR 5 PY 1999 VL 446 IS 1 BP 30 EP 34 DI 10.1016/S0014-5793(99)00181-7 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 175YF UT WOS:000079123100008 PM 10100609 ER PT J AU Chen, RW Chuang, DM AF Chen, RW Chuang, DM TI Long term lithium treatment suppresses p53 and Bax expression but increases Bcl-2 expression - A prominent role in neuroprotection against excitotoxicity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CEREBELLAR GRANULE CELLS; CYTOCHROME-C; APOPTOSIS; INHIBITION; RELEASE; MITOCHONDRIA; PROTEASE; NEURONS; AP-1 AB This study was undertaken to investigate the molecular mechanisms underlying the neuroprotective actions of lithium against glutamate excitotoxicity with a focus on the role of proapoptotic and antiapoptotic genes. Long term, but not acute, treatment of cultured cerebellar granule cells with LiCl induces a concentration-dependent decrease in mRNA and protein levels of proapoptotic p53 and Bax; conversely, mRNA and protein levels of cytoprotective Bcl-2 are remarkably increased. The ratios of Bcl-2/Bax protein levels increase by approximately 5-fold after lithium treatment for 5-7 days. Exposure of cerebellar granule cells to glutamate induces a rapid increase in p53 and Bax mRNA and protein levels with no apparent effect on Bcl-2 expression. Pretreatment with LiCl for 7 days prevents glutamate-induced increase in p53 and Bax expression and maintains Bcl-2 in an elevated state. Glutamate exposure also triggers the release of cytochrome c from the mitochondria into the cytosol. Lithium pretreatment blocks glutamate-induced cytochrome c release and cleavage of lamin B1, a nuclear substrate for caspase-3. These results strongly suggest that lithium-induced Bcl-2 up-regulation and p53 and Bax down-regulation play a prominent role in neuroprotection against excitotoxicity. Our results further suggest that lithium, in addition to its use in the treatment of bipolar depressive illness, may have an expanded use in the intervention of neurodegeneration. C1 NIMH, Mol Neurobiol Sect, BPB, NIH, Bethesda, MD 20892 USA. RP Chuang, DM (reprint author), NIMH, Mol Neurobiol Sect, BPB, NIH, Bldg 10,Rm 3N212,10 Ctr Dr,MSC 1272, Bethesda, MD 20892 USA. EM chuang@helix.nih.gov NR 30 TC 254 Z9 275 U1 0 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 5 PY 1999 VL 274 IS 10 BP 6039 EP 6042 DI 10.1074/jbc.274.10.6039 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 172BQ UT WOS:000078902800004 PM 10037682 ER PT J AU Sueyoshi, T Kawamoto, T Zelko, I Honkakoski, P Negishi, M AF Sueyoshi, T Kawamoto, T Zelko, I Honkakoski, P Negishi, M TI The repressed nuclear receptor CAR responds to phenobarbital in activating the human CYP2B6 gene SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INDUCTION; DEXAMETHASONE; EXPRESSION; ELEMENTS; BINDING; P450 AB The endogenous CYP2B6 gene becomes phenobarbital (PB) inducible in androstenol-treated HepG2 cells either transiently or stably transfected with a nuclear receptor CAR expression vector. The PB induction mediated by CAR is regulated by a conserved 51-base pair element called PR-responsive enhancer module (PBREM) that has now been located between -1733 and -1683 bp in the gene's 5'-flanking region. An in vitro translated CAR acting as a retinoid X receptor alpha heterodimer binds directly to the two nuclear receptor sites NR1 and NR2 within PBREM, In a stably transfected HepG2 cell line, both PBREM and NR1 are activated by PB and PR-type compounds such as chlorinated pesticides, polychlorinated biphenyls and chlorpromazine, In addition to PBREM, CAR also transactivates the steroid/rifampicin-response element of the human CYP3A4 gene in HepG2 cells. Thus, activation of the repressed nuclear receptor CAR appears to be a versatile mediator that regulates PB induction of the CYP2B and other genes. C1 NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. Univ Kuopio, Dept Pharmaceut, FIN-70211 Kuopio, Finland. RP Negishi, M (reprint author), NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. RI Zelko, Igor/L-2673-2013; Kawamoto, Takeshi/D-7938-2015; OI Zelko, Igor/0000-0003-3976-3884; Kawamoto, Takeshi/0000-0003-3337-1775; Honkakoski, Paavo/0000-0002-4332-3577 NR 24 TC 506 Z9 521 U1 1 U2 10 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 5 PY 1999 VL 274 IS 10 BP 6043 EP 6046 DI 10.1074/jbc.274.10.6043 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 172BQ UT WOS:000078902800005 PM 10037683 ER PT J AU Gallagher, PG Sabatino, DE Romana, M Cline, AP Garrett, LJ Bodine, DM Forget, BG AF Gallagher, PG Sabatino, DE Romana, M Cline, AP Garrett, LJ Bodine, DM Forget, BG TI A human beta-spectrin gene promoter directs high level expression in erythroid but not muscle or neural cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTION FACTOR GATA-1; PORPHOBILINOGEN DEAMINASE GENE; HUMAN SKELETAL-MUSCLE; KRUPPEL-LIKE FACTOR; PRE-MESSENGER-RNA; DEVELOPMENTAL EXPRESSION; MAMMALIAN-CELLS; CACCC ELEMENT; GLYCOPHORIN-B; PROTEINS AB beta-Spectrin is an erythrocyte membrane protein that is defective in many patients with abnormalities of red blood cell shape including hereditary spherocytosis and elliptocytosis. It is expressed not only in erythroid tissues but also in muscle and brain. We wished to determine the regulatory elements that determine the tissue-specific expression of the beta-spectrin gene. We mapped the 5'-end of the beta-spectrin erythroid cDNA and cloned the 5'-flanking genomic DNA containing the putative beta-spectrin gene promoter. Using transfection of promoter/reporter plasmids in human tissue culture cell lines, in vitro DNase I footprinting analyses, and gel mobility shift assays, a beta-spectrin gene erythroid promoter with two binding sites for GATA-1 and one site for CACCC-related proteins was identified. All three binding sites were required for full promoter activity; one of the GATA-1 motifs and the CACCC-binding motif were essential for activity. The beta-spectrin gene promoter was able to be transactivated in heterologous cells by forced expression of GATA-1. In transgenic mice, a reporter gene directed by the beta-spectrin promoter was expressed in erythroid tissues at all stages of development. Only weak expression of the reporter gene was detected in muscle and brain tissue, suggesting that additional regulatory elements are required for high level expression of the beta-spectrin gene in these tissues. C1 Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06520 USA. Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06520 USA. Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA. Natl Human Genome Res Inst, Hematopoiesis Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. RP Gallagher, PG (reprint author), Yale Univ, Sch Med, Dept Pediat, 333 Cedar St,POB 208064, New Haven, CT 06520 USA. NR 73 TC 28 Z9 28 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 5 PY 1999 VL 274 IS 10 BP 6062 EP 6073 DI 10.1074/jbc.274.10.6062 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 172BQ UT WOS:000078902800009 PM 10037687 ER PT J AU Louis, JM Oroszlan, S Tozser, J AF Louis, JM Oroszlan, S Tozser, J TI Stabilization from autoproteolysis and kinetic characterization of the human T-cell leukemia virus type 1 proteinase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; I-ASSOCIATED MYELOPATHY; ESCHERICHIA-COLI; HIV-1 PROTEASE; RETROVIRAL PROTEINASES; BACTERIAL EXPRESSION; ASPARTIC PROTEINASE; RATIONAL DESIGN; ANEMIA VIRUS; SPECIFICITY AB We have developed a system for expression and purification of wild-type human T-cell leukemia virus type 1 (HTLV-1) proteinase to attain sufficient quantities for structural, kinetic, and biophysical investigations. However, similar to the human immunodeficiency virus type 1 (HIV-1) proteinase, HTLV-1 proteinase also undergoes autoproteolysis rapidly upon renaturation to produce two products. The site of this autoproteolytic cleavage was mapped, and a resistant HTLV-1 proteinase construct (L40I) as well as another construct, wherein the two cysteine residues were exchanged to alanines, were expressed and purified. Oligopeptide substrates representing the naturally occurring cleavage sites in HTLV-1 were good substrates of the HTLV-1 proteinase. The kinetic parameters k(cat) and K-m were nearly identical for all the three enzymes. Although three of four peptides representing HTLV-1 proteinase cleavage sites were fairly good substrates of HIV-1 proteinase, only two of nine peptides representing HIV-1 proteinase cleavage sites were hydrolyzed by the HTLV-1 proteinase, suggesting substantial differences in the specificity of the two enzymes. The large difference in the specificity of the two enzymes was also demonstrated by inhibition studies. Of the several. inhibitors of HIV-1 or other retroviral proteinases that were tested on HTLV-1 proteinase, only two inhibit the enzyme with a K-i lower than 100 nM. C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. Debrecen Univ Med, Sch Med, Dept Biochem & Mol Biol, H-4012 Debrecen, Hungary. NCI, Mol Virol & Carcinogenesis Lab, ABL, Basic Res Program,Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Louis, JM (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM jmlouis@helix.nih.gov; tozser@indi.biochem.dote.hu RI Tozser, Jozsef/A-7840-2008; OI Tozser, Jozsef/0000-0003-0274-0056; Tozser, Jozsef/0000-0001-5076-8729 NR 50 TC 44 Z9 47 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 5 PY 1999 VL 274 IS 10 BP 6660 EP 6666 DI 10.1074/jbc.274.10.6660 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 172BQ UT WOS:000078902800085 PM 10037763 ER PT J AU Torchin, CD Yonekawa, WD Kapetanovic, IM Kupferberg, HJ AF Torchin, CD Yonekawa, WD Kapetanovic, IM Kupferberg, HJ TI Chiral high-performance liquid chromatographic analysis of enantiomers of losigamone, a new candidate antiepileptic drug SO JOURNAL OF CHROMATOGRAPHY B LA English DT Article DE enantiomer separation; losigamone; antiepileptic drug ID PHARMACOLOGY; METABOLISM; ISOMERS AB An assay based on a single-step liquid-liquid extraction from human plasma followed by high-performance Liquid chromatography on a chiral column was developed for the measurement of enantiomers of a racemic new candidate antiepileptic drug. Excellent intra- and inter-assay accuracy and precision and recovery were demonstrated in the desired concentration range of 0.031 to 5.00 mu g/ml. The method is free from interferences by other anticonvulsant drugs and their metabolites. The method is being used in a clinical trial of losigamone. (C) 1999 Elsevier Science B.V. All rights reserved. C1 NINDS, Epilepsy Therapeut Res Branch, NIH, Bethesda, MD 20892 USA. RP Kapetanovic, IM (reprint author), NINDS, Epilepsy Therapeut Res Branch, NIH, Bethesda, MD 20892 USA. NR 11 TC 5 Z9 6 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 PD MAR 5 PY 1999 VL 724 IS 1 BP 101 EP 108 DI 10.1016/S0378-4347(98)00568-4 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 175PN UT WOS:000079103700011 PM 10202962 ER PT J AU Boyer, PL Lisziewicz, J Lori, F Hughes, SH AF Boyer, PL Lisziewicz, J Lori, F Hughes, SH TI Analysis of amino insertion mutations in the fingers subdomain of HIV-1 reverse transcriptase SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE HIV-1; reverse transcriptase; drug resistance ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1; RESISTANCE; REPLICATION; INHIBITOR; HYDROXYUREA; COMBINATION AB In response to dideoxy inosine/hydroxyurea dual therapy, HIV-1 (human immunodeficiency virus type-1) variants were isolated that had a small amino acid insertion and flanking amino acid substitutions in the fingers subdomain of HIV-1. We have analyzed the reverse transcriptase variants for their effects on HIV-1 reverse transcriptase activity. The data suggests that the inserted amino acid residues are responsible for low-level resistance to the nucleoside analog ddITP, while the role of the flanking amino acid substitutions is to compensate for the deleterious effects of the insertion. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. Georgetown Univ, Res Inst Genet & Human Therapy, Washington, DC 20007 USA. Policlin San Matteo, IRCCS, RIGHT, I-27100 Pavia, Italy. RP Hughes, SH (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, POB B, Frederick, MD 21702 USA. NR 26 TC 25 Z9 25 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD MAR 5 PY 1999 VL 286 IS 4 BP 995 EP 1008 DI 10.1006/jmbi.1998.2508 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 174DY UT WOS:000079019900004 PM 10047477 ER PT J AU Hortnagel, K Voloshin, ON Kinal, HH Ma, N Schaffer-Judge, C Camerini-Otero, RD AF Hortnagel, K Voloshin, ON Kinal, HH Ma, N Schaffer-Judge, C Camerini-Otero, RD TI Saturation mutagenesis of the E-coli RecA loop L2 homologous DNA pairing region reveals residues essential for recombination and recombinational repair SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE RecA protein; homologous recombination; recombinational repair; DNA pairing; ATPase activity ID SINGLE-STRANDED-DNA; HUMAN RAD51 PROTEIN; PEPTIDE LIBRARIES; AMINO-ACIDS; YEAST; BINDING; SELECTION; EXCHANGE; COMPLEX; GENES AB The disordered mobile loop L2 of the Escherichia coli RecA protein is known to play a central role in DNA binding and pairing. To investigate the local chemical environment in relation to function we performed saturation mutagenesis of the loop L2 region (amino acid positions 193-212) using a site-directed mutagenesis procedure, and determined the recombinational proficiency of the 380 mutants using genetic assays for homologous recombination and recombinational repair. Residues Asn193, Gln194, Arg196, Glu207, Thr209, Gly211, and Gly212 were identified as stringently required for recombinational events in bacterial cells. In addition, our findings suggest the involvement of loop L2 in the ATPase activity of RecA, and a role for residues Gln194, Arg196, Lys198 and Thr209 in the DNA-dependent hydrolysis of ATP. Finally, since 20 residue peptides that comprise this region can pair homologous DNAs by forming filamentous beta-structures, we propose how the information from the mutant analysis might facilitate the use of a simplified amino acid alphabet to design beta-structure forming L2 peptides with improved RecA-like activities. C1 NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. RP Camerini-Otero, RD (reprint author), NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. NR 55 TC 31 Z9 31 U1 0 U2 5 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD MAR 5 PY 1999 VL 286 IS 4 BP 1097 EP 1106 DI 10.1006/jmbi.1998.2515 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 174DY UT WOS:000079019900011 PM 10047484 ER PT J AU Silva, GH Dalgaard, JZ Belfort, M Van Roey, P AF Silva, GH Dalgaard, JZ Belfort, M Van Roey, P TI Crystal structure of the thermostable archaeal intron-encoded endonuclease I-DmoI SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE homing endonuclease; crystal structure; LAGLIDADG motif; intron-encoded ID SITE-SPECIFIC ENDONUCLEASE; PI-SCEI ENDONUCLEASE; ANOMALOUS DIFFRACTION; HOMING ENDONUCLEASE; DNA-BINDING; RECOGNITION; MACROMOLECULES; REFINEMENT; RESOLUTION; MOBILITY AB I-DmoI is a 22 kDa endonuclease encoded by an intron in the 23 S rRNA gene of the hyperthermophilic archaeon Desulfurococcus mobilis. The structure of I-DmoI has been determined to 2.2 Angstrom resolution using multi-wavelength anomalous diffraction techniques. I-DmoI, a protein of the LAGLIDADG motif family, represents the first structure of a freestanding endonuclease with two LAGLIDADG motifs, and the first of a thermostable homing endonuclease. I-DmoI consists of two similar alpha/beta domains (alpha beta beta alpha beta beta alpha) related by pseudo 2-fold symmetry. The LAGLIDADG motifs are located at the carboxy-terminal end of the first alpha-helix of each domain. These helices form a two-helix bundle at the interface between the domains and are perpendicular to a saddle-shaped DNA binding surface, formed by two four-stranded antiparallel beta-sheets. Despite substantially different sequences, the overall fold of I-DmoI is similar to that of two other LAGLIDADG proteins for which the structures are known, I-CreI and the endonuclease domain of PI-SceI. The three structures differ most in the loops connecting the beta-strands, relating to the respective DNA target site sizes and geometries. In addition, the absence of conserved residues surrounding the active site, other than those within the LAGLIDADG motif, is of mechanistic importance. Finally, the carboxy-terminal domain of I-DmoI is smaller and has a more irregular fold than the amino-terminal domain, which is more similar to I-CreI, a symmetric homodimeric endonuclease. This is reversed compared to PI-SceI, where the amino-terminal domain is more similar to carboxy-terminal domain of I-DmoI and to I-CreI, with interesting evolutionary implications. C1 New York Dept Hlth, Wadsworth Ctr, Albany, NY 12201 USA. SUNY Albany, Sch Publ Hlth, Dept Biomed Sci, Albany, NY 12201 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Ft Detrick, MD 21702 USA. RP Van Roey, P (reprint author), New York Dept Hlth, Wadsworth Ctr, Albany, NY 12201 USA. OI Belfort, Marlene/0000-0002-1592-5618 FU NIGMS NIH HHS [GM56966, GM39422, GM44844] NR 36 TC 78 Z9 79 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD MAR 5 PY 1999 VL 286 IS 4 BP 1123 EP 1136 DI 10.1006/jmbi.1998.2519 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 174DY UT WOS:000079019900013 PM 10047486 ER PT J AU Rioux, A Fabre, V Lesch, KP Moessner, R Murphy, DL Lanfumey, L Hamon, M Martres, MP AF Rioux, A Fabre, V Lesch, KP Moessner, R Murphy, DL Lanfumey, L Hamon, M Martres, MP TI Adaptive changes of serotonin 5-HT2A receptors in mice lacking the serotonin transporter SO NEUROSCIENCE LETTERS LA English DT Article DE serotonin transporter; knock-out mice; 5-HT2A receptor; cerebral cortex; down regulation; striosomes ID BASAL GANGLIA; RAT; ANTIDEPRESSANT; ANTAGONIST; EXPRESSION; CORTEX; SITES; BRAIN AB The serotonin transporter (5-HTT) plays a key-role in the control of serotoninergic neurotransmission and is the target of some antidepressants. Possible adaptive changes in brain 5-HT2A receptors were investigated in knock-out mice that do not express the 5-HTT. Autoradiographic labeling of these receptors by the selective antagonist [H-3]MDL 100,907 and saturation experiments with cortical membranes revealed: (1) a new localization of these receptors in the external field of striatum (possibly in striosomes); (2) regional variations in adaptive changes in the density of 5-HT2A receptors in 5-HT-/- mutants (-30-40% in the claustrum, cerebral cortex and lateral striatum; no significant change in the striatum core) as compared to wild-type mice. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Fac Med Pitie Salpetriere, INSERM, U288, F-75634 Paris 13, France. Univ Wurzburg, Dept Psychiat, D-97080 Wurzburg, Germany. NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. RP Hamon, M (reprint author), Fac Med Pitie Salpetriere, INSERM, U288, 91 Blvd Hop, F-75634 Paris 13, France. RI Lanfumey, Laurence/F-7695-2013; Lesch, Klaus-Peter/J-4906-2013 OI Lesch, Klaus-Peter/0000-0001-8348-153X NR 21 TC 76 Z9 76 U1 2 U2 4 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 5 PY 1999 VL 262 IS 2 BP 113 EP 116 DI 10.1016/S0304-3940(99)00049-X PG 4 WC Neurosciences SC Neurosciences & Neurology GA 175RK UT WOS:000079108600011 PM 10203244 ER PT J AU Yao, ZJ Gao, Y Voigt, JH Ford, H Burke, TR AF Yao, ZJ Gao, Y Voigt, JH Ford, H Burke, TR TI Synthesis of Fmoc-protected 4-carboxydifluoromethyl-L-phenylalanine: A phosphotyrosyl mimetic of potential use for signal transduction studies SO TETRAHEDRON LA English DT Article DE amino acids and derivatives; asymmetric synthesis; molecular design; peptide analogues/mimetics ID SOLID-PHASE SYNTHESIS; INHIBITORY PEPTIDES; ACIDS; TYROSINE AB 4-(Carboxymethyl)phenylalanine (2) and its alpha,alpha-difluoro homologue 4-(carboxydifluoromethyl)-phenylalanine (3) have been described as phosphotyrosyl mimetics. Herein we report the synthesis of N-Fmoc 4-(0-tert-butyl carboxymethyl)-phenylalanine (4) and N-Fmoc 4-(0-tert-butyl carboxydifluoromethyl)phenylalanine (5) in high enantiomeric purity. These analogues bear orthogonal protection suitable for the preparation of inhibitors directed against a variety of signal transduction pathways, including SH2 and PTP domains and protein-tyrosine phosphatases. Published by Elsevier Science Ltd. C1 NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Burke, TR (reprint author), NCI, Med Chem Lab, Div Basic Sci, NIH, Bldg 37,Rm 5C06, Bethesda, MD 20892 USA. RI Burke, Terrence/N-2601-2014; Yao, Zhu-Jun/E-7635-2015 NR 21 TC 20 Z9 20 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4020 J9 TETRAHEDRON JI Tetrahedron PD MAR 5 PY 1999 VL 55 IS 10 BP 2865 EP 2874 DI 10.1016/S0040-4020(99)00076-9 PG 10 WC Chemistry, Organic SC Chemistry GA 171LK UT WOS:000078865000006 ER PT J AU Tao, T Skiadopoulos, MH Durbin, AP Davoodi, F Collins, PL Murphy, BR AF Tao, T Skiadopoulos, MH Durbin, AP Davoodi, F Collins, PL Murphy, BR TI A live attenuated chimeric recombinant parainfluenza virus (PIV) encoding the internal proteins of PIV type 3 and the surface glycoproteins of PIV type 1 induces complete resistance to PIV1 challenge and partial resistance to PIV3 challenge SO VACCINE LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; PARA-INFLUENZA; SENDAI VIRUS; PROTECTIVE IMMUNITY; WEANLING HAMSTERS; VACCINIA VIRUSES; SUBUNIT VACCINE; HEALTHY INFANTS; COTTON RATS; EXPRESSION AB The recovery of wild type and attenuated human parainfluenza type 3 (PIV3) recombinant viruses has made possible a new strategy to rapidly generate a live-attenuated vaccine virus for PIV1. We previously replaced the coding sequences for the hemagglutinin-neuraminidase (HN) and fusion (F) proteins of PIV3 with those of PIV1 in the PIV3 antigenomic cDNA. This was used to recover a fully-viable, recombinant chimeric PTV3-PIV1 virus, termed rPIV3-1, which bears the major protective antigens of PIV1 and is wild type-like with regard to growth in cell culture and in hamsters [Tao T, Durbin AP, Whitehead SS, Davoodi F, Collins FL, Murphy BR. Recovery of a fully viable chimeric human parainfluenza virus (PIV) type 3 in which the hemagglutinin-neuraminidase and fusion glycoprotein have been replaced by those of PIV type I. J Virol 1998;72:2955-2961]. Here we report the recovery of a derivative of rPIV3-1 carrying the three temperature-sensitive and attenuating amino acid coding changes found in the L gene of the live-attenuated cp45 PIV3 candidate vaccine virus. This virus, termed rPIV3-1.cp45L, is temperature-sensitive with a shut-off temperature of 38 degrees C, which is similar to that of the recombinant rPIV3cp45L, which possesses the same three mutations. rPIV3-1.cp45L is attenuated in the respiratory tract of hamsters to the same extent as rPIV3cp45L. Infection of hamsters with rPIV3-1.cp45L generated a moderate level of hemagglutination-inhibiting antibodies against wild type PIV1 and induced complete resistance to challenge with wild type PIV1. This demonstrates that this novel attenuated chimeric virus is capable of inducing a highly effective immune response against PIV1. It confirms previous observations that the surface glycoproteins of parainfluenza viruses are sufficient to induce a high level of resistance to homologous virus challenge. Unexpectedly, infection with recombinant chimeric virus rPIV3-1.cp45L or rPIV3-1, each bearing the surface glycoprotein genes of PIV1 and the internal genes of PIV3, also induced a moderate lever of resistance to replication of wild type PIV3 challenge virus. This indicates that the internal genes of PIV3 can independently induce protective immunity against PIV3 in rodents, albeit a lower level of resistance than that induced by the surface glycoproteins. Thus, a reverse genetics system for PIV3 has been used successfully to produce a live attenuated PIV1 vaccine candidate that is attenuated and protective in experimental infection in hamsters. Published by Elsevier Science Ltd. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Tao, T (reprint author), NIAID, Infect Dis Lab, NIH, Ctr Dr,MSC 0720, Bethesda, MD 20892 USA. FU NIAID NIH HHS [AI-000087] NR 38 TC 26 Z9 27 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD MAR 5 PY 1999 VL 17 IS 9-10 BP 1100 EP 1108 DI 10.1016/S0264-410X(98)00327-2 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 175YD UT WOS:000079122900013 PM 10195620 ER PT J AU Franke, ED Hoffman, SL Sacci, JB Wang, R Charoenvit, Y Appella, E Chesnut, R Alexander, J Del Guercio, MF Sette, A AF Franke, ED Hoffman, SL Sacci, JB Wang, R Charoenvit, Y Appella, E Chesnut, R Alexander, J Del Guercio, MF Sette, A TI Pan DR binding sequence provides T-cell help for induction of protective antibodies against Plasmodium yoelii sporozoites SO VACCINE LA English DT Article DE malaria; immunization; Pan-DR epitope peptides ID CIRCUMSPOROZOITE PROTEIN; B-CELL; VACCINE; FALCIPARUM; EPITOPES; ANTIGEN; MICE AB Pan-DR epitope (PADRE) peptides have demonstrated the capacity to deliver help for antibody responses in vivo, They were also found, fortuitously, to be able to provide significant helper T-cell activity in vivo. This suggested that linear constructs, containing the PADRE epitope, might be as efficient at generating an immune response as large multivalent antigens. Plasmodium falciparum and P. yoelii PADRE constructs were capable of inducing a high titre IgG antibody response that recognized intact sporozoites. We now report that these antibodies can inhibit sporozoite invasion of hepatocytes in vitro and that mice immunized with the PyCSP-PADRE linear construct were protected when challenged with P. yoelii sporozoites. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 USN, Med Res Inst, Malaria Program, Rockville, MD 20852 USA. Univ Maryland, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. NCI, Cell Biol Lab, Bethesda, MD 20892 USA. Epimmune Inc, San Diego, CA 92121 USA. RP Hoffman, SL (reprint author), USN, Med Res Inst, Malaria Program, 12300 Washington Ave, Rockville, MD 20852 USA. RI Villasante, Eileen/G-3602-2011 FU NIAID NIH HHS [N01-AI-45241] NR 19 TC 23 Z9 24 U1 2 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD MAR 5 PY 1999 VL 17 IS 9-10 BP 1201 EP 1205 DI 10.1016/S0264-410X(98)00341-7 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 175YD UT WOS:000079122900026 PM 10195633 ER PT J AU Gao, ZH Zhong, GM AF Gao, ZH Zhong, GM TI Calcineurin B- and calmodulin-binding preferences identified with phage-displayed peptide libraries SO GENE LA English DT Article DE Ca2+-binding protein; calcium; protein-protein interaction; motif ID DEPENDENT PROTEIN PHOSPHATASE; MOLECULAR-CLONING; CATALYTIC SUBUNIT; FILAMENTOUS PHAGE; DOMAIN; COMPLEX; BACTERIOPHAGE; FKBP12-FK506; AFFINITY; TARGETS AB Calcineurin B (CnB) and calmodulin (CaM) are two structurally similar but functionally distinct 'EF-hand' Ca2+-binding proteins. CnB is the regulatory subunit of the CaM-stimulated protein phosphatase, calcineurin. CaM is a unique multifunctional protein that interacts with and modulates the activity of many target proteins. CnB and CaM are both required for the full activation of the phosphatase activity of calcineurin and are not interchangeable. The two proteins recognize distinct binding sites on calcineurin A subunit (CnA) and perform different functions. Phage-displayed peptide libraries (pIII and pVIII libraries) were screened with CnB and CaM to isolate peptides that could then be compared to determine if there were binding preferences of the two proteins. The Ca2+-dependent binding of phage-displayed peptides to CnB and CaM is specifically blocked by synthetic peptides derived from the CnB-binding domain of CnA and the CaM-binding domain of myosin light chain kinase respectively. Both CnB- and CaM-binding peptides have a high content of tryptophan and leucine, but CnB-binding peptides are more hydrophobic than CaM-binding peptides. CnB-binding peptides are negatively charged with clusters of hydrophobic residues rich in phenylalanine, whereas the CaM-binding peptides are positively charged and often contain an Arg/Lys-Trp motif. The binding preferences identified with peptide libraries are consistent with the features of the CnB-binding domains of all CnA isoforms and the CaM-binding domains of CaM targets. (C) 1999 Elsevier Science B.V. All rights reserved. C1 NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Gao, ZH (reprint author), Univ Utah, Dept Oncol Sci, 5C334 SOM, Salt Lake City, UT 84132 USA. NR 34 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD MAR 4 PY 1999 VL 228 IS 1-2 BP 51 EP 59 DI 10.1016/S0378-1119(99)00007-4 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 177JU UT WOS:000079207500006 PM 10072758 ER PT J AU De, J Lai, WS Thorn, JM Goldsworthy, SM Liu, XY Blackwell, TK Blackshear, PJ AF De, J Lai, WS Thorn, JM Goldsworthy, SM Liu, XY Blackwell, TK Blackshear, PJ TI Identification of four CCCH zinc finger proteins in Xenopus, including a novel vertebrate protein with four zinc fingers and severely restricted expression SO GENE LA English DT Article DE AU-rich element; deadenylation; mid-blastula transition; mRNA stability ID PRIMARY RESPONSE GENE; C-ELEGANS EMBRYOS; MESSENGER-RNA; TRANSCRIPTION FACTOR; NUCLEOTIDE-SEQUENCE; TRISTETRAPROLIN; DEGRADATION; FAMILY; TIS11; HOMOLOG AB Tristetraprolin (TTP, the prototype of a class of CCCH zinc finger proteins, is a phosphoprotein that is rapidly and transiently induced by growth factors and serum in fibroblasts. Recent evidence suggests that a physiological function of TTP is to inhibit tumor necrosis factor alpha secretion from macrophages by binding to and destabilizing its mRNA (Carballo, E., Lai, W.S., Blackshear, P.J., 1998. Science, 281, 1001-1005). To investigate possible functions of CCCH proteins in early development of Xenopus, we isolated four Xenopus cDNAs encoding members of this class. Based on 49% overall amino acid identity and 84% amino acid identity within the double zinc finger domain, one of the Xenopus proteins (XC3H-1) appears to be the homologue of TTP. By similar analyses, XC3H-2 and XC3H-3 are homologues of ERF-1 (cMG1, TIS11B) and ERF-2 (TIS11D). A fourth protein, XC3H-4, is a previously unidentified member of the CCCH class of vertebrate zinc finger proteins; it contains four Cx(8)Cx(5)Cx(3)H repeats, two of which are YKTEL Cx(8)Cx(5)Cx(3)H repeats that are closely related to sequences found in the other CCCH proteins, Whereas XC3H-1, XC3H-2, and XC3H-3 were widely expressed in adult tissues, XC3H-4 mRNA was not detected in any of the adult tissues studied except for the ovary. Its expression appeared to be limited to the ovary, oocyte, egg and the early embryonic stages leading up to the mid-blastula transition. Its mRNA was highly expressed in oocytes of all ages, and was enriched in the animal pole cytosol of mature oocytes. Maternal expression was also seen with the other three messages, suggesting the possibility that these proteins are involved in regulating mRNA stability in oocyte maturation and/or early embryogenesis. (C) 1999 Elsevier Science B.V. All rights reserved. C1 NIEHS, Off Clin Res, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Signel Transduct, Res Triangle Pk, NC 27709 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA. RP Blackshear, PJ (reprint author), NIEHS, Off Clin Res, A2-05,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM black009@niehs.nih.gov FU NICHD NIH HHS [P0 HD17461] NR 43 TC 40 Z9 44 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD MAR 4 PY 1999 VL 228 IS 1-2 BP 133 EP 145 DI 10.1016/S0378-1119(98)00617-9 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 177JU UT WOS:000079207500014 PM 10072766 ER PT J AU Grimbacher, B Holland, SM Gallin, JI Greenberg, F Hill, SC Malech, HL Miller, JA O'Connell, AC Puck, JM AF Grimbacher, B Holland, SM Gallin, JI Greenberg, F Hill, SC Malech, HL Miller, JA O'Connell, AC Puck, JM TI Hyper-IgE syndrome with recurrent infections - An autosomal dominant multisystem disorder SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HYPERIMMUNOGLOBULINEMIA-E SYNDROME; INTERFERON-GAMMA PRODUCTION; JOBS SYNDROME; CLEIDOCRANIAL DYSPLASIA; T-CELLS; INTERLEUKIN-4; ASSOCIATION; DEFICIENCY; LYMPHOMA; OSTEOPOROSIS AB Background The hyper-IgE syndrome with recurrent infections is a rare immunodeficiency characterized by recurrent skin and pulmonary abscesses and extremely elevated levels of IgE in serum. Associated facial and skeletal features have been recognized, but their frequency is unknown, and the genetic basis of the hyper-IgE syndrome is poorly understood. Methods We studied 30 patients with the hyper-IgE syndrome and 70 of their relatives. We took histories, reviewed records, performed physical and dental examinations, took anthropometric measurements, and conducted laboratory studies. Results Nonimmunologic features of the hyper-IgE syndrome were present in all patients older than eight years. Seventy-two percent had the previously unrecognized feature of failure or delay of shedding of the primary teeth owing to lack of root resorption. Common findings among patients were recurrent fractures (in 57 percent of patients), hyperextensible joints (in 68 percent), and scoliosis tin 76 percent of patients 16 years of age or older). The classic triad of abscesses, pneumonia, and an elevated IgE level was identified in 77 percent of all patients and in 85 percent of those older than eight. In 6 of 23 adults (26 percent), IgE levels declined over time and came closer to or fell within the normal range. Autosomal dominant transmission of the hyper-IgE syndrome was found, but with variable expressivity. Of the 27 relatives at risk for inheriting the hyper-IgE syndrome, 10 were fully affected, 11 were unaffected, and 6 had combinations of mild immunologic, dental, and skeletal features of the hyper-IgE syndrome. Conclusions The hyper-IgE syndrome is a multisystem disorder that affects the dentition, the skeleton, connective tissue, and the immune system. It is inherited as a single-locus autosomal dominant trait with variable expressivity. (N Engl J Med 1999;340:692-702.) (C) 1999, Massachusetts Medical Society. C1 NIH, Natl Human Genome Res Inst, Genet & Mol Biol Branch, Immunol Genet Sect, Bethesda, MD 20892 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Radiol, Bethesda, MD 20892 USA. NIDCR, NIH, Bethesda, MD 20892 USA. NIH, Natl Human Genome Res Inst, Genet Dis Branch, Bethesda, MD 20892 USA. RP Puck, JM (reprint author), NIH, Natl Human Genome Res Inst, Genet & Mol Biol Branch, Immunol Genet Sect, Bldg 49,Rm 3A14,40 Convent Dr, Bethesda, MD 20892 USA. OI O'Connell, Anne C/0000-0002-1495-3983 NR 62 TC 360 Z9 374 U1 1 U2 13 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 4 PY 1999 VL 340 IS 9 BP 692 EP 702 DI 10.1056/NEJM199903043400904 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 172ZB UT WOS:000078955200004 PM 10053178 ER PT J AU Levy, D Thom, TJ AF Levy, D Thom, TJ TI Rates of death from coronary heart disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NHLBI, Framingham, MA 01702 USA. NHLBI, Bethesda, MD 20892 USA. RP Levy, D (reprint author), NHLBI, Framingham, MA 01702 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 4 PY 1999 VL 340 IS 9 BP 731 EP 732 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 172ZB UT WOS:000078955200013 ER PT J AU Rojas, JM Subleski, M Coque, JJR Guerrero, C Saez, R Li, BQ Lopez, E Zarich, N Aroca, P Kamata, T Santos, E AF Rojas, JM Subleski, M Coque, JJR Guerrero, C Saez, R Li, BQ Lopez, E Zarich, N Aroca, P Kamata, T Santos, E TI Isoform-specific insertion near the Grb2-binding domain modulates the intrinsic guanine nucleotide exchange activity of hSos1 SO ONCOGENE LA English DT Article DE hSos1; isoforms; Ras activation; GEF activity; oocyte maturation ID EPIDERMAL GROWTH-FACTOR; RECEPTOR TYROSINE KINASES; ACTIVATED PROTEIN-KINASE; NIH 3T3 CELLS; SIGNAL-TRANSDUCTION; OOCYTE MATURATION; FACTOR SON; PHOSPHATIDYLINOSITOL 3-KINASE; MONOCLONAL-ANTIBODIES; XENOPUS OOCYTES AB Two human hSos1 isoforms (Isf I and Isf II; Rojas et al,, Oncogene 12, 2291-2300, 1996) defined by the presence of a distinct 15 amino acid stretch in one of them, were compared biologically and biochemically using representative NIH3T3 transfectants overexpressing either one. We showed that hSos1-Isf II is significantly more effective than hSos1-Isf I to induce proliferation or malignant transformation of rodent fibroblasts when transfected alone or in conjunction with normal H-Ras (Gly12), The hSos1-Isf II-Ras cotransfectants consistently exhibited higher saturation density, lower cell-doubling times, increased focus-forming activity and higher ability to grow on semisolid medium and at low serum concentration than their hSos1-Isf I-Ras counterparts. Furthermore, the ratio of GTP/GDP bound to cellular p21(ras) was consistently higher in the hSos1-Isf II-transfected clones, both under basal and stimulated conditions. However, no significant differences were detected in vivo between Isf I- and Isf II-transfected clones regarding the amount, stability and subcellular localization of Sos1-Grb2 complex, or the level of hSos1 phosphorylation upon cellular stimulation, Interestingly, direct Ras guanine nucleotide exchange activity assays in cellular lysates showed that Isf II transfectants consistently exhibited about threefold higher activity than Isf I transfectants under basal, unstimulated conditions. Microinjection into Xenopus oocytes of purified peptides corresponding to the C-terminal region of both isoforms (encompassing the 15 amino acid insertion area and the first Grb2-binding motif) showed that only the Isf II peptide, but not its corresponding Isf I peptide, was able to induce measurable rates of meiotic maturation, and synergyzed with insulin, but not progesterone, in induction of GVBD. Our results suggest that the increased biological potency displayed by hSos1-Isf II is due to higher intrinsic guanine nucleotide exchange activity conferred upon this isoform by the 15 a.a. insertion located in proximity to its Grb2 binding region. C1 NCI, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, Lab Biochem Physiol, Frederick, MD 21071 USA. RP Santos, E (reprint author), NCI, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. RI Guerrero, Carmen/F-1776-2010 OI Guerrero, Carmen/0000-0002-8747-6831 NR 56 TC 7 Z9 8 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR 4 PY 1999 VL 18 IS 9 BP 1651 EP 1661 DI 10.1038/sj.onc.1202483 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 174GB UT WOS:000079025000001 PM 10208427 ER PT J AU Srivastava, RK Srivastava, AR Cho-Chung, YS Longo, DL AF Srivastava, RK Srivastava, AR Cho-Chung, YS Longo, DL TI Synergistic effects of retinoic acid and 8-Cl-cAMP on apoptosis require caspase-3 activation in human ovarian cancer cells SO ONCOGENE LA English DT Article DE retinoic acid; caspase protein kinase A; cytochrome c; apoptosis ID DEPENDENT PROTEIN-KINASE; MITOCHONDRIAL PERMEABILITY TRANSITION; RECEPTOR-BETA; POLY(ADP-RIBOSE) POLYMERASE; CATALYTIC SUBUNIT; UP-REGULATION; CYTOCHROME-C; ELEMENT; SUPPRESSION; GROWTH AB We investigated the intracellular mechanisms of retinoic acid (9-cis-RA, 13-cis-RA or all-trans-RA) and a cyclic AMP analog 8-Cl-cAMP on growth-inhibition and apoptosis in human ovarian cancer NIH: OVCAR-3 and OVCGR-8 cells, The cyclic AMP analog, 8-Cl-cAMP, acted synergistically with RA in inducing and activating retinoic acid receptor beta (RAR beta) which correlated with the growth inhibition, cell cycle arrest, and apoptosis in both cell types. In addition, combined treatment of cells with RA plus 8-Cl-cAMP resulted in the release of cytochrome c, loss in mitochondrial membrane potential and activation of caspase-3 followed by cleavage of anti-poly(ADP-ribose)polymerase and DNA-dependent protein kinase (catalytic subunit), Interestingly, inhibition of caspase-3 activation blocked RA plus 8-Cl-cAMP induced apoptosis, Furthermore, mutations in a CRE-related motif within the RAR beta promoter resulted in loss of both transcriptional activation of RAR beta and synergy between RA and 8-Cl-cAMP, Thus, RAR beta can mediate RA and/or cyclic AMP action in ovarian cancer cells by promoting apoptosis, Loss of RAR beta expression, therefore, may contribute to the tumorigenicity of human ovarian cancer cells, These findings suggest that RA and 8-Cl-cAMP act in a synergistic fashion in inducing apoptosis via caspase-3 activation, and may have potential for combination biotherapy for the treatment of malignant disease such as ovarian cancer. C1 NIA, Immunol Lab, NIH, Baltimore, MD 21224 USA. NCI, Med Branch, Bethesda, MD 20892 USA. NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. RP Srivastava, RK (reprint author), NIA, Immunol Lab, NIH, Box 28,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 45 TC 29 Z9 30 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR 4 PY 1999 VL 18 IS 9 BP 1755 EP 1763 DI 10.1038/sj.onc.1202464 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 174GB UT WOS:000079025000010 PM 10208436 ER PT J AU Goff, DC Howard, G Wang, CH Folsom, AR Rosamond, WD Cooper, LS Chambless, LE AF Goff, DC Howard, G Wang, CH Folsom, AR Rosamond, WD Cooper, LS Chambless, LE TI Trends in severity of hospitalized myocardial infarction: The ARIC study 1987-1994. SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, Bethesda, MD 20892 USA. Univ Minnesota, Minneapolis, MN USA. Univ N Carolina, Chapel Hill, NC USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 2 PY 1999 VL 99 IS 8 MA 1 BP 1104 EP 1104 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 171BC UT WOS:000078841500021 ER PT J AU Smith, NL Psaty, BM Furberg, CD White, R Lima, JAC Newman, A Manolio, TA AF Smith, NL Psaty, BM Furberg, CD White, R Lima, JAC Newman, A Manolio, TA TI Temporal trends in the use of anticoagulants among older adults with atrial fibrillation SO CIRCULATION LA English DT Meeting Abstract C1 Johns Hopkins Univ, Hagerstown, MA USA. NHLBI, Bethesda, MD 20892 USA. Univ Calif Davis, Davis, CA USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Washington, Seattle, WA 98195 USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 2 PY 1999 VL 99 IS 8 MA 3 BP 1104 EP 1104 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 171BC UT WOS:000078841500023 ER PT J AU Hunt, KJ Brown, CA Chambless, LE Evans, GW Folsom, AR Sharrett, AR Tegeler, CH Heiss, G AF Hunt, KJ Brown, CA Chambless, LE Evans, GW Folsom, AR Sharrett, AR Tegeler, CH Heiss, G TI Mineralized carotid atherosclerosis on B-mode ultrasound predicts CHD: The Atherosclerosis Risk in Communities (ARIC) study. SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, Bethesda, MD 20892 USA. Univ Minnesota, Minneapolis, MN USA. Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. Univ N Carolina, Chapel Hill, NC USA. Wake Forest Univ, Baptist Med Ctr, Winston Salem, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 2 PY 1999 VL 99 IS 8 MA 14 BP 1106 EP 1106 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 171BC UT WOS:000078841500034 ER PT J AU Wilson, PWF O'Donnell, CJ Kiel, DP Hannan, M Cupples, A AF Wilson, PWF O'Donnell, CJ Kiel, DP Hannan, M Cupples, A TI Lumbar aortic calcification is an important predictor of vascular morbidity and mortality SO CIRCULATION LA English DT Meeting Abstract C1 Boston Univ, Boston, MA 02215 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Harvard Univ, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 2 PY 1999 VL 99 IS 8 MA 15 BP 1106 EP 1106 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 171BC UT WOS:000078841500035 ER PT J AU Iribarren, C Sidney, S Liu, K Markovitz, JH Bild, DE Roseman, JM AF Iribarren, C Sidney, S Liu, K Markovitz, JH Bild, DE Roseman, JM TI Hostility predicts coronary artery calcification in young adults: the CARDIA study SO CIRCULATION LA English DT Meeting Abstract C1 Kaiser Permanente Med Care Program, Div Res, Oakland, CA 94611 USA. NHLBI, Bethesda, MD 20892 USA. Northwestern Univ, Sch Med, Chicago, IL 60611 USA. Univ Alabama, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 2 PY 1999 VL 99 IS 8 MA 19 BP 1107 EP 1107 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 171BC UT WOS:000078841500039 ER PT J AU Osganian, SK Stampfer, MJ Spiegelman, D Rimm, E Cutler, JA Montgomery, DH Lytle, LA Webber, LS Nader, PR Bausserman, LL Feldman, HA AF Osganian, SK Stampfer, MJ Spiegelman, D Rimm, E Cutler, JA Montgomery, DH Lytle, LA Webber, LS Nader, PR Bausserman, LL Feldman, HA TI Serum homocysteine in adolescents: Demographic variation and relation to folate and vitamin levels in a large sample of US children. SO CIRCULATION LA English DT Meeting Abstract C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Miriam Hosp, Providence, RI 02906 USA. Brown Univ, Sch Med, Providence, RI 02912 USA. NHLBI, Bethesda, MD 20892 USA. New England Res Inst, Watertown, MA 02172 USA. Tulane Univ, Sch Publ Hlth & Trop Med, New Orleans, LA 70118 USA. Univ Calif San Diego, La Jolla, CA 92093 USA. Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA. Univ Texas, Hlth Sci Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 2 PY 1999 VL 99 IS 8 MA 23 BP 1107 EP 1107 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 171BC UT WOS:000078841500043 ER PT J AU Windhauser, MM Proschan, MA Swain, J Obarzanek, E AF Windhauser, MM Proschan, MA Swain, J Obarzanek, E TI Moderate alcohol intake is associated with blood pressure response to the DASH diet SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Pennington Biomed Res Ctr, Baton Rouge, LA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 2 PY 1999 VL 99 IS 8 MA 21 BP 1107 EP 1107 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 171BC UT WOS:000078841500041 ER PT J AU Cushman, M Arnold, AM Kuller, LH Psaty, BM Manolio, TA Burke, GL Polak, JF Tracy, RP AF Cushman, M Arnold, AM Kuller, LH Psaty, BM Manolio, TA Burke, GL Polak, JF Tracy, RP TI C-reactive protein and risks of myocardial infarction, stroke and death in an elderly cohort SO CIRCULATION LA English DT Meeting Abstract C1 Harvard Univ, Boston, MA 02115 USA. NHLBI, Bethesda, MD 20892 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Vermont, Burlington, VT USA. Univ Vermont, Colchester, VT USA. Univ Washington, Seattle, WA 98195 USA. Wake Forest Univ, Winston Salem, NC 27109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 2 PY 1999 VL 99 IS 8 MA 30 BP 1108 EP 1108 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 171BC UT WOS:000078841500050 ER PT J AU Wu, TJ Trevisan, M Genco, R Dorn, J Falkner, K Sempos, C AF Wu, TJ Trevisan, M Genco, R Dorn, J Falkner, K Sempos, C TI Periodontal disease as a risk factor for CVD, CHD, and STROKE: The first National Health and Nutrition Examination Survey (NHANES I) and its follow-up study SO CIRCULATION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. SUNY Buffalo, Buffalo, NY 14260 USA. NR 0 TC 7 Z9 7 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 2 PY 1999 VL 99 IS 8 MA P1 BP 1109 EP 1109 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 171BC UT WOS:000078841500051 ER PT J AU Kimm, SYS Glynn, NW Obarzanek, E AF Kimm, SYS Glynn, NW Obarzanek, E CA NGHS Collaborative Res Grp TI Obesity and its relationship to physical activity and inactivity during adolescence SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, Bethesda, MD 20892 USA. Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 2 PY 1999 VL 99 IS 8 MA P27 BP 1113 EP 1113 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 171BC UT WOS:000078841500077 ER PT J AU Kuller, LH Velentgas, P Barzilay, J Beauchamp, NJ O'Leary, DH Savage, PJ AF Kuller, LH Velentgas, P Barzilay, J Beauchamp, NJ O'Leary, DH Savage, PJ TI Diabetes mellitus, subclinical cardiovascular disease and risk of incident cardiovascular disease and all-cause mortality SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, DECA, Rockville, MD USA. Johns Hopkins Radiol, Baltimore, MD USA. Kaiser Permanente, Tucker, GA USA. Tufts Univ, New England Med Ctr, Boston, MA 02111 USA. Univ Pittsburgh, GSPH, Pittsburgh, PA USA. Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 2 PY 1999 VL 99 IS 8 MA P36 BP 1114 EP 1114 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 171BC UT WOS:000078841500086 ER PT J AU Heckbert, SR Savage, PJ Barzilay, JI Bittner, V Smith, NL Psaty, BM Dobs, A Kuller, LH Orchard, TJ AF Heckbert, SR Savage, PJ Barzilay, JI Bittner, V Smith, NL Psaty, BM Dobs, A Kuller, LH Orchard, TJ TI Diabetes impaired fasting glucose, and the prevalence of microvascular disease in the elderly SO CIRCULATION LA English DT Meeting Abstract C1 Emory Univ, Sch Med, Atlanta, GA USA. Johns Hopkins Univ, Baltimore, MD USA. NHLBI, Bethesda, MD 20892 USA. Univ Alabama, Birmingham, AL USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 2 PY 1999 VL 99 IS 8 MA P39 BP 1115 EP 1115 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 171BC UT WOS:000078841500089 ER PT J AU Liao, DP Din-Dzietham, R Mo, JP Klein, R Jones, D Chambless, LE Hubbard, L Sharrett, RA AF Liao, DP Din-Dzietham, R Mo, JP Klein, R Jones, D Chambless, LE Hubbard, L Sharrett, RA TI Carotid arterial elasticity and retinal arteriolar narrowing SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. Penn State Univ, Coll Med, Hershey, PA USA. Univ Mississippi, Jackson, MS 39216 USA. Univ N Carolina, Chapel Hill, NC USA. Univ Wisconsin, Madison, WI USA. Univ Wisconsin, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 2 PY 1999 VL 99 IS 8 MA P45 BP 1116 EP 1116 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 171BC UT WOS:000078841500095 ER PT J AU Rosamond, WD Weatherley, BD Folsom, AR Cai, JW Lamar, V Cooper, LS AF Rosamond, WD Weatherley, BD Folsom, AR Cai, JW Lamar, V Cooper, LS TI Trends in attack rates and aspects of medical rare for unstable angina SO CIRCULATION LA English DT Meeting Abstract C1 Univ N Carolina, Chapel Hill, NC USA. Univ Minnesota, Minneapolis, MN USA. NHLBI, Bethesda, MD 20892 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 2 PY 1999 VL 99 IS 8 MA P64 BP 1119 EP 1119 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 171BC UT WOS:000078841500114 ER PT J AU Rodriguez, BL Curb, JD Sakkinen, P Bild, DE Burchfiel, CM Abbott, R Schatz, I Yano, K Tracy, R AF Rodriguez, BL Curb, JD Sakkinen, P Bild, DE Burchfiel, CM Abbott, R Schatz, I Yano, K Tracy, R TI The association between C-reactive protein, diabetes and other CVD risk factors among elderly Japanese-American men; The Honolulu Heart Program SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, NIH, Jackson, MS USA. NHLBI, NIH, Bethesda, MD 20892 USA. Univ Hawaii, Honolulu, HI 96822 USA. Univ Vermont, Colchester, VT USA. Univ Virginia, Charlottesville, VA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 2 PY 1999 VL 99 IS 8 MA P68 BP 1120 EP 1120 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 171BC UT WOS:000078841500118 ER PT J AU Wilson, PWF D'Agostino, RB Franzblau, C Silbershatz, H Wolf, PA AF Wilson, PWF D'Agostino, RB Franzblau, C Silbershatz, H Wolf, PA TI C-reactive protein, serum amyloid A protein, cardiovascular disease and death: The Framingham Heart Study experience SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, Framingham Heart Study, Framingham, MA USA. Boston Univ, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 2 PY 1999 VL 99 IS 8 MA P74 BP 1121 EP 1121 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 171BC UT WOS:000078841500124 ER PT J AU Ellison, RC Zhang, YQ Knox, S Arnett, DK Province, MA AF Ellison, RC Zhang, YQ Knox, S Arnett, DK Province, MA TI Lifestyle determinants of HDL-cholesterol: The NHLBI Family Heart Study SO CIRCULATION LA English DT Meeting Abstract C1 Washington Univ, St Louis, MO USA. Univ Minnesota, Minneapolis, MN USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 2 PY 1999 VL 99 IS 8 MA P94 BP 1124 EP 1124 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 171BC UT WOS:000078841500144 ER PT J AU Nagaich, AK Zhurkin, VB Durell, SR Jernigan, RL Appella, E Harrington, RE AF Nagaich, AK Zhurkin, VB Durell, SR Jernigan, RL Appella, E Harrington, RE TI p53-induced DNA bending and twisting: p53 tetramer binds on the outer side of a DNA loop and increases DNA twisting SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE wild-type p53; p53 DNA binding domain; DNA-protein complex; A-tract phasing analysis; bent DNA ID CRYSTAL-STRUCTURE; DOMAIN PEPTIDES; SEQUENCE; PROTEIN; SITE; OLIGOMERIZATION; ACTIVATION; ELEMENTS; COMPLEX AB DNA binding activity of p53 is crucial for its tumor suppressor function. Our recent studies have shown that four molecules of the DNA binding domain of human p53 (p53DBD) bind the response elements with high cooperativity and bend the DNA. By using A-tract phasing experiments, we find significant differences between the bending and twisting of DNA by p53DBD and by full-length human wild-type (wt) p53. Our data show that four subunits of p53DBD bend the DNA by 32-36 degrees degrees, whereas wt p53 bends it by 51-57 degrees. The directionality of bending is consistent with major groove bends at the two pentamer junctions in the consensus DNA response element. More sophisticated phasing analyses also demonstrate that p53DBD and wt p53 overtwist the DNA response element by approximate to 35 degrees and approximate to 70 degrees, respectively. These results are in accord with molecular modeling studies of the tetrameric complex Within the constraints imposed by the protein subunits, the DNA can assume a range of conformations resulting from correlated changes in bend and twist angles such that the p53-DNA tetrameric complex is stabilized by DNA overtwisting and bending toward the major groove at the CATG tetramers. This bending is consistent with the inherent sequence-dependent anisotropy of the duplex. Overall, the four p53 moieties are placed laterally in a staggered array on the external side of the DNA loop and have numerous interprotein interactions that increase the stability and cooperativity of binding. The novel architecture of the p53 tetrameric complex has important functional implications including possible p53 interactions with chromatin. C1 Arizona State Univ, Dept Microbiol, Tempe, AZ 85287 USA. NCI, Lab Expt & Computat Biol, NIH, Bethesda, MD 20892 USA. RP Zhurkin, VB (reprint author), Arizona State Univ, Dept Microbiol, Tempe, AZ 85287 USA. RI Jernigan, Robert/A-5421-2012 FU NCI NIH HHS [CA70274]; NIGMS NIH HHS [GM53517] NR 37 TC 82 Z9 82 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 2 PY 1999 VL 96 IS 5 BP 1875 EP 1880 DI 10.1073/pnas.96.5.1875 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 172ZP UT WOS:000078956600015 PM 10051562 ER PT J AU Valenzuela, DM Griffiths, JA Rojas, J Aldrich, TH Jones, PF Zhou, H McClain, J Copeland, NG Gilbert, DJ Jenkins, NA Huang, T Papadopoulos, N Maisonpierre, PC Davis, S Yancopoulos, GD AF Valenzuela, DM Griffiths, JA Rojas, J Aldrich, TH Jones, PF Zhou, H McClain, J Copeland, NG Gilbert, DJ Jenkins, NA Huang, T Papadopoulos, N Maisonpierre, PC Davis, S Yancopoulos, GD TI Angiopoietins 3 and 4: Diverging gene counterparts in mice and humans SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE angiogenesis; tie receptor tyrosine kinase; vascular endothelial growth factor ID TIE2 RECEPTOR; ANGIOGENESIS; EXPRESSION; LETHALITY; LIGAND AB The angiopoietins have recently joined the members of the vascular endothelial growth factor family as the only known growth factors largely specific for vascular endothelium. The angiopoietins include a naturally occurring agonist, angiopoietin-1, as well as a naturally occurring antagonist, angiopoietin-2, both of which act by means of the Tie2 receptor. We now report our attempts to use homology-based cloning approaches to identify new members of the angiopoietin family. These efforts have led to the identification of two new angiopoietins, angiopoietin-3 in mouse and angiopoietin-3 in human; we have also identified several more distantly related sequences that do not seem to be true angiopoietins, in that they do not bind to the Tie receptors. Although angiopoietin-3 and angiopoietin-4 are strikingly more structurally diverged from each other than are the mouse and human versions of angiopoietin-1 and angiopoietin-2, they appear to represent the mouse and human counterparts of the same gene locus, as revealed in our chromosomal localization studies of all of the angiopoietins in mouse and human. The structural divergence of angiopoietin-3 and angiopoietin-4 appears to underlie diverging functions of these counterparts. Angiopoietin-3 and angiopoietin-4 have very different distributions in their respective species, and angiopoietin-3 appears to act as an antagonist, whereas angiopoietin-4 appears to function as an agonist. C1 Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA. NCI, Frederick Canc Res & Dev Ctr, Adv Biosci Labs Basic Res Program, Mammalian Genet Lab, Frederick, MD 21702 USA. RP Yancopoulos, GD (reprint author), Regeneron Pharmaceut Inc, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA. NR 18 TC 310 Z9 338 U1 1 U2 7 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 2 PY 1999 VL 96 IS 5 BP 1904 EP 1909 DI 10.1073/pnas.96.5.1904 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 172ZP UT WOS:000078956600020 PM 10051567 ER PT J AU Buters, JTM Sakai, S Richter, T Pineau, T Alexander, DL Savas, U Doehmer, J Ward, JM Jefcoate, CR Gonzalez, FJ AF Buters, JTM Sakai, S Richter, T Pineau, T Alexander, DL Savas, U Doehmer, J Ward, JM Jefcoate, CR Gonzalez, FJ TI Cytochrome P450 CYP1B1 determines susceptibility to 7,12-dimethylbenz[a]anthracene-induced lymphomas SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID AROMATIC HYDROCARBON METABOLISM; CELL-LINE; MOUSE; GENE; RAT; EXPRESSION; DIOXIN; DISRUPTION; MICROSOMES; SUBFAMILY AB CYP1B1-null mice, created by targeted gene disruption in embryonic stem cells, were born at the expected frequency from heterozygous matings with no observable phenotype, thus establishing that CYP1B1 is not required for mouse development. CYP1B1 was not detectable in cultured embryonic fibroblast (EF) or in different tissues, such as lung, of the CYP1B1-null mouse treated with the aryl hydrocarbon receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin whereas the equivalent wild-type EF cells express basal and substantial inducible CYP1B1 and lung expresses inducible CYP1B1, CYP1A1 is induced to far higher levels than CYP1B1 in liver, kidney, and lung in wild-type mice and is induced to a similar extent in CYP1B1-null mice. 7,12-dimethylbenz[a]anthracene (DMBA) was toxic in wild-type EFs that express CYP1B1 but not CYP1A1. These cells effectively metabolized DMBA, consistent with CYP1B1 involvement in producing the procarcinogenic 3,4-dihydrodiol as a major metabolite, whereas CYP1B1-null EF showed no significant metabolism and were resistant to DMBA-mediated toxicity. When wild-type mice were administered high levels of DMBA intragastrically, 70% developed highly malignant lymphomas whereas only 7.5% of CYP1B1-null mice had lymphomas, Skin hyperplasia and tumors were also more frequent in wild-type mice. These results establish that CYP1B1, located exclusively at extrahepatic sites, mediates the carcinogenicity of DMBA. Surprisingly, CYP1A1, which has a high rate of DMBA metabolism in vitro, is not sufficient for this carcinogenesis, which demonstrates the importance of extrahepatic P450s in determining susceptibility to chemical carcinogens and validates the search for associations between P450 expression and cancer risk in humans. C1 NCI, NIH, Bethesda, MD 20892 USA. Tech Univ Munich, Inst Toxicol & Umwelthyg, D-80636 Munich, Germany. GSF, Natl Res Ctr Environm & Hlth, Inst Pathol, D-85764 Neuherberg, Germany. Tech Univ Munich, Inst Pathol, D-80636 Munich, Germany. Univ Wisconsin, Natl Inst Environm Hlth Sci, Ctr Dev & Mol Toxicol, Madison, WI 53706 USA. Univ Wisconsin, Dept Pharmacol, Madison, WI 53706 USA. RP Gonzalez, FJ (reprint author), NCI, NIH, Bldg 37,Room 3E-24, Bethesda, MD 20892 USA. RI Buters, Jeroen/G-5070-2011 FU NCI NIH HHS [CA 16265, R01 CA016265]; NIEHS NIH HHS [T32 ES007015, T32 ES07015] NR 36 TC 247 Z9 257 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 2 PY 1999 VL 96 IS 5 BP 1977 EP 1982 DI 10.1073/pnas.96.5.1977 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 172ZP UT WOS:000078956600033 PM 10051580 ER PT J AU Ghosh, S Watanabe, RM Hauser, ER Valle, T Magnuson, VL Erdos, MR Langefeld, CD Balow, J Ally, DS Kohtamaki, K Chines, P Birznieks, G Kaleta, HS Musick, A Te, C Tannenbaum, J Eldridge, W Shapiro, S Martin, C Witt, A So, A Chang, J Shurtleff, B Porter, R Kudelko, K Unni, A Segal, L Sharaf, R Blaschak-Harvan, J Eriksson, J Tenkula, T Vidgren, G Ehnholm, C Tuomilehto-Wolf, E Hagopian, W Buchanan, TA Tuomilehto, J Bergman, RN Collins, FS Boehnke, M AF Ghosh, S Watanabe, RM Hauser, ER Valle, T Magnuson, VL Erdos, MR Langefeld, CD Balow, J Ally, DS Kohtamaki, K Chines, P Birznieks, G Kaleta, HS Musick, A Te, C Tannenbaum, J Eldridge, W Shapiro, S Martin, C Witt, A So, A Chang, J Shurtleff, B Porter, R Kudelko, K Unni, A Segal, L Sharaf, R Blaschak-Harvan, J Eriksson, J Tenkula, T Vidgren, G Ehnholm, C Tuomilehto-Wolf, E Hagopian, W Buchanan, TA Tuomilehto, J Bergman, RN Collins, FS Boehnke, M TI Type 2 diabetes: Evidence for linkage on chromosome 20 in 716 Finnish affected sib pairs SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HEPATOCYTE NUCLEAR FACTOR-4-ALPHA; GENETICALLY COMPLEX TRAITS; AFFECTED RELATIVE PAIRS; SUSCEPTIBILITY LOCUS; VARIANCE-COMPONENTS; INSULIN-RESISTANCE; PEDIGREE ANALYSIS; GENE; MELLITUS; STRATEGIES AB We are conducting a genome scan at an average resolution of 10 centimorgans (cM) for type 2 diabetes susceptibility genes in 716 affected sib pairs from 477 Finnish families. To date, our best evidence for linkage is on chromosome 20 with potentially separable peaks located on both the long and short arms. The unweighted multipoint maximum logarithm of odds score (MLS) was 3.08 on 20p (location, (x) over cap = 19.5 cM) under an additive model, whereas the weighted MLS was 2.06 on 20q ((x) over cap = 57 cM, recurrence risk, <(lambda)over cap>(s) = 1.25, P = 0.009). Weighted logarithm of odds scores of 2.00 ((x) over cap = 69.5 cM,P = 0.010) and 1.92 ((x) over cap = 18.5 cM, P = 0.013) were also observed. Ordered subset analyses based on sibships with extreme mean values of diabetes related quantitative traits yielded sets of families who contributed disproportionately to the peaks. Two-hour glucose levels in offspring of diabetic individuals gave a MLS of 2.12 (P = 0.0018) at 9.5 cM. Evidence from this and other studies suggests at least two diabetes-susceptibility genes on chromosome 20. We have also screened the gene for maturity onset diabetes of the young I, hepatic nuclear factor 4-a (HNF-4 alpha) in 64 affected sibships with evidence for high chromosomal sharing at its location on chromosome 20q. We found no evidence that sequence changes in this gene accounted for the linkage results we observed. C1 NIH, Genet & Mol Biol Branch, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. Duke Univ, Med Ctr, Dept Med, Med Genet Sect, Durham, NC 27710 USA. Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Diabet & Genet Epidemiol Unit, Helsinki, Finland. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ So Calif, Dept Med, Los Angeles, CA 90089 USA. Univ So Calif, Sch Med, Dept Physiol & Biophys, Los Angeles, CA 90089 USA. RP Ghosh, S (reprint author), NIH, Genet & Mol Biol Branch, Natl Human Genome Res Inst, Room 1W108,Bldg 9,9000 Rockville Pike, Bethesda, MD 20892 USA. EM sghosh@alw.nih.gov RI Addington, Anjene/C-3460-2008 FU NHGRI NIH HHS [R01 HG000376, R01 HG00376, T32 HG000040, T32 HG00040]; NIDDK NIH HHS [F32 DK009525, F32 DK09525] NR 44 TC 171 Z9 179 U1 0 U2 4 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 2 PY 1999 VL 96 IS 5 BP 2198 EP 2203 DI 10.1073/pnas.96.5.2198 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 172ZP UT WOS:000078956600071 PM 10051618 ER PT J AU Perkins, EL Sterling, JF Hashem, VI Resnick, MA AF Perkins, EL Sterling, JF Hashem, VI Resnick, MA TI Yeast and human genes that affect the Escherichia coli SOS response SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE genome stability ID DNA-LIGASE-IV; SACCHAROMYCES-CEREVISIAE; EXPRESSION SELECTION; MOLECULAR-CLONING; SIMILARITY SEARCH; ANNEXIN-V; PROTEIN; REPAIR; ASSOCIATION; CELLS AB The sequencing of the human genome has led to the identification of many genes whose functions remain to be determined. Because of conservation of genetic function, microbial systems have often been used for identification and characterization of human genes. We have investigated the use of the Escherichia coli SOS induction assay as a screen for yeast and human genes that might play a role in DNA metabolism and/or in genome stability. The SOS system has previously been used to analyze bacterial and viral genes that directly modify DNA. An initial screen of meiotically expressed yeast genes revealed several genes associated with chromosome metabolism (e.g., RAD51 and HHT1 as well as others). The SOS induction assay was then extended to the isolation of human genes. Several known human genes involved in DNA metabolism, such as the Ku70 end-binding protein and DNA ligase IV, were identified, as well as a large number of previously unknown genes. Thus, the SOS assay can be used to identify and characterize human genes, many of which may participate in chromosome metabolism. C1 NIEHS, Chromosome Stabil Grp, Genet Mol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP NIEHS, Chromosome Stabil Grp, Genet Mol Lab, NIH, 111 TW Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA. EM resnick@niehs.nih.gov NR 51 TC 23 Z9 24 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 2 PY 1999 VL 96 IS 5 BP 2204 EP 2209 DI 10.1073/pnas.96.5.2204 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 172ZP UT WOS:000078956600072 PM 10051619 ER PT J AU Suzuki, K Mori, A Ishii, KJ Saito, J Singer, DS Klinman, DM Krause, PR Kohn, LD AF Suzuki, K Mori, A Ishii, KJ Saito, J Singer, DS Klinman, DM Krause, PR Kohn, LD TI Activation of target-tissue immune-recognition molecules by double-stranded polynucleotides SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; PROTEIN-KINASE PKR; I GENE-EXPRESSION; ANTIGEN PRESENTATION; EPITHELIAL-CELLS; CPG MOTIFS; DISEASE; INTERFERON; AUTOIMMUNITY; INDUCTION AB Abnormal expression of major histocompatibility complex (MHC) class I and class II in various tissues is associated with autoimmune disease. Autoimmune responses can be triggered by viral infections or tissue injuries. We show that the ability of a virus or a tissue injury to increase MHC gene expression is duplicated by any fragment of double-stranded (ds) DNA or dsRNA introduced into the cytoplasm of nonimmune cells. Activation is sequence-independent, is induced by ds polynucleotides as small as 25 bp in length, and is not duplicated by single-stranded polynucleotides. In addition to causing abnormal MHC expression, the ds nucleic acids increase the expression of genes necessary for antigen processing and presentation: proteasome proteins (e.g., LMP2), transporters of antigen peptides; invariant chain, HLA-DM, and the costimulatory molecule B7.1. The mechanism is different from and additive to that of gamma-interferon (gamma IFN), i.e., ds polynucleotides increase class I much more than class II, whereas gamma IFN increases class II more than class I. The ds nucleic acids also induce or activate Stat1, Stat3, mitogen-activated protein kinase, NF-kappa B, the class II transactivator, RPX5, and the IFN regulatory factor 1 differently from gamma IFN. CpG residues are not responsible for this effect, and the action of the ds polynucleotides could be shown in a variety of cell types in addition to thyrocytes. We suggest that this phenomenon is a plausible mechanism that might explain how viral infection of tissues or tissue injury triggers autoimmune disease; it is potentially relevant to host immune responses induced during gene therapy. C1 NIDDKD, Metab Dis Branch, Cell Regulat Sect, NIH, Bethesda, MD 20892 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. US FDA, Lab Retroviral Res, Ctr Biol & Evaluat Res, Bethesda, MD 20892 USA. US FDA, Lab DNA Viruses, Div Viral Prod, Ctr Biol & Evaluat Res, Bethesda, MD 20892 USA. RP Krause, PR (reprint author), NIDDKD, Metab Dis Branch, Cell Regulat Sect, NIH, Bethesda, MD 20892 USA. EM lenk@bdg10.niddk.nih.gov RI Ishii, Ken/B-1685-2012 OI Ishii, Ken/0000-0002-6728-3872 NR 39 TC 140 Z9 147 U1 1 U2 7 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 2 PY 1999 VL 96 IS 5 BP 2285 EP 2290 DI 10.1073/pnas.96.5.2285 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 172ZP UT WOS:000078956600086 PM 10051633 ER PT J AU Yanagi, M St Claire, M Emerson, SU Purcell, RH Bukh, J AF Yanagi, M St Claire, M Emerson, SU Purcell, RH Bukh, J TI In vivo analysis of the 3 ' untranslated region of the hepatitis C virus after in vitro mutagenesis of an infectious cDNA clone SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DEPENDENT RNA-POLYMERASE; SECONDARY STRUCTURE; GENOME RNA; IDENTIFICATION; SEQUENCE; 3'-TERMINUS; TRANSFECTION; PROTEIN; BINDING; END AB Large sections of the 3' untranslated region (UTR) of hepatitis C virus (HCV) were deleted from an infectious cDNA clone, and the RNA transcripts from seven deletion mutants were tested sequentially for infectivity in a chimpanzee. Mutants lacking all or part of the 3' terminal conserved region or the poly(U-UC) region were unable to infect the chimpanzee, indicating that both regions are critical for infectivity in vivo. However, the third region, the variable region, was able to tolerate a deletion that destroyed the two putative stem-loop structures within this region. Mutant VR-24 containing a deletion of the proximal 24 nt of the variable region of the 3' UTR was viable in the chimpanzee and seemed to replicate as well as the undeleted parent virus. The chimpanzee became viremic 1 week after inoculation with mutant VR-24, and the HCV genome titer increased over time during the early acute infection. Therefore, the poly(U-UC) region and the conserved region, but not the variable region, of the 3' UTR seem to be critical for in vivo infectivity of HCV. C1 NIAID, Infect Dis Lab, Hepatitis Viruses Sect, NIH, Bethesda, MD 20892 USA. NIAID, Infect Dis Lab, Mol Hepatitis Sect, Infect Dis Lab,NIH, Bethesda, MD 20892 USA. Bioqual Inc, Rockville, MD 20852 USA. RP Bukh, J (reprint author), NIAID, Infect Dis Lab, Hepatitis Viruses Sect, NIH, Bldg 7,Room 201,7 Ctr Dr,MSC 0740, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01-CO-56000]; NIAID NIH HHS [N01-AI-52705, N01-AI-45180, R21 AI052705] NR 35 TC 163 Z9 169 U1 0 U2 4 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 2 PY 1999 VL 96 IS 5 BP 2291 EP 2295 DI 10.1073/pnas.96.5.2291 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 172ZP UT WOS:000078956600087 PM 10051634 ER PT J AU Bukreyev, A Whitehead, SS Bukreyeva, N Murphy, BR Collins, PL AF Bukreyev, A Whitehead, SS Bukreyeva, N Murphy, BR Collins, PL TI Interferon gamma expressed by a recombinant respiratory syncytial virus attenuates virus replication in mice without compromising immunogenicity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE vaccine; immunization; paramyxovirus; cytokine ID IMMUNIZED BALB/C MICE; IMMUNODEFICIENT MICE; MESSENGER-RNA; RSV CHALLENGE; T-CELLS; INFECTION; GENE; GLYCOPROTEINS; CHIMPANZEES; DEPLETION AB Interferon gamma (IFN-gamma) has pleiotropic biological effects, including intrinsic antiviral activity as well as stimulation and regulation of immune responses. An infectious recombinant human respiratory syncytial virus (rRSV/mIFN-gamma) was constructed that encodes murine (m) IFN-gamma as a separate gene inserted into the G-F intergenic region. Cultured cells infected with rRSV/mIFN-gamma secreted 22 mu g mIFN-gamma per 10(6) cells. The replication of rRSV/mIFN-gamma, but not that of a control chimeric rRSV containing the chloramphenicol acetyl transferase (CAT) gene as an additional gene, was 63- and 20-fold lower than that of wild-type (wt) RSV in the upper and lower respiratory tract, respectively, of mice. Thus, the attenuation of rRSV/mIFN-gamma in vivo could be attributed to the activity of mIFN-gamma and not to the presence of the additional gene per se. The mice mere completely resistant to subsequent challenge with wt RSV. Despite its growth restriction, infection of mice with rRSV/mIFN-gamma induced a level of RSV-specific antibodies that, on day 56, was comparable to or greater than that induced by infection with wt RSV. Mice infected with rRSV/mIFN-gamma developed a high level of IFN-gamma mRNA and an increased amount of interleukin 12 p40 mRNA in their lungs, whereas other cytokine mRNAs tested were unchanged compared with those induced by wt RSV. Because attenuation of RSV typically is accompanied by a reduction in immunogenicity, expression of IFN-gamma by an rRSV represents a method of attenuation in which immunogenicity can be maintained rather than be reduced. C1 NIAID, Infect Dis Lab, Bethesda, MD 20892 USA. RP Collins, PL (reprint author), NIAID, Infect Dis Lab, Bldg 7,Room 100,7 Ctr Dr, Bethesda, MD 20892 USA. NR 28 TC 48 Z9 50 U1 1 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 2 PY 1999 VL 96 IS 5 BP 2367 EP 2372 DI 10.1073/pnas.96.5.2367 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 172ZP UT WOS:000078956600101 PM 10051648 ER PT J AU Chackerian, B Lowy, DR Schiller, JT AF Chackerian, B Lowy, DR Schiller, JT TI Induction of autoantibodies to mouse CCR5 with recombinant papillomavirus particles SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CHEMOKINE RECEPTOR; NEUTRALIZING EPITOPE; HIV-1 INFECTION; FUSION; RESIDUES; CLONING; ENTRY; INDIVIDUALS; SPECIFICITY AB The vertebrate immune system has evolved to respond vigorously to microbial infection but to ignore self-antigens. Evidence has emerged that B cell responses to viruses are initiated by immune recognition of ordered arrays of antigen on the viral surface. To test whether autoantibodies against a self-antigen can be induced by placing it in a context that mimics the ordered surface of a viral particle, a peptide representing an extracellular loop of the mouse chemokine receptor CCRS was incorporated into an immunodominant site of the bovine papillomavirus virus L1 coat protein, which self-assembles into virus-like particles. Mice inoculated with chimeric L1-CCR5 particles generated autoantibodies that bound to native mouse CCR5, inhibited binding of its ligand RANTES, and blocked HIV-1 infection of an indicator cell line expressing a human-mouse CCRS chimera. These results suggest a general method for inducing autoantibodies against self-antigens, with diverse potential basic research and clinical applications. C1 NIH, Cellular Oncol Lab, Bethesda, MD 20892 USA. RP Schiller, JT (reprint author), NIH, Cellular Oncol Lab, Bldg 36,Room 1D-32, Bethesda, MD 20892 USA. EM schillej@dc37a.nci.nih.gov NR 37 TC 77 Z9 80 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 2 PY 1999 VL 96 IS 5 BP 2373 EP 2378 DI 10.1073/pnas.96.5.2373 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 172ZP UT WOS:000078956600102 PM 10051649 ER PT J AU Hersh, D Monack, DM Smith, MR Ghori, N Falkow, S Zychlinsky, A AF Hersh, D Monack, DM Smith, MR Ghori, N Falkow, S Zychlinsky, A TI The Salmonella invasin SipB induces macrophage apoptosis by binding to caspase-1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SHIGELLA-FLEXNERI; EPITHELIAL-CELLS; INFECTED MACROPHAGES; PROTEIN SECRETION; EUKARYOTIC CELLS; IN-VIVO; TYPHIMURIUM; ENTRY; IPAB; IDENTIFICATION AB Recently, Salmonella spp. were shown to induce apoptosis in infected macrophages. The mechanism responsible for this process is unknown. In this report, we establish that the Inv-Spa type III secretion apparatus target invasin SipB is necessary and sufficient for the induction of apoptosis. Purified SipB microinjected into macrophages led to cell death. Binding studies show that SipB associates with the proapoptotic protease caspase-1. This interaction results in the activation of caspase-1, as seen in its proteolytic maturation and the processing of its substrate interleukin-1 beta. Caspase-1 activity is essential for the cytotoxicity. Functional inhibition of caspase-1 activity by acetyl-Tyr-Val-Ala-Asp-chloromethyl ketone blocks macrophage cytotoxicity, and macrophages lacking caspase-1 are not susceptible to Salmonella-induced apoptosis. Taken together, the data demonstrate that SipB functions as an analog of the Shigella invasin IpaB. C1 NYU, Sch Med, Dept Microbiol, Skirball Inst, New York, NY 10016 USA. NYU, Sch Med, Kaplan Canc Ctr, New York, NY 10016 USA. Stanford Univ, Sch Med, Dept Immunol & Microbiol, Stanford, CA 94305 USA. NCI, Intramural Res Support Program, Sci Applicat Int Corp, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Zychlinsky, A (reprint author), NYU, Sch Med, Dept Microbiol, Skirball Inst, 540 1st Ave, New York, NY 10016 USA. FU NIAID NIH HHS [R01 AI26195, R01 AI026195, AI42780] NR 36 TC 449 Z9 466 U1 1 U2 14 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 2 PY 1999 VL 96 IS 5 BP 2396 EP 2401 DI 10.1073/pnas.96.5.2396 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 172ZP UT WOS:000078956600106 PM 10051653 ER PT J AU Hyman, SE AF Hyman, SE TI Protecting patients, preserving progress: Ethics in mental health illness research SO ACADEMIC MEDICINE LA English DT Editorial Material C1 NIMH, Bethesda, MD 20892 USA. RP Hyman, SE (reprint author), NIMH, Bethesda, MD 20892 USA. NR 0 TC 16 Z9 16 U1 1 U2 1 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD MAR PY 1999 VL 74 IS 3 BP 258 EP 259 DI 10.1097/00001888-199903000-00015 PG 2 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 176PY UT WOS:000079161800023 PM 10099647 ER PT J AU Ding, L Zhang, YH Deacon, AM Ealick, SE Ni, YS Sun, P Coleman, WG AF Ding, L Zhang, YH Deacon, AM Ealick, SE Ni, YS Sun, P Coleman, WG TI Crystallization and preliminary x-ray diffraction studies of the lipopolysaccharide core biosynthetic enzyme ADP-L-glycero-D-mannoheptose 6-epimerase from Escherichia coli K-12 SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article; Proceedings Paper CT Annual Meeting American-Society-for-Biochemistry-and-Molecular-Biology CY AUG 24-29, 1997 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Biochem & Molec Biol ID RFAD GENE; BINDING AB ADP-L-glycero-D-mannoheptose 6-epimerase is a 240 kDa NAD-dependent nucleotide diphosphosugar epimerase from Escherichia coli K12 which catalyzes the interconversion of ADP-D-glycero-D-mannoheptose and ADP-L-glycero-D-mannoheptose. ADP-L-glycero-D-mannoheptose is a required intermediate for lipopolysaccharide inner-core and outer-membrane biosynthesis in several genera of pathogenic and non-pathogenic Gram-negative bacteria. ADP-L-glycero-D-mannoheptose 6-epimerase was overexpressed in E. coli and purified to apparent homogeneity by chromatographic methods. Three crystal forms of the epimerase were obtained by a hanging-drop vapor-diffusion method. A native data set for crystal form III was collected in-house on a Rigaku R-AXIS-IIC image plate at 3.0 Angstrom resolution. The form III crystals belong to the monoclinic space group P2(1). The unit-cell parameters are a = 98.94, b = 110.53, c = 180.68 Angstrom and beta = 90.94 degrees. Our recent results show that these crystals diffract to 2.0 Angstrom resolution at the Cornell High Energy Synchrotron Source. The crystal probably contains six 40 kDa monomers per asymmetric unit, with a corresponding volume per protein mass (V-m) of 4.11 Angstrom(3) Da(-1) and a solvent fraction of 70%. C1 NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. NIAID, Struct Biol Sect, Off Sci Director, NIH, Bethesda, MD 20892 USA. Cornell Univ, Dept Chem & Chem Engn, Ithaca, NY 14853 USA. RP Ding, L (reprint author), NIDDK, Lab Biochem & Genet, NIH, Bldg 8,Room 2A-02, Bethesda, MD 20892 USA. FU NCRR NIH HHS [RR-01646] NR 13 TC 3 Z9 4 U1 0 U2 0 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 PY 1999 VL 55 BP 685 EP 688 DI 10.1107/S0907444998014723 PN 3 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 177MW UT WOS:000079214700016 PM 10089470 ER PT J AU Zlotnick, A Palmer, I Kaufman, JD Stahl, SJ Steven, AC Wingfield, PT AF Zlotnick, A Palmer, I Kaufman, JD Stahl, SJ Steven, AC Wingfield, PT TI Separation and crystallization of T = 3 and T = 4 icosahedral complexes of the hepatitis B virus core protein SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID ESCHERICHIA-COLI; ELECTRON CRYOMICROSCOPY; CAPSID PROTEIN; C-TERMINUS; RNA; ANTIGEN; REPLICATION; MICROSCOPY; GENOME AB The icosahedral nucleocapsid of human hepatitis B virus is a homopolymer of the dimeric capsid protein also known as hepatitis B core antigen or HBcAg. Purified capsid protein obtained from an Escherichia coli expression system was reassembled into a mixture of T = 3 and T = 4 icosahedral particles consisting of 90 and 120 dimers, respectively. The two types of capsid were separated on a preparative scale by centrifugation through a sucrose gradient. In addition to this heterogeneity, the capsid protein has three cysteines, one of which has a great propensity for forming disulfide bonds between the two subunits, forming a dimer. To eliminate heterogeneity arising from oxidation, alanines were substituted for the cysteines. T = 3 and T = 4 capsids crystallized under similar conditions. Crystals of T = 3 capsids diffracted to similar to 8 Angstrom resolution; crystals of T = 4 capsids diffracted to 4 Angstrom resolution. C1 NIAMSD, Prot Express Lab, NIH, Bethesda, MD 20892 USA. NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. RP Wingfield, PT (reprint author), NIAMSD, Prot Express Lab, NIH, Bethesda, MD 20892 USA. NR 23 TC 21 Z9 21 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 PY 1999 VL 55 BP 717 EP 720 DI 10.1107/S090744499801350X PN 3 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 177MW UT WOS:000079214700027 PM 10089479 ER PT J AU Estrada, R Galarraga, J Orozco, G Nodarse, A Auburger, G AF Estrada, R Galarraga, J Orozco, G Nodarse, A Auburger, G TI Spinocerebellar ataxia 2 (SCA2): morphometric analyses in 11 autopsies SO ACTA NEUROPATHOLOGICA LA English DT Article DE Cuba; ataxia; cerebellum; polyglutamine; autopsy ID OLIVOPONTOCEREBELLAR ATROPHY; FAMILIES; DEGENERATION; PHENOTYPE; FEATURES; REPEAT; TYPE-2; LOCUS AB Eleven autopsies of patients from the large founder-population with dominantly inherited spinocerebellar ataxia 2 (SCA2) in Holguin, Cuba, were analyzed by the same observers, including quantitative microscopic evaluation. As expected in this disease with highly unstable polyglutamine expansions, considerable variability was observed, which correlated to age at onset and to progression of clinical symptoms. The degeneration of the olivopontocerebellar regions as in classical olivopontocerebellar atrophy occurred early and severely in SCA2. The neuropathological progression soon included neuronal loss in the substantia nigra, striatum, pallidum and later even the neocortex, while the dentate nucleus was consistently spared. This widespread degeneration pattern goes clearly beyond purely cerebellar degenerations such as SCA5 and 6 and beyond spinocerebellar degenerations such as SCA1, 3, 7, also involves regions known to degenerate in Huntington's disease, and is quite similar to the degeneration pattern in sporadic patients with multisystem atrophy. C1 NIH, Natl Human Genome Res Inst, Lab 49 3A18, Bethesda, MD 20892 USA. Inst Neurol & Neurosurg, Havana, Cuba. Lenin Hosp, Holguin, Cuba. Univ Hosp, Dusseldorf, Germany. RP Auburger, G (reprint author), NIH, Natl Human Genome Res Inst, Lab 49 3A18, 49 Convent Dr,MSC 4476, Bethesda, MD 20892 USA. NR 25 TC 112 Z9 115 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD MAR PY 1999 VL 97 IS 3 BP 306 EP 310 PG 5 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 168QG UT WOS:000078703300013 PM 10090679 ER PT J AU Simons-Morton, B Haynie, DL Crump, AD Saylor, KE Eitel, P Yu, K AF Simons-Morton, B Haynie, DL Crump, AD Saylor, KE Eitel, P Yu, K TI Expectancies and other psychosocial factors associated with alcohol use among early adolescent boys and girls SO ADDICTIVE BEHAVIORS LA English DT Article ID PREVENTION; DRINKING; SMOKING; RISK; ABUSE; ONSET AB Early experimentation with drinking increases the lifetime risk for substance abuse and other serious health and social problems. We studied factors associated with early alcohol experimentation by surveying 4,263 sixth- to eighth-grade students (67.1% White, 23.5% Black, 7.2% other races combined; 2.2% missing data) from seven schools in one suburban school district. The prevalence of drinking in the last 30 days was 12.1% for boys and 13.1% for girls (12.6% overall); 6.6% among sixth graders, 11.1% among seventh graders, and 19.5% among eighth graders. In multiple logistic regression analyses, controlling for grade, positive alcohol expectancies, perceived prevalence, and deviance acceptance were associated positively, self-control negatively, with drinking for both boys and girls. Among boys, grade point average was negatively associated with drinking. Among girls, propensity for risk-taking and problem-behaving friends were positively associated and high parental expectations were negatively associated with drinking. Alcohol use in our sample of early adolescent boys and girls was better explained by modifiable psychosocial factors such as alcohol expectancies, perceived prevalence, and self-control than by grade. (C) 1999 Elsevier Science Ltd. C1 Univ Maryland, College Pk, MD 20742 USA. NIH, Bethesda, MD 20892 USA. RP Simons-Morton, B (reprint author), NICHD, Prevent Res Branch, DESPR, Bldg 6100,Room 7B05,9000 Rockville Pike, Bethesda, MD 20892 USA. EM MORTONB@exchange.NIH.GOV OI Simons-Morton, Bruce/0000-0003-1099-6617; Haynie, Denise/0000-0002-8270-6079 NR 20 TC 42 Z9 42 U1 13 U2 14 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD MAR-APR PY 1999 VL 24 IS 2 BP 229 EP 238 DI 10.1016/S0306-4603(98)00095-1 PG 10 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 178XL UT WOS:000079294400007 PM 10336104 ER PT J AU Hanna, EZ Grant, BF AF Hanna, EZ Grant, BF TI Parallels to early onset alcohol use in the relationship of early onset smoking with drug use and DSM-IV drug and depressive disorders: Findings from the national longitudinal epidemiologic survey SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE alcohol; drugs; use; abuse; dependence ID MAJOR DEPRESSION; YOUNG-ADULTS; PSYCHIATRIC-DISORDERS; NICOTINE DEPENDENCE; GENERAL-POPULATION; UNITED-STATES; SUBSTANCE USE; TOBACCO; PROGRESSION; COMORBIDITY AB This paper endeavored to determine (1) if early onset of regular tobacco use is as predictive of drug use and depressive disorders as it is of alcohol use disorders; and (2) a a biological commonality, as measured by a family history of alcoholism and both early onset and severity of disease, among all three disorders can be evidenced in a large nationally representative sample. Prevalences of lifetime drug use, drug abuse end dependence, and major depressive disorders, as well as indices of their severity, were compared among smoking groups defined by age at onset of regular tobacco use and among nonsmokers. Linear logistic regression analyses, controlling for important covariates, including a family history positive for alcoholism, were conducted to assess the relationship between age at smoking onset and drug use, abuse and dependence, as well as depressive disorders. Both objectives were met. Moreover, results suggest that smoking may play an equally, if not even more, insidious role than drinking in the use and development of dependence on illicit substances and depression. C1 NIAAA, Rockville, MD USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Cambridge, England. RP Hanna, EZ (reprint author), NIAAA, DBE, Willco 514,6000 Execut Blvd,MSC7003, Bethesda, MD 20892 USA. EM ehanna@willco.niaaa.nih.gov NR 55 TC 65 Z9 66 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAR PY 1999 VL 23 IS 3 BP 513 EP 522 DI 10.1097/00000374-199903000-00020 PG 10 WC Substance Abuse SC Substance Abuse GA 178MN UT WOS:000079269900021 PM 10195827 ER PT J AU Cohen, SG AF Cohen, SG TI Anaphylaxis and poetry: Carl A. Dragstedt, MD, Ph.D. (1895-1983) SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Biographical-Item C1 NIAID, Bethesda, MD 20892 USA. RP Cohen, SG (reprint author), NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1088-5412 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD MAR-APR PY 1999 VL 20 IS 2 BP 135 EP 138 DI 10.2500/108854199778612554 PG 4 WC Allergy SC Allergy GA 213EX UT WOS:000081260700009 PM 10209692 ER PT J AU Stewart, P Fears, T Nicholson, HF Kross, BC Ogilvie, LK Zahm, SH Ward, MH Blair, A AF Stewart, P Fears, T Nicholson, HF Kross, BC Ogilvie, LK Zahm, SH Ward, MH Blair, A TI Exposure received from application of animal insecticides SO AMERICAN INDUSTRIAL HYGIENE ASSOCIATION JOURNAL LA English DT Article DE farm workers; livestock; insecticide application ID AGRICULTURAL RISK-FACTORS; NON-HODGKINS-LYMPHOMA; CASE-REFERENT; PESTICIDES; MINNESOTA; FARMERS; IOWA; MEN AB Part of an investigation of data collection methods in epidemiologic studies of farmers evaluated exposures received by farmers from the application of insecticides to animals. Twenty farmers were monitored during a normal application using a fluorescent dye surrogate for the active ingredient (Al). Two exposure measures were estimated, Al concentration and the time-weighted average for the application period (TWA(a)). Four application methods were used: high- (n=5) and low-pressure (n=3) spraying, backpack (n=2) and pour-on (n=10). The two farmers using a backpack sprayer had nondetectable levels of dye. Only two of the farmers using the pour-on method had detectable dye levels, but these levels were high. All of the low- and high-pressure sprayers had detectable amounts of dye, Multiple layers of clothing, gloves, and boots (n=10) were associated with a low mean Al concentration for the exposed farmers (18 mu g) and more than two-thirds of the farmers wearing this amount of clothing had nondetectable exposures. In contrast, clothing providing little or no protection was associated with a significantly higher (p<0.01) average Al concentration (4420 mu g), and less than a third of the farmers with this degree of protection had nondetectable exposures. Poor work practices (leaking equipment, contact with wet animals or fences, and back splash) were associated with statistically higher exposure levels (p<0.01) than the absence of such practices. There was a moderate statistically significant association between Al concentration and TWA(a) with total volume of the Al/dye/water mixture using the Spearman coefficient. Time was significantly inversely proportional to the two exposure measures. The association between the two exposure measures and Al volume was not significant. C1 NCI, Div Canc Etiol & Genet, Bethesda, MD 20892 USA. Univ Iowa, Inst Agr Med & Occupat Hlth, Iowa City, IA USA. RP Stewart, P (reprint author), NCI, Div Canc Etiol & Genet, EPS Room 8102,6120 Execut Blvd,MSC 7240, Bethesda, MD 20892 USA. NR 23 TC 5 Z9 5 U1 0 U2 1 PU AMER INDUSTRIAL HYGIENE ASSOC PI FAIRFAX PA 2700 PROSPERITY AVE #250, FAIRFAX, VA 22031-4307 USA SN 0002-8894 J9 AM IND HYG ASSOC J JI Am. Ind. Hyg. Assoc. J. PD MAR-APR PY 1999 VL 60 IS 2 BP 208 EP 212 DI 10.1080/00028899908984437 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 187QE UT WOS:000079797600009 PM 10222571 ER PT J AU Yanovski, SZ Bain, RP Williamson, DF AF Yanovski, SZ Bain, RP Williamson, DF TI Report of a National Institutes of Health-Centers for Disease Control and Prevention workshop on the feasibility of conducting a randomized clinical trial to estimate the long-term health effects of intentional weight loss in obese persons SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE obesity; randomized clinical trials; workshop; pharmacotherapy; behavior therapy; weight loss ID SEVERE CALORIC RESTRICTION; ALL-CAUSE MORTALITY; BODY-WEIGHT; INTERVENTION; MODERATE AB A workshop was convened in 1997 by the National institutes of Health and the Centers for Disease Control and Prevention to consider the need for and feasibility of conducting a randomized clinical trial to estimate the long-tenn health effects of intentional weight loss in obese persons. Although the benefits of weight loss in obese individuals may seem obvious, little information is available showing that intentional weight loss improves long-term health outcomes. Observational studies may be unable to provide convincing answers about the magnitude and direction of the health effects of intentional weight loss, Workshop participants agreed that a well-designed randomized clinical trial could answer several questions necessary for developing a rational clinical and public health policy for treating obesity. Such information will ultimately provide needed guidance on the risks and benefits of weight loss to health care providers and payers, as well as to millions of obese Americans. C1 NIDDKD, Div Digest Dis & Nutr, Bethesda, MD 20892 USA. George Washington Univ, Ctr Biostat, Rockville, MD USA. Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA USA. RP Yanovski, SZ (reprint author), Weight Control Informat Network, 1 Win Way, Bethesda, MD 20892 USA. EM sy29f@nih.gov NR 36 TC 30 Z9 30 U1 2 U2 3 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD MAR PY 1999 VL 69 IS 3 BP 366 EP 372 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 170XQ UT WOS:000078832700005 PM 10075318 ER PT J AU Stolzenberg-Solomon, RZ Miller, ER Maguire, MG Selhub, J Appel, LJ AF Stolzenberg-Solomon, RZ Miller, ER Maguire, MG Selhub, J Appel, LJ TI Association of dietary protein intake and coffee consumption with serum homocysteine concentrations in an older population SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE homocysteine; tHcy; diet; protein; coffee; folic acid; vitamin B-12; creatinine; vitamin supplements; observational study; elderly ID CORONARY-ARTERY DISEASE; NEURAL-TUBE DEFECTS; PLASMA TOTAL HOMOCYSTEINE; GENETIC RISK FACTOR; METHYLENETETRAHYDROFOLATE REDUCTASE; VASCULAR-DISEASE; HORDALAND HOMOCYSTEINE; METHIONINE METABOLISM; CARDIOVASCULAR-DISEASE; ELDERLY POPULATION AB Background: Elevated blood concentrations of total homocysteine (tHcy) have been implicated in the pathogenesis of atherosclerotic cardiovascular disease. Previous studies identified suboptimal nutritional status and dietary intake of folate, vitamin B-6, and vitamin B-12 as determinants of elevated tHcy. Objective: We identified other nutritional factors associated with tHcy in 260 retired schoolteachers in the Baltimore metropolitan area. Design: We performed observational analyses of baseline and 2-4-mo follow-up data collected in a study designed to test the feasibility of conducting a large-scale clinical trial of vitamin supplements by mail. The study population consisted of 151 women and 109 men with a median age of 63 y. At baseline, each participant completed a food-frequency questionnaire. At follow-up, fasting serum tHcy was measured. Results: In multivariable linear regression and generalized linear models, then was an independent. inverse dose-response relation between dietary protein and In tHcy (P = 0.002) and a positive, significant dose-response relation between coffee consumption and In tHcy (P for trend = 0.01). Other significant predictors of In tHcy were creatinine (positive; P = 0.0001) and prestudy use of supplemental B vitamins (inverse; P = 0.03), In stratified analyses restricted to persons receiving standard multivitamin therapy, the association of In tHcy with dietary protein and coffee persisted. Conclusions: These results support the hypothesis that increased protein intake and decreased coffee consumption may reduce tHcy and potentially prevent atherosclerotic cardiovascular disease and other disease outcomes. C1 NCI, Canc Prevent Studies Branch, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Johns Hopkins Med Inst, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21205 USA. Univ Penn, Dept Ophthalmol, Philadelphia, PA 19104 USA. Tufts Univ, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. RP Stolzenberg-Solomon, RZ (reprint author), NCI, Canc Prevent Studies Branch, 6006 Execut Blvd,Suite 321, Bethesda, MD 20892 USA. FU NCRR NIH HHS [RR00722]; NHLBI NIH HHS [HL02635] NR 59 TC 85 Z9 85 U1 0 U2 1 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD MAR PY 1999 VL 69 IS 3 BP 467 EP 475 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 170XQ UT WOS:000078832700019 PM 10075332 ER PT J AU Christen, WG Ajani, UA Glynn, RJ Manson, JAE Schaumberg, DA Chew, EC Buring, JE Hennekens, CH AF Christen, WG Ajani, UA Glynn, RJ Manson, JAE Schaumberg, DA Chew, EC Buring, JE Hennekens, CH TI Prospective cohort study of antioxidant vitamin supplement use and the risk of age-related maculopathy SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE antioxidants; maculopathy; age-related; prospective studies; vitamins ID RETINAL-PIGMENT EPITHELIUM; SENILE MACULAR DEGENERATION; BEAVER DAM EYE; LIPID-PEROXIDATION; CIGARETTE-SMOKING; OXIDATIVE DAMAGE; BETA-CAROTENE; E CONSUMPTION; DISEASE; PLASMA AB In a prospective cohort study, the authors examined whether self-selection for antioxidant vitamin supplement use affects the incidence of age-related maculopathy. The study population consisted of 21,120 US male physician participants in the Physicians' Health Study I who did not have a diagnosis of age-related maculopathy at baseline (1982). During an average of 12.5 person-years of follow-up, a total of 279 incident cases of age-related maculopathy with vision loss to 20/30 or worse were confirmed by medical record review. In multivariate analysis, as compared with nonusers of supplements, persons who used vitamin E supplements had a possible but nonsignificant 13% reduced risk of age-related maculopathy (relative risk = 0.87, 95 percent confidence interval (CI) 0.53-1.43), while users of multivitamins had a possible but nonsignificant 10% reduced risk (relative risk = 0.90, 95% CI 0.68-1.19), Users of vitamin C supplements had a relative risk of 1.03 (95% CI 0.71-1.50). These observational data suggest that among persons who self-select for supplemental use of antioxidant vitamin C or E or multivitamins, large reductions in the risk of age-related maculopathy are unlikely. Randomized trial data are accumulating to enable reliable detection of the existence of more plausible small-to-moderate benefits of these agents alone and in combination on age-related maculopathy. C1 Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. NEI, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Dept Ambulatory Care & Prevent, Boston, MA 02215 USA. RP Christen, WG (reprint author), Brigham & Womens Hosp, Dept Med, Div Prevent Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. FU Intramural NIH HHS [Z99 EY999999]; NCI NIH HHS [CA40360]; NEI NIH HHS [EY06633]; NHLBI NIH HHS [HL34595] NR 58 TC 41 Z9 42 U1 0 U2 0 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAR 1 PY 1999 VL 149 IS 5 BP 476 EP 484 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 171BU UT WOS:000078843200011 PM 10067908 ER PT J AU Tavormina, PL Bellus, GA Webster, MK Bamshad, MJ Fraley, AE McIntosh, I Szabo, J Jiang, W Jabs, EW Wilcox, WR Wasmuth, JJ Donoghue, DJ Thompson, LM Francomano, CA AF Tavormina, PL Bellus, GA Webster, MK Bamshad, MJ Fraley, AE McIntosh, I Szabo, J Jiang, W Jabs, EW Wilcox, WR Wasmuth, JJ Donoghue, DJ Thompson, LM Francomano, CA TI A novel skeletal dysplasia with developmental delay and acanthosis nigricans is caused by a Lys650Met mutation in the fibroblast growth factor receptor 3 gene SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID TYROSINE KINASE DOMAIN; THANATOPHORIC DYSPLASIA; TRANSMEMBRANE DOMAIN; FGFR3 MUTATIONS; POINT MUTATION; ACHONDROPLASIA; ACTIVATION; HYPOCHONDROPLASIA; DWARFISM; SUBSTITUTION AB We have identified a novel fibroblast growth factor receptor 3 (FGFR3) missense mutation in four unrelated individuals with skeletal dysplasia that approaches the severity observed in thanatophoric dysplasia type I (TD1), However, three of the four individuals developed extensive areas of acanthosis nigricans beginning in early childhood, suffer from severe neurological impairments, and have survived past infancy without prolonged life-support measures. The FGFR3 mutation (A1949T: Lys650Met) occurs at the nucleotide adjacent to the TD type II (TD2) mutation (A1948G: Lys650Glu) and results in a different amino acid substitution at a highly conserved codon in the kinase domain activation loop. Transient transfection studies with FGFR3 mutant constructs show that the Lys650Met mutation causes a dramatic increase in constitutive receptor kinase activity, approximately three times greater than that observed with the Lys650Glu mutation, We refer to the phenotype caused by the Lys650Met mutation as "severe achondroplasia with developmental delay and acanthosis nigricans" (SADDAN) because it differs significantly from the phenotypes of other known FGFR3 mutations. C1 Natl Human Genome Res Inst, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Univ Calif Irvine, Dept Biol Chem, Irvine, CA 92717 USA. Univ Calif San Diego, Dept Chem & Biochem, San Diego, CA 92103 USA. Univ Calif San Diego, Ctr Mol Genet, San Diego, CA 92103 USA. Univ Utah, Hlth Sci Ctr, Dept Pediat, Salt Lake City, UT USA. Johns Hopkins Univ, Sch Med, Ctr Med Genet, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Ctr Craniofacial Dev, Baltimore, MD 21205 USA. Burns & Allen Cedars Sinai Res Inst, Ahmanson Dept Pediat, Steven Spielberg Pediat Res Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Pediat, Los Angeles, CA 90024 USA. RP Francomano, CA (reprint author), Natl Human Genome Res Inst, Med Genet Branch, NIH, Rm 10C-101,MSC 1852,10 Ctr Dr, Bethesda, MD 20892 USA. OI Jiang, Wen/0000-0002-3283-1111; Jabs, Ethylin/0000-0001-8983-5466 FU NCI NIH HHS [CA40573]; NIDCR NIH HHS [DE11441, DE12581] NR 39 TC 93 Z9 98 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAR PY 1999 VL 64 IS 3 BP 722 EP 731 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 177HN UT WOS:000079204700009 PM 10053006 ER PT J AU Karafet, TM Zegura, SL Posukh, O Osipova, L Bergen, A Long, J Goldman, D Klitz, W Harihara, S de Knijff, P Wiebe, V Griffiths, RC Templeton, AR Hammer, MF AF Karafet, TM Zegura, SL Posukh, O Osipova, L Bergen, A Long, J Goldman, D Klitz, W Harihara, S de Knijff, P Wiebe, V Griffiths, RC Templeton, AR Hammer, MF TI Ancestral Asian source(s) of New World Y-chromosome founder haplotypes SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID MITOCHONDRIAL-DNA ANALYSIS; NATIVE-AMERICAN; MTDNA VARIATION; POPULATIONS; ORIGIN; NORTH; POLYMORPHISMS; AFFINITIES; EVOLUTION; LINEAGES AB Haplotypes constructed from Y-chromosome markers were used to trace the origins of Native Americans. Our sample consisted of 2,198 males from 60 global populations, including 19 Native American and 15 indigenous North Asian groups. A set of 12 biallelic polymorphisms gave rise to 14 unique Y-chromosome haplotypes that were unevenly distributed among the populations. Combining multiallelic variation at two Y-linked microsatellites (DYS19 and DXYS156Y) with the unique haplotypes results in a total of 95 combination haplotypes. Contra previous findings based on Y- chromosome data, our new results suggest the possibility of more than one Native American paternal founder haplotype. We postulate that, of the nine unique haplotypes found in Native Americans, haplotypes 1C and 1F are the best candidates for major New World founder haplotypes, whereas haplotypes 1B, 1I, and 1U may either be founder haplotypes and/or have arrived in the New World via recent admixture. Two of the other four haplotypes (YAP(+) haplotypes 4 and 5) are probably present because of post-Columbian admixture, whereas haplotype 1G may have originated in the New World, and the Old World source of the final New World haplotype (1D) remains unresolved. The contrasting distribution patterns of the two major candidate founder haplotypes in Asia and the New World, as well as the results of a nested cladistic analysis, suggest the possibility of more than one paternal migration from the general region of Lake Baikal to the Americas. C1 Univ Arizona, Lab Mol Systemat & Evoulut, Tucson, AZ 85721 USA. Univ Arizona, Dept Anthropol, Tucson, AZ 85721 USA. Russian Acad Sci, Inst Cytol & Genet, Lab Human Mol & Evolut Genet, Novosibirsk 630090, Russia. NIAAA, Sect Populat Genet & Linkage, NIH, Bethesda, MD USA. Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA. Univ Tokyo, Dept Biol Sci, Tokyo, Japan. Leiden Univ, Dept Human Genet, NL-2300 RA Leiden, Netherlands. Washington Univ, Dept Biol, St Louis, MO 63130 USA. Monash Univ, Dept Math, Clayton, Vic 3168, Australia. RP Hammer, MF (reprint author), Univ Arizona, Dept Ecol & Evolut Biol, Biosci W, Tucson, AZ 85721 USA. RI Templeton, Alan/F-5963-2011; Osipova, Ludmila/O-6480-2014; Goldman, David/F-9772-2010; Posukh, Olga/Q-6065-2016; OI Osipova, Ludmila/0000-0001-7602-1156; Goldman, David/0000-0002-1724-5405; Posukh, Olga/0000-0003-1352-3591; Bergen, Andrew/0000-0002-1237-7644 NR 49 TC 210 Z9 217 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAR PY 1999 VL 64 IS 3 BP 817 EP 831 DI 10.1086/302282 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 177HN UT WOS:000079204700020 PM 10053017 ER PT J AU Moysich, KB Mendola, P Schisterman, EF Freudenheim, JL Ambrosone, CB Vena, JE Shields, PG Kostyniak, P Greizerstein, H Graham, S Marshall, JR AF Moysich, KB Mendola, P Schisterman, EF Freudenheim, JL Ambrosone, CB Vena, JE Shields, PG Kostyniak, P Greizerstein, H Graham, S Marshall, JR TI An evaluation of proposed frameworks for grouping polychlorinated biphenyl (PCB) congener data into meaningful analytic units SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE polychlorinated biphenyls; epidemiologic studies; data reduction; methodological issues ID RISK ASSESSMENT; DIOXINS; TOXICITY; CHILDREN; HEALTH AB Background Polychlorinated biphenyls (PCBs) have been associated with a variety of health outcomes. Enhanced laboratory techniques can provide a relatively large number of individual PCB congeners for investigation. However to dare there are no established frameworks for grouping a large number of PCB congeners into meaningful analytic units. Methods In a case-control study of serum PCB levels on breast cancer risk, measured levels of 56 PCB congener peaks were available for analysis. We considered several approaches for grouping these compounds based on 1) chlorination, 2) factor analysis, 3) enzyme induction, 4) enzyme induction and occurrence, and 5) enzyme induction, occurrence, and other toxicological aspects. The utility of a framework was based on the mechanism of biologic actions within each framework, lack of collinearity among congener groups, and frequency of detection of PCB congener groups in measured serum levels of 192 healthy postmenopausal women. Results Most participants had detectable levels for the proposed PCB congeners groups, using degree of chlorination as a grouping framework. In addition, the previously proposed grouping approach based on enzyme induction, occurrence, and other toxicological aspects was an applicable alternative to the crude approach of grouping by degree of chlorination. Grouping these congeners with respect to P450 enzyme induction activity, and the previously proposed framework based on enzyme induction and occurrence, did not fit these data as well, because only a small proportion of participants had detectable levels for the congener groups with the greatest toxicological potential. Statistical grouping did not result in an interpretable and meaningful clustering of these exposures. Conclusions In these data, grouping with respect to degree of chlorination and the previously proposed framework based on enzyme induction, occurrence, and other toxicological aspects were the most useful approaches to reducing a large number of PCB congeners into meaningful analytic units. Factors affecting the utility of the proposed grouping frameworks are discussed. (C) 1999 Wiley-Liss, Inc. C1 Roswell Pk Canc Inst, Dept Canc Prevent Epidemiol & Biostat, Buffalo, NY 14263 USA. SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. NCI, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. SUNY Buffalo, Toxicol Res Ctr, Buffalo, NY 14260 USA. Arizona Canc Ctr, Tucson, AZ 85724 USA. RP Moysich, KB (reprint author), Roswell Pk Canc Inst, Dept Canc Prevent Epidemiol & Biostat, Elm & Carlton St, Buffalo, NY 14263 USA. RI Shields, Peter/I-1644-2012; OI Mendola, Pauline/0000-0001-5330-2844; Schisterman, Enrique/0000-0003-3757-641X FU NCI NIH HHS [CA 11535, CA/ES 62995] NR 25 TC 35 Z9 36 U1 0 U2 6 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD MAR PY 1999 VL 35 IS 3 BP 223 EP 231 DI 10.1002/(SICI)1097-0274(199903)35:3<223::AID-AJIM2>3.0.CO;2-L PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 163KW UT WOS:000078405500002 PM 9987555 ER PT J AU Port, FK Hulbert-Shearon, TE Wolfe, RA Bloembergen, WE Golper, TA Agodoa, LYC Young, EW AF Port, FK Hulbert-Shearon, TE Wolfe, RA Bloembergen, WE Golper, TA Agodoa, LYC Young, EW TI Predialysis blood pressure and mortality risk in a national sample of maintenance hemodialysis patients SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE hemodialysis mortality; blood pressure; diabetic end-stage renal disease; heart disease in dialysis; hypertension in dialysis; hypotension in dialysis ID DIABETIC-PATIENTS; HYPERTENSION; DISEASE AB The role of predialysis blood pressure (BP) as a risk factor for the high mortality in chronic hemodialysis (HD) patients has remained controversial. The objective of the current study was to further explore in a national random sample of 4,499 US hemodialysis patients any relationship of systolic or diastolic and predialysis or postdialysis BP with mortality, while considering subgroups of patients and controlling for other patient characteristics and comorbidities. The main finding of this study is the association of a low predialysis systolic BP with an elevated adjusted mortality risk (relative mortality risk [RR] = 1.86 for systolic BP < 110, P < 0.0001). No association with an elevated mortality risk could be observed for predialysis systolic hypertension (RR = 0.98 to 0.99, not significant [NS]), except for an elevated risk of cerebrovascular deaths. Postdialysis systolic BP was associated with an elevated mortality risk both for low and high BP levels as compared with midrange BP, Further evaluation of the elevated mortality risk associated with low predialysis systolic BP indicated similar patterns for both diabetic and nondiabetic subgroups and for patients with and without congestive heart failure (CHF) or coronary artery disease, although it was more pronounced among those with CHF. The level of predialysis fluid excess did not modify these results substantially, The findings from this historical prospective national study do not argue against the treatment of hypertension and suggest greater attention to postdialysis hypertension. The strikingly elevated mortality risk with low predialysis systolic BP suggests that low predialysis BP needs to be viewed with great concern and avoided where possible. (C) 1999 by the National Kidney Foundation, Inc. C1 Univ Michigan, KECC, Ann Arbor, MI 48103 USA. US Renal Data Syst, Ann Arbor, MI USA. Univ Arkansas, Little Rock, AR 72204 USA. NIDDKD, Bethesda, MD 20892 USA. Vet Adm Med Ctr, Ann Arbor, MI 48105 USA. RP Port, FK (reprint author), Univ Michigan, KECC, 315 W Huron St,Suite 240, Ann Arbor, MI 48103 USA. EM portb@umich.edu FU NIDDK NIH HHS [N01-DK-3-2202] NR 27 TC 286 Z9 295 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD MAR PY 1999 VL 33 IS 3 BP 507 EP 517 DI 10.1016/S0272-6386(99)70188-5 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 171RT UT WOS:000078878400012 PM 10070915 ER PT J AU Haider, AW Larson, MG O'Donnell, CJ Evans, JC Wilson, PWF Levy, D AF Haider, AW Larson, MG O'Donnell, CJ Evans, JC Wilson, PWF Levy, D TI The association of chronic cough with the risk of myocardial infarction: The Framingham Heart Study SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID C-REACTIVE PROTEIN; CHLAMYDIA-PNEUMONIAE INFECTION; BLOOD-CELL COUNT; CARDIOVASCULAR-DISEASE; CYTOMEGALOVIRUS-INFECTION; RESPIRATORY SYMPTOMS; CORONARY SYNDROMES; HEMOSTATIC FACTORS; ATHEROSCLEROSIS; INFLAMMATION AB PURPOSE: A persistent inflammatory response accompanying chronic infections may contribute to the risk of coronary atherothrombosis. Recent studies have reported an association between chronic respiratory infections and an increased risk of coronary heart disease; however, these reports have not accounted for important confounders such as impaired lung function. METHODS: We considered chronic cough as an indicator of chronic lung infection or inflammation in the original Framingham Heart Study participants aged 47 to 89 years. Chronic cough was defined as a cough present for at least 3 months in the preceding year and was categorized as either nonproductive or productive. The association of chronic cough with myocardial infarction was examined for six consecutive examination cycles (1965 to 1979) among participants free of myocardial infarction at the baseline examination. In a secondary analysis, plasma fibrinogen levels were measured during examination cycle 10 (1945 to 1967) in a subgroup of the study sample (n = 1,288). Multivariable logistic regression analysis was performed adjusting for age, gender, smoking status, forced vital capacity, and other known risk factors. RESULTS: The cross-sectional pooling method yielded 15,656 person-examinations in 3,637 subjects. During follow-up, there were 291 incident myocardial infarctions. Chronic nonproductive cough (odds ratio [OR] 1.8, 95% confidence interval [CI] 1.1 to 2.8) and chronic productive cough (OR 1.6, CI 1.1 to 2.4) were independent predictors of myocardial infarction. Results were unchanged when we further adjusted for a history of heart failure. Adjusted plasma fibrinogen levels (mean +/- SD) were greater in those with chronic nonproductive cough than among those without cough (3.2 +/- 0.6 g/L versus 2.9 +/- 0.6 g/dL, P = 0.001). CONCLUSIONS:These findings provide evidence that chronic cough, a clinical manifestation of pulmonary infection or chronic inflammation is associated with the risk of myocardial infarction. Acute phase reactants such as plasma fibrinogen may be implicated in this association. Prospective serologic studies of infections as predictors of coronary heart disease risk are warranted. (C) 1999 by Excerpta Medica, Inc. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Boston Univ, Sch Med, Prevent Med & Epidemiol Sect, Boston, MA 02118 USA. VAMC, Prevent Cardiol Dept, Massachusetts Vet Epidemiol Res & Informat Ctr, W Roxbury, MA USA. Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Harvard Med Sch, Div Cardiol, Boston, MA USA. Beth Israel Deaconess Med Ctr, Harvard Med Sch, Div Clin Epidemiol, Boston, MA USA. RP Levy, D (reprint author), NHLBI, Framingham Heart Study, 5 Thurber St, Framingham, MA 01702 USA. FU PHS HHS [N01-38038] NR 52 TC 29 Z9 32 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD MAR PY 1999 VL 106 IS 3 BP 279 EP 284 DI 10.1016/S0002-9343(99)00027-3 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 179DL UT WOS:000079310300003 PM 10190375 ER PT J AU Ostuni, JL Richert, ND Lewis, BK Frank, JA AF Ostuni, JL Richert, ND Lewis, BK Frank, JA TI Characterization of differences between multiple sclerosis and normal brain: A global magnetization transfer application SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article; Proceedings Paper CT 5th Annual Meeting of the International-Society-of-Magnetic-Resonance-in-Medicine CY APR 12-18, 1997 CL VANCOUVER, CANADA SP Int Soc Magnet Resonance Med ID APPEARING WHITE-MATTER; MICROSCOPIC DISEASE; TRANSFER RATIO; LESIONS; SPECTROSCOPY; IMAGES; BURDEN AB BACKGROUND AND PURPOSE: Although the exact nature of the physiological differences between normal and multiple sclerosis (MS) brains are unknown, it has been shown that their global magnetization transfer ratio (MTR) values are significantly different. To more fully understand these differences, we examined MTR values by using 30 distinct measures. We provide a unique illustration of these differences through a derived normal-to-MS transform. METHODS: Global MTR values for the group of normal subjects and for the group of MS subjects were characterized by 30 different measures involving simple statistics, histographic characteristics, MTR order information, and MTR range information. The measures that were significantly different with respect to these two groups were discovered. From the mean MTR histogram of the two groups, a transform was created to describe a conversion between the two brain states. Normal data were passed through this transform, creating a set of pseudo-MS data. The measures that were significantly different from the normal and pseudo-MS data were also obtained in order to verify the accuracy of the transform. RESULTS: Seventeen of the 30 measures were determined to be significantly different when comparing the sets of normal and MS data. The same set of 17 measures were found to be significantly different when comparing the normal and pseudo-MS data. CONCLUSION: The differences in the global MTR values of normal and MS subjects are statistically significant compared with a large number of measures (alpha = 0,05). A normal-to-MS transform is a novel method for illustrating these differences. C1 NIH, Lab Diagnost Radiol Res, Bethesda, MD 20892 USA. RP Ostuni, JL (reprint author), NIH, Lab Diagnost Radiol Res, Bldg 10,Room B1N256,10 Ctr Dr,MSC 1074, Bethesda, MD 20892 USA. NR 22 TC 15 Z9 15 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD MAR PY 1999 VL 20 IS 3 BP 501 EP 507 PG 7 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 187XB UT WOS:000079812700023 PM 10219419 ER PT J AU Katzman, GL Langford, CA Sneller, MC Koby, M Patronas, NJ AF Katzman, GL Langford, CA Sneller, MC Koby, M Patronas, NJ TI Pituitary involvement by Wegener's granulomatosis: A report of two cases SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID DIABETES-INSIPIDUS; HYPOPHYSITIS AB We describe two cases of pituitary involvement by Wegener's granulomatosis. At initial presentation, or during subsequent disease "flares," a pattern of pituitary abnormality was suggested. During periods of remission, we found the pituitary returned to a nearly normal appearance. Loss of the normal posterior pituitary T1 hyper intensity matched a clinical persistence of diabetes insipidus, suggesting there is permanent damage to this structure by the initial disease process. C1 NIH, Dept Radiol, Ctr Clin, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. Univ Maryland, Med Ctr, Dept Radiol, Baltimore, MD 21201 USA. RP Patronas, NJ (reprint author), NIH, Dept Radiol, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. NR 19 TC 32 Z9 33 U1 0 U2 1 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD MAR PY 1999 VL 20 IS 3 BP 519 EP 523 PG 5 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 187XB UT WOS:000079812700026 PM 10219422 ER PT J AU Hildesheim, A Hadjimichael, O Schwartz, PE Wheeler, CM Barnes, W Lowell, DM Willett, J Schiffman, M AF Hildesheim, A Hadjimichael, O Schwartz, PE Wheeler, CM Barnes, W Lowell, DM Willett, J Schiffman, M TI Risk factors for rapid-onset cervical cancer SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE rapid-onset cervical cancer; human papillomaviruses; epidemiology ID HUMAN PAPILLOMAVIRUS INFECTION; SQUAMOUS-CELL CARCINOMA; UTERINE CERVIX; ADENOCARCINOMA; NEOPLASIA; EPIDEMIOLOGY; CYTOLOGY; WOMEN AB OBJECTIVES: The current study was designed to elucidate risk factors associated with the development of cervical cancer during the course of routine Papanicolaou smear screening (rapid-onset cervical cancer). STUDY DESIGN: Four hundred eighty-three women diagnosed with invasive cervical cancer, representing 73% of all such tumors diagnosed in Connecticut between 1985 and 1990, were studied. Papanicolaou smear screening and risk factor information was obtained by questionnaire and physician record review. Results from human papillomavirus deoxyribonucleic acid testing by polymerase chain reaction of tumor samples were available for 278 study participants. Prediagnostic Papanicolaou smear slides were reviewed for 67% of cases with a screening history. Screening history information, slide review, and questionnaire data were used to classify women as having rapid-onset cervical cancer (n = 43), possible rapid-onset cervical cancer (n = 111), or normal-onset cervical cancer (n = 329). RESULTS: Compared with normal-onset cases, rapid-onset cases tended to be younger (P =.001) and were more likely to be white (P=.002), diagnosed with adenocarcinomas or adenosquamous carcinomas (P=.001), and diagnosed with early-stage disease (P=.001). Cases diagnosed as possible rapid-onset disease tended to have a profile that was intermediate to that observed far rapid-onset and normal-onset cases. Human papillomavirus deoxyribonucleic acid was detected in 75.2% of cases tested. Compared with women who tested positive for human papillomavirus type 16 or other, those positive for human papillomavirus type 18 had a relative risk for rapid-onset disease of 1.6 (95% confidence interval 0.52-4.9). No significant association was observed between type 18 and possible rapid-onset disease when possible rapid-onset cases were compared with women diagnosed with normal-onset cervical cancer (relative risk 0.67, 95% confidence interval 0.29-1.6). Oral contraceptive use, cigarette smoking, number of pregnancies, and a maternal history of cervical cancer were not significantly associated with rapid-onset disease. CONCLUSIONS: Results from this study suggest that the risk factors associated with the development of rapidonset cervical cancer are similar to those for normal-onset disease. C1 NCI, Interdisciplinary Studies Sect, Environm Epidemiol Branch, DCEG, Rockville, MD 20852 USA. Yale Univ, Sch Med, New Haven, CT 06520 USA. Univ New Mexico, Sch Med, Albuquerque, NM 87131 USA. Georgetown Univ, Washington, DC 20057 USA. RP Hildesheim, A (reprint author), NCI, Interdisciplinary Studies Sect, Environm Epidemiol Branch, DCEG, 6130 Execut Blvd,Room 443, Rockville, MD 20852 USA. NR 25 TC 82 Z9 84 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAR PY 1999 VL 180 IS 3 BP 571 EP 577 DI 10.1016/S0002-9378(99)70256-5 PN 1 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 176WP UT WOS:000079175300012 PM 10076130 ER PT J AU Bottoms, SF Paul, RH Mercer, BM MacPherson, CA Caritis, SN Moawad, AH Van Dorsten, JP Hauth, JC Thurnau, GR Miodovnik, M Meis, PM Roberts, JM McNellis, D Iams, JD AF Bottoms, SF Paul, RH Mercer, BM MacPherson, CA Caritis, SN Moawad, AH Van Dorsten, JP Hauth, JC Thurnau, GR Miodovnik, M Meis, PM Roberts, JM McNellis, D Iams, JD TI Obstetric determinants of neonatal survival: Antenatal predictors of neonatal survival and morbidity in extremely low birth weight infants SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE ultrasonography; perinatal mortality; very low birth weight ID RISK AB OBJECTIVE: The aim of the study was to compare clinical and ultrasonographic variables obtained before delivery as predictors of neonatal survival and morbidity in infants weighing less than or equal to 1000 g at birth. STUDY DESIGN: Maternal data available before the birth of singleton infants with birth weights less than or equal to 1000 g who were delivered at the 11 tertiary perinatal centers of the National institute of Child Health and Human Development Network of Maternal-Fetal Medicine Research Units were studied. Births that followed extramural delivery, antepartum stillbirths, multiple gestations, induced abortions, infants with major malformations, and fetuses delivered at <20 weeks' gestation were excluded. Ultrasonographic variables, including estimated fetal weight, obstetrically estimated gestational age, femur length, and biparietal diameter, and clinical variables, such as maternal race, antenatal care, substance abuse, medical treatment, reason for delivery, fetal gender, and presentation, were studied with logistic regression as predictors of neonatal outcome, including intrapartum stillbirth, neonatal death, and survival to 120 days after birth or to discharge from the hospital with or without the presence of markers of major morbidity. RESULTS: Eight hundred eight infants met enrollment criteria; 63 were excluded because of incomplete data and 32 were excluded because of malformations, leaving 713 for analysis, 386 of whom had an ultrasonographic examination within 3 days of delivery that recorded femur length, biparietal diameter, and estimated fetal weight. Forty-two percent of births were the result of preterm labor, 22% were the result of preterm ruptured membranes, 12% were the result of preeclampsia or eclampsia, 9% were the result of fetal distress, 4% were the result of placenta previa or abruptio placentae, and 2% were the result of intrauterine growth restriction. Perinatal mortality before 24 weeks' gestation exceeded 81% (19% stillbirths and 62% neonatal deaths) but declined sharply thereafter. Most survivors born before 26 weeks' gestation had serious morbidity. Fetal femur length and estimated gestational age predicted survival better than did biparietal diameter or estimated fetal weight. Infants who survived with markers of serious long-term morbidity could not be distinguished from those who survived without morbidity markers before delivery by ultrasonography or clinical data. Threshold Values for ultrasonographic measurements of biparietal diameter and femur length were developed to distinguish fetuses with no chance of survival. CONCLUSION: Ultrasonographic assessment of either fetal femur length or gestational age predicts neonatal mortality better than do other antenatal tests. No tests accurately predicted neonatal morbidity in infants weighing less than or equal to 1000 g at birth. C1 NICHHD, Network Maternal Fetal Med Res Unit, Bethesda, MD 20892 USA. RP Bottoms, SF (reprint author), NICHHD, Network Maternal Fetal Med Res Unit, Bethesda, MD 20892 USA. OI caritis, steve/0000-0002-2169-0712 FU NICHD NIH HHS [HD 19897, HD 21410, HD 21414] NR 9 TC 41 Z9 43 U1 1 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAR PY 1999 VL 180 IS 3 BP 665 EP 669 DI 10.1016/S0002-9378(99)70270-X PN 1 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 176WP UT WOS:000079175300027 PM 10076145 ER PT J AU Chapman, SJ Hauth, JC Bottoms, SF Iams, JD Sibai, B Thom, E Moawad, AH Thurnau, GR AF Chapman, SJ Hauth, JC Bottoms, SF Iams, JD Sibai, B Thom, E Moawad, AH Thurnau, GR TI Benefits of maternal corticosteroid therapy in infants weighing <= 1000 grams at birth after preterm rupture of the amnion SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE amniotic rupture; corticosteroids; prematurity ID RESPIRATORY-DISTRESS SYNDROME; CONTROLLED TRIAL; PREVENTION; BETAMETHASONE; MEMBRANES AB OBJECTIVE: The aim of the study was to determine the effects of antenatal maternal corticosteroid treatment on selected neonatal outcomes in infants weighing less than or equal to 1000 g at birth after preterm rupture of membranes. STUDY DESIGN: In a 1-year (1992-1993) prospective observational study, the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network collected outcome data for 766 infants who did not have a major fetal anomaly and who had a birth weight less than or equal to 1000 g (378 were born after preterm rupture of membranes). Only fetuses deemed potentially viable by the obstetrician were included in our analysis. Selected neonatal outcomes were compared between mothers who did and did not receive antenatal corticosteroids. Logistic regression variables included birth weight, sex, race, amnionitis, tocolytic therapies, mode of delivery, and surfactant use. RESULTS: Two hundred fourteen of the 378 infants whose mothers had preterm rupture of membranes were deemed potentially viable; 62 of these mothers received antenatal steroids and 152 did not. Groups were similar with respect to gestational age, birth weight, race, amnionitis, and delivery mode. Women who received antenatal steroids were more likely to have received tocolysis (P < .001). Univariate and regression analyses controlling for multiple confounders confirmed no neonatal benefits of maternal corticosteroid use. CONCLUSIONS: Corticosteroid treatment in women with preterm rupture of membranes was of no apparent benefit to neonates weighing less than or equal to 1000 g. C1 Univ Alabama Birmingham, Dept Obstet & Gynecol, Div Maternal Fetal Med, Birmingham, AL 35233 USA. NICHHD, Maternal Fetal Med Unit Network, Bethesda, MD 20892 USA. RP Chapman, SJ (reprint author), Univ Alabama Birmingham, Dept Obstet & Gynecol, Div Maternal Fetal Med, 618 S 20th St,Room OHB 451, Birmingham, AL 35233 USA. FU NICHD NIH HHS [HD27869, HD27915, HD27917] NR 17 TC 13 Z9 13 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAR PY 1999 VL 180 IS 3 BP 677 EP 682 DI 10.1016/S0002-9378(99)70272-3 PN 1 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 176WP UT WOS:000079175300029 PM 10076147 ER PT J AU Kimberlin, DF Hauth, JC Owen, J Bottoms, SF Iams, JD Mercer, BM Thom, EA Moawad, AH VanDorsten, JP Thurnau, GR AF Kimberlin, DF Hauth, JC Owen, J Bottoms, SF Iams, JD Mercer, BM Thom, EA Moawad, AH VanDorsten, JP Thurnau, GR TI Indicated versus spontaneous preterm delivery: An evaluation of neonatal morbidity among infants weighing <= 1000 grams at birth SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE extremely low birth weight; indicated delivery; spontaneous delivery ID SCHOOL-AGE; CHILDREN; SURVIVAL; LESS; PERFORMANCE; OUTCOMES; GROWTH; HEALTH AB OBJECTIVE: The aim of the study was to determine whether infants weighing less than or equal to 1000 g after birth who are born to women who undergo indicated preterm delivery have different neonatal outcomes than do those born as a result of either spontaneous preterm labor or preterm premature rupture of membranes. STUDY DESIGN: in a I-year observational study (1992-1993) the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network collected outcome data for 799 infants whose birth weights were less than or equal to 1000 g. Only singleton infants with gestational age >20 weeks who were not produced as the result of an induced abortion were included. Our analysis was further limited to infants without major congenital anomalies who survived >2 days, were deemed potentially viable by the obstetrician, and would have undergone a cesarean delivery for fetal indications (N = 411). The primary reason for delivery was categorized as indicated delivery, spontaneous preterm labor, or spontaneous preterm premature rupture of membranes. Selected neonatal outcomes were evaluated among infants born to women in each of these groups. Logistic regression analyses were used to control for the effects of other potentially confounding variables. RESULTS: A total of 156 of the 411 infants were born to women who underwent an indicated preterm delivery, whereas 160 were born after spontaneous preterm labor and 95 were delivered after preterm premature rupture of membranes. Univariate analyses revealed significantly lower incidences of grade III or IV intraventricular hemorrhage, grade III or IV retinopathy of prematurity, and seizure activity among infants born in an indicated preterm delivery than among those born after spontaneous preterm labor or preterm premature rupture of membranes. However, infants of women who underwent indicated preterm delivery had a more advanced mean gestational age at birth than did those born after spontaneous preterm labor or preterm premature rupture of membranes (28 +/- 2 weeks, 26 +/- 2 weeks, and 26 +/- I weeks. respectively, P < .001). Multiple logistic regression analysis was therefore used to control for the disparity in gestational age. Multivariate analyses did not confirm the apparent improvement in neonatal outcome in the indicated delivery group. CONCLUSION: In this population of infants weighing less than or equal to 1000 g, selected neonatal outcomes did not differ according to birth by indicated preterm delivery, spontaneous preterm labor, or preterm premature rupture of membranes. C1 Univ Alabama Birmingham, Dept Obstet & Gynecol, Div Maternal Fetal Med, Birmingham, AL 35233 USA. NICHHD, Maternal Fetal Med Unit Network, Bethesda, MD 20892 USA. RP Kimberlin, DF (reprint author), Univ Alabama Birmingham, Dept Obstet & Gynecol, Div Maternal Fetal Med, 618 S 20th St,room OHB 450, Birmingham, AL 35233 USA. FU NICHD NIH HHS [HD27917, HD27869, HD27915] NR 25 TC 23 Z9 24 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAR PY 1999 VL 180 IS 3 BP 683 EP 689 DI 10.1016/S0002-9378(99)70273-5 PN 1 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 176WP UT WOS:000079175300030 PM 10076148 ER PT J AU Martin, DF Dunn, JP Davis, JL Duker, JS Engstrom, RE Friedberg, DN Jaffe, GJ Kuppermann, BD Polis, MA Whitley, RJ Wolitz, RA Benson, CA AF Martin, DF Dunn, JP Davis, JL Duker, JS Engstrom, RE Friedberg, DN Jaffe, GJ Kuppermann, BD Polis, MA Whitley, RJ Wolitz, RA Benson, CA CA Int AIDS Soc USA TI Use of the ganciclovir implant for the treatment of cytomegalovirus retinitis in the era of potent antiretroviral therapy: Recommendations of the International AIDS Society - USA panel SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID SUSTAINED-RELEASE GANCICLOVIR; IMMUNODEFICIENCY-VIRUS INFECTION; INTRAVITREAL GANCICLOVIR; ORAL GANCICLOVIR; INTRAVENOUS CIDOFOVIR; INTRAOCULAR IMPLANT; RETINAL DETACHMENTS; CONTROLLED TRIAL; DISEASE; ZIDOVUDINE AB (PURPOSE)-P-.: To describe the risks, benefits, and recommended use of the ganciclovir implant for the treatment of human immunodeficiency virus-related cytomegalovirus (CMV) retinitis in the era of potent antiretroviral therapy. (METHODS)-M-.: A panel of physicians with expertise in the use of the ganciclovir implant and in the management of CMV retinitis was convened by the International AIDS Society-USA. The panel reviewed and discussed available data, and developed recommendations for the use of the ganciclovir implant, the surgical technique, and related management issues. Recommendations were rated according to the strength and quality of the supporting evidence. (RESULTS)-R-.: The effect of potent antiretroviral therapy on the immunologic status of patients with human immunodeficiency virus disease has changed the manifestation and course of CMV retinitis in many patients. The clinical management of CMV retinitis and the role of the ganciclovir implant are thus changing. Factors in the decision to choose the ganciclovir implant include the patient's potential for immunologic improvement, location and severity of CMV retinitis, and the risks and costs associated with implantation and concomitant oral ganciclovir therapy. (CONCLUSIONS)-C-.: The ganciclovir implant is safe and effective for the treatment of CMV retinitis. The indications for its use should be modified to account for increased patient survival and the potential for CMV retinitis to be controlled by effective antiretroviral therapy. Optimal use of the ganciclovir implant and discontinuation of therapy in selected patients with improvement in immunity may result in better long-term visual outcomes. (C) 1999 by Elsevier Science Inc. All rights reserved. C1 Emory Univ, Dept Ophthalmol, Atlanta, GA 30322 USA. Johns Hopkins Univ, Dept Ophthalmol, Baltimore, MD USA. Univ Miami, Dept Ophthalmol, Miami, FL 33152 USA. New England Med Ctr, Dept Ophthalmol, Boston, MA 02111 USA. Univ Calif Los Angeles, Dept Ophthalmol, Los Angeles, CA USA. NYU Med Ctr, Dept Ophthalmol, New York, NY 10016 USA. Duke Univ, Dept Ophthalmol, Durham, NC USA. Univ Calif Irvine, Dept Ophthalmol, Irvine, CA 92717 USA. NIAID, Bethesda, MD 20892 USA. Univ Alabama, Dept Pediat, Birmingham, AL USA. Kaiser Permanente, Dept Ophthalmol, San Francisco, CA USA. Univ Colorado, Dept Med, Denver, CO USA. RP Dunn, JP (reprint author), USA, Int AIDS Soc, 1001 B OReilly Ave,POB 29916, San Francisco, CA 94129 USA. EM info@iasusa.org OI Polis, Michael/0000-0002-9151-2268 NR 79 TC 49 Z9 50 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD MAR PY 1999 VL 127 IS 3 BP 329 EP 339 PG 11 WC Ophthalmology SC Ophthalmology GA 173KN UT WOS:000078979900013 PM 10088745 ER PT J AU Fredrickson, TN Lennert, K Chattopadhyay, SK Morse, HC Hartley, JW AF Fredrickson, TN Lennert, K Chattopadhyay, SK Morse, HC Hartley, JW TI Splenic marginal zone lymphomas of mice SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID B-CELL LYMPHOMAS; CHAIN GENE; ANTIGEN; LINEAGE; LYMPHOCYTES; DISTINCT; DIFFERENTIATION; ACTIVATION; MUTATIONS; MIGRATION AB Splenic marginal zone lymphomas (MZLs) have been found to occur at a high frequency in NFS.N mice congenic for high-expressing ecotropic murine leukemia virus (MuLV) genes from AKR and C58 mice. Based on morphological, immunological, and molecular studies of these mice, MZL is clearly recognizable as a distinct disease with a characteristic clinical behavior. MZL was staged according to the degree of accumulation and morphological change of cells within the splenic marginal zone, as follows: 1) a moderate Increase in normal-looking MZ cells,judged to be prelymphomatous, and 2) MZL in three variants: i) distinct enlargement of MZ by normal-looking cells (MZL), ii) distinct enlargement of MZ by basophilic centroblast-like cells (MZL+), and iii) extensive splenic involvement by centroblast-like cells (MZL++). The rate of mitosis and apoptosis increases with lymphoma grade. In most cases, emergence of a dominant IgH clonal pattern in paired splenic biopsy and necropsy samples was correlated with progression. MZLs were transplantable and homed to the spleen. MZL may constitute a commonly occurring lymphoma type unrecognized, in part, because of the centroblastic morphology of high-grade MZL and possible overgrowth of lower-grade MZL by more aggressive follicular lymphomas. C1 NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Registry Expt Canc, NIH, Bethesda, MD 20892 USA. Univ Kiel, Zentrum Pathol & Angew Krebsforsch, Kiel, Germany. RP Hartley, JW (reprint author), NIAID, Immunopathol Lab, NIH, Bldg 7,Room 302,7 Ctr Dr MSC-0760, Bethesda, MD 20892 USA. EM jhartley@atlas.niaid.nih.gov OI Morse, Herbert/0000-0002-9331-3705 FU NIAID NIH HHS [N01-AI-45203] NR 45 TC 34 Z9 35 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD MAR PY 1999 VL 154 IS 3 BP 805 EP 812 DI 10.1016/S0002-9440(10)65327-8 PG 8 WC Pathology SC Pathology GA 174EN UT WOS:000079021300018 PM 10079258 ER PT J AU Ferraris, JD Williams, CK Ohtaka, A Garcia-Perez, A AF Ferraris, JD Williams, CK Ohtaka, A Garcia-Perez, A TI Functional consensus for mammalian osmotic response elements SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE osmoregulation; osmotic stress; organic osmolytes; gene regulation; gene expression ID ALDOSE REDUCTASE GENE; SACCHAROMYCES-CEREVISIAE; ESCHERICHIA-COLI; MEDULLARY CELLS; STRESS; TRANSCRIPTION; PROMOTER; PROU; IDENTIFICATION; EXPRESSION AB The molecular mechanisms underlying adaptation to hyperosmotic stress through the accumulation of organic osmolytes are largely unknown. Yet, among organisms, this is an almost universal phenomenon. In mammals, the cells of the renal medulla are uniquely exposed to high and variable salt concentrations; in response, renal cells accumulate the osmolyte sorbitol through increased transcription of the aldose reductase (AR) gene. In cloning the rabbit AR gene, we found the first evidence of an osmotic response region in a eukaryotic gene. More recently, we functionally defined a minimal essential osmotic response element (ORE) having the sequence CGGAAAATCAC(C) (bp -1105 to -1094). In the present study, we systematically replaced each base with every other possible nucleotide and tested the resulting sequences individually in reporter gene constructs. Additionally, we categorized hyperosmotic response by electrophoretic mobility shift assays of a 17-bp sequence (-1108 to -1092) containing the native ORE as a probe against which the test constructs would compete for binding. In this manner, binding activity was assessed for the full range of osmotic responses obtained. Thus we have arrived at a functional consensus for the mammalian ORE, NGGAAAWDHMC(N). This finding should accelerate the discovery of genes previously unrecognized as being osmotically regulated. C1 NHLBI, Osmot Regulat Sect, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP NHLBI, Osmot Regulat Sect, Kidney & Electrolyte Metab Lab, NIH, Bldg 10,Rm 6N260,10 Ctr Dr,MSC 1603, Bethesda, MD 20892 USA. EM jdf@helix.nih.gov NR 29 TC 45 Z9 45 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 EI 1522-1563 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD MAR PY 1999 VL 276 IS 3 BP C667 EP C673 PG 7 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 174VH UT WOS:000079056400019 PM 10069994 ER PT J AU Pietrini, P Furey, ML Alexander, GE Mentis, MJ Dani, A Guazzelli, M Rapoport, SI Schapiro, MB AF Pietrini, P Furey, ML Alexander, GE Mentis, MJ Dani, A Guazzelli, M Rapoport, SI Schapiro, MB TI Association between brain functional failure and dementia severity in Alzheimer's disease: Resting versus stimulation PET study SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the Society-for-Neuroscience CY NOV 16-21, 1996 CL WASHINGTON, D.C. SP Soc Neurosci ID ENERGY-METABOLISM AB Objective: This study tested the hypothesis that regional cerebral glucose metabolism during neuronal activation is a more sensitive index of neuronal dysfunction and clinical severity in Alzheimer's disease than is glucose metabolism at rest. Methods: The subjects were 15 Alzheimer's disease patients with a wide range of Mattis Dementia Rating Scale scores (23-128). By using positron emission tomography, absolute glucose metabolism was measured in the parietal, occipital (visual areas), and temporal (auditory areas) cortical regions during rest (eyes/ears covered) and audiovisual stimulation. Results: In the parietal cortex, glucose metabolism correlated with dementia severity in both conditions. In contrast, in the relatively preserved visual and auditory cortical regions, glucose metabolism predicted dementia severity during stimulation but not at rest. Conclusions: These findings suggest that regional cerebral glucose metabolism during stimulation is a more sensitive index of the functional/metabolic failure of neuronal systems than is metabolism at rest. C1 NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. Univ Pisa, Dept Human & Environm Sci, Pisa, Italy. Univ Pisa, Dept Psychiat Neurobiol Pharmacol & Biotechnol, Pisa, Italy. RP Pietrini, P (reprint author), NIA, Neurosci Lab, NIH, Rm 6C414,Bldg 10,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Furey, Maura/H-5273-2013 NR 15 TC 44 Z9 44 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAR PY 1999 VL 156 IS 3 BP 470 EP 473 PG 4 WC Psychiatry SC Psychiatry GA 173FE UT WOS:000078969900022 PM 10080567 ER PT J AU Corti, MC Guralnik, JM Ferrucci, L Izmirlian, G Leveille, SG Pahor, M Cohen, HJ Pieper, C Havlik, RJ AF Corti, MC Guralnik, JM Ferrucci, L Izmirlian, G Leveille, SG Pahor, M Cohen, HJ Pieper, C Havlik, RJ TI Evidence for a Black-White crossover in all-cause and coronary heart disease mortality in an older population: The North Carolina EPESE SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID UNITED-STATES; RISK-FACTORS; TRENDS; AGE; AMERICANS; MEN AB Objectives. This cohort study evaluated racial differences in mortality among Blacks and Whites 65 years and older. Methods. A total of 4136 men and women (1875 Whites and 2261 Blacks) living in North Carolina were interviewed in 1986 and followed up for mortality until 1994. Hazard ratios (HRs) for all-cause and cause-specific mortality were calculated, with adjustment for sociodemographic and coronary heart disease (CHD) risk factors. Results. Black persons had higher mortality rates than Whites at young-old age (65-80 years) but had significantly lower mortality rates after age 80. Black persons age 80 or older had a significantly lower risk of all-cause mortality (HR of Blacks vs Whites, 0.75. 95% confidence interval [CI] = 0.62, 0.90) and of CHD mortality (HR 0.44; 95% CI = 0.30, 0.66). These differences were not observed for other causes of death. Conclusions. Racial differences in mortality are modified by age. This mortality crossover could be attributed to selective survival of the healthiest oldest Blacks or to other biomedical factors affecting longevity after age 80. Because the crossover was observed for CHD deaths only, age overreporting by Black older persons seems an unlikely explanation of the mortality differences. C1 NIA, Epidemiol Demog & Biometry Program, NIH, Bethesda, MD 20892 USA. Osped Camposampiero, Dept Geriatr, Padua, Italy. Osped I Fraticini, Dept Geriatr, Florence, Italy. Univ Tennessee, Dept Prevent Med, Memphis, TN USA. Duke Univ, Ctr Study Aging & Human Dev, Durham, NC USA. RP Corti, MC (reprint author), NIA, Epidemiol Demog & Biometry Program, NIH, 7201 Wisconsin Ave,Room 3C-309, Bethesda, MD 20892 USA. FU NIA NIH HHS [N01-AG-4-2110, N01-AG1-2102] NR 34 TC 42 Z9 43 U1 1 U2 2 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD MAR PY 1999 VL 89 IS 3 BP 308 EP 314 DI 10.2105/AJPH.89.3.308 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 170MU UT WOS:000078810100006 PM 10076478 ER PT J AU Sahyoun, NR Hochberg, MC Helmick, CG Harris, T Pamuk, ER AF Sahyoun, NR Hochberg, MC Helmick, CG Harris, T Pamuk, ER TI Body mass index, weight change, and incidence of self-reported physician-diagnosed arthritis among women SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID 1ST NATIONAL-HEALTH; OSTEO-ARTHRITIS; NHANES-I; FAT DISTRIBUTION; RISK-FACTORS; OSTEOARTHRITIS; DISABILITY; KNEE; ASSOCIATION; OBESITY AB Objectives. This study examined the relationship between body mass index (BMI), weight change, and arthritis in women. Methods. Data were taken from the 1982-1984 National Health and Nutrition Examination Survey Epidemiologic Follow-Up Study of 3617 women, aged 25 to 74 years. Results. Women with a BMI greater than 32 at initial interview were at significantly higher risk of developing arthritis than women with a BMI of 19 to 21.9. Compared with stable-weight women with a BMI of less than 25, women who were obese at initial interview (BMI > 29) and who subsequently maintained their weight or gained more than 10% of their body weight were at significantly higher risk of developing arthritis. Conclusions. Attaining and maintaining a healthy weight may reduce the risk of developing arthritis. C1 Natl Ctr Hlth Stat, Off Anal Epidemiol & Hlth Promot, Hyattsville, MD 20782 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. NIA, Bethesda, MD 20892 USA. RP Sahyoun, NR (reprint author), Natl Ctr Hlth Stat, Off Anal Epidemiol & Hlth Promot, 6525 Belcrest Rd,Room 775, Hyattsville, MD 20782 USA. NR 29 TC 27 Z9 28 U1 1 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD MAR PY 1999 VL 89 IS 3 BP 391 EP 394 DI 10.2105/AJPH.89.3.391 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 170MU UT WOS:000078810100020 PM 10076492 ER PT J AU Arnold, LL Doherty, TM Flor, AW Simon, JA Chou, JY Chan, WY Mansfield, BC AF Arnold, LL Doherty, TM Flor, AW Simon, JA Chou, JY Chan, WY Mansfield, BC TI Pregnancy-specific glycoprotein gene expression in recurrent aborters: A potential correlation to interleukin-10 expression SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Article DE cytokine; endometrium; recurrent spontaneous abortion ID SPONTANEOUS-ABORTION; HABITUAL ABORTION; HUMAN PLACENTA; BETA-1-GLYCOPROTEIN; TROPHOBLAST; INVITRO; WOMEN; CELLS; LEUKOCYTES; PRODUCTS AB PROBLEM: The expression of the pregnancy-specific glycoprotein (PSG) genes in the uterine endometrium of women experiencing recurrent first-trimester abortions, and potential correlations to cytokine expression were examined. METHOD OF STUDY: Endometrial RNA, isolated from women with a history of either repetitive first-trimester pregnancy losses or uncomplicated pregnancies, was isolated and analyzed for PSG transcripts by the reverse transcriptase-polymerase chain reaction method. PSG genes showing different patterns of expression were expressed in baculovirus, and the purified proteins examined for their effects on cytokine expression. RESULTS: The expression of PSG11 in the endometria of recurrent aborters was significantly lower than that of controls (P < 0.001). When tested on monocytes, PSG11 stimulated secretion of interleukin (IL)-10. CONCLUSIONS: The level of expression of the PSG11 gene in the uterine endometrium, during the peri-implantation period, correlates with the risk of pregnancy loss in some women experiencing recurrent spontaneous abortions. The ability of PSG11 to influence the secretion of IL-10 suggests that PSG11 may contribute to the local modulation of the inflammatory T helper-1 response seen in the endometrium of these women. C1 Georgetown Univ, Med Ctr, Dept Obstet & Gynecol, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Dept Pediat, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Dept Biochem & Mol Biol & Cell Biol, Washington, DC 20007 USA. NIAID, NIH, Bethesda, MD 20892 USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Chan, WY (reprint author), Georgetown Univ, Childrens Med Ctr, Dept Pediat, 3800 Reservoir Rd NW, Washington, DC 20007 USA. FU NICHD NIH HHS [R01-HD31553] NR 50 TC 22 Z9 23 U1 2 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1046-7408 J9 AM J REPROD IMMUNOL JI Am. J. Reprod. Immunol. PD MAR PY 1999 VL 41 IS 3 BP 174 EP 182 PG 9 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA 189CD UT WOS:000079885800002 PM 10326620 ER PT J AU Peters, JM Avol, E Navidi, W London, SJ Gauderman, WJ Lurmann, F Linn, WS Margolis, H Rappaport, E Gong, H Thomas, DC AF Peters, JM Avol, E Navidi, W London, SJ Gauderman, WJ Lurmann, F Linn, WS Margolis, H Rappaport, E Gong, H Thomas, DC TI A study of twelve southern California communities with differing levels and types of air pollution - I. Prevalence of respiratory morbidity SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID NORTH-AMERICAN CHILDREN; PULMONARY-FUNCTION; NITROGEN-DIOXIDE; CHRONIC EXPOSURE; UCLA POPULATION; HOME DAMPNESS; ACID AEROSOLS; SULFURIC-ACID; LUNG-FUNCTION; SYMPTOMS AB To study possible chronic respiratory effects of air pollutants, we Initiated a 10-yr prospective cohort study of Southern California children, with a study design focused on four pollutants: ozone, particulate matter, acids, and nitrogen dioxide (NO2), Twelve demographically similar communities were selected on the basis of historic monitoring information to represent extremes of exposure to one or more pollutants, in each community, about 150 public school students in grade 4, 75 in grade 7, and 75 in grade 10 were enrolled through their classrooms. informed consent and written responses to surveys about students' lifetime residential histories, historic and current health status, residential characteristics, and physical activity were obtained with the help of the parents. In the first testing season, 3,676 students returned questionnaires. We confirmed associations previously reported between respiratory morbidity prevalence and the presence of personal, demographic, and residential risk factors. Rates of respiratory illness were higher for males, those living in houses with pets, pests, mildew, and water damage, those whose parents had asthma, and those living in houses with smokers. Wheeze prevalence was positively associated with levels of both acid (odds ratio [OR] = 1.45; 95% confidence interval [CI], 1.14-1.83) and NO2 (OR = 1.54; 95% CI, 1.08-2.19) in boys. We conclude, based on this cross-sectional assessment: of questionnaire responses, that current levels of ambient air pollution in Southern California may be associated with effects on schoolchildren's respiratory morbidity as assessed by questionnaire. C1 Univ So Calif, Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. State Calif, Air Resources Board, Sacramento, CA USA. Sonoma Technol Inc, Petaluma, CA USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Peters, JM (reprint author), Univ So Calif, Sch Med, Dept Prevent Med, 1540 Alcazar St,CHP 236, Los Angeles, CA 90033 USA. EM jpeters@hsc.usc.edu RI Osborne, Nicholas/N-4915-2015; OI Osborne, Nicholas/0000-0002-6700-2284; London, Stephanie/0000-0003-4911-5290 FU NIEHS NIH HHS [5P30ES07048-02] NR 36 TC 253 Z9 263 U1 5 U2 20 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 BP 760 EP 767 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 175QQ UT WOS:000079106600011 PM 10051248 ER PT J AU Peters, JM Avol, E Gauderman, WJ Linn, WS Navidi, W London, SJ Margolis, H Rappaport, E Vora, H Gong, H Thomas, DC AF Peters, JM Avol, E Gauderman, WJ Linn, WS Navidi, W London, SJ Margolis, H Rappaport, E Vora, H Gong, H Thomas, DC TI A study of twelve southern California communities with differing levels and types of air pollution - II. Effects on pulmonary function SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID CROSS-SECTIONAL ANALYSIS; NORTH-AMERICAN CHILDREN; SULFURIC-ACID AEROSOLS; LUNG-FUNCTION; RESPIRATORY HEALTH; CHRONIC EXPOSURE; ASTHMATIC VOLUNTEERS; CIGARETTE-SMOKING; NITROGEN-DIOXIDE; UCLA POPULATION AB To study the possible chronic respiratory effects of air pollutants, we designed and initiated a 10-yr prospective study of Southern California public schoolchildren living in 12 communities with different levels and profiles of air pollution. The design of the study, exposure assessment methods, and survey methods and results related to respiratory symptoms and conditions are described Tn the accompanying paper. Pulmonary function tests were completed on 3,293 subjects. We evaluated cross-sectionally the effects of air pollution exposures based on data collected in 1986-1990 by existing monitoring stations and data collected by our study ham in 1994. Expected relationships were seen between demographic, physical, and other environmental factors and pulmonary function values. When the data were stratified by sex, an association was seen between pollution levels and lower pulmonary function in female subjects, with the associations being stronger for the 1994 exposure data than the 1986-1990 data. After adjustment, PM10, PM2.5, and NO2 were each significantly associated with lower FVC, FEV1, and maximal midexpiratoyy flow (MMEF); acid vapor with lower FVC, FEV1, peak expiratory flow rate (PEFR), and MMEF; and O-3 With lower PEFR and MMEF. Effects were generally larger In those girls spending more time outdoors. Stepwise regression of adjusted pulmonary function values for girls in the 12 communities showed that NO2 was most strongly associated with lower FVC (r = -0.74, p < 0.01), PM2.5 with FEV1 (r = -0.72, p < (8.04), O-3 with PEFR (r = -0.75, p < 0.005), and PM2.5 with MMEF (r = -0.80, p < 0.005). There was a statistically significant association between ozone exposure and decreased FVC and FEV1 in girls with asthma. For boys, significant associations were seen between peak O-3 exposures and lower FVC and FEV1, but only in those spending more time outdoors. These findings underline the importance of follow-up of this cohort. C1 Univ So Calif, Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. State Calif, Air Resources Board, Sacramento, CA USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Peters, JM (reprint author), Univ So Calif, Sch Med, Dept Prevent Med, 1540 Alcazar St,CHP 236, Los Angeles, CA 90033 USA. EM jpeters@hsc.usc.edu RI Osborne, Nicholas/N-4915-2015; OI Osborne, Nicholas/0000-0002-6700-2284; London, Stephanie/0000-0003-4911-5290 FU NIEHS NIH HHS [5P30ES07048-02] NR 41 TC 253 Z9 258 U1 2 U2 27 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 BP 768 EP 775 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 175QQ UT WOS:000079106600012 PM 10051249 ER PT J AU Cereda, MF Sparacino, ME Frank, AR Trawoger, R Kolobow, T AF Cereda, MF Sparacino, ME Frank, AR Trawoger, R Kolobow, T TI Efficacy of tracheal gas insufflation in spontaneously breathing sheep with lung injury SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID INTRATRACHEAL PULMONARY VENTILATION; POSITIVE AIRWAY PRESSURE; END-EXPIRATORY PRESSURE; MECHANICAL VENTILATION; RESPIRATORY-FAILURE; CATHETER POSITION; DEAD SPACE; EXCHANGE; SUPPORT; MODEL AB Tracheal gas insufflation (TGI) decreases dead space (VD) and can be combined with continuous positive airway pressure (CPAP) to decrease minute volume (VE) and effort of breathing. In 11 anesthetized sheep, we induced acute lung injury (ALI) through oleic acid (OA) infusion and studied the effects of TGI combined with CPAP (CPAP-TGI) at different TGI flows and with catheters of different designs. Sheep were randomized to two groups: Group A (n = 7) was placed on CPAP and CPAP-TGI at 10 and 15 L/min of insufflation flow delivered through a reverse thrust catheter (RTC). Group B (n = 4) was placed on CPAP and CPAP-TGI at a flow of 10 L/min delivered through a RTC, and through a straight flow catheter (SFC). Compared with CPAP alone, CPAP-TGI resulted in significantly lower VD, VE, pressure time product, and work of breathing. We found no additional benefit from TGI flow of 15 L/min, compared with 10 L/min, and no statistically significant difference between the SFC and the RTC. In conclusion, TGI can be combined with CPAP in this model of ALI to reduce ventilation and effort of breathing. C1 NHLBI, Sect Pulm & Cardiac Assist Devices, Pulm & Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Cereda, MF (reprint author), Univ Milan, Ist Anestesia & Rianimaz, Osped S Gerardo, Via Donizetti 106, I-20052 Monza, MI, Italy. NR 27 TC 13 Z9 14 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 BP 845 EP 850 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 175QQ UT WOS:000079106600024 PM 10051261 ER PT J AU Ahmad, F Cong, LN Holst, LS Wang, LM Landstrom, TR Pierce, JH Quon, MJ Degerman, E Manganiello, VC AF Ahmad, F Cong, LN Holst, LS Wang, LM Landstrom, TR Pierce, JH Quon, MJ Degerman, E Manganiello, VC TI Cyclic nucleotide phosphodiesterase 3B (PDE3B) is a downstream target of AKT/PKB and is involved in regulation of effects of PKB on cell proliferation/survival. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 NHLBI, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. RI Quon, Michael/B-1970-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A723 EP A723 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237104025 ER PT J AU Aoki, K Shoemaker, M Moss, J AF Aoki, K Shoemaker, M Moss, J TI Identification of stimulatory and inhibitory elements in the promoter of the mouse ADP-ribosyl arginine hydrolase gene. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A187 EP A187 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237101007 ER PT J AU Avila, NA Kelly, JA Johnson, DL Jones, E Albert, P Moss, J AF Avila, NA Kelly, JA Johnson, DL Jones, E Albert, P Moss, J TI Lymphangioleiomyomatosis: Correlation of PFTS and quantitative high resolution computed tomography (HRCT). SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 NHLBI, Dept Diagnost Radiol, CC, NIH, Bethesda, MD 20892 USA. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Off Biostat Res, DECA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A704 EP A704 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237103916 ER PT J AU Bonner, JC Rice, AB Kagan, E Zhang, P AF Bonner, JC Rice, AB Kagan, E Zhang, P TI Nitration of tyrosine on PDGF and EGF receptors by peroxynitrite is related to inhibition of growth factors-stimulated mitogenesis of rat lung myofibroblasts. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 NIEHS, Pulm Pathobiol Lab, Res Triangle Pk, NC 27709 USA. Uniformed Serv Univ Hlth Sci, Dept Pathol, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A884 EP A884 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237104944 ER PT J AU Bonner, JC Rice, AB Lindroos, PM Wang, YZ AF Bonner, JC Rice, AB Lindroos, PM Wang, YZ TI p38 MAP kinase is required for IL-1 beta-induced up-regulation of the PDGF alpha-receptor on pulmonary myofibroblasts. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 NIEHS, Pulm Pathobiol Lab, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A722 EP A722 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237104021 ER PT J AU Cervantes-Laurean, D McElvaney, NG Moss, J Levine, RL AF Cervantes-Laurean, D McElvaney, NG Moss, J Levine, RL TI Oxidation of either methionine 351 or methionine 358 in human alpha 1antitrypsin causes loss of anti-neutrophil elastase activity SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RI McElvaney, Noel/A-6809-2010; Levine, Rodney/D-9885-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A192 EP A192 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237101037 ER PT J AU Chu, SC Kelly, JA Chen, CC Albert, PS Moss, J AF Chu, SC Kelly, JA Chen, CC Albert, PS Moss, J TI Increased risk of osteoporosis and osteopenia in women with lymphangioleiomyomatosis (LAM) due to antiestrogen therapies end progressive lung disease. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Nucl Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A704 EP A704 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237103918 ER PT J AU Chu, SC Horiba, K Kelly, JA Usuki, J Holquin, F Ferrans, VJ Moss, J AF Chu, SC Horiba, K Kelly, JA Usuki, J Holquin, F Ferrans, VJ Moss, J TI Mesothelial origin of elevated CA125 in patients with lymphangioleiomyomatosis (LAM). SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A704 EP A704 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237103917 ER PT J AU Cowan, MJ Wu, T Yao, XL Logun, C Shelhamer, JH AF Cowan, MJ Wu, T Yao, XL Logun, C Shelhamer, JH TI Initial description of the promotor for the human p11 gene. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A445 EP A445 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237102464 ER PT J AU Cui, XL Alsaaty, S Lawrence, M Levine, SJ AF Cui, XL Alsaaty, S Lawrence, M Levine, SJ TI Identification and cloning of an aminopeptidase-like protein expressed by human pulmonary epithelial cells. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 NHLBI, Dept Crit Care Med, Ctr Clin, NIH, Bethesda, MD 20892 USA. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A447 EP A447 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237102479 ER PT J AU DePietro, M Correa, R Zeni, F Vodovotz, Y Natanson, C Wahl, S Roberts, A Fitz, Y Danner, R Banks, S Eichacker, PO AF DePietro, M Correa, R Zeni, F Vodovotz, Y Natanson, C Wahl, S Roberts, A Fitz, Y Danner, R Banks, S Eichacker, PO TI TGF-beta alters survival rates and lung injury dependent on the mortality of E-coli challenge in a rat pneumonia model. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 NIH, CCMD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A597 EP A597 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237103305 ER PT J AU Eissa, NT Haggerty, CM Palmer, CD Moss, J AF Eissa, NT Haggerty, CM Palmer, CD Moss, J TI Identification of residues critical for enzymatic activity in the domain encoded by exons 8 & 9 of the human inducible nitric oxide synthase. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A284 EP A284 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237101536 ER PT J AU Gao, G Al-Toukhi, D Gilbert-McClain, L Manganiello, VC AF Gao, G Al-Toukhi, D Gilbert-McClain, L Manganiello, VC TI Reciprocal changes in PDE3 and PDE4 isozymes during activation of cultured human monocytes by phorbol ester. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 NHLBI, PCCMB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A657 EP A657 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237103658 ER PT J AU Ghazizadeh, M Jin, EJ Kawanami, O Takemura, T Ohaki, Y Ferrans, VJ AF Ghazizadeh, M Jin, EJ Kawanami, O Takemura, T Ohaki, Y Ferrans, VJ TI Detection of chromosomal aneuploidy in bronchiolo-alveolar carcinoma by interphase cytogenetics. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 Nippon Med Sch, Dept Mol Pathol, Inst Gerontol, Kawasaki, Kanagawa, Japan. Japanese Red Cross Hosp Ctr, Dept Pathol, Tokyo, Japan. Hokusch Hosp, Pathol Sect, Nippon Med Sch, Chiba, Japan. NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A204 EP A204 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237101103 ER PT J AU Gladwin, MT Yao, XL Cowan, MJ Logun, C Huang, XL Shelhamer, JH AF Gladwin, MT Yao, XL Cowan, MJ Logun, C Huang, XL Shelhamer, JH TI Retinoic acid (RA) reduces p11 protein levels in a human bronchial cell line (beas-2b) by a posttranslational mechanism. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A447 EP A447 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237102478 ER PT J AU Gladwin, MT Yao, XL Cowan, MJ Logun, C Huang, XL Shelhamer, JH AF Gladwin, MT Yao, XL Cowan, MJ Logun, C Huang, XL Shelhamer, JH TI Reduction in p11 protein levels by retinoic acid (RA) increases CPLA(2) activity and enhances susceptibility to oxidative cell death. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A273 EP A273 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237101474 ER PT J AU Honig, EG O'Connor, GT Gilbert, IA Mangione, S Reibman, J Grum, CM Hindi-Alexander, M AF Honig, EG O'Connor, GT Gilbert, IA Mangione, S Reibman, J Grum, CM Hindi-Alexander, M TI Influence of training experience on performance on a medical resident asthma knowledge inventory. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 Emory Univ, Atlanta, GA 30322 USA. Boston Univ, Boston, MA 02215 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. NYU, New York, NY USA. Univ Michigan, Ann Arbor, MI 48109 USA. NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A241 EP A241 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237101308 ER PT J AU Huang, XL Yao, XL Gladwin, MT Cowan, MJ Logun, C Shelhamer, JH AF Huang, XL Yao, XL Gladwin, MT Cowan, MJ Logun, C Shelhamer, JH TI Arachidonic acid induces p11 protein expression in human bronchial epithelial cells. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A402 EP A402 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237102215 ER PT J AU Jawawickreme, SP Gray, T Eling, T Nettesheim, P AF Jawawickreme, SP Gray, T Eling, T Nettesheim, P TI Regulation of 15-lipoxygenase (15-LO) expression and mucin secretion by interleukin-4 in normal human tracheobronchial epithelial (NHTBE) cells. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Pulm Pathobiol Lab, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A36 EP A36 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237100129 ER PT J AU Jin, EJ Kawanami, O Ghazizadeh, M Jian, L Takemura, T Ohaki, Y Takeda, K Yu, ZX Ferrans, VJ AF Jin, EJ Kawanami, O Ghazizadeh, M Jian, L Takemura, T Ohaki, Y Takeda, K Yu, ZX Ferrans, VJ TI Mosaic-like distribution of endothelial cell antigens in areas of bronchopulmonary anastomoses in normal human lung. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 Nippon Med Sch, Inst Gerontol, Dept Mol Pathol, Kawasaki, Kanagawa, Japan. Japanese Red Cross Hosp Ctr, Dept Pathol, Tokyo, Japan. Hokusoh Hosp, Nippon Med Sch, Pathol Sect, Tokyo, Japan. NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A353 EP A353 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237101932 ER PT J AU Jonsson, S Vidarsson, G Kristinsson, KG Schneerson, R Schiffman, G Valdimarsson, H Jonsdottir, I AF Jonsson, S Vidarsson, G Kristinsson, KG Schneerson, R Schiffman, G Valdimarsson, H Jonsdottir, I TI Antibody response and serum opsonic effect after vaccination of patiens with chronic obstructive pulmonary disease (COPD) with a pneumococcus type 6B tetanus toxoid conjugate (PN6B-TT). SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 Univ Iceland, Reykjavik, Iceland. Natl Inst Child Hlth, Bethesda, MD USA. SUNY Stony Brook, Stony Brook, NY 11794 USA. RI Vidarsson, Gestur/A-9909-2009 OI Vidarsson, Gestur/0000-0001-5621-003X NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A751 EP A751 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237104168 ER PT J AU Jubran, A Preas, HL Suffredini, AF Tobin, MJ AF Jubran, A Preas, HL Suffredini, AF Tobin, MJ TI Is variational activity of breathing during endotoxemia in humans modulated by the cyclooxygenase pathway? SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 Loyola Univ, Hines VA Hosp, Hines, IL USA. NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A788 EP A788 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237104384 ER PT J AU Kawanami, O Jin, EJ Ghazizadeh, M Jian, L Takemura, T Ohaki, Y Takeda, K Yu, ZX Ferrans, VJ AF Kawanami, O Jin, EJ Ghazizadeh, M Jian, L Takemura, T Ohaki, Y Takeda, K Yu, ZX Ferrans, VJ TI Alterations in the expression of endothelial cell antigens in areas of bronchioloalveolar carcinoma of the lung. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 Nippon Med Sch, Inst Gerontol, Dept Mol Pathol, Kawasaki, Kanagawa, Japan. Red Cross Hosp Ctr, Dept Pathol, Tokyo, Japan. Hokusoh Hosp, Nippon Med Sch, Pathol Sect, Chiba, Japan. NHLBI, Pathol Sect, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A352 EP A352 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237101924 ER PT J AU Kim, YD Koo, JS Norford, D Gray, T Adler, K Nettesheim, P AF Kim, YD Koo, JS Norford, D Gray, T Adler, K Nettesheim, P TI Upregulation of mucin gene expression and mucin secretion in airway epithelial cells by inflammatory mediators. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 Yeungnam Univ, Med Ctr, Taegu, South Korea. NIEHS, Pulm Pathobiol Lab, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Coll Vet Med, Raleigh, NC 27695 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A36 EP A36 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237100131 ER PT J AU Knebel, W Rouhani, F Stocks, J Waldrop, D Smith, NK Brantly, M AF Knebel, W Rouhani, F Stocks, J Waldrop, D Smith, NK Brantly, M TI Serum half-life, lung epithelial lining fluid and serum concentration of alpha 1-antitrypsin following IV administration of increasing doses of alpha 1-antitrypsin. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 NHLBI, Ctr Clin, Dept Pharm, NIH, Bethesda, MD 20892 USA. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. Univ Texas, Ctr Hlth, Tyler, TX 75710 USA. Univ Florida, Coll Med, Gainesville, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A192 EP A192 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237101038 ER PT J AU Kristof, AS Marks-Konczalik, J Moss, J AF Kristof, AS Marks-Konczalik, J Moss, J TI Multiple signaling pathways mediate activation of the human inducible nitric oxide synthase (hiNOS) promoter by lipopolysaccharide (LPS) and cytokines in A549 cells. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A184 EP A184 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237100989 ER PT J AU Leidy, NK Knebel, A AF Leidy, NK Knebel, A TI The role of meaning, enjoyment, and symptoms in the functional performance of patients with COPD. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 NIH, NINR, Bethesda, MD 20892 USA. MEDTAP Int, Ctr Hlth Outcomes Res, Bethesda, MD USA. NIH, Ctr Clin, Dept Nursing, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A458 EP A458 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237102541 ER PT J AU Mandava, S Kolobow, T Vitale, G Foti, G Aprigliano, M Jones, M Muller, E AF Mandava, S Kolobow, T Vitale, G Foti, G Aprigliano, M Jones, M Muller, E TI Lethal systemic capillary leak syndrome associated with barotrauma. An experimental study. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 NHLBI, PCCMB, SPCAD, NIH, Bethesda, MD 20892 USA. RI Foti, Giuseppe/K-8627-2016 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A603 EP A603 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237103341 ER PT J AU Matsui, K Takeda, K Yu, ZX Stetler-Stevenson, W Travis, WD Moss, J Ferrans, VJ AF Matsui, K Takeda, K Yu, ZX Stetler-Stevenson, W Travis, WD Moss, J Ferrans, VJ TI Immunohistochemical study of estrogen (ER) and progesterone (PR) receptors in the abnormal smooth muscle cells (LAM cells) in pulmonary lymphangioleiomyomatosis (LAM). SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 NHLBI, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. Armed Forces Inst Pathol, Washington, DC 20306 USA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A704 EP A704 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237103920 ER PT J AU Matsui, K Takeda, K Yu, ZX Stetler-Stevenson, W Travis, WD Moss, J Ferrans, VJ AF Matsui, K Takeda, K Yu, ZX Stetler-Stevenson, W Travis, WD Moss, J Ferrans, VJ TI Role of matrix metalloproteinase (MMP) activation in the pamogwesis of pulmonary lymphangioleiomyomatosis (LAM). SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 NHLBI, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. Armed Forces Inst Pathol, Washington, DC 20306 USA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A704 EP A704 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237103919 ER PT J AU Novoradovskaya, N Lee, JH Brantly, M AF Novoradovskaya, N Lee, JH Brantly, M TI Secretion of pi*Z alpha-1-antitrypsin is regulated in part by chaperones. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 Univ Florida, Coll Med, Div Pulm & Crit Care Med, Gainesville, FL USA. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A191 EP A191 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237101033 ER PT J AU O'Grady, NP Preas, HL Pugin, J Martin, TR Suffredini, AF AF O'Grady, NP Preas, HL Pugin, J Martin, TR Suffredini, AF TI Inflammatory modulating proteins are found 48 hours after local endotoxin administration in humans. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 NIH, Dept Crit Care Med, Bethesda, MD USA. Univ Hosp Geneva, Geneva, Switzerland. Seattle VA Med Ctr, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A601 EP A601 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237103327 ER PT J AU O'Grady, NP Tropea, M Filie, A Reda, D Suffredini, AF AF O'Grady, NP Tropea, M Filie, A Reda, D Suffredini, AF TI Alterations in lymphocytes during the acute pulmonary inflammatory response to endotoxin in humans. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 NCI, Dept Crit Care Med, NIH, Bethesda, MD 20892 USA. NCI, Cytopathol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A601 EP A601 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237103326 ER PT J AU Ogasawara, M Kim, SC Adamik, R Moss, J Vaughan, M AF Ogasawara, M Kim, SC Adamik, R Moss, J Vaughan, M TI Regulation of the secretory apparatus: Molecular cloning and characterization of cytohesin-4, a new human cytohesin with guanine nucleotide-exchange activity for ADP-ribosylation factors. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A186 EP A186 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237101003 ER PT J AU Pacheco-Rodriguez, G Vitale, N Adamik, R Moss, J Vaughan, M AF Pacheco-Rodriguez, G Vitale, N Adamik, R Moss, J Vaughan, M TI Regulation of the secretory apparatus: Evidence for the specific interaction of cytohesin-1 and ARD1, a 64-kDa GTPase with an ADP-ribosylation factor-related domain. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RI Vitale, nicolas/G-5967-2014 OI Vitale, nicolas/0000-0002-4752-4907 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A186 EP A186 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237101004 ER PT J AU Paone, G Krein, P Rouhani, F Brantly, M AF Paone, G Krein, P Rouhani, F Brantly, M TI Human neutrophil peptides stimulate alveolar macrophage production of LTB4 and IL-8 SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. Univ Florida, Coll Med, Div Pulm & Crit Care Med, Gainesville, FL 32611 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A511 EP A511 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237102812 ER PT J AU Parent, C Esposito, C Kalil, A Natanson, C Sevransky, J Danner, R Banks, S Roettinger, A Obeid, J Fitz, Y Eichacker, PO AF Parent, C Esposito, C Kalil, A Natanson, C Sevransky, J Danner, R Banks, S Roettinger, A Obeid, J Fitz, Y Eichacker, PO TI Anti-inflammatory agents increase or decrease survival dependent on the severity of infectious challenge in sepsis models. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 NIH, CCMD, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A614 EP A614 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237103408 ER PT J AU Parent, C Natanson, C Cui, X Banks, S Eichacker, PQ AF Parent, C Natanson, C Cui, X Banks, S Eichacker, PQ TI Control mortality and exclusion criteria: Factors potentially altering the effects of anti-inflammatory therapies in clinical sepsis trials. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 NIH, CCMD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A263 EP A263 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237101418 ER PT J AU Rice, AB Moomaw, CR Morgan, DL Bonner, JC AF Rice, AB Moomaw, CR Morgan, DL Bonner, JC TI Amelioration of pulmonary fibrosis in rats using tyrosine kinase inhibitors specific for PDGF- or EGF receptor. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 NIEHS, Pulm Pathobiol Lab, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A71 EP A71 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237100329 ER PT J AU Rivera-Nieves, J Levine, RL Thompson, WC Moss, J AF Rivera-Nieves, J Levine, RL Thompson, WC Moss, J TI Mechanisms of protein modification by reactive oxygen species: Low molecular weight thiols mediate superoxide-dependent cross-linking of NADH to glyceraldehyde-3-phosphate dehydrogenase (GAPDH). SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RI Levine, Rodney/D-9885-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A883 EP A883 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237104939 ER PT J AU Rouhani, F Gahl, WA Tobias, C Jolley, C Brantly, M AF Rouhani, F Gahl, WA Tobias, C Jolley, C Brantly, M TI Cellular and cytokine characteristics of epithelial lining fluid in individuals with pulmonary fibrosis who harbor a 16-BP duplication in the Hermansky-Pudlak syndrome gene. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. NICHD, Sect Human Biochem Genet, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. Univ Florida, Coll Med, Div Pulm & Crit Care Med, Gainesville, FL 32611 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A503 EP A503 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237102775 ER PT J AU Sata, M Moss, J Vaughan, M AF Sata, M Moss, J Vaughan, M TI Regulation of the secretory apparatus: Molecular basis for the inhibitory effects of brefeldin A on guanine nucleotide-exchange proteins for ADP-ribosylation factors (ARFs). SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A186 EP A186 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237101002 ER PT J AU Scarborough, PE Bonner, JC Zeldin, DC AF Scarborough, PE Bonner, JC Zeldin, DC TI Prostaglandin E-2 alters the response of human lung fibroblasts to platelet-derived growth factors SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 NIEHS, Pulm Pathobiol Lab, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A454 EP A454 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237102519 ER PT J AU Sevransky, JE Vandivier, RW Quezado, ZMN Eichacker, PQ Danner, RL Banks, SM Bacher, J Thomas, ML Natanson, C AF Sevransky, JE Vandivier, RW Quezado, ZMN Eichacker, PQ Danner, RL Banks, SM Bacher, J Thomas, ML Natanson, C TI The effect of L-NMMA on TNF induced cardiac dysfunction SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. RI Quezado, Zenaide/O-4860-2016 OI Quezado, Zenaide/0000-0001-9793-4368 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A245 EP A245 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237101335 ER PT J AU Sheehan, J Howard, M Thornton, D Gray, T Koo, JS Nettesheim, P AF Sheehan, J Howard, M Thornton, D Gray, T Koo, JS Nettesheim, P TI Early passage normal human tracheobronchial epithelial cells produce MUC5AC and MUC5B mucins. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 Univ Manchester, Manchester, Lancs, England. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A474 EP A474 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237102625 ER PT J AU Stover, CK Yuan, Y Warrener, PG VanDevanter, DR Sherman, DR Langhorne, MH Tanaka, K Barry, CE Baker, WR AF Stover, CK Yuan, Y Warrener, PG VanDevanter, DR Sherman, DR Langhorne, MH Tanaka, K Barry, CE Baker, WR TI A novel compound series and development candidate for the treatment of tuberculosis. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 Pathogenesis Corp, Seattle, WA USA. NIAID, TB Res Sect, NIH, Rockville, MD USA. RI Barry, III, Clifton/H-3839-2012 NR 0 TC 0 Z9 1 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A16 EP A16 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237100016 ER PT J AU Su, WY Jaskot, RH Kodavanti, U Stetler-Stevenson, W Costa, DL Dreher, KL AF Su, WY Jaskot, RH Kodavanti, U Stetler-Stevenson, W Costa, DL Dreher, KL TI Air particulate-induction of pulmonary gelatinase A and B gene expression SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 Duke Univ, Med Ctr, Durham, NC USA. US EPA, Res Triangle Pk, NC 27711 USA. NCI, Bethesda, MD 20892 USA. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A28 EP A28 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237100079 ER PT J AU Sunday, ME Yoder, BA Torday, JS Sikorski, KA Cuttitta, F Emanuel, RL AF Sunday, ME Yoder, BA Torday, JS Sikorski, KA Cuttitta, F Emanuel, RL TI Bombesin-like peptide (BLP) as a mediator of lung injury in two different baboon models of bronchopulmonary dysplasia (BPD). SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. SW Fdn Biomed Res, San Antonio, TX 78284 USA. Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90509 USA. NCI, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A256 EP A256 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237101385 ER PT J AU Togawa, A Ogasawara, M Moss, J Vaughan, M AF Togawa, A Ogasawara, M Moss, J Vaughan, M TI Regulation of the secretory apparatus. Purification and cloning of a brefeldin A-inhibited guanine nucleotide-exchange protein for ADP-ribosylation factors. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 NHLBI, PCCMB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A186 EP A186 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237101001 ER PT J AU Torday, J Schultz, CJ Londos, C AF Torday, J Schultz, CJ Londos, C TI On the cell/molecular mechanism of neutral lipid trafficking in surfactant phospholipid production. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 Harbor UCLA Med Ctr, Torrance, CA 90509 USA. NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A892 EP A892 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237104992 ER PT J AU Travis, WD Matsui, K Moss, J Ferrans, VJ AF Travis, WD Matsui, K Moss, J Ferrans, VJ TI Nonspecific interstitial pneumonia: A spectrum of cellular and fibrotic interstitial pneumonia. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 Armed Forces Inst Pathol, Washington, DC 20306 USA. NHLBI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A65 EP A65 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237100294 ER PT J AU Vallyathan, V Ding, M Shi, X Li, JJ Leonard, S Ye, JP Colburn, NH Castranova, V AF Vallyathan, V Ding, M Shi, X Li, JJ Leonard, S Ye, JP Colburn, NH Castranova, V TI Involvement of vanadate-mediated reactive oxygen species in the activation of transcription factor AP-1. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 NIOSH, Morgantown, WV USA. NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A287 EP A287 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237101550 ER PT J AU Wang, YZ Bonner, JC AF Wang, YZ Bonner, JC TI Metal-induced activation of MAP kinase in rat pulmonary myofibroblasts is mediated by reactive oxygen species (ROS) and EGF receptor phosphorylation. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 NIEHS, Pulm Pathobiol Lab, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A284 EP A284 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237101535 ER PT J AU Yao, XL Huang, XL Gladwin, MT Cowan, MJ Logun, C Shelhamer, JH AF Yao, XL Huang, XL Gladwin, MT Cowan, MJ Logun, C Shelhamer, JH TI Interferon gamma and tumor necrosis factor alpha induce p11 production in human airway epithelial cells. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A448 EP A448 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237102486 ER PT J AU Yao, XL Cowan, MJ Gladwin, MT Lawrence, M Shelhamer, JH AF Yao, XL Cowan, MJ Gladwin, MT Lawrence, M Shelhamer, JH TI Dexamethasone inhibits cytosolic phospholipase A(2) activity in human epithelial cells by increasing p11 production. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A333 EP A333 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237101813 ER PT J AU Zhang, L Adler, K Sannes, P Bonner, JC AF Zhang, L Adler, K Sannes, P Bonner, JC TI Normal human bronchial epithelial cells produce heparin-binding epidermal growth factor (HB-EGF), a mitogen for human lung fibroblasts in vitro. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 NIEHS, Lab Pulm Pathobiol, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Coll Vet Med, Raleigh, NC 27606 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 1999 VL 159 IS 3 SU S BP A508 EP A508 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 230DT UT WOS:000082237102799 ER PT J AU Boyle, JE Lindroos, PM Rice, AB Zhang, LM Zeldin, DC Bonner, JC AF Boyle, JE Lindroos, PM Rice, AB Zhang, LM Zeldin, DC Bonner, JC TI Prostaglandin-E-2 counteracts interleukin-1 beta-stimulated upregulation of platelet-derived growth factor alpha-receptor on rat pulmonary myofibroblasts SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID HUMAN LUNG FIBROBLASTS; SMOOTH-MUSCLE CELLS; ALVEOLAR MACROPHAGES; CHRYSOTILE ASBESTOS; GENE-EXPRESSION; E(2) SYNTHESIS; FIBROSIS; PROLIFERATION; ACTIVATION; CYCLOOXYGENASE-2 AB The platelet-derived growth factor (PDGF) alpha-receptor (PDGF-R alpha) is upregulated during lung fibrogenesis, and induction of PDGF-R alpha on cultured lung myofibroblasts by interleukin (IL)-1 beta results in an increased mitogenic response to PDGF. Because IL-1 beta stimulates prostaglandin (PG) E-2 production, we investigated whether IL-1 beta could upregulate PDGF-R alpha via a PGE(2)-dependent mechanism. IL-1 beta increased the production of PGE, by rat lung myofibroblasts and the cyclooxygenase (COX) inhibitor indomethacin blocked IL-1 beta-induced PGE(2) production. However, indomethacin did not inhibit IL-1 beta-stitnulated upregulation of [I-125]PDGF-AA binding sites, indicating that PDGF-R alpha induction does not require PGE(2) synthesis. Instead, PGE(2) downregulated PDGF-R alpha protein and messenger RNA expression, and counteracted the IL-1 beta-stimulated increase in [I-125]PDGF-AA binding. Pretreatment of cells with indomethacin or the COX-2 specific inhibitor NS-398 attenuated the suppressive effect of exogenous PGE(2) on PDGF-R alpha, indicating that endogenous PGE(2) released by IL-1 beta treatment also contributed to downregulation of PDGF-R alpha. PDGF-R alpha expression was not altered by IL-1 beta or PGE(2). Pretreatment of myofibroblasts with IL-1 beta increased PDGF-stimulated mitogenesis, and this effect was blocked by coincubation with PGE(2). In contrast, PGE, enhanced epidermal growth factor- or basic fibroblast growth factor-2-stimulated cell proliferation similar to 50%. Because IL-1 beta upregulates both PGE(2) production and PDGF-R alpha expression, these data suggest that PGE(2) functions in a negative feedback loop to limit expression of PDGF-R alpha and suppress PDGF-stimulated myofibroblast proliferation. C1 NIEHS, Pulm Pathobiol Lab, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Div Pulm & Crit Care Med, Chapel Hill, NC USA. RP Bonner, JC (reprint author), NIEHS, Pulm Pathobiol Lab, POB 12233, Res Triangle Pk, NC 27709 USA. EM bonnerj@niehs.nih.gov NR 37 TC 26 Z9 26 U1 0 U2 1 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD MAR PY 1999 VL 20 IS 3 BP 433 EP 440 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 177DL UT WOS:000079192100009 PM 10030841 ER PT J AU Novoradovsky, A Brantly, ML Waclawiw, MA Chaudhary, PP Ihara, H Qi, L Eissa, NT Barnes, PM Gabriele, KM Ehrmantraut, ME Rogliani, P Moss, J AF Novoradovsky, A Brantly, ML Waclawiw, MA Chaudhary, PP Ihara, H Qi, L Eissa, NT Barnes, PM Gabriele, KM Ehrmantraut, ME Rogliani, P Moss, J TI Endothelial nitric oxide synthase as a potential susceptibility gene in the pathogenesis of emphysema in alpha 1-antitrypsin deficiency SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID LUNG-DISEASE; CAVEOLAE; DNA AB A role for endothelial nitric oxide synthase (NOS3) in the susceptibility of individuals with alpha 1-antitrypsin (alpha 1AT) deficiency to destructive lung disease was evaluated. Six polymorphic sites were identified within the NOS3 gene (i.e., -924A/G, -788C/T, -691C/T, 774C/T, 894G/T, and 1998C/G). The genotype distribution was determined in 339 patients and 94 control individuals. Frequency of the 774T allele in severely affected individuals was 0.417 versus 0.269 in control subjects (P = 0.018), whereas the 894T allele frequency was 0.427 versus 0.280 in control subjects (P = 0.024). Patients with less severe lung disease had the 774T and 894T allele frequencies of 0.289 and 0.344, respectively, similar to frequencies in a control group (P > 0.3). No direct correlation between pulmonary function and five other NOS3 polymorphisms was observed. Thus, functional allelic variants that are in linkage disequilibrium with the 774C/T and 894G/T may be present in the specified genomic area. These data are consistent with a modulatory role for NOS3 in destructive lung disease associated with alpha 1AT deficiency. C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. RP Moss, J (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, Bldg 10,Room 6D03,10 Ctr Dr,MSC 1590, Bethesda, MD 20892 USA. OI Rogliani, Paola/0000-0001-7801-5040 NR 19 TC 48 Z9 56 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD MAR PY 1999 VL 20 IS 3 BP 441 EP 447 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 177DL UT WOS:000079192100010 PM 10030842 ER PT J AU Pugin, J Widmer, MC Kossodo, S Liang, CM Preas, HL Suffredini, AF AF Pugin, J Widmer, MC Kossodo, S Liang, CM Preas, HL Suffredini, AF TI Human neutrophils secrete gelatinase B in vitro and in vivo in response to endotoxin and proinflammatory mediators SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID MATRIX METALLOPROTEINASE EXPRESSION; BACTERIAL-ENDOTOXIN; COLLAGENASE; RECEPTOR; CELLS; PURIFICATION; MACROPHAGES; MECHANISMS; GRANULES; SEPSIS AB Bacterial sepsis is characterized by a systemic inflammatory state, with activation of numerous cell types. Phagocytes participate in this phenomenon by secreting various proinflammatory cytokines and enzymes. Matrix metalloproteinases (MMPs) such as gelatinases are produced by phagocytes and are thought to play an important role in processes of cell transmigration and tissue remodeling. In this work, we show that endotoxin (lipopolysaccharide [LPS]) and other inflammatory mediators, such as tumor necrosis factor (TNF), interleukin-8, and granulocyte colony-stimulating factor, induce a rapid (within 20 min) release of gelatinase-B (MMP-9) zymogen in whole human blood, as determined by gelatin zymography. The polymorphonuclear neutrophil was identified as the cell responsible for this rapid secretion. as a result of the release of preformed enzymes stored in granules. Normal human subjects given LPS intravenously showed a similar pattern of proMMP-9 secretion, with maximum plasma levels reached 1.5 to 3 h after LPS administration (P = 0.0009). Prior administration of TNF receptor:Fc, a potent TNF antagonist, to subjects given LPS, only partially blunted the release of proMMP-9 (P = 0.033). Ibuprofen. a cyclooxygenase inhibitor, did not alter this pattern of release. Increased levels of proMMP-9 and proMMP-2, as well as activated forms of MMP-9, were found in plasma from two patients with gram-negative sepsis. The levers of MMPs paralleled die severity of clinical condition and a marker of the severity of sepsis, plasma procalcitonin. These data indicate that MMPs are released in whole blood in response to various inflammatory mediators and that they could serve as sensitive and early markers for cell activation during the course of bacterial sepsis. C1 Univ Hosp Geneva, Div Med Crit Care, Dept Med, CH-1211 Geneva 14, Switzerland. Univ Hosp Geneva, Dept Anesthesiol Surg Intens Care & Pharmacol, CH-1211 Geneva, Switzerland. NIH, Dept Crit Care Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Pugin, J (reprint author), Univ Hosp Geneva, Div Med Crit Care, Dept Med, 24 R Micheli du Crest, CH-1211 Geneva 14, Switzerland. NR 25 TC 161 Z9 163 U1 0 U2 3 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD MAR PY 1999 VL 20 IS 3 BP 458 EP 464 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 177DL UT WOS:000079192100012 PM 10030844 ER PT J AU Sempos, CT Bild, DE Manolio, TA AF Sempos, CT Bild, DE Manolio, TA TI Overview of the Jackson Heart Study: A study of cardiovascular diseases in African American men and women SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article; Proceedings Paper CT Symposium on Cardiovascular Disease in African Americans CY NOV, 1997 CL JACKSON, MISSISSIPPI SP Jackson Heart Study DE cardiovascular disease; heart disease; stroke; blood pressure; serum cholesterol; race; blacks; African Americans ID UNITED-STATES; RACIAL-DIFFERENCES; STROKE MORTALITY; RISK-FACTORS; BLACK; HYPERTENSION; HEALTH; DECLINE; ADULTS; WHITES AB The Jackson Heart Study is a partnership among Jackson State University, Tougaloo College, the University of Mississippi Medical Center and the National Institutes of Health's National Heart, Lung, and Blood Institute (NHLBI) and Office of Research on Minority Health. The purposes of the study are to: (1) establish a single-site cohort study to identify the risk factors for the development of cardiovascular diseases, especially those related to hypertension, in African American men and women; (2) build research capabilities in minority institutions by building partnerships; (3) attract minority students to careers in public health and epidemiology; and (4) establish an NHLBI Field Site in Jackson, Mississippi, similar to those established for the Framingham Heart Study and the Honolulu Heart Program. The study will consist of participants from the Jackson site of the Atherosclerosis Risk in Communities (ARIC) Study and a sample of residents from the Jackson metropolitan area. The study will have a sample size of approximately 6,500 men and women aged 35-84 years and will include approximately 400 families. Exam 1 is scheduled to take place in the spring of the year 2000. C1 NHLBI, Epidemiol & Biometry Program, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. RP Sempos, CT (reprint author), NIH, Off Res Minor Hlth, Bldg 1,Room 255, Bethesda, MD 20892 USA. NR 22 TC 48 Z9 49 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD MAR PY 1999 VL 317 IS 3 BP 142 EP 146 DI 10.1097/00000441-199903000-00002 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 179DV UT WOS:000079311100002 PM 10100686 ER PT J AU Benjamin, EJ Levy, D AF Benjamin, EJ Levy, D TI Why is left ventricular hypertrophy so predictive of morbidity and mortality? SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article; Proceedings Paper CT Symposium on Cardiovascular Disease in African Americans CY NOV, 1997 CL JACKSON, MISSISSIPPI SP Jackson Heart Study DE left ventricular hypertrophy; cohort studies; African American; echocardiography; prognosis ID CORONARY-ARTERY DISEASE; BLOOD-PRESSURE; CARDIOVASCULAR HEALTH; PROGNOSTIC IMPLICATIONS; ESSENTIAL-HYPERTENSION; MYOCARDIAL-INFARCTION; SYSTEMIC HYPERTENSION; CARDIAC-HYPERTROPHY; MILD HYPERTENSION; ELDERLY COHORT AB The prevalence, prognosis, and predictors of left ventricular hypertrophy (LVH) are reviewed, and theories of the pathogenesis of the relation between LVH and poor prognosis are summarized to highlight controversies in the field. In the Framingham Heart Study, which consists largely of white people, echocardiographic LVH has a prevalence of 14% in men and 18% in women. The prevalence of LVH is reported to be elevated in African Americans compared with whites, although the higher prevalence has been attributed to the increased prevalence of hypertension and obesity. Echocardiographic LVH is independently associated with a variety of cardiovascular endpoints, including coronary heart disease and stroke. Furthermore, after adjusting for other cardiovascular disease risk factors, LVH is associated with a doubling in mortality in both white and African American cohorts. Despite the intensive investigation of LVH, there remain many unanswered questions: To what extent do genetic or other factors account for the large portion of the variance in LVH that remains unexplained? What is the prognosis of LVH and left ventricular geometry in a population-based African American cohort? How does the development and progression of LVH relate to other risk factors and their treatment? What is the relation of LVH to poor prognosis? The proposed Jackson Heart Study will help address many important unanswered questions regarding LVH. C1 NHLBI, Framingham Heart Study, Boston, MA USA. Boston Med Ctr, Div Cardiol, Boston, MA USA. Boston Med Ctr, Div Prevent Med, Boston, MA USA. Harvard Univ, Sch Med, Beth Israel Deaconess Hosp, Div Cardiol, Boston, MA USA. Harvard Univ, Sch Med, Beth Israel Deaconess Hosp, Div Clin Epidemiol, Boston, MA USA. NHLBI, Bethesda, MD 20892 USA. RP Benjamin, EJ (reprint author), Framingham Heart Study, 5 Thurber St, Framingham, MA 01702 USA. EM emelia@fram.nhlbi.nih.gov FU NHLBI NIH HHS [N01-HC38038]; NINDS NIH HHS [5-R01-NS17950-16] NR 79 TC 109 Z9 118 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD MAR PY 1999 VL 317 IS 3 BP 168 EP 175 DI 10.1097/00000441-199903000-00006 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 179DV UT WOS:000079311100006 PM 10100690 ER PT J AU Collins, WE Kaslow, DC Sullivan, JAS Morris, CL Galland, GG Yang, CF Saekhou, AM Xiao, LH Lal, AA AF Collins, WE Kaslow, DC Sullivan, JAS Morris, CL Galland, GG Yang, CF Saekhou, AM Xiao, LH Lal, AA TI Testing the efficacy of a recombinant merozoite surface protein (MSP-1(19)) of Plasmodium vivax in Saimiri boliviensis monkeys SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID MULTIPLE ANTIGEN CONSTRUCT; AOTUS-NANCYMAI MONKEYS; SALVADOR I-STRAIN; T-CELL EPITOPES; CIRCUMSPOROZOITE PROTEIN; SCIUREUS-BOLIVIENSIS; ANOPHELINE MOSQUITOS; OWL MONKEYS; SPOROZOITE TRANSMISSION; TETANUS TOXIN AB Saimiri boliviensis monkeys were immunized with the yeast-expressed recombinant protein yP(2)P(30)Pv200(19). The antigen consisted of the C-terminus (amino acid Asn(1622)-Ser(1729)) of the merozoite surface protein 1 of the Plasmodium vivax Salvador I strain. Two universal T helper cell epitopes (P-2 and P-30) of tetanus toxin and six histidine residues for purification purposes were attached to the N- and C-termini, respectively. Four groups of five monkeys were given three immunizations at four-week intervals with either 250 mu g of yP(2)P(30)Pv200(19) formulated with nonionic block copolymer P1005, 250 mu g of antigen adsorbed to alum, 250 mu g of antigen in phosphate-buffered saline (PBS), or PBS alone. Five weeks after the last immunization, each animal was inoculated with 100,000 parasitized erythrocytes of the Salvador I strain of P. vivax. Animals were splenectomized one week after challenge to increase parasite densities; after seven weeks of infection, animals were treated. Eighteen weeks later, the animals were rechallenged with the homologous parasite. Following the first challenge, three monkeys immunized with the antigen with P1005 were protected; no animals were protected from rechallenge. One monkey immunized with yP(2)P(30)Pv200(19) with alum was protected; no protection was seen after rechallenge. Two monkeys immunized with antigen alone were protected; none were protected from rechallenge. One control animal had a low parasite count following primary infection; none were protected against rechallenge. Adverse reactions were only observed with animals receiving P1005. It is proposed that splenectomy of the monkeys prevented adequate assessment of the efficacy of this antigen. Identification of a monkey host that supports high density parasitemia without splenectomy appears needed before further testing of blood-stage vaccines against P. vivax. C1 Ctr Dis Control & Prevent, Div Parasit Dis, Natl Ctr Infect Dis, Atlanta, GA 30341 USA. Ctr Dis Control & Prevent, Sci Resources Program, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Collins, WE (reprint author), Ctr Dis Control & Prevent, Div Parasit Dis, Natl Ctr Infect Dis, Mailstop F-12,4770 Buford Highway, Atlanta, GA 30341 USA. RI Xiao, Lihua/B-1704-2013; Yang, Chunfu/G-6890-2013 OI Xiao, Lihua/0000-0001-8532-2727; NR 30 TC 39 Z9 40 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DRIVE SUITE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD MAR PY 1999 VL 60 IS 3 BP 350 EP 356 PG 7 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 182PG UT WOS:000079506900004 PM 10466960 ER PT J AU Sigueland, L Horn, A Moras, K Woody, G Weiss, R Blaine, J Bishop, S Barber, J Thase, M AF Sigueland, L Horn, A Moras, K Woody, G Weiss, R Blaine, J Bishop, S Barber, J Thase, M TI Cocaine-induced mood disorder: Prevalence rates and psychiatric symptoms in an outpatient cocaine-dependent sample SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID COMORBIDITY; ADDICTS AB This paper attempts to examine and compare prevalence rates and symptom patterns of DSM substance-incduced and other mood disorders. 243 cocaine-dependent outpatients with cocaine-induced mood disorder (CIMD) other mood disorders, or no mood disorder were compared on measures of psychiatric symptoms. prevalence rate for CIMD was 12% at baseline. Introduction of the DSM-IV diagnosis of CIMD did not substantially affect rates of the other depressive disorders. Patients with CIMD had symptom severity levels between those of patients with and without a mood disorder. These findings suggest some validity for the new DSM-IV diagnosis of CIMD, but also suggest that it requires further specification and replication. C1 Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Philadelphia Vet Hosp, Philadelphia, PA 19104 USA. Harvard Univ, McLean Hosp, Sch Med, Belmont, MA 02178 USA. NIDA, Bethesda, MD USA. Brookside Hosp, Nashua, NH USA. Univ Pittsburgh, Western Psychiat Inst & Clin, Pittsburgh, PA 15260 USA. RP Sigueland, L (reprint author), Univ Penn, Dept Psychiat, 3600 Market St,Room 705, Philadelphia, PA 19104 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD SPR PY 1999 VL 8 IS 2 BP 165 EP 169 PG 5 WC Substance Abuse SC Substance Abuse GA 198DH UT WOS:000080407000010 ER PT J AU Livneh, A Langevitz, P Shinar, Y Zaks, N Kastner, DL Pras, M Pras, E AF Livneh, A Langevitz, P Shinar, Y Zaks, N Kastner, DL Pras, M Pras, E TI MEFV mutation analysis in patients suffering from amyloidosis of familial Mediterranean fever SO AMYLOID-INTERNATIONAL JOURNAL OF EXPERIMENTAL AND CLINICAL INVESTIGATION LA English DT Article DE amyloidosis; FMF; pyrin; colchicine ID GENE; ARMENIANS; SPECTRUM AB Familial Mediterranean fever (FMF) is a major cause of AA amyloidosis. Recently, the gene (MEFV) causing this disease was cloned and 16 disease associated mutations have been described. We have analyzed 178 FMF;patients, 30 of whom also suffered from amyloidosis, for 4 mutations in MEFV. Mutations were identified in 29 of the FMF amyloidosis patients. 27 FMF amyloidosis patients were homozygous for M694V. One patient was found to be homozygous for both V726A and E148Q in another patient E148Q and V726A were found on one allele, while V726A was found on the second allele. Amyloidosis was far more common among patients homozygous for M694V compared to patients with other mutations (P<0.0001). In 3 patients homozygous for M694V, amyloidosis was the sole manifestation of the disease. C1 Chaim Sheba Med Ctr, Inst Human Genet, IL-62521 Tel Hashomer, Israel. Chaim Sheba Med Ctr, Heller Inst Med Res, IL-62521 Tel Hashomer, Israel. Chaim Sheba Med Ctr, Dept Med F, IL-62521 Tel Hashomer, Israel. Chaim Sheba Med Ctr, Dept Med C, IL-62521 Tel Hashomer, Israel. NIAMSD, Genet Sect, NIH, Bethesda, MD 20892 USA. RP Pras, E (reprint author), Chaim Sheba Med Ctr, Inst Human Genet, IL-62521 Tel Hashomer, Israel. EM epras@cc.tau.ac.il NR 25 TC 137 Z9 138 U1 0 U2 4 PU PARTHENON PUBLISHING GROUP PI CARNFORTH LANCASHIRE PA CASTERTON HALL, CARNFORTH LANCASHIRE LA6 2LA, ENGLAND SN 1350-6129 J9 AMYLOID JI Amyloid-Int. J. Exp. Clin. Investig. PD MAR PY 1999 VL 6 IS 1 BP 1 EP 6 DI 10.3109/13506129908993281 PG 6 WC Biochemistry & Molecular Biology; Medicine, General & Internal; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; General & Internal Medicine; Research & Experimental Medicine GA 183KG UT WOS:000079552300001 PM 10211405 ER PT J AU Sipe, J AF Sipe, J TI Part 2 - Revised nomenclature for serum amyloid A (SAA) SO AMYLOID-INTERNATIONAL JOURNAL OF EXPERIMENTAL AND CLINICAL INVESTIGATION LA English DT Editorial Material ID AMINO-ACID-SEQUENCE; A GENE FAMILY; COMPLEMENTARY-DNA; PROTEIN; IDENTIFICATION; EXPRESSION; COMPONENT; VARIANT RP Sipe, J (reprint author), NIH, Ctr Sci Review, 6701 Rockledge Dr, Bethesda, MD 20892 USA. NR 25 TC 75 Z9 77 U1 0 U2 5 PU PARTHENON PUBLISHING GROUP PI CARNFORTH LANCASHIRE PA CASTERTON HALL, CARNFORTH LANCASHIRE LA6 2LA, ENGLAND SN 1350-6129 J9 AMYLOID JI Amyloid-Int. J. Exp. Clin. Investig. PD MAR PY 1999 VL 6 IS 1 BP 67 EP 70 DI 10.3109/13506129908993291 PG 4 WC Biochemistry & Molecular Biology; Medicine, General & Internal; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; General & Internal Medicine; Research & Experimental Medicine GA 183KG UT WOS:000079552300009 PM 10211414 ER PT J AU Schaeberle, MD Morris, HR Turner, JF Treado, PJ AF Schaeberle, MD Morris, HR Turner, JF Treado, PJ TI Raman chemical imaging spectroscopy SO ANALYTICAL CHEMISTRY LA English DT Article ID ACOUSTOOPTIC TUNABLE FILTER; BREAST-TISSUE; MICROSCOPY; COMPOSITES; EXCITATION; STRESS; IMAGES; AOTF C1 ChemIcon Inc, Pittsburgh, PA 15208 USA. NIH, Bethesda, MD 20892 USA. Duquesne Univ, Pittsburgh, PA 15219 USA. RP Treado, PJ (reprint author), ChemIcon Inc, 7301 Penn Ave, Pittsburgh, PA 15208 USA. EM treado@chemimage.com NR 32 TC 54 Z9 55 U1 0 U2 18 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD MAR 1 PY 1999 VL 71 IS 5 BP 175A EP 181A PG 7 WC Chemistry, Analytical SC Chemistry GA 171AR UT WOS:000078840300008 PM 21651209 ER PT J AU Njoku, DB Martin, JL Pohl, LR AF Njoku, DB Martin, JL Pohl, LR TI Renal cysteine conjugate beta-lyase and compound A nephrotoxicity: Minimal evidence for an association SO ANESTHESIOLOGY LA English DT Letter C1 Johns Hopkins Hosp, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21287 USA. NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. NHLBI, Mol & Cellular Toxicol Sect, NIH, Bethesda, MD 20892 USA. RP Njoku, DB (reprint author), Johns Hopkins Hosp, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21287 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD MAR PY 1999 VL 90 IS 3 BP 921 EP 921 DI 10.1097/00000542-199903000-00043 PG 1 WC Anesthesiology SC Anesthesiology GA 172PB UT WOS:000078932000043 PM 10078700 ER PT J AU Berger, AC Buell, JF Venzon, D Baker, AR Libutti, SK AF Berger, AC Buell, JF Venzon, D Baker, AR Libutti, SK TI Management of symptomatic malignant melanoma of the gastrointestinal tract SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 51st Annual Meeting of the Society-of-Surgical-Oncology CY MAR 26-29, 1998 CL SAN DIEGO, CALIFORNIA SP Soc Surg Oncol DE metastatic melanoma; surgery; survival; chemotherapy; immunotherapy ID SMALL-BOWEL; METASTASES AB Background: Melanoma metastatic to the gastrointestinal (GI) tract is asymptomatic or presents with pain, bleeding, or obstruction. To determine whether surgery influences outcomes, we reviewed our experience with this patient population. Methods: Medical records of patients with metastatic melanoma to the GI tract were reviewed. Patients were divided into four groups, i.e., complete resection, partial debulking, unresectable, or unexplored. Analysis was performed using the Kaplan-Meier method. Results: Fifty patients with melanoma metastatic to the GI tract were identified (40 men and 10 women; mean age, 44 years). Presenting symptoms included pain (62%), bleeding (28%), and obstruction (18%). Diagnosis was confirmed using contrast studies (38%), endoscopy (20%), or computed tomography (30%). Thirty-six patients (61%) underwent a total of 39 operations. Seventeen patients underwent complete resection, whereas 14 underwent partial debulking. Five patients had unresectable lesions, and 14 patients did not undergo exploration because of medical contraindications. The operative mortality rate was 2.5% (1 of 39). The mean survival times for the unexplored and unresected groups were similar (4.1 months). Patients who underwent partial resection exhibited a longer mean survival time (8.9 months) than did patients in the unresected group (P < .001). The complete-resection group demonstrated a mean survival time of 23.5 months, which was significantly longer than that for patients who underwent less than complete resection (P < .0001). Conclusions: Metastatic melanoma to the GI tract can result in significant morbidity and death. Surgical resection can be performed safely. Patients for whom all sites of disease are completely resected experience significant improvements in survival times, compared with patients who undergo less than complete resection. For selected patients, surgical treatment of metastatic melanoma involving the GI tract is appropriate therapy. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Libutti, SK (reprint author), NCI, Surg Branch, NIH, Bldg 10,2B17,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Venzon, David/B-3078-2008 NR 18 TC 43 Z9 43 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD MAR PY 1999 VL 6 IS 2 BP 155 EP 160 DI 10.1007/s10434-999-0155-8 PG 6 WC Oncology; Surgery SC Oncology; Surgery GA 173CB UT WOS:000078962600011 PM 10082040 ER PT J AU Rose, EA Moskowitz, AJ Packer, M Sollano, JA Williams, DL Tierney, AR Heitjan, DF Meier, P Ascheim, DD Levitan, RG Weinberg, AD Stevenson, LW Shapiro, PA Lazar, RM Watson, JT Goldstein, DJ Gelijns, AC AF Rose, EA Moskowitz, AJ Packer, M Sollano, JA Williams, DL Tierney, AR Heitjan, DF Meier, P Ascheim, DD Levitan, RG Weinberg, AD Stevenson, LW Shapiro, PA Lazar, RM Watson, JT Goldstein, DJ Gelijns, AC CA REMATCH Invest TI The REMATCH trial: Rationale, design, and end points SO ANNALS OF THORACIC SURGERY LA English DT Article ID VENTRICULAR ASSIST DEVICE; HEART-FAILURE; CLINICAL-TRIALS; TRANSPLANTATION; QUESTIONNAIRE; MORTALITY; REGISTRY; SUPPORT; THERAPY; AGE AB Background. Because left ventricular assist devices have recently been approved by the Food and Drug Administration to support the circulation of patients with end-stage heart failure awaiting cardiac transplantation, these devices are increasingly being considered as a potential alternative to biologic cardiac replacement. The Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial is a multicenter study supported by the National Heart, Lung, and Blood Institute to compare long-term implantation of left ventricular assist devices with optimal medical management for patients with end-stage heart failure who require, but do not qualify to receive cardiac transplantation. Methods. We discuss the rationale for conducting REMATCH, the obstacles to designing this and other randomized surgical trials, the lessons learned in conducting the multicenter pilot study, and the features of the REMATCH study design (objectives, target population, treatments, end points, analysis, and trial organization). Conclusions. We consider what will be learned from REMATCH, expectations for expanding the use of left ventricular assist devices, and future directions for assessing clinical procedures. (Ann Thorac Surg 1999;67:723-30) (C) 1999 by The Society of Thoracic Surgeons. C1 Columbia Univ, Int Ctr Hlth Outcomes & Innovat Res, New York, NY 10032 USA. Columbia Univ, Coll Phys & Surg, Dept Surg, New York, NY USA. Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. Columbia Univ, Coll Phys & Surg, Dept Neurol, New York, NY USA. Columbia Univ, Sch Publ Hlth, Div Biostat, New York, NY 10032 USA. New York Presbyterian Hosp, New York, NY USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NHLBI, Bethesda, MD 20892 USA. RP Gelijns, AC (reprint author), Columbia Univ, Int Ctr Hlth Outcomes & Innovat Res, Harkness Pavil,Room 758,180 Ft Washington Ave, New York, NY 10032 USA. RI Heitjan, Daniel/D-1116-2009; OI Moskowitz, Alan/0000-0002-4412-9450 FU NHLBI NIH HHS [HL-53986] NR 27 TC 198 Z9 201 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD MAR PY 1999 VL 67 IS 3 BP 723 EP 730 DI 10.1016/S0003-4975(99)00042-9 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 187JD UT WOS:000079782800027 PM 10215217 ER PT J AU Elmore, E Sun, C Li, HR Wyatt, GP Buckmeier, JA Steele, VE Kelloff, GJ Redpath, JL AF Elmore, E Sun, C Li, HR Wyatt, GP Buckmeier, JA Steele, VE Kelloff, GJ Redpath, JL TI In vitro chemopreventive efficacy screening using human keratinocytes and the in vivo data correlation SO ANTICANCER RESEARCH LA English DT Article DE cancer prevention efficacy; in vitro; in vitro in vivo correlation; human keratinocytes; growth inhibition; involucrin expression; cytotoxicity AB Agents with potential cancer preventive activity were screened for efficacy in the Human Epidermal Cell (HEC) Assay. The HEC Assay measures inhibition of propane sultone-induced changes in the growth and/or differentiation in early passage keratinocyte cultures. The assay biomarkers were calcium tolerance, growth inhibition,:and involucrin induction. The HEC Assay also provides information on the cytotoxicity of the agents following acute and chronic exposure. Agents were evaluated at non-toxic doses in the HEC Assay. The HEC Assay has been used to screen twenty-eight agents for chemopreventive efficacy. A positive response in one or more endpoints of the HEC Assay correlates 100% (16/16) with a positive response in one or more of the animal cancer prevention models (J. Cell. Biochem., 26S:29-53, 1996). The overall sensitivity for predicting efficacy in animals is 84%. The available data suggest that a positive assay response appears to be highly predictive of efficacy in vivo. C1 Univ Calif Irvine, Dept Radiat Oncol, Irvine, CA 92697 USA. Mantech Environm Technol Inc, Cellular & Mol Toxicol Program, Res Triangle Pk, NC 27709 USA. Univ Calif Irvine, Dept Med, Irvine, CA 92697 USA. Univ Calif Irvine, Ctr Canc, Irvine, CA 92697 USA. NCI, Chemoprevent Branch, DCP, NIH, Bethesda, MD 20892 USA. RP Elmore, E (reprint author), Univ Calif Irvine, Dept Radiat Oncol, Irvine, CA 92697 USA. FU NCI NIH HHS [N01-CN-95172-04, N01-CN-15462-02, N01-CN-15462-01] NR 8 TC 4 Z9 4 U1 0 U2 2 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD MAR-APR PY 1999 VL 19 IS 2A BP 909 EP 918 PG 10 WC Oncology SC Oncology GA 202JQ UT WOS:000080649100003 PM 10368633 ER PT J AU White, EL Ross, LJ Steele, VE Kelloff, GJ Hill, DL AF White, EL Ross, LJ Steele, VE Kelloff, GJ Hill, DL TI Screening of potential cancer preventing chemicals as aromatase inhibitors in an in vitro assay SO ANTICANCER RESEARCH LA English DT Article DE chemoprevention; aromatase; vorozole; 4-hydroxyandrostenedione; ketoconazole; aminoglutethimide ID BREAST-CANCER; AROMATIZATION; CARCINOMA; WOMEN AB The inhibition of human placental aromatase was used to rank a series of compounds, with the objective of selecting compounds for further evaluation as chemopreventive agents. (+/-)-p-Aminoglutethimide, introduced over two decades ago as a treatment for breast cancer, had an IC50 of 6.5 mu M. Five compounds were more potent than aminoglutethimide in this assay: (+)- vorozole, 4-hydroxyandrostenedione, miconazole nitrate, plomestane, and 4-methoxy-androst-4-ene-3,17-dione. Other compounds with known chemoprevention activity,:such as curcumin and genistein, were inactive. This assay for aromatase inhibitors is a rapid, economical way of ranking compounds for further development as chemoprevention agents. C1 So Res Inst, Birmingham, AL 35205 USA. NCI, Rockville, MD 20852 USA. RP White, EL (reprint author), So Res Inst, 2000 9th Ave S, Birmingham, AL 35205 USA. FU NCI NIH HHS [N01-CN-65116, N01-CN-55139] NR 20 TC 5 Z9 5 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD MAR-APR PY 1999 VL 19 IS 2A BP 1017 EP 1020 PG 4 WC Oncology SC Oncology GA 202JQ UT WOS:000080649100018 PM 10368648 ER PT J AU Kearns, GL Abdel-Rahman, SM James, LP Blowey, DL Marshall, JD Wells, TG Jacobs, RF AF Kearns, GL Abdel-Rahman, SM James, LP Blowey, DL Marshall, JD Wells, TG Jacobs, RF CA Pediat Pharmacology Res Unit Network TI Single-dose pharmacokinetics of a pleconaril (VP63843) oral solution in children and adolescents SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ENTEROVIRUS; MENINGITIS; DIAGNOSIS AB Pleconaril is an orally active, broad-spectrum antipicornaviral agent which demonstrates excellent penetration into the central nervous system, liver, and nasal epithelium. In view of the potential pediatric use of pleconaril, we conducted a single-dose, open-label study to characterize the pharmacokinetics of this antiviral agent in pediatric patients. Following an 8- to 10-h period of fasting, 18 children ranging in age from 2 to 12 years (7.5 +/- 3.1 years) received a single 5-mg/kg of body weight oral dose of pleconaril solution administered with a breakfast of age-appropriate composition. Repeated blood samples (n = 10) were obtained over 24 h postdose, and pleconaril was quantified from plasma by gas chromatography. Plasma drug concentration-time data for each subject were fitted to the curve by using a nonlinear, weighted (weight = 1/Y-calc) least-squares algorithm, and model-dependent pharmacokinetic parameters were determined from the polyexponential parameter estimates. Preconaril was well tolerated hy all subjects. A one-compartment open-model with first-order absorption best described the plasma pleconaril concentration-time profile in 13 of the subjects over a 24-h postdose period. Pleconaril pharmacokinetic parameters (means +/- standard deviations) for these 13 patients were as follows. The maximum concentration of the drug in serum (C-max) was 1,272.5 +/- 622.1 ng/ml. The time to C-max was 4.1 +/- 1.5 h, and the lag time was 0.75 +/- 0.56 h. The apparent absorption rate constant was 0.75 +/- 0.48 1/h, and the elimination rate constant was 0.16 +/- 0.07 1/h. The area under the concentration-time curve from 0 to 24 h was 8,131.15 +/- 3,411.82 ng.h/ml. The apparent total plasma clearance was 0.81 +/- 0.86 liters/h/kg, and the apparent steady-state volume of distribution was 4.68 +/- 2.02 liters/kg. The mean elimination half-life of pleconaril was 5.7 h. The mean plasma pleconaril concentrations at both 12 h (250.4 +/- 148.2 ng/ml) and 24 h (137.9 +/- 92.2 ng/ml) after the single 5-mg/kg oral dose in children were higher than that: from in vitro studies reported to inhibit >90% of nonpolio enterovirus serotypes (i.e., 70 ng/ml). Thus, our data support the evaluation of a 5-mg/kg twice-daily oral dose of pleconaril for therapeutic trials in pediatric patients with enteroviral infections. C1 Childrens Mercy Hosp, Sect Pediat Clin Pharmacol & Expt Therapeut, Dept Pediat, Kansas City, MO 64108 USA. Childrens Mercy Hosp, Sect Pediat Nephrol, Kansas City, MO 64108 USA. Childrens Mercy Hosp, Sect Pediat Crit Care Med, Kansas City, MO 64108 USA. Univ Missouri, Dept Pediat, Kansas City, MO 64110 USA. Univ Missouri, Dept Pharmacol, Kansas City, MO 64110 USA. Univ Missouri, Dept Pharm Practice, Kansas City, MO 64110 USA. Arkansas Childrens Hosp, Sect Clin Pharmacol & Toxicol, Little Rock, AR 72202 USA. Arkansas Childrens Hosp, Nephrol Sect, Little Rock, AR 72202 USA. Arkansas Childrens Hosp, Sect Emergency Med, Little Rock, AR 72202 USA. Arkansas Childrens Hosp, Infect Dis Sect, Little Rock, AR 72202 USA. Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA. NICHHD, Pediat Pharmacol Res Unit, Bethesda, MD 20892 USA. RP Kearns, GL (reprint author), Childrens Mercy Hosp, Sect Pediat Clin Pharmacol & Expt Therapeut, Dept Pediat, 2401 Gillham Rd, Kansas City, MO 64108 USA. FU NICHD NIH HHS [U10 HD031313, 1 U10 HD31324-05, 1 U10 HD31313-05, U10 HD031324] NR 11 TC 23 Z9 25 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAR PY 1999 VL 43 IS 3 BP 634 EP 638 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 171BZ UT WOS:000078843700032 PM 10049279 ER PT J AU Piscitelli, SC Kelly, G Walker, RE Kovacs, J Falloon, J Davey, RT Raje, S Masur, H Polis, MA AF Piscitelli, SC Kelly, G Walker, RE Kovacs, J Falloon, J Davey, RT Raje, S Masur, H Polis, MA TI A multiple drug interaction study of stavudine with agents for opportunistic infections in human immunodeficiency virus-infected patients SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID CONTROLLED TRIAL; HIV-INFECTION; IN-VITRO; PHARMACOKINETICS; LAMIVUDINE; ZIDOVUDINE; INDINAVIR; AIDS AB The effects of multiple opportunistic infection medications on stavudine pharmacokinetics were evaluated. Ten patients with CD4 counts of less than 200 cells/mm(3) received stavudine (40 mg twice daily) in combination with one to three other drugs used to treat opportunistic infections. Serial blood samples for stavudine concentrations were collected after 1 week of therapy on each regimen and assayed for stavudine by using a validated high-pressure liquid chromatography method. Although the maximum concentration of drug in serum was significantly decreased when the drug was given in combination with three opportunistic infection medications, the area under the concentration-time curve did not significantly differ across various treatment regimens. Stavudine exposure was not significantly altered by multiple concomitant medications. Side effects were minor throughout the 3-month study period. The tolerability of stavudine, combined with its lack of drug interactions, makes it an attractive agent for use as part of a combination regimen. C1 NIAID, Ctr Clin, Dept Pharm, NIH, Bethesda, MD 20892 USA. NIAID, Ctr Clin, Dept Crit Care Med, NIH, Bethesda, MD 20892 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NCI, Clin Pharmacokinet Sect, NIH, Bethesda, MD 20892 USA. RP Piscitelli, SC (reprint author), NIAID, Ctr Clin, Dept Pharm, NIH, Bldg 10,Room 1N257, Bethesda, MD 20892 USA. OI Polis, Michael/0000-0002-9151-2268 NR 22 TC 9 Z9 9 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAR PY 1999 VL 43 IS 3 BP 647 EP 650 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 171BZ UT WOS:000078843700034 PM 10049281 ER PT J AU Moldovan, L Irani, K Moldovan, NI Finkel, T Goldschmidt-Clermont, PJ AF Moldovan, Leni Irani, Kaikobad Moldovan, Nicanor I. Finkel, Toren Goldschmidt-Clermont, Pascal J. TI The Actin Cytoskeleton Reorganization Induced by Rac1 Requires the Production of Superoxide SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Article AB The small GTPase rac1 controls actin redistribution to membrane ruffles in fibroblasts other cell types, as well as the activation of the NADPH oxidase in phagocytes. W e explored the possibility that these two processes could be related. W e used a replication-deficient adenoviral vector to overexpress the constitutively active form of rac1, rac(V12), in human and mouse aortic endothelial cells. W e show here that, in addition to membrane ruffle formation, racV12 induced an increase in the total amount of F-actin within endothelial cells. Concurrently, rac(V12)-overexpressing cells produced significantly higher amounts of free radicals, as detected by the fluorescent probe 5-(and-6)-chloromethyl-2',7'-dichloro-dihydrofluorescein diacetate, than cells infected with a control virus encoding the bacterial beta-galactosidase (Ad-beta Gal). To assess the specific role of superoxide in rac(V12)-induced actin reorganization, we co-expressed the human enzyme Cu,Zn-superoxide dismutase ( SOD), by means of another adenoviral vector construct. Overexpressed SOD reduced the concentration of superoxide detected in Adrac(V12)-transfected cells and reversed the effects of Ad-rac(V12) on the content of filamentous actin. MnTMPyP, an SOD mimetic, as well as the antioxidant N-acetyl cysteine, had similar effects, in that they reduced not only the free radicals production, but also ruffle formation and the concentration of F-actin within rac(V12)-overexpressing endothelial cells. Our data support the hypothesis that superoxide is one of the important mediators acting downstream of rac1 on the pathway of actin cytoskeleton remodeling in endothelial cells. Antiox. Redox Signal. 1, 29-43. C1 [Goldschmidt-Clermont, Pascal J.] Ohio State Univ, Heart & Lung Inst, Med Res Facil, Columbus, OH 43210 USA. [Moldovan, Leni; Moldovan, Nicanor I.; Goldschmidt-Clermont, Pascal J.] Ohio State Univ, Div Cardiol, Dept Internal Med, Columbus, OH 43210 USA. [Irani, Kaikobad] Johns Hopkins Univ, Sch Med, Div Cardiol, Dept Med, Baltimore, MD 21287 USA. [Finkel, Toren] NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. RP Goldschmidt-Clermont, PJ (reprint author), Ohio State Univ, Heart & Lung Inst, Med Res Facil, Suite 514 420 W 12th Ave, Columbus, OH 43210 USA. EM Goldschmidt-l@medctr.osu.edu FU National Institutes of Health [HL52315, GM053236-03]; American Heart Association FX thank Dr. R. Auerbach for the mouse aortic endothelial cell line. This work was supported by National Institutes of Health grants HL52315 and GM053236-03, and by an American Heart Association award (Established Investigator) to P.J.G.-C. NR 61 TC 59 Z9 61 U1 0 U2 7 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD SPR PY 1999 VL 1 IS 1 BP 29 EP 43 DI 10.1089/ars.1999.1.1-29 PG 15 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA V10YV UT WOS:000207500200003 PM 11225730 ER PT J AU Okamoto, M Fujiwara, M Kodama, E Yamamoto, O Shigeta, S Mitsuya, H Konno, K Yokota, T Baba, M AF Okamoto, M Fujiwara, M Kodama, E Yamamoto, O Shigeta, S Mitsuya, H Konno, K Yokota, T Baba, M TI Inhibition of human immunodeficiency virus replication by RD6-Y664, a novel benzylhydroxylamine derivative SO ANTIVIRAL CHEMISTRY & CHEMOTHERAPY LA English DT Article DE benzylhydroxylamine; anti-HIV-1 activity; structure-activity relationship ID REVERSE-TRANSCRIPTASE; CELL-LINE; INFECTION; THERAPY; ACTIVATION; ZIDOVUDINE; INDINAVIR; MKC-442; DRUGS; AIDS AB We have examined novel benzylhydroxylamine derivatives for their inhibitory effects on the replication of human immunodeficiency virus (HIV) in cell cultures. Among the series, O-(2-chloro-6-fluorobenzyl)hydroxylamine (RD6-Y664) was found to be the most potent inhibitor of HIV-1. The EC50 for HIV-1 strain IIIB was 1.6 mu g/ml with a selectivity index greater than 38 in MT-4 cells. It also inhibited the replication of other HIV strains including a non-nucleoside reverse transcriptase (RT) inhibitor-resistant mutant, a nucleoside RT inhibitor-resistant mutant and HIV-2, in acutely infected cells. However, the compound did not affect HIV-1 production in chronically infected cells. A time-of-addition experiment and detection of proviral DNA synthesis suggested that RD6-Y664 targeted an early step of the viral replication cycle, presumably a process prior to reverse transcription. In fact, an assay for HIV-1 RT revealed that the compound did not suppress enzyme activity. Furthermore, RD6-Y664 did not show any inhibition of gp120-CD4 interaction, or binding of anti-CXCR4 antibody to CXCR4. C1 Fukushima Med Univ, Sch Med, Dept Microbiol, Fukushima 9601295, Japan. Yamanouchi Pharmaceut, Inst Drug Discovey Res, Tokyo 1740051, Japan. NIH, Expt Retrovirol Sect, Med Branch, Bethesda, MD 20892 USA. Kagoshima Univ, Fac Med, Ctr Chron Viral Dis, Div Human Retroviruses, Kagoshima 8908520, Japan. Rat Drug Design Labs, Fukushima 9601242, Japan. RP Okamoto, M (reprint author), Sanwa Kagaku Kenkyusho, 363 Shiosaki, Hokusei, Mie 5110406, Japan. RI Kodama, Eiichi /C-4032-2009; Baba, Masanori/G-3867-2011 OI Kodama, Eiichi /0000-0002-6622-2752; NR 21 TC 5 Z9 7 U1 0 U2 0 PU INT MEDICAL PRESS PI LONDON PA 125 HIGH HOLBORN, LONDON WC1V 6QA, ENGLAND SN 0956-3202 J9 ANTIVIR CHEM CHEMOTH JI Antivir. Chem. Chemother. PD MAR PY 1999 VL 10 IS 2 BP 71 EP 77 PG 7 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Virology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Virology GA 184NB UT WOS:000079617300003 PM 10335401 ER PT J AU Johnson, J Murray, PK Maronpot, RR AF Johnson, J Murray, PK Maronpot, RR TI Improved method for ultrastructural preservation of Saccharomyces cerevisiae JHY-31-11D SO APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY LA English DT Article DE Saccharomyces; fixation; ultrastructure ID ELECTRON-MICROSCOPY; YEAST-CELLS AB Investigation in the National Institute of Environmental Health Sciences (NIEHS) laboratories of the possibility that the JHY-31-11D strain of Saccharomyces cerevisiae might provide a simple model for studying apoptosis was necessarily preceded by developing an electron microscopic protocol for superior preservation of ultrastructural detail. Since the biochemical composition of the thick cell wall of this particular strain of yeast presumably impeded penetration of routine fixatives, we developed a new combinational procedure in which a mixture of 2% paraformaldehyde, 2.6% glutaraldehyde, and 3% sucrose functioned as postfixative following the more traditional primary fixative, potassium permanganate (KMnO4), used at 4% concentration. Uranyl acetate(1%) was subsequently applied as Fixative and en bloc stain. All steps in our 4-day procedure were performed by suspending the cells in the reagents following light centrifugation in a tabletop microfuge, thus eliminating often troublesome agarose embedding and assuring consistent reproducibility of the method. No chemical treatments that might have altered wall structure and morphology were used. Our superior fixation results indicate the apparent importance of the concentration of the permanganate, the use of a double-aldehyde postfixative, and the order of the application of the fixatives. C1 NIEHS, Lab Expt Pathol, Electron Microscopy Unit, Res Triangle Pk, NC 27709 USA. RP NIEHS, Lab Expt Pathol, Electron Microscopy Unit, Mail Stop D2-05,111 T W Alexander Dr, Res Triangle Pk, NC 27709 USA. EM johnso32@niehs.nih.gov NR 30 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1541-2016 EI 1533-4058 J9 APPL IMMUNOHISTO M M JI Appl. Immunohistochem. PD MAR PY 1999 VL 7 IS 1 BP 81 EP 86 DI 10.1097/00022744-199903000-00016 PG 6 WC Anatomy & Morphology; Medical Laboratory Technology; Pathology SC Anatomy & Morphology; Medical Laboratory Technology; Pathology GA 187PM UT WOS:000079795500016 ER PT J AU Kiss, Z Petrovics, G Olah, Z Lehel, C Anderson, WB AF Kiss, Z Petrovics, G Olah, Z Lehel, C Anderson, WB TI Overexpression of protein kinase C-epsilon and its regulatory domains in fibroblasts inhibits phorbol ester-induced phospholipase D activity SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE protein kinase C-epsilon; phorbol ester; phospholipase D; phosphatidylcholine; phosphatidylethanolamine; platelet-derived growth factor ID D-MEDIATED HYDROLYSIS; ADP-RIBOSYLATION FACTOR; NIH 3T3 FIBROBLASTS; GROWTH-FACTOR; BREFELDIN-A; PHOSPHATIDYLCHOLINE BREAKDOWN; DIFFERENTIAL REGULATION; DOWN-REGULATION; KIDNEY-CELLS; D ACTIVATION AB In fibroblasts, the protein kinase C (PKC) activator phorbol la-myristate 13-acetate (PMA) stimulates phospholipase D (PLD)-mediated hydrolysis of both phosphatidylcholine (PtdCho) and phosphatidylethanolamine (PtdEtn) by PKC-alpha-mediated nonphosphorylating and phosphorylating mechanisms. Here we have used NIH 3T3 fibroblasts overexpressing hole PKC-epsilon and its regulatory, catalytic, and zinc finger domain fragments to determine if this isozyme also regulates PLD activity. Overexpression of hole PKC-epsilon inhibited the stimulatory effects of PMA (5-100 nM) on both PtdCho and PtdEtn hydrolysis. Overexpression of PKC-epsilon also was found to inhibit platelet-derived growth factor-induced PLD activity. Expression of the catalytic unit of PKC-epsilon had no effect on PMA-induced PLD activity. In contrast, expression of both the regulatory domain fragment and the zinc finger domain of PKC-epsilon resulted in significant inhibition of PMA-stimulated PtdCho and PtdEtn hydrolysis. Interestingly, although PKC-alpha also mediates the stimulatory effect of PMA on the synthesis of PtdCho by a phosphorylation mechanism, overexpression of hole PKC-epsilon or its regulatory domain fragments did not affect PMA-induced PtdCho synthesis. These results indicate that the PKC-epsilon system can act as a negative regulator of PLD activity and that this inhibition is mediated by its regulatory domain. (C) 1999 Academic Press. C1 Univ Minnesota, Hormel Inst, Austin, MN 55912 USA. NIH, NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. RP Kiss, Z (reprint author), Univ Minnesota, Hormel Inst, 801 16Th Ave NE, Austin, MN 55912 USA. EM kissx001@maroon.tc.umn.edu NR 44 TC 15 Z9 15 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD MAR 1 PY 1999 VL 363 IS 1 BP 121 EP 128 DI 10.1006/abbi.1998.1066 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 174EG UT WOS:000079020700015 PM 10049506 ER PT J AU Ma, YS Chao, CC Stadtman, ER AF Ma, YS Chao, CC Stadtman, ER TI Oxidative modification of glutamine synthetase by 2,2 '-azobis(2-amidinopropane) dihydrochloride SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE glutamine synthetase; reactive oxygen; free radicals; enzyme inactivation; 2,2 '-azobis(amidino propane) dihydrochloride; alkylperoxides; protein modification ID METAL-CATALYZED OXIDATION; MIXED-FUNCTION OXIDATION; BOVINE SERUM-ALBUMIN; AMINO-ACID-RESIDUES; MULTICATALYTIC PROTEASE; TRYPTOPHAN RESIDUES; LIPID-PEROXIDATION; XYLENOL ORANGE; LOW-DENSITY; PROTEINS AB In the present study, we examined the pattern of protein modification elicited by alkylperoxyl radicals and alkylperoxides. To this end, we exposed glutamine synthetase (GS) and the peptide melittin to solutions containing 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH), which is known to decompose in aqueous, aerobic solutions to yield alkyl radicals and alkylperoxides. Under our conditions, pH 7.4, 37 degrees C, the AAPH-dependent formation of alkylhydroperoxide increased linearly with time and led to 40% inactivation of GS in 1 h and to complete inactivation in 4 h. Complete inactivation was associated with the loss of 2 of 16 histidine residues, 6 of 17 tyrosine residues, 5 of 16 methionine residues, and all of the tryptophan residues (2 residues) per subunit, Inactivation of GS was associated also with some protein fragmentation and the formation of some higher molecular weight aggregates. Exposure of GS to AAPH led also to the generation of protein carbonyl derivatives (0.34 mol/mol subunit) and to formation of a significant amount (0.038 mol/mol subunits) of quinoprotein derivatives. To investigate the mechanism of tryptophan modification, the 26-amino-acid peptide, melittin, which contains one tryptophan but no histidine, tyrosine, or methionine residues, was treated with AAPH, N-Formylkynurenine was identified as the major product of tryptophan oxidation in melittin. (C) 1999 Academic Press. C1 NIH, NHLBI, Biochem Lab, Bethesda, MD 20892 USA. RP Stadtman, ER (reprint author), NIH, NHLBI, Biochem Lab, Bldg 3,Room 222,MSC-0342 Ctr Dr, Bethesda, MD 20892 USA. NR 54 TC 36 Z9 37 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD MAR 1 PY 1999 VL 363 IS 1 BP 129 EP 134 DI 10.1006/abbi.1998.1076 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 174EG UT WOS:000079020700016 PM 10049507 ER PT J AU Longnecker, MP Klebanoff, MA Gladen, BC Berendes, HW AF Longnecker, MP Klebanoff, MA Gladen, BC Berendes, HW TI Serial levels of serum organochlorines during pregnancy and postpartum SO ARCHIVES OF ENVIRONMENTAL HEALTH LA English DT Article ID POLYCHLORINATED-BIPHENYLS; CHOLESTEROL; PCBS AB In utero exposure to dichlorodiphenyldichloroethene and polychlorinated biphenyls, within the range found in the general U.S. population, may produce detectable effects in offspring. To design studies of the effects of in utero organochlorine exposure, we obtained data on the relationship between gestational and perinatal maternal levels in females on several occasions. We studied 67 pregnant women in the United States who agreed to have their blood drawn once during each trimester and once postpartum. We examined the Pearson correlation coefficient between the natural logarithm of levels (mu g/g serum lipid). The correlation, r, among revels in the first and third trimester was .86 and .77 for dichlorodiphenyldichloroethene and for polychlorinated biphenyls. Correlations among levels determined at other times (i.e., second trimester and postpartum) were similar. On the basis of these results, we suggest that in studies of the effects of in utero or perinatal exposure to the aforementioned compounds, the time when specimens are collected is not critical. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. NICHHD, Div Epidemiol Stat & Prevent Res, Rockville, MD USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Longnecker, MP (reprint author), NIEHS, Epidemiol Branch, POB 12233,MD A3-05, Res Triangle Pk, NC 27709 USA. OI Longnecker, Matthew/0000-0001-6073-5322 NR 28 TC 85 Z9 87 U1 0 U2 1 PU HELDREF PUBLICATIONS PI WASHINGTON PA 1319 EIGHTEENTH ST NW, WASHINGTON, DC 20036-1802 USA SN 0003-9896 J9 ARCH ENVIRON HEALTH JI Arch. Environ. Health PD MAR-APR PY 1999 VL 54 IS 2 BP 110 EP 114 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 175UW UT WOS:000079114800006 PM 10094288 ER PT J AU Benvenuti, F Mecacci, R Gineprari, I Bandinelli, S Benvenuti, E Ferrucci, L Baroni, A Rabuffetti, M Hallett, M Dambrosia, JM Stanhope, SJ AF Benvenuti, F Mecacci, R Gineprari, I Bandinelli, S Benvenuti, E Ferrucci, L Baroni, A Rabuffetti, M Hallett, M Dambrosia, JM Stanhope, SJ TI Kinematic characteristics of standing disequilibrium: Reliability and validity of a posturographic protocol SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article ID POSTURAL SWAY; ELDERLY PATIENTS; OBSTACLE COURSE; BALANCE; FALLS; STANCE; ORGANIZATION; PERFORMANCE; MOBILITY; SUBJECT AB Objective: To investigate retest reliability and concurrent validity of the fundamental measurements made of a posturographic protocol that employs quiet standing to quantify the severity and the nature of patients' postural disturbances. Study Design: Retrospective complete block design. Setting: Geriatric rehabilitation department. Participants: Thirty-six participants (age range, 67 to 86yrs) having normal, moderate, or severe levels of disequilibrium. Methods: Quiet standing was evaluated on three occasions using a three-dimensional motion analysis system and a force platform. Eight testing conditions, designed to vary task difficulty by controlling the contributions of vision, foot proprioception, and base-of-support width, were administered. Main Outcome Measures: Retest reliability of body sway, joint alignment, body position, and motor coordination indicators were evaluated by intraclass correlation coefficients (ICCs). Concurrent validity of protocol measures was evaluated by the prediction of disequilibrium from a stepwise linear discriminant analysis. Results: ICCs indicated high level of retest reliability for all variables but those of motor coordination, which was not influenced by testing conditions. Discriminant analysis resulted in a four-factor discriminator that included measures of body sway, position, alignment, and motor coordination. The derived linear discriminate function correctly classified 96% of the patients' level of disequilibrium. Conclusions: The posturographic protocol has the potential to be a useful tool for evaluating severity and nature of postural instability and the effects of pharmacologic and rehabilitative treatment. Results also indicate that combining direct body measurements with force-plate data has the potential to expose the underlying impairments that cause disequilibrium, determine their pathogenesis, and evaluate compensatory strategies. (C) 1999 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation. C1 Ist Nazl Ricovero & Cura Anziani I Fraticini, Unita Operat Geriatr, I-50125 Florence, Italy. Politecn Milan, Fdn Pro Juventute Don Gnocchi, Ctr Bioingn, I-20133 Milan, Italy. NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. NINDS, Biometry & Field Studies Branch, NIH, Bethesda, MD 20892 USA. NIH, Biomech Lab, Dept Rehabil Med, Ctr Clin, Bethesda, MD 20892 USA. RP Benvenuti, F (reprint author), Ist Nazl Ricovero & Cura Anziani I Fraticini, Unita Operat Geriatr, Viale Michelangelo 41, I-50125 Florence, Italy. NR 49 TC 61 Z9 66 U1 4 U2 12 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 EI 1532-821X J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD MAR PY 1999 VL 80 IS 3 BP 278 EP 287 DI 10.1016/S0003-9993(99)90138-7 PG 10 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 173RX UT WOS:000078994500007 PM 10084435 ER PT J AU Cushman, M Lemaitre, RN Kuller, LH Psaty, BM Macy, EM Sharrett, AR Tracy, RP AF Cushman, M Lemaitre, RN Kuller, LH Psaty, BM Macy, EM Sharrett, AR Tracy, RP TI Fibrinolytic activation markers predict myocardial infarction in the elderly - The cardiovascular health study SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE blood coagulation; fibrinolysis; myocardial infarction; elderly; risk factors ID LINKED IMMUNOSORBENT-ASSAY; C-REACTIVE PROTEIN; PLASMINOGEN-ACTIVATOR; SUBCLINICAL DISEASE; RISK-FACTORS; D-DIMER; PLASMA; INHIBITOR-1; ATHEROSCLEROSIS; ASSOCIATION AB Coagulation factor levels predict arterial thrombosis in epidemiological studies, but studies of older persons are needed. We studied 3 plasma antigenic markers of fibrinolysis, viz, plasminogen activator inhibitor-1 (PAI-1), fibrin fragment D-dimer, and plasmin-antiplasmin complex (PAP) for the prediction of arterial thrombosis in healthy elderly persons over age 65. The study was a nested case-control study in the Cardiovascular Health Study cohort of 5201 men and women greater than or equal to 65 years of age who were enrolled from 1989 to 1990. Cases were 146 participants without baseline clinical Vascular disease who developed myocardial infarction, angina, or coronary death during a follow-up of 2.4 years. Controls remained free of cardiovascular events and were matched 1:1 to cases with respect to sex, duration of follow-up, and baseline subclinical Vascular disease status. With increasing quartile of D-dimer and PAP levels but not of PAI-1, there was an independent increased risk of myocardial infarction or coronary death, but not of angina. The relative risk for D-dimer above versus below the median value (greater than or equal to 120 mu g/L) was 2.5 (95% confidence interval, 1.1 to 5.9) and for PAP above the median (greater than or equal to 5.25 nmol/L), 3.1 (1.3 to 7.7). Risks were independent of C-reactive protein and fibrinogen concentrations. There were no differences in risk by sex or presence of baseline subclinical disease. D-dimer and PAP, but not PAI-1, predicted future myocardial infarction in men and women over age 65. Relationships were independent of other risk factors, including inflammation markers. Results indicate a major role for these markers in identifying a high risk of arterial disease in this age group. C1 Univ Vermont, Dept Pathol, Colchester, VT 05446 USA. Univ Vermont, Dept Med, Colchester, VT 05446 USA. Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. NHLBI, Bethesda, MD 20892 USA. RP Tracy, RP (reprint author), Univ Vermont, Dept Pathol, 55A S Park Dr, Colchester, VT 05446 USA. EM rtracy@salus.uvm.edu FU NHLBI NIH HHS [R01-HL-46696, N0-HC-85079-85086]; PHS HHS [T3207594] NR 33 TC 190 Z9 196 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAR PY 1999 VL 19 IS 3 BP 493 EP 498 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 175EX UT WOS:000079081200004 PM 10073948 ER PT J AU Sakkinen, PA Cushman, M Psaty, BM Rodriguez, B Boineau, R Kuller, LH Tracy, RP AF Sakkinen, PA Cushman, M Psaty, BM Rodriguez, B Boineau, R Kuller, LH Tracy, RP TI Relationship of plasmin generation to cardiovascular disease risk factors in elderly men and women SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE blood coagulation; fibrinolysis; myocardial infarction; elderly; diabetes ID LINKED-IMMUNOSORBENT-ASSAY; APPARENTLY HEALTHY-MEN; C-REACTIVE PROTEIN; PRODUCT D-DIMER; MYOCARDIAL-INFARCTION; INSULIN-RESISTANCE; ACTIVATOR INHIBITOR-1; PAI-1; ATHEROSCLEROSIS; EVENTS AB Plasmin-alpha 2-antiplasmin complex (PAP) marks plasmin generation and fibrinolytic balance. We recently observed that elevated levels of PAP predict acute myocardial infarction in the elderly, yet little is known about the correlates of PAP. We measured PAP in 800 elderly subjects who were free of clinical cardiovascular disease in 2 cohort studies: the Cardiovascular Health Study and the Honolulu Heart Program. Median PAP levels did not differ between the Cardiovascular Health Study (6.05+/-1.46 nmol/L) and the Honolulu Heart Program (6.11+/-1.44 nmol/L), and correlates of PAP were similar in both cohorts. In CHS, PAP levels increased with age (r=0.30), procoagulant factors (eg, factor VIIc, r=0.15), thrombin activity (prothrombin fragment F1+2, r=0.29), and inflammation-sensitive proteins (eg, fibrinogen, r=0.44; factor VIIIc, r=0.37). PAP was associated with increased atherosclerosis as measured by the ankle-arm index (AAI) (P for trend, less than or equal to 0.001). PAP was negatively related to factors associated with the insulin resistance syndrome (IRS) (eg, fasting insulin, r=-0.26; body mass index, r=-0.26), possibly reflecting an association with plasminogen activator inhibitor-1 (r=-0.29). Although our study did not have sufficient power to detect a significant interaction, PAP and AAI appeared to be more weakly associated in subjects with more manifestations of the IRS: PAP appeared more strongly associated with AAI in the subgroup with 0 or 1 metabolic disorders (P less than or equal to 0.001; slope estimate, -0.14) compared with the subgroup with 2 or more metabolic disorders (P=0.10; slope estimate, -0.08) and in those with non-insulin-dependent diabetes mellitus (P=0.46; slope estimate, -0.04). Although PAP reflects reactive fibrinolysis and is associated with subclinical atherosclerosis, this relationship may be weaker in populations with characteristics of the IRS, possibly reflecting the inhibitory effects of plasminogen activator inhibitor-1 on PAP. Decreased fibrinolysis in the presence of subclinical disease in subjects with hyperinsulinemia or glucose intolerance is consistent with the premise that depressed plasmin generation may enhance the progression of atherosclerosis in these people. C1 Univ Vermont, Dept Pathol, Colchester, VT 05446 USA. Univ Vermont, Dept Biochem, Colchester, VT 05446 USA. Univ Vermont, Dept Med, Colchester, VT 05446 USA. Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Hawaii Manoa, Dept Med, Honolulu, HI 96822 USA. NHLBI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. RP Tracy, RP (reprint author), Univ Vermont, Dept Pathol, Aquatec Bldg,T205,55A S Park Dr, Colchester, VT 05446 USA. FU NHLBI NIH HHS [N01-HC-85086, N01-HC-85079, T-32-HL-07594] NR 40 TC 51 Z9 53 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAR PY 1999 VL 19 IS 3 BP 499 EP 504 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 175EX UT WOS:000079081200005 PM 10073949 ER PT J AU Newman, AB Shemanski, L Manolio, TA Cushman, M Mittelmark, M Polak, JF Powe, NR Siscovick, D AF Newman, AB Shemanski, L Manolio, TA Cushman, M Mittelmark, M Polak, JF Powe, NR Siscovick, D CA Cardiovascular Hlth Collaborative Res Grp TI Ankle-arm index as a predictor of cardiovascular disease and mortality in the cardiovascular health study SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE peripheral vascular diseases; ankle-arm index; ankle-brachial pressure index; cardiovascular diseases, epidemiology ID CORONARY-HEART-DISEASE; UNRECOGNIZED MYOCARDIAL-INFARCTION; PERIPHERAL ARTERIAL-DISEASE; BLOOD-PRESSURE INDEX; ATHEROSCLEROSIS RISK; OLDER ADULTS; PREVALENCE; PROGNOSIS; STROKE; COHORT AB Peripheral arterial disease (PAD) in the legs, measured noninvasively by the ankle-arm index (AAI) is associated with clinically manifest cardiovascular disease (CVD) and its risk factors. To determine risk of total mortality, coronary heart disease, or stroke mortality and incident versus recurrent CVD associated with a low AAI, we examined the relationship of the AAT to subsequent CVD events in 5888 older adults with and without CVD. The AAT was measured in 5888 participants greater than or equal to 65 years old at the baseline examination of the Cardiovascular Health Study. All participants had a detailed assessment of prevalent CVD and were contacted every 6 months for total mortality and CVD events (including CVD mortality, fatal and nonfatal myocardial infarction, congestive heart failure, angina, stroke, and hospitalized PAD). The crude mortality rate at 6 years was highest (32.3%) in those participants with prevalent CVD and a low AAI (P<0.9), and it was lowest in those with neither of these findings (8.7%, P<0.01), Similar patterns emerged from analysis of recurrent CVD and incident CVD. The risk for incident congestive heart failure (relative risk [RR]=1.61) and for total mortality (RR=1.62) in those without CVD at baseline but with a low AAI remained significantly elevated after adjustment for cardiovascular risk factors. Hospitalized PAD events occurred months to years after the AAI was measured, with an adjusted RR of 5.55 (95% CI, 3.08 to 9.98) in those at risk for incident events. A statistically significant decline in survival was seen at each 0.1 decrement in the AAI. An AAI of <0.9 is an independent risk factor for incident CVD, recurrent CVD, and mortality in this group of older adults in the Cardiovascular Health Study. C1 Univ Pittsburgh, Sch Med, Dept Med, Div Geriatr Med, Pittsburgh, PA 15213 USA. Univ Washington, Seattle, WA 98195 USA. NHLBI, Bethesda, MD 20892 USA. Univ Vermont, Colchester, VT USA. Univ Bergen, Bergen, Norway. Harvard Univ, Boston, MA 02115 USA. Johns Hopkins Univ, Baltimore, MD USA. RP Newman, AB (reprint author), Univ Pittsburgh, Sch Med, Dept Med, Div Geriatr Med, 3520 5th Ave,Suite 300, Pittsburgh, PA 15213 USA. EM anewman+@pitt.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU NHLBI NIH HHS [N01-HC-85080, N01-HC-85083, N01-HL-85079] NR 32 TC 543 Z9 574 U1 1 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAR PY 1999 VL 19 IS 3 BP 538 EP 545 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 175EX UT WOS:000079081200011 PM 10073955 ER PT J AU Jaron, D Lewin, PA AF Jaron, D Lewin, PA TI Vibroacoustic disease - Preface SO AVIATION SPACE AND ENVIRONMENTAL MEDICINE LA English DT Editorial Material C1 Drexel Univ, Sch Biomed Engn Sci & Hlth Syst, Biomed Ultrasound Res & Educ Ctr, Philadelphia, PA 19104 USA. NIH, Natl Ctr Res Resources, Bethesda, MD 20892 USA. RP Jaron, D (reprint author), Drexel Univ, Sch Biomed Engn Sci & Hlth Syst, Biomed Ultrasound Res & Educ Ctr, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AEROSPACE MEDICAL ASSOC PI ALEXANDRIA PA 320 S HENRY ST, ALEXANDRIA, VA 22314-3579 USA SN 0095-6562 J9 AVIAT SPACE ENVIR MD JI Aviat. Space Environ. Med. PD MAR PY 1999 VL 70 IS 3 SU S BP V EP V PG 1 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Sport Sciences SC Public, Environmental & Occupational Health; General & Internal Medicine; Sport Sciences GA 174YN UT WOS:000079064300001 ER PT J AU Izenwasser, S French, D Carroll, FI Kunko, PM AF Izenwasser, S French, D Carroll, FI Kunko, PM TI Continuous infusion of selective dopamine uptake inhibitors or cocaine produces time-dependent changes in rat locomotor activity SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE cocaine; dopamine; transporters; GBR 12909; continuous administration; locomotion; serotonin; norepinephrine ID HIGH-AFFINITY; SEROTONIN RELEASE; NEURONAL CARRIER; UPTAKE COMPLEX; GBR 12909; BINDING; TRANSPORTER; TOLERANCE; ACTIVATION; WITHDRAWAL AB Chronic continuous cocaine treatment produces a unique pattern of locomotor activation over time. An initial, progressive increase in locomotion is indicative of sensitization Unlike intermittent cocaine, this increase is subsequently reversed during the continuous exposure, and activity returns to pre-sensitization levels within days. To study the pharmacological mechanisms that underlie this phenomenon, osmotic minipumps containing cocaine or selective uptake inhibitors of dopamine (GBR 12909 or RTI-117), serotonin (fluoxetine), or norepinephrine (nisoxetine) were implanted into rats. Locomotor activity was measured for 1 h each day, beginning 4 h after pumps were implanted. In the cocaine group, activity was significantly elevated on the first day, peaked between the second and third days, then decreased to a plateau which remained significantly above control levels through 14 days. Peak activity in the GBR 12909 and RTI-117 animals occurred on the first day, followed by a significant decrease 24-48 h later, but not complete tolerance. Neither fluoxetine nor nisoxetine altered locomotor activity. The selective dopamine uptake inhibitors produced some of the effects of cocaine. The possibilities that cocaine interacts with the dopamine transporter in a qualitatively different manner from that of these selective dopamine uptake inhibitors, or that other monoamine systems are involved, are discussed. (C) 1999 Elsevier Science B.V. Ail rights reserved. C1 NIDA, Psychobiol Sect, Div Intramural Res, NIH, Baltimore, MD 21224 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. RP Izenwasser, S (reprint author), Univ Miami, Sch Med, Dept Neurol, 1501 NW 9th Ave, Miami, FL 33136 USA. RI Izenwasser, Sari/G-9193-2012 NR 37 TC 35 Z9 35 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD MAR PY 1999 VL 99 IS 2 BP 201 EP 208 DI 10.1016/S0166-4328(98)00104-1 PG 8 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 186ZL UT WOS:000079761400009 PM 10512586 ER PT J AU Koo, JS Jetten, AM Belloni, P Yoon, JH Kim, YD Nettesheim, P AF Koo, JS Jetten, AM Belloni, P Yoon, JH Kim, YD Nettesheim, P TI Role of retinoid receptors in the regulation of mucin gene expression by retinoic acid in human tracheobronchial epithelial cells SO BIOCHEMICAL JOURNAL LA English DT Article DE cell culture; differentiation; mucin secretion ID NUCLEAR RECEPTOR; CARCINOMA-CELLS; BETA GENE; ALPHA; IDENTIFICATION; LIGANDS; DIFFERENTIATION; ACTIVATION; PROLIFERATION; HETERODIMERS AB To investigate which retinoid receptors are critical in the regulation by all-trans-retinoic acid (RA) of the mucin genes MUC2, MUC5AC and MUC5B in cultured normal human tracheobronchial epithelial (NHTBE) cells, we used pan-RAR-, pan-RXR- and RAR- isotype (alpha, beta and gamma)-selective agonists and RAR alpha- and RAR gamma-selective antagonists (RAR is RA receptor and RXR is retinoid X receptor). RAR-, RAR alpha- and RAR gamma-selective agonists strongly induced mucin mRNAs in a dose-dependent manner, while the RAR beta-selective retinoid only weakly induced mucin gene expression at very high concentrations (1 mu M) The pan-RXR-selective agonist by itself did not induce mucin gene expression, but acted synergistically with suboptimal concentrations of the pan-RAR agonist. A retinoid with selective anti-activator-protein-1 activity only marginally induced mucin gene expression. The RAR alpha antagonist strongly inhibited mucin gene induction and mucous cell differentiation caused by RA and by the RAR alpha- and RAR gamma-selective retinoids. In contrast, the RAR gamma antagonist only weakly inhibited RAR alpha-selective-retinoid-induced mucin gene expression, but completely blocked mucin gene expression induced by the RAR gamma-selective retinoid. Our studies indicate that RAR alpha is the major retinoid receptor subtype mediating RA-dependent mucin gene expression and mucous cell differentiation, but that the RAR gamma isotype can also induce mucin genes. Furthermore these studies suggest that RAR beta is probably not (directly) involved in RA-induced mucin gene expression. C1 NIEHS, Pulm Pathobiol Lab, Res Triangle Pk, NC 27709 USA. Roche Biosci, Resp Dis, Palo Alto, CA 94304 USA. RP Nettesheim, P (reprint author), NIEHS, Pulm Pathobiol Lab, POB 12233, Res Triangle Pk, NC 27709 USA. RI Yoon, Joo-Heon/E-5781-2016; OI Jetten, Anton/0000-0003-0954-4445; Yoon, Joo-Heon/0000-0003-2404-7156 NR 49 TC 43 Z9 44 U1 0 U2 1 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD MAR 1 PY 1999 VL 338 BP 351 EP 357 DI 10.1042/0264-6021:3380351 PN 2 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 175XP UT WOS:000079121600015 PM 10024510 ER PT J AU Rudolf, MP Nieland, JD DaSilva, DM Velders, MP Muller, M Greenstone, HL Schiller, JT Kast, WM AF Rudolf, MP Nieland, JD DaSilva, DM Velders, MP Muller, M Greenstone, HL Schiller, JT Kast, WM TI Induction of HPV16 capsid protein-specific human T cell responses by virus-like particles SO BIOLOGICAL CHEMISTRY LA English DT Article DE cervical cancer; CTL; HLA-A*0201; human papilloma virus; vaccine ID HUMAN PAPILLOMAVIRUS TYPE-16; L1; EXPRESSION; LYMPHOCYTES; INTEGRIN; BINDING AB It has been postulated that upon binding to a cell surface receptor, papilloma virus-like particles (VLPs) gain entry into the cytosol of infected cells and the capsid proteins L1 and L2 can be processed in the MHC class I presentation pathway. Vaccination of mice with human papilloma virus-like particles consisting of capsid proteins L1 and L2 induced a CD8-mediated and perforin dependent protective immune response against a tumor challenge with human papilloma virus transformed tumor cells, which express only minute amounts of L1 protein. Here we show that HPV16 capsid proteins stimulate a MHC class I restricted CTL response with human peripheral blood lymphocytes (PBL) in vitro. The vigorous response was specific for VLP-infected target cells and was MHC class I restricted. Moreover we show the presence of at least one HLA-A*0201 restricted CTL epitope within the HPV-16 capsid proteins by using a VLP-'infected' HLA-A*0201 transfected human cell line as target cells. These results demonstrated that VLPs can induce a HPV16 capsid protein-specific immune response in humans, allowing the monitoring of immune responses induced by vaccines based on chimeric VLPs carrying additional immunogenic peptides or proteins in therapeutical applications in human patients. C1 Loyola Univ, Cardinal Bernardin Canc Ctr, Canc Immunol Program, Maywood, IL 60153 USA. Loyola Univ, Dept Immunol & Microbiol, Maywood, IL 60153 USA. NIH, Cellular Oncol Lab, Bethesda, MD 20892 USA. RP Kast, WM (reprint author), Loyola Univ, Cardinal Bernardin Canc Ctr, Canc Immunol Program, 2160 S 1st Ave, Maywood, IL 60153 USA. FU NCI NIH HHS [P01 CA74182, R01 CA74397] NR 22 TC 38 Z9 38 U1 0 U2 4 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 1431-6730 J9 BIOL CHEM JI Biol. Chem. PD MAR PY 1999 VL 380 IS 3 BP 335 EP 340 DI 10.1515/BC.1999.045 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 181ZK UT WOS:000079473900009 PM 10223336 ER PT J AU Hyman, SE AF Hyman, SE TI Introduction to the complex genetics of mental disorders SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material C1 NIMH, Bethesda, MD 20892 USA. RP Hyman, SE (reprint author), NIMH, 31 Ctr Dr,Rm 4A52, Bethesda, MD 20892 USA. NR 9 TC 31 Z9 31 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAR 1 PY 1999 VL 45 IS 5 BP 518 EP 521 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 175XE UT WOS:000079120600002 PM 10088041 ER PT J AU Malhotra, AK Goldman, D AF Malhotra, AK Goldman, D TI Benefits and pitfalls encountered in psychiatric genetic association studies SO BIOLOGICAL PSYCHIATRY LA English DT Article DE gene; genetics; allele; polymorphism; association; psychiatry ID DOPAMINE-D2 RECEPTOR GENE; GRADIENT GEL-ELECTROPHORESIS; POLYMORPHIC DNA MARKER; CLOZAPINE RESPONSE; 5-HT2A RECEPTOR; LINKAGE DISEQUILIBRIUM; ALLELIC VARIATION; AMERICAN-INDIANS; STRUCTURAL GENE; HIV-1 INFECTION AB The genetic association strategy is currently being applied to a number of psychiatric phenotypes including disease vulnerability, personality variation and clinical response to psychotropic drugs. Association studies offer the prospect of identification of the specific alleles that confer significant effects on clinical phenotype. However, if should be noted that this strategy has additional advantages as well as unique drawbacks. In this paper, we review the basic methodology utilized in each step of a typical psychiatric genetic association study and discuss their potential benefits and pitfalls with particular emphasis on the selection of clinical phenotype, the identification of a candidate gene, the selection of a candidate variant, clinical data set design, and the statistical analysis of association data, With appropriate design and execution, it is hoped that the association strategy will prove to be as successful in psychiatry as it has proven to be in other branches of medicine. Biol Psychiatry 1999;45: 544-550 (C) 1999 Society of Biological Psychiatry. C1 NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. Hillside Hosp, Unit Mol Psychiat, Glen Oaks, NY 11004 USA. RP Goldman, D (reprint author), NIAAA, Neurogenet Lab, NIH, 12420 Parklawn Dr,Pk 5 Bldg,Room 451, Rockville, MD 20852 USA. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 48 TC 75 Z9 77 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAR 1 PY 1999 VL 45 IS 5 BP 544 EP 550 DI 10.1016/S0006-3223(98)00365-5 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 175XE UT WOS:000079120600005 PM 10088044 ER PT J AU Moldin, S AF Moldin, S TI Summary of research SO BIOLOGICAL PSYCHIATRY LA English DT Review ID ATTENTION-DEFICIT HYPERACTIVITY; OBSESSIVE-COMPULSIVE DISORDER; LA-TOURETTE SYNDROME; MANIC-DEPRESSIVE ILLNESS; BIPOLAR AFFECTIVE-DISORDER; OLD-ORDER AMISH; SEROTONIN TRANSPORTER GENE; MAJOR AFFECTIVE-DISORDER; SCHIZOPHRENIA VULNERABILITY LOCUS; AUTOSOMAL-DOMINANT TRANSMISSION C1 NIMH, Bethesda, MD 20892 USA. RP Moldin, S (reprint author), NIMH, Bethesda, MD 20892 USA. NR 468 TC 19 Z9 19 U1 18 U2 19 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAR 1 PY 1999 VL 45 IS 5 BP 573 EP 602 PG 30 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 175XE UT WOS:000079120600009 ER PT J AU Han, L Nielsen, DA Rosenthal, NE Jefferson, K Kaye, W Murphy, D Altemus, M Humphries, J Cassano, G Rotondo, A Virkkunen, M Linnoila, M Goldman, D AF Han, L Nielsen, DA Rosenthal, NE Jefferson, K Kaye, W Murphy, D Altemus, M Humphries, J Cassano, G Rotondo, A Virkkunen, M Linnoila, M Goldman, D TI No coding variant of the tryptophan hydroxylase gene detected in seasonal affective disorder, obsessive-compulsive disorder, anorexia nervosa, and alcoholism SO BIOLOGICAL PSYCHIATRY LA English DT Article DE anorexia nervosa; obsessive-compulsive disorder; tryptophan hydroxylase gene; polymorphism; single-strand conformation polymorphism ID CEREBROSPINAL-FLUID; ACID; POLYMORPHISM; MUTATIONS; SEQUENCE; BEHAVIOR; DNA AB Background: The goal of this study was to evaluate the role of genetic variation in the coding sequence of tryptophan hydroxylase (TPH) in the pathogenesis of several psychiatric diseases in which altered serotonin function has been implicated: bipolar affective disorder (BP), obsessive-compulsive disorder (OCD), anorexia nervosa (AN), seasonal affective disorder (SAD), panic disorder (PD), and alcoholism (Alc), Methods: Ninety-three percent of the TPH coding sequence was screened by polymerase chain reaction single-strand conformation polymorphism (SSCP) for DNA sequence variations in 128 AN, 88 OCD, 72 SAD, 45 PD, and 36 BP patients and 142 normal volunteers. Also included in the screening were 61 Ale randomly selected from a Finnish alcoholic population in which art association of a TPH intron 7 polymorphism with suicidality was previously observed. Polymorphisms detected by SSCP were characterized by DNA sequencing and by allele-specific restriction enzyme digestion. Genotyping was then performed in 34 Finnish alcoholic suicide attempters. Results: A rare silent mutation was identified in exon 10 and is designated T1095C. The C1095 allele was found in I OCD and in 2 AN subjects; all 3 individuals were heterozygous (C1095/T1095) for the variant allele. No association was observed between this TPH T1095C variant with either OCD, AN, Ale, or suicidality. Conclusion: These results suggest that the coding sequence of the TPH gene does not contain abundant variants, and may not play a major role in vulnerability to several psychopathologies in which reduced serotonin turnover has been implicated. Biol Psychiatry 1999;45: 615-619 (C) 1999 Society of Biological Psychiatry. C1 NIAAA, NIH, Neurogenet Lab, Rockville, MD 20851 USA. RP Goldman, D (reprint author), NIAAA, NIH, Neurogenet Lab, 12420 Parklawn Dr,Pk 5 Bldg,Rm 451,MSC 8110, Rockville, MD 20851 USA. RI Nielsen, David/B-4655-2009; Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 17 TC 66 Z9 68 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAR 1 PY 1999 VL 45 IS 5 BP 615 EP 619 DI 10.1016/S0006-3223(98)00122-X PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 175XE UT WOS:000079120600011 PM 10088048 ER PT J AU Constantino, JN Murphy, DL Morris, JA AF Constantino, JN Murphy, DL Morris, JA TI Family psychiatric history, cerebrospinal fluid monoamine metabolites, and temperament in infants SO BIOLOGICAL PSYCHIATRY LA English DT Article DE monoamine metabolites; serotonin; temperament; behavior genetics; schizophrenia; antisocial personality disorder ID RHESUS-MONKEYS; HOMOVANILLIC-ACID; SEROTONIN FUNCTION; CSF 5-HIAA; DISORDER; TRAITS; BRAIN; HERITABILITY; ASSOCIATION; AGGRESSION AB Background: Variations in cerebrospinal fluid (CSF) levels of the monoamine metabolites 5-hydroxyindoleacetic acid, 3-methoxv-4-hydroxyphenylglycol, and homovanillic acid have been associated with behavioral abnormalities in nonhuman primates, and with psychopathology in studies of children and adults. Methods: We assayed monoamine metabolites in "leftover" spinal fluid from 167 neurologically normal newborn infants (0-3 months of age), and later (at age 18-21 months of age) obtained their family psychiatric histories and assessed their temperament using the Colorado Childhood Temperament Inventory (CCTI). Results: Family history of antisocial personality disorder predicted significantly lower scores for soothability (p =.003) at 18-21 months. There were no statistically significant associations between newborn monoamine metabolite levels and any aspect of temperament on the CCTI, Conclusions: These findings suggest complex relationships between genetic liability for psychiatric disorders and CSF monoamine metabolite levels; those relationships do not seem to be mediated by infant temperament. It appears likely that interindividual differences in monoamine metabolite levels change over the course of development in humans. Biol Psychiatry 1999;45:626-632 (C) 1999 Society of Biological Psychiatry. C1 Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. RP Constantino, JN (reprint author), Washington Univ, Sch Med, Dept Psychiat, 4940 Childrens Pl, St Louis, MO 63110 USA. FU NIMH NIH HHS [1R03MH56317-01] NR 42 TC 7 Z9 7 U1 3 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAR 1 PY 1999 VL 45 IS 5 BP 626 EP 632 DI 10.1016/S0006-3223(98)00170-X PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 175XE UT WOS:000079120600013 PM 10088050 ER PT J AU Gourovitch, ML Torrey, EF Gold, JM Randolph, C Weinberger, DR Goldberg, TE AF Gourovitch, ML Torrey, EF Gold, JM Randolph, C Weinberger, DR Goldberg, TE TI Neuropsychological performance of monozygotic twins discordant for bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE bipolar; psychiatric; neuropsychology; memory ID COGNITIVE CHANGES; SCHIZOPHRENIA; NEUROLEPTICS; MEMORY AB Background: A paradigm that involves cognitive assessment of monozygotic (MZ) twins discordant for a neuropsychiatric disorder there bipolar illness) allows for the examination of bath disease-specific impairments tin the comparison of affected to unaffected twins) and risk factors tin the comparison of unaffected twins to normal twins), Methods: Neuropsychological functions were evaluated in seven MZ twin pairs discordant for bipolar illness and seven pairs of normal MZ twins in an attempt to highlight cognitive abilities associated with manifestations of disease and genetic risk factors. Ar the time of testing, 3 of the affected twins were euthymic, 2 had depressive symptoms, and 2 had manic symptoms; all were receiving medication. All twins receive neuropsychological tests to evaluate intelligence, attention, visuospatial skills, language, learning and memory, and problem solving. Results: Statistical analyses revealed that the affected twins were significantly impaired as compared to the unaffected land normal) twins on some measures of visuospatial functioning and some verbal memory measures. In contrast to a sample of MZ twins discordant for schizophrenia studied previously, the cognitive impairments we observed in bipolar twins were mild in nature and fairly circumscribed. The unaffected twins performed significantly worse than normal controls on a Brown-Petersen memory task, verbal list learning, and overall Wechsler Memory Quotient. Conclusions: These data suggest that while some visuospatial deficits and verbal memory deficits may be features of bipolar disorder related to disease parameters, mild attenuations in overall memory or retrieval function may be related to genetic factors associated with the illness, Biol Psychiatry 1999;45:639-646 (C) 1999 Society of Biological Psychiatry. C1 NIMH, Clin Brain Disorders Branch, Intramural Res Program, NIH, Washington, DC USA. NIMH, Clin Serv Branch, Intramural Res Program, NIH, Washington, DC USA. RP Goldberg, TE (reprint author), St Elizabeth Hosp, Ctr Neurosci, NIMH, Clin Brain Disorders Branch, Washington, DC 20032 USA. NR 27 TC 131 Z9 135 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAR 1 PY 1999 VL 45 IS 5 BP 639 EP 646 DI 10.1016/S0006-3223(98)00148-6 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 175XE UT WOS:000079120600015 PM 10088052 ER PT J AU Schuckit, MA Mazzanti, C Smith, TL Ahmed, U Radel, M Iwata, N Goldman, D AF Schuckit, MA Mazzanti, C Smith, TL Ahmed, U Radel, M Iwata, N Goldman, D TI Selective genotyping for the role of 5-HT2A, 5-HT2C, and GABA(alpha 6) receptors and the serotonin transporter in the level of response to alcohol: A pilot study SO BIOLOGICAL PSYCHIATRY LA English DT Article DE alcoholism; genetics; longitudinal; serotonin; GABA(A alpha 6) ID QUANTITATIVE TRAIT LOCI; ETHANOL; SENSITIVITY; DEPENDENCE; GABA; MEN; GENE; SONS; ASSOCIATION; PREFERENCE AB Background: The vulnerability to alcohol dependence appears to be genetically influenced through a variety of mechanisms. One potentially genetically mediated channel may be a low level of response (LR) to alcohol, which has been seen in children of alcoholics and noted to predict future alcohol abuse and dependence. This pilot study uses a case and control genetic association approach to evaluate the possible role of five genotypes in both LR and alcoholism in informative subgroups of men with high and low LR scores documented 15 years earlier. Methods: As part of a larger study, 41 men, about 39 years old, were selected from among the first 113, completed 15-year follow-ups in a prospective study. The 17 subjects whose LRs at age 20 were in the lower third were compared on five polymorphisms of four genes with 24 men whose reactions to alcohol had been above the median, Results: The 14 men with the LL genotype of the serotonin transporter (5-HTT) polymorphism and the seven with the Pro/Ser genotype of the GAB(A alpha 6) polymorphism had demonstrated lower LR scores at about age 20, and had significantly higher proportions of alcoholics than the other genotypes for those loci. All four subjects with combined LL and Pro/Ser genotypes had developed alcoholism and demonstrated the lowest LR scores overall, There was no evidence that two polymorphisms of the 5-HT2A receptor gene and one of the 5-HT2C receptor gene were related to LR or alcoholism in this sample. Conclusions: These results are consistent with animal and human studies suggesting a possible role for genetic variation in the GABA(A alpha 6) and the serotonin transporter in the reaction to alcohol and the alcoholism risk. Biol Psychiatry 1999;45:647-651 (C) 1999 Society of Biological Psychiatry. C1 Vet Affairs Med Ctr, Dept Psychiat 116A, Alcohol Res Ctr, San Diego, CA 92161 USA. Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA. NIAAA, NIH, Rockville, MD 20852 USA. RP Schuckit, MA (reprint author), Vet Affairs Med Ctr, Dept Psychiat 116A, Alcohol Res Ctr, 3350 La Jolla Village Dr, San Diego, CA 92161 USA. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 FU PHS HHS [05526] NR 41 TC 186 Z9 191 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAR 1 PY 1999 VL 45 IS 5 BP 647 EP 651 DI 10.1016/S0006-3223(98)00248-0 PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 175XE UT WOS:000079120600016 PM 10088053 ER PT J AU Roberts, RL Wolf, KN Sprangel, ME Rall, WF Wildt, DE AF Roberts, RL Wolf, KN Sprangel, ME Rall, WF Wildt, DE TI Prolonged mating in prairie voles (Microtus ochrogaster) increases likelihood of ovulation and embryo number SO BIOLOGY OF REPRODUCTION LA English DT Article ID SEXUAL-BEHAVIOR; FEMALE; HORMONE; ESTRUS AB Prairie voles are induced ovulators that mate frequently in brief bouts over a period of similar to 24 h. We examined 1) impact of mating duration on ovulation and embryo number, 2) incidence of fertilization, 3) temporal pattern of embryo development, 4) embryo progression through the reproductive tract over time, and 5) embryo development in culture. Mating was videotaped to determine first copulation, and the ovaries were examined and the reproductive tracts flushed at 6, 8, 10, 12, 16, 20, and 24 h and 2, 3, and 4 days after first copulation. The number of mature follicles and fresh corpora lutea and the number and developmental stage of embryos were quantified. One, two-, and four-cell embryos were cultured in Whitten's medium. Mature follicles were present at the earliest time examined (6 h). Thirty-eight percent of females that had been paired for < 12 h after the first copulation ovulated, whereas all females paired greater than or equal to 12 h after the first copulation ovulated. Virtually all (> 99%) oocytes recovered from females paired for greater than or equal to 12 h after first copulation were fertilized. Pairing time after first copulation and mean copulation-bout duration were significant (p < 0.05) determinants of embryo number. Embryos entered the uterine horns and implanted on Days 3 and 4, respectively, after first copulation (Day 0). Embryos cultured in vitro underwent approximately one cell division per day, a rate similar to that in vivo. We conclude that prairie voles ovulate reliably after pairing for greater than or equal to 72 h, although some females showed exceptional sensitivity not predicted by the variables quantified. Prolonged mating for longer than 12 h increased the total embryos produced. This mechanism likely has adaptive significance for increasing offspring number. C1 Smithsonian Inst, Natl Zool Pk, Reprod Physiol Program, Washington, DC 20008 USA. Smithsonian Inst, Natl Zool Pk, Conservat & Res Ctr, Front Royal, VA 22630 USA. NIH, Vet Resources Program, Off Res Serv, Bethesda, MD 20892 USA. RP Roberts, RL (reprint author), NICHHD, Comparat Ethol Lab, POB 529,16701 Elmer Sch Rd, Poolesville, MD 20837 USA. EM lr123g@nih.gov RI Rall, William/C-5104-2008 NR 24 TC 18 Z9 18 U1 2 U2 4 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD MAR PY 1999 VL 60 IS 3 BP 756 EP 762 DI 10.1095/biolreprod60.3.756 PG 7 WC Reproductive Biology SC Reproductive Biology GA 170RY UT WOS:000078820900032 PM 10026127 ER PT J AU Johnson, ES Halabi, S Netto, G Lucier, G Bechtold, W Henderson, R AF Johnson, ES Halabi, S Netto, G Lucier, G Bechtold, W Henderson, R TI Detection of low level benzene exposure in supermarket wrappers by urinary muconic acid SO BIOMARKERS LA English DT Article DE benzene; muconic acid; biomarkers; supermarket; plastic wrap ID S-PHENYLMERCAPTURIC ACID; TRANS,TRANS-MUCONIC ACID; RISK ASSESSMENT; INDICATOR; WORKERS; MEAT; INDUSTRY; IMPROVEMENT; MORTALITY; CATECHOL AB Women who use the 'hot wire' and 'cool rod' machines to wrap meat in supermarkets are potentially exposed to law levels of benzene and polycyclic aromatic hydrocarbons present in fumes emitted during the thermal decomposition of the plastic used to wrap meat. In order to evaluate whether the benzene metabolite trans, trans-muconic acid (MA) can be used to monitor these low levels, we collected urine samples from supermarket workers, and assayed the urine for MA. Geometric mean after-shift MA levels were highest for subjects who used the 'hot wire' machine, i.e. > 300 ng mg(-1) creatinine (Cr). The corresponding levels for subjects who used the 'cool rod' machine were similar to those for subjects who did not use either type of machine, and were much lower These results indicate that urinary muconic acid has some potential for use in monitoring benzene exposures of less than 1 part per million (ppm). The study detected very high background MA levels (exceeding 2000 ng mg(-1) Cr) in some subjects, suggesting that individuals in thr general population without occupational exposure to benzene may have urinary MA levels equivalent to exposure to up to 2 ppm benzene in ambient air. However, since non-benzene sources of the metabolite cannot be completely ruled out as partially responsible for these high levels, the public health significance of this finding is not known at the moment. C1 Tulane Univ, Med Ctr, Dept Biostat & Epidemiol, New Orleans, LA 70112 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Div Biometry, Durham, NC 27710 USA. Lovelace Biomed & Environm Res Inst, Inhalat Toxicol Res Inst, Albuquerque, NM 87185 USA. RP Johnson, ES (reprint author), Tulane Univ, Med Ctr, Dept Biostat & Epidemiol, New Orleans, LA 70112 USA. NR 41 TC 14 Z9 14 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON EC4A 3DE, ENGLAND SN 1354-750X J9 BIOMARKERS JI Biomarkers PD MAR-APR PY 1999 VL 4 IS 2 BP 106 EP 117 PG 12 WC Biotechnology & Applied Microbiology; Toxicology SC Biotechnology & Applied Microbiology; Toxicology GA 179EH UT WOS:000079312300002 ER PT J AU Wu, MC Follmann, DA AF Wu, MC Follmann, DA TI Use of summary measures to adjust for informative missingness in repeated measures data with random effects SO BIOMETRICS LA English DT Article DE exponential family; informative censoring; linear model; sufficient statistics ID RANDOM-EFFECTS MODELS; LONGITUDINAL DATA; LINEAR-MODEL; INFERENCE; REGRESSION AB We discuss how to apply the conditional informative missing model of Wu and Bailey (1989, Biometrics 45, 939-955) to the setting where the probability of missing a visit depends on the random effects of the primary response in a time-dependent fashion. This includes the case where the probability of missing a visit depends on the true value of the primary response. Summary measures for missingness that are weighted sums of the indicators of missed visits are derived for these situations. These summary measures are then incorporated as covariates in a random effects model for the primary response. This approach is illustrated by analyzing data collected from a trial of heroin addicts where missed visits are informative about drug test results. Simulations of realistic experiments indicate that these time-dependent summary measures also work well under a variety of informative censoring models. These summary measures can achieve large reductions in estimation bias and mean squared errors relative to those obtained by using other summary measures. C1 NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. RP Wu, MC (reprint author), NHLBI, Off Biostat Res, 2 Rockledge Ctr MSC 7938, Bethesda, MD 20892 USA. EM mwu@cu.nih.gov NR 25 TC 15 Z9 15 U1 0 U2 1 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 1441 I ST, NW, SUITE 700, WASHINGTON, DC 20005-2210 USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD MAR PY 1999 VL 55 IS 1 BP 75 EP 84 DI 10.1111/j.0006-341X.1999.00075.x PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 183RK UT WOS:000079567100009 PM 11318181 ER PT J AU Freidlin, B Gastwirth, JL AF Freidlin, B Gastwirth, JL TI Unconditional versions of several tests commonly used in the analysis of contingency tables SO BIOMETRICS LA English DT Article DE Cochran-Armitage test; Cochran-Mantel-Haenszel test; contingency tables; exact inference; p-value; unconditional test ID P-VALUES; 2X2; POWER; TRIAL AB By focusing an a confidence interval fora nuisance parameter, Berger and Boos(1994, Journal of the American Statistical Association 89, 1012-1016) proposed new unconditional tests. In particular, they showed that, for a 2 x 2 table, this procedure generally was more powerful than Fisher's exact test. This paper utilizes and extends their approach to obtain unconditional tests for combining several 2 x 2 tables and testing for trend and homogeneity in a 2 x K table. The unconditional procedures are compared to the conditional ones by reanalyzing some published biomedical data. C1 NCI, Biometr Res Branch, Bethesda, MD 20892 USA. George Washington Univ, Dept Stat, Washington, DC 20052 USA. RP Freidlin, B (reprint author), NCI, Biometr Res Branch, 6130 Execut Blvd EPN Rm 739, Bethesda, MD 20892 USA. NR 19 TC 9 Z9 9 U1 0 U2 2 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 1441 I ST, NW, SUITE 700, WASHINGTON, DC 20005-2210 USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD MAR PY 1999 VL 55 IS 1 BP 264 EP 267 DI 10.1111/j.0006-341X.1999.00264.x PG 4 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 183RK UT WOS:000079567100032 PM 11318165 ER PT J AU Nam, JM AF Nam, JM TI Power and sample size for testing homogeneity of relative risks in prospective studies SO BIOMETRICS LA English DT Article DE power; sample size; score test; testing homogeneity of relative risks; prospective studies ID INTERVAL ESTIMATION; TABLES; RATIO AB Power and sample-size formulas for testing the homogeneity of relative risks using the score method are presented. The homogeneity score test (Gart, 1985, Biometrika 72, 673-677) is formally equivalent to the Pearson chi-square test, although they look different. Results of this paper may be useful in assessing the validity of the model of a common relative risk before combining several 2 x 2 tables or in designing a prospective study for detecting heterogeneity of relative risks. C1 NCI, Biostat Branch, Bethesda, MD 20892 USA. RP Nam, JM (reprint author), NCI, Biostat Branch, Execut Plaza N,Room 403,6130 Execut Blvd,MSC 7368, Bethesda, MD 20892 USA. NR 19 TC 9 Z9 10 U1 0 U2 1 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 1441 I ST, NW, SUITE 700, WASHINGTON, DC 20005-2210 USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD MAR PY 1999 VL 55 IS 1 BP 289 EP 293 DI 10.1111/j.0006-341X.1999.00289.x PG 5 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 183RK UT WOS:000079567100037 PM 11318170 ER PT J AU Gu, MG Follmann, D Geller, NL AF Gu, MG Follmann, D Geller, NL TI Monitoring a general class of two-sample survival statistics with applications SO BIOMETRIKA LA English DT Article DE clinical trial; failure time data; group sequential monitoring; Pepe-Fleming statistic ID KAPLAN-MEIER STATISTICS; TRIALS; TESTS AB This paper considers a general class of statistics for testing the equality of two survival distributions in clinical trials with sequential monitoring. The tests can be expressed as Lebesgue-Stieltjes integrals of a weight function with respect to the difference between two survival distributions. Prominent members of this class include the two-sample difference in Kaplan-Meier estimates, the test of medians (Brookmeyer & Crowley, 1982), a truncated version of Efron's (1967) test and the Pepe-Fleming statistic (Pepe & Fleming, 1989, 1991). Statistics in this class are shown to converge to a Gaussian process, indexed by information time, under both null and local alternatives even if different statistics are used at different information times. Properly standardised, statistics in a subclass converge to Gaussian processes with independent increments so that the usual group sequential techniques for monitoring a clinical trial can be applied. The design of a trial comparing two treatments with respect to mother-to-newborn transmission of HIV is used to illustrate practical aspects of monitoring. C1 Chinese Univ Hong Kong, Dept Stat, Hong Kong, Peoples R China. NHLBI, Off Biostat Res, Rockledge Ctr 2, Bethesda, MD 20892 USA. RP Gu, MG (reprint author), Chinese Univ Hong Kong, Dept Stat, Hong Kong, Peoples R China. EM minggao@cuhk.edu.hk; follmann@helix.nih.gov; ng@helix.nih.gov NR 16 TC 9 Z9 9 U1 2 U2 6 PU BIOMETRIKA TRUST PI LONDON PA UNIV COLLEGE LONDON GOWER ST-BIOMETRIKA OFFICE, LONDON, ENGLAND WC1E 6BT SN 0006-3444 J9 BIOMETRIKA JI Biometrika PD MAR PY 1999 VL 86 IS 1 BP 45 EP 57 DI 10.1093/biomet/86.1.45 PG 13 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 183RG UT WOS:000079566800004 ER PT J AU Verheijen, JC van der Marel, GA van Boom, JH Bayly, SF Player, MR Torrence, PF AF Verheijen, JC van der Marel, GA van Boom, JH Bayly, SF Player, MR Torrence, PF TI 2 ',5 '-oligoadenylate-peptide nucleic acids (2-5A-PNAs) activate RNase L SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE antisense; RNA; PNA; 2-5A; nucleic acids; peptides and polypeptides; chemotherapy ID ANTISENSE OLIGONUCLEOTIDES; 2-5A ANTISENSE; TARGETING RNA; CHIMERAS; INHIBITION; POLYAMIDE; CLEAVAGE; SYSTEM; PNA; DNA AB To potentiate the 2-5A (2',5'-oligoadenylate)-antisense and peptide nucleic acid (PNA) approaches to regulation of gene expression, composite molecules were generated containing both 2-5A and PNA moieties. 2-5A-PNA adducts were synthesized using solid-phase techniques. Highly cross-linked polystyrene beads were functionalized with glycine tethered through a p-hydroxymethylbenzoic acid linker and the PNA domain of the chimeric oligonucleotide analogue was added by sequential elongation of the amino terminus with the monomethoxytrityl protected N-(2-aminoethyl)-N-(adenin-1-ylacetyl)glycinate. Transition to the 2-5A domain was accomplished by coupling of the PNA chain to dimethoxytrityl protected N-(2-hydroxyethyl)-N-(adenin-1-ylacetyl)glycinate, Finally, (2-cyanoethyl)-N,N-diisopropyl-4-O-(4,4-dimethoxytrityl)butylphosphoramidite and the corresponding (2-cyanoethyl)-N, N-diisopropylphosphoramidite of 5-O-(4,4'-dimethoxytrityl)-3-O-(tert-butyldimethylsilyl)-N-6-benzoyladenosine were the synthons employed to add the 2 butanediol phosphate linkers and the four 2',5'-linked riboadenylates. The 5'-phosphate moiety was introduced with 2-[[2-(4,4'-dimethoxytrityloxy)ethyl]sulfonyl]ethyl-(2-cyanoethyl)-N,N-diisopropylphosphoramidite. Deprotection with methanolic NH3 and tetraethylammonium fluoride afforded the desired products, 2-5A-pnaA(4), 2-5A-pnaA(8) and 2-5A-pnaA(12). When evaluated for their ability to cause the degradation of two different RNA substrates by the 2-5A-dependent RNase L, these new 2-5A-PNA conjugates were found to be potent RNase L activators. The union of 2-5A and PNA presents fresh opportunities to explore the biological and therapeutic implications of these unique approaches to antisense. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 NIDDKD, Sect Biomed Chem, Med Chem Lab, NIH, Bethesda, MD 20982 USA. Gorlaeus Labs, Leiden Inst Chem, NL-2300 RA Leiden, Netherlands. RP Torrence, PF (reprint author), NIDDKD, Sect Biomed Chem, Med Chem Lab, NIH, Bethesda, MD 20982 USA. NR 32 TC 21 Z9 22 U1 0 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD MAR PY 1999 VL 7 IS 3 BP 449 EP 455 DI 10.1016/S0968-0896(98)00258-2 PG 7 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 181UK UT WOS:000079460700004 PM 10220031 ER PT J AU Kinard, TA de Vries, G Sherman, A Satin, LS AF Kinard, TA de Vries, G Sherman, A Satin, LS TI Modulation of the bursting properties of single mouse pancreatic beta-cells by artificial conductances SO BIOPHYSICAL JOURNAL LA English DT Article ID INDUCED ELECTRICAL-ACTIVITY; INSULIN-SECRETING CELLS; SENSITIVE K+ CHANNELS; 2 CALCIUM CURRENTS; B-CELLS; INTRACELLULAR ATP; POTASSIUM CHANNEL; ACTION-POTENTIALS; DYNAMIC-CLAMP; CA2+ CURRENT AB Glucose triggers bursting activity in pancreatic islets, which mediates the Ca2+ uptake that triggers insulin secretion. Aside from the channel mechanism responsible for bursting, which remains unsettled, it is not clear whether bursting is an endogenous property of individual beta-cells or requires an electrically coupled islet. While many workers report stochastic firing or quasibursting in single cells, a few reports describe single-cell bursts much longer (minutes) than those of islets (15-60 s). We studied the behavior of single cells systematically to help resolve this issue. Perforated patch recordings were made from single mouse beta-cells or hamster insulinoma tumor cells in current clamp at 30-35 degrees C, using standard K+-rich pipette solution and external solutions containing 11.1 mM glucose. Dynamic clamp was used to apply artificial K-ATP and Ca2+ channel conductances to cells in current clamp to assess the role of Ca2+ and K-ATP channels in single cell firing. The electrical activity we observed in mouse beta-cells was heterogeneous, with three basic patterns encountered: 1) repetitive fast spiking; 2) fast spikes superimposed on brief (<5 s) plateaus; or 3) periodic plateaus of longer duration (10-20 s) with small spikes. Pattern 2 was most similar to islet bursting but was significantly faster. Burst plateaus lasting on the order of minutes were only observed when recordings were made from cell clusters. Adding g(Ca) to cells increased the depolarizing drive of bursting and lengthened the plateaus, whereas adding g(KATP) hyperpolarized the cells and lengthened the silent phases. Adding g(Ca) and g(KATP) together did not cancel out their individual effects but could induce robust bursts that resembled those of islets, and with increased period. These added currents had no slow components, indicating that the mechanisms of physiological bursting are likely to be endogenous to single beta-cells. It is unlikely that the fast bursting (class 2) was due to oscillations in g(KATP) because it persisted in 100 mu M tolbutamide. The ability of small exogenous currents to modify beta-cell firing patterns supports the hypothesis that single cells contain the necessary mechanisms for bursting but often fail to exhibit this behavior because of heterogeneity of cell parameters. C1 Virginia Commonwealth Univ, Med Coll Virginia Campus, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Physiol, Richmond, VA 23298 USA. Univ Alberta, Dept Math Sci, Edmonton, AB T6G 2G1, Canada. NIDDKD, NIH, Math Res Branch, Bethesda, MD 20892 USA. RP Satin, LS (reprint author), Virginia Commonwealth Univ, Med Coll Virginia Campus, Dept Pharmacol & Toxicol, Box 980524, Richmond, VA 23298 USA. EM lsatin@hsc.vcu.edu FU NIDDK NIH HHS [DK46409] NR 58 TC 78 Z9 78 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD MAR PY 1999 VL 76 IS 3 BP 1423 EP 1435 PG 13 WC Biophysics SC Biophysics GA 173GG UT WOS:000078972300024 PM 10049324 ER PT J AU Kraft, T Xu, S Brenner, B Yu, LC AF Kraft, T Xu, S Brenner, B Yu, LC TI The effect of thin filament activation on the attachment of weak binding cross-bridges: A two-dimensional X-ray diffraction study on single muscle fibers SO BIOPHYSICAL JOURNAL LA English DT Article ID ACTOMYOSIN ADENOSINE-TRIPHOSPHATASE; FROG SARTORIUS MUSCLE; RABBIT PSOAS FIBERS; LOW IONIC-STRENGTH; MYOSIN SUBFRAGMENT-1; STRUCTURAL-CHANGES; FORCE GENERATION; SKELETAL-MUSCLE; ELECTRON CRYOMICROSCOPY; TROPONIN-TROPOMYOSIN AB To study possible structural changes in weak cross-bridge attachment to actin upon activation of the thin filament, two-dimensional (2D) x-ray diffraction patterns of skinned fibers from rabbit psoas muscle were recorded at low and high calcium concentration in the presence of saturating concentrations of MgATP gamma S, a nucleotide analog for weak binding states. We also studied 2D x-ray diffraction patterns recorded under relaxing conditions at an ionic strength above and below 50 mM, because it had been proposed from solution studies that reducing ionic strength below 50 mM also induces activation of the thin filament. For this project a novel preparation had to be established that allows recording of 2D x-ray diffraction patterns from single muscle fibers instead of natural fiber bundles. This was required to minimize substrate depletion or product accumulation within the fibers. When the calcium concentration was raised, the diffraction patterns recorded with MgATP gamma S revealed small changes in meridional reflections and layer line intensities that could be attributed in part to the effects of calcium binding to the thin filament (increase in I(380), decrease in first actin layer line intensity, increase in I(59)) and in part to small structural changes of weakly attached cross-bridges (e.g., increase in I(143) and I(72)). Calcium-induced small-scale structural rearrangements of cross-bridges weakly attached to actin in the presence of MgATP gamma S are consistent with our previous observation of reduced rate constants for attachment and detachment of cross-bridges with MgATP gamma S at high calcium. Yet, no evidence was found that weakly attached cross-bridges change their mode of attachment toward a stereospecific conformation when the actin filament is activated by adding calcium. Similarly, reducing ionic strength to less than 50 mM does not induce a transition from nonstereospecific to stereospecific attachment. C1 Hannover Med Sch, D-30625 Hannover, Germany. NIH, Bethesda, MD 20892 USA. RP Kraft, T (reprint author), Hannover Med Sch, D-30625 Hannover, Germany. EM kraft.theresia@mh-hannover.de NR 70 TC 25 Z9 25 U1 1 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 1999 VL 76 IS 3 BP 1494 EP 1513 PG 20 WC Biophysics SC Biophysics GA 173GG UT WOS:000078972300030 PM 10049330 ER PT J AU La Penna, G Mormino, M Pioli, F Perico, A Fioravanti, R Gruschus, JM Ferretti, JA AF La Penna, G Mormino, M Pioli, F Perico, A Fioravanti, R Gruschus, JM Ferretti, JA TI Smoluchowski dynamics of the vnd/NK-2 homeodomain from Drosophila melanogaster: First-order mode-coupling approximation SO BIOPOLYMERS LA English DT Article DE Smoluchowski diffusion; protein dynamics; molecular dynamics simulations; homeodomain containing protein; nmr relaxation ID TIME-CORRELATION-FUNCTION; ONE-DIMENSIONAL SYSTEMS; ROUSE-ZIMM MODEL; MOLECULAR-DYNAMICS; NK-2 HOMEODOMAIN; RELAXATION; POLYMER; DNA; MACROMOLECULES; SPECTROSCOPY AB This work is the first in a series devoted to applying mode coupling diffusion theory to the derivation of local dynamics properties of proteins in solution. The first-order mode-coupling approximation, or optimized Rouse-Zimm local dynamics (ORZLD), is applied here to derive the rotational dynamics of the bonds and compare the calculated with the experimental nmr (15)N spin-lattice relaxation time behavior of the vnd/NK-2 homeodomain from Drosophila melanogaster. The starting point for the calculations is the experimental three-dimensional structure of the homeodomain determined by multidimensional nmr spectroscopy. The results of the computations are compared with experimentally measured (15)N spin-lattice relaxation times T(1), at 34.5 and 60.8 MHz to check the first-order approximation. To estimate the relative importance of internal and overall rotation, both rigid and fluctuating dynamic models are examined with fluctuations evaluated using molecular dynamics (MD) simulations. The correlation times for the fundamental bond vector time correlation function and for the second-order bond orientational TCF are obtained as a function of the residue number for vnd/NK-2. The stability of the corresponding local dynamics pattern for the fluctuating structure as a function of the length of the MD trajectory is presented Diffusive dynamics, which is essentially free of model parameters even at first order in the,mode-coupling diffusion approach, confirm that local dynamics of proteins can be described in terms of rotational diffusion of a fluctuating quasi-rigid structure. The comparison with the nmr data shows that the first-order mode coupling diffusion approximation accounts for the correct order of magnitude of the results and of important qualitative aspects of the data sensitive to conformational changes. Indications are obtained from this study to efficiently extend the theory to higher order in the mode-coupling expansion. These results demonstrate the promise of the mode-coupling approach, where the local dynamics of proteins is described in terms of rotational diffusion of a fluctuating quasi-rigid structure, to analyze nmr spin-lattice relaxation behavior. (C) 1999 John Wiley & Sons, Inc. C1 CNR, Ist Studi Chimicofis Macromol Sintet & Nat, I-16149 Genoa, Italy. CNR, Ist Cibernet & Biofis, I-16149 Genoa, Italy. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Perico, A (reprint author), CNR, Ist Studi Chimicofis Macromol Sintet & Nat, Via De Marini 6, I-16149 Genoa, Italy. RI La Penna, Giovanni/E-5241-2011 OI La Penna, Giovanni/0000-0002-8619-4867 NR 43 TC 12 Z9 12 U1 1 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PD MAR PY 1999 VL 49 IS 3 BP 235 EP 254 PG 20 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 162WX UT WOS:000078371000005 PM 9990841 ER PT J AU Carella, AM Lerma, E Corsetti, MT Dejana, A Basta, P Vassallo, F Abate, M Soracco, M Benvenuto, F Figari, O Podesta, M Piaggio, G Ferrara, R Sessarego, M Parodi, C Pizzuti, M Rubagotti, A Occhini, D Frassoni, F AF Carella, AM Lerma, E Corsetti, MT Dejana, A Basta, P Vassallo, F Abate, M Soracco, M Benvenuto, F Figari, O Podesta, M Piaggio, G Ferrara, R Sessarego, M Parodi, C Pizzuti, M Rubagotti, A Occhini, D Frassoni, F TI Autografting with Philadelphia chromosome-negative mobilized hematopoietic progenitor cells in chronic myelogenous leukemia SO BLOOD LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; BONE-MARROW TRANSPLANTATION; NATURAL-KILLER-CELLS; INTERFERON-ALPHA; AUTOLOGOUS TRANSPLANTATION; CHRONIC PHASE; STEM-CELLS; BLOOD; CML; INTERLEUKIN-2 AB Intensive chemotherapy given in early chronic phase of chronic myelogenous leukemia (CML) has resulted in high numbers of circulating Philadelphia (Ph) chromosome-negative hematopoietic progenitor cells (HPC). We have autografted 30 consecutive patients with CML in chronic phase with HPC collected in this way to facilitate restoration of Ph-negative hematopoiesis in bone marrow after high-dose therapy. Hematopoietic recovery to greater than 0.5 x 10(9)/L neutrophils and to greater than 25 x 10(9)/L platelets occurred in all patients, a median of 13 (range, 9 to 32) days and 16 (range, 6 to 106) days postautograft, respectively. Regenerating marrow cells were Ph-negative in 16 (53%) patients and greater than 66% Ph-negative in 10 (33%) patients. Twenty-eight patients are alive 6 to 76 months (median, 24 months) after autografting. Three patients have developed blast crisis from which 2 have died. Eight patients are in complete cytogenetic remission at a median of 20 (range, 6 to 44) months with a median ratio BCR-ABL/ABL of 0.002 (range, <0.001 to 0.01). Eight patients are in major cytogenetic remission at a median of 22 (range, 6 to 48) months. No patient died as a consequence of the treatment. All patients had some degree of stomatitis that was severe in 15 (50%) patients. Gastrointestinal and hepatic toxicities were observed in about one fourth of patients. Thus, autografting with Ph-negative mobilized HPC can result in prolonged restoration of Ph negative hematopoiesis for some patients with CML; moreover, most autograft recipients report normal or near normal activity levels, suggesting that this procedure need not to be associated either with prolonged convalescence or with chronic debility. (C) 1999 by The American Society of Hematology. C1 Osped San Martino Genova, Dept Hematol, Hematol ABMT Unit, I-16148 Genoa, Italy. Univ Genoa, Natl Canc Inst, Dept Oncol, Biostat Unit, I-16126 Genoa, Italy. Univ Genoa, DIMI, I-16126 Genoa, Italy. RP Carella, AM (reprint author), Osped San Martino Genova, Dept Hematol, Hematol ABMT Unit, Via Acerbi 10-22, I-16148 Genoa, Italy. EM amcarella@smartino.ge.it NR 48 TC 60 Z9 62 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 1 PY 1999 VL 93 IS 5 BP 1534 EP 1539 PG 6 WC Hematology SC Hematology GA 168TM UT WOS:000078708800013 PM 10029581 ER PT J AU Yao, L Sgadari, C Furuke, K Bloom, ET Teruya-Feldstein, J Tosato, G AF Yao, L Sgadari, C Furuke, K Bloom, ET Teruya-Feldstein, J Tosato, G TI Contribution of natural killer cells to inhibition of angiogenesis by interleukin-12 SO BLOOD LA English DT Article ID INTERFERON-INDUCIBLE PROTEIN-10; STIMULATORY FACTOR INTERLEUKIN-12; ENDOTHELIAL GROWTH-FACTOR; NECROSIS IN-VIVO; NK CELLS; RECOMBINANT IL-12; HUMAN-LYMPHOCYTES; TUMOR-REGRESSION; GAMMA PRODUCTION; T-LYMPHOCYTES AB Interleukin-12 (IL-12) inhibits angiogenesis in vivo by inducing interferon-gamma (IFN-gamma) and other downstream mediators. Here, we report that neutralization of natural killer (NK) cell function with antibodies to either asialo GM1 or NK 1.1 reversed IL-12 inhibition of basic fibroblast growth factor (bFGF)-induced angiogenesis in athymic mice. By immunohistochemistry, those sites where bFGF-induced neovascularization was inhibited by IL-12 displayed accumulation of NK cells and the presence of IP-10-positive cells. Based on expression of the cytolytic mediators perforin and granzyme B, the NK cells were locally activated. Experimental Burkitt lymphomas treated locally with IL-12 displayed tumor tissue necrosis, vascular damage, and NK-cell infiltration surrounding small vessels. After activation in vitro with IL-12 NK cells from nude mice became strongly cytotoxic for primary cultures of syngeneic aortic endothelial cells. Cytotoxicity was neutralized by antibodies to IFN-gamma. These results document that NK cells are required mediators of angiogenesis inhibition by IL-12 and provide evidence that NK-cell cytotoxicity of endothelial cells is a potential mechanism by which IL-12 can suppress neovascularization. C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol Prod, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. NCI, Pathol Lab, Hematopathol Sect, Bethesda, MD 20892 USA. RP Yao, L (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Hematol Prod, Bldg 29A,Room 2D06,8800 Rockville Pike, Bethesda, MD 20892 USA. RI Sgadari, Cecilia/H-4302-2016 OI Sgadari, Cecilia/0000-0003-0364-4912 NR 52 TC 153 Z9 158 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 1 PY 1999 VL 93 IS 5 BP 1612 EP 1621 PG 10 WC Hematology SC Hematology GA 168TM UT WOS:000078708800022 PM 10029590 ER PT J AU Socie, G Curtis, RE Deeg, HJ Horowitz, MM AF Socie, G Curtis, RE Deeg, HJ Horowitz, MM TI New malignant diseases after allogeneic BMT performed in childhood for acute leukemia. SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract C1 Hop St Louis, Serv Hematol Greffe Moelle, Paris, France. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Med Coll Wisconsin, IBMTR, Milwaukee, WI 53226 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAR PY 1999 VL 23 SU 1 MA 428 BP S130 EP S130 PG 1 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 183PV UT WOS:000079562900433 ER PT J AU Catalan, MJ Ishii, K Honda, M Samii, A Hallett, M AF Catalan, MJ Ishii, K Honda, M Samii, A Hallett, M TI A PET study of sequential finger movements of varying length in patients with Parkinson's disease SO BRAIN LA English DT Article DE Parkinson's disease; SMA; parietal; premotor; PET ID POSITRON EMISSION TOMOGRAPHY; SUPPLEMENTARY MOTOR AREA; CEREBRAL BLOOD-FLOW; FUNCTIONAL-ANATOMY; CORTICAL AREAS; ACTIVATION; CORTEX; PERFORMANCE; APOMORPHINE; OCULOMOTOR AB To study the difficulty that patients with Parkinson's disease have in performing long sequential movements, we used (H2O)-O-15 PET to assess the regional cerebral blood flow (rCBF) associated with the performance of simple repetitive movements, well-learned sequential finger movements of varying length and self-selected movements. Sequential finger movements in the Parkinson's disease patients were associated with an activation pattern similar to that found in normal subjects, but Parkinson's disease patients showed relative overactivity in the precuneus, premotor and parietal cortices, Increasing the complexity of movements resulted in increased rCBF in the premotor and parietal cortices of normal subjects; the Parkinson's disease patients showed greater increases in these same regions and had additional significant increases in the anterior supplementary motor area (SMA)/cingulate. Performance of self-selected movements induced significant activation of the anterior SMA/cingulate in normal subjects but not in Parkinson's disease patients. We conclude that in Parkinson's disease patients more cortical areas are recruited to perform sequential finger movements; this may be the result of increasing corticocortical activity to compensate for striatal dysfunction. C1 NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. Hosp Univ San Carlos, Serv Neurol, Madrid, Spain. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bldg 10,Room 5N226,10 Ctr Dr MSC 1428, Bethesda, MD 20892 USA. NR 53 TC 148 Z9 151 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD MAR PY 1999 VL 122 BP 483 EP 495 DI 10.1093/brain/122.3.483 PN 3 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 179QU UT WOS:000079340800010 PM 10094257 ER PT J AU Enger, SM Ross, RK Paganini-Hill, A Longnecker, MP Bernstein, L AF Enger, SM Ross, RK Paganini-Hill, A Longnecker, MP Bernstein, L TI Alcohol consumption and breast cancer oestrogen and progesterone receptor status SO BRITISH JOURNAL OF CANCER LA English DT Article DE alcohol; oestrogen receptors; progesterone receptors; breast neoplasms; epidemiology ID IOWA WOMENS HEALTH; POSTMENOPAUSAL WOMEN; GONADAL-HORMONES; RISK-FACTORS; LUTEINIZING-HORMONE; ESTROGEN-RECEPTORS; PROGNOSTIC FACTORS; PITUITARY; POPULATION; ESTRADIOL AB We examined the role of alcohol on the risk of breast cancer by the joint oestrogen receptor (ER) and progesterone receptor (PR) status or the tumour using data from two case-control studies conducted in Los Angeles County, USA. Eligible premenopausal patients were 733 women aged less than or equal to 40 years and first diagnosed from 1 July 1983 to 1 January 1989. Eligible postmenopausal patients were 1169 women aged 55-64 years and first diagnosed from 1 March 1987 to 31 December 89. Patients were identified by the University of Southern California Cancer Surveillance Program. Neighbourhood controls were individually matched to patients by parity (premenopausal patients) and birth date (+/- 3 years). ER and PR status were obtained from medical records for 424 premenopausal and 760 postmenopausal patients. The analyses included 714 premenopausal and 1091 postmenopausal control subjects. Alcohol use was generally not associated with premenopausal risk of breast cancer, regardless of hormone-receptor status. Among the postmenopausal women, those who consumed, on average, greater than or equal to 27 g of alcohol/d experienced an odds ratio (OR) of 1.76 [95% confidence interval (CI) 1.14-2.71] for ER-positive/PR-positive breast cancer relative to women who reported no alcohol consumption. Alcohol use was less clearly associated with risk of other receptor types among postmenopausal women. These data suggest that alcohol may preferentially increase risk of ER-positive/PR-positive breast cancer in postmenopausal women. C1 Kaiser Permanente Med Care Program, Dept Res & Evaluat, Pasadena, CA 91188 USA. Univ So Calif, Dept Prevent Med, Los Angeles, CA 90033 USA. Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Enger, SM (reprint author), Kaiser Permanente Med Care Program, Dept Res & Evaluat, 100 S Los Robles Ave,2nd Floor,So Calif, Pasadena, CA 91188 USA. OI Longnecker, Matthew/0000-0001-6073-5322 FU NCI NIH HHS [CA44546, CA17054, N01-CN25404] NR 36 TC 53 Z9 53 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD MAR PY 1999 VL 79 IS 7-8 BP 1308 EP 1314 DI 10.1038/sj.bjc.6690210 PG 7 WC Oncology SC Oncology GA 168NQ UT WOS:000078699500050 PM 10098777 ER PT J AU Ciolino, HP Yeh, GC AF Ciolino, HP Yeh, GC TI The flavonoid galangin is an inhibitor of CYP1A1 activity and an agonist/antagonist of the aryl hydrocarbon receptor SO BRITISH JOURNAL OF CANCER LA English DT Article DE galangin; flavonoid; DMBA; CYP1A1; EROD ID RAT-LIVER MICROSOMES; BREAST-CANCER CELLS; REGULATORY ELEMENTS; MAMMARY-CANCER; QUERCETIN; MCF-7; METABOLISM; CHEMOPREVENTION; PROLIFERATION; ACTIVATION AB The effect or the dietary flavonoid galangin on the metabolism of 7,12-dimethylbenz[a]anthracene (DMBA), the activity of cytochrome P-450 1A1 (CYP1A1), and the expression of CYP1A1 in MCF-7 human breast carcinoma cells was investigated. Galangin inhibited the catabolic breakdown of DMBA, as measured by thin-layer chromatography, in a dose-dependent manner. Galangin also inhibited the formation of DMBA-DNA adducts, and prevented DMBA-induced inhibition of cell growth. Galangin caused a potent, dose-dependent inhibition of CYP1A1 activity, as measured by ethoxyresorufin-O-deethylase activity in intact cells and in microsomes isolated from DMBA-treated cells. Analysis of the inhibition kinetics by double-reciprocal plot demonstrated that galangin inhibited CYP1A1 activity in a noncompetitive manner. Galangin caused an increase in the level of CYP1A1 mRNA, indicating that it may be an agonist of the aryl hydrocarbon receptor, but it inhibited the induction of CYP1A1 mRNA by DMBA or by 2,3,5,7-tetrachlorodibenzo-p-dioxin (TCDD). Galangin also inhibited the DMBA- or TCDD-induced transcription of a reporter vector containing the CYP1A1 promoter. Thus, galangin is a potent inhibitor of DMBA metabolism and an agonist/antagonist of the AhR, and may prove to be an effective chemopreventive agent. C1 NCI, Frederick Canc Res & Dev Ctr, NIH,Div Basic Sci, Basic Res Lab,Cellular Def & Carcinogenesis Sect, Frederick, MD 21702 USA. RP Ciolino, HP (reprint author), NCI, Frederick Canc Res & Dev Ctr, NIH,Div Basic Sci, Basic Res Lab,Cellular Def & Carcinogenesis Sect, Bldg 560 Rm 12-05,POB B, Frederick, MD 21702 USA. NR 44 TC 95 Z9 99 U1 0 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD MAR PY 1999 VL 79 IS 9-10 BP 1340 EP 1346 DI 10.1038/sj.bjc.6690216 PG 7 WC Oncology SC Oncology GA 175XK UT WOS:000079121100004 PM 10188874 ER PT J AU Horti, J Dixon, SC Logothetis, CJ Guo, Y Reed, E Figg, WD AF Horti, J Dixon, SC Logothetis, CJ Guo, Y Reed, E Figg, WD TI Increased transcriptional activity of prostate-specific antigen in the presence of TNP-470, an angiogenesis inhibitor SO BRITISH JOURNAL OF CANCER LA English DT Article DE prostate-specific antigen; androgen-independent prostate cancer; TNP-470; AGM-1883; androgen receptor ID TUMOR-GROWTH; CANCER; FUMAGILLIN; AGM-1470; PROLIFERATION; EXPRESSION; CELLS; MICE AB Prostate-specific antigen, PSA, is regarded as a reliable surrogate marker for androgen-independent prostate cancer (AIPC). Concern has been raised that investigational agents may affect PSA secretion without altering tumour growth or volume. In a phase I trial, several patients with AIPC had elevated serum PSA levels while receiving TNP-470 that reversed upon discontinuation. TNP-470 inhibits capillary growth in several angiogenesis models. These observations prompted us to determine if TNP-470, or its metabolite, AGM-1883, altered PSA secretion. Intracellular protein and transcriptional levels of PSA and androgen receptor were also determined. The highest TNP-470 concentration produced a 40.6% decrease in cell number; AGM-1883 had minimal effects on cell viability. PSA secretion per cell was induced 1.1- to 1.5-fold following TNP-470 exposure. The same trend was observed for AGM-1883. PSA and AR were transcriptionally upregulated within 30 min after exposure to TNP-470. PSA transcription was increased 1.4-fold, while androgen receptor (AR) transcription was induced 1.2-fold. The increased PSA transcriptional activity accounts for the increased PSA secretion. Increased AR transcription was also reflected at the protein level. In conclusion, TNP-470 and AGM-1883 both up-regulated PSA making clinical utilization of this surrogate marker problematic. C1 NCI, Med Branch, Div Clin Sci, Bethesda, MD 20892 USA. Univ Texas, Md Anderson Canc Ctr, Dept Med Oncol, Houston, TX 77030 USA. RP Figg, WD (reprint author), NCI, Med Branch, Div Clin Sci, Bldg 10,Room 5Ao1, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 27 TC 23 Z9 23 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD MAR PY 1999 VL 79 IS 9-10 BP 1588 EP 1593 DI 10.1038/sj.bjc.6690253 PG 6 WC Oncology SC Oncology GA 175XK UT WOS:000079121100041 PM 10188911 ER PT J AU Szallasi, A Biro, T Szabo, T Modarres, S Petersen, M Klusch, A Blumberg, PM Krause, JE Sterner, O AF Szallasi, A Biro, T Szabo, T Modarres, S Petersen, M Klusch, A Blumberg, PM Krause, JE Sterner, O TI A non-pungent triprenyl phenol of fungal origin, scutigeral, stimulates rat dorsal root ganglion neurons via interaction at vanilloid receptors SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE triprenyl phenols; scutigeral; non-pungent vanilloids; resiniferatoxin; capsaicin; vanilloid receptors ID CAPSAICIN RECEPTOR; INTRAVESICAL CAPSAICIN; SENSORY NEURONS; RESINIFERATOXIN BINDING; POSITIVE COOPERATIVITY; PHARMACOLOGY; CURRENTS; CELLS; DESENSITIZATION; MECHANISMS AB 1 A [H-3]-resiniferatoxin (RTX) binding assay utilizing rat spinal cord membranes was employed to identify novel vanilloids in a collection of natural products of fungal origin. Of the five active compounds found (scutigeral, acetyl-scutigeral, ovinal, neogrifolin, and methyl-neogrifolin), scutigeral (K-i=19 mu M), isolated from the edible mushroom Albatrellus ovinus, was selected for further characterization. 2 Scutigeral induced a dose-dependent Ca-45 uptake by rat dorsal root ganglion neurons with an EC50 of 1.6 mu M, which was fully inhibited by the competitive vanilloid receptor antagonist capsazepine (IC50 = 5.2 mu M). 3 [H-3]-RTX binding isotherms were shifted by scutigeral (10-80 mu M) in a competitive manner. The Schild plot of the data had a slope of 0.8 and gave an apparent K-d estimate for scutigeral of 32 mu M. 4 Although in the above assays scutigeral mimicked capsaicin, it was not pungent on the human tongue up to a dose of 100 nmol per tongue, nor did it provoke protective wiping movements in the rat (up to 100 mu M) upon intraocular instillation. 5 In accord with being non-pungent, scutigeral (5 mu M) did not elicit a measurable inward current in isolated rat dorsal root ganglion neurons under voltage-clamp conditions. It did, however, reduce the proportion of neurons (from 61 to 15%) that responded to a subsequent capsaicin (1 mu M) challenge. In these neurons, scutigeral both delayed (from 27 to 72 s) and diminished (from 5.0 to 1.9 nA) the maximal current evoked by capsaicin. 6 In conclusion, scutigeral and its congeners form a new chemical class of vanilloids, the triprenyl phenols. Scutigeral promises to be a novel chemical lead for the development of orally active, non-pungent vanilloids. C1 NCI, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO USA. Karolinska Inst, Dept Pharmacol, Stockholm, Sweden. Univ Wurzburg, Dept Physiol, Wurzburg, Germany. Univ Lund, Dept Organ Chem 2, Lund, Sweden. RP Szallasi, A (reprint author), NCI, Bldg 37,Rm 3A13,37 Convent Dr MSC 4255, Bethesda, MD 20892 USA. EM szallasi@exchange.nih.gov NR 51 TC 48 Z9 50 U1 0 U2 4 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD MAR PY 1999 VL 126 IS 6 BP 1351 EP 1358 DI 10.1038/sj.bjp.0702440 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 181NV UT WOS:000079448400009 PM 10217528 ER PT J AU El-Masri, HA Portier, CJ AF El-Masri, HA Portier, CJ TI Replication potential of cells via the protein kinase C-MAPK pathway: Application of a mathematical model SO BULLETIN OF MATHEMATICAL BIOLOGY LA English DT Article ID PARTIAL-HEPATECTOMY; MITOTIC CLOCK; FISSION YEAST; DNA-BINDING; JUN; ACTIVATION; PHOSPHORYLATION; CYCLE; PROLACTIN; GROWTH AB A mechanistically based mathematical model is used to investigate some of the important factors in priming hepatocytes to enter the G(1) phase of the cell cycle. The considers all of the relevant biochemical mechanisms from signal-receptor binding to the elevation of AP-1(activation protein transcription factor) levels. Focus is centered on the chain of biochemical events governing the sequential activation of protein kinase C (PKC), mitogen-activated protein kinase (MAPK) and AP-1. Factors such as amplitude and duration of growth factors signals, the kinetics of guanosine diphosphate (GDP) to guanosine triphosphate (GTP) conversion, and the negative feedback control mechanisms governing initial steps in cellular replication were theoretically examined. The results of our theoretical assessments support the finding that specific mutations along the PKC-API pathways can have a critical effect on the rate at which cells enter the division cycle. (C) 1999 Society for Mathematical Biology. C1 Novigen Sci Inc, Washington, DC 20036 USA. NIEHS, Lab Computat Biol & Risk Anal, Res Triangle Pk, NC 27709 USA. RP El-Masri, HA (reprint author), Novigen Sci Inc, 1730 Rhode Isl Ave NW,Suite 1100, Washington, DC 20036 USA. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 23 TC 15 Z9 15 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0092-8240 J9 B MATH BIOL JI Bull. Math. Biol. PD MAR PY 1999 VL 61 IS 2 BP 379 EP 398 DI 10.1006/bulm.1998.0077 PG 20 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 186YQ UT WOS:000079759300009 PM 17883216 ER PT J AU Rosenberg, SA AF Rosenberg, SA TI A new era of cancer immunotherapy: Converting theory to performance SO CA-A CANCER JOURNAL FOR CLINICIANS LA English DT Editorial Material AB The major impact of recent scientific advances. such as the discovery of genes and gene products, has been to facilitate development of immunotherapies based on the specific stimulation sf immune reactions against characterized tumor antigens. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Rosenberg, SA (reprint author), NCI, Surg Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 6 TC 25 Z9 25 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0007-9235 J9 CA-CANCER J CLIN JI CA-Cancer J. Clin. PD MAR-APR PY 1999 VL 49 IS 2 BP 70 EP + DI 10.3322/canjclin.49.2.70 PG 5 WC Oncology SC Oncology GA 177XH UT WOS:000079236000005 PM 11198888 ER PT J AU Friedman, HS Kerby, T Fields, S Zilisch, JE Graden, D McLendon, RE Houghton, PJ Arbuck, S Cokgor, I Friedman, AH AF Friedman, HS Kerby, T Fields, S Zilisch, JE Graden, D McLendon, RE Houghton, PJ Arbuck, S Cokgor, I Friedman, AH CA Brain Tumor Ctr Duke TI Topotecan treatment of adults with primary malignant glioma SO CANCER LA English DT Article DE glioma; topotecan; chemotherapy; brain tumor ID RADIATION-THERAPY; ONCOLOGY-GROUP; RADIOTHERAPY; CHEMOTHERAPY; PROCARBAZINE; CCNU; XENOGRAFTS; SURGERY; TUMORS; BCNU AB BACKGROUND. Topotecan activity was evaluated for the treatment of malignant glioma. METHODS. Sixty-three patients with newly diagnosed (n = 25) or recurrent (n = 38) malignant glioma were treated with topotecan {AU: Please verify all dosages here and throughout text.}at a dose of 2.6 mg/m(2) over a 72-hour period weekly. Recurrent tumors included glioblastoma multiforme (GBM) (n = 28) and anaplastic astrocytoma (AA) (n = 10). Newly diagnosed tumors included GBM (n = 14), AA (n = 8), and anaplastic oligodendroglioma (n = 3). RESULTS, Partial responses were observed in 2 of 14 evaluable patients with newly diagnosed GEM, 1 of 8 patients with newly diagnosed AA, 3 of 10 patients with recurrent AA, and none of 28 patients with recurrent GBM. Four patients with recurrent AA and 7 patients with recurrent GEM demonstrated stable disease (range, 8-52 weeks; median, 21 weeks). Toxicity was limited to infrequent National Cancer Institute Common Toxicity Criteria Grade 3 myelosuppression. CONCLUSIONS. These results suggest that topotecan has modest activity against malignant glioma and continued evaluation of its effectiveness may be warranted when alternative schedules or combination regimens are used. Cancer 1999;85:1160-5. (C) 1999 American Cancer Society. C1 Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. St Jude Childrens Res Hosp, Dept Mol Pharmacol, Memphis, TN 38105 USA. SmithKline Beecham Pharmaceut, King Of Prussia, PA 19406 USA. NCI, Dev Chemotherapy Sect,Invest Drug Branch, Canc Therapy Evaluat Program, Div Canc Treatment Diag & Ctr, Bethesda, MD 20892 USA. RP Friedman, HS (reprint author), Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA. FU NCI NIH HHS [CA 57725]; NINDS NIH HHS [NS 30245, NS 20023] NR 18 TC 53 Z9 53 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD MAR 1 PY 1999 VL 85 IS 5 BP 1160 EP 1165 DI 10.1002/(SICI)1097-0142(19990301)85:5<1160::AID-CNCR21>3.0.CO;2-F PG 6 WC Oncology SC Oncology GA 172LY UT WOS:000078926800021 PM 10091802 ER PT J AU Ung, A Kramer, TR Schiffman, M Herrero, R Bratti, MC Burk, RD Swanson, CA Sherman, ME Hutchinson, ML Alfaro, M Morales, J Balmaceda, I Hildesheim, A AF Ung, A Kramer, TR Schiffman, M Herrero, R Bratti, MC Burk, RD Swanson, CA Sherman, ME Hutchinson, ML Alfaro, M Morales, J Balmaceda, I Hildesheim, A TI Soluble interleukin 2 receptor levels and cervical neoplasia: Results from a population-based case-control study in Costa Rica SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HUMAN PAPILLOMAVIRUS INFECTION; INTRAEPITHELIAL NEOPLASIA; ASSOCIATION; WOMEN; RESPONSES; BEHAVIOR; E7 AB Progression from infection with human papillomavirus (HPV) to cervical cancer in some women is thought to involve a permissive host environment, one in which immune response is mobilized in an inappropriate manner, In a previous study (A, Hildesheim et al,, Cancer Epidemiol, Biomark, Prev,, 6: 807-813, 1997), increasing levels of soluble interleukin 2 receptor (sIL-2R), a known proxy for general immune activation, was found to be positively associated with increasing levels of cervical neoplasia, We attempted to confirm this finding by conducting a nested case-control study of 478 women within a 10,000-woman population-based cohort in Costa Rica, We selected for the study all of the women diagnosed (at enrollment into the cohort) with: (a) low-grade squamous intraepithelial lesions (LSIL, n = 191); (b) high-grade squamous intraepithelial lesions (HSIL, n = 130); or (c) cancer (n = 37), Controls were 120 cytologically normal, HPV-negative women selected from a random sample of the entire cohort. A questionnaire was administered to participants to elicit information on cervical cancer risk factors. All of the women received a pelvic examination during which cervical cells were collected and used for HPV DNA testing by PCR. Blood samples were also collected. Plasma obtained from the blood samples was tested for sIL-2R levels by ELISA. Results indicated that sIL-2R levels increased with age. Among controls, we observed that 44.3% of women over the age of 50 had high levels of sIL-2R (defined as >735 units/ml) compared with 15.8% of women <30 years of age (P = 0.008). When women with cervical disease (LSIL+) were compared with controls, women in the upper quartile of the sIL-2R distribution had an age-adjusted odds ratio (OR) of 2.1 [95% confidence interval (CI), 1.1-4.1]. Comparing each advancing state of neoplasia with its precursor, we found that women with LSIL had higher sIL-2R levels than controls (OR for upper quartile of sIL-2R, 2.3; 95% CI, 1.1-5.2; comparing LSIL cases with controls); women diagnosed with HSIL were similar to the LSIL group (OR for upper quartile of sIL-2R, 1.1; 95% CI, 0.5-2.4; comparing HSIL cases with LSIL cases); and those with cancer had higher sIL-2R levels than subjects with an HSIL diagnosis (OR for upper quartile of sIL-2R = 1.8; 95% CI, 0.5-7.1; comparing cancer cases with HSIL cases). These data suggest that among our study subjects, sIL-2R levels most likely rise as a response to the events of infection and cancerous invasion, but that sIL-2R levels are unlikely to be predictive of disease progression among women with LSIL. C1 NCI, Div Canc Epidemiol & Genet, Environm Epidemiol Branch, Interdisciplinary Studies Sect, Bethesda, MD 20892 USA. Howard Hughes Res Scholars Program, Bethesda, MD 20814 USA. USDA, Beltsville Human Nutr Res Ctr, Carotenoids Res Unit, Beltsville, MD 20705 USA. WHO, Int Agcy Res Canc, Lyon 08, France. Yeshiva Univ Albert Einstein Coll Med, Liver Res Ctr, Bronx, NY 10461 USA. Johns Hopkins Univ Hosp, Dept Pathol, Baltimore, MD 21205 USA. Tufts Univ, Sch Med, Dept Pathol, Boston, MA 02111 USA. Caja Costaricense Seguro Social, San Jose, Costa Rica. RP Hildesheim, A (reprint author), NCI, Div Canc Epidemiol & Genet, Environm Epidemiol Branch, Interdisciplinary Studies Sect, EPN 443, Bethesda, MD 20892 USA. NR 18 TC 8 Z9 8 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 1999 VL 8 IS 3 BP 249 EP 253 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 173MT UT WOS:000078984900007 PM 10090303 ER PT J AU Gammon, MD Hibshoosh, H Terry, MB Bose, S Schoenberg, JB Brinton, LA Bernstein, JL Thompson, WD AF Gammon, MD Hibshoosh, H Terry, MB Bose, S Schoenberg, JB Brinton, LA Bernstein, JL Thompson, WD TI Cigarette smoking and other risk factors in relation to p53 expression in breast cancer among young women SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID TUMOR-SUPPRESSOR GENE; MARKER-IMMUNOSTAINING INTENSITY; 60-HERTZ MAGNETIC-FIELDS; STORED PARAFFIN SLIDES; CELL NUCLEAR ANTIGEN; AGE 45 YEARS; LUNG-CANCER; ALCOHOL-CONSUMPTION; OCCUPATIONAL EXPOSURES; ORAL-CONTRACEPTIVES AB p53 mutations may be a fingerprint for cigarette smoking and other environmental carcinogens, including breast carcinogens. This study was undertaken to explore whether p53 mutations are associated with environmental or other suspected or established risk factors for breast cancer. p53 protein detection by immunohistochemistry (which is more easily quantified in large epidemiological studies than are mutations, and are highly correlated with them) was determined for 378 patients from a case-control study of breast cancer. In this population-based sample of women under the age of 45 Sears, 44.4% (168/378) of the cases had p53 protein detected by immunohistochemistry (p53+), Polytomous logistic regression was used to calculate the odds ratios (ORs) for p53+ and p53- breast cancer, as compared with the controls, in relation to cigarette smoking and other factors. The ratio of the ORs was used as an indicator of heterogeneity in risk for p53+ versus p53- cancer. The ratio of the ORs in a multivariate model was substantially elevated among women with a greater than high school education [2.39; 95% confidence interval (CI), 1.43-4.00], current cigarette smokers (1.96; 95% CI, 1.10-3.52), and users of electric blankets, water beds, or mattresses (1.78; 95% CI, 1.11-2.86). Nonsignificant heterogeneity was noted for family history of breast cancer and ethnicity but not for other known or suspected risk factors, Coupled with the strong biological plausibility of the association, our data support the hypothesis that in breast cancer, as with other tumors, p53 protein immunohistochemical detection may be associated with exposure to environmental carcinogens such as cigarette smoking. C1 Columbia Univ, Joseph L Mailman Sch Publ Hlth, Div Epidemiol, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Pathol, New York, NY 10032 USA. New Jersey State Dept Hlth & Sr Serv, Appl Canc Epidemiol Program, Trenton, NJ 08625 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. CUNY, Mt Sinai Med Ctr, Dept Community & Prevent Med, New York, NY 10029 USA. Univ So Maine, Dept Appl Sci, Portland, ME 04103 USA. RP Gammon, MD (reprint author), Columbia Univ, Joseph L Mailman Sch Publ Hlth, Div Epidemiol, 622 W 168th St,PH18, New York, NY 10032 USA. EM mdg2@columbia.edu RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 FU NCI NIH HHS [1R21CA/ES66224] NR 74 TC 37 Z9 37 U1 2 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 1999 VL 8 IS 3 BP 255 EP 263 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 173MT UT WOS:000078984900008 PM 10090304 ER PT J AU Quan, N Zhang, ZB Demetrikopoulos, MK Kitson, RP Chambers, WH Goldfarb, RH Weiss, JM AF Quan, N Zhang, ZB Demetrikopoulos, MK Kitson, RP Chambers, WH Goldfarb, RH Weiss, JM TI Evidence for involvement of B lymphocytes in the surveillance of lung metastasis in the rat SO CANCER RESEARCH LA English DT Article ID ACTIVATED KILLER CELLS; ANTIMETASTATIC ACTIVITY; MONOCLONAL-ANTIBODY; TUMOR SITE; INTERFERON; ANTIGEN; CANCER AB These studies examined the composition of lymphocytes within the lung after the introduction of tumor cells that metastasize to the lung in rats. i.v. delivery of MADB106 tumor cells into syngeneic Fischer 344 rats caused dose- and time-dependent development of lung tumors, with surface metastases evident 7 days after injection and markedly increased 11 das after injection. The total number of lymphocytes recovered from the lung was increased 11 days after injection hut not 7 days after injection, When lymphocytes from the lung, spleen, and blood were subjected to fluorescence-activated cell sorting analysis, the most conspicuous change nas an increase in the percentage of CD45RA + cells (i.e., B lymphocytes in the rat) in the lung, with no changes seen in the percentage of natural killer (NKR-P1+), CD4+, or CD8+ cells in the lung. Analysis of the time course showed that B lymphocytes increased in the lung soon after i.v. tumor injection, with an initial peak seen 6 h after injection. Rapid influx of B lymphocytes into lung after i.v, tumor cell injection Has also observed in another syngeneic tumor model, i.e., after injection of CC531 cells into WAG rats. To determine whether the influx of B lymphocytes into the lung might participate in tumor surveillance, a high dose of antibody (100 mu g to rat B lymphocytes was given to immunoneutralize these cells; this produced an increase in lung tumors in both models. Finally, Fischer 344 rats Here given a s.c, injection of MADB106 tumor cells that made them resistant to lung tumors when given a later i.v. injection of these tumor cells. These animals were found to have an elevated level of B lymphocytes residing in the lung associated with the resistance to lung tumor. These findings suggest that early responses of B lymphocytes are important in protection against tumor development in two rat models of cancer. C1 Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA. Univ Pittsburgh, Inst Canc, Dept Pathol, Pittsburgh, PA 15213 USA. Univ N Texas, Hlth Sci Ctr, Dept Mol Biol & Immunol, Ft Worth, TX 76107 USA. NIMH, Funct Neuroanat Sect, Bethesda, MD 20892 USA. RP Weiss, JM (reprint author), Emory W Campus,1256 Briarcliff Rd NE, Atlanta, GA 30306 USA. FU NIMH NIH HHS [MH10952] NR 19 TC 26 Z9 30 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 1 PY 1999 VL 59 IS 5 BP 1080 EP 1089 PG 10 WC Oncology SC Oncology GA 172MF UT WOS:000078927700017 PM 10070966 ER PT J AU Schut, HAJ Snyderwine, EG AF Schut, HAJ Snyderwine, EG TI DNA adducts of heterocyclic amine food mutagens: implications for mutagenesis and carcinogenesis SO CARCINOGENESIS LA English DT Review ID HUMAN-LIVER-MICROSOMES; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B> PYRIDINE PHIP; 2-AMINO-3-METHYLIMIDAZO<4,5-F> QUINOLINE IQ; MAMMARY EPITHELIAL-CELLS; CULTURED MAMMALIAN-CELLS; MOUSE FORESTOMACH TUMORS; P-32 POSTLABELING METHOD; COLONIC ABERRANT CRYPTS; N-ACETOXY DERIVATIVES; CHINESE-HAMSTER CELLS AB The heterocyclic amines (HCAs) are a family of mutagenic/carcinogenic compounds produced during the pyrolysis of creatine, amino acids and proteins. The major subclass of HCAs found in the human diet comprise the amino-imidazoazaarenes (AIAs) 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). All, except DiMeIQx, have been shown to be carcinogenic in animals. These compounds are present in cooked muscle meats at the p.p.b. level. Since the discovery of the HCAs in the late 1970s, many studies have examined the DNA adducts of these compounds. This review compiles the literature on AIA-DNA adducts including their identification and characterization, pathways of formation, mutagenesis in vitro and in vivo, and their association with carcinogenesis in animal models. It is now known that metabolic activation leading to the formation of DNA adducts is critical for mutagenicity and carcinogenicity of these compounds. All of the AIAs studied adduct to the guanine base, the major adduct being formed at the C8 position, Two AIAs, IQ and MeIQx, also form minor adducts at the NZ position of guanine, A growing body of literature has reported on the mutation spectra induced by AIA-guanine adducts, Studies of animal tumors induced by AIAs have begun to relate AIA-DNA adduct-induced mutagenic events with the mutations found in critical genes associated with oncogenesis. Several studies have demonstrated the feasibility of chemoprevention of AIA tumorigenesis, Only a few studies have reported on the detection of AZA-DNA adducts in human tissues; difficulties persist in the routine detection of ALA-DNA adducts in humans for the purpose of biomonitoring of exposure to AIAs, The AIAs are nevertheless regarded as possible human carcinogens, and future research on AIA-DNA adducts is likely to help address the role of AIAs in human cancer. C1 NCI, Chem Carcinogenesis Sect, Expt Carcinogenesis Lab, Div Basic Sci, Bethesda, MD 20892 USA. Med Coll Ohio, Dept Pathol, Toledo, OH 43614 USA. RP Snyderwine, EG (reprint author), NCI, Chem Carcinogenesis Sect, Expt Carcinogenesis Lab, Div Basic Sci, Bldg 37,Room 3C28,37 Convent Dr MSC 4255, Bethesda, MD 20892 USA. EM elizabeth_snyderwine@nih.gov FU NCI NIH HHS [CA47484]; PHS HHS [BPA263-00028827] NR 300 TC 270 Z9 274 U1 4 U2 28 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAR PY 1999 VL 20 IS 3 BP 353 EP 368 DI 10.1093/carcin/20.3.353 PG 16 WC Oncology SC Oncology GA 174ZL UT WOS:000079066400001 PM 10190547 ER PT J AU Li, H Schut, HAJ Conran, P Kramer, PM Lubet, RA Steele, VE Hawk, EE Kelloff, GJ Pereira, MA AF Li, H Schut, HAJ Conran, P Kramer, PM Lubet, RA Steele, VE Hawk, EE Kelloff, GJ Pereira, MA TI Prevention by aspirin and its combination with alpha-difluoromethylornithine of azoxymethane-induced tumors, aberrant crypt foci and prostaglandin E-2 levels in rat colon SO CARCINOGENESIS LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; FAMILIAL ADENOMATOUS POLYPOSIS; LARGE-BOWEL CANCER; ORNITHINE DECARBOXYLASE; CHEMOPREVENTIVE AGENTS; COLORECTAL-CANCER; SULINDAC SULFIDE; F344 RATS; CARCINOGENESIS; INHIBITION AB The dose-response relationship in male F344 rats was determined for the ability of aspirin administered in the diet to prevent azoxymethane (AOM)-induced colon cancer and aberrant crypt foci (ACF) and to reduce prostaglandin E-2 (PGE(2)) levels. Starting at either 7 or 22 weeks of age, the rats received aspirin. All rats received two doses of AOM (15 mg/kg each on days 7 and 14) and were killed on day 36, The lowest concentrations of aspirin to prevent ACF or reduce PGE2 levels were 600 and 400 mg/kg, respectively. To evaluate the prevention of tumors, rats received either 0 or 400 mg/kg aspirin for a total of 39 weeks with AOM (30 mg/kg) administered 7 days after the start of treatment. Aspirin had no effect on the yield of colon tumors. In a second experiment, rats started to receive 0, 200, 600 or 1800 mg/kg aspirin or 1000 mg/kg a-difluoromethylornithine (DFMO) +/- aspirin. Eight and 15 days later, all the rats received 15 mg/kg AOM, Eleven weeks later, animals that were receiving the control diet started to receive 0, 200, 600 or 1800 mg/kg aspirin; 1000 or 3000 mg/kg DFMO; or 1000 mg/kg DFMO + 200 or 600 mg/kg aspirin. The animals were killed 32 weeks later. DFMO effectively reduced the yield of colon tumors when administered starting either before or after AOM while aspirin was much weaker. The combination of aspirin + DFMO administered after AOM was synergistic. Both aspirin and DFMO decreased the Mitotic Index, while apoptosis was increased only by DFMO, Our results demonstrated that aspirin and DFMO could prevent colon cancer when administered after AOM, Furthermore, aspirin reduced ACF, PGE(2) levels and mitosis at concentrations that did not prevent cancer. In contrast, the ability to enhance apoptosis did correlate with the prevention of cancer. C1 Med Coll Ohio, Dept Pathol, Toledo, OH 43614 USA. NCI, Chemoprevent Branch, Div Canc Prevent & Control, Bethesda, MD 20892 USA. RP Pereira, MA (reprint author), Med Coll Ohio, Dept Pathol, 3000 Arlington Ave, Toledo, OH 43614 USA. EM mpereira@mco.edu FU NCI NIH HHS [N01-CN-25295-01, N01-CN-55174-01, N01-CN-55175-01] NR 50 TC 68 Z9 69 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAR PY 1999 VL 20 IS 3 BP 425 EP 430 DI 10.1093/carcin/20.3.425 PG 6 WC Oncology SC Oncology GA 174ZL UT WOS:000079066400011 PM 10190557 ER PT J AU Brodie, C Bogi, K Acs, P Lazarovici, P Petrovics, G Anderson, WB Blumberg, PM AF Brodie, C Bogi, K Acs, P Lazarovici, P Petrovics, G Anderson, WB Blumberg, PM TI Protein kinase C-epsilon plays a role in neurite outgrowth in response to epidermal growth factor and nerve growth factor in PC12 cells SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID FACTOR-INDUCED DIFFERENTIATION; PHEOCHROMOCYTOMA CELLS; TYROSINE PHOSPHORYLATION; PHORBOL ESTERS; NEURONAL DIFFERENTIATION; SIGNAL TRANSDUCTION; PC-12 CELLS; ACTIVATION; SPECIFICITY; EXPRESSION AB In this study, we examined the role of specific protein kinase C (PKC) isoforms in the differentiation of PC12 cells in response to nerve growth factor (NGF) and epidermal growth factor (EGF), PC12 cells express PKC-alpha, -beta, -gamma, -delta, -epsilon, -mu, and -xi, For PKC-epsilon, -E, and -xi, NGF and EGF exerted differential effects on translocation. Unlike overexpression of PKC-alpha and -delta, overexpression of PKC-epsilon caused enhanced neurite outgrowth in response to NGF. In the PKC-epsilon-overexpressing cells, EGF also dramatically induced neurite outgrowth, arrested cell proliferation, and induced a sustained phosphorylation of mitogen-activated protein kinase (MAPK), in contrast to its mitogenic effects on control cells or cells overexpressing PKC-alpha and -delta. The induction of neurite outgrowth by EGF was inhibited by the MAPK kinase inhibitor PD95098. In cells overexpressing a PKC-epsilon dominant negative mutant, NGF induced reduced neurite outgrowth and a more transient phosphorylation of MAPK than in controls. Our results suggest an important role for PKC-epsilon in neurite outgrowth in PC12 cells, probably via activation of the MAPK pathway. C1 NCI, Mol Mech Tumor Promot Sect, LCCTP, NIH, Bethesda, MD 20892 USA. NCI, Signal Transduct Sect, LCO, NIH, Bethesda, MD 20892 USA. Bar Ilan Univ, Fac Life Sci, Gonda Goldschmied Ctr, IL-52900 Ramat Gan, Israel. RP Blumberg, PM (reprint author), NCI, Mol Mech Tumor Promot Sect, LCCTP, NIH, Bldg 37,Room 3A01,37 Convent Dr MSC 4255, Bethesda, MD 20892 USA. NR 54 TC 77 Z9 78 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD MAR PY 1999 VL 10 IS 3 BP 183 EP 191 PG 9 WC Cell Biology SC Cell Biology GA 176YM UT WOS:000079180000006 PM 10099832 ER PT J AU Li, Q Zhang, L Tsang, B Gardner, K Bostick-Bruton, F Reed, E AF Li, Q Zhang, L Tsang, B Gardner, K Bostick-Bruton, F Reed, E TI Phorbol ester exposure activates an AP-1-mediated increase in ERCC-1 messenger RNA expression in human ovarian tumor cells SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Article DE AP-1; ERCC-1 mRNA; ERCC-1 gene transcription; nucleotide excision repair; ovarian cancer; phorbol ester ID DNA EXCISION-REPAIR; INTERSTRAND CROSS-LINKS; TRANSCRIPTIONAL REGULATION; CANCER PATIENTS; CISPLATIN; PROTEINS; FOS; JUN; CHEMOTHERAPY; SURVIVAL AB ERCC-1 is an essential gene in the nucleotide excision repair pathway, and may be essential for life. However, the mechanism of transcriptional activation and regulation of ERCC-1 gene expression is unclear. We therefore investigated the effect of the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on the expression of the ERCC-1 gene in A2780/CP70 human ovarian carcinoma cells. TPA induced a four- to sixfold increase in steady-state ERCC-1 messenger RNA (mRNA) levels that was time- and concentration-dependent. Nuclear run-on experiments demonstrated that the rate of transcription of ERCC-1 was approximately 2.8-fold higher in TPA-treated cells than in the controls. TPA stimulation of A2780/CP70 cells also resulted in a rapid but transient induction of c-jun and c-fos as determined by Northern and Western blot analyses, which peaked about 2 h before the peak in ERCC-1 expression. Electrophoretic mobility shift assays of nuclear extracts from TPA-treated cells revealed an increase in DNA-binding activity specific for the AP-1-like binding site in the 5'-flanking region of ERCC-1. c-Jun and c-Fos proteins were confirmed to be the components of the activated AP-1 complex by supershift analysis. The increase in AP-1 activity occurs immediately before the increase in ERCC-1 transcription. The increase in AP-1 DNA-binding activity and the increase in ERCC-1 mRNA expression were prevented by pretreatment with cycloheximide. These data suggest that AP-1 may contribute to the upregulation of ERCC-1 in response to TPA in human ovarian cancer cells. C1 NCI, Med Ovarian Canc Sect, Dev Therapeut Dept, Med Branch,NIH, Bethesda, MD 20892 USA. NCI, Mol Oncol Sect, Pediat Branch, NIH, Bethesda, MD 20892 USA. NCI, Med Ovarian Canc Sect, Med Branch, NIH, Bethesda, MD 20892 USA. RP Reed, E (reprint author), NCI, Med Ovarian Canc Sect, Dev Therapeut Dept, Med Branch,NIH, Bldg 10,Room 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. EM reed92@helix.nih.gov NR 45 TC 29 Z9 31 U1 0 U2 0 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD MAR PY 1999 VL 55 IS 3 BP 456 EP 466 DI 10.1007/s000180050302 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 186GB UT WOS:000079719600008 PM 10228559 ER PT J AU Bergman, AC Alaiya, AA Wendler, W Binetruy, B Shoshan, M Sakaguchi, K Bergman, T Kronenwett, U Auer, G Appella, E Jornvall, H Linder, S AF Bergman, AC Alaiya, AA Wendler, W Binetruy, B Shoshan, M Sakaguchi, K Bergman, T Kronenwett, U Auer, G Appella, E Jornvall, H Linder, S TI Protein kinase-dependent overexpression of the nuclear protein pirin in c-JUN and RAS transformed fibroblasts SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Article DE two-dimensional gel electrophoresis; mass spectrometry; cell transformation ID CELLS; ACTIVATION; IDENTIFICATION; COOPERATION; EXPRESSION; PEPTIDES; GENES AB Signalling via the protein kinase Raf-MEK-ERK pathway is of major importance for transformation by oncogenes. To identify genes affected by inhibition of this pathway, c-JUN transformed rat fibroblasts were treated with a MEK1 inhibitor (PD98059) and subjected to two-dimensional gel electrophoresis after cell lysis. Gene products with expression influenced by MEK1 inhibition were determined by mass spectrometry of fragments from in-gel tryptic digestions. The expression of pirin, a nuclear factor I-interacting protein, was lowered after inhibition of MEK1. Western blot analysis revealed increased expression of pirin in RAS and c-JUN transformed cells in the absence of PD98059. Inhibition of MEK1 also led to reduced expression of alpha-enolase, phosphoglycerate kinase, elongation factor 2 and heterogeneous nuclear ribonucleoprotein A3, the latter two being detected as truncated proteins. In contrast, the level of ornithine aminotransferase was increased. We conclude that inhibition of MEK1 results in major alterations of protein expression in c-JUN transformed cells, suggesting that this pathway is important for oncogene-induced phenotypic changes. C1 Karolinska Hosp, Radiumhemmet, Res Lab, Dept Pathol & Oncol, S-17176 Stockholm, Sweden. Natl Ctr Sci Res, Dept Canc Res, F-94801 Villejuif, France. Univ Munich, Dept Biochem, D-81377 Munich, Germany. Karolinska Hosp, Dept Pathol & Oncol, Unit Cell & Mol Anal, S-17176 Stockholm, Sweden. Karolinska Inst, Dept Med Biochem & Biophys, S-17177 Stockholm, Sweden. NCI, Cell Biol Labs, NIH, Bethesda, MD 20892 USA. RP Linder, S (reprint author), Karolinska Hosp, Radiumhemmet, Res Lab, Dept Pathol & Oncol, S-17176 Stockholm, Sweden. RI Binetruy, Bernard/A-6465-2009 NR 16 TC 16 Z9 17 U1 2 U2 7 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD MAR PY 1999 VL 55 IS 3 BP 467 EP 471 DI 10.1007/s000180050303 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 186GB UT WOS:000079719600009 PM 10228560 ER PT J AU Page, JE Pilcher, AS Yagi, H Sayer, JM Jerina, DM Dipple, A AF Page, JE Pilcher, AS Yagi, H Sayer, JM Jerina, DM Dipple, A TI Mutational consequences of replication of M13mp7L2 constructs containing cis-opened benzo[a]pyrene 7,8-diol 9,10-epoxide-deoxyadenosine adducts SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID (+)-ANTI-BENZOPYRENE DIOL EPOXIDE; SITE-SPECIFIC MUTAGENESIS; SINGLE-STRANDED VECTOR; SEQUENCE CONTEXT; DNA-ADDUCTS; ESCHERICHIA-COLI; IN-VITRO; DEOXYADENOSINE; FREQUENCY; TEMPLATES AB The four adducts that arise by cis ring opening of the four optically active benzo[a]pyrene diol epoxides by the exocyclic N-6-amino group of deoxyadenosine were incorporated synthetically into each of two different oligonucleotide 16-mers, 5'-TTTXGAGTCTGCTCCC-3' [context I(A)] and 5'-CAGXTTTAGAGTCTGC-3' [context, II(A)], at the X position. The eight resultant oligonucleotides were separately ligated into bacteriophage M13mp7L2 and replicated in Escherichia coli that had been SOS-induced, and the progeny were analyzed to evaluate the consequences of replication past these adducts. The presence of these adducts reduced plaque yields substantially However, the progeny obtained exhibited high frequencies of base substitution mutation ranging from 9 to 68%, depending upon the individual adduct and the sequence context in which it was placed. For most of the adducts, A --> T transversion was the mutation found most, frequently in either sequence context, and mutation frequencies in context I(A) were always substantially greater than those in context II(A). In context I(A), adducts with an R configuration at the site of nucleoside attachment were more mutagenic than those with an S configuration. In both sequence contexts that were studied, the cis adduct arising from the (7S,8R)-diol (SS,10R)-epoxide was the most mutagenic adduct. These findings clearly show that individual mutation frequencies are determined by the combined effects of both adduct; structure and sequence context. C1 NCI, Chem Carcinogenesis Lab, ABL Basic Res Program, FCRDC, Frederick, MD 21702 USA. NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Page, JE (reprint author), NCI, Chem Carcinogenesis Lab, ABL Basic Res Program, FCRDC, Frederick, MD 21702 USA. NR 25 TC 26 Z9 26 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD MAR PY 1999 VL 12 IS 3 BP 258 EP 263 DI 10.1021/tx980244l PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 177BG UT WOS:000079187100005 PM 10077488 ER PT J AU Bornstein, MH Haynes, OM Pascual, L Painter, KM Galperin, C AF Bornstein, MH Haynes, OM Pascual, L Painter, KM Galperin, C TI Play in two societies: Pervasiveness of process, specificity of structure SO CHILD DEVELOPMENT LA English DT Review ID MOTHER-CHILD INTERACTION; SYMBOLIC PLAY; UNITED-STATES; PRETENSE PLAY; 2ND YEAR; LANGUAGE; BEHAVIOR; TODDLERS; AMERICAN; JAPAN AB The present study compared Argentine (N = 39) and U.S. (N = 43) children and their mothers on exploratory, symbolic, and social play and interaction when children were 20 months of age. Patterns of cultural similarity and difference emerged. In both cultures, boys engaged in more exploratory play than girls, and girls engaged in more symbolic play than boys; mothers of boys engaged in more exploratory play than mothers of girls, and mothers of girls engaged in more symbolic play than mothers of boys. Moreover, in both cultures, individual variation in children's exploratory and symbolic play was specifically associated with individual variation in mothers' exploratory and symbolic play, respectively. Between cultures, U.S. children and their mothers engaged in more exploratory play, whereas Argentine children and their mothers engaged in more symbolic play. Moreover, Argentine mothers exceeded U.S. mothers in social play and verbal praise of their children. During an early period of mental and social growth, general developmental processes in play may be pervasive, but dyadic and cultural structures are apparently specific. Overall, Argentine and U.S. dyads utilized different modes of exploration, representation, and interaction-emphasizing "other-directed" acts of pretense versus "functional" and "combinatorial" exploration, for example-and these individual and dyadic allocentric versus idiocentric stresses accord with larger cultural concerns of collectivism versus individualism in the two societies. C1 NICHHD, Comparat Ethol Lab, NIH, Bethesda, MD 20892 USA. Univ Buenos Aires, Buenos Aires, DF, Argentina. Univ Belgrano, Buenos Aires, DF, Argentina. RP Bornstein, MH (reprint author), NICHHD, Comparat Ethol Lab, NIH, Bldg 31,Room B2B15,9000 Rockville Pike, Bethesda, MD 20892 USA. EM Marc_H_Bornstein@nih.gov NR 103 TC 57 Z9 59 U1 2 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0009-3920 J9 CHILD DEV JI Child Dev. PD MAR-APR PY 1999 VL 70 IS 2 BP 317 EP 331 DI 10.1111/1467-8624.00024 PG 15 WC Psychology, Educational; Psychology, Developmental SC Psychology GA 187QJ UT WOS:000079798000005 PM 10218257 ER PT J AU McCoy, AL Bubb, MR Plotz, PH Davis, JC AF McCoy, AL Bubb, MR Plotz, PH Davis, JC TI Inclusion body myositis long after dermatomyositis: A report of two cases SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Article DE dermatomyositis; polymyositis; inclusion body myositis; inflammatory; myopathy; autoimmunity ID MEDIATED CYTO-TOXICITY; INFLAMMATORY MYOPATHIES; SJOGRENS-SYNDROME; MONONUCLEAR-CELLS; POLYMYOSITIS; MANIFESTATIONS; EXPRESSION AB Dermatomyositis, polymyositis, and inclusion body myositis are rare illnesses which appear to be distinct in clinical and pathologic features, pathogenesis, natural history, and response to therapy. We report two patients who first developed dermatomyositis, and then, after a disease-free interval of many years, developed inclusion body myositis. This may have useful therapeutic implications for patients with dermatomyositis whose illness bocomes refractory to treatment. C1 NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. RP Plotz, PH (reprint author), NIAMSD, Arthrit & Rheumatism Branch, NIH, Clin Ctr 9N244, Bethesda, MD 20892 USA. NR 32 TC 10 Z9 10 U1 0 U2 0 PU CLINICAL & EXPER RHEUMATOLOGY PI PISA PA VIA SANTA MARIA 31, 56126 PISA, ITALY SN 0392-856X J9 CLIN EXP RHEUMATOL JI Clin. Exp. Rheumatol. PD MAR-APR PY 1999 VL 17 IS 2 BP 235 EP 239 PG 5 WC Rheumatology SC Rheumatology GA 186GD UT WOS:000079719800015 PM 10342053 ER PT J AU Davis, TA Czerwinski, DK Levy, R AF Davis, TA Czerwinski, DK Levy, R TI Therapy of B-cell lymphoma with anti-CD20 antibodies can result in the loss of CD20 antigen expression SO CLINICAL CANCER RESEARCH LA English DT Article ID NON-HODGKINS-LYMPHOMA; MONOCLONAL-ANTIBODY; IDEC-C2B8; EMERGENCE; TRIAL AB Rituximab is a chimeric antibody with human gamma-1 and kappa constant regions and murine variable regions. It recognizes the CD20 antigen, a pan B-cell marker. Therapeutic trials in patients with B-cell non-Hodgkin's lymphoma (NHL) have shown significant efficacy with a primary response rate of 50%, and a secondary response rate of 44% after repeat treatments in prior responders. The selection for proliferating tumor cells that no longer express CD20 may compromise repeated treatment. We have identified a patient who developed a transformed NHL that lost CD20 protein expression after two courses of therapy with rituximab, In a pretreatment lymph node biopsy, 83% of B cells (as defined by CD19 and surface immunoglobulin) expressed surface CD20. A biopsy from the recurrent tumor after two courses of rituximab revealed a diffuse large cell NHL where 0% of B cells expressed CD20 with no evidence of bound rituximab. Cytoplasmic staining showed no CD20 protein. Sequencing of immunoglobulin heavy chain cDNA identified identical variable sequences in the initial and recurrent lymphomas, confirming the association between the two tumors. Literature and database review suggests that approximately 98% of diffuse large cell lymphomas express CD20, which suggests that these tumors rarely survive without CD20. This is the first identified case of loss of CD20 expression in a lymphoma that has relapsed after rituximab therapy, although several other cases have since been identified. Considering the significant number of patients treated with anti-CD20 antibodies, this may occur only rarely and is unlikely to preclude recurrent therapy with anti-CD20 antibodies in the majority of patients. However, because many patients have relapsed after anti-CD20 antibody therapy and have not been biopsied to identify clones with down-regulated CD20 antigen, we do not currently know the true frequency of this phenomenon. When possible, patients should undergo evaluation for CD20 expression before repeated courses of anti-CD20 therapy. C1 Stanford Univ, Sch Med, Div Med Oncol, Stanford, CA 94305 USA. NCI, NIH, Rockville, MD 20852 USA. RP Levy, R (reprint author), Stanford Univ, Dept Med, Div Oncol, SUM M207, Stanford, CA 94305 USA. FU NCI NIH HHS [CA33399, CA34233] NR 12 TC 175 Z9 179 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR PY 1999 VL 5 IS 3 BP 611 EP 615 PG 5 WC Oncology SC Oncology GA 176DY UT WOS:000079136700018 PM 10100713 ER PT J AU Li, HW Alonso-Vanegas, M Colicos, MA Jung, SS Lochmuller, H Sadikot, AF Snipes, GJ Seth, P Karpati, G Nalbantoglu, J AF Li, HW Alonso-Vanegas, M Colicos, MA Jung, SS Lochmuller, H Sadikot, AF Snipes, GJ Seth, P Karpati, G Nalbantoglu, J TI Intracerebral adenovirus-mediated p53 tumor suppressor gene therapy for experimental human glioma SO CLINICAL CANCER RESEARCH LA English DT Article ID CELLS; MUTANT; BRAIN; DEATH; ASTROCYTOMA; PROGRESSION; APOPTOSIS AB Malignant gliomas of astrocytic origin are good candidates for gene therapy because they have proven incurable with conventional treatments. Although mutation or inactivation of the p53 tumor suppressor gene occurs at early stages in gliomas and is associated with tumor progression, many tumors including high-grade glioblastoma multiforme carry a functionally intact p53 gene. To evaluate the effectiveness of p53-based therapy in glioma cells that contain endogenous wild-type p53, a clinically relevant model of malignant human glioma was established in athymic nu/nu mice. Intracerebral, rapidly growing tumors were produced by stereotactic injection of the human U87 MG glioma cell line that had been genetically modified for tracking purposes to express the Escherichia coli lacZ gene encoding beta-galactosidase. Overexpression of the p53 gene by adenovirus-mediated delivery into the tumor mass resulted in rapid cell death with the eradication of beta-galactosidase-expressing glioma cells through apoptosis. In long-term experiments, the survival of mice treated with the p53 adenoviral recombinant was significantly longer than that of mice that had received control adenoviral recombinant. During the observation period of 1 year, a complete cure was achieved in 27% of animals after a single injection of p53 adenoviral recombinant, and 38% of the animals were tumor free in the group receiving multiple injections of p53 adenoviral recombinant into a larger tumor mass. These experiments demonstrate that overexpression of p53 in gliomas, even in the presence of endogenous functional wildtype p53. leads to efficient elimination of tumor cells. These results point to the potential therapeutic usefulness of this approach for all astrocytic brain tumors. C1 McGill Univ, Montreal Neurol Inst, Dept Neurol & Neurosurg, Montreal, PQ H3A 2B4, Canada. McGill Univ, Dept Neuropathol, Montreal, PQ H3A 2B4, Canada. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. RP Nalbantoglu, J (reprint author), McGill Univ, Montreal Neurol Inst, Dept Neurol & Neurosurg, 3801 Univ St, Montreal, PQ H3A 2B4, Canada. OI Lochmuller, Hanns/0000-0003-2324-8001 NR 20 TC 48 Z9 50 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR PY 1999 VL 5 IS 3 BP 637 EP 642 PG 6 WC Oncology SC Oncology GA 176DY UT WOS:000079136700022 PM 10100717 ER PT J AU Stearns, ME Garcia, FU Fudge, K Rhim, J Wang, M AF Stearns, ME Garcia, FU Fudge, K Rhim, J Wang, M TI Role of interleukin 10 and transforming growth factor beta 1 in the angiogenesis and metastasis of human prostate primary tumor lines from orthotopic implants in severe combined immunodeficiency mice SO CLINICAL CANCER RESEARCH LA English DT Article ID TISSUE INHIBITOR; IV COLLAGENASE; METALLOPROTEINASES TIMP; COLORIMETRIC ASSAY; GENE-EXPRESSION; MOPC-315 TUMOR; HUMAN-MELANOMA; CELLS; CYTOKINE; PROLIFERATION AB Transfection of primary human prostate tumor cells (i.e., HPCA-10a, 10b, 10c, and 10d lines) with the transforming growth factor (TGF)-beta 1 gene stimulated anchorage independent growth and promoted tumor growth, angiogenesis, and metastasis after orthotopic implantation in severe combined immunodeficiency mice, In contrast, interleukin (IL)-10 transfected cells or cells cotransfected with these two genes exhibited reduced growth rates and significantly reduced angiogenesis and metastasis after 8, 12, and 16 weeks. Enzyme-linked immunosandwich assays confirmed that the respective tumors expressed elevated levels of TGF-beta 1 and IL-10 in vivo. ELISAs further showed that TGF-beta 1 expression induced matrix metalloproteinases-2 (MMP-2) expression, whereas IL-10 down-regulated MMP-2 expression while up regulating TIMP-1 in the transfected cells. Also, tumor factor VIII levels correlated with TGF-beta 1 and MMP-2 expression and inversely with IL-10 and TIMP-1 levels. More importantly, mouse survival was zero after 4-6 months in mice bearing TGF-beta 1- and MMP-2-expressing tumors and increased significantly in mice implanted with IL-10- and TIMP-1-expressing tumors (i.e., to >80% survival). Analysis of the metastatic lesions showed that they expressed TGF-beta 1 and MMP-2 but barely detectable levels of IL-10 or TIMP-1, suggesting that IL-10 and TIMP-1 might normally block tumor growth, angiogenesis, and metastasis. C1 Med Coll Penn & Hahnemann Univ, Dept Pathol & Lab Med, Philadelphia, PA 19102 USA. NCI, NIH, Frederick, MD 21702 USA. RP Stearns, ME (reprint author), MCP HUH Univ, Dept Pathol & Lab Med, MS 435,Broad & Vine St, Philadelphia, PA 19102 USA. NR 29 TC 96 Z9 106 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR PY 1999 VL 5 IS 3 BP 711 EP 720 PG 10 WC Oncology SC Oncology GA 176DY UT WOS:000079136700031 PM 10100726 ER PT J AU Sokol, GM Van Meurs, KP Wright, LL Rivera, O Thorn, WJ Chu, PM Sams, RL AF Sokol, GM Van Meurs, KP Wright, LL Rivera, O Thorn, WJ Chu, PM Sams, RL TI Nitrogen dioxide formation during inhaled nitric oxide therapy SO CLINICAL CHEMISTRY LA English DT Article ID PERSISTENT PULMONARY-HYPERTENSION; RESPIRATORY-DISTRESS-SYNDROME; DIODE-LASER ABSORPTION; NEWBORN; OXYGENATION; AIR AB Background: Nitrogen dioxide (NO2) is a toxic byproduct of inhalation therapy with nitric oxide (NO). The rate of NO2 formation during NO therapy is controversial. Methods: The formation of NO2 was studied under dynamic flows emulating a base case NO ventilator mixture containing 80 ppm NO in a 90% oxygen matrix. The difficulty in measuring NO2 concentrations below 2 ppm accurately was overcome by the use of tunable diode laser absorption spectroscopy. Results: Using a second-order model, the rate constant, k, for NO2 formation was determined to be (1.19 +/- 0.11) x 10(-11) ppm(-2) s(-1), which is in basic agreement with evaluated data from atmospheric literature. Conclusions: Inhaled NO can be delivered safely in a well-designed, continuous flow neonatal ventilatory circuit, and NO2 formation can be calculated reliably using the rate constant and circuit dwell time. (C) 1999 American Association for Clinical Chemistry. C1 Indiana Univ, Dept Pediat, Indianapolis, IN 46202 USA. Stanford Univ, Med Ctr, Dept Pediat, Stanford, CA 94304 USA. NICHHD, Neonatal Network, Bethesda, MD 20892 USA. Childrens Hosp, Natl Med Ctr, Dept Biomed Engn, Washington, DC 20010 USA. NIST, Div Analyt Chem, Gaithersburg, MD 20899 USA. RP Sokol, GM (reprint author), Indiana Univ, Sch Med, Div Neonatal Perinatal MEd, 702 Barnhill Dr,Room rr-208, Indianapolis, IN 46202 USA. EM gsokol@iupui.edu FU NICHD NIH HHS [U10 HD27856] NR 25 TC 23 Z9 25 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD MAR PY 1999 VL 45 IS 3 BP 382 EP 387 PG 6 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 173KE UT WOS:000078979100009 PM 10053039 ER PT J AU Fleisher, TA Dorman, SE Anderson, JA Vail, M Brown, MR Holland, SM AF Fleisher, TA Dorman, SE Anderson, JA Vail, M Brown, MR Holland, SM TI Detection of intracellular phosphorylated STAT-1 by flow cytometry SO CLINICAL IMMUNOLOGY LA English DT Article AB We have applied flow cytometry to the investigation of interferon-gamma activation of human monocytes. This approach uses monoclonal antibodies that distinguish between the native and phosphorylated forms of STAT-1. It enables rapid and quantitative assessment of STAT-1 phosphorylation on a discrete cell basis and is both more sensitive and less time consuming than immunoblotting. Furthermore, it allows for discrimination between a mixture of cells that differ in their response to interferon-gamma. This approach should allow for the evaluation of different intracellular signaling pathways using a combination of monoclonal reagents that are specific for native and activation modified proteins. Application of this form of testing should prove valuable in screening for signaling defects in selected patients with recurrent infections. In addition, this technique should permit dissection of a full range of cellular signaling pathways at the protein level. C1 NIAID, Warren Grant Magnuson Clin Ctr, Serv Immunol, NIH, Bethesda, MD 20892 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Fleisher, TA (reprint author), NIAID, Warren Grant Magnuson Clin Ctr, Serv Immunol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 11 TC 86 Z9 91 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD MAR PY 1999 VL 90 IS 3 BP 425 EP 430 DI 10.1006/clim.1998.4654 PG 6 WC Immunology SC Immunology GA 178BF UT WOS:000079245100017 PM 10075873 ER PT J AU Polis, MA AF Polis, MA TI Editorial response: Cytomegalovirus retinitis in persons with AIDS - A Shift in the Treatment paradigm? SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID COMBINED ANTIRETROVIRAL THERAPY; RELEASE GANCICLOVIR IMPLANT; IMMUNE-DEFICIENCY SYNDROME; CONTROLLED TRIAL; NATURAL-HISTORY; VIRUS; INFECTION; DISEASE; MANIFESTATIONS; PREVALENCE C1 NIAID, Immunoregulat Lab, Bethesda, MD 20892 USA. RP Polis, MA (reprint author), NIAID, Immunoregulat Lab, Bldg 10,Room 11C103,10 Ctr Dr, Bethesda, MD 20892 USA. EM mpolis@nih.gov OI Polis, Michael/0000-0002-9151-2268 NR 38 TC 3 Z9 3 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAR PY 1999 VL 28 IS 3 BP 534 EP 536 DI 10.1086/515168 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 175RZ UT WOS:000079110000017 PM 10194073 ER PT J AU Trollfors, B Taranger, J Lagergard, T Sundh, V Bryla, DA Schneerson, R Robbins, JB AF Trollfors, B Taranger, J Lagergard, T Sundh, V Bryla, DA Schneerson, R Robbins, JB TI Serum IgG antibody responses to pertussis toxin and filamentous hemagglutinin in nonvaccinated and vaccinated children and adults with pertussis SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID LEUKOCYTOSIS-PROMOTING FACTOR; BORDETELLA-PERTUSSIS; CONTROLLED TRIAL; WHOOPING-COUGH; TOXOID VACCINE; DIAGNOSIS; EFFICACY; SEROLOGY; ANTIGEN; ELISA AB Levels of IgG antibody to pertussis toxin (PT) and filamentous hemagglutinin (FHA) were measured in paired serum samples from 781 patients fulfilling at least one laboratory criterion for pertussis that was suggested by an ad hoc committee sponsored by the World Health Organization. The patients were participants or family members of participants in a double-blind efficacy trial of a monocomponent pertussis toroid vaccine. Of 596 nonvaccinated children, 90% had significant (two-fold or more) rises in PT IgG and FHA Ige levels. Only 17 (32%) of 53 children previously vaccinated with three doses of pertussis toroid had rises in PT IgG levels because they already had elevated PT Ige levels in their acute-phase serum samples, PT IgG and FHA IgG levels were significantly higher in acute-phase serum samples from 29 adults than in acute-phase serum samples from the nonvaccinated children. Nevertheless, significant rises in levels of PT IgG (79% of samples) and FHA Ige (90%) were demonstrated in adults. In conclusion, assay of PT Ige and FHA IgG in paired serum samples is highly sensitive for diagnosing pertussis in nonvaccinated individuals. Assay of PT IgG levels in paired sera is significantly less sensitive for diagnosis of pertussis for children vaccinated with pertussis toxoid. C1 Univ Gothenburg, Dept Pediat, Gothenburg, Sweden. Univ Gothenburg, Dept Med Microbiol & Immunol, Gothenburg, Sweden. Univ Gothenburg, Dept Geriatr Med, Gothenburg, Sweden. NICHHD, NIH, Bethesda, MD 20892 USA. RP Trollfors, B (reprint author), Goteborg Pertussis Vaccine Trial, St Paulig 6, S-41660 Gothenburg, Sweden. NR 23 TC 10 Z9 10 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAR PY 1999 VL 28 IS 3 BP 552 EP 559 DI 10.1086/515172 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 175RZ UT WOS:000079110000021 PM 10194077 ER PT J AU Park, MK Hospenthal, DR Bennett, JE AF Park, MK Hospenthal, DR Bennett, JE TI Treatment of hydrocephalus secondary to cryptococcal meningitis by use of shunting SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID CEREBRAL CRYPTOCOCCOSIS; VENTRICULOPERITONEAL AB Hydrocephalus can be associated with increased morbidity and mortality in cryptococcal meningitis if left untreated. Both ventriculoperitoneal and ventriculoatrial shunting have been used in persons with cryptococcosis complicated by hydrocephalus, but the indications for and complications, success, and timing of these interventions are not well known. To this end, we reviewed the clinical courses of 10 non-human immunodeficiency virus-infected patients with hydrocephalus secondary to cryptococcal meningitis who underwent shunting procedures, Nine of 10 patients who underwent shunting had noticeable improvement in dementia and gait. Two patients required late revision of their shunts. Shunt placement in eight patients with acute infection did not disseminate cryptococcal infection into the peritoneum or bloodstream, nor did shunting provide a nidus from which Cryptococcus organisms proved difficult to eradicate. Shunting procedures are a safe and effective therapy for hydrocephalus in patients with cryptococcal meningitis and need not be delayed until patients are mycologically cured. C1 NIAID, Clin Mycol Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, Infect Dis Serv, Washington, DC 20307 USA. RP Bennett, JE (reprint author), NIAID, Clin Mycol Sect, Clin Invest Lab, NIH, Bldg 10,Room 11C304,MSC-1882, Bethesda, MD 20892 USA. NR 8 TC 44 Z9 48 U1 1 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAR PY 1999 VL 28 IS 3 BP 629 EP 633 DI 10.1086/515161 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 175RZ UT WOS:000079110000034 PM 10194090 ER PT J AU Tavel, JA Miller, KD Masur, H AF Tavel, JA Miller, KD Masur, H TI Guide to major clinical trials of antiretroviral therapy in human immunodeficiency virus-infected patients: Protease inhibitors, non-nucleoside reverse transcriptase inhibitors, and nucleotide reverse transcriptase inhibitors SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID PLACEBO-CONTROLLED TRIAL; ADEFOVIR DIPIVOXIL; HIV-1 INFECTION; DOUBLE-BLIND; CELL COUNTS; SAFETY; PHARMACOKINETICS; NEVIRAPINE; ZIDOVUDINE; SAQUINAVIR AB In this AIDS Commentary, Drs. Tavel, Miller, and Masur of the National Institutes of Health present this compilation of clinical trials of antiretroviral therapy in HIV-infected patients, which complements two similar reviews published as AIDS Commentaries in Clinical Infectious Diseases (1995;20:1145-51 and 1996;23:15-27). Whereas the previous compilations focused on trials of nucleoside analogues, this review is based on published articles and abstracts of clinical trials of protease inhibitors, non-nucleoside reverse transcriptase inhibitors, and nucleotide reverse transcriptase inhibitors in HIV-infected patients. The intent is to present a thorough, but not necessarily exhaustive, review of studies that have shaped our principles of antiretroviral therapy. Preference is given to clinical endpoint trials, proof-of-concept trials that have influenced the standard of care for HIV treatment, double-blind, randomized trials, and large trials with long-term patient followup. Smaller trials that address important questions are also included. C1 NIAID, NIH, Bethesda, MD 20892 USA. NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. RP Tavel, JA (reprint author), NIAID, NIH, Bldg 10,Room 115231,9000 Rockville Pike, Bethesda, MD 20892 USA. EM jtavel@atlas.niaid.nih.gov NR 98 TC 35 Z9 36 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAR PY 1999 VL 28 IS 3 BP 643 EP 676 DI 10.1086/515179 PG 34 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 175RZ UT WOS:000079110000038 PM 10194094 ER PT J AU Smeriglio, VL Wilcox, HC AF Smeriglio, VL Wilcox, HC TI Prenatal drug exposure and child outcome - Past, present, future SO CLINICS IN PERINATOLOGY LA English DT Article ID UTERO COCAINE EXPOSURE; IN-UTERO; MECONIUM ANALYSIS; PREGNANCY; INFANTS; MARIJUANA; AROUSAL; FETAL; PREVALENCE; NEWBORNS AB This article provides historical context on the study of prenatal drug exposure and child outcome, traces attention to the issue over time, discusses prevalence approaches and estimates, characterizes studies of prenatal drug exposure and child outcome, and examines research challenges and directions. Challenges and directions discussed are: determination of drug exposure, with special attention to measuring levels of prenatal exposure and detecting postnatal passive exposure; assessment of child outcome, including comments on neuroimaging; changes in drug use, with comment on current methamphetamine concerns; human subjects issues; and study design and statistical analysis considerations. The article also highlights some resources directly relevant to providing services for drug-using pregnant women and their children. C1 NIDA, CAMCODA, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Mental Hyg, Baltimore, MD USA. RP Smeriglio, VL (reprint author), NIDA, CAMCODA, NIH, Room 5198,MSC9593,6001 Execut Blvd, Bethesda, MD 20892 USA. NR 61 TC 14 Z9 14 U1 1 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0095-5108 J9 CLIN PERINATOL JI Clin. Perinatol. PD MAR PY 1999 VL 26 IS 1 BP 1 EP + PG 17 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 185TJ UT WOS:000079686200003 PM 10214540 ER PT J AU Leshner, AI AF Leshner, AI TI Prenatal drug exposure and child outcome - Foreword SO CLINICS IN PERINATOLOGY LA English DT Editorial Material C1 NIDA, NIH, Bethesda, MD 20892 USA. RP Leshner, AI (reprint author), NIDA, NIH, 6001 Execut Blvd, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0095-5108 J9 CLIN PERINATOL JI Clin. Perinatol. PD MAR PY 1999 VL 26 IS 1 BP XI EP XI PG 1 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 185TJ UT WOS:000079686200001 ER PT J AU Gonzalez-Heydrich, J Steingard, RJ Putnam, F Beardslee, W Kohane, IS AF Gonzalez-Heydrich, J Steingard, RJ Putnam, F Beardslee, W Kohane, IS TI Using 'off the shelf', computer programs to mine additional insights from published data: diurnal variation in potency of ACTH stimulation of cortisol secretion revealed SO COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE LA English DT Article DE data mining; mathematical models; hormone interactions; adrenocortical sensitivity; adrenal rhythm; biological database ID ADRENAL RESPONSIVENESS; ADRENOCORTICOTROPIN; RHYTHM; AXIS; SENSITIVITY; HORMONE AB We describe the use of available computer programs to mine additional insights from published data. Graphs from four studies of ACTH and cortisol plasma levels collected throughout the 24 h day in humans were scanned into digital form and the data points extracted. To investigate the magnitude of ACTH stimulation of cortisol secretion across the 24 h, Monte Carlo methods were used to fit the parameters of a computer model of the ACTH-adrenal axis to the extracted data. ACTH was found to have a greater effect on cortisol secretion during the peaks of the cycle than at the nadir. This finding could not be explained by previously published dose response curves of ACTH effect. This implies that other modulators influence the effect of ACTH on the adrenal. This study also demonstrates how available computer programs can be used to examine models of physiologic regulation using data already available in the literature. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Childrens Hosp, Dept Psychiat, Boston, MA 02115 USA. Cambridge Hosp, Dept Psychiat, Div Child Psychiat, Cambridge, MA 02139 USA. NIMH, Unit Dev Traumatol, Bethesda, MD 20892 USA. Childrens Hosp, Dept Endocrinol, Boston, MA 02115 USA. RP Gonzalez-Heydrich, J (reprint author), Childrens Hosp, Dept Psychiat, 300 Longwood Ave, Boston, MA 02115 USA. RI Kohane, Isaac Kohane/K-3716-2012 OI Kohane, Isaac Kohane/0000-0003-2192-5160 FU NIMH NIH HHS [MH19126] NR 23 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-2607 J9 COMPUT METH PROG BIO JI Comput. Meth. Programs Biomed. PD MAR PY 1999 VL 58 IS 3 BP 227 EP 238 DI 10.1016/S0169-2607(98)00086-8 PG 12 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Engineering, Biomedical; Medical Informatics SC Computer Science; Engineering; Medical Informatics GA 165VV UT WOS:000078543300003 PM 10094227 ER PT J AU Sokol, RZ Okuda, H Stanczyk, FZ Wolfe, GW Delaney, JC Chapin, RE AF Sokol, RZ Okuda, H Stanczyk, FZ Wolfe, GW Delaney, JC Chapin, RE TI Normative reproductive indices for male and female adult Sprague-Dawley rats SO CONTRACEPTION LA English DT Article DE rat; luteinizing hormone; testosterone; estradiol; sperm ID LUTEINIZING-HORMONE; ESTROUS-CYCLE; DOSE LEVELS; LH; TESTOSTERONE; AMPLITUDE; PITUITARY; SECRETION AB The Sprague-Dawley rat is traditionally used as the experimental model for the study of contraceptive agents and reproductive toxicants. Until recently, the normative values used to compare hormone levels after drug exposure were based on the values generated by radioimmunoassay methods developed 30 years ago. To ascertain normative reproductive indices for adult female and male Sprague-Dawley rats over a 6-month age period, we measured luteinizing hormone, testosterone, anal estradiol using commercially available kits that employ updated assay techniques. In addition, sperm indices were correlated with reproductive hormones over the same time period. Animals were killed at 107, 128, 156, 212, and 268 days of age irrespective (for females) of cycle stage. Serum LH levels did not change with increasing age; however, the female rats had significantly higher LH values than did the males at comparable ages (p < 0.001). Testosterone levels and sperm parameters did not significantly change with increasing age. Estradiol levels were significantly higher in 107-day-old female rats than they were in female rats in all older age groups (p < 0.01). The values reported can be used in designing and interpreting data generated in ongoing, long term toxicological and contraceptive studies using the rat animal model. (C) 1999 Elsevier Science Inc. All rights reserved. C1 Univ So Calif, Sch Med, Dept Med, Los Angeles, CA 90033 USA. ROW Sci Inc, Gaithersburg, MD USA. NIEHS, Reprod Toxicol Grp, Res Triangle Pk, NC USA. RP Sokol, RZ (reprint author), Univ So Calif, Womens & Childrens Hosp, Sch Med, Dept Obstet & Gynecol, 1240 N Mission Rd, Los Angeles, CA 90033 USA. OI Chapin, Robert/0000-0002-5997-1261 NR 22 TC 15 Z9 15 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0010-7824 J9 CONTRACEPTION JI Contraception PD MAR PY 1999 VL 59 IS 3 BP 203 EP 207 DI 10.1016/S0010-7824(99)00017-7 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 205HK UT WOS:000080815100009 PM 10382084 ER PT J AU Beekmann, SE Henderson, DK Magnuson, WG AF Beekmann, SE Henderson, DK Magnuson, WG TI Unfinished business: Assessing the efficacy of extraluminal silver ions on the prevention of microbial colonization and catheter-associated infection SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE central venous catheter; bacterial; colorization, of catheters; nosocomial infection ID CENTRAL VENOUS CATHETERS; BLOOD-STREAM INFECTION; CONTROLLED TRIAL; BACTERIAL-COLONIZATION; CHLORHEXIDINE; SULFADIAZINE; ADHERENCE; CUFF C1 Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA. NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Beekmann, SE (reprint author), Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA. NR 15 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD MAR PY 1999 VL 27 IS 3 BP 456 EP 458 DI 10.1097/00003246-199903000-00006 PG 3 WC Critical Care Medicine SC General & Internal Medicine GA 182LH UT WOS:000079500100006 PM 10199511 ER PT J AU Bell, MJ Kochanek, PM Heyes, MP Wisniewski, SR Sinz, EH Clark, RSB Blight, AR Marion, DW Adelson, PD AF Bell, MJ Kochanek, PM Heyes, MP Wisniewski, SR Sinz, EH Clark, RSB Blight, AR Marion, DW Adelson, PD TI Quinolinic acid in the cerebrospinal fluid of children after traumatic brain injury SO CRITICAL CARE MEDICINE LA English DT Article DE head injury; inflammation; shaken infant syndrome; neurotoxin; child abuse; macrophage; quinolinic acid; NMDA; head trauma; excitotoxicity ID INTRAVENTRICULAR INFUSION; NEUROLOGICAL DISEASE; L-TRYPTOPHAN; SPINAL-CORD; AMINO-ACIDS; HEAD-INJURY; RAT; MODEL; EXCITOTOXICITY; ACCUMULATION AB Objective: To measure quinolinic acid, a macrophage-derived neurotoxin, in the cerebrospinal fluid (CSF) of children after traumatic brain injury (TBI) and to correlate CSF quinolinic acid concentrations to clinically important variables. Design: A prospective, observational study. Setting: The pediatric intensive care unit in Children's Hospital of Pittsburgh, a tertiary care, university based children's hospital. Patients: Seventeen critically ill children following severe TBI (Glasgow Coma Scale score <8) whose care required the place ment of an intraventricular catheter for continuous drainage of CSF, interventions: None, Measurements and Main Results: Patients ranged in age from 2 mos to 16 yrs (mean 6.0 yrs), CSF was collected immediately on placement of the ventricular catheter and daily thereafter, Quinolinic acid concentration was measured by gas chromatography/mass spectroscopy in 69 samples (4.0 +/- 0.4 [SEM] samples per patient), CSF quinolinic acid concentration progressively increased after injury (p = .034, multivariate analysis) and was increased in nonsurvivors vs, survivors (p = .002, multivariate analysis). CSF quinolinic acid concentration was not associated with age. Although overall CSF quinolinic acid concentration was not associated with shaken injury (p = .16, multivariate analysis), infants suffering with shaken infant syndrome had increased admission CSF quinolinic acid concentrations compared with children with accidental mechanisms of injury (p = .027, Mann-Whitney Rank Sum test), Conclusions: A large and progressive increase in the macrophage-derived neurotoxin quinolinic acid is seen following severe TBI in children, The increase is strongly associated with increased mortality, Increased CSF quinolinic acid concentration on admission in children with shaken infant syndrome could reflect a delay in presentation to medical attention or age-related differences in quinolinic acid production, These findings raise the possibility that quinolinic acid may play a role in secondary injury after TBI in children and suggest an interaction between inflammatory and excitotoxic mechanisms of injury following TBI. C1 Safar Ctr Resuscitat Res, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Anesthesiol & Crit Care Med, Pittsburgh, PA USA. Univ Pittsburgh, Dept Pediat, Pittsburgh, PA USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA USA. Univ Pittsburgh, Dept Neurol Surg, Pittsburgh, PA USA. Childrens Natl Med Ctr, Dept Pediat & Crit Care Med, Washington, DC 20010 USA. Univ N Carolina, Dept Neurol Surg, Chapel Hill, NC USA. NIMH, Lab Neurotoxicol, Bethesda, MD 20892 USA. RP Kochanek, PM (reprint author), Safar Ctr Resuscitat Res, 3434 5th Ave, Pittsburgh, PA 15260 USA. RI Kochanek, Patrick/D-2371-2015; OI Kochanek, Patrick/0000-0002-2627-913X; Wisniewski, Stephen/0000-0002-3877-9860 FU NINDS NIH HHS [NS30318] NR 24 TC 39 Z9 41 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD MAR PY 1999 VL 27 IS 3 BP 493 EP 497 DI 10.1097/00003246-199903000-00023 PG 5 WC Critical Care Medicine SC General & Internal Medicine GA 182LH UT WOS:000079500100022 PM 10199527 ER PT J AU Solomon, SD AF Solomon, SD TI Interventions for acute trauma response SO CURRENT OPINION IN PSYCHIATRY LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; RANDOMIZED CONTROLLED TRIAL; SURVIVORS; VICTIMS; PTSD; ACCIDENTS; DISASTER; ASSAULT; FOLLOW AB The acute stress disorder diagnosis was included in DSM-IV to facilitate both the early prediction of those trauma victims who will later develop post-traumatic stress disorder, as well as the formation of interventions that can prevent chronic psychiatric impairment. Although several treatments for acute trauma response have been developed, thus far only cognitive behavioural therapy has received empiric support for its efficacy in treating acute stress disorder. In contrast, the most popular early intervention strategy, psychologic debriefing, has been found to be at best harmless or actually damaging. Waiting 6 weeks after a trauma before providing therapy will assist in determining those victims whose prognosis is poor without formal mental health intervention, Because trauma victims tend to be reluctant to use mental health services, therapists may need to go into the community to provide treatment in the acute phase of trauma response. Curr Opin Psychiatry 12:175-180. (C) 1999 Lippincott Williams & Wilkins. C1 NIH, Off Behav & Social Sci Res, Bethesda, MD 20893 USA. RP Solomon, SD (reprint author), NIH, Off Behav & Social Sci Res, 7550 Wisconsin Ave Room 8C16, Bethesda, MD 20893 USA. EM ssolomon@nih.gov NR 38 TC 7 Z9 7 U1 7 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0951-7367 J9 CURR OPIN PSYCHIATR JI Curr. Opin. Psychiatr. PD MAR PY 1999 VL 12 IS 2 BP 175 EP 180 DI 10.1097/00001504-199903000-00006 PG 6 WC Psychiatry SC Psychiatry GA 175EK UT WOS:000079079900006 ER PT J AU Hofmeister, R Khaled, AR Benbernou, N Rajnavolgyi, E Muegge, K Durum, SK AF Hofmeister, R Khaled, AR Benbernou, N Rajnavolgyi, E Muegge, K Durum, SK TI Interleukin-7: physiological roles and mechanisms of action SO CYTOKINE & GROWTH FACTOR REVIEWS LA English DT Review DE interleukin-7; interleukin-7 receptor; signal transduction; apoptosis; V(D)J-recombination ID RECEPTOR-GAMMA-CHAIN; T-CELL DEVELOPMENT; STIMULATES TYROSINE PHOSPHORYLATION; C-MYC INDUCTION; SEVERE COMBINED IMMUNODEFICIENCY; INOSITOL PHOSPHOLIPID TURNOVER; DEFECTIVE LYMPHOID DEVELOPMENT; LYMPHOBLASTIC-LEUKEMIA CELLS; TRANSDUCING ADAPTER MOLECULE; FETAL LIVER CULTURES AB Interleukin-7 (IL-7), a product of stromal cells, provides critical signals to lymphoid cells at early stages in their development. Two types of cellular responses to IL-7 have been identified in lymphoid progenitors: (1) a trophic effect and (2) an effect supporting V(D)J recombination. The IL-7 receptor is comprised of two chains, IL-7R alpha and gamma(c). Following receptor crosslinking, rapid activation of several classes of kinases occurs, including members of the Janus and Src families and PI3-kinase. A number of transcription factors are subsequently activated including STATs, c-myc, NFAT and AP-1. However, it remains to be determined which, if any, previously identified pathway leads to the trophic or V(D)J endpoints. The trophic response to IL-7 involves protecting lymphoid progenitors from a death process that resembles apoptosis. This protection is partly mediated by IL-7 induction of Bcl-2. however other IL-7-induced events are probably also involved in the trophic response. The V(D)J response to IL-7 is partly mediated through increased production of Rag proteins (which cleave the target locus) and partly by increasing the accessibility of a target locus to cleavage through chromatin remodeling. Published by Elsevier Science Ltd. C1 NCI, Mol Immunoregulat Lab, Frederick, MD 21702 USA. SAIC, Frederick, MD 21702 USA. RP Durum, SK (reprint author), NCI, Mol Immunoregulat Lab, Frederick, MD 21702 USA. EM durums@mail.ncifcrf.gov RI Rajnavolgyi, Eva/D-4384-2013 NR 237 TC 177 Z9 181 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6101 J9 CYTOKINE GROWTH F R JI Cytokine Growth Factor Rev. PD MAR PY 1999 VL 10 IS 1 BP 41 EP 60 DI 10.1016/S1359-6101(98)00025-2 PG 20 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 216GT UT WOS:000081433600005 PM 10379911 ER PT J AU Nee, LE Lippa, CF AF Nee, LE Lippa, CF TI Alzheimer's disease in 22 twin pairs 13-year follow-up: Hormonal, infectious and traumatic factors SO DEMENTIA AND GERIATRIC COGNITIVE DISORDERS LA English DT Article DE Alzheimer's disease; estrogen; twin trauma ID DEMENTIA; RISK AB We obtained follow-up data on 22 sets of twins where at least one twin had Alzheimer's disease (AD), The concordance rate for monozygotic twins (n = 17 pairs) was 59%, whereas that for dizygotic twins was 40%. In our series 8 monozygotic twins had hysterectomies; all had AD. The twins with hysterectomies also had a tendency to develop AD at an earlier age than their co-twin, Five twins with serious systemic infection developed AD, and they tended to have earlier onset than their corresponding twin, We found no strong evidence that head injury predisposed to AD. C1 NINDS, Family Studies Unit, Med Neurol Branch, Ctr Clin, Bethesda, MD 20892 USA. Allegheny Univ Hlth Sci, Dept Neurol, MCP Div, Philadelphia, PA 19102 USA. RP Nee, LE (reprint author), NINDS, Family Studies Unit, Med Neurol Branch, Ctr Clin, Room 5N226,9000 Rockville Pike, Bethesda, MD 20892 USA. EM lindanee@codon.nih.gov FU NIA NIH HHS [AG13623] NR 16 TC 35 Z9 38 U1 1 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-8008 J9 DEMENT GERIATR COGN JI Dement. Geriatr. Cogn. Disord. PD MAR-APR PY 1999 VL 10 IS 2 BP 148 EP 151 DI 10.1159/000017115 PG 4 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 172VZ UT WOS:000078947100014 PM 10026389 ER PT J AU Ghiani, CA Eisen, AM Yuan, XQ DePinho, RA McBain, CJ Gallo, V AF Ghiani, CA Eisen, AM Yuan, XQ DePinho, RA McBain, CJ Gallo, V TI Neurotransmitter receptor activation triggers p27(Kip1) and p21(CIP1) accumulation and G(1) cell cycle arrest in oligodendrocyte progenitors SO DEVELOPMENT LA English DT Article DE norepinephrine; O-2A cells; glia; cyclin kinase inhibitors; glutamate receptors; cAMP; voltage-dependent K+ channels ID DEPENDENT KINASE INHIBITOR; BETA-ADRENERGIC RECEPTORS; CENTRAL-NERVOUS-SYSTEM; POSTNATAL RAT FOREBRAIN; MOUSE FETAL DEVELOPMENT; GLIAL PRECURSOR CELLS; CHANNEL EXPRESSION; PRIMARY CULTURES; OPTIC-NERVE; SUBVENTRICULAR ZONE AB We examined the pathways that link neurotransmitter receptor activation and cell cycle arrest in oligodendrocyte progenitors, We had previously demonstrated that glutamate receptor activation inhibits oligodendrocyte progenitor proliferation and lineage progression. Here, using purified oligodendrocyte progenitors and cerebellar slice cultures, we show that norepinephrine and the beta-adrenergic receptor agonist isoproterenol also inhibited the proliferation, but in contrast to glutamate, isoproterenol stimulated progenitor lineage progression, as determined by O4 and O1 antibody staining, This antiproliferative effect was specifically attributable to a beta-adrenoceptor-mediated increase in cyclic adenosine monophosphate, since analogs of this cyclic nucleotide mimicked the effects of isoproterenol on oligodendrocyte progenitor proliferation, while alpha-adrenoceptor agonists were ineffective. Despite the opposite effects on lineage progression, both isoproterenol and the glutamate receptor agonist kainate caused accumulation of the cyclin-dependent kinase inhibitors p27(Kip1) and p21(CIP1), and G(1) arrest, Studies with oligodendrocyte progenitor cells from INK4a(-/-) mice indicated that the G(1) cyclin kinase inhibitor p16(INK4a) as well as p19(ARF) were not required for agonist-stimulated proliferation arrest. Our results demonstrate that beta-adrenergic and glutamatergic receptor activation inhibit oligodendrocyte progenitor proliferation through a mechanism that may involve p27(Kip1) and p21(CIP1); but while neurotransmitter-induced accumulation of p27(Kip1) is associated with cell cycle arrest, it does not by itself promote oligodendrocyte progenitor differentiation. C1 NICHD, Lab Cellular & Mol Neurophysiol, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Gallo, V (reprint author), NICHD, Lab Cellular & Mol Neurophysiol, NIH, Bethesda, MD 20892 USA. EM vgallo@helix.nih.gov OI Ghiani, Cristina/0000-0002-9867-6185 NR 84 TC 75 Z9 77 U1 1 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD MAR PY 1999 VL 126 IS 5 BP 1077 EP 1090 PG 14 WC Developmental Biology SC Developmental Biology GA 180UJ UT WOS:000079403300022 PM 9927607 ER PT J AU Daubresse, G Deuring, R Moore, L Papoulas, O Zakrajsek, I Waldrip, WR Scott, MP Kennison, JA Tamkun, JW AF Daubresse, G Deuring, R Moore, L Papoulas, O Zakrajsek, I Waldrip, WR Scott, MP Kennison, JA Tamkun, JW TI The Drosophila kismet gene is related to chromatin-remodeling factors and is required for both segmentation and segment identity SO DEVELOPMENT LA English DT Article DE polycomb group; trithorax group; transcription; chromatin; homeotic; BRM; Drosophila; kismet ID HETEROCHROMATIN-ASSOCIATED PROTEIN; DOSAGE-DEPENDENT MODIFIERS; ABDOMINAL-B DOMAIN; BITHORAX COMPLEX; MEDIATED REPRESSION; MOLECULAR-GENETICS; BINDING PROTEIN; POLYCOMB; MELANOGASTER; EXPRESSION AB The Drosophila kismet gene was identified in a screen for dominant suppressors of Polycomb, a repressor of homeotic genes. Here we show that kismet mutations suppress the Polycomb mutant phenotype by blocking the ectopic transcription of homeotic genes. Loss of zygotic kismet function causes homeotic transformations similar to those associated with loss-of-function mutations in the homeotic genes Sex combs reduced and Abdominal-B. kismet is also required for proper larval body segmentation. Loss of maternal kismet function causes segmentation defects similar to those caused by mutations in the pair-rule gene even-skipped. The kismet gene encodes several large nuclear proteins that are ubiquitously expressed along the anterior-posterior axis. The Kismet proteins contain a domain conserved in the trithorax group protein Brahma and related chromatin-remodeling factors, providing further evidence that alterations in chromatin structure are required to maintain the spatially restricted patterns of homeotic gene transcription. C1 Univ Calif Santa Cruz, Dept Biol, Santa Cruz, CA 95064 USA. Stanford Univ, Howard Hughes Med Inst, Sch Med, Dept Genet & Dev Biol, Stanford, CA 94305 USA. NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP Tamkun, JW (reprint author), Univ Calif Santa Cruz, Dept Biol, Santa Cruz, CA 95064 USA. FU Howard Hughes Medical Institute; NCI NIH HHS [CA70404]; NIGMS NIH HHS [GM49883, R01 GM049883] NR 72 TC 97 Z9 98 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD MAR PY 1999 VL 126 IS 6 BP 1175 EP 1187 PG 13 WC Developmental Biology SC Developmental Biology GA 184PW UT WOS:000079622400009 PM 10021337 ER PT J AU Campione, M Steinbeisser, H Schweickert, A Deissler, K van Bebber, F Lowe, LA Nowotschin, S Viebahn, C Haffter, P Kuehn, MR Blum, M AF Campione, M Steinbeisser, H Schweickert, A Deissler, K van Bebber, F Lowe, LA Nowotschin, S Viebahn, C Haffter, P Kuehn, MR Blum, M TI The homeobox gene Pitx2: mediator of asymmetric left-right signaling in vertebrate heart and gut looping SO DEVELOPMENT LA English DT Article DE left-right asymmetry; Pitx2; homeobox gene; mouse; zebrafish; Xenopus ID CHICK EMBRYOGENESIS; NODAL EXPRESSION; ACTIN BUNDLES; MOUSE EMBRYOS; XENOPUS; MORPHOGENESIS; TRANSCRIPTION; PATHWAY; SITUS; GASTRULATION AB Left-right asymmetry in vertebrates is controlled by activities emanating from the left lateral plate. How these signals get transmitted to the forming organs is not known. A candidate mediator in mouse, frog and zebrafish embryos is the homeobox gene Pitx2, It is asymmetrically expressed in the left lateral plate mesoderm, tubular heart and early gut tube. Localized Pitx2 expression continues when these organs undergo asymmetric looping morphogenesis, Ectopic expression of Xnr1 in the right lateral plate induces Pitx2 transcription in Xenopus. Misexpression of Pitx2 affects situs and morphology of organs. These experiments suggest a role for Pitx2 in promoting looping of the linear heart and gut. C1 Forschungszentrum Karlsruhe, Inst Genet, D-76021 Karlsruhe, Germany. Max Planck Inst Entwicklungsbiol, Abt 5, Dept Cell Biol, D-72076 Tubingen, Germany. Max Planck Inst Entwicklungsbiol, Abt 3, Dept Genet, D-72076 Tubingen, Germany. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Univ Bonn, Inst Anat, D-53115 Bonn, Germany. RP Blum, M (reprint author), Forschungszentrum Karlsruhe, Inst Genet, POB 3640, D-76021 Karlsruhe, Germany. RI Campione, Marina/G-9001-2013; Kuehn, Michael/A-4573-2014 OI Kuehn, Michael/0000-0002-7703-9160 NR 51 TC 228 Z9 231 U1 1 U2 14 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD MAR PY 1999 VL 126 IS 6 BP 1225 EP 1234 PG 10 WC Developmental Biology SC Developmental Biology GA 184PW UT WOS:000079622400013 PM 10021341 ER PT J AU Francis-West, PH Abdelfattah, A Chen, P Allen, C Parish, J Ladher, R Allen, S MacPherson, S Luyten, FP Archer, CW AF Francis-West, PH Abdelfattah, A Chen, P Allen, C Parish, J Ladher, R Allen, S MacPherson, S Luyten, FP Archer, CW TI Mechanisms of GDF-5 action during skeletal development SO DEVELOPMENT LA English DT Article DE GDF-5; joint; chondrogenesis; proliferation; cell adhesion ID GROWTH-FACTOR-BETA; LIMB CARTILAGE DIFFERENTIATION; TGF-BETA; CHICK LIMB; MORPHOGENETIC PROTEINS; GROWTH/DIFFERENTIATION FACTOR-5; MICROMASS CULTURE; MOUSE LIMB; BUD CELLS; CHONDROGENESIS AB Mutations in GDF-5, a member of the TGF-beta superfamily, result in the autosomal recessive syndromes brachypod (bp) in mice and Hunter-Thompson and Grebe-type chondrodysplasias in humans. These syndromes are all characterised by the shortening of the appendicular skeleton and loss or abnormal development of some joints. To investigate how GDF-5 controls skeletogenesis, we overexpressed GDF-5 during chick limb development using the retrovirus, RCASBP, This resulted in up to a 37.5% increase in length of the skeletal elements, which was predominantly due to an increase in the number of chondrocytes. By injecting virus at different stages of development, we show that GDF-5 can increase both the size of the early cartilage condensation and the later developing skeletal element. Using in vitro micromass cultures as a model system to study the early steps of chondrogenesis, we show that GDF-5 increases chondrogenesis in a dose-dependent manner. We did not detect changes in proliferation, However, cell suspension cultures showed that GDF-5 might act at these stages by increasing cell adhesion, a critical determinant of early chondrogenesis. In contrast, pulse labelling experiments of GDF-5-infected limbs showed that at later stages of skeletal development GDF-5 can increase proliferation of chondrocytes. Thus, here we show two mechanisms of how GDF-5 may control different stages of skeletogenesis. Finally, our data show that levels of GDF-5 expression/activity are important in controlling the size of skeletal elements and provides a possible explanation for the variation in the severity of skeletal defects resulting from mutations in GDF-5. C1 Guys Kings & St Thomas Sch Dent, Dept Craniofacial Dev, London SE1 9RT, England. NIDR, Bone Res Branch, NIH, Bethesda, MD 20892 USA. Univ Wales, Sch Mol & Med Biosci, Cardiff CF1 3YF, S Glam, Wales. UZ Leuven, Dept Rheumatol, B-3212 Pellenberg, Belgium. RP Francis-West, PH (reprint author), Guys Kings & St Thomas Sch Dent, Dept Craniofacial Dev, Guys Tower,Floor 28,London Bridge, London SE1 9RT, England. EM pfrancis@hgmp.mrc.ac.uk; Frank.luyten@uz.kuleuven.ac.be RI Ladher, Raj/B-3001-2008 FU Wellcome Trust NR 64 TC 222 Z9 234 U1 2 U2 7 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD MAR PY 1999 VL 126 IS 6 BP 1305 EP 1315 PG 11 WC Developmental Biology SC Developmental Biology GA 184PW UT WOS:000079622400020 PM 10021348 ER PT J AU McCrae, RR Costa, PT de Lima, MP Simoes, A Ostendorf, F Angleitner, A Marusic, I Bratko, D Caprara, GV Barbaranelli, C Chae, JH Piedmont, RL AF McCrae, RR Costa, PT de Lima, MP Simoes, A Ostendorf, F Angleitner, A Marusic, I Bratko, D Caprara, GV Barbaranelli, C Chae, JH Piedmont, RL TI Age differences in personality across the adult life span: Parallels in five cultures SO DEVELOPMENTAL PSYCHOLOGY LA English DT Article; Proceedings Paper CT 49th Annual Scientific Meeting of the Gerontological-Society-of-America CY NOV 15-21, 1996 CL WASHINGTON, D.C. SP Gerontol Soc Amer ID PSYCHOSOCIAL DEVELOPMENT; 5-FACTOR MODEL; NEO; STABILITY; VALIDITY; SCALES AB Both cross-sectional and longitudinal studies in the United States have shown consistent changes between college age and middle adulthood. There appear to be declines in 3 of the 5 major factors of personality-Neuroticism, Extraversion, and Openness-and increases in Agreeableness and Conscientiousness. To examine cross-cultural generalizability of these findings, translations of the Revised NEO Personality Inventory were administered to samples in Germany, Italy, Portugal, Croatia, and South Korea (N = 7,363). Similar patterns of age differences were seen in each country, for both men and women. Common trends were also seen for the more specific traits that define the major factors. Because these nations differ substantially in culture and recent history, results suggest the hypothesis that these are universal maturational changes in adult personality. C1 NIA, Gerontol Res Ctr, Intramural Res Program, Personal Stress & Coping Sect, Baltimore, MD 21224 USA. Univ Coimbra, Dept Psychol, Coimbra, Portugal. Univ Bielefeld, Dept Psychol, D-4800 Bielefeld, Germany. Univ Zagreb, Dept Psychol, Zagreb 41000, Croatia. Univ Rome La Sapienza, Dept Psychol, Rome, Italy. Sogang Univ, Dept Psychol, Seoul, South Korea. RP McCrae, RR (reprint author), NIA, Gerontol Res Ctr, Intramural Res Program, Personal Stress & Coping Sect, Box 3,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM jeffm@mvx.grc.nia.nih.gov OI P. de Lima, Margarida/0000-0002-6239-1137; Costa, Paul/0000-0003-4375-1712 NR 56 TC 292 Z9 296 U1 5 U2 49 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0012-1649 J9 DEV PSYCHOL JI Dev. Psychol. PD MAR PY 1999 VL 35 IS 2 BP 466 EP 477 DI 10.1037//0012-1649.35.2.466 PG 12 WC Psychology, Developmental SC Psychology GA 170VQ UT WOS:000078828100014 PM 10082017 ER PT J AU Harris, MI Eastman, RC Cowie, CC Flegal, KM Eberhardt, MS AF Harris, MI Eastman, RC Cowie, CC Flegal, KM Eberhardt, MS TI Racial and ethnic differences in glycemic control of adults with type 2 diabetes SO DIABETES CARE LA English DT Article ID NIDDM; HYPERGLYCEMIA; AMERICANS; DISEASE AB OBJECTIVE - To evaluate glycemic control in a representative sample of U.S, adults with type 2 diabetes. RESEARCH DESIGN AND METHODS - The Third National Health and Nutrition Examination Survey included national samples of non-Hispanic whites, non-Hispanic blacks, and Mexican Americans aged greater than or equal to 20 years. Information on medical history and treatment of diabetes was obtained to determine those who had been diagnosed with type 2 diabetes by a physician before the survey (n = 1,480). Easting plasma glucose and HbA(1c) were measured, and the frequencies of sociodemographic and clinical variables related to glycemic control were determined. RESULTS - A higher proportion of non-Hispanic blacks were treated with insulin and a higher proportion of Mexican Americans were treated with oral agents compared with non-Hispanic whites, but the majority of adults in each racial or ethnic group (71-83%) used pharmacologic treatment for diabetes. Use of multiple daily insulin injections was more common in whites. Blood glucose self-monitoring was less common in Mexican Americans, but most patients had never self-monitored. HbA(1c) values in the nondiabetic range were found in 26% of non-Hispanic whites, 17% of non-Hispanic blacks, and 20% of Mexican Americans. Poor glycemic control (HbA(1c) >8%) was more common in non-Hispanic black women (50%) and Mexican-American men (45%) compared with the other groups (35-38%),but HbA(1c) for both sexes and for all racial and ethnic groups was substantially higher than normal levels. Those with HbA(1c) >8% included 52% of insulin-treated patients and 42% of those taking oral agents. There was no relationship of glycemic control to socioeconomic status or access to medical care in any racial or ethnic group. CONCLUSIONS - These data indicate that many patients with ripe 2 diabetes in the U.S. have poor glycemic control, placing them at high risk of diabetic complications. Non-Hispanic black women, Mexican-American men, and patients treated with insulin and oral agents were disproportionately represented among those in poor glycemic control. Clinical, public health, and research efforts should focus on more effective methods to control blood glucose in patients with diabetes. C1 NIDDKD, Bethesda, MD 20892 USA. Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. RP Harris, MI (reprint author), NIDDK, NIH, Bldg 45,Room 5AN24, Bethesda, MD 20892 USA. RI Flegal, Katherine/A-4608-2013; OI Flegal, Katherine/0000-0002-0838-469X NR 19 TC 443 Z9 452 U1 2 U2 9 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAR PY 1999 VL 22 IS 3 BP 403 EP 408 DI 10.2337/diacare.22.3.403 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 170LD UT WOS:000078806400006 PM 10097918 ER PT J AU Weyer, C Gautier, JF Danforth, E AF Weyer, C Gautier, JF Danforth, E TI Development of beta(3)-adrenoceptor agonists for the treatment of obesity and diabetes - An update SO DIABETES & METABOLISM LA English DT Review DE beta 3 adrenoreceptor; beta 3 adrenoreceptor agonist; brown adipose tissue; obesity; type 2 diabetes; treatment ID BETA-ADRENOCEPTOR AGONIST; BROWN ADIPOSE-TISSUE; ADRENERGIC-RECEPTORS; SKELETAL-MUSCLE; BETA-3-ADRENERGIC RECEPTOR; UNCOUPLING PROTEIN-3; ENERGY-EXPENDITURE; METABOLIC-RATE; BODY-WEIGHT; MICE AB Beta(3)-adrenoceptor (beta(3)-AR) agonists were found to have remarkable anti-obesity and anti-diabetic effects in rodents shortly after their discovery in the early 1980s. Despite these promising qualities, several pharmaceutical problems and theoretical concerns have slowed the development of these products as therapeutic agents in humans during the last 15 years. To date, the pharmaceutical industry has not been successful in developing a beta(3)-AR agonist for use in the treatment of human obesity and type 2 diabetes. Pharmaceutical problems in this area concern important differences between rodent and human beta(3)-AR and the difficulty in finding a compound with sufficient bioavailability that is a highly selective and full agonist at the human receptor. Some of these problems seem to have been solved with the cloning of the human beta(3)-AR, which has made it possible to develop novel compounds directly and specifically against the human receptor. However, several theoretical concerns still remain. These include the major question as to whether the number of biologically active beta(3)-ARs in adult humans is sufficient to produce relevant metabolic effects and, if so, whether their long-term stimulation is safe a nd free of unwarranted side effects. In addition, the mechanisms of action of beta(3)-AR agonists remain poorly understood. Recent studies using CL 316,243, a highly selective beta(3)-adrenergic compound, have provided new insights into the potential mechanisms of action of these drugs in rodents as well as the first evidence that treatment with a highly selective beta(3)-AR agonist exerts relevant metabolic effects in humans. It appears that chronic beta(3)-adrenergic stimulation in white adipose tissue increases the expression of newly discovered mitochondrial uncoupling proteins (UCP 2 and 3) and a "reawakening" of dormant brown adipocytes. In addition, beta(3)-ARs may be present in skeletal muscle where ectopic expression of UCP-1 has been reported. If these findings are confirmed, tissues other than brown fat may play an important role in mediating beta(3)-adrenergic effects on thermogenesis and substrate oxidation. In humans, treatment with CL 316,243 for 8 weeks, in spite of limited bioavailability, induced marked plasma concentration-dependent increases in insulin sensitivity, lipolysis, and fat oxidation in lean volunteers, without causing beta(1)-, or beta(2)-mediated side effects. These results clearly indicate that favourable metabolic effects can be achieved by selective beta(3)-AR stimulation in humans. The compounds of the next generation currently emerging from preclinical development are full agonists at the human beta(3)-AR. These agents have demonstrated promising results in non-human primates. It will be interesting to see whether their efficacy in clinical trials is superior to that achieved with previous (rodent) beta(3)-AR agonists and, if so, whether their effects will eventually translate into weight loss and improved metabolic control that could facilitate their use as effective drugs for the treatment of obesity and Type 2 diabetes in humans. C1 NIH, Clin Diabet & Nutr Sect, Phoenix, AZ 85016 USA. Univ Vermont, NIDDKD, Burlington, VT 05405 USA. RP Weyer, C (reprint author), NIH, Clin Diabet & Nutr Sect, 4212 N 16th St,Rm 5-41, Phoenix, AZ 85016 USA. EM cweyer@phx.niddh.nih.gov NR 94 TC 91 Z9 92 U1 0 U2 6 PU MASSON EDITEUR PI MOULINEAUX CEDEX 9 PA 21 STREET CAMILLE DESMOULINS, ISSY, 92789 MOULINEAUX CEDEX 9, FRANCE SN 1262-3636 J9 DIABETES METAB JI Diabetes Metab. PD MAR PY 1999 VL 25 IS 1 BP 11 EP 21 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 184XC UT WOS:000079638200002 PM 10335419 ER PT J AU Simsir, A Fetsch, P Mehta, D Zakowski, M Abati, A AF Simsir, A Fetsch, P Mehta, D Zakowski, M Abati, A TI E-cadherin, N-cadherin, and calretinin in pleural effusions: The good, the bad, the worthless SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Article DE E-cadherin; N-cadherin; calretinin; effusion; immunocytochemistry ID MALIGNANT MESOTHELIOMA; SEROUS EFFUSIONS; EXTRAPULMONARY MALIGNANCIES; DIFFERENTIAL EXPRESSION; LUNG ADENOCARCINOMAS; GASTRIC CARCINOMAS; SELECTIVE MARKER; EPITHELIAL-TYPE; HUMAN CANCERS; CELLS AB The distinction between reactive mesothelial cells (RMC), malignant mesothelioma (MM), and metastatic adenocarcinoma (ACA) in pleural effusions may be impossible based on morphology alone, E-cadherin, N-cadherin, and calretinin ai-e newly described immunocytochemical markers, which can potentially be utilised for facilitating this distinction. E-cadherin and N-cadherin ai-e calcium-dependent intercellular adhesion molecules expressed in epithelial cells and mesenchymal/mesothelial cells, respectively The differential expression of E-cadherins in epithelial cells and N-cadherins in mesothelial cells has been utilized to differentiate reactive mesothelial cells, MMs and ACAs. Calretinin is a calcium-binding protein within the family of EF-hand proteins. It is abundantly expressed in peripheral and central nervous tissues, and has been shown to consistently immunoreact with mesothelial cells, We studied cell block sections from 77 pleural effusions (22 RMC, 26 MM, and 29 ACA) to investigate the potential immunocytochemical, use use of anti-E-cadherin?, anti-N-cadherin and anti-calretinin antibodies for differentiating between RMC, MM, and ACA in pleural effusions. A modified avidin-biotin peroxidase complex (ABC) method was used E-cadherin immunostaining was observed in 14% of RMC, 46% of MMs, and 97% of ACAs. A distinct membrane staining pattern was seen in ACAs. The pattern of staining was cytoplasmic in all reactive RMC and varied from membrane to cytoplasmic in MMs. Anti-N-cadherin immunoreacted with 77% of RMC, 35% of MMs, and 48% of ACAs, Twenty-seven percent of RMC, 58% of MMs, and 31% of ACAs immunoreacted with anti-calretinin. Based on these results, rye conclude that anti-E-cadherin is a potentially useful marker in the distinction of ACA cells om RMC. However it is nor as useful for rite distinction of ACA and MM. Anti-N-cadherin and anti-calretinin did not reliably distinguish between reactive mesothelial, MM, and ACA cells in pleural effusions. Published 1999 Wiley-Liss, Inc.(dagger). C1 NCI, Cytopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Abati, A (reprint author), NCI, Cytopathol Sect, Pathol Lab, NIH, Bldg 10,Room 2A19,10 Ctr Dr MSC 1500, Bethesda, MD 20892 USA. NR 27 TC 67 Z9 69 U1 3 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 8755-1039 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD MAR PY 1999 VL 20 IS 3 BP 125 EP 130 DI 10.1002/(SICI)1097-0339(199903)20:3<125::AID-DC3>3.0.CO;2-V PG 6 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 172DN UT WOS:000078908100003 PM 10086235 ER PT J AU Lei, XD Kaufman, S AF Lei, XD Kaufman, S TI Characterization of expression of the gene for human pterin carbinolamine dehydratase/dimerization cofactor of HNF1 SO DNA AND CELL BIOLOGY LA English DT Article ID HYDROXYLASE-STIMULATING PROTEIN; AMINO-ACID HYDROXYLASES; GTP-CYCLOHYDROLASE-I; PHENYLALANINE-HYDROXYLASE; 4A-CARBINOLAMINE DEHYDRATASE; 7-SUBSTITUTED PTERINS; TRANSCRIPTION; RAT; LIVER; 7-TETRAHYDROBIOPTERIN AB Pterin carbinolamine dehydratase/dimerization cofactor of HNF1 (PCD/DCoH) is a dual-function protein, In the cytoplasm it acts as a dehydratase in the regeneration of tetrahydrobiopterin, the cofactor for aromatic amino acid hydroxylases, In the nucleus, it functions as a dimerization cofactor of HNF1 and increases the transcriptional activity of HNF1, To deepen our understanding of this protein, we characterized its expression in human tissues and cells. Human PCD/DCoH was present predominantly in liver and kidney, with significant amounts in testis and ovary, trace amounts in lung, and undetectable levels in whole brain, heart, and spleen, It was expressed in all of the cells that were examined, Importantly, it was also present in the nucleus of HeLa cells, which lack HNF1, and in the cytoplasm of fibroblasts that have little or no tetrahydrobiopterin, The expression of human PCD/DCoH in the liver and nonhepatic cells was compared at both the mRNA and protein levels. Although the mRNA level in liver was only fourfold higher than that in keratinocytes and fibroblasts, the hepatic PCD/DCoH protein level was 20-fold higher than that in normal human epidermal keratinocytes and dermal fibroblasts, Cloning of the 5' and 3' untranslated region (UTR) of human keratinocyte PCD/DCoH revealed that it has 53 bp more of GC-rich 5' untranslated sequence than the published liver PCD/DCoH, In vitro transcription and translation analysis showed that the longer 5' UTR resulted in about a 35% decrease in translation efficiency, These data show that human PCD/DCoH is not only present in cells where tetrahydrobiopterin is synthesized or HNF1 is present but is a widely distributed protein, Its differential expression in different tissues and cells is regulated not only at the transcriptional level but also at the translational level. C1 NIMH, Neurochem Lab, Bethesda, MD 20892 USA. RP Kaufman, S (reprint author), NIMH, Neurochem Lab, Bldg 36,Room 3D-30, Bethesda, MD 20892 USA. NR 33 TC 7 Z9 8 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD MAR PY 1999 VL 18 IS 3 BP 243 EP 252 DI 10.1089/104454999315466 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA 178NJ UT WOS:000079272300007 PM 10098606 ER PT J AU Teipel, SJ Hampel, H Pietrini, P Moller, HJ Rapoport, SI AF Teipel, SJ Hampel, H Pietrini, P Moller, HJ Rapoport, SI TI PET in Alzheimer's disease - From resting-state to activation studies SO DRUG NEWS & PERSPECTIVES LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL BLOOD-FLOW; GLUCOSE-METABOLISM; BEHAVIORAL ACTIVATION; COGNITIVE IMPAIRMENT; VISUAL-STIMULATION; NETWORK ANALYSIS; HIGH-RESOLUTION; STRIATE CORTEX; HUMAN-BRAIN AB Alzheimer's disease (AD) is a neurodegenerative process associated with aging. Due to the relative increase in the elderly population in industrialized countries, AD has evolved to a significant challenge for Western societies with regard to socioeconomic resources, clinical and family care and research capacities. Much progress has been made over the last years using neuroimaging methods to better understand brain structure and function in healthy aging and in AD. This article describes the influence of positron emission tomography (PET) studies on the paradigm shift towards a more functionally oriented view of the disease. Special emphasis is put on the contribution of PET to our knowledge of AD pathophysiology and on its use in clinical differential diagnosis. We examine new analysis techniques that have been implemented in recent years to interpret PET data, including discriminant and path analysis, as well as neural network modeling. In addition, we review activation paradigms that have been used in AD-PET studies since 1987. We summarize evidence about altered cognitive processing in AD derived from PET studies during subject stimulation that supports the maintenance of neuronal plasticity in early AD. We further review the differential diagnostic power of PET. In conclusion, we outline present use and future perspectives of activation PET for clinical trials in which drug efficacy in AD can be predicted and monitored. (C) 1999 Prous Science. All rights reserved. C1 Univ Munich, Alzheimers Res Grp, Geriatr Res Branch, Dept Psychiat, D-80336 Munich, Germany. NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. NR 73 TC 2 Z9 2 U1 0 U2 0 PU PROUS SCIENCE, SA PI BARCELONA PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0214-0934 J9 DRUG NEWS PERSPECT JI Drug News Perspect. PD MAR PY 1999 VL 12 IS 2 BP 83 EP 90 DI 10.1358/dnp.1999.12.2.863623 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 188LG UT WOS:000079848000004 ER PT J AU Yarmola, E Chrambach, A Nguyen, VQ Yergey, AL AF Yarmola, E Chrambach, A Nguyen, VQ Yergey, AL TI Mass spectrometric analysis of the electroeluates of fluorescent proteins after preparative electrophoresis in the automated HPGE-1000 apparatus SO ELECTROPHORESIS LA English DT Article DE mass spectrometry; fluorescent proteins; electroeluates; automated gel electrophoresis with periodic fluorescence scanning apparatus ID SUBCELLULAR-SIZED PARTICLES; GEL-ELECTROPHORESIS; POLYMER-SOLUTION; SDS-PROTEIN; SEPARATION; RECOVERY; DNA AB Bands of green fluorescent protein (GFP) and R-phycoerythrin (PHYCO) in gel electrophoresis on the automated apparatus for gel electrophoresis with periodic fluorescence scanning (HPGE), the HPGE-1000 apparatus, were retrieved from the gel by electroelution. While PHYCO was recovered in a single volume of electroeluate buffer after the predicted migration time, GFP fluorescence was lost under the same conditions and could only be recovered using multiple changes or electroeluate buffer. The multiple volumes of buffer necessitated pooling, concentration, and storage, conditions under which a minor GFP component, GFP-II, formed artifactually. PHYCO after electroelution also exhibits a minor component present in the original preparation. The electroeluate of GFP, transferred into a mass spectrometer after pooling, concentration and storage, is indistinguishable in mass from the original preparation. C1 NICHD, Macromol Anal Sect, Lab Cellular & Mol Biphys, NIH, Bethesda, MD 20892 USA. Russian Acad Sci, Lab Biopolymer Phys, Engelhardt Inst Mol Biol, Moscow, Russia. NICHD, Sect Mass Spectrometry & Metab, Lab Cellular & Mol Biophys, NIH, Bethesda, MD USA. RP Chrambach, A (reprint author), NICHD, Macromol Anal Sect, Lab Cellular & Mol Biphys, NIH, Bldg 10,Room 9D50, Bethesda, MD 20892 USA. EM acc@cu.nih.gov NR 18 TC 4 Z9 5 U1 0 U2 2 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD MAR PY 1999 VL 20 IS 3 BP 445 EP 451 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 183FZ UT WOS:000079544700003 PM 10217150 ER PT J AU Yang, X Letterio, JJ Lechleider, RJ Chen, L Hayman, R Gu, H Roberts, AB Deng, CX AF Yang, X Letterio, JJ Lechleider, RJ Chen, L Hayman, R Gu, H Roberts, AB Deng, CX TI Targeted disruption of SMAD3 results in impaired mucosal immunity and diminished T cell responsiveness to TGF-beta SO EMBO JOURNAL LA English DT Article DE bacterial infections; gene targeting; inflammation; SMAD3; TGF-beta signaling ID GROWTH-FACTOR-BETA; MAD-RELATED PROTEIN; ORAL TOLERIZATION; TUMOR-SUPPRESSOR; RECEPTOR; CHEMOTAXIS; PHOSPHORYLATION; NEUTROPHIL; RESPONSES; PATHWAY AB SMAD3 is one of the intracellular mediators that transduces signals from transforming growth factor-beta (TGF-beta) and activin receptors. We show that SMAD3 mutant mice generated by gene targeting die between 1 and 8 months due to a primary defect in immune function. Symptomatic mice exhibit thymic involution, enlarged lymph nodes, and formation of bacterial abscesses adjacent to mucosal surfaces. Mutant T cells exhibit an activated phenotype in vivo, and are not inhibited by TGF-beta 1 in vitro. Mutant neutrophils are also impaired in their chemotactic response toward TGF-beta, Chronic intestinal inflammation is infrequently associated with colonic adenocarcinoma in mice older than 6 months of age. These data suggest that SMAD3 has an important role in TGF-beta-mediated regulation of T cell activation and mucosal immunity, and that the loss of these functions is responsible for chronic infection and the lethality of Smad3-null mice. C1 NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Inst Biotechnol, Beijing 100071, Peoples R China. RP Deng, CX (reprint author), NIDDK, Genet Dev & Dis Branch, NIH, 10-9N105, Bethesda, MD 20892 USA. EM chuxiad@bdg10.niddk.nih.gov RI deng, chuxia/N-6713-2016 NR 61 TC 610 Z9 659 U1 0 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD MAR 1 PY 1999 VL 18 IS 5 BP 1280 EP 1291 DI 10.1093/emboj/18.5.1280 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 177AH UT WOS:000079184600018 PM 10064594 ER PT J AU Shao, RG Cao, CX Zhang, HL Kohn, KW Wold, MS Pommier, Y AF Shao, RG Cao, CX Zhang, HL Kohn, KW Wold, MS Pommier, Y TI Replication-mediated DNA damage by camptothecin induces phosphorylation of RPA by DNA-dependent protein kinase and dissociates RPA : DNA-PK complexes SO EMBO JOURNAL LA English DT Article DE camptothecin; DNA damage; DNA-dependent protein kinase; RPA2 phosphorylation ID SINGLE-STRANDED-DNA; S-PHASE CHECKPOINT; RADIATION-INDUCED PHOSPHORYLATION; SIMIAN VIRUS-40 DNA; ATAXIA-TELANGIECTASIA; BINDING PROTEIN; TOPOISOMERASE-I; CELL-LINES; SACCHAROMYCES-CEREVISIAE; CLEAVABLE COMPLEXES AB Replication protein A (RPA) is a DNA single-strand binding protein essential for DNA replication, recombination and repair. In human cells treated with the topoisomerase inhibitors camptothecin or etoposide (VP-16), we find that RPA2, the middle-sized subunit of RPA, becomes rapidly phosphorylated, This response appears to be due to DNA-dependent protein kinase (DNA-PK) and to be independent of p53 or the ataxia telangiectasia mutated (ATM) protein. RPA2 phosphorylation in response to camptothecin required ongoing DNA replication. Camptothecin itself partially inhibited DNA synthesis, and this inhibition followed the same kinetics as DNA-PK activation and RPA2 phosphorylation, DNA-PK activation and RPA2 phosphorylation were prevented by the cell-cycle checkpoint abrogator 7-hydroxystaurosporine (UCN-01), which markedly potentiates camptothecin cytotoxicity. The DNA-PK catalytic subunit (DNA-PKcs) was found to bind RPA which was replaced by the Ku autoantigen upon camptothecin treatment. DNA-PKcs interacted directly with RPA1 in vitro. We propose that the encounter of a replication fork with a topoisomerase-DNA cleavage complex could lead to a juxtaposition of replication fork-associated RPA and DNA double-strand end-associated DNA-PK, leading to RPA2 phosphorylation which may signal the presence of DNA damage to an S-phase checkpoint mechanism. C1 NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Univ Iowa, Dept Biochem, Iowa City, IA 52242 USA. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. EM pommier@nih.gov RI Wold, Marc/F-5806-2010 NR 54 TC 258 Z9 259 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD MAR 1 PY 1999 VL 18 IS 5 BP 1397 EP 1406 DI 10.1093/emboj/18.5.1397 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 177AH UT WOS:000079184600029 PM 10064605 ER PT J AU Facklam, R Beall, B Efstratiou, A Fischetti, V Johnson, D Kaplan, E Kriz, P Lovgren, M Martin, D Schwartz, B Totolian, A Bressen, D Hollingshead, S Rubin, F Scott, J Tyrrell, G AF Facklam, R Beall, B Efstratiou, A Fischetti, V Johnson, D Kaplan, E Kriz, P Lovgren, M Martin, D Schwartz, B Totolian, A Bressen, D Hollingshead, S Rubin, F Scott, J Tyrrell, G TI emm typing and validation of provisional M types for group A streptococci SO EMERGING INFECTIOUS DISEASES LA English DT Article ID GROUP-A STREPTOCOCCI; GENE-SEQUENCES; PYOGENES; DIVERSITY; PROTEINS AB This report discusses the following issues related to typing of group A streptococci (GAS): The development and use of the 5' emm variable region sequencing (emm typing) in relation to the existing serologic typing system; the designation of emm types in relation to M types; a system for validation of new emm types; criteria for validation of provisional M types to new M-types; a list of reference type cultures for each of the M-type or emm-type strains of GAS; the results of the first culture exchange program for a quality control testing system among the national and World Health Organization collaborating centers for streptococci; and dissemination of new approaches to typing of GAS to the international streptococcal community. C1 Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. Cent Publ Hlth Lab, London NW9 5HT, England. Rockefeller Univ, New York, NY 10021 USA. Univ Minnesota, Minneapolis, MN USA. Natl Publ Hlth Inst, Prague, Czech Republic. Natl Ctr Streptococcus, Edmonton, AB, Canada. ESR, Communicable Dis Grp, Porirua, New Zealand. Russian Acad Med Sci, Inst Expt Med, St Petersburg P 22, Russia. Yale Univ, New Haven, CT USA. Univ Alabama, Birmingham, AL USA. NIH, Bethesda, MD 20892 USA. Emory Univ, Atlanta, GA 30322 USA. RP Facklam, R (reprint author), Ctr Dis Control & Prevent, 1600 Clifton Rd,Mail Stop C02, Atlanta, GA 30333 USA. RI Totolian, Artem/J-4218-2014; Krizova, Pavla/M-6120-2015 OI Totolian, Artem/0000-0002-3310-9294; NR 19 TC 121 Z9 124 U1 0 U2 7 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD MAR-APR PY 1999 VL 5 IS 2 BP 247 EP 253 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 186NH UT WOS:000079735500009 PM 10221877 ER PT J AU Nieman, LK AF Nieman, LK TI The evaluation of ACTH-dependent Cushing's syndrome SO ENDOCRINOLOGIST LA English DT Review ID DIFFERENTIAL-DIAGNOSIS; HORMONE; METYRAPONE; OVERNIGHT; TESTS AB The causes of endogenous Cushing's syndrome include primary excess ACTH production (ACTH-dependent forms) and primary adrenal cortisol production. Because hypercortisolism suppresses normal ACTH secretion, ACTH levels are low in the primary adrenal forms and are normal or increased in patients with ACTH-dependent Cushing's syndrome. Excess ACTH production by a pituitary corticotrope tumor, termed Cushing's disease, is more common (80%) than nonpituitary, or "ectopic", ACTH secretion (20%). Most patients with ectopic ACTH secretion cannot be differentiated clinically from those with Cushing's disease, so biochemical tests must be used. Inferior petrosal sinus sampling can identify a pituitary source of ACTH because of the increase in petrosal ACTH concentration compared with peripheral blood. This test has near 100% diagnostic accuracy, but it is costly and invasive. The corticotropin-releasing hormone stimulation test and overnight 8 mg dexamethasone suppression test lack these drawbacks, but they have less sensitivity for Cushing's disease (93% and 71%, respectively) when cutpoints that exclude all patients with ectopic ACTH secretion are used. MRI of the pituitary gland reveals a tumor in about 50% of patients with Cushing's disease; conversely, imaging of the chest and abdomen is essential for localizing tumors producing ACTH ectopically. C1 NICHHD, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Nieman, LK (reprint author), Bldg 10,Room 9S261 MSC 1834,10 Ctr Dr, Bethesda, MD 20892 USA. NR 15 TC 2 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-2144 J9 ENDOCRINOLOGIST JI Endocrinologist PD MAR-APR PY 1999 VL 9 IS 2 BP 93 EP 98 DI 10.1097/00019616-199903000-00005 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 183UK UT WOS:000079571800005 ER PT J AU Montrose-Rafizadeh, C Avdonin, P Garant, MJ Rodgers, BD Kole, S Yang, H Levine, MA Schwindinger, W Bernier, M AF Montrose-Rafizadeh, C Avdonin, P Garant, MJ Rodgers, BD Kole, S Yang, H Levine, MA Schwindinger, W Bernier, M TI Pancreatic glucagon-like peptide-1 receptor couples to multiple G proteins and activates mitogen-activated protein kinase pathways in Chinese hamster ovary cells SO ENDOCRINOLOGY LA English DT Article ID BETA-GAMMA-SUBUNITS; GASTRIC-INHIBITORY POLYPEPTIDE; PROINSULIN GENE-EXPRESSION; HETEROTRIMERIC G-PROTEINS; MAP KINASE; SIGNAL-TRANSDUCTION; INSULIN-SECRETION; PHOSPHOLIPASE-C; 3T3-L1 ADIPOCYTES; RIN-1046-38 CELLS AB Chinese hamster ovary (CHO) cells stably expressing the human insulin receptor and the rat glucagon-like peptide-1 (GLP-1) receptor (CHO/GLPR) were used to study the functional coupling of the GLP-1 receptor with G proteins and to examine the regulation of the mitogen-activated protein (MAP) kinase signaling pathway by GLP-1. We showed that ligand activation of GLP-1 receptor led to increased incorporation of GTP-azidoanilide into G(s)alpha, G(q/11)alpha, and G(i1.2)alpha, but not G(i3)alpha. GLP-1 increased p38 MAP kinase activity 2.5- and 2.0-fold over the basal level in both CHO/GLPR cells and rat insulinoma cells (RIN 1046-38), respectively. Moreover, GLP-1 induced phosphorylation of the immediate upstream kinases of p38, MKK3/MKK6, in CHO/GLPR and RIN 1046-38 cells. Ligand-stimulated GLP-1 receptor produced 1.45- and 2.7-fold increases in tyrosine phosphorylation of 42-kDa extracellular signal-regulated kinase (ERK) in CHO/GLPR and RIN 1046-38 cells, respectively. In CHO/GLPR cells, these effects of GLP-1 on the ERK and p38 MAP kinase pathways were inhibited by pretreatment with cholera toxin (CTX), but not with pertussis toxin. The combination of insulin and GLP-1 resulted in an additive response (1.6-fold over insulin alone) that was attenuated by CTX. In contrast, the ability of insulin alone to activate these pathways was insensitive to either toxin. Our study indicates a direct coupling between the GLP-1 receptor and several G proteins, and that CTX-sensitive proteins are required for GLP-1-mediated activation of MAP kinases. C1 NIA, Clin Invest Lab, NIH, Baltimore, MD 21224 USA. Russian Acad Sci, Inst Dev Biol, Moscow, Russia. Johns Hopkins Univ, Dept Med, Baltimore, MD 21205 USA. RP Montrose-Rafizadeh, C (reprint author), Eli Lilly & Co, Lilly Corp Ctr, Drop Code 1543, Indianapolis, IN 46285 USA. EM montrose@lilly.com OI Bernier, Michel/0000-0002-5948-368X; Levine, Michael/0000-0003-0036-7809 NR 61 TC 119 Z9 123 U1 2 U2 4 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 1999 VL 140 IS 3 BP 1132 EP 1140 DI 10.1210/en.140.3.1132 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 169EC UT WOS:000078733700016 PM 10067836 ER PT J AU Fantin, VR Lavan, BE Wang, Q Jenkins, NA Gilbert, DJ Copeland, NG Keller, SR Lienhard, GE AF Fantin, VR Lavan, BE Wang, Q Jenkins, NA Gilbert, DJ Copeland, NG Keller, SR Lienhard, GE TI Cloning, tissue expression, and chromosomal location of the mouse insulin receptor substrate 4 gene SO ENDOCRINOLOGY LA English DT Article ID SIGNAL-TRANSDUCTION; PHOSPHOTYROSINE PROTEIN; CYTOKINE ACTION; IRS-1; MICE; FAMILY; LOCALIZATION; ADIPOCYTES; DISRUPTION; RESISTANCE AB The insulin receptor substrates (IRSs) are key proteins in signal transduction from the insulin receptor. Recently, we discovered a fourth member of this family, designated IRS-4, cloned its complementary DNA from the human embryonic kidney 293 cell Line, and characterized its signaling properties in this cell line. As part of an investigation of the physiological role of this IRS, we have now cloned the mouse IRS-4 gene and determined its tissue expression and chromosomal location. The coding region of the mouse IRS-4 gene contains no introns, and in this regard is the same as that of the genes for IRS-1 and -2. The predicted amino acid sequence of mouse IRS-I is highly homologous with that of human IRS-4; the pleckstrin homology domain, the phosphotyrosine-binding domain, and the tyrosine phosphorylation motifs are especially well conserved. The tissue distribution of IRS-4 in the mouse was determined by analysis for the expression of its messenger RNA by RT-PCR and for the protein itself by immunoprecipitation and immunoblotting. The messenger RNA was detected in skeletal muscle, brain, heart, kidney, and liver, but the protein itself was not detected in any tissue. These results indicate that IRS-4 is a very rare protein. The chromosomal locations of the mouse IRS-4 and IRS-3 genes were determined by interspecific backcross analysis and were found to be on chromosomes X and 5, respectively. As the mouse genes for IRS-1 and -2 are on chromosomes 1 and 8, respectively, each IRS gene resides on a different chromosome. C1 Dartmouth Coll, Sch Med, Dept Biochem, Hanover, NH 03755 USA. NCI, Mammalian Genet Lab, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Lienhard, GE (reprint author), Dartmouth Coll, Sch Med, Dept Biochem, Vail Bldg, Hanover, NH 03755 USA. EM gustav.e.lienhard@dartmouth.edu FU NIDDK NIH HHS [DK-42816] NR 32 TC 51 Z9 54 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD MAR PY 1999 VL 140 IS 3 BP 1329 EP 1337 DI 10.1210/en.140.3.1329 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 169EC UT WOS:000078733700040 PM 10067860 ER PT J AU Smith, RD Baukal, AJ Dent, P Catt, KJ AF Smith, RD Baukal, AJ Dent, P Catt, KJ TI Raf-1 kinase activation by angiotensin II in adrenal glomerulosa cells: Roles of G(i), phosphatidylinositol 3-kinase, and Ca2+ influx SO ENDOCRINOLOGY LA English DT Article ID SMOOTH-MUSCLE-CELLS; PROTEIN-COUPLED RECEPTORS; BETA-GAMMA-SUBUNITS; CARDIAC MYOCYTES; TYROSINE-KINASE; MEDIATED ACTIVATION; SIGNALING PATHWAY; RAS; P21(RAS); HYPERTROPHY AB Little is known of the mechanisms leading to mitogen-activated protein kinase (MAPK) activation via G(q)-coupled receptors. We therefore examined the pathways by which angiotensin II(Ang II) activates Raf-1 kinase, an upstream intermediate in the pathway to MAPK, via the G-coupled AT(1) angiotensin receptor in bovine adrenal glomerulosa (BAG) cells. Ang II caused a rapid and transient activation of Raf-1 that reached a peak at 5-10 min. Ang II was a potent stimulus of Raf-1 activation with an ED50 of 10 piu and a maximal response at 1 nM, although higher Ang II concentrations elicited a submaximal response. Ang II-stimulated Raf-1 activity was unaffected by down-regulation of protein kinase C and intracellular Ca2+ chelation (using BAPTA) but was partially inhibited by pertussis toxin, and was abolished by manumycin A. Removal of extracellular Ca2+ (by EGTA) or blockade oft type Ca2+ channels (by nifedipine), as well as inhibition of MEK-1 kinase (by PD98059), enhanced Raf-1 activity, whereas wortmannin (100 nM) inhibited approximately one half of Ang II-stimulated Raf-1 activity. Hence, Raf-1 kinase activation by Ang II in BAG cells is dependent on Ras, is mediated in part via G(i) and phosphatidylinositol 3-kinase, and is negatively regulated via Ca2+ influx and a downstream signaling element(s). C1 NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. Virginia Commonwealth Univ, Mol Radiol Sect, Richmond, VA 23298 USA. RP Catt, KJ (reprint author), NICHD, ERRB, NIH, Bldg 49,Room 6A-36,49 Convent Dr, Bethesda, MD 20892 USA. EM catt@helix.nih.gov FU NIDDK NIH HHS [R-01-DK-52825] NR 39 TC 40 Z9 40 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD MAR PY 1999 VL 140 IS 3 BP 1385 EP 1391 DI 10.1210/en.140.3.1385 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 169EC UT WOS:000078733700047 PM 10067866 ER PT J AU Krsmanovic, LZ Martinez-Fuentes, AJ Arora, KK Mores, N Navarro, CE Chen, HC Stojilkovic, SS Catt, KJ AF Krsmanovic, LZ Martinez-Fuentes, AJ Arora, KK Mores, N Navarro, CE Chen, HC Stojilkovic, SS Catt, KJ TI Autocrine regulation of gonadotropin-releasing hormone secretion in cultured hypothalamic neurons SO ENDOCRINOLOGY LA English DT Article ID RAT ESTROUS-CYCLE; GNRH NEURONS; NEUROPEPTIDE RELEASE; RHESUS-MONKEY; LOOP FEEDBACK; RECEPTORS; LHRH; ACTIVATION; NEUROSECRETION; CASTRATION AB Episodic hormone secretion is a characteristic feature of the hypothalamo-pituitary-gonadal system, in which the profile of gonadotropin release from pituitary gonadotrophs reflects the pulsatile secretory activity of GnRH-producing neurons in the hypothalamus. Pulsatile release of GnRH is also evident in vitro during perifusion of immortalized GnRH neurons (GT1-7 cells) and cultured fetal hypothalamic cells, which continue to produce bioactive GnRH for up to 2 months. Such cultures, as well as hypothalamic tissue from adult rats, express GnRH receptors as evidenced by the presence of high-affinity GnRH binding sites and GnRH receptor transcripts. Furthermore, individual GnRH neurons coexpress GnRH and GnRH receptors as revealed by double immunostaining of hypothalamic cultures. In static cultures of hypothalamic neurons and GT1-7 cells, treatment with the GnRH receptor antagonist, [D-pGlu(1), D-Phe(2), D-Trp(3,6)]GnRH caused a prominent increase in GnRH release. In perifused hypothalamic cells and GT1-7 cells, treatment with the GnRH receptor agonist, des-Gly(10)-[D-Ala(6)] GnRH N-ethylamide, reduced the frequency and increased the amplitude of pulsatile GnRH release, as previously observed in GT1-7 cells. In contrast, exposure to the GnRH antagonist analogs abolished pulsatile secretion and caused a sustained and progressive increase in GnRH release. These findings have demonstrated that GnRH receptors are expressed in hypothalamic GnRH neurons, and that receptor activation is required for pulsatile GnRH release in vitro. The effects of GnRH agonist and antagonist analogs on neuropeptide release are consistent with the operation of an ultrashort-loop autocrine feedback mechanism that exerts both positive and negative actions that are necessary for the integrated control of GnRH secretion from the hypothalamus. C1 NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Catt, KJ (reprint author), NICHD, Endocrinol & Reprod Res Branch, NIH, Bldg 49,Room 6A-336, Bethesda, MD 20892 USA. EM catt@helix.nih.gov OI MORES, Nadia/0000-0002-4197-0914 NR 51 TC 90 Z9 91 U1 0 U2 2 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 1999 VL 140 IS 3 BP 1423 EP 1431 DI 10.1210/en.140.3.1423 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 169EC UT WOS:000078733700052 PM 10067871 ER PT J AU Wagner, BL Pollio, G Giangrande, P Webster, JC Breslin, M Mais, DE Cook, CE Vedeckis, WV Cidlowski, JA McDonnell, DP AF Wagner, BL Pollio, G Giangrande, P Webster, JC Breslin, M Mais, DE Cook, CE Vedeckis, WV Cidlowski, JA McDonnell, DP TI The novel progesterone receptor antagonists RTI 3021-012 and RTI 3021-022 exhibit complex glucocorticoid receptor antagonist activities: Implications for the development of dissociated antiprogestins SO ENDOCRINOLOGY LA English DT Article ID STEROID-HORMONE RECEPTORS; BREAST-CANCER; HISTONE DEACETYLASE; N-COR; TRANSCRIPTIONAL REPRESSION; RESPONSE ELEMENTS; AGONIST ACTIVITY; CELL; SMRT; RU486 AB We have identified two novel compounds (RTI 3021-012 and RTI 3021-022) that demonstrate similar affinities for human progesterone receptor (PR) and display equivalent antiprogestenic activity. As with most antiprogestins, such as RU486, RTI 3021-012, and RTI 3021-022 also bind to the glucocorticoid receptor (GR) with high affinity. Unexpectedly, when compared with RU486, the RTI antagonists manifest significantly less GR antagonist activity. This finding indicates that, with respect to antiglucocorticoid function, receptor binding affinity is not a good predictor of biological activity. We have determined that the lack of a clear correlation between the GR binding affinity of the RTI compounds and their antagonist activity reflects the unique manner in which they modulate GR signaling. Previously, we proposed a two step "active inhibition" model to explain steroid receptor antagonism: 1) competitive inhibition of agonist binding; and 2) competition of the antagonist bound receptor with that activated by agonists for DNA response elements within target gene promoters. Accordingly, we observed that RU486, RTI 3021-012, and RTI 302-1022, when assayed for PR antagonist activity, accomplished both of these steps. Thus, all three compounds are "active antagonists" of PR function. When assayed on GR, however, RU486 alone functioned as an active antagonist. RTI 3021-012 and RTI 3021-022, on the other hand, functioned solely as "competitive antagonists" since they were capable of high affinity GR binding, but the resulting ligand receptor complex was unable to bind DNA. These results have important pharmaceutical implications supporting the use of mechanism based approaches to identify nuclear receptor modulators. Of equal importance, RTI 3021-012 and RTI 3021-022 are two new antiprogestins that may have clinical utility and are likely to be useful as research reagents with which to separate the effects of antiprogestins and antiglucocorticoids in physiological systems. C1 Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. NIEHS, Mol Endocrinol Grp, NIH, Res Triangle Pk, NC 27709 USA. Louisiana State Univ, Sch Med, Dept Biochem & Mol Biol, New Orleans, LA 70112 USA. Ligand Pharmaceut Inc, San Diego, CA 92121 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. RP McDonnell, DP (reprint author), Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Box 3813, Durham, NC 27710 USA. EM McDon016@acpub.duke.edu NR 41 TC 59 Z9 60 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 1999 VL 140 IS 3 BP 1449 EP 1458 DI 10.1210/en.140.3.1449 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 169EC UT WOS:000078733700055 PM 10067874 ER PT J AU Curtis, KM Savitz, DA Weinberg, CR Arbuckle, TE AF Curtis, KM Savitz, DA Weinberg, CR Arbuckle, TE TI The effect of pesticide exposure on time to pregnancy SO EPIDEMIOLOGY LA English DT Article DE agriculture; fertility; fecundity; infertility; pesticides; pregnancy; reproduction; parental exposures ID FECUNDABILITY; WOMEN AB The Ontario Farm Family Health Study Provided data for examination of the effects of Pesticide exposure on time to pregnancy. In this retrospective cohort study of farm couples in Ontario, Canada, the farm operator, husband. and wife completed. questionnaires juring 1991-1992. We asked about pesticides used on the farm and pesticide activities of the husband and wife for each month of trying to conceive. After exclusions, 2,012 planned Pregnancies remained fur analysis. We used an analog of the Cox proportional hazards model to calculate conditional fecundability ratios (conditional on pregnancy). There was no strong or consistent pattern of associations of pesticide exposure with time to pregnancy. During exposure intervals in which women participated in pesticide activities (during most of which thr men also participated), however, 6 of 13 pesticide exposure categories were associated with a decrease in fecundability (conditional fecundability ratio range = 0.51-0.80). For exposure intervals in which only the men participated in pesticide activities or in which neither men nor women participated in pesticide activities but pesticides had been used on the farm, conditional fecundability ratios ranged from 0.75 to 1.50, with no apparent consistency among pesticide classes, chemical families, or active ingredients. C1 Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC USA. Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. Hlth Canada, Bur Reprod & Child Hlth, Ottawa, ON, Canada. RP Curtis, KM (reprint author), Ctr Dis Control & Prevent, Div Reprod Hlth, MS K-34,4770 Buford Highway NE, Atlanta, GA 30341 USA. FU NIEHS NIH HHS [5-T32-ES07018, R01 ES05502] NR 13 TC 69 Z9 71 U1 2 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAR PY 1999 VL 10 IS 2 BP 112 EP 117 DI 10.1097/00001648-199903000-00005 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 169KC UT WOS:000078746100005 PM 10069244 ER PT J AU Shaw, GM Velie, EM Katz, EA Morland, KB Schaffer, DM Nelson, V AF Shaw, GM Velie, EM Katz, EA Morland, KB Schaffer, DM Nelson, V TI Maternal occupational and hobby chemical exposures as risk factors for neural tube defects SO EPIDEMIOLOGY LA English DT Article DE anencephaly; chemicals; congenital anomalies; maternal occupation; pregnancy; spina bifida; teratogens ID CONGENITAL-MALFORMATIONS; ENVIRONMENT; EMPLOYMENT AB In a case control study, we investigated whether occupational and nonoccupational (hobbies) chemical exposures to women in the periconceptional period increased their risk for having neural tube defect-affected pregnancies. Women were asked about occupational tasks and hobbies performed during the 3 months before through 3 months after conception. Based on her reported occupational tasks and hobbies, an industrial hygienist assigned a priori defined exposure categories to each task and hobby. The exposure categories included 74 chemical groups, 9 "end-use" chemical groups, and organic solvents. Face-to-face interviews were conducted with mothers of 538 (88% of eligible) infants or fetuses with neural tube defect and mothers of 539 (88%) randomly selected, nonmalformed, live born infants from a population-based 1989-1991 cohort of California births (N = 703,518), Our results suggested that maternal exposures in the periconceptional period to a variety of chemicals associated. with occupational and nonoccupational activities did not contribute substantially to risk of neural tube defects in offspring. We observed no effect estimate greater than 2.0 for maternal exposures to the chemical agent groups studied. We did not observe substantially elevated risks associated with maternal exposures to any of the end-use chemical groups or to organic solvents, Considering occupational exposures only among women who worked did not substantially alter results. Adjustment for maternal vitamin use, race/ethnicity, or education level also did not substantially alter the observed associations. C1 March Dimes Birth Defects Fdn, Calif Birth Defects Monitoring Program, Emeryville, CA 94608 USA. NCI, NIH, Bethesda, MD 20892 USA. Calif Dept Hlth Serv, Berkeley, CA 94704 USA. Univ N Carolina, Raleigh, NC USA. Kaiser Permanente, Oakland, CA USA. RP Shaw, GM (reprint author), March Dimes Birth Defects Fdn, Calif Birth Defects Monitoring Program, 1900 Powell St,Suite 1050, Emeryville, CA 94608 USA. NR 28 TC 26 Z9 26 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAR PY 1999 VL 10 IS 2 BP 124 EP 129 DI 10.1097/00001648-199903000-00007 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 169KC UT WOS:000078746100007 PM 10069246 ER PT J AU Bialer, M Johannessen, SI Kupferberg, HJ Levy, RH Loiseau, P Perucca, E AF Bialer, M Johannessen, SI Kupferberg, HJ Levy, RH Loiseau, P Perucca, E TI Progress report on new antiepileptic drugs: a summary of the fourth Eilat conference (EILAT IV) SO EPILEPSY RESEARCH LA English DT Article DE antiepileptic drugs; drug development; epilepsy; clinical trials ID COMPLEX PARTIAL SEIZURES; ANALOGS DIZOCILPINE MK-801; VAGUS NERVE-STIMULATION; VAGAL-STIMULATION; (+/-)-5-AMINOCARBONYL-10,11-DIHYDRO-5H-DIBENZOCYCLOHEPTEN-5,10-IMIN E ADCI; ANTICONVULSANT ACTIVITY; NMDA ANTAGONISTS; DOUBLE-BLIND; BLOOD-FLOW; ADD-ON AB The Fourth Eilat Conference on New Antiepileptic Drugs (AEDs) was held at the Royal Beach Hotel, Eilat, Israel, from 6th to 10th September 1998. Epileptologists and scientists from 20 countries attended the conference, which was held to discuss a number of issues in drug development, including outcome assessment in epilepsy (long-term efficacy, qualify of life, safety), cost-effectiveness, an update on drugs in development, a progress report on recently marketed AEDs, and controversies in strategies for drug development. This review focuses on drugs in development and recently marketed AEDs. Drugs in development include ADCI, AWD 131-138, DP16, ganaxolone (CCD 1042), levetiracetam (ucb L059), losigamone, pregabalin (isobutyl GABA [CI-1008]), remacemide hydrochloride, retigabine (D-23129), rufinamide (CGP 33101), soretolide (D2916), TV1901, and 534U87. New information on the safety and efficacy of recently marketed drugs (felbamate, fosphenytoin, gabapentin, lamotrigine, oxcarbazepine, tiagabine, topiramate, vigabatrin, zonisamide) and of a new antiepileptic device, the neurocybernetic prosthesis (NCP), has become available. This paper summarizes the presentations made at the conference. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Hebrew Univ Jerusalem, Fac Med, Sch Pharm, IL-91120 Jerusalem, Israel. Hebrew Univ Jerusalem, Fac Med, David R Bloom Ctr Pharm, IL-91120 Jerusalem, Israel. Natl Ctr Epilepsy, Sandvika, Norway. NINDS, Epilepsy Branch, NIH, Bethesda, MD 20892 USA. Univ Washington, Dept Pharmaceut, Seattle, WA 98195 USA. Univ Washington, Dept Neurol Surg, Seattle, WA 98195 USA. Bordeaux Univ, Hop Pellegrin, Dept Neurol, Bordeaux, France. Univ Pavia, Dept Internal Med & Therapeut, Clin Pharmacol Unit, I-27100 Pavia, Italy. RP Bialer, M (reprint author), Hebrew Univ Jerusalem, Fac Med, Sch Pharm, IL-91120 Jerusalem, Israel. NR 102 TC 162 Z9 164 U1 0 U2 4 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 1999 VL 34 IS 1 BP 1 EP 41 DI 10.1016/S0920-1211(98)00108-9 PG 41 WC Clinical Neurology SC Neurosciences & Neurology GA 194MB UT WOS:000080196500001 PM 10194110 ER PT J CA Natl Inst Drug Abuse TI NIH consensus panel recommends expanding access to and improving methadone treatment programs for heroin addiction SO EUROPEAN ADDICTION RESEARCH LA English DT Editorial Material C1 NIDA, Publ Informat Branch, Rockville, MD 20857 USA. RP NIDA, Publ Informat Branch, 5600 Fishers Lane, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1022-6877 J9 EUR ADDICT RES JI Eur. Addict. Res. PD MAR PY 1999 VL 5 IS 1 BP 50 EP 51 PG 2 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 179LW UT WOS:000079329800006 ER PT J AU Lyman, CA Garrett, KF Peter, J Gonzalez, C Walsh, TJ AF Lyman, CA Garrett, KF Peter, J Gonzalez, C Walsh, TJ TI Increased adherence of fluconazole-resistant isolates of Candida species to explanted esophageal mucosa SO EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES LA English DT Article ID EPITHELIAL-CELLS; AIDS PATIENTS; ALBICANS; ADHESION; HYDROPHOBICITY; SURFACES; STRAINS AB The adherence of fluconazole-resistant and fluconazole-susceptible isolates of Candida albicans to explanted rabbit esophageal mucosa was examined in vivo. Among six Candida albicans isolates collected from HIV-infected patients, three fluconazole-resistant (MIC>64 mu g/ml) isolates attached more avidly than three fluconazole-susceptible strains (MIC less than or equal to 0.5 mu g/ml) to esophageal mucosa (P less than or equal to 0.05). When three strains each of six different Candida spp. were compared, the more inherently fluconazole-resistant isolates adhered more avidly in the following order: Candida glabrata>Candida krusei>Candida albicans fluconazole-sensitive >Candida tropicalis>Candida parapsilosis, Nonetheless, fluconazole-resistant Candida albicans demonstrated the greatest degree of adherence in comparison to all fluconazole-susceptible Candida albicans (P<0.001) and to all Candida spp. tested (P<0.001), Thus, the refractoriness of esophageal candidiasis in patients infected with fluconazole-resistant isolates may be related to both in vitro drug resistance and increased mucosal adherence. C1 NCI, Pediat Oncol Branch, Immunocompromised Host Sect, Bethesda, MD 20892 USA. RP Lyman, CA (reprint author), NCI, Pediat Oncol Branch, Immunocompromised Host Sect, Bldg 10,Room 13N240, Bethesda, MD 20892 USA. NR 14 TC 5 Z9 6 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0934-9723 J9 EUR J CLIN MICROBIOL JI Eur. J. Clin. Microbiol. Infect. Dis. PD MAR PY 1999 VL 18 IS 3 BP 213 EP 216 DI 10.1007/s100960050262 PG 4 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 195QV UT WOS:000080263600011 PM 10357058 ER PT J AU Courret, N Prina, E Mougneau, E Saraiva, EM Sacks, DL Glaichenhaus, N Antoine, JC AF Courret, N Prina, E Mougneau, E Saraiva, EM Sacks, DL Glaichenhaus, N Antoine, JC TI Presentation of the Leishmania antigen LACK by infected macrophages is dependent upon the virulence of the phagocytosed parasites SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE antigen presentation; LACK; Leishmania; macrophage; parasite virulence ID AMASTIGOTE CYSTEINE PROTEINASES; CLASS-II MOLECULES; CD4(+) T-CELLS; AMAZONENSIS AMASTIGOTES; BALB/C MICE; PROMASTIGOTES; MEXICANA; IMMUNOLOCALIZATION; IDENTIFICATION; COMPARTMENT AB We have previously demonstrated that murine macrophages (M Phi,) infected with Leishmania promastigotes, in contrast to M Phi infected with the amastigote stage of these parasites, are able to present the Leishmania antigen LACK (Leishmania homologue of receptors for activated C kinase) to specific, I-A(d)-restricted T cell hybrids and to the T cell clone 9.1-2. These T cells react with the LACK (158-173) peptide, which is immunodominant in BALB/c mice. Here, we show that the level of stimulation of the LACK-specific T cell hybridoma OD12 by promastigote-infected M Phi is clearly dependent upon the differentiation state of the internalized parasites. Thus, shortly after infection with log-phase or stationary-phase promastigotes of L. major or of L. amazonensis, M Phi strongly activated OD12. The activity was transient and rapidly lost. However, under the same conditions, activation of OD12 by M Phi infected with metacyclic promastigotes of L. major or of L. amazonensis was barely detectable. At the extreme, M Phi, infected with amastigotes were incapable to stimulate OD12. Thus, the presentation of LACK by infected M Phi, correlates with the degree of virulence of the phagocytosed parasites, the less virulent being the best for the generation/expression of LACK (158-173)-I-A(d) complexes. While the intracellular killing of the parasites appears to be an important condition for the presentation of LACK, it is not the only requisite. The partial or total destruction of intracellular L. amazonensis amastigotes does not allow the presentation of LACK to OD12. A preferential interaction of LACK (158-173) with recycling rather than newly synthesized MHC class II molecules does not explain the transient presentation of LACK by M Phi, infected with log-phase or stationary-phase promastigotes because brefeldin A strongly inhibited the presentation of LACK to OD12. Taken together, these results suggest that virulent stages of Leishmania, namely metacyclics and amastigotes, have evolved strategies to avoid or minimize their recognition by CD4(+) T lymphocytes. C1 Inst Pasteur, F-75724 Paris, France. CNRS, UPR 411, Inst Pharmacol Mol & Cellulaire, Valbonne, France. NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA. RP Antoine, JC (reprint author), Inst Pasteur, 25 Rue Dr Roux, F-75724 Paris, France. RI PRINA, Eric/B-1374-2014 NR 33 TC 64 Z9 67 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD MAR PY 1999 VL 29 IS 3 BP 762 EP 773 DI 10.1002/(SICI)1521-4141(199903)29:03<762::AID-IMMU762>3.0.CO;2-4 PG 12 WC Immunology SC Immunology GA 176KE UT WOS:000079149600005 PM 10092078 ER PT J AU Dudley, E Hornung, F Zheng, LX Scherer, D Ballard, D Lenardo, M AF Dudley, E Hornung, F Zheng, LX Scherer, D Ballard, D Lenardo, M TI NF-chi B regulates Fas/APO-1/CD95- and TCR-mediated apoptosis of T lymphocytes SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE lpr mouse; tumor necrosis factor; programmed cell death ID INDUCED CELL-DEATH; AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME; TUMOR-NECROSIS-FACTOR; FAS GENE-MUTATIONS; KAPPA-B; SIGNALING COMPLEX; ACTIVATION; TNF; CD95; ALPHA AB The maintenance of lymphocyte homeostasis by apoptosis is a critical regulatory mechanism in the normal immune system. The transcription factor NF-kappa B has been shown to play a role in protecting cells against death mediated by TNF. We show here that NF-kappa B also has a role in regulating Fas/APO-1/CD95-mediated death, a major pathway of peripheral T cell death. Transfection of Jurkat cells with the NF-kappa B subunits p50 and p65 confers resistance against Fas-mediated apoptosis. Reciprocally, inhibition of NF-kappa B activation by a soluble peptide inhibitor or a dominant form of the NF-kappa B inhibitor, I kappa B, makes the cells more susceptible to Fas-mediated apoptosis. Furthermore, inhibition of NF-kappa B activation by a soluble peptide inhibitor rendered a T cell hybridoma more susceptible to TCR-mediated apoptosis. Correspondingly, transfection of p50 and p65 provided considerable protection from TCR-mediated apoptosis. These observations were corroborated by studies on Fas-mediated death in primary T cells. Concanavalin A-activated cycling T cell blasts from mice that are transgenic for the dominant I kappa B molecule have increased sensitivity to Fas-mediated apoptosis, associated with a down-regulation of NF-kappa B complexes in the nucleus. In addition, blocking TNF, itself a positive regulator of NF-kappa B, with neutralizing antibodies renders the cells more susceptible to anti-Fas-mediated apoptosis. In summary, our results provide compelling evidence that NF-kappa B protects against Fas-mediated death and is likely to be an important regulator of T cell homeostasis and tolerance. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Vanderbilt Univ, Nashville, TN USA. Howard Hughes Med Inst, Nashville, TN USA. RP Lenardo, M (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,RM 11N311,10 Ctr Dr MSC 1892, Bethesda, MD 20892 USA. EM lenardo@nih.gov NR 32 TC 78 Z9 78 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD MAR PY 1999 VL 29 IS 3 BP 878 EP 886 DI 10.1002/(SICI)1521-4141(199903)29:03<878::AID-IMMU878>3.0.CO;2-9 PG 9 WC Immunology SC Immunology GA 176KE UT WOS:000079149600018 PM 10092091 ER PT J AU Donkor, IO Abdel-Ghany, YS Kador, PF Mizoguchi, T Bartoszko-Malik, A Miller, DD AF Donkor, IO Abdel-Ghany, YS Kador, PF Mizoguchi, T Bartoszko-Malik, A Miller, DD TI Synthesis and biological activity of aldose reductase inhibitors with Michael acceptor substituents SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article DE Michael accepters; aldose reductase; aldehyde reductase; diabetic complications; alrestatin ID GALACTOSE-FED DOGS; HUMAN PSOAS MUSCLE; DIABETIC COMPLICATIONS; ALDEHYDE REDUCTASE; CRYSTAL-STRUCTURE; BINDING SITE; SPECIFICITY; ZOPOLRESTAT; PREVENTION AB Derivatives of alrestatin (15) and alconil (6-8) possessing Michael acceptor substituents were synthesized as aldose reductase inhibitors. The alrestatin derivatives demonstrated enhanced aldose reductase inhibitory activity. The most potent reversible inhibitor of the series (compound 3) was 15-fold more active than alrestatin. Additionally, lipophilic analogues of alrestatin selectively inhibited rat lens aldose reductase versus rat kidney aldehyde reductase. Unlike alrestatin derivatives, alconil derivatives with similar substituents did not demonstrate significant reversible or irreversible inhibition of aldose reductase. (C) Elsevier, Paris. C1 Univ Tennessee, Dept Pharmaceut Sci, Memphis, TN 38163 USA. Ohio State Univ, Coll Pharm, Div Med Chem & Nat Prod, Columbus, OH 43210 USA. NEI, Lab Ocular Therapeut, NIH, Bethesda, MD 20892 USA. RP Miller, DD (reprint author), Univ Tennessee, Dept Pharmaceut Sci, Memphis, TN 38163 USA. NR 24 TC 3 Z9 3 U1 0 U2 2 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0223-5234 J9 EUR J MED CHEM JI Eur. J. Med. Chem. PD MAR PY 1999 VL 34 IS 3 BP 235 EP 243 DI 10.1016/S0223-5234(99)80056-7 PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 199XA UT WOS:000080508300005 ER PT J AU Safieddine, S Wenthold, RJ AF Safieddine, S Wenthold, RJ TI SNARE complex at the ribbon synapses of cochlear hair cells: analysis of synaptic vesicle- and synaptic membrane-associated proteins SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE guinea-pig; rat; SNAP-25; synaptobrevin; synaptotagmin; syntaxin ID GUINEA-PIG COCHLEA; ACETYLCHOLINE-RECEPTOR; CALCIUM CHANNELS; SYNTAXIN FAMILY; RAT-BRAIN; SYNAPTOTAGMIN; SYNAPTOPHYSIN; FUSION; SYNAPTOBREVIN; EXPRESSION AB Neurotransmitters are released via exocytosis of synaptic vesicles involving a fusion complex consisting of a set of highly conserved proteins, which form a multiprotein complex resulting in the docking of synaptic vesicles at the site of release. There are three major differences between cochlear hair cell synapses and CNS synapses: (i) hair cells have a specialized structure, the synaptic ribbon, to which synaptic vesicles are attached; (ii) hair cells can maintain high and sustained release of neurotransmitter; and (iii) hair cells lack synaptophysin and synapsin. These differences suggest that an unconventional mechanism of neurotransmitter release may be involved at ribbon synapses. In this study we used different and complementary approaches to determine whether or not ribbon-containing hair cells of the cochlea express any component of the core fusion complex found in conventional synapses. Syntaxin 1, the synaptic membrane synaptosome-associated protein (SNAP)-25 and vesicle-associated membrane protein (VAMP or synaptobrevin) were found to be present in the organ of Corti of both rat and guinea-pig, as shown by reverse transcription polymerase chain reaction and Western blotting. In situ hybridization and immunocytochemistry showed mRNA and protein expression, respectively, in both inner and outer hair cells. Synaptotagmins I and II, generally considered to play major roles in neurotransmitter release at central synapses, were not detected in the organ of Corti. C1 NIDCD, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Safieddine, S (reprint author), NIDCD, Neurochem Lab, NIH, Bldg 36,Room 5D08,36 Convent Dr,MSC-4162, Bethesda, MD 20892 USA. EM safieddi@nidcd.nih.gov NR 64 TC 108 Z9 112 U1 0 U2 6 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD MAR PY 1999 VL 11 IS 3 BP 803 EP 812 DI 10.1046/j.1460-9568.1999.00487.x PG 10 WC Neurosciences SC Neurosciences & Neurology GA 176RB UT WOS:000079164600007 PM 10103074 ER PT J AU Bengzon, J Okabe, S Lindvall, O McKay, RDG AF Bengzon, J Okabe, S Lindvall, O McKay, RDG TI Suppression of epileptogenesis by modification of N-methyl-D-aspartate receptor subunit composition SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article ID HETEROMERIC NMDA RECEPTORS; AMINO-ACID ANTAGONISTS; LONG-TERM POTENTIATION; GYRUS GRANULE CELLS; RAT-BRAIN; KINDLING MODEL; TYROSINE PHOSPHORYLATION; MESSENGER-RNAS; EPILEPSY; EXPRESSION AB The effects of altered N-methyl-D-aspartate (NMDA) receptor subunit composition on seizure development in kindling epilepsy were assessed in transgenic mice expressing high neuronal levels of NR2D under control of the calcium/calmodulin kinase II alpha subunit (alpha CaMKII) promoter. The NR2D subunit is normally present at very low levels in the mature forebrain. Transgenic mice showed a marked reduction of amygdala kindling development. Spread of epileptic activity was retarded and generalized seizures appeared later in animals overexpressing NR2D compared with wild-type mice. The progressive lengthening of epileptiform activity, which normally occurs in kindling, was also dampened in transgenic animals. We conclude that NMDA receptor subunit composition determines the progression of experimental epilepsy. C1 Univ Lund Hosp, Wallenberg Neurosci Ctr, Sect Restorat Neurol, S-22185 Lund, Sweden. Natl Inst Biosci & Human Technol, Tsukuba, Ibaraki 305, Japan. NINDS, Mol Biol Lab, Bethesda, MD 20892 USA. RP Univ Lund Hosp, Wallenberg Neurosci Ctr, Sect Restorat Neurol, S-22185 Lund, Sweden. EM johan.bengzon@neurol.lu.se NR 45 TC 21 Z9 21 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0953-816X EI 1460-9568 J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD MAR PY 1999 VL 11 IS 3 BP 916 EP 922 DI 10.1046/j.1460-9568.1999.00500.x PG 7 WC Neurosciences SC Neurosciences & Neurology GA 176RB UT WOS:000079164600018 PM 10103085 ER PT J AU Muller, FMC Groll, AH Walsh, TJ AF Muller, FMC Groll, AH Walsh, TJ TI Current approaches to diagnosis and treatment of fungal infections in children infected with human immune deficiency virus SO EUROPEAN JOURNAL OF PEDIATRICS LA English DT Review DE mucosal and invasive fungal infections; yeasts and filamentous fungi; dimorphic fungi; molecular diagnosis; antifungals ID HUMAN-IMMUNODEFICIENCY-VIRUS; PNEUMOCYSTIS-CARINII PNEUMONIA; PENICILLIUM-MARNEFFEI INFECTION; AMPHOTERICIN-B AMBISOME; CRYPTOCOCCAL MENINGITIS; DISSEMINATED HISTOPLASMOSIS; HIV-INFECTION; PULMONARY ASPERGILLOSIS; IMMUNOCOMPROMISED CHILDREN; INVASIVE ASPERGILLOSIS AB The prolonged survival of profoundly immunocompromised patients has revealed mucosal and invasive fungal infections to be major causes of morbidity and mortality in advanced HIV disease in children of all age groups. Antifungal resistance has become a clinically relevant problem. Paediatricians caring for HIV-infected children need to be aware of these increasingly frequent and often life-threatening infectious complications. This article reviews what is currently known about epidemiology, clinical presentation, diagnosis and treatment of mucosal and invasive fungal infections in children and adolescents with HIV disease. Candida spp. have become a leading bloodstream isolate in hospitalised patients; mucosal candidiasis is the most prevalent opportunistic infection in HIV-infected patients, and in both invasive and superficial infections, non Candida albicans spp. are on the increase. Invasive pulmonary aspergillosis has surfaced as an HIV-associated complication and previously uncommon fungi are more frequently encountered. HIV-infected individuals are particularly susceptible to Peumocystis carinii, Cryptococcus neoformans and infections by endemic fungi, such as Histoplasma capsulatum, Coccidioides immitis, Penicillium marneffei, and others. Newer immunological and molecular-based methods provide early and rapid diagnosis and monitoring. Potent and broad-spectrum third generation triazoles and novel fungicidal lipopeptides of the echinocandin class of antifungal antibiotics have entered clinical trials. Immunmodulation by recombinant cytokines and antifungal vaccines are very actively pursued inroads to adjunctive and preventive immunotherapy. Conclusion Mucosal and invasive fungal infections will remain important complications in HIV-infected children of all age groups. Interventional studies and well documented case series are needed to improve the molecular diagnosis, treatment and prevention of invasive fungal infections in the paediatric HIV-infected population. C1 NCI, Pediat Oncol Branch, Immunocompromised Host Sect, Bethesda, MD 20892 USA. RP Muller, FMC (reprint author), Univ Wurzburg, Inst Mol Infekt Biol, Rontgenring 11, D-97070 Wurzburg, Germany. EM fmmueller@mail.uni-wuerzburg.de NR 110 TC 24 Z9 26 U1 1 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6199 J9 EUR J PEDIATR JI Eur. J. Pediatr. PD MAR PY 1999 VL 158 IS 3 BP 187 EP 199 DI 10.1007/s004310051047 PG 13 WC Pediatrics SC Pediatrics GA 171VL UT WOS:000078884700001 PM 10094436 ER PT J AU Detrick, B Hooks, JJ Keiser, J Tabbara, I AF Detrick, B Hooks, JJ Keiser, J Tabbara, I TI Detection of cytomegalovirus proteins by flow cytometry in the blood of patients undergoing hematopoietic stem cell transplantation SO EXPERIMENTAL HEMATOLOGY LA English DT Article DE cytomegalovirus; hematopoietic stem cell; transplantation; flow cytometry; antigenemia ID BONE-MARROW TRANSPLANTATION; POLYMERASE CHAIN-REACTION; LOWER MATRIX PROTEIN; GANCICLOVIR PROPHYLAXIS; IMMUNE GLOBULIN; VIRUS INFECTION; MESSENGER-RNA; LEUKOCYTES; RECIPIENTS; DIAGNOSIS AB Cytomegalovirus (CMV) infection and associated diseases continue to be a major complication encountered by patients undergoing high-dose chemoradiotherapy and hematopoietic stem cell transplantation (HSCT), A number of studies revealed that identification of CMV in the blood of HSCT patients was a predictor of future CMV disease. The purpose of this study was to determine if CMV proteins detected by flow cytometry could be a rapid and more quantitative way to monitor CMV infections and CMV antigenemia in HSCT patients. Preliminary studies showed that CMV immediate early (IE), early (E), and late (L) tegument proteins were specifically identified in CMV-infected cell lines and not in uninfected cells, We evaluated CMV antigen detection by flow cytometry in blood samples collected before and after transplantation in 56 serially collected blood samples from 17 HSCT patients and CMV protein expression was compared to CMV isolation, CMV IE and E proteins were not detected in any of the samples analyzed. However, CMV L protein detection by flow cytometry correlated with virus isolation in serially collected blood samples, Samples from 14 patients were evaluated by both techniques, at the same time intervals, There was a 100% correlation (8/8) between the lack of CMV antigen detection by flow cytometry and the failure to isolate infectious virus. Moreover, 5 of 6 patients who were positive for CMV L antigen by flow cytometry also were positive by virus isolation techniques. When flow cytometry and virus isolation did not detect CMV antigen on the same day, CMV positivity was first detected by flow cytometry, Then, 1-2 weeks later, positive virus isolation was documented. This study indicates that flow cytometric identification of CMV antigenemia correlates with isolation of CMV in HSCT patients and may be a predictive test for the rapid detection of CMV in the blood. (C) 1999 International Society for Experimental Hematology, Published by Elsevier Science Inc. C1 NEI, Immunol & Virol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. George Washington Univ, Med Ctr, Dept Pathol, Washington, DC 20037 USA. George Washington Univ, Med Ctr, Dept Microbiol & Immunol, Washington, DC 20037 USA. George Washington Univ, Med Ctr, Dept Internal Med, Washington, DC 20037 USA. RP Hooks, JJ (reprint author), NEI, Immunol & Virol Sect, Immunol Lab, NIH, Bldg 10,Room 6N228, Bethesda, MD 20892 USA. NR 32 TC 6 Z9 7 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD MAR PY 1999 VL 27 IS 3 BP 569 EP 575 DI 10.1016/S0301-472X(98)00076-9 PG 7 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 174HN UT WOS:000079028800023 PM 10089921 ER PT J AU Perantoni, AO AF Perantoni, AO TI Adhesion molecules in the kidney: From embryo to adult SO EXPERIMENTAL NEPHROLOGY LA English DT Review DE integrins; cadherins; selectins; basement membrane proteins; gene targeting ID SELECTIN-DEFICIENT MICE; EPITHELIAL-MESENCHYMAL INTERACTIONS; CELL-MATRIX INTERACTIONS; HUMAN MESANGIAL CELLS; PROTEIN-KINASE-C; LAMININ-A-CHAIN; E-CADHERIN; DIFFERENTIAL EXPRESSION; INTERCELLULAR-ADHESION; EXTRACELLULAR-MATRIX AB Multiple members from every major family of cell adhesion molecules (CAMs) have been implicated in the development, maintenance, or repair of renal tissues and include several isoforms of integrins, cell-bound glycoproteins, cadherins, immunoglobulin cell adhesion molecules, and selectins. In combination, they mediate a variety of cell-basement membrane and cell-cell interactions believed to direct morphogenesis and cell migration and regulate cell growth and apoptosis, in addition to generating a functional barrier for blood filtration and helping manage inflammatory responses in the kidney. The expression of some CAMs is transient during and critical to normal nephrogenesis, varying with specific stages of development, but often ultimately resulting in the constitutive production of other members in mature tissues. While gene-targeting studies have successfully implicated individual CAMs in renal cell functions, e.g., alpha(3)beta(1) and alpha(8)beta(1) integrins, the loss of others bears no renal phenotype due to redundancy of homologous family members or to the severity of the defect early in embryogenesis. This review summarizes the studies of various CAMs found in normal embryonic or adult kidney, describes their spatiotemporal expression patterns, and discusses their involvement in renal processes. C1 NCI, Comparat Carcinogenesis Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Perantoni, AO (reprint author), NCI, Comparat Carcinogenesis Lab, Frederick Canc Res & Dev Ctr, Bldg 538,Room 205E, Frederick, MD 21702 USA. RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X NR 253 TC 17 Z9 17 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-7782 J9 EXP NEPHROL JI Exp. Nephrol. PD MAR-APR PY 1999 VL 7 IS 2 BP 80 EP 102 PG 23 WC Urology & Nephrology SC Urology & Nephrology GA 215EM UT WOS:000081369000002 PM 10213863 ER PT J AU Huang, STJ Cidlowski, JA AF Huang, STJ Cidlowski, JA TI Glucocorticoids inhibit serum depletion-induced apoptosis in T lymphocytes expressing Bcl-2 SO FASEB JOURNAL LA English DT Article DE programmed cell death; protection; growth factors ID CELL-DEATH; CYTOCHROME-C; DNA FRAGMENTATION; S49 CELLS; ACTIVATION; THYMOCYTES; PREVENTS; CED-9; BAX; MITOCHONDRIA AB Depletion of growth factors and glucocorticoids are known to induce apoptosis and inhibit growth in T lymphocytes. We have examined the effect of Bcl-2 expression on the cellular response to growth factor depletion in the presence or absence of glucocorticoids, Cell growth was determined by cell counting and viability was quantitated by dye exclusion. Apoptosis was evaluated by flow cytometry, analysis of DNA integrity, and enzymatic determination of caspase3-like activity. Serum depletion and glucocorticoid administration inhibited cell growth and stimulated apoptosis in Bcl-2 negative cells. Cotreatment with both stimuli had additive effects on apoptosis but not on inhibition of cell growth. Bcl-2 expression abrogated the repressive effect of glucocorticoids on apoptosis but not on cell growth. In contrast, neither apoptosis nor growth inhibition induced by serum depletion of cells was blocked by Bcl-2 expression. However, glucocorticoid treatment of Bcl-2-overexpressing cells protected them from apoptosis induced by serum depletion. Glucocorticoid protection of Bcl-2-overexpressing cells from serum depletion-induced apoptosis was mimicked by other inducers of apoptosis, which act to inhibit protein synthesis. These data suggest that Bcl-2 expression can switch the effect of glucocorticoids from proapoptotic to antiapoptotic when lymphocytes expressing Bcl-2 are exposed to other apoptotic stimuli. C1 NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Dept Cell & Mol Physiol, Chapel Hill, NC 27599 USA. RP Cidlowski, JA (reprint author), NIEHS, Lab Signal Transduct, NIH, POB 12233,MD E2-02, Res Triangle Pk, NC 27709 USA. RI Huang, Se-Te/F-6881-2013 NR 35 TC 27 Z9 30 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 1999 VL 13 IS 3 BP 467 EP 476 PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 174CF UT WOS:000079016000006 PM 10064613 ER PT J AU Reszka, KJ Matuszak, Z Chignell, CF Dillon, J AF Reszka, KJ Matuszak, Z Chignell, CF Dillon, J TI Oxidation of biological electron donors and antioxidants by a reactive lactoperoxidase metabolite from nitrite (NO2-): An EPR and spin trapping study SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE EPR; ascorbate; trolox C; cysteine; glutathione; spin trapping; DMPO; radical; LPO; nitrite; nitrogen dioxide radical ID VITAMIN-E ANALOG; NICOTINAMIDE ADENINE-DINUCLEOTIDE; OXIDE SYNTHASE ACTIVITY; NITROGEN-DIOXIDE; HORSERADISH-PEROXIDASE; HYDROGEN-PEROXIDE; FREE-RADICALS; TROLOX-C; ANTIMICROBIAL ACTIVITY; REDUCTION POTENTIALS AB We report that a lactoperoxidase (LPO) metabolite derived from nitrite (NO2-) catalyses one-electron oxidation of biological electron donors and antioxidants such as NADH, NADPH, cysteine, glutathione, ascorbate, and Trolox C. The radical products of the reaction have been detected and identified using either direct EPR or EPR combined with spin trapping. While LPO/H2O2 alone generated only minute amounts of radicals from these compounds, the yield of radicals increased sharply when nitrite was also present. In aerated buffer (pH 7) the nitrite-dependent oxidation of NAD(P)H by LPO/H2O2 produced superoxide radical, O-2(.-), which was detected as a DMPO/(O2H)-O-. adduct. We propose that in the LPO/H2O2/NO2-/biological electron donor systems the nitrite functions as a catalyst because of its preferential oxidation by LPO to a strongly oxidizing metabolite, most likely a nitrogen dioxide radical (NO2)-N-., which then reacts with the biological substrates more efficiently than does LPO/H2O2 alone. Because both nitrite and peroxidase enzymes are ubiquitous our observations point at a possible mechanism through which nitrite might exert its biological and cytotoxic action in vivo, and identify some of the physiological targets which might be affected by the peroxidase/H2O2/nitrite systems. Published by Elsevier Science Inc. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Columbia Univ, Dept Ophthalmol, New York, NY 10027 USA. RP Reszka, KJ (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 64 TC 32 Z9 32 U1 2 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD MAR PY 1999 VL 26 IS 5-6 BP 669 EP 678 DI 10.1016/S0891-5849(98)00244-5 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 177UJ UT WOS:000079229200020 PM 10218656 ER PT J AU Boirivant, M Marini, M Di Felice, G Pronio, AM Montesani, C Tersigni, R Strober, W AF Boirivant, M Marini, M Di Felice, G Pronio, AM Montesani, C Tersigni, R Strober, W TI Lamina propria T cells in Crohn's disease and other gastrointestinal inflammation show defective CD2 pathway-induced apoptosis SO GASTROENTEROLOGY LA English DT Article; Proceedings Paper CT 97th Annual Meeting of the American-Gastroenterological-Association, Digestive Disease Week CY MAY 10-16, 1997 CL WASHINGTON, D.C. SP Amer Gastroenterol Assoc ID FAMILY PROTEASE INHIBITORS; INTERFERON-GAMMA; BOWEL-DISEASE; ACTIVATION; DEATH; LYMPHOCYTES; BCL-2; RESPONSIVENESS; COLITIS; MUCOSA AB Background & Aims: Normal human lamina propria lymphocytes manifest increased unstimulated apoptosis compared with peripheral lymphocytes, which ave en hanced after stimulation via the CD2 activation pathway. This activation-induced apoptosis down-regulates cell expansion and cytokine production, in previous studies, it was shown that lamina propria T cells from patients with Crohn's disease and ulcerative colitis manifest abnormal proliferation and cytokine production. It was therefore of interest to determine if such cells also showed abnormal patterns of apoptosis. Methods: Apoptosis was evaluated by propidium iodide staining of cells followed by flow cytometric: analysis. Fas expression and Bcl-2 levels in cells were evaluated by immunofluorescence. Results: Lamina propria lymphocytes from patients with Crohn's disease and ulcerative colitis as well as from 2 patients with diverticulitis showed defective CD2 pathway-induced apoptosis. Studies of the mechanisms of this defect focusing on cells from patients with Crohn's disease showed that Crohn's disease lamina propria lymphocytes from inflamed tissues express the same amount of cell surface Fas but are less sensitive to Fas-mediated apoptosis than control cells. In addition, lamina propria lymphocytes from inflamed Crohn's disease tissues manifest increased expression of Bcl-2 after CD2 pathway stimulation and elevated Bcl-2 levels in cultures of unstimulated T cells. Conclusions: T cells isolated from areas of inflammation in Crohn's disease, ulcerative colitis, and other inflammatory states manifest decreased CD2 pathway-induced apoptosis. Studies of cells from inflamed Crohn's disease tissue indicate that this defect is accompanied by elevated Bcl-2 levels. These changes are probably caused by the chronic inflammation and may aggravate the underlying disease processes that are present. C1 Ist Super Sanita, Immunol Lab, I-00161 Rome, Italy. Univ Rome La Sapienza, Clin Chirurg 6, Rome, Italy. Osped Nuovo Regina Margherita, Div Chirurg, Rome, Italy. NIAID, Mucosal Immun Sect, NIH, Bethesda, MD 20892 USA. RP Boirivant, M (reprint author), Ist Super Sanita, Immunol Lab, Viale Regina Elena 299, I-00161 Rome, Italy. RI Pronio, Annamaria/J-4232-2012; DI FELICE, GABRIELLA/B-9985-2016; BOIRIVANT, MONICA/B-9977-2016 OI DI FELICE, GABRIELLA/0000-0001-7387-9683; NR 30 TC 212 Z9 212 U1 0 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAR PY 1999 VL 116 IS 3 BP 557 EP 565 DI 10.1016/S0016-5085(99)70177-0 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 171ZG UT WOS:000078894400012 PM 10029614 ER PT J AU Podskalny, J AF Podskalny, J TI Training, career development, and small business support from the National Institutes of Health SO GASTROINTESTINAL ENDOSCOPY LA English DT Article; Proceedings Paper CT NIH Workshop on Endoscopic Research Priorities CY DEC 12-13, 1998 CL BETHESDA, MARYLAND SP NIH C1 NIDDKD, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. RP Podskalny, J (reprint author), NIDDKD, Div Digest Dis & Nutr, NIH, Bldg 45,Rm 6AN-12E,45 Ctr Dr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD MAR PY 1999 VL 49 IS 3 BP S96 EP S99 DI 10.1016/S0016-5107(99)70537-7 PN 2 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 174YQ UT WOS:000079064500024 PM 10049460 ER PT J AU Rade, JJ Cheung, M Miyamoto, S Dichek, DA AF Rade, JJ Cheung, M Miyamoto, S Dichek, DA TI Retroviral vector-mediated expression of hirudin by human vascular endothelial cells: implications for the design of retroviral vectors expressing biologically active proteins SO GENE THERAPY LA English DT Article DE gene therapy; endothelial cells; hirudin; signal peptide; thrombin ID TISSUE PLASMINOGEN-ACTIVATOR; RECOMBINANT GENE-EXPRESSION; THROMBIN-SPECIFIC INHIBITOR; SMOOTH-MUSCLE CELLS; IN-VIVO; CORONARY ANGIOPLASTY; NEOINTIMA FORMATION; ARTERIAL-WALL; INSECT CELLS; SIGNAL AB We constructed a hirudin cDNA cassette, HV-1.1, that encodes mature hirudin variant-1 fused to the signal peptide of human tissue-type plasminogen activator (t-PA). The cassette was subclonced into retroviral vectors and used to transduce human vascular endothelial cells in vitro. Hirudin antigen and activity were measured by ELISA and thrombin inhibition assays, respectively. Transduced cells secreted up to 35 +/- 2 ng/10(6) cells/24 h of biologically active hirudin; expression was stable for at least 7 weeks. Recombinant hirudin, expressed from the HV-1.1 cassette had a specific activity of 7.1 +/- 0.2 antithrombin units per microgram (ATU/mu g), compared with specific activities of approximately 12 ATU/mu g for both native leech hirudin and recombinant hirudin produced in yeast. Protein sequencing and mass spectroscopic analysis revealed the presence of an extra N-terminal serine residue, indicating aberrant cleavage of the t-PA signal peptide and likely accounting for the diminished activity We therefore constructed a second cDNA cassette, HV-1.2, in which hirudin secretion was directed by the signal peptide of human growth hormone. Hirudin expressed from the HV-1.2 cassette had a specific activity of 13.5 +/- 0-2 ATU/mu g. Protein sequencing and mass spectroscopic analysis demonstrated proper cleavage of the growth hormone signal peptide. Thus, we achieved high level retrovirus-mediated. secretion of biologically active hirudin from endothelial cells in vitro. Use of these vectors may permit sustained local antagonism of thrombin activity in vivo. C1 Johns Hopkins Univ, Sch Med, Div Cardiol, Baltimore, MD 21287 USA. NHLBI, Mol Hematol Branch, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Univ Calif San Francisco, Gladstone Inst Cardiovasc Dis, San Francisco, CA 94141 USA. RP Rade, JJ (reprint author), Johns Hopkins Univ, Sch Med, Div Cardiol, Carnegie 565-C,600 N Wolfe St, Baltimore, MD 21287 USA. FU NHLBI NIH HHS [HL53222] NR 63 TC 6 Z9 8 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD MAR PY 1999 VL 6 IS 3 BP 385 EP 392 DI 10.1038/sj.gt.3300824 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 173WH UT WOS:000079002400011 PM 10435088 ER PT J AU Caplen, NJ Higginbotham, JN Scheel, JR Vahanian, N Yoshida, Y Hamada, H Blaese, RM Ramsey, WJ AF Caplen, NJ Higginbotham, JN Scheel, JR Vahanian, N Yoshida, Y Hamada, H Blaese, RM Ramsey, WJ TI Adeno-retroviral chimeric viruses as in vivo transducing agents SO GENE THERAPY LA English DT Article DE adenovirus; retrovirus; gene therapy ID INDUCIBLE GENE-EXPRESSION; IN-VIVO; VECTOR; CELLS; TUMORS; RESCUE; VITRO AB Several hybrid viral gene transfer systems have been described that exploit the favorable features of the two parent viral species. We have developed a hybrid adeno-retroviral vector system to generate a retroviral vector in situ. The system consists of adenoviruses encoding MoMLV gag.pol (Axtet.gag.pol), the VSV-G viral envelope (Axtet. VSV-G), the retroviral vector LXSN expressing the neomycin phosphotransferase gene (AV-LXSN) and a transcriptional regulator to control expression of gag.pol and envelope (AV-rtTA). In vitro, biologically active retroviral vector preparations were generated following adenoretroviral transduction of 9L rat glioma cells. In vivo the transcomplementing adeno-retroviruses were co-administered intratumorally into subcutaneous 9L glioma tumors in rats and human A375 melanoma xenografts in nude mice. In the 9L rat model, G418(R) cell cultures were only obtained when 9L cells were harvested from tumors injected with all four transcomplementing adeno-retroviruses. Molecular I analysis of DNA extracted from 9L G418(R) populations derived both in vitro and in vivo showed appropriate integration of the LXSN proviral sequence. Tumor cells were I harvested 1, 3 and 4 weeks after adeno-retrovirus administration to the human A375 xenografts. The percentage of G418(R) colonies recovered from tumors transduced with all of the transcomplementing adeno-retroviruses increased with time, whereas no increase was observed in tumors transduced with AV-LXSN alone. DNA extracted from G418(R) A375 cell populations showed the presence of integrated proviral sequences only in animals that received the full complement of adeno-retroviruses. These results demonstrate that adenoviral vectors expressing transcomplementing genes for retroviral proteins and retroviral vector RNAs can be used for in situ transduction of target cells. all four transcomplementing adeno-retroviruses. Molecular I analysis of DNA extracted from 9L G418(R) populations derived both in vitro and in vivo showed appropriate integration of the LXSN proviral sequence. Tumor cells were I harvested 1, 3 and 4 weeks after adeno-retrovirus administration to the human A375 xenografts. The percentage of G418(R) colonies recovered from tumors transduced with all of the transcomplementing adeno-retroviruses increased with time, whereas no increase was observed in tumors transduced with AV-LXSN alone. DNA extracted from G418(R) A375 cell populations showed the presence of integrated proviral sequences only in animals that received the full complement of adeno-retroviruses. These results demonstrate that adenoviral vectors expressing transcomplementing genes for retroviral proteins and retroviral vector RNAs can be used for in situ transduction of target cells. C1 Natl Human Genome Res Inst, Clin Gene Therapy Branch, NIH, Bethesda, MD 20892 USA. Japanese Fdn Canc Res, Inst Canc, Dept Mol Biotherapy Res, Canc Chemotherapy Ctr, Tokyo 170, Japan. RP Ramsey, WJ (reprint author), Natl Human Genome Res Inst, Clin Gene Therapy Branch, NIH, 10 Ctr Dr,10C103, Bethesda, MD 20892 USA. RI Caplen, Natasha/H-2768-2016 OI Caplen, Natasha/0000-0002-0001-9460 NR 20 TC 37 Z9 37 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD MAR PY 1999 VL 6 IS 3 BP 454 EP 459 DI 10.1038/sj.gt.3300835 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 173WH UT WOS:000079002400019 PM 10435096 ER PT J AU Murakami, MS Copeland, TD Vande Woude, GF AF Murakami, MS Copeland, TD Vande Woude, GF TI Mos positively regulates Xe-Wee1 to lengthen the first mitotic cell cycle of Xenopus SO GENES & DEVELOPMENT LA English DT Article DE Mos; Xe-Wee1; Xenopus embryonic cell cycle ID DNA-DAMAGE CHECKPOINT; PROTEIN-KINASE HOMOLOG; WEE1 TYROSINE KINASE; MAP KINASE; FISSION YEAST; MEIOTIC MATURATION; EGG EXTRACTS; M-PHASE; PHOSPHORYLATION SITES; NEGATIVE REGULATION AB Several key developmental events occur in the first mitotic cell cycle of Xenopus; consequently this cycle has two gap phases and is similar to 60-75 min in length. In contrast, embryonic cycles 2-12 consist only of S and M phases and are 30 min in length. Xe-Wee1 and Mos are translated and degraded in a developmentally regulated manner. Significantly, both proteins are present in the first cell cycle. We showed previously that the expression of nondegradable Mos, during early interphase, delays the onset of M phase in the early embryonic cell cycles. Here we report that Xe-Wee1 is required for the Mos-mediated NI-phase delay. We find that Xe-Wee1 tyrosine autophosphorylation positively regulates Xe-Wee1 and is only detected in the first 30 min of the first cell cycle. The level and duration of Xe-Wee1 tyrosine phosphorylation is elevated significantly when the first cell cycle is elongated with nondegradable Mos. Importantly, we show that the tyrosine phosphorylation of Xe-Wee1 is required for the Mos-mediated M-phase delay. These findings indicate that Mos positively regulates Xe-Wee1 to generate the G(2) phase in the first cell cycle and establish a direct link between the MAPK signal transduction pathway and Wee1 in vertebrates. C1 NCI, Frederick Canc Res & Dev Ctr, Div Basic Sci, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, ABL, Basic Res Program, Frederick, MD 21702 USA. RP Vande Woude, GF (reprint author), NCI, Frederick Canc Res & Dev Ctr, Div Basic Sci, Frederick, MD 21702 USA. EM woude@ncifcrf.gov NR 90 TC 30 Z9 30 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 EI 1549-5477 J9 GENE DEV JI Genes Dev. PD MAR 1 PY 1999 VL 13 IS 5 BP 620 EP 631 DI 10.1101/gad.13.5.620 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 176QK UT WOS:000079163100012 PM 10072389 ER PT J AU Cormack, BP Falkow, S AF Cormack, BP Falkow, S TI Efficient homologous and illegitimate recombination in the opportunistic yeast pathogen Candida glabrata SO GENETICS LA English DT Article ID SACCHAROMYCES-CEREVISIAE; TOPOISOMERASE-I; GENES; DNA; TRANSFORMATION; PREFERENCE; CLONING; CONSTRUCTION; INTEGRATION; VAGINITIS AB The opportunistic pathogen Candida glabrata causes significant disease in humans. To develop genetic tools to investigate the pathogenicity of this organism, we have constructed ura3 and his3 auxotrophic strains by deleting the relevant coding regions in a C. glabrata clinical isolate. Linearized plasmids carrying a Saccharomyces cerevisiae URA3 gene efficiently transformed the ura3 auxotroph to prototrophy. Homologous recombination events were observed when the linearized plasmid carried short terminal regions homologous with the chromosome. In contrast, in the absence of any chromosomal homology, the plasmid integrated by illegitimate recombination into random sites in the genome. Sequence analysis of the target sites revealed that for the majority of illegitimate transformants there was no microhomology with the integration site. Approximately 0.25% of the insertions resulted in amino acid auxotrophy, suggesting that insertion was random at a gross level. Sequence analysis suggested that illegitimate recombination is nonrandom at the single-gene level and that the integrating plasmid has a preference for inserting into noncoding regions of the genome. Analysis of the relative numbers of homologous and illegitimate recombination events suggests that C. glabrata possesses efficient systems for both homologous and nonhomologous recombination. C1 Stanford Univ, Sch Med, Dept Microbiol & Immunol, Stanford, CA 94305 USA. NIAID, Rocky Mt Labs, Hamilton, MT 59840 USA. RP Cormack, BP (reprint author), Johns Hopkins Med Sch, Dept Mol Biol & Genet, PCTB 522,725 N Wolfe St, Baltimore, MD 21205 USA. NR 24 TC 96 Z9 102 U1 0 U2 2 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD MAR PY 1999 VL 151 IS 3 BP 979 EP 987 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 173DN UT WOS:000078966100007 PM 10049916 ER PT J AU Southard-Smith, EM Angrist, M Ellison, JS Agarwala, R Baxevanis, AD Chakravarti, A Pavan, WJ AF Southard-Smith, EM Angrist, M Ellison, JS Agarwala, R Baxevanis, AD Chakravarti, A Pavan, WJ TI The Sox10(Dom) mouse: Modeling the genetic variation of Waardenburg-Shah (WS4) syndrome SO GENOME RESEARCH LA English DT Article ID ENDOTHELIN-B RECEPTOR; LINKAGE ANALYSIS; SOX GENES; MEGACOLON; SEQUENCE; MUTATION; DISEASE; DOMAIN; MICE; MELANOCYTES AB Hirschsprung disease (HSCR) is a multigenic neurocristopathy clinically recognized by aganglionosis of the distal gastrointestinal tract. Patients presenting with aganglionosis in association with hypopigmentation are classified as Waardenburg syndrome type 4 (Waardenburg-Shah, WS4). Variability in the disease phenotype of WS4 patients with equivalent mutations suggests the influence of genetic modifier loci in this disorder. Sox10(Dom)/+ mice exhibit variability of aganglionosis and hypopigmentation influenced by genetic background similar to that observed in WS4 patients. We have constructed Sox10(Dom)/+ congenic lines to segregate loci that modify the neural crest defects in these mice. Consistent with previous studies, increased lethality of Sox10(Dom)/+ animals resulted From a C57BL/6J locus(i). However, we also observed an increase in hypopigmentation in conjunction with a C3HeB/FeJLe-a/a locus(i). Linkage analysis localized a hypopigmentation modifier of the Dom phenotype to mouse chromosome 10 in close proximity to a previously reported modifier of hypopigmentation for the endothelin receptor B mouse model of WS4. To evaluate further the role of SOX10 in development and disease, we have performed comparative genomic analyses. An essential role for this gene in neural crest development is supported by zoo blot hybridizations that reveal extensive conservation throughout vertebrate evolution and by similar Northern blot expression profiles between mouse and man. Comparative sequence analysis of the mouse and human SOX10 gene have defined the exon-intron boundaries of SOX10 and facilitated mutation analysis leading to the identification of two new SOX10 mutations in individuals with WS4. Structural analysis of the HMG DNA-binding domain was performed to evaluate the effect of human mutations in this region. C1 NIH, Genet Dis Res Branch, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA. NIH, Genome Technol Branch, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. Case Western Reserve Univ, Ctr Human Genet, Cleveland, OH 44106 USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. RP Pavan, WJ (reprint author), NIH, Genet Dis Res Branch, Natl Human Genome Res Inst, Bldg 10, Bethesda, MD 20892 USA. RI Southard-Smith, Michelle/C-3488-2012 FU NICHD NIH HHS [HD28088] NR 36 TC 105 Z9 106 U1 1 U2 6 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD MAR PY 1999 VL 9 IS 3 BP 215 EP 225 PG 11 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 177JB UT WOS:000079205900001 PM 10077527 ER PT J AU Paavola, P Avela, K Horelli-Kuitunen, N Barlund, M Kallioniemi, A Idanheimo, N Kyttala, M de la Chapelle, A Palotie, A Lehesjoki, AE Peltonen, L AF Paavola, P Avela, K Horelli-Kuitunen, N Barlund, M Kallioniemi, A Idanheimo, N Kyttala, M de la Chapelle, A Palotie, A Lehesjoki, AE Peltonen, L TI High-resolution physical and genetic mapping of the critical region for Meckel syndrome and Mulibrey Nanism on chromosome 17q22-q23 SO GENOME RESEARCH LA English DT Article ID HUMAN GENOME; FIBER-FISH; LINKAGE-DISEQUILIBRIUM; INSITU HYBRIDIZATION; MAP; DNA; ASSIGNMENT; DISEASE; CLONING; LOCUS AB Previously, we assigned the genes For two autosomal recessive disorders, Meckel syndrome (MKS; MIM 249000) and Mulibrey Nanism [MUL (muscle-liver-brain-eye Nanism) MIM 253250] that are enriched in the Finnish population, to overlapping genomic regions on chromosome 17q. Now, we report the construction of a bacterial clone contig over the critical region for both disorders. Several novel CA-repeat markers were isolated from these clones, which allowed refined mapping of the MKS and MUL loci using haplotype and linkage disequilibrium analysis. The localization of the MKS locus was narrowed to <1 cM between markers D17S1290 and 132-CA, within an similar to 800-kb region. The MUL locus was refined into an similar to 1400-kb interval between markers D17S1290 and 52-CA. The whole MKS region falls within the MUL region. In the common critical region, the conserved haplotypes were different in MKS and MUL patients. A trancript map was constructed by assigning expressed sequence tags (ESTs) and genes, derived from the human gene map, to the bacterial clone contig. Altogether, four genes and a total of 20 ESTs were precisely localized. These data provide the molecular tools for the final identification of the MKS and the MUL genes. C1 Univ Helsinki, Dept Med Genet, Haartman Inst, Helsinki 00014, Finland. Folkhalsan Inst Genet, Helsinki 00280, Finland. Univ Helsinki, Dept Clin Chem & Biomed, Helsinki 00029, Finland. Univ Helsinki, Cent Hosp, Dept Lab, Helsinki 00029, Finland. NIH, Canc Genet Lab, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. Ohio State Univ, Coll Med, Ctr Comprehens Canc, Columbus, OH 43210 USA. Natl Publ Hlth Inst, Dept Human Mol Genet, SF-00300 Helsinki, Finland. RP Lehesjoki, AE (reprint author), Univ Helsinki, Dept Med Genet, Haartman Inst, Haartmaninkatu 3, Helsinki 00014, Finland. EM Anna-Elina.Lehesjoki@helsinki.fi; LPeltonen@mednet.ucla.edu OI Kallioniemi, Anne/0000-0003-3552-8158 NR 40 TC 17 Z9 18 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD MAR PY 1999 VL 9 IS 3 BP 267 EP 276 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 177JB UT WOS:000079205900007 PM 10077533 ER PT J AU Lubin, JH AF Lubin, JH TI Comment on "On the discrepancies between epidemiologic studies of lung cancer and residential radon and Cohen's ecologic regression" - Response SO HEALTH PHYSICS LA English DT Letter C1 NCI, Div Epidemiol & Genet, Bethesda, MD 20892 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 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 1999 VL 76 IS 3 BP 317 EP 318 PG 2 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 166BQ UT WOS:000078556700018 ER PT J AU Stachlewitz, RF Seabra, V Bradford, B Bradham, CA Rusyn, I Germolec, D Thurman, RG AF Stachlewitz, RF Seabra, V Bradford, B Bradham, CA Rusyn, I Germolec, D Thurman, RG TI Glycine and uridine prevent D-galactosamine hepatotoxicity in the rat: Role of Kupffer cells SO HEPATOLOGY LA English DT Article ID TUMOR NECROSIS FACTOR; LIVER; APOPTOSIS; DEATH; ENDOTOXIN; HEPATITIS; MACROPHAGES; HEPATOCYTES; MECHANISM; ADHERENCE AB Extrahepatic factors, such as increased gut permeability and bacteria from the gut, have been shown to play a role in D-galactosamine toxicity in rats. Because bacterial endotoxin activates Kupffer cells, the purpose of this study was to clarify the role of Kupffer cells in the mechanism of D-galactosamine hepatotoxicity in rats and determine whether uridine, a compound that rescues animals from D-galactosamine toxicity, affects Kupffer cells. Rats were fed control or glycine (5%) containing diets to prevent Kupffer cell activation or treated with gadolinium chloride (GdCl3, 20 mg/kg) to destroy Kupffer cells selectively before injection of D-galactosamine (500 mg/kg, intraperitoneally). D-galactosamine caused panlobular focal hepatocellular necrosis, polymorphonuclear cell infiltration, and increased serum transaminases significantly at 24 hours. Dietary glycine or pretreatment with GdCl3 prevented these effects. D-galactosamine caused a transient increase in circulating endotoxin that was maximal at 1 hour and was blunted significantly by dietary glycine, Additionally, antisera to tumor necrosis factor-alpha (TNF-alpha) prevented hepatotoxicity caused by D-galactosamine, Moreover, apoptosis in hepatocytes caused by D-galactosamine occurred before necrosis (6 hours) and was prevented by glycine, GdCl3, TNF-alpha antiserum, and uridine. Thus, it was hypothesized that TNF-alpha from Kupffer cells causes apoptosis after D-galactosamine administration in the rat, Indeed, increases in TNF-alpha. messenger RNA (mRNA) were detected as early as 2.5 hours after D-galactosamine treatment. Previous work proposed that uridine blocks D-galactosamine toxicity by preventing inhibition of mRNA synthesis. In view of these results, the possibility that uridine might affect Kupffer cells was investigated. Uridine significantly blunted the increase in [Ca2+](i) and release of TNF-alpha caused by endotoxin in isolated Kupffer cells and prevented apoptosis caused by D-galactosamine treatment in vivo. These data support the hypothesis that uridine prevents D-galactosamine hepatotoxicity not only by rescuing the hepatocyte in the late phases of the injury but also preventing TNF-alpha release from Kupffer cells thereby blocking apoptosis that occurs early after D-galactosamine treatment. Taken together, these data strongly support the role of Kupffer cell activation by endotoxin early after D-galactosamine treatment as an important event in the mechanism of hepatotoxicity in the rat. C1 Univ N Carolina, Dept Pharmacol, Hepatobiol & Toxicol Lab, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA. Univ N Carolina, Curriculum Toxicol, Chapel Hill, NC 27599 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Univ N Carolina, Dept Pharmacol, Hepatobiol & Toxicol Lab, CB 7365, Chapel Hill, NC 27599 USA. EM thurman@med.unc.edu RI Rusyn, Ivan/S-2426-2016 FU NIAAA NIH HHS [AA03624] NR 38 TC 102 Z9 112 U1 0 U2 3 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 1999 VL 29 IS 3 BP 737 EP 745 DI 10.1002/hep.510290335 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 172FB UT WOS:000078911700018 PM 10051475 ER PT J AU Lorenz, MGO Kantor, JA Schlom, J Hodge, JW AF Lorenz, MGO Kantor, JA Schlom, J Hodge, JW TI Induction of anti-tumor immunity elicited by tumor cells expressing a murine LFA-3 analog via a recombinant vaccinia virus SO HUMAN GENE THERAPY LA English DT Article ID T-CELLS; CYTOLYTIC ACTIVITY; LYMPHOCYTE-T; CD2; RECEPTOR; COSTIMULATION; ACTIVATION; LIGAND; IMMUNOGENICITY; SPECIFICITY AB T cell activation requires binding of the T cell receptor to the major histocompatibility molecule-peptide complex in the presence of adhesion and/or costimulatory molecules such as B7-1 (CD80), B7-2 (CD86), ICAM-1 (CD54), and CD2. The major ligand of CD2 is CD48, the murine analog of human leukocyte function-associated antigen 3 (LFA-3). To determine the effect of LFA-3 expression on the immunogenicity of tumor cells, we constructed a recombinant vaccinia virus containing the murine LFA-3 gene (designated rV-LFA-3). rVLFA-3 was shown to be functional in vitro in terms of expression of LFA-3, T cell proliferation, adhesion, and cytotoxicity. Subcutaneous inoculation of rV-LFA-3-infected murine colon adenocarcinoma tumor cells (MC38) into immunocompetent syngeneic C57BL/6 mice resulted in complete lack of tumor growth. Inoculation of MC38 cells infected with equal doses of control wild-type vaccinia virus resulted in tumor growth in all animals. In addition, partial immunological protection was demonstrated against subsequent challenge with uninfected parental tumor cells up to 56 days after vaccination with rV-LFA-3-infected cells, Anti-tumor memory was also demonstrated by using gamma-irradiated MC38 cells and cells from another carcinoma model (CT26), These studies demonstrate that expression of LFA-3 via a poxvirus vector can be used to induce antitumor immunity. C1 NCI, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, 10 Ctr Dr,Bldg 10,Room 8B07, Bethesda, MD 20892 USA. EM js141c@nih.gov RI Hodge, James/D-5518-2015 OI Hodge, James/0000-0001-5282-3154 NR 32 TC 19 Z9 19 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD MAR 1 PY 1999 VL 10 IS 4 BP 623 EP 631 DI 10.1089/10430349950018698 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 175RG UT WOS:000079108300009 PM 10094205 ER PT J AU Sellers, SE Tisdale, JF Bodine, DM Williams, DA Karlsson, S Meztger, M Donahue, RE Dunbar, CE AF Sellers, SE Tisdale, JF Bodine, DM Williams, DA Karlsson, S Meztger, M Donahue, RE Dunbar, CE TI No discrepancy between in vivo gene marking efficiency assessed in peripheral blood populations compared with bone marrow progenitors or CD34(+) cells SO HUMAN GENE THERAPY LA English DT Article ID COLONY-STIMULATING FACTOR; HEMATOPOIETIC STEM-CELLS; IN-VIVO; RETROVIRAL VECTORS; NONHUMAN-PRIMATES; AUTOLOGOUS TRANSPLANTATION; GROWTH-FACTORS; EXPRESSION; TRANSDUCTION; LEUKEMIA AB Reports of 1- to 2-log higher gene transfer levels in purified CD34(+) cells or marrow CFU compared with levels in mature circulating blood cells after transplantation of retrovirally transduced primitive human hematopoietic cells have resulted in concern that transduced progenitors do not contribute proportionally to ongoing hematopoiesis (Kohn et al,, 1995; Brenner, 1996), To study the issue in a relevant large animal, we analyzed samples of mature blood cells, marrow CD34-enriched cells and marrow CD34-depleted cells, and marrow CFU from a cohort of 11 rhesus transplanted with retrovirally transduced cells and followed for up to 5.5 years. They were transplanted with CD34-enriched bone marrow (BM) or G-CSF/SCF-mobilized peripheral blood (PB) cells transduced with vectors containing either neo, human glucocerebrosidase, or murine adenosine deaminase genes. There were no significant differences between the levels of vector sequences found in BM CD34(+) cells, BM CD34(-) cells, PB granulocytes, or PB mononuclear cells (MNCs) in any animal. In four animals transplanted with SCF/G-CSF-primed BM cells and analyzed 3-6 months posttransplantation, the percentage of CFU containing the neo vector appeared to be 1 log higher than the representation of marked cells in the PB of these animals, but this discrepancy did not persist at time points greater than 6 months posttransplantation. The level of CFU marking was no higher than PB granulocyte or MNC marking at any time points in the other animals. Low levels of mature gene-modified cells probably reflect poor transduction of repopulating stem cells, not a block in differentiation or specific immune rejection of mature cells. This study represents the longest follow-up of primates transplanted with transduced hematopoietic cells, and it is encouraging that the levels of vector-containing cells appear stable for up to 5 years. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Hematopoiesis Sect, NIH, Bethesda, MD 20892 USA. Indiana Univ, Sch Med, Indianapolis, IN 46202 USA. Univ Lund, Lund, Sweden. RP Dunbar, CE (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,Room 7C103,9000 Rockville Pike, Bethesda, MD 20892 USA. EM dunbarc@gwgate.nhlbi.nih.gov NR 35 TC 13 Z9 13 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD MAR 1 PY 1999 VL 10 IS 4 BP 633 EP 640 DI 10.1089/10430349950018706 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 175RG UT WOS:000079108300010 PM 10094206 ER PT J AU Puhlmann, M Gnant, M Brown, CK Alexander, HR Bartlett, DL AF Puhlmann, M Gnant, M Brown, CK Alexander, HR Bartlett, DL TI Thymidine kinase-deleted vaccinia virus expressing purine nucleoside phosphorylase as a vector for tumor-directed gene therapy SO HUMAN GENE THERAPY LA English DT Article ID PROMOTERS; CANCER; CELLS AB Tumor-directed gene therapy faces many obstacles. Lack of tissue targeting and low in vivo transduction efficiency represent some of the limitations for a successful therapeutic outcome. A thymidine kinase-deleted mutant vaccinia virus has been shown in marker studies to replicate selectively in tumor tissue in animal models. Purine nucleoside phosphorylase (PNP), from E. coli, converts the nontoxic prodrug 6-methylpurine deoxyriboside (6-MPDR) to the toxic purine 6-methylpurine. In this study, we investigated the cytotoxic properties of PNP, expressed by an optimized synthetic early/late promoter in a vaccinia virus (vMPPNP). In vitro cytotoxicity of psoralen-inactivated vMPPNP (1 mu g of psoralen, 4 min of LWUV [365 nm]) at the maximum tolerated dose (MTD) of 6-MPDR (80 mu M) reduced cell viability by day 3 to 1.7%. At an MOI of 0.002, replication-competent vMPPNP and 6-MPDR (80 mu M) caused reduction of cell viability to 19.8% within 4 days. Furthermore, there was complete abrogation of viral replication after intracellular conversion of prodrug into the active toxin. The potency of such a system was similar among all histologies tested. Finally, the cytotoxic efficacy has been shown to be more rapid and complete than that of cytosine deaminase (CD), a more established enzyme/prodrug system. When virus was delivered intraperitoneally into athymic mice with hepatic metastases, followed by administration of prodrug, there was a significant prolongation of survival and a 30% cure rate. In summary, owing to its tumor-targeting capabilities, high transduction efficiency, and high gene expression, a vaccinia virus expressing PNP could prove to be a potent and valuable vector for tumor-targeted gene therapy. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Bartlett, DL (reprint author), NCI, Surg Branch, NIH, Bldg 10,Rm 2B17,10 Ctr Dr, Bethesda, MD 20892 USA. EM dbart@nih.gov OI Gnant, Michael/0000-0003-1002-2118 NR 18 TC 65 Z9 66 U1 0 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 EI 1557-7422 J9 HUM GENE THER JI Hum. Gene Ther. PD MAR 1 PY 1999 VL 10 IS 4 BP 649 EP 657 DI 10.1089/10430349950018724 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 175RG UT WOS:000079108300012 PM 10094208 ER PT J AU Li, SSL Tseng, HM Yang, TP Liu, CH Teng, SJ Huang, HW Chen, LM Kao, HW Chen, JH Tseng, JN Chen, A Hou, MF Huang, TJ Chang, HT Mok, KT Tsai, JH AF Li, SSL Tseng, HM Yang, TP Liu, CH Teng, SJ Huang, HW Chen, LM Kao, HW Chen, JH Tseng, JN Chen, A Hou, MF Huang, TJ Chang, HT Mok, KT Tsai, JH TI Molecular characterization of germline mutations in the BRCA1 and BRCA2 genes from breast cancer families in Taiwan SO HUMAN GENETICS LA English DT Article ID OVARIAN-CANCER; SUSCEPTIBILITY GENE AB A total of 18 families with multiple cases of breast cancer were identified from southern Taiwan, and 5 of these families were found to carry cancer-associated germline mutations in the BRCA1 and BRCA2 genes. One novel cryptic splicing mutation of the BRCA1 gene, found in two unrelated families, was shown to be a deletion of 10 bp near the branch site in intron 7. This mutation causes an insertion of 59 nucleotides derived from intron 7 and results in a frameshift, leading to premature translational termination of BRCA1 mRNA in exon 8. Deletions of 2670delC, 3073delT and 6696-7delTC in the BRCA2 gene were found in three other breast cancer families. All three deletions are predicted to generate frameshifts and to result in the premature termination of BRCA2 protein translation. Several genetic polymorphisms in both BRCA1 and BRCA2 genes were also detected in this investigation. C1 Natl Sun Yat Sen Univ, Inst Biomed Sci, Kaohsiung 80424, Taiwan. NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. Kaohsiung Med Coll, Dept Surg, Kaohsiung, Taiwan. Kaohsiung Med Coll, Dept Internal Med, Kaohsiung, Taiwan. Vet Gen Hosp, Dept Surg, Kaohsiung, Taiwan. RP Li, SSL (reprint author), Natl Sun Yat Sen Univ, Inst Biomed Sci, Kaohsiung 80424, Taiwan. RI Hou, Ming-Feng/D-5506-2009 NR 20 TC 41 Z9 48 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD MAR PY 1999 VL 104 IS 3 BP 201 EP 204 DI 10.1007/s004390050936 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 190DR UT WOS:000079947300001 PM 10323242 ER PT J AU Currier, JR Stevenson, KS Kehn, PJ Zheng, K Hirsch, VM Robinson, MA AF Currier, JR Stevenson, KS Kehn, PJ Zheng, K Hirsch, VM Robinson, MA TI Contributions of CD4(+), CD8(+), and CD4(+)CD8(+) T cells to skewing within the peripheral T cell receptor beta chain repertoire of healthy macaques SO HUMAN IMMUNOLOGY LA English DT Article DE macaque; T lymphocytes; T cell receptors; TCR repertoire; double-positive T cells ID SIMIAN IMMUNODEFICIENCY VIRUS; PRIMARY IMMUNE-RESPONSE; RHESUS-MONKEYS; RHEUMATOID-ARTHRITIS; ANTIGEN RECEPTOR; MONOCLONAL-ANTIBODIES; NORMAL INDIVIDUALS; IN-VIVO; LYMPHOCYTES; DIVERSITY AB Diversity in the peripheral T cell receptor repertoire of rhesus (Macaca mulatta) and pig-tailed macaques (Macaca nemestrina) has been studied by examining the profile of CDR3 lengths in TCR beta chains. Expressed CDR3 length distribution profiles for individual TCRBV families were obtained from total peripheral blood mononuclear cells (PBMC) and T cell subsets isolated from PBMC. These studies reveal that the T cell receptor repertoire of PBMC from healthy macaques often exhibits skewing in TCRBV family CDR3 profiles. The skewing of TCRBV family CDR3 profiles was evident as discrete expanded length(s) and was detected in up to 50% of the PBMC profiles. Analyses of separated T cell populations demonstrated that the CD8(+) T cell subset was responsible for the majority of observed skewing in CDR3 length profiles. However, CD4(+) T cells were also shown to contribute to the skewed peripheral PBMC repertoire in these animals. While certain TCRBV families frequently displayed skewed profiles, there was no concordance in the particular CDR3 lengths expanded among the different animals. Furthermore, an additional feature of the peripheral blood of the animals studied was the presence of an unusual population of extrathymic CD4(+) and CD8(+) (double-positive)T cells (up to 9.6% in the PBMC of rhesus macaques). The double-positive T cells could be differentiated from CD4 single-positive and CD8 single-positive T cells by their increased surface expression of LFA-1 and decreased CD62L expression. The percentage of the double-positive T cells was higher in rhesus than pig-tailed macaques and contributed substantially to the peripheral T cell repertoire. Human Immunology 60, 209-222 (1999). (C) American Society for Histocompatibility and Immunogenetics, 1999 Published by Elsevier Science Inc. C1 NIAID, Immunogenet Lab, Rockville, MD 20852 USA. NIAID, Mol Microbiol Lab, Rockville, MD 20852 USA. RP Robinson, MA (reprint author), NIAID, Immunogenet Lab, Twinbrook 2 Facil,12441 Parklawn Dr, Rockville, MD 20852 USA. NR 39 TC 22 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD MAR PY 1999 VL 60 IS 3 BP 209 EP 222 DI 10.1016/S0198-8859(98)00109-8 PG 14 WC Immunology SC Immunology GA 188VW UT WOS:000079870800004 PM 10321957 ER PT J AU Schilling, G Becher, MW Sharp, AH Jinnah, HA Duan, K Kotzuk, JA Slunt, HH Ratovitski, T Cooper, JK Jenkins, NA Copeland, NG Price, DL Ross, CA Borchelt, DR AF Schilling, G Becher, MW Sharp, AH Jinnah, HA Duan, K Kotzuk, JA Slunt, HH Ratovitski, T Cooper, JK Jenkins, NA Copeland, NG Price, DL Ross, CA Borchelt, DR TI Intranuclear inclusions and neuritic aggregates in transgenic mice expressing a mutant N-terminal fragment of huntingtin SO HUMAN MOLECULAR GENETICS LA English DT Article ID HD GENE; NEURODEGENERATIVE DISEASES; NEUROLOGICAL PHENOTYPE; OXIDATIVE STRESS; CAG REPEATS; IN-VIVO; DISORDERS; PROTEIN; PRESENILIN-1; DYSFUNCTION AB Huntington's disease (HD) is an inherited, neurodegenerative disorder caused by the expansion of a glutamine repeat in the N-terminus of the huntingtin protein. To gain insight into the pathogenesis of HD, we generated transgenic mice that express a cDNA encoding an N-terminal fragment (171 amino acids) of huntingtin with 82, 44 or 18 glutamines, Mice expressing relatively low steady-state levels of N171 huntingtin with 82 glutamine repeats (N171-82Q) develop behavioral abnormalities, including loss of coordination, tremors, hypokinesis and abnormal gait, before dying prematurely. In mice exhibiting these abnormalities, diffuse nuclear labeling, intranuclear inclusions and neuritic aggregates, all immunoreactive with an antibody to the N-terminus (amino acids 1-17) of huntingtin (AP194), were found in multiple populations of neurons. None of these behavioral or pathological phenotypes were seen in mice expressing N171-18Q, These findings are consistent with the idea that N-terminal fragments of huntingtin with a repeat expansion are toxic to neurons, and that N-terminal fragments are prone to form both intranuclear inclusions and neuritic aggregates. C1 Johns Hopkins Univ, Dept Pathol, Div Neuropathol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Dept Psychiat, Baltimore, MD 21205 USA. Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Dept Neurosci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Program Cellular & Mol Med, Baltimore, MD 21205 USA. NCI, Ctr Canc, Mammalian Genet Lab, Frederick, MD USA. RP Borchelt, DR (reprint author), Johns Hopkins Univ, Dept Pathol, Div Neuropathol, Baltimore, MD 21205 USA. EM drbor@welchlink.welch.jhu.edu RI Ross, Christopher/H-8395-2013 FU NINDS NIH HHS [NS16375] NR 34 TC 487 Z9 497 U1 0 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAR PY 1999 VL 8 IS 3 BP 397 EP 407 DI 10.1093/hmg/8.3.397 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 173VH UT WOS:000079000100002 PM 9949199 ER PT J AU Sneige, N Lagios, MD Schwarting, R Colburn, W Atkinson, E Weber, D Sahin, A Kemp, B Hoque, A Risin, S Sabichi, A Boone, C Dhingra, K Kelloff, G Lippman, S AF Sneige, N Lagios, MD Schwarting, R Colburn, W Atkinson, E Weber, D Sahin, A Kemp, B Hoque, A Risin, S Sabichi, A Boone, C Dhingra, K Kelloff, G Lippman, S TI Interobserver reproducibility of the Lagios nuclear grading system for ductal carcinoma in situ SO HUMAN PATHOLOGY LA English DT Article; Proceedings Paper CT 87th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 28-MAR 06, 1998 CL BOSTON, MASSACHUSETTS SP US & Canadian Acad Pathol DE ductal carcinoma in situ; nuclear grade; interobserver reproducibility; breast carcinoma ID IN-SITU; BREAST-CANCER; AGREEMENT; INSITU; IRRADIATION AB Several studies have shown an association between high nuclear grade or necrosis of ductal carcinoma in situ (DCIS) lesions and the risk of local disease recurrence in patients with DCIS treated surgically with less than mastectomy. Although criteria for separating low from high nuclear grade lesions have been published, no information exists regarding interobserver reproducibility (IR). To assess IR in the classification of DCIS, six surgical pathologists from four institutions used the Lagios grading system to grade 125 DCIS lesions. Before meeting to evaluate the cases, a training set of 12 glass slides, including cases chosen to present conflicting cues for classification, was mailed to the participants with a written criteria summary. This was followed by a working session in which criteria were reviewed and agreed on. The pathologists then graded the lesions independently. The area of interest was marked on each slide before grading. After initial grading, the pathologists met again to resolve discrepant lesion classifications. A complete agreement among raters was achieved in 43 (35%) cases, with five of six raters agreeing in another 45 (36%) cases. In no case did two raters differ by more than one grade. The pairwise kappa agreement values ranged from fair:to substantial (0.30 to 0.61). Generalized kappa value indicated moderate agreement (0.46, standard error = 0.02). kappa statistics for the distinction between grades 1 and 2 and 2 and 3 were 0.29 and 0.48, respectively, (standard error = 0.02). Only one of the six raters differed significantly in scoring. With adherence to specific criteria, IR in the classification of DCIS cases can be obtained in most cases. Although these pathologists made a few grading system modifications, further refinements are needed, especially if grading will influence future therapy. HUM PATHOL 30:257-262. Copyright (C) 1999 by W.B. Saunders Company. C1 Univ Texas, MD Anderson Canc Ctr, Dept Anat Pathol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Biomath, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Clin Canc Prevent, Houston, TX 77030 USA. St Marys Med Sch, Breast Canc Consultat Serv, San Francisco, CA USA. Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. Tarzana Med Ctr, Dept Pathol, Tarzana, CA USA. NCI, Div Canc Prevent & Control, Chemoprevent Branch, Bethesda, MD 20892 USA. Eli Lilly Corp, Indiana, IN USA. RP Sneige, N (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Anat Pathol, Box 53,1515 Holcombe Blvd, Houston, TX 77030 USA. FU NCI NIH HHS [N0I-CN-65004] NR 23 TC 35 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 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD MAR PY 1999 VL 30 IS 3 BP 257 EP 262 DI 10.1016/S0046-8177(99)90002-3 PG 6 WC Pathology SC Pathology GA 174TM UT WOS:000079051400003 PM 10088542 ER PT J AU Shen, TL Park, WS Boni, R Saini, N Pham, T Lash, AE Vortmeyer, AO Zhuang, ZP AF Shen, TL Park, WS Boni, R Saini, N Pham, T Lash, AE Vortmeyer, AO Zhuang, ZP TI Detection of loss of heterozygosity on chromosome 9q22.3 in microdissected sporadic basal cell carcinoma SO HUMAN PATHOLOGY LA English DT Article DE basal cell carcinoma; loss of heterozygosity; Drosophila patched; chromosome 9 ID TUMOR-SUPPRESSOR GENE; HUMAN HOMOLOG; PCR CONTAMINATION; BREAST; CANCER; LIGHT AB Identification of loss of heterozygosity (LOH) at specific genetic loci in cancer cells suggests the presence of a tumor suppressor gene within the deleted region. A basal cell carcinoma (BCC) susceptibility gene, human homolog of drosophila patched (PTC), has been recently cloned and localized on chromosome 9q22.3. Mutation and deletion of this region has been reported in BCCs using frozen tumor tissue. The objective of this study was to test whether LOH of human PTC on chromosome 9q22 could be detected in archival sporadic BCCs. We studied 20 randomly selected sporadic BCCs by microdissection and polymerase chain reaction using paraffin-embedded, formalin-fixed material on glass slides. In all cases, analysis was performed with the polymorphic markers D9S53, D9S15, D9S287, and D9S303. The LOH frequencies were 30%, 42%, 56%, and 75% with D9S15, D9S287, D9S53, and D9S303, respectively. LOH at 9q22 was identified in 12 of 20 cases (60%) with at least one marker. Seven cases showed LOH with two markers, two cases with three markers, and one case showed LOH with all four markers. The results indicate that BCC LOH can be frequently identified in paraffin-embedded BCC after routine processing. HUM PATHOL 30:284-287. This is a US government work. There are no restrictions on its use. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Vet Hosp, Dept Pathol, Washington, DC USA. George Washington Univ, Dept Pathol, Washington, DC USA. RP Zhuang, ZP (reprint author), NCI, Pathol Lab, NIH, Bldg 10,Room 2A33,9000 Rockville Pike, Bethesda, MD 20892 USA. OI Lash, Alex/0000-0003-3787-1590 NR 19 TC 30 Z9 30 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD MAR PY 1999 VL 30 IS 3 BP 284 EP 287 DI 10.1016/S0046-8177(99)90006-0 PG 4 WC Pathology SC Pathology GA 174TM UT WOS:000079051400007 PM 10088546 ER PT J AU Kumar, S Pack, S Kumar, D Walker, R Quezado, M Zhuang, ZP Meltzer, P Tsokos, M AF Kumar, S Pack, S Kumar, D Walker, R Quezado, M Zhuang, ZP Meltzer, P Tsokos, M TI Detection of EWS-FLI-1 fusion in Ewing's sarcoma peripheral primitive neuroectodermal tumor by fluorescence in situ hybridization using formalin-fixed paraffin-embedded tissue SO HUMAN PATHOLOGY LA English DT Article DE Ewing's sarcoma; t(11;22); fluorescence in situ hybridization; reverse-transcriptase polymerase chain reaction (RT-PCR); formalin-fixed tissue ID ROUND-CELL TUMORS; ALVEOLAR RHABDOMYOSARCOMA; CHROMOSOME-TRANSLOCATION; CHIMERIC TRANSCRIPTS; INSITU HYBRIDIZATION; DNA CONTENT; NEUROEPITHELIOMA; DIAGNOSIS; FAMILY; GENE AB The balanced translocation t(11;22)(q24;q12) is specific for the Ewings sarcoma/peripheral primitive neuroectodermal tumors (ES/PNETs) and results in the EWS/FLI-1 fusion transcript, which can be detected by reverse transcription polymerase chain reaction (RT-PCR). Recent studies also have used fluorescence in situ hybridization (FISH) to show the translocation; however, most of these have been performed on cell lines or touch preparations and short-term cultures of tumors. Moreover, the existing probes generally have shown only the break in the specific chromosomes rather than the translocation itself. We describe our findings with a new set of probes that localize to 22q12 (EWS) and 11q24 (FLI-1) and directly show the translocation as juxtaposed red-green signals on der(22) in nuclei extracted from formalin-fixed, paraffin-embedded tissues. After establishing the specificity of the probes (on metaphase spreads and interphase nuclei in two translocation-positive cell lines and normal peripheral blood lymphocytes), we evaluated 11 ES/PNETs and 10 other tumors (four alveolar rhabdomyosarcomas, three neuroblastomas, two lymphomas, one extramedullary myeloid tumor) using a two-color FISH assay. All 11 ES/PNETs showed fusion signals in 20% to 80% of evaluable nuclei. In two lymphoma cases, random overlapping signals were present in 2% and 4% of nuclei, whereas the remaining eight tumors were negative. The presence of t(11;22) was confirmed by RT-PCR in 10 of 11 ES/PNETs. We conclude that FISH analysis with this newly designed probe pair is a specific and sensitive method of detecting t(11;22) on routinely processed tissue and can be useful in the differential diagnosis of ES/PNETs from other small round blue cell tumors when only fixed tissue is available. HUM PATHOL 30:324-330. Copyright (C) 1999 by W.B. Saunders Company. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NIH, Canc Genet Branch, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. RP Kumar, S (reprint author), NCI, Pathol Lab, NIH, Bldg 10,Room 2N202,10 Ctr Dr,MSC 1500, Bethesda, MD 20892 USA. RI Pack, Svetlana/C-2020-2014 NR 26 TC 58 Z9 60 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD MAR PY 1999 VL 30 IS 3 BP 324 EP 330 DI 10.1016/S0046-8177(99)90012-6 PG 7 WC Pathology SC Pathology GA 174TM UT WOS:000079051400013 PM 10088552 ER PT J AU Greenhouse, S Castle, PE Dean, J AF Greenhouse, S Castle, PE Dean, J TI Antibodies to human ZP3 induce reversible contraception in transgenic mice with 'humanized' zonae pellucidae SO HUMAN REPRODUCTION LA English DT Article DE contraception; human ZP3; knockout mice; monoclonal antibodies; spermatozoon-ovum interactions ID ZONA-PELLUCIDA-3 PEPTIDE VACCINE; SPERM-EGG INTERACTION; MONOCLONAL-ANTIBODIES; RECEPTOR ACTIVITY; MOUSE OOCYTES; FEMALE MICE; PROTEIN; GENES; FERTILIZATION; IDENTIFICATION AB The initial spermatozoon-egg interaction of mammalian fertilization is mediated by the zona pellucida, an extracellular matrix composed of three glycoproteins (ZP1, ZP2, ZP3). These proteins are sufficiently conserved between human and mouse to form chimeric zonae pellucidae, and genetically engineered mice in which the endogenous mouse ZP3 has been replaced by human ZP3 have 'humanized' zonae, but normal fertility. Administration of monoclonal antibodies to mouse ZP3 does not affect fertility in these animals, but administration of antibodies to human ZP3 results in long-term, reversible contraception. The antibodies coat the zonae pellucidae surrounding growing oocytes within the ovary and their presence in the zona matrix inhibits, but does not eliminate, sperm binding. The contraceptive effect is attributed to steric hindrance that decreases sperm binding and prevents penetration through the zona pellucida. The resumption of fertility is associated with the disappearance of antibodies from the zona matrix, No adverse effect on mating behaviour, ovarian histology or fetal development (if administered after fertilization) is detected in treated females. These results suggest that transgenic mice expressing human proteins will prove useful in assessing contraceptive efficacy of zona epitopes in the rational design of immunocontraception directed at the human zona pellucida. C1 NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. George Washington Univ, Dept Obstet & Gynecol, Washington, DC 20037 USA. RP NIDDK, Cellular & Dev Biol Lab, NIH, Bldg 6,Room B1-26,6 Ctr Dr MSC 2715, Bethesda, MD 20892 USA. NR 38 TC 19 Z9 19 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 EI 1460-2350 J9 HUM REPROD JI Hum. Reprod. PD MAR PY 1999 VL 14 IS 3 BP 593 EP 600 DI 10.1093/humrep/14.3.593 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 180ME UT WOS:000079389100007 PM 10221681 ER PT J AU Patrick, G AF Patrick, G TI The effects of vibroacoustic music on symptom reduction SO IEEE ENGINEERING IN MEDICINE AND BIOLOGY MAGAZINE LA English DT Article ID PLACEBO C1 NIH, Recreat Therapy Rehabil Med Dept, Ctr Clin, Bethesda, MD 20892 USA. RP Patrick, G (reprint author), NIH, Recreat Therapy Rehabil Med Dept, Ctr Clin, 10 Ctr Dr,MSC 1950, Bethesda, MD 20892 USA. NR 20 TC 5 Z9 7 U1 0 U2 5 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 0739-5175 J9 IEEE ENG MED BIOL JI IEEE Eng. Med. Biol. Mag. PD MAR-APR PY 1999 VL 18 IS 2 BP 97 EP 100 DI 10.1109/51.752987 PG 4 WC Engineering, Biomedical; Medical Informatics SC Engineering; Medical Informatics GA 177VP UT WOS:000079232000014 PM 10101674 ER PT J AU Rosenberg, SA AF Rosenberg, SA TI A new era for cancer immunotherapy based on the genes that encode cancer antigens SO IMMUNITY LA English DT Review ID CYTOLYTIC T-LYMPHOCYTES; TUMOR-INFILTRATING LYMPHOCYTES; HUMAN-MELANOMA; IN-VIVO; HLA-A2 MELANOMAS; BETA-CATENIN; REGRESSION ANTIGENS; IMMUNE-RESPONSES; TYROSINASE GENE; CELL-LINES C1 NCI, Surg Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Rosenberg, SA (reprint author), NCI, Surg Branch, Div Clin Sci, NIH, Bldg 10, Bethesda, MD 20892 USA. EM sar@nih.gov NR 79 TC 433 Z9 441 U1 3 U2 20 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAR PY 1999 VL 10 IS 3 BP 281 EP 287 DI 10.1016/S1074-7613(00)80028-X PG 7 WC Immunology SC Immunology GA 181RJ UT WOS:000079455700001 PM 10204484 ER PT J AU Bhandoola, A Cibotti, R Punt, JA Granger, L Adams, AJ Sharrow, SO Singer, A AF Bhandoola, A Cibotti, R Punt, JA Granger, L Adams, AJ Sharrow, SO Singer, A TI Positive selection as a developmental progression initiated by alpha beta TCR signals that fix TCR specificity prior to lineage commitment SO IMMUNITY LA English DT Article ID T-CELL-RECEPTOR; MAJOR HISTOCOMPATIBILITY COMPLEX; THYMOCYTE DEVELOPMENT; CD4(+)CD8(+) THYMOCYTES; NEGATIVE SELECTION; TRANSGENIC MICE; CD8 LINEAGE; EXPRESSION; THYMUS; PRECURSORS AB During positive selection, immature thymocytes commit to either the CD4(+) or CD8(+) T cell lineage ("commitment") and convert from short-lived thymocytes into long-lived T cells ("rescue"). By formal precursor-progeny analysis, we now identify what is likely to be the initial positive selection step signaled by alpha beta TCR, which we have termed "induction". During induction, RAG mRNA expression is downregulated, but lineage commitment does not occur. Rather, lineage commitment (which depends upon the MHC class specificity of the alpha beta TCR) only occurs after downregulation of RAG expression and the consequent fixation of alpha beta TCR specificity. We propose that positive selection can be viewed as a sequence of increasingly selective developmental steps (induction-->commitment-->rescue) that are signaled by alpha beta TCR engagements of intrathymic ligands. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Singer, A (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 54 TC 26 Z9 26 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAR PY 1999 VL 10 IS 3 BP 301 EP 311 DI 10.1016/S1074-7613(00)80030-8 PG 11 WC Immunology SC Immunology GA 181RJ UT WOS:000079455700003 PM 10204486 ER PT J AU Zhang, WG Sommers, CL Burshtyn, DN Stebbins, CC DeJarnette, JB Trible, RP Grinberg, A Tsay, HC Jacobs, HM Kessler, CM Long, EO Love, PE Samelson, LE AF Zhang, WG Sommers, CL Burshtyn, DN Stebbins, CC DeJarnette, JB Trible, RP Grinberg, A Tsay, HC Jacobs, HM Kessler, CM Long, EO Love, PE Samelson, LE TI Essential role of LAT in T cell development SO IMMUNITY LA English DT Article ID PROTEIN-TYROSINE KINASES; KILLER NK CELLS; MICE LACKING; ANTIGEN RECEPTORS; MUTANT MICE; INHIBITORY RECEPTOR; SIGNAL-TRANSDUCTION; THYMOCYTES; CHAIN; SYK AB The linker molecule LAT is a substrate of the tyrosine kinases activated following TCR engagement. Phosphorylated LAT binds many critical signaling molecules. The central role of this molecule in TCR-mediated signaling has been demonstrated by experiments in a LAT-deficient cell line. To probe the role of LAT in T cell development, the LAT gene was disrupted by targeting. LAT-deficient mice appeared healthy. Flow cytometric analysis revealed normal B cell populations but the absence of any mature peripheral T cells. Intra; thymic development was blocked within the CD4(-)CD8(-) stage. No gross abnormality of NK or platelet function was observed. LAT is thus critical to both T cell activation and development. C1 NICHHD, Sect Lymphocyte Signaling, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. NIAID, Immunogenet Lab, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Div Hematol Oncol, Washington, DC 20007 USA. RP Samelson, LE (reprint author), NICHHD, Sect Lymphocyte Signaling, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RI Long, Eric/G-5475-2011 OI Long, Eric/0000-0002-7793-3728 NR 55 TC 406 Z9 413 U1 1 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAR PY 1999 VL 10 IS 3 BP 323 EP 332 DI 10.1016/S1074-7613(00)80032-1 PG 10 WC Immunology SC Immunology GA 181RJ UT WOS:000079455700005 PM 10204488 ER PT J AU Lucas, B Stefanova, I Yasutomo, K Dautigny, N Germain, RN AF Lucas, B Stefanova, I Yasutomo, K Dautigny, N Germain, RN TI Divergent changes in the sensitivity of maturing T cells to structurally related ligands underlies formation of a useful T cell repertoire SO IMMUNITY LA English DT Article ID PROTEIN-TYROSINE KINASE; INTERCELLULAR-ADHESION MOLECULE-1; RECEPTOR TRANSGENIC MICE; POSITIVE SELECTION; NEGATIVE SELECTION; ANTIGEN RECEPTOR; ANTAGONIST LIGANDS; THYMOCYTE SELECTION; CD4+8+ THYMOCYTES; CLONAL DELETION AB CD4(+)CD8(+) thymocyte differentiation requires TCR signaling induced by self-peptide/MHC ligands. Nevertheless, the resulting mature T cells are not activated by these self-complexes, whereas foreign ligands can be potent stimuli. Here, we show that the signaling properties of TCR change during thymocyte maturation, differentially affecting responses to related peptide/MHC molecule complexes and contributing to this discrimination. Weak agonists for CD4(+)CD8(+) thymocytes lose potency during development, accompanied by a change in TCR-associated phosphorylation from an agonist to a partial agonist/antagonist pattern. in contrast, sensitivity to strong agonists is maintained, along with full signaling. This yields a mature T cell pool highly responsive to foreign antigen while possessing a wide margin of safety against activation by self-ligands. C1 NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. Inst Necker, INSERM, U345, F-75730 Paris 15, France. RP Germain, RN (reprint author), NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 77 TC 127 Z9 127 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAR PY 1999 VL 10 IS 3 BP 367 EP 376 DI 10.1016/S1074-7613(00)80036-9 PG 10 WC Immunology SC Immunology GA 181RJ UT WOS:000079455700009 PM 10204492 ER PT J AU Plummer, FA Ball, TB Kimani, J Fowke, KR AF Plummer, FA Ball, TB Kimani, J Fowke, KR TI Resistance to HIV-1 infection among highly exposed sex workers in Nairobi: what mediates protection and why does it develop? SO IMMUNOLOGY LETTERS LA English DT Article; Proceedings Paper CT 2nd International Symposium on Immunological Correlates of Protection from HIV Infection and Disease CY APR 17-20, 1998 CL ST ANNES COLL, OXFORD, ENGLAND HO ST ANNES COLL DE HIV-1; prostitutes; MHC; resistance; immunity ID T-CELL CLONE; SCHISTOSOMA-MANSONI; MYCOBACTERIAL INFECTION; RESPONSES; SUSCEPTIBILITY; GENE; INTERLEUKIN-4; PROSTITUTES; T-HELPER-1; PROTEINS AB Variability in susceptibility to infection and disease caused by infectious agents is a characteristic of all populations. Among susceptible individuals exposed to an infection: not all become infected and among infected individuals, not all develop disease. It seems logical that variability in susceptibility to infection and disease would apply to infection and disease with human immunodeficiency viruses. However, until recently, it has been generally held that there is no natural immunity to HIV-1 and that once infected, all individuals would ultimately succumb to AIDS. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Univ Nairobi, Dept Med Microbiol, Nairobi, Kenya. Univ Manitoba, Dept Med Microbiol & Med, Winnipeg, MB R3E 0W3, Canada. NCI, Expt Immunol Branch, Lab Genom Divers, Frederick, MD 21701 USA. RP Plummer, FA (reprint author), Univ Nairobi, Dept Med Microbiol, POB 19676, Nairobi, Kenya. EM plummer@form-net.com OI Fowke, Keith/0000-0001-8227-6649 NR 47 TC 57 Z9 58 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 J9 IMMUNOL LETT JI Immunol. Lett. PD MAR PY 1999 VL 66 IS 1-3 BP 27 EP 34 DI 10.1016/S0165-2478(98)00182-5 PG 8 WC Immunology SC Immunology GA 178GU UT WOS:000079258500006 PM 10203031 ER PT J AU Haigwood, NL Pierce, CC Robertson, MN Watson, AJ Montefiori, DC Rabin, M Lynch, JB Kuller, L Thompson, J Morton, WR Benveniste, RE Hu, SL Greenberg, P Mossman, SP AF Haigwood, NL Pierce, CC Robertson, MN Watson, AJ Montefiori, DC Rabin, M Lynch, JB Kuller, L Thompson, J Morton, WR Benveniste, RE Hu, SL Greenberg, P Mossman, SP TI Protection from pathogenic SIV challenge using multigenic DNA vaccines SO IMMUNOLOGY LETTERS LA English DT Article; Proceedings Paper CT 2nd International Symposium on Immunological Correlates of Protection from HIV Infection and Disease CY APR 17-20, 1998 CL ST ANNES COLL, OXFORD, ENGLAND HO ST ANNES COLL DE HIV-1; SIV; vaccines; genetic immunization; antibody; cytokine; CTL ID SIMIAN IMMUNODEFICIENCY VIRUS; RHESUS MACAQUES; SUBUNIT VACCINES; INFECTION; RESPONSES; GP160; IMMUNIZATION; VACCINATION; INFLUENZA; PROTEIN AB To assess DNA immunization as a strategy for protecting against HIV infection in humans, we utilized SIVmne infection of Macaca fascicularis as a vaccine challenge model with moderate pathogenic potential. We compared the efficacy of DNA immunization alone and in combination with subunit protein boosts. All of the structural and regulatory genes of SIVmne clone 8 were cloned into mammalian expression vectors under the control of the CMV IE-1 promoter. Eight M. fascicularis were immunized twice with 3 mg of plasmid DNA divided between two sites; intramuscular and intradermal. Four primed macaques received a further two DNA immunizations at weeks 16-36, while the second group of four were boosted with 250 mu g recombinant gp160 plus 250 mu g recombinant Gag-Pol particles formulated in MF-59 adjuvant. Half of the controls received four immunizations of vector DNA; half received two vector DNA and two adjuvant immunizations. As expected, humoral immune responses were stronger in the macaques receiving subunit boosts, but responses were sustained in bath groups. Significant neutralizing antibody titers to SIVmne were detected in one of the subunit-boosted animals and in none of the DNA-only animals prior to challenge. T-cell proliferative responses to gp160 and to Gag were detected in all immunized animals after three immunizations, and these responses increased after four immunizations. Cytokine profiles in PHA-stimulated PBMC taken on the day of challenge showed trends toward Th1 responses in 2/4 macaques in the DNA vaccinated group and in 1/4 of the DNA plus subunit vaccinated macaques; Th2 responses in 3/4 DNA plus subunit-immunized macaques; and Th0 responses in 4/4 controls. In bulk CTL culture, SIV specific lysis was low or undetectable, even after four immunizations. However, stable SIV Gag-Pol- and env-specific T-cell clones (CD3(+) CD8(+)) were isolated after only two DNA immunizations, and Gag-Pol- and Nef-specific CTL lines were isolated on the day of challenge. All animals were challenged at week 38 with SIVmne uncloned stock by the intrarectal route. Based on antibody anamnestic responses (western, ELISA, and neutralizing antibodies) and virus detection methods (co-culture of PBMC and LNMC, nested set PCR- of DNA from PBMC and LNMC, and plasma QC-PCR), there were major differences between the groups in the challenge outcome. Surprisingly, sustained low virus loads were observed only in the DNA group, suggesting that four immunizations with DNA only elicited more effective immune responses than two DNA primes combined with two protein boosts. Multigenic DNA vaccines such as these, bearing all structural and regulatory genes, show significant promise and may be a safe alternative to live-attenuated vaccines. (C) 1999 Published by Elsevier Science B.V. All rights reserved. C1 Seattle Biomed Res Inst, Seattle, WA 98109 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Duke Univ, Med Ctr, Durham, NC 27710 USA. Univ Washington, Reg Primate Res Ctr, Seattle, WA 98195 USA. NCI, Viral Carcinogenesis Lab, Frederick, MD 21702 USA. RP Haigwood, NL (reprint author), Seattle Biomed Res Inst, 4 Nickerson St, Seattle, WA 98109 USA. EM haigwood@u.washington.edu RI Hu, Shiu-Lok/A-3196-2008 OI Hu, Shiu-Lok/0000-0003-4336-7964 FU NCRR NIH HHS [RR00166]; NIAID NIH HHS [AI 26503] NR 23 TC 40 Z9 41 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 J9 IMMUNOL LETT JI Immunol. Lett. PD MAR PY 1999 VL 66 IS 1-3 BP 183 EP 188 DI 10.1016/S0165-2478(98)00156-4 PG 6 WC Immunology SC Immunology GA 178GU UT WOS:000079258500028 PM 10203053 ER PT J AU Jwang, B Yerushalmi, N Kreitman, RJ Engberg, J Pastan, I AF Jwang, B Yerushalmi, N Kreitman, RJ Engberg, J Pastan, I TI An scFv phage clone that binds to human beta(2)-microglobulin SO IMMUNOTECHNOLOGY LA English DT Article DE anti-beta(2)-microglobulin antibody; phage display; scFv antibody; single-chain HLA-A2 ID MELANOMA ANTIGEN GP100; MONOCLONAL-ANTIBODIES; GENES; IMMUNOTOXINS; LYMPHOCYTES; EXPRESSION; PROTEINS; DISPLAY; HLA AB Using phage display technology, a novel mouse scFv phage clone DI was generated from mice immunized with single-chain HLA-A2, the human MHC class I molecules. D1 recognized a determinant in beta(2)-microglobulin. It reacted with beta(2)-microglobulin associated with the heavy chain of HLA-A2, recombinant beta(2)-microglobulin made in Escherichia coli or beta(2)-microglobulin prepared from human urine. The heavy chain variable region of D1 belongs to gene Family VII and the light chain variable region belongs to the kappa chain gene family XI according to the Kabat database. Published by Elsevier Science B.V. C1 NCI, Mol Biol Lab, DBS, Bethesda, MD 20892 USA. NR 21 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1380-2933 J9 IMMUNOTECHNOLOGY JI Immunotechnology PD MAR PY 1999 VL 4 IS 3-4 BP 231 EP 236 DI 10.1016/S1380-2933(98)00023-2 PG 6 WC Biotechnology & Applied Microbiology; Immunology SC Biotechnology & Applied Microbiology; Immunology GA 184ZC UT WOS:000079642800007 PM 10231092 ER PT J AU Perry, LL Feilzer, K Hughes, S Caldwell, HD AF Perry, LL Feilzer, K Hughes, S Caldwell, HD TI Clearance of Chlamydia trachomatis from the murine genital mucosa does not require perforin-mediated cytolysis or Fas-mediated apoptosis SO INFECTION AND IMMUNITY LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; TUMOR-NECROSIS-FACTOR; GENE KNOCKOUT MICE; TRACT INFECTION; DEFICIENT MICE; TNF-ALPHA; CELLS; GAMMA; IMMUNITY; RESPONSES AB The molecular mechanisms of resistance to genital infection with the mouse pneumonitis (MoPn) strain of Chlamydia trachomatis are unknown. A role for major histocompatibility complex class II-restricted, interleukin-12-dependent CD4(+) T cells has been established, but the functional activity of these cells does not depend on secretion of gamma interferon, Here we examined the potential contribution of T-cell-mediated cytotoxicity and apoptosis to mucosal clearance of MoPn by using mice deficient in the molecular mediators of target cell lysis, Animals lacking perforin, Fas, Fas ligand, or both perforin and Fas ligand were infected genitally with C. trachomatis MoPn and monitored for expression of immunity to chlamydial antigens and clearance of MoPn from the genital mucosa, In each case, the profile of spleen cytokine production, the magnitude of the host antibody response, and the kinetics of chlamydial clearance were similar to those of genetically intact controls. Compensatory overproduction of tumor necrosis factor alpha, an alternate mediator of apoptosis in certain cell types, did not appear to account for the ability of mutant mice to resolve Chlamydia infections. These results fail to support CD4(+) T-cell-mediated apoptosis or CD8(+) T-cell-mediated cytotoxicity as being critical to the clearance of C. trachomatis MoPn urogenital infections. C1 NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Caldwell, HD (reprint author), NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. NR 46 TC 49 Z9 49 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAR PY 1999 VL 67 IS 3 BP 1379 EP 1385 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 169FF UT WOS:000078736300049 PM 10024585 ER PT J AU Armstrong, LR Dembry, LM Rainey, PM Russi, MB Khan, AS Fischer, SH Edberg, SC Ksiazek, TG Rollin, PE Peters, CJ AF Armstrong, LR Dembry, LM Rainey, PM Russi, MB Khan, AS Fischer, SH Edberg, SC Ksiazek, TG Rollin, PE Peters, CJ TI Management of a Sabia virus-infected patient in a US hospital SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID LASSA FEVER; NIGERIA AB OBJECTIVE: To describe the hospital precautions used to isolate a Sabia virus (arenavirus: Arenaviridae)-infected patient in a US hospital and to protect hospital staff and visitors. DESIGN: Investigation of a single case of arenavirus laboratory-acquired infection and associated case-contacts. SETTING: A 900-bed, tertiary-care, university-affiliated medical center. PATIENTS OR OTHER PARTICIPANTS: The. case-patient became ill with Sabia Virus infection. The case-contacts consisted of healthcare workers, coworkers, friends, and relatives of the case-patient. INTERVENTION: Enhanced isolation precautions for treatment of a viral hemorrhagic fever (VHF) patient were implemented in the clinical laboratory and patient-care setting to prevent nosocomial transmission. The enhanced precautions included preventing aerosol spread of the virus from the patient or his clinical specimens. All case-contacts were tested for Sabia Virus antibodies and monitored for signs and symptoms of early disease. RESULTS: No cases of secondary infection occurred among 142 case-contacts. CONCLUSIONS: With the frequency of worldwide travel, patients with VHF can be admitted to a local hospital at any time in the United States. The use of enhanced isolation precautions for VHF appeared to be effective in preventing secondary cases by limiting the number of contacts and promoting proper handling of laboratory specimens. Patients with VHF can be managed safely in a local hospital setting, provided that appropriate precautions are planned and implemented. C1 Ctr Dis Control & Prevent, Special Pathogens Branch, Div Viral & Rickettsial Dis, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. Ctr Dis Control & Prevent, Viral Exanthems & Herpesvirus Branch, Div Viral & Rickettsial Dis, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. Yale Univ, Sch Med, Dept Epidemiol & Infect Control, New Haven, CT USA. Yale Univ, Sch Med, Dept Lab Med, New Haven, CT 06510 USA. Yale Univ, Sch Med, Occupat & Environm Med Program, New Haven, CT 06510 USA. Yale New Haven Hosp, Occupat Hlth Serv, New Haven, CT 06504 USA. NIH, Dept Clin Pathol, Bethesda, MD 20892 USA. RP Rollin, PE (reprint author), Ctr Dis Control & Prevent, Special Pathogens Branch, Div Viral & Rickettsial Dis, Natl Ctr Infect Dis, 1600 Clifton Rd NE,Mail Stop G-14, Atlanta, GA 30333 USA. NR 21 TC 18 Z9 19 U1 0 U2 2 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD MAR PY 1999 VL 20 IS 3 BP 176 EP 182 DI 10.1086/501607 PG 7 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 176CB UT WOS:000079132400009 PM 10100543 ER PT J AU Krause, PR Straus, SE AF Krause, PR Straus, SE TI Herpesvirus vaccines - Development, controversies, and applications SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID SIMPLEX VIRUS TYPE-2; VARICELLA-ZOSTER VIRUS; CONGENITAL CYTOMEGALOVIRUS-INFECTION; RENAL-TRANSPLANT RECIPIENTS; PLACEBO-CONTROLLED TRIAL; GENITAL HERPES; GLYCOPROTEIN-D; UNITED-STATES; PROTECTIVE IMMUNITY; HEALTHY-CHILDREN AB Herpesviruses present difficult challenges in vaccine development because of their ability to evade immune clearance. Data and recommendations regarding the live-attenuated varicella vaccine are discussed. Approaches to developing vaccines to prevent herpes simplex virus (HSV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV)-associated illnesses also are considered. C1 US FDA, Ctr Biol Evaluat & Res, OVRR, Lab DNA Viruses, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Krause, PR (reprint author), US FDA, Ctr Biol Evaluat & Res, OVRR, Lab DNA Viruses, 29A-1C16,HFM-457,29 Lincoln Dr, Bethesda, MD 20892 USA. NR 88 TC 20 Z9 20 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD MAR PY 1999 VL 13 IS 1 BP 61 EP + DI 10.1016/S0891-5520(05)70043-X PG 22 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 185DA UT WOS:000079651800007 PM 10198792 ER PT J AU Soto, NE Lutwick, LI AF Soto, NE Lutwick, LI TI Poliovirus immunizations - What goes around, comes around SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID UNITED-STATES; PARALYTIC POLIOMYELITIS; VACCINE; LIVE; EXPERIENCE; CHALLENGE; DISEASE AB Although poliovirus vaccination is not new the recent changes in ACIP recommendations involving polio vaccinations are. Currently, wild type poliovirus has been eliminated in the Western hemisphere, but vaccine-associated cases (VAPP) still occur. The new recommendations are intended to continue providing protection and to eliminate VAPP cases from occurring in vaccinees or close contacts. C1 Vet Adm Med Ctr, Infect Dis IIIE, Dept Med, Div Infect Dis, Brooklyn, NY 11209 USA. NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. Dept Vet Affairs, New York Harbor Hlth Care Syst, Brooklyn, NY USA. SUNY Hlth Sci Ctr, Brooklyn, NY 11203 USA. RP Lutwick, LI (reprint author), Vet Adm Med Ctr, Infect Dis IIIE, Dept Med, Div Infect Dis, 800 Poly Pl, Brooklyn, NY 11209 USA. EM lutwick.larry@brooklyn.va.gov NR 72 TC 1 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD MAR PY 1999 VL 13 IS 1 BP 265 EP + DI 10.1016/S0891-5520(05)70054-4 PG 15 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 185DA UT WOS:000079651800018 PM 10198803 ER PT J AU Krcmery, V Mateicka, F Krupova, I Trupl, J Kunova, A AF Krcmery, V Mateicka, F Krupova, I Trupl, J Kunova, A TI Bacteremia due to ciprofloxacin-resistant Pseudomonas aeruginosa in cancer patients: Risk factors for resistance and outcome of 25 episodes. A case-control study SO INFECTIOUS DISEASES IN CLINICAL PRACTICE LA English DT Article ID ESCHERICHIA-COLI; EMERGENCE AB The aim of this study was to investigate whether quinolone resistance in Pseudomonas aeruginosa has clinical significance, e.g., whether ciprofloxacin (CIP)resistant P, aeruginosa bacteremia (CR PAB) causes more infection-associated death than do sensitive strains. another study objective was to observe specific risk factors related to CR PAB in a group of bacteremias that were identified in a cancer patient population from a single cancer center that had had a consistent antibiotic policy for the previous 7 years. There were several risk factors associated with CIP-resistant bacteremia (cases) compared with controls: resistance to ceftazidime and amikacin was significantly higher (P <.01 and P <.02, respectively) among cases that were CIP-resistant (72% of CR Pas were also resistant to ceftazidime, and 64% were also resistant to amikacin). Previous prophylaxis with quinolones was not a significant risk factor for CR PAB, but prior therapy with aminoglycosides was (36% vs. 16%, respectively; P<.05), Bacteremia with a documented site of infection was less frequently observed among cases (P <.01) compared with the controls. Outcome was similar in both groups: cases infected with CR Pas had attributable (12%) or crude mortality (24% vs. 20%; P = not significant) similar to that of controls infected with CIP-sensitive organisms. C1 NCI, Dept Hematol, Bethesda, MD 20892 USA. NCI, Dept Microbiol, Bethesda, MD 20892 USA. NCI, Dept Med, Bethesda, MD 20892 USA. St Elizabeth Canc Inst, Bratislava, Slovakia. Postgrad Med Sch, Dept Chemotherapy, Bratislava, Slovakia. Univ Trnava, Sch Publ Hlth, Dept Med, Trnava, Slovakia. Univ Scranton, Sch Hlth Adm, Dept Hlth Management, Scranton, PA 18510 USA. RP Krcmery, V (reprint author), Heydukova 10, Bratislava 81250, Slovakia. NR 17 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1056-9103 J9 INFECT DIS CLIN PRAC JI Infect. Dis. Clin. Pract. PD MAR-APR PY 1999 VL 8 IS 3 BP 158 EP 161 DI 10.1097/00019048-199903000-00013 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 169KH UT WOS:000078746600013 ER PT J AU Brownlees, J Gough, G Thomas, S Watts, P Cohen, J Coffin, R Latchman, DS AF Brownlees, J Gough, G Thomas, S Watts, P Cohen, J Coffin, R Latchman, DS TI Distinct responses of the herpes simplex virus and varicella zoster virus immediate early promoters to the cellular transcription factors Brn-3a and Brn-3b SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY LA English DT Article ID HUMAN TRIGEMINAL GANGLIA; EARLY GENE-62 PROMOTER; NEURONAL CELLS; POU-DOMAIN; SENSORY NEURONS; PROTEIN; FAMILY; EXPRESSION; ELEMENTS; BINDING AB The related viruses herpes simplex virus (HSV) and varicella tester virus (VZV) show distinct but related patterns of latent infection and reactivation in human sensory ganglia. The cellular POU family transcription factors Brn-3a and Brn-3b are expressed in sensory ganglia and bind to the TAATGARAT (R stands for purine) regulatory motifs in the immediate-early gene promoters of these viruses. We show that Brn-3a activates the full length HSV IE1 promoter whereas Brn-3b represses its activity. In contrast both Brn-3a and Brn-3b activate the full length VZV IE promoter. The response of the full length VZV promoter to Brn-3b is not observed with a minimal VZV immediate-early promoter lacking any TAATGARAT elements and cannot be restored by addition of either the upstream TAATGARAT-containing region of the HSV IE promoter or a VZV TAATGARAT-like element to this minimal promoter. The unique effect of Brn-3b on the full length VZV immediate early gene promoter may play a key role in the distinct pattern of latent infection and reactivation observed with this virus in vivo. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 UCL, Sch Med, Windeyer Inst Med Sci, Dept Mol Pathol, London W1P 6DB, England. Glaxo Wellcome Med Res Ctr, Stevenage, Herts, England. NIAID, Clin Invest Lab, Med Virol Sect, Bethesda, MD 20892 USA. RP Latchman, DS (reprint author), UCL, Sch Med, Windeyer Inst Med Sci, Dept Mol Pathol, Windeyer Bldg,46 Cleveland St, London W1P 6DB, England. NR 40 TC 3 Z9 3 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1357-2725 J9 INT J BIOCHEM CELL B JI Int. J. Biochem. Cell Biol. PD MAR-APR PY 1999 VL 31 IS 3-4 BP 451 EP 461 DI 10.1016/S1357-2725(98)00151-4 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 182DB UT WOS:000079482300012 PM 10224669 ER PT J AU Adami, J Gridley, G Nyren, O Dosemeci, M Linet, M Glimelius, B Ekbom, A Zahm, SH AF Adami, J Gridley, G Nyren, O Dosemeci, M Linet, M Glimelius, B Ekbom, A Zahm, SH TI Sunlight and non-Hodgkin's lymphoma: A population-based cohort study in Sweden SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID ULTRAVIOLET-LIGHT; SKIN-CANCER; EXPOSURE; ASSOCIATION; HUMANS AB Indirect evidence, notably ecological comparisons and an association with skin cancer, links non-Hodgkin's lymphoma (NHL) with exposure to sunlight. We conducted a population-based, nationwide cohort study with exposure to outdoor work inferred from job titles reported in the population and housing censuses in 1960 and/or 1970 and by classifying each individual's work and home addresses according to latitude. Follow-up for cancer incidence was accomplished through record linkages with the virtually complete Swedish Cancer Registry. The cohort included all Swedish residents who were recorded as gainfully employed in both censuses. Altogether 4,171,175 individuals contributing 69,639,237 person-years accrued through 1989 were included in the analyses. We identified 10,381 cases of NHL, 4,018 cases of chronic lymphocytic leukemia(CLL), 11,398 cases of malignant melanoma (MM) and 11,913 cases of squamous cell skin cancer (SCC). We calculated age-adjusted relative risks for NHL, CLL, MM and SCC in strata based on estimated residential and occupational sunlight exposure. Interaction effects were considered for pesticide and solvent exposure. NHL, MM and SCC, but not CLL, were positively associated with increasingly southerly residential latitude, with stronger associations seen for skin cancer compared to NHL. Occupational sun exposure was not associated with the risk of developing any of the studied cancers. Pesticides and solvents also were not related to an increased risk of NHL, nor did these exposures enhance effects of residential or occupational sunlight exposure. Our results provide some support for an association of sunlight exposure with NHL incidence based on the associations seen using geographic latitude of residence as a proxy for exposure. Although type of occupation may be an imperfect index of the biologically relevant ultraviolet (UV) light dose, our data on individual exposure are not consistent with an important role of sunlight in the etiology of NHL. Int. J. Cancer 80:641-645, 1999. (C) 1999 Wiley-Liss, Inc. C1 Karolinska Inst, Dept Med Epidemiol, SE-17177 Stockholm, Sweden. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Hosp, Dept Oncol, Uppsala, Sweden. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Adami, J (reprint author), Karolinska Inst, Dept Med Epidemiol, Box 281, SE-17177 Stockholm, Sweden. EM Johanna.Adami@mep.ki.se RI Zahm, Shelia/B-5025-2015 NR 37 TC 85 Z9 86 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAR 1 PY 1999 VL 80 IS 5 BP 641 EP 645 DI 10.1002/(SICI)1097-0215(19990301)80:5<641::AID-IJC1>3.0.CO;2-Z PG 5 WC Oncology SC Oncology GA 162XX UT WOS:000078373600001 PM 10048959 ER PT J AU Levine, PH Dosik, H Joseph, EM Felton, S Bertoni, MA Cervantes, J Moulana, V Miotti, AB Goberdhan, LJ Lee, SL Daouad, A DaCosta, M Jaffe, ES Axiotis, CA Cleghorn, FR Kahn, A Welles, SL AF Levine, PH Dosik, H Joseph, EM Felton, S Bertoni, MA Cervantes, J Moulana, V Miotti, AB Goberdhan, LJ Lee, SL Daouad, A DaCosta, M Jaffe, ES Axiotis, CA Cleghorn, FR Kahn, A Welles, SL TI A study of adult T-cell leukemia/lymphoma incidence in central Brooklyn SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID VIRUS TYPE-I; NON-HODGKIN-LYMPHOMA; LEUKEMIA-LYMPHOMA; HTLV-I; SOUTH FLORIDA; CLASSIFICATION; JAMAICA; RISK AB Adult T-cell leukemia/lymphoma (ATL), a rare outcome of infection with human T-lymphotropic virus (HTLV-I), is endemic in central Brooklyn, which has a large Caribbean migrant population. Previous studies have suggested that HTLV-I prevalence in central Brooklyn may be similar to that recorded in the Caribbean islands. We established a pilot 1-year surveillance program to identify cases of ATL in 7 of I 0 hospitals serving the residents of 18 zip codes of central Brooklyn with a combined population of 1,184,670, Of the 6,198 in-patient beds in the catchment area, approximately 83% were covered, Twelve incident cases of ATL were ascertained, all among persons of Afro-Caribbean descent, indicating an annual incidence in African-Americans in this community of approximately 3.2/100,000 person-years. Unexplained hypercalcemia was the most useful screening method, identifying 3 of 5 patients not referred for possible ATL by a local hematologist, The female:male ratio was 3:1. The age pattern was different from that reported in the Caribbean Basin and closer to the pattern seen in Japan. Our study supports evidence that HTLV-I infection and ATL are endemic in central Brooklyn and suggests that a more intensive surveillance program for this disease coupled with intervention efforts to reduce HTLV-I transmission are warranted, Int. J. Cancer 80:662-666, 1999, Published 1999 Wiley-Liss, Inc. C1 NCI, Div Canc Epidemiol & Genet, Viral Epidemiol Branch, NIH, Bethesda, MD 20892 USA. George Washington Univ, Sch Publ Hlth, Washington, DC USA. George Washington Univ, Hlth Serv, Washington, DC USA. Interfaith Med Ctr, Brooklyn, NY USA. Res Triangle Inst, Washington, DC USA. Wyckoff Hts Med Ctr, Brooklyn, NY USA. Woodhull Med Ctr, Brooklyn, NY USA. St Marys Hosp, Brooklyn, NY USA. Brooklyn Hosp, Dept Hematol Oncol, Brooklyn, NY USA. Brookdale Hosp, Dept Hematol, Brooklyn, NY USA. St Josephs Hosp, Brooklyn, NY USA. SUNY Hlth Sci Ctr, Brooklyn, NY 11203 USA. Kings Cty Hosp, Brooklyn, NY USA. New York State Canc Registry, New York, NY USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN USA. RP Levine, PH (reprint author), NCI, Div Canc Epidemiol & Genet, Viral Epidemiol Branch, NIH, EPN 434, Bethesda, MD 20892 USA. EM ZPL@CU.NIH.GOV NR 20 TC 10 Z9 10 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAR 1 PY 1999 VL 80 IS 5 BP 662 EP 666 DI 10.1002/(SICI)1097-0215(19990301)80:5<662::AID-IJC5>3.3.CO;2-9 PG 5 WC Oncology SC Oncology GA 162XX UT WOS:000078373600005 PM 10048963 ER PT J AU Cormier, JN Panelli, MC Hackett, JA Bettinotti, MP Mixon, A Wunderlich, J Parker, LL Restifo, NP Ferrone, S Marincola, FM AF Cormier, JN Panelli, MC Hackett, JA Bettinotti, MP Mixon, A Wunderlich, J Parker, LL Restifo, NP Ferrone, S Marincola, FM TI Natural variation of the expression of HLA and endogenous antigen modulates ctl recognition in an in vitro melanoma model SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID IN-VIVO; T-LYMPHOCYTES; CELL-LINES; PEPTIDE; CANCER; GP100; REGRESSION; RELEVANCE; FREQUENCY; MART-1 AB Increasing attention has been devoted to elucidating the mechanism of lost or decreased expression of MHC or melanoma-associated antigens (MAAs), which may lead to tumor escape from immune recognition. Loss of expression of HLA class I or MAA has, as an undisputed consequence, loss of recognition by HLA class I-restricted cytotoxic T cells (CTLs). However, the relevance of down-regulation remains in question in terms of frequency of occurrence, Moreover the functional significance of epitope down-regulation, defining the relationship between MHC/epitope density and CTL interactions. is a matter of controversy, particularly with regard to whether the noted variability of expression of MHC/epitope occurs within a range likely to affect target recognition by CTLs. In this study, bulk metastatic melanoma cell lines originated from 25 HLA-A*0201 patients were analyzed for expression of HLA-A2 and MAAs. HLA-AZ expression was heterogeneous and correlated with lysis by CTLs. Sensitivity to lysis was also independently affected by the amount of ligand available for binding at concentrations of 0.001 to 1 mM. Natural expression of MAA was variable, independent from the expression of HLA-A*0201, and a significant co-factor determining recognition of melanoma targets. Thus, the naturally occurring variation in the expression of MAA and/or HLA documented by our in vitro results modulates recognition of melanoma targets and may (i) partially explain CTL-target interactions in vitro and (ii) elucidate potential mechanisms for progressive escape of tumor cells from immune recognition in vivo. Int. J. Cancer: 80,781-790(1999), Published 1999 Wiley-Liss, Inc. C1 NCI, Surg Branch, Div Clin Sci, Bethesda, MD 20892 USA. NIH, HLA Lab, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. New York Med Coll, Dept Microbiol & Immunol, Valhalla, NY 10595 USA. RP Marincola, FM (reprint author), NCI, Surg Branch, Div Clin Sci, Bldg 10,Room 2B42, Bethesda, MD 20892 USA. RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999] NR 19 TC 61 Z9 63 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAR 1 PY 1999 VL 80 IS 5 BP 781 EP 790 DI 10.1002/(SICI)1097-0215(19990301)80:5<781::AID-IJC24>3.0.CO;2-A PG 10 WC Oncology SC Oncology GA 162XX UT WOS:000078373600024 PM 10048982 ER PT J AU Fogt, F Zimmerman, RL Mulligan, N Vortmeyer, AO Poremba, C Harris, CA Alsaigh, N Tomaszewski, JE Nikulasson, ST AF Fogt, F Zimmerman, RL Mulligan, N Vortmeyer, AO Poremba, C Harris, CA Alsaigh, N Tomaszewski, JE Nikulasson, ST TI BCL-2 expression and inhibin-A in adrenal neoplasms: A comparative study SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Article DE adrenal cortex; pheochromocytoma; adrenal cortical carcinoma; BCL-2; inhibin-A; immunohistochemistry ID ADRENOCORTICAL CARCINOMA; DIFFERENTIAL-DIAGNOSIS; CORTICAL TUMORS; CELL APOPTOSIS; PHEOCHROMOCYTOMAS AB Differential diagnosis between adrenal cortical and adrenal medullary lesions may be difficult in many cases. Different immunohistochemical, histochemical tools as well as ultrastructural diagnostic techniques have been employed to aid in differentiating between these lesions. Recently, both inhibin-A and BCL-2 have been shown to stain selectively adrenal cortical tissue and its derived neoplasms but not adrenal medulla or pheochromocytomas. In this study we compared the staining reactions of inhibin-A and BCL-2 in cases of adrenal cortical adenomas and carcinomas as well as pheochromocytomas. We found that both inhibin-A and BCL-2 stained cortical derived tissues, but not medullary derived tissues. Staining intensity for inhibin-A was significantly weaker than for BCL-2. We found that fixation techniques may influence the staining reactivity, as some cases did not immunoreact with any of the antibodies. We conclude that both inhibin-A, and, preferentially, BCL-2 are useful additions to a staining protocol to help in the differential diagnosis of cortical and medullary neoplasms. C1 Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA. Univ Munster, Dept Pathol, D-4400 Munster, Germany. Univ Iceland, Dept Pathol, Reykjavik, Iceland. Boston Univ, Mallory Inst Pathol, Boston, MA USA. NIH, Pathol Lab, Bethesda, MD 20892 USA. Dianon Syst, Stratford, CT USA. RP Fogt, F (reprint author), Univ Penn, Presbyterian Med Ctr, Dept Pathol & Lab Med, 39th & Market St,551 Wright Saunders Bldg, Philadelphia, PA 19104 USA. NR 15 TC 5 Z9 5 U1 0 U2 0 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PD MAR PY 1999 VL 3 IS 3 BP 271 EP 274 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 169WN UT WOS:000078772300005 PM 10028050 ER PT J AU Troiano, RP Flegal, KM AF Troiano, RP Flegal, KM TI Overweight prevalence among youth in the United States: Why so many different numbers? SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article; Proceedings Paper CT Conference on Obesity in Childhood and Adolescence - Assessment, Prevention and Treatment CY MAY, 1997 CL MINNEAPOLIS, MINNESOTA SP Sch Public Hlth, Div Epidemiol, Public Hlth Nutrit & Nutrit Coordinationg Ctr, Consortium Maternal & Child Hlth Bureau Title V Training Programs, Hlth Resources & Serv Adm, US Dept HHS DE body weight; body mass index; health surveys; nutrition assessment; child; adolescence; NHANES; reference values ID BODY-MASS INDEX; CHILDREN; ADOLESCENTS; OBESITY; HEALTH; PERCENTILES; CHILDHOOD; FATNESS; AGE; RELIABILITY AB Several recent publications have presented different estimates for the prevalence of overweight among youth in the United States. Prevalence estimates range from 11-24%, despite describing the same results from the third National Health and Nutrition Examination Survey (NHANES III). This paper discusses the variety and evolution of different overweight prevalence estimates. Issues of definition, measurements, criteria selection and comparison groups are considered and implications for estimates of the prevalence of overweight among youth are explored. Reference percentiles for body mass index (BMI) from several publications are compared, The differences in published estimates from NHANES III are noted and explained. C1 NCI, DCCPS, ARB, NIH, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Div Hlth Examinat Stat, Hyattsville, MD 20782 USA. RP Troiano, RP (reprint author), NCI, DCCPS, ARB, NIH, Execut Plaza N,Rm 313,6130 Execut Blvd,MSC 7344, Bethesda, MD 20892 USA. RI Flegal, Katherine/A-4608-2013 NR 51 TC 65 Z9 65 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD MAR PY 1999 VL 23 SU 2 BP S22 EP S27 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 185GG UT WOS:000079659300005 PM 10340801 ER PT J AU Hung, G Faudoa, R Li, XK Xeu, Z Brackmann, DE Hitselberg, W Saleh, E Lee, F Gutmann, DH Slattery, WI Rhim, JS Lim, D AF Hung, G Faudoa, R Li, XK Xeu, Z Brackmann, DE Hitselberg, W Saleh, E Lee, F Gutmann, DH Slattery, WI Rhim, JS Lim, D TI Establishment of primary vestibular schwannoma cultures from neurofibromatosis type-2 patients SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE neurofibromatosis 2; schwannomas; Schwann cell; primary culture ID GENE-PRODUCT; CELL TUMORS; NF2 GENE; MUTATIONS; PROTEIN; DIFFERENTIATION; PROLIFERATION; EXPRESSION; GROWTH; TISSUES AB Primary cultures were established from vestibular schwannomas of NF2 patients. The cultured tumor cells were selectively amplified by growth factor supplemented medium and characterized by immunocytochemistry. NF2 cDNA was amplified by RT-PCR and mutations were detected by both the non-isotopic RNase cleavage assay and direct DNA sequencing, no detectable wild-type NF2 transcript was found in cDNA from the cultured cells. Distinguishable morphology and growth rate differences have been observed in different passages of the primary cells. The data suggest that a pure schwannoma primary culture can be established and could be very useful in vitro model for further understanding the NF2 gene function in Schwann cells. C1 House Ear Inst, Dept Cell & Mol Biol, Los Angeles, CA 90057 USA. San Vincent Hosp, Los Angeles, CA USA. Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. Natl Canc Inst, Lab Biochem Physiol, Frederick, MD USA. RP Hung, G (reprint author), House Ear Inst, Dept Cell & Mol Biol, 2100 W Third St, Los Angeles, CA 90057 USA. NR 28 TC 12 Z9 12 U1 0 U2 0 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD MAR PY 1999 VL 14 IS 3 BP 409 EP 415 PG 7 WC Oncology SC Oncology GA 169VQ UT WOS:000078770100002 PM 10024671 ER PT J AU De Angelis, E Grassi, M Gullick, WJ Johnson, GR Rossi, GB Tempesta, A De Angelis, F De Luca, A Salomon, DS Normanno, N AF De Angelis, E Grassi, M Gullick, WJ Johnson, GR Rossi, GB Tempesta, A De Angelis, F De Luca, A Salomon, DS Normanno, N TI Expression of cripto and amphiregulin in colon mucosa from high risk colon cancer families SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE cripto; amphiregulin; colon carcinoma ID FACTOR-RELATED PEPTIDES; IMMUNOHISTOCHEMICAL DETECTION; COLORECTAL TUMORS; GROWTH; PROLIFERATION; CELLS; OLIGODEOXYNUCLEOTIDES; INHIBITION; CARCINOMAS; PROGNOSIS AB We assessed the expression of the epidermal growth factor (EGF)-related peptides, cripto-I (CR-I) and amphi-regulin (AR), in a small panel of human colon adenomas and carcinomas. CR-I immunoreactivity was found in 17/31 (55%) of colon adenomas, and in 33/39 (84%) colon carcinomas. AR immunostaining was observed in 16/26 adenomas (61%) and in 20/26 carcinomas (77%). CR-I and AR staining were also assessed in 29 specimens from 24 individuals that belong to families with high incidence of colorectal carcinoma, and in 5 non-high risk individuals. Expression of CR-I was detected in 18/29 (62%) of high risk colon mucosa specimens, but only in 1/5 (20%) specimens from non-high risk individuals, while AR staining was found in 20/29 (69%) and in 4/5 (80%) of colon mucosa samples from high and low risk individuals, respectively. A majority (21/29; 72%) of the specimens from the high risk individuals had a high proliferative rate, as measured by Ki-67 staining. A statistically significant correlation was found between high proliferative rate, increased expression of CR-I and reduced expression of AR in the mucosa specimens from high risk individuals, suggesting that these might represent early events in colon tumorigenesis. C1 Fdn Pascale, ITN, Serv Oncol Sperimentale D, I-80131 Naples, Italy. Fdn Pascale, Serv Endoscopia, ITN, I-80131 Naples, Italy. Hammersmith Hosp, Imperial Canc Res Fund, Mol Oncol Unit, London W12 0HS, England. NCI, Tumor Growth Factor Sect, LTIB, NIH, Bethesda, MD 20892 USA. US FDA, DCB, Bethesda, MD 20892 USA. RP Normanno, N (reprint author), Fdn Pascale, ITN, Serv Oncol Sperimentale D, I-80131 Naples, Italy. RI De Luca, Antonella/J-8737-2016; OI De Luca, Antonella/0000-0001-5762-447X; Normanno, Nicola/0000-0002-7158-2605 NR 16 TC 19 Z9 20 U1 1 U2 1 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD MAR PY 1999 VL 14 IS 3 BP 437 EP 440 PG 4 WC Oncology SC Oncology GA 169VQ UT WOS:000078770100005 PM 10024674 ER PT J AU Melchior, SW Brown, LG Figg, WD Quinn, JE Santucci, RA Brunner, J Thuroff, JW Lange, PH Vessella, RL AF Melchior, SW Brown, LG Figg, WD Quinn, JE Santucci, RA Brunner, J Thuroff, JW Lange, PH Vessella, RL TI Effects of phenylbutyrate on proliferation and apoptosis in human prostate cancer cells in vitro and in vivo SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE prostate cancer; phenylbutyrate; cell cycle; apoptosis; xenografts ID SODIUM PHENYLACETATE; GROWTH ARREST; IN-VITRO; DIFFERENTIATION; CARCINOMA; HYPERAMMONEMIA; INHIBITION; RESISTANCE; ANDROGENS; XENOGRAFT AB Phenylbutyrate (PB) is a potent differentiating agent and currently under investigation for the treatment of prostate cancer (CaP) and other malignancies. We have studied the impact of PB in vitro and in vivo on differentiation, proliferation and apoptosis in the LNCaP and LuCaP 23.1 prostate cancer xenograft models. In vitro we found that i) PB increased PSA secretion/cell, ii) inhibited cell proliferation in a time- and dose-dependent manner resulting in a cell cycle arrest in G1-phase and iii) induced apoptosis at concentrations of 2.5 mM after 3 days of treatment. In PB treated animals tumor growth stabilized or regressed. Combination of castration and PB treatment had a synergistic antiproliferative effect. The growth-inhibitory and differentiating properties and a low toxicity profile of PB provide rationale for further clinical studies in patients with CaP. C1 Univ Washington, Dept Urol, Seattle, WA 98195 USA. NCI, Clin Pharmacol Branch, NIH, Bethesda, MD 20892 USA. Univ Kliniken Mainz, Urol Klin & Poliklin, D-55131 Mainz, Germany. RP Melchior, SW (reprint author), Univ Mainz, Sch Med, Dept Urol, Langenbeckstr 1, D-55131 Mainz, Germany. RI Figg Sr, William/M-2411-2016 FU NIDDK NIH HHS [1 P50 DK/CS4756-03] NR 29 TC 39 Z9 41 U1 0 U2 0 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD MAR PY 1999 VL 14 IS 3 BP 501 EP 508 PG 8 WC Oncology SC Oncology GA 169VQ UT WOS:000078770100014 PM 10024683 ER PT J AU Wei, SJC Chang, RL Wong, CQ Cui, XX Dandamudi, N Lu, YP Merkler, KA Sayer, JM Conney, AH Jerina, DM AF Wei, SJC Chang, RL Wong, CQ Cui, XX Dandamudi, N Lu, YP Merkler, KA Sayer, JM Conney, AH Jerina, DM TI The ratio of deoxyadenosine to deoxyguanosine adducts formed by (+)-(7R, 8S, 9S, 10R)-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene in purified calf thymus DNA and DNA in V-79 cells is independent of dose SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE benzo[a]pyrene; diol epoxides; DNA adducts; V-79 cells ID BENZOPYRENE 7,8-DIOL-9,10-EPOXIDES; DEPENDENT DIFFERENCES; ENANTIOMERS; EPOXIDE; PROFILE; REGION AB The hypothesis that the decrease in the proportion of mutations at AT base pairs in Chinese hamster V-79 cells treated with increasing doses of (+)-(R,S,S,R)-benzo[a]pyrene diol epoxide ((+)-BPDE) is due to saturation of A 'hot spots' for adduct formation was investigated by comparing the ratio of dA to dG adducts formed at high (0.48 mu M) and low (0.04 mu M) doses of [H-3]-labeled (+)-BPDE. The dA to dG adduct ratio was similar in both calf thymus DNA and the genomic DNA in V-79 cells, and did not change with dose. For the V-79 cells, this ratio was also unaffected by a 24-h post treatment repair incubation. C1 NIDDKD, Sect Oxidat Mechanisms, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Rutgers State Univ, Coll Pharm, Dept Biol Chem, Canc Res Lab, Piscataway, NJ 08854 USA. RP Jerina, DM (reprint author), NIDDKD, Sect Oxidat Mechanisms, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA49756]; NIEHS NIH HHS [ES05022] NR 14 TC 14 Z9 14 U1 0 U2 0 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD MAR PY 1999 VL 14 IS 3 BP 509 EP 513 PG 5 WC Oncology SC Oncology GA 169VQ UT WOS:000078770100015 PM 10024684 ER PT J AU Brawley, O AF Brawley, O TI The study of untreated syphilis in the Negro male: Regarding Brawley IJROBP 40 : 5-8,1998 - Response SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Letter C1 NCI, Off Special Populat Res, Bethesda, MD 20892 USA. RP Brawley, O (reprint author), NCI, Off Special Populat Res, EPS-20, Bethesda, MD 20892 USA. NR 2 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAR 1 PY 1999 VL 43 IS 4 BP 940 EP 941 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 177CY UT WOS:000079190900031 ER PT J AU Katz, PP Showstack, JA Lake, JR Brown, RS Dudley, RA Colwell, ME Wiesner, RH Zetterman, RK Everhart, J AF Katz, PP Showstack, JA Lake, JR Brown, RS Dudley, RA Colwell, ME Wiesner, RH Zetterman, RK Everhart, J TI Methods to estimate and analyze medical care resource use - An example from liver transplantation SO INTERNATIONAL JOURNAL OF TECHNOLOGY ASSESSMENT IN HEALTH CARE LA English DT Article DE resource use; billing data; methods; health care costs; liver transplantation ID CYCLOSPORINE; COSTS AB This paper describes a method to construct a standardized health care resource use database, Billing and clinical data were analyzed for 916 patients who received liver transplantations at three medical centers over a 4-year period. Data were checked for completeness by assessing whether each patient's bill included charges covering specified dates and for specific services, and for accuracy by comparing a sample of bills to medical records. Detailed services were matched to a standardized service list from one of the centers, and a single price list was applied. For certain services, clinical data were used to estimate service use or, if a match was not possible, adjusted charges for the services were used, Twenty-three patients were eliminated from the database because of incomplete resource use data. There was very good correspondence between bills and medical records, except for blood products. Direct matches to the standardized service list accounted for 69.3% of services overall; 9.4% of services could not be matched to the standardized service list acid were thus adjusted for center and/or time period. Clinical data were used to estimate resource use for blood products, operating room time, and medications; these estimations accounted for 21.3% of services overall. A database can be constructed that allows comparison of standardized resource use and avoids biases due to accounting, geographic, or temporal factors, Clinical data are essential for the creation of such a database. The methods described are particularly useful in studies of the cost-effectiveness of medical technologies. C1 Univ Calif San Francisco, Inst Hlth Policy Studies, San Francisco, CA 94143 USA. Columbia Presbyterian Med Ctr, Ctr Liver Dis & Transplantat, New York, NY 10032 USA. Mayo Clin & Mayo Fdn, Liver Transplant Off, Rochester, MN 55905 USA. Univ Nebraska, Med Ctr, Dept Surg, Omaha, NE 68198 USA. NIDDK, Bethesda, MD 20892 USA. RP Katz, PP (reprint author), Univ Calif San Francisco, Inst Hlth Policy Studies, 1388 Sutter St, San Francisco, CA 94143 USA. RI Showstack, Jonathan/L-6556-2013 OI Showstack, Jonathan/0000-0002-1367-419X FU NIDDK NIH HHS [N01-DK-0-2251, N01-DK-0-2252, N01-DK-0-2253] NR 14 TC 24 Z9 24 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0266-4623 J9 INT J TECHNOL ASSESS JI Int. J. Technol. Assess. Health Care PD SPR PY 1999 VL 15 IS 2 BP 366 EP 379 PG 14 WC Health Care Sciences & Services; Public, Environmental & Occupational Health; Medical Informatics SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Medical Informatics GA 224CN UT WOS:000081879400008 PM 10507195 ER PT J AU Nims, RW Beebe, LE Utermahlen, WE Thomas, PE Lubet, RA AF Nims, RW Beebe, LE Utermahlen, WE Thomas, PE Lubet, RA TI Induction of hepatic cytochromes P450 by dietary 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) in the B6C3F1 mouse: Dose-dependence and pharmacodynamics SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Article DE B6C3F1 mice; cytochrome(s) P450 induction; pharmacodynamics; TCPOBOP ID PHENOBARBITAL-LIKE INDUCER; MONO-OXYGENASE ACTIVITY; SUBSTITUTED CONGENERS; RAT; DEALKYLATION; DISTINGUISH; HEPATOCYTES; ISOZYMES; LIVER; ASSAY AB The dose-response relationships for hepatic cytochrome P450 (CYP) induction by 1,4-bis(2-[3,5-dichloropyridyloxy])benz (TCPOBOP) were examined in the male B6C3F1 mouse. TCPOBOP, administered for 14 days at 0.393-96.2 ppm in the diet, caused concentration-dependent induction of hepatic CYP subfamily 2B (CYP2B) protein and of benzyloxyresorufin O-dealkylation, The ED50 values for CYP2B induction, calculated on the basis of immunoreactive CYP2B protein and benzyloxyresorufin O-dealkylation, were 1.2 ppm and 2.2 ppm dietary TCPOBOP, respectively, The maximal catalytic activities observed mere 74-95-fold higher than control values. These induction levels were 2.3-2.6-fold greater than those resulting from exposure of the mice to 500 ppm dietary phenobarbital (a prototypic CYP2B inducer). The EC50 values of TCPOBOP for hepatic CYP2B induction were <0.3 mu mol/l (serum) and <3.3 mu mol/kg (liver), Increases in immunoreactive CYP subfamily 1A and subfamily 3A proteins were also detected, although the maximal induction levels for these subfamilies mere relatively low ( Arg substitution SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID PERINATAL OSTEOGENESIS IMPERFECTA; TRABECULAR BONE; I PROCOLLAGEN; PARENTAL MOSAICISM; RAT; GLYCOSYLATION; COL1A2; OVARIECTOMY; CARTILAGE; CLEAVAGE AB Mutations in the type I collagen genes have been identified as the cause of all four types of osteogenesis imperfecta (OI), We now report a mutation that extends the phenotype associated with structural abnormalities in type I collagen, Two siblings presented with a history of back pain and were diagnosed with juvenile osteoporosis, based on clinical and radiological examination. Radiographs showed decreased lumbar bone density and multiple compression fractures throughout the thoracic and lumbar spines of both patients, One child has moderate short stature and mild neurosensory hearing loss. However, neither child has incurred the long bone fractures characteristic of OI, Protein studies demonstrated electrophoretically abnormal type I collagen in samples from both children. Enzymatic cleavage of RNA:RNA hybrids identified a mismatch in type I collagen alpha 2 (COL1A2) mRNA, DNA sequencing of COL1A2 cDNA subclones defined the mismatch as a single-base mutation (1715G --> A) in both children. This mutation predicts the substitution of arginine for glycine at position 436 (G436R) in the helical domain of the alpha 2(I) chain. Analysis of genomic DNA identified the mutation in the asymptomatic father, who is presumably a germ-line mosaic carrier. The presence of the same heterozygous mutation in two siblings strongly suggests that the probands display the full phenotype, Taken together, the clinical, biochemical, and molecular findings of this study extend the phenotype associated with type I collagen mutations to cases with only spine manifestations and variable short stature into adolescence. C1 NICHHD, Sect Connect Tissue Disorders, Heritable Disorders Branch, Bethesda, MD 20892 USA. Univ Virginia, Dept Pediat, Charlottesville, VA USA. RP Marini, JC (reprint author), NICHHD, Sect Connect Tissue Disorders, Heritable Disorders Branch, Bethesda, MD 20892 USA. RI Dawson, Paul/B-1268-2012 NR 28 TC 8 Z9 12 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD MAR PY 1999 VL 14 IS 3 BP 449 EP 455 DI 10.1359/jbmr.1999.14.3.449 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 168MX UT WOS:000078697800015 PM 10027910 ER PT J AU Takayama, S Sieber, SM Dalgard, DW Thorgeirsson, UP Adamson, RH AF Takayama, S Sieber, SM Dalgard, DW Thorgeirsson, UP Adamson, RH TI Effects of long-term oral administration of DDT on nonhuman primates SO JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY LA English DT Article DE DDT; long-term oral administration; nonhuman primate; monkey ID BREAST-CANCER; ORGANOCHLORINE PESTICIDES; POLYCHLORINATED-BIPHENYLS; HEPATOCARCINOGENESIS; RISK; MICE AB Because of reports on tumorigenic activity in different animal species exposed to DDT a decision was made in 1969 to evaluate the long-term effects of DDT on 24 cynomolgus and rhesus monkeys. DDT (20 mg/kg) was given in the diet for 130 months, followed by an observation period that ended in 1994. The two cases of malignant tumor detected in the DDT group included a metastatic hepatocellular carcinoma in a 233-month-old male and a well-differentiated adenocarcinoma of the prostate in a 212-month-old monkey. Benign tumors detected in the DDT group included three cases of leiomyoma, two of which were uterine and one, esophageal. No tumor was detected in the control group of 17 monkeys. Fatty changes in the liver were observed in 52.9% of the DDT group and 29.4% of the control group. More specific signs of hepatotoxicity were documented microscopically in seven DDT monkeys. Severe tremors and histological evidence of CNS and spinal cord abnormalities were observed in six DDT monkeys. The present findings show clear evidence of hepatic and CNS toxicity following long-term DDT administration to cynomolgus and rhesus monkeys. However, the two cases involving malignant tumors of different types are inconclusive with respect to a carcinogenic effect of DDT in nonhuman primates. C1 NCI, Div Basic Sci, Bethesda, MD 20892 USA. Corning Hazleton Labs Amer Inc, Vienna, VA 22183 USA. RP Thorgeirsson, UP (reprint author), NCI, Div Basic Sci, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01-BC-40510] NR 32 TC 24 Z9 26 U1 2 U2 6 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0171-5216 J9 J CANCER RES CLIN JI J. Cancer Res. Clin. Oncol. PD MAR-APR PY 1999 VL 125 IS 3-4 BP 219 EP 225 DI 10.1007/s004320050266 PG 7 WC Oncology SC Oncology GA 187VM UT WOS:000079808800014 PM 10235477 ER PT J AU Jester, JV Moller-Pedersen, T Huang, JY Sax, CM Kays, WT Cavangh, HD Petroll, WM Piatigorsky, J AF Jester, JV Moller-Pedersen, T Huang, JY Sax, CM Kays, WT Cavangh, HD Petroll, WM Piatigorsky, J TI The cellular basis of corneal transparency: evidence for 'corneal crystallins' SO JOURNAL OF CELL SCIENCE LA English DT Article DE keratocyte; crystallin; corneal transparency; aldehyde dehydrogenase class 1; transketolase ID VIVO CONFOCAL MICROSCOPY; ANGLE LIGHT-SCATTERING; MAJOR SOLUBLE-PROTEIN; ALDEHYDE DEHYDROGENASE; LENS CRYSTALLINS; BOVINE CORNEA; EYE LENS; PHOTOREFRACTIVE KERATECTOMY; STRUCTURAL PROTEIN; RABBIT CORNEAS AB In vivo corneal light scattering measurements using a novel confocal microscope demonstrated greatly increased backscatter from corneal stromal fibrocytes (keratocytes) in opaque compared to transparent corneal tissue in both humans and rabbits. Additionally, two water-soluble proteins, transketolase (TKT) and aldehyde dehydrogenase class 1 (ALDHI), isolated from rabbit keratocytes showed unexpectedly abundant expression (similar to 30% of the soluble protein) in transparent corneas and markedly reduced levels in opaque scleral fibroblasts or keratocytes from hazy, freeze injured regions of the cornea, Together these data suggest that the relatively high expressions of TKT and ALDH1 contribute to corneal transparency in the rabbit at the cellular level, reminiscent of enzyme-crystallins in the lens. We also note that ALDH1 accumulates in the rabbit corneal epithelial cells, rather than ALDH3 as seen in other mammals, consistent with the taxon-specificity observed among lens enzyme-crystallins, Our results suggest that corneal cells, like lens cells, may preferentially express water-soluble proteins, often enzymes, for controlling their optical properties. C1 Univ Texas, SW Med Ctr, Dept Ophthalmol, Dallas, TX 75235 USA. Aarhus Univ Hosp, Dept Ophthalmol, DK-8000 Aarhus, Denmark. NEI, Mol & Dev Biol Lab, Bethesda, MD 20892 USA. RP Jester, JV (reprint author), Univ Texas, SW Med Ctr, Dept Ophthalmol, Dallas, TX 75235 USA. EM jester@cmjjsgi.swmed.edu FU NEI NIH HHS [EY07348] NR 65 TC 245 Z9 258 U1 1 U2 19 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD MAR PY 1999 VL 112 IS 5 BP 613 EP 622 PG 10 WC Cell Biology SC Cell Biology GA 179HL UT WOS:000079320700003 PM 9973596 ER PT J AU Valdez, AC Cabaniols, JP Brown, MJ Roche, PA AF Valdez, AC Cabaniols, JP Brown, MJ Roche, PA TI Syntaxin 11 is associated with SNAP-23 on late endosomes and the trans-Golgi network SO JOURNAL OF CELL SCIENCE LA English DT Article DE SNARE; syntaxin; SNAP-23; protein transport; endosome ID MANNOSE 6-PHOSPHATE RECEPTOR; SYNAPTIC VESICLE DOCKING; MEMBRANE-FUSION COMPLEX; APICAL PLASMA-MEMBRANE; CANINE KIDNEY-CELLS; T-SNARE; CLOSTRIDIAL NEUROTOXINS; PROTEIN-TRANSPORT; EPITHELIAL-CELLS; IN-VITRO AB SNARE proteins are known to play a role in regulating intracellular protein transport between donor and target membranes. This docking and fusion process involves the interaction of specific vesicle-SNAREs (e.g. VAMP) with specific cognate target-SNAREs (e.g, syntaxin and SNAP-23), Using human SNAP-23 as the bait in a yeast two-hybrid screen of a human B-lymphocyte cDNA library, we have identified the 287-amino-acid SNARE protein syntaxin 11, Like other syntaxin family members, syntaxin 11 binds to the SNARE proteins VAMP and SNAP-23 in vitro and also exists in a complex with SNAP-23 in transfected HeLa cells and in native human B lymphocytes. Unlike other syntaxin family members, no obvious transmembrane domain is present in syntaxin 11. Nevertheless, syntaxin 11 is predominantly membrane-associated and colocalizes with the mannose 6-phosphate receptor on late endosomes and the trans-Golgi network. These data suggest that syntaxin 11 is a SNARE that acts to regulate protein transport between late endosomes and the trans-Golgi network in mammalian cells. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Roche, PA (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM paul.roche@nih.gov NR 50 TC 73 Z9 75 U1 0 U2 0 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD MAR PY 1999 VL 112 IS 6 BP 845 EP 854 PG 10 WC Cell Biology SC Cell Biology GA 184LP UT WOS:000079613900008 PM 10036234 ER PT J AU Radhakrishna, H Al-Awar, O Khachikian, Z Donaldson, JG AF Radhakrishna, H Al-Awar, O Khachikian, Z Donaldson, JG TI ARF6 requirement for Rac ruffling suggests a role for membrane trafficking in cortical actin rearrangements SO JOURNAL OF CELL SCIENCE LA English DT Article DE ARF6; Rac; Rho; actin; lamellipodium ID ADP-RIBOSYLATION FACTOR; GTP-BINDING PROTEIN; RECEPTOR-MEDIATED ENDOCYTOSIS; PHOSPHOLIPASE-D; RAC1-INTERACTING PROTEIN; GOLGI MEMBRANES; PLASMA-MEMBRANE; NADPH OXIDASE; STRESS FIBERS; RHO-GTPASES AB The ARF6 GTPase regulates a novel endosomal-plasma membrane recycling pathway and influences cortical actin remodeling. Here we examined the relationship between ARF6 and Rad, a Rho family GTPase, implicated in cortical actin rearrangements. Endogenous Rad colocalized with ARF6 at the plasma membrane and on the ARF6 recycling endosome in untransfected HeLa and primary human fibroblast cells. In transfected HeLa cells Rad and ARF6 also colocalized, Cells expressing wild-type ARF6 or Rad formed actin-containing surface protrusions and membrane ruffles, respectively, upon treatment with the G protein activator aluminum fluoride. Aluminum fluoride-treatment of cells transfected with equivalent amounts of plasmid resulted in enhanced membrane ruffling, with protrusions appearing as Rac expression was lowered. Go-expression of the dominant negative, GTP binding-defective ARF6 T27N mutant inhibited the aluminum fluoride-induced ruffling observed in cells expressing Rad, and the constitutive ruffling observed in cells expressing the activated Rad Q61L mutant. In contrast, co-expression of the GTP-binding-defective, T17N mutant of either Rad or Cdc42 with ARF6 did not inhibit the aluminum fluoride-induced surface protrusions, nor did inactivation of Rho with C3-transferase. These observations suggest that ARF6, a non-Rho family GTPase, can, by itself, alter cortical actin and can influence the ability of Rad to form lamellipodia, in part, by regulating its trafficking to the plasma membrane. C1 NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Donaldson, JG (reprint author), NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. EM jdonalds@helix.nih.gov NR 51 TC 242 Z9 244 U1 1 U2 4 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD MAR PY 1999 VL 112 IS 6 BP 855 EP 866 PG 12 WC Cell Biology SC Cell Biology GA 184LP UT WOS:000079613900009 PM 10036235 ER PT J AU Tada, H Sasada, R Kawaguchi, Y Kojima, I Gullick, WJ Salomon, DS Igarashi, K Seno, M Yamada, H AF Tada, H Sasada, R Kawaguchi, Y Kojima, I Gullick, WJ Salomon, DS Igarashi, K Seno, M Yamada, H TI Processing and juxtacrine activity of membrane-anchored betacellulin SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE betacellulin; membrane-anchored growth factor; pancreatic cell differentiation; isoforms; juxtacrine stimulation ID EPIDERMAL GROWTH-FACTOR; AMYLOID PRECURSOR PROTEIN; FACTOR-ALPHA PRECURSOR; CELL-SURFACE; BIOLOGICAL-ACTIVITIES; ALKALINE-PHOSPHATASE; FACTOR RECEPTOR; PHORBOL ESTER; EGF FAMILY; BINDING AB Betacellulin (BTC) was originally isolated as a secreted growth factor from a mouse pancreatic beta-tumor cell line, whereas the cDNA sequence predicts that ETC is synthesized as a larger transmembrane protein. In the present study, we have characterized the membrane-anchored forms of BTC, using Chinese hamster ovary (CHO) cells, mouse fibroblast A9 cells, and a human breast cancer cell line MCF-7, all of which were stably transfected with human ETC cDNA. A9 and MCF-7 transfectants produced membrane-anchored ETC isoforms of 21, 25, 29, and 40 kDa on the cell surface, as well as a secreted BTC isoform. CHO transfectants secreted little ETC but accumulated the membrane-anchored isoforms. The cleavage of the membrane-anchored forms to release a secreted from of ETC was not enhanced by biological mediators such as a phorbol ester, which stimulates the cleavage of other membrane-anchored growth factors. The membrane-anchored forms of ETC expressed on the transfected cells induced the insulin production and/or promoted the growth in subclones of AR42J rat pancreatic cells. These results suggest that the membrane-anchored ETC can function as a juxtacrine factor in regulating the growth and differentiation of pancreatic endocrine cells. J. Cell. Biochem. 72.423-134, 1999. (C) 1999 Wiley-Liss, Inc. C1 Okayama Univ, Fac Engn, Dept Biosci & Biotechnol, Okayama 7008530, Japan. Takeda Chem Ind Ltd, Div Discovery Res, Discovery Res Labs 2, Ibaragi 30042, Japan. Gunma Univ, Inst Mol & Cellular Regulat, Maebashi, Gumma 371, Japan. Hammersmith Hosp, Imperial Canc Res Fund, Oncol Unit, London W12 0NN, England. NCI, Tumor Growth Factor Sect, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. RP Tada, H (reprint author), Okayama Univ, Fac Engn, Dept Biosci & Biotechnol, 3-1-1 Tsushima Naka, Okayama 7008530, Japan. RI YAMADA, Hidenori/B-2639-2011 NR 43 TC 41 Z9 41 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 1 PY 1999 VL 72 IS 3 BP 423 EP 434 DI 10.1002/(SICI)1097-4644(19990301)72:3<423::AID-JCB11>3.0.CO;2-P PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 158UN UT WOS:000078135700011 PM 10022523 ER PT J AU Chong, HY Vodovotz, Y Cox, GW Barcellos-Hoff, MH AF Chong, HY Vodovotz, Y Cox, GW Barcellos-Hoff, MH TI Immunocytochemical localization of latent transforming growth factor-beta 1 activation by stimulated macrophages SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID FACTOR-BETA; TGF-BETA; ENDOTHELIAL-CELLS; HUMAN KERATINOCYTES; COLLAGEN FORMATION; IN-SITU; EXPRESSION; INDUCTION; RECEPTOR; DIFFERENTIATION AB Transforming growth factor-beta 1 (TGF-beta) is secreted in a latent form consisting of mature TGF-beta noncovalently associated with its amino-terminal propeptide, which is called latency associated peptide (LAP). Biological activity depends upon the release of TGF-beta from the latent complex following extracellular activation, which appears to be the key regulatory mechanism controlling TGF-beta action. We have identified two events associated with latent TGF-beta (LTGF-beta) activation in vivo: increased immunoreactivity of certain antibodies that specifically detect TGF-beta concomitant with decreased immunoreactivity of antibodies to LAP. Macrophages stimulated in vitro with interferon-gamma and lipopolysaccharide reportedly activate LTGF-beta via cell membrane-bound protease activity. We show through dual immunostaining of paraformaldehyde-fixed macrophages that such physiological TGF-beta activation is accompanied by a loss of LAP immunoreactivity with concomitant revelation of TGF-beta epitopes. The induction of TGF-beta immunoreactivity colocalized with immunoreactive betaglycan/RIII in activated macrophages, suggesting that LTGF-beta activation occurs on the cell surface. Confocal microscopy of metabolically active macrophages incubated with antibodies to TGF-beta and betaglycan/RIII prior to fixation supported the localization of activation to the cell surface. The ability to specifically detect and localize LTGF-beta activation provides an important tool for studies of its regulation. J. Cell. Physiol. 178:275-283, 1999. (C) 1999 Wiley-Liss, Inc. C1 Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, Berkeley, CA 94720 USA. NCI, Radiat Biol Branch, Bethesda, MD 20892 USA. NCI, Macrophage Cell Biol Sect, Expt Immunol Lab, Bethesda, MD 20892 USA. RP Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, Bldg 74-174,1 Cyclotron Rd, Berkeley, CA 94720 USA. EM MHBarcellos-Hoff@lbl.gov NR 45 TC 29 Z9 29 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9541 EI 1097-4652 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD MAR PY 1999 VL 178 IS 3 BP 275 EP 283 DI 10.1002/(SICI)1097-4652(199903)178:3<275::AID-JCP1>3.0.CO;2-Q PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 164JP UT WOS:000078460700001 PM 9989773 ER PT J AU Koong, SS Reynolds, JC Movius, EG Keenan, AM Ain, KB Lakshmanan, MC Robbins, J AF Koong, SS Reynolds, JC Movius, EG Keenan, AM Ain, KB Lakshmanan, MC Robbins, J TI Lithium as a potential adjuvant to I-131 therapy of metastatic, well differentiated thyroid carcinoma SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID TRIIODOTHYRONINE WITHDRAWAL; RADIOIODINE THERAPY; CANCER; IODINE; SCANS AB As lithium inhibits the release of iodine from the thyroid but does not change iodine uptake, it may potentiate I-131 therapy of thyroid cancer. The effects of lithium on the accumulation and retention of I-131 in metastatic lesions and thyroid remnants were evaluated in 15 patients with differentiated thyroid carcinoma. Two I-131 turnover studies were performed while the patients were hypothyroid. One was performed while the patient received lithium; the second served as a control study. From a series of gamma-camera images, it was found that lithium increased I-131 retention in 24 of 31 metastatic lesions and in 6 of 7 thyroid remnants. A comparison of I-131 retention during lithium with that during the control period showed that the mean increase in the biological or retention half-life was 50% in tumors and 90% in remnants. This increase occurred in at least 1 lesion in each patient and was proportionally greater in lesions with poor I-131 retention. When the control biological half life was less than 3 days, lithium prolonged the effective half-life, which combines both biological turnover and isotope decay, in responding metastases by more than 50%. More I-131 also accumulated during lithium therapy, probably as a consequence of its effect on iodine release. The increase in the accumulated I-131 and the lengthening of the effective half-life combined to increase the estimated I-131 radiation dose in metastatic tumor by 2.29 +/- 0.58 (mean +/- SEM) times. These studies suggest that lithium may be a useful adjuvant for I-131 therapy of thyroid cancer, augmenting both the accumulation and retention of I-131 in lesions. C1 NIDDKD, Dept Nucl Med, Warren Grant Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. NIDDKD, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. RP Reynolds, JC (reprint author), NIDDKD, Dept Nucl Med, Warren Grant Magnuson Clin Ctr, NIH, Bldg 10,Room 1C-401, Bethesda, MD 20892 USA. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 23 TC 87 Z9 101 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 1999 VL 84 IS 3 BP 912 EP 916 DI 10.1210/jc.84.3.912 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 176JC UT WOS:000079147100015 PM 10084570 ER PT J AU Vottero, A Stratakis, CA Ghizzoni, L Longui, CA Karl, M Chrousos, GP AF Vottero, A Stratakis, CA Ghizzoni, L Longui, CA Karl, M Chrousos, GP TI Androgen receptor-mediated hypersensitivity to androgens in women with nonhyperandrogenic hirsutism: Skewing of X-chromosome inactivation SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article; Proceedings Paper CT 80th Annual Meeting of the Endocrine-Society CY JUN 21-29, 1998 CL NEW ORLEANS, LA SP Endocrine Soc ID PROSTATE-CANCER; CAG REPEAT; TRINUCLEOTIDE REPEAT; FRAGILE-X; GENE; AGE; EXPANSION; IDENTIFICATION; METHYLATION; LYONIZATION AB Idiopathic hirsutism may result from an increase in the androgen receptor (AR)-mediated sensitivity of the hair follicle. The AR gene is located on the X-chromosome and contains a highly polymorphic trinucleotide repeat (CAGn) in its first exon, whose length and methylation pattern affect both AR expression and function. We analyzed these CAG repeats in the genomic DNA from 16 nonhyperandrogenic hirsute patients (Ferriman score: 16 +/- 4.7, mean +/- SD) and 10 normal controls (Ferriman score: 3 +/- 1.4), who were similar in their hormonal profiles. We found no difference in the number of CAG repeats between hirsute patients and controls, and no correlation between number of repeats and the Ferriman score or hormonal values. However, alter DNA digestion with methylation-sensitive HpaII and measurement of the optical density, we found a marked decrease in the hirsute group (P < 0.0001), which was greater than in the control group (P = 0.0003). In addition, in the hirsute patients, the shorter of the two alleles was preferentially less methylated (P = 0.007), suggesting skewing of X-chromosome inactivation in the patients but not in the controls. When the mean optical density of both alleles was correlated with the Ferriman score, we observed a significant negative correlation (P = 0.02, r = -0.45), which became stronger when the shorter alleles were analyzed separately (P = 0.01; r = -0.48). We conclude that nonhyperandrogenic hirsutism is associated with skewing of X-chromosome inactivation in peripheral blood lymphocytes. This leads to the longer of the two AR alleles being preferentially methylated, allowing for the shorter land presumably, more functional) allele to be expressed on the active X-chromosome. Further studies need to be performed to investigate whether this phenomenon is present in androgen-sensitive tissues in these patients. C1 NICHD, Sect Pediat Endocrinol, DEB, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Dept Pediat, Washington, DC 20007 USA. Univ Parma, Dept Pediat, I-43100 Parma, Italy. RP Vottero, A (reprint author), NICHD, Sect Pediat Endocrinol, DEB, NIH, Bldg 10,Room 10N262,10 Ctr Dr,MSC 1862, Bethesda, MD 20892 USA. EM votteroa@cc1.nichd.nih.gov NR 31 TC 69 Z9 71 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 1999 VL 84 IS 3 BP 1091 EP 1095 DI 10.1210/jc.84.3.1091 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 176JC UT WOS:000079147100046 PM 10084600 ER PT J AU Figueiredo, BC Stratakis, CA Sandrini, R DeLacerda, L Pianovsky, MAD Giatzakis, C Young, HM Haddad, BR AF Figueiredo, BC Stratakis, CA Sandrini, R DeLacerda, L Pianovsky, MAD Giatzakis, C Young, HM Haddad, BR TI Comparative genomic hybridization analysis of adrenocortical tumors of childhood SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article; Proceedings Paper CT 80th Annual Meeting of the Endocrine-Society CY JUN 21-29, 1998 CL NEW ORLEANS, LA SP Endocrine Soc ID CULTURED ADRENAL-CELLS; LINE P53 MUTATIONS; GROWTH-FACTOR-II; CANCER; GENE; NEOPLASMS; EXPRESSION; CHROMOSOME; CARCINOMA; TRANSLOCATION AB Although several genes have been investigated in adrenal tumorigenesis, the genetic background of adrenocortical tumors (ACT) remains poorly characterized. In southern Brazil, the annual incidence of ACT is unusually high, ranging from 3.4-4.2/million children, compared with a worldwide incidence of 0.3/million children younger than 15 yr. Environmental factors have been implicated because the distribution of these tumors follows a regional, rather than a familial, pattern. However, decreased penetrance of a particular gene defect cannot be excluded. Because linkage or other traditional genetic analyses would not be appropriate to investigate the defect(s) associated with ACT in this population, we used comparative genomic hybridization (CGH) to screen for DNA sequence copy number changes in 9 nonfamilial ACT (6 carcinomas and 3 adenomas) from unrelated patients from this region. Six female (aged 10 months to 6 3/4 yr) and 3 male (1 1/12 to 3 1/4 yr) patients were studied. Three carcinomas were at stage I, 1 was at stage II, and another was at stage III. Two carcinomas had evidence of invasion of the vena cave, and 3 were more than 3 cm in size. All patients underwent surgical excision of their turners; chemotherapy was administered to cancer patients. Currently, all patients are alive and in remission, with the exception of 1 patient with stage III cancer. High mol wt DNA was extracted from tumor tissue obtained at surgery and frozen at -70 C. This DNA was labeled and used for CGH according to standard procedures. Digital image analysis was performed to detect chromosomal gains or losses. CGH evaluation revealed extensive genetic aberrations in both adenomas and carcinomas; there were no significant differences relative to age, gender, size, or stage of the tumor (P > 0.1). Chromosomes and chromosomal regions 1q, 5p, 5q, 6p, 6q, 8p, 8q, 9q, 10p, 11q, 12q, 13q, 14q, 15q, 16, 18q, 19, and 20q demonstrated gains, whereas 2q, 3, 4, 9p, 11, 13q, 18, 20p, and Xq showed losses. The most striking finding was consistent copy number gain of chromosomal region 9q34 in 8 of the 9 tumors. We conclude that both benign and malignant ACT from southern Brazil show multiple genetic aberrations, including a consistent gain of chromosomal region 9q34. This genomic area may harbor genetic defects that predispose to ACT formation and are shared by the patients who were investigated in this study or are accumulated epigenetically under the influence of a common factor, such as an environmental mutagen. C1 NICHHD, Unit Genet & Endocrinol, Sect Pediat Endocrinol, Dev Endocrinol Branch,NIH, Bethesda, MD 20892 USA. Univ Fed Parana, Dept Pediat, Div Endocrinol, Curitiba, Parana, Brazil. Georgetown Univ, Dept Pediat, Div Pediat Endocrinol, Washington, DC 20007 USA. Georgetown Univ, Dept Obstet & Gynecol, Washington, DC 20007 USA. Georgetown Univ, Inst Mol & Human Genet, Washington, DC 20007 USA. RP Stratakis, CA (reprint author), NICHHD, Unit Genet & Endocrinol, Sect Pediat Endocrinol, Dev Endocrinol Branch,NIH, Bldg 10,Room 10N262,10 Ctr Dr,MSC1862, Bethesda, MD 20892 USA. EM stratakc@cc1.nichd.nih.gov NR 44 TC 90 Z9 93 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 1999 VL 84 IS 3 BP 1116 EP 1121 DI 10.1210/jc.84.3.1116 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 176JC UT WOS:000079147100050 PM 10084604 ER PT J AU Stratakis, CA Carney, JA Kirschner, LS Willenberg, HS Brauer, S Ehrhart-Bornstein, M Bornstein, SR AF Stratakis, CA Carney, JA Kirschner, LS Willenberg, HS Brauer, S Ehrhart-Bornstein, M Bornstein, SR TI Synaptophysin immunoreactivity in primary pigmented nodular adrenocortical disease: Neuroendocrine properties of tumors associated with Carney complex SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GASTRIC-INHIBITORY POLYPEPTIDE; CUSHINGS-SYNDROME; ADRENAL-GLAND; CARDIAC MYXOMAS; ENDOCRINE OVERACTIVITY; CORTICAL-CELLS; DIFFERENTIATION; NEOPLASIA; GENE; IDENTIFICATION AB Carney complex (CNC) is characterized by lentiginosis and myxomatosis together with a variety of endocrine, neural crest-derived, and other tumors, including primary pigmented nodular adrenocortical disease (PPNAD). PPNAD is characterized by lipofuscin-containing, autonomously functioning, cortisol-producing nodules surrounded by mostly atrophic adrenocortical and normal adrenomedullary tissue. The nature and origin of the tumors, including the myxomas and PPNAD, are unclear. In this study, seven paraffin embedded PPNAD tumors, one skin myxoma, and two cell lines tone myxoma and one PPNAD) established from patients with CNC were stained with antisera for synaptophysin (SYN), neuron-specific enolase, chromogranin A, tyrosine hydroxylase, and the neural cell adhesion molecule (NCAM). In addition, one PPNAD specimen and one myxoma were analyzed by electron microscopy. The results showed that chromogranin A and tyrosine hydroxylase stained adrenomedullary tissue, but not the PPNAD nodules or the extranodular adrenal cortex. SYN, neuron-specific enolase, and NCAM also stained the medulla. PPNAD nodules and the PPNAD cell line, but not the extranodular adrenal cortex, stained intensely for SYN. The myxoma cell line, but not; normal fibroblasts, stained for SYN and NCAM. Ultrastructural analysis of a PPNAD tumor and a skin myxoma revealed a well developed rough endoplasmic reticulum, prominent mitochondria, and vesicle-like structures dispersed throughout the cytoplasm. We conclude that immunostaining for SYN, a marker protein for neuroendocrine cells, clearly distinguishes PPNAD nodules from surrounding adrenocortical tissue and can be helpful in the detection of small nodules in apparently unaffected cortex. The cells of a cutaneous myxoma were also stained positive by two of the three neuroendocrine markers. Finally, both PPNAD and myxoma cells demonstrated ultrastructural features suggestive of neuroendocrine properties. These results support the previously suggested hypothesis that the genetic mechanism leading to CNC involves genes with a neuroendocrine role. C1 NICHHD, Unit Genet & Endocrinol, Sect Pediat Endocrinol,Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Univ Leipzig, D-04103 Leipzig, Germany. Univ Dusseldorf, Diabet Res Inst, Dusseldorf, Germany. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. RP Stratakis, CA (reprint author), NICHHD, Unit Genet & Endocrinol, Sect Pediat Endocrinol,Dev Endocrinol Branch, NIH, Bldg 10,Room 10N262, Bethesda, MD 20892 USA. EM stratakc@cc1.nichd.nih.gov NR 35 TC 36 Z9 40 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 1999 VL 84 IS 3 BP 1122 EP 1128 DI 10.1210/jc.84.3.1122 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 176JC UT WOS:000079147100051 PM 10084605 ER PT J AU Hu, ZZ Zhuang, L Meng, JP Leondries, M Dufau, ML AF Hu, ZZ Zhuang, L Meng, JP Leondries, M Dufau, ML TI The human prolactin receptor gene structure and alternative promoter utilization: The generic promoter hPIII and a novel human promoter hP(N) SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID EXPRESSION AB The 5'-untranslated region of the human prolactin receptor (hPRLR) gene contains two alternative first exons, hE1(3), the human counterpart of the rat and mouse E1(3) and a novel human type of alternative first exon termed hE1(N), also a common non-coding exon 2 and a third exon containing the translation initiation codon. hE1(3) was localized similar to 800 bp 5' from the hE1(N) in the genome. The two distinct first exons hE1(3) and hE1(N) are expressed in human breast tissue, breast cancer cells, gonads and liver. Overall, the transcript containing hE1(3) is prevalent in most tissues. The coding region of the gene comprises eight exons (exon 3-10), in which exon 10 encodes most of the intracellular domain. hE1(3) and hE1(N) are transcribed from alternative promoters hPIII and hP(N), respectively. The hPIII, containing identical Sp1 and C/EBP elements as in the rodent promoters, shares 81% similarity in the region -480/-106 to both the rat and mouse. The novel promoter hP(N) contains putative binding sites for ETS-family proteins and a half-site for nuclear receptors. Therefore, both promoters likely utilize distinct mechanisms in controlling the hPRLR gene transcription. The different promoter utilization of the hPRLR gene in diverse tissues may confer differential prolactin response through activation of different promoters. C1 NICHHD, Sect Mol Endocrinol, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Dufau, ML (reprint author), NICHHD, Sect Mol Endocrinol, Endocrinol & Reprod Res Branch, NIH, Bldg 49,Rm 6A36, Bethesda, MD 20892 USA. NR 10 TC 43 Z9 56 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 1999 VL 84 IS 3 BP 1153 EP 1156 DI 10.1210/jc.84.3.1153 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 176JC UT WOS:000079147100057 PM 10084611 ER PT J AU Boone, JH Wilkins, TD Nash, TE Brandon, JE Macias, EA Jerris, RC Lyerly, DM AF Boone, JH Wilkins, TD Nash, TE Brandon, JE Macias, EA Jerris, RC Lyerly, DM TI TechLab and Alexon Giardia enzyme-linked immunosorbent assay kits detect cyst wall protein 1 SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID MONOCLONAL-ANTIBODY; LAMBLIA; ANTIGENS; IDENTIFICATION; EXPRESSION AB A Giardia lamblia antigen detected by the TechLab Giardia Test (TechLab, Inc., Blacksburg, Va.) and the Alexon ProSpecT Giardia microplate assay (Alexon, Inc., Sunnyvale, Calif.) was purified by immunoaffinity chromatography from supernatant fluids of encystment cultures. Two major proteins (M-r 22,000 and 26,000) were observed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Coomassie staining that did not resemble the GSA65 antigen reportedly detected by the Alexon test. These proteins reacted intensely with the monoclonal antibodies used in both commercial enzyme-linked immunosorbent assays (ELISAs). Both proteins had identical N-terminal amino acid sequences and were identified as cyst wall protein 1 (CWP1), The 26-kDa form appeared early during encystment followed by the appearance of the 22-kDa form, Recombinant CWP1 (M-r 26,000) was strongly positive in both commercial tests. CWP1 was stable in human stool specimens, resistant to degradation by proteases and N- and O-glycanases, and unaffected by oxidation with sodium periodate. Two minor proteins with M(r)s of 32,000 and 39,000 were detected in CWP1 preparations by using a sensitive fluorescent protein stain. Both were identified as CWP2, and neither reacted with the monoclonal antibodies from the commercial tests. We analyzed 535 stool specimens for CWP1 by using both commercial ELISAs and resolved discrepant results by using routine ova and parasite examination (O&P) and on immunofluorescence antibody assay. The presence of CWP1 correlated well between both ELISAs (98.7% correlation). Our results demonstrate that both commercial ELISAs detect CWP1, which is a useful diagnostic marker because it is highly stable, is secreted in large amounts by encysting trophozoites, and correlates well with O&P. C1 TechLab Inc, Corp Res Ctr, Blacksburg, VA 24060 USA. Virginia Polytech Inst & State Univ, Fralin Biotech Ctr, Blacksburg, VA 24061 USA. NIAID, Bethesda, MD 20892 USA. Sacred Heart Med Ctr, Spokane, WA 99220 USA. Virus Reference Labs, San Antonio, TX 78229 USA. DeKalb Med Ctr, Decatur, GA 30033 USA. RP Boone, JH (reprint author), TechLab Inc, Corp Res Ctr, 1861 Pratt Dr, Blacksburg, VA 24060 USA. NR 19 TC 22 Z9 24 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAR PY 1999 VL 37 IS 3 BP 611 EP 614 PG 4 WC Microbiology SC Microbiology GA 166MC UT WOS:000078579500023 PM 9986821 ER PT J AU Diehl, V Sextro, M Franklin, J Hansmann, ML Harris, N Jaffe, E Poppema, S Harris, M Franssila, K van Krieken, J Marafioti, T Anagnostopoulos, I Stein, H AF Diehl, V Sextro, M Franklin, J Hansmann, ML Harris, N Jaffe, E Poppema, S Harris, M Franssila, K van Krieken, J Marafioti, T Anagnostopoulos, I Stein, H TI Clinical presentation, course, and prognostic factors in lymphocyte-predominant Hodgkin's disease and lymphocyte-rich classical Hodgkin's disease: Report from the European Task Force on Lymphoma Project on Lymphocyte-Predominant Hodgkin's disease SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LARGE-CELL LYMPHOMA; FOLLICULAR LYMPHOMA; REED-STERNBERG; THERAPY; PATTERN; CHAIN AB Purpose: Recent studies have suggested that lymphocyte-predominant Hodgkin's disease (LPHD) is both clinically and pathologically distinct from or her forms of Hodgkin's disease, including classical Hodgkin's disease (CHD), However, large-scale clinical studies were tacking, This multicenter, retrospective study investigated the clinical characteristics and course of LPHD patients and lymphocyte-rich classical Hodgkin's disease (LRCHD) patients classified according to morphologic and immunophenotypic criteria, Materials and Methods: Clinical data and biopsy material of all available cases initially submitted as LPHD were collected from 17 European and American centers, stained, and reclassified by expert pathologists. Results: The 426 assessable cases were reclassified as LPHD (51%), LRCHD (27%), CHD (5%), non-Hodgkin's lymphoma (3%), and reactive lesion (3%); 11% of cases were not assessable. Patients with LPHD and LRCHD were predominantly male, with early-stage disease and few risk factors. Patients with LRCHD were significantly older, Survival and failure-free survival rates with adequate therapy were similar for patients with LPHD and LRCHD, and were stage-dependent and not significantly better than stage-comparable results for CHD (German trial data), Twenty seven percent of relapsing LPHD patients had multiple relapses, which is significantly more than the 5% of relapsing LRCHD patients who had multiple relapses. Lymphocyte-predominant Hodgkin's disease patients herd significantly superior survival after relapse compared with LRCHD or CHD patients; however, this was partly due to the younger average age of LPHD patients, Conclusion: The two subgroups of LPHD and LRCHD bore a close clinical resemblance that was distinct from CHD; the course was similar to that of comparable nodular sclerosis and mixed cellularity patients, Thorough staging is necessary to detect advanced disease in LPHD and LRCHD patients. The question of how to treat such patients, either by reducing treatment intensity or following a "watch and wait" approach, remains unanswered, (C) 1999 by American Society of Clinical Oncology. C1 Univ Cologne, Dept Internal Med, Cologne, Germany. Univ Frankfurt, Dept Pathol, D-6000 Frankfurt, Germany. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NCI, Bethesda, MD 20892 USA. Univ Groningen, Groningen, Netherlands. Christie Hosp Manchester, Manchester, Lancs, England. Univ Helsinki, Cent Hosp, Helsinki, Finland. Akad Ziekenhuis, Leiden, Netherlands. Free Univ Berlin, Klinikum Benjamin Franklin, D-12200 Berlin, Germany. RP Diehl, V (reprint author), Innere Med Klin 1, D-50924 Cologne, Germany. RI Marafioti, Teresa/B-4493-2009; Poppema, Sibrand/D-1204-2012; van Krieken, Joannes/D-4138-2009 OI van Krieken, Joannes/0000-0001-6544-1040 NR 35 TC 189 Z9 201 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR PY 1999 VL 17 IS 3 BP 776 EP 783 PG 8 WC Oncology SC Oncology GA 173GM UT WOS:000078972800007 PM 10071266 ER PT J AU Rosenberg, SA Yang, JC Schwartzentruber, DJ Hwu, P Marincola, FM Topalian, SL Seipp, CA Einhorn, JH White, DE Steinberg, SM AF Rosenberg, SA Yang, JC Schwartzentruber, DJ Hwu, P Marincola, FM Topalian, SL Seipp, CA Einhorn, JH White, DE Steinberg, SM TI Prospective randomized trial of the treatment of patients with metastatic melanoma using chemotherapy with cisplatin, dacarbazine, and tamoxifen alone or in combination with interleukin-2 and interferon alfa-2b SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID MALIGNANT-MELANOMA; CARMUSTINE AB Purpose: The combination of chemotherapy with immunotherapeutic agents such as interleukin-a and interferon alfa-2b has been reported to provide improved treatment results in patients with metastatic melanoma, compared with the use of chemotherapy alone, We have performed a prospective randomized trial in patients with metastatic melanoma, comparing treatment with chemotherapy to treatment with chemoimmunotherapy. Patients and Methods: One hundred two patients with metastatic melanoma were prospectively randomized to receive chemotherapy composed of tamoxifen, cisplatin, and dacarbazine or this same chemotherapy followed by interferon alfa-2b and interleukin-2 Objective responses, survival, and toxicity in the two groups were evaluated at a median potential follow-vp of 42 months. Results: In 52 patients randomized to receive chemotherapy, there were 14 objective responses (27%), including four complete responses. in SO patients randomized to receive chemoimmunotherapy, there were 22 objective responses (44%) (P-2 = .071), including three complete responses. In both treatment groups, the duration of partial responses was often short, and there was a trend toward a survival advantage for patients receiving chemotherapy alone (P-2 = .052; median survival of 15.8 months compared with 10.7 months). Treatment-related toxicities were greater in patients receiving chemoimmunotherapy, Conclusion: With the treatment regimens used in this study the addition of immunotherapy to combination chemotherapy increased toxicity but did not increase survival, The use of combination chemoimmunotherapy regimens is nat recommended in the absence of well-designed, prospective, randomized protocols showing the benefit of this treatment strategy. (C) 1999 by American Society of Clinical Oncology. C1 NCI, Div Clin Sci, Surg Branch, NIH, Bethesda, MD 20892 USA. NCI, Dept Biostat, NIH, Bethesda, MD 20892 USA. NCI, Data Management Sect, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Rosenberg, SA (reprint author), NCI, Div Clin Sci, Surg Branch, NIH, 9000 Rockville Pike,Bldg 10,Room 2B42, Bethesda, MD 20892 USA. EM steven_rosenberg@nih.gov NR 22 TC 218 Z9 222 U1 2 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR PY 1999 VL 17 IS 3 BP 968 EP 975 PG 8 WC Oncology SC Oncology GA 173GM UT WOS:000078972800032 PM 10071291 ER PT J AU McCaskill-Stevens, W Pinto, H Marcus, AC Comis, R Morgan, R Plomer, K Schoentgen, S AF McCaskill-Stevens, W Pinto, H Marcus, AC Comis, R Morgan, R Plomer, K Schoentgen, S TI Recruiting minority cancer patients into cancer clinical trials: A pilot project involving the Eastern Cooperative Oncology Group and the National Medical Association SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID COMMUNITY; CARE; POPULATIONS; PHYSICIANS; PROGRAM; BLACK AB Purpose: Minority accrual onto clinical trials is of significant interest to cooperative oncology study groups. The Eastern Cooperative Oncology Group (ECOG) conducted ct study to identify barriers and solutions to African American accrual onto clinical trials. Methods: We hypothesize that the National Medical Association (NMA) might provide insight into ways to increase minority participation and that ECOG might facilitate that participation. Four sites were selected in which NMA chapters existed and ECOG main institutions with less than half of the corresponding percentage of minorities in their communities entered trials for 1992, Fifteen workshops were conducted using discussions and open-ended, serf-administered questionnaires. Results: Seventy percent of NMA physicians cited mistrust of the research centers, fear of losing patients, and a lack of respect from ECOG institutions as the most important barriers to minority cancer patient referrals, compared with 30% for ECOG physicians. Sixty-nine percent of NMA and 43% of ECOG physicians cited a lack of information about specific trials. Nearly half of NMA physicians (47%) cited a lack of minority investigators as a barrier, compared with 4% of ECOG physicians. Solutions by both groups were improved communication (73%) and culturally relevant educational materials (40%), ECOG physicians cited more minority outreach staff as a potential solution (22% v 6%). NMA physicians cited increased involvement of referring physicians (44% v4%). Conclusion: NMA physicians who serve a significant sector of the African American population demonstrated a willingness to participate and work with a cooperative group effort to increase participation of minority patients and investigators. (C) 1999 by American Society of Clinical Oncology. C1 NCI, Div Canc Prevent, NIH, Rockville, MD 20852 USA. Stanford Med Ctr, Div Oncol, Stanford, CA USA. AMC Canc Res Ctr, Denver, CO USA. Eastern Cooperat Oncol Grp, Philadelphia, PA USA. Natl Med Assoc, Merrillville, IN USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. RP McCaskill-Stevens, W (reprint author), NCI, Div Canc Prevent, NIH, 6130 Execut Blvd,Room 300, Rockville, MD 20852 USA. EM wm57h@nih.gov NR 18 TC 58 Z9 58 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR PY 1999 VL 17 IS 3 BP 1029 EP 1039 PG 11 WC Oncology SC Oncology GA 173GM UT WOS:000078972800039 PM 10071298 ER PT J AU Bluman, LG Rimer, BK Berry, DA Borstelmann, N Iglehart, JD Regan, K Schildkraut, J Winer, EP AF Bluman, LG Rimer, BK Berry, DA Borstelmann, N Iglehart, JD Regan, K Schildkraut, J Winer, EP TI Attitudes, knowledge, and risk perceptions of women with breast and/or ovarian cancer considering testing for BRCA1 and BRCA2 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID FAMILY HISTORY; HEREDITARY BREAST; DECISION-MAKING; GENE BRCA1; SUSCEPTIBILITY; IMPACT; TRIAL AB Purpose: This study examined baseline knowledge, beliefs, and risk perceptions among a group of 200 women with breast and/or ovarian cancer who participated in a trial designed to improve decision making about genetic testing for BRCA1 and BRCA2. Patients and Methods: Women were identified by self-referral, physician referral, and tumor registry extraction and invited to participate in a randomized trial in which testing for BRCA I and BRCA2 was offered free of charge, Subjects completed baseline questionnaires and interviews that assessed knowledge, attitudes, and perceptions of risk of having an alteration in BRCA1 or BRCA2. Results: Sixty percent of women overestimated their chances of having a BRCA1 or BRCA2 mutation compared with estimates from a BRCA 1/BRCA2 risk model. Women who have at least three relatives with breast or ovarian cancer were one third (95% confidence interval, 0.2 to 0.6) as likely to overestimate their risk of having a BRCA1 or BRCA2 mutation compared with women who have two or fewer affected relatives. Knowledge wets limited about BRCA1 and BRCA2 mutations and cancer risk associated with gene mutations, Eighty-four percent of the women indicated a probable or definite interest in testing. Conclusion: A high proportion of the high-risk women in this study had knowledge deficits about BRCA1 and BRCA2 and overestimated their risk of having a mutation, Although some degree of caution should be used in generalizing the results of this study to practice settings, the data provide insight into the challenges clinicians will face in communicating with patients about cancer genetics. (C) 1999 by American Society of Clinical Oncology. C1 Dana Farber Canc Inst, Breast Oncol Ctr, Dept Care Coordinat, Boston, MA 02115 USA. Dana Farber Canc Inst, Gillette Ctr Womens Canc, Boston, MA 02115 USA. Duke Univ, Med Ctr, Canc Prevent Detect & Control Res Program, Durham, NC 27706 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27706 USA. Duke Univ, Inst Stat & Decis Sci, Durham, NC 27706 USA. NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. RP Bluman, LG (reprint author), Dana Farber Canc Inst, Breast Oncol Ctr, Dept Care Coordinat, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA 68438] NR 43 TC 91 Z9 91 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR PY 1999 VL 17 IS 3 BP 1040 EP 1046 PG 7 WC Oncology SC Oncology GA 173GM UT WOS:000078972800040 PM 10071299 ER PT J AU Desper, R Jiang, F Kallioniemi, OP Moch, H Papadimitriou, CH Schaffer, AA AF Desper, R Jiang, F Kallioniemi, OP Moch, H Papadimitriou, CH Schaffer, AA TI Inferring tree models for oncogenesis from comparative genome hybridization data SO JOURNAL OF COMPUTATIONAL BIOLOGY LA English DT Article DE algorithms; branching; cancer genetics; comparative genome hybridization; renal cancer; tree inference ID RENAL-CELL CARCINOMA; TUMOR-SUPPRESSOR GENE; CLONAL EVOLUTION; MUTATIONS; CANCER; HETEROGENEITY AB Comparative genome hybridization (CGH) is a laboratory method to measure gains and losses of chromosomal regions in tumor cells. It is believed that DNA gains and losses in tumor cells do not occur entirely at random, but partly through some flow of causality. Models that relate tumor progression to the occurrence of DNA gains and losses could be very useful in hunting cancer genes and in cancer diagnosis. We lay some mathematical foundations for inferring a model of tumor progression from a CGH data set. We consider a class of tree models that are more general than a path model that has been developed for colorectal cancer, We derive a tree model inference algorithm based on the idea of a maximum-weight branching in a graph, and we show that under plausible assumptions our algorithm infers the correct tree. We have implemented our methods in software, and we illustrate with a CGH data set for renal cancer. C1 Rutgers State Univ, Dept Math, Piscataway, NJ 08854 USA. Univ Basel, Inst Pathol, Basel, Switzerland. Natl Human Genome Res Inst, Canc Genet Branch, NIH, Bethesda, MD USA. Univ Calif Berkeley, Dept Elect Engn & Comp Sci, Berkeley, CA 94720 USA. Natl Human Genome Res Inst, Inherited Dis Res Branch, NIH, Baltimore, MD USA. RP Schaffer, AA (reprint author), Rutgers State Univ, Dept Math, Piscataway, NJ 08854 USA. RI Kallioniemi, Olli/H-5111-2011; Schaffer, Alejandro/F-2902-2012; Kallioniemi, Olli/H-4738-2012 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 35 TC 120 Z9 123 U1 0 U2 6 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1066-5277 J9 J COMPUT BIOL JI J. Comput. Biol. PD SPR PY 1999 VL 6 IS 1 BP 37 EP 51 DI 10.1089/cmb.1999.6.37 PG 15 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 182MW UT WOS:000079503600003 PM 10223663 ER PT J AU Post, RM Kimbrell, TA McCann, UD Dunn, RT Osuch, EA Speer, AM Weiss, SRB AF Post, RM Kimbrell, TA McCann, UD Dunn, RT Osuch, EA Speer, AM Weiss, SRB TI Repetitive transcranial magnetic stimulation as a neuropsychiatric tool: Present status and future potential SO JOURNAL OF ECT LA English DT Article DE repetitive transcranial magnetic stimulation; electroconvulsive therapy; depression; affective disorders; long-term depression; long-term potentiation; positron emission tomography; mechanisms; brain imaging ID POSTTRAUMATIC-STRESS-DISORDER; POSITRON EMISSION TOMOGRAPHY; DORSOLATERAL PREFRONTAL CORTEX; AMYGDALA-KINDLED SEIZURES; LONG-TERM POTENTIATION; CEREBRAL BLOOD-FLOW; HUMAN MOTOR CORTEX; ELECTROCONVULSIVE-THERAPY; AFFECTIVE-ILLNESS; CONTINGENT TOLERANCE AB Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising therapeutic intervention in the treatment of affective disorders. The differences in the type of electrical stimulation required for therapeutic efficacy by rTMS and electroconvulsive therapy (ECT) are discussed. In contrast to ECT, rTMS would not appear to require the generation of a major motor seizure to achieve therapeutic efficacy. Accordingly, it carries the potentially important clinical advantages of not requiring anesthesia and of avoiding side effects such as transient memory loss. Preclinical studies on long-term potentiation (LTP) and long-term depression (LTD) in hippocampal and amygdala slices, as well as clinical data from neuroimaging studies, have provided encouraging clues for potential frequency-dependent effects of rTMS. Preliminary evidence from positron emission tomography (PET) scans suggests that higher frequency (20 Hz) stimulation may increase brain glucose metabolism in a transsynaptic fashion, whereas lower frequency (1 Hz) stimulation may decrease it. Therefore, the ability of rTMS to control the frequency as well as the location of stimulation, in addition to its other advantages, has opened up new possibilities for clinical explorations and treatments of neuropsychiatric conditions. C1 NIMH, Biol Psychiat Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Post, RM (reprint author), NIMH, Biol Psychiat Branch, Natl Inst Hlth, Bldg 10,Rm 3N212,10 Ctr Dr,MSC 1272, Bethesda, MD 20892 USA. RI Osuch, Elizabeth/B-5009-2015 OI Osuch, Elizabeth/0000-0001-5946-1862 NR 87 TC 70 Z9 75 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1095-0680 J9 J ECT JI J. ECT PD MAR PY 1999 VL 15 IS 1 BP 39 EP 59 PG 21 WC Behavioral Sciences; Psychiatry SC Behavioral Sciences; Psychiatry GA 268NU UT WOS:000084423100004 PM 10189618 ER PT J AU Cao, H Agarwal, SK Burnside, J AF Cao, H Agarwal, SK Burnside, J TI Cloning and expression of a novel chicken sulfotransferase cDNA regulated by GH SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID GROWTH-HORMONE RECEPTOR; I MESSENGER-RNA; ESTROGEN SULFOTRANSFERASE; DIFFERENTIAL DISPLAY; GENE-EXPRESSION; DEOXYRIBONUCLEIC-ACID; MOLECULAR-CLONING; DWARF CHICKENS; GUINEA-PIG; RAT-LIVER AB We have used mRNA differential display to compare gene expression in normal and GH receptor-deficient dwarf chickens, and report here the characterization of one differentially expressed gene, which shows significant sequence identity to the sulfotransferase gene family. Partial cDNA clones were isolated from a chicken liver cDNA library and an additional sequence was obtained using 5' rapid amplification of cDNA ends. A complete cDNA probe hybridizes to three transcripts (2.4, 2.0 and 1.45 kb) on Northern blots of chicken liver RNA, which differ in the length of the 3' untranslated region. All three transcripts are expressed at higher levels in normal vs dwarf chickens, as expected for a GH-regulated gene. The expression of this sulfotransferase mRNA was also detected in skeletal muscle, but not other tissues. The administration of GH to chickens increased the hepatic expression within 1 h, suggesting this sulfotransferase could be directly regulated by GH. Sulfotransferase activity, using estradiol or corticosterone as substrate, is detected in cells transfected with an expression vector containing the full-length cDNA. The sequence of this sulfotransferase does not show significant similarity with ally subfamily of the sulfotransferases and its endogenous substrate is presently unknown. However, we speculate that GH activation of sulfotransferase activity could play a role in reducing concentrations of growth-antagonistic steroid hormones in GH target tissues. These results demonstrate the usefulness of differential display in this model system to identify genes that play a role in mediating GH action. C1 Univ Delaware, Dept Biol, Newark, DE 19717 USA. Univ Delaware, Dept Anim & Food Sci, Newark, DE 19717 USA. RP Burnside, J (reprint author), NIDDK, NIH, Metab Dis Branch, Bldg 10,Room 9C-101, Bethesda, MD 20892 USA. RI Nolen, Danielle/A-5250-2010; Crozier, Laura/C-5891-2011; Agarwal, Sunita/D-1428-2016 OI Agarwal, Sunita/0000-0002-7557-3191 NR 43 TC 9 Z9 9 U1 0 U2 0 PU SOC ENDOCRINOLOGY PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4NQ, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD MAR PY 1999 VL 160 IS 3 BP 491 EP 500 DI 10.1677/joe.0.1600491 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 175MF UT WOS:000079097700018 PM 10076195 ER PT J AU Zieler, H Nawrocki, JP Shahabuddin, M AF Zieler, H Nawrocki, JP Shahabuddin, M TI Plasmodium gallinaceum ookinetes adhere specifically to the midgut epithelium of Aedes aegypti by interaction with a carbohydrate ligand SO JOURNAL OF EXPERIMENTAL BIOLOGY LA English DT Article DE malaria; mosquito; Aedes aegypti; midgut; transmission; blocking; insect; carbohydrate; sialic acid; Plasmodium gallinaceum ID FALCIPARUM-INFECTED ERYTHROCYTES; N-ACETYLNEURAMINIC ACID; CHONDROITIN SULFATE-A; SIALIC-ACID; LIQUID-CHROMATOGRAPHY; GLYCOLYLNEURAMINIC ACIDS; CONTAINING GLYCOPROTEINS; MALARIA PARASITES; SURFACE-ANTIGENS; BINDING ANTIGEN AB During the course of its development in the mosquito and transmission to a new vertebrate host, the malaria parasite must interact with the mosquito midgut and invade the gut epithelium. To investigate how the parasite recognizes the midgut before invasion, we have developed an in vitro adhesion assay based on combining fluorescently labelled ookinetes with isolated midgut epithelia from blood-fed mosquitoes, Using this assay, we found that Plasmodium gallinaceum ookinetes readily adhered to midguts of Aedes aegypti, mimicking the natural recognition of the epithelium by the parasite, This interaction is specific: the ookinetes preferentially adhered to the lumen (microvillar) side of the gut epithelium and did not bind to other mosquito tissues, Conversely, the binding was not due to a non-specific adhesive property of the midguts, because a variety of other cell types, including untransformed P. gallinaceum zygotes or macrogametes, did not show similar binding to the midguts, High concentrations of glycosylated (fetuin, orosomucoid, ovalbumin) or non-glycosylated (bovine serum albumin) proteins, added as non-specific competitors, failed to compete with the ookinetes in binding assays. We also found that the adhesion of ookinetes to the midgut surface is necessary for sporogonic development of the parasite in the mosquito. Antibodies and other reagents that blocked adhesion in vitro also reduced oocyst formation when these reagents were combined with mature ookinetes and fed to mosquitoes. Chemical modification of the midguts with sodium periodate at pH5.5 destroyed adhesion, indicating that the ookinete binds to a carbohydrate ligand on the surface of the midgut, The ligand is sensitive to periodate concentrations of less than 1 mmol l(-1), suggesting that it may contain sialic-acid-like sugars. Furthermore, free N-acetylneuraminic acid competed with the ookinetes in binding assays, while other monosaccharides had no effect. However, in agreement with the current belief that adult insects do not contain sialic acids, we were unable to detect any sialic acids in mosquito midguts using the most sensitive HPLC-based fluorometric assay currently available, We postulate that a specific carbohydrate group is used by the ookinete to recognize the midgut epithelium and to attach to its surface. This is the first receptor-ligand interaction demonstrated for the ookinete stage of a malaria parasite. Further characterization of the midgut ligand and its parasite counterpart may lead to novel strategies of blocking oocyst development in the mosquito. C1 NIAID, Med Entomol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Shahabuddin, M (reprint author), NIH, Parasit Dis Lab, Bldg 4,Room 126,4 Ctr Dr MSC 0425, Bethesda, MD 20892 USA. EM mshahabudd@atlas.niaid.nih.gov NR 76 TC 62 Z9 63 U1 2 U2 4 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0022-0949 EI 1477-9145 J9 J EXP BIOL JI J. Exp. Biol. PD MAR PY 1999 VL 202 IS 5 BP 485 EP 495 PG 11 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 178XU UT WOS:000079295100001 PM 9929452 ER PT J AU Pieper, R Christian, RE Gonzales, MI Nishimura, MI Gupta, G Settlage, RE Shabanowitz, J Rosenberg, SA Hunt, DF Topalian, SL AF Pieper, R Christian, RE Gonzales, MI Nishimura, MI Gupta, G Settlage, RE Shabanowitz, J Rosenberg, SA Hunt, DF Topalian, SL TI Biochemical identification of a mutated human melanoma antigen recognized by CD4(+) T cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE melanoma; antigen; CD4(+) T cells; HLA-DR1; triosephosphate isomerase ID TUMOR-INFILTRATING LYMPHOCYTES; HUMAN TRIOSEPHOSPHATE ISOMERASE; CARCINOMA PROTEINS; CRYSTAL-STRUCTURE; TYROSINASE GENE; PEPTIDE; IMMUNOTHERAPY; SUBSTITUTION; RECEPTOR; DATABASE AB CD4(+) T cells play a critical role in generating and maintaining immune responses against pathogens and alloantigens, and evidence suggests an important role for them in antitumor immunity as well. Although major histocompatibility complex class II-restricted human CD4(+) T cells with specific antitumor reactivities have been described, no standard method exists for cloning the recognized tumor-associated antigen (Ag). In this study, biochemical protein purification methods were used in conjunction with novel mass spectrometry sequencing techniques and molecular cloning to isolate a unique melanoma Ag recognized by a CD4+ tumor-infiltrating lymphocyte (TIL) line. The HLA-DR beta 1*0101-restricted Ag was determined to be a mutated glycolytic enzyme, triosephosphate isomerase (TPI). A C to T mutation identified by cDNA sequencing caused a Thr to Ile conversion in TPI, which could be detected in a tryptic digest of tumor-derived TPI by mass spectrometry. The Thr to Ile conversion created a neoepitope whose T cell stimulatory activity was enhanced at least 5 logs compared with the wild-type peptide. Analysis of T cell recognition of serially truncated peptides suggested that the mutated amino acid residue was a T cell receptor contact. Defining human tumor Ag recognized by T helper cells may provide important dues to designing more effective immunotherapies for cancer. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. Univ Virginia, Dept Chem, Charlottesville, VA 22908 USA. RP Topalian, SL (reprint author), NCI, Surg Branch, NIH, Bldg 10,Rm 2B47, Bethesda, MD 20892 USA. EM suzanne_topalian@nih.gov RI Hunt, Donald/I-6936-2012 OI Hunt, Donald/0000-0003-2815-6368 NR 36 TC 143 Z9 146 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAR 1 PY 1999 VL 189 IS 5 BP 757 EP 765 DI 10.1084/jem.189.5.757 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 173EJ UT WOS:000078968000002 PM 10049939 ER PT J AU Schuler, T Qin, ZH Ibe, S Noben-Trauth, N Blankenstein, T AF Schuler, T Qin, ZH Ibe, S Noben-Trauth, N Blankenstein, T TI T helper cell type 1-associated and cytotoxic T lymphocyte-mediated tumor immunity is impaired in interleukin 4-deficient mice SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE tumor vaccination; interleukin 4; T cell immunity; interleukin 4-deficient mice ID INTERLEUKIN-4-DEFICIENT MICE; MAMMARY ADENOCARCINOMA; INTERFERON-GAMMA; IL-4; GENE; ANTIGENS; VACCINATION; RESISTANCE; RESPONSES; DEFICIENT AB It is widely accepted that cellular immune responses are induced by CD4(+) T helper 1 (Th1) cells secreting interleukin (IL)-2 and interferon (IFN)-gamma. Tumor immunity is often mediated by cytotoxic T lymphocytes (CTLs) whose activation is supported by Th1 cytokines. Since IL-4 directs Th2 development and has been shown to inhibit Th1-dominated responses, we assumed that IL-4-deficient (IL-4(-/-)) mice would develop vigorous CTL-mediated tumor immunity compared with IL-4-competent (IL-4(+/+)) mice. Surprisingly, IL-4(-/-) mice were severely impaired to develop tumor immunity to both a mammary adenocarcinoma line and a colon carcinoma line. The lack of tumor immunity in IL-4(-/-) mice was associated with reduced IFN-gamma production, diminished levels of tumor-reactive serum IgG2a, and undetectable CTL activity, indicating a defective Th1 response in the absence of endogenous IL-4. Anti-IL-4 monoclonal antibody blocked tumor immunity in IL-4(+/+) mice when administered at the time of immunization but not at the time of challenge. Additionally, tumor immunity could be induced in IL-4(-/-) mice, if IL-4 was provided by gene-modified cells together with immunizing tumor cells. These results demonstrate that tumor immunity requires IL-4 in the priming phase for the generation of effector calls rather than for their maintenance and exclude secondary, developmental defects in the "knockout" strain. Together, our results demonstrate a novel and previously unanticipated role of IL-4 for the generation of Th1-associated, CTL-mediated tumor immunity. C1 Max Delbruck Ctr Mol Med, D-13122 Berlin, Germany. NIH, Immunol Lab, Rockville, MD USA. RP Schuler, T (reprint author), Max Delbruck Ctr Mol Med, Robert Rossle 10, D-13122 Berlin, Germany. NR 48 TC 131 Z9 135 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAR 1 PY 1999 VL 189 IS 5 BP 803 EP 810 DI 10.1084/jem.189.5.803 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 173EJ UT WOS:000078968000007 PM 10049944 ER PT J AU Seeff, LB AF Seeff, LB TI Dilemma of the natural history of hepatitis C SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Editorial Material ID NON-B-HEPATITIS; TRANSFUSION-ASSOCIATED HEPATITIS; NON-A; HEPATOCELLULAR-CARCINOMA; VIRUS; ANTIBODIES; PREVALENCE C1 NIDDK, NIH, Bethesda, MD 20892 USA. RP Seeff, LB (reprint author), NIDDK, NIH, 31 Ctr Dr,Room GA18, Bethesda, MD 20892 USA. EM seeffL@extra.niddk.nih.gov NR 28 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL SCIENCE ASIA PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON, VICTORIA 3053, AUSTRALIA SN 0815-9319 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD MAR PY 1999 VL 14 IS 3 BP 199 EP 201 DI 10.1046/j.1440-1746.1999.01837.x PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 185KV UT WOS:000079668900001 PM 10197486 ER PT J AU Shirokova, N Gonzalez, A Kirsch, WG Rios, E Pizarro, G Stern, MD Cheng, HP AF Shirokova, N Gonzalez, A Kirsch, WG Rios, E Pizarro, G Stern, MD Cheng, HP TI Calcium sparks: Release packets of uncertain origin and fundamental role SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Article ID FROG SKELETAL-MUSCLE; CA2+ RELEASE; SARCOPLASMIC-RETICULUM; CARDIAC-MUSCLE; VOLTAGE-DEPENDENCE; ELEMENTARY EVENTS; TIME-COURSE; RAT-HEART; FIBERS; RYANODINE C1 Rush Univ, Dept Mol Biophys & Physiol, Chicago, IL 60612 USA. Univ Republ, Fac Med, Dept Biofis, Montevideo, Uruguay. NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Shirokova, N (reprint author), Rush Univ, Dept Mol Biophys & Physiol, Chicago, IL 60612 USA. NR 62 TC 42 Z9 43 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD MAR PY 1999 VL 113 IS 3 BP 377 EP 384 DI 10.1085/jgp.113.3.377 PG 8 WC Physiology SC Physiology GA 173EF UT WOS:000078967700004 PM 10051514 ER PT J AU Stern, MD Song, LS Cheng, HP Sham, JSK Yang, HT Boheler, KR Rios, E AF Stern, MD Song, LS Cheng, HP Sham, JSK Yang, HT Boheler, KR Rios, E TI Local control models of cardiac excitation-contraction coupling - A possible role for allosteric interactions between ryanodine receptors SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Article DE sarcoplasmic reticulum; Monte Carlo; calcium-induced calcium release; dihydropyridine receptor; diad junction ID CALCIUM-RELEASE CHANNEL; FROG SKELETAL-MUSCLE; SARCOPLASMIC-RETICULUM; CA2+-RELEASE CHANNELS; CA2+ CHANNELS; HEART-MUSCLE; RAT-HEART; INACTIVATION; ADAPTATION; ACTIVATION AB In cardiac muscle, release of activator calcium from the sarcoplasmic reticulum occurs by calcium-induced calcium release through ryanodine receptors (RyRs),which are clustered in a dense, regular, two-dimensional lattice array at the diad junction. We simulated numerically the stochastic dynamics of RyRs and L-type sarcolemmal calcium channels interacting via calcium nano-domains in the junctional cleft. Four putative RyR gating schemes based on single-channel measurements in lipid bilayers all failed to give stable excitation-contraction coupling, due either to insufficiently strong inactivation to terminate locally regenerative calcium-induced calcium release or insufficient cooperativity to discriminate against RyR activation by background calcium. If the ryanodine receptor was represented, instead, by a phenomenological four-state gating scheme, with channel opening resulting from simultaneous binding of two Ca2+ ions, and either calcium-dependent or activation-linked inactivation, the simulations gave a good semiquantitative accounting for the macroscopic features of excitation-con traction coupling. It was possible to restore stability to a model based on a bilayer-derived gating scheme, by introducing allosteric interactions between nearest-neighbor RyRs so as to stabilize the inactivated state and produce cooperativity among calcium binding sites on different RyRs. Such allosteric coupling between RyRs may be a function of the foot process and lattice array, explaining their conservation during evolution. C1 NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. Johns Hopkins Med Inst, Div Pulm & Crit Care Med, Baltimore, MD 21224 USA. Rush Univ, Sch Med, Chicago, IL 60612 USA. RP Stern, MD (reprint author), NIA, Cardiovasc Sci Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM sternM@grc.nia.nih.gov RI Song, Long-Sheng/D-5899-2012 FU NIAMS NIH HHS [AR41526] NR 48 TC 191 Z9 195 U1 1 U2 8 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD MAR PY 1999 VL 113 IS 3 BP 469 EP 489 DI 10.1085/jgp.113.3.469 PG 21 WC Physiology SC Physiology GA 173EF UT WOS:000078967700011 PM 10051521 ER PT J AU Sacktor, N Gray, S Kawas, C Herbst, J Costa, P Fleg, J AF Sacktor, N Gray, S Kawas, C Herbst, J Costa, P Fleg, J TI Systolic blood pressure within an intermediate range may reduce memory loss in an elderly hypertensive cohort SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article ID RISK-FACTORS; ALZHEIMERS-DISEASE; COGNITIVE FUNCTION; BRAIN; FRAMINGHAM; DEMENTIA AB The objective of this study was to determine if maintenance of systolic blood pressure (BP) within a high range or low range among treated hypertensive patients increases the risk of memory decline. Biennial neuropsychological evaluations were performed on 158 hypertensive subjects. Decline/year was measured on the Cued Selective Reminding test (total free recall and delayed recall) in three systolic BP groups (low-i.e., mean systolic BP during the follow-up period < 135 mm Hg; intermediate-i.e., 135 mm Hg I mean systolic BP less than or equal to 150 mm Hg; high-i.e., mean systolic BP > 150 mm Hg). In total free recall, the three systolic BP groups had significantly different declines per year (P =.02), with patients in the high subgroup showing the greatest decline. In delayed recall, the three systolic BP groups also showed significantly different declines per year (P =.04), with patients in the low subgroup having the greatest decline. Chronically elevated systolic BP > 150 mm Hg is associated with accelerated memory decline compared to older treated hypertensive patients with systolic BP in an intermediate range. Chronically maintained systolic BP within a low normal range < 135 mm Hg in older treated hypertensive subjects may be associated with accelerated memory decline, specifically in a test of delayed memory recall, compared to patients with systolic BP in an intermediate range. Optimal regulation of systolic BP may be a potential modifiable risk factor to prevent or minimize memory loss in older hypertensive patients. C1 Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Div Cardiol, Baltimore, MD USA. NIA, Lab Personal & Cognit, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Sacktor, N (reprint author), Johns Hopkins Bayview Med Ctr, 4940 Eastern Ave, Baltimore, MD 21224 USA. OI Costa, Paul/0000-0003-4375-1712 FU NIA NIH HHS [AG05146, AG08325] NR 28 TC 20 Z9 21 U1 0 U2 0 PU DECKER PERIODICALS INC PI HAMILTON PA 4 HUGHSON STREET SOUTH PO BOX 620, LCD 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 0891-9887 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD SPR PY 1999 VL 12 IS 1 BP 1 EP 6 DI 10.1177/089198879901200102 PG 6 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 215ZW UT WOS:000081416700001 PM 10447147 ER PT J AU Garon, CF Oury, JH Duran, CMG AF Garon, CF Oury, JH Duran, CMG TI Virus-like particles in the mitral and tricuspid valves explanted from a patient treated with fenfluramine-phentermine SO JOURNAL OF HEART VALVE DISEASE LA English DT Letter C1 NIAID, Rocky Mt Labs, Hamilton, MT 59840 USA. Int Heart Inst Montana Fdn, Missoula, MT USA. RP Garon, CF (reprint author), NIAID, Rocky Mt Labs, Hamilton, MT 59840 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU I C R PUBLISHERS PI NORTHWOOD PA CRISPIN HOUSE, 12/A SOUTH APPROACH, MOOR PARK, NORTHWOOD, ENGLAND HA6 2ET SN 0966-8519 J9 J HEART VALVE DIS JI J. Heart Valve Dis. PD MAR PY 1999 VL 8 IS 2 BP 232 EP 232 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 203NP UT WOS:000080714000018 PM 10224584 ER PT J AU Jevremovic, D Billadeau, DD Scoon, RA Dick, CJ Irvin, BJ Zhang, WG Samelson, LE Abraham, RT Leibson, PJ AF Jevremovic, D Billadeau, DD Scoon, RA Dick, CJ Irvin, BJ Zhang, WG Samelson, LE Abraham, RT Leibson, PJ TI Cutting edge: A role for the adaptor protein LAT in human NK cell-mediated cytotoxicity SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; TYROSINE PHOSPHORYLATION; ACTIVATION; COMPLEX; KINASE; SLP-76; PHOSPHOPROTEIN; STIMULATION; RECOGNITION; RECEPTORS AB Stimulation of NK cell-mediated cytotoxicity involves the coupling of proximal Src and Syk family protein tyrosine kinases to downstream effecters. However, the mechanisms linking these second messenger pathways are incompletely understood. Here, we describe a key role for the LAT (p36) adaptor protein in human NK cell activation. LAT is tyrosine phosphorylated upon stimulation of NK cells through Fc gamma RIII receptors and following direct contact with NK-sensitive target cells. This NK stimulation induces the association of LAT with several phosphotyrosine-containing proteins. In addition to the biochemical evidence showing LAT involvement in NK cell activation, a genetic model shows that LAT is required for FcR-dependent phosphorylation of phospholipase C-gamma. Furthermore, overexpression of LAT in NK cells leads to increased Ab-dependent cell-mediated cytotoxicity and "natural cytotoxicity," thus demonstrating a functional role for LAT in NK cells. These data suggest that LAT is an important adaptor protein for the regulation of human NK cell-mediated cytotoxicity. C1 Mayo Clin & Mayo Fdn, Dept Immunol, Rochester, MN 55905 USA. NIH, Sect Lymphocyte Signaling, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. RP Leibson, PJ (reprint author), Mayo Clin & Mayo Fdn, Dept Immunol, 200 1st St SW, Rochester, MN 55905 USA. FU NCI NIH HHS [CA-09441, CA-47752] NR 26 TC 59 Z9 60 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 1999 VL 162 IS 5 BP 2453 EP 2456 PG 4 WC Immunology SC Immunology GA 168NK UT WOS:000078699000001 PM 10072481 ER PT J AU Saeki, H Moore, AM Brown, MJ Hwang, ST AF Saeki, H Moore, AM Brown, MJ Hwang, ST TI Cutting edge: Secondary lymphoid-tissue chemokine (SLC) and CC chemokine receptor 7 (CCR7) participate in the emigration pathway of mature dendritic cells from the skin to regional lymph nodes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LANGERHANS CELLS; MIGRATION; CHEMOATTRACTANT; MODEL AB Dendritic cells (DCs) emigrate to regional lymph nodes (LNs) during immune responses via afferent lymphatic channels. Secondary lymphoid-tissue chemokine (SLC), a CC chemokine, is expressed in secondary lymphoid organs and mediates the chemotaxis of lymphocytes and DCs via its receptor, CC chemokine receptor 7 (CCR7). By dual-label fluorescence confocal microscopy, we showed MHC class II-positive cells within SLC-staining lymphatic channels in the mouse dermis. SLC was a potent in vitro chemoattractant for cultured, migratory skin DCs, and it enhanced the emigration of MHC class II-positive DCs from mouse skin explants by an average of 2.5-fold. Mature or cytokine-activated, but not resting, Langerhans cells expressed CCR7 mRNA by RT-PCR. Anti-SLC Abs, but not control or anti-eotaxin Abs, blocked the in vivo migration of Cr-51-labeled, skin-derived DCs from footpads to draining LNs by 50% (n = 9, p < 0.005). Thus, we provide direct evidence that SLC and CCR7 participate in the emigration of DCs from peripheral tissue to LNs via lymphatics. C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. RP Hwang, ST (reprint author), NCI, Dermatol Branch, 10 Ctr Dr, Bethesda, MD 20892 USA. EM samhwang@pop.nci.nih.gov NR 26 TC 441 Z9 449 U1 1 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 1999 VL 162 IS 5 BP 2472 EP 2475 PG 4 WC Immunology SC Immunology GA 168NK UT WOS:000078699000005 PM 10072485 ER PT J AU Perera, LP Goldman, CK Waldmann, TA AF Perera, LP Goldman, CK Waldmann, TA TI IL-15 induces the expression of chemokines and their receptors in T lymphocytes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; PROTEIN-COUPLED RECEPTOR; NATURAL-KILLER-CELLS; INTERLEUKIN-2 RECEPTOR; GROWTH-FACTOR; MOLECULAR-CLONING; HIV-1 ENTRY; BETA-CHAIN; IN-VITRO; INFECTION AB IL-15 is a T cell growth factor that shares many biological activities with IL-2 and uses the same beta/gamma polypeptides of the IL-2R complex for signal transduction, Accumulating evidence implicates an important role for this cytokine in the inflammatory response of the host. Consistent with such a role, IL-15 has been shown to be a chemoattractant for T lymphocytes, NK cells, and neutrophils. Extending these observations, we now show that IL-15 is a potent inducer of CC-, CXC-, and C-type chemokines in T lymphocytes, In addition, me demonstrate that IL-15 induces CC chemokine receptors, but not CXC chemokine receptors, in a dose-dependent manner. Thus, our findings suggest that the proinflammatory effects of IL-15 at least in part may be due to the induction of chemokines and their receptors in T cells. Furthermore, we demonstrate that IL-15 promotes entry and replication of macrophage-tropic HIV in T lymphocytes and suggest a plausible mechanism by which IL-15, a cytokine that is elevated in HIV-infected individuals, may promote the transition of HIV displaying the M-tropic phenotype primarily associated with the initial transmission into the T cell-tropic phenotype that predominates as the disease progresses. C1 NCI, Metab Branch, Div Clin Sci, Bethesda, MD 20892 USA. RP Perera, LP (reprint author), NCI, Metab Branch, Div Clin Sci, Bldg 10,Room 4B40,10 Ctr Dr,MSC1374, Bethesda, MD 20892 USA. NR 64 TC 75 Z9 78 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 1999 VL 162 IS 5 BP 2606 EP 2612 PG 7 WC Immunology SC Immunology GA 168NK UT WOS:000078699000022 PM 10072502 ER PT J AU Rizzo, LV Morawetz, RA Miller-Rivero, NE Choi, R Wiggert, B Chan, CC Morse, HC Nussenblatt, RB Caspi, RR AF Rizzo, LV Morawetz, RA Miller-Rivero, NE Choi, R Wiggert, B Chan, CC Morse, HC Nussenblatt, RB Caspi, RR TI IL-4 and IL-10 are both required for the induction of oral tolerance SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EXPERIMENTAL AUTOIMMUNE UVEORETINITIS; MYELIN BASIC-PROTEIN; RETINOID-BINDING PROTEIN; GROWTH-FACTOR-BETA; TGF-BETA; ACTIVE SUPPRESSION; MYASTHENIA-GRAVIS; S-ANTIGEN; T-CELLS; MICE AB Protection from the development of experimental autoimmune uveitis (EAU) can be induced by feeding mice interphotoreceptor retinoid binding protein before uveitogenic challenge with the same protein. Two different regimens are equally effective in inducing protective tolerance, although they seem to do so through different mechanisms: one involving regulatory cytokines (IL-4, IL-10, and TGF-beta), and the other with minimal involvement of cytokines, Here we studied the importance of IL-4 and IL-10 for the development of oral tolerance using mice genetically engineered to lack either one or both of these cytokines, In these animals we were able to protect against EAU only through the regimen inducing cytokine-independent tolerance. When these animals were fed a regimen that in the wild-type animal is thought to predominantly induce regulatory cells and is associated with cytokine secretion, they were not protected from EAU. Interestingly, both regimens were associated with reduced IL-2 production and proliferation in response to interphotoreceptor retinoid binding protein. These findings indicate that both IL-4 and IL-10 are required for induction of protective oral tolerance dependent on regulatory cytokines, and that one cytokine cannot substitute for the other in this process. These data also underscore the fact that oral tolerance, manifested as suppression of proliferation and IL-2 production, is not synonymous with protection from disease. C1 Univ Sao Paulo, Inst Ciencias Biomed, Dept Imunol, Lab Imunol Clin, BR-05508900 Sao Paulo, Brazil. NEI, Immunol Lab, Bethesda, MD 20892 USA. NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Rizzo, LV (reprint author), Univ Sao Paulo, Inst Ciencias Biomed, Dept Imunol, Lab Imunol Clin, Av Prof Lineu Prestes 1730,Cidade Univ, BR-05508900 Sao Paulo, Brazil. EM lvrizzo@biomed.icb2.usp RI Rizzo, Luiz Vicente/B-4458-2009; OI Morse, Herbert/0000-0002-9331-3705 NR 45 TC 88 Z9 94 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 1999 VL 162 IS 5 BP 2613 EP 2622 PG 10 WC Immunology SC Immunology GA 168NK UT WOS:000078699000023 PM 10072503 ER PT J AU Agarwal, RK Chan, CC Wiggert, B Caspi, RR AF Agarwal, RK Chan, CC Wiggert, B Caspi, RR TI Pregnancy ameliorates induction and expression of experimental autoimmune uveitis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TRANSFORMING GROWTH FACTOR-BETA-1; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; RETINOID-BINDING PROTEIN; KOYANAGI-HARADA SYNDROME; T-CELLS; RHEUMATOID-ARTHRITIS; FACTOR-BETA; IN-VIVO; GENETIC SUSCEPTIBILITY; FUNCTIONAL-PROPERTIES AB Female patients suffering from autoimmune uveitis are reported to experience a temporary remission during pregnancy. Experimental autoimmune uveitis (EAU) is a model fur human uveitis, Here we examine the effect of pregnancy on the development of EAU and its associated immunological responses. Susceptible C57BL/6 mice were immunized with interphotoreceptor retinoid-binding protein (IRBP), EAU scores and Ag-specific responses mere evaluated 21 days later. Mice immunized during pregnancy developed significantly less EAU than nonpregnant controls. Their lymph node cells and splenocytes produced a distinct pattern of cytokines in response to IRBP: reduced IFN-gamma and IL-12 p40, but unchanged levels of TNF-alpha, IL-4, IL-5, and IL-10, Anti-IRBP Ab isotypes revealed an up-regalation of IgG1, indicating a possible Th2 bias at the humoral level. Ag-specific proliferation and delayed hypersensitivity, as well as mitogen-induced IFN-gamma production, remained undiminished, arguing against an overall immune deficit. Interestingly, pregnant mice that received an infusion of IRBP-primed lymphoid cells from nonpregnant donors also developed reduced EAU, suggesting that pregnancy suppresses not only the generation, but also the function of mature uveitogenic effector T cells, Pregnant mice at the time of immunization exhibited elevated levels of TGF-beta, but not of IL-10, in the serum. We suggest that protection from. EAU during pregnancy is due primarily to a selective reduction of Ag-specific Th1 responses with only marginal enhancement of Th2 function, and that these effects may in part be secondary to elevated systemic levels of TGF-beta. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Caspi, RR (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Room 10N222,10 Ctr Dr,MSC 1857, Bethesda, MD 20892 USA. EM rcaspi@helix.nih.gov NR 65 TC 37 Z9 38 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 1999 VL 162 IS 5 BP 2648 EP 2654 PG 7 WC Immunology SC Immunology GA 168NK UT WOS:000078699000027 PM 10072507 ER PT J AU Beadling, C Druey, KM Richter, G Kehrl, JW Smith, KA AF Beadling, C Druey, KM Richter, G Kehrl, JW Smith, KA TI Regulators of G protein signaling exhibit distinct patterns of gene expression and target G protein specificity in human lymphocytes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GTPASE-ACTIVATING PROTEINS; T-CELL PROLIFERATION; ALPHA-SUBUNITS; PHASEOLUS-VULGARIS; ANTIGEN RECEPTOR; RGS PROTEIN; BINDS; PROGRESSION; INHIBITION; PATHWAYS AB The newly recognized regulators of G protein signaling (RGS) attenuate heterotrimeric G protein signaling pathways. We have cloned an IL-2-induced gene from human T cells, cytokine-responsive gene 1, which encodes a member of the RGS family, RGS16. The RGS16 protein binds G(i alpha) and G(q alpha) proteins present in T cells, and inhibits G(i)- and G(q)-mediated signaling pathways. By comparison, the mitogen-induced RGS2 inhibits G(q) but not G(i) signaling. Moreover, the two RGS genes exhibit marked differences in expression patterns. The IL-2-induced expression of the RGS16 gene in T cells is suppressed by elevated cAMP, whereas the RGS2 gene shows a reciprocal pattern of regulation by these stimuli. Because the mitogen and cytokine receptors that trigger expression of RGS2 and RGS16 in T cells do not activate heterotrimeric G proteins, these RGS proteins and the G proteins that they regulate may play a heretofore unrecognized role in T cell functional responses to Ag and cytokine activation. C1 Cornell Univ, Coll Med, Div Immunol, Dept Med, New York, NY 10021 USA. Cornell Univ, Grad Sch Med Sci, Program Immunol, New York, NY 10021 USA. NIAID, Lab Allerg Dis, NIH, Rockville, MD 20852 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Smith, KA (reprint author), Cornell Univ, Coll Med, Div Immunol, Dept Med, LC-907,525 E 68th St, New York, NY 10021 USA. EM kasmith@mail.med.cornell.edu OI Kehrl, John/0000-0002-6526-159X FU NIAID NIH HHS [R01-AI32031-22] NR 40 TC 82 Z9 83 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 1999 VL 162 IS 5 BP 2677 EP 2682 PG 6 WC Immunology SC Immunology GA 168NK UT WOS:000078699000031 PM 10072511 ER PT J AU Powell, JD Lerner, CG Schwartz, RH AF Powell, JD Lerner, CG Schwartz, RH TI Inhibition of cell cycle progression by rapamycin induces T cell clonal anergy even in the presence of costimulation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IL-2 GENE-EXPRESSION; UBIQUITIN-PROTEASOME PATHWAY; INTERLEUKIN-2 PRODUCTION; MONOCLONAL-ANTIBODY; SIGNAL-TRANSDUCTION; INDUCTION; ANTIGEN; ACTIVATION; RECEPTOR; CD28 AB Costimulation (signal 2) has been proposed to inhibit the induction of T cell clonal anergy by either directly antagonizing negative signals arising from TCR engagement (signal 1) or by synergizing with signal 1 to produce IL-2, which in turn leads to proliferation and dilution of negative regulatory factors. To better define the cellular events that lead to the induction of anergy, we used the immunosuppressive agent rapamycin, which blocks T cell proliferation in late G1 phase but does not affect costimulation-dependent IL-2 production. Our data demonstrate that full T cell activation (signal 1 plus 2) in the presence of rapamycin results in profound T cell anergy, despite the fact that these cells produce copious amounts of IL-2, Similar to conventional anergy (induction by signal 1 alone), the rapamycin-induced anergic cells show a decrease in mitogen-activated protein kinase activation, and these cells can be rescued by culture in IL-2, Interestingly, the rapamycin-induced anergic cells display a more profound block in IL-3 and IFN-gamma production upon rechallenge. Finally, in contrast to rapamycin, full T cell activation in the presence of hydroxyurea (which inhibits the cell cycle in early S phase) did not result in anergy, These data suggest that it is neither the direct effect of costimulation nor the subsequent T cell proliferation that prevents anergy induction, but rather the biochemical events that occur upon progression through the cell cycle from G1 into S phase. C1 NIAID, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Schwartz, RH (reprint author), NIAID, Cellular & Mol Immunol Lab, NIH, Bldg 4,Room 111,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 49 TC 188 Z9 190 U1 1 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 1999 VL 162 IS 5 BP 2775 EP 2784 PG 10 WC Immunology SC Immunology GA 168NK UT WOS:000078699000044 PM 10072524 ER PT J AU Yu, CR Ortaldo, JR Curiel, RE Young, HA Anderson, SK Gosselin, P AF Yu, CR Ortaldo, JR Curiel, RE Young, HA Anderson, SK Gosselin, P TI Role of a STAT binding site in the regulation of the human perforin promoter SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PORE-FORMING PROTEIN; NATURAL-KILLER-CELLS; GENE-EXPRESSION; T-CELLS; TRANSCRIPTION FACTORS; MOUSE; IL-2; CYTOTOXICITY; LYMPHOCYTES; MICE AB The pore-forming protein perforin is preferentially expressed in NK and cytotoxic T cells. To investigate the molecular regulation of human perforin gene transcription, the activity of the human perforin promoter was analyzed in human NK and T cell lines using various promoter fragments linked to a luciferase reporter gene. A core promoter was identified within 55 bp upstream of the transcription start site. This promoter region contains a guanine/cytosine box and has basal activity in YT, Kit225-k6, and Jurkat cells. A strong enhancer activity was identified between positions -1136 and -1076, a region that includes a STAT-like element. This enhancer region was active in YT cells, which have constitutive perforin expression and activated STAT3 protein, but not in Kit225-k6 or Jurkat cells, which do not have constitutive perforin expression. Mutation of the STAT binding site resulted in a dramatic down-regulation of promoter activity. Electrophoretic mobility shift assays, using a probe containing the STAT element of the perforin promoter, indicated that this element can bind STAT3 from YT cells. Moreover, the STAT element was shown to bind STAT5a/b induced by IL-2 as well as STAT1 alpha induced by IL-6 in human NK cells. Together, these results suggest that STAT proteins play a key role in perforin gene transcription and provide a model by which cytokines can regulate perforin gene expression. C1 NCI, Intramural Res Support Program, Sci Applicat Int Corp, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Div Basic Sci, Expt Immunol Lab, Frederick, MD 21702 USA. RP Anderson, SK (reprint author), NCI, Intramural Res Support Program, Sci Applicat Int Corp, Frederick Canc Res & Dev Ctr, Bldg 560,Rm 31-93, Frederick, MD 21702 USA. RI Anderson, Stephen/B-1727-2012 OI Anderson, Stephen/0000-0002-7856-4266 FU NCI NIH HHS [N01-CO-56000] NR 31 TC 57 Z9 60 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 1999 VL 162 IS 5 BP 2785 EP 2790 PG 6 WC Immunology SC Immunology GA 168NK UT WOS:000078699000045 PM 10072525 ER PT J AU Sudarshan, C Galon, J Zhou, YJ O'Shea, JJ AF Sudarshan, C Galon, J Zhou, YJ O'Shea, JJ TI TGF-beta does not inhibit IL-12- and IL-2-induced activation of Janus kinases and STATs SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; NATURAL-KILLER-CELLS; IFN-GAMMA PRODUCTION; CLASS-II TRANSACTIVATOR; MHC GENE-EXPRESSION; HUMAN T-CELLS; TYROSINE PHOSPHORYLATION; SIGNAL-TRANSDUCTION; RECEPTOR SUBUNITS; HUMAN-LYMPHOCYTES AB The immune system is an important target for the cytokine TGF-beta 1, whose actions on lymphocytes are largely inhibitory. TGF-beta has been reported to inhibit IL-12- and IL-2-induced cell proliferation and IFN-gamma production by T cells and NK cells; however, the mechanisms of inhibition have not been clearly defined, It has been suggested by some studies that TGF-beta blocks cytokine-induced Jams kinase (JAK) and STAT activation, as in the case of IL-2, In contrast, other studies with cytokines like IFN-gamma have not found such an inhibition. The effect of TGF-beta on the IL-12-signaling pathway has not been addressed. We examined this and found that TGF-beta 1 did not have any effect on IL-12-induced phosphorylation of JAK2, TYK2, and STAT4 although TGF-beta 1 inhibited IL-2- and IL-12-induced IFN-gamma production. Similarly, but in contrast to previous reports, we found that TGF-beta 1 did not inhibit IL-2-induced phosphorylation of JAK1, JAK3, and STAT5A, Furthermore, gel shift analysis showed that TGF-beta 1 did not prevent: activated STAT4 and STAT5A from binding to DNA. Our results demonstrate that the inhibitory effects of TGF-beta on IL-2- and IL-12-induced biological activities are not attributable to inhibition of activation of JAKs and STATs, Rather, our data suggest the existence of alternative mechanisms of inhibition by TGF-beta. C1 NIAMSD, Lymphocyte Cell Biol Sect, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. RP Sudarshan, C (reprint author), NIAMSD, Lymphocyte Cell Biol Sect, Arthrit & Rheumatism Branch, NIH, Bldg 10,Room 9N 252,10 Ctr Dr,MSC 1820, Bethesda, MD 20892 USA. NR 48 TC 31 Z9 31 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 1999 VL 162 IS 5 BP 2974 EP 2981 PG 8 WC Immunology SC Immunology GA 168NK UT WOS:000078699000068 PM 10072548 ER PT J AU McKee, MD Clay, TM Rosenberg, SA Nishimura, MI AF McKee, MD Clay, TM Rosenberg, SA Nishimura, MI TI Quantitation of T-cell receptor frequencies by competitive PCR: Generation and evaluation of novel TCR subfamily and clone specific competitors SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE CTL clone; tumor infiltrating lymphocytes; competitive PCR; T cell receptor ID TUMOR-INFILTRATING LYMPHOCYTES; POLYMERASE CHAIN-REACTION; CYTOKINE MESSENGER-RNA; MELANOMA ANTIGEN GP100; INTERNAL STANDARDS; GENE-EXPRESSION; RT-PCR; ADOPTIVE IMMUNOTHERAPY; MULTIPLE EPITOPES; DIFFERENTIAL PCR AB T cell receptor (TCR) V gene usage has been used to characterize the immune response to bacteria, viruses, allografts, self antigens, tumor antigens, and superantigens. Sensitive methods to detect changes in the frequency of TCR subfamilies or clonotypes might be useful in evaluating the efficacy of vaccines against infectious agents, immunotherapy treatments for cancer patients, or the status of autoimmune diseases. Two HLA-A2 restricted CTL clones expressing BV17 were isolated from a tumor infiltrating lymphocytes (TIL) culture of a patient with metastatic melanoma. One clone recognized the MART-1((27-35)) peptide and the other clone recognized the gp100((209-217)) peptide. The frequency of each of these CTL clones in an expanding TIL culture was measured using a novel competitive RT-PCR (cRT-PCR) strategy. cRT-PCR uses a single primer pair to amplify template cDNA simultaneously with a modified DNA competitor molecule. A rapid two-step PCR technique followed by a single cloning step was used to generate a TCR BV17 subfamily specific competitor or competitors specific for the MART-1((27-35)) reactive CTL clone (CO-41) and the gp100((209-217)) reactive CTL clone (CO-4). Each competitor contained a segment of the TCR BC region that served as an internal reference standard. Using the BV17 competitor we were able to accurately and reproducibly measure cDNA templates at a frequency as low as 1/100,000 using cDNA samples of known TCRBV subfamily composition. This competitor was used to monitor the frequency of BV17 expressing T cells in the TTL and PMBC of a patient with metastatic melanoma. We determined that the frequency of BV17 expressing T cells increased from 4.5% of the culture on day 35 to 60.7% of the culture on day 58. Expansion of the BV17 subfamily was due predominantly to the expansion of the CO-4 clone. This method can be used to meaningfully quantify the precursor frequency of T cell mRNA in prepared samples via TCR subfamily or TCR sequence specific primers. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Nishimura, MI (reprint author), NCI, Surg Branch, NIH, Bldg 10,Rm 2B06, Bethesda, MD 20892 USA. NR 51 TC 12 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD MAR PY 1999 VL 22 IS 2 BP 93 EP 102 DI 10.1097/00002371-199903000-00001 PG 10 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 175QE UT WOS:000079105400001 PM 10093034 ER PT J AU Khleif, SN Abrams, SI Hamilton, JM Bergmann-Leitner, E Chen, A Bastian, A Bernstein, S Chung, YM Allegra, CJ Schlom, J AF Khleif, SN Abrams, SI Hamilton, JM Bergmann-Leitner, E Chen, A Bastian, A Bernstein, S Chung, YM Allegra, CJ Schlom, J TI A phase I vaccine trial with peptides reflecting ras oncogene mutations of solid tumors SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE Ras peptides; ras oncogene mutations; Ras vaccination ID CD8(+) T-CELLS; K-RAS; COLORECTAL-CANCER; TH1 CLONES; P21 RAS; LYMPHOCYTES; EPITOPES; PATIENT; CD4(+); ADENOCARCINOMA AB Mutations in the ras genes occur in 20% of all human cancers. These genes, in turn, produce mutated proteins that are unique to cancer cells, rendering them distinguishable from normal cells by the immune system. Thus, mutated Ras proteins may form potential targets for immune therapy. We conducted a phase I/pilot clinical trial in patients with advanced cancers to test the toxicity and the ability to induce an immune response by vaccination with 13-mer mutated Ras peptides reflecting codon 12 mutations. These peptides corresponded to each of the patient's own tumor Ras mutation. Patients were vaccinated monthly x 3 subcutaneously with the specific Ras peptide along with Deter adjuvant (RiBi ImmunoChem Research, Inc., Hamilton, MT, U.S.A.) at one of five different peptide dose levels (100, 500, 1,000, 1,500, and 5,000 mu g). Three out of 10 evaluable patients generated a mutant Ras specific CD4+ and/or CD8+ T-cell immune response. The CD8+ cytotoxic cells specific for Gly to Val mutation at codon 12 were capable of lysing an HLA-A2-matched tumor cell line carrying the corresponding mutant but not the wild-type ras gene. The treatment has been well tolerated with no evidence of serious acute or delayed systemic side effects on any of the five dose levels. We demonstrated that we can generate in cancer patients specific T-lymphocyte responses that detect single amino acid differences in Ras oncoproteins. Neither the immune responses nor the minor side effects seen were found to be dose dependent. This approach may provide a unique opportunity for generating a tumor-directed therapy. Also, in vitro stimulation of these cells with the corresponding peptide generated specific T-cell lines that could be used for adoptive immune therapy. C1 NCI, Med Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. RP Khleif, SN (reprint author), NCI, Dept Genet, Med Branch, Div Clin Sci,Naval Hosp Bethesda, Bldg 8,Rm 5101, Bethesda, MD 20889 USA. RI Bergmann-Leitner, Elke/B-3548-2011 OI Bergmann-Leitner, Elke/0000-0002-8571-8956 NR 34 TC 70 Z9 73 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD MAR PY 1999 VL 22 IS 2 BP 155 EP 165 DI 10.1097/00002371-199903000-00007 PG 11 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 175QE UT WOS:000079105400007 PM 10093040 ER PT J AU Kim, CJ Chan, CC Rosenberg, SA AF Kim, CJ Chan, CC Rosenberg, SA TI Ophthalmologic evaluation in patients undergoing immunization with melanoma-associated antigens SO JOURNAL OF IMMUNOTHERAPY LA English DT Letter ID TUMOR-INFILTRATING LYMPHOCYTES; CYTOLYTIC T-LYMPHOCYTES; HIGH-DOSE INTERLEUKIN-2; ACTIVATED KILLER-CELLS; HUMAN GENE MAGE-3; METASTATIC MELANOMA; ADVANCED CANCER; IDENTIFICATION; IMMUNOTHERAPY; PEPTIDES C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NEI, Immunol Lab, Bethesda, MD 20892 USA. RP Kim, CJ (reprint author), NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NR 17 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD MAR PY 1999 VL 22 IS 2 BP 182 EP 183 DI 10.1097/00002371-199903000-00010 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 175QE UT WOS:000079105400010 PM 10093043 ER PT J AU Stiehm, ER Lambert, JS Mofenson, LM Bethel, J Whitehouse, J Nugent, R Moye, J Fowler, MG Mathieson, BJ Reichelderfer, P Nemo, GJ Korelitz, J Meyer, WA Sapan, CV Jimenez, E Gandia, J Scott, G O'Sullivan, MJ Kovacs, A Stek, A Shearer, WT Hammill, H AF Stiehm, ER Lambert, JS Mofenson, LM Bethel, J Whitehouse, J Nugent, R Moye, J Fowler, MG Mathieson, BJ Reichelderfer, P Nemo, GJ Korelitz, J Meyer, WA Sapan, CV Jimenez, E Gandia, J Scott, G O'Sullivan, MJ Kovacs, A Stek, A Shearer, WT Hammill, H CA Ped AIDS Clin Trials Grp Protoc 185 Team TI Efficacy of zidovudine and human immunodeficiency virus (HIV) hyperimmune immunoglobulin for reducing perinatal HIV transmission from HIV-infected women with advanced disease: Results of pediatric AIDS clinical trials group protocol 185 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 37th Interscience Conference on Antimicrobial Agents and Chemotherapy CY SEP 28-OCT 02, 1997 CL TORONTO, CANADA ID VERTICAL TRANSMISSION; PASSIVE-IMMUNIZATION; MONOCLONAL-ANTIBODY; PREGNANT-WOMEN; PREVENTION; MACAQUES; MECHANISMS; REDUCTION; CHALLENGE; PROTECTS AB Pediatric AIDS Clinical Trials Group protocol 185 evaluated whether zidovudine combined with human immunodeficiency virus (HIV) hyperimmune immunoglobulin (HIVIG) infusions administered monthly during pregnancy and to the neonate at birth would significantly lower perinatal HIV transmission compared with treatment with zidovudine and intravenous immunoglobulin (MG) without HIV antibody. Subjects had baseline CD4 cell counts less than or equal to 500/mu L (22% had counts <200/mu L) and required zidovudine for maternal health (24% received zidovudine before pregnancy), Transmission was associated with lower maternal baseline CD4 cell count (odds ratio, 1.58 per 100-cell decrement; P = .005; 10.0% vs. 3.6% transmission for count <200 vs. greater than or equal to 200/mu L) but not with time of zidovudine initiation (5.6% vs. 4.8% if started before vs. during pregnancy; P = .75), The Kaplan-Meier transmission rate for HIVIG recipients was 4.1% (95% confidence interval, 1.5%-6.7%) and for MG recipients was 6.0% (2.8%-9.1%) (P = .36), The unexpectedly low transmission confirmed that zidovudine prophylaxis is highly effective, even for women with advanced HN disease and prior zidovudine therapy, although it limited the study's ability to address whether passive immunization diminishes perinatal transmission. C1 NICHHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Rockville, MD 20852 USA. NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. NHLBI, Div Blood Dis & Resources, NIH, Bethesda, MD 20892 USA. WESTAT Corp, Rockville, MD 20850 USA. N Amer Biol, Boca Raton, FL USA. Univ Miami, Sch Med, Miami, FL USA. San Juan City Hosp, San Juan, PR USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. Univ So Calif, Med Ctr, Los Angeles, CA USA. Univ Maryland, Inst Human Virol, Baltimore, MD 21201 USA. Quest Diagnost, Baltimore, MD USA. RP Mofenson, LM (reprint author), NICHHD, Pediat Adolescent & Maternal AIDS Branch, NIH, 6100 Execut Blvd,Room 4B11, Rockville, MD 20852 USA. EM LM65D@nih.gov OI Mofenson, Lynne/0000-0002-2818-9808 FU NHLBI NIH HHS [HL-57128]; NIAID NIH HHS [AI-27565]; NICHD NIH HHS [HD-33162] NR 35 TC 96 Z9 102 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAR PY 1999 VL 179 IS 3 BP 567 EP 575 DI 10.1086/314637 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 183RF UT WOS:000079566700005 PM 9952362 ER PT J AU Bostic, JR Brown, KE Young, NS Koenig, S AF Bostic, JR Brown, KE Young, NS Koenig, S TI Quantitative analysis of neutralizing immune responses to human parvovirus B19 using a novel reverse transcriptase polymerase chain reaction based assay SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 7th International Parvovirus Workshop CY SEP, 1997 CL HEIDELBERG, GERMANY ID HUMAN-IMMUNODEFICIENCY-VIRUS; LEUKEMIA-CELL LINE; INFECTION; B19-PARVOVIRUS; REGION; ANTIBODIES; EPITOPES; SURFACE; ANEMIA; UNIQUE AB Infection with human parvovirus B19 causes fifth disease, acute and chronic red cell aplasia, fetal hydrops, arthropathy, and other disorders, Antiviral antibodies limit B19 infection in vivo; however, the identification of serologic markers of protection has been hampered by the lack of a quantitative assay for parvovirus neutralization. A novel in vitro test for parvovirus neutralization has been developed using reverse transcriptase-polymerase chain reaction to detect viral transcripts in a B19-permissive cell line, Parvovirus neutralizing activity was measured in sera from naturally infected individuals, and common features of sera with high neutralizing capacity were identified as protection correlates. Sera that suppressed B19 replication in vitro demonstrated IgG reactivity with capsid proteins VP1 and VP2, but no linear relationship between antibody titer and neutralizing capacity was observed, Sera from experimental animals and human volunteers immunized with a virus-like particle vaccine candidate exhibited B19 neutralizing titers equal to or greater than those observed in natural infections. C1 Medimmune Inc, Gaithersburg, MD 20878 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Bostic, JR (reprint author), Medimmune Inc, 35 W Watkins Mill Rd, Gaithersburg, MD 20878 USA. NR 29 TC 25 Z9 27 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAR PY 1999 VL 179 IS 3 BP 619 EP 626 DI 10.1086/314648 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 183RF UT WOS:000079566700011 PM 9952368 ER PT J AU Cooper, PJ Awadzi, K Ottesen, EA Remick, D Nutman, TB AF Cooper, PJ Awadzi, K Ottesen, EA Remick, D Nutman, TB TI Eosinophil sequestration and activation are associated with the onset and severity of systemic adverse reactions following the treatment of onchocerciasis with ivermectin SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID MAZZOTTI REACTION; DIETHYLCARBAMAZINE; MICROFILARIAE; INFLAMMATION; GRANULOCYTES; VOLVULUS AB To investigate the role of eosinophil activation and sequestration in the development and severity of adverse reactions after the treatment of Onchocerca volvulus infection, 40 O. volvulus-infected Ghanaians were randomized to receive placebo or standard- or high-dose ivermectin, Subjects were examined for typical physiologic and clinical events before and up to 48 h after treatment, Plasma samples were tested for interleukin (IL)-5 and eosinophil degranulation products (e.g., eosinophil-derived neurotoxin, EDN). After treatment, peripheral eosinophil counts declined in ivermectin-treated groups (P < .001), whereas circulating levels of IL-5 (P < .01) and EDN (P < .05) increased. Cumulative levels of IL-5 and EDN correlated with reaction scores (P < .01), High-dose ivermectin was associated with more-severe reactions, more-profound eosinopenia, and higher circulating levels of IL-5 and EDN, compared with the standard dose. These results suggest that eosinophil sequestration and activation/degranulation are associated with the initiation and severity of ivermectin-associated adverse reactions. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Hohoe Hosp, Onchocerciasis Chemotherapy Res Ctr, Hohoe, Ghana. WHO, CH-1211 Geneva, Switzerland. Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI USA. RP Cooper, PJ (reprint author), NIAID, Parasit Dis Lab, NIH, 9000 Rockville Pike,Bldg 4,Room 126, Bethesda, MD 20892 USA. NR 14 TC 15 Z9 15 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAR PY 1999 VL 179 IS 3 BP 738 EP 742 DI 10.1086/314647 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 183RF UT WOS:000079566700033 PM 9952390 ER PT J AU Malech, HL AF Malech, HL TI Progress in gene therapy for chronic granulomatous disease SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Interplantary-Society Conference CY MAY 30-JUN 02, 1997 CL PORT LUDLOW, WASHINGTON SP Interplanetary Soc ID PERIPHERAL-BLOOD PROGENITORS; ASPERGILLUS-FUMIGATUS; HOST-DEFENSE; TARGET-CELLS; RETROVIRUS AB Progress in development of gene therapy for chronic granulomatous disease (CGD), an inherited defect in leukocyte oxidase deficiency, is reviewed. The use of retrovirus vectors to transfer oxidase enzyme subunit cDNA sequence into hematopoietic progenitors results in correction of oxidase activity in neutrophils differentiating from transduced progenitors. In CGD mouse knockouts (X-linked gp91phox-deficient CGD and autosomal recessive p47phox-deficient CGD), gene therapy correction of the CGD defect resulted in appearance of oxidase-normal neutrophils in the peripheral blood and increased host resistance to challenge with fungi or bacteria. In a phase I clinical trial of ex vivo gene therapy of p47phox-deficient CGD, prolonged production (2-6 months) of a low number (1:5000) of oxidase-normal neutrophils was achieved. This therapy might prove beneficial in a setting of prolonged infection in CGD patients, in which even transient production of autologous gene-corrected neutrophils might augment host defense. C1 NIAID, NIH, Host Def Lab, Bethesda, MD 20892 USA. RP Malech, HL (reprint author), NIAID, NIH, Host Def Lab, Bldg 10,Room 11N113,10 Ctr Dr,MSC 1886, Bethesda, MD 20892 USA. NR 15 TC 35 Z9 36 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAR PY 1999 VL 179 SU 2 BP S318 EP S325 DI 10.1086/513852 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 202DT UT WOS:000080637400008 PM 10081502 ER PT J AU Yang, JM Nam, K Kim, HC Lee, JH Park, JK Wu, K Lee, ES Steinert, PM AF Yang, JM Nam, K Kim, HC Lee, JH Park, JK Wu, K Lee, ES Steinert, PM TI A novel glutamic acid to aspartic acid mutation near the end of the 2B rod domain in the keratin 1 chain in epidermolytic hyperkeratosis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE epidermolytic hyperkeratosis; glutamic acid; keratin ID INTERMEDIATE FILAMENTS; DISEASE; H1 AB We report a mutation in a mild case of epidermolytic hyperkeratosis that results in a glutamic acid to aspartic acid substitution in a novel location, codon 477 or position 106 of the 2B rod domain of the keratin 1 chain. This residue has been conserved in all intermediate filament chains and lies near the beginning of the highly conserved helix termination sequence and just prior to the predicted molecular overlap region. Keratin filaments assembled in vitro from chains bearing this substitution are abnormal, indicating that the glutamic acid residue is critically involved in ionic interactions in intermediate levels of filament structure. C1 Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Dermatol,Kangnam Ku, Seoul 135710, South Korea. Sungkyunkwan Univ, Samsung Biomed Res Inst, Clin Res Ctr, Sch Med, Seoul, South Korea. Chungnam Natl Univ, Coll Med, Dept Dermatol, Taejon, South Korea. NIAMSD, Skin Biol Lab, NIH, Bethesda, MD USA. RP Yang, JM (reprint author), Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Dermatol,Kangnam Ku, 50 Ilwon Dong, Seoul 135710, South Korea. NR 16 TC 21 Z9 22 U1 0 U2 3 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAR PY 1999 VL 112 IS 3 BP 376 EP 379 DI 10.1038/sj.jid.5600439 PG 4 WC Dermatology SC Dermatology GA 172KF UT WOS:000078921500019 PM 10084317 ER PT J AU Dadachova, E AF Dadachova, E TI Preparation of Au-198(I)-labelled gold-chloroquine complex [Au-198(PPh3)(CQ)]PF6 as a potential antimalarial agent SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE [Au-198(PPh3)(CQ)]PF6 x(2)H(2)O; Au-199; malaria; radiotherapy; radioisotopes; chloroquine-resistance ID ACTIVITY IN-VITRO; METAL-BASED CHEMOTHERAPY; PLASMODIUM-FALCIPARUM; TROPICAL DISEASES; VIVO AB Au-198(I)-labelled gold-chloroquine complex [Au-198(PPh3)(CQ)]PF6 has been prepared for the enhancement of antimalarial action against chloroquine-resistant strains of Plasmodium falciparum of recently reported [Au(PPh3)(CQ)]PF6. [Au-198(PPh3)(CQ)]PF6 was synthesized via 3-step route starting with irradiated in the reactor for 2 hours Au foil and purified on Sep-Pak(R) C18 cartridge. Specific activity of the complex was 1.5 mCi/mg. The possibility of using metal complexes radiolabelled with therapeutic radioisotopes for treatment of chloroquine-resistant malaria is discussed. C1 Australian Nucl Sci & Technol Org, Radiopharmaceut R&D, Menai, NSW 2234, Australia. RP Dadachova, E (reprint author), NCI, Radiat Oncol Branch, NIH, Bldg 10,Room B3B69, Bethesda, MD 20892 USA. NR 16 TC 5 Z9 6 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD MAR PY 1999 VL 42 IS 3 BP 287 EP 292 DI 10.1002/(SICI)1099-1344(199903)42:3<287::AID-JLCR189>3.0.CO;2-O PG 6 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 170RB UT WOS:000078818900010 ER PT J AU Finkel, T AF Finkel, T TI Signal transduction by reactive oxygen species in non-phagocytic cells SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article; Proceedings Paper CT 33rd Annual Meeting of the Society-for-Leukocyte-Biology on Molecular Mechanisms of Leukocyte Signal Transduction CY AUG 22-25, 1998 CL UNIV CA SAN DIEGO, LA JOLLA, CALIFORNIA SP Soc Leukocyte Biol HO UNIV CA SAN DIEGO DE NADPH oxidase; ras; rac; p53; apoptosis ID SMOOTH-MUSCLE CELLS; NADPH OXIDASE; HYDROGEN-PEROXIDE; GENERATION; FIBROBLASTS; ACTIVATION; INVOLVEMENT; APOPTOSIS; INDUCTION; PROTEINS AB A growing body of evidence suggests a potential role for oxygen-derived radicals such as superoxide anions and hydrogen peroxide as intracellular signaling molecules. Recently, progress has been made regarding the regulation of oxidant production in non-phagocytic cells, Significant gaps in understanding persist, however, especially in regard to the source(s) of oxidant production and the direct intracellular target(s) of oxygen radicals, Nonetheless, numerous recent studies have implicated a dynamic change in the intracellular redox state as an important determinant in a host of cellular decisions ranging from growth, to apoptosis, to cellular senescence. C1 NIH, Bethesda, MD 20892 USA. RP Finkel, T (reprint author), NIH, Bldg 10,Room 7B15,10 Ctr Dr, Bethesda, MD 20892 USA. EM finkelt@gwgate.nhlbi.nih.gov NR 34 TC 189 Z9 195 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD MAR PY 1999 VL 65 IS 3 BP 337 EP 340 PG 4 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 172BM UT WOS:000078902300009 PM 10080536 ER PT J AU Danilkovitch, A Leonard, EJ AF Danilkovitch, A Leonard, EJ TI Kinases involved in MSP/RON signaling SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article; Proceedings Paper CT 33rd Annual Meeting of the Society-for-Leukocyte-Biology on Molecular Mechanisms of Leukocyte Signal Transduction CY AUG 22-25, 1998 CL UNIV CA SAN DIEGO, LA JOLLA, CA SP Soc Leukocyte Biol HO UNIV CA SAN DIEGO DE PI3-K; AKT; FAK; c-Src; MAPK; JNK ID MACROPHAGE-STIMULATING PROTEIN; HEPATOCYTE GROWTH-FACTOR; TYROSINE KINASE; FACTOR-RECEPTOR; GENE-PRODUCT; FAMILY; RON; IDENTIFICATION; EXPRESSION; ACTIVATION AB Macrophage stimulating protein (MSP) belongs to the plasminogen-related kringle domain family. In addition to stimulation of macrophages, MSP acts on other cell types including epithelial and hematopoietic cells. The MSP receptor is a transmembrane tyrosine kinase called RON in humans and STK in mice. MSP/receptor interaction induces activation of signal transduction pathways that mediate MSP biological activities, Cytoplasmic kinases are intracellular messengers occupying an important role in signal transduction. We have identified kinases that participate in RON signaling. In addition to previously identified involvement of phosphatidylinositol 3-kinase (PI3-K), JNK, and MAPK, we found that FAK, c-Src, and AKT are rapidly and transiently activated by MSP, FAK, MAPK, and c-Src are involved in MSP-induced cell proliferation. MAPK and c-Src are components of one signal transduction cascade, and MAPK is downstream of c-Src, FAK also regulates MSP-induced cell growth, but via a path different from c-Src/MAPK. AKT kinase is a component of a separate branch of the RON/PI3-K pathway that mediates the MSP anti-apoptotic effect on epithelial cells, PIS-IC regulates MSP-induced adhesion and motility but via downstream components different from AKT. Thus, occupancy of the RON receptor by MSP activates distinct signal transduction pathways that mediate several cellular responses. C1 NCI, Immunobiol Lab, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Danilkovitch, A (reprint author), NCI, Immunobiol Lab, Frederick Canc Res & Dev Ctr, Bldg 560,Room 12-46, Frederick, MD 21702 USA. EM danilkovitch@mail.ncifcrf.gov NR 48 TC 35 Z9 35 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD MAR PY 1999 VL 65 IS 3 BP 345 EP 348 PG 4 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 172BM UT WOS:000078902300011 PM 10080538 ER PT J AU Brousseau, ME Hoeg, JM AF Brousseau, ME Hoeg, JM TI Transgenic rabbits as models for atherosclerosis research SO JOURNAL OF LIPID RESEARCH LA English DT Review DE apolipoproteins; atherosclerosis; lipid enzymes; transgenic; New Zealand White; Watanabe Heritable Hyperlipidemic ID APOLIPOPROTEIN-A-I; INTERMEDIATE DENSITY LIPOPROTEINS; ESTER TRANSFER PROTEIN; RNA-EDITING PROTEIN; MESSENGER-RNA; CHOLESTEROL ACYLTRANSFERASE; HEPATIC LIPASE; HYPERCHOLESTEROLEMIC RABBIT; HEREDITARY HYPERLIPIDEMIA; REMNANT LIPOPROTEINS AB Several characteristics of the rabbit make it an excellent model for the study of lipoprotein metabolism and atherosclerosis, New Zealand White (NZW) rabbits have low plasma total cholesterol concentrations, high cholesteryl ester transfer protein activity, low hepatic lipase (HL) activity, and lack an analogue of human apolipoprotein (apo) A-II, providing a unique system in which to assess the effects of human transgenes on plasma lipoproteins and atherosclerosis susceptibility. Additionally, rabbit models of human lipoprotein disorders, such as the Watanabe Heritable Hyperlipidemic (WHHL) and St. Thomas' Hospital strains, models of familial hypercholesterolemia and familial combined hyperlipidemia, respectively, allow for the assessment of candidate genes for potential use in the treatment of dyslipoproteinemic patients. To date, transgenes for human apo(a), apoA-I, apoB, apoE(2), apoE(3), HL, and lecithin:cholesterol acyltransferase (LCAT), as well as for rabbit apolipoprotein B mRNA-editing enzyme catalytic polypeptide 1 (APOBEC-1), have been expressed in NZW rabbits, whereas only those for human apoA-I and LCAT have been introduced into the WHHL background, All of these transgenes have been shown to have significant effects on plasma lipoprotein concentrations. In both NZW and WHHL rabbits, human apoA-I expression was associated with a significant reduction in the extent of aortic atherosclerosis, which was similarly the case for LCAT in rabbits having at least one functional LDL receptor allele. Conversely, expression of apoE(2) in NZW rabbits caused increased susceptibility to atherosclerosis. These studies provide new insights into the mechanisms responsible for the development of atherosclerosis, emphasizing the strength of the rabbit model in cardiovascular disease research. Brousseau, M. E., and J. M. Hoeg. Transgenic rabbits as models for atherosclerosis research. J, Lipid Res. 1999. C1 Tufts Univ, Lipid Metab Lab, JM, USDA HNRCA, Boston, MA 02111 USA. NHLBI, Mol Dis Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Brousseau, ME (reprint author), Tufts Univ, Lipid Metab Lab, JM, USDA HNRCA, 711 Washington St, Boston, MA 02111 USA. NR 51 TC 62 Z9 64 U1 0 U2 1 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD MAR PY 1999 VL 40 IS 3 BP 365 EP 375 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 173EG UT WOS:000078967800001 PM 10064724 ER PT J AU Aletras, AH Ding, SJ Balaban, RS Wen, H AF Aletras, AH Ding, SJ Balaban, RS Wen, H TI DENSE: Displacement encoding with stimulated echoes in cardiac functional MRI SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE cardiac; function; STEAM; PC; phase contrast; stimulated echoes; heart ID SPATIAL MODULATION; MYOCARDIAL MOTION; WALL-MOTION; HUMAN-HEART; TRACKING; MAGNETIZATION; STRAIN; DEFORMATION; INFARCTION; IMAGES AB Displacement encoding with stimulated echoes (DENSE) was developed for high-resolution myocardial displacement mapping. Pixel phase is modulated by myocardial displacement and data spatial resolution is limited only by pixel size. 2D displacement vector maps were generated for the systolic action in canines with 0.94 x 1.9 mm nominal in-plane resolution and 2.3 mm/pi displacement encoding. A radial strain of 0.208 was measured across the free left ventricular wall over 105 ms during systole. DENSE displacement maps require small first-order gradient moments for encoding. DENSE magnitude images exhibit black-blood contrast which allows for better myocardial definition and reduced motion related artifacts. C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP Aletras, AH (reprint author), NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RI Balaban, Robert/A-7459-2009; Wen, Han/G-3081-2010; OI Balaban, Robert/0000-0003-4086-0948; Wen, Han/0000-0001-6844-2997; Aletras, Anthony/0000-0002-3786-3817 FU Intramural NIH HHS [Z01 HL004606-11] NR 28 TC 235 Z9 235 U1 0 U2 9 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD MAR PY 1999 VL 137 IS 1 BP 247 EP 252 DI 10.1006/jmre.1998.1676 PG 6 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 174KL UT WOS:000079034300030 PM 10053155 ER PT J AU Ishima, R Louis, JM Torchia, DA AF Ishima, R Louis, JM Torchia, DA TI Transverse H-1 cross relaxation in H-1-N-15 correlated H-1 CPMG experiments SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE NMR; transverse relaxation; CPMG; perdeuterated protein; spin lock ID NUCLEAR AB Transverse H-1 cross relaxation was observed in Carr-Purcell-Meiboom-Gill (CPMG) experiments by recording N-15-H-1 correlated spectra of amides in HIV protease that was perdeuterated at nonexchangeable sites. Perdeuteration suppresses H-1-H-1 J coupling and improves spectral resolution and sensitivity. Measurements of cross-peak intensities, arising from cross relaxation, were made as a function of (i) Delta f, the frequency difference between the spins, and (ii) tau(CPMG), one-half of the duration between CPMG pi pulses. Cross peaks were observed when tau(CPMG) was less than 1/(2 Delta f), in agreement with theoretical calculations. C1 Natl Inst Dent & Craniofacial Res, Mol Struct Biol Unit, NIH, Bethesda, MD 20892 USA. NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Torchia, DA (reprint author), Natl Inst Dent & Craniofacial Res, Mol Struct Biol Unit, NIH, Bethesda, MD 20892 USA. NR 5 TC 10 Z9 10 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD MAR PY 1999 VL 137 IS 1 BP 289 EP 292 DI 10.1006/jmre.1998.1672 PG 4 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 174KL UT WOS:000079034300038 PM 10053163 ER PT J AU Zhang, J Andrade, ZA Yu, ZX Andrade, SG Takeda, K Sadirgursky, M Ferrans, VJ AF Zhang, J Andrade, ZA Yu, ZX Andrade, SG Takeda, K Sadirgursky, M Ferrans, VJ TI Apoptosis in a canine model of acute Chagasic myocarditis SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE Trypanosoma cruzi; apoptosis; acute myocarditis; dog; nick end labeling; electron microscopy ID PROGRAMMED CELL-DEATH; NITRIC-OXIDE SYNTHASE; TRYPANOSOMA-CRUZI; DNA FRAGMENTATION; HEART-FAILURE; MITOCHONDRIAL-DNA; PRESSURE-OVERLOAD; TARGET-CELLS; INFARCTION; MYOCYTES AB Histologic, ultrastructural and nick end labeling studies were made to evalute the occurrence of apoptosis in the hearts of dogs with acute myocarditis due to experimental infection with T. cruzi. The best results for the detection of apoptosis by nick end labeling were obtained by a method combining the use of terminal deoxynucleotidyl transferase, CoCl2 and fluorescein-conjugated deoxyuridine triphosphate. followed by counterstaining of DNA with 4'6-diamidino-2-phenylindole (DAPI) and examination by laser scanning confocal fluorescence microscopy. Apoptosis was found in: (1) cardiac myocytes: (2) endothelial cells of capillaries and venules: (3) immune effector cells, including macrophages, interstitial dendritic cells (antigen-presenting cells) and granular and agranular lymphocytes, and (4) intra- and extracellular forms of T, cruzi. The apoptosis in myocytes and endothelial cells affected cells that were not infected by T, cruzi and was probably caused by the release of toxic mediators of inflammation. The apoptosis of immune effector cells could be related either to the subsidence of inflammation or to modulation (and even failure) of the immune response. The finding of apoptosis in T, cruzi confirms the results of other studies showing that this phenomenon occurs during the differentiation of trypomastigotes in vitro. Thus. apoptosis constitutes an important and multifactorial event in the pathogenesis of acute Chagasic myocarditis. (C) 1999 Academic Press. C1 NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. US FDA, Div Appl Pharmacol Res, Laurel, MD 20708 USA. Ministerio Saude, Fundacao Oswaldo Cruz, Ctr Pesquisas Goncalo Muniz, BR-41945 Salvador, BA, Brazil. RP Ferrans, VJ (reprint author), NHLBI, Pathol Sect, NIH, Bld 10 2N240,10 Ctr Dr MSC-1518, Bethesda, MD 20892 USA. NR 49 TC 42 Z9 43 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD MAR PY 1999 VL 31 IS 3 BP 581 EP 596 DI 10.1006/jmcc.1998.0893 PG 16 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 174EQ UT WOS:000079021500010 PM 10198189 ER PT J AU Grishin, NV AF Grishin, NV TI A novel approach to phylogeny reconstruction from protein sequences SO JOURNAL OF MOLECULAR EVOLUTION LA English DT Article DE substitution rates; amniote phylogeny; evolutionary distance; phylogenetic tree ID SUBSTITUTION RATE VARIES; MAXIMUM-LIKELIHOOD-ESTIMATION; AMINO-ACID SUBSTITUTIONS; EVOLUTIONARY TREES; DNA-SEQUENCES; SITES; PARSIMONY; DISTANCE; CONSISTENCY; MODELS AB The reliable reconstruction of tree topology from a set of homologous sequences is one of the main goals in the study of molecular evolution. If consistent estimators of distances from a multiple sequence alignment are known, the distance method is attractive because the tree reconstruction is consistent. To obtain a distance estimate d, the observed proportion of differences p (p-distance) is usually "corrected" for multiple and back substitutions by means of a functional relationship d = f(p) In this paper the conditions under which this correction of p-distances will not alter the selection of the tree topology are specified. When these conditions are not fulfilled the selection of the tree topology may depend on the correction function applied. A novel method which includes estimates of distances not only between sequence pairs, but between triplets, quadruplets, etc., is proposed to strengthen the proper selection of correction function and tree topology. A ''super'' tree that includes all tree topologies as special cases is introduced. C1 Univ Texas, SW Med Ctr, Dept Pharmacol, Dallas, TX 75235 USA. RP Grishin, NV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM grishin@ncbi.nlm.nih.gov NR 44 TC 8 Z9 8 U1 0 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0022-2844 J9 J MOL EVOL JI J. Mol. Evol. PD MAR PY 1999 VL 48 IS 3 BP 264 EP 273 DI 10.1007/PL00006469 PG 10 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 170MD UT WOS:000078808700006 PM 10093215 ER PT J AU Aravind, L Koonin, EV AF Aravind, L Koonin, EV TI Novel predicted RNA-binding domains associated with the translation machinery SO JOURNAL OF MOLECULAR EVOLUTION LA English DT Article DE RNA-binding domains; ribosomal protein S4; archaeosine transglycosylase; pseudouridine synthase; translation machinery ID ARCHAEAL TRANSFER-RNA; RIBOSOMAL-PROTEIN S4; MESSENGER-RNA; ESCHERICHIA-COLI; SACCHAROMYCES-CEREVISIAE; PSEUDOURIDINE SYNTHASE; SEQUENCE DATABASES; BACILLUS-SUBTILIS; MOTIF; RECOGNITION AB Two previously undetected domains were identified in a variety of RNA-binding proteins, particularly RNA-modifying enzymes, using methods for sequence profile analysis. A small domain consisting of 60-65 amino acid residues was detected in the ribosomal protein S4, two families of pseudouridine synthases, a novel family of predicted RNA methylases, a yeast protein containing a pseudouridine synthetase and a deaminase domain, bacterial tyrosyl-tRNA synthetases, and a number of uncharacterized, small proteins that may be involved in translation regulation. Another novel domain, designated PUA domain, after PseudoUridine synthase and Archaeosine transglycosylase, was detected in archaeal and eukaryotic pseudouridine synthases, archaeal archaeosine synthases, a family of predicted ATPases that may be involved in RNA modification, a family of predicted archaeal and bacterial rRNA methylases. Additionally, the PUA domain was detected in a family of eukaryotic proteins that also contain a domain homologous to the translation initiation factor eIF1/SUI1; these proteins may comprise a novel type of translation factors. Unexpectedly, the PUA domain was detected also in bacterial and yeast glutamate kinases; this is compatible with the demonstrated role of these enzymes in the regulation of the expression of other genes. We propose that the S4 domain and the PUA domain bind RNA molecules with complex folded structures, adding to the growing collection of nucleic acid-binding domains associated with DNA and RNA modification enzymes. The evolution of the translation machinery components containing the S4, PUA, and SUI1 domains must have included several events of lateral gene transfer and gene loss as well as lineage-specific domain fusions. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. Texas A&M Univ, Dept Biol, College Stn, TX 77843 USA. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. NR 56 TC 139 Z9 145 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0022-2844 J9 J MOL EVOL JI J. Mol. Evol. PD MAR PY 1999 VL 48 IS 3 BP 291 EP 302 DI 10.1007/PL00006472 PG 12 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 170MD UT WOS:000078808700009 PM 10093218 ER PT J AU Rall, JE AF Rall, JE TI An introduction to clinical research in psychiatry SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Book Review C1 NIH, Bethesda, MD 20892 USA. RP Rall, JE (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD MAR PY 1999 VL 187 IS 3 BP 195 EP 195 DI 10.1097/00005053-199903000-00015 PG 1 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 176EZ UT WOS:000079139500015 ER PT J AU Liesi, P Stewart, RR Akinshola, BE Wright, JM AF Liesi, P Stewart, RR Akinshola, BE Wright, JM TI Weaver cerebellar granule neurons show altered expression of NMDA receptor subunits both in vivo and in vitro SO JOURNAL OF NEUROBIOLOGY LA English DT Article DE cerebellum; neuronal migration; NMDA receptor; weaver mouse ID D-ASPARTATE RECEPTOR; CALCIUM-DEPENDENT INACTIVATION; POSTSYNAPTIC DENSITY FRACTION; OUTGROWTH-PROMOTING DOMAIN; LONG-TERM POTENTIATION; MOUSE CEREBELLUM; TYROSINE PHOSPHORYLATION; DIFFERENTIAL EXPRESSION; POSTNATAL-DEVELOPMENT; GLUTAMATE RECEPTORS AB Biochemical, immunocytochemical, and molecular biological techniques were used to investigate the expression of N-methyl-D-aspartate (NMDA) receptor subunits in migration-deficient weaver mouse cerebellum in vivo and in primary cultures of the vermal weaver granule neurons with or without a rescue by verapamil, We found that both NMDAR1(zeta 1) message and protein were expressed by the weaver granule neurons in situ, Immunocytochemical and biochemical analyses indicated that granule neurons of the weaver cerebellum expressed R1(zeta 1) and R2A(epsilon 1) subunits but showed little expression of the R2B(epsilon 2) subunit, In weaver cerebellum, the R2B(epsilon 2) subunit was primarily expressed in nerve fibers of the internal granule cell layer and white matter. Reverse-transcriptase-polymerase chain reaction followed by sequence analysis of the R1(zeta 1) subunit indicated that the zeta 1 subunit amplicons of both normal and weaver cerebella were identical, and that splice variants with exon 22 (1-2) and with or without exon 5 (a/b) or exon 21 (1-4) were detectable. The R2A(epsilon 1), and R2B(epsilon 2) subunits of the normal and weaver mouse cerebellum revealed no primary structural differences between the normal and weaver NMDA receptor subunits or the cloned mouse NMDA receptor subunits, In vermal cultures, normal granule neurons expressed all three NMDA receptor subunits (zeta 1, epsilon 1, and epsilon 2), whereas the weaver neurons failed to express the epsilon 2 subunit, Rescue of the weaver neurons by verapamil induced expression of the epsilon 2 protein along the granule neuronal surfaces. The present results suggest that lack of the epsilon 2 subunit in the weaver cerebellum may relate to the lack of functional NMDA receptors and/or to the migratory failure of the weaver granule neurons. Our data further suggest that NMDA receptor-mediated neurotoxicity is an unlikely mediator of neuronal death of the weaver granule neurons. In fact, downregulation of the NMDA receptor expression and function may be a protective measure of the weaver granule neurons to reduce calcium entry via these receptors. (C) 1999 John Wiley & Sons, Inc.* C1 NIAAA, Mol & Cellular Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Liesi, P (reprint author), Univ Helsinki, Inst Biomed, Brain Lab, POB 9,Siltavuorenpenger 20A, FIN-00014 Helsinki, Finland. FU NLM NIH HHS [LMCN-SE-15] NR 61 TC 9 Z9 9 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0022-3034 J9 J NEUROBIOL JI J. Neurobiol. PD MAR PY 1999 VL 38 IS 4 BP 441 EP 454 DI 10.1002/(SICI)1097-4695(199903)38:4<441::AID-NEU1>3.0.CO;2-V PG 14 WC Neurosciences SC Neurosciences & Neurology GA 172BN UT WOS:000078902400001 PM 10084680 ER PT J AU Pancrazio, JJ Ma, W Grant, GM Shaffer, KM Kao, WY Liu, QY Manos, P Barker, JL Stenger, DA AF Pancrazio, JJ Ma, W Grant, GM Shaffer, KM Kao, WY Liu, QY Manos, P Barker, JL Stenger, DA TI A role for inwardly rectifying K+ channels in differentiation of NG108-15 neuroblastoma x glioma cells SO JOURNAL OF NEUROBIOLOGY LA English DT Article DE differentiation; HERG; immunocytochemistry; inward rectifier; neuroblastoma; patch clamp; potassium channel; resting membrane potential; RT-PCR; serum-free medium ID HYBRID-CELLS; POTASSIUM CONDUCTANCE; CURRENTS; PROLIFERATION; RECTIFIER; SIGNAL; LINE AB The whole-cell patch-clamp technique was used to assess the current carried by inwardly rectifying K+ channels (K-ir) and the resting membrane potential (RMP) during long-term culture of NG108-15 cells. Culture of this cell line in serum-free medium triggers differentiation of a type I, neuron-like cell type followed hy an eventual predominance of a type III proliferative cell type, NG108-15 K-ir currents, which strongly resemble currents carried by human ether-ago-go related gene (HERG) K+ channels, exhibited significantly smaller current density for the more depolarized undifferentiated cells in growth media (GM) and type II cells compared to the neuron-like type I cells. Detailed examination of the transition from undifferentiated GM cells to type I cells revealed a shift in the voltage dependence of K-ir activation which paralleled the more hyperpolarized RMP, neurite outgrowth, and biochemical differentiation characteristic of type I cells. Reverse-transcription polymerase chain reaction experiments using primers for the rat variant of HERG, RERG, revealed a a nearly twofold increase in RERG mRNA as cells differentiate from GM to type I, a finding entirely consistent with the increased K-ir current density derived from patch-clamp recordings, Administration of CsCl (5 mM) blocked K-ir currents and depolarized the RMP of type I cells. Furthermore, culture of NG108-15 cells in serum-free medium but with CsCl added significantly prevented neurite extension, an effect which was entirely reversible upon subsequent removal of CsCl, In contrast, other K+ channel inhibitors (4-aminopyridine and tetraethylammonium), at concentrations without marked effects on K-ir, failed to affect neurite extension. These results suggest an important role of the K-ir channels in determining the RMP and triggering morphological differentiation of the cell line. (C) 1999 John Wiley & Sons, Inc. C1 USN, Res Lab, Ctr Biomol Sci & Engn, Washington, DC 20375 USA. NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. RP Stenger, DA (reprint author), USN, Res Lab, Ctr Biomol Sci & Engn, Code 6910, Washington, DC 20375 USA. RI Pancrazio, Joseph/M-3206-2015 OI Pancrazio, Joseph/0000-0001-8276-3690 NR 31 TC 15 Z9 15 U1 0 U2 2 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0022-3034 J9 J NEUROBIOL JI J. Neurobiol. PD MAR PY 1999 VL 38 IS 4 BP 466 EP 474 DI 10.1002/(SICI)1097-4695(199903)38:4<466::AID-NEU3>3.0.CO;2-8 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 172BN UT WOS:000078902400003 PM 10084682 ER PT J AU Klett, CPR Bonner, TI AF Klett, CPR Bonner, TI TI Identification and characterization of the rat M1 muscarinic receptor promoter SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE M1 muscarinic receptor promoter; rat ID SPONTANEOUSLY HYPERTENSIVE RATS; NECROSIS-FACTOR-ALPHA; ACETYLCHOLINE-RECEPTOR; MESSENGER-RNA; GENE PROMOTER; ALERTING STIMULI; EXPRESSION; REGION; CLONING; CELLS AB Five subtypes of the muscarinic receptor have been cloned from both the rat and human genomes, Although all five genes have the coding sequences in a single exon, their structures 5' of the initiation codon are largely uncharacterized, except for the M4 receptor. In the brain, muscarinic receptors mediate motor and memory function by interaction with their ligand acetylcholine. In addition, the M1 muscarinic subtype has been implicated in behavior, stress-adaptive cardiovascular reflexes, and blood pressure regulation. In the current study the M1 muscarinic receptor noncoding 5'-flanking region has been identified and characterized, including the promoter and two 5' noncoding exons located similar to 13-14 kb from the coding exon, Similar to the M4 muscarinic receptor gene the M1 promoter is GC-rich, contains no TATA box, but has two potential CAAT boxes and several putative binding sites for transcription factors such as SP1 and AP-1-3, The transcription initiation site was identified by RNase protection and primer extension. Promoter activity was confirmed in transient expression assays, using luciferase reporter constructs. A 0.89-kb fragment consisting of 480 bp of the promoter, exon 1, and part of intron 1 expressed luciferase activity in two M1 receptor-expressing cell lines (CCL-107 and CCL-147), whereas a longer fragment (1.5 kb) that extends into intron 2 demonstrated significantly increased luciferase activity. The constructs exhibited responses indicating the presence of functional glucocorticoid-, acute-phase-, and heat shock-responsive elements. C1 Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA. NIMH, Genet Sect, Bethesda, MD 20892 USA. RP Klett, CPR (reprint author), Univ Mississippi, Med Ctr, Dept Physiol & Biophys, 2500 N State St, Jackson, MS 39216 USA. FU NHLBI NIH HHS [HL51971] NR 46 TC 20 Z9 29 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 1999 VL 72 IS 3 BP 900 EP 909 DI 10.1046/j.1471-4159.1999.0720900.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 166XM UT WOS:000078603200002 PM 10037460 ER PT J AU Perrone-Capano, C Crispino, M Menichini, E Kaplan, BB Giuditta, A AF Perrone-Capano, C Crispino, M Menichini, E Kaplan, BB Giuditta, A TI Ribosomal RNAs synthesized by isolated squid nerves and ganglia differ from native ribosomal RNAs SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE ribosomal RNA; RNA synthesis; squid; nerve lesion; ganglia ID PROTEIN-SYNTHESIS; GIANT-AXON AB The large rRNA of the squid comprises two chains that may be dissociated by healing at 65 degrees C. A single chain constitutes the small rRNA, Surprisingly, the RNAs synthesized by dissected squid fin nerves and stellate nerves and ganglia differed in size from native rRNAs and did not manifest thermal instability. Nonetheless, they resembled native rRNAs in relative abundance, subcellular distribution, lack of poly(A), and metabolic stability. In addition, newly synthesized RNA was localized in nerve and glial cells, as shown by autoradiographic analysis, and was assembled into 80S ribosomes, which supported the synthesis of neuron-specific neurofilament proteins. Following incubation of nerves and ganglia for >10 h, native rRNAs started to disappear, while two major newly synthesized RNAs progressively accumulated. As a result, after 20 h, native rRNAs were substituted by the two novel RNAs. With use of P-32-cDNA synthesized from the latter RNAs as a probe, the novel RNAs demonstrated a considerable degree of homology with native rRNA in northern analysis. Taken together, the data suggest that in dissected squid nerves and ganglia, the synthesis of native rRNAs is gradually terminated while two novel rRNAs are being synthesized, presumably as a correlate of reactive gliosis and/or neuronal degeneration/regeneration. C1 Univ Naples Federico II, Dipartimento Fisiol Gen & Ambientale, I-80134 Naples, Italy. CNR, Ist Int Genet & Biofis, I-80125 Naples, Italy. NIMH, Div Intramural Res Programs, NIH, Bethesda, MD 20892 USA. RP Perrone-Capano, C (reprint author), Univ Naples Federico II, Dipartimento Fisiol Gen & Ambientale, Via Mezzocannone 8, I-80134 Naples, Italy. RI Perrone-Capano, Carla/O-7708-2015 OI Perrone-Capano, Carla/0000-0002-6327-9753 FU NINDS NIH HHS [NS30715] NR 21 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 1999 VL 72 IS 3 BP 910 EP 918 DI 10.1046/j.1471-4159.1999.0720910.x PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 166XM UT WOS:000078603200003 PM 10037461 ER PT J AU Saunders, PA Chen, RW Chuang, DM AF Saunders, PA Chen, RW Chuang, DM TI Nuclear translocation of glyceraldehyde-3-phosphate dehydrogenase isoforms during neuronal apoptosis SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE glyceraldehyde-3-phosphate dehydrogenase isoforms; nuclear translocation; apoptosis; caspase; cerebellar granule cells ID CEREBELLAR GRANULE CELLS; URACIL-DNA GLYCOSYLASE; NF-KAPPA-B; CYTOCHROME-C; NITRIC-OXIDE; INDUCTION; PROTEIN; GENE; TRANSCRIPTION; ACTIVATION AB Treatment with cytosine beta-D-arabinoside (AraC; 300 mu M) induced a time-dependent accumulation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) protein in nuclei purified from cultured cerebellar granule cells, with a concomitant degradation of lamin B1, a nuclear membrane protein and a substrate of CPP32/caspase-3. Moreover, Asp-Glu-Val-Asp-fluoromethyl ketone (DEVD-fmk), a CPP32-selective antagonist, dose-dependently suppressed AraC-induced apoptosis of these neurons. Nuclear accumulation of GAPDH protein was associated with a progressive decrease in the activity of uracil-DNA glycosylase (UDG), one of the nuclear functions of GAPDH, The nuclear dehydrogenase activity of GAPDH was initially increased after treatment and then decreased parallel to UDG activity. Six GAPDH isoforms were detected in the nuclei of AraC-treated cells. The more alkaline isoforms, 1-3, constituted the bulk of the nuclear GAPDH, and the remaining isoforms, 4-6, were the minor species. Levels of all six isoforms were increased after treatment with AraC for 16 h; a 4-h treatment increased levels of only isoforms 4 and 5. Thus, it appears that various GAPDH isoforms are differentially regulated and may have distinct apoptotic roles. Pretreatment with GAPDH antisense oligonucleotide blocked the nuclear translocation of GAPDH isoforms, and the latter process occurred concurrently with a decrease in cytosolic GAPDH isoforms, Sodium nitroprusside-induced NAD labeling of nuclear GAPDH showed a 60% loss of GAPDH labeling after AraC treatment, suggesting that the active site of GAPDH may be covalently modified, denatured, or improperly folded. The unfolded protein response elicited by denatured GAPDH may contribute to AraC-induced neuronal death. C1 NIMH, Mol Neurobiol Sect, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. RP Chuang, DM (reprint author), NIMH, Mol Neurobiol Sect, Biol Psychiat Branch, NIH, Bldg 10,Room 3N212,10 Ctr Dr MSC 1272, Bethesda, MD 20892 USA. NR 43 TC 100 Z9 103 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 1999 VL 72 IS 3 BP 925 EP 932 DI 10.1046/j.1471-4159.1999.0720925.x PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 166XM UT WOS:000078603200005 PM 10037463 ER PT J AU Leitner, B Lovisetti-Scamihorn, P Heilmann, J Striessnig, J Blakely, RD Eiden, LE Winkler, H AF Leitner, B Lovisetti-Scamihorn, P Heilmann, J Striessnig, J Blakely, RD Eiden, LE Winkler, H TI Subcellular localization of chromogranins, calcium channels, amine carriers, and proteins of the exocytotic machinery in bovine splenic nerve SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE NESP55; synaptophysin; VAMP; VMAT2 carrier; syntaxin; SNAP-25 ID DENSE CORE VESICLES; VESICULAR MONOAMINE TRANSPORTER; SECRETOGRANIN-II SECRETONEURIN; ADRENAL CHROMAFFIN GRANULES; SMALL SYNAPTIC VESICLES; TOXIN LIGHT-CHAIN; TETANUS TOXIN; IMMUNOLOGICAL CHARACTERIZATION; PROHORMONE CONVERTASES; REGULATED EXOCYTOSIS AB Subcellular fractionation of bovine splenic nerves, which consist mainly of sympathetic nerve fibers, has been useful for characterizing cellular organelles en route to the terminal. In the present study we have characterized the subcellular distribution of both secretory and membrane proteins. A newly discovered chromogranin-like protein, NESP55, was found in large dense-core vesicles. The endogenous processing of NESP55 was comparable to that of chromogranins but more limited than that of secretogranin II and chromogranin B. For membrane proteins three major types of distribution were found. The amine carrier VMAT2 was confined to large dense-core vesicles. VAMP or synaptobrevin was present both in large dense-core vesicles and in lighter vesicles, whereas SNAP-25, syntaxin, and two types (N and L) of Ca(2+) channels were found in a special population of lighter vesicles but were not present in large dense-core vesicles or at the most in very low concentrations. The plasma membrane norepinephrine transporter was apparently present in a separate type of vesicle, but this requires further study. These results further characterize vesicles en route to the terminal and establish for the first time that peptides involved in exocytosis (syntaxin, SNAP-25, and N- and L-type Ca(2+) channels) are apparently transported to the terminal in a special type of vesicle. The exclusive presence of the amine carrier in large dense-core vesicles indicates that the formation of small dense-core vesicles in the terminals requires a reuse of membrane components of large dense-core vesicles. C1 Univ Innsbruck, Dept Pharmacol, A-6020 Innsbruck, Austria. Univ Innsbruck, Dept Biochem Pharmacol, A-6020 Innsbruck, Austria. Vanderbilt Univ, Med Ctr, Ctr Mol Neurosci, Nashville, TN USA. NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. RP Winkler, H (reprint author), Univ Innsbruck, Dept Pharmacol, Peter Mayr Str 1A, A-6020 Innsbruck, Austria. OI Eiden, Lee/0000-0001-7524-944X NR 53 TC 25 Z9 25 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 1999 VL 72 IS 3 BP 1110 EP 1116 DI 10.1046/j.1471-4159.1999.0721110.x PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 166XM UT WOS:000078603200024 PM 10037482 ER PT J AU Balijepalli, S Tirumalai, PS Swamy, KV Boyd, MR Mieyal, JJ Ravindranath, V AF Balijepalli, S Tirumalai, PS Swamy, KV Boyd, MR Mieyal, JJ Ravindranath, V TI Rat brain thioltransferase: Regional distribution, immunological characterization, and localization by fluorescent in situ hybridization SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE thiol-disulfide oxidoreductase; thioltransferase; glutaredoxin; oxidative stress; brain; glutathione ID PIG-LIVER THIOLTRANSFERASE; RED-BLOOD-CELLS; OXIDATIVE STRESS; CYTOPLASMIC THIOLTRANSFERASE; DISULFIDE OXIDOREDUCTASE; S-THIOLATION; GLUTATHIONE; PURIFICATION; GLUTAREDOXIN; PROTEINS AB Thioltransferase (TTase) is a member of the family of thiol-disulfide oxidoreductases that are involved in the maintenance of sulfhydryl homeostasis in cells by catalyzing thiol-disulfide interchange reactions. One of the major consequences of oxidative stress in brain is the formation of protein-glutathione mixed disulfides (through oxidation of protein thiols), which can be reversed by TTase during the recovery of brain from oxidative stress. We therefore examined the presence of TTase in brain regions from rat. In the rat, TTase activity in the whole brain was comparable with the corresponding activity in liver, but significantly higher in hippocampus. The enzyme activity was significantly lower in striatum and cerebellum compared with activity in whole brain. Rat brain TTase shared immunological similarity with the human red blood cell enzyme, but not with the pig liver enzyme. The constitutive expression of the mRNA to TTase was demonstrable by northern blotting. Localization of the TTase mRNA in rat brain by fluorescent in situ hybridization showed the presence of high amounts of mRNA in the olfactory bulb, cortex, and hippocampus and its predominant localization in the neurons. TTase mRNA was also present in Purkinje cells in the cerebellum, in giant reticular neurons in the midbrain, and in the striatal and thalamic neurons. This study demonstrates the constitutive presence of a functional TTase system in brain and delineates the regional and cellular localization of the enzyme in rat brain. C1 Natl Inst Mental Hlth & Neurosci, Dept Neurochem, Bangalore 560029, Karnataka, India. NCI, FDRDC, Lab Drug Discovery Res & Dev, Dev Therapeut Program, Frederick, MD USA. Case Western Reserve Univ, Dept Pharmacol, Cleveland, OH 44106 USA. RP Ravindranath, V (reprint author), NIMHANS, Dept Neurochem, Hosur Rd, Bangalore 560029, Karnataka, India. NR 33 TC 27 Z9 28 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 1999 VL 72 IS 3 BP 1170 EP 1178 DI 10.1046/j.1471-4159.1999.0721170.x PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 166XM UT WOS:000078603200032 PM 10037490 ER PT J AU Bassan, M Zamostiano, R Davidson, A Pinhasov, A Giladi, E Perl, O Bassan, H Blat, C Gibney, G Glazner, G Brenneman, DE Gozes, I AF Bassan, M Zamostiano, R Davidson, A Pinhasov, A Giladi, E Perl, O Bassan, H Blat, C Gibney, G Glazner, G Brenneman, DE Gozes, I TI Complete sequence of a novel protein containing a femtomolar-activity-dependent neuroprotective peptide SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE vasoactive intestinal peptide; apolipoprotein E; learning and memory; neuronal survival; molecular cloning; mRNA ID VASOACTIVE-INTESTINAL-PEPTIDE; E-DEFICIENT MICE; GROWTH-FACTOR PRECURSOR; CENTRAL-NERVOUS-SYSTEM; AMYLOID-BETA-PEPTIDE; ALZHEIMERS-DISEASE; APOLIPOPROTEIN-E; NEURONAL SURVIVAL; OXIDATIVE STRESS; FATTY NEUROPEPTIDE AB The vulnerability of neurons and the irreversibility of loss make discoveries of neuroprotective compounds fundamentally important. Here, the complete coding sequence of a novel protein (828 amino acids, pl 5.99), derived from mouse neuroglial cells, is revealed. The sequence contained (1) a neuroprotective peptide, NAPVSIPQ, sharing structural and immunological homologies with the previously reported, activity-dependent neurotrophic factor; (2) a glutaredoxin active site; and (3) a zinc binding domain. Gene expression was enriched in the mouse hippocampus and cerebellum and augmented in the presence of the neuropeptide vasoactive intestinal peptide, in cerebral cortical astrocytes. In mixed neuron-astrocyte cultures, NAPVSIPQ provided neuroprotection at subfemtomolar concentrations against toxicity associated with tetrodotoxin (electrical blockade), the p-amyloid peptide (the Alzheimer's disease neurotoxin), N-methyl-D-aspartate (excitotoxicity), and the human immunodeficiency virus envelope protein. Daily NAPVSIPQ injections to newborn apolipoprotein E-deficient mice accelerated the acquisition of developmental reflexes and prevented short-term memory deficits. Comparative studies suggested that NAPVSIPQ was more efficacious than other neuroprotective peptides in the apolipoprotein E-deficiency model. A potential basis for rational drug design against neurodegeneration is suggested with NAPVSIPQ as a lead compound. The relative enrichment of the novel mRNA transcripts in the brain and the increases found in the presence of vasoactive intestinal peptide, an established neuroprotective substance, imply a role for the cloned protein in neuronal function. C1 Tel Aviv Univ, Sackler Sch Med, Dept Clin Biochem, IL-69978 Tel Aviv, Israel. NICHD, Sect Dev & Mol Pharmacol, Dev Neurobiol Lab, NIH, Bethesda, MD USA. RP Gozes, I (reprint author), Tel Aviv Univ, Sackler Sch Med, Dept Clin Biochem, IL-69978 Tel Aviv, Israel. NR 60 TC 234 Z9 240 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 1999 VL 72 IS 3 BP 1283 EP 1293 DI 10.1046/j.1471-4159.1999.0721283.x PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 166XM UT WOS:000078603200044 PM 10037502 ER PT J AU Huang, KP Huang, FL Chen, HC AF Huang, KP Huang, FL Chen, HC TI Hypoxia/ischemia induces dephosphorylation of rat brain neuromodulin/GAP-43 in vivo SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE neuromodulin/GAP-43; ischemia/hypoxia; in vivo phosphorylation sites; dephosphorylation; oxidation ID PROTEIN-KINASE-C; GROWTH-ASSOCIATED PROTEIN; B-50 GAP-43; CONE PROTEIN; PHOSPHORYLATION SITE; SYNAPTIC PLASTICITY; CALMODULIN-BINDING; MASS-SPECTROMETRY; MEMBRANE SKELETON; NEUROGRANIN AB The in vivo state of phosphorylation and the modification of two Cys residues of neuromodulin/GAP-43 (Nm) were analyzed by electrospray ionization-mass spectrometry (ES-MS). The protein was purified from rat brain with homogenization buffer containing 1% Nonidet P-40, protease inhibitors, protein phosphatase inhibitors, and sulfhydryl reagent, 4-vinylpyridine. Nm was purified by HPLC and ion-exchange chromatography, and the various fractions were identified by ES-MS as unphosphorylated and mono-, di-, tri-, and tetraphosphorylated species. All of these Nm species contained 2 mot of added 4-vinylpyridine per mot of Nm, suggesting that the two Cys residues are in the reduced form in the brain. In vivo, the majority of Nm is in the phosphorylated form (similar to 80%), of which the levels of the mono- and diphospho forms are higher than those of the tri- and tetraphospho species. Four in vivo phosphorylation sites, Ser(41), Thr(95), Ser(142), and Thr(172), were identified by amino acid sequencing and tandem ES-MS of the peptides derived from Lys-C endoproteinase digestion. Among these sites, only Ser(41) is a known target of PKC, whereas the kinases responsible for the phosphorylation of the other three novel sites are unknown. Hypoxia/ischemia caused a preferential dephosphorylation of Ser(41) and Thr(172), whereas Thr(95) is the least susceptible to dephosphorylation. C1 NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP NICHHD, Endocrinol & Reprod Res Branch, NIH, Bldg 49,Room 6A36,49 Convent Dr MSC 4510, Bethesda, MD 20892 USA. NR 48 TC 22 Z9 23 U1 0 U2 1 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 1999 VL 72 IS 3 BP 1294 EP 1306 DI 10.1046/j.1471-4159.1999.0721294.x PG 13 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 166XM UT WOS:000078603200045 PM 10037503 ER PT J AU Weiss, MD Dalakas, MC Lauter, CJ Willison, HJ Quarles, RH AF Weiss, MD Dalakas, MC Lauter, CJ Willison, HJ Quarles, RH TI Variability in the binding of anti-MAG and anti-SGPG antibodies to target antigens in demyelinating neuropathy and IgM paraproteinemia SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE variability; anti-MAG; anti-SGPG; antibodies neuropathy ID MYELIN-ASSOCIATED GLYCOPROTEIN; SULFATED GLUCURONYL GLYCOLIPIDS; PERIPHERAL-NERVE MYELIN; M-PROTEINS; MONOCLONAL GAMMOPATHY; SENSORY NEUROPATHY; POLYNEUROPATHY; REACTIVITY; SERUM; HNK-1 AB Densitometry of immunostained Western blots or thin layer chromatograms and enzyme-linked immunosorbent assays (ELISAs) were used to compare the relative strengths of IgM binding to myelin-associated glycoprotein (MAG). PO glycoprotein, peripheral myelin protein-22 (PMP-22), sulfate-3-glucuronyl paragloboside (SGPG)I and other potential target antigens in a series of eleven patients with sensory or sensorimotor demyelinating neuropathy and IgM paraproteinemia. The IgM from all patients exhibited reactivity with both MAG and SGPG, and then was a statistically significant correlation between the overlay assays and ELISAs for measuring the strength of IgM binding to MAG and to SGPG. However, the data revealed variations in the relative strengths with which the antibodies bound to the potential target antigens and heterogeneity in their fine specificities. First, there was a poor correlation between the strength of binding to,MAG and to SGPG, respectively Second, reactivity with MAG or SGPG in a few of the patients was only detected by one of the two assay systems. Third, about one-third of the patients' IgM absolutely required the sulfate on SGPG for reactivity,whereas the others retained some reactivity after removal of the sulfate. Fourth, IgM from two of the patients exhibited unusually strong reactivity with the proteins of compact myelin, PO and PMP22, These relative differences in strengths of antibody binding to the potential antigens were compared with the patients' clinical presentations and with their responses to intravenous immunoglobulin (IVIg) therapy in a clinical trial in which they participated. For the most part, these variations did not correlate with clinical presentation, which was relatively homogeneous in this series of patients. However. an inverse relationship was noted between degree of reactivity to MAG by ELISA and response to IVIg. Two of the patients who responded had only mild elevations of IgM antibodies to nerve glycoconjugates and exhibited some unusual immunochemical and clinical characteristics in comparison to the other patients, The results demonstrate differences in the relative strengths with which anti-MAG and anti-SGPG IgM antibodies from different patients bind to potential neural target antigens which may affect pathogenic mechanisms and response to therapy. Published by Elsevier Science B.V. C1 NINDS, Myelin & Brain Dev Sect, Mol & Cellular Neurobiol Lab, NIH, Bethesda, MD 20892 USA. NINDS, Neuromuscular Dis Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Weiss, MD (reprint author), NINDS, Myelin & Brain Dev Sect, Mol & Cellular Neurobiol Lab, NIH, Bldg 49,Room 2A-35,49 Convent Dr, Bethesda, MD 20892 USA. NR 45 TC 45 Z9 46 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 EI 1872-8421 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD MAR 1 PY 1999 VL 95 IS 1-2 BP 174 EP 184 DI 10.1016/S0165-5728(98)00247-1 PG 11 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 183JT UT WOS:000079551000019 PM 10229128 ER PT J AU Khasar, SG McCarter, G Levine, JD AF Khasar, SG McCarter, G Levine, JD TI Epinephrine produces a beta-adrenergic receptor-mediated mechanical hyperalgesia and in vitro sensitization of rat nociceptors SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID DEPENDENT PROTEIN-KINASE; ROOT GANGLION NEURONS; RESISTANT NA+ CURRENT; SENSORY NEURONS; NORADRENALINE HYPERALGESIA; IN-VITRO; BRADYKININ; STRESS; PAIN; PROSTAGLANDINS AB Hyperalgesic and nociceptor sensitizing effects mediated by the beta-adrenergic receptor were evaluated in the rat. Intradermal injection of epinephrine, the major endogenous ligand for the beta-adrenergic receptor, into the dorsum of the hindpaw of thr rat produced a dose-dependent mechanical hyperalgesia, quantified by the Randall-Selitto paw-withdrawal test. Epinephrine-induced hyperalgesia was attenuated significantly by intradermal pretreatment with propranolol, a beta-adrenergic receptor antagonist, but not by phentolamine, an alpha-adrenergic receptor antagonist. Epinephrine-induced hyperalgesia developed rapidly; it was statistically significant by 2 min after injection, reached a maximum effect within 5 min, and lasted Ih. injection of a more beta-adrenergic receptor-selective agonist, isoproterenol, also produced dose-dependent hyperalgesia, which was attenuated by propranolol but not phentolamine. Epinephrine-induced hyperalgesia was not affected by indomethacin, an inhibitor of cyclo-oxygenase, or by surgical sympathectomy. It was attenuated significantly by inhibitors of the adenosine 3',5'-cyclic monophosphate signaling pathway (the adenylyl cyclase inhibitor, SQ 22536, and the protein kinase A inhibitors, Rp-adenosine 3',5'-cyclic monophosphate and WIPTIDE), inhibitors of the protein kinase C signaling pathway (chelerythrine and bisindolylmaleimide) and a alpha-opioid receptor agonist DAMGO ([D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin). Consistent with the hypothesis that epinephrine produces hyperalgesia by a direct action on primary afferent nociceptors, it was found to sensitize small-diameter dorsal root ganglion neurons in culture, i.e., to produce an increase in number of spikes and a decrease in latency to firing during a ramped depolarizing stimulus. These effects were blocked by propranolol. Furthermore epinephrine, like several other direct-acting hyperalgesic agents, caused a potentiation of tetrodotoxin-resistant sodium current, an effect that was abolished by Rp-adenosine 3',5'-cyclic monophosphate and significantly attenuated by bisindolylmaleimide. Isoproterenol also potentiated tetrodotoxin-resistant sodium current. In conclusion, epinephrine produces cutaneous mechanical hyperalgesia and sensitizes cultured dorsal root ganglion neurons in the absence of nerve injury via an action at a beta-adrenergic receptor. These effects of epinephrine are mediated by both the protein kinase A and protein kinase C second-messenger pathways. C1 Univ Calif San Francisco, NIH, Dept Med, Div Neurosci,Pain Ctr, San Francisco, CA 94143 USA. Univ Calif San Francisco, NIH Pain Ctr, Dept Oral & Maxillofacial Surg, Program Biomed Sci, San Francisco, CA 94143 USA. RP Levine, JD (reprint author), Univ Calif San Francisco, NIH, Dept Med, Div Neurosci,Pain Ctr, Box 0440,C-522, San Francisco, CA 94143 USA. FU NINDS NIH HHS [NS-21445, NS-21647] NR 55 TC 184 Z9 190 U1 2 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAR PY 1999 VL 81 IS 3 BP 1104 EP 1112 PG 9 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 178AB UT WOS:000079242300014 PM 10085337 ER PT J AU Haak, LL AF Haak, LL TI Metabotropic glutamate receptor modulation of glutamate responses in the suprachiasmatic nucleus SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Review ID PROTEIN-KINASE-C; OPTIC-NERVE STIMULATION; IN-SITU HYBRIDIZATION; CALCIUM-CHANNEL; SIGNAL-TRANSDUCTION; NEUROPEPTIDE-Y; CA2+ CHANNELS; RETINOHYPOTHALAMIC TRACT; SYNAPTIC TRANSMISSION; HIPPOCAMPAL-NEURONS AB Glutamate is the primary excitatory transmitter in the suprachiasmatic nucleus (SCN). Ionotropic glutamate receptors (iGluRs) mediate transduction of light information from the retina to the SCN, an important circadian clock phase shifting pathway. Metabotropic glutamate receptors (mGluRs) may play a significant modulatory role. mGluR modulation of SCN responses to glutamate was investigated with fura-2 calcium imaging in SCN exp]ant cultures. SCN neurons showed reproducible calcium responses to glutamate, kainate, and N-methyl-D-aspartate (NMDA). Although the type I/II mGluR agonists L-CCG-I and t-ACPD did not evoke calcium responses, they did inhibit kainate- and NMDA-evoked calcium rises. This interaction was insensitive to pertussis toxin Protein kinase A (PKA) activation by 8-bromo-cAMP significantly reduced iGluR inhibition by mGluR agonists. The inhibitory effect of mGluRs was enhanced by activating protein kinase C (PKC) and significantly reduced in the presence of the PKC inhibitor H7. Previous reports show that L-type calcium channels can be modulated by PKC and PKA. In SCN cells, about one-half of the calcium rise evoked by kainate or NMDA was blocked by the L-type calcium channel antagonist nimodipine. Calcium rises evoked by K+ were used to test whether mGluR inhibition of iGluR calcium rises involved calcium channel modulation. These calcium rises were primarily attributable to activation of voltage-activated calcium channels. PKC activation inhibited K+-evoked calcium rises, but PKC inhibition did nest affect L-CCG-I inhibition of these rises. In contrast, 8Br-cAMP had no effect alone but blocked L-CCG-I inhibition. Taken together, these results suggest that activation of mGluRs, likely type II, modulates glutamate-evoked calcium responses in SCN neurons. mGluR inhibition of iGluR calcium rises can be differentially influenced by PKC or PKA activation. Regulation of glutamate-mediated calcium influx could occur at L-type calcium channels, K+ channels, or at GluRs. it is proposed that mGluRs may he important regulators of glutamate: responsivity in the circadian system. C1 Stanford Univ, Dept Biol Sci, Program Neurosci, Stanford, CA 94305 USA. RP Haak, LL (reprint author), NIH, Lab Cellular & Mol Neurophysiol, Bldg 49,Rm 5C-28, Bethesda, MD 20892 USA. RI Haak, Laurel/C-4986-2008 OI Haak, Laurel/0000-0001-5109-3700 FU NIMH NIH HHS [MH-17047-15] NR 102 TC 27 Z9 27 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAR PY 1999 VL 81 IS 3 BP 1308 EP 1317 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 178AB UT WOS:000079242300034 PM 10085357 ER PT J AU Pozzo-Miller, LD Inoue, T Murphy, DD AF Pozzo-Miller, LD Inoue, T Murphy, DD TI Estradiol increases spine density and NMDA-dependent Ca2+ transients in spines of CA1 pyramidal neurons from hippocampal slices SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID LONG-TERM POTENTIATION; DENDRITIC SPINES; BRAIN-SLICES; ESTROUS-CYCLE; CALCIUM; RAT; FLUCTUATION; RECEPTORS; ENTRY; CELLS AB To investigate the physiological consequences of the increase in spine density induced by estradiol in pyramidal neurons of the hippocampus, He performed simultaneous whole cell recordings and Ca2+ imaging in CAI neuron spines and dendrites in hippocampal slices. Four- to eight-days in vitro slice cultures were exposed to 17 beta-estradiol (EST) for an additional 4- to 8-day period, and spine density was assessed by confocal microscopy of DiI-labeled CAI pyramidal neurons. Spine density was doubled in both apical and basal dendrites of the CA1 region in EST-treated slices; consistently, a reduction in cell input resistance was observed in EST-treated CAI neurons. Double immunofluorescence staining of presynaptic (synaptophysin) and postsynaptic (alpha-subunit of CaMKII) proteins showed an increase in synaptic density after EST treatment. The slops of the input/output curves of both alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) and N-methyl-D-aspartate: (NMDA) postsynaptic currents were steeper in EST-treated CAI neurons, consistent with the observed increase in synapse density. To characterize NMDA-dependent synaptic currents and dendritic Ca2+ transients during Schaffer collaterals stimulation, neurons were maintained at +40 mV in the presence of nimodipine, picrotoxin, and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). No differences in resting spine or dendritic Ca2+ levels were observed between control and EST-treated CAI neurons. Intracellular Ca transients during afferent stimulation exhibited a faster slope and reached higher levels in spines than in adjacent dendrites. Peak Ca2+ levels were larger in both spines and dendrites of EST-treated CAI neurons. Ca2+ gradients between spine heads and dendrites during afferent stimulation were also larger in EST-treated neurons. Both spine and dendritic Ca2+ transients during afferent stimulation were reversibly blocked by D,L-2-amino-5-phosphonovaleric acid (D,L-APV. The increase in spine density and the enhanced NMDA-dependent Ca2+ signals in spines and dendrites induced by EST may underlie a threshold reduction for induction of NMDA-dependent synaptic plasticity in the hippocampus. C1 NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. Univ Tokyo, Inst Med Sci, Dept Mol Neurobiol, Tokyo 108, Japan. RP Pozzo-Miller, LD (reprint author), Univ Alabama, Dept Neurobiol, CIRC 429,1719 6th Ave S, Birmingham, AL 35294 USA. OI Inoue, Takafumi/0000-0002-2728-0060 NR 34 TC 132 Z9 133 U1 1 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAR PY 1999 VL 81 IS 3 BP 1404 EP 1411 PG 8 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 178AB UT WOS:000079242300042 PM 10085365 ER PT J AU Reynolds, JH Chelazzi, L Desimone, R AF Reynolds, JH Chelazzi, L Desimone, R TI Competitive mechanisms subserve attention in macaque areas V2 and V4 SO JOURNAL OF NEUROSCIENCE LA English DT Article DE spatial attention; monkey; extrastriate cortex; V2; V4; model ID SELECTIVE VISUAL-ATTENTION; INFERIOR TEMPORAL CORTEX; CORTICAL AREAS; NEURONAL RESPONSES; NEURAL MECHANISMS; TARGET SELECTION; MONKEY; PARIETAL; MODULATION; STIMULUS AB It is well established that attention modulates visual processing in extrastriate cortex. However, the underlying neural mechanisms are unknown. A consistent observation is that attention has its greatest impact on neuronal responses when multiple stimuli appear together within a cell's receptive field. One way to explain this is to assume that multiple stimuli activate competing populations of neurons and that attention biases this competition in favor of the attended stimulus, In the absence of competing stimuli, there is no competition to be resolved. Accordingly, attention has a more limited effect on the neuronal response to a single stimulus. To test this interpretation, we measured the responses of neurons in macaque areas V2 and V4 using a behavioral paradigm that allowed us to isolate automatic sensory processing mechanisms from attentional effects. First, we measured each cell's response to a single stimulus presented alone inside the receptive field or paired with a second receptive field stimulus, while the monkey attended to a location outside the receptive field. Adding the second stimulus typically caused the neuron's response to move toward the response that was elicited by the second stimulus alone. Then, we directed the monkey's attention to one element of the pair. This drove the neuron's response toward the response elicited when the attended stimulus appeared alone. These findings are consistent with the idea that attention biases competitive interactions among neurons, causing them to respond primarily to the attended stimulus. A quantitative neural model of attention is proposed to account for these results. C1 NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. Univ Verona, Dipartimento Sci Neurol & Vis, Sez Fisiol, I-37100 Verona, Italy. RP Desimone, R (reprint author), NIMH, Neuropsychol Lab, NIH, 49 Convent Dr MSC 4415,Bldg 49,Room 1B80, Bethesda, MD 20892 USA. RI Chelazzi, Leonardo/B-6084-2011 OI Chelazzi, Leonardo/0000-0001-8566-0611 NR 44 TC 757 Z9 770 U1 1 U2 23 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAR 1 PY 1999 VL 19 IS 5 BP 1736 EP 1753 PG 18 WC Neurosciences SC Neurosciences & Neurology GA 168CC UT WOS:000078672300019 PM 10024360 ER PT J AU Zhao, WQ Lawen, A Ng, KT AF Zhao, WQ Lawen, A Ng, KT TI Changes in phosphorylation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) in processing of short-term and long-term memories after passive avoidance learning SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE day-old chicks; learning and memory; retrieval; CaMKII; immunoprecipitation; anti-phosphoserine antibody; anti-phosphothreonine antibody ID POSTSYNAPTIC DENSITY; CALMODULIN; POTENTIATION; BRAIN; CHICK; INHIBITION; EXPRESSION; INDUCTION; CURRENTS; LESIONS AB Characteristic autophosphorylation of calcium/calmodulin-dependent protein kinase II (CaMKII) and its consequences have made this kinase an interesting target in studying the molecular pathway for important neuronal functions including learning and memory formation. In this article, we use immunoprecipitation and immunoblotting methods to detect changes in phosphorylation of CaMKII during memory formation in 1-day-old chicks trained in a single trial passive avoidance task, A 60-kDa protein has been immunoprecipitated from the chick brain with an anti-rabbit CaMKII antibody. This protein shows strong and specific immunoactivities with antibodies against the calmodulin binding site of CaMKII, and the N and C terminals of beta-CaMKII, Commercially available anti-phosphoserine and anti-phosphothreonine antibodies are shown to sensitively detect phosphorylation of purified CaMKII, The basal phosphorylation of CaMKII from the intermediate medial hyperstriatum ventrale (IMHV) and lobus parolfactorius (LPO) regions of the chick brain is shown to be largely right hemisphere-lateralized. When chicks are subjected to a passive avoidance training experience, a specific increase in CaMKII phosphorylation is induced in the IMHV and LPO of the left hemisphere from those chicks whose memory for the training experience is successfully retrieved, While this specific increase in CaMKII phosphorylation is seen in both the left IMHV and left LPO in short-term memory, it is detectable only in the left LPO associated with long-term memory retrieval, The present results provide evidence that in vivo changes in phosphorylation of CaMKII are associated specifically with processing of distinct memory stages, which take place in specific brain regions, (C) 1999 Wiley-Liss, Inc. C1 Monash Univ, Dept Psychol, Clayton, Vic 3168, Australia. Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic 3168, Australia. RP Zhao, WQ (reprint author), NINDS, Lab Adapt Syst, NIH, Bethesda, MD 20892 USA. RI Lawen, Alfons/A-6598-2008 OI Lawen, Alfons/0000-0001-6553-9945 NR 28 TC 19 Z9 20 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD MAR 1 PY 1999 VL 55 IS 5 BP 557 EP 568 DI 10.1002/(SICI)1097-4547(19990301)55:5<557::AID-JNR3>3.0.CO;2-P PG 12 WC Neurosciences SC Neurosciences & Neurology GA 170VD UT WOS:000078827000003 PM 10082078 ER PT J AU Luo, JJ Wallace, W Riccioni, T Ingram, DK Roth, GS Kusiak, JW AF Luo, JJ Wallace, W Riccioni, T Ingram, DK Roth, GS Kusiak, JW TI Death of PC12 cells and hippocampal neurons induced by adenoviral-mediated FAD human amyloid precursor protein gene expression SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE Alzheimer's disease; gene transfer; cell culture; cell death; neurodegeneration ID NERVE GROWTH-FACTOR; CEREBRAL CORTICAL-NEURONS; IMPAIRS GLUCOSE-TRANSPORT; TRANSGENIC ANIMAL-MODELS; ALZHEIMERS-DISEASE; BETA-PROTEIN; IN-VITRO; RECOMBINANT ADENOVIRUS; PARKINSONS-DISEASE; NEURITE OUTGROWTH AB We used adenoviral-mediated gene transfer of human amyloid precursor proteins (h-APPs) to evaluate the role of various h-APPs in causing neuronal cell death. We were able to infect PC12 cells with very high efficiency because similar to 90% of the cells were cytochemically positive for beta-galactosidase activity when an adenoviral vector containing LacZ cDNA was used to infect cells. Cells infected with adenovirus containing h-APP cDNA showed high-level transcription and expression of h-APP as measured by reverse transcriptase-polymerase chain reaction and Western immunoblot analyses, respectively. Intracellular and extracellular levels of h-APP were elevated approximately 17- and 24-fold in cultures infected with recombinant adenovirus containing wild-type mutant and 13- and 17-fold with V642F mutant. No elevation in h-APP was seen in cultures infected with antisense h-APP or null adenovirus, H-APP levels were maximal 3 days after infection. Overexpression of V642F mutant h-APP in PC12 cells and hippocampal neurons resulted in about a twofold increase in death compared with overexpression of wild-type h-APP. These results demonstrate the usefulness of recombinant adenoviral mediated gene transfer in cell culture studies and suggest that overexpression of a familial Alzheimer's disease mutant APP may be toxic to neuronal cells. (C) 1999 Wiley-Liss, Inc. C1 NIA, GRC, LBC, MNU,NIH, Baltimore, MD 21224 USA. NIA, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. NIA, Cellular & Mol Biol Lab, Baltimore, MD 21224 USA. RP Luo, JJ (reprint author), NIA, GRC, LBC, MNU,NIH, Mail Stop 12,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM luoj@vax.grc.nia.nih.gov NR 93 TC 36 Z9 38 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD MAR 1 PY 1999 VL 55 IS 5 BP 629 EP 642 DI 10.1002/(SICI)1097-4547(19990301)55:5<629::AID-JNR10>3.0.CO;2-Y PG 14 WC Neurosciences SC Neurosciences & Neurology GA 170VD UT WOS:000078827000010 PM 10082085 ER PT J AU Oldfield, EH AF Oldfield, EH TI Direct convective macromolecule delivery - Response SO JOURNAL OF NEUROSURGERY LA English DT Letter C1 NINDS, Bethesda, MD 20892 USA. RP Oldfield, EH (reprint author), NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD MAR PY 1999 VL 90 IS 3 BP 611 EP 611 PG 1 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 170KX UT WOS:000078805800039 ER PT J AU Yao, ZS Zhang, ML Sakahara, H Nakamoto, Y Higashi, T Zhao, S Sato, N Arano, Y Konishi, J AF Yao, ZS Zhang, ML Sakahara, H Nakamoto, Y Higashi, T Zhao, S Sato, N Arano, Y Konishi, J TI The relationship of glycosylation and isoelectric point with tumor accumulation of avidin SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE avidin modification; glycosylation; isoelectric point; tumor accumulation ID BIOTINYLATED MONOCLONAL-ANTIBODIES; BRAIN-BARRIER TRANSPORT; RADIOLABELED STREPTAVIDIN; IMMUNOGLOBULIN-G; CELLULAR UPTAKE; OVARIAN-CANCER; BIODISTRIBUTION; INTRAPERITONEAL; BINDING; PROTEIN AB Radiolabeled avidin markedly accumulated in intraperitoneal tumors and was cleared rapidly from circulation when given intraperitoneally. This study investigated the mechanisms of the tumor localization of avidin. Methods: Avidin was deglycosylated through endoglycosydase-H digestion and/or neutralized by acetylation of its lysine amino acids with acetic acid N-hydroxysuccinimide ester, Avidin and modified avidins were analyzed using sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS/PAGE) and isoelectric focusing. A tumor model was established by intraperitoneal injection of human colon cancer cells, LS180, in nude mice. Avidin and modified avidins were labeled with In-111 using diethyleneamine pentaacetic acid-biotin and were administered intraperitoneally into the tumor-bearing mice. The biodistribution of radioactivity was examined 2 and 24 h postinjection, Results: Deglycosylated avidins revealed a major band of smaller molecules on SDS/PAGE. The isoelectric point of neutralized avidins was reduced to less than 5, whereas that of unneutralized avidins was more than 9.5. Biodistribution study demonstrated that liver uptake was decreased by deglycosylation and kidney accumulation was decreased by neutralization, respectively. The blood clearance was remarkably slowed by combined modification of deglycosylation and neutralization. The tumor uptake of radioactivity was reduced by either deglycosylation or neutralization and was further decreased with combined modification. Conclusion: Both high glycosylation and positive charge of avidin contributed to its accumulation in tumor. This study may facilitate development of a new vehicle for the delivery of therapeutic agents to intraperitoneal tumors. C1 Kyoto Univ, Fac Med, Dept Nucl Med, Kyoto, Japan. Kyoto Univ, Fac Pharmaceut Sci, Dept Radiopharmaceut Chem, Kyoto 606, Japan. RP Yao, ZS (reprint author), NIH, Dept Nucl Med, Bldg 10,Rm 1C-401,10 Ctr Dr,MSC 1180, Bethesda, MD 20892 USA. RI Zhao, Songji/D-5511-2012 NR 34 TC 37 Z9 38 U1 2 U2 4 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAR PY 1999 VL 40 IS 3 BP 479 EP 483 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 173NL UT WOS:000078986600024 PM 10086714 ER PT J AU Rose, SR Municchi, G AF Rose, SR Municchi, G TI Six-hour and four-hour nocturnal sampling for growth hormone SO JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM LA English DT Article DE somatotropin; nocturnal GH secretion; short stature; GH deficiency; diagnosis; growth disorders; physiology; puberty ID CLINICAL RESEARCH-CENTER; SHORT STATURE; CHILDREN; SECRETION; PUBERTY; BOYS; PROFILES; GIRLS AB Overnight sampling for growth hormone (GET) is research tool for quantifying characteristics of spontaneous GH secretion. However, the study is costly in assays and blood volume, particularly that required from a small child. Design and patients: Existing overnight GH data from 126 normal children and from 227 children with GH deficiency or short stature were reanalyzed, examining 6-h and 4-h segments of this data for accuracy in representing each child's 12-h GH secretion. The goal was to see whether the test could be made shorter and more practical without losing accuracy. Results: The 6-h segment 2200-0400 h consistently contained the majority of GH peaks, Correlation was high between GH values from 2200-0400 h and from the 12-h period. Normal 95% confidence limits (CL) for GH during 2200-0400 h were derived from data in normal children for gender and each pubertal stage. Data from short children were compared with the normal 6-h 95% CL. In short children, GH values low for 12-h were also low for 6-h, Only a few children with normal 12-h values (1.5% of normals, 0.5% with short stature) had GH values outside 95% CL for 6-h. Conclusions: Six-hour GH sampling (2200-0400 h) is accurate and cost-efficient compared to the 12-h overnight GH study. These studies are primarily useful in research settings. C1 Univ Tennessee, Dept Pediat, Memphis, TN USA. NICHD, NIH, Bethesda, MD USA. RP Rose, SR (reprint author), 50 N Dunlap,4th Floor, Memphis, TN 38103 USA. FU NCRR NIH HHS [5MO1-RR00997] NR 15 TC 9 Z9 9 U1 0 U2 0 PU FREUND PUBLISHING HOUSE LTD PI LONDON PA STE 500, CHESHAM HOUSE, 150 REGENT ST, LONDON W1R 5FA, ENGLAND SN 0334-018X J9 J PEDIATR ENDOCR MET JI J. Pediatr. Endocrinol. Metab. PD MAR-APR PY 1999 VL 12 IS 2 BP 167 EP 173 PG 7 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 181ZE UT WOS:000079472800007 PM 10392363 ER PT J AU Lehrnbecher, T Kontny, HU Jeschke, R AF Lehrnbecher, T Kontny, HU Jeschke, R TI Metastatic Crohn's disease in a 9-year-old boy SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article ID METRONIDAZOLE C1 NIH, Pediat Oncol Branch, Bethesda, MD 20892 USA. Univ Wurzburg, Dept Pediat, D-97070 Wurzburg, Germany. RP Lehrnbecher, T (reprint author), NIH, Pediat Oncol Branch, Bldg 10,Room 13N240, Bethesda, MD 20892 USA. NR 14 TC 11 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD MAR PY 1999 VL 28 IS 3 BP 321 EP 323 DI 10.1097/00005176-199903000-00021 PG 3 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 177TK UT WOS:000079227000020 PM 10067737 ER PT J AU Rayyis, SF Ambalavanan, N Wright, L Carlo, WA AF Rayyis, SF Ambalavanan, N Wright, L Carlo, WA TI Randomized trial of "slow" versus "fast" feed advancements on the incidence of necrotizing enterocolitis in very low birth weight infants SO JOURNAL OF PEDIATRICS LA English DT Article ID PATHOGENESIS AB Objective: To determine whether the rate of feed advancement affects the incidence of necrotizing enterocolitis (NEC). Study design: Prospective randomized controlled trial involving 185 formula-fed infants with birth weight 501 to 1500 g and gestational age less than or equal to 34 weeks. Infants were randomized into 2 groups: "slow" (n = 98), who received 15 cc/kg/d increments (a 10-day schedule to full feeds) and "fast" (n = 87), who received 35 cc/kg/d increments (a 5-day schedule to full feeds) of Similac Special Care 20 cal/oz. Feeds were increased only if well tolerated as defined by a protocol. Results: The incidence of NFC (Bell stage greater than or equal to II) was similar in both groups (slow 13% and fast 9%, P = .5). The incidence of perforation (Bell stage III) was also similar in both groups (slow 4% and fast 2%, P = .8). Feeds were started at a comparable postnatal age in both groups (median age: slow 5 days and fast 4 days, P = .9). Although the neonates in the fast group attained full enteral intake earlier (median days [25th and 75th percentiles]: slow 15 [12, 21] and fast 11 [8, 15], P < .001) and regained their birth weight earlier (slow 15 [11, 20] and fast 12 [8, 15], P < .05), their ages at discharge were not statistically different (slow 47 [31, 67] and fast 43 [29, 62], P = .3) Conclusions: A greater than twofold difference in the rate of feed advancement from 15 cc/kg/d to 35 cc/kg/d did not affect the incidence of NEC 2 stage II. Factors other than feed advancement appear to be more important in the pathogenesis or progression of NEC. C1 Univ Alabama, Dept Pediat, Birmingham, AL 35233 USA. NICHHD, Bethesda, MD 20892 USA. RP Carlo, WA (reprint author), Univ Alabama, Dept Pediat, 525 New Hillman Bldg,619 S 19th St, Birmingham, AL 35233 USA. NR 15 TC 79 Z9 85 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD MAR PY 1999 VL 134 IS 3 BP 293 EP 297 DI 10.1016/S0022-3476(99)70452-X PG 5 WC Pediatrics SC Pediatrics GA 173NC UT WOS:000078985800010 PM 10064664 ER PT J AU Grether, JK Nelson, KB Dambrosia, JM Phillips, TM AF Grether, JK Nelson, KB Dambrosia, JM Phillips, TM TI Interferons and cerebral palsy SO JOURNAL OF PEDIATRICS LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; ALPHA; COMPLEMENT; THERAPY; GAMMA; BRAIN; CYTOKINES; LESIONS; C3A AB Objective: To explore the association of neonatal interferons (IFNs) with spastic cerebral palsy (CP) and with other measured substances. Study design: Assays of archived neonatal blood of 31 predominantly term children with CP and 65 children in a control group were obtained by recycling immunoaffinity chromatography with laser-enhanced fluorescence and chemiluminescence detection. Results: Fourteen of 31 children with spastic CP had concentrations of IFNs-alpha, beta, and gamma exceeding any control. Levels of interleukins-1 6, 8, tumor necrosis factor-alpha, chemokines, colony stimulating factors, transforming growth factor-beta, complement components and regulators, certain neuropeptides, and thyroid hormones also differed from control levels in these 14 children. The 17 children with CP whose IFN concentrations were within the control range had levels of inflammatory cytokines higher than but near to control values; 13 of these 17 had values for coagulation factors that exceeded control values. Seven of 9 children with spastic diplegia had high IFNs, and 8 of 10 hemiplegic children had normal IFNs. Conclusion: Neonatal IFNs exceeding control concentrations were associated with other biochemical and clinical indicators of inflammation and with spastic diplegia. In these children with CP, IFNs within the control range were associated with concentrations of other inflammatory markers that were near to control values and with spastic hemiplegia. C1 Calif Dept Hlth Serv, Calif Birth Defects Monitoring Program, Emeryville, CA USA. NINDS, Neuroepidemiol & Biometry & Field Studies Branch, Bethesda, MD 20892 USA. George Washington Univ, Med Ctr, Immunochem Lab, Washington, DC 20037 USA. RP Nelson, KB (reprint author), 7550 Wisconsin Ave,Rm 714, Bethesda, MD 20892 USA. NR 34 TC 67 Z9 68 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD MAR PY 1999 VL 134 IS 3 BP 324 EP 332 DI 10.1016/S0022-3476(99)70458-0 PG 9 WC Pediatrics SC Pediatrics GA 173NC UT WOS:000078985800016 PM 10064670 ER PT J AU Lou, Q Pastan, I AF Lou, Q Pastan, I TI A Lewis(y) epitope mimicking peptide induces anti-Lewis(y) immune responses in rabbits and mice SO JOURNAL OF PEPTIDE RESEARCH LA English DT Article DE carbohydrate antigen; immunotoxin; mAb B3 ID HUMAN-IMMUNODEFICIENCY-VIRUS; GROWTH-FACTOR RECEPTORS; MONOCLONAL-ANTIBODIES; PSEUDOMONAS EXOTOXIN; CARBOHYDRATE; IMMUNOTOXIN; MIMICRY; LIBRARIES; ANTIGENS; CLONING AB Lewis(y) carbohydrate antigens are abundant on the surface of many carcinomas. Mab B3 directed against this carbohydrate antigen has been used to make an immunotoxin that is very cytotoxic to cancer cells expressing the Lewis(y) antigen. Mab B3 was also used to screen a phage-displayed peptide library and identified a peptide mimicking the Lewis(y) epitope. In this report, we demonstrate that the Lewis(y) epitope-mimicking peptide induces anti-Lewis(y) immune responses in both rabbits and mice. In addition, Lewis(y) antigens induce antipeptide immune responses. These results indicate that carbohydrate-mimicking peptides provide a novel strategy to elicit immune responses for tumor-associated carbohydrates. C1 NCI, Div Basic Sci, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Div Basic Sci, Mol Biol Lab, NIH, 37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 37 TC 18 Z9 18 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1397-002X J9 J PEPT RES JI J. Pept. Res. PD MAR PY 1999 VL 53 IS 3 BP 252 EP 260 DI 10.1034/j.1399-3011.1999.00025.x PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 188YH UT WOS:000079876600004 PM 10231713 ER PT J AU Gasior, M Shoaib, M Yasar, S Jaszyna, M Goldberg, SR AF Gasior, M Shoaib, M Yasar, S Jaszyna, M Goldberg, SR TI Acquisition of nicotine discrimination and discriminative stimulus effects of nicotine in rats chronically exposed to caffeine SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID SCHEDULE-CONTROLLED BEHAVIOR; LOCOMOTOR-ACTIVITY; DRUG DISCRIMINATION; RECEPTOR LIGANDS; RHESUS-MONKEYS; COCAINE; DOPAMINE; HUMANS; MECHANISMS; TOLERANCE AB Caffeine and nicotine are the main psychoactive ingredients of coffee and tobacco, with a high frequency of concurrent use in humans. This study examined the effects of chronic caffeine exposure on 1) rates of acquisition of a nicotine discrimination (0.1 or 0.4 mg/kg, s.c., training doses) and 2) the pharmacological characteristics of the established nicotine discrimination in male Sprague-Dawley rats. Once rats learned to lever-press reliably under a fixed ratio of 10 schedule for food pellets, they were randomly divided into two groups; 12 animals were maintained continuously on caffeine added to the drinking water (3 mg/ml) and another 12 control rats continued to drink tap water. In each group of water- and caffeine-drinking rats, there were six rats trained to discriminate 0.1 mg/kg of nicotine from saline and six rats trained to discriminate 0.4 mg/kg of nicotine from saline. Regardless of the training dose of nicotine, both water- and caffeine-drinking groups required a comparable number of training sessions to attain reliable stimulus control, although there was a trend for a slower acquisition in the caffeine-drinking group trained with 0.1 mg/kg of nicotine. Tests for generalization to different doses of nicotine revealed no significant differences in potency of nicotine between water- and caffeine-drinking groups. The nicotinic-receptor antagonist mecamylamine blocked the discriminative effects of 0.1 and 0.4 mg/kg nicotine with comparable potency and efficacy in water- and caffeine-drinking groups. There was a dose-related generalization to both the 0.1 and 0.4 mg/kg nicotine cue (maximum average of 51-83%) in water-drinking rats after i.p. treatment with d-amphetamine, cocaine, the selective dopamine uptake inhibitor GBR-12909, apomorphine, and the selective dopamine D1 receptor agonist SKF-82958, but not in caffeine-drinking rats (0-22%). There was no generalization to the nicotine cues after i.p. treatment with caffeine or the selective D2 (NPA) and D3 (PD 128,907) dopamine-receptor agonists in water- and caffeine-drinking rats. The dopamine-release inhibitor CGS 10746B reduced the discriminative effects of 0.4 mg/kg nicotine in water-drinking rats, but not in caffeine-drinking rats. There was no evidence of development of tolerance or sensitization to nicotine's effects throughout the study. in conclusion, chronic caffeine exposure (average, 135 mg/kg/day) did not affect the rate of acquisition of the nicotine discrimination, but it did reduce the dopaminergic component of the nicotine-discriminative cue. The reduction of the dopaminergic component of the nicotine cue was permanent, as this effect was still evident after the caffeine solution was replaced with water in caffeine-drinking rats. That nicotine could reliably serve as a discriminative stimulus in the absence of the dopaminergic component of its discriminative cue may differentiate nicotine from "classical dopaminergic" drugs of abuse such as cocaine and amphetamine. C1 NIDA, Intramural Res Program, Preclin Pharmacol Lab, NIH, Baltimore, MD 21224 USA. RP Gasior, M (reprint author), NIDA, Intramural Res Program, Preclin Pharmacol Lab, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mgasior@intra.nida.nih.gov NR 81 TC 32 Z9 32 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD MAR PY 1999 VL 288 IS 3 BP 1053 EP 1073 PG 21 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 172BZ UT WOS:000078903600019 PM 10027843 ER PT J AU Salvati, P Maj, R Caccia, C Cervini, MA Fornaretto, MG Lamberti, E Pevarello, P Skeen, GA White, HS Wolf, HH Faravelli, L Mazzanti, M Mancinelli, E Varasi, M Fariello, RG AF Salvati, P Maj, R Caccia, C Cervini, MA Fornaretto, MG Lamberti, E Pevarello, P Skeen, GA White, HS Wolf, HH Faravelli, L Mazzanti, M Mancinelli, E Varasi, M Fariello, RG TI Biochemical and electrophysiological studies on the mechanism of action of PNU-151774E, a novel antiepileptic compound SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID LIPID-PEROXIDATION; CALCIUM CHANNELS; CELL-CULTURE; RAT-BRAIN; ANTICONVULSANT; LAMOTRIGINE; PHENYTOIN; NEURONS; NEUROTRANSMITTERS; CARBAMAZEPINE AB PNU-151774E [(S)-(+)-2-(4-(3-fluorobenzyloxy)benzylamino) propanamide methanesulfonate], a new anticonvulsant that displays a wide therapeutic window, has a potency comparable or superior to that of most classic anticonvulsants. PNU-151774E is chemically unrelated to current antiepileptics. In animal seizure models it possesses a broad spectrum of action. In the present study, the action mechanism of PNU-151774E has been investigated using electrophysiological and biochemical assays. Binding studies performed with rat brain membranes show that PNU-151774E has high affinity for binding site 2 of the sodium channel receptor, which is greater than that of phenytoin or lamotrigine (IC50, 8 mu M versus 47 and 185 mu M, respectively). PNU-151774E reduces sustained repetitive firing in a use-dependent manner without modifying the first action potential in hippocampal cultured neurons. In the same preparation PNU-151774E inhibits tetrodotoxin-sensitive fast sodium currents and high voltage-activated calcium currents under voltage-clamp conditions. These electrophysiological activities of PNU-151774E correlate with its ability to inhibit veratrine and KCI-induced glutamate release in rat hippocampal slices (IC50, 56.4 and 185.5 mu M, respectively) and calcium inward currents in mouse cortical neurons. On the other hand, PNU-151774E does not affect whole-cell gamma-aminobutryic acid- and glutamate-induced currents in cultured mouse cortical neurons. These results suggest that PNU-151774E exerts its anticonvulsant activity, at least in part, through inhibition of sodium and calcium channels, stabilizing neuronal membrane excitability and inhibiting transmitter release. The possible relevance of these pharmacological properties to its antiepileptic potential is discussed. C1 Pharmacia & Upjohn SpA, Cent Nervous Syst Preclin Res, Nerviano, MI, Italy. Pharmacia & Upjohn SpA, Dept Chem, Nerviano, MI, Italy. Univ Utah, Dept Pharmacol & Toxicol, Natl Inst Hlth, Natl Inst Neurol Disorders & Stroke Anticonvulsant, Salt Lake City, UT USA. Univ Milan, Dept Gen Physiol & Biochem, Milan, Italy. Ist Clin Perfezionamento, Dept Neurosci, Milan, Italy. Thomas Jefferson Univ, Dept Neurol, Philadelphia, PA 19107 USA. RP Maj, R (reprint author), Pharmacia & Upjohn SpA, Cent Nervous Syst Preclin Res, Via Commercio, I-63046 Marino Del Tronto, Ascoli Piceno, Italy. RI Mazzanti, Michele/A-8941-2011 NR 40 TC 50 Z9 50 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD MAR PY 1999 VL 288 IS 3 BP 1151 EP 1159 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 172BZ UT WOS:000078903600029 PM 10027853 ER PT J AU Witkin, JM Savtchenko, N Mashkovsky, M Beekman, M Munzar, P Gasior, M Goldberg, SR Ungard, JT Kim, J Shippenberg, T Chefer, V AF Witkin, JM Savtchenko, N Mashkovsky, M Beekman, M Munzar, P Gasior, M Goldberg, SR Ungard, JT Kim, J Shippenberg, T Chefer, V TI Behavioral, toxic, and neurochemical effects of sydnocarb, a novel psychomotor stimulant: Comparisons with methamphetamine SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID SQUIRREL-MONKEYS; DOPAMINE; COCAINE; RATS; AMPHETAMINE; DRUGS AB Sydnocarb (3-(beta-phenylisopropyl)-N-phenylcarbamoylsydnonimine) is a psychostimulant in clinical practice in Russia as a primary and adjunct therapy for a host of psychiatric disorders, including schizophrenia and depression. It has been described as a stimulant with an addiction liability and toxicity less than that of amphetamines. The present study undertook to evaluate the psychomotor stimulant effects of sydnocarb in comparison to those of methamphetamine. Sydnocarb increased locomotor activity of mice with reduced potency (similar to 10-fold) and efficacy compared with methamphetamine. Sydnocarb blocked the locomotor depressant effects of haloperidol at doses that were inactive when given alone. The locomotor stimulant effects of both methamphetamine and sydnocarb were dose-dependently blocked by the dopamine D1 and D2 antagonists SCH 39166 and spiperone, respectively; blockade generally occurred at doses of the antagonists that did not depress locomotor activity when given alone. In mice trained to discriminate methamphetamine from saline, sydnocarb fully substituted for methamphetamine with a 9-fold lower potency. When substituted for methamphetamine under self-administration experiments in rats, 10-fold higher concentrations of sydnocarb maintained responding by its i.v, presentation. Sydnocarb engendered stereotypy in high doses with approximately a 2-fold lower potency than methamphetamine. However, sydnocarb was much less efficacious than methamphetamine in inducing stereotyped behavior. Both sydnocarb and methamphetamine increased dialysate levels of dopamine in mouse striatum; however, the potency and efficacy of sydnocarb was less than methamphetamine. The convulsive effects of cocaine were significantly enhanced by the coadministration of nontoxic doses of methamphetamine but not of sydnocarb. Taken together, the present findings indicate that sydnocarb has psychomotor stimulant effects that are shared by methamphetamine while demonstrating a reduced behavioral toxicity. C1 NIDA, Drug Dev Grp, Addict Res Ctr, NIH, Baltimore, MD 21224 USA. NIDA, Integrat Neurosci Unit, Addict Res Ctr, NIH, Baltimore, MD 21224 USA. Minist Publ Hlth Russia, Ctr Chem Drugs, Moscow, Russia. RP Witkin, JM (reprint author), NIDA, Drug Dev Grp, Addict Res Ctr, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM jwitkin@intra.nida.nih.gov NR 38 TC 24 Z9 25 U1 1 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD MAR PY 1999 VL 288 IS 3 BP 1298 EP 1310 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 172BZ UT WOS:000078903600047 PM 10027871 ER PT J AU Winn, DM Johnson, CL Kingman, A AF Winn, DM Johnson, CL Kingman, A TI Periodontal disease estimates in NHANES III: Clinical measurement and complex sample design issues SO JOURNAL OF PUBLIC HEALTH DENTISTRY LA English DT Article DE periodontal diseases; epidemiology; examiner reliability; survey sampling; NHANES III ID ATTACHMENT LEVEL; NATIONAL-HEALTH AB Objective: This paper evaluates the possibility that examiner bias or other factors contributed to an observed decline in pocket depth and gingivitis between the two three-year sequential periods of time (or phases) covered by the Third National Health and Nutrition Examination Survey (NHANES ill). Methods: Prevalences of periodontal conditions were analyzed using data from two sets of repeat oral health examinations by examining dentists of NHANES III sample persons. The first set includes sample persons who were examined twice by the same examining dentist at an interval of one to six weeks. The second set includes sample persons who were assessed on the same day by both an examining dentist and a reference dentist. Other possible sources of error also were evaluated. Results: Overall kappa statistics measuring agreement between or within dental examiners were within the range observed for other periodontal disease surveys. While differences were found among dentists in the prevalence of pocket depth of 4 mm or more, for each group of sample persons assessed by a reference examiner-examining dentist pair, the reference examiner's periodontal measurements closely corresponded to measurements made by the examining dentists. Conclusions: Differences between dental examiners in prevalences of periodontal conditions may be due in part to the fact that examinees were not randomly assigned to examiners. As a result, the sample persons examined by each dentist may not have been alike in characteristics thought to affect periodontal disease status. These findings suggest that the observed declines in periodontal health status between phases is not due to examiner bias. This unexplained decline may be the result of sampling variation. It is recommended that combined six-year survey results be presented whenever possible. C1 Natl Inst Dent & Craniofacial Res, Div Intramural Res, NIH, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Div Hlth Examinat Stat, Hyattsville, MD 20782 USA. RP Winn, DM (reprint author), Natl Inst Dent & Craniofacial Res, Div Intramural Res, NIH, Natcher Bldg,Room 4AS-43D,45 Ctr Dr MSC 6401, Bethesda, MD 20892 USA. NR 23 TC 18 Z9 18 U1 1 U2 1 PU AAPHD NATIONAL OFFICE PI PORTLAND PA 3760 SW LYLE COURT, PORTLAND, OR 97221 USA SN 0022-4006 J9 J PUBLIC HEALTH DENT JI J. Public Health Dent. PD SPR PY 1999 VL 59 IS 2 BP 73 EP 78 DI 10.1111/j.1752-7325.1999.tb03238.x PG 6 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA 239LP UT WOS:000082769900002 PM 10965471 ER PT J AU Burns, DN Nourjah, P Wright, DJ Minkoff, H Landesman, S Rubinstein, A Goedert, JJ Nugent, RP AF Burns, DN Nourjah, P Wright, DJ Minkoff, H Landesman, S Rubinstein, A Goedert, JJ Nugent, RP TI Changes in immune activation markers during pregnancy and postpartum SO JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Article DE biological markers; hepatitis C; immunity; pregnancy; T-lymphocytes ID IMMUNODEFICIENCY-VIRUS TYPE-1; BLOOD MONONUCLEAR-CELLS; SOLUBLE INTERLEUKIN-2 RECEPTORS; LYMPHOCYTE-T SUBSETS; CHRONIC HEPATITIS-C; INTERFERON-GAMMA; HIV-INFECTION; SERUM LEVELS; FAS LIGAND; CLINICAL-APPLICATION AB Changes in CD4+ cell levels and other immune parameters have been reported to occur during pregnancy but the timing of these alterations and their relationship to changes in immune function have not been well characterized. In addition, the influence of sociodemographic, obstetric, and other covariates on these relationships is largely unknown. We measured three immune activation markers, soluble interleukin-2 receptor (sIL-2R(alpha)), soluble CD8 antigen (sCD8), and neopterin during pregnancy and postpartum in 170 HIV-1-seronegative women enrolled in the Mothers and Infants Cohort Study. Ante-partum and postpartum changes in these markers were examined using multivariable longitudinal random effects models. Neopterin levers began to rise well before delivery and were in decline by 2 months postpartum. sIL-2R(alpha) and sCD8 levels increased at or near delivery and peaked by 2 months postpartum. After adjustment for other variables, the peak in sIL-2R(alpha) was greater among women with pre-term than full-term deliveries (P = 0.05). All three markers were higher in whiles than non-whites and in 'hard' drug users than non-users (P less than or equal to 0.001 for each). After adjustment for these and other variables, hepatitis C virus (HCV) seropositivity was associated with higher levels of sCD8 and neopterin (P less than or equal to 0.001 for each) but not sIL-2R(alpha) (P = 0.27). These longitudinal data indicate that a state of broad immune activation develops at or near delivery. A number of maternal variables appear to influence the magnitude of these changes. (C) 1999 Elsevier Science ireland Ltd. All rights reserved. C1 NICHHD, Pediat Adolescent & Maternal AIDS Branch, Ctr Res Mothers & Children, NIH, Bethesda, MD 20892 USA. Westat Corp, Rockville, MD USA. SUNY Hlth Sci Ctr, Dept Obstet & Gynecol, Brooklyn, NY 11203 USA. SUNY Hlth Sci Ctr, Dept Med, Brooklyn, NY 11203 USA. Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA. NCI, Viral Epidemiol Branch, NIH, Bethesda, MD 20892 USA. RP NICHHD, Pediat Adolescent & Maternal AIDS Branch, Ctr Res Mothers & Children, NIH, Suite 4B11,6100 Execut Bldg, Bethesda, MD 20892 USA. EM db98d@nih.gov FU NCI NIH HHS [N0-1-CP-61013]; NICHD NIH HHS [N0-1-HD-8-2913, R0-1-HD-25714] NR 73 TC 30 Z9 32 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-0378 J9 J REPROD IMMUNOL JI J. Reprod. Immunol. PD MAR PY 1999 VL 42 IS 2 BP 147 EP 165 DI 10.1016/S0165-0378(98)00085-0 PG 19 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA 181RW UT WOS:000079456900006 PM 10221737 ER PT J AU Farina, M Schemmel, A Weissmuller, G Cruz, R Kachar, B Bisch, PM AF Farina, M Schemmel, A Weissmuller, G Cruz, R Kachar, B Bisch, PM TI Atomic force microscopy study of tooth surfaces SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article DE tooth surface; atomic force microscopy; analytical microscopy; biomineralization ID RADULA TEETH; ENAMEL; MINERALIZATION; FLUORIDE; MOLLUSCA AB Atomic force microscopy (AFM) was used to study tooth surfaces in order to compare the pattern of particle distribution in the outermost layer of the tooth surfaces, Human teeth and teeth from a rodent (Golden hamster), from a fish (piranha), and from a grazing mollusk (chiton) with distinct feeding habits were analyzed in terms of particle arrangement, packing, and size distribution. Scanning electron microscopy and transmission electron microscopy were used for comparison. It was found that AFM gives high-contrast, high-resolution images and is an important tool as a source of complementary and/or new structural information, All teeth were cleaned and some were etched with acidic solutions before analysis. It was observed that human enamel (permanent teeth) presents particles tightly packed in the outer surface, whereas enamel from the hamster (continuously growing teeth) shows particles of less dense packing. The piranha teeth have a thin cuticle covering the long apatite crystals of the underlying enameloid, This cuticle has a rough surface of particles that have a globular appearance after the brief acidic treatment. The similar appearance of the in vivo naturally etched tooth surface suggests that the pattern of globule distribution may be due to the presence of an organic material. Elemental analysis of this cuticle indicated that calcium, phosphorus, and iron are the main components of the structure while electron microdiffraction of pulverized cuticle particles showed a pattern consistent with hydroxyapatite, The chiton mineralized tooth cusp had a smooth surface in an unabraded region and a very rough structure with the magnetite crystals (already knows to make part of the structure) protruding from the surface. It was concluded that the structures analyzed are optimized for efficiency in feeding mechanism and life span of the teeth. (C) 1999 Academic Press. C1 Univ Fed Rio de Janeiro, Ctr Ciencias Saude, Dept Anat, BR-21941590 Rio De Janeiro, Brazil. Univ Munich, Munich, Germany. Univ Fed Rio de Janeiro, Inst Biofis Carlos Chagas Filho, BR-21949900 Rio De Janeiro, Brazil. NIDCD, Sect Struct Biol, NIH, Bethesda, MD 20892 USA. RP Farina, M (reprint author), Univ Fed Rio de Janeiro, Ctr Ciencias Saude, Dept Anat, BR-21941590 Rio De Janeiro, Brazil. RI Farina, Marcos/I-3744-2014 NR 27 TC 37 Z9 48 U1 1 U2 20 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD MAR PY 1999 VL 125 IS 1 BP 39 EP 49 DI 10.1006/jsbi.1998.4069 PG 11 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 184CA UT WOS:000079590700005 PM 10196115 ER PT J AU Boyd, GM AF Boyd, GM TI Alcohol and the family: Opportunities for prevention SO JOURNAL OF STUDIES ON ALCOHOL LA English DT Editorial Material ID ADOLESCENCE; PROGRAM AB Objective: The intent of this supplement issue is to present current research on the role of Families in the development of alcohol-related risk, to assess the potential of efficacy of family-based preventive interventions and to identify new directions for research. Method: The National Institute on Alcohol Abuse and Alcoholism convened a working group of family and alcohol researchers in December 1996, to address these issues in a 2-day meeting. Results: The articles presented in this supplement reflect the major presentations and discussions at that meeting. Conclusions: There is theoretical and empirical support for the potential efficacy of universal and selective family-based preventive interventions for children. Studies testing the generalizability of intervention approaches are especially needed. Some additional preintervention research is needed, but should be directed toward questions with direct applicability to intervention development. Relatively little is known about family influences on adult risk, and the potential efficacy of family interventions for adults is not known at this time. C1 NIAAA, Prevent Res Branch, Bethesda, MD 20892 USA. RP Boyd, GM (reprint author), NIAAA, Prevent Res Branch, Willco Bldg,6000 Execut Blvd,Suite 505, Bethesda, MD 20892 USA. NR 13 TC 1 Z9 1 U1 1 U2 1 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 0096-882X J9 J STUD ALCOHOL JI J. Stud. Alcohol PD MAR PY 1999 SU 13 BP 5 EP 9 PG 5 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA 184GJ UT WOS:000079602400001 ER PT J AU Litten, RZ Allen, JP AF Litten, RZ Allen, JP TI Medications for alcohol, illicit drug, and tobacco dependence - An update of research findings SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE pharmacotherapy; alcohol dependence; naltrexone; acamprosate; bupropion; medication compliance ID FACILITATES SMOKING CESSATION; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; OPIOID DEPENDENCE; DOPAMINE TRANSPORTER; DISULFIRAM TREATMENT; WEANED ALCOHOLICS; CLINICAL-TRIAL; HEROIN-ADDICTS; BUPRENORPHINE AB Physiologic, behavioral, and social factors contribute to dependence on alcohol, nicotine, and other drugs. During the past decade substantial research has focused on identification/development of medications to assist in reducing urge to use these substances. This article describes these agents and reviews recent research findings on them. (C) 1999 Elsevier Science Inc. All rights reserved. C1 NIAAA, NIH, Bethesda, MD 20892 USA. RP Allen, JP (reprint author), NIAAA, NIH, Suite 505,6000 Execut Blvd, Bethesda, MD 20892 USA. NR 57 TC 26 Z9 26 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD MAR PY 1999 VL 16 IS 2 BP 105 EP 112 DI 10.1016/S0740-5472(98)00028-2 PG 8 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 162UH UT WOS:000078364800001 PM 10023607 ER PT J AU Henry, MC Perlmutter, SJ Swedo, SE AF Henry, MC Perlmutter, SJ Swedo, SE TI Anorexia, OCD, and streptococcus SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Letter C1 NIMH, Pediat & Dev Neuropsychiat Branch, Bethesda, MD 20892 USA. RP Henry, MC (reprint author), NIMH, Pediat & Dev Neuropsychiat Branch, Bethesda, MD 20892 USA. NR 3 TC 10 Z9 10 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAR PY 1999 VL 38 IS 3 BP 228 EP 228 DI 10.1097/00004583-199903000-00002 PG 1 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 170XJ UT WOS:000078832100002 PM 10087678 ER PT J AU DiGiovanna, JJ Kraemer, KH AF DiGiovanna, JJ Kraemer, KH TI Sunscreens and vitamin D levels - Reply SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Letter C1 Brown Univ, Sch Med, Dept Dermatol, Dermatopharmacol Div, Providence, RI 02912 USA. Rhode Isl Hosp, Providence, RI USA. NCI, Mol Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP DiGiovanna, JJ (reprint author), Brown Univ, Sch Med, Dept Dermatol, Dermatopharmacol Div, Providence, RI 02912 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAR PY 1999 VL 40 IS 3 BP 497 EP 497 PG 1 WC Dermatology SC Dermatology GA 171MH UT WOS:000078867300023 ER PT J AU Kitsiou, AN Bacharach, SL Bartlett, ML Srinivasan, G Summers, RM Quyyumi, AA Dilsizian, V AF Kitsiou, AN Bacharach, SL Bartlett, ML Srinivasan, G Summers, RM Quyyumi, AA Dilsizian, V TI N-13-ammonia myocardial blood flow and uptake - Relation to functional outcome of asynergic regions after revascularization SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CORONARY-ARTERY DISEASE; LEFT-VENTRICULAR DYSFUNCTION; CELL-MEMBRANE INTEGRITY; N-13 AMMONIA; F-18 FLUORODEOXYGLUCOSE; VIABLE MYOCARDIUM; IDENTIFICATION; REINJECTION; METABOLISM; TOMOGRAPHY AB OBJECTIVES In this study we determined whether N-13-ammonia uptake measured late after injection provides additional insight into myocardial viability beyond its value as a myocardial blood flow tracer. BACKGROUND Myocardial accumulation of N-13-ammonia is dependent-on both regional blood flow and metabolic trapping. METHODS Twenty-six patients with chronic coronary artery disease and left ventricular dysfunction underwent prerevascularization N-13-ammonia and F-18-deoxyglucose (FDG) positron emission tomography, and thallium single-photon emission computed tomography Pre- and postrevascularization wall-motion abnormalities were assessed using gated cardiac magnetic resonance imaging or gated radionuclide angiography. RESULTS Wall motion improved in 61 of 107 (57%) initially asynergic regions and remained abnormal in 46 after revascularization. Mean absolute myocardial blood flow was significantly higher in regions that improved compared to regions that did not improve after revascularization (0.63 +/- 0.27 vs. 0.52 +/- 0.25 ml/min/g, p < 0.04). Similarly, the magnitude of late N-13-ammonia uptake and FDG uptake was significantly higher in regions that improved (90 +/- 20% and 94 +/- 25%, respectively) compared to regions that did not improve after revascularization (67 +/- 24% and 71 +/- 25%, p < 0.001 for both, respectively). However, late 13N-ammonia uptake was a significantly better predictor of functional improvement after revascularization (area under the receiver operating characteristic [ROC] curve = 0.79) when compared to absolute blood how (area under the ROC curve = 0.63, p < 0.05). In addition, there was a linear relationship between late 13N-ammonia uptake and FDG uptake (r = 0.68, p < 0.001) as well as thallium uptake (r = 0.76, p < 0.001) in all asynergic regions. CONCLUSIONS These data suggest that beyond its value as a perfusion tracer, late 13N-ammonia uptake provides useful information regarding functional recovery after revascularization. The parallel relationship among N-13-ammonia, FDG, and thallium uptake supports the concept that uptake of N-13-ammonia as measured from the late images may provide important insight regarding cell membrane integrity and myocardial viability. (C) 1999 by the American College of Cardiology. C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Nucl Med, Bethesda, MD 20892 USA. RP Dilsizian, V (reprint author), NHLBI, Cardiol Branch, NIH, Bldg 10,Room 7B-15, Bethesda, MD 20892 USA. NR 33 TC 41 Z9 42 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 1 PY 1999 VL 33 IS 3 BP 678 EP 686 DI 10.1016/S0735-1097(98)00630-5 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 176YF UT WOS:000079179400013 PM 10080468 ER PT J AU Prasad, A Husain, S Quyyumi, AA AF Prasad, A Husain, S Quyyumi, AA TI Abnormal flow-mediated epicardial vasomotion in human coronary arteries is improved by angiotensin-converting enzyme inhibition - A potential role of bradykinin SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID ENDOTHELIUM-DEPENDENT HYPERPOLARIZATION; COLD PRESSOR TEST; NITRIC-OXIDE; SMOOTH-MUSCLE; METABOLIC CONTROL; RELAXING FACTOR; HUMAN FOREARM; HUMAN HEART; GUIDE WIRE; BLOOD-FLOW AB OBJECTIVES. This study nas performed to determine whether angiotensin converting enzyme (ACE) inhibition improves endothelium-dependent flow-mediated vasodilation in patients with atherosclerosis or its risk factors and whether this is mediated by enhanced bradykinin activity. BACKGROUND. Abnormal coronary vasomotion due to endothelial dysfunction contributes to myocardial ischemia in patients with atherosclerosis, and its reversal may have an antiischemic action. Previous studies have shown that ACE inhibition improves coronary endothelial responses to acetylcholine, but whether this is accompanied by improved responses to shear stress remains unknown. METHODS. In 19 patients with mild atherosclerosis, metabolic vasodilation was assessed during cardiac pacing. Pacing was repeated during separate intracoronary infusions of low-dose bradykinin (BK) and enalaprilat. Endothelium-dependent and -independent vasodilation was estimated with intracoronary BK and sodium nitroprusside respectively. RESULTS. Enalaprilat did not-alter either resting coronary vascular tone or dilation with sodium nitroprusside, but potentiated BK-mediated dilation. Epicardial segments that constricted abnormally with pacing (-5 +/- 1%) dilated (3 +/- 2%) with pacing in the presence of enalaprilat (p = 0.002). Similarly, BK at a concentration (62.5 ng/min) that did not alter resting diameter in the constricting segments also improved the abnormal response to a 6 +/- 1% dilation (p < 0.001). Cardiac pacing-induced reduction in coronary vascular resistance of 27 +/- 4% (p < 0.001) remained unchanged after enalaprilat. CONCLUSIONS. Thus ACE inhibition: A) selectively improved endothelium-dependent but not-independent dilation, and B) abolished abnormal flow-mediated epicardial vasomotion in patients with endothelial dysfunction, in part; by increasing endogenous BK activity. (C) 1999 by the American College of Cardiology. C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. RP Quyyumi, AA (reprint author), NHLBI, Cardiol Branch, NIH, Bldg 10,Rm 7B15,10 Ctr Dr,MSC 1650, Bethesda, MD 20892 USA. NR 46 TC 41 Z9 41 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 1 PY 1999 VL 33 IS 3 BP 796 EP 804 DI 10.1016/S0735-1097(98)00611-1 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 176YF UT WOS:000079179400029 PM 10080484 ER PT J AU Slavkin, HC AF Slavkin, HC TI Entering the era of molecular dentistry SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID HYPOHIDROTIC ECTODERMAL DYSPLASIA C1 Natl Inst Dent & Cranofacial Res, Bethesda, MD 20892 USA. RP Slavkin, HC (reprint author), Natl Inst Dent & Cranofacial Res, 31 Ctr Dr,MSC 2290,Bldg 31,Room 2C39, Bethesda, MD 20892 USA. NR 19 TC 9 Z9 10 U1 0 U2 0 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD MAR PY 1999 VL 130 IS 3 BP 413 EP 417 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 173ED UT WOS:000078967500024 PM 10085665 ER PT J AU Konig, S Fales, HM AF Konig, S Fales, HM TI Calibration of mass ranges up to m/z 10,000 in electrospray mass spectrometers SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article ID CLUSTER IONS; IONIZATION; PROTEINS AB We report that the cesium salts of monobutyl phthalate, heptafluorobutyric acid, tridecafluoroheptanoic acid, and perfluorosebacic acid generate salt/cluster ions that provide calibration peaks for electrospray mass spectrometers. In the case of the cesium salt of tridecafluoroheptanoic acid ions are available up to m/z 10,000. (C) 1999 American Society for Mass Spectrometry. C1 NHLBI, NIH, LBC, Bethesda, MD 20892 USA. RP Fales, HM (reprint author), NHLBI, NIH, LBC, Bldg 10,Rm 7N318,10 Ctr Dr MSC 1676, Bethesda, MD 20892 USA. RI Konig, Simone/B-6504-2008 OI Konig, Simone/0000-0003-0672-7246 NR 14 TC 17 Z9 17 U1 2 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD MAR PY 1999 VL 10 IS 3 BP 273 EP 276 DI 10.1016/S1044-0305(98)00150-0 PG 4 WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA 170LL UT WOS:000078807100012 ER PT J AU Knepper, MA Kim, GH Fernandez-Llama, P Ecelbarger, CA AF Knepper, MA Kim, GH Fernandez-Llama, P Ecelbarger, CA TI Regulation of thick ascending limb transport by vasopressin SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article; Proceedings Paper CT Symposium on Vasopressin-Regulated Transporters in the Urinary Concentrating Mechanism at the Annual Meeting of the American-Society-of-Nephrology CY OCT 26, 1998 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Nephrol ID CYCLIC-ADENOSINE-MONOPHOSPHATE; DEPENDENT ADENYLATE-CYCLASE; HENLES LOOP; RAT-KIDNEY; RABBIT KIDNEY; ANTIDIURETIC-HORMONE; V2 RECEPTOR; BICARBONATE ABSORPTION; INTRACELLULAR CALCIUM; ARGININE VASOPRESSIN AB Body fluid tonicity is controlled largely through the regulation of renal water excretion mediated by the peptide hormone vasopressin (1). Renal water conservation occurs as a result of the combined functions of the loop of Henle and the collecting duct, both of which are regulated by vasopressin. The loop of Henle is responsible for countercurrent multiplication, a process that concentrates the interstitial fluid of the renal medulla relative to the systemic plasma. The collecting duct is the site at which water permeability is regulated by vasopressin to result in variable osmotic equilibration with the hypertonic medullary interstitium. In this brief review, we summarize current knowledge regarding the role of the thick ascending limb in the regulation of renal water excretion by vasopressin. C1 NHLBI, Renal Mech Sect, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Ecelbarger, CA (reprint author), NHLBI, Renal Mech Sect, Kidney & Electrolyte Metab Lab, NIH, Bldg 10,Room 6N260,10 Ctr Dr MSC 1603, Bethesda, MD 20892 USA. EM garyeck@aol.com RI chen, xuanlan/H-4158-2011; OI Kim, Gheun-Ho/0000-0002-8445-9892 FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999]; NHLBI NIH HHS [Z01-HL-01282]; NIDDK NIH HHS [K01 DK002672] NR 75 TC 67 Z9 68 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD MAR PY 1999 VL 10 IS 3 BP 628 EP 634 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 170LP UT WOS:000078807400022 PM 10073614 ER PT J AU Hilbert, SL Luna, RE Zhang, J Wang, Y Hopkins, RA Yu, ZX Ferrans, VJ AF Hilbert, SL Luna, RE Zhang, J Wang, Y Hopkins, RA Yu, ZX Ferrans, VJ TI Allograft heart valves: The role of apoptosis-mediated cell loss SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID SULFOXIDE-INDUCED APOPTOSIS; DIFFERENTIATION; DEATH AB Objective: The purpose of this study was to determine whether apoptosis of endothelial and connective tissue cells is responsible for the loss of cellularity observed in implanted aortic allograft valves. Methods: Fresh (n = 6) and cryopreserved (n = 4) aortic allograft valves were retrieved at 2 days to 20 weeks after implantation in an ovine model. Sections of these valves were studied with the use of histologic and electron microscopic methods, nick end-labeling and dual immunostaining for factor VIII-related antigen and proliferating cell nuclear antigen, followed by counterstaining for DNA and laser scanning confocal fluorescence microscopic observation. Results: The endothelial cells and cusp connective tissue cells of implanted valvular allografts showed loss of proliferating cell nuclear antigen (indicative of cessation of mitotic activity) and evidence of apoptosis (nick end labeling). The latter was manifested by nuclear condensation and pyknosis, positive nick end labeling, and formation of intra- and extracellular apoptotic bodies derived from the fragmentation of apoptotic cells, These changes began to develop at 2 days after implantation, peaking at 10 to 14 days, and became complete by 20 weeks, at which time the valves had the typical acellular morphologic features of allografts implanted for long periods of time. Conclusions: Apoptosis occurs in endothelial cells and cuspal connective tissue cells of implanted allografts and appears to be a cause of their loss of cellularity. This apoptosis may be related to various factors, including immunologic and chemical injury, and hypoxia during valve processing and reperfusion injury at the time of implantation. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Dept Surg, Washington, DC 20007 USA. Brown Univ, Sch Med, Dept Surg, Providence, RI 02912 USA. RP Hilbert, SL (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-150,9200 Corp Blvd, Rockville, MD 20850 USA. NR 24 TC 34 Z9 38 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD MAR PY 1999 VL 117 IS 3 BP 454 EP 462 DI 10.1016/S0022-5223(99)70324-7 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 172KB UT WOS:000078921100005 PM 10047647 ER PT J AU Li, X Jeffers, LJ Garon, C Fischer, ER Scheffel, J Moore, B Reddy, KR deMedina, M Schiff, ER AF Li, X Jeffers, LJ Garon, C Fischer, ER Scheffel, J Moore, B Reddy, KR deMedina, M Schiff, ER TI Persistence of hepatitis C virus in a human megakaryoblastic leukaemia cell line SO JOURNAL OF VIRAL HEPATITIS LA English DT Article DE confocal laser-scanning microscope; hepatitis C virus; megakaryocyte; MEG-01 cell line; replication; thrombocytopenia ID POLYMERASE CHAIN-REACTION; ALPHA-INTERFERON THERAPY; THROMBOCYTOPENIC PURPURA; FLOW-CYTOMETRY; INFECTION; LOCALIZATION; CHROMOSOME; CDNA AB Thrombocytopenia is a frequent clinical finding in patients with hepatitis C virus (HCV) infection, Platelets from patients with HCV infection have been identified as carriers of HCV RNA in our previous studies. The present study was designed to further investigate the possibility of HCV replication in megakaryoblasts from which platelets are eventually released. A megakaryoblastic cell line (MEG-01), established from a chronic myelogenous leukaemia patient 13 years ago, was used for this study, The MEG-01 cells were inoculated with fresh serum from a patient with HCV infection and renamed MEG-01-I cells, Surprisingly, both MEG-01 and MEG-01-I were positive by HCV reverse transcription-polymerase chain reaction (RT-PCR) for the existence of HCV RNA and minus-strand HCV RNA, regardless of inoculation, This was further confirmed by in situ RT-PCR, The HCV antigens, such as core, envelope, and non-structural (NS)3 and NS4, were also present in both cell lines, as identified by Western blotting and indirect immunofluorescence staining, In addition, virus-like particles were observed by electron microscopy in the MEG-01 cell line as well as in the MEG-01-I cell line, These findings indicate that the megakaryoblasts are vulnerable to HCV infection and that replication of HCV can occur in these cells, This may help us to better understand the pathogenesis of thrombocytopenia in patients with HCV infection. The MEG-01 cell line, which may have been continuously shedding HCV for years, should be a useful model for experimental research into HCV. C1 Vet Adm Med Ctr, Div Hepatol, Miami, FL 33125 USA. Univ Miami, Sch Med, Ctr Liver Dis, Miami, FL USA. NIAID, Rocky Mt Labs, Hamilton, MT 59840 USA. Abbott Labs, Abbott Pk, IL 60064 USA. RP Jeffers, LJ (reprint author), Vet Adm Med Ctr, Div Hepatol, 1201 NW,16th St, Miami, FL 33125 USA. NR 20 TC 18 Z9 19 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 1352-0504 J9 J VIRAL HEPATITIS JI J. Viral Hepatitis PD MAR PY 1999 VL 6 IS 2 BP 107 EP 114 DI 10.1046/j.1365-2893.1999.00140.x PG 8 WC Gastroenterology & Hepatology; Infectious Diseases; Virology SC Gastroenterology & Hepatology; Infectious Diseases; Virology GA 181HV UT WOS:000079436700003 PM 10607221 ER PT J AU Gigler, A Dorsch, S Hemauer, A Williams, C Kim, S Young, NS Zolla-Pazner, S Wolf, H Gorny, MK Modrow, S AF Gigler, A Dorsch, S Hemauer, A Williams, C Kim, S Young, NS Zolla-Pazner, S Wolf, H Gorny, MK Modrow, S TI Generation of neutralizing human monoclonal antibodies against parvovirus B19 proteins SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; POLYMERASE CHAIN-REACTION; IMMUNE-RESPONSE; NS-1 PROTEIN; INFECTION; GENOME; REGION; GENES; IDENTIFICATION; PERSISTENCE AB Infections caused by human parvovirus B19 are known to be controlled mainly by neutralizing antibodies. To analyze the immune reaction against parvovirus B19 proteins, four cell lines secreting human immunoglobulin G monoclonal antibodies (MAbs) were generated from two healthy donors and one human immunodeficiency virus type I-seropositive individual with high serum titers against parvovirus. One MAb is specific for nonstructural protein NS1 (MAb 1424), two MAbs are specific for the unique region of minor capsid protein VP1 (MAbs 1418-1 and 1418-16), and one MAb is directed to major capsid protein VP2 (MAb 860-55D). Two MAbs, 1418-1 and 1418-16, which were generated from the same individual have identity in the cDNA sequences encoding the variable domains, with the exception of four base pairs resulting in only one amino acid change in the light chain. The NS1- and VP1-specific MAbs interact with linear epitopes, whereas the recognized epitope in VP2 is conformational. The MAbs specific for the structural proteins display strong virus-neutralizing activity. The VP1- and VP2-specific MAbs have the capacity to neutralize 50% of infectious parvovirus B19 in vitro at 0.08 and 0.73 mu g/ml, respectively, demonstrating the importance of such antibodies in the clearance of B19 viremia. The NS1-specific MAb mediated weak neutralizing activity and required 47.7 mu g/ml for 50% neutralization. The human MAbs with potent neutralizing activity could be used for immunotherapy of chronically B19 virus-infected individuals and acutely infected pregnant women. Furthermore, the knowledge gained regarding epitopes which induce strongly neutralizing antibodies may be important for vaccine development. C1 Univ Regensburg, Inst Med Mikrobiol & Hyg, D-95053 Regensburg, Germany. NYU Med Ctr, Dept Pathol, New York, NY 10016 USA. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. Vet Affairs Med Ctr, New York, NY 10010 USA. RP Modrow, S (reprint author), Univ Regensburg, Inst Med Mikrobiol & Hyg, Franz Josef Str Allee 11, D-95053 Regensburg, Germany. NR 35 TC 99 Z9 101 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 1999 VL 73 IS 3 BP 1974 EP 1979 PG 6 WC Virology SC Virology GA 166XT UT WOS:000078603800027 PM 9971777 ER PT J AU van Dinten, LC Rensen, S Gorbalenya, AE Snijder, EJ AF van Dinten, LC Rensen, S Gorbalenya, AE Snijder, EJ TI Proteolytic processing of the open reading frame 1b-encoded part of arterivirus replicase is mediated by nsp4 serine protease and is essential for virus replication SO JOURNAL OF VIROLOGY LA English DT Article ID EQUINE ARTERITIS VIRUS; INFECTIOUS-BRONCHITIS VIRUS; STRAND RNA-SYNTHESIS; STRUCTURAL PROTEINS; ENCODED PROTEINASES; CYSTEINE PROTEASES; MINUS-STRAND; PAPAIN-LIKE; VIRAL-RNA; IDENTIFICATION AB The open reading frame (ORF) 1b-encoded part of the equine arteritis virus (EAV) replicase is expressed by ribosomal frameshifting during genome translation, which results in the production of an ORF1ab fusion protein (345 kDa). Four ORF1b-encoded processing products, nsp9 (p80), nsp10 (p50), nsp11 (p26), and nsp12 (p12), have previously been identified in EAV-infected cells (L. C. van Dinten, A. L. M. Wassenaar, A. E. Gorbalenya, W. J. M. Spaan, and E. J. Snijder, J. Virol. 70:6625-6633, 1996). In the present study, the generation of these four nonstructural proteins was shown to be mediated by the nsp4 serine protease, which is the main viral protease (E. J. Snijder, A. L. M. Wassenaar, L. C. van Dinten, W. J. M. Spaan, and A. E. Gorbalenya, J. Biol. Chem. 271:4864-4871, 1996). Mutagenesis of candidate cleavage sites revealed that Glu-2370/Ser, Gln-2837/Ser, and Glu-3056/Gly are the probable nsp9/10, nsp10/11, and nsp11/12 junctions, respectively. Mutations which abolished ORF1b protein processing were introduced into a recently developed infectious cDNA clone (L. C. van Dinten, J. A. den Boon, A. L. M. Wassenaar, W. J. M. Spaan, and E. J. Snijder, Proc. Natl. Acad. Sci. USA 94:991-997, 1997). An analysis of these mutants showed that the selective blockage of ORF1b processing affected different stages of EAV reproduction. In particular, the mutant with the nsp10/11 cleavage site mutation Gln-2837-->Pro displayed an unusual phenotype, since it was still capable of RNA synthesis but was incapable of producing infectious virus. C1 Leiden Univ, Med Ctr, Dept Virol, NL-2300 RC Leiden, Netherlands. Russian Acad Med Sci, Inst Poliomyelitis & Viral Encephalitis, Moscow 142782, Russia. NCI, Frederick Canc Res & Dev Ctr, SAIC, Adv Biomed Comp Ctr, Frederick, MD 21702 USA. RP Snijder, EJ (reprint author), Leiden Univ, Med Ctr, Dept Virol, LUMC P4-26,POB 9600, NL-2300 RC Leiden, Netherlands. EM Snijder@Virology.azl.nl RI Gorbalenya, Alexander/J-4818-2012 OI Gorbalenya, Alexander/0000-0002-4967-7341 FU NCI NIH HHS [N01-CO-5600] NR 58 TC 78 Z9 81 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 1999 VL 73 IS 3 BP 2027 EP 2037 PG 11 WC Virology SC Virology GA 166XT UT WOS:000078603800033 PM 9971783 ER PT J AU Bies, J Nazarov, V Wolff, L AF Bies, J Nazarov, V Wolff, L TI Identification of protein instability determinants in the carboxy-terminal region of c-myb removed as a result of retroviral integration in murine monocytic leukemias SO JOURNAL OF VIROLOGY LA English DT Article ID INDUCED PROMONOCYTIC LEUKEMIAS; LEUCINE-ZIPPER; PEST SEQUENCES; DIFFERENTIATION; TRANSFORMATION; ACTIVATION; CELLS; DEGRADATION; VIRUS; PROTEOLYSIS AB The c-myb oncogene has been a target of retroviral insertional mutagenesis in murine monocytic leukemias. One mechanism by which c-myb can be activated is through the integration of a retroviral provirus into the central portion of the locus, causing premature termination of c-myb transcription and translation. We had previously shown that a leukemia-specific c-Myb protein, truncated at the site of proviral integration by 248 amino acids, had approximately a fourfold-increased half-life compared to the normal c-Myb protein, due to its ability to escape rapid degradation by the ubiquitin-26S proteasome pathway. Here we provide evidence for the existence of more than one instability determinant in the carboxy-terminal region of the wild-type protein, which appear to act independently of each other. The data were derived from examination of premature termination mutants and deletion mutants of the normal protein, as well as analysis of another carboxy-terminally truncated protein expressed in leukemia. Evidence is provided that one instability determinant is located in the terminal 87 amino acids of the protein and another is located in the vicinity of the internal region that has leucine zipper homology, In leukemias, different degrees of protein stability are attained following proviral integration depending upon how many determinants are removed. Interestingly, although PEST sequences (rich in proline, glutamine, serine, and threonine), often associated with degradation, are found in c-Myb, deletion of PEST-containing regions had no effect on protein turnover. This study provides further insight into how inappropriate expression of c-Myb may contribute to leukemogenesis. In addition, it will facilitate further studies aimed at characterizing the specific role of individual regions of the normal protein in targeting to the 26S proteasome. C1 NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. Slovak Acad Sci, Canc Res Inst, Bratislava, Slovakia. RP Wolff, L (reprint author), NCI, Cellular Oncol Lab, NIH, Bldg 37,Room 2B04,37 Convent Dr, Bethesda, MD 20892 USA. NR 28 TC 26 Z9 26 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 1999 VL 73 IS 3 BP 2038 EP 2044 PG 7 WC Virology SC Virology GA 166XT UT WOS:000078603800034 PM 9971784 ER PT J AU Davis, MD Wonderling, RS Walker, SL Owens, RA AF Davis, MD Wonderling, RS Walker, SL Owens, RA TI Analysis of the effects of charge cluster mutations in adeno-associated virus Rep68 protein in vitro SO JOURNAL OF VIROLOGY LA English DT Article ID SITE-SPECIFIC INTEGRATION; DOMINANT-NEGATIVE MUTANT; DNA HELICASE ACTIVITY; ADENOASSOCIATED VIRUS; WILD-TYPE; TERMINAL REPEATS; DIRECTED MUTAGENESIS; NUCLEOTIDE-SEQUENCE; INVITRO RESOLUTION; MAMMALIAN-CELLS AB The Rep78 and Rep68 proteins of adeno-associated virus type 2 (AAV) are multifunctional proteins which are required for viral replication, regulation of AAV promoters, and preferential integration of the AAV genome into a region of human chromosome 19. These proteins bind the hairpin structures formed by the AAV inverted terminal repeat (ITR) origins of replication, make site- and strand-specific endonuclease cuts within the AAV ITRs, and display nucleoside triphosphate-dependent helicase activities. Additionally, several mutant Rep proteins display negative dominance in helicase and/or endonuclease assays when they are mixed with wild-type Rep78 or Rep68, suggesting that multimerization may be required for the helicase and endonuclease functions. Using overlap extension PCR mutagenesis, we introduced mutations within clusters of charged residues throughout the Rep68 moiety of a maltose binding protein-Rep68 fusion protein (MBP-Rep68 Delta) expressed in Escherichia call cells. Several mutations disrupted the endonuclease and helicase activities; however, only one amino-terminal-charge cluster mutant protein (D40A-D42A-D44A) completely lost AAV hairpin DNA binding activity. Charge duster mutations within two other regions abolished both endonuclease and helicase activities. One region contains a predicted alpha-helical structure (amino acids 371 to 393), and the other contains a putative 3,4 heptad repeat (coiled-coil) structure (amino acids 441 to 483). The defects displayed by these mutant proteins correlated with a weaker association with wild-type Rep68 protein, as measured in coimmunoprecipitation assays. These experiments suggest that these regions of the Rep molecule are involved in Rep oligomerization events critical for both helicase and endonuclease activities. C1 NIDDK, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. RP Owens, RA (reprint author), NIDDK, Mol & Cellular Biol Lab, NIH, Bldg 8,Rm 309,8 Ctr Dr,MSC 0840, Bethesda, MD 20892 USA. NR 71 TC 22 Z9 22 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 1999 VL 73 IS 3 BP 2084 EP 2093 PG 10 WC Virology SC Virology GA 166XT UT WOS:000078603800040 PM 9971790 ER PT J AU Trus, BL Gibson, W Cheng, NQ Steven, AC AF Trus, BL Gibson, W Cheng, NQ Steven, AC TI Capsid structure of simian cytomegalovirus from cryoelectron microscopy: Evidence for tegument attachment sites SO JOURNAL OF VIROLOGY LA English DT Article ID HERPES-SIMPLEX VIRUS; ASSEMBLY PROTEIN-PRECURSOR; CHANNEL CATFISH VIRUS; CARBOXY-TERMINAL END; READING FRAME; COILED COILS; C-TERMINUS; VP26; DNA; IDENTIFICATION AB We have used cryoelectron microscopy and image reconstruction to study B-capsids recovered from both the nuclear and the cytoplasmic fractions of cells infected with simian cytomegalovirus (SCMV). SCMV, a representative betaherpesvirus, could thus be compared with the previously described B-capsids of the alphaherpes-viruses, herpes simplex virus type 1 (HSV-1) and equine herpesvirus 1 (EHV-1), and of channel catfish virus, an evolutionarily remote herpesvirus. Nuclear B-capsid architecture is generally conserved with SCMV, but it is 4% larger in inner radius than HSV-1, implying that its similar to 30% larger genome should be packed more tightly. Isolated SCMV B-capsids retain a relatively well preserved inner shell (or "small core") of scaffolding-assembly protein, whose radial-density profile indicates that this protein is similar to 16-nm long and consists of two domains connected by a low density linker. As with HSV-1, the herons but not the pentons of the major capsid protein (151 kDa) bind the smallest capsid protein (similar to 8 kDa). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed cytoplasmic B-capsid preparations to contain proteins similar in molecular weight to the basic phosphoprotein (similar to 119 kDa) and the matrix proteins (65 to 70 kDa). Micrographs revealed that these particles had variable amounts of surface-adherent material not present on nuclear B-capsids that we take to be tegument proteins. Cytoplasmic B-capsids were classified accordingly as lightly, moderately, or heavily tegumented. By comparing the three corresponding density maps with each other and with the nuclear B-capsid, two interactions were identified between putative tegument proteins and the capsid surface. One is between the major capsid protein and a protein estimated by electron microscopy to be 50 to 60 kDa; the other involves an elongated molecule estimated to be 100 to 120 kDa that is anchored on the triplexes, most likely on its dimer subunits. Candidates for the proteins bound at these sites are discussed. This first visualization of such linkages makes a step towards understanding the organization and functional rationale of the herpesvirus tegument. C1 NIAMS, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. NIH, Computat Biosci & Engn Lab, CIT, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Virol Labs, Baltimore, MD 21205 USA. RP Steven, AC (reprint author), NIAMS, Struct Biol Lab, NIH, Bldg 6,Rm B2-34,6 Ctr Dr,MSC 2717, Bethesda, MD 20892 USA. EM Alasdair_Steven@nih.gov FU NIAID NIH HHS [R56 AI013718, AI13718, R01 AI013718] NR 74 TC 76 Z9 76 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 1999 VL 73 IS 3 BP 2181 EP 2192 PG 12 WC Virology SC Virology GA 166XT UT WOS:000078603800051 PM 9971801 ER PT J AU Campbell, S Rein, A AF Campbell, S Rein, A TI In vitro assembly properties of human immunodeficiency virus type 1 Gag protein lacking the p6 domain SO JOURNAL OF VIROLOGY LA English DT Article ID ROUS-SARCOMA VIRUS; BACULOVIRUS-INFECTED CELLS; IN-VITRO; NUCLEOCAPSID PROTEIN; HIV-1 GAG; CAPSID PROTEIN; LIPID-PROTEIN; RECOMBINANT BACULOVIRUS; FUNCTIONAL DOMAINS; CRYSTAL-STRUCTURE AB Human immunodeficiency virus type 1 (HIV-1) normally assembles into particles of 100 to 120 nm in diameter by budding through the plasma membrane of the cell. The Gag polyprotein is the only viral protein that is required for the formation of these particles. We have used an in vitro assembly system to examine the assembly properties of purified, recombinant HIV-1 Gag protein and of Gag missing the C-terminal p6 domain (Gag Delta p6). This system was used previously to show that the CA-NC fragment of HIV-1 Gag assembled into cylindrical particles. We now report that both HIV-1 Gag and Gag Delta p6 assemble into small, 25- to 30-nm-diameter spherical particles in vitro. The multimerization of Gag Delta p6 into units larger than dimers and the formation of spherical particles required nucleic acid. Removal of the nucleic acid with NaCl or nucleases resulted in the disruption of the multimerized complexes. We conclude from these results that (i) N-terminal extension of HIV-1 CA-NC to include the MA domain results in the formation of spherical, rather than cylindrical, particles; (ii) nucleic acid is required for the assembly and maintenance of HIV-1 Gag Delta p6 virus-like particles in vitro and possibly in vivo; (iii) a wide variety of RNAs or even short DNA oligonucleotides will support assembly; (iv) protein-protein interactions within the particle must be relatively weak; and (v) recombinant HIV-1 Gag Delta p6 and nucleic acid are not sufficient for the formation of normal-sized particles. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. RP Campbell, S (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, POB B, Frederick, MD 21702 USA. EM campbells@mail.ncifcrf.gov NR 58 TC 208 Z9 211 U1 0 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 1999 VL 73 IS 3 BP 2270 EP 2279 PG 10 WC Virology SC Virology GA 166XT UT WOS:000078603800060 PM 9971810 ER PT J AU Chan, SY Speck, RF Power, C Gaffen, SL Chesebro, B Goldsmith, MA AF Chan, SY Speck, RF Power, C Gaffen, SL Chesebro, B Goldsmith, MA TI V3 recombinants indicate a central role for CCR5 as a coreceptor in tissue infection by human immunodeficiency virus type 1 SO JOURNAL OF VIROLOGY LA English DT Review ID POLYMERASE CHAIN-REACTION; PROTEIN-COUPLED RECEPTOR; CENTRAL-NERVOUS-SYSTEM; T-CELL-LINE; CHEMOKINE RECEPTORS; MACROPHAGE TROPISM; HIV-1 INFECTION; HUMAN BRAIN; IN-VIVO; CD4-INDEPENDENT INFECTION AB Binding of the human immunodeficiency virus type 1 (HIV-I) envelope glycoprotein gp120 to both CD4 and one of several chemokine receptors (coreceptors) permits entry of virus into target cells. Infection of tissues may establish latent viral reservoirs as well as cause direct pathologic effects that manifest as clinical disease such as HIV-associated dementia. We sought to identify the critical coreceptors recognized by HIV-1 tissue-derived strains as well as to correlate these coreceptor preferences with site of infection and dementia diagnosis. To reconstitute coreceptor use, we cloned HIV-1 envelope V3 sequences encoding the primary determinants of coreceptor specificity from 13 brain-derived and 6 colon-derived viruses into an isogenic (NL4-3) viral background. All V3 recombinants utilized the chemokine receptor CCR5 uniformly and efficiently as a coreceptor but not CXCR4, BOB/GPR15, or Bonzo/STRL33. Other receptors such as CCR3, CCR8, and US28 were inefficiently and variably used as coreceptors by various envelopes. CCR5 without CD4 present did not allow for detectable infection by any of the tested recombinants. In contrast to the pathogenic switch in coreceptor specificity frequently observed in comparisons of blood-derived viruses early after HIV-1 seroconversion and after onset of AIDS, the characteristics of these V3 recombinants suggest that CCR5 is a primary coreceptor for brain- and colon-derived viruses regardless of tissue source or diagnosis of dementia. Therefore, tissue infection may not depend significantly on viral envelope quasispeciation to broaden coreceptor range but rather selects for CCR5 use throughout disease progression. C1 Gladstone Inst Virol & Immunol, San Francisco, CA 94110 USA. Univ Calif San Francisco, Sch Med, Dept Med, San Francisco, CA 94143 USA. Univ Calgary, Dept Clin Neurosci, Calgary, AB T2N 1N4, Canada. NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. RP Goldsmith, MA (reprint author), Gladstone Inst Virol & Immunol, POB 419100, San Francisco, CA 94110 USA. EM mgoldsmith@gladstone.ucsf.edu RI Gaffen, Sarah/B-1560-2009; Power, Christopher/C-7181-2013; Speck, Roberto/O-2433-2016; OI Power, Christopher/0000-0002-5131-9711 NR 111 TC 60 Z9 63 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 1999 VL 73 IS 3 BP 2350 EP 2358 PG 9 WC Virology SC Virology GA 166XT UT WOS:000078603800068 PM 9971818 ER PT J AU Mariani, R Wong, S Mulder, LCF Wilkinson, DA Reinhart, AL LaRosa, G Nibbs, R O'Brien, TR Michael, NL Connor, RI Macdonald, M Busch, M Koup, RA Landau, NR AF Mariani, R Wong, S Mulder, LCF Wilkinson, DA Reinhart, AL LaRosa, G Nibbs, R O'Brien, TR Michael, NL Connor, RI Macdonald, M Busch, M Koup, RA Landau, NR TI CCR2-64I polymorphism is not associated with altered CCR5 expression or coreceptor function SO JOURNAL OF VIROLOGY LA English DT Article ID LONG-TERM SURVIVOR; CHEMOKINE RECEPTOR GENE; VIRUS TYPE-1 INFECTION; HIV-1 INFECTION; DISEASE PROGRESSION; DELETION ALLELE; INDIVIDUALS; RESISTANCE; TRANSMISSION; NEF AB A polymorphism in the gene encoding CCR2 is associated with a delay in progression to AIDS in human immunodeficiency virus (HIV)-infected individuals. The polymorphism, CCR2-64I, changes valine 64 of CCR2 to isoleucine. However, it is not clear whether the effect on AIDS progression results from the amino acid change or whether the polymorphism marks a genetically linked, yet unidentified mutation that mediates the effect. Because the gene encoding CCR5, the major coreceptor for HIV type 1 primary isolates, ties, 15 kb 3' to CCR2, linked mutations in the CCR5 promoter or other regulatory sequences could explain the association of CCR2-64I with slowed AIDS pathogenesis. Here, we show that CCR2-64I is efficiently expressed on the cell surface but does not have dominant negative activity on CCR5 coreceptor function. A panel of peripheral blood mononuclear cells (PBMC) from uninfected donors representing the various CCR5/CCR2 genotypes was assembled. Activated primary CD4(+) T cells of CCR2 64I/64I donors expressed cell surface CCR5 at levels comparable to those of CCR2 +/+ donors. A slight reduction in CCR5 expression was noted, although this was not statistically significant. CCR5 and CCR2 mRNA levels were nearly identical for each of the donor PBMC, regardless of genotype. Cell surface CCR5 and CCR2 levels were more variable than mRNA transcript levels, suggesting that an alternative mechanism may influence CCR5 cell surface levels. CCR2-64I is linked to the CCR5 promoter polymorphisms 208G, 303A, 627C, and 676A; however, in transfected promoter reporter constructs, these did not affect transcriptional activity. Taken together, these findings suggest that CCR2-64I does not act by influencing CCR5 transcription of mRNA levels. C1 Rockefeller Univ, Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA. Univ Texas, SW Med Ctr, Div Infect Dis, Dallas, TX 75235 USA. Leukosite Inc, Cambridge, MA 02142 USA. Beatson Inst Canc Res Campaign, Glasgow G61 1BD, Lanark, Scotland. NCI, Viral Epidemiol Branch, Rockville, MD 20852 USA. Walter Reed Army Inst Res, Div Retrovirol, Rockville, MD 20850 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Irwin Mem Blood Ctr, San Francisco, CA 94118 USA. RP Landau, NR (reprint author), Salk Inst Biol Studies, Infect Dis Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM landau@salk.edu FU NCI NIH HHS [R01 CA72149, R01 CA43252]; NIAID NIH HHS [R01 AI072149, R29 AI36057] NR 53 TC 50 Z9 52 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 1999 VL 73 IS 3 BP 2450 EP 2459 PG 10 WC Virology SC Virology GA 166XT UT WOS:000078603800080 PM 9971830 ER PT J AU Muralidhar, S Pumfery, AM Hassani, M Sadaie, MR Kishishita, R Brady, JN Doniger, J Medveczky, P Rosenthal, LJ AF Muralidhar, S Pumfery, AM Hassani, M Sadaie, MR Kishishita, R Brady, JN Doniger, J Medveczky, P Rosenthal, LJ TI Identification of kaposin (open reading frame K12) as a human herpesvirus 8 (Kaposi's sarcoma-associated herpesvirus) transforming gene (vol 72, pg 4980, 1998) SO JOURNAL OF VIROLOGY LA English DT Correction C1 Georgetown Univ, Med Ctr, Dept Microbiol & Immunol, Washington, DC 20007 USA. NCI, Mol Virol Lab, Bethesda, MD 20892 USA. Univ S Florida, Dept Med Microbiol & Immunol, Tampa, FL 33612 USA. RP Rosenthal, LJ (reprint author), Georgetown Univ, Med Ctr, Dept Microbiol & Immunol, Washington, DC 20007 USA. RI Medveczky, Peter/A-6846-2012 NR 1 TC 6 Z9 8 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 1999 VL 73 IS 3 BP 2568 EP 2568 PG 1 WC Virology SC Virology GA 166XT UT WOS:000078603800095 ER PT J AU Nichols, DK Weyant, RS Lamirande, EW Sigler, L Mason, RT AF Nichols, DK Weyant, RS Lamirande, EW Sigler, L Mason, RT TI Fatal mycotic dermatitis in captive brown tree snakes (Boiga irregularis) SO JOURNAL OF ZOO AND WILDLIFE MEDICINE LA English DT Article DE brown tree snake; Boiga irregularis; dermatitis; fungus; Chrysosporium; Nannizziopsis vriesii ID PHEROMONES; EPIDERMIS AB Cutaneous fungal infections occurred in four captive brown tree snakes (Boiga irregularis). The ventral scales were most commonly affected, and lesions began as areas of erythema and edema with vesicle formation, followed by development of caseous brown plaques. Lesions usually started where Ventral scales overlapped and spread rapidly. All snakes died within 14 days after clinical signs were first noted. The deaths of three of the snakes were directly attributable to the cutaneous disease; the other snake died from renal failure and visceral gout, most likely induced by gentamicin therapy. Histologically, lesions consisted of epidermal hyperplasia and hyperkeratosis, with foci of epidermal necrosis, intraepidermal vesicle formation, and subacute inflammation of the underlying dermis. These lesions were associated with bacteria and numerous septate, branched fungal hyphae within the epidermis and overlying serocelluar crusts. Hyphae that penetrated through the superficial surface of the epidermis often formed terminal arthroconidia. The same species of fungus was isolated in pure culture from the skin of three snakes, but fungal cultures were not performed on samples from the fourth snake. The fungus has been identified as the Chrysosporium anamorph of Nannizziopsis vriesii based on its formation of solitary dermatophytelike aleurioconidia and alternate and fission arthroconidia. The source of the fungus in this outbreak was not determined; however, the warm, moist conditions under which the snakes were housed likely predisposed them to opportunistic cutaneous fungal infections. C1 NHLBI, Lab Sci Sect, Vet Resources Program, NIH, Bethesda, MD 20892 USA. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. Univ Alberta, Devonian Bot Garden, Microfungus Collect, Edmonton, AB T6G 2E1, Canada. RP Nichols, DK (reprint author), Natl Zool Pk, Dept Pathol, Washington, DC 20008 USA. NR 28 TC 32 Z9 35 U1 3 U2 17 PU AMER ASSOC ZOO VETERINARIANS PI MEDIA PA 6 NORTH PENNELL ROAD, MEDIA, PA 19063 USA SN 1042-7260 J9 J ZOO WILDLIFE MED JI J. Zoo Wildl. Med. PD MAR PY 1999 VL 30 IS 1 BP 111 EP 118 PG 8 WC Veterinary Sciences SC Veterinary Sciences GA 194QU UT WOS:000080205700016 PM 10367652 ER PT J AU Huang, SC Zhuang, ZP Weil, RJ Pack, S Wang, CY Krutzsch, HC Pham, TA Lubensky, IA AF Huang, SC Zhuang, ZP Weil, RJ Pack, S Wang, CY Krutzsch, HC Pham, TA Lubensky, IA TI Nuclear/cytoplasmic localization of the multiple endocrine neoplasia type 1 gene product, menin SO LABORATORY INVESTIGATION LA English DT Article ID TUMOR-SUPPRESSOR GENE; SPORADIC GASTRINOMAS; REGION; PROTEIN; 11Q13 AB Although the gene responsible for multiple endocrine neoplasia, type 1 (MEN1) has been identified recently, the function of its gene product, menin, is not known. To examine menin's biological role, we created an N-terminal tagged fusion protein to follow the distribution of menin in the cell. In all cell lines tested, menin was found both in the nucleus and the cytoplasm, but its localization was dependent on the phase of the cell cycle; during a nondividing phase, menin was found in the nucleus, during and immediately after cell division, it was found in the cytoplasm. To confirm the cellular localization seen with the N-terminal tagged protein, we developed and purified peptide-specific antibodies. One of these antibodies (NCI 624), which recognizes a domain (aa 383-395) of menin, was used in immunofluorescence studies to corroborate the N-terminal tagging results. Further confirmation of menin localization was obtained in a pituitary tumor cell line derived from a familial MEN1 patient, which contained a mixed cell population with either none, or one functional copy of the MEN1 gene. Our results indicate that menin functions principally as a nuclear protein but may be found in the cytoplasm during cell division. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Lubensky, IA (reprint author), NCI, Pathol Lab, NIH, Bldg 10,Room 2A 33, Bethesda, MD 20892 USA. EM lubensky@box-l.nih.gov RI Pack, Svetlana/C-2020-2014 NR 18 TC 47 Z9 48 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD MAR PY 1999 VL 79 IS 3 BP 301 EP 310 PG 10 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 177ZM UT WOS:000079241000006 PM 10092066 ER PT J AU Iwai, N Martinez, A Miller, MJ Vos, M Mulshine, JL Treston, AM AF Iwai, N Martinez, A Miller, MJ Vos, M Mulshine, JL Treston, AM TI Autocrine growth loops dependent on peptidyl alpha-amidating enzyme as targets for novel tumor cell growth inhibitors SO LUNG CANCER LA English DT Article DE autocrine growth factors; lung cancer; peptide hormone; tumor growth inhibition; post-translational processing ID MONOOXYGENASE PAM ENZYMES; LUNG-CANCER; STABLE INTERMEDIATE; FACTOR-I; EXPRESSION; ACID; LINES; PROLIFERATION; BIOSYNTHESIS; MECHANISM AB Many small cell lung tumors are dependent in vitro and in vivo on autocrine growth loops. The prototypical small cell lung cancer autocrine growth factor, gastrin-releasing peptide (GRP), is one of many peptide hormones which require post-translational carboxy-terminal alpha-amidation for bioactivity. We have reported that neuroendocrine human lung tumor cell lines express the bifunctional enzyme PAM which catalyzes the biosynthesis of alpha-amidated peptides in a two-step process, and have:recently shown that non-small cell lung cancer cell lines and tumors, generally considered to be non-endocrine in nature, also express PAM. We have also shown that two chemical classes of PAM inhibitors, substrate analogues and specific copper chelators, inhibit amidating enzyme activity in cell-free extracts. Here we demonstrate in vitro growth inhibition of lung cancer tumor cell lines by both these classes of PAM inhibitors using the MTT assay and the clonogenic assay. Growth inhibition in a small cell lung cancer cell line can be overcome by exogenous addition of synthetic a-amidated GRP. Similar growth-suppressive effects are seen in cell lines stably transfected with a vector expressing antisense PAM RNA. These data support the mechanism of inhibition for a new type of chemotherapeutic/intervention agent, directed at synthesis and activation of peptide growth factors, and support our postulate that cr-amidated peptide hormones are a common component in lung tumor autocrine growth biology which can be inhibited by targeting the biochemical mechanisms necessary for growth factor synthesis. (C) 1999 Elsevier Science Ireland Ltd. Al rights reserved. C1 NCI, Dept Cell & Canc Biol, Med Branch, Div Clin Sci, Bethesda, MD 20892 USA. RP Mulshine, JL (reprint author), NCI, Dept Cell & Canc Biol, Med Branch, Div Clin Sci, Bldg 10,Rm 13N62, Bethesda, MD 20892 USA. RI Martinez, Alfredo/A-3077-2013 OI Martinez, Alfredo/0000-0003-4882-4044 NR 40 TC 21 Z9 22 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD MAR PY 1999 VL 23 IS 3 BP 209 EP 222 DI 10.1016/S0169-5002(99)00015-X PG 14 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 210QL UT WOS:000081116100003 PM 10413197 ER PT J AU Corn, M AF Corn, M TI Getting to the core of medical informatics training SO M D COMPUTING LA English DT Article C1 Natl Lib Med, Bethesda, MD 20209 USA. RP Corn, M (reprint author), Natl Lib Med, Bethesda, MD 20209 USA. NR 1 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0724-6811 J9 M D COMPUT JI M D Comput. PD MAR-APR PY 1999 VL 16 IS 2 BP 25 EP 27 PG 3 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA 201AT UT WOS:000080573000014 PM 10375880 ER PT J AU Epstein, FH Wolff, SD Arai, AE AF Epstein, FH Wolff, SD Arai, AE TI Segmented k-space fast cardiac imaging using an echo-train readout SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE magnetic resonance; cardiac imaging; echoplanar imaging ID RESIDUAL MYOCARDIAL VIABILITY; BREATH-HOLD; MRI; RESOLUTION; SCANNER; SYSTEM; HEART AB A segmented k-space fast gradient-echo pulse sequence with an echo-train readout (FGRE-ET) was developed for high-quality cine imaging of the heart in reduced scan times. Using segmented FGRE-ET, cine images of the heart can be acquired in as few as 1-5 heart beats and do not display the geometric distortion and flow-related artifacts typically associated with cardiac echoplanar imaging (EPI). Segmented FGRE-ET was compared with conventional segmented FGRE and with conventional multi-phase EPI in normal volunteers. Segmented FGRE-ET was found to have reduced temporal blurring compared with segmented FGRE for cine imaging in 4 heart beats (P < 0.05). Also, segmented FGRE-ET did not display geometric distortion characteristic of conventional EPI (P < 0.05). Segmented FGRE-ET may be particularly applicable to functional cardiac stress testing because it allows versatile cine imaging in very short breath-holds. Magn Reson Med 41:609-613, 1999. Published 1999 Wiley-Liss, Inc.dagger. C1 Gen Elect Med Syst, Appl Sci Lab, Waukesha, WI USA. NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP Epstein, FH (reprint author), NIH, Bldg 10,Room B1D161,10 Ctr Dr MSC 1061, Bethesda, MD 20892 USA. NR 21 TC 64 Z9 64 U1 0 U2 2 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD MAR PY 1999 VL 41 IS 3 BP 609 EP 613 DI 10.1002/(SICI)1522-2594(199903)41:3<609::AID-MRM25>3.0.CO;2-2 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 179GH UT WOS:000079317800025 PM 10204886 ER PT J AU Bertuzzi, S Porter, FD Pitts, A Kumar, M Agulnick, A Wassif, C Westphal, H AF Bertuzzi, S Porter, FD Pitts, A Kumar, M Agulnick, A Wassif, C Westphal, H TI Characterization of Lhx9, a novel LIM/homeobox gene expressed by the pioneer neurons in the mouse cerebral cortex SO MECHANISMS OF DEVELOPMENT LA English DT Article DE Lhx9; LIM; homeobox; eye; limb; cortex; pioneer neurons; Cajal; Retzius; preplate ID LIM HOMEOBOX GENE; ORGANIZATION; NEOCORTEX; FOREBRAIN; PROTEINS AB In order to explain the phenotype observed in Lhx2 mutant embryos, we previously proposed that an Lhx2 related gene might exist. We now have cloned a new LIM/homeobox gene called Lhx9. Lhx9 is closely related to Lhx2 and is expressed in the developing central nervous system (CNS). Lhx9 and Lhx2 have expression patterns that overlap in some areas but are distinct in others. Thus, in some developmental domains these two highly related proteins may be functionally redundant. Lhx9 is expressed in the pioneer neurons of the cerebral cortex, while Lhx2 is expressed throughout the cortical layers. Postnatally, Lhx9 is expressed in the inner nuclei of the cerebellum, while Lhx2 is in the granular layer. In the developing limbs, both genes are highly expressed in a similar pattern. Based on the expression pattern and the developmental regulation of Lhx9, we propose that Lhx9 may be involved in the specification or function of the pioneer neurons of the cerebral cortex. We show that both Lhx9 and Lhx2 bind the LIM domain binding protein Ldb1/Nli1/Clim2. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 NICHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD USA. NICHD, Unit Mol Dysmorphol, Hereditable Disorders Branch, NIH, Bethesda, MD USA. RP Bertuzzi, S (reprint author), Salk Inst Biol Studies, Mol Neurobiol Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA. OI Wassif, Christopher/0000-0002-2524-1420 NR 14 TC 34 Z9 37 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD MAR PY 1999 VL 81 IS 1-2 BP 193 EP 198 DI 10.1016/S0925-4773(98)00233-0 PG 6 WC Developmental Biology SC Developmental Biology GA 186WW UT WOS:000079754600019 PM 10330499 ER PT J AU Choyke, PL Siegel, MJ Craft, AW Green, DM DeBaun, MR AF Choyke, PL Siegel, MJ Craft, AW Green, DM DeBaun, MR TI Screening for Wilms tumor in children with Beckwith-Wiedemann syndrome or idiopathic hemihypertrophy SO MEDICAL AND PEDIATRIC ONCOLOGY LA English DT Article DE hemihypertrophy; Wilms tumor; ultrasound; cancer screening; epidemiology; cancer ID ANIRIDIA AB Background. Children with Beckwith-Wiedemann syndrome and idiopathic hemihypertrophy (BWS/HH) are at increased risk for developing Wilms tumor and screening with abdominal sonography is frequently recommended. However, there is a paucity of published data supporting this strategy. The purpose of this study was to determine whether sonographic screening at intervals of 4 months or less reduced the proportion of late-stage Wilms Tumor (WT) in children with BWS/HH. Procedure. A case series analysis was employed to compare the proportion of late-stage (stage III or IV) Wilms tumor in patients with BWS/HH who were screened with sonography (n = 15) to the proportion of late-stage Wilms tumor in unscreened patients with BWS/HH (n = 59). Patients were identified from the BWS Registry and from previously published studies. Screened patients had sonograms at intervals of 4 months or less. Results. None of the 12 screened children with Wilms tumor had late-stage disease, whereas 25 of 59 (42%) of unscreened children had late-stage Wilms tumor, a difference that was statistically significant (P < 0.003). Three children had false positive screening studies. They were operated on for suspected Wilms tumor but the lesions proved to be complicated renal cysts (n = 2) or nephroblastomatosis (n = 1). Conclusions. This study suggests that children with BWS/HH may benefit from screening sonograms at intervals of 4 months OF less. However, false positive screening exams may result in unnecessary surgery. Given the rarity of BWS/HH, a larger, prospective international screening study is necessary to determine if the benefits of screening outweigh the risks. (C) 1999 Wiley-Liss, Inc. C1 NCI, NIH, Genet Epidemiol Branch, Bethesda, MD 20892 USA. NIH, Dept Radiol, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. Royal Victoria Infirm, Dept Child Hlth, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England. Roswell Pk Canc Inst, Dept Pediat, Buffalo, NY USA. SUNY Coll Buffalo, Sch Med & Biomed Sci, Dept Pediat, Buffalo, NY 14222 USA. Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. RP DeBaun, MR (reprint author), NCI, NIH, Genet Epidemiol Branch, Bethesda, MD 20892 USA. NR 19 TC 65 Z9 67 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0098-1532 J9 MED PEDIATR ONCOL JI Med. Pediatr. Oncol. PD MAR PY 1999 VL 32 IS 3 BP 196 EP 200 DI 10.1002/(SICI)1096-911X(199903)32:3<196::AID-MPO6>3.0.CO;2-9 PG 5 WC Oncology; Pediatrics SC Oncology; Pediatrics GA 168UD UT WOS:000078710800006 PM 10064187 ER PT J AU Hallett, M AF Hallett, M TI Is focal dystonia a central nervous system problem? (Performing arts medicine, CNS) SO MEDICAL PROBLEMS OF PERFORMING ARTISTS LA English DT Article; Proceedings Paper CT 16th Annual Symposium on Medical Problems of Musicians and Dancers at the Annual Meeting of PAMA CY JUN 18-21, 1998 CL ASPEN, COLORADO ID PRIMARY SOMATOSENSORY CORTEX; REPETITIVE STRAIN INJURY; ULNAR NEUROPATHY; MUSICIANS; MODEL; HAND C1 Natl Inst Health, NINDS, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), Natl Inst Health, NINDS, Room 5N226, Bethesda, MD 20892 USA. EM hallett@codon.nih.gov NR 29 TC 2 Z9 2 U1 3 U2 3 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 0885-1158 J9 MED PROBL PERFORM AR JI Med. Probl. Perform. Artist. PD MAR PY 1999 VL 14 IS 1 BP 4 EP 7 PG 4 WC Medicine, General & Internal; Music SC General & Internal Medicine; Music GA 177VB UT WOS:000079230800004 ER PT J AU Tataranni, PA Cizza, G Snitker, S Gucciardo, F Lotsikas, A Chrousos, GP Ravussin, E AF Tataranni, PA Cizza, G Snitker, S Gucciardo, F Lotsikas, A Chrousos, GP Ravussin, E TI Hypothalamic-pituitary-adrenal axis and sympathetic nervous system activities in Pima Indians and Caucasians SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID BODY-WEIGHT GAIN; HORMONE-SECRETION; STRESS; GLUCOCORTICOIDS; RATS; SUPPRESSION AB It has been proposed that both hypercortisolism and low sympathetic nervous system (SNS) activity contribute to obesity. Because glucocorticoids inhibit SNS activity, we hypothesized that hypercortisolism and low SNS activity may be found in association in Pima Indians, a population with a high prevalence of obesity. We therefore measured indices of hypothalamic-pituitary-adrenal (HPA) axis and SNS activities in 39 nondiabetic men, 20 Pimas (age, 30 +/- 5 years; weight, 94 +/- 26 kg; 35% +/- 8% body fat [mean +/- SD]) and 19 Caucasians (33 +/- 9 years, 91 +/- 23 kg, 28% rt 11% body fat). HPA axis activity was assessed by measurements of morning fasting plasma corticotropin (ACTH) and cortisol concentrations and 24-hour urinary free cortisol (UFC) excretion. SNS activity was assessed as muscle sympathetic nerve activity (MSMA) by microneurography and by measurement of catecholamines (fasting plasma concentration and 24-hour urinary excretion). Plasma ACTH and cortisol and UFC were similar in Pimas and Caucasians. MSNA was positively correlated with percent body fat (r = .49, P = .002) and was lower in Pimas compared with Caucasians after adjustment for percent body fat (24 +/- 9 v 31 +/- 10 bursts/min, P = .04). We conclude that Pima Indians, a population with a high prevalence of obesity, have lower SNS activity but normal HPA axis activity compared with Caucasians. This is a US government work. There are no restrictions on its use. C1 NIDDK, Clin Diabet & Nutr Sect, NIH, Phoenix, AZ 85016 USA. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Tataranni, PA (reprint author), NIDDK, Clin Diabet & Nutr Sect, NIH, 4212 N 16th St,Room 541A, Phoenix, AZ 85016 USA. NR 32 TC 19 Z9 19 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD MAR PY 1999 VL 48 IS 3 BP 395 EP 399 DI 10.1016/S0026-0495(99)90092-6 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 173UG UT WOS:000078997700022 PM 10094120 ER PT J AU Leak, LV Yu, ZX Jones, M Ferrans, VJ AF Leak, LV Yu, ZX Jones, M Ferrans, VJ TI Characterization of a transformed ovine lymphatic endothelial cell line SO MICROCIRCULATION LA English DT Article DE transformed lymphatic endothelium; lymphangiogenesis; vascular endothelial cell-growth factor receptor-3 (VEGFR-3); tissue plasminogen activator; von Willebrand factor ID KAPOSI-SARCOMA; TISSUE-CULTURE; VEGF-C; GROWTH; MODEL AB Objective: To develop a non-tumor-derived stable lymphatic endothelial cell line that exhibits rapid growth rate without serum and exogenous growth factors, while still maintaining hey features characteristic of the non-transformed lymphatic endothelium. Methods: Lymphatic endothelial cells were isolated from ovine mesenteric lymphatic vessels, grown to confluence and transfected with SV40 DNA using the calcium phosphate method. The resulting cell line was characterized using morphological, immunocytochemical, flow cytometric analysis, and immunoprecipatitation and Western blotting methods. Results: The resulting cell line (sheep lymphatic endothelial transformed cell line, SLET-1) underwent rapid proliferation in the absence of growth factors and reduced concentrations of serum. In addition, key morphological and functional properties of the non-transformed lymphatic endothelium were retained. These include the ability to form confluent monolayer cultures; the expression of the lymphatic endothelial-specific VEGFR-3 (FLT-4) tyrosine kinase receptor, ale biosynthesis and secretion of von Willebrand factor and plasminogen activators. In addition, SLET-1 cells express cell surface antigens found on LEC that may act as antibody targets in various immune reactions. Monolayer cultures of the SLET-1 cells incubated with endothelial cell-growth factor forced tubular structures, indicating the retention of the capacity to differentiate. Conclusion: The SLET-1 cell Line retained key morphological and functional properties characteristic of the non-transformed lymphatic endothelium. The ability to form capillary-like tubular structures provides an important cell Line for defining the role of specific proteins that are involved in the lymphangiogenic (formation of new lymphatic vessels) process. Thus, this transformed lymphatic endothelial cell line provides an in vitro model that map have widespread utility in studying regulatory mechanisms of lymphatic endothelial cell function and differentiation. C1 Howard Univ, Coll Med, Dept Anat, EE Just Lab Cellular Biol, Washington, DC 20059 USA. NHLBI, Pathol Sect, NIH, Bethesda, MD USA. NHLBI, Lab Anim Med & Surg, Bethesda, MD 20892 USA. RP Leak, LV (reprint author), Howard Univ, Coll Med, Dept Anat, EE Just Lab Cellular Biol, Washington, DC 20059 USA. FU NIGMS NIH HHS [S06GM08016] NR 30 TC 6 Z9 6 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1073-9688 J9 MICROCIRCULATION JI Microcirculation PD MAR PY 1999 VL 6 IS 1 BP 63 EP 73 DI 10.1038/sj.mn.7300049 PG 11 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 209CZ UT WOS:000081031300007 PM 10100190 ER PT J AU Bortell, R Kanaitsuka, T Stevens, LA Moss, J Mordes, JP Rossini, AA Greiner, DL AF Bortell, R Kanaitsuka, T Stevens, LA Moss, J Mordes, JP Rossini, AA Greiner, DL TI The RT6 (Art2) family of ADP-ribosyltransferases in rat and mouse SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article; Proceedings Paper CT 12th International Symposium on ADP-ribosylation reactions - From Bacterial Pathogenesis to Cancer CY MAY 10-14, 1997 CL CANCUN, MEXICO SP Univ N Texas Hlth Sci Ctr DE ART; mono-ADP-ribosyltransferase; RT6; immune regulation; autoimmunity ID DIFFERENTIATION MARKER RT6; T-CELL DIFFERENTIATION; PRONE BB RATS; LYMPHOCYTE ALLOANTIGEN RT6.1; RECENT THYMIC EMIGRANTS; BREEDING WORCESTER RAT; AMINO-ACID-SEQUENCE; DIABETES-MELLITUS; ADOPTIVE TRANSFER; BACTERIAL TOXINS AB Recent evidence suggests that a new member of the mono-ADP-ribosyltransferase/NAD glycohydrolase family, RT6, may be important in immune regulation. RT6 is expressed in two allelic forms and is present on post-thymic T cells in the rat. RT6-expressing T cells in the rat may have a regulatory role, a conclusion based on their ability to prevent autoimmune diabetes in the BB rat model of insulin-dependent diabetes mellitus. This observation led to investigation of RT6 at a molecular and biochemical level resulting in the determination that RT6 protein exists as both glycosylated and non-glycosylated glycosylphosphatidylinositol (GPI)-linked cell surface molecules, RT6, like many GPI-linked proteins, can mediate cell signal transduction events associated with T cell activation, and is also present in a soluble form in the circulation. The discovery that RT6 is an NAD glycohydrolase and auto-ADP-ribosyltransferase led to the ongoing investigations into the role that enzymatic activity may have in the immunoregulatory function of rat RT6(+) T cells. A homologue of rat RT6, termed Rt6, has been identified in the mouse. Rt6 is predominately an ADP-ribosyltransferase enzyme as determined using simple guanidino compounds (e.g. arginine) as ribose accepters. Abnormalities in mouse Rt6 mRNA are associated with the expression of autoimmunity. In the present manuscript, we review recent data on RT6/Rt6, and discuss the potential mechanisms by which RT6-expressing cells, and perhaps RT6 protein itself, may mediate immune regulation. C1 Univ Massachusetts, Med Ctr, Dept Med, Worcester, MA USA. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Greiner, DL (reprint author), 373 Plantat St,Biotech 2,Suite 218, Worcester, MA 01605 USA. FU NIDDK NIH HHS [DK25306, DK36024, DK41235] NR 73 TC 28 Z9 28 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD MAR PY 1999 VL 193 IS 1-2 BP 61 EP 68 DI 10.1023/A:1006951809531 PG 8 WC Cell Biology SC Cell Biology GA 190VQ UT WOS:000079986300010 PM 10331639 ER PT J AU Moss, J Balducci, E Cavanaugh, E Kim, HJ Konczalik, P Lesma, EA Okazaki, IJ Park, M Shoemaker, M Stevens, LA Zolkiewska, A AF Moss, J Balducci, E Cavanaugh, E Kim, HJ Konczalik, P Lesma, EA Okazaki, IJ Park, M Shoemaker, M Stevens, LA Zolkiewska, A TI Characterization of NAD : arginine ADP-ribosyltransferases SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article; Proceedings Paper CT 12th International Symposium on ADP-ribosylation reactions - From Bacterial Pathogenesis to Cancer CY MAY 10-14, 1997 CL CANCUN, MEXICO SP Univ N Texas Hlth Sci Ctr DE ADP-ribosylation; bacterial toxins; glycosylphosphatidylinositol-linked proteins; NAD glycohydrolases ID ADENINE-DINUCLEOTIDE NAD; SKELETAL-MUSCLE; MOLECULAR CHARACTERIZATION; T-CELLS; INTEGRIN; SURFACE; CONSERVATION; MYOTUBES; BINDING; ENZYMES AB NAD:arginine mono-ADP-ribosyltransferases catalyze the transfer of ADP-ribose from NAD to the guanidino group of arginine on a target protein. Deduced amino acid sequences of one family (ART1) of mammalian ADP-ribosyltransferases, cloned from muscle and lymphocytes, show hydrophobic amino and carboxyl termini consistent with glycosylphosphatidylinositol (GPI)-anchored proteins. The proteins, overexpressed in mammalian cells transfected with the transferase cDNAs, are released from the cell surface with phosphatidylinositol-specific phospholipase C (PI-PLC), and display immunological and biochemical characteristics consistent with a cell surface, GPI-anchored protein. In contrast, the deduced amino acid sequence of a second family (ART5) of transferases, cloned from murine lymphoma cells and expressed in high abundance in testis, displays a hydrophobic amino terminus, consistent with a signal sequence, but lacks a hydrophobic signal sequence at its carboxyl terminus, suggesting that the protein is destined for export. Consistent with the surface localization of the GPI-linked transferases, multiple surface substrates have been identified in myotubes and activated lymphocytes, and, notably, include integrin alpha subunits. Similar to the bacterial toxin ADP-ribosyltransferases, the mammalian transferases contain the characteristic domains involved in NAD binding and ADP-ribose transfer, including a highly acidic region near the carboxy terminus, which, when disrupted by in vitro mutagenesis, results in a loss of enzymatic activity. The carboxyl half of the protein, synthesized as a fusion protein in E. coli, possessed NADase, but not ADP-ribosyltransferase activity. These findings are consistent with the existence at the carboxyl terminus of ART1 of a catalytically active domain, capable of hydrolyzing NAD, but not of transferring ADP-ribose to a guanidino acceptor. C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Moss, J (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, Bldg 10,Room 6D-03,10 Ctr Dr MSC 1590, Bethesda, MD 20892 USA. NR 19 TC 13 Z9 13 U1 0 U2 3 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD MAR PY 1999 VL 193 IS 1-2 BP 109 EP 113 DI 10.1023/A:1006924514074 PG 5 WC Cell Biology SC Cell Biology GA 190VQ UT WOS:000079986300017 PM 10331646 ER PT J AU Moss, J Vaughan, M AF Moss, J Vaughan, M TI Activation of toxin ADP-ribosyltransferases by eukaryotic ADP-ribosylation factors SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article; Proceedings Paper CT 12th International Symposium on ADP-ribosylation reactions - From Bacterial Pathogenesis to Cancer CY MAY 10-14, 1997 CL CANCUN, MEXICO SP Univ N Texas Hlth Sci Ctr DE ADP-ribosylation factor; guanine nucleotide-exchange protein; brefeldin A; Sec7 domain; cytohesin-1 ID NUCLEOTIDE-EXCHANGE PROTEIN; CHOLERA-TOXIN; PHOSPHOLIPASE-D; REGULATORY COMPONENT; ADENYLATE-CYCLASE; HOMOLOGY DOMAINS; GTP HYDROLYSIS; FACTOR ARF; SEC7; PURIFICATION AB ADP-ribosylation factors (ARFs) are members of a multigene family of 20-kDa guanine nucleotide-binding proteins that are regulatory components in several pathways of intracellular vesicular trafficking. The relatively small (similar to 180-amino acids) ARF proteins interact with a variety of molecules (in addition to GTP/GDP, of course). Cholera toxin was the first to be recognized, hence the name. Later it was shown that ARF also activates phospholipase D. Different parts of the molecule are responsible for activation of the two enzymes. In vesicular trafficking, ARF must interact with coatomer to recruit it to a membrane and thereby initiate vesicle budding. ARF function requires that it alternate between GTP- and GDP-bound forms, which involves interaction with regulatory proteins. Inactivation of ARF-GTP depends on a GTPase-activating protein or GAP, A guanine nucleotide-exchange protein or GEP accelerates release of bound GDP from inactive ARF-GDP to permit GTP binding. Inhibition of GEP by brefeldin A (BFA) blocks ARF activation and thereby vesicular transport. In cells, it causes apparent disintegration of Golgi structure. Both BFA-sensitive and insensitive GEPs are known. Sequences of peptides from a BFA-sensitive GEP purified in our laboratory revealed the presence of a Sec7 domain, a sequence of similar to 200 amino acids that resembles a region in the yeast Sec7 gene product, which is involved in Golgi vesicular transport. Other proteins of unknown function also contain Sec7 domains, among them a lymphocyte protein called cytohesin-1. To determine whether it had GEP activity, recombinant cytohesin-1 was synthesized in E. coli. It preferentially activated class I ARFs 1 and 3 and was not inhibited by BFA but failed to activate ARF5 (class II). There are now five Sec7 domain proteins known to have GEP activity toward class I ARFs. It remains to be determined whether there are other Sec7 domain proteins that are GEPs for ARFs 4, 5, or 6. C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Moss, J (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, Bldg 10,Room 5N307,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 30 TC 16 Z9 17 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD MAR PY 1999 VL 193 IS 1-2 BP 153 EP 157 DI 10.1023/A:1006993000870 PG 5 WC Cell Biology SC Cell Biology GA 190VQ UT WOS:000079986300023 PM 10331652 ER PT J AU Carrier, F Georgel, PT Pourquier, P Blake, M Kontny, HU Antinore, MJ Gariboldi, M Myers, TG Weinstein, JN Pommier, Y Fornace, AJ AF Carrier, F Georgel, PT Pourquier, P Blake, M Kontny, HU Antinore, MJ Gariboldi, M Myers, TG Weinstein, JN Pommier, Y Fornace, AJ TI Gadd45, a p53-responsive stress protein, modifies DNA accessibility on damaged chromatin SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID AMINO-ACID SEQUENCE; TRANSCRIPTION FACTOR; TOPOISOMERASE-II; PYRIMIDINE DIMERS; REMODELING FACTOR; BINDING PROTEIN; CLEAVAGE SITES; CELL-CYCLE; REPAIR; GENE AB This report demonstrates that Gadd45, a p53-responsive stress protein, can facilitate topoisomerase relaxing and cleavage activity in the presence of core histones. A correlation between reduced expression of Gadd45 and increased resistance to topoisomerase I and topoisomerase II inhibitors in a variety of human cell lines was also found. Gadd45 could potentially mediate this effect by destabilizing histone-DNA interactions since it was found to interact directly with the four core histones. To evaluate this possibility, we investigated the effect of Gadd45 on preassembled mononucleosomes. Our data indicate that Gadd45 directly associates with mononucleosomes that have been altered by histone acetylation or UV radiation. This interaction resulted in increased DNase I accessibility on hyperacetylated mononucleosomes and substantial reduction of T4 endonuclease V accessibility to cyclobutane pyrimidine dimers on W-irradiated mononucleosomes but not on naked DNA. Both histone acetylation and UV radiation are thought to destabilize the nucleosomal structure. Hence, these results imply that Gadd45 can recognize an altered chromatin state and modulate DNA accessibility to cellular proteins. C1 NCI, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. RP Carrier, F (reprint author), Univ Maryland, Sch Med, 108 N Greene St, Baltimore, MD 21201 USA. EM fcarr001@umaryland.edu RI Carrier, France/C-3063-2008; Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 86 TC 187 Z9 194 U1 0 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 1999 VL 19 IS 3 BP 1673 EP 1685 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 168MY UT WOS:000078697900006 PM 10022855 ER PT J AU Ashcroft, M Kubbutat, MHG Vousden, KH AF Ashcroft, M Kubbutat, MHG Vousden, KH TI Regulation of p53 function and stability by phosphorylation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DNA-BINDING; MONOCLONAL-ANTIBODIES; IN-VIVO; MDM2; MUTATION; TRANSACTIVATION; SITE; OLIGOMERIZATION; TRANSFORMATION; SUPPRESSION AB The p53 tumor suppressor protein can be phosphorylated at several sites within the N- and C-terminal domains, and several protein kinases have been shown to phosphorylate p53 in vitro. In this study, we examined the activity of p53 proteins with combined mutations at all of the reported N-terminal phosphorylation sites (p53N-term), all of the C-terminal phosphorylation sites (p53C-term), or all of the phosphorylation sites together (p53N/C-term). Each of these mutant proteins retained transcriptional transactivation functions, indicating that phosphorylation is not essential for this activity of p53, although a subtle contribution of the C-terminal phosphorylation sites to the activation of expression of the endogenous p21(Waf1/Cip1)-encoding gene aas detected. Mutation of the phosphorylation sites to alanine did not affect the sensitivity of p53 to binding to or degradation by Mdm2, although alteration of residues 15 and 37 to aspartic acid, which could mimic phosphorylation, resulted in a slight resistance to Mdm2-mediated degradation, consistent with recent reports that phosphorylation at these sites inhibits the p53-Mdm2 interaction. However, expression of the phosphorylation site mutant proteins in both wild-type p53-expressing and p53-null lines showed that all of the mutant proteins retained the ability to be stabilized following DNA damage. This indicates that phosphorylation is not essential for DNA damage-induced stabilization of p53, although phosphorylation could clearly contribute to p53 stabilization under some conditions. C1 NCI, ABL Basic Res Program, FCRDC, Frederick, MD 21702 USA. RP Vousden, KH (reprint author), NCI, ABL Basic Res Program, FCRDC, Bldg 560,Room 22-96,W 7th St, Frederick, MD 21702 USA. EM vousden@ncifcrf.gov NR 49 TC 316 Z9 319 U1 3 U2 14 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 1999 VL 19 IS 3 BP 1751 EP 1758 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 168MY UT WOS:000078697900013 PM 10022862 ER PT J AU Masumi, A Wang, IM Lefebvre, B Yang, XJ Nakatani, Y Ozato, K AF Masumi, A Wang, IM Lefebvre, B Yang, XJ Nakatani, Y Ozato, K TI The histone acetylase PCAF is a phorbol-ester-inducible coactivator of the IRF family that confers enhanced interferon responsiveness SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID REGULATORY FACTOR FAMILY; SEQUENCE-BINDING-PROTEIN; TRANSCRIPTION FACTOR; DNA-BINDING; GENE; ACTIVATION; ACETYLTRANSFERASE; CELLS; IDENTIFICATION; EXPRESSION AB Transcription factors of the interferon regulatory factor (IRF) family bind to the type I interferon (IFN)-responsive element (ISRE) and activate transcription from IFN-inducible genes. To identify cofactors that associate with IRF proteins, DNA affinity binding assays were performed with nuclear extracts prepared from tissue culture cells. The results demonstrated that the endogenous IRFs bound to the ISRE are complexed with the histone acetylases, PCAF, GCN5, and p300/CREB binding protein and that histone acetylase activities are accumulated on the IRF-ISRE complexes. By testing recombinant proteins, we show that PCAF directly binds to some but not all members of the IRF family through distinct domains of the two proteins. This interaction was functionally significant, since transfection of PCAF strongly enhanced IRF-1- and IRF-2-dependent promoter activities, Further studies shelved that expression of PCAF and other histone acetylases was markedly induced in U937 cells upon phorbol ester treatment, which led to increased recruitment of PCAF to the IRF-ISRE complexes. Coinciding with the induction of histone acetylases, phorbol ester markedly enhanced IFN-alpha-stimulated gene expression in U937 cells. Supporting the role for PCAF in conferring IFN responsiveness, transfection of PCAF into U937 cells led to a large increase in IFN-alpha-inducible promoter activity. These results demonstrate that PCAF is a phorbol ester-inducible coactivator of the IRF proteins which contributes to the establishment of type I IFN responsiveness. C1 NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. RP Ozato, K (reprint author), NICHHD, Lab Mol Growth Regulat, NIH, Bldg 6,Rm 2A01, Bethesda, MD 20892 USA. EM ozatok@nih.gov NR 61 TC 84 Z9 85 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 1999 VL 19 IS 3 BP 1810 EP 1820 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 168MY UT WOS:000078697900019 PM 10022868 ER PT J AU Wong, C Rougier-Chapman, EM Frederick, JP Datto, MB Liberati, NT Li, JM Wang, XF AF Wong, C Rougier-Chapman, EM Frederick, JP Datto, MB Liberati, NT Li, JM Wang, XF TI Smad3-Smad4 and AP-1 complexes synergize in transcriptional activation of the c-Jun promoter by transforming growth factor beta SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CELL-CYCLE ARREST; TGF-BETA; II RECEPTOR; GENE-EXPRESSION; PROTO-ONCOGENE; SMAD PROTEINS; CANCER CELLS; INDUCTION; BINDING; AUTOINDUCTION AB Transcriptional regulation by transforming growth factor beta (TGF-beta) is a complex process which is likely to involve cross talk between different DNA responsive elements and transcription factors to achieve maximal promoter activation and specificity. Here, me describe a concurrent requirement for two discrete responsive elements in the regulation of the c-Jun promoter, one a binding site for a Smad3-Smad4 complex and the other an AP-1 binding site. The two elements are located 120 bp apart in the proximal c-Jun promoter, and each was able to independently bind its corresponding transcription factor complex. The effects of independently mutating each of these elements were nonadditive; disruption of either sequence resulted in complete or severe reductions in TGF-beta responsiveness. This simultaneous requirement for two distinct and independent DNA binding elements suggests that Smad and AP-1 complexes function synergistically to mediate TGF-beta-induced transcriptional activation of the c-Jun promoter. C1 Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27708 USA. NCI, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Wang, XF (reprint author), Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Box 3813, Durham, NC 27708 USA. FU NIDDK NIH HHS [DK45756] NR 61 TC 186 Z9 198 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 1999 VL 19 IS 3 BP 1821 EP 1830 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 168MY UT WOS:000078697900020 PM 10022869 ER PT J AU John, S Vinkemeier, U Soldaini, E Darnell, JE Leonard, WJ AF John, S Vinkemeier, U Soldaini, E Darnell, JE Leonard, WJ TI The significance of tetramerization in promoter recruitment by Stat5 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RECEPTOR-ALPHA GENE; DNA-BINDING ACTIVITY; JAK-3 JANUS KINASE; IL-2 RECEPTOR; SIGNAL TRANSDUCERS; T-LYMPHOCYTES; INTERLEUKIN-2; TRANSCRIPTION; EXPRESSION; CHAIN AB Stat5a and Stat5b are rapidly activated by a wide range of cytokines and growth factors, including interleukin-2 (IL-2). We have previously shown that these signal transducers and activators of transcription (STAT proteins) are key regulatory proteins that bind to two tandem gamma interferon-activated site (GAS) motifs within an IL-2 response element (positive regulatory region LU [PRRIII]) in the human IL-2R alpha promoter. In this study, we demonstrate cooperative binding of Stat5 to PRRIII and explore the molecular basis underlying this cooperativity. We demonstrate that formation of a tetrameric Stat5 temples is essential for the IL-2-inducible activation of PRRIII. Stable tetramer formation of Stat5 is mediated through protein-protein interactions involving a tryptophan residue conserved in all STATs and a lysine residue in the Stat5 N-terminal domain (N domain). The functional importance of tetramer formation is shown by the decreased levels of transcriptional activation associated,vith mutations In these residues. Moreover, the requirement for STAT protein-protein interactions for gene activation from a promoter with tandemly linked GAS motifs can be relieved by strengthening the avidity of protein-DNA interactions for the individual binding sites. Taken together, these studies demonstrate that a dimeric but tetramerization-deficient Stat5 protein can activate only a subset of target sites. For functional activity on a wider range of potential recognition sites, N-domain-mediated oligomerization is essential. C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. Rockefeller Univ, Mol Cell Biol Lab, New York, NY 10021 USA. Rockefeller Univ, Lab Mol Biophys, New York, NY 10021 USA. RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10,Rm 7N252,10 Ctr Dr, Bethesda, MD 20892 USA. EM wjl@helix.nih.gov NR 38 TC 143 Z9 145 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 1999 VL 19 IS 3 BP 1910 EP 1918 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 168MY UT WOS:000078697900029 PM 10022878 ER PT J AU Bost, F McKay, R Bost, M Potapova, O Dean, NM Mercola, D AF Bost, F McKay, R Bost, M Potapova, O Dean, NM Mercola, D TI The Jun kinase 2 isoform is preferentially required for epidermal growth factor-induced transformation of human A549 lung carcinoma cells SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Review ID ACTIVATED PROTEIN-KINASES; FACTOR RECEPTOR GENE; C-ALPHA EXPRESSION; SIGNAL-TRANSDUCTION; ANTISENSE OLIGONUCLEOTIDES; NUDE-MICE; ULTRAVIOLET-RADIATION; THERAPEUTIC AGENTS; INDUCED APOPTOSIS; CANCER-CELLS AB We have previously found that epidermal growth factor (EGF) mediates growth through the Jun N-terminal kinase/stress-activated kinase (JNK/SAPK) pathway in A549 human lung carcinoma cells. As observed here, EGF treatment also greatly enhances the tumorigenicity of A549 cells, suggesting an important role for JNK in cancer cell growth (F. Best, R McKay, N. Dean, and D. Mercola, J. Biol. Chem. 272:33422-33429, 1997). Several isoforms families of JNK, JNK1, JNK2, and JNK3, have been isolated; they arise from alternative splicing of three different genes and have distinct substrate binding properties. Here we have used specific phosphorothioate oligonucleotides targeted against the two major isoforms, JNK1 and JNK2, to discriminate their roles in EGF-induced transformation. Multiple antisense sequences have been screened, and two high-affinity and specific candidates have been identified. Antisense JNK1 eliminated steady-state mRNA and JNK1 protein expression with a 50% effective concentration (EC50) of <0.1 mu M but did not alter JNK2 mRNA or protein levels. Conversely, antisense JNK2 specifically eliminated JNK2 steady-state mRNA and protein expression with an EC50 of 0.1 mu M. Antisense JNK1 and antisense JNK2 inhibited by 40 and 70%, respectively, EGF-induced total JNK activity, whereas sense and scrambled-sequence control oligonucleotides had no effect. The elimination of mRNA, protein, and JNK activities lasted 48 and 72 h following a single Lipofectin treatment with antisense JNK1 and JNK2, respectively, indicating sufficient duration for examining the impact of specific elimination on the phenotype. Direct proliferation assays demonstrated that antisense JNK2 inhibited EGF-induced doubling of growth as well as the combination of active antisense oligonucleotides did. EGF treatment also induced colony formation in soft agar. This effect was completely inhibited by antisense JNK2 and combined-antisense treatment but not altered by antisense JNK1 alone. These results show that EGF doubles the proliferation (growth in soft agar as well as tumorigenicity in athymic mice) of A549 lung carcinoma cells and that the JNK2 isoform but net JNK1 is utilized for mediating the effects of EGF. This study represents the first demonstration of a cellular phenotype regulated by a JNK isoform family, JNK2. C1 Sidney Kimmel Canc Ctr, San Diego, CA 92121 USA. ISIS Pharmaceut, Dept Mol Pharmacol, Carlsbad, CA 92008 USA. NIA, NIH, Baltimore, MD 21224 USA. Burnham Inst, La Jolla, CA 92037 USA. RP Mercola, D (reprint author), Sidney Kimmel Canc Ctr, 10835 Altman Row, San Diego, CA 92121 USA. EM danmercola@skcc.org FU NCI NIH HHS [CA56834, CA76173] NR 100 TC 129 Z9 133 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 1999 VL 19 IS 3 BP 1938 EP 1949 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 168MY UT WOS:000078697900032 PM 10022881 ER PT J AU Tran, HT Gordenin, DA Resnick, MA AF Tran, HT Gordenin, DA Resnick, MA TI The 3 '-> 5 ' exonucleases of DNA polymerases delta and epsilon and the 5 '-> 3 ' exonuclease Exo1 have major roles in postreplication mutation avoidance in Saccharomyces cerevisiae SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MISMATCH REPAIR GENES; SIMPLE REPETITIVE DNA; CELL NUCLEAR ANTIGEN; DOUBLE-STRAND BREAK; ESCHERICHIA-COLI; MITOTIC RECOMBINATION; IN-VITRO; YEAST; REPLICATION; REQUIREMENT AB Replication fidelity is controlled by DNA polymerase proofreading and postreplication mismatch repair. We have genetically characterized the roles of the 5'-->3' Exo1 and the 3'-->5' DNA polymerase exonucleases in mismatch repair in the yeast Saccharomyces cerevisiae by using various genetic backgrounds and highly sensitive mutation detection systems that are based on long and short homonucleotide runs. Genetic interactions were examined among DNA polymerase epsilon (pol2-4) and delta (pol3-01) mutants defective in 3'-->5' proofreading exonuclease, mutants defective in the 5'-->3' exonuclease Exo1, and mismatch repair mutants (msh2, msh3, or msh6). These three exonucleases play an important role in mutation avoidance. Surprisingly, the mutation rate in an exo1 pol3-01 mutant was comparable to that in an msh2 pol3-01 mutant, suggesting that they participate directly in postreplication mismatch repair as well as in other DNA metabolic processes. C1 NIEHS, Mol Genet Lab, Chromosome Stabil Grp, Res Triangle Pk, NC 27709 USA. St Petersburg State Univ, Dept Genet, St Petersburg 199034, Russia. RP Resnick, MA (reprint author), NIEHS, Mol Genet Lab, Chromosome Stabil Grp, 101 TW Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA. NR 48 TC 143 Z9 143 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 1999 VL 19 IS 3 BP 2000 EP 2007 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 168MY UT WOS:000078697900038 PM 10022887 ER PT J AU Andreev, J Simon, JP Sabatini, DD Kam, J Plowman, G Randazzo, PA Schlessinger, J AF Andreev, J Simon, JP Sabatini, DD Kam, J Plowman, G Randazzo, PA Schlessinger, J TI Identification of a new Pyk2 target protein with Arf-GAP activity SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ADP-RIBOSYLATION FACTOR; GTPASE-ACTIVATING PROTEIN; POST-GOLGI VESICLES; TYROSINE KINASE; ACID PHOSPHOLIPIDS; MAMMALIAN-CELLS; PLASMA-MEMBRANE; BINDING-PROTEIN; SH3 DOMAIN; RAT-LIVER AB Protein tyrosine kinase Pyk2 is activated by a variety of G-protein-coupled receptors and by extracellular signals that elevate intracellular Ca2+ concentration. We have identified a new Pyk2 binding protein designated Pap. Pap is a multidomain protein composed of an N-terminal alpha-helical region with a coiled-coil motif, followed by a pleckstrin homology domain, an Arf-GAP domain, an ankyrin homology region, a proline-rich region, and a C-terminal SH3 domain. We demonstrate that Pap forms a stable complex with Pyk2 and that activation of Pyk2 leads to tyrosine phosphorylation of Pap in living cells. Immunofluorescence experiments demonstrate that Pap is localized in the Golgi apparatus and at the plasma membrane, where it is colocalized with Pyk2. In addition, in vitro recombinant Pap exhibits strong GTPase-activating protein (GAP) activity towards the small GTPases Arf1 and Arf5 and weak activity towards Arf6. Addition of recombinant Pap protein to Golgi preparations prevented Arf-dependent generation of post-Golgi vesicles in vitro. Moreover, overexpression of Pap in cultured cells reduced the constitutive secretion of a marker protein. We propose that Pap functions as a GAP for Arf and that Pyk2 may be involved in regulation of vesicular transport through its interaction with Pap. C1 NYU, Med Ctr, Dept Pharmacol, New York, NY 10016 USA. NYU, Med Ctr, Dept Cell Biol, New York, NY 10016 USA. NYU, Med Ctr, Skirball Inst, New York, NY 10016 USA. NCI, Div Basic Sci, Cellular Oncol Lab, Bethesda, MD 20892 USA. Sugen Inc, S San Francisco, CA 94080 USA. RP Schlessinger, J (reprint author), NYU, Med Ctr, Dept Pharmacol, 550 1st Ave, New York, NY 10016 USA. RI PLOWMAN, Greg/E-2012-2011 NR 62 TC 129 Z9 137 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 1999 VL 19 IS 3 BP 2338 EP 2350 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 168MY UT WOS:000078697900071 PM 10022920 ER PT J AU Dang, VD Benedik, MJ Ekwall, K Choi, J Allshire, RC Levin, HL AF Dang, VD Benedik, MJ Ekwall, K Choi, J Allshire, RC Levin, HL TI A new member of the Sin3 family of corepressors is essential for cell viability and required for retroelement propagation in fission yeast SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SACCHAROMYCES RETROTRANSPOSON TY5; IMMUNODEFICIENCY-VIRUS TYPE-1; RNA-POLYMERASE-III; TRANSCRIPTIONAL REPRESSION; SCHIZOSACCHAROMYCES-POMBE; HISTONE DEACETYLASE; CHROMATIN STRUCTURE; DNA-BINDING; RETROVIRAL INTEGRATION; REVERSE-TRANSCRIPTASE AB Tf1 is a long terminal repeat (LTR)-containing retrotransposon that propagates within the fission yeast Schizosaccharomyces pombe. LTR-retrotransposons possess significant similarity to retroviruses and therefore serve as retrovirus models. To determine what features of the host cell are important for the proliferation of this class of retroelements, we screened for mutations in host genes that reduced the transposition activity of Tf1. We report here the isolation and characterization of pst1(+), a gene required for Tf1 transposition. The predicted amino acid sequence of Pst1p possessed high sequence homology with the Sin3 family of proteins, known for their interaction with histone deacetylases. However, unlike the SIN3 gene of Saccharomyces cerevisiae, pst1(+) is essential for cell viability. Immunofluorescence microscopy indicated that Pst1p was localized in the nucleus. Consistent with the critical role previously reported for Sin3 proteins in the histone acetylation process, we found that the growth of the strain with the pst1-1 allele was supersensitive to the specific histone deacetylase inhibitor trichostatin A. However, our analysis of strains with the pst1-1 mutation was unable to detect any changes in the acetylation of specific lysines of histones H3 and H4 as measured in bulk chromatin. Interestingly, the pst1-1 mutant strain produced wild-type levels of TM-encoded proteins and cDNA, indicating that the defect in transposition occurred after reverse transcription. The results of immunofluorescence microscopy showed that the nuclear localization of the TM capsid protein was disrupted in the strain with the pst1-1 mutation, indicating an important role of pst1(+) in modulating the nuclear import of Tf1 virus-like particles. C1 NICHHD, Lab Eukaryot Gene Regulat, NIH, Bethesda, MD 20892 USA. Western Gen Hosp, MRC, Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland. RP NICHHD, Lab Eukaryot Gene Regulat, NIH, Bethesda, MD 20892 USA. EM Henry_Levin@nih.gov RI Benedik, Michael/H-2478-2011 OI Benedik, Michael/0000-0002-7435-0092 NR 86 TC 22 Z9 24 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 1999 VL 19 IS 3 BP 2351 EP 2365 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 168MY UT WOS:000078697900072 PM 10022921 ER PT J AU Crandall, KA Kelsey, CR Imamichi, H Lane, HC Salzman, NP AF Crandall, KA Kelsey, CR Imamichi, H Lane, HC Salzman, NP TI Parallel evolution of drug resistance in HIV: Failure of nonsynonymous/synonymous substitution rate ratio to detect selection SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE human immunodeficiency virus; phylogeny; drug resistance; drug therapy; convergent evolution; parallel evolution ID IMMUNODEFICIENCY-VIRUS TYPE-1; ACTIVE ANTIRETROVIRAL THERAPY; EFFECTIVE POPULATION-SIZE; NUCLEOTIDE SUBSTITUTION; CONVERGENT EVOLUTION; CLADOGRAM ESTIMATION; MOLECULAR EVOLUTION; PROTEASE INHIBITOR; SEQUENCE DATA; MUTATIONS AB Parallel or convergent evolution at the molecular level has been difficult to demonstrate especially when rigorous statistical criteria are applied. We present sequence data from the protease gene from eight patients infected with the human immunodeficiency virus (HIV-1). These patients have been on multiple drug therapies for at least 2 years. We present sequence data from two timepoints: time zero-the initiation of drug therapy-and a subsequent timepoint between 59 and 104 weeks after the initiation of drug therapy. In addition to the sequence data, we present viral load data from both initial and final timepoints. Our phylogenetic analyses indicate significant evolution of virus from initial to final time points, even in three of eight patients who show low viral loads. Of the five patients who escaped drug therapy, identical amino acid replacements were seen in all five patients at two different codon positions, an indication of parallel evolution. We also measured genetic diversity for these patients and found no correlation between genetic diversity and viral load. Finally, we calculated the nonsynonymous and synonymous substitution rates and showed that the ratio of nonsynonymous to synonymous substitution compared to the value of one may be a poor indicator of natural selection. C1 Brigham Young Univ, Dept Zool, Provo, UT 84602 USA. NCI, SAIC Frederick, Frederick Canc Res & Dev Ctr, NIH, Bethesda, MD 20892 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Crandall, KA (reprint author), Brigham Young Univ, Dept Zool, 574 Widtsoe Bldg, Provo, UT 84602 USA. EM keith_crandall@byu.edu OI Crandall, Keith/0000-0002-0836-3389 NR 49 TC 110 Z9 115 U1 0 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0737-4038 EI 1537-1719 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD MAR PY 1999 VL 16 IS 3 BP 372 EP 382 PG 11 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 176PK UT WOS:000079160500007 PM 10331263 ER PT J AU Nuwaysir, EF Bittner, M Trent, J Barrett, JC Afshari, CA AF Nuwaysir, EF Bittner, M Trent, J Barrett, JC Afshari, CA TI Microarrays and toxicology: The advent of toxicogenomics SO MOLECULAR CARCINOGENESIS LA English DT Article DE toxicology; gene expression; animal bioassay ID DENSITY OLIGONUCLEOTIDE ARRAYS; GENE-EXPRESSION PATTERNS; CDNA MICROARRAYS; DNA MICROARRAY; PROBE ARRAYS; HUMAN GENOME; LARGE-SCALE; HYBRIDIZATION; CLONES; POLYMORPHISMS AB The availability of genome-scale DNA sequence information and reagents has radically altered life-science research. This revolution has led to the development of a new scientific subdiscipline derived from a combination of the fields of toxicology and genomics. This subdiscipline, termed toxicogenomics, is concerned with the identification of potential human and environ mental toxicants, a nd their putative mechanisms of action, through the use of genomics resources. One such resource is DNA microarrays or "chips," which allow the monitoring of the expression levels of thousands of genes simultaneously. Here we propose a general method by which gene expression, as measured by cDNA microarrays, can be used as a highly sensitive and informative marker for toxicity. Our purpose is to acquaint the reader with the development and current state of microarray technology and to present our view of the usefulness of microarrays to the field of toxicology. Mel. Carcinog. 24: 153-159, 1999. (C) 1999 Wiley-Liss, Inc. C1 NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. Natl Human Genome Res Inst, Canc Genet Lab, Bethesda, MD USA. RP Nuwaysir, EF (reprint author), NIEHS, Mol Carcinogenesis Lab, 111 Alexander Dr, Res Triangle Pk, NC 27709 USA. FU NIEHS NIH HHS [ES07017-24] NR 39 TC 436 Z9 469 U1 5 U2 47 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD MAR PY 1999 VL 24 IS 3 BP 153 EP 159 DI 10.1002/(SICI)1098-2744(199903)24:3<153::AID-MC1>3.0.CO;2-P PG 7 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 185BP UT WOS:000079648500001 PM 10204799 ER PT J AU Shen, JC Wang, TTY Chang, S Hursting, SD AF Shen, JC Wang, TTY Chang, S Hursting, SD TI Mechanistic studies of the effects of the retinoid N-(4-hydroxyphenyl)retinamide on prostate cancer cell growth and apoptosis SO MOLECULAR CARCINOGENESIS LA English DT Article DE fenretinide; N-(4-hydroxyphenyl)retinamide; prostate cancer; LNCaP ID FENRETINIDE; LNCAP; CHEMOPREVENTION; REGRESSION; RETINAMIDE; CYCLE; DEATH; BCL-2; ACID AB To explore the mechanisms underlying the chemopreventive effects of the synthetic retinoid N-(4-hydroxyphenyl)retinamide (4-HPR) in prostate cancer, we evaluated the anti-proliferative and apoptosis-inducing effects of 4-HPR in the androgen-sensitive human prostate cancer cell line LNCaP. 4-HPR decreased the number of viable LNCaP cells las measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay) in a dose-dependent manner. Although 4-HPR exerted a modest G(1) cell-cycle block (as determined by flow cytometry), its effect on reduced cell number appeared to result primarily from induction of apoptosis las measured by an enzyme-linked immunosorbent assay and flow-cytometric assays). The mitogenic effects of R1881, a non-metabolizable androgen that potently induces LNCaP cell proliferation, was completely blocked by greater than 0.5 mu M 4-HPR. Furthermore, increasing the R1881 concentration in the presence of 2.0 mu M 4-HPR increased apoptotic cell death. 4-HPR decreased prostate-specific antigen (PSA) protein levels in conditioned medium and decreased PSA mRNA expression. 4-HPR also decreased the ratio of bcl-2 to bax mRNA expression in LNCaP cells by approximately 45%, indicating that the apoptotic effects of 4-HPR may be mediated, at least in part, by alterations in the bcl-2/bax-regulated apoptotic pathway. N-acetylcysteine (4 mM) completely blocked the anti-proliferative and apoptotic-inducing effects of 4-HPR suggesting that an oxidative mechanism may be involved. We concluded that (i) 4-HPR exerts growth-suppressive and apoptotic effects on LNCaP cells, (ii) 4-HPR can interact with androgen to suppress proliferation and induce apoptosis, (iii) the apoptotic effects of 4-HPR may be mediated in part by the bcl-2/bax pathway, and (iv) a pro-oxidant mechanism may contribute to the anti-proliferative a nd a apoptotic-inducing effects of 4-HPR. Mol. Carcinog. 24:160-168, 1999. (C) 1999 Wiley-Liss, Inc. C1 Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. NCI, Frederick Canc Res Ctr, Frederick, MD 21701 USA. Univ Texas, MD Anderson Canc Ctr, Dept Carcinogenesis, Smithville, TX USA. RP Hursting, SD (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, 1515 Holcombe Blvd,Box 189, Houston, TX 77030 USA. NR 26 TC 27 Z9 28 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD MAR PY 1999 VL 24 IS 3 BP 160 EP 168 DI 10.1002/(SICI)1098-2744(199903)24:3<160::AID-MC2>3.0.CO;2-M PG 9 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 185BP UT WOS:000079648500002 PM 10204800 ER PT J AU Ito, M Yuan, CX Malik, S Gu, W Fondell, JD Yamamura, S Fu, ZY Zhang, XL Qin, J Roeder, RG AF Ito, M Yuan, CX Malik, S Gu, W Fondell, JD Yamamura, S Fu, ZY Zhang, XL Qin, J Roeder, RG TI Identity between TRAP and SMCC complexes indicates novel pathways for the function of nuclear receptors and diverse mammalian activators SO MOLECULAR CELL LA English DT Article ID RNA-POLYMERASE-II; MEDIATE TRANSCRIPTIONAL ACTIVATION; COACTIVATOR; DOMAIN; CLONING; BINDING; PROTEIN; VP16 AB The human thyroid hormone receptor-associated protein (TRAP) complex, an earlier described coactivator for nuclear receptors, and an SRB- and MED-containing cofactor complex (SMCC) that mediates activation by Ga14-p53 are shown to be virtually the same with respect to specific polypeptide subunits, coactivator functions, and mechanisms of action (activator interactions). In parallel with ligand-dependent interactions of nuclear receptors with the TRAP220 subunit, p53 and VP16 activation domains interact directly with a newly cloned TRAP80 subunit. These results indicate novel pathways for the function of nuclear receptors and other activators (p53 and VP16) through a common coactivator complex that is likely to target RNA polymerase II. Identification of the TRAP230 subunit as a previously predicted gene product also suggests a coactivator-related transcription defect in certain disease states. C1 Rockefeller Univ, Biochem & Mol Biol Lab, New York, NY 10021 USA. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Roeder, RG (reprint author), Rockefeller Univ, Biochem & Mol Biol Lab, New York, NY 10021 USA. NR 37 TC 325 Z9 339 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD MAR PY 1999 VL 3 IS 3 BP 361 EP 370 DI 10.1016/S1097-2765(00)80463-3 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 181TV UT WOS:000079459300010 PM 10198638 ER PT J AU Xu, XL Weaver, Z Linke, SP Li, CL Gotay, J Wang, XW Harris, CC Ried, T Deng, CX AF Xu, XL Weaver, Z Linke, SP Li, CL Gotay, J Wang, XW Harris, CC Ried, T Deng, CX TI Centrosome amplification and a defective G(2)-M cell cycle checkpoint induce genetic instability in BRCA1 exon 11 isoform-deficient cells SO MOLECULAR CELL LA English DT Article ID EARLY EMBRYONIC LETHALITY; BREAST-CANCER; DNA-DAMAGE; NUCLEAR PHOSPHOPROTEIN; GAMMA-IRRADIATION; MEIOTIC CELLS; P53; MUTATIONS; MOUSE; RAD51 AB Germline mutations of the Brca1 tumor suppressor gene predispose women to breast and ovarian cancers, To study mechanisms underlying BRCA1-related tumorigenesis, we derived mouse embryonic fibroblast cells carrying a targeted deletion of exon 11 of the Brca1 gene. We show that the mutant cells maintain an intact G(1)-S cell cycle checkpoint and proliferate poorly, However, a defective G(2)-M checkpoint in these cells is accompanied by extensive chromosomal abnormalities. Mutant fibroblasts contain multiple, functional centrosomes, which lead to unequal chromosome segregation, abnormal nuclear division, and aneuploidy. These data uncover an essential role of BRCA1 in maintaining genetic stability through the regulation of centrosome duplication and the G(2)-M checkpoint and provide a molecular basis for the role of BRCA1 in tumorigenesis. C1 NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Deng, CX (reprint author), NIDDKD, Genet Dev & Dis Branch, NIH, 10-9N105, Bethesda, MD 20892 USA. RI Wang, Xin/B-6162-2009; deng, chuxia/N-6713-2016 NR 43 TC 613 Z9 623 U1 2 U2 15 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD MAR PY 1999 VL 3 IS 3 BP 389 EP 395 DI 10.1016/S1097-2765(00)80466-9 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 181TV UT WOS:000079459300013 PM 10198641 ER PT J AU Lim, CS Baumann, CT Htun, H Xian, WJ Irie, M Smith, CL Hager, GL AF Lim, CS Baumann, CT Htun, H Xian, WJ Irie, M Smith, CL Hager, GL TI Differential localization and activity of the A- and B-forms of the human progesterone receptor using green fluorescent protein chimeras SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID GLUCOCORTICOID RECEPTORS; SUBNUCLEAR TRAFFICKING; CELLS; PHOSPHORYLATION; PROMOTER; MECHANISM; TEMPLATES AB Subcellular localization and transcriptional activity of green fluorescent protein-progesterone receptor A and B chimeras (GFP-PRA and GFP-PRB) were examined in living mammalian cells. Both GFP-PRA and B chimeras were found to be similar in transcriptional activity compared with their non-GFP counterparts. GFP-PRA and PRA were both weakly active, while GFP-PRB and PRE gave a 20- to 40-fold induction using a reporter gene containing the full-length mouse mammary tumor virus long-terminal repeat linked to the luciferase gene (pLTRluc). Using fluorescence microscopy, nuclear/cytoplasmic distributions for the unliganded and hormone activated forms of GFP-PRA and GFP-PRB were characterized. The two forms of the receptor were found to have distinct intracellular distributions; GFP-PRA was found to be more nuclear than GFP-PRB in four cell lines examined. The causes for and implications of this differential localization of the A and B forms of the human PR are discussed. C1 NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. RP Hager, GL (reprint author), NCI, Lab Receptor Biol & Gene Express, NIH, Bldg 41,Room B602, Bethesda, MD 20892 USA. NR 25 TC 101 Z9 105 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD MAR PY 1999 VL 13 IS 3 BP 366 EP 375 DI 10.1210/me.13.3.366 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 172MY UT WOS:000078929400002 PM 10076994 ER PT J AU Zhou, LX Chen, H Xu, P Cong, LN Sciacchitano, S Li, YH Graham, D Jacobs, AR Taylor, SI Quon, MJ AF Zhou, LX Chen, H Xu, P Cong, LN Sciacchitano, S Li, YH Graham, D Jacobs, AR Taylor, SI Quon, MJ TI Action of insulin receptor substrate-3 (IRS-3) and IRS-4 to stimulate translocation of GLUT4 in rat adipose cells SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID TYROSINE KINASE-ACTIVITY; PHOSPHATIDYLINOSITOL 3-KINASE; GLUCOSE-TRANSPORT; 3T3-L1 ADIPOCYTES; PHOSPHOTYROSINE PROTEIN; DOCKING PROTEIN; DNA-SYNTHESIS; DOMAIN; OVEREXPRESSION; MEDIATE AB The insulin receptor initiates insulin action by phosphorylating multiple intracellular substrates. Previously, we have demonstrated that insulin receptor substrates (IRS)-1 and -2 can mediate insulin's action to promote translocation of GLUT4 glucose transporters to the cell surface in rat adipose cells. Although IRS-1, -2, and -4 are similar in overall structure, IRS-3 is approximate to 50% shorter and differs with respect to sites of tyrosine phosphorylation. Nevertheless, as demonstrated in this study, both IRS-3 and IRS-4 can also stimulate translocation of GLUT4. Rat adipose cells were cotransfected with expression Vectors for hemagglutinin (HA) epitope-tagged GLUT4 (GLUT4-HA) and human IRS-1, murine IRS-3, or human IRS-4. Overexpression of IRS-1 led to a 2-fold increase in cell surface GLUT4-HA in cells incubated in the absence of insulin; overexpression of either IRS-3 or IRS-4 elicited a larger increase in cell surface GLUT4-HA. Indeed, the effect of IRS-3 in the absence of insulin was approximate to 40% greater than the effect of a maximally stimulating concentration of insulin in cells not overexpressing IRS proteins. Because phosphatidylinositol (PI) 3-kinase is essential for insulin-stimulated translocation of GLUT4 we also studied a mutant IRS-3 molecule (IRS-3-F4) in which Phe was substituted for Tyr in all four YXXM motifs (the phosphorylation sites predicted to bind to and activate PI 9-kinase). Interestingly, overexpression of IRS-3-F4 did not promote translocation of GLUT4-HA, but actually inhibited the ability of insulin to stimulate translocation of GLUT4-HA to the cell surface. Our data suggest that IRS-3 and IRS-4 are capable of mediating PI 3-kinase-dependent metabolic actions of insulin in adipose cells, and that IRS proteins play a physiological role in mediating translocation of GLUT4. C1 NHLBI, Hypertens Endocrine Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. RP Quon, MJ (reprint author), NHLBI, Hypertens Endocrine Branch, NIH, Bldg 10,Room 8C-103,10 Ctr Dr MSC 1754, Bethesda, MD 20892 USA. RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 NR 45 TC 39 Z9 40 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD MAR PY 1999 VL 13 IS 3 BP 505 EP 514 DI 10.1210/me.13.3.505 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 172MY UT WOS:000078929400015 PM 10077007 ER PT J AU Wolfgang, M van Putten, JPM Hayes, SF Koomey, M AF Wolfgang, M van Putten, JPM Hayes, SF Koomey, M TI The comP locus of Neisseria gonorrhoeae encodes a type IV prepilin that is dispensable for pilus biogenesis but essential for natural transformation SO MOLECULAR MICROBIOLOGY LA English DT Article ID GENERAL SECRETORY PATHWAY; GRAM-NEGATIVE BACTERIA; PSEUDOMONAS-AERUGINOSA; BACILLUS-SUBTILIS; GENETIC-TRANSFORMATION; TWITCHING MOTILITY; PILIN; COMPETENCE; PROTEIN; METHYLATION AB The expression of type IV pill (Tfp) by Neisseria gonorrhoeae has been shown to be essential for natural genetic transformation at the level of sequence-specific uptake of DNA, All previously characterized mutants defective in this step of transformation either lack Tfp or are altered in the expression of Tfp-associated properties, such as twitching motility, autoagglutination and the ability to bind to human epithelial cells. To examine the basis for this relationship, we identified potential genes encoding polypeptides sharing structural similarities to PiIE, the Tfp subunit, within the N. gonorrhoeae genome sequence database. We found that disruption of one such gene, designated comP (for competence-associated prepilin), leads to a severe defect in the capacity to take up DNA in a sequence-specific manner, but does not alter Tfp biogenesis or expression of the Tfp-associated properties of autoagglutination, twitching motility and human epithelial cell adherence. Indirect evidence based on immunodetection suggests that ComP is expressed at very low levels relative to that of PiIE. The process of DNA uptake in gonococci, therefore, is now known to require the expression of at least three distinct components: Tfp, the recently identified PiIT protein and ComP. C1 Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA. NIAID, Rocky Mt Labs, Microbial Struct & Funct Lab, NIH, Hamilton, MT USA. NIAID, Rocky Mt Labs, Microscopy Branch, NIH, Hamilton, MT USA. Univ Oslo, Ctr Biotechnol, Oslo, Norway. RP Koomey, M (reprint author), Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA. OI van Putten, Jos/0000-0002-4126-8172 FU NCRR NIH HHS [M01 RR 00042]; PHS HHS [A127837] NR 39 TC 70 Z9 70 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD MAR PY 1999 VL 31 IS 5 BP 1345 EP 1357 DI 10.1046/j.1365-2958.1999.01269.x PG 13 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 176LY UT WOS:000079153900006 PM 10200956 ER EF